August 11, 2008

AIDS and Ophthalmology, 2008

Author Affiliations

Copyright 2008 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2008

Arch Ophthalmol. 2008;126(8):1143-1146. doi:10.1001/archopht.126.8.1143

In 1981, a new disease, characterized by opportunistic infections (OIs) and unusual neoplasms, was reported to the Centers for Disease Control and Prevention.1 This disease, AIDS, was soon thereafter discovered to be caused by the human immunodeficiency virus (HIV), which invades cells of the immune system, particularly CD4+ T cells, resulting in their loss and the subsequent immune deficiency. From the beginning, it was evident that the eye was a frequent target organ in AIDS.2 The most frequent ocular manifestation was HIV retinopathy, consisting of cotton-wool spots with or without intraretinal hemorrhages.2,3 Histologic and fluorescein angiographic studies also demonstrated the presence of other vascular abnormalities, including microaneurysms and telangiectatic vessels.35 The most devastating ocular complications were ocular OIs, particularly cytomegalovirus (CMV) retinitis. Cytomegalovirus retinitis affected an estimated 30% of patients with AIDS sometime during the course of AIDS,6 and the rate among patients with CD4+ T-cell counts lower than 50 cells/μL was 0.20 cases/person-year (PY).7 By the early 1990s, CMV retinitis became the most common intraocular infection seen by ophthalmologists at major urban centers.8 Drugs to treat CMV retinitis were introduced in the late 1980s, including ganciclovir sodium (Cytovene; Roche Pharmaceuticals, Nutley, New Jersey; approved in 1989) and foscarnet sodium (Foscavir; AstraZeneca LP, Wilmington, Delaware; approved in 1991), and later, cidofovir (Vistide; Gilead Sciences, Inc, Foster City, California; approved in 1996) and fomivirsen sodium (Vitravene; Novartis Ophthalmics AG, Bulach, Switzerland, and Isis Pharmaceuticals, Inc, Carlsbad, California; approved in 1998). Treatment was initially given intravenously at higher doses for 2 to 3 weeks (induction therapy), followed by lifetime therapy at lower doses to prevent relapse of the disease (maintenance therapy or secondary prophylaxis). An oral form of ganciclovir with poor bioavailability was introduced and then replaced by valganciclovir hydrochloride (Valcyte; Roche Pharmaceuticals; approved in 2001), which had a good bioavailability after oral administration and produced ganciclovir blood levels similar to those of intravenous ganciclovir.9 Intravitreal injections of ganciclovir and foscarnet also were used to deliver higher drug concentrations to the retina and avoid systemic adverse effects. To improve local delivery of ganciclovir, a sustained-released implant (Vitrasert; Bausch & Lomb, Inc, San Dimas, California; approved 1996), which lasts approximately 6 months, was developed and Food and Drug Administration approved in 1996.10 However, because CMV is a systemic infection, local delivery of anti-CMV agents was associated with high rates of contralateral ocular and visceral disease and with an increased mortality.3,1113 Because of the disadvantages of local therapy, the implant typically was combined first with oral ganciclovir14 and now with valganciclovir.

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