Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression,
although not safely. Propranolol 0.1% eye micro-drops administered to newborns with
stage 2 ROP are well-tolerated, but not sufficiently effective.
Methods: A multi-center open-label trial was conducted to assess the safety
and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1
ROP. The progression of the disease was evaluated with serial ophthalmologic
examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol
plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities
and co-intervention incidences, together with ROP progression, were compared
with a historical control group in the same centers participating in the trial.
Filippi et al. Propranolol Micro-Drops for ROP
Results: Ninety-eight newborns were enrolled and compared with the historical control
group. Populations were not perfectly homogeneous (as demonstrated by the differences
in the Apgar score and the different incidence rate in surfactant administration and
oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower
than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI
0.297– 0.916). No adverse effects related to propranolol were observed and the mean
propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL.
Unexpectedly, three newborns treated with oral propranolol before the appearance of
ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required
laser photocoagulation treatment.
Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared
to reduce the ROP progression expected on the basis of a comparison with a
historical control group. Propranolol administered too early appears to favor a more
aggressive ROP, suggesting that a β-adrenoreceptor blockade is only useful during the
proliferative phase. Further randomized placebo-controlled trials are required to confirm
the current results