Marc O. Yoshizumi

Classification of Proliferative Vitreoretinopathy Used in the Silicone Study

The Silicone Study is a multicenter randomized clinical trial that compares a long-acting gas with silicone oil for the surgical treatment of proliferative vitreoretinopathy (PVR). As part of the study, a topographic classification of PVR has been developed that is based on the characteristic patterns of retinal distortion produced by the contraction of proliferative membranes on the retina or within the vitreous base. This classification is used to document the extent and anatomic distribution of PVR present preoperatively and to help standardize the surgical treatment. Experience has shown that this classification facilitates the identification of these membranes and their systematic dissection, and the authors therefore suggest that it be used to augment the Retina Society classification of PVR.

Transscleral iontophoresis of foscarnet.

Current local treatments of cytomegalovirus retinopathy may result in serious intraocular complications. Using an animal model, we investigated transscleral iontophoresis as a technique for delivery of foscarnet to the vitreous. Using a probe tip surface area of 0.19 mm2, a current of 1 mA, and a duration of ten minutes, transscleral iontophoresis of 0.5 ml of a 24-mg/ml foscarnet solution was administered to 72 normal rabbits. Vitreous aspiration was performed at 12 intervals (15 minutes, 30 minutes, and one, two, four, eight, 16, 24, 32, 40, 48, and 60 hours) after iontophoresis, and samples were analyzed by high-performance liquid chromatography to determine the vitreous pharmacokinetics of foscarnet. A peak foscarnet concentration of 200 +/- 31 microM (mean +/- standard deviation) was attained four hours after iontophoresis and was well below the concentration reported to cause retinal toxicity. Therapeutic levels were maintained until 60 hours after iontophoresis. The elimination half-life was approximately 24 hours. No toxic effects to anterior chamber structures were observed by biomicroscopy. Transscleral iontophoresis of foscarnet may provide an effective and safe technique for local treatment of cytomegalovirus retinopathy in patients with acquired immunodeficiency syndrome.

Taxol treatment of experimental proliferative vitreoretinopathy

Taxol is a potent stabilizer of microtubules, and inhibitor of in vitro replication, migration, and contraction of fibroblasts. It has been found to limit the development of experimental tractional retinal detachments in nonvitrectomized rabbit eyes. We used taxol in vitrectomized, phakic rabbit eyes with experimentally induced proliferative vitreoretinopathy and tractional retinal detachments. Taxol was dissolved in 30% DMSO because of poor aqueous solubility. A single 0.1 ml intravitreal dose of 2 × 10−4M taxol in 30% DMSO was injected immediately after 250000 heterologous corneal fibroblasts had been injected; 0.1 ml of 30% DMSO was injected into control eyes. Taxol reduced the incidence of tractional retinal detachments seen 3–4 weeks later. When taxol injection was delayed for 3 days after the initial intravitreal injection of fibroblasts into nonvitrectomized eyes, the extent of retinal detachments was reduced, but the incidence of retinal detachment was unchanged from the untreated eyes at the end of 4 weeks. These data indicate that taxol may be most useful when given early in the course of proliferative vitreoretinopathy.

Safety of repeated intravitreous injections of antibiotics and dexamethasone.

PURPOSE To determine the retinotoxicity of repeated intravitreous injections of vancomycin, ceftazidime, and dexamethasone in rabbit eyes. METHODS Twenty pigmented New Zealand rabbits were divided into two groups. In Group 1, the right eyes received repeated intravitreous injections with vancomycin 0.3 mg, ceftazidime 0.7 mg, and dexamethasone sodium phosphate 0.13 mg at three consecutive 48-hour intervals. Group 2 right eyes received three times higher dose of the same intravitreous drugs as used in Group 1, repeated at the same frequency. All left eyes served as control eyes. Retinotoxicity was monitored by slit-lamp biomicroscopy, indirect ophthalmoscopy, electroretinography, and light and electron microscopy. RESULTS No evidence of retinotoxicity was found in Group 1 eyes. Photopic A-waves were significantly elevated, and 30- and 50-Hz flicker fusion amplitudes were significantly depressed in Group 2 eyes. No changes were found by clinical or histopathologic examination in the retinas of either group. CONCLUSIONS Three repeated intravitreous injections at 48-hour intervals of a combination of vancomycin, ceftazidime, and dexamethasone in rabbit eyes at dosages that approximate drug concentrations recommended for human endophthalmitis were nontoxic. Similar injections at three times higher doses resulted in mild electroretinogram changes.

Topical and intravenous gentamicin in traumatically lacerated eyes

Intravenous or topical gentamicinThe authors have no commercial or proprietary interest in the gentamicin nor are they sponsored by the manufacturers of the drug in any capacity may be the initial mode of treatment for lacerated or ruptured eyes by emergency room physicians while awaiting ophthalmic consultation and surgical repair. The purpose of this study was to determine the possibility of having retinotoxic intravitreal gentamicin concentrations in experimentally lacerated rabbit eyes treated with either intravenous or topical gentamicin separately or in combination with each other. Nontoxic concentrations of gentamicin were found in the vitreous bodies by all routes of drug administration. After 3 h intravitreal concentrations of gentamicin were: 0.20–0.30 μg/ml when treated intravenously, 0–2.9 μg/ml when treated topically, and 0.20–0.51 μg/ml when treated both intravenously and topically. While the upper range of topically applied gentamicin concentrations (2.9 μg/ml) is therapeutic for some pathogens, the wide range of intravitreal concentrations (0–2.9 μg/ml) achieved does not indicate that topically applied gentamicin with or without intravenously administered gentamicin can reliably achieve therapeutic concentrations.

Ocular Toxicity of Experimental Intravitreal DMSO

AbstractDimethyl sulfoxide (DMSO) is a universal solvent which may be a suitable solvent for intraocular drugs. In this experimental study, the toxic effect of intravitreal DMSO in rabbits is examined. Single and multiple intravitreal injections of 1%, 10%, 50%, and 100% DMSO were made. Single injections produced no long-term toxic effect. Toxic effects were seen in the lens with cataract formation when injected with multiple doses of DMSO. Transient retinal toxicity was seen 1 hr after injection of DMSO, but cleared completely in 1 month.

Ocular Iontophoretic Supplementation of Intravenous Foscarnet Therapy

PURPOSE Reactivation of cytomegalovirus retinopathy during intravenous antiviral therapy is usually treated with higher doses of drug. We sought to determine whether ocular iontophoresis increases the intravitreal foscarnet concentration attained by intravenous injection. METHODS We injected foscarnet (120 mg/kg or 180 mg/kg) intravenously into 24 rabbits and determined the time of maximal concentrations in serum and vitreous humor. We injected the same doses into 24 additional rabbits and administered ocular foscarnet iontophoresis one hour later. Vitreous humor concentrations were assayed at one, four, eight, 24, 60, and 120 hours after iontophoresis and compared with those from injection alone. RESULTS Maximum serum and vitreous humor concentrations were achieved one hour after each intravenous dose. Maximum vitreous humor concentrations were achieved four hours after 120 mg/kg intravenous doses plus iontophoresis and eight hours after 180-mg/kg intravenous doses plus iontophoresis. Vitreous humor levels were significantly higher in eyes receiving intravenous foscarnet (120 mg/kg, P < .0001; 180 mg/kg, P < .0001) plus ocular Foscarnet iontophoresis than in those receiving intravenous foscarnet alone. Vitreous humor foscarnet levels in eyes receiving 120 mg/kg intravenously did not differ significantly from those in the group receiving 180 mg/kg intravenously (P < .1). The intravenous dose did not significantly affect vitreous humor levels after iontophoresis (P < .1). Vitreous concentrations fell below therapeutic levels (25 microM) in all eyes 60 hours after intravenous foscarnet and ocular foscarnet iontophoresis. CONCLUSIONS Ocular iontophoresis significantly increased intravitreous foscarnet concentrations above those attained by intravenous injection alone and may be an effective alternative to increasing the intravenous drug dose in patients with reactivated cytomegalovirus retinopathy.