Treating retinopathy of prematurity with dexamethasone eye drops: a difference-in-differences study in Sweden using register data.

Objective: To estimate the effect of dexamethasone eye drops on the risk of progression from type 2 retinopathy of prematurity (ROP) to ROP requiring traditional treatments.

Design: Register-based cohort study SUBJECTS AND CONTROLS: Preterm infants born before 30 weeks gestation during 2015-2018 (control years) and 2020-2021 (intervention years), registered in the Swedish quality register for ROP (SWEDROP) at four Swedish sites were included. In one of these sites, the intervention site, topical dexamethasone was introduced during the later period when type 2 ROP was diagnosed.

Methods: The frequency of traditional ROP treatments (laser ablation or intravitreal injection of anti-vascular endothelial growth factor) was compared between the two time periods at sites that had, and had not, introduced topical dexamethasone during the later period. Analyses were conducted both on infants with severe ROP and on all included infants. The difference-in-differences statistical method was used.

Main outcome measures: The proportion of infants that required traditional ROP treatment in each group and the interaction odds ratio, adjusted for potential confounding factors.

Results: At the intervention site, the incidence of traditional ROP treatment fell from 23/32 (72%) to 4/32 (13%, p < 0.001) in infants with severe ROP, and from 23/409 (5.6%) to 4/217 (1.8%, p = 0.03) in all screened infants. For the three control sites, the equivalent numbers were from 82/175 (47%) to 32/57 (56%, p = 0.22), and 82/950 (8.6%) to 32/441 (7.3%, p = 0.38). The difference-in-differences analyses resulted in an adjusted interaction odds ratio of 0.05 (95% CI 0.01-0.22; p < 0.001) for infants with severe ROP, suggesting a markedly larger decline in occurrence of traditional ROP treatments at the intervention site.

Conclusion: In this population of infants with severe ROP, the introduction of dexamethasone eye drops was associated with a significant reduction in the proportion of infants requiring traditional ROP treatments. A timely administration of low-dose dexamethasone eye drops may serve as a simple, cost-effective, and noninvasive intervention to reduce one of the leading causes of severe visual impairment worldwide. Further studies are needed to confirm our findings.