FUNGAL DISEASE

CANDIDIASIS

Ocular involvement accompanies systemic Candida infection and candidemia in approximately two-thirds of cases. The initial Candida lesion is a focal necrotizing granulomatous retinitis with or without choroiditis, characterized by fluffy white exudative lesions associated with cells in the vitreous overlying the lesion. Such lesions may spread to involve the optic nerve and macula. Endophthalmitis, Roth's spots, and exudative retinal detachment may occur. Spread into the vitreous cavity may result in the formation of a vitreous abscess, sometimes described as "a string of pearls." Anterior uveitis occurs, and a hypopyon may form.

Treatment consists of systemic administration of amphotericin B, flucytosine, and ketoconazole. Early vitrectomy may prevent macular damage.

MUCORMYCOSIS

Mucormycosis is a rare, often fatal infection occurring in debilitated patients, particularly poorly controlled diabetics. The fungi (Rhizopus, Mucor, and Absidia) attack through the upper respiratory tract and invade the arterioles, producing necrotic tissue. Clinical features are the pathognomonic black hemipalate, proptosis, and an ischemic globe with blindness due to ophthalmic artery occlusion. Death occurs from cerebral abscess.

Treatment includes removal of the affected tissue, intravenous amphotericin B (preferably liposomal), and management of the underlying medical condition.

ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)

AIDS is caused by human immunodeficiency virus (HIV), a retrovirus. The virus infects mature T helper cells and leads to immunosuppression, the severity of which depends on the balance between the rates of destruction and replacement of T cells. The persistent immunodeficiency gives rise to opportunistic infections. The virus has been recovered from various body fluids, including blood, semen, saliva, tears, and cerebrospinal fluid.

Transmission & Prevention of AIDS

Transmission of HIV is primarily by exchange of bodily fluids during sexual contact or through the use of contaminated needles by intravenous drug abuse. Transmission may also occur when contaminated blood products are transfused. The virus is not transmitted by casual contact, but because it is found in tears, conjunctival cells, and blood, health care workers must take reasonable precautions when handling infectious waste or when at risk of contact with body fluids.

Clinical Findings

The spectrum of clinical disease is wide, presumably due to the degree of immunologic damage and the frequency and nature of opportunistic infections. Typically, an acute flu-like illness occurs a few weeks after infection, followed months later by weight loss, fever, diarrhea, lymphadenopathy, and encephalopathy. The commonest ocular findings are retinal microvasculopathy with cotton-wool spots (Figure 15-30) and hemorrhages and conjunctival vasculopathy characterized by comma vessels, sludging of the blood, and linear hemorrhages. The cause of these findings is unknown, but they are sometimes associated with increased plasma viscosity and may represent immune complex deposition.

The hallmark of AIDS is the high incidence of infections, which are frequently multiple, opportunistic, and severe. The eye is involved in 30% of cases, and both the anterior segment and the retina may be affected. Viral opportunistic infections of the retina are most common, particularly cytomegalovirus. Typically there is a hemorrhagic necrotic retinopathy spreading from vascular arcades and associated with arteriolar occlusions. The vitreous is quiet; retinal detachment may occur. Involvement of the optic nerve results in gross optic disk edema and severe sudden and irreversible visual loss. Diagnosis is usually based on circumstantial evidence of positive antibody titers in blood, urine, or cerebrospinal fluid. Ocular fluids and retinal specimens are rarely examined. Treatment is with either ganciclovir or foscarnet. Both are virostatic drugs that stop progression of disease but do not eradicate the virus from the eye. Neutropenia is the most important side effect of ganciclovir, and renal damage of foscarnet. Local administration of both drugs is effective in controlling ocular infection but not systemic spread. A standard regimen is a 2-week induction course of intravenous therapy followed by maintenance oral therapy. Alternatively, intravitreal implant or repeated intravitreal injections may be supplemented by oral treatment. Cidofovir may also be used, but ocular complications include uveitis, ocular hypotension, and ciliary body necrosis.

Treatment of the HIV infection is complicated and involves combinations ("triple therapy") of protease inhibitors and reverse transcriptase inhibitors, usually given in 3-month cycles. These regimens may result in a dramatic drop in the HIV viral load, increase in CD4 counts, and improved well-being for the patient. It may be possible to stop anti-cgcytomegalovirus (CMV) therapy when the CD4 count has risen above 200/L for 3 months.

Herpes simplex retinitis begins in the peripheral retina, advances to involve the entire fundus, and is associated with arteriolar occlusion. The retinitis almost always occurs concurrently with herpes simplex encephalitis, and this serves to distinguish herpes simplex from cytomegalovirus retinitis, which is rarely complicated by encephalitis. Treatment is with acyclovir, but maintenance therapy is required. A virulent form of retinitis, progressive outer retinal necrosis, is attributed to herpes zoster.

Toxoplasma chorioretinitis is usually bilateral, acquired (congenital infections are rarely reactivated in AIDS), and associated with substantial vitreous reaction; candidal endophthalmitis is rarely seen except in drug addicts. Less common organisms that typically involve the choroid are Pneumocystis carinii, Cryptococcus, and Mycobacterium avium-intracellulare. Choroidal infection is blood-borne and portends imminent demise.

Herpes zoster ophthalmicus is a rare presenting feature of HIV infection and may be very severe, with anterior segment necrosis and ophthalmoplegia. Similarly, syphilis in association with HIV infection produces a severe blinding uveitis. Herpes simplex, molluscum contagiosum, and Kaposi's sarcoma frequently affect the eyelids and surrounding tissues. The combination of rifabutin and clarithromycin or cidofovir may precipitate symptomatic uveitis.

Neuro-ophthalmologic problems are divided into those related directly to HIV infection of the brain, such as optic neuropathy and intranuclear ophthalmoplegia, and those caused by cerebral abscesses or encephalitis, commonly due to Cryptococcus, lymphoma, or toxoplasmosis.

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