title: 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-microg intravitreous cidofovir injections at a single institution.
  
  
  METHODS
  The study design was a nonrandomized, consecutive case series.
  
  
  METHODS
  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.
  
  
  METHODS
  A total of 296 injections of 20 microg 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Ophthalmology, Shiley Eye Center, University of California at San Diego, La Jolla 92093-0946, USA.
authors.forename: I
authors.initials: I
authors.lastname: Taskintuna
authors.forename: F M
authors.initials: FM
authors.lastname: Rahhal
authors.forename: N A
authors.initials: NA
authors.lastname: Rao
authors.forename: C A
authors.initials: CA
authors.lastname: Wiley
authors.forename: A J
authors.initials: AJ
authors.lastname: Mueller
authors.forename: A S
authors.initials: AS
authors.lastname: Banker
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J F
authors.initials: JF
authors.lastname: Arevalo
authors.forename: W R
authors.initials: WR
authors.lastname: Freeman
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy*; D000328:Adult; D000869:Anterior Eye Segment / Q000187:drug effects / Q000473:pathology; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001344:Autopsy; D000077404:Cidofovir; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy*; D003596:Cytosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005500:Follow-Up Studies; D005654:Fundus Oculi; D006801:Humans; D007267:Injections; D007500:Iritis / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015814:Ocular Hypotension / Q000139:chemically induced* / Q000473:pathology; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000648:ultrastructure; D011446:Prospective Studies; D014822:Vitreous Body
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir