Purpose: To investigate the safety and efficacy of ranibizumab for the treatment of choroidal neovascularization (CNV) secondary to causes other than age-related macular degeneration (AMD).Design: Multicenter, randomized, 12-month clinical trial.Participants: Thirty patients with CNV due to causes other than AMD, including pathologic myopia, ocular histoplasmosis, and angioid streaks.Methods: Participants were randomly assigned 1: 1 to monthly intravitreal injections of 0.5 mg ranibizumab or 3 monthly injections followed by dosing as needed (pro re nata [PRN]) at monthly follow-up visits.Main Outcome Measures: Outcome measures included the incidence of ocular and nonocular adverse events, the percentage of patients gaining >= 15 letters of visual acuity (VA) at 6 and 12 months from baseline, the percentage of patients losing >= 15 letters of VA at 6 and 12 months from baseline, and mean change in VA and central retinal thickness (CRT) at 6 and 12 months from baseline.Results: No serious ocular or systemic adverse events related to ranibizumab or the injection procedure were reported. Among patients who received monthly ranibizumab injections, 8 of 12 (66.7%) gained >= 15 letters of VA at both 6 and 12 months, and among patients who received PRN injections, 9 of 14 (64.3%) and 8 of 14 (57.1%) gained >= 15 letters of VA at 6 and 12 months, respectively. No patient in the study lost >= 15 letters of VA. Mean VA improved significantly from baseline by 23.9 +/- 5.4 (P = 0.001) and 21.1 +/- 4.3 letters (P = 0.0003) at 6 months and by 26.9 +/- 5.3 (P = 0.0003) and 19.2 +/- 3.8 letters (P = 0.0002) at 12 months in the monthly and PRN treatment arms, respectively. Mean CRT decreased significantly from baseline by 103.4 +/- 18.9 (P = 0.0005) and 161.1 +/- 43.7 mu m (P = 0.0034) at 6 months and by 109.3 +/- 19.5 (P = 0.0004) and 166.6 +/- 38.4 mu m (P = 0.001) at 12 months in the monthly and PRN treatment groups, respectively. No statistically significant difference was found between treatment groups in change in VA or CRT at any time point.Conclusions: Intravitreal ranibizumab, given as monthly injections or as 3 monthly injections followed by PRN dosing, showed a promising efficacy and safety profile in the treatment of CNV due to causes other than AMD.

PURPOSE:To explore the role of integrin alpha5beta1 in proliferative vitreoretinopathy (PVR) pathogenesis by evaluating the expression alpha5beta1 on ARPE-19 cells and patient proliferative membranes, quantifying the inhibitory effects of JSM6427 (a small molecule alpha5beta1 inhibitor) on ARPE-19 cell adhesion and migration, and assessing the therapeutic potential of JSM6427 in a rabbit retinal detachment model.METHODS:Expression of alpha5beta1 was evaluated on activated ARPE-19 cells by flow cytometry and on PVR membranes by immunohistochemistry. ARPE-19 cells were used in fibronectin-dependent adhesion and migration assays with various concentrations of JSM6427; IC(50) was calculated. In the rabbit model, eyes were intravitreally injected with vehicle or JSM6427 on day 0 or 1 after retinal detachment; BrdU was administered intravitreally on day 3, and retinal tissues were harvested on day 3 (4 hours later) or 7. Retinal scarring, cellular proliferation, and inflammatory responses were quantified, and retinal morphology was analyzed in retinal sections.RESULTS:Activated ARPE-19 cells and PVR membranes expressed high levels of alpha5beta1; expression was low in control eyes. JSM6427 provided a dose-dependent blockade of ARPE-19 cell adhesion to fibronectin (IC(50), 7.1 +/- 2.5 microM) and inhibition of migration (IC(50), 6.0 +/- 4.5 microM). In the rabbit model, intravitreal injection of JSM6427 provided significant inhibition of proliferation of retinal cells (Müller cells, microglia, and macrophages) on days 3 and 7 after detachment and inhibition of inflammatory response and retinal scarring on day 7 after detachment.CONCLUSIONS:JSM6427 is a promising treatment for PVR, with data suggesting that inhibition of alpha5beta1-fibronectin interactions addresses multiple pathways involving retinal pigment epithelial, glial, and inflammatory cells.

PURPOSE:To assess vitreous concentrations of nonsteroidal antiinflammatory drugs (NSAIDs) and prostaglandin E(2) in patients treated with NSAIDs before vitrectomy.METHODS:This was an investigator-masked, randomized, multicenter study. Patients received ketorolac 0.4% 4 times a day, bromfenac 0.09% 2 times a day, nepafenac 0.1% 3 times a day, or no NSAID for 3 days before surgery. Nonsteroidal antiinflammatory drugs and prostaglandin E(2) levels were determined in vitreous samples collected at the beginning of surgery.RESULTS:Thirty-one patients were included in the analyses. The mean (SD) vitreous concentrations were as follows: ketorolac 2.8 (3.2) ng/mL, bromfenac 0.96 (0.31) ng/mL, nepafenac 1.1 (0.6) ng/mL, and amfenac 2.0 (0.8) ng/mL aligned with the initial concentrations of the topical NSAIDs. Mean (SD) vitreous prostaglandin E(2) levels of the control patients and those treated with ketorolac 0.4%, bromfenac 0.09%, or nepafenac 0.1% were 270.6 (91.7) pg/mL, 189.6 (50.2) pg/mL, 247.2 (38.3) pg/mL, and 267.7 (99.7) pg/mL, respectively. Patients treated with ketorolac 0.4% had significantly lower prostaglandin E(2) levels than those treated with no NSAID (P = 0.047) or nepafenac 0.1% (P = 0.028).CONCLUSION:All three NSAIDs penetrated into the vitreous cavity. Topical therapy with ketorolac may lower preoperative vitreous prostaglandin E(2) levels, which may have a clinical impact on the management of prostaglandin-mediated diseases, including cystoid macular edema.

Purpose: A multi-institutional, randomized clinical trial was performed to assess the safety and feasibility of the TheraSight system for treatment of wet age-related macular degeneration (wet-AMD). The HDR 103Pd applicator, clinical trial, and our clinical experience with the TheraSight system are presented in this report.