ABSTRACT. Objective. Retinopathy of prematurity (ROP) is a potentially avoidable cause of blindness in children. The proportion of blindness as a result of ROP varies greatly among countries depending on their level of development, being influenced by the availability of neonatal care, neonatal outcomes, and whether effective screening and treatment programs are in place. The objective of this study was to compare characteristics of premature infants who developed severe ROP between 1996 and 2002 in highly developed countries with less developed countries.Methods. This was an observational study. A questionnaire was completed by ophthalmologists in countries with low, moderate, and high development rankings (3 highly developed countries and from 10 less welldeveloped countries) who screen for ROP in which they supplied birth weights and gestational ages (GAs) of infants who were treated for threshold ROP or identified with more advanced stages of the disease. Birth weights and GAs of infants with severe ROP were measured.Results. The mean birth weights of infants from highly developed countries ranged from 737 to 763 g compared with values ranging from 903 to 1527 g in less developed countries. Mean GAs of infants from highly developed countries ranged from 25.3 to 25.6 weeks compared with 26.3 to 33.5 weeks in less developed countries. A total of 13.0% of 1091 infants from poorly developed countries exceeded United Kingdom screening criteria; 3.6% exceeded a criteria of <34 weeks' GA and/or <1750 g birth weight.Conclusions. These findings suggest that larger, more mature infants are developing severe ROP in countries with low/moderate levels of development compared with highly developed countries. ROP screening programs need to use criteria that are appropriate for their local population. Pediatrics 2005;115:e518-e525. URL: www. pediatrics.org/cgi

Background:Retinopathy of prematurity (ROP) is a leading cause of potentially avoidable childhood blindness worldwide. We estimated ROP burden at the global and regional levels to inform screening and treatment programs, research, and data priorities.Methods:Systematic reviews and meta-analyses were undertaken to estimate the risk of ROP and subsequent visual impairment for surviving preterm babies by level of neonatal care, access to ROP screening, and treatment. A compartmental model was used to estimate ROP cases and numbers of visually impaired survivors.Results:In 2010, an estimated 184,700 (uncertainty range: 169,600–214,500) preterm babies developed any stage of ROP, 20,000 (15,500–27,200) of whom became blind or severely visually impaired from ROP, and a further 12,300 (8,300–18,400) developed mild/moderate visual impairment. Sixty-five percent of those visually impaired from ROP were born in middle-income regions; 6.2% (4.3–8.9%) of all ROP visually impaired infants were born at >32-wk gestation. Visual impairment from other conditions associated with preterm birth will affect larger numbers of survivors.Conclusion:Improved care, including oxygen delivery and monitoring, for preterm babies in all facility settings would reduce the number of babies affected with ROP. Improved data tracking and coverage of locally adapted screening/treatment programs are urgently required.

Background: Current therapy does not eradicate ocular morbidity and visual disability following retinopathy of prematurity. Anti-vascular endothelial growth factor treatment provides a potentially new treatment. Methods: Infants with birth weight <1,500g meeting established criteria for ROP treatment were recruited in 87 neonatal and ophthalmology centres in 26 countries. We performed a randomised, multicentre, open-label, 3arm, parallel-group study evaluating efficacy and safety of intravitreal injection of ranibizumab 0•2mg or ranibizumab 0•1mg against laser therapy. The primary outcome was treatment success, defined as survival with no active retinopathy, unfavourable structural outcomes or the need for an additional treatment modality at or before 24 weeks. Findings: Treatment success occurred in 56/70 (80%) infants receiving ranibizumab 0•2mg compared with 57/76 (75%) receiving ranibizumab 0•1mg and 45/68 (66%) infants following laser therapy. The odds ratio of a successful outcome following ranibizumab 0•2mg compared with laser therapy was 2•19 (95% confidence interval 0•99-4•82; p=0•051). One infant had an unfavourable structural outcome following ranibizumab 0•2mg, compared to five following ranibizumab 0•1mg and seven after laser therapy. Ranibizumab 0•2mg was effective in both Zone I and Zone II disease. Ranibizumab 0•1mg offered no advantage over 0•2 mg. Death, serious and non-serious systemic and ocular adverse events were evenly distributed between the three groups. Interpretation: In the treatment of retinopathy of prematurity, ranibizumab 0•2mg was effective with fewer unfavourable ocular outcomes than laser therapy and with an acceptable short-term safety profile. Funding: Novartis Pharma; RAINBOW ClinicalTrials.gov number, NCT02375971.

Major malformations of the human eye, including microphthalmia and anophthalmia, are examples of phenotypes that recur in families yet often show no clear Mendelian inheritance pattern. Defining loci by mapping is therefore rarely feasible. Using a candidate-gene approach, we have identified heterozygous coding-region changes in the homeobox gene OTX2 in eight families with ocular malformations. The expression pattern of OTX2 in human embryos is consistent with the eye phenotypes observed in the patients, which range from bilateral anophthalmia to retinal defects resembling Leber congenital amaurosis and pigmentary retinopathy. Magnetic resonance imaging scans revealed defects of the optic nerve, optic chiasm, and, in some cases, brain. In two families, the mutations appear to have occurred de novo in severely affected offspring, and, in two other families, the mutations have been inherited from a gonosomal mosaic parent. Data from these four families support a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. Four additional families display complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. The high incidence of mosaicism and the reduced penetrance have implications for genetic counseling.

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