D-Penicillamine administration and the incidence of retinopathy of prematurity

We compared the development of retinopathy of prematurity (ROP) among 49 preterm neonates:; 15 who were treated during the first 2 weeks of life with D-penicillamine and 34 who were not.

During a 15-month period beginning 1 March, 2005, 15 preterm neonates <1000 g birth weight or < or =29 weeks gestation enterally received a 14-day course of D-penicillamine, and 34 did not, in an open-label non-randomized trial. We compared the outcomes of developing 'ROP any stage' and 'ROP requiring surgery' in the recipients vs the non-recipients. Potential toxicities of the D-penicillamine were examined by comparing specific laboratory tests, growth velocities, transfusion requirements, discharge hemoglobin concentrations and supplemental O(2) at discharge.

The 34 non-treated and the 15 D-penicillamine treated patients were of similar gestational age (26.5+/-1.8 vs 26.6+/-2.2 weeks, mean+/-s.d.) and birth weight (887+/-222 vs 849+/-187 g). Four of the 34 non-recipients died. Eighteen of the 30 survivors (60%) developed ROP and seven of the 30 (23%) had ROP surgery. One of the 15 D-penicillamine recipients died. Three of the 14 survivors (21%) developed ROP (P=0.01 vs non-recipients) and all three had ROP laser surgery. No increase in elevated creatinine, direct or indirect bilirubin, thrombocytopenia or neutropenia was apparent in those treated with D-penicillamine. The D-penicillamine recipients did not receive more transfusions and did not have lower hemoglobin concentrations at discharge. They did not have lower velocities of weight gain at 14, 28 and 56 days, and were not discharged on supplemental O(2) at a rate exceeding that of the non-recipients.

In this non-randomized, single-centered comparison analysis, a 14-day course of D-penicillamine resulted in no apparent short-term toxicity. The treatment was associated with elimination of Stage I and Stage II ROP, decreasing the overall odds of developing ROP from 60 to 21%. However, this approach did not reduce the odds of ROP surgery. Perhaps higher doses of D-penicillamine or longer treatment periods or other prophylactic approaches will be required to reduce ROP surgery among the most immature neonates.