Topical dexamethasone eye drops may reduce progression to treatment-requiring retinopathy of prematurity in extremely preterm infants, although the primary endpoint was not met in a randomized clinical trial published in JAMA Pediatrics.
The double-masked DROPROP randomized clinical trial enrolled 100 infants born before 30 weeks' gestational age at six university hospitals and eight county hospitals in Sweden between 2022 and 2025. Infants with prethreshold retinopathy of prematurity (ROP) were randomly assigned to receive topical dexamethasone (1 mg/mL) or placebo for up to 12 weeks. The primary analysis followed the intention-to-treat principle and adjusted for gestational age and study site.
The primary outcome was progression to type 1 ROP requiring invasive treatment with laser photocoagulation or intravitreal anti-vascular endothelial growth factor therapy. Secondary outcomes included time to treatment-requiring disease, recurrence following treatment, and prespecified safety outcomes, including intraocular pressure, growth, glucose abnormalities, and adverse events.
Treatment-requiring type 1 ROP developed in 20% of infants who received dexamethasone compared with 38% of those who received placebo, representing a 47% relative risk reduction. However, the difference did not reach statistical significance. Similar findings were observed in the per-protocol analysis, in which treatment-requiring disease occurred in 19% of infants receiving dexamethasone vs 39% of those receiving placebo.
The intervention as not associated with significant between-group differences in time to progression to type 1 ROP or recurrence following invasive treatment. Nine infants required additional treatment for recurrent disease, including four in the dexamethasone group and five in the placebo group. Exploratory subgroup analyses suggested a greater reduction in progression among infants with birth weights greater than 660 g and those who received parenteral nutrition for fewer than 14 days, although these findings were considered hypothesis generating.
Rates of adverse events were similar between groups. No clinically significant difference in intraocular pressure was observed between groups, and rates of serious adverse events and confirmed sepsis were similar. Salivary cortisol concentrations decreased during treatment but returned to baseline following discontinuation.
The investigators noted that the trial may have been underpowered because both the observed treatment effect and the placebo event rate were lower than anticipated, reducing its ability to detect a statistically significant difference. In addition, seven infants underwent invasive treatment despite not meeting centrally confirmed criteria for type 1 ROP, primarily for logistical reasons, which may have influenced the treatment estimates.
"Although not statistically significant, the findings from this RCT suggest a potential benefit of topical dexamethasone in preventing the need for invasive ROP treatment. Larger RCTs are needed before adoption into national guidelines to ensure optimal care and confirmed safety and to identify potential subgroups of infants who may benefit most," wrote lead study author Ann Hellström, MD, PhD, of the University of Gothenburg, and colleagues.
Disclosures: Hellström reported that her sister is the chief executive officer of ADDI Medical AB, which provided the study's electronic health platform, although she reported no financial interest in the company. Öhnell reported grant funding during the conduct of the study. No other disclosures were reported.
Source: JAMA Pediatrics
