Dexamethasone Eye Drops to Prevent Treatment-Requiring Retinopathy of Prematurity: The DROPROP Randomized Clinical Trial.

Importance: Current treatment for type 1 retinopathy of prematurity (ROP), including laser photocoagulation and intravitreal anti-vascular endothelial growth factor therapy, is invasive but necessary to prevent blindness. Experimental evidence and limited clinical experience suggest that topical steroids may reduce disease progression and the need for invasive treatment. Objective: To evaluate whether dexamethasone eye drops reduce the proportion of preterm infants with prethreshold ROP progressing to treatment-requiring type 1 ROP. Design, Setting, and Participants: The DROPROP trial was a double-masked randomized clinical trial at 6 university hospitals and 8 county hospitals in Sweden. It evaluated infants born before 30 weeks' gestational age (GA), from 2022 to 2025, with severe ROP. Data analysis was performed from November 2025 to January 2026. Exposures: Infants were randomized to receive dexamethasone eye drops (1 mg/mL) or placebo (saline). One eye drop was administered every day or every other day for up to 12 weeks. Main Outcomes and Measures: The primary outcome was progression to type 1 ROP requiring invasive treatment. Logistic regression adjusted for GA and site was used for the primary analysis. Intention-to-treat analysis was performed. Adverse events were monitored as safety outcomes. Results: Among 100 infants, the mean (SD) GA at birth was 25.1 (1.4) weeks, 42 (42.0%) were female, and the mean (SD) birth weight was 712.9 (202.1) g. In the intention-to-treat population, type 1 ROP occurred in 10 of 50 infants (20.0%) in the dexamethasone group and 19 of 50 infants (38.0%) in the placebo group (adjusted odds ratio, 0.44; 95% CI, 0.17-1.12; P = .08), corresponding to a relative risk reduction of 47%. In the per-protocol population, type 1 ROP occurred in 9 of 48 infants (18.8%) in the dexamethasone group vs 19 of 49 infants (38.8%) in the placebo group (adjusted odds ratio, 0.40; 95% CI 0.15-1.05). No clinically significant differences in adverse events were observed between groups. Conclusions and Relevance: Timely administration of topical dexamethasone numerically reduced the risk of prethreshold ROP progressing to treatment-requiring type 1 ROP. Although the analysis did not reach statistical significance, these findings suggest that topical dexamethasone may be a safe, noninvasive strategy to reduce the need for invasive treatment. Trial Registration: euclinicaltrials.eu Identifier: 2023-505318-97-00.