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.

; for the Imaging and Informatics in Retinopathy of Prematurity (i-ROP) Research Consortium IMPORTANCE Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. The decision to treat is primarily based on the presence of plus disease, defined as dilation and tortuosity of retinal vessels. However, clinical diagnosis of plus disease is highly subjective and variable. OBJECTIVE To implement and validate an algorithm based on deep learning to automatically diagnose plus disease from retinal photographs. DESIGN, SETTING, AND PARTICIPANTS A deep convolutional neural network was trained using a data set of 5511 retinal photographs. Each image was previously assigned a reference standard diagnosis (RSD) based on consensus of image grading by 3 experts and clinical diagnosis by 1 expert (ie, normal, pre-plus disease, or plus disease). The algorithm was evaluated by 5-fold cross-validation and tested on an independent set of 100 images. Images were collected from 8 academic institutions participating in the Imaging and Informatics in ROP (i-ROP) cohort study. The deep learning algorithm was tested against 8 ROP experts, each of whom had more than 10 years of clinical experience and more than 5 peer-reviewed publications about ROP.

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.

This statement revises a previous statement on screening of preterm infants for retinopathy of prematurity (ROP) that was published in 2006. ROP is a pathologic process that occurs only in immature retinal tissue and can progress to a tractional retinal detachment, which can result in functional or complete blindness. Use of peripheral retinal ablative therapy by using laser photocoagulation for nearly 2 decades has resulted in a high probability of markedly decreasing the incidence of this poor visual outcome, but the sequential nature of ROP creates a requirement that at-risk preterm infants be examined at proper times and intervals to detect the changes of ROP before they become permanently destructive. This statement presents the attributes on which an effective program for detecting and treating ROP could be based, including the timing of initial examination and subsequent reexamination intervals. Pediatrics 2013;131:189-195

To measure agreement of plus disease diagnosis among retinopathy of prematurity (ROP) experts. Methods: A set of 34 wide-angle retinal photographs from infants with ROP was compiled on a secure Web site and was interpreted independently by 22 recognized ROP experts. Diagnostic agreement was analyzed using 3-level (plus, pre-plus, or neither) and 2-level (plus or not plus) categorizations. Results: In the 3-level categorization, all experts agreed on the same diagnosis in 4 of 34 images (12%), and the mean weighted statistic for each expert compared with all others was between 0.21 and 0.40 (fair agreement) for 7 experts (32%) and between 0.41 and 0.60 (moderate agreement) for 15 experts (68%). In the 2-level categorization, all experts who provided a diagnosis agreed

and is inventor for US patents and patent applications on artificial intelligence, imaging and deep learning, as well as on foreign patents. Drs NM Bressler and P Burlina are the co-inventor and patent holders for a deep learning system for retinal diseases.

This policy statement revises a previous statement on screening of preterm infants for retinopathy of prematurity (ROP) that was published in 2013. ROP is a pathologic process that occurs in immature retinal tissue and can progress to a tractional retinal detachment, which may then result in visual loss or blindness. For more than 3 decades, treatment of severe ROP that markedly decreases the incidence of this poor visual outcome has been available. However, severe, treatment-requiring ROP must be diagnosed in a timely fashion to be treated effectively. The sequential nature of ROP requires that infants who are at-risk and preterm be examined at proper times and intervals to detect the changes of ROP before they become destructive. This statement presents the attributes of an effective program to detect and treat ROP, including the timing of initial and follow-up examinations.

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