Severe retinopathy of prematurity in infants with birth weights less than 1250 grams: incidence and outcome of treatment with pharmacologic serum levels of vitamin E in addition to cryotherapy from 1985 to 1991.

OBJECTIVE: To determine the effect of vitamin E prophylaxis and treatment on the sequelae of severe (threshold) retinopathy of prematurity (ROP) in infants treated with cryotherapy at Pennsylvania Hospital from 1985 to 1991.

STUDY DESIGN: Beginning on day 0, all infants with birth weights < or = 1250 gm received supplements of vitamin E using standard preparations. Serum E levels of 23 to 58 mumol/L (1 to 2.5 mg/dl) were targeted for infants with immature retinal vasculature or ROP of stage 2 or less in severity, and levels of 58 to 81 mumol/L (2.5 to 3.5 mg/dl) for infants with prethreshold ROP. At diagnosis of threshold ROP, treatment with a parenteral investigational new drug preparation of alpha-tocopherol was begun to raise serum levels to the pharmacologic range (93 to 116 mumol/L or 4 to 5 mg/dl). Within 3 days of diagnosis, and at the discretion of the retinal specialist, one or both eyes were treated with cryotherapy. Visual outcome at 4 years was compared with the 42-month outcome reported for eyes in the infants randomly assigned to treatment in the 1986-1987 Multicenter Trial of Cryotherapy for ROP (CRYO-ROP).

RESULTS: Threshold ROP developed in 22 of 450 surviving infants (age 3 months). All were treated with pharmacologic serum levels of vitamin E; 17 infants were also treated with cryotherapy (10 in one eye and 7 in both eyes). These 17 infants, in comparison with infants in the CRYO-ROP trial (n = 187), were at least at equal risk for poor visual outcome on the basis of birth weight, gestational age, the percentage of zone 1 ROP, and mean interval from appearance of ROP to diagnosis of prethreshold ROP, which was shorter at Pennsylvania Hospital (4.1 days for the Pennsylvania Hospital group, 10.3 days for the CRYO-ROP group). However, on the basis of the mean number of days from diagnosis of prethreshold to threshold ROP (12.5 days for Pennsylvania Hospital, 10.5 days for CRYO-ROP) and the extent of extraretinal neovascularization at threshold (mean 7.9 sectors for Pennsylvania Hospital, 9.7 for CRYO-ROP), progression of retinopathy beyond the prethreshold stage had slowed and visual outcome in the eyes of infants at Pennsylvania Hospital treated with both cryotherapy and vitamin E (worse eye used for those treated with bilateral cryotherapy) was better than that reported for the treated eye of infants in the CRYO-ROP group (percentage of favorable visual acuity, 76% vs 48%, p = 0.04; percentage of normal structure posterior retinal pole, 71% vs 38%, p < or = 0.02).

CONCLUSIONS: In this small case series, the combination of cryotherapy with anti-oxidant prophylaxis and treatment appeared to decrease the severity and sequelae of threshold ROP. This hypothesis deserves testing in a large, randomized clinical trial.