SEVERE RETINOPATHY OF PREMATURITY IN INFANTS WITH BIRTH WEIGHTS LESS-THAN 1250 GRAMS - INCIDENCE AND OUTCOME OF TREATMENT WITH PHARMACOLOGICAL SERUM LEVELS OF VITAMIN-E IN ADDITION TO CRYOTHERAPY FROM 1085 TO 1991

Objective: To determine the effect of vitamin E prophylaxis and treatm ent 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 birt h weights less than or equal to 1250 gm received supplements of vitami n E using standard preparations, Serum E levels of 23 to 58 mu mol/L ( 1 to 2.5 mg/dl) were targeted for infants with immature retinal vascul ature or ROP of stage 2 or less in severity, and levels of 58 to 81 mu mol/L (2.5 to 3.5 mg/dl) for infants with prethreshold ROP, At diagno sis of threshold ROP, treatment with a parenteral investigational new drug preparation of alpha-tocopherol was begun to raise serum levels t o the pharmacologic range (93 to 116 mu mol/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 y ears was compared with the 42-month outcome reported for eyes in the i nfants randomly assigned to treatment in the 1986-1987 Multicenter Tri al 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 l east at equal risk for poor visual outcome on the basis of birth weigh t, gestational age, the percentage of zone 1 ROP, and mean interval fr om appearance of ROP to diagnosis of prethreshold ROP, which was short er at Pennsylvania Hospital (4.1 days for the Pennsylvania Hospital gr oup, 10,3 days for the CRYO-ROP group), However, on the basis of the m ean number of days from diagnosis of prethreshold to threshold ROP (12 .5 days for Pennsylvania Hospital, 10.5 days for CRYO-ROP) and the ext ent of extraretinal neovascularization at threshold (mean 7.9 sectors for Pennsylvania Hospital, 9.7 for CRYO-ROP), progression of retinopat hy 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 cryoth erapy) 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 less than or equal to 0.02). Conclusions: In this small cas e series, the combination of cryotherapy with antioxidant prophylaxis and treatment appeared to decrease the severity and sequelae of thresh old ROP, This hypothesis deserves testing in a large, randomized clini cal trial.