RESUMEN
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 µm (P = 0.0034) at 6 months and by 109.3 ± 19.5 (P = 0.0004) and 166.6 ± 38.4 µm (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.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Estrías Angioides/complicaciones , Anticuerpos Monoclonales/administración & dosificación , Neovascularización Coroidal/tratamiento farmacológico , Histoplasmosis/complicaciones , Miopía Degenerativa/complicaciones , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Adulto , Anticuerpos Monoclonales Humanizados , Neovascularización Coroidal/etiología , Neovascularización Coroidal/fisiopatología , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Ranibizumab , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Agudeza Visual/fisiologíaRESUMEN
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.