Earl A. Palmer

The incidence and course of retinopathy of prematurity: findings from the early treatment for retinopathy of prematurity study.

Objectives. To estimate the incidence of retinopathy of prematurity (ROP) in the Early Treatment for Retinopathy of Prematurity (ETROP) Study and compare these results with those reported in the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study. Methods. The ETROP Study, as part of its protocol, screened 6998 infants at 26 centers throughout the United States. Serial eye examinations were conducted for infants born weighing <1251 g, making it possible to estimate the frequency of ROP in different birth weight and gestational age categories. ROP was categorized according to the International Classification for ROP. Results. The incidence of any ROP was 68% among infants of <1251 g. The findings were compared with those for infants born in 1986 and 1987 in the CRYO-ROP Study. The overall incidences of ROP were similar in the 2 studies, but there was more zone I ROP in the ETROP Study. Among infants with ROP, more-severe ROP (prethreshold) occurred for 36.9% of infants in the ETROP Study and 27.1% of infants in the CRYO-ROP Study. The gestational age of onset of ROP of different severities has changed very little since the CRYO-ROP Study was conducted. Conclusions. ROP remains a common important problem among infants with birth weights of <1251 g. The incidence of ROP, time of onset, rate of progression, and time of onset of prethreshold disease have changed little since the CRYO-ROP natural-history study.

Screening Examination of Premature Infants for Retinopathy of Prematurity

This statement revises a previous statement on screening of preterm infants for retinopathy of prematurity (ROP) that was published in 2006. ROP is a pathologic process that occurs only in immature retinal tissue and can progress to a tractional retinal detachment, which can result in functional or complete blindness. Use of peripheral retinal ablative therapy by using laser photocoagulation for nearly 2 decades has resulted in a high probability of markedly decreasing the incidence of this poor visual outcome, but the sequential nature of ROP creates a requirement that at-risk preterm infants be examined at proper times and intervals to detect the changes of ROP before they become permanently destructive. This statement presents the attributes on which an effective program for detecting and treating ROP could be based, including the timing of initial examination and subsequent reexamination intervals.

Development of Myopia in Infants with Birth Weights Less than 1251 Grams

The authors report on the incidence of myopia in a large group of premature infants with birth weights of less than 1251 g followed as part of the multicenter study of Cryotherapy for Retinopathy of Prematurity. None of the eyes reported here underwent cryotherapy. Eyes were refracted using cycloplegic retinoscopy at 3 months (n = 2916), 12 months (n = 2626), and 24 months (n = 961 at 5 of the 23 centers) after term. Myopia was observed in approximately 20% of the children at each test age. The percentage of high myopia (greater than or equal to 5 diopters) doubled from 2% to 4.6% between 3 and 12 months and remained stable thereafter. Lower birth weight and increasing severity of retinopathy of prematurity (ROP) were strong predictors of myopia and high myopia. In addition, anisometropia, astigmatism, and the presence of posterior pole residua from ROP also were associated with a higher incidence of myopia and high myopia.

Plasma Timolol in glaucoma Patients

Plasma timolol levels were measured in our timolol-treated glaucoma patients employing three protocols: (1) measurements in ten patients over age 60 on chronic timolol therapy before, one hour, and three hours after receiving one drop of 0.5% timolol, (2) measurements in nine adult patients, with and without punctal occlusion, and (3) random measurement of plasma timolol in children on chronic timolol therapy while under general anesthesia. In the ten patients over age 60 years, baseline mean plasma timolol was 0.34 ng/ml, increasing to a mean of 1.34 ng/ml one hour after receiving drops. When punctal occlusion was applied, the mean one-hour plasma timolol diminished to 0.9 ng/ml, approximately 40% less than that observed without punctal occlusion. The plasma timolol levels examined in nine determinations in five children ranged from a low 3.5 ng/ml in a five-year-old child to 34 ng/ml in a three-week-old infant.

Severity of Neonatal Retinopathy of Prematurity Is Predictive of Neurodevelopmental Functional Outcome at Age 5.5 Years

Objective. The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. Methods. Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). Results. Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. Conclusion. Severity of neonatal ROP seems to be a marker for functional disability at age 5.5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial

PURPOSE To evaluate the effect of cryotherapy on refractive error status between ages 3 months and 10 years in children with birth weights of less than 1251 g in whom severe retinopathy of prematurity (ROP) developed in one or both eyes during the neonatal period. DESIGN Randomized clinical trial. PARTICIPANTS Two hundred ninety-one children in whom severe ROP developed during the neonatal period. INTERVENTION Cryotherapy for ROP. MAIN OUTCOME MEASURES Cycloplegic Refraction METHODS The children underwent repeated follow-up eye examinations, including cycloplegic retinoscopy, between 3 months and 10 years after term due date. Refractive error data from all eyes that were randomized to cryotherapy were compared with data from all eyes that were randomized to serve as controls. Refractive error data were also compared for a subset of children who had both a treated and a control eye that could be refracted. RESULTS At all ages, the proportion of treated eyes that were unable to be refracted because of retinal detachment, media opacity, or pupillary miosis was approximately half the proportion of the control eyes that were unable to be refracted. When data from all eyes that could be refracted were considered, the distribution of refractive errors between fewer than 8 diopters (D) of myopia and more than 8 D of hyperopia was similar for treated and control eyes at all ages. The proportion of eyes with 8 D or more of myopia was much higher in treated than in control eyes at all ages after 3 months. In the subset of children who had a treated eye and a control eye that could be refracted, distributions of refractive errors in treated versus control eyes were similar at most ages. CONCLUSIONS In both treated and control eyes, there was an increase in the prevalence of high myopia between 3 and 12 months of age. Between 12 months and 10 years of age, there was little change in distribution of refractive error in treated or control eyes. The higher prevalence of myopia of 8 D or more in treated eyes, as compared with control eyes, may be the result of cryotherapys preservation of retinal structure in eyes that, in the absence of cryotherapy, would have progressed to retinal detachment.

Visual acuity of eyes after vitrectomy for retinopathy of prematurity : Follow-up at 5 1/2 years

PURPOSE To provide long-term follow-up on the structural status and visual function at 5 1/2 years of age for 128 eyes of 98 infants who participated in the multicenter randomized clinical trial of cryotherapy for retinopathy of prematurity in whom total retinal detachment developed from retinopathy of prematurity (ROP) by the 3-month study examination. Fifty-four patients had lensectomy-vitrectomy procedures in one or both eyes before 1 year of age (n=72 eyes), and 44 patients did not (n=56 eyes). METHODS When the children were 5 1/2 years of age, an eye examination was performed and residua of ROP was assessed. Recognition acuity (Early Treatment of Diabetic Retinopathy Study chart) and grating visual acuity (Teller acuity card procedure) assessments were undertaken by testers who were masked to the status of each of the childs eyes. RESULTS At least partial retinal attachment was present at 5 1/2 years in 21% compared with 28% at 1 year of age (not significant). All except one of the eyes tested at 5 1/2 years had vision limited to light perception or no light perception, regardless of whether a vitrectomy had been performed. One eye that underwent vitrectomy had minimal pattern vision. The two eyes that were reported previously to have minimal pattern vision at 1 year of age were blind at the longer-term follow-up. CONCLUSIONS The poor visual outcome after a lensectomy-vitrectomy procedure for retinal detachment due to ROP demands that emphasis be placed on prevention of retinal detachment in premature infants.

How safe are ocular drugs in pediatrics

In comparison with that of adults, the smaller body mass of children raises questions of dosage. In addition, manifestations of ocular drug toxicity are different in some respects. The ocular drugs causing serious adverse ocular or systemic side effects in children include glaucoma medications, corticosteroids, phenylephrine, and the anticholinergic cycloplegics. The reported complications from using these medications in children will be briefly reviewed, and strategies for minimizing the risk of their adverse effects will be suggested, including a discussion of dosages and techniques of administration.

The incidence of ophthalmologic interventions in children with birth weights less than 1251 grams: Results through 5 1/2 years

OBJECTIVE This study aimed to report the frequency of ophthalmologic surgical and medical therapies provided to children with birth weights less than 1251 g who had all stages of retinopathy of prematurity (ROP). In addition, this study aimed to report the initial age at which such procedures are provided and to report the frequency of cerebrospinal fluid shunts. DESIGN Observational case series with prospective data collection. PARTICIPANTS Children from the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) with birth weights less than 1251 g served as subjects. Group A included 257 children from all 23 CRYO-ROP study centers who had threshold ROP, who had participated in the randomized trial of cryotherapy, and who had survived to age 1 year. Group B included 1208 children from 5 of the 23 study centers who had varying severity of ROP (69 had threshold ROP) and who had participated in a 5 1/2-year study of the natural history of ROP. MAIN OUTCOME MEASURES Investigators documented medical and surgical ophthalmologic interventions through age 5 1/2 years as well as cerebrospinal fluid shunting surgery for hydrocephalus through age 2 years. RESULTS Group A was composed of 257 children with threshold ROP who underwent 226 ocular interventions in addition to cryotherapy (0.9 intervention per child). The most common treatments performed on the randomized cohort of children were vitrectomy (26% of patients), lensectomy (18%), amblyopia therapy (20%), and strabismus surgery (10%). Cataract surgery not associated with vitrectomy was performed infrequently (2%) and was performed equally often in treated and control eyes. Amblyopia therapy was prescribed as often for treated as for control eyes. Cerebrospinal fluid shunts were placed in 11% of these children. Group B was composed of 1208 natural history patients who underwent 239 ophthalmologic interventions (0.4 intervention per child). Strabismus surgery was the most commonly performed procedure for the natural history cohort of children (6% of the children). Amblyopia therapy was prescribed for 7% of the natural history patients. Cerebrospinal fluid shunts were required by 3% of the natural history infants, more often in children with more severe ROP. CONCLUSIONS These premature infants underwent a large number of ophthalmologic treatments during the first 5 1/2 years of life. The long-term costs of both extreme prematurity and ROP include not only the initial ablative therapy for ROP and societal loss due to blindness that still occurs in some cases, but also the ongoing costs of caring for eye problems.

Prevalence and course of strabismus through age 6 years in participants of the Early Treatment for Retinopathy of Prematurity randomized trial

PURPOSE To present strabismus data for children who participated in the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. METHODS The prevalence of strabismus, categorized as present or absent, was tabulated for all children with history of high-risk prethreshold retinopathy of prematurity (ROP) who participated in the ETROP randomized trial and were examined at 9 months to 6 years of age. Relationships among strabismus and demographic measures, eye characteristics, and neurodevelopmental factors were analyzed. RESULTS Among the 342 children evaluated at 6 years, the prevalence of strabismus was 42.2%. Even with favorable acuity scores in both eyes, the prevalence of strabismus was 25.4%, and with favorable structural outcomes in both eyes the prevalence of strabismus was 34.2%. Of children categorized as visually impaired as the result of either ocular or cerebral causes, 80% were strabismic at the 6-year examination. Of 103 study participants who were strabismic at 9 months, 77 (74.8%) remained so at 6 years. Most strabismus was constant at both the 9-month (62.7%) and the 6-year examination (72.3%). After multiple logistic regression analysis, risk factors for strabismus were abnormal fixation behavior in one or both eyes (P < 0.001), history of amblyopia (P < 0.003), unfavorable structural outcome in one or both eyes (P = 0.025), and history of anisometropia (P = 0.04). Strabismus surgery was performed for 53 children. By 6 years, the cumulative prevalence of strabismus was 59.4%. CONCLUSIONS Most children with a history of high-risk prethreshold ROP develop strabismus at some time during the first 6 years of life.