David B. Schaffer

Effect of sustained pharmacologic vitamin E levels on incidence and severity of retinopathy of prematurity: A controlled clinical trial

The incidence and severity of retinopathy of prematurity (ROP) as affected by vitamin E prophylaxis at pharmacologic serum levels (5 mg/dl) were evaluated in a double-masked clinical trial of infants with a birth weight less than or equal to 2000 gm or a gestational age less than or equal to 36 weeks. The infants were enrolled by age 5 days and randomly assigned to receive parenterally administered, and later orally administered, free alpha-tocopherol (vitamin E) or its placebo. Study medication was continued until retinal vascularization was complete or active ROP had subsided, except in infants with a diagnosis of severe disease, in whom vitamin E was substituted for study medication. Acute ROP data were collected on 755 infants. Logistic regression analysis, with control for immaturity, oxygen exposure, and other illness risk factors, showed a decrease in incidence of ROP in vitamin E-treated infants (p = 0.003, all infants; p = 0.035, infants weighing less than or equal to 1500 gm at birth). Among the 424 infants weighing less than or equal to 1500 gm at birth, the age at enrollment influenced treatment effect (age day 0 to 1, p = 0.006 (n = 288) vs age day 2 to 5, p greater than 0.1 (n = 136]. Overall, 77.6% of infants with ROP had mild disease. Moderate to severe ROP was confined to infants weighing greater than or equal to 1500 gm at birth (25 given placebo, 25 given vitamin E), with progression to severe disease in nine placebo-treated versus three vitamin E-treated infants (p = 0.048). The incidence of severe ROP per se was not significantly decreased (all birth weights, p = 0.086; less than or equal to 1500 gm birth weight, p = 0.080); the sample size was too small, however, to assess this end point adequately. An increased incidence of sepsis and late-onset necrotizing enterocolitis was found among vitamin E-treated infants weighing less than or equal to 1500 gm at birth who received study medication for greater than or equal to 8 days (p = 0.006). Because most ROP is mild in degree and regresses completely, the risk/benefit ratio of pharmacologic prophylaxis for ROP is unfavorable. Treatment of moderate and severe ROP with vitamin E above physiologic serum levels (greater than 3 mg/dl) appears promising and should be further investigated. The interpretation of cicatricial outcome was confounded by the small number of patients involved and by subsequent treatment of severe ROP in placebo-treated infants with vitamin E.

Vitamin E and Retinopathy of Prematurity: Follow-up at One Year

Five hundred forty-five infants weighing less than 1501 g at birth were entered into a randomized, prospective study to determine the effect of high serum levels (5 mg/dL) of vitamin E used prophylactically to try to prevent or alter the natural course of retinopathy of prematurity (ROP) and its sequel, retrolental fibroplasia (RLF). Three hundred twenty-eight infants were available for the one- to two-year eye examination. Although there was a trend (P = 0.072) toward less severe RLF among vitamin E-treated infants, the incidence of RLF was 11/162 (6.8%) in the placebo treated (P) infants, and 12/166 (7.2%) in the vitamin E-treated (E) infants. The incidences of hyperopia, myopia, anisometropia, strabismus and amblyopia were also similar in both the P and E groups.

Variations in Extraocular Muscle Number and Structure in Craniofacial Dysostosis

Five of 12 patients with craniofacial dysostosis who needed strabismus surgery had anomalies of extraocular muscle structure and number. Two cul-de-sac incisions per eye are sufficient to investigate all muscles for anomalies and add little time or risk to the planned strabismus procedure. The origin of these anomalies and their frequency in craniofacial stenosis are unknown.

Cryotherapy for Active Retinopathy of Prematurity

Twenty-eight patients with bilateral symmetrical Stage 3 retinopathy of prematurity (ROP) and plus disease had one eye assigned to cryotherapy and the other to control. The majority of patients weighed under 1000 grams at birth and females outnumbered males by nearly a two-to-one ratio.+ Cryotherapy was generally performed at a gestational age of less than 40 weeks and a mean chronologic age of 10 weeks. Eleven patients showed improvement in both the treated and untreated eyes possibly due to variables among prematures not identified in the study. Eleven other patients experienced improvement in the treated eye and progression in the untreated eye. Using the binomial distribution on the latter group the P value was 0.0005 with a one-tailed hypothesis test and 0.001 with a two-tailed test, suggesting that in the sampled population cryotherapy appears to be preferred over no treatment.

VITAMIN E SUPPLEMENTATION AND THE RETINOPATHY OF PREMATURITY

The effect of high-dosage E treatment (Rx) initiated at the stage of 3-plus active disease (target serum E levels, 5-6 mg/dl) was evaluated by a standardized scoring system of visual morbidity at the one to two year eye exam among infants cared for in the University of Pennsylvania Neonatal Complex (1976-1978). The incidence of legal blindness in both eyes or worse was decreased from 71 to 40% in E Rx (n = 10) as compared to non-E Rx (n = 14) infants, and the number of infants with minimal visual morbidity was increased. Pilot studies (1972-76; target serum E level, 1.5 and 3.0 mg/dl) of the prophylactic effect of E Rx from birth on showed a decrease in mean severity of acute stage disease and a decrease in sequelae at one to two years. A strikingly difference in visual morbidity following resolved low-grade ROP was seen when prestudy infants (1968-72) who were fed early iron supplements and given formulas with low E:PUFA ratios were compared to non-E Rx as well as to E Rx 1972-76 infants. Vitamin E seems to exert a beneficial effect at all stages of ROP, perhaps because of its broadly based regulatory role.

Infantile nystagmus: A prospective study of spasmus nutans, congenital nystagmus, and unclassified nystagmus of infancy*

Prospectively collected data on 52 study and 56 control children were used to analyze the diagnostic and prognostic criteria commonly applied to infants with nystagmus. None distinguished among spasmus nutans, congenital nystagmus, and undifferentiated nystagmus. Compared with control children, the affected children had a higher incidence of electroencephalographic abnormalities, strabismus, other neurologic abnormalities, and family history of nystagmus. Except for a higher incidence in multiparous women, no environmental pre-or perinatal circumstances differentiated the study children from control children. Cessation before the fifth year occurred in 70 per cent of those without and in 30 per cent of those with associated strabismus or other neurologic abnormalities.

Systemic Complications Associated with Retinal Cryoablation for Retinopathy of Prematurity

Eighty infants with proliferative retinopathy of prematurity (ROP) were treated with peripheral retinal cryoablation. Among the serious systemic complications encountered were three instances of respiratory arrest and one of cardiorespiratory arrest. Recommendations that may help prevent these adverse systemic effects in premature infants include: (1) avoidance of excess subconjunctival anesthetic doses, (2) preoperative administration of systemic atropine to minimize the oculocardiac reflex, (3) consideration of an analgesic agent to decrease the pain and exhaustion, and (4) cardiorespiratory monitoring in a hospital setting, with an intravenous line in place, at the time of treatment.

A classification of retrolental fibroplasia to evaluate vitamin E therapy.

A refined classification of the stages of the retinopathy of prematurity (RLF) based on the experience of over 7500 examinations during the past decade is presented. We have been using the basic elements of this classification since 1972 in order to evaluate the influence of vitamin E on retrolental fibroplasia (RLF). It is our impression that it provides a more accurate clinical method of following the course of the retinopathy and a tool for assessing the factors other than prematurity and hyperoxia that may play a subtle role in the development of RLF.

Ocular Alignment after Craniofacial Reconstruction

We undertook a retrospective study of 160 patients to ascertain if craniofacial reconstruction affected ocular alignment. In most patientspre-existing alignment and binocularity were unaffected by craniofacial surgery; thus, correction of any strabismus can be performed on a child without concern for disruption of muscle tissue by later craniofacial surgery.

The Ophthalmologic Manifestations of the Cardio-Facio-Cutaneous Syndrome

The cardio-facio-cutaneous (CFC) syndrome is an uncommon multiple congenital anomalies/mental retardation syndrome whose major manifestations are congenital heart defects, relative macrocephaly, stunted growth, ectodermal dysplasia, characteristic facial appearance, and psychomotor developmental delay. All described cases were sporadic and cytogenetically normal. We report three additional patients with this diagnosis. All three patients developed strabismus, requiring extraocular muscle surgery. Two of our patients also had nystagmus. Combining the 18 previously reported cases with our additional 3, 9 of 21 had strabismus, 10 of 21 had ptosis, and 6 of 21 had nystagmus. Ophthalmic craniofacial abnormalities of hypoplastic supraorbital ridges, prominent epicanthal folds, and antimongoloid slant of the palpebral fissures were also common features contributing to the characteristic facies described for this syndrome. The ophthalmologist could aid in the diagnosis and treatment of these patients because of the prominent ophthalmologic symptomatology of the CFC syndrome.