Importance: Retinopathy of prematurity (ROP) is a potentially blinding retinal disease with poorly defined epidemiology. Understanding of which infants are most at risk for developing ROP may foster targeted detection and prevention efforts.Objective: To identify changes in ROP incidence in the US from 2003 to 2019.Design, Setting, and Participants: This retrospective database cohort study used the Healthcare Cost and Utilization Project Kids’ Inpatient Databases. These nationwide databases are produced every 3 years, include data from over 4000 hospitals, and are designed to generate national estimates of health care trends in the US. Participants included pediatric newborns at risk for ROP development between 2003 and 2019. Data were analyzed from September 30, 2021, to January 13, 2022.Exposures: Premature or low-birth-weight infants with relevant International Classification of Diseases, Ninth Revision or Tenth Revision codes were considered ROP candidates. Infants with ROP were identified using relevant codes.Main Outcomes and Measures: ROP incidence in selected subpopulations (based on database-reported race and ethnicity, sex, location, income) was measured. To determine whether incidences varied across time or subpopulations, χ² tests of independence were used.Results: This study included 125 212 ROP discharges (64 715 male infants [51.7%]) from 23 187 683 births. The proportion of premature infants diagnosed with ROP increased from 4.4% (11 720 of 265 650) in 2003 to 8.1% (27 160 of 336 117) in 2019. Premature infants from the lowest median household income quartile had the greatest proportional increase of ROP diagnoses from 4.9% (3244 of 66 871) to 9.0% (9386 of 104 235; P < .001). Premature Black infants experienced the largest increase from 5.8% (2124 of 36 476) to 11.6% (7430 of 63 925; P < .001) relative to other groups (2.71%; 95% CI, 2.56%-2.87%; P < .001). Hispanic infants experienced the second largest increase from 4.6% (1796 of 39 106) to 8.2% (4675 of 57 298; P < .001) relative to other groups (−0.16%; 95% CI, −0.29% to −0.03%; P = .02). The Southern US experienced the greatest proportional growth of ROP diagnoses, increasing from 3.7% (3930 of 106 772) to 8.3% (11 952 of 144 013; P < .001) relative to other groups (1.61%; 95% CI, 1.51%-1.71%; P < .001). ROP diagnoses proportionally increased in urban areas and decreased in rural areas.Conclusions and Relevance: This cohort study found that ROP incidence among premature infants increased from 2003 to 2019, especially among Black and Hispanic infants. Infants from the lowest-income areas persistently had the highest proportional incidence of ROP, and all regions experienced a significant increase in ROP incidence with the most drastic changes occurring in the South. These trends suggest that ROP is a growing problem in the US and may be disproportionately affecting historically marginalized groups.

Subretinal gene therapy trials began with the discovery of RPE65 variants and their association with Leber congenital amaurosis. The RPE65 protein is critical for the normal functioning of the visual phototransduction cascade. RPE65 gene knockout animal models were developed and showed similar diseased phenotypes to their human counterparts. Proof of concept studies were carried out in these animal models using subretinal RPE65 gene replacement therapy, resulting in improvements in various visual function markers including electroretinograms, pupillary light responses, and object avoidance behaviors. Positive results in animal models led to Phase 1 human studies using adeno-associated viral vectors. Results in these initial human studies also showed positive impact on visual function and acceptable safety. A landmark Phase 3 study was then conducted by Spark Therapeutics using a dose of 1.5 x10¹¹ vector genomes after dose-escalation studies confirmed its efficacy and safety. Multi-luminance mobility testing was used to measure the primary efficacy endpoint due to its excellent reliability in detecting the progression of inherited retinal diseases. After the study met its primary endpoint, the Food and Drug Administration approved voretigene neparvovec (Luxturna^®) for use in RPE65-associated inherited retinal diseases.