Journal Reading Mata

Supervisor : Prof. DR. Dr. H.H.B. Mailangkay, Sp. M (K)

Department Of Ophtalmology Atma Jaya Faculty of Medicine Jakarta

Introduction Choroidal neovascularization (CNV) one of the

most important causes of vision loss Myopic CNV leading cause of visual impairment in patients younger than 50 years The only approved treatment photodynamic therapy (PDT) + verteporfin (Visudyne) stability of visual acuity did not persist in the 24 month follow up examination

Introduction CNV in age-related macular degeneration (AMD)

treated with PDT replaced with drugs that bind vascular endothelial growth factor (VEGF) Ranibizumab (Lucentis) humanized antibody fragment vs VEGF-A Ranibizumab vs Bevacizumab (Avastin) smaller molecular weight There is no general consensus as to the best treatment regimen for myopic patients

Methods Purpose To identify predictive factors that could affect final visual acuity and the need for retreatment after treating myopic CNV with ranibizumab Design Prospective, consecutive, nonrandomized pilot study Sample 67 eyes of 67 patients with subfoveal or non-subfoveal myopic CNV

Methods Inclusion criteria: Minimum SE -6 D + retinal signs of pathologic myopia BCVA of 24 letters or more Active myopic CNV angiographic leakage and/or intraretinal edema and/or subretinal fluid determined by OCT Patients who had been treated minimum of 3 months previously with PDT /2 months previously with sodium pegaptanid (Macugen)

Methods Exclusion criteria: Presence of active CNV secondary to a disease other than pathologic myopia Concomitant disease that could compromise vision or fixation Previous thromboembolic episodes Allergy to fluorescein Fertile woman not using contraception

Methods Complete ophthalmology examination: BCVA using ETDRS charts (letters) Anterior segment slit-lamp examination IOP measurement Detailed dilated fundus examination with special attention to the macular area and retinal preiphery Retinography Digital fluorescein angiography: to detect leakage comparing the late-phase and early phase images OCT Stratus determinations of CMT and retinal architecture

Methods 3 loading doses of intravitreal ranibizumab at baseline

and at 1 and 2 months Single injection retreatment: Anatomic activity (intraretinal edema or subretinal fluid

detected in the OCT and/or myopic CNV leakage in the FA) Visual loss of at least 5 letters compared with the best BCVA at any visit

Retreatment suspended cystoid macular

edema

Methods Monthly follow up examination : BCVA IOP determination OCT Retinography Ocular and systemic adverse effects FA at 3 and 12 months and at the end of follow up, if

there was visual loss or worsening of symptoms without evidence of deterioration in OCT, if increase CNV area by retinography Progression of chorioretinal atrophy assesed at 12 months and at the end of follow up

RESULTS The mean age of the 67 patient included in our study :

(17 men, 50 women) was 59 (+-12.8)years. The average SE was -11.1 (+-3.3) D Three of 67 eyes (4.5%) had undergone refractive surgery and 13 eyes (19.4%) cataract surgery Forty two of the eyes (62.7%) prior treatment 40 eyes (59.7%) shows subfoveal myopic CNV. Mean FU was 15.9 months (range, 6-27 months)

RESULTS Mean baseline BCVA was 53.4(+-12.4) letters. Rose to 61.2(+-12.8)letters 1st intravitreal ranibizumab

injection Rose to 65.9 (+-23.8) 3rd Mean BCVA 65.3(+-13.5) letters at 12 months (n=59), 68.3 letters at 21 months (n=17), 78.6 letters at 24 months (n=9). At the and of FU : mean BCVA produced were 7.8 (+-9.8) letters after 1st injection, 12.6(+-11.6) after 3rd injection Average changes 12 months, 24 months , the end of FU 12.4(+-13), 19.1 (+-9.1), 12(+_14.6)letters.

RESULTS At the end of FU, 9 eyes (13.4%) lost more than 1

letter 4 of which lost more than 15 letters 5 eyes (7.5%) showed the same BCVA 53 eyes (79.1%) showed a gain 27 eyes (40.3%) improving by more than 15 letters

RESULTS Mean BCVA rose from 54.7 (+-12.7) letters at baseline

to 70.4 (+-13.1) letters at the end of FU for 25 naive eyes And form 52.6(+-12.3) letters to 62.5(+_17.1) letters in 42 eyes undergoing prior treatment

RESULTS CMT decreased from 308.5 (+-87.4) micrometer at

baseline to 217.9 (+-37.8) micrometer at 3 months, 216.8 (+-39.3) micrometer at 12 months, and 214.8 (+35.7) micrometer at the end of follow up The average reduction 70.9 (+-55.9) after 1st injection, 90.5(+-77.9) micro after loading dose. At 12 mo: CMT was 93.7 (+-78.6) micro

RESULTS Our data revealed an inverse relationship between

BCVA and CMT up until 24 months, with maximum inverse correlation produced at 6 months (P=0.001) Mean GLD fell : 1.7 (+-0.8) micro to 1.5 (+-0.8)micro after loading dose, remained 1.5 (+-0.8)micro at 12 months and at the end of study.

RESULTS Mean CNV area decreased from 1.8(+-1.7)mm3 to 1.5

(+-1.5)mm3 at 3 months, 12 months and at the end of FU 58.2% (39/57) of the patients retinochoroidal atrophy around the myopic CNV. At the end of FU, rose to 70.2 % (47/67) 8 eyes with no initial sign of atrophy develope this condition during the course of treatment 10 eyes with baseline atrophy worsened This increase in atrophy was significant (p=0.001)

RESULTS The average number of injections given was 4.2(+-1.7).

At 12 months 3.9 (+-1.1) (n=59). At 18 months 4.7(+-2.2) (n=19) 36 of 67 eyes received only loading dose The predictive factor of visual acuity at the end of FU identified by linear regression were baseline BCVA and a non subfoveal CNV location

RESULTS Non subfoveal lesion achieved a mean increase in

BCVA of 8.3 letters compared to subfoveal lesions. The factor age (-0.23[95%CI -0.5;0.1;P=.09]) and myopic CNV area (-1.79[95%CI -3.7;0.1;P=0.7]) showed a tendency to act as negative prognostic factors

RESULTS The predictive factors associated with a need for

ranibizumab retreatment during follow up identified by logistic regression were CNV location and prior treatment. Baseline fibrosis could not be significantly correlated with the number of injection given 2 eyes that developed mild acute anterior uveitis after the second and the third injections, respectively responded well to topical anti inflammatory treatment No other ocular or systemic complications were recorded during follow up

DISCUSSION First ranibizumab injection Mean BCVA improvement 7.8 letters Third ranibizumab injection Mean BCVA improvement 12.6 letters Persisted 16 months Reinforce the effect of the initial dose End of study Vision continued to improve ( 3 follow up visits) Not significant (small sample size)

DISCUSSION No difference in visual outcome detected between

treatment-naive and previously treated patients Not really comparable with different studies Confirm the good visual and anatomic outcomes

described for ranibizumab ( Mones and associates, Lalloum and associates, Silva and associates, Lai and associates) and bevacizumab (Ikuno and associates) Different patient numbers Times to follow up Treatment regimens

DISCUSSION Mones and associates 2009 Intravitreal Ranibizumab For Choroidal Neovascularization Secondary To Pathologic Myopia Single ranibizumab followed by PRN Mean visual gain 9.53 letters, 27% gained more than 3 lines at 12 months Improvement significantly better in naive eyes than in those undergoing prior treatment 74% cases need retreatment No effects on retinochoroidal atrophy, although indicate a need for longer follow-up Also found improvement on BCVA but no effects on retinochoroidal atrophy, although Mones indicate a need for longer follow-up

DISCUSSION Lalloum and associates 2010 Intravitreal Ranibizumab For Choroidal Neovascularization Complicating Pathologic Myopia Nonloading dosing of ranibizumab 46,7% eyes gained 3 lines of vision Naive patients gained more vision The visual and OCT results over a similar follow up

period (17 months ) are consistent with Lalloum, despite the mean number of injection was higher (4.2 vs 3) and sample almost doubled

DISCUSSION Silva and associates -2010 Intravitreal ranibizumab for myopic choroidal neovascularization Single ranibizumab injections followed by PRN over 12 months Mean visual gain 8 letters, 24% gaining 3 lines, 21% show worse visual acuity (result of not having administered an initial loading dose or could be attributed to an effect of prior PDT) Both naive and previously PDT-treated eyes responded to treatment Mean BCVA higher and recorded persistent beyond 12 months.

Silva confimed that loading dose is not necessary and many outhors warn a need to avoid injections in patients with highly myopic. But our findings suggest a loading dose is save and effective at achieving an improved and maintained BCVA.

DISCUSSION Lai and associates 2009 Intravitreal Ranibizumab For The Primaery Treatment Of Choroidal Neovascularization Secondary To Pathologic Myopia Loading dose of ranibizumab for myopic CNV Mean visual improvement 3 lines 92.7% had gained at least 1 line at 12 months Mean number of injections was 3.8 81.3% only needed loading dose The mean number of injection was higher (4.2 vs 3.8) even with

shorter follow-up. The number of patients not requiring retreatment was 53.7% compared with Lai was 81.3%, because that all the eyes examined by Lai were naive while 62.7% of our series had received prior treatment.

DISCUSSION Ikuno and associates 2009 Intravitreal Bevacizumab For Choroidal Neovascularization Attributable To Pathological Myopia: One Years Results Suggested limited negative effect of the spread of atrophy Expansion of chorioretinal atrophy over years involves a poor visual prognosis in patients with with myopic CNV Detected an increase in chorioretinal atrophy even the

mean vision improvement persisteng over 24 months. But the worsening atrophy observed can be resulted from the natural progression of high myopia or to possible negative impact of ranibizumab or of prior to PDT such as Ikuno suggest from Bevacizumab

DISCUSSION Tatar and associates 2006 Expression Of VEGF And PEDF In Choroidal Neovascular Membranes Following Verteporfin Photodynamic Therapy Enhanced VEGF secretion (angiogenic stimulus and increased excretion leads to blood vessels leakage) in eyes previously treated with PDT compared to naive eyes Pathogenesis of CNV differs in myopia and AMD but the

enhanced of VEGF expression related to PDT-treated myopic CNV. This could explain the higher need of retreatment. Beside that, the recurrent CNV is more resistant to anti-VEGF than primary CNV

DISCUSSION Hayashi and associates 2005 Characteristics Of Patients With A Favorable Natural Course Of Myopic Choroidal Neovascularization 5 years observation of myopic CNV Concluded that patients with good visual prognosis were younger and had smaller CNV and a better visual aquity. Moreover, juxtafoveal CNV was more frequient in these patients. Suggest that ranibizumab may not alter the natural

progression of myopic CNV. But a longer follow up (more than 2 years) needed to determine whether ranibizumab is capable of maintaining the visual aquity gain achieved besides slowing the natural course of myopic CNV

ANALYSIS Positive predictive factor for treatment outcome Starting BCVA emerged

Higher BCVA baseline associated with reduced receptor damage Usually not affect the zone of maximal vision

Non-subfoveal CNV

Negative predictive factor suggested nonsignificant Age Myopic CNV

CONCLUSION 3 initial ranibizumab injections monthly beneficial in

myopic CNV Proven safe and effective Non-subfoveal myopic CNV patients were only require

the first 3 scheduled with no need for retreatments Baseline BCVA and location of myopic CNV emerged as predictive factors for visual outcome

Location of myopic CNV and prior treatment was

associated with the need for retreatment

CONCLUSION Limitation Small number of eyes observed as sample Short time of follow up Lack of control group Suggestion The good visual and anatomic outcomes persisting over 24 months and the absence of complications prompt a need to further assess.