Objective: To determine whether earlier treatment of high-risk, prethreshold retinopathy of prematurity (ROP) improves retinal structural outcome at 2 years of age. Methods: Infants with bilateral high-risk prethreshold ROP had one eye randomly assigned to treatment with peripheral retinal ablation. The fellow eye was managed conventionally, and either treated at threshold ROP or observed if threshold was never reached. In patients with asymmetrical disease, the highrisk, prethreshold eye was randomised to earlier treatment or to conventional management. At 2 years of age, children were examined comprehensively by certified ophthalmologists to determine structural outcomes for their eyes. For the purposes of this study, an unfavourable structural outcome was defined as (1) a posterior retinal fold involving the macula, (2) a retinal detachment involving the macula or (3) retrolental tissue or ''mass'' obscuring the view of the posterior pole. Results of the 2-year examination were compared with those from the 9 months examination. Results: Data were available on 339 of 374 (90.6%) surviving children. Unfavourable structural outcomes were reduced from 15.4% in conventionally managed eyes to 9.1% in earlier-treated eyes (p = 0.002) at 2 years of age. Ophthalmic side effects (excluding retinal structure) from the ROP or its treatment were similar in the earlier-treated eyes and the conventionally managed eyes. Conclusion:The benefit of earlier treatment of high-risk prethreshold ROP on retinal structure endures to 2 years of age, and is not counterbalanced by any known side effect caused by earlier intervention. Earlier treatment improves the chance for long-term favourable retinal structural outcome in eyes with high-risk prethreshold ROP. Long-term follow-up is planned to determine structural and functional outcomes at 6 years of age.T he Early Treatment for Retinopathy Of Prematurity (ETROP) Study showed that retinal ablation for highrisk prethreshold retinopathy of prematurity (ROP) improved structural and functional outcomes, compared with conventional management, when infants were examined at 9 months' corrected age. 1 The study randomised infants who had both prethreshold disease and a risk for unfavourable structural outcome >15%. 2However, eyes of infants may change over time.3 Myopia, strabismus and late retinal detachments all increase in frequency in the months and years after successful treatment of ROP.3 4 In the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study, a wide distribution of optotype acuities developed after successful treatment, with 75% showing acuities worse than 20/40 when children reached 10 and 15 years of age.3 5 Time will tell whether the ETROP cohort will show the same distribution of functional outcomes as occurred in the CRYO-ROP Study.In the CRYO-ROP Study, only a few infants had threshold disease in zone I, 6 but in the ETROP Study, 40% of all randomised children had zone I disease. This group of children may be particularly vulnerable to complications of myopia, stra...

Few interventions and treatments for premature infants have undergone the rigors of a randomized controlled trial (RCT), the cornerstone of evidence-based healthcare. Multiple barriers in establishing a quality evidence base for the care of preterm infants are examined including the systematic exclusion of children from drug trials, vulnerability of the infants, burden to families of the consent process for RCTs, and the lack of standard measurements and subgroup definitions that impede systematic reviews. Delays in getting evidence into practice are highlighted, including clinician knowledge of existing evidence, attitudes about the evidence, and behavior. Landmark trials are used as examples. Finally, a call for the research community to develop guidance on good clinical research practice for preterm infants is offered that will allow the synthesis of the totality of evidence.