AIDS and its ocular presentation

AIDS , PATHOPHYSIOLOGY SIGN SYMPTOMS DIAGNOSIS AND OCULAR MANIFESTATIONS

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Presenter : Pabita Dhungel

B.optometry

Presentation layout• Introduction• Global prevalence • Mode of transmission • Pathophysiology • Symptoms • Sign • Ocular manifestation • Summary

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introduction

• AIDS – caused by retrovirus ( HIV- virus)• Eye involvement – 90% Autopsy cases• Ocular complication in 75% of pts with AIDS• Visual morbidity & blindness – leading cause

of suicide in pt. with AIDS• Maybe the first sign of HIV infection – imp.

Role of Eye consultant to make a sight saving & life sustaining Diagnosis

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Classification of HIV

• Two serological types• HIV – 1 (world wide)• HIV – 2 (West Africa & Portugal)• HIV – 1 • HIV – 2

1.Type M 1. Type A, B,C,D and E

2. Type O

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Global prevalence

• In 2009, WHO estimated 33.4 million people worldwide living with HIV/AIDS, with 2.7 million new cases of HIV infection per year and 2.0 million deaths due to AIDS

• In 2007, UNAIDS estimated 33.2 million people worldwide had AIDS that year,2.1 million deaths that year including 3,30,000 children

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Contd…

• According to UNAIDS 2009 report, 60 million people have been infected since the start of pandemic , with 25 million deaths, and 14 million orphaned children in southern Africa alone

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Global picture

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AIDS prevalence in Nepal

National centre for Aids &Std Control ,Teku 2009/12/1

• Cumulative no.of reported HIV infections(17th OCT 09)

=14,787( M=9701 +F=5086)

Enrolled in HIV care=13,005

Enrolled in ART = 3,423 Total Deaths =450People living with HIV as of 31 Dec 2006 (Nepal)

Total -8893Adults- 5999Women -2510Children under 15 years- 364Newly infected with HIV in 2006- 2681AIDS deaths in 2006 - 81 8

History

• 1st reported on June 5, 1981 when the U.S Centers for Disease Control recorded a cluster of Pneumocystis cariniipneumonia (now still classified as PCP but known to be caused by Pneumocystis jirovecii) in five homosexual men in Los Angeles

• Its cause HIV,identified in the early 1980s

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Mode of transmission

• Sexual contact – 70% of cases• IV drug use – 27%• Blood transfusion – 2-3%• Perinatal transmission – 1%• HIV has been isolated from all body fluids

including tears, semen, vaginal fluids, preseminal fluids, and breast milk from infected person

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Pathophysiology

• HIV attaches to T-cells & monocytes /macrophage that display a membrane Ag-complex known as CD4.

• The target cells of HIV show different cytopathic effects• CD4 + helper T-cells – decrease in number – immunodef. –

opportunistic infections• Macrophage – decreased migration response to

chemoattractants -defective intracellular killing of mircroorg. (eg.

Toxo. , Candida.) - impaired Ag presentation -excessive production of TNF-alpha –leads to

dementia , wasting , unexplained fever.

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Flowchart

Binding to CD4 Internalization Uncoating Reverse transcriptase

Integrated proviral DNA

Productive infection Latent infection

Mature HIV production

Cell lysis

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Sign and Symptoms

• Symptoms are usually result of decrease in Immunity, opportunistic infections are common affecting nearly every organ system

• High chance of developing cancers like Kaposi sarcoma, cervical cancer and lymphomas

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System related Symptoms

• Pulmonary• Pneumocystis pneumonia is common in HIV infected

individuals• 1st indication of AIDS in untested individuals• Doesn’t occur unless the CD4 count is less than 200

cells/µL of blood• TB with HIV co-infection is major world health

problem

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Pulmonary contd…

• In early HIV(CD4 count >300 cells/µL) TB typically present as pulmonary disease

• In advanced cases of HIV it occurs as extrapulmonary affecting bone marrow, bone, urinary and gastrointestinal tracts , liver, regional lymph nodes and the CNS

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Gastrointestinal

• Esophagitis is common due to fungal (candidiasis) or viral (herpes simplex-1 or CMV) infections, rarely Mycobacterium

• Unexplained chronic diarrhoea due to bacterial (Salmonella, Shigella, Listeria or Campylobacter) and parasitic and opportunistic infections like cryptosporidiosis, microsporidiosis and viruses viz astrovirus, adenovirus, rotavirus , CMV etc

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Neurological and psychiatric

• Toxoplasmosis caused by Toxoplasma gonadii infects the brain causing toxoplasma encephalitis affecting eyes and lungs

• Cryptococcal meningi caused by Cryptococcus neoforman causing fevers, headache, fatigue, vomiting and also seizures and confusion

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Contd…

• Progressive multifocal leukoencephalopathy (PML) is a demylinating disease with gradual destruction of myelin sheath impairing transmission of nerve impulses

• Caused by virus called JC virus which occurs in 70% of population in latent form, causing disease only when immune system has been weakened as in the case of AIDS patients

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Contd…

• AIDS dementia complex (ADC) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV infected brain macrophages and microglia

• Prevalence is 10-20% in Western countries

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Tumors

• High incidence due to co-infection with oncogenic DNA virus, especially Epstein – Barr virus (EBV), Kaposi’s Sarcoma- Associated Herpesvirus (KSHV) and Human Papillomavirus (HPV)

• Kaposi’s sarcoma is the most common tumor in HIV infected patients

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• Lymphomas often arises in extranodal sites such as gastrointestinal tracts

• AIDS patients are at increased risk of certain tumors like Hodgkin’s disease , rectal carcinomas, hepatocellular carcinomas, head and neck cancers and lungs cancer

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Other infections

• Includes opportunistic infections causing low grade fevers and weight loss

• Opportunistic inf. with Mycobacterium avium intracellulare and CMV causes colitis, CMV retinitis leading to blindness

• Penicilliosis due to Penicillium marneffei is 3rd most common opportunistic infection (after extrapulmonary TB and cryptococcosis)

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Diagnosis

• Lab. Inv. – depends on : • Demonstration of virus sp. Ab by ELISA and

Western Blot • Viral Ag by EIA( Enzyme immunoassay)• Detection of HIV Nucleic acid by PCR• Viral P24 Ag detection

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WHO staging diagnosis

• Given by WHO in September 2005• Stage I: asymptomatic and not catagorized as

AIDS• Stage II: minor mucocutaneous and recurrent

URTI(upper respiratory tract infection)• Stage III: chronic diarrhoea, pulmonary TB• Stage IV: toxoplasmosis of brain, candiasis of

oesophagus, trachea, lungs, Kaposi’s sarcoma

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HIV Staging with CD4 counts

• CD4 counts Normal- 600- 1500 cells/cumm• 250-500/cumm– oral candidiasis , disseminated TB• 150-200/cumm- Kaposi sarcoma, Lymphoma,

Cryptosporidiosis• 75-125/cumm – pneumocystis carinii, mycobact.

avium, HS, toxo, cryptococcosis, esophageal candida• <50 cell/cumm- CMV retinitis

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Ophthalmic Manifestations of HIV Infection

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CMV Retinitis

• Most common ocular infection in pts. with AIDS, & maybe the initial manifestation

• Prior to HAART (Highly Active Antiretroviral Therapy)- 15-40% of AIDS pts.

• Untreated CMV – is a progressive and destructive infection- leads to blindness

• CMV – double stranded DNA virus, herpetoviridae

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Clinical Features

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• Brush Fire- leading active border due to spread by direct extension

• optic nerve involvement

• RD

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Diagnosis

• Blood C/S• Urine C/S• PCR( sensitive & specific – 46 days – 6 months)

to dev. CMV retinitis• Fundus exam. Is essential – pt. with CMV +

blood ,urine c/s or extraocular CMV disease

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MANAGEMENT

• Drugs Used: ( Virostatic)

1.Gancyclovir 2.Foscarnet 3.Cidofovir4.Formivirsen

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Toxoplasma Retinochoroiditis

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• Decreased vision • Moderate granulomatous uveitis ( AC+Vit-

cells)• Retina : Focal areas of necrotizing retinitis Abs of pre existing scars (pr 4-6%)• ~ 25% pts. –intracranial involvement( Imp. to

do intracranial imaging study in all AIDS pts. With ocular toxpl.)

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• D/D- CMV retinitis , PORN

• T/T: Pyrimethamine(50mg/dailly)+ sulfanamide(4-

6gm/daily)+clindamycin(300mg x QID) –folinic acid

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HIV Retinopathy• Most common ocular finding in

AIDS pts(50-70%)• Features: cotton wool spots, retinal

hmg, miroaneurysms• Infection capillary

endothelium & retinal tissue• Deposition of immunocomplex• Disseminated intravascular

microangiopathy• Increased RBC aggregation• Increased blood viscosity• Capillary closure Ischemia

Cotton wool spots( along vascular arcade, focal area of NFL ischemia)

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Progressive Outer Retinal Necrosis (PORN)

• Caused by Herpes Zoster (HZ)

• Rapid destruction of retina

• Disease starts in one eye – fellow eye usu. Involves subsequently

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• Deep outer retinal lesions in a circumferential pattern in the peripheral retina

• lesion coalesce ,progress to full thickness retinal necrosis in a matter of days

• Rapid diminution of vision ( sparing of the perivascular retina)

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PORN - Diagnosis

• H/o HZ inf. In the skin or elsewhere • Rapid progressive & sparing of the retinal

vessels and the adj. area• CD4 < 50 cells/mm3D/D• CMV retinitis /toxoplasmosis.

RetinochoroiditisT/T• I.V. gangciclovir /foscarnet with acyclovir• Oral sorivudine

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Acute Retinal Necrosis (ARN)

• Caused by: HZ & HS• Clinical features:• Decreased vision with pain • Photophobia • Floaters • Granulomatous uveitis • Marked vitritis• Multiple white opaque patches of

thickened retina (periphery) enlarges gradually & coalaesce

• RD• 1/3 B/L involvement

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Other Forms Of Retinitis

• Protozoa : Pneumocystis carinii choroiditis• Fungal : Cryptococcosis• Candidiasis• Bacterial : Tubercular retinitis• Spirochaete : Treponema Pallidum

Syphilitic retinitis

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Herpes Zoster ophthalmicus

• If young pts have HZ of the face or eyelids Suspect HIV infection

• Corneal involvement: persistent, chr. Epithelial keratitis• T/T: Systemic acyclovir : I.V 10mg/kg/8hrly oral 600-800mg 5x daily conjunctivitis, keratitis, uveitis –t/t accordingly• Regular FU

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Herpes Simplex infection

Keratitis:• Prolonged course• Multiple recurrence• Involve the limbus

Bacterial & Fungal Keratitis– More aggressive & likely to cause perforation– Difficult or non responsive to t/t– Microsporidia– Punctate epithelial keratopathy– Mild conjunctivitis

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Molluscum Contagiosum (MC)• Causative agent: • DNA Virus ( Poxvirus)• Eyelids:• Umbilicated skin papule• Multiple >10 B/L• Size: large >5mm• Resistant to therapy• Follicular conjunctivitis• T/T:• Surgical excision• cautery, cryotherapy to the

base

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conjunctival Squamous cell carcinoma

• third most common neoplasm associated to HIV infection.• occurs due to Papilloma Virus infection.• appears as a pink, gelatinous growth, usually in the

interpalpebral area. Often an engorgedblood vessel feeding the tumour is seen.

• It may extend onto the cornea, but deep invasion and metastasis are rare.

• •The treatment of choice is local excision and cryotherapy• but the presence of orbital invasion is an indication of

exenteration

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Conjuctival SCC

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Trichomegaly

• Trichomegaly or hypertrichosis is an exaggerated growth of the eye lashes found in the later stages of the disease

• The cause is not known• When symptomatic or

for cosmetic reasons the eyelashes can be trimmed

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Dry Eye

• • Sicca syndrome is frequent among patients with HIV infection

• •Patients complain of burning uncomfortable red

• eyes.• causes of dry eye in HIV

infection from blepharitis, due to destruction of the

• lacrimal glands.• •T/T with tear supplements

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Anterior uveitis

• HIV related anterioruveitis can be:• – Direct manifestation of the human

immunodeficiency virus infection• – autoimmnune in origin• – drug induced ie: rifabutin, secondary to direct toxic

effect upon the non-pigmented epithelium of the ciliary body

• –Any of the different infections• associated with AIDS, ie: Herpes Zoster Virus, Herpes

Simplex Virus,Cytomegalovirus, Toxoplasma gondii, Syphilis 49

• Candida albicans endophthalmitis• •Infection with candida albicansis rare. • Candida albicans is the commonest cause of fungal

endophthalmitis• •Affected patients usually have a history of drug

abuse • •In the initial stages, floaters are the main symptom.

As the condition progresses, whitish “puff-balls”and vitreous strands develop. Later, similar infiltrates appear in the choroid and retina

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• •The treatment depends on the severity of the ocular involvement and systemic disease. The original foci should be removed. The drugs of choice are Amphotericine BBand Fluconazol

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Non Infectious Ocular Manifestation

Kaposi’s Sarcoma• 30% of the pts/ with AIDS• Multifocal malignant

sarcomaOcular• Eyelid• Conjunctiva inf. Fornix• Orbit ProptosisPtosisOcular nerve palsy

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Other Non infective Ocular Manifestation

• Keratoconjunctivitis sicca: 10-15%• Thrombocytopenia – Subconjunctival

Hemorrhage• Peripheral corneal ulceration• CN palsy• Papilloedema

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