Ocular Manifestations of HIV

Beka Aberra C2

Outline

Introduction Adnexal manifestations of HIV infection Anterior segment Posterior segment In Children In Developing countries Drug related ocular toxicity

Objectives

• Know incidence and prevalence of ocular diseases in HIV patients.• Identify common ocular diseases in HIV patients.• Know the clinical manifestations of common ocular diseases.• Reach a diagnosis of common ocular diseases.• Know the outline of management and workup.

Epidemiology

A cross-sectional clinical evaluation of HIV/AIDS patients at Gondar Hospital University was undertaken between January and June 2004.Results: 125 adult patients were enrolled in the Hospital from January to June 2004. The majority were males (N=69) and the mean age was 34 (range: 16-80 years). About 90% of the patients were in clinical stages III & IV determined according to the WHO clinical staging method and 60% of them had at least one ocular manifestation.

Ocular manifestations related to HIV/AIDS in 125 patients, Gondar University Hospital, Northwest Ethiopia, 2004Ocular diagnosis Number of patients (%)• Retinal Microvaculopathy 30 (24)• Neuro-ophthalmic disorders 12 (9.6)• Uveitis 9 (7.2)• Ophthalmic herpes zoster 7 (5.6)• Molluscum Contagiosum 6 (4.8)• Conjunctival carcinoma 5 (4)• Seborrheic blepharitis 3 (2.4)• Vernal conjunctivitis 1 (0.8)• Sub conjucnctival haemorrhage 2 (1.6)Total 75 (60)

Ocular manifestations of HIV/AIDS patients in Ethiopia and Other African Countries Manifestation Ethiopia Burundi Malawi

(N=125) (N=154) (N=99)• Frequency of ocular manifestation 60% 19% 20%• Retinal Microvasculopthy 24% 16% 17%• Herpes zonster Ophthalmicus 5.6% 1% NA• Anterior Uveitis 7.2% 4% 2%• CMV retinitis <1% 1% 1%• Neuro-ophthalmic disorders 9.6% NA NA• Conjunctival carcinoma 4% NA NA

NA: Not Available

Posterior segment manifestations•Retinal Vasculopathy•Opportunistic Infections•Unusual Malignancies•Neuro-Ophthalmologic abnormalities

Retinal Vasculopathy

• Retinal microvasculopathy occurs in more than 50% of HIV-infected patients.

• The most commonly observed manifestation is cotton-wool spots as in the figure , although intraretinal hemorrhages, micro aneurysms, and, uncommonly, retinal ischemia also occur.

• Hypotheses regarding the pathogenesis of retinal microvasculopathy is HIV induced increase in plasma viscosity, HIV-related immune complex deposition, and direct infection of the conjunctival vascular endothelium by HIV.

• HIV-associated retinal microvasculopathy is typically asymptomatic, but may play a role in the progressive optic nerve atrophy, loss of color vision, contrast sensitivity, and visual field are observed in HIV-infected patients.

Opportunistic Infections

Causes of infectious retinitis, including Cytomegalovirus (A), Varicella-zoster virus (B), Herpes simplex virus (C), Toxoplasmosis (D) in four different patients with AIDS.

Cytomegalovirus Retinitis• CMV retinitis affects 30% to 40% of HIV-infected patients. • CMV retinitis typically occurs at CD4+ T-lymphocyte counts of less than 50

cells/mm3, and almost always at counts less than 100 cells/mm3. • Affected patients typically report gradual visual field loss or the onset of

floaters**. Clinical examination shows geographic retinal thickening and opacification.• Treatment of CMV retinitis is a complicated, rapidly evolving field. Current

FDA-approved treatments for active retinitis include intravenous Gancyclovir, Foscarnet, and Cidofovir. Any of the same medicines or the recently approved oral formulation of Gancyclovir can be used for maintenance therapy.• Local therapy with intravitreal injection of Gancyclovir, foscarnet, or Cidofovir,

or via implantation of a slow-release Gancyclovir-containing reservoir, is also possible.

Varicella-Zoster Virus Retinitis• VZV is the second most common cause of necrotizing retinitis in HIV-infected

individuals, affecting approximately 5% of large cohorts with AIDS. • Like CMV, VZV produces retinal whitening , occasionally accompanied by intraretinal

hemorrhages. However, VZV retinitis is usually distinguished by its rapid progression, multifocal nature, and initial involvement of deep retinal layers. The risk of retinal detachment is greater than observed with CMV retinitis. • Treatment involves the use of intravenous and intravitreal antivirals, typically

combination therapy with acyclovir and foscarnet.Herpes Simplex Virus Retinitis• Herpes simplex virus is a rare cause of retinitis in HIV-infected patients. Like VZV

retinitis, onset of symptoms and disease progression is rapid. Clinical appearance may mimic VZV retinitis. • Treatment should include prompt use of intravenous and intravitreal antivirals, again

most typically acyclovir and foscarnet.

Toxoplasmosis Retinochoroiditis• Ocular toxoplasmosis affects less than 1% of HIV-infected patients in most countries.

Toxoplasmosis retinochoroiditis in HIV-positive patients is usually distinguished by the occurrence of a moderate to severe anterior chamber and vitreous inflammation, a relative lack of retinal hemorrhage, and the presence of a smooth rather than granular edge. • Moreover, unlike toxoplasmosis retinochoroiditis in immunocompetent patients,

HIV-infected patients often have multifocal and bilateral disease, with no evidence of inactive toxoplasmosis scars. • Testing should include serology for IgG and IgM toxoplasmosis antibodies, but may

be negative in profoundly immunosuppressed patients. • Treatment consists of pyrimethamine in combination with a sulfonamide or

clindamycin, either alone or in combination. Chronic or repeated therapy is often necessary. • Atovaquone has been used successfully in the treatment of toxoplasmosis

retinochoroiditis in an HIV-positive patient, but it is expensive and has yet to be shown to be superior to more standard combination therapy

Bacterial and Fungal Retinitis• Ocular syphilis is the most common intraocular bacterial

infection in HIV-positive patients, affecting up to 2% of patients. Patients may present with either an iridocyclitis or a more diffuse intraocular inflammation, with or without retinal or optic nerve involvement. • Laboratory testing should include both (RPR) or (VDRL) test and

[FTA-ABS] or [MHA-TP]) test. Rarely, these test may be negative in HIV-positive patients despite active intraocular disease. • Treatment includes intravenous penicillin G, 24 million units/day

for 7 to 10 days. Recurrences can occur even after adequate treatment.

INFECTIOUS CHOROIDITISInfectious choroiditis is uncommon in HIV-infected patients, accounting for less than 1 %.

Up to one third of cases have concurrent CMV retinitis.

Fig. 13. Acute (A) and healed (B) Pneumocystis carinii choroiditis in a patient with AIDS.

Unusual Malignancies

INTRAOCULAR LYMPHOMA• HIV-infected patients are at increased risk for developing non-Hodgkin's

lymphoma. • Although uncommon, cases of intraocular lymphoma have been reported in

HIV-infected patients, and are composed primarily of B cells. • Treatment includes radiation and chemotherapy.

ORBITAL & NEURO-OPHTHALMIC MANIFESTATIONS OF HIV INFECTIONOrbital Neuro-ophthalmicOrbital lymphoma PapilledemaOrbital cellulitis Optic neuritisOrbital Kaposi's sarcoma Optic atrophy

Cranial nerve palsiesOcular Motility disordersVisual field defects

ORBITAL MANIFESTATIONS OF HIV INFECTION• Orbital complications, most commonly orbital lymphoma or

orbital cellulitis, occur in well under 1% of HIV-infected patients. • Treatment of orbital cellulitis includes systemic antibiotics

and, as needed, surgical debridement.

NEURO-OPHTHALMIC MANIFESTATIONS OF HIV INFECTION• Neuro-ophthalmic manifestations occur in 10% to 15% of HIV-infected

patients. • Most common findings include ONH edema related to either

papilledema or direct optic neuritis; nonspecific optic atrophy; CN palsies (especially of the 6th nerve); occulomotor abnormalities, such as nystagmus, gaze palsies, internuclear ophthalmoparesis, and skew deviation (Strabismus) ; and visual field defects. • In most instances, evaluation includes MRI, followed by a LP for cell

count, cytology, culture, and Ab and Ag testing. • Treatment includes radiation and chemotherapy in the case of

lymphoma, and specific antibiotic therapy for identified infectious causes. There is currently no treatment for HIV encephalopathy or progressive multifocal leukoencephalopathy.

Fig. 14. Optic disc edema with surrounding cotton-wool spots and intraretinal hemorrhages due to neurosyphilis (A) and cryptococcal meningitis with papilledema (B) in two different patients with AIDS.

• Children appear to have fewer ocular manifestations of HIV infection and an especially low incidence of CMV retinitis. • The reason for this difference is unknown, but may relate to an altered

immune response to HIV or a lower prevalence of CMV seropositivity in children. • HIV-infected children are, however, at increased risk for

neurodevelopmental delay, a condition often associated with neuro-ophthalmic complications. • A fetal AIDS-associated embryopathy, with downward obliquity of the

eyes, prominent palpebral fissures, hypertelorism, and blue sclerae, has also been described.

OCULAR MANIFESTATION OF HIV INFECTION IN CHILDREN

OCULAR MANIFESTATION OF HIV INFECTION IN THE DEVELOPING WORLD

• The majority of HIV-infected persons live in the developing world, particularly in sub-Saharan Africa and Southeast Asia. • Studies of the ocular complications of HIV infection in these

parts of the world are only beginning to appear, but suggest that CMV retinitis is less frequent than observed in developed countries, and that otherwise rare ocular opportunistic infections, such as toxoplasmosis and tuberculosis, affect 2% to 10% of patients with AIDS.

DRUG-RELATED OCULAR TOXICITY IN HIV-INFECTED PATIENTS• Rifabutin- intraocular inflammation uveitis- 33%• Cidofovir- uveitis and intraocular hypotony - 25- 30%• Didanosine- retinal pigment epithelial abnormalities; mottling and

hypertrophy accompanied by overall decreased retinal function .• Gancyclovir & Acyclovir- corneal epithelial inclusion termed corneal

lipidosis.• Lastly, long-term Atovaquone can cause vortex keratopathy.

Workup

• Detailed history and complete ophthalmologic examination• Fundoscopic examination (retinal nerve fiber loss in HIV retinopathy)• Fluorescein stain corneal dendrites with terminal bulbs.• VDRL for Syphilis.• India ink for fungal infections. • PCR, viral culture.• Gram’s stain; AFB; Giemsa staining.• Baseline investigations (before starting antiviral drugs)

Bibliography• Duane's Foundations of Ophthalmology.2007; • UNAIDS, AIDS epidemic update: Special report on HIV/AIDS:

December 2006. Available from: http://data.unaids.org/pub/Epireport/2006/2006_Epiupdate_en.pdf. [Last accessed on 2007 Oct 31]• Article on Ocular Manifestations of HIV/AIDS patients in

Gondar University Hospital, north west Ethiopia• UNAIDS/WHO. ADIS Epidemic Update; 2004.• Disease Prevention and Control Department, MOH. AIDS in

Ethiopia: Fifth Report. June 2004

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