Risk Calculator for Retinopathy of Prematurity Requiring Treatment

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. 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. 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). 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. (Funded by Research to Prevent Blindness and others; ClinicalTrials.gov number, NCT00622726.).

Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease that affects premature infants. Despite improvements in neonatal care and management guidelines, ROP remains a leading cause of childhood blindness worldwide. Current screening guidelines are primarily based on two risk factors: birth weight and gestational age; however, many investigators have suggested other risk factors, including maternal factors, prenatal and perinatal factors, demographics, medical interventions, comorbidities of prematurity, nutrition, and genetic factors. We review the existing literature addressing various possible ROP risk factors. Although there have been contradictory reports, and the risk may vary between different populations, understanding ROP risk factors is essential to develop predictive models, to gain insights into pathophysiology of retinal vascular diseases and diseases of prematurity, and to determine future directions in management of and research in ROP.

To present the final results of the Early Treatment for Retinopathy of Prematurity Study. Infants with bilateral high-risk prethreshold retinopathy of prematurity (ROP) (n = 317) had one eye randomized to early retinal ablative treatment and the fellow eye managed conventionally (control eye). In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early or to conventional management. High risk was determined using a model based on the Cryotherapy for Retinopathy of Prematurity natural history cohort. The primary outcome was visual acuity assessed by masked testers using the Teller acuity card procedure. Structural examinations were performed at 6 and 9 months. Grating acuity results showed a reduction in unfavorable visual acuity outcomes with earlier treatment, from 19.8% to 14.3% (P < .005). Unfavorable structural outcomes were reduced from 15.6% to 9.0% (P < .001) at 9 months. Further analysis supported retinal ablative therapy for eyes with type I ROP, defined as zone I, any stage ROP with plus disease; zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3 with plus disease. The analysis supported a "wait and watch" approach to type II ROP, defined as zone I, stage 1 and 2 without plus disease, or zone II, stage 3 without plus disease. These eyes should be considered for treatment only if they progress to type I ROP or threshold. Early treatment of high-risk prethreshold ROP significantly reduced unfavorable outcomes in both primary and secondary (structural) measures.