M. Nasir

Ranibizumab for the Treatment of Macular Edema Associated with Perfused Central Retinal Vein Occlusions

PURPOSE Assessment of biological effect, visual acuity changes, and safety of intravitreal (IVT) ranibizumab in patients with macular edema associated with perfused central retinal vein occlusion (CRVO). DESIGN Ongoing, prospective, open-label, single-center, uncontrolled study. PARTICIPANTS Ten adult patients with macular edema associated with perfused CRVO. METHODS Patients were randomly assigned to receive 3 monthly IVT injections of either 0.3 or 0.5 mg ranibizumab (n = 5 at each dose). Additional injections were administered quarterly as needed over the ensuing 21 months at the physicians discretion for recurrent or persistent macular edema. MAIN OUTCOME MEASURES The predetermined primary endpoint was the percentage of patients gaining >or=15 letters of best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity (BCVA). The secondary endpoints include the mean change in BCVA and central retinal thickness (CRT) measured by optical coherence tomography, the rate of progression to ischemic CRVO, extent of intraocular hemorrhage, retinal vein diameter, optic nerve head swelling, and the incidence and severity of ocular and nonocular adverse events. RESULTS After 3, 6, and 9 months of follow-up, 40%, 10%, and 30% of patients, respectively, gained >or=15 letters in BCVA; mean BCVA improved by 12+/-20 letters, 3+/-21 letters, and 1+/-24 letters, respectively, compared with baseline; CRT showed a mean decrease of 272+/-244 microm, 88+/-178 microm, and 119+/-153 microm, compared with baseline. No significant differences were observed between the 0.3- and 0.5-mg doses. Most patients experienced decreases in the extent of retinal hemorrhage, retinal vein diameter, and optic nerve head swelling at months 3 and 6 compared with baseline. No patients progressed to ischemic CRVO or experienced a severe adverse event that was attributed to ranibizumab. CONCLUSIONS Ranibizumab is generally well-tolerated and may improve BCVA and decrease CRT. The improvements in BCVA and CRT observed during the initial monthly injection period (0 to 3 months) were possibly lost to the recurrence of macular edema in between ranibizumab injection during the quarterly treatments (3 to 9 months). The extent of retinal hemorrhage, retinal vein diameter, and nerve swelling continued to normalize for most of the patients from baseline to 6 months. Follow-up is ongoing, and alternative dosing regimens are being evaluated.

Recombinant Hirudin Prevents Postoperative Fibrin Formation after Experimental Cataract Surgery

PURPOSE The authors studied the effect of a direct acting antithrombin agent, desulfatohirudin variant 1 (Revasc, Ciba-Geigy, Ltd., Basel, Switzerland), on postoperative fibrin formation after cataract surgery in rabbits. METHODS Phacoemulsification was performed in a masked fashion on 28 eyes of 28 New Zealand white rabbits. Ten control group eyes had lactated Ringers solution in the infusion and an intracameral injection (approximately 1.5 ml) at the end of the case. Ten group 1 eyes received hirudin 100 micrograms/ml in the infusion and intracameral injection. Eight group 2 eyes had 100 micrograms/ml hirudin in the intracameral injection only. Using slit-lamp examination, all eyes were graded for the amount of fibrin and intraocular hemorrhage in a masked fashion on postoperative day 1. RESULTS Comparison of the mean postoperative fibrin grade (0-4) in group 1 (mean = 0.3), group 2 (mean = 0.25) and the control group (mean = 3.4) revealed a statistically significant difference between hirudin-treated and control eyes (P = 0.0002 for group 1, P = 0.0005 for group 2). No intraocular hemorrhage was noted in any group. CONCLUSIONS Recombinant hirudin significantly decreases postoperative fibrin formation in a rabbit cataract extraction model. Intracameral injection of hirudin alone appears to be at least as effective as infusion of hirudin throughout the case. With further study, this agent has potential for use in cataract surgery on patients known to be at high risk for postoperative fibrin formation.

Recombinant hirudin for prevention of experimental postoperative intraocular fibrin

PURPOSE To determine the efficacy of a specific antithrombin agent (recombinant desulphatohirudin variant 1 [Revasc, Ciba-Geigy, Ltd., Basel, Switzerland]) administered in the infusion fluid to prevent early postoperative fibrin formation in a rabbit lensectomy and vitrectomy model. METHODS Standard fragmatome lensectomies and core vitrectomies were performed prospectively in a masked fashion on ten control eyes with lactated Ringers infusion and on ten eyes treated with 10 microgram of recombinant hirudin/ml in the infusate. The amounts of fibrin and hemorrhage were graded in a masked fashion by using slit-lamp examination and indirect ophthalmoscopy on postoperative days 1 through 5 and on day 7. RESULTS The difference in the mean grade of fibrin formed on the first postoperative day in the eyes treated with recombinant hirudin (mean, 0.9) in relation to the mean grade of fibrin in the control eyes (mean, 3.5) was statistically significant (P = .004). This difference was also significant on the second postoperative day (P = .01). None of the treated eyes developed intraoperative or postoperative hemorrhage. CONCLUSIONS Recombinant desulphatohirudin variant 1 is an effective inhibitor of postoperative fibrin formation in a rabbit model and is not associated with an increased risk of intraoperative or postoperative bleeding at the tested dose. This drug may be a useful adjunct in vitreous surgery for both proliferative vitreoretinopathy and the complications of proliferative diabetic retinopathy.