INFLUENCE OF INTRAVITREAL INJECTIONS OF HPMPC AND RELATED NUCLEOSIDE ANALOGS ON INTRAOCULAR-PRESSURE IN GUINEA-PIG EYES

PURPOSE. Cidofovir (HPMPC) is a potent long-acting anticytomegalovirus agent. In humans, its dose-limiting intravitreal toxicity results in the lowering of intraocular pressure (IOP). The purpose of the present study was to determine the effects of HPMPC and various acyclic nucle oside phosphonate (ANP) analogues when administered intravitreally in guinea pig eyes and to establish the structural and functional relatio n of these compounds in connection with their effects on the ciliary b ody and retina. METHODS. Ninety-six guinea pig eyes were injected with various doses of HPMPC and ANP analogues. RESULTS. Severe lowering of IOP with structural alterations of the ciliary body was observed when doses were administered that achieved final intravitreal concentratio ns greater than 25 mu g/ml HPMPC, 200 mu g/ml cyclic HPMPC (cHPMPC), 2 5 mu g/ml (S)-HPMPA, and 625 mu g/ml PMEG. Concentrations of 25 mu g/m l HPMPC, 200 mu g/ml cHPMPC or less, and all concentrations of (R)-HPM PA, HPMPU, PMEA, PMEC, PMEDAP, (R)-PMPA, and (S)-PMPA did not lower IO P significantly, nor did they cause significant histologic changes. CO NCLUSIONS. Of the HPMP series, the cyclic analogue of HPMPC (cHPMPC) a nd HPMPC are the least toxic of the compounds that show potent anti-hu man cytomegalovirus activity (HCMV). PMEG, the most potent anti-HCMV c ompound of the PME series, is toxic at higher doses. Further evaluatio n of lower doses is needed. Compounds of the PMP series are not toxic, but they show no anti-HCMV activities. The IOP-lowering effect of the se compounds appears to be associated with an effect on the ciliary bo dy.