Oral Propranolol Versus Placebo for Early Stages of Retinopathy of Prematurity (ROP): A Pilot, Randomized and Prospective Study.

Retinopathy of prematurity (ROP) affects the retinal microvasculature, mostly of very-low-birth-weight (VLBW: < 1500g) premature infants, and is a significant complication of extreme prematurity leading sometimes to devastating consequences. Although ROP is usually mild with no harm, it happens not very rarely to be aggressive causing neo-vascularization (NV) in the immature retina that at times can progress to severe fibrovascular proliferation, retinal detachment and blindness (1). Major risk factors for ROP are low gestational age, low birth weight, hyperoxia, respiratory distress syndrome (RDS) and intraventricular hemorrhage (IVH) (2) as well as postnatal steroid therapy (3). Of note is one report showing that the use of beta-blocking agents by the mother before birth was found to be associated with the development of ROP (4). However, so far no one reported a similar effect of the postnatal use of beta blockers on ROP.

The incidence of ROP is inversely related to gestational age (GA) and birth weight (BW). The condition develops in 51% of infants with a birth weight (BW) <1700 g (5). In infants weighing less than 1250 g, 50% show some evidence of ROP and 10% progress to stage III ROP. According to the Israeli VLBW-Database in 2007, 23.9% of infants develop ROP (all stages), while 4.8% develop severe ROP (stage III-IV) (4). Worldwide, at least 50,000 children are blind from ROP (2,7). In South Africa it accounts for 10.6% of cases of childhood blindness (8). In the US, annually, 500-700 children become blind due to ROP, and 2100 infants will be affected by cicatricial sequelae, such as myopia, strabismus, as well as late-onset retinal detachment (1).

LASER photocoagulation of the ischemic retina is the therapy of choice for moderate to severe ROP and is required in 19.8%, 7.7%. 1.5% and 0.6% of infants weighing 500-749g, 750-999g, 1000-1249g, 1250-1499g, respectively (2). In Israel, 4% of VLBW infants needed LASER photocoagulation or cryo therapy during 2007 (6).

The pathogenesis of ROP is multifactorial and two pathogenetic theories have been proposed:

(A) One-phase theory: Mesenchymal spindle cells when exposed to extrauterine hyperoxia, develop gap junctions that interfere with normal vascular formation and trigger a neovascular response (9).