Comparative study between intravitreal ranibizumab and ...

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Vol. 78 - nº 4 - Julho/Agosto 2019

Publicação bimestral

ISSN 0034-7280Versão impressa

Publicação oficial da Sociedade Brasileira de Oftalmologia

Optical coherence tomography and congenital retinoschisis

Study of asphericity coefficient and longitudinal spherical aberration surface corneal

Indexado nas bases de dados Scielo, Scopus e Lilacs

w Comparative study between intravitreal ranibizumab and triamcinolone treatment of diabetic macular edema as regard to optical coherence tomography changes and visual acuity

w Causes of death and discard of donated corneal tissues: Federal District eye bank analysis 2014 -2017

w Avaliação econômica do glaucoma primário de ângulo aberto

w Autofluorescência em um caso de distrofia macular anular concêntrica benigna

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Associada a ABEC - Associação Brasileira

de Editores Científicos

Publicação bimestral Rev Bras Oftalmol, v. 78, n. 4, p. 213-280, Jul./Ago. 2019

RevistaBrasileira de

OftalmologiaPUBLICAÇÃO OFICIAL:

SOCIEDADE BRASILEIRA DE OFTALMOLOGIA

Indexada nas bases de dados:

ISSN 0034-7280(Versão impressa)

ISSN 1982-8551(Versão eletrônica)

Sociedade Brasileira de Oftalmologia

Editor ChefeArlindo José Freire Portes (RJ)

Co-editoresAndré Luis Freire Portes (RJ)André Luiz Land Curi (RJ)Bruno Machado Fontes (RJ)Carlos Eduardo Leite Arieta (SP)Hamilton Moreira (PR)Juliana Almodin Colalilo (PR) Liana Maria Vieira de Oliveira Ventura (PE)Marcony R. Santhiago (RJ)Mario Martins dos Santos Motta (RJ)Miguel Ângelo PadilhaNewton Kara-Junior (SP)Renato Ambrósio Jr. (RJ) Ricardo Augusto Paletta Guedes (MG)Rodrigo Pessoa Cavalcanti Lira (PE)Silvana Artioli Schellini (SP)

Corpo Editorial InternacionalChristopher Rapuano - Phyladelphia - EUAEsmeralda Costa - Coimbra - PortugalFelipe A. A. Medeiros - Califórnia - EUA Francisco Rodríguez Alvira – Bogotá – ColombiaHelena Felipe – Lisboa - PortugalJean Jacques De Laey - Ghent - BélgicaJean-Philippe Nordmann - Paris - FrançaJesús Merayo-LLoves - Oviedo - EspanhaKevin M. Miller - Califórnia - EUAKeweh Mansouri - Paris - FraçaLihteh Wu – San José - Costa RicaLiliana Werner - Utah - EUAPaulo Torres - Lisboa - Portugal

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Presidente:Edna Emilia Gomes da Motta Almodin (PR)

Presidentes Regionais:Sul: Sergio Kwitiko (RS)

Sudeste: Eduardo Martines (SP)Nordeste: Mario Ursulino Machado Carvalho (SE)

Centro Oeste: Maria Regina Vieira Angelo Marques (MT)Norte: Cláudio do Carmo Chaves (AM)

Secretário Geral:Helder Alves da Costa Filho (RJ)

1º Secretário: Oswaldo Ferreira Moura Brasil (RJ)

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Associação Brasileira de Catarata e Cirurgia RefrativaPresidente: Walton Nosé

Associação Maranhense de OftalmologiaPresidente: Stephan Neves Noleto

Associação Matogrossense de OftalmologiaPresidente: Renato J. Bett Correia

Associação Pan-Americana de Banco de OlhosPresidente: Alvio Isao Shiguematsu

Associação Paranaense de OftalmologiaPresidente: Marcello Fonseca

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Sociedade Brasileira de Ecografia em OftalmologiaPresidente: Norma Allemann

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Sociedade Capixaba de OftalmologiaPresidente: Fernando Baldessin Marim

SOCIEDADES FILIADAS À SOCIEDADE BRASILEIRA DE OFTALMOLOGIA

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Victor Cvintal (SP) Suplentes:

Tânia Mara Cunha Schaefer (PR)Paulo Ferrara de Almeida Cunha (MG)Lizabel Vieira Barbosa Gamperli (MS)

Sociedade Catarinense de OftalmologiaPresidente: Ayrton Roberto Bravo RamosSociedade Cearense de Oftalmologia

Presidente: George Emilio Sobreira CarneiroSociedade Goiana de OftalmologiaPresidente: Fernando Heitor de Paula

Sociedade Norte-Nordeste de OftalmologiaPresidente: David da Rocha Lucena

Sociedade de Oftalmologia do AmazonasPresidente: Leonardo Bivar

Sociedade de Oftalmologia da BahiaPresidente: Amilton de Almeida Sampaio Júnior

Sociedade de Oftalmologia do Nordeste MineiroPresidente: Mauro César Gobira Guimarães

Sociedade de Oftalmologia de PernambucoPresidente: Marcelo Maia Valença

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Sociedade de Oftalmologia do Rio Grande do SulPresidente: Isabel Habeyche Cardoso

Sociedade de Oftalmologia do Sul de MinasPresidente: Mansur Elias Ticly Junior

Sociedade Paraense de OftalmologiaPresidente: Carlos Henrique Vasconcelos de Lima

Sociedade Paraibana de OftalmologiaPresidente: Gustavo Dalia

Sociedade Piauiense de OftalmologiaPresidente: Almira Noronha

Sociedade Sergipana de OftalmologiaPresidente: Gustavo Barreto de Melo

Diretoria da SBO 2019-2020

215

Publicação bimestral Rev Bras Oftalmol, v. 78, n. 4, p. 213-280, Jul./Ago 2019

Editorial 217 Micro-invasive glaucoma surgeries. Are they worth it?

Cirurgias micro-invasivasdo glaucoma. Vale a pena? Ricardo Augusto Paletta Guedes

.

Original Article 219 Comparative study between intravitreal ranibizumab and triamcinolone treatment of diabetic

macular edema as regard to optical coherence tomography changes and visual acuity Estudo comparativo entre o tratamento intravítreo com ranibizumabe e triancinolona do

edema macular diabético quanto às alterações na tomografia de coerência óptica e na acui-dade visual

Mansour Hassan Ahmed, Mohammed Othman Abd El Khalek, Mohamed Mostafa Fathy Dabees, Mohamed Maher El-Hefni, Dina Abd El Hamid Mahmoud Shalaby

227 Causes of death and discard of donated corneal tissues: Federal District eye bank analysis 2014 -2017Causa mortis dos doadores e motivo de descarte das córneas: banco de olhos do Distrito Federal 2014-2017

Diogo Souza Loiola, Sônia Nair Báo, Thayssa Neiva da Fonseca Victer, Micheline Borges Lucas, Maria Regi-na Catai Chalita, Thatiane Lima Sampaio

233 Economic evaluation of primary open-angle glaucomaAvaliação econômica do glaucoma primário de ângulo aberto

Sirley Maria de Freitas, Ricardo Augusto Paletta Guedes, Daniela Marcelo Gravina, Vanessa Maria Paletta Guedes, Alfredo Chauobah, Carlos Eduardo de Mello Gomes

Contents - Sumário


Oftalmologia

Disponível eletronicamente: Coordenação deAperfeiçoamento de Pessoal de Nível Superiorwww.sboportal.org.br

http://www.capes.gov.br

ISSN 0034-7280(Versão impressa)

ISSN 1982-8551(Versão eletrônica)

LILACSLiteratura Latino-americana em Ciências da Saúde

SciELOScientific ElectronicLibrary OnLine

Fundada em 01 de junho de 1942CODEN: RBOFA9

PUBLICAÇÃO OFICIAL:SOCIEDADE BRASILEIRA DE OFTALMOLOGIA

Indexada nas bases de dados:

www.freemedicaljournals.com

216

239 Methodology of teaching anatomy of the ocular globeMetodologia de ensino de anatomia do globo ocularAna Paula Amador Pinheiro Cardoso, Hicaro Donato Granhen, Gabriel Felipe Lyra Silva, Rafael de Azevedo Silva, Franklin Coelho Nascimento

242 Evaluation of the color vision acuity pattern of undergraduates of health courses in a Brazilian universityAvaliação do padrão de acuidade visual para cores de acadêmicos da área de saúde em Universidade brasileira

Pedro Henrique Oliveira Oliveira Ribeiro, Geraldo José Medeiros Fernandes, Flávia Beatriz de Andrade Oliveira Ribeiro

246 Influence of visual symptoms in school performance of adolescents Influência dos sintomas visuais no desempenho escolar de adolescentes Camila Pantoja Azevedo, Lucas Emannuel dos Santos Bordallo, Lucas Motta Gadelha Silva, Monaliza dos

Santos Pessoa 250 Reduced visual acuity screening in a Primary Care Unit Triagem de acuidade visual reduzida em uma unidade de Atenção Primária à Saúde Carlos Fernando Adani Pereira, Roberta Costa, Luiz Antonio Del Ciampo, Ivan Ferraz, 255 Treatment of aniseikonia induced by optical correction of anisometropia in elementary

school childrenTratamento da aniseiconia induzida na correção óptica de anisometropia em escolares do ensino fundamental

Helio Paulo Primiano Junior, Luiz Fernando Orlandin, Marcus Vinicius Takatsu, Milton Ruiz Alves, Milton Ruiz Rodrigues Alves

Case Report

260 Fundus autofluorescence in a case of benign concentric annular macular dystrophyAutofluorescência em um caso de distrofia macular anular concêntrica benignaClarissa dos Reis Pereira, Maurício B. Pereira, Eduardo de França Damasceno

264 Transient retinal artery occlusion after phacoemulsification under local anesthetic blockOclusão arterial retiniana transitória após facoemulsificação sob bloqueio anestésico

João Hélio do Nascimento Ribeiro Valentim, Bruno Sá Antunes de Souza, Ícaro Silva Lopes, Leandro Lopes Troncoso, Alexandre Mendonça de Barros Junior

268 In vivo confocal microscopy as a diagnostic tool in Schnyder Corneal Dystrophy’s case Microscopia confocal no auxílio diagnóstico de Distrofia Corneana de Schnyder

Débora Biazim, Diego Casagrande, Paula Kataguiri 271 Tolosa Hunt Syndrome, a painful ophthalmoplegia

Síndrome de Tolosa-Hunt, uma oftalmoplegia dolorosa Maxuel Nogueira dos Santos Junior, Dr Alex Eduardo Siva, Renata Cristina Franzon Bonatti

Review Article 274 Healing: use of collagen matrix

Cicatrização: uso de matriz de colágeno Ana Cláudia Alves Pereira, Kleber Cunha Clemente, Bianca Hayashi Borges da Silva, Vitória Oshiro Orro

Authors Instructions 278 Authors Instructions

217Editorial

The technical difficulties and potential risk of complications of filtering surgeries partly explain why surgical reccommendation is usually left to cases where clinical or laser treatment failed. This paradigm is probably inadequate for the treatment of glaucomatous optic neuropathy. Earlier surgical intervention would save the ocular surface, reduce costs in the long term, and

solve the problem of poor adherence to eye drops.(1)

This need led to the search for better tolerated surgical techniques with a higher safety profile. Micro-invasive glaucoma surgery (MIGS) propose to fill this gap: glaucoma surgery to be performed earlier in the disease continuum.

MIGS is an English acronym for Micro-Invasive Glaucoma Surgery or Minimally Invasive Glaucoma Surgery. The Micro-Invasive version is preferred by most authors recently. MIGS actually corresponds to a group of surgical procedures aimed at improving the safety and predictability of surgical treatment of glaucoma.(1-3) These procedures mostly avoid, or limit in some cases, conjunctival manipulation. They have some characteristics in common:(1-3) the internal ab approach; little traumatic approach; proven efficacy; high safety profile, and fast visual recovery.

The efficacy and safety studies of most MIGS do not compare to traditional filtering surgeries, despite the guidelines and recommendations of the World Glaucoma Association.(4) The fact that MIGS are commonly associated with cataract surgery makes comparisons difficult.

If MIGS is generally less effective than filtering techniques (which remains to be proven!), the rarity of its complications and its excellent safety profile have greatly improved the benefit/risk ratio. (3) It allows the indication of MIGS to be made at earlier stages of glaucoma, where the pressure target to be reached is not as demanding as in very advanced glaucomas. The advantages would be clear: IOP consistently controlled in 24 hours, decrease in the amount of drops per day with all its advantages (less impact on quality of life, decrease in long term costs, and less impact on the ocular surface), improved adherence to treatment, high safety profile.(1,3)

MIGS can be classified according to their mechanism of action. There are those who propose to facilitate the flow of aqueous humor drainage by conventional means (trabecular, Schlemm’s canal and collector channel), performing a trabecular ablation such as trabeculotomy techniques (Trabecutome®, ABIC®, and GATT® Kahook Dual Blade®) or a trabecular by-pass with device implant ( iStent®, iStent Inject® or Hydrus®). Others provide suprachoroidal drainage such as iStent Supra® and CyPass®. A third group of techniques create a new subconjutnival drainage pathway through direct communication between the anterior chamber and the subconjunctival space (XEN gel Stent® or InnFocus®).(1,3)

The micro-invasive glaucoma surgery (MIGS) requires the selection of appropriate cases to get the most expected result. Not all types of MIGS have the same indications and contraindications. However, it is necessary to evaluate the correct indications of the different MIGS techniques within the reasoning of the treatment of glaucoma. (1,3)

MIGS are classically indicated for primary or secondary open-angle glaucomas, and are often indicated in association with cataract extraction surgery. They are contraindicated in narrow-angle or closed-angle glaucoma, and neovascular glaucoma. (1,3)

In Brazil, the MIGS with greater penetration among surgeons are those making a trabecular by-pass through the use of iStent® or iStent Inject® implants (Glaukos Inc., San Clemente, USA). They were the first MIGS techniques to be approved for use in the Brazilian population (2017 for iStent, and 2018 for iStent Inject).

The initial results in the Brazilian population with these trabecular bypass techniques are quite promising, leading to significant blood pressure reduction.(5) Guedes et. al. analyzed the cases in which they used iStent or iStent Inject in association with cataract surgery within 6 months of follow-up. From a similar intraocular pressure (IOP) in the preoperative period (16.5 mmHg in the iStent group, and 17.3 mmHg in the iStent Inject group), patients reached the end of 6 months with significantly lower IOPs (13.9 mmHg and 12.7 mmHg, respectively in the iStent or iStent Inject groups). All patients in the iStent Inject group (model with two implants in the same injector) achieved a final IOP of less than 18 mmHg, whereas in the iStent group (single implant model) 86.8% achieved this level of IOP. (5)

Micro-invasive glaucoma surgeries. Are they worth it?

Cirurgias micro-invasivas do glaucoma. Vale a pena?

Ricardo Augusto Paletta Guedes1 https://orcid.org/0000-0002-9451-738X.

1Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.

Rev Bras Oftalmol. 2019; 78 (4): 217-8

218 Guedes, RAP

The reduction in average number of eye drops per patient was also significant. On average, there was a reduction of 1 to 2 eye drops per patient during the follow-up period, reaching approximately 70% of patients without the need of glaucoma eye drops at the end of 6 months. (5)

MIGS will be increasingly used in Brazil both by glaucoma surgeons and cataract surgeons, thus allowing to increase the options of the surgical treatment of open-angle glaucoma to the earliest stages of the disease. This will allow for a paradigm shift in the treatment of glaucoma, and perhaps help preventing glaucoma from progressing to more advanced stages. It is expected that a more effective blood pressure control (with surgery) earlier in the history of the disease can prevent more serious cases in the future, thus avoiding the need of more invasive and riskier surgeries. In addition to robust clinical evidence and speculation about the impact of using MIGS for glaucoma progression in the future, there is data available suggesting that the use of MIGS would be more cost-effective. A study carried out in Colombia showed that iStent use in surgeries combined with cataract (related to the use of Timolol Maleate 0.5% eye drops, when needed) was the most cost-effective alternative compared to laser trabeculoplasty or different prostaglandins (associated with the use of a fixed combination of Timolol Maleate 0.5% and Dorzolamide Hydrochloride 2%, when needed).(6)Another study carried out in Canada compared the use of iStent Inject (isolated use without being associated with cataract surgery) to the use of different combinations of medications for the treatment of open-angle glaucoma.(7) In said study, iStent Inject was the most cost-effective and fully dominated alternative, that is, the cheapest and the most effective from the perspective of the public health system and in a period of 15 years.(7) The device was only completely dominated from the 4th year follow-up. Before that, the device was not cost-effective.(7) Studies like these show the true impact that this type of surgery can have, not only for the individual but also for the community and health systems, avoiding direct medical costs, direct non-medical costs, and future indirect costs.

Given what MIGS offers and what the results attest, there is room for these techniques to be used safely and effectively. Therefore, it is worth going deeper on the theoretical and practical knowledge of these innovative surgical techniques.

RefeRences

1. Guedes RA, Suzuki Jr E, Omi CA, Guedes VM, editores. Manual prático para cirurgias microinvasivas do glaucoma (MIGS). Rio de Janeiro: Cultura Médica; 2019.

2. Saheb H, Ahmed II. Micro-invasive glaucoma surgery: current perspectives and future directions. Curr Opin Ophthalmol. 2012;23(2):96–104.3. Ansari E. An Update on Implants for Minimally Invasive Glaucoma Surgery (MIGS). Ophthalmol Ther. 2017;6(2):233–41.4. Shaarawy T, Sherwood M, Grehn F. Guidelines on design and reporting of glaucoma surgical trials. Amsterdam, The Netherlands: Kugler

Publications; 2010.5. Guedes RA, Gravina DM, Lake JC, Guedes VM, Chaoubah A. Intermediate results of iStent or iStent Inject combined with cataract surgery in

a real-world setting: a longitudinal retrospective study. Ophthalmol Ther. 2019;8(1):87–100.6. Ordóñez JE, Ordóñez A, Osorio UM. Cost-effectiveness analysis of iStent trabecular micro-bypass stent for patients with open-angle glaucoma

in Colombia. Curr Med Res Opin. 2019;35(2):329–40.7. Patel V, Ahmed I, Podbielski D, Falvey H, Murray J, Goeree R. Cost-effectiveness analysis of standalone trabecular micro-bypass stents in patients

with mild-to-moderate open-angle glaucoma in Canada. J Med Econ. 2019;22(4):390-401.


RBO_Jul_Ago_2019_Inglês_Revisão 01.indd 218 29/06/2019 17:49:23

219original articlE

Received for publication 14/01/2019 - Accepted for publication 06/05/2019.The authors declare no conflicts of interests.

Estudo comparativo entre o tratamento intravítreo com ranibizumabe e triancinolona do edema macular diabético quanto às alterações na tomografia de coerência óptica e na acuidade visual

Comparative study between intravitreal ranibizumab and triamcinolone treatment of diabetic macular edema as regard to optical

coherence tomography changes and visual acuity

1 Beni-Suef University, Egypt. 2 Research Institute of Ophalmology, Egypt.

AbstrAct

Objectives: To compare the effect of intravitreal Ranibizumab (0.3mg) and Triamicinolone (4mg) on different parameters in spectral domain OCT and their relation to visual acuity of patients with diabetic macular edema. Methods: This study is designed as a prospective randomized study. Patients were randomly divided into 2 groups receiving either Pro re nata intravitreal Ranibizumab (0.3mg) or Triamicinolone acetonide (4mg), to whom Spectral Domain OCT was done as well as best corrected Log MAR visual acuity. Results: 40 patients were included in this study. Comparison and correlation of mean BCVA and mean CMT among and within treatment groups of our study revealed strong and significant relationship between both parameters and showing equal effect of both treatment types regarding them with the consideration that Triamicinolone acetonide treated group (Group B) showed statistically significant lower CMT compared to Ranibizumab treated group (Group A) at three and six months. Also both showed equal effectivity regarding improvement of the photoreceptors integrity and in turn the improvement of the BCVA. Meanwhile the association of CMT and IS/OS integrity was found to be significant only at six months in both groups (p =0.009 in Group A; p =0.031 in Group B). The fading initial effect of a single ranibizumab injection on macular edema can be augmented by following that one injection with two injections of the loading dose. Triamicinolone effect after single injection began to fade at 3 months. Conclusion: Both treatment types had good effect on reduction of CMT and improvement of BCVA and the IS/OS junction with difference in sustainability of their effects due to difference in their pharmacokinetics and need for repeated injections.

Keywords: Macular edema, Diabetic retinopathy; Tomography, optical coherence anti-VEGF, Triamicinolone

Mansour Hassan Ahmed1 https://orcid.org/0000-0003-4601-3918Mohammed Othman Abd El Khalek1 https://orcid.org/0000-0002-5014-0445Mohamed Mostafa Fathy Dabees2 https://orcid.org/0000-0002-9742-084XMohamed Maher El-Hefni2 https://orcid.org/0000-0003-3992-9872Dina Abd El Hamid Mahmoud Shalaby2 https://orcid.org/0000-0003-3039-1199

Resumo

Objetivos: Comparar o efeito do ranibizumabe intravítreo (0,3mg) e triacmicinolona (4mg) em diferentes parâmetros do domínio espectral da OCT e sua relação com a acuidade visual de pacientes com edema macular diabético. Métodos: Este estudo foi concebido como um estudo prospectivo randomizado. Os pacientes foram divididos aleatoriamente em 2 grupos que receberam Ranibizumab Pro rata intravitreal (0,3mg) ou acetonido de Triamicinolona (4mg), a quem foi realizada a Spectral Domain OCT, bem como a melhor acuidade visual de Log MAR corrigida. Resultados: Quarenta pacientes foram incluídos neste estudo. A comparação e a correlação da acuidade visual média e CMT média entre e dentro de grupos de tratamento do nosso estudo revelaram uma relação forte e significativa entre ambos os parâmetros e mostrando um efeito igual de ambos os tipos de tratamento, considerando que o grupo tratado com acetonido Triamicinolona (Grupo B) apresentou significância estatística. menor CMT comparado ao grupo tratado com Ranibizumab (Grupo A) aos três e seis meses. Também ambos mostraram igual efetividade em relação à melhoria da integridade dos fotorreceptores e, por sua vez, a melhora do BCVA. Enquanto isso, a associação de CMT e IS / OS integridade foi significativa apenas aos seis meses em ambos os grupos (p = 0,009 no Grupo A; p = 0,031 no Grupo B). O efeito inicial enfraquecido de uma única injeção de ranibizumabe no edema macular pode ser aumentado seguindo-se aquela injeção com duas injeções da dose de ataque. O efeito triamicinolona após injeção única começou a diminuir aos 3 meses. Conclusão: Ambos os tipos de tratamento tiveram bom efeito na redução da CMT e melhora do BCVA e da junção IS / OS com a diferença na sustentabilidade de seus efeitos devido à diferença em sua farmacocinética e necessidade de injeções repetidas.

Descritores: Edema macular; Retinopatia diabética; Tomografia de coerência óptica; anti-VEGF; Triancinolona



220

IntRoductIon

Diabetic Mellitus (DM), a chronic metabolic disorder, is a major public health problem due to its associated complications.(1) One of the major complications of DM

is diabetic retinopathy (DR), which is an important cause of preventable blindness. DR is characterized by the progressive damage in the retinal microvasculature. It can be classified into non proliferative DR (NPDR) and proliferation DR (PDR).(2, 3)

In most cases, DR is featured with increased vascular permeability, leading to fluid accumulation and retinal hemorrhages in the macula, all of which referred to DME. (4- 6) The two most important causes of visual impairment secondary to DR are diabetic macular edema (DME) and proliferative DR (PDR). The prevalence of DME is 3% in mild non proliferative retinopathy and rises to 38% in eyes with moderate-to-severe non proliferative retinopathy, eventually reaching 71% in eyes with proliferative retinopathy.(7)

There are many different techniques for examining the macular area, including biomicroscopy, fluorescein angiography, and optical coherence tomography (OCT). Fluorescein angiography (FA) has played a central role in understanding the pathophysiology of various retinal diseases being used as an important clinical tool in the diagnosis and treatment of DME.(8-11) Fundamentally, the focal laser protocol in Early Treatment Diabetic Retinopathy Study (ETDRS) was based on speculating the pathogenesis of DME by FA.(12)

Subthreshold micropulse diode laser photocoagulation is a treatment that theoretically avoids damaging the inner neurosensory retina, thereby reducing potential complications such as paracentral scotomata and enlargement of post-treatment scars. This technique was first described in the late 1990s and since then there has been some randomized controlled trials (RCTs) comparing this technique to modified ETDRS laser treatment.(13,14) Vujosevic et al. found improvement of central retinal sensitivity in the micropulse group, but its deterioration in the modified ETDRS group.(15) Micropulse laser thus may offer a new, less aggressive laser approach in the treatment of clinically significant macular edema.

Structural modification of diabetic vitreous occurs secondary to enzymatic and non-enzymatic collagen glycation. (16) Accumulation of advanced glycation end products (AGEs) in the vitreous of hyperglycemic patients promotes collagen crosslinking and may be the cause of VMT in diabetic eyes. (17) AGE accumulates along the posterior vitreous cortex and the ILM, where it may cause structural alterations that promote vitreoretinal traction. Vitrectomy to remove the posterior hyaloid and ILM may be beneficial in two ways: (1) by removing AGE ligand-induced mechanical traction between the posterior cortical vitreous and the ILM of macula; and (2) removal of AGEs may also inhibit the activation of the RAGE axis and its pro inflammatory effects. Muller cells lie between the ILM and ELM and in close apposition with capillaries. In diabetic eyes, upregulation of VEGF in Muller cells may increase the vasopermeability of the retinal endothelial cells. The DRCR.net examined the role of vitrectomy and membrane peeling in the treatment of DME with a tractional component in a small, prospective cohort study(18) At six months postoperatively, VA improved by more than 2 lines in 38% of eyes. The mean decrease in macular thickness on OCT was approximately 160 μm, with 43% of patients having macular thickness of less than 250 μm.(19)

methods

This study is designed as a prospective randomized study that involves a total of 40 diabetic patients with diabetic macular edema treated with intravitreal injections, to whom Spectral Domain OCT was done as well as best corrected Log MAR visual acuity.

The inclusion criteria

1. Type 1 or 2 diabetes mellitus with non-tractional diabetic macular edema with foveal thickness ≥300 μm

The exclusion criteria1. Involve any patient with concurrent macular diseases as

macular degeneration2. Any significant media opacities (as cataract or vitreous

haemorrhage) that hinder fundus examination &OCT imaging, any macular edema from other causes (including history of uveitis, retinal detachment, recurrent ERMs or vitreomacular traction)

3. Any type of previous macular treatment (macular laser photocoagulation, vitrectomy, intravitreal steroids &/or antiangiogenic drugs);

4. Any intraocular surgery at least 4 months before the study involvement

5. Ischaemic maculopathy

Pre-operative and post-operative evaluation:

Each patient underwent a complete ophthalmic examination, with determination of Best Corrected Visual Acuity (BCVA), anterior segment examination, indirect ophthalmoscopy & 90-D lens biomicroscopy. Thereafter, SD-OCT+/- Fundus fluorescein angiography was performed to every patient before treatment and after treatment at intervals of 1, 3 and 6 months from the injection. (Optovue RTVue-100; Optovue Inc, Fremont, CA) {RTVue scans used the three-dimensional (3D) macular scan protocol set to 6 ⅹ 6 mm containing 101 horizontal line scans each consisting of 513 A scans evaluated with Optovue analysis software version 4.0.5.39 or higher}

The injection was done in the operating theater in Research Institute of Ophthalmology under topical anaesthesia and full aseptic conditions which was made once with either Lucentis (ranibizumab injection) [Group A] or Triamcinolone Acetonide [Group B] (20 patients with Triamcinolone & The other 20 patients with Lucentis).

Triamcinolone acetonide in a single-use bottle (40 mg/ml, 1ml bottle), is drawn into a 1-cc tuberculin syringe after cleansing the top of the bottle with an alcohol wipe. A separate 27 or 26 gauge needle is placed onto the syringe, which is then inverted to remove air bubbles. The excess triamcinolone is discarded till 0.1 ml (4 mg) remains in the syringe. The injection site is usually the inferotemporal quadrant to avoid drug deposition in front of the visual axis. The stab is given 3-3.5 mm from the limbus (in aphakic and pseudophakic patients) and 3.5-4 mm from the limbus in phakic patients to ensure against passage of the needle through the vitreous base.

Lucentis (ranibizumab) 0.3 mg (0.05 mL of 6 mg/mL LUCENTIS solution) is recommended to be administered by intravitreal injection once a month. It is withdrawn through a 5-micron, 19-gauge filter needle attached to a 1-cc tuberculin syringe. The filter needle should be discarded after withdrawal of the vial contents and should not be used for intravitreal injection. The filter needle should be replaced with a sterile 30-gauge x 1/2-


Ahmed MH, El Khalek MOA, Deabees MMF, El Hefni MM, Mahmoud DAEH


221Comparative study between intravitreal ranibizumab and triamcinolone treatment of diabetic macular edema as regard to optical coherence...

inch needle for the intravitreal injection. The contents should be expelled until the plunger tip is aligned with the line that marks 0.05 mL on the syringe.

Statistical methodology:

Data were analyzed using SPSSwin statistical package version 21 (SPSS Inc., Chicago, IL). Numerical data were expressed as mean and standard deviation (Mean ± SD) or Median and range as appropriate according to Normal distribution curve and Histogram.

Qualitative data were expressed as frequency and percentage. Chi-square test or (Fisher’s exact test) used to examine the relation between qualitative or categorical variables. Repeated categorical variables tested by Cochrane test.

For quantitative data, comparison between the two treatment groups were done using either student t-test or Mann-Whitney test (non-parametric t-test) as appropriate. Visual acuity at baseline & 1 month, 3 months or 6 months were analyzed using paired t-test. Repeated measure ANOVA analyze changes along time in VA & CMT. All tests are two tailed and a p-value ≤ 0.05 was considered significant.

Bivariate correlation analysis either by Pearson correlation or Spearman Rho correlation was done to examine the relationship between two numeric data or graphically summarized by Scatter dot diagram. It indicated:

• Strength of the relationship (strong or weak) • Direction of the relationship:

- Positive (direct): variables move in the same direction- Negative (inverse): variables move in opposite direction

The interpretation of correlation:

• From 0 to 0.25 (– 0.25): no or little relationship• From 0.25 to 0.50 (- 0.25 to – 0.50) fair degree of relationship • From 0.50 to 0.75 (–0.50 to – 0.75) moderate to good

relationship.• Greater than 0.75 (or – 0.75): very good to excellent

relationship.

Results

Demographic data:

Age:

The mean age of our patients was 56.7 ± 6.182 years in Group A and 60 ± 5.487 years in Group B. Comparison between the two groups was insignificant with P = 0.082

Sex distribution:

There were 55% females and 45% males in Group A and 50% females and 50% males in Group B. Comparison between the two groups was insignificant with P = 0.752

Pre-operative examination:

Mean IOP (mmHg):

The mean IOP in our patients was 16.5+/- 2.05mm in Group A and in Group B 15.2+/- 2.931 mm.

Mean central macular thickness (CMT):

The Mean CMT in our patients was 525.95 ± 102.792 μm in Group A and 569.35 ± 177.447 μm in Group B.

Mean BCVA (Log MAR):

The Mean BCVA in our patients was 0.675 ± 0.1372 in Group A and 0.765 ± 0.230 in Group B.

The Inner segment / outer segment junction status (IS/OS):

The percentage of intact IS/OS on OCT was 35% vs 65% interrupted IS/OS in Group A and was the same in Group B.

Post-operative examination:

Mean IOP (mmHg):

IOP remained unchanged as compared to preoperative mean at one, three and six months in Group A. However, IOP revealed an increase in the mean IOP at one, three and six months as compared to baseline mean.

Comparison between both study groups was statistically difference at one month (p<0.002), three months (p<0.001) and six months (p<0.000). (Table 1)

Group B showed statistically significant higher mean IOP compared to Group A at all points.

Study Group Preoperative Postoperative

1 month 3 months 6 months

Group A 16.5+/-2.05 16.5+/-2.05 16.5+/-2.05 16.5+/-2.05

Group B 15.20+/-2.931 20.85+/-5.133 23.70+/-8.196 23.80+/-10.943

Table 1 Comparison between study groups regarding IOP over time

Mean Central macular thickness:

Since the main aim of the study is to compare the effect of Ranibizumab and Triamicinolone regarding their effect on OCT parameters in Diabetic macular edema patients and its correlation to Visual acuity and since the initial effect of Ranibizumab fade at 1 months it was necessary to reinject in patients with CMT above 300 um. At one month, All Ranibizumab patients but one received another injection. At three months only five patients in Ranibizumab group need another injection. On the other hand Group B need not receive another injection during study time.

Evaluation of postoperative CMT revealed a reduction in the mean CMT at one, three and six months in both groups compared with preoperative mean CMT (mean CMT at baseline).

In Group A, a statistically significant difference was observed at One (p = 0.010), three (p< 0.001) and six months (p< 0.001) postoperatively. In Group B, a statistically significant difference was observed at one (p<0.001), three (p< 0.001) and six months (p = 0.025) postoperatively. (Figure 1)

Figure 1: Mean OCT CMT in both treatment groups over time.



222

Comparison between the two study groups revealed stat is t ical ly s ignif icant di f ference in mean CMT at three and six months only (p< 0.001) postoperatively.

Group B showed statistically significant lower CMT compared to Group A at three and six months. (Table 2) (Figure 2).

Inner segment/Outer segment junction on OCT:

Within Group A the percentage of intact IS/OS was 35% and interrupted IS/OS was 65% at baseline. There was an improvement in IS/OS integrity at one month (Intact IS/OS were 70% and 30% were interrupted; but this improvement wasn’t maintained at three months (Intact IS/OS were 55% and 45% were interrupted), and six month (Intact IS/OS were 80% and 20% showed interruption). The improvement at one and six months was found significant. (p =0.004)

Group B showed similar percentages at baseline. The improvement was observed in 1 month (45% Intact IS/OS vs 55% interrupted IS/OS) and 3 months (65% were intact vs 35% interrupted IS/OS); that wasn’t found to be of significance, but

Table 2 Comparison between study groups regarding CMT change on OCT over time

Treatment type N Mean Standard Deviation P-value

OCT CMT at baseline Ranibizumab 20 525.95 102.792 0.351 Triamcinolone 20 569.35 177.447 OCT CMT at 1 month Ranibizumab 20 433.05 97.403 < 0.001 Triamcinolone 20 222.70 45.978 OCT CMT at 3months Ranibizumab 20 394.05 90.612 < 0.001 Triamcinolone 20 211.25 82.405 OCT CMT at 6months Ranibizumab 20 355.55 97.396 0.623 Triamcinolone 20 376.70 163.825

Figure 2: CMT on OCT along time in both treatment groups

Mean BCVA (Log MAR):

In Group A, There was a statistically significant improvement in the mean BCVA at three months (p =0.003) and six months (p =0.001). Group B showed significant improvement at one (p<0.001), three months (p<0.001) and six months (p =0.015). (Figure 3)

Figure 3: Mean VA in both treatment groups over time

Comparison between the two study groups revealed statistical difference at one & three months (p < 0.001) but no significant difference at six months postoperatively. (Table 3) (Figure 4)

Treatment type N Mean Standard Deviation P-value

Baseline Visual acuity Ranibizumab 20 0.675 0.1372 0.143 Triamcinolone 20 0.765 0.2300 Visual acuity at 1 month Ranibizumab 20 0.590 0.1210 < 0.001 Triamcinolone 20 0.385 0.0813 Visual acuity at 3 month Ranibizumab 20 0.540 0.1353 < 0.001 Triamcinolone 20 0.330 0.1129 Visual acuity at 6 month Ranibizumab 20 0.495 0.1099 0.557 Triamcinolone 20 0.525 0.1970

Table 3 Comparison between study groups regarding VA change on OCT over time

Figure 4: Log MAR VA along time in both treatment groups





again this improvement began to fade at 6 months (50% were intact vs 50% interrupted IS/OS). Comparison between both groups showed no significant difference along time of the study. (Figure 5)

Figure 5: OCT intact IS/OS along time in both treatment groups

Correlation and association between different parameters in both treatment Groups:

In both treatment groups, there was a significant and strong correlation between VA and CMT at baseline (p<0.001) and at one (p<0.001 in Group A and p = 0.003 in Group B) (Figure 6, 7), three (p<0.001) and six months (p<0.001) of treatment.

Comparing VA to the integrity of IS/OS on OCT along time in both groups revealed significant association at three [mean BCVA was 0.473 in patients with intact IS/OS vs 0.622 in those with interrupted IS/OS in Group A; mean BCVA was 0.285 in patients with intact IS/OS vs 0.414 in those with interrupted IS/OS in Group B] (p =0.010 in Group A & p=0.045 in Group B) and six months [mean BCVA was 0.463 in patients with intact IS/OS vs 0.625 in those with interrupted IS/OS in Group A; mean BCVA was 0.440 in patients with intact IS/OS vs 0.610 in those with interrupted IS/OS in Group B] (p = 0.005 in Group A & p =0.051 in Group B). Group B also revealed significant association at baseline [mean BCVA was 0.629 in patients with intact IS/OS vs 0. 838 in those with interrupted IS/OS] (p =0.016)

Regarding CMT and IS/OS on OCT, Group B showed a significant association at baseline [mean CMT in patients with intact IS/OS was 459.71 μm while in those with interrupted IS/OS mean CMT was 628.38 μm] and six months [mean CMT in patients with intact IS/OS was 299.70 μm while in those with interrupted IS/OS mean CMT was 453.70 μm (p =0.010 & 0.031 respectively) while Group A showed significant association at three [mean CMT in patients with intact IS/OS was 334.73 μm while in those with interrupted IS/OS mean CMT was 466.56 μm] (p ⅹ0.001) and at six months [mean CMT in patients with intact IS/OS was 328.69 μm while in those with interrupted IS/OS mean CMT was 463 μm] (p =0.009).

Example to a case treated with intravitreal Triamicinolone acetonide (Group B): (Figure 8)

Figure 6 and 7: Correlation between CMT & VA in Group A and Group B at one month

Example of a case treated with intravitreal Ranibizumab (Group A): (Figure 9)

Figure 8: A case treated with triamicinolone acetonide. OCT at baseline, 1-3-6 months



224

dIscussIon

DME is one of the main causes of visual impairment in patients with diabetic retinopathy. (20) A recent pooled analysis of 35 population-based studies in the United States, Australia, Europe, and Asia indicates that the global, age-standardized prevalence of diabetic retinopathy and diabetic macular edema (DME) in diabetic patients younger than 80 years of age is approximately 35% and 7.5%, respectively. (21) The existing burden of disease, high prevalence and incidence, life course characterized by development of chronic complications, decreased quality of life and increased cost of health care make diabetes one of the leading public health problems worldwide.(22)

Anti-VEGF drugs and corticosteroids have been proven, not only to suppress DME, but also to prevent or slow the disease progression of DR per se.(23)The fact that so many patients are proving to be resistant to treatment would suggest that different pathological mechanisms must be involved.(24)Also, Authors have found that some eyes with DME have poor visual outcomes despite complete resolution of edema.(25)

The SD OCT machines technology enhanced our ability to examine retinal microstructure and obtain more reliable measurements.(26) Several studies have found a modest correlation between OCT-measured retinal thickness and visual acuity.

Figure 9: A case treated with Ranibizumab. OCT at baseline, 1-3-6 months

Central retinal thickness has a more significant effect on visual acuity than does the age, fluorescein leakage, hemoglobin A1c, perifoveal capillary blood-flow velocity, or severity of peri¬foveal capillary occlusion. (27,28) Several studies showed that many factors influence visual function in eyes with DME, including morphologic pattern of edema (cystic or diffuse retinal thickening), duration of retinal edema, retinal perfusion, total retinal volume, vitreomacular interface abnormalities(29) macular ischemia, photoreceptor dysfunction and accumulated subfoveal hard exudates. (30)

Despite the relevance, it is unknown whether the IS/OS line seen on OCT images truly corresponds to the histologic junction of the inner and outer segments. Spaide and Curcio speculated that this highly reflective band was located at the ellipsoid in the inner segments, considering the correlation between the microstructure on the SD-OCT images and the histologic findings. (31) The OCT reflectivity changed around the line after light exposure, which suggested that the line may represent photoreceptor function per se.(32,33) Many authors have found out that visual acuity has a positive correlation with the survival rate of ELM and IS/OS, (34) and that the postoperative status of the photorecep¬tors is related to the final visual function after restoration of normal retinal morphology following surgery for persistent DME (25) or epiretinal membrane.(35) Shin and associates reported that ELM disruption predicts poor visual outcomes after treatment with triamcinolone. (36)

To our knowledge, there have been limited trials that compared Triamicinolone acetonide to Ranibizumab in treatment of diabetic macular edema over short term and monitored their effects on visual acuity, CMT and IS/OS junction on SD-OCT. (37) One of the drawbacks of our study is that we could not give a percentage to the integrity of IS/OS layers in our classification, as assumed by some authors.(38) Any disruption of the inner segment/outer seg¬ment (IS/OS) line was searched for within the central 1 mm of the fovea. If the IS/OS line appeared to be complete at the fovea in all scans, we diagnosed it as an intact IS/OS. Any discontinuity or inter¬ruption of the IS/OS line in one scan or more was considered an interrupted IS/OS layer. Limitation to our study was the small sample size mainly.

The Differences between results and effect of both treatment groups may be attributed to the half-life of ranibizumab in the vitreous cavity 2.73 +/- 0.38 days (39) compared to the longer half -life of Triamicinolone, which is 18.6 days (40)

Maheshwary et al., in 2010 claimed a strong trend suggesting a relationship between macular volume and visual acuity, although borderline significance was found (P =0.07). They used macular volume instead of central retinal thickness as an indicator of edema severity. The Diabetic Retinopathy Clinical Research Network (DRCR.net) showed that total macular volume may be used when macular edema is more diffuse and represents a more global measurement of macular edema. (41) A statistically significant correlation between percentage disruption of the IS/OS junction and visual acuity was found (P =0.0312). The relationship between visual acuity and the percentage disruption held true in both treated and untreated eyes Also a relationship between macular volume and percent disruption of the IS/OS junction was found. Because IS/OS junction line integrity is an independent predictor of vision, Maheshwary and his associates recommended that clinicians may recall that for each percentage disruption, a decrease by 0.33 ETDRS letters can be anticipated. As noticed they used percent disruption as their indicator of IS/OS disease and not a simple grading of presence or absence of disruption.

Paccola et al. (42) reported that a single IVTA had more effect on reduction of CMT in patients with DME compared with one





intravitreal bevacizumab (IVB) during an eight-week period. Oh et al. (43) also reported that CMT reduction was maintained until three months after IVTA injection, while in the IVB group, CMT reduction was maintained until two months after injection.

Massin et al. (44) also demonstrated a significant reduction of CMT for at least three months. Although ranibizumab was used here instead of bevacizumab, however the results of Paccola and the other studies are in accordance with the conclusions here. Moreover the interrelationship between anti-VEGF drugs used in treatment of DME support using those studies to be compared to ours.

Similarly, according to Paccola and his associates, more favorable BCVA improvement was observed with IVTA compared with that of IVB as early as four weeks after treatment and persisting up to 12 weeks. Similarly, other reports have shown significant visual acuity improvements after IVTA. (45-47)

However this differs a little bit than the conclusions of Karst el al., specially regarding CMT. The CMT was found be thinner in the Ranibizumab treated group than the Triamicinolone treated ones at 3 months in Karst study. (37) But this can be explained by different dose and regimen used to inject Ranibizumab in their study (three monthly injections of 0.5 mg ranibizumab vs single injection of 0.3 mg ranibizumab in our study)

Sakamoto et al. in 2009 found postoperative IS/OS junction status to be related to the visual acuity after resolution of diabetic macular edema by vitrectomy. Retinal sensitivity, measured at 40 points within the central 10 degrees of the macula with the Micro Perimeter, was used by Kameda et al. to objectively assess the macular function beside analysis of best-corrected visual acuity (BCVA), central macular thickness (CMT), photoreceptor inner and outer segments (IS/OS) line. Their study found retinal sensitivity after IVTA for DME to show, albeit relatively slow, significant improvement than did BCVA or CMT. The nasal quadrant of the macula showed more improvement than did any other quadrant. In addition, cases with a discontinuous IS/OS line within 500 μm of the center of the fovea showed significantly worse BCVA and retinal sensitivity at 2 degrees. Those conclusions support the improvement of IS/OS noticed with the treatment by IVTA and the positive effect of its integrity correlated with the improvement of macular function clinically in the form of improvement of BCVA (48)

Fursova el al. investigated the morphological changes and visual acuity response to ranibizumab therapy in patients with different OCT types of diabetic macular edema (DME) as well as different state of the inner and outer photoreceptor segments (IS and OS) and the external limiting membrane (ELM); to study relationships between functional and morphological parameters before and after the treatment with ranibizumab. The most favorable type of DME in terms of preserving the integrity of photoreceptor segments and the ELM was sponge-like edema, while DME with neuroepithelial detachment and mixed-type DME were prognostically unfavorable. The last two types prevented any statistically significant improvement of the main clinical factor – VA –even after complete reduction of the edema. (49) This not only showed similar conclusions to our study but also tried to classify diabetic macular edema into categories according to the integrity of IS/OS and ELM and so their predictive clue to the final visual outcome.

conclusIon

In conclusion, our data on the overall treatment response assessed as a change in BCVA and CMT are in accordance with previous studies, which have proven the clinical efficacy of

Ranibizumab and Triamcinolone for DME therapy. This study also found an association between IS/OS integrity on SD-OCT and visual acuity in both treatment types but especially in Ranibizumab group, it means that patients with DME having an intact IS/OS junction would have a better visual outcome and this may be used as a predictive factor for evaluating these cases. So, CMT and integrity of the photoreceptor IS/OS layer are significant predictors of VA in patients with DM, which may help to predict the outcome after treatment and to choose the best treatment modality. Further studies have to be held comparing Ranibizumab and Triamicinolone acetonide regarding their effect on different OCT parameters and their reflectance over the improvement of macular function in patients of DME in both short term and long term situations.

RefeRences

1. Dodda D, Ciddi V. Plants used in the management of diabetic complications. Indian J Pharm Sci. 2014;76(2):97–106.

2. Shah CA. Diabetic retinopathy: A comprehensive review. Indian J Med Sci. 2008;62(12):500–19.

3. Zhang W, Liu H, Al-Shabrawey M, Caldwell RW, Caldwell RB. Inflammation and diabetic retinal microvascular complications. J Cardiovasc Dis Res. 2011;2(2):96–103.

4. Scholl S, Kirchhof J, Augustin AJ. Pathophysiology of macular edema. Ophthalmologica. 2010;224 Suppl 1:8–15.

5. Augustin A, Loewenstein A, Kuppermann BD. Macular edema. General pathophysiology. Dev Ophthalmol. 2010;47:10–26.

6. Virgili G, Menchini F, Murro V, Peluso E, Rosa F, Casazza G. Optical coherence tomography (OCT) for detection of macular oedema in patients with diabetic retinopathy. Cochrane Database Syst Rev. 2011;(7):CD008081.

7. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984;91(12):1464–74.

8. Olk RJ, Lee CM. Diabetic Retinopathy: Practical Management. Philadelphia (PA): Lippincott; 1993. p. 1–181.

9. Antcliff RJ, Stanford MR, Chauhan DS, Graham EM, Spalton DJ, Shilling JS, et al. Comparison between optical coherence tomography and fundus fluorescein angiography for the detection of cystoid macular edema in patients with uveitis. Ophthalmology. 2000;107(3):593–9.

10. Bresnick GH. Diabetic maculopathy. A critical review highlighting diffuse macular edema. Ophthalmology. 1983;90(11):1301–17.

11. Byeon SH, Chu YK, Lee H, Lee SY, Kwon OW. Foveal ganglion cell layer damage in ischemic diabetic maculopathy: correlation of optical coherence tomographic and anatomic changes. Ophthalmology. 2009;116(10):1949–59.e8.

12. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. ETDRS Report No. 1. Arch Ophthalmol. 1985;10:1796–806.

13. Friberg TR. Infrared micropulsed laser treatment for diabetic macular edema—subthreshold versus threshold lesions. Semin Ophthalmol. 2001;16(1):19–24.

14. Figueira J, Khan J, Nunes S, Sivaprasad S, Rosa A, de Abreu JF, et al. Prospective randomised controlled trial comparing sub-threshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema. Br J Ophthalmol. 2009;93(10):1341–4.

15. Vujosevic S, Bottega E, Casciano M, Pilotto E, Convento E, Midena E. Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation. Retina. 2010;30(6):908–16.



226

16. Sebag J, Nie S, Reiser K, Charles MA, Yu NT. Raman spectroscopy of human vitreous in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 1994;35(7):2976–80.

17. Barile GR, Pachydaki SI, Tari SR, Lee SE, Donmoyer CM, Ma W, et al. The RAGE axis in early diabetic retinopathy. Invest Ophthalmol Vis Sci. 2005;46(8):2916–24.

18. Haller JA, Qin H, Apte RS, Beck RR, Bressler NM, Browning DJ, et al.; Diabetic Retinopathy Clinical Research Network Writing Committee. Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology. 2010;117(6):1087–1093.e3.

19. Kumar A, Roy S, Sinha S. Pathogenesis and management of diabetic macular edema. Cur Indian Eye Res. 2014;1(1):3-16.

20. Brown JC, Solomon SD, Bressler SB, Schachat AP, DiBernardo C, Bressler NM. Detection of diabetic foveal edema: contact lens biomicroscopy compared with optical coherence tomography. Arch Ophthalmol. 2004;122(3):330–5.

21. Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al.; Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556–64.

22. Tomic M, Vrabec R, Poljicanin T, Ljubic S, Duvnjak L. Diabetic macular edema: traditional and novel treatment. Acta Clin Croat. 2017;56(1):124–32.

23. Wykoff CC. Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy. Curr Opin Ophthalmol. 2017 ;28(3):213-8.

24. Romero-Aroca P, Baget-Bernaldiz M, Pareja-Rios A, Lopez-Galvez M, Navarro-Gil R, Verges R. Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory. J Diabetes Res. 2016;2016:2156273.

25. Sakamoto A, Nishijima K, Kita M, Oh H, Tsujikawa A, Yoshimura N. Association between foveal photoreceptor status and visual acuity after resolution of diabetic macular edema by pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmol. 2009;247(10):1325–30.

26. Polito A, Del Borrello M, Isola M, Zemella N, Bandello F. Repeatability and reproducibility of fast macular thickness mapping with stratus optical coherence tomography. Arch Ophthalmol. 2005;123(10):1330–7.

27. Fong DS, Strauber SF, Aiello LP, Beck RW, Callanan DG, Danis RP, et al.; Writing Committee for the Diabetic Retinopathy Clinical Research Network. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol. 2007;125(4):469–80.

28. Baskin DE. Optical coherence tomography in diabetic macular edema. Curr Opin Ophthalmol. 2010;21(3):172–7.

29. Blumenkranz MS, Haller JA, Kuppermann BD, Williams GA, Ip M, Davis M, et al. Correlation of visual acuity and macular thickness measured by optical coherence tomography in patients with persistent macular edema. Retina. 2010;30(7):1090–4.

30. Otani T, Kishi S. Tomographic findings of foveal hard exudates in diabetic macular edema. Am J Ophthalmol. 2001;131(1):50–4.

31. Spaide RF, Curcio CA. Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model. Retina. 2011;31(8):1609–19.

32. Bizheva K, Pflug R, Hermann B, Povazay B, Sattmann H, Qiu P, et al. Optophysiology: depth-resolved probing of retinal physiology with functional ultrahigh-resolution optical coherence tomography. Proc Natl Acad Sci USA. 2006;103(13):5066–71.

33. Srinivasan VJ, Wojtkowski M, Fujimoto JG, Duker JS. In vivo measurement of retinal physiology with high-speed ultrahigh-resolution optical coherence tomography. Opt Lett. 2006;31(15):2308–10.

34. Otani T, Yamaguchi Y, Kishi S. Correlation between visual acuity and foveal microstructural changes in diabetic macular edema. Retina. 2010;30(5):774–80.

35. Mitamura Y, Hirano K, Baba T, Yamamoto S. Correlation of visual recovery with presence of photoreceptor inner/outer segment junction in optical coherence images after epiretinal membrane surgery. Br J Ophthalmol. 2009;93(2):171–5.

36. Shin HJ, Lee SH, Chung H, Kim HC. Association between photoreceptor integrity and visual outcome in diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. 2012;250(1):61–70.

37. Karst SG, Lammer J, Mitsch C, Schober M, Mehta J, Scholda C, et al. Detailed analysis of retinal morphology in patients with diabetic macular edema (DME) randomized to ranibizumab or triamcinolone treatment. Graefes Arch Clin Exp Ophthalmol. 2018;256(1):49–58.

38. Maheshwary AS, Oster SF, Yuson RM, Cheng L, Mojana F, Freeman WR. The association between percent disruption of the photoreceptor inner segment-outer segment junction and visual acuity in diabetic macular edema. Am J Ophthalmol. 2010;150(1):63–67.e1.

39. Christoforidis JB, Briley K, Binzel K, Bhatia P, Wei L, Kumar K, et al. Systemic Biodistribution and Intravitreal Pharmacokinetic Properties of Bevacizumab, Ranibizumab, and Aflibercept in a Nonhuman Primate Model. Invest Ophthalmol Vis Sci. 2017;58(13):5636–45.

40. Beer PM, Bakri SJ, Singh RJ, Liu W, Peters GB 3rd, Miller M. Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection. Ophthalmology. 2003;110(4):681–6.

41. Browning DJ, Glassman AR, Aiello LP, Bressler NM, Bressler SB, Danis RP, et al.; Diabetic Retinopathy Clinical Research Network. Optical coherence tomography measurements and analysis methods in optical coherence tomography studies of diabetic macular edema. Ophthalmology. 2008;115(8):1366–71.

42. Paccola L, Costa RA, Folgosa MS, Barbosa JC, Scott IU, Jorge R. Intravitreal triamcinolone versus bevacizumab for treatment of refractory diabetic macular oedema (IBEME study). Br J Ophthalmol. 2008;92(1):76–80.

43. Oh SB, Moon JW, Kim HC. Comparison of effects of intravitreal triamcinolone and bevacizumab in the treatment of diabetic macular edema. J Korean Ophthalmol Soc. 2009;50(8):1190–6.

44. Massin P, Audren F, Haouchine B, Erginay A, Bergmann JF, Benosman R, et al. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology. 2004;111(2):218–24.

45. Martidis A, Duker JS, Greenberg PB, Rogers AH, Puliafito CA, Reichel E, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002;109(5):920–7.

46. Sutter FK, Simpson JM, Gillies MC. Intravitreal triamcinolone for diabetic macular edema that persists after laser treatment: three-month efficacy and safety results of a prospective, randomized, double-masked, placebo-controlled clinical trial. Ophthalmology. 2004;111(11):2044–9.

47. Bonini-Filho MA, Jorge R, Barbosa JC, Calucci D, Cardillo JA, Costa RA. Intravitreal injection versus sub-Tenon’s infusion of triamcinolone acetonide for refractory diabetic macular edema: a randomized clinical trial. Invest Ophthalmol Vis Sci. 2005;46(10):3845–9.

48. Kameda T, Nishijima K, Unoki N, Sakamoto A, Hayashi H, Oh H, et al. Geographic pattern of central retinal sensitivity after intravitreal triamcinolone for diabetic macular edema. Graefes Arch Clin Exp Ophthalmol. 2011;249(1):3–9.

49. Fursova AZ, Chubar’ NV, Tarasov MS, Saifullina IF, Pustovaya GG. [Clinicalassociations between photoreceptor status and visual outcomes in diabetic macular edema]. Vestn Oftalmol. 2017;133(1):11-18. Russian.

Corresponding Author: Dina Abd El Hamid Mahmoud, M.B.Bch. M.Sc, Department of Ophthalmology, Research Institute of Ophthalmology, Egypt. E-mail: [email protected]




227

Causes of death and discard of donated corneal tissues: Federal District

eye bank analysis 2014 -2017Causa mortis dos doadores e motivo de descarte das córneas:

banco de olhos do Distrito Federal 2014-2017

1 Department of Cell Biology, Universidade de Brasília, Brasília, DF, Brazil. 2 Distrito Federal Eye Bank, Brasília, DF, Brazil. 3 Federal Institute of Brasilia, Brasília, DF, Brazil.

artigo original

Recebido para publicação em 01/03/2019 - Aceito para publicação em 24/06/2019.Os autores declaram não haver conflito de interesses.


Diogo Souza Loiola1 https://orcid.org/000-0003-19684441 Sônia Nair Báo1 https://orcid.org/000-0002-9873-3098Thayssa Neiva da Fonseca Victer1 https://orcid.org/0000-0003-38205311Micheline Borges Lucas2 https://orcid.org/000-0003-3670-0204Maria Regina Catai Chalita2 https://orcid.org/0000-0003-0084-736XThatiane Lima Sampaio3 https://orcid.org/000-0002-4311-6105

AbstRAct

Objective: The aim of this study is to identify the causes for discarding corneas at the Eye Bank of the Federal District in Brasilia, Brazil, and describe the social and demographic variables and Causa Mortis of cornea donors from 2014 to 2017. Methods: We conducted an exploratory and social-epidemiologic descriptive study regarding cornea donation. The data base information was obtained from the corneal donor’s medical records analysis. All of the potential donors’ records (cause of death, cause of cornea discard, month of donation, age, gender, and time of death, corneal enucleation and preservation), from 2014 to 2017 were included in the study. Results: We looked at 1,574 corneal donor notifications. Demographic characteristics displayed significant differences in gender distribution (male, 74.8% and female, 25.2%), and the average donor age was 40 ± 15.9 years. 25% of the causes of death were from cardiovascular disease followed by 19.6% from sharp or blunt instrument injury, 14.2% resulted from multiple traumas. We described 3,074 donated corneas from the DF Eye Bank, where 2.6% has not been uptaken. Of those 3,074 corneal tissues, nearly 60% (n=1,836) have been transplanted and 40% (n=1,238) were discarded. Regarding the causes of discard, 68% (n=841) were due to positive or indeterminate serological blood tests and 39% (n=486) because of matureness (expired medium guaranteed period of corneal preservation). Conclusions: Specific issues such as violent causes of death, gender disproportion and total time of corneal processing can be better managed to reduce procurement times, and availability, of corneal tissue for transplantation.

Keywords: Cornea; Epidemiology; Eye bank; Corneal transplantation; Brazil.

Resumo

Objetivo: Identificar as causas do descarte de córneas no Banco de Olhos do Distrito Federal, em Brasília, Brasil, descrever as variáveis sociodemográficas e causa de morte dos doadores de córnea de 2014 a 2017. Métodos: Foi realizado um estudo descritivo exploratório e socioepidemiológico sobre as doações de córnea. As informações da base de dados foram obtidas a partir da análise dos prontuários dos doadores. Todos os registros dos potenciais doadores (causa da morte, causa do descarte, mês de doação, idade, sexo e tempo de morte, enucleação e preservação da córnea), de 2014 a 2017, foram incluídos no estudo. Resultados: Analisamos 1.574 notificações de doadores. Características demográficas apresentaram diferenças significativas na distribuição por sexo (masculino, 74,8% e feminino, 25,2%). A idade média dos doadores foi de 40 ± 15,9 anos. 25% das causas de morte foram de doenças cardiovasculares, seguidas de 19,6% de perfurações por arma de fogo e 14,2% de múltiplos traumas. Descrevemos as 3.074 córneas doadas ao Banco de Olhos do DF e onde apenas 2,6% não foram captadas. Dos 3.074 tecidos da córnea, quase 60% (n = 1.836) foram transplantados e 40% (n = 1.238) foram descartados. Quanto às causas de descarte, 68% (n = 841) foram devidas a exames sorológicos positivos ou indeterminados e 39% (n = 486) por tempo de vencimento (período máximo de preservação da córnea). Conclusões: Questões específicas como causas violentas de morte, desproporção de gênero e tempo total de processamento da córnea podem ser melhor gerenciadas para reduzir o tempo de captação e a disponibilidade de tecido para transplante.

Descritores: Córnea; Epidemiologia; Banco de olhos; Transplante de córnea; Brasil


228 Loiola DS, Báo SN, Victer TNF, Lucas MB, Chalita MRC, Sampaio TL


IntRoductIon

It is estimated that 36 million people are considered legally blind and another 216.6 million people are classified as vision impaired worldwide.(1, 2) The main causes for these

impairments are uncorrected refractive errors, representing 43%, and cataracts with 33% of the cases. In cases of blindness, cataract corresponds to 51%, glaucoma 8%, and 34% from other disorders.(3, 4) In this scenario, nearly 5.1% of vision impairment were caused by corneal opacities.(5) Trachoma, and vitamin A deficiency, sclerocornea, limbal cornea dermoids and keratitis are diseases which causes corneal opacities.(5,6)

Cornea transplant is the most common and successful form tissue transplantation and is considered the primary treatment for restoring vision to patients with corneal blindness. Beyond those, keratoconus and Fuchs’ dystrophy are the most important pathologies to use corneal transplant as treatment strategy.(2,7)

Corneal transplants have been performed all over the world and in 2012 alone almost 184.576 were done in 116 countries.(3) Of those, 8% (nearly 15.000) were performed in Brazil, which, is a leader in tissue and solid organ transplantation worldwide by the public health system (SUS).(3,4,8)

From 2010 to 2017, 113,219 corneal transplants were performed in Brazil, which is significantly higher than other solid organs transplantation such as kidney (43.224) and liver (12.038).(9,10) Beyond the increasing numbers of corneal transplantations, the procurement process has also increased when compared to transplantation per capita rate.(3,11) Until December of 2017, 9, 266 patients were on the general waiting list for corneal transplants in Brazil and 2.14% (199/9,266) of those are from the Federal District (DF).(10) From 2009 to 2016, the number of potential donors grew 36.10%, but the proportion of effective and potential donations increased only 3.8%, so the challenge of improving the donor selection process is still important.(12, 13)

The collection, processing and distribution of corneal buttons is the responsibility of the Eye Banks (EB), part of SUS, which organize their workflow in accordance with the Pan American Association of Eye Banks (APABO) and the Eye Bank Association of America (EBBA). The standardization of procedures by the EB are necessary once they have had a direct influence on the final quality of the cornea tissue and, consequently, the post-operative success.(2, 11, 14)

The National Agency for Health Surveillance (ANVISA) in Brazil regulates the Eye Banks work through the “Resolução da Diretoria Colegiada’’ (RDC) n° 55/2015, (15) available on the institution website. This legal rule standardizes the potential donor selection process using the family interview, medical records analysis, the deceased body evaluation and the tissue quality itself.(14, 15) The total cost of family interview, harvesting and processing the corneas by the eye banks is paid by the public health system. The cornea tissue cannot be sold or be part of any kind of financial transaction. Transplantations costs made outside of SUS health services, must have private resources except for the tissue which is donated.(15) Because of the infectious and transmissible diseases risks, the RDC n° 55/2015 also establishes the tissue contraindication parameters, such as the donor serological tests for tissue approval for transplantation.(16)

The aim of this study was to identify the causes for discarding corneas from the Eye Bank of the Federal District

and to describe the social and demographic variables and causa mortis of corneal donors from 2014 to 2017.

methods

We conducted an exploratory and descriptive study regarding cornea donation to the DF Eye Bank located in an important tertiary public hospital. The DF Eye Bank was founded in 2003 as a non-profit entity, which conducts active searches for donations within the Instituto Hospital de Base do Distrito Federal (Latitude: 15° 46′ 48″ S, Longitude: 47° 55′ 45″ W), which is in the Central-Western region of the country and has a population of approximately 3 million people. This information is available on the Brazilian Institute of Geography and Statistics (IBGE) website.(17)

The project was approved by the Ethics Committee for Human Experimentation of DF Health Secretary and the Health Sciences Faculty (University of Brasília) under the 158 protocol number CAAE45898115.8.0000.0030.

The data collection was performed through analysis of corneal donor’s medical records, and organized in a database using Excel software (Microsoft Corporation, USA).

All the potential donors’ characteristics (cause of death, cause of cornea discard, month of donation, age, gender, time interval of death, corneal enucleation and preservation) from 2014 to 2017 were included in the study. We processed and analyzed the data using the Statistical Package for Social Science software (SPSS) (IBM, USA). The collected information was described as measures of frequency and absolute numbers and percentages. For the results analyses the Pearson chi-square was used (P<0.05) to comparison between the analyzed years and non parametric Wilcoxon test to compare the time intervals T1 (between time of death and the eye globe enucleation) and T2 (between eye globe enucleation and cell medium preservation) over the time. All the statistics tests used p-value<0.005.

Results

From 2014 to 2017, we observed 1,574 corneal donor notifications at DF Eye Bank Institution and 1.77% (28/1,574) of them were excluded from the medical records analysis because they did not have all the variable information. The year 2015 had the highest number (29.3%, n=454) of donations and 2017 had the lowest (21.6%, n=335) though they also had the greatest number of excluded registrations (16/28) (Table 1). Demographic characteristics showed disproportionate in gender distribution between male (74.8%, n= 1,157) and female (25.2%, n= 389), as shown in Table 1.

The average donor age during the studied period was 40 ± 15.9 years (Table 1). The

age range of the majority of cornea donors was 51-60 (21.9%) but the 41-50 (21.5%) age range had almost the same number of donors, and all of them presented the same variation throughout the observed period, including those two most representative ranges cited below (Table 2).

By each year month were observed cornea donation average about 128 ± 29.3 per year.

The aggregate data demonstrated that June presented the biggest number of donations over the past 4 years as shown in Figure 1.


229


Causes of death and discard of donated corneal tissues: Federal District eye bank analysis 2014 -2017

Table 1 Demographic characteristics from cornea donors

Year Mean SD N % N % N % p-value†2014 40 ± 16.2 91 24.7 277 75.3 368 100 Reference2015 41 ± 15.6 118 26.0 336 74.0 454 100 0.6792016 39 ± 16.1 86 22.1 303 77.9 389 100 0.4052017 41 ± 15.1 95 28.4 240 71.6 335 100 0.305Total 40 ± 15.9 389 25.2 1157 74.8 1546 100

Age Female Male Total

† Chi-Square (df=1). p-value: Chi-square comparison between years SD: Standard Deviation

Table 2 Age Distribution of Cornea Donors from the DF/Brazil Eye Bank of Brazil

2014 2015 2016 2017 Total

Age range N % N % N % N % N %

≤10 5 1.4 4 0.9 7 1.8 9 2.7 25 1.611 - 20 51 1.9 63 13.9 70 18.0 37 11.0 221 14.321 - 30 74 20.1 68 15.0 54 13.9 46 13.7 242 15.731 - 40 59 16.0 69 15.2 59 15.2 47 14.0 234 15.141- 50 64 17.4 107 23.6 74 19.0 87 26.0 332 21.551- 60 73 19.8 95 20.9 96 24.7 74 22.1 338 21.961-70 40 10.9 48 10.6 29 7.5 35 10.4 152 9.8≥ 71 2 0.5 0 0.0 0 0.0 0 0.0 2 0.1

Total 368 100 454 100 389 100 335 100 1546 100

Figure 1: Corneal donations monthly distributed.

Figure 2: Cornea donors' causes of death.

Brazilian law establishes a legal requirement to collect eye tissues only within 6 hours after death. The time intervals between death and eye globe enucleation (T1) and between eye globe enucleation and corneal button preservation in medium storage solution (T2) demonstrates that T1 averages in 2014 were 7.7 hours (h) and have decreased over the years to 7.3 h in 2015 and 2016 and 7.4 h in 2017 as shown in table 3.

In the T2 comparison, we observed an increase between 2016 and 2017. The median values and comparison between the total time of corneal processing (from the moment of death until medium preservation) is not significantly related to the causes of death according to the result of the independent-sample median test, p value = 0,114. The statistical comparison between T1 and T2 for the same year are different according to the related-sample Wilcoxon signed rank test result, p value <0,001. Therefore, they are different from each other, and evidenced by the increase of total time of 9.2 hours in 2017 when compared to 2014, demonstrating that in 2017, the T2 intervals had more hours than the T1.

The causes for discarding corneal buttons’ were distinguished in two different groups, one containing all the systemic causes, and the other ophthalmic or tissue intrinsic causes. 3,092 corneas were donated to the DF Eye Bank from 2014 to 2017 and 3% (n= 18/3,092) have not been uptaken. So, in total 3,074 corneas were uptaken and processed by ANVISA’s orientation(15), nearly 60%

Table 3 Comparison between the time of death, enucleation and preservation interval

Interval Mean SD Mean SD Mean SD Mean SDperiod

T1 7.7 5.5 7.3 4.7 7.3 5.3 7.4 4.9

T2 6.7 4.6 6.7 3.9 6.2 3.9 6.7 4.3

Total 8.2 5.2 8.4 5.0 8.0 4.6 9.2 5.6(T1 toT2)

2014 2015 2016 2017

T1= Time between death and enucleation (in hours)T2= Time between enucleation and preservation in medium (in hours)SD = Standard Deviation


230 Loiola DS, Báo SN, Victer TNF, Lucas MB, Chalita MRC, Sampaio TL


(n=1,836) were transplanted and 40% (n=1,238) were discarded. As shown in table 4, the major causes of discard from systemic causes were positive or indeterminate serological tests (68.3%, n=424) and indeterminate donor’s causa mortis (14.4%, n= 90). For the corneal self-tissue, the most prevalent causes of discard were matureness, which is the exceeded time of tissue preservation storage, with 39.3% (n=245) and stromal infiltration with 37.2% (n=232). Considering that each donor has two corneal tissues, the number of samples not taken up (n=18) demonstrates the case that only one corneal tissue was preserved and the other

Table 4 Causes corneal tissue discard

Sistemic causes N %

Infectious causa mortis (sepsis) 58 9,3Cancer 2 0,3Indeterminated causa mortis 86 13,8Contraindication 15 2,4Positive or Indeterminate Serology 424 68,3

Total 585 47,0

Ophtalmic causes

Non-biological artifact 82 13,1Stromal infiltrate 232 37,2Corneal leukoma 1 0,2Non-viabletissue 40 6,4

Total 355 28,5

External causes

Technical failure 8 1,3Inadequate serological samples 27 4,3Not uptake 18 2,9Matureness 245 39,3

Total 298 23,9

was not.

dIscussIon

The gender distribution results are similar when compared with data previously described by our study group, such as 73.3% for male and 26.5% for female from the 2004 to 2013 analysis.(4)

Other studies worldwide have described different results; some of them with greater discrepancies (18, 19) and others with more equal proportion between genders.(20-22) Despite this, the male gender is almost always the largest proportion among all studies, principally due to the fact that they are the main victims of external causes of death.(23) Violent and non-violent causes of death may influence the discrepancy between genders among the population in the Federal District. External

causes of death are expected, and have been discussed previously by this work group.(4,18, 23) Hopkinson et al.(24) proposed that gender can influence the donor and recipient incompatibility related to corneal rejection and failure, thereby, the gender distribution information is used to improve technical procedures, health policies and clinical conduct.

The mean donor age of our study was 40 ± 15.9 years (Table 1) consistent with other recent studies, (4, 18, 20) but still lower than other national and internationally published studies.(21, 25-28)

From 2014 to 2017, the month of December had the lowest

absolute number of donations, at least half (3.9% n= 61) when compared to the rest of the year’s average as shown in Figure 1. Systematic monthly information regarding donations of corneas collected throughout the year and compared with other years improves the physical, technical and financial management of the eye bank.(29) The scientific literature regarding epidemiological analysis of cause of death, for corneal tissue donors, demonstrates heterogeneity of those causes nomenclature and classifications. Therefore, in order to analyze these types of results in a general way, the etiological cause of death must be considered even if the Eye Bank Association of America (EBAA) has established their own unique classifications.(30) In light of that, the most frequent causes of death were cardiovascular diseases (25.1%, n=388) (Figure 2), which was previously described in the state of São Paulo(21, 31) and Cascavel city (Paraná State)(28) in Brazil and agrees with U.S Eye Banks results from 2011 to 2016.(30) Thus, other studies have also demonstrated the frequency and importance of the heart or cardiac disease as significant non-external cause of death, some with minor and others with higher representative results.(4, 25, 32) The second most observed external cause of death was sharp/blunt instrument injury (19.6%) which was also described in DF, Brazil by our group, as well as worldwide.(18, 19, 27, 33) The historical and increasing prevalence of this type of death may reflect the violent social environment in Brazil.(18, 23, 28) ANVISA’s RDC n° 55/2015 establishes the maximum range for time interval between death, eye globe enucleation, corneal preservation and storage conditions. The results observed in Table 3 showed a slight decrease in T1 interval from 2014 to 2017 and maintenance of T2 results. Overall average from time between and preservation was homogeneous throughout the analyzed period. The average time for the same period from the state of Goiás (6.5±4.3 hours) is lower when compared to our results.(18)

The main concern is that this average (7.7–7.4 hours) does not comply with ANVISA’s standardized time.(15) This T2 average and the total (T1+T2) time increased in 2017 (9.2 hours), when compared to 2014, 2015 and 2016, and resulted from the necessary changes to the adequacy of the Bank’s services per the new ANVISA RDC n°55(15) legal standards in 2015. Although Eye Bank studies in São Paulo have not observed any difference in the total time interval average, they have shown lower quality tissue samples.(34) The impact is the major chances of corneal epithelial defects, exposing the tissue to traumatismes and decreasing their quality to transplant.(34) Some studies demonstrated the proportion of discarded and transplanted cornea tissue as about 10-16.3% in São Paulo, 21.9% in the state of Rio Grande do Norte (35) and 24% in the state of Minas Gerais.(36) Table 4 shows that we observed almost 40% (n=1,238) discard rate in the Federal District, a higher result when compared to São Paulo and Rio Grande do Norte , and even the global average, (37) about 35%, but lower than the state of Ceará at 49.1.(38) In general, the causes for discarding are distributed and separated into three different groups: systemic, ophthalmic and external causes.

Several studies have described positive diagnosis by blood screening for infectious diseases. Once all potential deceased organ donors are serologically screened(15, 16) for HIV-1 and -2 antibody, human T cell lymphotropic virus (HTLV)-1 and -2 antibody, HCV antibody, Anti-HBc and HBsAg, the results of infectious disease prevalence are described in Brazil(14, 19)

and worldwide.(39) Therefore, corroboration with positive or undetermined serological results are the major cause of cause


231

of discarded corneal tissue (68.3%. n=424) from our study. Despite the lower rate of positive cornea donor samples, compared to 20% worldwide(39) and 1- 32% in local states,(14, 27, 28) our results consider all the undetermined serological results that could explain the rate of increase when compared to others. The reduced availability of validated serological cadaveric tests has been discussed as a possibility for false-positive results related to discrepancies between in vivo and postmortem serological performance.(4, 16)

Analyzing social, demographic and technical indicators, using statistical tools to correlate epidemiological data, mitigates the improvement of public health measures of transplant centers and consequently improves the population’s access to the quality service. The total cost of family interview, harvesting and processing the corneas by the eye banks is paid by the public health system (SUS) the entire cost of the family interview, harvesting, and processing by the eye bank is paid by the public health system (SUS).

The Eye Banks have a new challenge to enhance safety and effectiveness of corneal transplantation. As discussed in this study, some specific issues such as violent causes of death, gender disproportion and total interval time of corneal processing management seek to reduce those procurement processes and increase availability of corneal tissue for transplantation. The donor’s medical records analysis, personal clinical history, serological screening tests and tissue evaluation are influential factors for effective corneal transplantation. In this study, we noticed the significance of standardizing some Eye Bank procedures. We observed that the cause of death and discard classification is not standardized and as a result, it shows a heterogeneity of nomenclatures. For an effective data analysis, a reclassification based on etiological causes and guided by the Brazilian Ministry of Health’s technical document ‘’The death certificate: a necessary and important document’’(40) is highly recommended.

Acknowledgement

The authors would like to acknowledge MSc. Silvano Barbosa, from Health Ministry of Brazil, for his support with statistical execution and data analysis and all the Distrito Federal Eye Bank staff for the logistical and technical support.

RefeRences

1. Bourne RR, Flaxman SR, Braithwaite T, Cicinelli MV, Das A, Jonas JB, et al.; Vision Loss Expert Group. Magnitude, temporal trends, and projections of the global prevalence of blindness and distance and near vision impairment: a systematic review and meta-analysis. Lancet Glob Health. 2017;5(9):e888–97.

2. Lambert NG, Chamberlain WD. The structure and evolution of eye banking: a review on eye bank’s historical, present, and future contribution to corneal transplantation. J Biorepository Sci App Med. 2017; (5):23-40.

3. Gain P, Jullienne R, He Z, Aldossary M, Acquart S, Cognasse F, et al. Global Survey of Corneal Transplantation and Eye Banking. JAMA Ophthalmol. 2016;134(2):167–73.

4. Sampaio TL, Rodrigues IP, Pontes DF, Ribeiro TK, Yamagushi CK, de Araújo WN, et al. Suitability of Corneal Tissue for Transplantation Derived From Violent Death: A 10-Year Analysis. Transplant Proc. 2015;47(10):2973–7.

5. Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, et al. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004;82(11):844–51.

6. Katzman LR, Reiser BJ. Pediatric corneal opacities. Pediatric Ophtalmology Education Center; 2016. [cited 2018. [cited 2019 Jun 15]. Available from: https://www.aao.org/disease-review/pediatric-corneal-opacities

7. Yin XT, Tajfirouz DA, Stuart PM. Murine corneal transplantation: a model to study the most common form of solid organ transplantation. J Vis Exp. 2014;93(93 e51830):e51830.

8. Associação Brasileira de Transplante de Órgãos (ABTO). Registro Brasileiro de Transplantes. Dimensionamento dos Transplantes no Brasil e em cada estado 2005-2012. RBT. 2012;18(4):3-94. [citado 2018 Jun 12]. Disponível em: http://www.abto.org.br/abtov03/Upload/file/RBT/2012/RBT-dimensionamento2012.pdf

9. Associação Brasileira de Transplante de Órgãos (ABTO). Registro Brasileiro de Transplantes. Dimensionamento dos Transplantes no Brasil e em cada estado, 2008-2015. RBT. 2015; 21(4):3-81. [citado 2018 Jun 12]. Disponível em: http://www.abto.org.br/abtov03/Upload/file/RBT/2015/anual-n-associado.pdf

10. Associação Brasileira de Transplante de Órgãos (ABTO). Registro Brasileiro de Transplantes. Dimensionamento dos Transplantes no Brasil e em cada estado, 2010-2017. RBT. 2017; 23(4):3-97. [citado 2018 Jun 12]. Disponível em: http://www.abto.org.br/abtov03/Upload/file/RBT/2017/rbt-imprensa-leitura-compressed.pdf

11. Almeida HG, Hida RY, Kara N. Review of developments in corneal transplantation in the regions of Brazil - Evaluation of corneal transplants in Brazil. Clinics (São Paulo). 2016;71(9):537–43.

12. Associação Brasileira de Transplante de Órgãos (ABTO). Registro Brasileiro de Transplantes. Dimensionamento dos Transplantes no Brasil e em cada estado, 2009-2016. RBT. 2016;22(4):3-97. [citado 2018 Jun 12]. Disponível em: http://www.abto.org.br/abtov03/Upload/file/RBT/2016/RBT2016-leitura.pdf

13. Torres IB, Araujo MS, Benites MF, Moreira H. Comparação entre potenciais e efetivos doadores de córnea no Hospital Universitário Evangélico de Curitiba. J Bras Transpl. 2006;9(3):615-19.

14. Santos CG, Pacini KM, Adán CB, Sato EH. Motivos do descarte de córneas captadas pelo banco de olhos do Hospital São Paulo em dois anos. Rev Bras Oftalmol. 2010;69(1):18–22.

15. Agência Nacional de Vigilância Sanitária (ANVISA). Resolução Da Diretoria Colegiada-Rdc N° 55, de 11 de Dezembro de 2015. Dispõe sobre as boas práticas em tecidos humanos para uso terapêutico. Diário Oficial da União nº 238 Brasília, DF, 14 de dezembro de 2015. p. 14-102.

16. Victer TN, Dos Santos CS, Báo SN, Sampaio TL. Deceased tissue donor serology and molecular testing for HIV, hepatitis B and hepatitis C viruses: a lack of cadaveric validated tests. Cell Tissue Bank. 2016;17(4):543–53.

17. Instituto Brasileiro de Geografia e Estatística (IBGE). População. [citado 2018 Jun 12]. Disponível em: https://www.ibge.gov.br/estatisticas-novoportal/sociais/populacao.html

18. Silva RE, Morato RM, Veneziano RT, Rodrigues FW. Perfil epidemiológico dos doadores de córnea do Estado de Goiás. Rev Bras Oftalmol. 2016;75(4):274–8.

19. Rocon PC, Almeida AV, Paro FM. Epidemiological profile of cornea and organ donors in five hospitals in the State of Espírito Santo, Brazil. Rev Bras Pesq Saúde. 2015;17(1):56–64.

20. Crawford AZ, McKelvie J, Craig JP, McGhee CN, Patel DV. Corneal Transplantation in Auckland, New Zealand, 1999-2009: Indications, Patient Characteristics, Ethnicity, Social Deprivation, and Access to Services. Cornea. 2017;36(5):546–52.

21. Adán CB, Diniz AR, Perlatto D, Hirai FE, Sato EH. Dez anos de doação de córneas no Banco de Olhos do Hospital São Paulo: perfil dos doadores de 1996 a 2005. Arq Bras Oftalmol. 2008;71(2):176–81.

Causes of death and discard of donated corneal tissues: Federal District eye bank analysis 2014 -2017



232

22. Michelon VG, Michelon T, Garcia VD, Marcon AS. Activity of the Eyes bank at Santa Casa Hospital, Southern Brazil between 2003 and 2007. J Bras Transpl. 2009;12(3):1132–7.

23. de Moura EC, Gomes R, Falcão MT, Schwarz E, das Neves AC, Santos W. Gender inequalities in external cause mortality in Brazil, 2010. Cien Saude Colet. 2015;20(3):779–88.

24. Hopkinson CL, Romano V, Kaye RA, Steger B, Stewart RM, Tsagkataki M, et al.; National Health Service Blood Transplant Ocular Tissue Advisory Group and Contributing Ophthalmologists (OTAG Study 20). The influence of donor and recipient gender incompatibility on corneal transplant rejection and failure. Am J Transplant. 2017;17(1):210–7.

25. Krohn J, Hovding G. The influence of donor age and cause of death on corneal endothelial cell density. Acta Ophthalmol Scand. 2005;83(6):746–50.

26. Andersen J, Ehlers N. The influence of donor age and post mortem time on corneal graft survival and thickness when employing banked donor material. Acta Ophthalmol. 1988;66(3):313–7.

27. Santos NC, Bezerra VL, Melo EC. Características das doações de córnea no estado do Piauí. Rev Bras Oftalmol. 2014;73(6):351–7.

28. Shiratori CN, Hirai FE, Sato EH. Characteristics of corneal donors in the Cascavel Eye Bank: impact of the anti-HBc test for hepatitis B. Arq Bras Oftalmol. 2011;74(1):17–20.

29. Marinho A, Cardoso SS, Almeida VV. Desigualdade de transplantes de órgãos no Brasil: Análise do perfil dos receptores por sexo e raça ou cor. In: Textos para Discussão; IPEA; 2011. [citado 2018 Jun 12]. Disponível em: http://www.ipea.gov.br/portal/index.php?option=com_content&view=article&id=9811

30. Eye Bank Association of America. 2016 Eye Banking Statistical Report. Washington, DC: Eye Bank Association of America; 2017. [cited 2018 Jun 12]. Available from: http://restoresight.org/wp-content/uploads/2017/04/2016_Statistical_Report-Final-040717.pdf

31. Sano RY, Sano FT, Dantas MC, Lui AC, Sano ME, Neto AL. [Analysis of the transplanted corneas at Santa Casa de São Paulo Eye Bank]. Arq Bras Oftalmol. 2010;73(3):254–8.

32. Chen LX, Liu QH. Influence factors for successful corneal donation among Chinese adults: data from Nanjing between 2001 and 2012. Int J Ophthalmol. 2014;7(6):984–7.

33. Paz AC, Ribeiro PC, Mascarenhas MD, Silva MV. Caracterização dos doadores de órgãos e tecidos para transplante do estado do Piauí, de 2000 a 2009. Enferm Foco. 2011;2(2):124–7.

34. Zantut F, Holzchuh R, Boni RC, Mackus EC, Zantut PR, Nakano C, et al. [Comparative analysis of the donor cornea quality and of the interval between death and preservation before and after new sanitary and technique rules in a University Eye Bank]. Arq Bras Oftalmol. 2012;75(6):398–401.

35. Freire IL, Araújo RO, Almeida QL, Vasconcelos Q, Dantas BA, Silva MF, et al. Causas do descarte de córneas captadas pelo banco de tecidos oculares do Rio Grande do Norte. Rev Pesq Cuidado Fundam Online. 2015;7(1):1867-74.

36. Saldanha BO, Oliveira RE Jr, Araújo PL, Pereira WA, Simão Filho C. Causes of non use of corneas donated in 2007 in Minas Gerais. Transplant Proc. 2009;41(3):802–3.

37. Farge EJ, Cox WG, Khan MM. An eye banking program for selecting donor corneas for surgical distribution. Cornea. 1995;14(6):578–82.

38. Moscoso L. Descarte de córneas chega a quase 50%. Diário do Nordeste. 2010 Aug 08. [citado 2018 Jun 12]. Disponível em: http://diariodonordeste.verdesmares.com.br/cadernos/cidade/descarte-de-corneas- chega-a-quase-50-1.407995

39. Bensoussan D, Jeulin H, Decot V, Agrinier N, Venard V. Analyses of the effects of collection and processing time on the results of serology testing of cadaveric cornea donors. Diagn Microbiol Infect Dis. 2010;68(1):40–5.

40. Brasil. Ministério da Saúde. A Declaração de óbito: documento necessário e importante. Brasília, DF: Ministério da Saúde; 2007. [citado 2018 Jun 12]. Disponível em: http://www.portalmedico.org.br/arquivos/cartilha_do_cfm_ms.pdf

Corresponding author: Sônia Nair Báo University of Brasilia, Federal District, Brazil, 73380-900 Phone and fax Number: +55.61.3107-3122. E-mail: [email protected]

Loiola DS, Báo SN, Victer TNF, Lucas MB, Chalita MRC, Sampaio TL



233original articlE

Resumo

Objetivo: Avaliar a relação custo-utilidade do tratamento inicial com laser ou medicamentos do glaucoma primário de ângulo aberto (GPAA) no Brasil, considerando de um lado os custos totais e de outro lado o impacto na qualidade de vida dos pacientes. Métodos: O estudo foi realizado com base em um modelo de Markov, onde uma coorte teórica de portadores de GPAA em estágio inicial foi gerada. Os parâmetros usados no modelo foram obtidos na literatura e incluíram: custos médicos diretos (consultas, exames, tratamento); custos não médicos diretos (gasto com hospedagem, transporte, alimentação, acompanhante); custos indiretos (relacionados à incapacidade para o trabalho); valores de utilidade (qualidade de vida medida em QALY – quality-adjusted life year); e probabilidade de transição entre os estágios de saúde. Três estratégias de tratamento foram testadas no modelo: (1) sem tratamento; (2) tratamento inicial com colírios; (3) tratamento inicial com trabeculoplastia a laser. A medida de desfecho foi a razão de custo-utilidade incremental (RCUI). A robustez do modelo foi testada através de análise de sensibilidade. Resultados: As estratégias (2) e (3) de tratamento inicial do GPAA geraram ganhos em qualidade de vida em relação à (1) no Brasil. Iniciar o tratamento com laser gerou ganho médio de 1 QALY, enquanto que com medicamentos propiciou um ganho de 2 QALYs em média. Dentre as três estratégias testadas, a estratégia (2) foi a custo-efetiva e foi dominante sobre as demais, pois foi ao mesmo tempo a mais barata e a mais efetiva. Conclusão: Tanto a trabeculoplastia a laser quanto os medicamentos como tratamentos primários do GPAA inicial geraram ganhos significativos de qualidade de vida. A estratégia de se iniciar o tratamento com medicações foi custo-efetiva, quando se considera os custos totais. A alternativa de tratamento inicial através de trabeculoplastia a laser não foi custo-efetiva.

Descritores: Glaucoma primário de ângulo aberto/terapia; Tratamento com laser; Análise de custo-efetividade; Qualidade de vida

AbstrAct

Objective: To evaluate the cost-utility relation of the initial treatment with laser or primary open-angle glaucoma medications (PLA) in Brazil, considering on the one hand the total costs and on the other side the impact on patients’ quality of life. Methods: The study was performed based on a Markov model, where a theoretical cohort of early-stage GPAA carriers was generated. The parameters used in the model were obtained in the literature and included: direct medical costs (consultations, examinations, treatment); direct non-medical costs (accommodation, transportation, meals, companions); indirect costs (related to incapacity for work); utility values (quality of life measured in QALY - quality-adjusted life year); and probability of transition between stages of health. Three treatment strategies were tested in the model: (1) without treatment; (2) initial treatment with eye drops; (3) initial treatment with laser trabeculoplasty. The measure of outcome was the incremental cost-utility ratio (RCUI). The robustness of the model was tested through sensitivity analysis. Results: The strategies (2) and (3) of the initial treatment of POAG generated gains in quality of life in relation to (1) in Brazil. Initiating the laser treatment generated an average gain of 1 QALY, whereas with medication it gave a gain of 2 QALYs on average. Among the three strategies tested, strategy (2) was cost-effective and was dominant over the other strategies, since it was at the same time the cheapest and the most effective strategy. Conclusion: Both laser trabeculoplasty and medications as primary treatments of early-stage POAG have generated significant gains in quality of life. The strategy of starting treatment with medications was cost-effective, whereas laser trabeculoplasty strategy was not cost-effective, when non-medical costs (direct and indirect) are included.

Keywords: Open-angle primary glaucoma/therapy; Laser treatment; Cost-effectiveness analysis, Quality of life

Sirley Maria de Freitas1 https://orcid.org/0000-0003-1684-901X.Ricardo Augusto Paletta Guedes2 https://orcid.org/0000-0002-9451-738X.Daniela Marcelo Gravina3 https://orcid.org/0000-0001-8975-5837.Vanessa Maria Paletta Guedes3 https://orcid.org/0000-0003-2406-0983.Alfredo Chauobah4 https://orcid.org/0000-0002-2459-9164.Carlos Eduardo de Mello Gomes4 https://orcid.org/0000-0001-7504-7629.

1 Postgraduate Program in Health, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil. 2 Instituto de Olhos Paletta Guedes Juiz de Fora, MG, Brazil; Universidade Federal de Juiz de Fora Juiz de Fora, MG, Brazil. 3 Instituto de Olhos Paletta Guedes, Juiz de Fora, MG, Brazil. 4 Department of Statistics, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.

Avaliação econômica do glaucoma primário de ângulo aberto

The authors declare no conflicts of interests.Received for publication 04/12/2018 - Accepted for publication 05/06/2019.

Economic evaluation of primary open-angle glaucoma



234

IntRoductIon

In the world today, it is of great importance to know the costs related to a particular disease and its consequences. The economic impact of the blindness for the individual and the

society is very huge.(1,2) Among the main causes of blindness in Brazil, we emphasize primary open-angle glaucoma (POAG), accounting for approximately 12% of causes of blindness. (3,4)

Blindness by POAG, unlike other more frequent causes such as cataract and refractive errors, is irreversible.(5)

The impact of POAG in the patients’ daily activities begins well before blindness finally appears. The quality of life of glaucoma patients is impacted in a variety of ways: from the type and cost of treatment to the progressive loss of sight, to a non-negligible psychological impact.(6)

The economic impact assessment of POAG shall include both medical and non-medical direct and indirect costs.(7) Some authors have already determined the costs related to glaucoma in several countries, including Brazil.(8-14) However, Brazilian data is still incipient.(7)

Among the main types of health economic evaluation studies, cost-utility studies are very important since they assess both the costs and impact on the quality and/or amount of life related to that pathology under study.(7) In Brazil, Guedes et al made a cost-utility evaluation for the treatment of POAG in 2016.(15) They had found that for patients with POAG in early stage both the strategy of initial treatment with laser trabeculoplastia and the strategy of initiating the treatment with eye drops were cost-effective under the perspective of the financier Brazilian Unified Health System (paying for the services). In the present study, the authors took into account only the direct medical costs, leaving aside non-medical costs (direct and indirect).(15)

Many patients and/or caregivers have to travel long distances to referral centers for glaucoma treatment. Therefore, non-medical costs such as transportation, accommodation, food, care giver, working days missed, social security benefits, etc. can have a significant economic impact.(16)

The objective of the present study was to carry out a cost-utility assessment of POAG from the society perspective, that is, taking into account on the one hand the total costs (medical, non-medical, direct and indirect), and on the other the impact on the quality of life of patients with POAG in Brazil.

methods

The present research was carried out at Universidade Federal de Juiz de Fora, and it is a cohort of a bigger research project ongoing at said University, called the Economic Evaluation of Primary Open Angle Glaucome, and the approval at the Ethics Committee of UFJF was duly obtained under number 116/2010.

The present study consisted in evaluating a hypothetical population of patients with early-stage POAG (MD [mean deviation] index of the Humphrey perimetry > -6 dB) with the construction of an economic evaluation model. The age of entry into the model was 40 years. The Brazilian public health system (SUS) was used as the reference for this study.

The cost perspective was that of the society, that is, the total medical and non-medical, direct and indirect costs were taken into account.

The initial treatment alternatives for POAG analyzed in this study were: (1) no treatment; (2) initial treatment with eye drops (clinical treatment); (3) initial treatment with laser trabeculoplasty (laser treatment). The objective of including an alternative without treatment is to simulate one cohort of patients who remain without knowledge on the disease, and which POAG progresses without the patient taking any treatment. These patients do not have non-medical direct costs (transport, accommodation, feeding, etc), but have indirect costs (loss of productivity, disability, working days missed, both themselves and the care givers. Many will only diagnose glaucoma late in the progression of the disease, when blindness is virtually installed.

The study horizon was the average life expectancy of the Brazilian population, according to the Brazilian Institute of Geography and Statistics (IBGE). The cohort of hypothetical patients entered the model at age 40, and life expectancy was adjusted every year according to the IBGE life table. Both costs and effectiveness were discounted by 5%, as recommended by the Brazilian Ministry of Health.

For the analysis of the impact on quality of life, the values of utility for glaucoma patients in Brazil were taken into account, as described by Paletta Guedes et al.(17) These values were identified by the method Time Trade Off, from interviews with glaucoma patients in many progression periods of the pathology.

The direct medical costs were obtained from the perspective of SUS as the payer of services in the Reference Centers for the treatment of glaucoma in the public system. Included in this category are appointments, examinations, medications, surgeries, etc.

Non-medical direct costs (accommodation, food, displacement, caregivers) and indirect costs (loss of productivity) were obtained in a previous study by the same research group, including the costs of the patients’ caregivers. In this previous study, monetary values were obtained in a cross-sectional study with interviews of glaucoma patients attending a SUS Reference Center for the treatment of glaucoma in the city of Juiz de Fora, in the state of Minas Gerais.

The costs of the interventions were extracted from the SUS table of medical procedures and fees. Frequencies of medical visits and examinations were obtained from what is established for the SUS Glaucoma Reference Centers. The price of the medicines was the amount paid by SUS to the Reference Centers.

In the alternative clinical treatment, the average number of eye drops per patient and the ratio of eye drops types at each evolutionary stage were obtained from the literature.

In the alternative laser treatment, laser trabeculoplasty was performed in both eyes in the first year. There was the possibility of a new application in each eye, if necessary (following the suggestion of Cantor et al, we add 21% in the cost of the initial trabeculoplastia to cover the costs of a possible new laser application).(18) In subsequent years, the literature costs of reintroducing eye drops to glaucoma were considered (50% of laser efficacy at the end of the year, i.e., 50% of patients without the need of eye drops, and 50% with the need for eye drops).(15)

Adverse events of the laser were not taken into account in the costs due to the low incidence. The monetary values are in reais (R$) and refer to the year 2018.

A Markov model was built for the cost-utility analysis. The model had the following stages: (1) Initial glaucoma; (2) Moderate


Freitas SM, Guedes RAP, Gravina DM, Guedes VMP, Gomes CEM, Chaoubah A


235



glaucoma; (3) Severe Glaucoma; (4) Blindness in the best eye; and (5) Death. Stage 1 (initial glaucoma) was the entry stage in the model, and stage 5 (Death) was the terminal stage. Every year, cohort members could stay at the same stage or progress to the next stage according to transition probabilities. Participants who progressed should follow the following pathway: Initial Glaucoma, Moderate Glaucoma, Severe Glaucoma, and Blindness, without skipping stages or returning to earlier stages. The transition probabilities between the stages for each alternative studied (observation, clinical treatment, and laser treatment) were taken from the literature.(15) Patients of any stage (1 to 4) could reach stage 5 (Death) without going through the other stages, according to the annual probability of death for the Brazilian population. The choice for Markov modeling was based on the characteristics of the pathology under study: a chronic disease with recurrent costs (chronic use of eye drops, medical visits, and examinations).

In the construction of the model, some assumptions were adopted. The duration of each cycle in the model was 1 year. The entire cohort was 40 years old, since it is from this age on that the prevalence of POAG begins to increase. In the clinical treatment strategy, the first line of treatment was performed with the use of prostaglandin analogues. In the event of failure to achieve the target intraocular pressure, the following eye drops were used: timolol maleate 0.5%, and dorzolamide hydrochloride 2%, following this sequence. This choice was based on the clinical experience of two of the authors (specialists in glaucoma), and also following the guidance of the Brazilian Glaucoma Society. In the strategy of laser treatment as initial therapy, the application of laser (selective trabeculoplasty) in 360° of trabeculae in both eyes during the first year was considered. If necessary, repetition of laser trabeculoplasty was allowed once again. In laser failure to control intraocular pressure, patients were reintroduced with hypotensive medication in the following sequence: prostaglandin analogue and timolol maleate 0.5%. No comparative economic study between eye drops and laser included laser complications. Studies using models are approximations of reality aiming to evaluate the average patient. Individual variabilities and rare complications are difficult to model. The probabilities of transition between the stages were fixed, that is, there were no adjustments in the probability with the progression of the model. Another assumption was that average utility values for each health condition (initial, moderate, severe glaucoma, and blindness) are not influenced by the type of treatment strategy.(15)

The outcome measure used in the present study was the incremental cost-utility ratio (ICUR) showing the incremental cost per benefit achieved (R$/QALY).

The robustness of the model was tested by the univariate sensitivity analysis using the Tornado diagram for the variables with the greatest impact on the result.

Data collection was carried out in Microsoft Excel 2010, and the cost-utility analysis was carried out on TreeAge Pro 2011 Health Care software (Tree Age Software, Williamstown, Massachusetts, USA).

Results

The parameters used in the construction of the Markov model are shown in Tables 1, 2 and 3. Table 1 shows the values of the different medical resources and their costs for SUS. The

values of each type of cost (medical direct, nonmedical direct, and indirect) for each stage of the treatment model and strategy are set out in table 2. The values of utility used in this study are shown in table 3.

The final cost results for each treatment strategy of the POAG, the gains in quality of life, and the cost-utility ratio are shown in table 4.

The sensitivity analysis by the tornado diagram shows that the variable with the greatest impact on the model would be the age of entry (Figure 1), accounting for 96% of the model risk. Even so, redoing the model with different entry ages (50, 60 or 70) the result remained unchanged. Age only influences the outcome when the patients’ entry occurs with values below 30 years, which is very rare for the POAG. The other parameters of the model (costs, utilities and transition probabilities) had little influence on the result, demonstrating the robustness of this result.

dIscussIon

The present study presents an unpublished result in the literature. The results of the present study demonstrate that the clinical treatment of POAG is cost-effective from a society perspective. In addition, this treatment strategy (initial clinical) is

Table 1 Resources used and associated

costs used in the model

Resouses Frequency Code Unit Value (months) (SUS)* (R$)

Initial appointmenta 12 03.01.01.010-2 57.74

Follow-up appointmentb 3 03.03.05.001-2 17.74

Use of 1 medicationc 3 03.03.05.005-5 127.98

Use of 2 medicationd 3 03.03.05.018.7 146.64

Use of 3 medicatione 3 03.03.05.022-5 226.02

Monoculat Nottrabeculoplasty applicable 04.05.05.012-7 45.00

New application of NotTrabeculoplastyf applicable 04.05.05.012-7 9.45

* Code of the procedures table of the Brazilian Unified Health System (SUS), table SIGTAP (http://sigtap.datasus.gov.br/tabela-unificada/app/sec/inicio.jsp)

a. Initial appointment: includes complete ophthalmologic examination with tonometry, fundoscopy and campimetry.

b. Follow-up appointment: includes complete ophthalmologic examination with tonometry and fundoscopy.

c. Use of 1 medication of the type prostaglandin analogue

d. Use of 2 medications: prostaglandin analog + timolol maleate 0.5%

e. Use of 3 medications: prostaglandin analog + timolol maleate 0.5% + dorzolamide hydrochloride 2%

f. The cost of a new trabeculoplasty was included as a 21% increase in the cost of the first trabeculoplasty.


236 Freitas SM, Guedes RAP, Gravina DM, Guedes VMP, Gomes CEM, Chaoubah A


Table 2 Cost of each evolutionary stage of glaucoma according to the treatment strategy

Treatment strategy Stage of Direct medical Direct medical Indirect cost (R$) Total cost (R$) POAG cost (R$) non mical cost (R$)

Without treatment Initial 0.00 0.00 20.156.75 20.156.75 Moderate 0.00 0.00 26.988.16 20.156.75 Severe 0.00 0.00 27.263.82 27.263.82 Blindness 0.00 0.00 27.263.82 27.263.82Clinical Treatment Initial 909.61 587.47 20.156.75 21.653.83 Moderate 969.08 660.52 26.988.16 28.617.76 Severe 1.043.97 708.54 27.263.82 29.016.33 Blindness 1.091.80 708.54 27.263.82 29.064.16Laser Treatment: (First year) Initial 547.12 587.47 20.156.75 21.291.34 Moderate 547.12 660.52 26.988.16 28.195.80 Severe 547.12 708.54 27.263.82 28.519.48 Blindness 547.12 708.54 27.263.82 28.519.48Laser Treatment: (Subsequent years) Initial 438.22 587.47 20.156.75 21.182.44 Moderate 438.22 660.52 26.988.16 28.086.90 Severe 438.22 708.54 27.263.82 28.410.58 Blindness 438.22 708.54 27.263.82 28.410.58

a) Clinical Treatment: Average annual cost based on:

• Initial annual appointment + 4 follow-up appointments + Eye drops needed for 1 year of treatment at SUS referral center

• Amount ratio of eye drops used at each evolutionary stage of glaucoma;

• Number of eye drops per year;

• Price of eye drops paid by SUS to the Reference Centers;

• Cost of adverse effects: Only costs associated with Asthma Crisis secondary to the inadvertent use of Beta-Blockers in these patients were included. Relative Risk = 2.29. There was an increase of 23.8% in the final average cost per patient.

b) Laser Treatment:

• First year counts for: 1 Initial appointment + 4 Follow-up appointments + Trabeculoplasty in 2 eyes + Eye drops necessary to complement the treatment + new trabeculoplasty.

• Subsequent years: 1 Initial appointment + 4 Follow-up appointments + Eye drops necessary to complement the treatment.

• Efficacy estimated at 50% at the end of the first year, i.e., 50% of patients without eye drops. The other 50% were divided as follows: 25% requiring prostaglandin analogs, and 25% requiring prostaglandin analog + timolol maleate 0.5%.

• The cost of repeating Trabeculoplasty was added at initial cost (21% more), according to a study by Cantor et al. 2008.

• Adverse events due to the use of timolol maleate 0.5% (Asthma crisis): A 23.8% increase in the average value of PG + Ti 0.5% was added.

• The cost was considered the same for all evolutionary stages of glaucoma.

Table 3 Average utility values for each stage

(health condition) of the model(17)

Health conditions Utility value

Initial glaucoma 0.8563

Moderate glaucoma 0.7966

Severe glaucoma 0.7512

Blindness 0.5700

Death 0.0000

Source: Paletta Guedes et al. (17)

Table 4 Total costs, utilities (Quality-adjusted life year – QALY)

and cost-utility analys

Treatment Total Incremental Effectiveness Incremental RCUI strategy Cost Cost (QALY) Effectiveness (R$ / (R$) (QALY) (QALY) QALY) Clinical Treatment 384.549.36 *** 13.89 *** *** Without Treatment 393.384.22 8.834.86 11.76 -2.13 Dominated Laser Treatment 410.642.10 26.092.74 12.79 -1.1 Dominated

QALY: quality-adjusted life year; RCUI: Incremental cost-utility ratio.


237


dominant over the other treatment strategy tested in the model: initial laser treatment. Clinical treatment is still dominant over non-treatment of POAG.

Cost-utility studies are important because they jointly assess the impact of costs and quality of life related to a given health intervention. According to the guidelines of the Ministry of Health, cost-effectiveness and cost-utility studies should be encouraged, as they aid in decision-making process by managers, physicians and patients.(7) Despite the scarcity of robust data for the studies of economic evaluation in health, the authors managed in an unpublished way to build a model to study this subject of great importance.

Brazil has developed a lot in the treatment of POAG with the public policy for glaucoma treatment. This government program created the Reference Centers for glaucoma treatment where patients can have care, follow-up, and treatment necessary for their disease.(10)

Guedes et al carried out a cost-utility analysis of POAG treatment from a SUS perspective, and found that for each evolutionary stage of glaucoma there is a more cost-effective treatment strategy.(8) In the early stages of POAG, both clinical treatment and laser treatment were cost-effective.(15) An important proviso is that the costs considered in the study by Guedes et al were only the direct medical costs. They reflect the impact of the costs for the Brazilian public health system (SUS) and its importance for the planning of resources destined to SUS.

In the present study, a model similar to that of Guedes et al was created with a significant change: the costs considered in the present study included direct non-medical costs and indirect costs in the analysis. The intent was to analyze the economic impact of glaucoma for society as a whole. The results show that when we include non-medical costs (direct and indirect), the cost-effectiveness situation changes a bit. The only cost-effective treatment becomes the clinical treatment, that is, it is more effective and cheaper when compared to laser treatment and non-treatment of POAG.

The results presented in this evaluation show that non-medical costs have an important social impact because they change an alternative (laser treatment) that was cost-effective from the point of view of the payer into a dominated alternative when the perspective changes to the total costs.

The results of gains in quality of life are worth discussing. The “non-treatment” strategy generates an average gain of 11.76 quality-adjusted life years (QALYs) per patient for the remainder of their life expectancy. Treating glaucoma with both strategies (eye drops or laser) generates significant gains in the quality of life measured in QALY. There is an average gain of 1.03 QALYs with the laser treatment strategy over non-treatment. The average gain was even higher with the clinical treatment: 2.13 QALYs. Therefore, there is a real gain in quality of life when POAG is identified and treated in the early evolutionary stages. QALY represents the one-year quality of life lived in perfect health.(7)

Quando se compara os ganhos em qualidade de vida entre as duas estratégias de tratamento, observa-se que o tratamento clínico gera em média 1,1 QALYs a mais em relação ao tratamento inicial com laser ao final da expectativa de vida média da população brasileira.

Clinical treatment is considered the reference alternative for the treatment of POAG, and was the most cost-effective because it was both cheaper and more effective than all the alternatives tested in the model. When the strategies evaluated have higher cost and lower effectiveness, there is no numerical result for the incremental cost-utility ratio. It is only said that the alternative analyzed was dominated. Both non-treatment of POAG and laser treatment were dominated by the reference treatment, which consists of starting with eye drops in the following order: prostaglandins, timolol maleate 0.5%, and dorzolamide hydrochloride 2%. These results can serve as the basis for establishing guidelines for SUS Reference Centers.

The results show acceptable robustness since most of the uncertainty of the model consists on the age of entry. The prevalence and incidence of POAG begins to increase in the general population after 40 years, the age chosen for entry into the model. The results were tested for different entry ages (30, 50, 60 and 70), and no significant changes were observed in the results. Laser tends to improve its cost-effectiveness in younger patients because it allows patients to spend some time with fewer eye drops of chronic use. From the age of 60 onwards (entry in the model), the strategy of “non-treatment of glaucoma” becomes a non-dominated alternative, but less cost-effective than the clinical treatment, without considering the possibility of ethical conflict of diagnosing a treatable disease and deciding not to treat.

Some limitations should be considered when analyzing the present results. The present study used a hypothetical population model, and had the scarce literature on the subject as data source. The model did not stratify patients according to risk factors for progression, such as race, thickness and biomechanics of the cornea, family history of blindness, perfusion pressure, etc. Like any model-based study, the results are influenced by the availability of data in the literature and the adoption of assumptions.

The possibility of resorting to anti-glaucomatous surgery in the event of failure of whatever initial treatment was not considered. Another fact that was not taken into account was adherence and persistence to treatment with eye drops. This can lead to an increase in the rate of progression of the disease, affecting the probabilities of higher transitions. The low adherence could be a source of cost error, because using less medication the bottle would last longer and the patient would buy fewer bottles. In the present study, this fact was not relevant since the cost perspective was that of SUS funding, so it did not matter if the patient used the medication or not, he would get a new bottle every 3 months. If the perspective of costs was that of


Figure 1: Sensitivity analysis by the Tornado Diagram


238


the Supplementary or Private Health, the cost variations would happen among the regions of the Country limiting the study to the region of data collection.

The transition probabilities between health states of the models were obtained in the literature and come from multicenter clinical trials. It is known that in this type of study the results are often not the same as those obtained in daily clinical practice. Study patients are closely controled and monitored, which minimizes leakage and improves adherence and persistence. On the other hand, there are no real-life population studies showing the progression rate and outcomes of the natural history of glaucoma (treated versus untreated).

Finally, it is very important to be careful in generalizing the results of this study to patients with other types of glaucoma and those being treated in the supplementary health system or outside the reference centers of SUS for glaucoma treatment. As the non-medical costs were extracted in a survey in the city of Juiz de Fora - MG, generalization to other parts of Brazil may be limited.

This hypothetical cohort study demonstrates that the strategy of initiating treatment of initial POAG with medications was cost-effective when considering the total costs (medical and non-medical, direct and indirect) over a life expectancy horizon of the Brazilian population. The initial treatment alternative with the use of selective laser trabeculoplasty was not cost-effective. Both strategies showed important and significant gains in quality of life when compared to the strategy of not treating POAG.

RefeRences

1. Resnikoff S, Pararajasegaram R. Blindness prevention programmes: past, present, and future. Bull World Health Organ. 2001;79(3):222–6.

2. Rein DB, Zhang P, Wirth KE, Lee PP, Hoerger TJ, McCall N, et al. The economic burden of major adult visual disorders in the United States. Arch Ophthalmol. 2006;124(12):1754–60.

3. Sakata K, Sakata LM, Sakata VM, Santini C, Hopker LM, Bernardes R, et al. Prevalence of glaucoma in a South brazilian population: projeto Glaucoma. Invest Ophthalmol Vis Sci. 2007;48(11):4974–9.

4. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262–7.

5. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363(9422):1711–20.

6. Guedes RA. Quality of life and glaucoma. Rev Bras Oftalmol. 2015;74(3):131–2.

7. Guedes RA, Guedes VM, Chaoubah A. Cost-effectiveness in glaucoma. Concepts, results and current perspective. Rev Bras Oftalmol. 2016;75(4):336–41.

8. Guedes RA, Guedes VM, Gomes CE, Chaoubah A. Maximizing cost-effectiveness by adjusting treatment strategy according to glaucoma severity. Medicine (Baltimore). 2016;95(52):e5745.

9. Philippe Nordmann J, Lafuma A, Berdeaux G. Modelling the lifetime economic consequences of glaucoma in France. J Med Econ. 2009;12(1):9–16.

10. Guedes RA, V.M. Growing costs in glaucoma: update and its impact in public health. Rev Atenção Prim Saúde. 2008;11(4):444-50.

11. Lee PP, Kelly SP, Mills RP, Traverso CE, Walt JG, Doyle JJ, et al.; Costs of Glaucoma Study Group. Glaucoma in the United States and europe: predicting costs and surgical rates based upon stage of disease. J Glaucoma. 2007;16(5):471–8.

12. Lee PP, Levin LA, Walt JG, Chiang T, Katz LM, Dolgitser M, et al. Cost of patients with primary open-angle glaucoma: a retrospective study of commercial insurance claims data. Ophthalmology. 2007;114(7):1241–7.

13. Lee PP, Walt JG, Doyle JJ, Kotak SV, Evans SJ, Budenz DL, et al. A multicenter, retrospective pilot study of resource use and costs associated with severity of disease in glaucoma. Arch Ophthalmol. 2006;124(1):12–9.

14. Traverso CE, Walt JG, Kelly SP, Hommer AH, Bron AM, Denis P, et al. Direct costs of glaucoma and severity of the disease: a multinational long term study of resource utilisation in Europe. Br J Ophthalmol. 2005;89(10):1245–9.

15. Guedes RA, Guedes VM, Gomes CE, Chaoubah A, Cost-utility of primary open-angle glaucoma in Brazil. Rev Bras Oftalmol. 2016;75(1):7–13.

16. Schehlein EM, Im LT, Robin AL, Onukwugha E, Saeedi OJ. Nonmedical out-of-pocket patient and companion expenditures associated with glaucoma care. J Glaucoma. 2017;26(4):343–8.

17. Paletta Guedes RA, Paletta Guedes VM, Freitas SM, Chaoubah A. Utility values for glaucoma in Brazil and their correlation with visual function. Clin Ophthalmol. 2014;8:529–35.

18. Cantor LB, Katz LJ, Cheng JW, Chen E, Tong KB, Peabody JW. Economic evaluation of medication, laser trabeculoplasty and filtering surgeries in treating patients with glaucoma in the US. Curr Med Res Opin. 2008;24(10):2905–18.

Corresponding author: Sirley Maria de Freitas Rua Oscar Vidal, n 79, Centro, Juiz de Fora – MG, Brasil, ZIP Code: 36010-060. E-mail: [email protected]

Freitas SM, Guedes RAP, Gravina DM, Guedes VMP, Gomes CEM, Chaoubah A


239original articlE


Methodology of teaching anatomy of the ocular globe

Metodologia de ensino de anatomia do globo ocular

1 Academic Course in Medicine, Centro Universitário Metropolitano da Amazônia, Belém, PA, Brazil 2 Centro Universitário Metropolitano da Amazônia, Belém, PA, Brazil.

AbstrAct

Objective: The objective of the present study was to develop a methodology that approximates the student of the content addressed in the classes of anatomy of the eyeball. Methods: A circular incision was made in the orbital blade of the frontal bone of a human cadaver of a health institution and, to access the orbital structures, the area structures were dissected creating a pathway for the injection of a solution of white silicone rubber between the lens and the retina with subsequent enucleation and final dissection. Results: The use of the technique allowed the students of the course to construct the tactile knowledge of the organ in question and transform the theoretical knowledge into practice, recognizing muscles, functionality, blood vessels and ocular structures during the dissection procedure. Conclusion: The methodology used in the present study is a viable option for teaching the anatomy of the eye.

Keywords: Ophthalmology; Health, education; Medicine; Dissection; Cadaver; Eye; Vision, ocular; Motor Skills; Teaching; Methodology.

Ana Paula Amador Pinheiro Cardoso1 https://orcid.org/0000-0002-5840-314X Hicaro Donato Granhen1 https://orcid.org/0000-0002-5412-1129 Gabriel Felipe Lyra Silva1 https://orcid.org/0000-0001-5964-524X Rafael de Azevedo Silva1 https://orcid.org/0000-0002-1691-8778 Franklin Coelho Nascimento2 https://orcid.org/0000-0003-4005-8250

Resumo

Objetivo: O objetivo do presente estudo foi desenvolver uma metodologia que aproxime o discente do conteúdo abordado nas aulas de anatomia do globo ocular. Métodos: Foi realizada uma incisão circular na lâmina orbital do osso frontal de um cadáver humano de uma instituição em saúde e, para acessar as estruturas orbitárias, foram dissecadas as estruturas da área criando uma via para a injeção de uma solução de borracha de silicone branca entre o cristalino e a retina com posterior enucleação e dissecação final. Resultados: O emprego da técnica permitiu que os discentes do curso construíssem o conhecimento tátil do órgão em questão e transformando o saber teórico em prático, reconhecendo músculos, funcionalidade, vasos sanguíneos e estruturas oculares durante o procedimento de dissecação. Conclusão: A metodologia empregada no presente estudo é uma opção viável para o ensino da anatomia do olho.

Descritores: Oftalmologia; Educação Médica; Medicina; Dissecação; Cadáver; Olho; Visão Ocular; Destreza motora; Ensino; Metodologia

Study carried out at Centro Universitário Metropolitano da Amazônia, Belém, PA, Brazil



240

IntRoductIon

The act of observing, the discovery of variations, the manual training of surgical instruments, and the comparison between normal and abnormal give anatomical dissection a teaching

of unique potentialities with learning benefits (tactile sensation of the organs and real topographic anatomy as it is a human body) when compared to any other teaching methodology, be it artificial industrial models, slides in the classroom, or study in bibliographical literature.(1-3)

The visual apparatus has part of its structures contained in cavities difficult to access for study during an anatomical dissection.(4) The eye bulb is within a bone cavity - the orbit - comprising parts of the maxillary, sphenoid, ethmoid, frontal, zygomatic, lacrimal and palatine bones. It is associated with certain accessory structures, that is, muscles, fascia, eyebrow, eyelids, conjunctiva and lacrimal apparatus.(4)

In a possible corpse study, the orbital cavity can be achieved through the neurocranium, viscerocranium, or by combined accesses, which require specific devices and have risks of injuring an area at the time of the procedure, making it improper for the study.(4)

It is common for many researchers and educational institutions to neglect the dissection of the ocular globe and its structures in human cadavers or animal parts caused by the dehydration that formaldehyde (the substance used to preserve these parts) generates in the vitreous humor and aqueous humor, and therefore dehydration of the ocular globe itself, becoming extremely friable for thorough dissection.(5)

Therefore, the objective of the present study is to report the development of a technique that proposes the filling of the ocular globe, facilitating the visualization of adjacent structures and the study of Anatomy.

methods

Access to the orbital structures was initiated with a circular incision with an oscillating electric saw with semicircular blade in the orbital blade of the frontal bone in a cadaver that has already undergone the craniotomy process to study encephalic structures (Figure 1).

With the aid of a magnifying glass, luminous focus and

surgical instruments such as scissors and anatomical tweezers, the area was dissected in order to expose the structures of the ocular globe and extrinsic muscles, and create access for the injection of silicone rubber.

After this step, a cut was performed between the crystalline and the retina, giving access to the area where the vitreous humor would be, cannulating it with a scalpel 20, and finally injecting a solution of white silicone rubber (Figure 2).

Six hours after injecting the content, the enucleation of the ocular globe and adjacent structures was performed for the final dissection and teaching of the anatomy in classes during the course (Figure 3 and 4).

Results And dIscussIon

During the Medicine graduation, the course proposes several methodologies for teaching the anatomy, physiology and content of various specialties required for the training of efficient general practitioners in their clinical or surgical routine.

One of these areas is Ophthalmology, which studies anatomy, pathologies, and other contexts that can affect the human sight. However, this specialty is often neglected by students during graduation for reasons such as difficulty in learning anatomy, deficit of practical study, and the lack of a methodology that can bring the student closer to the subject addressed.(6)

In this sense, dissection becomes an option to soften this problem. During the procedures carried out in the ocular globe, students need to diligently study the anatomy of the eye and its muscle groups in order to reduce the risk of injuring an area during dissection, learning and understanding the need of this content for medical training, and exposing the extrinsic musculature of the eye, the frontal nerve, the optic nerve, and the ophthalmic artery.

Several studies point to the need to narrow visual knowledge (lessons and readings) with the practical tactile activity of touching and feeling the texture of the organ studied, and to achieve this goal, synthetic industrial plastic simulators are built with maximum reliability. However, these devices can not generate that

Cardoso APAP, Granhen HD, Silva GFL, Silva RA, Nascimento FC


Figure 2: Injection of liquid silicone rubber between the crystalline and the retina.

Figure 1: Exposure of the orbital structures after the circular incision procedure in the frontal bone.


241Methodology of teaching anatomy of the ocular globe

conclusIon

The methodology employed for the dissection of the cadaver’s ocular globe is, in the view of the authors who performed the procedure, an efficient alternative for teaching the anatomy of the eye, being a low cost option making it possible to study Anatomy with the participation of the students. In order to do so, other educational institutions having a human cadaver for studies should be encouraged to use techniques to prepare the ocular globe for more practical eye anatomy classes during medical graduation.

RefeRences

1. Marques P, Cristina S. A dissecação como ferramenta pedagógica no ensino da Anatomia em Portugal. Interface (Botucatu). 2014;18(48):165-76.

2. Lobo L. Educação médica nos tempos modernos. Rev Bras Educ. Med. 2015;39(2):328-32.

3. Belarmino L, Martins F, Franco M. Aspirações Médicas: Análise dos Alunos do Internato das Instituições de Ensino Superior do Estado do Pará. Rev Bras Educ Méd. 2016;40(4):685-93.

4. Sampedro A, Barbón J. El globo ocular y anexos en la “Anatomía completa del hombre” de Martín Martínez (s. XVIII). Arch Soc Esp Oftalmol. 2010; 85(8):282-4.

5. Castro M. El aula de Anatomía y el laboratorio de disección: Una aproximación etnográfica al estudio de la anatomía humana. Cuad Antropol Soc. 2016;43:129-42.

6. Sousa I, Silva C, Caldas C. Especialidade médica: escolhas e influências. Rev Bras Educ Med. 2014;38(1):79-86.

7. Silva R, Luz M, Granhen H, Mendonça E, Luz M, Nascimento F. Modelo experimental para estudo de anatomia humana em cadáveres. PRMJ. 2018;1(2): e13

8. Damasceno E, Damasceno P, Costa A. Ensino de oftalmologia na graduação médica: Estudo comparativo de aprendizado na oftalmoscopia direta com oftalmoscópio convencional e de campo amplo (Panoptic). Rev Bras Oftalmol. 2009; 68(4):231-6.

9. Kara A, Passos L, Kara F, Kara N. Ensino extracurricular em Oftalmologia: grupos de estudos / ligas de alunos de graduação. Rev Bras Educ Med. 2007 ;31(2):166-72.

10. Androwiki J, Scravoni I, Ricci L, Fagundes D, Ferraz C. Evaluation of a simulation tool in ophthalmology: application in teaching funduscopy. Arq Bras Oftalmol. 2015; 78(1):36-9.


real tactile sensation of a real human organ, bringing the need of practical dissection classes with the human corpse.(4,7)

Upon understanding the importance of these practical classes, some studies show that medical schools neglect the ocular area during the preparation of a human corpse for study material of students and professors, preferring to expose areas such as mediastinum, abdominal cavity, limb muscle groups, and encephalic region.(6-10) The eyes, if not properly prepared concomitantly with these other areas, end up losing its vitreous humor content, disturbing the later study of this organ.(10)

Thus, the procedure performed by the present study is beneficial according to the authors when demonstrating the anatomy of the eye from a preparation and injection of a solution of white silicone rubber, expanding the ocular globe in place of the vitreous humor, besides contributing to the study of the students about the anatomy of the area, and being a methodology with low cost when compared to the purchase of industrial parts of a human body (Figure 3 and 4).

Figure 4: Lateral view of the enucleated and dissected ocular globe evidencing the muscles.

Figure 3: Frontal view of the enucleated and dissected ocular globe.

Corresponding author: Rafael de Azevedo Silva Av. Visconde de Souza Franco, 72 - Reduto - Belém - Brazil E-mail: [email protected]


242original articlE

Resumo

Objetivo: O objetivo do estudo é analisar a acuidade visual média para cores de estudantes da área de saúde e discutir o impacto das doenças que a afetam nessa população. Deficiências cromáticas interferem de forma significativa no dia a dia de profissionais da área da saúde que necessitam de discernir diferentes matizes em diversas situações de sua prática profissional. Métodos: Participaram da pesquisa 64 voluntários, estudantes de cursos da área de saúde da Universidade Federal de Alfenas, sendo que 1 homem foi excluído por não se adequar aos critérios de inclusão. Dois grupos foram analisados, de acordo com o sexo, com o teste de Farnsworth Munsell 100-Hue. Resultados: Não houve diferenças significativas entre os olhos e entre os grupos analisados. O padrão de visão de cores encontra-se entre 35 e 40, de acordo com a Pontuação do Erro Total. A questão de gênero não influencia no padrão geral da qualidade de visão de cores de estudantes da área de saúde, quando retirados aqueles que apresentam distúrbios da visão cromática. Conclusão: Devem ser realizadas triagens e orientação para estudantes de cursos da área de saúde para que, cientes da sua condição de apresentar algum tipo de distúrbio cromático, possam tomar a decisão adequada sobre qual carreira seguir para que tal limitação não interfira na qualidade de sua vida diária.

Descritores: Visão de cores; Defeitos da visão cromática; Percepção de cores; Testes de percepção de cores

AbstrAct

Objective: The goal of the study is to analyze the color vision acuity pattern in undergraduates of health courses and to discuss the impact of these diseases in this population. Color deficiencies interfere significantly in the daily routine of professionals in the health area who need to discern different color hues in several situations of their everyday practice. Methods: Sixty-four volunteers, undergraduates of health courses of the Federal University of Alfenas (UNIFAL-MG), participated in the study. One man was excluded because he did not fit the inclusion criteria. Two groups were analyzed according to sex with the Farnsworth Munsell 100-Hue test. Results: There were no significant differences between the eyes and between the groups analyzed. The color vision acuity pattern is between 35 and 40, according to the Total Error Score. The gender issue does not influence the general pattern of the color vision acuity of the health courses undergraduates when those with color vision disorders are removed. Conclusion: Screenings and guidance should be given to undergraduates of health courses so that, aware of their condition of presenting some type of color disorder, they shall make the appropriate decision on which career to follow so that such limitation does not interfere with the quality of their daily life.

Keywords: Color vision; Color vision defects; Color perception; Color perception tests

Pedro Henrique Oliveira Oliveira Ribeiro1 https://orcid.org/0000-0002-9271-5083.Geraldo José Medeiros Fernandes2 https://orcid.org/0000-0002-7633-3026.Flávia Beatriz de Andrade Oliveira Ribeiro3 https://orcid.org/0000-0001-6921-1218.

1 Medicine School, Universidade Federal de Alfenas, Alfenas, MG, Brazil. 2 Department of Anatomy, Universidade José do Rosário Vellano, Alfenas, MG, Brazil. 3 Department of Ophthalmolgy, Universidade Federal de Alfenas, Alfenas, MG, Brazil.

Evaluation of the color vision acuity pattern of undergraduates of health

courses in a Brazilian university

The authors declare no conflicts of interests.Received for publication 13/11/2018 - Accepted for publication 07/06/2019

Avaliação do padrão de acuidade visual para cores de acadêmicos da área de saúde em Universidade brasileira

This study was performed at the Federal University of Alfenas (UNIFAL-MG).



243

IntRoductIon

Health professionals shall have a precise color vision for adequate evaluation and selection of clinical, laboratory and imaging exams in their routine. Therefore, those who

present some type of color deficiency have difficulties in the diary exercising of their profession.

One of the few studies in the scope, shows severe difficulties for physicians to adequately measure skin color in relation to pallor, cyanosis, erythema, cutaneous rashes and jaundice, and difficulty in performing ophthalmoscopy and otoscopy, exemplifying only a few practical and vital situations whose impact from low color visual acuity hinders the professional exercise of those affected.

The largest cohort one on the subject, performed in the United Kingdom, evaluated the impact of congenital color deficiencies on the occupational trajectory of about 430 subjects after screening about 12,000 people using the Ishihara test. Some professional areas were considered as highly dependent on color vision, such as the Armed Forces, Medicine, Pharmacy, Civil Aviation, Electrical Engineering, among others, in order to evaluate the presence of people with color deficiencies among them. The study showed that there is no professional orientation to assist such persons in the occupational choice, so that there is no great difference between the jobs occupied by color-blind and non-color-blind people, even in cases where a precise color vision is relevant.

In Iran, a study involving professionals from a large hospital in the capital, Tehran, showed that 2.4% of the staff had color vision deficiencies, a condition that interfered directly in the performance of their duties. Therefore, it was proposed to screen for such a problem, which is neglected, but directly impacts on the quality of services performed by them. Papers even advocate screening for medical students before graduation, in order to guide them about the difficulties faced in the course related to the constant need of using color vision, a fact endorsed by the literature reviewed who concluded that early screening helps the student to deal with the difficulties of his pathological condition in relation to his profession. Quality of life questionnaires were developed for patients suffering from color vision deficiency in order to assess and verify the impact of this condition on their quality of daily life.

Therefore, studies that define color vision normality patterns in different populations are important, as well as the measurement of the color vision acuity, due to its high impact on the lives of those affected. For this, several tests are used, such as the Ishihara test and the Farnworth Munsell 100-Hue test (FM 100-Hue), both performed in the present study. The literature indicates a relationship between the results of the FM 100-HUE test and the nonverbal IQ of the evaluated ones, observing that those with higher IQ scores present better results in relation to the lower IQ groups, both in children and adults. Several studies using FM 100-Hue are performed in specific populations, such as systemic lupus erythematosus patients, young smokers and Bantu people.

In Brazil, studies with FM 100-Hue were performed in groups of workers affected by mercury, alcoholics, type II diabetes, Leber’s optic neuropathy, and with individuals with congenital color deficiencies. But no papers were found involving the university population of health courses in Brazil, being it the focus of the present study.

In Turkey, a paper dealing with researches done in medical students was performed, evaluating the color vision acuity, using the Ishihara test and the FM 100-Hue. This similar study evaluated the color vision acuity of undergraduates of health courses, showing the importance of carrying out the same screening research on subjects in Brazil. The study evaluated the ocular dominance for color vision and its acuity, being the only one in the literature found with similar population selected. The present article evaluates the color vision acuity pattern through Ishihara and FM 100-Hue tests in undergraduates of health courses, with the intention of becoming a reference for further studies and screenings involving the same tests in other universities.

methods

The volunteers were submitted to the following tests: 15-plate Ishihara and Farnsworth Munsell 100-Hue in the N614 room of the Federal University of Alfenas (UNIFAL-MG), under the same lighting conditions. The undergraduates performed the tests on both eyes, first occluding the left one with a buffer and, after performing the test on the right eye, the same test was carried out on the left one, with the right eye being occluded. For the screening of normal subjects, the 15-plate Ishihara test was used: if the threshold of normality (more than 10 correct hits) was reached, the Farnsworth Munsell 100-Hue test was then used to measure the normality pattern of F group and M groups. Because of such a triage, one male volunteer did not reach the normal screening standard and, as being found to have color blindness, was dispensed and referred for specialized ophthalmologic treatment in a secondary outpatient clinic.

The results of the Ishihara and Farnsworth Munsell 100-Hue tests with 64 volunteer undergraduates from the Federal University of Alfenas (UNIFAL-MG) of health courses (medical, nursing and physiotherapy) were analyzed, being all subjects divided into a 28 men group (M group) and a 38 women group (F group), respecting the epidemiological differences in the prevalence of color deficiency on both genders, after the participants have signed the informed consent form and approval of the Research Ethics Committee of the university.

The results were analyzed using the Farnsworth Munsell 100-Hue test software, by the Total Error Score tool or TES, which evaluates the participants according to the color vision acuity as scoring possible errors in the correct sequence of color arrangement in the test. The lower the TES, the greater the color visual acuity. The volunteer with TES under 20 has the color vision acuity above the population’s mean in the analyzed eye; between 20 and 100, the color vision acuity equal to the population’s mean; and above 100, a low color vision acuity in relation to the population’s mean analyzed in the test. We also analyzed the mean of the color vision acuity for all participants in each group for both eyes.

Analysis of Variance (ANOVA) and Tukey’s test were used for comparison between male and female groups and for comparison between right and left eyes within the same group, considering a significance level of 5%.

Results

The F group, with 36 volunteers, corresponds to 56.25% of the study participants, while the M group, with 28 volunteers, 43.75% of those that were analyzed. One participant in M group


Evaluation of the color vision acuity pattern of undergraduates of health courses in a Brazilian university


244

was not included because he did not reach the minimum inclusion criterion after 15-plate Ishihara test screening.

In the M group, 7 participants with the color vision acuity higher than average (TES < 20), 18 with the color vision acuity within the mean recommended for the test (20 < TES < 100) and 2 with the color vision acuity less than average (TES > 100) were found concerning the right eye. For the left one, there were 9 participants with the color vision acuity above average, 16 with the color vision acuity within the mean and 2 with the color vision acuity below it.

In the F group, 11 participants with the color vision acuity higher than average (TES < 20), 23 with the color vision acuity within the mean recommended for the test (20 < TES < 100) and 2 with the color vision acuity less than average (TES > 100) were found concerning the right eye. For the left one, there were 14 participants with the color vision acuity above average, 20 with the color vision acuity within the mean and 2 with the color vision acuity below it.

The parameter analyzed and used to stablish the pattern proposed in the present study was the Total Error Score (TES), which is the basic parameter taken by the Farnsworth Munsell 100-Hue test for it evaluates the number of changes and distortions in the correct color sequences of the test. It was observed that there were no statistically significant differences between M and F groups, on the right and left eyes. An important finding was that, for the right eye, the M group had an average of 37.7, while the F group had a mean of 39.3; therefore, its mean color vision acuity pattern was higher than that of the M group. This fact, however, from the statistical point of view, is not significant using p = 0.05. The standard error for the right eye was 6.22.

For the left eye, the M group showed a mean of 38.0, while the F group had an average of 35.2, reversing what was found above. The mean visual acuity pattern was higher in the F group than that in the M group, but not statistically significant at p = 0.05. The standard error for analysis of the left eye was 5.96.

Finally, the comparative analysis between right and left eyes for M and F groups was performed. We found, on average, a higher color vision acuity on the left eye in both groups, without statistical significance. In the M group, the left eye pattern was 37.9, while the right one pattern was 39.1. In turn, the pattern for the F group was 35.2 on the left eye and 39.3 on the right eye. The standard error for the analyzes was, respectively, 7.01 and 5.54.

dIscussIon

The results of the test make it possible to conclude that, on average, students presented between 35 and 40 points in TES, a number that is within the average of the general population. This implies that the majority of volunteers, regardless of gender, did not display any type of color deficiency or visual acuity below the pattern that would hampers their daily occupational activities.

It is also important to emphasize that there was no discrepancy in the color vision acuity between the groups included in the study. Therefore, the hypothesis that sex does not influence the color vision pattern is confirmed when patients with some type of color deficiency are removed from the evaluation. Another finding was a slight dominance of the left eye in relation to the right for color visual acuity, which corroborates the data of a study with 50 Turkish medical students.

Another point to be discussed is the screening performed for inclusion in the study, through the 15-plate Ishihara Test.

Concerning the participants, 1.5% were excluded due to the positivity for a color vision deficiency, a number close to that found in a study which was 2.4%. The literature shows prevalence variations between 6% and 10% in general society. Therefore, in our sample, lower levels of prevalence were found in relation to the general population. This can be explained by the difficulty made explicit by studies for such people to deal with different needs of using color discrimination in their profession, thus choosing another type of area where it is not necessary routinely. A scientist physician reports his difficulties, as colorblind, to enter into the medical profession and into the student routine.

The creation of a Brazilian pattern for the color vision acuity in undergraduates /of health courses also makes it possible to carry out more detailed screening and studies on the subject, including for the guidance of students and professionals who present some kind of color deficiency, as defended by some authors. Some authors report that there is no support for people who are diagnosed with such disorder and who are enrolled in medicine, something that can be solved through screenings and further studies, both with trained professionals and with academics, as an example of lack of orientation of undergraduates about color deficiencies. In a Brazilian study, 13 students from the Federal University of São Carlos interviewed, from courses in the area of exact, human and health sciences, addressing the difficulties undergone by them in graduation, such as questions and prejudices of colleagues and problems with teaching materials and diagnoses, corroborating the importance of studying a pattern to evaluate the interference of such deficiencies in the lives of academics and to increase the interest and diffusion of studies in the area, as well as increasing the occupational orientation for people who have difficulties in certain tasks due to such disorders. A review advocates that “screening” should be adopted in order to guide potential carriers of these disorders for their professional career, reinforcing the importance of screening for the future of such individuals.

conclusIons

After completing the study that determines the color vision acuity pattern for undergraduates of health courses in Brazil, using the Farnsworth Munsell 100-Hue test, we could conclude that the average points in TES parameter (Total Error Score) was between 35 and 40, for both eyes and genders, when individuals with color deficiency are excluded. Based on this, we try to encourage studies about the importance of the color vision acuity in the occupational field, more specifically in health sciences, highly affected by such disorders.

The study, in agreement with the literature, suggests the screening of health professionals prior to or shortly after entering college, in order to clarify this population about the color vision deficiency and the difficulties they will face during their studies and in the profession. They should not be discouraged to work in this area, but rather be oriented so that they can face such difficulty with more discernment and information about the subject.

The present study was carried out with solid methodology and on a theme not previously explored deeply in Brazilian literature, which demonstrates its importance. The main deficiency of the study may be related to the number of participants, a fact, however, that does not invalidate it.


Ribeiro PHO, Fernanades GJM, Ribeiro FBAO


245Evaluation of the color vision acuity pattern of undergraduates of health courses in a Brazilian university

Corresponding author: Pedro Henrique Oliveira Ribeiro Juscelino Barbosa Street, 885,Alfenas-MG. Phone: (35) 99939-6622. E-mail: [email protected]

RefeRences

1. Spalding JAB. Colour vision deficiency in the medical profession. Br J Gen Pract. 1999;49(443):469-75.

2. Cumberland P, Rahi JS, Peckham CS. Impact of congenital colour vision deficiency on education and unintentional injuries: findings from the 1958 British birth cohort. BMJ. 2004;329(7474):1074–5.

3. Dargahi H, Einollahi N, Dashti N. Color blindness defect and medical laboratory technologists: unnoticed problems and the care for screening. Acta Med Iran. 2010;48(3):172–7.

4. Spalding JA, Cole BL, Mir FA. Advice for medical students and practitioners with colour vision deficiency: a website resource. Clin Exp Optom. 2010;93(1):39–41.

5. Goh SS, ChanVX, Tan NC. Colour vision deficiency: is it a handicap? A narrative review of its impact on medical & dental education and practice. Proc Singapore Healthcare. 2014; 23(2):149-7.

6. Barry JA, Mollan S, Burdon MA, Jenkins M, Denniston AK. Development and validation of a questionnaire assessing the quality of life impact of Colour Blindness (CBQoL). BMC Opthalmol. 2017; 179(17):179.

7. Cranwell MB, Pearce B, Loveridge C, Hurlbert AC. Performance on the Farnsworth-Munsell 100-hue test is significantly related to nonverbal IQ. Invest Ophthalmol Vis Sci. 2015;56(5):3171–8.

8. Piñero DP, Monllor B, Camps VJ, de Fez D. Multichannel perimetric alterations in systemic lupus erythematosus treated with hydroxychloroquine. J Optom. 2017;10(2):135–8.

9. Arda H, Mirza GE, Polat OA, Karakucuk S, Oner A, Gumus K. Effects of chronic smoking on color vision in young subjects. Int J Ophthalmol. 2015;8(1):77–80.

10. Kaimbo Wa, Kaimbo D, Spileers W, Missotten L. [The Farnsworth-Munsell 100 Hue test in the Bantu population. Preliminary results]. J Fr Ophtalmol. 1994;17(11):664–7. French.

11. Ventura DF, Simões AL, Tomaz S, Costa MF, Lago M, Costa MT, et al. Colour vision and contrast sensitivity losses of mercury intoxicated industry workers in Brazil. Environ Toxicol Pharmacol. 2005;19(3):523–9.

12. Brasil A, Castro AJ, Martins IC, Lacerda EM, Souza GS, Herculano AM, et al. Colour Vision Impairment in Young Alcohol Consumers. PLoS One. 2015;10(10):e0140169.

13. Andrade LC, Souza GS, Lacerda EM, Nazima MT, Rodrigues AR, Otero LM, et al. Influence of retinopathy on the achromatic and chromatic vision of patients with type 2 diabetes. BMC Ophthalmol. 2014;14(104):104.

14. Quiros PA, Torres RJ, Salomao S, Berezovsky A, Carelli V, Sherman J, et al. Colour vision defects in asymptomatic carriers of the Leber’s hereditary optic neuropathy (LHON) mtDNA 11778 mutation from a large Brazilian LHON pedigree: a case-control study. Br J Ophthalmol. 2066;90(2):150-3.

15. Koçtekin B, Gündoⅹan NÜ, Altıntaⅹ AG, Yazıcı AC. Relation of eye dominancy with color vision discrimination performance ability in normal subjects. Int J Ophthalmol. 2013;6(5):733–8.

16. Spalding JA. Confessions of a colour blind physician. Clin Exp Optom. 2004;87(4-5 Suppl 5):344–9.

17. Melo DG, Galon JEV, Fontanella BJB. Os ´´daltônicos´´ e suas dificuldades: condição negligenciada no Brasil? Physis: Rev Saúde Coletiva. 2014; 24(4):1229-53.

18. Ramachandran N, Wilson GA, Wilson N. Is screening for congenital colour vision deficiency in school students worthwhile? A review. Clin Exp Optom. 2014;97(6):499–506.



246original articlE


Influence of visual symptoms in school performance of adolescents

Influência dos sintomas visuais no desempenho escolar de adolescentes

1 Academic Course in Medicine, Centro Universitário do Pará, Belém, PA, Brazil. 2 Academic Course in Medicine, Universidade do Estado do Pará, Belém, PA, Brazil. 3 Department of Public Health, Universidade do Estado do Pará, Belém, PA, Brazil.

AbstrAct

Purpose: To investigate if there was an association between visual symptoms and academic performance. A secondary objective was to estimate the prevalence of visual symptoms among students in a public school. Methods: A cross-sectional and quantitative study was made with 100 students, attending the sixth or seventh grades in a public school participated in this study. The evaluation of visual symptoms was done through the Visual Efficiency Inventory (IEV), translated and validated version of the College of Optometrists in Vision Development Quality of Life (COVD-QOL) questionnaire. The academic performance was evaluated through the application of a test containing 10 questions, equally divided between the disciplines of portuguese and mathematics. The results were analyzed by means of descriptive statistics, Spearman’s coefficient and the Student’s t-test for p<0.05. Results: Of the 100 students, 52% were male. The prevalence of visual symptoms founded was 72%, with the highest scores in the IEV obtained by the girls. It was not observed a significant relationship between visual symptoms and academic performance. Conclusion: A high prevalence of visual symptoms was observed among students, but there was no significant relationship between visual symptoms and academic performance.

Keywords: Symptom assessment; Academic performance; Surveys and questionnaires; Student health; Vision disorders

Camila Pantoja Azevedo1 https://orcid.org/0000-0002-9275-1439Lucas Emannuel dos Santos Bordallo2 https://orcid.org/0000-0002-8508-1879Lucas Motta Gadelha Silva2 https://orcid.org/0000-0003-3283-0589Monaliza dos Santos Pessoa3 https://orcid.org/0000-0002-4163-8081

Resumo

Objetivo: Avaliar a relação entre sintomas visuais e rendimento escolar, identificando, também, a prevalência de sintomas visuais em escolares matriculados em uma escola pública. Métodos: Estudo quantitativo e transversal, no qual foram avaliados 100 estudantes matriculados no sexto ou sétimo ano do ensino fundamental II da EEEFM Jarbas Passarinho. A avaliação de sintomas visuais se deu por meio do Inventário de Eficiência Visual (IEV), versão traduzida e validada do questionário College of Optometrists in Vision Development Quality of Life (COVD-QOL). O rendimento escolar foi avaliado por meio da aplicação de uma prova contendo 10 questões, divididas igualmente entre as disciplinas de português e matemática. Utilizou-se o coeficiente de correlação de postos de Spearman para analisar a relação entre desempenho acadêmico e sintomas visuais, e o teste t-student para avaliar diferenças entre as variáveis. Resultados: Dos 100 participantes, 52% eram do sexo masculino. A prevalência de sintomas visuais encontrada foi de 72%, com as maiores pontuações no IEV obtidas pelas meninas. Não houve relação significante entre os sintomas visuais e o desempenho escolar. Conclusão: O presente estudo encontrou uma prevalência de sintomas visuais elevada entre os estudantes participantes da pesquisa, porém, não houve uma relação estatisticamente significante entre os sintomas visuais e o desempenho escolar.

Descritores: Avaliação de sintomas; Desempenho acadêmico; Inquéritos e questionários; Saúde do estudante; Transtornos da visão

Institution: Universidade do Estado do Pará



247

IntRoductIon

Sight is one of the most important sources of communication between the brain and the external environment, so that in childhood visual deficits can be detrimental to development

and learning.(1) Said deficits, especially when undiagnosed and followed, may be responsible for alterrations in quality and performance in several areas of a person’s life.(1-3)

Therefore, instruments for an early identification of those individuals who are more likely to present some visual alteration are required, and the College of Optometrists in Vision Development Quality of Life (COVD-QOL) questionnaire will be emphasized in this paper.

COVD-QOL comprises 30 questions related to visual symptoms and its influence on several aspects of personal and social development.(4) The questionnaire in its reduced version comprising 19 questions is also indicated as an instrument of analysis of visual symptoms due to its greater practicality and levels of reliability similar to the questionnaire in its full version. (4-7)

Despite its simplicity and efficiency as an instrument for screening visual deficits, COVD-QOL is an instrument built in English. Thus, in view of the need for questionnaires with these characteristics in the Portuguese language, the translation and cross-cultural adaptation of the COVD-QOL was carried out and validated, and it became known as the Visual Efficiency Inventory (IEV).(8)

The present study aimed to use the IEV to analyze the prevalence of visual symptoms and their relation with school performance in a public school in the city of Belém, aiming at the early identification of students with possible ocular diseases.

methods

This is a cross-sectional, quantitative study in which data was collected with the application of the questionnaire. All participants of the present survey were studied according to the principles of the Declaration of Helsinki and the Nuremberg Code, subject to the Research Involving Human Subjects Regulations (Res. CNS 466/12) of the National Health Council, after submitting the draft to the Center for Research and Extension of Medicine and the Ethics Committee of Universidade do Estado do Pará, and after consent of the participants and their legal guardians with the Free and Informed Assent Term (TALE) and Free and Informed Consent Term (TCLE), respectively.

The research comprised students enrolled regularly in the morning or afternoon period between the sixth and seventh grade at Escola Estadual Jarbas Passarinho located in the district of Marco, in the city of Belém, Pará. It included students of both genders aged 10 to 17 years with or without prior visual problems, and who were regularly attending classes.

Data related to visual symptoms were collected using the IEV. The questionnaire was applied in a short version, using as references the questions selected in the short version of COVD-QOL. In responding to the IEV the participant indicated in each question the frequency with which they presented the symptoms in a scale of Likert, where zero represented “never”, one “rarely”, two “sometimes”, three “frequently”, and four “always”. These responses were summed to generate a score. According to what was pre-established by the questionnaire used, participants were considered as having significant visual symptoms when they obtained scores equal to or greater than 20.

Influence of visual symptoms in school performance of adolescents

Those students who for some reason refused to participate in the survey were excluded, as those who could not answer the questionnaires by themselves, and those who did not submit the TALE and/or TCLE signed, or who were not present at the time of application of the questionnaires.

For the analysis of the academic performance there was the application of a test with ten objective questions scoring a point each, being divided equally between the school subjects of Portuguese and mathematics. The questions were previously selected by the researchers with the help of the institution’s pedagogical team, and the Brazil Test (in its version used by the Ministry of Education in 2015) was used as a source for the selection of questions.

The test and the questionnaire were carried out in the classroom in the presence of the researchers in a period of 50 minutes per class. All students were able to fill the study in this period.

The data collected was stored as a spreadsheet in the programs Microsoft Excel 2016 and Microsoft Word 2016. Data analysis was performed using the softwares Graphpad Prism 5 and Microsoft Excel 2016.

We evaluated the relation between the scores obtained in the IEV and the test applied by a non-parametric method using the Spearman’s rank correlation coefficient. Differences between the variables were analyzed using the Student’s t-test. The significance level adopted was p=5%.

Results

We invited 120 students to participate in the study, of which 20 were included in the exclusion criteria, thus obtaining a participation of 100 students (83.33%). Of the participants, 49 were in the 6th grade, and 51 in the 7th grade. Regarding the distribution by gender, in the 6th grade there were 24 girls and 25 boys, and in the 7th grade there were 24 girls and 27 boys. The average age among those who attended the 6th and 7th grades was respectively 11.6 and 12.9 (Figure 1).

The prevalence of visual symptoms found among participants, according to the criteria of the questionnaire used, was 72%. There was no statistically significant difference between genders regarding school performance (p=0.53). However, the average score on the questionnaire of visual symptoms among girls was higher than that found among boys (p=0.0004 ) (Table 1).

There was no significant relation between the scores obtained in the IEV and the academic performance (r = -0.10 and p = 0.29 ) (Figure 2)

Figure 1: Distribution of students participating in the survey according to the grade and age.



248 Azevedo CP, Bordallo LES, Silva LMG, Pessoa MS


dIscussIon

The present study observed a weak relation between the visual symptoms detected by the IEV and school performance. These findings corroborate the studies carried out in Curitiba and Amazonas in which 242 and 1,050 children were evaluated, respectively.(9-10) However, there are studies showing a significant relation between the academic performance and visual deficits. Among these studies, we can emphasize those carried out in the cities of Pouso Alegre (MG), Juiz de Fora (MG), and in the Ophthalmology service of Projeto Saúde é Cidadania/Ação Comunitária in the Northeast of Rio Grande do Sul.(1,11-12) The studies concluded that low visual acuity was related to lower grades and higher rate of school failure in a statistically significant way.

It is worth mentioning that the method used to evaluate visual acuity can vary in each study, being the Snellen table the most used one.(13) The present study used the visual symptoms as a reference, which represent consequences of low visual acuity. Thus, it is possible that there are significant divergences between the results found in the present survey and those found in the current literature, which can be taken into account in order to more reliably adapt a practical and easy-to-apply method such as the IEV to the Brazilian context.

Besides, the prevalence of visual symptoms was shown to be up to ten times greater than the prevalence of visual deficits found in Brazilian studies. The prevalence of 72% found among the students studied contrasted significantly with the prevalence

Figure 2: Distribution of grades obtained by students regarding the score obtained in the Visual Efficiency Inventory.

Table 1 Average school performance and scores

obtained in the Visual Efficiency Inventory according to gender and grade

Gender Grade Mathematics Portuguese Score (Year) (Average) (Average)

Female 6º 2.51 3.12 31.00Male 6º 2.54 3.16 24.70 Female 7º 2.08 2.91 35.50Male 7º 2.92 2.77 24.74

found in other Brazilian cities, such as: Juiz de Fora (MG) 34.8%, Londrina (PR) 17.1%, Pelotas (RS) 15.1%, Sorocaba (SP) 13.1%, Manaus (AM) 7%, Passo Fundo (RS) 10.9%, Pouso Alegre (MG) 11.4%, Vitória (ES) 6%, Curitiba (PR) 7.03%, Campo Grande (MG) 14.2%, Belo Horizonte (MG) 10.3%, and Herval d’Oeste (SC) 9.43%. (1,9,12,14-22)

Facing this divergence, the authors considered two possible scenarios. The first one admits that the prevalence of 72% found reliably represents the context studied. Therefore, it is suggested that other studies are carried out with this population to confirm said result, as well as to identify the local factors influencing the visual acuity of this population, since the prevalence found is above all previous studies.

The second possible scenario admits that the method used overestimated the visual symptoms of the study population. Among the possible biases, the authors emphasize four alternatives indicated as “frequently” in almost all questionnaires filled, even when the other alternatives were marked as “never”. These alternatives are: “clumsy(a), stumbles in things”; “mismanage the time”; “loses things”; “forgetful/weak memory”. Therefore, it is suggested that further studies are carried out taking into account this possible bias, thus finding results that represent reality more accurately.

The prevalence of visual symptoms was shown to be more present in females in both groups in a statistically significant way. These data corroborates the results found in previous studies, emphasizing the higher incidence of visual impairment in females.(10,15,20,23)

Finally, it should be emphasized that the discussion about the degree of influence between visual deficits and school performance is old.(2) Of course, there are several factors to influence learning. However, even if low visual acuity is not the main factor in some cases, it certainly contributes to hinder the learning process when associated with other determinants. Thus, it is the ophthalmologist’s main role to provide the child with conditions to learn to their maximum level, through the early identification of cases of low visual acuity.(2-3)

conclusIon

The present study found a high prevalence of visual symptoms among the students participating in the research. However, there was no statistically significant relation between visual symptoms and school performance. Therefore, it is suggested that similar studies be performed later, taking into account the data obtained in the present study as well as the difficulties and possible biases reported by the authors.

RefeRences

1. Silva CM, Almeida DR, Bernardes RR, Bazzano FC, Mesquita Filho M, Magalhães CH, et al. Desempenho escolar: interferência da acuidade visual. Rev Bras Oftalmol. 2013;72(3):168-71.

2. Degrazia J, Pellin J, Degrazia DF. Detecção e prevenção das deficiências visuais na infância e sua relação com a educação. Rev AMRIGS. 2010; 54(4):466-70.

3. Shin HS, Park SC, Park CM. Relationship between accommodative and vergence dysfunctions and academic achievement for primary school children. Ophthalmic Physiol Opt. 2009; 29(6):615-24.

4. Maples WC, Hoenes R. The College of Optometrists in Vision Development checklist related to vision function: expert opinions. Optometry. 2009; 80(12):688-94.


249Influence of visual symptoms in school performance of adolescents

Rev Bras Oftalmol. 2019; 78 (4):246-9

16. Gianini RJ, Masi E, Coelho EC, Oréfice FR, Moraes RA. Prevalênciade baixa acuidade visual em escolares da rede pública, Sorocaba. Rev Saude Publica. 2004; 38(2):201-8.

17. Ribeiro JA, Saraiva AS, Araujo AL, Franca MS. Promoção da saúde e cultura cidadã envolvendo uma abordagem oftalmológica emescolares na Colônia Antônio Aleixo (CAA), Manaus-AM: umaexperiência no ensino médico. Rev Bras Educ Med. 2006; 30(2):87-92.

18. Estacia P, Stramari LM, Schuch SB, Negrello D, Donato L. Prevalência de erros refrativos em escolares da primeira série do ensinofundamental da região Nordeste do Rio Grande do Sul. Rev BrasOftalmol. 2007; 66(5):297-303.

19. Laignier MR, Castro MA, Sá PS. De olhos abertos: investigandoacuidade visual em alunos de uma escola municipal de vitória. EscAnna Nery. 2010; 14(1):113-9.

20. Zanoni LZ, Biberg-Salum TG, Consolo CE, Espindola YD.Prevalência de baixa acuidade visual em alunos de primeiro ano do ensino fundamental de uma escolar pública. Rev AMRIGS. 2010;54(1):19-24.

21. Ribeiro GB, Coelho AL, Chaves PH, Macedo RL, Silva TA. Avaliação oftalmológica de crianças de escolas públicas de Belo Horizonte/MG: um panorama acerca da baixa acuidade visual. Rev Bras Oftalmol. 2015; 74(5):288-91.

22. Oliveira RS, Parizotto AV, Caleffi MF, Beal C, Yen SS, Vicensi MC. Avaliação da acuidade visual em escolares no município de Hervald’Oeste, Santa Catarina, Brasil. Rev Bras Med Fam Comunidade.2013; 8(28):180-6.

23. Porcionato JM, Antoniassi AC, Goto C, Murari JN. Acuidade visual em estudantes das escolas de uma comunidade Ribeirinha do Baixo Madeira – RO. Rev Cuid. 2016; 10(2):116-22.

5. Abi Bakar NF, Ai Hong C Pik Pin G. COVD-QOL questionnaire: an adaptation for school vision screening using Rasch analysis. J Optom. 2012; 5(4):182-7.

6. Gerchak D, Maples WC, Hoenes R. Test retest reliability of theCOVD-QOL short form on elementary school children. J BehavOptom. 2006; 17(3):65-9.

7. Vaughn W, Maples WC, Hoenes R. The association betweenvision quality of life and academics as measured by the College ofOptometrists in Vision Development Quality of Life questionnaire. Optometry. 2006; 77(3):116-23.

8. Nunes AF, Nunes AJ, Monteiro PM, Pato MA. Desempenho visual: validação do inventário de eficiência visual em estudantes. Rev Bras Oftalmol. 2015; 74(2):92-8.

9. Moreira Neto CA, Moreira AT, Moreira LB. Relação entre acuidade visual e condições de trabalho escolar em crianças de um colégio do ensino fundamental público de Curitiba. Rev Bras Oftalmol. 2014; 73(4):216-9.

10. Régis-Aranha LA, Moraes FH, Santos ST, Heufemann NE,Magalhães WO, Zacarias RO Filho, Pinto AB. Acuidade visual edesempenho escolar de estudantes em um município na AmazôniaBrasileira. Esc Anna Nery. 2017; 21(2):1-6.

11. Simionato EZ, Soldera J, Rizzon ES, Pires EM, Bassani FR, ÁrticoLG. Relação da baixa acuidade visual com reprovação escolar emcrianças do nordeste do Rio Grande do Sul. Arq Catarin Med. 2007; 36(3):72-5.

12. Toledo CC, Paiva AP, Camilo GB, Sotto Maior MR, Leite IC, Guerra MR. Detecção precoce de deficiência visual e sua relação com orendimento escolar. Rev Assoc Med Bras. 2010; 56(4):415-9.

13. Zapparoli M, Klein F, Moreira H. Avaliação da acuidade visualSnellen. Arq Bras Oftalmol. 2009; 72(6): 783-8.

14. Lopes GJ, Casella AM, Chui CA. Prevalência de acuidade visualreduzida nos alunos da primeira série do ensino fundamental dasredes pública estadual e privada de Londrina-PR, no ano de 2000. Arq Bras Oftalmol. 2002; 65(6):659-64.

15. Granzoto JA, Ostermann CS, Brum LF, Pereira PG, Granzoto T.Avaliação da acuidade visual em escolares da 1ª série do ensinofundamental. Arq Bras Oftalmol. 2003; 66(2):167-71.

Corresponding author: Lucas Motta Gadelha Silva E-mail: [email protected]


250original articlE

Received for publication 22/01/2019 - Accepted for publication 23/05/2019.

The authors declare no conflicts of interests.

Reduced visual acuity screening in a Primary Care Unit

Triagem de acuidade visual reduzida em uma unidade de Atenção Primária à Saúde

1 Department of Child Care and Pediatrics, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. 2 School Health Center, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. 3 Department of Child Care and Pediatrics, School of Medicine of Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

Resumo

Objetivo: Determinar a frequência de acuidade visual reduzida em crianças e adolescentes que frequentam o programa de puericultura de uma unidade de atenção primária à saúde. Métodos: Estudo transversal com 290 crianças e adolescentes na faixa etária dos 5 aos 18 anos, atendidos em uma unidade básica de saúde da cidade de Ribeirão Preto (SP) durante o primeiro semestre de 2018. Para as avaliações foram utilizados um questionário estruturado e a tabela de acuidade visual de Snellen. Resultados: Foram avaliados 290 indivíduos, sendo 53,2% do sexo feminino. Desse total, 66 (22,7%) foram encaminhados para consulta com oftalmologista, sendo 34 (51,5%) do sexo masculino e 32 (48,5%) do sexo feminino. Foram confirmados 31 casos de erros refracionais: astigmatismo (35,5%), astigmatismo associado (25,8%), hipermetropia (29%) e miopia (9,6%). 24 (77,4%) dos pacientes com acuidade visual reduzida receberam prescrição para uso de lentes corretivas. Conclusões: A prevalência de baixa acuidade visual na amostra estudada foi de 10,7%, com predomínio de astigmatismo, e sem diferença estatisticamente significativa entre os sexos. Destaque-se a importância de se realizarem avaliações completas nos programas de Atenção Básica à Saúde, principalmente a triagem oftalmológica como uma das ferramentas mais importantes para a prevenção da cegueira.

Descritores: Acuidade visual/diagnóstico, Unidade Básica de Saúde; Saúde ocular; Criança; Adolescente

AbstrAct

Objective: to determine the frequency of reduced visual acuity in children and adolescents attending the child care program of a primary health care unit. Methods: A cross-sectional study was carried out with 290 children and adolescents aged 5 to 18 years attending a primary health unit in the city of Ribeirão Preto (SP) during the first half of 2018. A structured questionnaire Snellen’s visual acuity table. Results: 290 subjects were evaluated, 53.2% female. Of these, 66 (22.7%) were referred to ophthalmologists, 34 (51.5%) were male and 32 (48.5%) were female. We confirmed 31 cases of refractive errors: astigmatism (35.5%), associated astigmatism (25.8%), hypermetropia (29%) and myopia (9.6%). 24 (77.4%) of patients with reduced visual acuity received prescription for corrective lenses.Conclusions: the prevalence of low visual acuity in the studied sample was 10.7%, with a predominance of astigmatism, and with no statistically significant difference between the sexes. It is important to emphasize the importance of performing comprehensive evaluations in the Primary Health Care programs, especially ophthalmologic screening as one of the most important tools for blindness prevention.

Keywords: Visual acuity/diagnosis; Basic Health Unit; Eye health; Child; Adolescent.


Carlos Fernando Adani Pereira1 https://orcid.org/0000-0003-2394-7953Roberta Costa2 https://orcid.org/0000-0002-6665-9428Luiz Antonio Del Ciampo3 https://orcid.org/0000-0002-6016-9823Ivan Ferraz3 https://orcid.org/0000-0003-3464-6523


251

IntRoductIon

The most integrative sense of the human being to his outer world is sight, comprising a set of complex interconnected functions, with visual acuity being the most important

among them.(1,2) Normal sight is vital for the choices and performance of work activities in humans, and the visual impairment developed in childhood will have a great influence on these choices, bringing profound disadvantages to the individual, their family, and society, with great emotional, social and economic costs.(3) There may also be impairments in learning, social contacts, and in the child’s adaptive process.(4-6) Among adolescents, visual impairment may be a risk factor for understanding subjects related to sexuality and risk behaviors due to failures in the advertisement material, and the lack of training of people who can act in the orientation of these individuals.(7)

When detected early, low visual acuity makes it possible to adopt measures to avoid severe and late consequences of ocular disease, both in childhood and in adolescence.(6,8,9) In relation to other types of hearing and physical impairments, visual impairment is the most prevalent one, with morbidity equivalent to heart diseases, rheumatology, and diabetes, and also has profound limitations in daily life.(10)

Globally, more than 285 million people are visually impaired, of which 250 million suffer from low vision, and almost 39 million are blind.(11) In Brazil, it is estimated that the prevalence of blindness is 0.6 per thousand children, which results in almost 30,000 children deprived of the sense of sight.(12)

The distribution of low visual acuity is not uniform worldwide, with developing countries being the countries where most of the cases are found.(13) In Latin America, refractive error is one of the most frequent eye diseases, and the use of glasses is among the most economical and effective treatments to return the vision to its normality.(3,14-16)

Visual acuity measurement is the most important instrument for assessing sight, and is among the most used procedures in ophthalmology clinics and in visual tracking programs. (17,18) The visual acuity table is inexpensive, reliable, non-invasive, of rapid application, and does not require a long time of examiner training.(19) This method can initially be applied to 5-year-old children, a common practice in developed countries, as the optimal range for detection and treatment of ophthalmological impairments ranges from birth to six years of age, when the visual development is complete.(18,20)

Primary Care has the role of highlighting the most prevalent population diseases, providing continuous and well-structured health services, being committed to the quality of life of the users. Some examples of ocular conditions that may be followed by the primary health care team to reduce the overload of specialized services are visual acuity measurement, conjunctivitis, social rehabilitation of the visually impaired, guidance to loyalty to ocular treatment, screening, and referral of people and risk groups for certain diseases, guidance on correct use and side effects of some medications.(13,21)

objECtIves

To know the frequency and causes of low visual acuity among patients treated in a Basic Health Unit.

Reduced visual acuity screening in a Primary Care Unit


mAteRIAls And methods

This is a cross-sectional descriptive study carried out at a primary health unit (UBS) in the city of Ribeirão Preto (SP) including users aged between 5 and 18 years. The data was evaluated by a descriptive analysis of ratios, medians, and standard deviation of the confidence interval. The population sample was statistically scaled considering the prevalence of 17.5%, with an error of estimation of 2.5%, and confidence level of 95%, making a total of 259 patients.(22-24)

Two instruments were used to carry out the study: 1) a questionnaire validated as a screening method, which included questions related to gender, age, place of residence, self-perception of sight, and whether the subject had already had an ophthalmologic examination(4,15); 2) a Snellen table installed in a quiet environment with good lighting and positioned on a windowless wall and at a distance of 5 meters from the patient.

The line of optotypes corresponding to 0.8 and 1.0 was positioned at the eye level of the examinee. Before starting the test, the patients learned to correctly identify the position of the optotypes. The test was carried out on each eye separately with the use of an occluder, and the patients who previously wore glasses were examined with optical correction. For the standardization of the exam, the correct reading equal to or greater than 2/3 of the optotypes was considered the final visual acuity. For example, in a line with six optotypes, the child should correctly interpret at least four of them.

The criteria used to refer patients for specialized ophthalmologic appointment were: 1) visual acuity equal to or less than 0.7 in one or both eyes; 2) visual acuity test result with difference of two lines or more (example: right eye = 0.8, and left eye = 1.0); 3) suggestive signs of low visual acuity and/or presence of anatomical alterations; 4) difficulty in carrying out the exam due to lack of understanding of the patients.(8,25)

The study included individuals aged between 5 and 18 years who attended the appointment in the ambulatory of child care/pediatric or hebiatrics, and who agreed to participate authorized by the Free and Informed Consent Term. Individuals with symptoms compromising their general condition were not included in the study. All individuals with ocular alterations detected in the study had their data recorded in the medical records for continuity of follow-up in Primary Care.

The study was approved by the Research Ethics Committee of Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, CAAE 56551216.6.0000.5440.

Results

During the evaluation period in the first half of 2018, all 329 users were invited to participate in the study, being aged between five and 18 years who attended routine appointments at the outpatient of childand adolescent care during the study period, in order to reach the minimum number of individuals that could comprise the sample calculated of 259 individuals. Of these, 39 (11.8%) individuals refused to submit to the evaluations, resulting in 290 individuals comprising the sample, of which 136 (46.8%) were males and 154 (53.2%) were females. After the initial procedures, 22.7% (66/290) were referred for ophthalmologic appointment, being 34 (51.5%) males and 32 (48.5%) females, as they presented some visual problem during


252 Ciampo LAD, Cardoso AL, Nascimento CFG, Teles LPM, Mendonça CQ, Ferraz I, Costa R, Pereira CFA


screening (low visual acuity and/or other ophthalmological diseases). Among the 66 individuals referred, 59 (89.4%) attended the appointment scheduled with an ophthalmologist. Of these, 24 (40.7%) were considered emmetrope and received medical discharge; 31 (52.5%) presented refractive errors thus distributed: hypermetropia = 9 (29.0%), myopia = 3 (9.6%), astigmatism = 11 (35.5%), and associated astigmatism = 8 (25.8%), as can be observed in table 1. Among the 31 individuals with refractive errors, 24 (77.4%) required corrective lenses. We also diagnosed 1 (1.6%) case of calyx, 1 (1.6%) of conjunctivitis, and 1 (1,6%) of hordeolus.

Among all the individuals evaluated, 7(2.4%) reported having had an ophthalmologic examination before 6 years of age, and 11 (3.8%) reported having good sight but presented low visual acuity in the tests.

Table 1 Distribution of confirmed diagnoses of reduced visual acuity according to gender after specialized evaluation.

Ribeirão Preto, 2018.

Male Female p-ValueDiagnosis n % n %

Astigmatism 7 46.6 4 25.0 0.384Hypermetropia 4 26.6 5 31.2 0.834Associeted Astigmatism 3 20.0 5 31.2 0.581Myopia 1 6.7 2 12.5 0.617Total 15 100 16 100

dIscussIon

The present study showed that 66 (22.7%) individuals participating in the study had ocular complaints (reduced visual acuity and/or other ophthalmological problems), and required referral for evaluation with an ophthalmologist. Other studies described in the literature evaluating similar populations of individuals reported lower frequencies of referral to the ophthalmologist, varying between 15.1% in Pelotas-RS(4) and 17.1% in the city of Londrina-PR.(26) Even lower frequencies were found (8.1%), as in the study carried out in the city of Botucatu-SP,(27) and another (10.8%) in the city of Passo Fundo-RS.(28) On the other hand, a study carried out in Guarulhos-SP detected higher frequencies of ocular complaints and referral to the ophthalmologist.(29)

In the global context, a survey conducted in Turkey(30)

showed that 17.5% of elementary school students had ocular worsenig, whereas another study in Canada(31) also with children younger than 10 years of age found prevalence ranging from 10, 5% and 13.8%.

The literature has recorded discussions about differences in the prevalence of visual problems in view of methodological variations, evaluation tools, and also population characteristics related to social, biological and nutritional factors.(9,32) Different methodologies used for visual screening and referral to specialized services may prejudice the comparison between the different studies. However, this is not an obstacle to the continuity of preventive programs.(20,33) It should be emphasized that these tests are easy to perform, inexpensive, and effective for detecting eye problems and providing information to demonstrate the regional realities.(6,34)

Of the individuals referred to the ophthalmological service, 81.8% attended the specialized appointment, which represents a failure rate of 18.2%. This absence rate was lower than those found in studies carried out in the states of Rio Grande do Sul(27) (48%), Paraná (21), and São Paulo(35).

In some countries such as South Korea, absence to the ophthalmological appointment reached 56.6%.(34) In the present study, the high rate of attendance at the ophthalmologic appointment can be related to factors such as awareness on the importance of sight emphasized to the parents by the researcher during the application of the tests, and also the possible formation of a closer bond with the patient that is usually established in the Child Care Programs. Such an attendance rate values the preventive action of the study, since most ocular worsenings can be treated or minimized with simple and effective actions.(36)

The evaluation carried out by specialist found 40.7% emmetropic individuals. Among the other 59.3%, visual worsenings were confirmed, with more than half (52.5%) diagnosed with refractive errors. The present study demonstrated agreement with other authors who found refractive error as the most common cause of reduced visual acuity in childhood.(9,30,37) The most common refractive error was astigmatism (35.5%), followed by hypermetropia (29%), associated astigmatism (25.8%), and myopia (9.65). Regarding distribution by gender, no statistically significant difference was found. Astigmatism associated with hypermetropia was found in 22.5%, and astigmatism associated with myopia in 3.3%. These data was similar to that observed in a study carried out in Santa Catarina where astigmatism was also more prevalent, followed by hypermetropia and myopia.(38) Similar results were also observed in a study carried out in Rio Grande do Sul, where hypermetropia was was the most common refractive error, followed by astigmatism and myopia.(28) Astigmatism associated with hypermetropia represented 30.6% of refractive errors, and 9% when associated with myopia.

Another study carried out in São Paulo reinforced the need to change the concept that hypermetropia would be the most prevalent refractive error, presenting different data from the present study with hypermetropic astigmatism being the most common refractive error, followed by myopic astigmatism, astigmatism, hypermetropia, and myopia.(27) In a survey carried out in Turkey(30) the most common refractive disorders were astigmatism and hypermetropia, whereas in Tanzania it was observed that almost all students with refractive errors had myopia.(33) In South Korea, astigmatism was the most prevalent ametropia among students, reaching almost 78% of the population sample.(34)

Regarding gender, studies with a prevalence similar to the current one can be found, with 49.2% for males and 50.8% for females,(29) although some authors show a higher prevalence in females,(4,39) whereas others in males. (38,39)

The prevalence of individuals who wear glasses (9.2%) found in the present study was higher when compared to a study carried out in Londrina- PR,(21) which was between 2.4% and 3.6%. Another study showed that in Rio Grande do Sul 3%(4) of the subjects wore glasses, whereas in the city of Tubarão-SC(37) the use of corrective lenses was reported by 4.9% of subjects. At international level, a study carried out in Turkey found 12.1% of individuals wearing glasses.(30)

The characteristics of the population of the present study may help explain the difference in the frequency of corrective lens use compared to the other studies mentioned, since most of the participants were regularly followed in a child care program


253Reduced visual acuity screening in a Primary Care Unit


at the health unit, which would allow more frequent and early detection of various health problems, including the visual ones.

In the present study, 2.4% of individuals who reported good sight but with reduced visual acuity underwent screening tests. This prevalence was lower when compared to studies carried out in Brazil(4) and Turkey(30), with frequencies of discrepancies between what was reported by the individual and what was found during the examination, of 14.2% and 10.6% respectively. Once again, regular follow-up in the basic health unit making it possible to diagnose health problems including the visual ones could explain these findings.

The fact that only 7(1.5%) individuals report the ophthalmologic examination before the age of 6 confirms existing data in the literature pointing out that preventive ocular health campaigns are practically nonexistent in this age group, delaying and even even making it impossible to diagnose ocular diseases such as strabismus and amblyopia.(40-42)

The results obtained in the present study show that the screening test of reduced visual acuity can be carried out in Primary Care and should have its place in the health care programs of children and adolescents. Although this study presents some limitations such as the non-representativeness for the city of the population sample using the health services of this UBS and the use of the Snellen scale for the detection of low visual acuity (which may have influenced the frequency of the visual worsenings observed), a moderate prevalence of low visual acuity was observed, and refractive errors constituted the most common cause of the worsenings detected. Said results may help disseminating the importance and need of having comprehensive evaluations in Primary Health Care programs, emphasizing ophthalmologic screening as one of the most important tools for the prevention of blindness. Thus, getting Ophthalmology and Primary Care closer can be a proposal for the prevention of visual problems.(17,22) Methods of care can be developed for physicians with general training (pediatricians, family physicians, and clinicians), and periodic appointments of their patients to detect deviations from normality.(23)

RefeRences

1. Gagliardo HG, Nobre MI. Intervenção precoce na criança com baixavisão. Rev Neurocien. 2001;9(1):16–9.

2. Lee YB, Choi DG. Binocular visual acuity interaction in children:summation and inhibition. Can J Ophthalmol. 2017;52(2):214–8.

3. Armond JE, Temporini ER, Alves MR. Promoção da saúde ocularna escola: percepções de professores sobre erros de refração. ArqBras Oftalmol. 2001;64(5):395–400.

4. Granzoto JA, Ostermann CS, Brum LF, Pereira PG, Granzoto T.Avaliação da Acuidade visual em escolares da 1.a série do ensinofundamental. Arq Bras Oftalmol. 2003;66(2):167–71.

5. Toledo CC, Paiva AP, Camilo GB, Sotto-Maior MR, Leite IC, Guerra MR. Detecção precoce de deficiência visual e sua relação com orendimento escolar. Rev Assoc Med Bras. 2010;56(4):415–9.

6. Dan VJ. Prevalência de baixa acuidade visual em escolares do oeste paulista. Rev Urutágua. 2016;33:132–8.

7. Moura GR, Pedro EN. Adolescentes portadores de deficiênciavisual: percepções sobre sexualidade. Rev Lat Am Enfermagem.2006;14(2):220–6.

8. De Fendi LI, Arruda GV, Fonseca EC, Bosso EP, OttaianoJA. Qualidade da avaliação da acuidade visual realizada pelosprofessores do programa “ Olho no olho” da cidade de Marília, SP. Arq Bras Oftalmol. 2008;71(4):509–13.

9. Harrington SC, Stack J, Saunders K, O’Dwyer V. Refractive errorand visual impairment in Ireland schoolchildren. Br J Ophthalmol. 2018; Oct 12. pii: bjophthalmol-2018-312573. doi: 10.1136/bjophthalmol-2018-312573.

10. Castro SS, César CL, Carandina L, Barros MB, Alves MC, Goldbaum M. Deficiência visual, auditiva e física: prevalência e fatoresassociados em estudo de base populacional. Cad Saude Publica.2008;24(8):1773–82.

11. World Health Organization (WHO). Global data on visual impairments 2010 [Internet]. Genève: WHO; 2010. [cited 2013 Feb 28]. Available from: http://www.who.int/blindness/GLOBALDATAFINALforweb.pdf

12. Avila M, Alves MR, Nishi M. As condições de saúde ocular no Brasil. São Paulo: Conselho Brasileiro de Oftalmologia; 2015. 147 p.

13. Guedes RP. As estratégias de prevenção em saúde ocular no âmbito da saúde coletiva e da Atenção Primária à Saúde – APS. Rev At PrimSaúde. 2007;10:66–73.

14. Galvis V, Tello A, Otero J, Serrano AA, Gómez LM, CastellanosY. Refractive errors in children and adolescents in Bucaramanga(Colombia). Arq Bras Oftalmol. 2017;80(6):359–63.

15. Arieta EL, Delgado NM, kara-José N, Temporini ER, Alves MR, Moreira Filho DC. Refractive errors and cataract as causes of visual impairment in Brazil. Ophthalmic Epidemiol. 2003;10(1):15–22.

16. Temporini EC, Kara-José N. A perda da visão - Estratégias dePrevenção. Arq Bras Oftalmol. 2004;67(4):597–601.

17. Hered RW, Wood DL. Preschool vision screening in primary carepediatric practice. Public Health Rep. 2013;128(3):189–97.

18. Vieira JK, Rezende GX, Anastácio LB, Freitas Filho RT, Benevides HC, Fonseca JM, et al. Prevalência de baixa acuidade visual emescolares. Rev Bras Oftalmol. 2018;77(4):175–9.

19. Jose R, Sachdeva S. School eye screening and the National Program for Control of Blindness. Indian Pediatr. 2009;46(3):205–8.

20. Solebo AL, Rahi J. Epidemiology, aetiology and management ofvisual impairment in children. Arch Dis Child. 2014;99(4):375–9.

21. Del Ciampo LA, Ricco RG, Daneluzzi JC, Del Ciampo IR, FerrazIS, Almeida CA. O programa de saúde da família e a Puericultura. Cien Saude Colet. 2006;11(3):739–43.

22. Portes AJ. Oftalmologia e atenção primária a saúde. Rev BrasOftalmol. 2012;71(6):351–2.

23. Marsh-Tootle WL, Wall TC, Tootle JS, Person SD, Kristofco RE.Quantitative pediatric vision screening in primary care settings inAlabama. Optom Vis Sci. 2008;85(9):849–56.

24. Lopes GJ, Casella AM, Chui CA. Prevalência de acuidade visualreduzida nos alunos da primeira série do ensino fundamental dasredes pública estadual e privada de Londrina-PR, no ano de 2000. Arq Bras Oftalmol. 2002;65(6):659–64.

25. Muñoz B, West SK. Blindness and visual impairment in the Americasand the Caribbean. Br J Ophthalmol. 2002;86(5):498–504.

26. Salomão SR, Mitsuhiro MR, Belfort R Jr. Visual impairment andblindness: an overview of prevalence and causes in Brazil. An Acad Bras Cienc. 2009;81(3):539–49.

27. Oliveira CA, Hisatomi KS, Leite CP, Schellini SA, Padovani CR,Padovani CR. Erros de refração como causas de baixa visual emcrianças da rede de escolas públicas da regional de Botucatu - SP.Arq Bras Oftalmol. 2009;72(2):194–8.

28. Estacia P, Stramari LM, Schuch SB, Negrello D, Donato L. Prevalência de erros refrativos em escolares da primeira série do ensinofundamental da região Nordeste do Rio Grande do Sul. Rev BrasOftalmol. 2007;66(5):297-303.

29. Noma R, Carvalho RS, Kara-José N. Why are there defaulters in eye health projects? Clinics (Sao Paulo). 2011;66(9):1585–9.

30. Caca I, Cingu AK, Sahin A, Ari S, Dursun ME, Dag U, et al.Amblyopia and refractive errors among school-aged childrenwith low socioeconomic status in southeastern Turkey. J PediatrOphthalmol Strabismus. 2013;50(1):37–43.


254

31. Robinson B, Bobier WR, Martin E, Bryant L. Measurement of thevalidity of a preschool vision screening program. Am J Public Health. 1999;89(2):193–8.

32. Zhang X, Wang Y, Huang D, Sun Q, Zhao X, Ding H, et al. Prevalence of reduced visual acuity among preschool children in easternChina and comparison at a 5-year interval. Clin Exp Ophthalmol.2018;46(9):994–1001.

33. Wedner SH, Ross DA, Todd J, Anemona A, Balira R, Foster A.Myopia in secondary school students in Mwanza City, Tanzania:the need for a national screening programme. Br J Ophthalmol.2002;86(11):1200–6.

34. Lim HT, Yu YS, Park SH, Ahn H, Kim S, Lee M, et al. The SeoulMetropolitan Preschool Vision Screening Programme: results fromSouth Korea. Br J Ophthalmol. 2004;88(7):929–33.

35. Noma R, Carvalho RS, Kara-José N. Validity of recall absentschoolchildren to free eye health projects. Arq Bras Oftalmol.2012;75(1):16–9.

36. Rashad MA, Elaziz KM, Fawzy SM, Latif AA, Latif MA. Screening of primary school children for amblyopia and amblyogenic factors in Central Cairo, Egypt. J Ophtalmol 2018, Article ID 8425319 [ahead of print].

37. Fissmer LE, Lima GC, Netto AA, Corrêa M, Auwaerter GA, Fissmer JF. Avaliação da acuidade visual de alunos do Ensino fundamentalde uma escola da rede pública de Tubarão – SC. Arq Catarin Med. 2005;34:15–9.

38. Zanoni LZ. Prevalência da baixa acuidade visual em alunos doprimeiro ano do ensino fundamental de uma escola pública. RevAMRIGS. 2002;54:19–24.

39. De Oliveira RS, Parizotto AV, Caleffi MF, Beal C, Yeh WS, VicensiMC. Avaliação da acuidade visual em escolares no município deHerval d’Oeste, Santa Catarina, Brasil. Rev Bras Med Fam Com.2013;8(28):180–6.

40. Couto Júnior AS, Pinto GR, Oliveira DA, Holzmeister D, Portes AJ, Neurauter R, et al. Prevalência das ametropias e oftalmopatias emcrianças pré-escolares e escolares em favelas do Alto da Boa Vista, Rio de Janeiro, Brasil. Rev Bras Oftalmol. 2007;66(5):304–8.

41. Couto Júnior AS, Jardim JL, Oliveira DA, Gobetti TC, Portes AJ,Neurauter R. Alterações oculares em crianças pré-escolares eescolares no município de Duque de Caxias, Rio de Janeiro, Brasil. Rev Bras Oftalmol. 2010;69(1):7–11.

42. Rocha MN, Ávila MP, Isaac DL. Mendonça LS, Akanish L, Auad LJ. Prevalência de doenças oculares e causas de comprometimento visual em crianças atendidas em um Centro de Referência em Oftalmologia do centro-oeste do Brasil. Rev Bras Oftalmol. 2014;73(4):225–9.

Corresponding author: Luiz Antonio Del Ciampo Av. Bandeirantes, 3900 - Ribeirão Preto - São Paulo - Brazil Zip code: 14049-900 E-mail: [email protected]

Ciampo LAD, Cardoso AL, Nascimento CFG, Teles LPM, Mendonça CQ, Ferraz I, Costa R, Pereira CFA



255

Tratamento da aniseiconia induzida na correção óptica de anisometropia em escolares do ensino fundamental

Resumo

Objetivos: Comparar a aniseiconia e a estereopsia em escolares anisometropes do primeiro ano do ensino fundamental corrigidos com lentes oftálmicas de estoque com curvas-base selecionadas para minimizar a diferença de tamanho interocular das imagens retínicas e com lentes iseicônicas sugeridas pelo software Aniseikonia Inspector 3 e verificar a preferência dos escolares por uma destas formas de correção. Métodos: Dezenove escolares com anisometropia ≥ 1,5 D em meridianos correspondentes no uso de óculos com lentes oftálmicas de estoque e com lentes iseicônicas foram avaliados para aniseiconia (software Aniseikonia Inspector 3) e estereopsia (teste Stereo Fly test com símbolos LEA. A preferência por uma das formas de correção foi verificada após 40-50 dias de uso dos óculos. Resultados: As médias e os desvios-padrão das aniseiconias vertical e horizontal no uso de óculos com lentes oftálmicas de estoque e com lentes iseicônicas foram, respectivamente, -1,05% ± 2,20% e -1,37% ± 2,36% (p=0,82739) e -0,895% ± 2,23% e -1,16% ± 2,03% (p=0,77018). 31,6% dos escolares corrigidos com lentes iseicônicas e 21,1% dos escolares corrigidos com lentes oftálmicas de estoque identificaram os optotipos que sugerem estereopsia < 100 segundos de arco (p= 0,475). Em relação à preferência, 4/15 (26,7%) escolheram os óculos com lentes iseicônicas, 2/15 (13,3%) escolheram os óculos com lentes oftálmicas de estoque e para 9/15 (60%) a escolha foi indiferente. Conclusão: A aniseiconia induzida nos escolares anisometropes corrigidos com lentes iseicônicas sugeridas pelo software Aniseikonia Inspector 3 foi similar ao obtido na correção com lentes oftálmicas de estoque com curvas-base selecionadas para minimizar a diferença de tamanho interocular das imagens retínicas.

Descritores: Anisometropia; Aniseiconia; Estereopsia; Saúde ocular; Transtornos da visão; Saúde escolar; Criança.

1 Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil. 2 Pontifícia Universidade Católica de São Paulo, São Paulo, Brazil.


original articlE

Treatment of aniseikonia induced by optical correction of anisometropia

in elementary school children

AbstrAct

Objectives: To compare the aniseikonia and the stereopsis in school children anisometropes of the first-year of elementary school corrected with stock ophthalmic lenses with base curve selected to minimize the interocular size difference of retinal images and with size lenses suggested by the software Aniseikonia Inspector 3, and to check the preference of them for one of these forms of correction. Methods: Nineteen school children with anisometropia ≥ 1.5 D in corresponding meridians, in the use of glasses with stock ophthalmic lenses and with size lenses were evaluated for aniseikonia (software Aniseikonia Inspector 3) and stereopsis (Stereo Fly test with LEA symbols). The preference for one of the forms of correction was verified after 40-50 days of wearing glasses. Results: The mean and standard deviations of the vertical and horizontal aniseikonia in the use of glasses with stock ophthalmic lenses and with size lenses were, respectively, -1.05% ± 2.20% and-1.37% ± 2.36% (p = 0,82739) and -0.895% ± 2.23% and -1.16% ± 2.03% (p = 0,77018). 31.6% of the school children corrected with size lenses and 21.1% of the students corrected with stock ophthalmic lenses identified the optotypes that suggest stereopsis less than 100 seconds of arc (p = 0.475). Regarding the preference, 4/15 (26.7%) of the students chose the glasses with size lenses, 2/15 (13.3%) chose the glasses with stock ophthalmic lenses, and for 9/15 (60%) the choice was indifferent. Conclusion: The induced aniseikonia in school children with anisometropia corrected with size lenses suggested by the software Aniseikonia Inspector 3 was similar to that obtained in the correction with stock ophthalmic lenses with base curves selected to minimize the difference of interocular size of retinal images.

Keywords: Anisometropia; Aniseikonia; Stereopsis; Eye health; Vision disorders; School health; Child.

Helio Paulo Primiano Junior1 https://orcid.org/0000-0002-9013-0284Luiz Fernando Orlandin1 https://orcid.org/0000-0002-9650-0733Marcus Vinicius Takatsu1 https://orcid.org/0000-0003-0034-4455Milton Ruiz Alves1 https://orcid.org/0000-0001-6759-5259Milton Ruiz Rodrigues Alves2 https://orcid.org/0000-0001-6412-799X


Institution where the study was carried out: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.


256

IntRoductIon

Anisometropia is the name given to the condition in which the refractive error is different between the eyes. (1,2) It may result from interocular differences in

the refractive power (refractive anisometropia), or axial length (axial anisometropia).(1,2) In population studies, the prevalence of anisometropia ranges from 1-20% depending on the criteria adopted, age, and characteristics of the sample distribution.(3-6) In children aged 6-8 years, the prevalence of anisometropia in spherical equivalent (EE) ≥1D was estimated at 8.5%; and in children aged 12-13 years in 9.4%.(7-9) Anisometropia is one of the main causes of amblyopia and strabismus in children.(10-11)

In the optical correction of the anisometropias the refractive disparity is changed by power disparity generating the aniseiconia that is defined by the difference in size or shape of the cortical representations of the images coming from both eyes. (1) Although most eyeglass wearers have a mild aniseiconia (<1%), values ≥2% are considered clinically significante, and may trigger symptoms that may negatively impact the quality of life.(12) The symptoms arising from aniseiconia are highly variable, and are related not only to the type and magnitude of anisometropia, but also to the optical correction used and the user’s ability to adapt to this correction.(12)

When the optical correction of anisometropia has the intention of treating aniseiconia, then changes in the frontal curvatures (basal curves), thicknesses, facets and refractive indices of ophthalmic lenses can alter the sizes of the retinal images. (3,13,14) In general, lenses with flatter front curvatures minify the retinal image, and lenses with more curved frontal curvatures magnify it.(3,12) According to this rule, in the optical correction of an anisometrope patient, the choice of stock lens with flatter anterior curvature for the eye forming the larger retinal image and directing the other stock lens with more curved frontal curvatuta to the eye forming the smaller retinal image can reduce aniseiconia by 2-3 %.(14)

The software Aniseikonia Inspector 3 (Optical Diagnostics) measures aniseiconia, and suggests modifications in the frontal curvatures, thicknesses, facets, and vertex distance of ophthalmic lenses, that is, it proposes the making of iseiconic lenses for its treatment. (15,16) On the other hand, the choice of stock lenses with frontal curvatures (base curves) selected to minimize the difference in the interocular size of the retinal images since the base curve is the most important modifiable factor of lenses in relation to aniseiconia(17) may be the most affordable and least expensive solution.

The objective of the present study was to compare induced aniseiconia in the optical correction of anisometropia to the choice of stock ophthalmic lenses with appropriate base curves and to the iseiconic lenses suggested by the software Aniseikonia Inspector in first grade students. And as specific objectives are to compare the stereopsis and check the preference of anisometrope students by one of these two forms of optical correction.

methods

A prospective analytical observational study was carried out at the ambulatory of Clínica Oftalmológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) between May 2017 and June 2018. The study was approved by the Ethics Committee for Research Project Analysis

of HCFMUSP. Signature of the free and informed consent term was obtained from the parents or legal representative of the participants.

The study population consisted of 19 schollers from the first grade of elementary school enrolled in public schools in the city of São Paulo aged between 7 and 9 years. The students previously underwent visual screening by teachers, and were referred to HCFMUSP for ophthalmological evaluation as part of the program Visão do Futuro. Students with anisometropia ≥1.5D were included in the corresponding meridians with corrected visual acuity ≥0.8 in both eyes. Strabic, amblyopic (interocular corrected visual acuity difference of 2 or more lines on the Snellen optometric scale) students with opacity of the ocular optic media, neurological disorders, and/or mental retardation were excluded.

The study was carried out in two stages. In the first stage, a complete ophthalmologic assessment (measurement of visual acuity, extrinsic ocular motility, biomicroscopy and ophthalmoscopy) was carried out, with refraction under cycloplegia (instillation of two drops of cyclopentolate 1% in the lower conjunctival sac every five minutes, about 30 minutes after the instillation of the second drop manual and computed scintigraphy were carried out with the use of the Topcon KR8000 automatic refractometer. The subjective clinical refractometry was performed using the Topcon VT10 manual refractor, Japan. In the end, the best corrected visual acuity was recorded with the values of the prescription of the refractive error. The students then had the aniseiconia measured using the software Aniseikonia Inspector 3. The optical correction of anisometropia was mounted in a test frame with green and red filters to dissociate the images of both eyes. The student was positioned in front of the computer monitor with the software Aniseikonia Inspector 3. The use of the green filter in the right eye was standardized. The test began with the student pointing out on the computer screen which of the two rectangular boxes presented was higher; then they continued to point out which of the rectangular boxes presented was larger. If the images look the same for the schollchild, the examiner would select the “E” button for equal. After completing the evaluation, the software Aniseikonia Inspector suggested iseiconic lenses with modifications in the frontal curvatures, thicknesses, and facets to reduce the aniseiconia induced by the optical correction. The results of the aniseiconia evaluation were obtained in percentage of magnification along with a value of consistency that allowed considering the results reliable or inconsistent. By definition, aniseiconia is expressed as a relative difference in size and shape of the image relative to the right eye. For example, if the aniseiconia measured is -3%, this means that it would be necessary to magnify the image of the right eye by 3% to cancel out the aniseiconia induced by that optical correction. The aniseiconia was measured in the vertical and horizontal meridians in the angular field of 4°, as suggested in the manual of the Aniseikonia Inspector 3.(15)

The prescription for the correction of the refractive errors was sent for the preparation of two glasses: one to be made with the iseiconic lenses suggested by the software Aniseikonia Inspector 3, and the other with stock lenses. Both lenses were CR-39. In the case of stock lenses (semi-finished blocks), the base curves were chosen by searching the values in surfacing tables(18). In the stock lenses, only the posterior surface was surfed. In the iseiconic lenses, both surfaces were surfed. The two glasses were prepared with identical acetate frames. To facilitate

Primiano Junior HP, Orlandin LF, Takatsu MV, Alves MRR, Alves MR



257Treatment of aniseikonia induced by optical correction of anisometropia in elementary school children


the identification, the glasses with iseiconic lenses had a discrete marking on the inner portion of the right frame.

In the second stage of the investigation, aniseiconia, stereopsia and the student preference were evaluated by one of the two forms of correction. The Aniseikonia Inspector 3 test was carried out with the student wearing glasses with the stock lenses, and with the iseiconic lenses interpolating the green filter on the right eye and red one on the left eye to dissociate the images and allow the measurement of aniseiconia. Stereopsia was measured with each of the optical corrections using the Stereo Fly test with the LEA symbols (Stereo Optical Co. Inc., USA). Students who identified the optotypes suggesting the presence of stereopsis <100 seconds of arch were considered with normal stereopsia, with the other students being considered subnormal.

During the delivery of the glasses, the legal gardian was informed that the student should wear each of the glasses for 20 days. The order of choice informed for wearing glasses was previously determined randomly. The legal guardian was informed that they would be contacted after 40-50 days of delivery of the glasses to inform the student’s preference for one of the optical corrections received.

Demographic data and test results were recorded on individual records, and a tabulated database was created in Microsoft Excel® spreadsheets. The calculations and statistical analyzes were carried out with the aid of the softwares R (R Core Team, 2018)(19) and Past - version 3.20(20). In order to graphically analyze the variation of the lens parameters (frontal curvature, thickness, and position of the lens facet in the bevel) in relation to the factors treatment (digital surfacing and iseiconic lenses prescribed by the software) and eye (right and left), non-metric multidimensional multivariate analyzes with Euclidean distance (N-MDS - Non-metric Multidimensional Scaling) were carried out.

The confidence intervals (95% CI) were calculated for the analysis of aniseiconia and esteropsia with the use of the digital and iseiconic surfacing lenses (software). The normality of the variables was tested using the Shapiro-Wilk normality test (α = 0.05). In the analyzes of aniseiconia and stereopsis, the variables were compared with the paired Student’s t test (α = 0.05).

Results

The study population consisted of 19 students aged between 7 and 9 years, of which 15 (79%) were female.

Table 1 shows the distribution of refractive errors, axial lengths, and interocular differences of axial lengths.

A non-metric multidimensional multivariate analyzes, N-MDS, with Euclidean distance (Table 2 and Figures 1 and 2)was carried out to graphically analyze the parameter variation of the stock and iseiconic lenses.

Figure 1 graphically compares the set of parameters of stock (Optical) and iseiconic (Software) lenses by non-metric multidimensional multivariate analyzes N-MDS, with Euclidean distance (stress = 0.053).

Figure 2 shows that the parameter variation of stock (Optical) and iseiconic (Software) lens in the reduced space of the N-MDS ordering was not influenced by the eye factor (right or left).

Table 3 presents the results of vertical and horizontal aniseiconias measured with the use of stock (Optic) and iseiconic (Software) lenses.

Table 4 and figure 3 show the results of stereopsia evaluations in the use of stock (Optic) and iseiconic (Software) lenses. Stereopsia values <100 seconds of arc were considered normal.

Regarding preference for glasses: 13.3% (2/15) students reported preferring glasses with conventional lenses, 26.7% (4/15) chose glasses with iseiconic lenses, and 60% (9/15) students mentioned no difference in the choice of glasses.

dIscussIon

To identify the best cost-effective treatment for aniseiconia induced by optical correction of anisometrope students included in the present study we have to answer the following two questions: (1) Can we treat aniseiconia with stock lenses with selected base curves to minimize the difference of interocular size of retinal images? or (2) Should we treat aniseiconia with the iseiconic lenses suggestedby the software Aniseikonia Inspector 3?

When the optical correction of anisometropia is intended to treat aniseiconia, manipulation of the parameters (base curve, thickness, vertex distance, and refractive index) can be used to modify the size of the retinal image.(2) Nomograms and complicated calculations are not always necessary, considering that the frontal curvature seems to be the most important modifiable factor.(3) In a study carried out in 2016, Al-Habdan found that by keeping the other parameters alike, lenses with flatter base curves minimized the retinal image, whereas lenses with more curved base curves magnified the retinal image.(21)

In the present study, the results of the N-MDS order showed statistically significant differences between the lens sets of parameters (stress = 0.053, Figure 1) that were not influenced by the eye factor (right or left) (stress = 0.055, Figure 2).

The differences between vertical (p = 0.82739) and horizontal (p = 0.77018) aniseiconia values induced in the optical correction by stock lenses and iseiconic lenses in anisometropic students were not statistically significant (Table 3). These results suggest that the treatment of induced aniseiconia in the optical correction of anisometrope students can be done with selected stock lenses with appropriate frontal curvatures (base curves). The choice of stock lenses resulted in the best cost-benefit due to dispensing iseiconic lenses, which are less accessible and certainly more expensive.

The study verified that the majority of the students in the use of both optical corrections presented subnormal stereopsia, with a slight tendency to better retention of stereopsis in the use of the iseiconic lenses (Table 4 and Figure 3). However, there was no statistically significant difference between the two optical corrections (p=0.475).

Regarding the preference, 2 (13.3%) students chose glasses with stock lenses, 4 (26.7%) preferred glasses with iseiconic lenses, and for 9 (60%) the choice was indifferent.

The limitations of the study were: (1) the small casuistry; (2) the nature of selection of students who included only non-amblyopic and non-strabismic anisometropes and wearers ofglasses for at least one year, which undermined the generalizationof data; (3) the use of only CR-39 material for the manufactureof the glass lenses, and (4) information about the preference forone of the glasses having been obtained by contacting the legalguardian of the student.

conclusIon

As a conclusion, it was verified in the present study that the optical correction of anisometropic students with stock lenses with


258 Primiano Junior HP, Orlandin LF, Takatsu MV, Alves MRR, Alves MR

base curves selected to minimize the interocular size difference of the retinal images obtained results similar to those found in the use of the iseiconic lenses suggested by the software Aniseikonia Inspector 3.


N Sfe Cyl Cyl Axis Sfe Cyl Cyl Axis Axl Axl Diff RE RE RE LE LE LE RE LE Biom

1 7.00 -4.00 180 4.00 -2.00 180 20.14 20.68 0.54

2 0.25 -1.00 95 -1.50 -1.75 53 22.61 23.22 0.61

3 -1.75 -3.50 180 2.00 -2.25 180 23.98 22.36 1.62

4 -2.25 -2.75 20 -0.25 -2.75 175 24.97 24.04 0.93

5 -5.25 -1.00 160 -1.75 -2.75 180 25.43 24.74 0.69

6 -4.00 -3.50 180 -0.25 -2.50 165 25.23 23.32 1.91

7 -1.50 -2.00 15 0.00 -0.50 165 22.42 22.15 0.27

8 -7.50 -4.00 15 -1.75 -3.25 170 25.27 23.31 1.96

9 -4.25 -1.50 180 -1.75 -0.75 15 26.02 24.83 1.19

10 -6.75 -2.00 90 -1.00 0.50 60 26.41 23.93 2.48

11 0.50 -0.25 130 -2.50 -0,75 150 22.94 24.56 1.62

12 -4.25 -1.75 165 -2.00 -1.50 15 25.25 24.16 1.09

13 -3.00 -1.00 155 -6.00 -0.75 50 23.48 24.16 0.68

14 -5.25 -2.50 165 -1.50 -2.75 15 23.85 23.14 0.71

15 2.00 -2.00 180 4.00 -3.50 180 22.29 22.12 0.17

16 -0.50 -2.75 175 -2.25 -1.50 10 22.58 22.97 0.39

17 -4.00 -2.50 30 1.50 -1.25 170 25.18 22.75 2.43

18 3.25 -1.50 170 5.25 -3.00 180 21.12 20.63 0.49

19 4.75 -4.50 180 2.50 -1.00 105 20.67 20.87 0.20

Table 1 Distribution of refractive errors, axial lengths, and interocular differences of axial lengths.

Refractive errors in diopters; Sfe: spherical component; Cil: cylindrical component and Cyl axis; RE right eye; LE left eye; AxL: Axial length in mm, and Diff: interocular difference of axial length

Parameters Iseiconic Lens Conventional Lens Software Optic

Average SD IC 95% Average SD IC 95%

D1 5.93 2.17 5.23 6.60 3.29 1.86 2.69 3.87

T 2.87 1.50 2.35 3.28 2.42 0.75 2.16 2.64

Facet 39.26 8.31 36.58 41.95 29.47 2.26 28.95 30.26

Table 2 Average values, standard deviations, and 95% CI confidence intervals of the parameters frontal curvature (D1), thickness

(t), and facet of conventional and iseiconic lenses

D1 frontal curvature in diopters, t central thickness in mm, facet in percentage

Figure 1: . Graphical representation of the parameter variations of the digital and iseonic surfacing lenses obtained by means of non-metric multidimensional multivariate analyzes, N-MDS, with Euclidean distance (stress = 0.053)

Figure 2: Graphical representation of the parameter variations of the digital and iseonic surfacing lenses obtained by means of non-metric multidimensional multivariate analyzes, N-MDS, showing that in the reduced space of the N-MDS order there is no statistically significant influence of the right or left eye factor (stress = 0.055)

Table 3 Results of the values (average and standard deviation) of vertical and horizontal aniseiconia measured with the use of digital (Optic) and iseonic (Software) surfacing lenses

Aniseiconia Optic Software df P-value

Vertical -1.05% (2.20%) -1.37% (2.36%) 18 0.82739

Horizontal -0.89% (2.23%) -1.16% (2.03%) 18 0.77018

Paired Student t test

Table 4 Results of the evaluation of steropsia by the Titmus

test in the use of digital (optical) and iseonic (Software) surfacing lenses – ration of students <100 seconds

of arc of stereopsia/total

Correction N <100 Average (SD) t Df P-value

Optic 19 21.1% 0.21 (0.42) 0.722 18 0.475

Software 19 31.6% 0.32 (0.48)

Paired Student t test


259

RefeRences

1. Sousa SJ. Revisando as anisometropias. Arq Bras Oftalmol.2002;65(1):114–7.

2. Sorsby A, Leary G, Richards M. The optical components inanisometropia. Vision Res. 1962;2(1-4):43–51.

3. Kulp MA, Raasch TW, Polasky M. Patients with anisometropia and aniseikonia. In: Benjamin WJ, editor. Borish’s Clinical RefractionElsevier Houston. 2006. p. 1479–522.

4. de Vries J. Anisometropia in children: analysis of a hospitalpopulation. Br J Ophthalmol. 1985;69(7):504–7.

5. Phelps WL, Muir J. Anisometropia and strabismus. Am Orthopt J.1977;27(1):131–3.

6. Woodruff ME, Samek MJ. A study of the prevalence of sphericalequivalent refractive states and anisometropia in Amerindpopulations in Ontario. Can J Public Health. 1977;68(5):414–24.

7. Hu YY, Wu JF, Lu TL, Wu H, Sun W, Guo DD, et al. Prevalence and Associations of Anisometropia in Children. Invest Ophthalmol VisSci. 2016;57(3):979–88.

8. O’Donoghue L, McClelland JF, Logan NS, Rudnicka AR, OwenCG, Saunders KJ. Profile of anisometropia and aniso-astigmatismin children: prevalence and association with age, ocular biometricmeasures, and refractive status. Invest Ophthalmol Vis Sci.2013;54(1):602–8.

Corresponding author: Hélio Paulo Primiano Júnior R. Voluntários da Pátria, 1723 - Araraquara - São Paulo - BrazilZIP Code: 14801-320Phone: +55 16 33331589E-mail: [email protected]

Treatment of aniseikonia induced by optical correction of anisometropia in elementary school children


Figure 3: Graphical representation of the ratio of students with less than 100 seconds of arc of stereopsia/total in use of digital (Optic) and iseiconic lenses (Software)

9. Afsari S, Rose KA, Gole GA, Philip K, Leone JF, French A, et al.Prevalence of anisometropia and its association with refractiveerror and amblyopia in preschool children. Br J Ophthalmol.2013;97(9):1095–9.

10. Laird K. Anisometropia. In: Grosvenor T, Flom T, Flom MC, editors. Refractive anomalies: research and clinical applications. Portsmouth: Butterwortth-Heineman; 1991.

11. Abrahamsson M, Sjöstrand J. Natural history of infantileanisometropia. Br J Ophthalmol. 1996;80(10):860–3.

12. Scheiman M, Wick B. Refractive Amblyopia. In Scheiman M, Wick, editors. Clinical management of binocular vision. Philadelphia:Lippincott. 2002. p.471- 88.

13. Alves MR, Sousa MB, Medeiros FW. Anisometropia. In: Alves MR, Polati M, Sousa SJ, editors. Refratometria ocular e a arte da prescrição médica. 5th ed. Rio de Janeiro: Cultura Médica; 2017. p. 91–119.

14. Rutstein RP, Fullard RJ, Wilson JA, Gordon A. Aniseikonia induced by cataract surgery and its effect on binocular vision. Optom Vis Sci. 2015;92(2):201–7.

15. User’s Manual Aniseikonia Inspector ™ version 3 - OpticalDiagnostics. [Internet]. [cited 2018 Oct 7]. Available from: http://www.opticaldiagnostics.com/products/ai/ai_manual.pdf

16. Kehler LA, Fraine L, Lu P. Evaluation of the aniseikonia inspectorversion 3 in school-aged children. Optom Vis Sci. 2014;91(5):528–32.

17. Kundart J. Diagnosis and treatment of aniseikonia: A case report and review. Optom Vis Perform. 2018;6:112–8.

18. Jallie M. Ophthalmic lenses & Dispensing. Portsmouth: Butterworth-Heinemann; 1999.

19. Core Team R. R - A Language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2018.

20. Hammer O, Harper DA, Ryan PD. Past: Software package foreducation and data analysis. Palenteon Eletronica. 2014;4(1):1–9.

21. Al Habdan N. Treating aniseikonia with stock base curve manipulation in asymptomatic adults [Internet]. Oregon: Pacific University Common Knowledge; 2016. [cited 2019 Jan 24]. Available from: https://commons.pacificu.edu/cgi/viewcontent.cgi?article=1014&context=opt


260


casE rEport

Autofluorescência em um caso de distrofia macular anular concêntrica benigna

Fundus autofluorescence in a case of benign concentric annular macular dystrophy

Resumo

A distrofia macular anular concêntrica benigna (DMACB) é uma patologia retiniana rara e provavelmente subdiagnosticada em nosso meio, que se caracteriza por um defeito retiniano em bull’s eye sem uso prévio de antimaláricos, associado à preservação relativa da acuidade visual. Devido à escassez de publicações sobre o tema, existem poucos dados referentes aos resultados dos exames complementares nesta patologia. No presente artigo, apresenta-se a descrição da autofluorescência em um caso clássico de DMACB, ainda inédita na literatura, podendo acrescentar achados importantes para auxiliar no diagnóstico e seguimento da doença.

Descritores: Distrofia retiniana; Distrofia macular; Autofluorescência retiniana; Oculopatias.

AbstrAct

The benign concentric annular macular dystrophy (BCAMD) is a very rare and probably underdiagnosed eye disease, characterized by a retinal fault in bull’s eye pattern, without the association with antimalarial use, but related with good visual acuity. Since there aren’t many publications about this condition, is hard to find data regarding the results of complementary examination. In this article, is presented the description of fundus autofluorescence in a classic BCAMD case, yet unpublished, and capable of helping the diagnosis and follow-up of this pathology.

Keywords: Retinal dystrophy; Macular dystrophy; Fundus Autofluorescence; Eye disease.

1 Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brazil. 2 Universidade Federal Fluminense, Niterói, Rio de Janeiro, RJ, Brazil.

Clarissa dos Reis Pereira1 https://orcid.org/0000-0001-5006-0288 Maurício B. Pereira2 https://orcid.org/0000-0002-1527-4448 Eduardo de França Damasceno2 https://orcid.org/0000-0002-7881-3584



261

IntRoductIon

Benign concentric annular macular dystrophy (BCAMD) is a rare condition with no estimated incidence.(1) The disease was first described by Deutman in 1974,(2)

and is characterized by a ring of hypopigmentation around a seemingly normal fovea (bull’s eye) but without previous history of antimalarials use.(2) In general, visual acuity is good or slightly impaired, and there may be dyschromatopsia, especially in the blue-yellow spectrum.(1-4) It has an autosomal dominant inheritance,(2) being important to consider the family history as a contributing factor for the diagnosis.(1) Although rare, its importance lies in the differential diagnosis of other macular degenerations that do not have a benign visual prognosis.(1,3-6)

Complementary examinations help in the differentiation of such more serious pathological conditions. Fluorescein angiography shows a Retinal pigment epithelial window defect translated by ring hyperfluorescence around the fovea.(1,3,4) The visual field may demonstrate typical annular scotoma or only paracentral defects;(1-4) the full-field electroretinogram (ERG) tends to be normal since it is a disease restricted to the macular region.(1,3-6) There are rare descriptions of optical coherence tomography (OCT) in the literature reporting sensorineural retinal atrophy associated with RPE thickening with areas of high and low reflectivity below it.(7)

To date, few cases have been reported, and there is no scientific publication on the autofluorescence pattern exclusively in this condition. Thus, the importance of such a description is justified to add data in the evaluation of BCAMD.

objectIve

To describe the findings of autofluorescence in a classic case of benign concentric macular annular dystrophy, adding data to the diagnosis of this rare condition which is one of the differential diagnoses of target maculopathies.

cAse RepoRt

SS, 68 years old, male, complaining of LVA after phacoemulsification of the LE about 1 year ago. He denies pain, ocular hyperemia or other symptoms. He denies complications or post-surgical trauma. He has systemic arterial hypertension well controlled with Losartan 50 mg/day. He denies other comorbidities or the use of other medications throughout life. There are no relevant data in family history. It was not possible to examine his parents as they had already died; the patient has no siblings. His children did not want to be examined so far.

At ophthalmologic examination, corrected vision was 20/25 RE (-1,25 ESF), and 20/50 LE (-2,75 ESF). Ishihara test revealed dyschromatopsia (2 plates/16). The anterior segment biomicroscopy showed 2+ corticonuclear cataract in the RE, and topical IOL in the LE, with no evidence of posterior capsule opacity. There were no signs of previous ocular inflammation, and the IOP was normal in BE. Fundoscopy showed an increase in the excavation/disc ratio of 0.6Vx0.6H in the RE and 0.5VX0.6H in the LE, and a ring of hypopigmentation concentric to the fovea (bull’s eye) in BE, with a more pronounced atrophy in the LE, where it was also observed hyperpigmented lesion adjacent to the ring in the inferior temporal region suggestive of bony spicule (Figures 1 and 2).


OCT revealed significant atrophy of the sensorineural retina with a central thickness of 170 microns in the RE and 150 microns in the LE. There was also a slight thickening of RPE with areas of hypo- and hyperreflectivity sub-RPE more evident in the LE (Figure 3).

The full field ERG was normal (Figure 4), and the computerized visual field (CVF) strategy 60.2 (Humphrey, Zeiss, Germany) showed typical annular scotoma (Figure 5) with relative preservation of the 10th central in the CVF strategy 10.2 (Figure 6), although the parameters were not fully reliable due to the patient’s difficulty in maintaining the fixation in the first campimetry carried out..

Figure 1: Color retinography of the RE and LE revealing the characteristic image of bull’s-eye macular atrophy.

Figura 2: Enlarged color retinography of the RE and LE revealing the characteristic image of bull’s-eye macular atrophy and pigmented lesion in the LE.

Figure 3: OCT optical section showing significant atrophy of the foveal sensorineural retina.

Fundus autofluorescence in a case of benign concentric annular macular dystrophy


262


Figure 7: Autofluorescence retinographies of the RE and LE.

Autofluorescence showed concentric ring hypo autofluorescence to a discreetly hypoaurofluorescent fovea in BE. In the LE, we also observed small satellites to the ring, also hypoautofluorecent (Figure 7).

Adding the clinical and complementary findings, besides considering the preservation of visual acuity in the sixth decade of life, to the typical findings of target maculopathy with no history of antimalarials use, the diagnosis of BCAMD was determined keeping the patient under ambulatory follow-up twice a year.

Figure 4: Full field ERG

Figure 5: Computerized visual campimetry (60.2) of the RE and LE

Figure 6: Computerized visual campimetry (10.2) of the RE and LE

dIscussIon

Despite its first description in 1974 by Deutman, (2) BCAMD remains a rare entity to date, with few cases reported in the literature. Because of its mostly benign nature and difficulty in accessing specialized care, it may be underdiagnosed in our country.

Satisfactory visual acuity was initially reported as a striking finding of this condition, but some evidence already contradicts this statement presenting cases with progression of tapetorretin dystrophy, (4,5) consequent worsening of VA, dyschromatopsia (mainly involving the blue-yellow spectrum), and exceptionally the development of bony spicules and/or subretinal neovascular membrane.(4,5)

However, the importance of this condition still lies in the differential diagnosis of other pathologies with expectation of worse vision, such as cone dystrophy, retinal toxicity by antimalarials, Stargardt’s disease, and central aerolar choroidal atrophy. (1-6)

Inheritance is autosomal dominant with wide variability of clinical expression. (1,2) There is a possible association with mutations in the IMPG1 gene located on chromosome 6. (5,6)

The most typical finding of BCAMD is a concentric and bilateral atrophy of RPE around the fovea (1-6) manifesting in fluorescein angiography as a hyperfluorescent ring concentric to the macular region. (3,4,6)

The OCT in this condition has already been described by Burton et al., (7) but their findings are nonspecific. Despite this, the patient in the case reported has a very similar pattern to the above, which corroborates his diagnosis and reaffirms this complementary examination as one of the tools to elucidate BCAMD.

The Full Field ERG tends to be normal as it is a macula-restricted disease. (3-6) Multifocal ERG would be more expressive in this case.

The visual field reflects the defect found in the fundoscopy, evidencing annular scotoma corresponding to the ring of atrophy of the RPE surrounding the fovea. However, this ring pattern is not mandatory for the diagnosis, since the degree of macular lesion may be heterogeneous, revealing only paracentral defects also typical of BCAMD. (1,3,4)

Regarding autofluorescence in BCAMD, there are still no exclusive reports in the literature up to the present moment. Autofluorescence is a property of the retinal cells due to the production of lipofuscin in the external photoreceptor segments.(8) This metabolite is phagocytosed by RPE under normalconditions.(8) However, when there is a pathology involvingthe RPE-photoreceptor complex this process of metabolizinglipofuscin is impaired, causing its accumulation.(8) The more

Câmara SN, Barbosa Júnior JB, Barbosa KCR


263Fundus autofluorescence in a case of benign concentric annular macular dystrophy

Corresponding author: Maurício B. Pereira R. Alberto de Sequeira, 59 – Tijuca – Rio de Janeiro - BrazilZIP Code:20260-160E-mail: [email protected]


lipofuscin, the greater the autofluorescence of the tissue.(8) However, with the progression of the involvement and consequent death of the photoreceptors, there is a reduction of the pigment, decreasing autofluorescence.(8) Therefore, it is possible to consider this test as a good marker of RPE integrity, being useful to evaluate the progression of retinal dystrophies.(8)

In the patient of the reported case, we found hypoauto fluorescence in concentric halo in the macular region translating a marked atrophy of the RPE in this area. This alteration can be justified by the age of the patient who is already at the end of the sixth decade of life, corroborating evidence that the disease presents a structural progression that may or may not correlate with the functional damages since there is no marked low vision in this case, despite the typical annular scotoma in CVF 60.2.

Thus, it is possible to consider the autofluorescence examination as another tool for the diagnosis and follow-up of BCAMD, which has few publications, as it is such a rare condition and thus still poorly understood.

RefeRences

1. Mendonça LS, Lavigne LC, Chaves LF, Garcia JM, Isaac DL, ÁvilaM. Benign concentric annular macular dystrophy. Rev Bras Oftalmol. 2015;74(3):183–5.

2. Deutman AF. Benign concentric annular macular dystrophy. Am JOphthalmol. 1974;78(3):384–96.

3. Salinas Alamán A, Sádaba Echarri LM, Corcóstegui Crespo I, García Layana A. Benign concentric annular macular dystrophy. Arch SocEsp Oftalmol. 2005;80(1):45–8.

4. Pérez Alvarez MJ, Clement Fernández F. Benign concentricannular macular dystrophy: two cases. Arch Soc Esp Oftalmol.2003;78(8):451–4.

5. Van den Biesen PR, Deutman AF, Pinckers AJ. Evolution ofbenign concentric annular macular dystrophy. Am J Ophthalmol.1985;100(1):73–8.

6. Gómez-Faiña P, Alarcón-Valero I, Buil Calvo JA, Calsina-Prat M,Martín-Moral D, Lillo-Sopena J, et al. Benign concentric annularmacular dystrophy. Arch Soc Esp Oftalmol. 2007;82(6):373–6.

7. Burton BJ, Holder GE, Duguid G, Gregory-Evans K. Opticalcoherence tomography findings in benign concentric annulardystrophy. Eye (Lond). 2005;19(6):699–701.

8. Côco M, Baba NT, Sallum JM. Avaliação da autofluorescência dofundo de olho nas distrofias de retina com o aparelho HeidelbergRetina Angiograph2. Arq Bras Oftalmol. 2007;70(5):739–45.


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Received for publication 02/01/2018 - Accepted for publication 08/03/2019.The authors declare no conflicts of interests..

casE rEport

Oclusão arterial retiniana transitória após facoemulsificação sob bloqueio anestésico

Transient retinal artery occlusion after phacoemulsification under local anesthetic block

AbstrAct

We here in report the case of a patient subjected to cataract surgery through phacoemulsification under local anesthetic block, without intra-operative complications. The patient presented important visual impairment in the first post-operative day. Fundoscopy showed pallor resembling cherry-red spots at the macula. Fluorescein angiography did not depict signs of vascular occlusion and the spectral-domain optical coherence tomography showed increased reflectivity in the inner layers of the retina, thus suggesting local thickening and edema. The current case led to the diagnostic hypothesis of transient retinal arterial occlusion.

Keywords: Retinal artery occlusion; Cataract extraction; Phacoemulsification; Cataract/surgery.

Resumo

Relatamos um caso de um paciente submetido a facectomia por facoemulsificação sob bloqueio anestésico peribulbar, sem intercorrências per-operatória, que apresentou no primeiro dia de pós-operatório baixa visual significativa. À fundoscopia observou-se palidez em aspecto de mácula em cereja. A angiofluoresceinografia não demonstrou sinais de oclusão vascular e a tomografia de coerência óptica mostrou aumento da refletividade das camadas internas da retina, sugerindo espessamento e edema local. No caso descrito foi aventada hipótese diagnóstica de oclusão arterial retiniana transitória.

Descritores: Oclusão da artéria retiniana; Extração de catarata; Facoemulsificação; Catarata/cirurgia.

1 Hospital Municipal da Piedade, Rio de Janeiro, RJ, Brazil. 2 Departamento of Cataract, Hospital Municipal da Piedade, Rio de Janeiro, RJ, Brazil. 3 Departament of Retina, Hospital Municipal da Piedade, Rio de Janeiro, RJ, Brazil.


João Hélio do Nascimento Ribeiro Valentim1 https://orcid.org/0000-0001-6777-0278Bruno Sá Antunes de Souza1,2 https://orcid.org/0000-0002-9246-9695Ícaro Silva Lopes1,2 https://orcid.org/0000-0003-4413-1027Leandro Lopes Troncoso2 https://orcid.org/0000-0002-2269-095XAlexandre Mendonça de Barros Junior1,3 https://orcid.org/0000-0002-3821-283X


265

IntRoductIon

Senile cataract is considered a public health issue due to its large incidence. The number of recorded cases grows in a yearly basis and the affected people demand surgical treatment.

Cataract surgery is the most cost-effective intervention for vision recovery, besides representing great impact on society. (1,2)

Patients’ expectations about cataract surgery increased after the introduction of new tools and enhanced techniques in the surgical methods. Most surgeries end up with excellent results; patients, as well as surgeons, do not tolerate eventual complications.(3)

Anesthesia in cataract surgery has evolved from general to local block (retrobulbar, peribulbar, subconjunctival or sub-Tenon anesthesia) and, subsequently, to topical anesthesia. With regard to local anesthesia, peribulbar blocking is the safest alternative in comparison to the retrobulbar one, since the needle used in it is shorter and its tip stays out of the retrobulbar space. Possible complications due to the retrobulbar anesthesia include retrobulbar bleeding, eyeball penetration, direct injury in the optic nerve, drug toxicity and mechanical compression due to the anesthetic volume.(4,5)

Retinal artery occlusion is a rare complication in cataract surgeries conducted through phacoemulsification; however, it is potentially devastating. Transient retinal artery occlusion (TRAO) is a challenge; moreover, diagnostic delay can cover fundoscopic and fluorescein angiographic abnormalities, which are only visible in the acute stage of the disease. Spectral domain optical coherence tomography (SD-OCT) is the only imaging modality capable of providing objective TRAO evidences in the late stages of the disease.(6)

cAse RepoRt

The case regards a 71-year-old, white, male, smoker (smoking load of 40 packs year) patient with history of systemic arterial hypertension (under irregular treatment). He presented to a medical screening in the cataract sector of Piedade Municipal Hospital. The visual acuity measurement recorded 0.2 with the best correction and 1.0 in the super pin hole in both eyes. Biomicroscopy presented transparent corneas, wide anterior chamber with no reaction, trophic irises, isochoric and photoreagent pupils, nuclear III / VI and subcapsular posterior III / V cataract in both eyes according to the LOCS III classification(7). Goldmann applanation tonometry showed intraocular pressure (IOP) of 15 / 16 mmHg. Biomicroscopy of the posterior segment only depicted typical alterations of hypertensive retinopathy: the presence of pathological arteriovenous junctions and the narrowing of the arteriolar caliber.

The patient underwent uneventful cataract surgery through phacoemulsification and intraocular lens implantation in the right eye. The procedure was conducted under peribulbar anesthetic blocking, which was performed by anesthetist, by using 2% lidocaine solution without vasoconstrictor, 0.5% bupivacaine and hyaluronidase.

The patient presented visual acuity of hand movement in the operated eye in the first post-operative day, besides no other complains or symptoms. The biomicroscopic exam (Figure 1) depicted diffuse subconjunctival bleeding, transparent cornea with edema (1+/4+), wide anterior chamber with no reaction, photoreagent pupil, trophic iris, topical intraocular lens and IOP

of 18 mmHg. The posterior segment presented pallor macular region with edema of cherry-red spot aspect, thus suggesting occlusion of the central retinal artery. Fluorescein angiography did not evidence signs of arterial or venous flow obstruction or any other significant changes (Figure 2), whereas SD-OCT showed thickening of and edema in the inner layers of the retina (Figure 3); both exams were performed 24 hours after the surgical procedure. The patient was subjected to carotid transthoracic echocardiogram and Eco Doppler, that presented changes compatible to his age.


Figure 3: OCT-SD recording the increase in macular thickness

Figure 1: First postoperative day. A. Diffuse direct lighting biomicroscopy; B. Optical cut lighting evidencing corneal edema (1 + / 4 +); C. Optical section illumination under mydriasis showing intraocular lens implanted inside the capsular bag;

Figure 2: A. Color retinography showing macular ischemia image (macula in cherry); B. Arteriovenous flurescein angiography; C. Fluorescein angiography, venous phase;

The patient had partial visual acuity improvement 72 hours after the surgery, with central positive scotoma and visual acuity of counting fingers at one meter in the temporal peripheral vision field, without any improvement in the super pin hole. He attended regular follow-ups for 90 days, but he did not show evolutive visual acuity improvement. Based on the current frame, the patient was posteriorly underwent to cataract phacoemulsification in the left eye performed by an expert surgeon, under topical anesthesia (1% lidocaine, 1ml solution in anterior chamber), without complications either throughout surgery or in post-operative stages. The patient reached vision 1.0 with no optical correction.

Transient retinal artery occlusion after phacoemulsification under local anesthetic block


266

dIscussIon

The introduction of new surgical techniques in phacoemulsi-fication, such as the use of small incisions, was followed by changes in the choice of the anesthetic technique. The akinetic blocks performed with needles, such as the retrobulbar and peribulbar blockings, have been slowly replaced by methods that do not use needles, such as the topical anesthesia, which leads to good results and to low complication levels, because it is less invasive.(8)

TRAO is a potentially sub-diagnosed cause of acute post-operative vision loss in patients subjected to cataract surgery through phacoemulsification under local anesthesia (sub-Tenon, peribulbar and retrobulbar).(6)

There are different levels of visual complications depending on the extension and duration of the vascular occlusion or spasm.(9, 10) Privation with anoxia for longer than 97 minutes is already enough to cause irreversible cell damage; after 4 hours there is massive irreversible retinal damage.(11) Accordingly, short-duration TRAO may not produce visual symptoms; therefore, it may not be diagnosed.(11,12)

Morgan et al.(13) and Sullivan et al.(14) described the adverse effects of retrobulbar anesthesia such as retrobulbar bleeding, central retinal artery occlusion (CRAO) and complication with potential risk of vision loss.

Behera et al.(15) reported two retinal artery occlusion cases deriving from direct injuries in the optic nerve during the anesthetic procedure. The accidental insertion of a needle in the optic nerve may have disastrous consequences, which include bleeding in the optic nerve sheath, retrobulbar bleeding and anesthesia of the brainstem. The retinal vascular occlusion and the Purtscher’s retinopathy are the other possible vascular complications. The pathophysiology has been in many ways attributed to the direct penetration of the needle in the optic nerve, to drug toxicity, to mechanical compressions or to vasospasm due to an adjuvant vasoconstriction agent.

TRAO and CRAO reports after phacoemulsification are only found in small series of cases and in all the reports procedures were performed under local anesthetic block.(5, 6, 12, 16, 17) There are no publications on TRAO and CRAO after phacoemulsification with topical anesthesia, thus suggesting a possible mechanical effect caused by the anesthetic volume injected in the orbital region.(16) Local anesthesia is adopted worldwide in cataract surgeries and in other procedures; however, there are growing evidences that these anesthetic techniques are associated with IOP increase and with reduced ocular blood flow right after the administration of the anesthetic volume.(18-24)

Swamy et al.(17) suggested that the anesthetic fluid (sub-Tenon or peribulbar) can be withheld in the periocular connective tissue and cause focal mechanical compression of the central retinal artery. Compression is caused by fluid flow into the intraconal connective tissue or by its extraconal permanence in the sub-Tenon space after the peribulbar and sub-Tenon anesthesia, respectively. The pre-operative, post-anesthesia mechanical compression with the Honan balloon facilitates the flow passing, besides contributing to flow reduction in the central retinal artery.

Creese et al.(16) suggest that the transitory spasm or occlusion of the central retinal artery causes arterial hypofunction and subsequent ischemia or retinal infarction, with permanent vision loss. Thus, the clinical presentations of CRAO and TRAO can be seen as a spectrum of the same entity of the disease. The entire retina is affected when the ocular perfusion pressure through

the central retinal artery is significantly reduced; it gets clinically pallor and the macular region gets cherry-red spots typical of CRAO. If hypoxia is transitory, the clinical aspect of TRAO is not apparent, since the ischemia would be more limited to the internal nuclear layer of adjacent layers. It is possible that the eyes with pre-existing low retinal perfusion are more susceptible to transitory compression or spasm in the central retinal artery due to an underlying vasculopathy, just as in the presented case. The patient in the current study presented risk factors such as systemic arterial hypertension (under irregular treatment) and smoking.

With regard to the here in presented case, and based on the patient’s risk factors for vascular diseases, it is worth taking into account the hypothesis that the presence of underlying arterial disease with pre-existing tissue hypoperfusion was made worst by increased intraorbital pressure, which was caused by the anesthetic injection. The compression caused by the anesthetic fluid may have led to increased IOP and to temporary reduction of the retinal artery flow. Thus, as TRAO can be a devastating condition, topical anesthesia must be the option of choice, since it is a safer anesthetic administration method, mainly in patients with known vascular disease.

RefeRences

1. José NK, Arieta CE, Temporini ER, Kang KM, Ambrosio LE.Tratamento cirúrgico de catarata senil: óbices para o paciente. ArqBras Oftalmol. 1996;59(6):573–7.

2. Kara-José N, Temporini ER. Cirurgia de catarata: o porquê dosexcluídos. Rev Panam Salud Publica. 1999;6(4):242–8.

3. Fesharaki H, Peyman A, Rowshandel M, Peyman M, Alizadeh P,Akhlaghi M, et al. A comparative study of complications of cataract surgery with phacoemulsification in eyes with high and normal axial length. Adv Biomed Res. 2012;1:67.

4. El-Hindy N, Johnston RL, Jaycock P, Eke T, Braga AJ, Tole DM, etal.; UK EPR user group. The Cataract National Dataset ElectronicMulti-centre Audit of 55,567 operations: anaesthetic techniques and complications. Eye (Lond). 2009;23(1):50–5.

5. Vinerovsky A, Rath EZ, Rehany U, Rumelt S. Central retinal artery occlusion after peribulbar anesthesia. J Cataract Refract Surg.2004;30(4):913–5.

6. Yusuf IH, Fung TH, Wasik M, Patel CK. Transient retinal arteryocclusion during phacoemulsification cataract surgery. Eye (Lond). 2014;28(11):1375–9.

7. Chylack LT Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA,Bailey IL, et al.; The Longitudinal Study of Cataract Study Group. The Lens Opacities Classification System III. Arch Ophthalmol.1993;111(6):831–6.

8. Reddy SC, Thevi T. Local anaesthesia in cataract surgery. Int JOphthalmic Res. 2017;3(1):204–10.

9. Burger SK, Saul RF, Selhorst JB, Thurston SE. Transient monocular blindness caused by vasospasm. N Engl J Med. 1991;325(12):870–3.

10. Korenfeld MS, Vasospasm and transient monocular blindness. NEngl J Med. 1992;326(12):838–9. Comment on Transient monocular blindness caused by vasospasm. [N Engl J Med. 1991]

11. Hayreh SS, Zimmerman MB, Kimura A, Sanon A. Centralretinal artery occlusion. Retinal survival time. Exp Eye Res.2004;78(3):723–36.

12. Feibel RM, Guyton DL. Transient central retinal artery occlusionafter posterior sub-Tenon’s anesthesia. J Cataract Refract Surg.2003;29(9):1821–4.

13. Morgan CM, Schatz H, Vine AK, Cantrill HL, Davidorf FH, GitterKA, et al. Ocular complications associated with retrobulbar injections. Ophthalmology. 1988;95(5):660–5.


Valentim JNHR, Souza BSA, Lopes ÍS, Troncoso LL, Barros Junior AM


267Transient retinal artery occlusion after phacoemulsification under local anesthetic block

14. Sullivan KL, Brown GC, Forman AR, Sergott RC, FlanaganJC. Retrobulbar anesthesia and retinal vascular obstruction.Ophthalmology. 1983;90(4):373–7.

15. Behera UC, Panda L, Gupta S, Modi RR. Subconjunctivalhemorrhage and vision loss after regional ocular anaesthesia. IntOphthalmol. 2017;38(3):1309-12.

16. Creese K, Ong D, Sandhu SS, Ware D, Alex Harper C, Al-Qureshi SH, et al. Paracentral acute middle maculopathy as a finding in patients with severe vision loss following phacoemulsification cataract surgery. Clin Exp Ophthalmol. 2017;45(6):598–605.

17. Swamy BN, Merani R, Hunyor A. Central retinal artery occlusionafter phacoemulsification. Retin Cases Brief Rep. 2010;4(3):281–3.

18. Hessemer V. Anästhesie-Effekte auf den okulären Kreislauf. Synopsiseiner Studie. Fortschr Ophthalmol. 1991;88(5):577–87.

19. Bowman R, Liu C, Sarkies N. Intraocular pressure changes afterperibulbar injections with and without ocular compression. Br JOphthalmol. 1996;80(5):394–7.

20. Joshi N, Reynolds A, Porter EJ, Rubin AP, Kinnear PE. An assessment of intraocular pressure during fractionated peribulbar anaesthesia. Eye (Lond). 1996;10(Pt 5):565–8.

21. Findl O, Dallinger S, Menapace R, Rainer G, Georgopoulos M, Kiss B, et al. Effects of peribulbar anesthesia on ocular blood flow in patients undergoing cataract surgery. Am J Ophthalmol. 1999;127(6):645–9.


Corresponding author: Bruno Sá Antunes de Souza Department of Ophthalmology - Hospital da Piedade Rua da Capela, no. 96 - Piedade - Rio de Janeiro, RJ - Brazil - 20740-310 Phone/fax: +55-32-98809-2280 E-mail: [email protected]

22. Chang BY, Hee WC, Ling R, Broadway DC, Beigi B. Local anaesthetic techniques and pulsatile ocular blood flow. Br J Ophthalmol.2000;84(11):1260–3.

23. Watkins R, Beigi B, Yates M, Chang B, Linardos E. Intraocularpressure and pulsatile ocular blood flow after retrobulbar andperibulbar anaesthesia. Br J Ophthalmol. 2001;85(7):796–8.

24. Pianka P, Weintraub-Padova H, Lazar M, Geyer O. Effect of sub-Tenon’s and peribulbar anesthesia on intraocular pressure and ocular pulse amplitude. J Cataract Refract Surg. 2001;27(8):1221–6.


268 casE rEport


Microscopia confocal no auxílio diagnóstico de Distrofia Corneana de Schnyder

In vivo confocal microscopy as a diagnostic tool in Schnyder Corneal Dystrophy’s case

AbstrAct

Schnyder’s corneal dystrophy (SCD) is a rare corneal condition characterized by cholesterol and phospholipids deposition in the stroma and Bowman’s layer. We present a case report of a patient who had a progressive corneal stromal haze in both eyes since he was 15 years old. Etiological diagnosis of SCD was well established by In Vivo Confocal Microscopy (IVCM).

Keywords: Corneal dystrophies, hereditary/diagnosis; Microscopy, confocal; Corneal stroma

Resumo

Neste relato, descrevemos um caso de Distrofia corneana de Schnyder que apresentou o desfecho de seu diagnóstico baseado em achados característicos na microscopia confocal, ferramenta que se aponta em destaque no universo oftalmológico.

Descritores: Distrofias hereditárias da córnea/diagnóstico; Microscopia confocal; Estroma corneano.

Débora Biazim1 https://orcid.org/0000-0002-2153-0364Diego Casagrande1 https://orcid.org/0000-0001-5158-5457Paula Kataguiri2 https://orcid.org/0000-0002-7972-548X

¹ Third year resident at Centro de Oftalmologia Tadeu Cvintal, São Paulo, SP, Brazil. 2 Department of Ophthalmology, Faculdade de Medicina do ABC, Santo André, SP, Brazil; Confocal Microscopy Service, Centro de Oftalmologia Tadeu Cvintal, São Paulo, SP, Brazil.

Study carried out at Centro de Oftalmologia Tadeu Cvintal – São Paulo, SP, Brazil.



269

IntRoductIon

Schnyder’s corneal dystrophy (SCCD) is a rare autosomal dominant disorder characterized by the appearance of disc-shaped corneal opacity, which begins in the first decade of life

and has a gradual progression of its intensity. Histopathologically, there are lipid deposits in the anterior stroma, especially in the central region. (1) Corneal crystals are present in 50% of pa-tients, so the International Committee for Corneal Dystrophies Classificaion modified the original name of Schnyder’s corneanacristalinian dystrophy for Schnyder’s corneal dystrophy in 2008. (2,3)

As for other corneal dystrophies, complementary examinations are necessary to diagnose this disorder. Among these, we highlight confocal microscopy, a method that is being used more frequently in the ophthalmologic universe, allows images of corneal structures in high resolution(4-6) and which provided us with characteristic and sufficient data for the conclusion of our case.

cAse RepoRt

A 55-year-old male, a trader, born in São Paulo, was admitted to our ser-vice with complaint of opacification of both eyes (BE) for 20 years, with progressive worsening in recent months. Concomitantly, it reported con-striction of the peripheral field without complaint of central visual acuity (VA), and in the right eye (RE) the symptomatology was more exacerbat-ed. Personal pathological history: treatment for hypercholesterolemia and the presence of genuvalgum, without other systemic comorbidities or previous ophthalmological disorders. Family pathological history: mother and brother with “whitish” eyes.

At the ophthalmologic exam, VA in the best correction in RE: 20/100 (under refraction: -1,25DE -0,25DC at 180°) and in left eye (LE): 20/20 (under refraction: -1.00DE - 0.50° C to 170°); to biomicroscopy, whitish corneal opacities arranged concentrically sparing central region and limbar, being worse in RE (Figure 1) and fundoscopy, poor visualization, requiring ultrasonographic documentation of normal intraocular structures.

Patient presents an excellent VA in LE and interestingly, the formation of a pinhole (Figure 2) and, therefore, the conduct for this eye, so far, expectant.

Due to the clinical-ophthalmologic findings, the initial diagnosis was lipid degeneration, and as a therapeutic approach to the complaint of the patient in RE, a penetrating transplant was performed, and in the postoperative period (Figure 3), patient, under refraction -0,25DE -3 , 00DC at 30 °, presented VA: 20/40

Due to the diagnostic doubt, we submitted the patient to the in vivo con-focal microscopy (IVCM) (Heidelberg Retina Tomograph 3 with Rostock Cornea Module, Heidelberg EngineeringGmbH, Heidelberg, Germany), in which we obtained normal images of the transplanted eye (Figure 4) and alterations in LE (Figure 5), such as: reduction of subepithelial nerve plexus density, marked reduction of keratocytes in the stroma and accumulation of needle-shaped material in anterior stroma, signaling a second, more accurate and reliable diagnosis: Schnyder’s Corneal Dystrophy, which also fit better into the clinical-epidemiological aspect of this report.

dIscussIon

Schnyder’s corneal dystrophy (SCCD) is a rare bilateral condition of autosomal dominant inheritance with variable expression. Their characteristics were first described in 1924 by the Germans van Went and Wibaut, (7) who took the first step in

Figure 1: Biomicroscopy of the right eye shows whitish corneal opacities arranged concentrically.

Figure 2: Biomicroscopy of the left eye shows a whitish corneal opacity arranged concentrically sparing the central region and the formation of a pinhole.

Figure 3: Biomicroscopy of the right eye after corneal penetrating transplantation shows transparent corneal button in 5-year follow-up.

Figure 4: Examination of confocal microscopy of the transplanted eye (RE) shows corneal stroma with structure and cellularity within normality.


In vivo confocal microscopy as a diagnostic tool in Schnyder Corneal Dystrophy’s case

Figure 5: Examination of confocal microscopy of the left eye shows changes such as reduction of subepithelial nerve plexus density, marked reduction of ker-atocytes in the stroma and accumulation of needle-shaped material in an-terior stroma.


270


Corresponding author: Paula Kataguiri Rua Caraíbas, 666 - apto.101 - São Paulo - SP - Brazil ZIP Code 05020-000 Phone/Fax: (11) 98135-9627 E-mail: [email protected]

Biazim DF, Casagrande D, Kataguiri P

describing findings that would later be grouped into a specific corneal dystrophy. This pathology is formed by the appearance of polychromatic thin subepithelial crystals in the central region of the cornea, which can reach the stroma and assume a discoid pattern in most of the affected ones. (8) Histologically, there are accumulations of cholesterol and neutral fat in the epithelium, Bowman’s layer and anterior corneal stroma. (9,10)

The corneal alterations can already be seen in the first decade of life, with slow progression until the 20 and 30 years of age, and an intensified increase of the opacities after the fourth decade (1) manifestation analogous to that of our patient, as he resorted to ophthalmologic care when it was already in late adulthood.

The main systemic finding is hypercholesterolemia, however, it has already been reported in the literature that there is no correlation between blood cholesterol levels and the severity of the disease (11) and that its systemic reduction does not prevent the progression of the disease. (12) In addition, we have a description of genuvalgum as another possible component of the clinical picture of SCCD, (5) both of which are present in our report.

Often, the SCCD hypothesis requires complementary tests to be validated, due to the countless possibilities of differential diagnoses, including Bietti’s crystalline dystrophy, Tangier’s disease, cystinosis, type 2 tyrosinemia, infective keratopatiacristaliana, gout, multiple myeloma, as well as, after using certain substances used for treatment under the most diverse conditions, being exemplified by chloroquine, clofazimine, chlorpromazine and gold. (13)

An important weapon for distinguishing such pathologies is genetic analysis and biomolecular profile. In this context, the description of the mutation in the UBIAD1 gene is responsible for the development of Schnyder’s Dystrophy (14) making the diagnosis more accurate. However, genetic mapping often remains within an ideal world, forcing us to look for other diagnostic tools. Invented in 1955, confocal microscopy in vivo, a method that allows the diagnosis of numerous corneal disorders, (15,16) including the diagnosis of Schnyder’s Dystrophy.

The IVCM allows non-invasive corneal optic section and other structures in real time and at the cellular level. Images are obtained from different depths and allow an 800-fold increase of the corneal structures. (1)

The trajectory for the creation of this equipment was not banal. The contact with the microscope universe was first made in the mid-1950s, when pioneers Marvin and Minsky (17)

developed the first confocal microscope in order to study neural networks in vivo. In 1986, LempEt al. (18) inaugurated in vitro cornea research, and his study contributed to the development of tandem scanningconfocalmicroscope (TSCM) with the objective lens horizontally, which made it suitable for ophthalmologic use. Already in the early 90s, Cavanagh(13) was the pioneer of corneal studies in vivo with confocal microscopy. To finish the script, Masters and Thaer, in 1994 made a new variation of the IVCM, generating SSMC (scanning-slitconfocalmicroscope), base system used in the current models. (19,20)

This device was shown to be an advance on specular microscopy because it is effective in evaluating all layers of the cornea, including partially opaque corneal conditions, due to edema or scarring, (5) which makes it very useful in SCCD, even for this report, in view of the high degree of opacity present, which would preclude an accurate evaluation of all corneal lamellae.

In our case, left-sided IVCM findings, such as: decreased subepithelial nerve plexus density associated with marked reduction of stroma keratocytes and accumulation of needle-shaped material in anterior stroma are corresponding characteristics evidenced in scientific publications correlated with the diagnosis of Schnyder’s dystrophy. (5, 15, 16)

conclusIon

Finally, we did not present histopathological and genetic evidence due to sufficient clinical-epidemiological data and typical findings of the SCCD in the confocal microscopy to close the diagnosis, highlighting the magnitude of this equipment in the arsenal of complementary examinations of Ophthalmology.

RefeRences

1. Alves MR. Hofling-Lima AL, Nishiwaki-Dantas MC. Doenças externasoculares e córnea. 4th ed. Alves MR, editor. Rio de Janeiro: CulturaMédi-ca; 2016.

2. Nowinska AK, Wylegala E, Teper S, Lyssek-Boron A, Aragona P,Roszkowska AM, et al. Phenotype-genotype correlation in patientswith Schnyder corneal dystrophy. Cornea. 2014;33(5):497–503.

3. Weiss JS, Møller HU, Aldave AJ, Seitz B, Bredrup C, Kivelä T, et al. IC3D classification of corneal dystrophies. edition 2. Cornea. 2015;34(2):117–59.

4. Erie JC, McLaren JW, Patel SV. Confocal microscopy in ophthalmology. Am J Ophthalmol. 2009;148(5):639–46.

5. Kobayashi A, Fujiki K, Murakami A, Sugiyama K. In vivo laser confocal microscopy findings and mutational analysis for Schnyder’s crystalline corneal dystrophy. Ophthalmology. 2009;116(6):1029–37.e1.

6. Werner LP, Werner L, Dighiero P, Legeais JM, Renard G.Confocal microscopy in Bowman and stromal corneal dystrophies.Ophthalmology. 1999 Sep;106(9):1697–704.

7. Van Went JM, Wibaut F. Een zyeldzame erfelijke hoornvliesaandoening. Ned Tydschr Geneesks. 1924;68(1st half, B): 2996-7

8. Lisch W, Weidle E, Lisch C, Rice T, Beck E, Utermann G. Schnyder’s dys-trophy. Progression and metabolism. Ophthalmic Paediatr Genet. 1986;7(1): 45-56.

9. Garner A, Tripathi RC. Hereditary crystalline stromal dystrophy ofSchnyder. II. Histopathology and ultrastructure. Br J Ophthalmol.1972;56(5):400–8.

10. Weller RO, Rodger FC. Crystalline stromal dystrophy: histochemistryand ultrastructure of the cornea. Br J Ophthalmol. 1980;64(1):46–52.

11. Vesaluoma MH, Linna TU, Sankila EM, Weiss JS, Tervo TM. In vivocon-focal microscopy of a family with Schnyder crystalline cornealdystrophy. Ophthalmology. 1999;106(5):944–51.

12. Weiss JS, Khemichian AJ. Differential diagnosis of Schnyder cornealdystrophy. Dev Ophthalmol. 2011;48:67–96.

13. Cavanagh HD, Petroll WM, Alizadeh H, He YG, McCulley JP, Jester JV. Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology. 1993;100(10):1444–54.

14. Kobayashi A, Fujiki K, Fujimaki T, Murakami A, Sugiyama K. In vivo la-ser confocal microscopic findings of corneal stromal dystrophies.Arch Ophthalmol. 2007;125(9):1168–73.

15. Jing Y, Wang L. Morphological evaluation of Schnyder’s crystallinecorneal dystrophy by laser scanning confocal microscopy andFourier-domain optical coherence tomography. Clin Exp Ophthalmol. 2009;37(3):308–12.

16. Ciancaglini M, Carpineto P, Doronzo E, Nubile M, Zuppardi E, Mastro-pasqua L. Morphological evaluation of Schnyder’s central crystalline dys-trophy by confocal microscopy before and after phototherapeutic keratectomy [x]. J Cataract Refract Surg. 2001;27(11):1892–5.

17. Minsky M. Memoir on inventing the confocal microscope. Scanning1988;10:128-38.

18. Lemp MA, Dilly PN, Boyde A. Tandem-scanning (confocal)microscopy of the full-thickness cornea. Cornea. 1985-1986;4(4):205-9.

19. Masters BR, Thaer AA. Real-time scanning slit confocal microscopy of the in vivo human cornea. Appl Opt. 1994 Feb 1;33(4):695-701. doi: 10.1364/AO.33.000695.

20. Masters BR, Thaer AA. In vivo human corneal confocal microscopyof identical fields of subepithelial nerve plexus, basal epithelial, andwing cells at different times. Microsc Res Tech. 1994 Dec 1;29(5):350-6.


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The authors dwclare no conflicts of interests.

Síndrome de Tolosa-Hunt, uma oftalmoplegia dolorosa

Tolosa Hunt Syndrome, a painful ophthalmoplegia

Resumo

A síndrome de Tolosa-Hunt (STH) é uma doença rara caracterizada por oftalmoplegia dolorosa unilateral de início súbito causada por uma inflamação granulomatosa inespecífica no seio cavernoso ou fissura orbital superior (ou ambos). A oftalmoparesia ocorre quando os nervos cranianos III, IV e VI são acometidos pela inflamação. Disfunções pupilares podem estar presentes e está relacionado com acometimento das fibras simpáticas que passam pelo seio cavernoso na porção da artéria carótida interna ou fibras parassimpáticas ao redor do nervo oculomotor. O acometimento do primeiro ramo do trigêmeo pode provocar parestesia território correspondente à distribuição desde ramo (testa). Raramente, pode haver extensão da inflamação para além do seio cavernoso ou fissura orbital superior podendo acometer também o nervo óptico. Há uma boa resposta com o uso de corticoides e pode haver remissões espontâneas. Recidivas ocorrem em 40% dos casos. A doença é mais comum após a segunda década de vida. Afeta ambos os gêneros de forma igualitária. O presente estudo trata-se de um relato de caso de um paciente que se apresentou com oftalmoplegia dolorosa de início súbito à direita com 4 dias de evolução seguido de amaurose ipslateral após um dia do início da dor.

Descritores: Síndrome de Tolosa-Hunt; Oftalmoplegia; Cefaleia; Síndrome de nervos cranianos

AbstrAct

Tolosa-Hunt syndrome (STH) is a rare disease characterized by sudden onset unilateral painful ophthalmoplegia caused by non-specific granulomatous inflammation in the cavernous sinus or superior orbital fissure (or both). Ophthalmoparesis occurs when the cranial nerves III, IV and VI are affected by inflammation. Pupillary dysfunctions may be present and is related to involvement of the sympathetic fibers that pass through the cavernous sinus in the portion of the internal carotid artery or parasympathetic fibers around the oculomotor nerve. The involvement of the first branch of the trigeminal can cause paresthesia corresponding to the distribution from the first branch (forehead). Rarely, there may be extension of inflammation beyond the cavernous sinus or superior orbital fissure and may also affect the optic nerve. There is a good response with the use of corticosteroids and there may be spontaneous remissions. Relapses occur in 40% of cases. The disease is most common after the second decade of life. It affects both genders equally. The present study is a case report of a patient who presented with painful ophthalmoplegia of sudden onset on the right with 4 days of evolution followed by ipsilateral amaurosis after one day of onset of pain.

Keywords: Tolosa-Hunt syndrome; Ophthalmoplegia; Headache; Cranial nerves syndrome

1 Department of Neurology, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.

Maxuel Nogueira dos Santos Junior1 https://orcid.org/0000-0002-3451-6107Alex Eduardo Siva1 https://orcid.org/0000-0002-0999-0165Renata Cristina Franzon Bonatti1 https://orcid.org/0000-0001-7452-2563

Study carried out at Hospital de Clínicas da Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.



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improvement of direct photomotor response in the right eye, and cure of paresthesia in the territory of the ophthalmic branch of the trigeminal nerve.

dIscussIon

The case reported initially presented painful ophthalmoplegia to be studied, and with laboratory and imaging examinations it was possible to suggest the diagnostic hypothesis of THS, with the choice for treatment in immunosuppressive doses with glucocorticoids.(8-10)

THS is a rare disease of unknown etiology of equal distribution between genders, with a higher incidence after the age of 20 years. The most affected nerves are the oculomotor (85%), abducent (70%), ophthalmic branch of the trigeminal nerve (30%), and trochlear (29%).The syndrome is usually unilateral, but can rarely be presented bilaterally (4-5%).(3) Involvement of the maxillary and mandibular branches of the trigeminal as well as oculomotor nerve (present in the case reported) and facial nerve have also been reported when there is an extension of the inflammatory process beyond the cavernous sinus.(3) Without treatment, symptoms usually regress spontaneously within 8 weeks in most cases. It is important to emphasize that most patients with painful ophthalmoplegia (> 75% of cases) will not be diagnosed with THS. Tumors and vascular causes are the most common ones.(12) The vast majority of differential diagnoses can be made withan MRI of the encephalon.(7,11,12) The diagnosis is made based on3 pillars: clinical presentation, image examination, and responseto corticosteroid therapy.(3) Biopsy is rarely performed due totechnical difficulties.(2)

The diagnostic criteria for THS according to the ICHD-3 beta 2013 are:

A. Unilateral pain meeting criterion CB. Both of the following:1. Granulomatous inflammation of the cavernous sinus,

superior orbital fissure or orbit demonstrated by MRI or biopsy.2. Paresis of one or more of the III, IV and/or IV ipsilateral

cranial nervesC. Evidence of causality demonstrated by both of the

following:1. Headache preceding paresis of the III, IV and/or VI

nerves for <2 weeks or developed with it2. Headache located around the eye and ipsilateral

eyebrowD. Not better explained by another diagnosis of ICHD-3

beta.(7)

There is usually a dramatic response with corticosteroid therapy, with resolution of pain in 24-72 hours (40% in the first 72 hours, and 78% in up to 1 week). Ophtalmoplegia presents a slower resolution (2-8 weeks).(13) Infrequently, residual neurological deficits may persist indefinitely. Relapses usually occur in half of the patients, ranging from months to years, and are more common in young people, and always require additional investigations to rule out inflammatory and neoplastic diseases.(14) There is no evidence that corticosteroid therapy alters the prognosis in frequency of relapses or persistent ophthalmoplegia. Regarding patients not responding to corticosteroid therapy, it is possible to use second-line therapy options. Therefore, a small group of patients will need association with immunosuppressants (acting as a corticosteroid sparger or as a potentiator in patients not responsive to corticosteroids).(13) The most commonly used medications are cyclosporine, azathioprine, methotrexate, mycophenolate mofetil,

IntRoductIon

The THS is a rare disease with an incidence of 1 case per 1 million per year, and characterized by painful ophthalmoplegia caused by an idiopathic granulomatous

inflammation in the cavernous sinus with good response to the use of glucocorticoids that was known some years after its first description in 1954 by Tolosa.(1-3) It is generally considered a benign condition, but permanent neurological deficits may occur, and relapses are frequent requiring prolonged immunosuppressive therapy in these cases.(4)

The present study aims to describe the pathophysiological and clinical characteristics, and the differential diagnosis, considering that it is an exclusion diagnosis and therapeutic measures according to the International Headache Society (IHS-2013) with the presentation of a clinical case. (5-7)

cAse RepoRt

The study describes the case of a patient treated in the ambulatory by the ophthalmology team of Hospital Escola da Universidade Federal do Triângulo Mineiro (UFTM), being hospitalized and transferred to the neurology service of said hospital. Diagnostic criteria was used according to the international classification of headache - The International Classification of Headache Disorders 3 Beta (ICHD-3 beta 2013) were used.(7) After excluding other differential diagnoses, the patient was treated with steroid therapy with good response. The follow-up time was only two months due to patient non-attendance to the ambulatory follow-up.

Male patient, 58 years old, hypertensive wiwth chronic kidney disorder with previous transplantation (1998), with placement of 2 stents in the circumflex artery 2 months before, alcoholic and smoker. He was on tacrolimus, prednisone 5mg daily, furosemide, clonidine, ASA, clopidogrel, and simvastatin when admitted to the UFTM Hospital after appointment with an ophthalmology team with report of intense periocular pain on the right started 4 days before with progress in hours for ophthalmoplegia due to involvement of the III, IV and VI cranial nerves on the right, followed by ipsilateral amaurosis by involvement of the II cranial nerve within 24 hours after the onset of pain. The following laboratory tests were carried out with normal results: hemogram, fasting glycemia, glycated hemoglobin, electrolytes, ESR, PRC, FAN, anti-HIV, VDRL, FTA-ABS, P-ANCA, C-ANCA, protein electrophoresis, and thyroid function. Lumbar puncture was also carried out to study cerebrospinal fluid with normal results, including cultures. Then, an imaging study was performed by magnetic resonance imaging (MRI) of the brain (Figures 1 and 2), which demonstrated inflammatory alterations in superior orbital fissure and in the right cavernous sinus, consistent with THS according to the clinical condition after exclusion of other differential diagnoses. Corticosteroid therapy was iniciated with prednisone 1mg/kg/day until solving the pain, which occurred 10 days after initiation of therapy, and then the corticosteroid therapy dose was gradually reduced for a period of 2 weeks. Hospitalization lasted 12 days, and 2 months after discharge the patient had a new MRI of the encephalon with significant reduction of the alterations when compared to the initial examination. It evolved with significant improvement of ophthalmoplegia and mild improvement of visual acuity, remaining with mild ophthalmoparesia after 2 months. There was


Santos Junior MN, Silva AE, Bonatti RCF


273Tolosa Hunt Syndrome, a painful ophthalmoplegia

and infliximab. There are some reports on use of radiotherapy in cases of relapse and in cases where initial treatment with corticosteroids is contraindicated.(13) Follow-up is carried out with encephalon MRI every 2 months to ensure the treatment is being effective and that no evidence of another etiology develops. Typically, radiological improvement comes much later than clinical improvement. After radiological normalization, MRI is suggested every 6 months for a period of 2 years.(14)

We then conclude with the present case study that due to the lack of a high specificity for the diagnosis of this pathology it is still necessary that it is made as an exclusion diagnosis. However, it should always be suspected in light of a suggestive clinical presentation based on the ICHD-3 beta criteria.(7)

Corresponding author: Maxuel Nogueira dos Santos Junior R. Jangadeiros Alagoanos, n. 1521, Pajuçara. Maceió – AL, Brazil.E-mail: [email protected]

Figure 1: Axial cut of MRI in T2 enlargement and hypersignal sequence in cavernous sinus and right orbit.

Figure 2: Coronal MRI cut in post-contrast T1 sequence showing enlargement and contrast hypercaptation in cavernous sinus region and right orbit.

RefeRences

1. Cohn DF, Carasso R, Streifler M. Painful ophthalmoplegia: theTolosa-Hunt syndrome. Eur Neurol. 1979; 18(6):373-81.

2. Hunt WE. Tolosa-Hunt syndrome: one cause of painfulophthalmoplegia. J Neurosurg. 1976; 44(5):544-9.

3. Kline LB, Hoyt WF. The Tolosa-Hunt syndrome. J Neurol NeurosurgPsychiatry. 2001; 71(5):577-82.

4. Gimenez-Roldan S, Guillem A, Munoz L. [Long-term risk of relapses in Tolosa-Hunt syndrome]. Neurologia. 2006; 21(7):382-5. Spanish.

5. La Mantia L, Curone M, Rapoport AM, Bussone G, InternationalHeadache Society. Tolosa-Hunt syndrome: critical literature review based on IHS 2004 criteria. Cephalalgia. 2006; 26(7):772-81.

6. Colnaghi S, Versino M, Marchioni E, Pichiecchio A, Bastianello S,Cosi V, et al. ICHD-II diagnostic criteria for Tolosa-Hunt syndrome in idiopathic inflammatory syndromes of the orbit and/or the cavernous sinus. Cephalalgia. 2008; 28(6):577-84.

7. Headache Classification Committee of the International Headache Society (IHS).The International Classification of HeadacheDisorders. 3rd ed (betaversion). London: Sage; 2013.

8. Yagi A, Sato N, Taketomi A, Nakajima T, Morita H, Koyama Y, et al. Normal cranial nerves in the cavernous sinuses: contrast-enhancedthree-dimensional constructive interference in the steady state MR imaging. AJNR Am J Neuroradiol. 2005; 26(4):946-50.

9. Kobor J, Voros E, Deak A. Magnetic resonance imaging in Tolosa-Hunt syndrome. Eur J Pediatr. 2004; 163(12):753-4.

10. La Mantia L, Erbetta A, Bussone G. Painful ophthalmoplegia: anunresolved clinical problem. Neurol Sci. 2005; 26 (Suppl 2):s79-82.

11. Go JL, Rajamohan AG. Imaging of the sella and parasellar region. Radiol Clin North Am. 2017; 55 (1):83-101.

12. Lane R, Davies P. Ophthalmoplegic migraine: the case forreclassification. Cephalalgia. 2010; 30(6):655-61.

13. Foubert-Samier A, Sibon I, Maire JP, Tison F. Long-term cure ofTolosa-Hunt syndrome after low-dose focal radiotherapy. Headache. 2005; 45 (4):389-91.

14. Johnston JL. Parasellar syndromes. Curr Neurol Neurosci Rep.2002;2(5):423-31.



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The authors declare no conflicts of interests.

Healing: use of collagen matrix

Cicatrização: uso de matriz de colágeno

1 Universidade Federal de Mato Grosso do Sul, Campo Grande, MS, Brazil. Glaucoma Department of Hospital de Olhos, Campo Grande, MS, Brazil; Glaucoma Department of Santa Casa de Misericórdia, Campo Grande, MS, Brazil. 2 Residency Program in Ophthalmology, Santa Casa de Misericórdia, Campo Grande, MS, Brazil. 3 Medicine Course, Universidade Estadual de Mato Grosso do Sul, Campo Grande, MS, Brazil.

Resumo

A matriz de colágeno Ologen TM é um novo agente antifibrótico composto por uma matriz porosa de atelocolageno tipo I e glicosaminoglicanos reticulados, que pode ser utilizado como uma alternativa para a modulação da cicatrização nas cirurgias. Por ser altamente poroso e biodegradável, este implante auxilia nos processos de reparação fisiológicos que ocorrem no tecido conjuntivo e epitelial da lesão, sem a formação de tecido fibrótico, o qual acarreta insucesso cirúrgico e elevação da PIO. A Trabeculectomia (TREC) é considerada a cirurgia padrão para o tratamento do glaucoma, no entanto as taxas de sucesso cirúrgico a médio e longo prazo estão relacionadas a cicatrização do sítio operatório, envolvendo principalmente o tecido conjuntival e tenoniano. O processo de cicatrização é divido em 4 fases principais: coagulativa, inflamatória, proliferativa e remodeladora, com uma série de cascatas químicas e fatores bioquímicos liberados na tentativa de restabelecer a hemostasia. Diversas pesquisas na literatura já demonstraram os efeitos benéficos na cicatrização ao utilizar a matriz de colágeno Ologen em cirurgias oftalmológicas, além das possíveis complicações. Os resultados dos atuais estudos com implante de Ologen para o tratamento de glaucoma são encorajadores e promissores. No entanto, ensaios clínicos randomizados futuros com seguimento a longo prazo são necessários para avaliarmos a segurança e a eficácia do novo implante na modulação da cicatrização, alcançando melhores taxas de sucesso cirúrgico.

Descritores: Cicatrização; Glaucoma/cirurgia; Ologen.

AbstrAct

The Ologen™ collagen matrix is a new antifibrotic agent composed of a porous matrix of type I atelocolagene and cross-linked glycosaminoglycans, which can be used as an alternative for the modulation of healing in surgeries. Because it is highly porous and biodegradable, this implant assists in the physiological repair processes that occur in the connective and epithelial tissue of the lesion without the formation of fibrotic tissue, which leads to surgical failure and IOP elevation. The Trabeculectomy (TREC) is considered the standard surgery for the treatment of glaucoma; however, the surgical success rates in the medium and long term are related to surgical site healing, mainly involving conjunctival and tenonian tissue. The healing process is divided into 4 main phases: coagulative, inflammatory, proliferative and remodeling, with a series of chemical cascades and biochemical factors released in an attempt to restore hemostasis. Since several researches in the literature have already demonstrated the beneficial effects on healing by using the Ologen collagen matrix in ophthalmic surgeries, in addition to possible complications. The results of current Ologen implant studies for the treatment of glaucoma are encouraging and promising. However, future randomized clinical trials with long-term follow-up are necessary to evaluate the safety and efficacy of the new implant in modulating healing, achieving better rates of surgical success.

Keywords: Healing; Glaucoma/surgery; Ologen.

Ana Cláudia Alves Pereira1 https://orcid.org/0000-0002-6464-947XKleber Cunha Clemente2 https://orcid.org/0000-0002-2766-948XBianca Hayashi Borges da Silva3 https://orcid.org/0000-0001-7228-1495Vitória Oshiro Orro3 https://orcid.org/0000-0002-2348-4779



275

the heAlIng pRocess

Classically, trabeculectomy (TREC) is considered the standard surgery for the treatment of glaucoma. However, the surgical success rates in the medium and long term are related to surgical site healing, mainly involving conjunctival and tenonian tissue. The healing process is divided into 4 main phases: coagulative, inflammatory, proliferative, and remodeling (Figure 1), with a series of chemical cascades and biochemical factors released in an attempt to restore hemostasis.(1)

In the earliest stages, the process is controlled by the immediate release of plasma proteins, blood cells, platelets, and local hormones by initially sealing the injured vessels. With tissue injury, there is the release of histamine, serotonin, and bradykinin causing vasodilation and increased blood flow at the site.(2) In the later stages, activated platelets play a key role by releasing chemical growth factors. These substances act as powerful inflammatory chemoattractants, and at the same time the coagulation factors are activated progressing with the first phase of healing.(3,4)

The microenvironment with its altered physicochemical composition initiates the influx of neutrophils and monocytes (later tissue macrophages), inaugurating the inflammatory phase. Growth factors released from macrophages and cytokines secreted by T-lymphocytes play a very important stimulatory roel in the initial phase and regulatory action in the late healing phase.(5,6)

The proliferative phase begins with the proliferation of epithelial cells in the periphery of the wound concomitant with angiogenesis and fibroplasia (production of collagen by fibroblasts), generating a new tissue matrix. Its main function is to restore the continuity of the damaged tissue, working as a framework for cell migration. The fibroblast is the main protagonist of this process, because in addition to the production of the main constituent of the cell matrix it differs in myofibroblast, which is a more contractile phenotype responsible for the traction of the wound margins.

Over time, this primitive fibrovascular tissue develops into a mature scar in the final stage of healing. The degradation of the extracellular matrix is mediated by plasminogen activators, and the matrix metalloproteinases by the removal of hyaluronic acid and fibronectin from the tissue. Fibroblast apoptosis is an important event in the remodeling phase, causing the wound to

become as close as possible to the initial tissue.(5,6) Its maturation is characterized by an increase in resistance without an increase in the amount of collagen because there is a balance between production and destruction of the collagen fibers during this period by the action of collagenases. The stages of healing are not mutually exclusive but overlapping in time.(7)

heAlIng modulAtoRs

Antimetabolite drugs, such as 5-fluorouracil (5 FU) and mitomycin C (MMC), are used to control healing in antiglaucomatous surgeries, especially in Trabeculectomy (Trec) and Non-Penetrating Surgeries (EPNP), in order to prevent the formation of scars and improve the success rate of surgeries. However, these substances are associated with increased complication rates such as blister leakage, hypotonia, choroidal detachment, blebitis, hypotonic maculopathy, and endophthalmitis.(6)

Ologen™ collagen matrix is a new antifibrotic agent comprising a porous matrix of atelocolagene type I and crosslinked glycosaminoglycans which can be used as an alternative for the modulation of healing in surgeries. Because it is highly porous and biodegradable, this implant assists in the physiological repair processes occuring in the connective and epithelial tissues of the lesion without the formation of fibrotic tissue, which leads to surgical failure and elevation of IOP.

It is believed that pores of the collagen matrix ranging in size from 20 to 200 mm guide randomly proliferating fibroblasts during the remodeling phase. A dynamic physiological reservoir is created to preserve the functionality of the surgery by the formation of a subconjunctival space. The healing process is prevented by the interaction between the tissue and the collagen matrix by optimizing and stabilizing the structure and composition of the ocular tissues, creating a mature fistula, as can be observed in the trabeculectomy surgery (Figures 2 and 3).

Figure 1: Cell repair process during and after the surgical process.

Source: Adapted from https://www.iogen.fi/wp-content/uploads/2017/10/ologen-trab-brochure_english-1.pdf

Figure 2: (A): A 38-year-old female submitted to TREC with MMC where we observe a diffuse avascular central blister with cystic area; (B): A 52-year-old man of the group TREC with ologen where we observe a diffuse blister with almost normal vascularization.

Source: Cillino et al. (2016).(7)


Cicatrização: uso de matriz de colágeno


276

Figure 3: TREC postoperative (PO) with OLO implant in left eye. A: 3 days of PO, B: 30 days of PO, C: 5 months of PO, D: 10 months of PO and E: 11 months of PO.

Source: Anguelov (2013).(8)

OlogenTM collagen matrix is available in different shapes and sizes (Figure 4). Its biodegradation occurs in a period of 3 to 6 months depending on the conditions of the inflammation and the degree of infiltration.

Thus, this new implant can be used as an antifibrotic device in different ophthalmologic surgeries, such as TREC (Fig. 5), EPNP, revision of fistulas or drainage implants, in order to create a healthy vascular blister especially in surgeries where the use of antimetabolites is not recommended, as in the elderly, patients with scleral or fine conjunctival tissue, a non-superior blister, history of MMC, and associated complications, among others.(8,9) (Table 1).

Figure 4: Ologen ^TM Collagen Matrix and its models.

Source: Adapted from https://www.ologen.com/product/

Results In the lIteRAtuRe

Evaluating the safety and efficacy of TREC with Ologen implant versus TREC with MMC, Ji et al.(10) carried out a meta-analysis with 6 randomized clinical trials finding a lower IOP reduction for surgeries with OLOGEN implants compared to MMC surgeries in all the intervals studied, except in the studies followed for more than 24 months. The complications reported were hypotonia with choroidal detachment, seidel, shallow anterior chamber, all with spontaneous resolution, similar in the 2 groups: TREC with Ologen implant and with MMC. There was no significant difference in the reduction of medications for glaucoma and in the success rate when comparing the 2 groups.

In a retrospective study of 24 patients (33 eyes) with POAG, Dada et al.(11) evaluated the results of TREC with the use of subconjunctival Ologen combined with low dose of MMC (0.1 mg/ml for 1 min). All eyes reached IOP ≤ 15mmHg, and only in the 6-month visit 2 eyes required hypotensive eye drops. Two eyes with shallow anterior chamber and hypotonia were reported during the

Figure 5: Trabeculectomy with Ologen implant. A: Trapezoidal scleral flap of 2.5 x 1.5 mm half-thickness made in the upper area. B: Trec was carried out with punch. C: The Ologen implant was positioned over the scleral flap without the use of any sutures. D: The conjunctiva was closed with nylon 10-0.

Source: Perez et al. (2016).(9)

Table 1 Advantages and Benefits of the Collagen Matrix OlogenTM

Characteristics Advantage Benefits

Porous Better remodeling Physiologicalstructure in host tissues reserve system

90%of atelocollagen Low rejeiction rate Minimal immune type I response

Natural Mimetiza ECM for Singular tissue biodegradation the regulation of growth

physical consistency

Flexible Long-term stabbilty Particularof biomechanical maintenance

tissue spaceExceptional Ready for use and Good adaptabilitydimensions easy to handle to ocular tissue

during surgery diversity

Source: Translated from http://www.aeonastron.com/product.php?catId=6


Pereira ACA, Clemente KC, Silva BHB, Orro VO


277Cicatrização: uso de matriz de colágeno

first week, with Seidel suggestive of leakage of conjunctival lesion. There was exposure of the implant in 1 eye after the first week of follow-up. Both were treated with conjunctive resuture. Two other eyes developed a Tenon’s cyst at the 8th and 12th postoperative week with elevation of IOP, being treated with infiltrations of 5mg of 5-fluorouracil.

Ologen Collagen Matrix has been used to repair drainage tube exposure as it acts as a tectonic support and biological activities to promote cellular infiltration by the host conjunctival stroma to the surroundings, thus reducing the thinning/erosion of the allogenic graft. (12)

El-Saied et al.(13) carried out a prospective, comparative study in 40 eyes of 40 patients with uncontrolled secondary glaucoma followed by failure of TREC with MMC (0.4 mg/ml for 2 min) and three needling attempts with a month interval. Trabeculectomy with Ologen implant was performed 1 month after the last needling. The patients were divided into two groups: Group A comprising 18 eyes of 18 patients with secondary open angle glaucoma, and group B with 22 eyes of 22 patients with secondary closed angle glaucoma. Patients from both groups achieved surgical success with IOP levels ranging from 5 to 18 mmHg. In said study, no intraoperative or postoperative complications were observed, except one eye that developed Dellen.

Dietlein et al.(14) used the Ologen implant in 12 patients who had previously undergone TREC with MMC and were suffering from subsequent ocular hypotonia. They obtained improvement in the IOP levels in the postoperative follow-up. In addition, 9 patients presented improvement in the visual acuity. However, some complications reported in the study were ocular hypotonia, and blister leak with implant exposure 2 weeks after surgery. For resolution, a rotational conjunctival flap was required. Another patient with ocular hypotonia and leakage developed corneal Dellen treated with artificial tears. The cases of choroidal detachment had spontaneous resolution, and 2 patients required hypotensive eye drops at the end of the follow-up period.

In a prospective, comparative study of 16 patients (20 eyes) with congenital glaucoma due to Sturge-Weber syndrome, Mohamed et al.(15) randomized patients into two groups, one group receiving MMC (0.3 mg/ml for 2 min), and another receiving Ologen. An average IOP of 12 mmHg was obtained for those treated with MMC, and 13 mmHg for those treated with Ologen. However, higher levels of postoperative complications were obtained in the MMC group, such as a thin blister with polycysts in 6 eyes, blebitis in 1 eye treated with topical antibiotic, and shallow anterior chamber in 2 eyes, with spontaneous resolution.

Other studies such as Hafez(16) obtained similar results with the use of Ologen in 20 eyes of 15 patients with congenital glaucoma.

conclusIon

Os resultados dos atuais estudos com implante de Ologen para o tratamento de glaucoma são encorajadores e promissores. No entanto, ensaios clínicos randomizados futuros com seguimento a longo prazo são necessários para avaliarmos a segurança e a eficácia do novo implante na modulação da cicatrização, alcançando melhores taxas de sucesso cirúrgico.

RefeRences

1. Atreides SP, Skuta GL, Reynolds AC. Wound healing modulation in glaucoma filtering surgery. Int Ophthalmol Clin. 2004;44(2):61–106.

2. Coleman AL. Advances in glaucoma treatment and management:surgery. Invest Ophthalmol Vis Sci. 2012;53(5):2491–4.

3. Seibold LK, Sherwood MB, Kahook MY. Wound modulation afterfiltration surgery. Surv Ophthalmol. 2012;57(6):530–50.

4. Tazima MF, Vicente YA, Moriya T. Biologia da ferida e cicatrização. Medicina (B Aires). 2008;41(3):259–64.

5. Contran RS, Kumar V, Collins T. Robbins: Patologia estrutural efuncional. Rio de Janeiro: Guanabara Koogan; 2001. p. 44–100.

6. Palanca-Capistrano AM, Hall J, Cantor LB, Morgan L, Hoop J,WuDunn D. Long-term outcomes of intraoperative 5-fluorouracilversus intraoperative mitomycin C in primary trabeculectomysurgery. Ophthalmology. 2009;116(2):185–90.

7. Cillino S, Casuccio A, Di Pace F, Cagini C, Ferraro LL, Cillino G.Biodegradable collagen matrix implant versus mitomycin-C intrabeculectomy: five-year follow-up. BMC Ophthalmol. 2016;16(1):24.

8. Anguelov B. Clinical cases of surgical revision with OlogenTMimplantation in eyes with glaucoma and Ex-PRESS¨ implant.Bulgarian Forum Glaucoma. 2013;3(4):172-82.

9. Perez CI, Mellado F, Jones A, Colvin R. Trabeculectomy Combined with collagen matrix implant (Ologen). J Glaucoma. 2017;26(1):54–8.

10. Ji Q, Qi B, Liu L, Guo X, Zhong J. Efficacy and Safety of OlogenImplant Versus Mitomycin C in Primary Trabeculectomy: A Meta-analysis of Randomized Clinical Trials. J Glaucoma. 2015;24(5):e88–94.

11. Dada T, Kusumesh R, Bali SJ, Sharma S, Sobti A, Arora V, et al.Trabeculectomy with combined use of subconjunctival collagenimplant and low-dose mitomycin C. J Glaucoma. 2013;22(8):659–62.

12. Oana S, Vila J. Tube Exposure Repair. J Curr Glaucoma Pract. 2012 Sep;6(3):139–42.

13. El-Saied HM, Abdelhakim MA. Trabeculectomy with ologen insecondary glaucomas following failed trabeculectomy with MMC:comparative study. Eye (Lond). 2016 Aug;30(8):1126-34

14. Dietlein TS, Lappas A, Rosentreter A. Secondary subconjunctivalimplantation of a biodegradable collagen-glycosaminoglycan matrix to treat ocular hypotony following trabeculectomy with mitomycinC. Br J Ophthalmol. 2013;97(8):985–8.

15. Mohamed TH, Salman AG, Elshinawy RF. Trabeculectomy withOlogen implant versus mitomycin C in congenital glaucomasecondary to Sturge Weber Syndrome. Int J Ophthalmol.2018;11(2):251–5.

16. Hafez MI. Trabeculectomy with collagen matrix implantation versus trabeculectomy with mitomycin C application for the treatmentof primary congenital glaucoma. J Egyptian Ophthalmol Soc.2015;108(2):26–31.


Autor correspondente: Dra. Ana Cláudia Alves Pereira Hospital de Olhos MS (HOMS)Universidade Federal do Mato Grosso do Sul (UFMS)Universidade Estadual do Mato Grosso do Sul (UEMS) E-mail: [email protected]


278


Instruções aos autores

A Revista Brasileira de Oftalmologia (Rev Bras Oftal-mol.) - ISSN 0034-7280, publicação científica da Sociedade Brasileira de Oftalmologia, se propõe a divulgar artigos que contribuam para o aperfeiçoamento e o desenvolvimento da prática, da pesquisa e do ensino da Oftalmologia e de especialidades afins. Todos os manuscritos, após aprovação pelos Editores, serão avaliados por dois ou três revisores qualificados (peer review), sendo o anonimato garantido em todo o processo de julgamento. Os comentários dos revisores serão devolvidos aos autores para modificações no texto ou justificativa de sua conservação. Somente após aprovações finais dos revisores e editores, os manuscritos serão encaminhados para publicação. O manuscrito aceito para publicação passará a ser propriedade da Revista e não poderá ser editado, total ou parcialmente, por qualquer outro meio de divulgação, sem a prévia autorização por escrito emitida pelo Editor Chefe. Os artigos que não apresentarem mérito, que contenham erros significativos de metodologia, ou não se enquadrem na política editorial da revista, serão rejeitados não cabendo recurso.

Os artigos publicados na Revista Brasileira de Oftalmo-logia seguem os requisitos uniformes proposto pelo Comitê Internacional de Editores de Revistas Médicas, atualizado em fevereiro de 2006 e disponível no endereço eletrônico http://www.icmje.org

APRESENTAÇÃO E SUBMISSÃO DOS MANUSCRITOS

O artigo enviado deverá ser acompanhado de carta assinada por todos os autores, autorizando sua publicação, declarando que o mesmo é inédito e que não foi, ou está sendo submetido à publicação em outro periódico e foi aprovado pela Comissão de Ética em Pesquisa da Instituição em que o mesmo foi realizado.

A esta carta devem ser anexados:• Declaração de Conflitos de Interesse, quando per-

tinente. A Declaração de Conflitos de Interesses, segundo Resolução do Conselho Federal de Medicina nº 1595/2000, veda que em artigo científico seja feita promoção ou propa-ganda de quaisquer produtos ou equipamentos comerciais;

• Informações sobre eventuais fontes de financiamentoda pesquisa;

• Artigo que trata de pesquisa clínica com seres hu-manos deve incluir a declaração de que os participantes assinaram Termo de Consentimento Livre Informado.

Todas as pesquisas, tanto as clínicas como as experi-mentais, devem ter sido executadas de acordo com a Decla-ração de Helsinki.

A Revista Brasileira de Oftalmologia não endossa a opi-nião dos autores, eximindo-se de qualquer responsabilidade em relação a matérias assinadas.

Os artigos podem ser escritos em português, espanhol, inglês ou francês. A versão “on-line” da revista poderá ter artigos apenas em inglês.

A Revista Brasileira de Oftalmologia recebe para publi-cação: Artigos Originais de pesquisa básica, experimentação clínica ou cirúrgica; Divulgação e condutas em casos clínicos de relevante importância; Revisões de temas específicos, Atualizações; Cartas ao editor. Os Editoriais serão escritos a convite, apresentando comentários de trabalhos relevantes da própria revista, pesquisas importantes publicadas ou co-municações dos editores de interesse para a especialidade. Artigos com objetivos comerciais ou propagandísticos serão recusados. Os manuscritos deverão obedecer as seguintes estruturas:

Artigo Original: Descreve pesquisa experimental ou investigação clínica - completa e nunca publicada - prospec-

tiva ou retrospectiva, randomizada ou duplo cego. Deve ter: Título em português e inglês, Resumo estruturado, Descri-tores; Abstract, Keywords, Introdução, Métodos, Resultados, Discussão, Conclusão e Referências.

Artigo de Revisão: Tem como finalidade examinar a bi-bliografia publicada sobre um determinado assunto, fazendo uma avaliação crítica e sistematizada da literatura sobre um determinado tema e apresentar as conclusões importantes, ba-seadas nessa literatura. Somente serão aceitos para publicação quando solicitado pelos Editores. Deve ter: Texto, Resumo, Descritores, Título em Inglês, Abstract, Keywords e Referências.

Artigo de Atualização: Revisões do estado-da-arte sobre determinado tema, escrito por especialista a convite dos Editores. Deve ter: Texto, Resumo, Descritores, Título em Inglês, Abstract, Keywords e Referências.

Relato de Caso: Deve ser informativo e não deve conter detalhes irrelevantes. Só serão aceitos os relatos de casos clíni-cos de relevada importância, quer pela raridade como entidade nosológica, quer pela não usual forma de apresentação. O consentimento do paciente é obrigatório e sempre que o relato de caso requerer o uso de imagem do participante, deverá ser obtida a autorização do uso de imagem no termo de consenti-mento ou em documento separado A apresentação do Relato de caso deve conter: Introdução, Descrição objetiva do caso, Discussão, Resumo, Descritores, Título em nglês, Abstract e Keywords e Referências.

Cartas ao Editor: Têm por objetivo comentar ou discutir trabalhos publicados na revista ou relatar pesquisas originais em andamento. Serão publicadas a critério dos Editores, com a respectiva réplica quando pertinente.

Preparo do Manuscrito:A) Folha de Rosto deverá conter:• Título do artigo, em português e inglês, contendo entre

dez e doze palavras, sem considerar artigos e preposições. O Título deve ser motivador e deve dar idéia dos objetivos e do conteúdo do trabalho;

• Nome completo de cada autor, sem abreviaturas,porém se o autor já possui um formato utilizado em suas publicações, deve informar à secretaria da revista;

• Indicação do grau acadêmico e/ou função acadêmica e a afiliação institucional de cada autor, separadamente. Se houver mais de uma afiliação institucional, indicar apenas a mais relevante. Cargos e/ou funções administrativas não devem ser indicadas.

• Indicação da Instituição onde o trabalho foi realizado;• Nome, endereço, e-mail do autor correspondente;• Fontes de auxílio à pesquisa, se houver;• Declaração de inexistência de conflitos de interesse.

B) Segunda folhaResumo e Descritores: Resumo, em português e inglês,

com no máximo 250 palavras. Para os artigos originais, deverá ser estruturado (Objetivo, Métodos, Resultados, Conclusão), ressaltando os dados mais significativos do trabalho. Para Re-latos de Caso, Revisões ou Atualizações, o resumo não deverá ser estruturado. Abaixo do resumo, especificar no mínimo cinco e no máximo dez descritores (Keywords) que definam o assunto do trabalho. Os descritores deverão ser baseadosno DeCS - Descritores em Ciências da Saúde - disponível noendereço eletrônico http://decs.bvs.br/

Abaixo do Resumo, indicar, para os Ensaios Clínicos, o número de registro na base de Ensaios Clínicos (http://clinicaltrials.gov)*

C) TextoDeverá obedecer rigorosamente a estrutura para cada

categoria de manuscrito.

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Em todas as categorias de manuscrito, a citação dos autores no texto deverá ser numérica e sequencial, utilizando algarismos arábicos entre parênteses e sobrescritos. As citações no texto deverão ser numeradas sequencialmente em números arábicos sobrepostos, devendo evitar a citação nominal dos autores.

Introdução: Deve ser breve, conter e explicar os obje-tivos e o motivo do trabalho.

Métodos: Deve conter informação suficiente para sa-ber-se o que foi feito e como foi feito. A descrição deve ser clara e suficiente para que outro pesquisador possa reproduzir ou dar continuidade ao estudo. Descrever a metodologia estatística empregada com detalhes suficientes para permitir que qualquer leitor com razoável conhecimento sobre o tema e o acesso aos dados originais possa verificar os resultados apresentados. Evitar o uso de termos imprecisos tais como: aleatório, normal, significativo, importante, aceitável, sem defini-los. Os resultados da pesquisa devem ser relatados neste capítulo em sequência lógica e de maneira concisa.

Informação sobre o manejo da dor pós-operatório, tanto em humanos como em animais, deve ser relatada no texto (Resolução nº 196/96, do Ministério da Saúde e Normas Internacionais de Proteção aos Animais).

Resultados: Sempre que possível devem ser apresenta-dos em Tabelas, Gráficos ou Figuras.

Comitê de Ética e Pesquisa (CEP): Informar quando o artigo foi aprovado pelo Comitê de Ética e Pesquisa e o número do Certificado de Apresentação para Apreciação Ética (CAAE).

Discussão: Todos os resultados do trabalho devem ser discutidos e comparados com a literatura pertinente.

Conclusão: Devem ser baseadas nos resultados obtidos.Agradecimentos: Devem ser incluídos colaborações de

pessoas, instituições ou agradecimento por apoio financeiro, auxílios técnicos, que mereçam reconhecimento, mas não justificam a inclusão como autor.

Referências: Devem ser atualizadas contendo, prefe-rencialmente, os trabalhos mais relevantes publicados, nos últimos cinco anos, sobre o tema. Não deve conter trabalhos não referidos no texto. Quando pertinente, é recomendável incluir trabalhos publicados na RBO. As referências deverão ser numeradas consecutivamente, na ordem em que são mencionadas no texto e identificadas com algarismos ará-bicos. A apresentação deverá seguir o formato denominado “Vancouver Style”, conforme modelos abaixo. Os títulos dos periódicos deverão ser abreviados de acordo com o estilo apresentado pela National Library of Medicine, disponível, na “List of Journals in NCBI Database” disponível; no endereço: https://www.ncbi.nlm.nih.gov/nlmcatalog/journals.

Para todas as referências, citar todos os autores até seis. Quando em número maior, citar os seis primeiros autores seguidos da expressão et al.

Artigos de Periódicos:Dahle N, Werner L, Fry L, Mamalis N. Localized, central

optic snowflake degeneration of a polymethyl methacrylate intraocular lens: clinical report with pathological correlation. Arch Ophthalmol. 2006;124(9):1350-3.

Arnarsson A, Sverrisson T, Stefansson E, Sigurdsson H, Sasaki H, Sasaki K, et al. Risk factors for five-year incident age-related macular degeneration: the Reykjavik Eye Study. Am J Ophthalmol. 2006;142(3):419-28.

Livros:Yamane R. Semiologia ocular. 2a ed. Rio de Janeiro:

Cultura Médica; 2003.Capítulos de Livro:Oréfice F, Boratto LM. Biomicroscopia. In: Yamane R.

Semiologia ocular. 2ª ed. Rio de Janeiro:Cultura Médica; 2003.

Dissertações e Teses:Cronemberger S. Contribuição para o estudo de alguns

aspectos da aniridia [tese]. São Paulo: Universidade Federal de São Paulo; 1990.

Publicações eletrônicas:Herzog Neto G, Curi RLN. Características anatômicas

das vias lacrimais excretoras nos bloqueios funcionais ou sín-drome de Milder. Rev Bras Oftalmol [periódico na Internet]. 2003 [citado 2006 jul 22];62(1):[cerca de 5p.]. Disponível em: www.sboportal.org.br

Tabelas e Figuras: Todas as tabelas e figuras também devem ser enviadas em arquivo digital, as primeiras pre-ferencialmente em arquivos Microsoft Word® e as demais em arquivos Microsoft Excel®, Tiff ou JPG. As grandezas, unidades e símbolos utilizados nas tabelas devem obedecer a nomenclatura nacional.

Legendas: As legendas usando espaço duplo, acompa-nhando as respectivas figuras (gráficos, fotografias e ilustra-ções) e tabelas. Cada legenda deve ser numerada em alga-rismos arábicos, correspondendo as suas citações no texto.

Abreviaturas e Siglas: Devem ser precedidas do nome completo quando citadas pela primeira vez no texto ou nas legendas das tabelas e figuras.

Se as ilustrações já tiverem sido publicadas, deverão vir acompanhadas de autorização por escrito do autor ou editor, constando a fonte de referência onde foi publicada.

O texto deve apresentar em espaço duplo, no formato 210mm x 297mm ou A4, em páginas separadas e numera-das, com margens de 3cm e letras de tamanho que facilite a leitura (recomendamos as de nº 14). O texto deve conter as respectivas ilustrações, digitadas no programa Word.

A Revista Brasileira de Oftalmologia reserva o direito de não aceitar para avaliação os artigos que não preencham os critérios acima formulados.

Versão português-inglês: Seguindo os padrões dos prin-cipais periódicos mundiais, a Revista Brasileira de Oftalmo-logia contará com uma versão eletrônica em inglês de todas as edições. Desta forma a revista impressa continuará a ser em português e a versão eletrônica será em inglês.

A Sociedade Brasileira de Oftalmologia se compromete a custear a tradução dos artigos para língua inglesa, porém seus autores uma vez que tenham aprovado seus artigos se disponham a traduzir a versão final para o inglês, está será publicada na versão eletrônica antecipadamente a publicação impressa (ahead of print).

* É obrigatório para todos autores que desejam publicar os seus artigos na Revista Brasileira de Oftalmologia o envio do Identificador Digital do Orcid. Mais informações sobre o cadastramento e a obtenção do ID Orcid poderá ser encon-trado o site - https://orcid.org

* Nota importante: A “Revista Brasileira de Oftalmolo-gia” em apoio às políticas para registro de ensaios clínicos da Organização Mundial de Saúde (OMS) e do Intemational Committee of Medical Joumal Editors (ICMJE), reconhecendo a importância dessas iniciativas para o registro e divulgação internacional de informação sobre estudos clínicos, em aces-so somente aceitará para publicação, a partir de 2008, os artigos de pesquisas clínicas que tenham recebido um número de identificação em um dos Registros de Ensaios Clínicos validados pelos critérios estabelecidos pela OMS e ICMJE, disponível no endereço: http://clinicaltrials.gov ou no site do Pubmed, no item <ClinicalTrials.gov>.

O número de identificação deverá ser registrado abaixo do resumo.

Os trabalhos poderão ser submetidos pela Internet, pelo site - rbo.emnuvens.com.br

280


Declaração dos Autores (é necessária a assinatura de todos os autores)

Em consideração ao fato de que a Sociedade Brasileira de Oftalmologia está interessada em editar o manuscrito a ela encaminhado

pelo(s) o(s) autor(es) abaixo subscrito(s), transfere(m) a partir da presente data todos os direitos autorais para a Sociedade Brasileira

de Oftalmologia em caso de publicação pela Revista Brasileira de Oftalmologia do manuscrito............................................................. .

Os direitos autorais compreendem qualquer e todas as formas de publicação, tais como na mídia eletrônica, por exemplo. O(s) autor

(es) declara (m) que o manuscrito não contém, até onde é de conhecimento do(s) mesmo(s), nenhum material difamatório ou ilegal,

que infrinja a legislação brasileira de direitos autorais.

Certificam que, dentro da área de especialidade, participaram cientemente deste estudo para assumir a responsabilidade por

ele e aceitar suas conclusões.

Certificam que, com a presente carta, descartam qualquer possível conflito financeiro ou de interesse que possa ter com o

assunto tratado nesse manuscrito.

Título do Manuscrito

Nome dos Autores

Minha assinatura abaixo indica minha total concordância com as três declarações acima.


Oftalmologia

DATA ASSINATURA DO AUTOR ORCID / /





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