D-Penicillamine prevents mild ROP

Christensen RD, Alder SC, Richards^,SC, et al. D-Penicillamine administration and the incidence of retinopathy of prematurity. J Perinatol (Feb 2007);27:103–111. Full Text | PDF

Objective: 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.

Methods: During a 15-month period beginning 1 March, 2005, 15 preterm neonates <1000 g birth weight 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.

Results: 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.

Conclusions: 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.

Comments: D-Penicillamine, a heavy metal chelator, was felt to be a good candidate to reduce ROP by reducing oxygen free radical activity, and by decreasing the bioavailability of vascular endothelial growth factor (VEGF). It appears to be safe, but it was only only useful in preventing the mild cases of ROP. Too bad! D-Penicillamine does not appear to protect against the development of surgical ROP, and least not in the doses and duration used in this study. Perhaps other factors besides VEGF are involved in causing the severe version of ROP. See 3-059 for a discussion of the role of insulin-like growth factor 1 (IGF-1) in causing severe ROP. ABK.

Date: 13 Mar 2007
Time: 03:43:43

It is delighting to see studies conducted by Christensen et al in the United States. These works can be considered as the first international replication of Hungarian observation and clinical trials. Although the Utah-studies were performed quarter of a century later and D-penicillamine was administered enterally (not intravenously!), the results confirmed our findings of controlled trials, namely no babies had retinopathy with birth weight above 750g and no adverse effects were observed. Consequently I agree with the conclusion of the authors that multicentered, randomized, placebo-controlled trials are warranted. It seems to me that D-penicillamine does indeed reduce the retinal neovascularization, but not sufficiently to prevent the most severe cases occuring among babies with average birth weight under 600g. Thus I also suggest that the dosing regimen needs improvement, particularly among those 22 to 25 weeks gestation. For instance, for these patients we might consider a higher dose, or treting them for more than two weeks, or both.

UserName: Lajos Lakatos MD
Institution: Department of Pediatrics, Kenézy Hospital, Debrecen, Hungary
telephone: 36 52 511-760
email: lakatosl@kenezykorhaz.hu

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