A course of topical dexamethasone may reduce progression to treatment-requiring retinopathy of prematurity (ROP), according to results from the first randomized clinical trial to investigate the approach. Although the JAMA Pediatrics study did not meet its primary statistical endpoint, the researchers observed a potentially clinically meaningful reduction in severe disease – without any accompanying increase in adverse events.
Current treatments for type 1 ROP, including retinal laser photocoagulation and intravitreal anti-VEGF injections, are effective but invasive. Treatment may require anesthesia, while laser causes permanent ablation of peripheral retina and anti-VEGF therapy necessitates prolonged monitoring for late recurrence. A noninvasive intervention capable of preventing progression could therefore reduce both the treatment burden and the risk of associated complications.
Funded by the Swedish Research Council, Sweden's largest research funding body, the double-masked DROPROP trial enrolled 100 infants born before 30 weeks’ gestation at 14 Swedish hospitals. Eligible infants had pre-threshold ROP: stage 1 or 2 disease without plus disease in zone I, or stage 2 or 3 disease in posterior zone II without plus disease.
Participants were randomized equally to preservative-free dexamethasone eye drops (Dexafree, Théa) at 1 mg/mL or saline placebo. Depending on ROP stage, one drop was administered to each eye either daily or every other day for up to 12 weeks. Retinal images were reviewed by a masked committee of pediatric ophthalmologists, with at least three members required to confirm both eligibility and progression to treatment-requiring type 1 ROP.
In the intention-to-treat analysis, type 1 ROP developed in 10 of 50 infants receiving dexamethasone, compared with 19 of 50 receiving placebo – rates of 20 and 38 percent, respectively. After adjustment for gestational age and study site, the odds ratio was 0.44, corresponding to a relative risk reduction of 47 percent. However, the confidence interval crossed unity and the result did not reach statistical significance.
The per-protocol findings were similar: 18.8 percent of dexamethasone-treated infants developed type 1 ROP, versus 38.8 percent in the placebo group. The treatment did not significantly alter the timing of progression or the rate of recurrence following laser or anti-VEGF therapy.
Adverse-event rates were shown to be comparable between the groups. No clinically significant differences in intraocular pressure, glucose regulation, infection, or serious adverse events were identified. Salivary cortisol levels fell during dexamethasone treatment but returned to baseline after treatment ended, highlighting the potential for systemic absorption and the need for careful monitoring.
The investigators do caution that the study was underpowered to confirm the observed effect: progression in the placebo group was lower, and the treatment effect smaller, than anticipated during sample-size calculations. Before adapting any national guidelines, the authors state that larger trials – including studies in populations from low- and middle-income countries, as well as studies with more infants – will be necessary before topical dexamethasone can enter routine practice. Nevertheless, the results offer an intriguing prospect: a low-cost eye drop that could help some premature infants avoid invasive retinal treatment.
