Adverse Events and Autopsy Findings after Intravitreous Cidofovir (HPMPC) Therapy in Patients with Acquired Immune Deficiency Syndrome (AIDS)

Abstract

Objective: The purpose of the study is to evaluate the adverse events and autopsy findings in a series of consecutive 20-µg intravitreous cidofovir injections at a single institution.Design: The study design was a nonrandomized, consecutive case series.Participants: Seventy-six patients with acquired immune deficiency syndrome with cytomegalovirus retinitis were studied prospectively. Sixty-three patients had 1 month's follow-up or longer, and this comprised the study group. In addition, histopathologic findings from 18 eyes of 9 patients were studied at autopsy.Intervention: A total of 296 injections of 20 µg cidofovir were given in 115 eyes. Sixty-three patients who had 246 injections in 93 eyes had 1 month's follow-up or longer for the evaluation of adverse events.Main Outcome Measures: Postinjection chronic hypotony associated with permanent visual loss, transient hypotony, iritis, and its long-term sequela (posterior synechia and cataract, retinal detachment, extraocular cytomegalovirus involvement) were the outcomes of interest in this study. Additionally, light and electron microscopic studies of human eyes were performed.Results: The most severe adverse event was postinjection chronic hypotony. This phenomenon was associated with permanent visual loss. This was observed in 1 % of the injections and 3% of the eyes of the patients (95% confidence interval, 0%–6%). Transient hypotony associated with mild-to-moderate visual loss developed in 14%, but vision recovered to baseline levels in these eyes subsequently. Analysis showed that transient hypotony in the injected eye could predict postinjection chronic hypotony in the fellow eye (two-tailed Fisher's exact test, P = 0.02). The incidence of iritis was 32%; posterior synechia and cataract were the long-term sequela of the iritis and developed in 19% and 11 % of the eyes, respectively. The incidence of retinal detachment was lower (6%). Histopathologic evaluation of the eyes showed mild-to-moderate atrophy of the nonpigmented epithelium of the ciliary body and no other evidence of intraocular toxicity.Conclusions: The most serious adverse event was postinjection chronic hypotony, which occurred in 3% of eyes. Episodes of transient hypotony appear to indicate that the fellow eye was predisposed to chronic hypotony. Therefore, it may be prudent to give intravitreous injections at least 2 weeks apart in the fellow eye to evaluate the clinical response of the injected eye.