LOW-DOSE INTRAVITREAL CIDOFOVIR (HPMPC) THERAPY OF CYTOMEGALOVIRUS RETINITIS IN PATIENTS WITH ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME

Purpose: The authors have shown that long-term treatment of cytomegalo virus (CMV) retinitis with 20-mu g intravitreal injections of cidofovi r (HPMPC) is highly effective but may be associated with iritis and pr ofound hypotony. They evaluated the efficacy and safety of 10-mu g int ravitreal injections of cidofovir and made comparisons with their find ings of 20-mu g injections. Methods: The current study was conducted a s a nonrandomized consecutive case series at the AIDS Ocular Research Unit of the University of California at San Diego. Twenty-seven eyes o f 18 patients were injected with 10 mu g intravitreal cidofovir and ha d complete follow-up. These were compared with another consecutive ser ies of 24 eyes of 17 patients injected with 20 Ixg of cidofovir. Main Outcome Measures: The main outcome in this study was the incidence of failure to respond to treatment with 10-mu g injections. The authors a lso compared the time to progression of CMV retinitis after the initia l intravitreal injections of 10 mu g and 20 mu g of cidofovir. Seconda ry outcomes included incidence of iritis and changes in intraocular pr essure (IOP) after cidofovir injections. Results: The median time to r etinitis progression was 45 days after a single intravitreal injection of 10 mu g cidofovir compared with 55 days with the authors' series o f 20-mu g injections. This difference was statistically significant (P = 0.033, log-rank test) and appeared to be due principally to a 26% i ncidence of primary failure in the 10-mu g group (progression greater than or equal to 750 mu m within 28 days, P = 0.0017 Wilcoxon test). P rogression after a second injection of 10 mu g cidofovir was more rapi d (32 days, P = 0.037). The incidence of iritis after 10-mu g injectio ns was 2.2% compared with 23% with 20-mu g injections (P = 0.003, Fish er's exact test, two-tailed). There was less decrease in IOP between t he baseline injection and subsequent visits in the 10-mu g group. Conc lusions: Treatment of CMV retinitis with 10-mu g intravitreal cidofovi r injection was not as effective as with 20 mu g and may allow develop ment of drug resistance, but there were fewer side effects with the 10 -mu g dose. The drug appears to have a narrow therapeutic index, and o ther attempts at reducing the side effects while preserving the long-a cting effect, such as liposome delivery, may be warranted.