Ophthalmic Manifestations of HIV Infection

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Ophthalmic Manifestations of HIV Infection

Author(s): Kalpana Suresh. Vol. 3, No. 4 (2006-08 - 2006-09). Review Article.ISSN No: 0973-516X. Indian Journal of Pactising Doctor

Kalpana Suresh

Dr. Kalpana Suresh, M.S.,F.R.C.S (Glasg) is Associate Professor & Consultant Ophthalmologist, Sri Ramachandra Medical College & RI (DU), Porur, Chennai-600116

Numerous ophthalmic manifestations of HIV infection may involve the anterior or posterior segment of the eye. Anterior segment findings include tumors of the periocular tissues and a variety of external infections. Posterior segment changes include an HIV-associated retinopathy and a number of opportunistic infections of the retina and choroid.

Due to the potentially devastating and rapid course of retinal infections, all persons with HIV disease should undergo routine ophthalmologic evaluations. In patients with early-stage HIV disease (CD4 count >300 cells/ìL), ocular syndromes associated with immunosuppression are uncommon.

Nonetheless, eye infections associated with sexually transmitted diseases (STDs) such as herpes simplex virus, gonorrhea, and chlamydia may be more frequent in HIV-infected persons. Therefore, clinicians should screen for HIV in the presence of these infections.

Anterior Segment Diseases

a) Kaposi Sarcoma: Kaposi sarcoma is a highly vascular tumor that appears as multiple red nodules on the eyelids and conjunctiva. It may appear as a persistent subconjunctival hemorrhage. It does not invade the eye, and no treatment is necessary if it causes no symptoms. Otherwise, it is treated by cryotherapy, surgical excision, radiation, or chemotherapy

Infections

Herpes Zoster Ophthalmicus: Herpes zoster ophthalmicus (HZO) is characterized by a vesiculobullous rash over the ophthalmic branch of the trigeminal nerve and may be associated with keratitis, conjunctivitis, blepharitis, and uveitis. Although HZO most commonly affects older individuals, it may be an initial manifestation of HIV infection in a young person.1

Adults with an acute, moderate-tosevere skin rash may receive acyclovir orally and bacitracin ointment for skin lesions. In the presence of uveitis, topical prednisolone and cycloplegic should be applied. In cases of retinitis, choroiditis, or cranial nerve involvement, intravenous acyclovir is indicated.

Herpes Simplex Keratitis: Herpes simplex virus (HSV) can cause painful and often recurrent corneal ulcerations with a characteristic branching or dendritic pattern on slit lamp examination. HSV keratitis often is associated with corneal scarring and iritis. It requires prolonged course of treatment, and recurs frequently. Treatment consists of topical acyclovir and cycloplegic drugs, with debridement of the ulcer using a cotton-tip applicator. Oral acyclovir (400 mg twice daily for 1 year) decreases the risk of recurrent HSV keratitis by 50%.2

Fungal Infections: Defects in cellular immunity also may play a role in susceptibility to corneal infections. Spontaneous fungal keratitis secondary to Candida has been observed in persons with advanced HIV disease and a history of antecedent trauma.

Syphilis: It causes the following lesions in the posterior segment – chorioretinitis, retinal perivasculitis, intraretinal hemorrhage, papillitis, and panuveitis. Ocular involvement may be unilateral or bilateral and is associated with evidence of central nervous system infection in up to 85% of patients.3 Therefore, lumbar puncture and cerebrospinal fluid analysis is recommended for the evaluation of patients with ocular syphilis who are seropositive for HIV. Syphilis can run a more rapid and aggressive course in HIVinfected patients than in immunocompetent individuals.

Antibiotic regimens recommended for the treatment of syphilis in immunocompetent patients may not be appropriate for patients with concomitant HIV disease. Administration of intravenous penicillin for longer periods resulted in improvement of vision in HIVpositive patients with ocular syphilis.

Uveitis

Uveitis occurs with, and may be the first sign of, several chronic infections seen frequently in patients with HIV disease, including tuberculosis, syphilis, histoplasmosis, coccidioidomycosis, and toxoplasmosis. Unexplained uveitis in an HIV-infected patient should prompt a search for an underlying infection.

Posterior Segment Diseases

Infection with HIV predisposes the retina, choroid, and optic nerve to a variety of disorders that may be divided broadly into two categories: those associated with noninfectious causes and those due to infections.

a) Manifestations Not Associated with Opportunistic Infections

Retina: HIV retinopathy is a noninfectious microvascular disorder characterized by cotton-wool spots, microaneurysms, retinal hemorrhages, telangiectatic vascular changes and areas of capillary nonperfusion. These are the most common retinal manifestation of HIV disease and are clinically apparent in about 70% of persons with advanced HIV disease.

Cotton-wool spots occur in approximately 50-60% of patients with advanced HIV disease and are the earliest and most consistent finding in HIV retinopathy (Figure 1). They represent infarcts of the nerve fiber layer. They are not vision threatening. They can be distinguished by their smaller size, superficial location, lack of progression, and tendency to resolve over weeks to months.

Optic Disk: Noninfectious optic nerve involvement in patients with HIV disease includes papilledema, anterior ischemic optic neuropathy, and optic atrophy. Papilledema usually occurs in patients with advanced HIV disease and CNS malignancies.

Manifestations Due to Opportunistic Infections

A number of infections of the retina and choroid have been reported to affect individuals with advanced HIV disease. The more commonly encountered debilitating infections are included in this review.

Cytomegalovirus Retinitis: CMV retinitis is the most common retinal infection in patients with HIV disease, occurring in 15-40% of patients with advanced HIV disease. It is bilateral in 30-50% of patients. It occurs when the CD4 count falls below 50 cells/ìL.

CMV is a DNA virus classified in the herpes group of viruses. CMV invades retinal cells with resultant retinal necrosis. Retinal lesions appear as multiple granular white dots with hemorrhage (Figure 2). They enlarge and coalesce over time and follow the vascular arcades. Frosted branch angiitis may be seen in conjunction with CMV retinitis (Figure 3). After several weeks, retinal lesions atrophy.4 The underlying retinal pigment epithelium demonstrates pigment loss and migration, resulting in increased visualization of the underlying choroidal vasculature.

CMV retinitis responds to initial therapy. Recurrence usually begins at the margins of previously active infection and tends to "smolder" rather than actively progress. It will continue to spread, slowly but inexorably, if the treatment regimen is not altered. Patients with recurrent infection, while they are on appropriate levels of maintenance therapy, have an especially poor prognosis for preservation of sight, even with the use of increased doses of medication.

With the introduction of effective Anti-Retroviral Therapy (ART), the incidence of CMV retinitis has been noted to decrease by about 75%. Prior to the availability of effective ART, the median time to progression of treated CMV was 3- 9 months.

Ganciclovir Intraocular Implant

Direct intraocular administration of ganciclovir has the benefit of achieving therapeutic levels by bypassing the bloodretinal barrier. Furthermore, systemic absorption is minimal. Therefore, systemic complications are avoided, but protection of contralateral eye is not achieved. Therefore, oral prophylaxis with ganciclovir often is used in combination with the intraocular device.5 The ganciclovir intraocular device (GIOD) consists of a 6-mg pellet of ganciclovir. The resultant sustained linear drug release provides 3 or 6 months (depending on pellet construction) of anti- CMV activity. (Figure 4).

Surgical Management of Retinal Detachment

Retinal detachments secondary to CMV retinitis occur in 17-34% of patients6. Surgery should be considered in all patients with bilateral CMV retinitis because the eye with the retinal detachment ultimately may be the betterseeing eye. Vitrectomy with an intraocular silicone oil tamponade is the preferred operation in these patients. Scleral buckling is a different surgical technique in which a silicone sponge or band is affixed to the equator of the globe to support and keep the retina in position. For this procedure to be successful, the detachment should be small. Pneumatic retinopexy is a procedure that involves the injection of a gas bubble into the globe, with subsequent positioning of the patient so that the bubble's natural upward force pushes the retina back into position. Retinal laser or cryopexy may be used to "surround" and tack down the retina around a small peripheral retinal detachment in patients who are unable or unwilling to undergo surgical intervention.

Toxoplasma Retinochoroiditis

Toxoplasma gondii is a protozoan parasite, the life cycle of which includes encysted and active forms. In HIVinfected patients it causes multifocal sites of retinochoroidal infection with less frequent vitritis.7 Bilateral eye involvement also may be seen in patients with HIV disease, and proliferative vitreoretinopathy may accompany later stages of the disorder.

Toxoplasma retinochoroiditis may be confused with other forms of retinitis, but it usually can be differentiated by the presence of intense, almost fluffy, areas of retinal whitening with accompanying vitritis (Figure 5). Toxoplasmosis commonly involves the central nervous system in patients with advanced HIV disease and results in neurologic manifestations in 10-40% of affected individuals.

Serologic studies have been relatively unreliable for the diagnosis of toxoplasmosis in HIV-infected patients. However, toxoplasmosis is unlikely in a patient with a negative IgG anti- Toxoplasma antibody.

Patients with vision-threatening lesion may warrant a therapeutic trial using pyrimethamine and either sulfadiazine or clindamycin in standard dosages.8 Maintenance therapy with pyrimethamine and either sulfadiazine or clindamycin results in fewer relapses of infection than does pyrimethamine alone, and may need to be continued indefinitely while CD4 counts remain low.

Candida Endophthalmitis

Typical candidal fungal lesions appear as fluffy white "mounds," which are frequently bilateral and superficially located, and often extend into the vitreous. There usually is an overlying vitritis, and vitreous abscesses may be seen. Candida retinitis is not commonly seen in HIVinfected patients, but may be more likely in the setting of intravenous sources of infection (including indwelling catheters).

Bacterial Retinitis

Bacterial chorioretinitis, although infrequently seen, should be considered in patients with advanced HIV disease who present with posterior segment infection unresponsive to treatment for suspected viral, fungal, or protozoan causes.

Cryptococcus Chorioretinitis

Cryptococcus neoformans is a yeast that causes ocular infection in immunosuppressed individuals. CNS involvement with Cryptococcus in HIVinfected patients is relatively common and often results in meningitis with secondary ocular findings. Choroiditis and chorioretinitis from cryptococcal infection also have been observed in HIV-infected patients. Visual loss may occur which has been attributed to cryptococcal involvement of afferent tissues including the optic nerve, chiasm, and tract

Pneumocystis Choroiditis

Pneumocystis carini causes pneumonia (PCP), the most common systemic infection in patients with HIV disease in developed countries. Multiple pale yellow-white choroidal lesions, usually in both eyes, clinically characterize Pneumocystis choroiditis.9 The lesions generally are round or ovoid and of variable size, and may coalesce to form large confluent regions resulting in choroidal necrosis. If this process involves the foveal area, loss of central vision may occur. Of note is the almost total lack of an associated inflammatory response in the retina, vitreous, and anterior segment.

Acute Retinal Necrosis

Acute retinal necrosis (ARN) is a rapidly progressive viral uveitis. Peripheral retinal whitening, that progresses to necrosis over several days, characterizes ARN. Bilateral involvement may occur, and retinal detachments with proliferative vitreoretinopathy commonly occur10. Several viral pathogens have been associated with ARN. Varicella-zoster has been the most frequently implicated virus. HSV and CMV also have been associated with this disorder. Whereas ARN responds to treatment with intravenous acyclovir in immunocompetent individuals, it is much more recalcitrant to treatment in HIVinfected patients. The currently recommended treatment involves standard induction dosages of ganciclovir or foscarnet, with adjunctive high-dose intravenous acyclovir.

References

Cole EL et al. Herpes zoster ophthalmicus and acquired immune deficiency syndrome. Arch Ophthalmol 1984; 102:1027-9. Herpetic Eye Disease Study Group. Acyclovir for the prevention of recurrent herpes simplex virus eye disease. N Engl J Med 1998; 339:300-6. Levy JH, Liss RA, Maguire AM. Neurosyphilis and ocular syphilis in patients with concurrent human immunodeficiency virus infection. Retina 1989; 9:175-80. Fay MT, Freeman WR et al. Atypical retinitis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1988; 105:483-90. DF et al. Oral ganciclovir for patients with CMV retinitis treated with ganciclovir implant. Ganciclovir Study Group. N Engl J Med 1999; 340:1063-70. Broughton WL, Cupples HP, Parver LM. Bilateral retinal detachment following cytomegalovirus retinitis. Arch Ophthalmol 1978; 96:618-9. Quinlan P, Jabs JA. Ocular toxoplasmosis. Retina 1989;89:563 Schmitz K, Fabricius EM, Brommer H. [Prevalence, morphology and therapy of toxoplasmosis chorioretinitis in AIDS]. Fortschr Ophthalmol 1991; 88:698-704. Urayama A, Yamada N, Sasaki T, et al. Unilateral acute uveitis with retinal periarteritis and detachment. Jpn J Clin Ophthalmol 1971;25:607. Freeman WR et al. Demonstration of herpes group virus in acute retinal necrosis syndrome. Am J Ophthalmol 1986; 102:701-9.

Figures and Legends

Fig 1. Cotton wool spots are the most common non-infectious retinal manifestation of AIDS.

Fig 2. CMV infection of the retina produces widespread retinal necrosis and hemorrhage.

Fig 3. Frosted branch angiitis may be associated with CMV infection

Fig 4. The ganciclovir implant as seen through a dilated pupil (it is not visible in the undilated state).

Fig 5. Toxoplasmic retinochoroiditis often presents as a zone of retinal whitening and thickening with vitritis and less retinal hemorrhage than is usually seen with cytomegalovirus retinitis

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