Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

Abstract

BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety.

The Expanding Role of Vascular Endothelial Growth Factor Inhibitors in Ophthalmology

“…The recent Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity (BEAT-ROP) trial determined that intravitreal bevacizumab was superior to laser photoablation (adverse outcomes: 4% vs 22%; Pϭ.003) for eyes with zone 1 disease, but not for eyes with zone 2 disease (Pϭ.27). 69 Although these results appear promising, the precise role of bevacizumab in the management of retinopathy of prematurity is evolving.…”

Refractive errors after the use of bevacizumab for the treatment of retinopathy of prematurity: 2-year outcomes

“…6 In the last several years, anti-vascular endothelial growth factor (VEGF) agents have emerged as a new treatment for ROP, and promising experiences have been reported. [8][9][10] However, only a few case series have reported the refractive outcomes after the injection of an anti-VEGF agent in these ROP patients. [9][10][11][12] These reports showed lower prevalences of myopia and high myopia in anti-VEGF-treated patients than in laser-treated patients.…”

Terapia anti-angiogénica con ranibizumab en el tratamiento de retinopatía de la prematuridad

“…La administración de drogas y alimentos de los Estados Unidos (The Food and Drug Administration, FDA) aprobó el bevacizumab (Avastin, Genentech, San Francisco) intravenoso en 2004 para el tratamiento de cáncer de colon metastásico, comprobando reducción en el número y tamaño de los vasos nutricios de células metástasicas. El uso "offlabel" para enfermedades neovasculares a nivel oftalmológico se inició después (13). Posteriormente los estudios multicéntricos, aleatorizados como el BEAT ROP del 2011, entre otros, evidenciaron la eficacia del Bevacizumab intravítreo (Roche AG, Basilea, Suiza) para estadios de ROP (5,7,13).…”

“…El uso "offlabel" para enfermedades neovasculares a nivel oftalmológico se inició después (13). Posteriormente los estudios multicéntricos, aleatorizados como el BEAT ROP del 2011, entre otros, evidenciaron la eficacia del Bevacizumab intravítreo (Roche AG, Basilea, Suiza) para estadios de ROP (5,7,13). El Ranibizumab (Lucentis, Genentech, San Francisco) para tratamiento de ROP se ha estudiado en la literatura en pocas series de casos en combinación con láser, cuenta con registro Invima en nuestro país pero su uso es "offlabel" para ROP.…”