Incidence and Early Course of Retinopathy of Prematurity.

In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (ROP), 4099 infants weighing less than 1251 g at birth underwent sequential ophthalmic examinations, beginning at age 4 to 6 weeks, to monitor the incidence and course of ROP. Overall, 65.8% of the infants developed ROP to some degree; 81.6% for infants of less than 1000 g birth weight. As expected, ROP incidence and severity were higher in lower birth weight and gestational age categories. Black infants appeared less susceptible to ROP, of all severity categories, than nonblack infants. The timing of retinal vascular events correlated more closely with postconceptional age than with postnatal age, implicating the level of maturity more than postnatal environmental influences in governing the timing of these vascular events. These results include the current incidence of various severity stages of ROP found in the United States and provide new. insight into the development of ROP.

A hybrid method in combining treatment effects from matched and unmatched studies.

The most common data structures in the biomedical studies have been matched or unmatched designs. Data structures resulting from a hybrid of the two may create challenges for statistical inferences. The question may arise whether to use parametric or nonparametric methods on the hybrid data structure. The Early Treatment for Retinopathy of Prematurity study was a multicenter clinical trial sponsored by the National Eye Institute. The design produced data requiring a statistical method of a hybrid nature. An infant in this multicenter randomized clinical trial had high-risk prethreshold retinopathy of prematurity that was eligible for treatment in one or both eyes at entry into the trial. During follow-up, recognition visual acuity was accessed for both eyes. Data from both eyes (matched) and from only one eye (unmatched) were eligible to be used in the trial. The new hybrid nonparametric method is a meta-analysis based on combining the Hodges-Lehmann estimates of treatment effects from the Wilcoxon signed rank and rank sum tests. To compare the new method, we used the classic meta-analysis with the t-test method to combine estimates of treatment effects from the paired and two sample t-tests. We used simulations to calculate the empirical size and power of the test statistics, as well as the bias, mean square and confidence interval width of the corresponding estimators. The proposed method provides an effective tool to evaluate data from clinical trials and similar comparative studies.

Astigmatism progression in the early treatment for retinopathy of prematurity study to 6 years of age.

PURPOSE: To examine the prevalence of astigmatism (≥ 1.00 diopter [D]) and high astigmatism (≥ 2.00 D) from 6 months after term due date to 6 years of age in preterm children with birth weight of less than 1251 g in whom high-risk prethreshold retinopathy of prematurity (ROP) developed and who participated in the Early Treatment for ROP study. DESIGN: Observational cohort study. PARTICIPANTS: Four hundred one infants in whom high-risk prethreshold ROP developed in 1 or both eyes and were randomized to early treatment (ET) versus conventional management (CM). Refractive error was measured by cycloplegic retinoscopy. Eyes were excluded if they underwent additional retinal, glaucoma, or cataract surgery. INTERVENTION: Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP or to receive treatment only if threshold ROP developed. MAIN OUTCOME MEASURES: Astigmatism and high astigmatism at each study visit. RESULTS: For both ET and CM eyes, there was a consistent increase in prevalence of astigmatism over time, increasing from 42% at 4 years to 52% by 6 years for the group of ET eyes and from 47% to 54%, respectively, in the CM eyes. There was no statistically significant difference between the slopes (rate of change per month) of the ET and CM eyes for both astigmatism and high astigmatism (P = 0.75). CONCLUSIONS: By 6 years of age, astigmatism of 1.00 D or more developed in more than 50% of eyes with high-risk prethreshold ROP, and nearly 25% of such eyes had high astigmatism (≥ 2.00 D). Presence of astigmatism was not influenced by timing of treatment, zone of acute-phase ROP, or presence of plus disease. However, there was a trend toward higher prevalence of astigmatism and high astigmatism in eyes with ROP residua. Most astigmatism was with-the-rule (75°-105°). More eyes with type 2 than type 1 ROP had astigmatism by 6 years. These findings reinforce the need for follow-up eye examinations through early grade school years in infants with high-risk prethreshold ROP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Retinopathy of prematurity in infants weighing less than 500 grams at birth enrolled in the early treatment for retinopathy of prematurity study.

PURPOSE: To describe patient characteristics, classification, and onset of prethreshold retinopathy of prematurity (ROP), and ocular findings at 6 months corrected age in infants with birth weights <500 g who were enrolled in the Early Treatment for Retinopathy of Prematurity (ETROP) Study. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Sixty-three infants with birth weights <500 g who developed ROP and were enrolled in the ETROP Study. METHODS: Infants <1251 g at birth were logged at 26 study centers from October 1, 2000, to September 30, 2002, and underwent examinations for ROP. Infants who developed ROP and whose parents/legal guardians consented were enrolled in the ETROP Study. Infants who developed high-risk prethreshold ROP were randomized; 1 eye was treated early with peripheral retinal ablation and the other eye was managed conventionally, or, in asymmetric cases, the high-risk eye was randomized to early peripheral retinal ablation or conventional management. All eyes reaching prethreshold ROP were examined when infants reached 6 months corrected age. MAIN OUTCOME MEASURES: Retinopathy of prematurity incidence, characteristics, and ocular findings among participants. RESULTS: Thirty-four infants reached prethreshold or worse severity in 1 or both eyes. Retinopathy of prematurity was located in zone I in 43.3% of all prethreshold eyes, and plus disease was present in 46.7%. Median postmenstrual age for diagnosis of all prethreshold ROP was 36.1 weeks, but earlier (35.1 weeks) for eyes that developed high-risk prethreshold ROP. In the 27 surviving infants with prethreshold ROP, ophthalmic examination at 6 months corrected age showed a normal posterior pole in 22 (81.5%), a favorable structural outcome with posterior pole abnormalities in 4 (14.8%), and an unfavorable structural outcome (stage 4B) in 1 (3.7%). One infant developed amblyopia, 4 infants developed nystagmus, 4 infants developed strabismus, and 8 infants developed myopia >-5.00 diopters. CONCLUSIONS: This is the first report on characteristics of prethreshold ROP in infants with birth weights <500 g. These infants are at high risk for developing prethreshold ROP, although many initially achieve a favorable structural outcome. They are at risk of developing strabismus, nystagmus, high myopia, and abnormal retinal structure and should therefore receive continued long-term follow-up. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Astigmatism in the Early Treatment for Retinopathy Of Prematurity Study: findings to 3 years of age.

PURPOSE: To examine the prevalence of astigmatism (> or =1.00 diopter [D]) and high astigmatism (> or =2.00 D) at 6 and 9 months corrected age and 2 and 3 years postnatal age, in preterm children with birth weight of less than 1251 g in whom high-risk prethreshold retinopathy of prematurity (ROP) developed and who participated in the Early Treatment for Retinopathy of Prematurity (ETROP) Study. DESIGN: Randomized, controlled clinical trial. PARTICIPANTS: Four hundred one infants in whom prethreshold ROP developed in one or both eyes and who were randomized after they were determined to have a high risk (> or =15%) of poor structural outcome without treatment using the Risk Management of Retinopathy of Prematurity (RM-ROP2) program. Refractive error was measured by cycloplegic retinoscopy. Eyes with additional retinal, glaucoma, or cataract surgery were excluded. INTERVENTION: Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP (early treated [ET]) or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. MAIN OUTCOME MEASURES: Astigmatism and high astigmatism at each visit. Astigmatism was classified as with-the-rule (WTR; 75 degrees -105 degrees ), against-the-rule (ATR; 0 degrees -15 degrees and 165 degrees -180 degrees ), or oblique (OBL; 16 degrees -74 degrees and 106 degrees -164 degrees ). RESULTS: The prevalence of astigmatism in ET and CM eyes was similar at each test age. For both groups, there was an increase in prevalence of astigmatism from approximately 32% at 6 months to approximately 42% by 3 years, mostly occurring between 6 and 9 months. Among eyes that could be refracted, astigmatism was not influenced by zone of acute-phase ROP, presence of plus disease, or retinal residua of ROP. Eyes with astigmatism and high astigmatism most often had WTR astigmatism. CONCLUSIONS: By age 3 years, nearly 43% of eyes treated at high-risk prethreshold ROP developed astigmatism of > or =1.00 D and nearly 20% had astigmatism of > or =2.00 D. Presence of astigmatism was not influenced by timing of treatment of acute-phase ROP or by characteristics of acute-phase or cicatricial ROP. These findings reinforce the need for follow-up eye examinations in infants with high-risk prethreshold ROP. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Progression of myopia and high myopia in the early treatment for retinopathy of prematurity study: findings to 3 years of age.

PURPOSE: Examine the prevalence of myopia and high myopia, at 6 and 9 months postterm and 2 and 3 years postnatal in preterm children with birth weights < 1251 g who developed high-risk prethreshold retinopathy of prematurity (ROP) in the neonatal period and participated in the Early Treatment for ROP Study. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Four hundred one infants who developed prethreshold ROP and were determined to have a significant risk (>/=15%) of poor structural outcomes without treatment. Children underwent cycloplegic retinoscopy at examinations between 6 months postterm and 3 years' postnatal age. INTERVENTION: Eyes were randomized to receive treatment at high-risk prethreshold ROP (early treated [ET]) or conventional management (CM), with treatment only if threshold ROP developed. MAIN OUTCOME MEASURES: Myopia (spherical equivalent >/= 0.25 diopters [D]) or high myopia (>/=5.00 D) at each visit. RESULTS: Prevalences of myopia were similar in treated eyes in the ET and CM groups, increasing from approximately 58% to 68% between 6 and 9 months, with little change thereafter. Both ET and CM eyes showed an increasing prevalence of high myopia, approximately 19% at 6 months and increasing 4% to 8% at successive examinations. Zone of ROP and presence or absence of plus disease had little effect on prevalence of myopia or high myopia between ages 6 months and 3 years. However, eyes with ROP residua (straightened temporal vessels or macular heterotopia) showed a higher prevalence of myopia and high myopia than eyes without residua. CONCLUSIONS: Approximately 70% of high-risk prethreshold ROP eyes were myopic in early childhood, and the proportion with high myopia increased steadily between ages 6 months and 3 years. Timing of treatment of high-risk prethreshold ROP did not influence refractive error development. There was little difference in prevalence of myopia or high myopia between eyes with zone I and eyes with zone II ROP, nor between eyes with plus disease and eyes with no plus disease. However, prevalence of myopia and high myopia was higher in eyes with retinal residua of ROP than in eyes with normal-appearing posterior poles, highlighting the importance of follow-up eye examinations of infants who had prethreshold ROP.

Severe visual impairment in children with mild or moderate retinal residua following regressed threshold retinopathy of prematurity.

PURPOSE: To describe clinical features of patients from the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) trial who, after developing severe ROP in infancy, had minimal or moderate retinal residua in at least one eye but a visual acuity of worse than 20/200 in both eyes at the 10 year examination. METHODS: Data from the 10 year CRYO-ROP Trial follow-up exams were evaluated to identify all patients with retinal outcomes of no retinopathy of prematurity (ROP) residua, straightened temporal vessels, or macular heterotopia in at least one eye, but visual acuity less than 20/200 in both eyes. Presence of optic atrophy, nystagmus, and optic disk cupping and developmental survey results were examined. RESULTS: Of 247 patients examined at 10 years, 16 met our inclusion criteria. At the last age at which the following data were recorded, seven had optic atrophy at the 10 year examination, one had optic disk cupping >0.5 at the 5(1/2) year examination, and eight had nystagmus under binocular conditions at the 24 month examination. Nine patients had a below-normal developmental test score on the Functional Independence Measure for Children (WeeFIM). After clinical data interpretation, we concluded that the predominant cause of visual impairment was postgeniculate disease in five patients, ROP in six patients, and combined anterior and posterior visual pathway disease in two patients; in three patients data were insufficient to make a determination. CONCLUSIONS: Poor visual function with mild to moderate retinal residua of severe ROP in at least one eye is relatively rare. In such patients, anterior, posterior, or combined visual pathway disease can occur.

Visual acuity at 10 years in Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study eyes: effect of retinal residua of retinopathy of prematurity.

OBJECTIVE: To describe recognition (letter) acuity at age 10 years in eyes with and without retinal residua of retinopathy of prematurity (ROP). DESIGN: Presence and severity of ROP residua were documented by a study ophthalmologist. Masked testers measured monocular recognition visual acuity (Early Treatment of Diabetic Retinopathy Study) when the children were 10 years old. Two hundred forty-seven of 255 surviving Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) randomized trial patients participated. A reference group of 102 of 104 Philadelphia-based CRYO-ROP study participants who did not develop ROP was also tested. RESULTS: More severe retinal residua were associated with worse visual acuity, regardless of whether retinal ablation was performed to treat the severe acute-phase ROP. However, within each ROP residua category, there was a wide range of visual acuity results. CONCLUSIONS: This is the first report of the relation between visual acuity (Early Treatment of Diabetic Retinopathy Study charts) and structural abnormalities related to ROP in a large group of eyes that developed threshold ROP in the perinatal period. Visual deficits are greater in eyes with more severe retinal residua than in eyes with mild or no residua. However, severity of ROP residua does not predict the visual acuity of an individual eye because within a single residua category, acuity may range from near normal to blind.

Outcome of eyes developing retinal detachment during the Early Treatment for Retinopathy of Prematurity Study (ETROP).

OBJECTIVE: To report the structural and visual outcomes of eyes in which retinal detachment developed from retinopathy of prematurity (ROP) in the Early Treatment of Retinopathy of Prematurity (ETROP) Study. Method Infants in the ETROP Study with bilateral high-risk prethreshold ROP had 1 eye randomized to early treatment, with the fellow eye managed conventionally. In infants with asymmetric disease, the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management. When a retinal detachment was detected, observation or vitreoretinal surgery (ie, scleral buckling and/or vitrectomy) was provided at the discretion of the individual investigator. At 9 months corrected age, retinal examinations were performed and visual acuities were assessed by masked testers using grating acuity. RESULTS: The ETROP Study enrolled 401 patients with high-risk prethreshold ROP. Retinal detachments occurred in 89 eyes of 63 patients. Follow-up was available for 78 eyes of 56 patients. The detachments were bilateral in 21 patients (38%) and were classified as stage 4A in 30 eyes, stage 4B in 14 eyes, and stage 5 in 16 eyes. Detachments were not classified in 18 eyes. Twelve eyes of 11 patients were observed and 66 eyes of 52 patients underwent vitreoretinal surgery. Attachment of the macula at 9 months persisted or was achieved in 17 (30%) of 56 eyes after vitrectomy with or without scleral buckle, in 6 (60%) of 10 eyes after scleral buckle only, and in 2 (17%) of 12 eyes followed up without surgery. Favorable visual acuity (> or =1.85 cycles/degree) was found in 13 (17%) of the 78 eyes. All 6 eyes that maintained normal visual acuity (> or =3.70 cycles/degree) had a stage 4A detachment (1 of 6 managed by observation, 3 of 6 by scleral buckle, and 2 of 18 by vitrectomy). Eleven eyes with stage 5 detachment underwent vitreoretinal surgery, resulting in 6 with no light perception, 3 with light perception only, and 2 with detection of only the low vision card. CONCLUSIONS: In the ETROP Study, the outcome of retinal detachment owing to ROP was generally poor. Vitreoretinal surgery for retinal detachment was associated with macular attachment in 16 of 48 eyes. Normal acuity was maintained after surgical repair of stage 4A retinal detachment in 5 (21%) of 24 eyes. Vitreoretinal surgery for stage 5 disease was associated with some structural successes but poor functional outcomes.

Prevalence and course of strabismus in the first year of life for infants with prethreshold retinopathy of prematurity: findings from the Early Treatment for Retinopathy of Prematurity study.

OBJECTIVE: To present strabismus data for premature infants with prethreshold retinopathy of prematurity (ROP) enrolled in the Early Treatment for Retinopathy of Prematurity study. DESIGN: The prevalence of strabismus was tabulated for all of the infants with high-risk prethreshold disease who participated in the randomized trial of the Early Treatment for Retinopathy of Prematurity study and were examined at 6 and/or 9 months' corrected age as well as for all of the infants with low-risk prethreshold disease who were examined at 6 months' corrected age. MAIN OUTCOME MEASURES: Presence or absence of strabismus at 6 and 9 months' corrected age. RESULTS: The prevalence of strabismus at 6 months was higher for infants with high-risk prethreshold ROP than for those with low-risk prethreshold ROP (20.3% vs 9.6%, respectively; P<.001). Risk factors associated with the development of strabismus at 9 months include abnormal fixation behavior, presence of amblyopia, and outborn birth status (ie, born outside of a study-affiliated hospital). At 9 months, 30% of infants with high-risk prethreshold ROP had strabismus, although only 42% showed strabismus at 6 months. Thirty percent of infants with strabismus at 6 months showed normal alignment at 9 months. CONCLUSIONS: Infants with high-risk prethreshold ROP show significant variability in the presence vs absence of strabismus in the first year of life; thus, conservative management is recommended. APPLICATION TO CLINICAL PRACTICE: Ophthalmologists managing strabismus in infants who have high-risk prethreshold ROP should be aware of the significant variability in ocular alignment during the first year of life.

Prevalence of myopia at 9 months in infants with high-risk prethreshold retinopathy of prematurity.

PURPOSE: To examine the prevalence of myopia and high myopia at 9 months corrected age in premature infants who participated in the multicenter randomized trial of Early Treatment for Retinopathy of Prematurity (ETROP). DESIGN: Randomized, controlled clinical trial. PARTICIPANTS: Four hundred one infants with birth weights of <1251 g in whom prethreshold ROP developed in one or both eyes and who were determined to have a significant risk (> or =15%) of poor structural outcomes without treatment, based on the risk management for ROP program. INTERVENTION: Infants with bilateral high-risk prethreshold ROP (n = 317) had 1 eye randomized to early treatment, and the fellow eye was managed conventionally. In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management (control). Eyes randomized to early treatment at high-risk prethreshold ROP and eyes randomized to conventional management in which threshold ROP developed received peripheral retinal photocoagulation or cryotherapy. Conventionally managed eyes in which threshold ROP did not develop were observed. Cycloplegic retinoscopy data were obtained at 9 months corrected age from 321 eyes treated early and 307 eyes managed conventionally. MAIN OUTCOME MEASURES: Prevalence of myopic (spherical equivalent > or = 0.25 diopters [D]) and highly myopic (> or =5.00 D) eyes in each group. RESULTS: The prevalence of myopia (64.5% vs. 69.4%; P = 0.06) and high myopia (25.5% vs. 28.3%; P = 0.20) was similar between eyes treated at high-risk prethreshold and high-risk prethreshold eyes managed conventionally. Among high-risk eyes managed conventionally, the prevalence of myopia (78.2% vs. 53.3%) and high myopia (37.6% vs. 11.2%) was higher when threshold ROP developed than when regression without treatment occurred. Among eyes treated at high-risk prethreshold ROP, the prevalence of myopia (93.3% vs. 91.7% vs. 60.6%) and of high myopia (53.3% vs. 33.3% vs. 20.8%) was higher in eyes with abnormal angle of temporal retinal vessels or macular ectopia than in eyes with no retinal residua. This also held true for conventionally managed eyes. CONCLUSIONS: Early treatment at high-risk prethreshold did not place eyes at greater risk of myopia and high myopia than did conventional management of eyes with high-risk prethreshold ROP.

15-year outcomes following threshold retinopathy of prematurity: final results from the multicenter trial of cryotherapy for retinopathy of prematurity.

OBJECTIVE: To report the ocular structure and visual acuity outcomes at age 15 years, and the incidence of retinal detachment between 10 and 15 years of age, for patients in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP). METHODS: Subjects were 254 survivors from 291 preterm children with birth weights less than 1251 g and severe (threshold) retinopathy of prematurity (ROP) in one or both eyes, who participated in the CRYO-ROP trial. At age 15 years, unfavorable ocular structure was posterior retinal fold or worse judged by study-certified ophthalmologists. Unfavorable distance visual acuity was 20/200 or worse measured by study-certified testers using Early Treatment of Diabetic Retinopathy Study recognition acuity charts. RESULTS: Thirty percent of treated eyes and 51.9% of control eyes (P<.001) had unfavorable structural outcomes. Between 10 and 15 years of age, new retinal folds, detachments, or obscuring of the view of the posterior pole occurred in 4.5% of treated and 7.7% of control eyes. Unfavorable visual acuity outcomes were found in 44.7% of treated and 64.3% of control eyes (P<.001). CONCLUSION: The benefit of cryotherapy for treatment of threshold ROP, for both structure and visual function, was maintained across 15 years of follow-up. New retinal detachments, even in eyes with relatively good structural findings at age 10 years, suggest value in long-term, regular follow-up of eyes that experience threshold ROP.

The early treatment for ROP (ETROP) randomized trial: study results and nursing care adaptations.

The Early Treatment for Retinopathy of Prematurity (ETROP) study, funded by the National Eye Institute, has shown that early treatment of high-risk prethreshold retinopathy of prematurity (ROP) improves retinal and visual outcomes at 9 months corrected age. These favorable study results have yielded new guidelines for treatment of infants with ROP This paper reviews the study methodology and results and outlines the neonatal and ophthalmic nursing interventions influenced by this new treatment schedule. Four critical phases, screening/examination, treatment, evaluation, and follow-up, are identified, and key nursing objectives and tasks are discussed.

Risk analysis of prethreshold retinopathy of prematurity.

OBJECTIVE: To present a new multifactorial algorithm to integrate important risk factors for unfavorable retinal outcome in eyes that reached prethreshold retinopathy of prematurity (ROP) in the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study. A computerized risk model (RM-ROP2) was developed from this algorithm to identify high-risk prethreshold eyes for enrollment in the Early Treatment for Retinopathy of Prematurity randomized trial. METHODS: Data were analyzed from 613 eyes (1 eye per infant) in the natural history cohort of the Multicenter Trial for Cryotherapy for Retinopathy of Prematurity. These eyes were selected from infants in whom 1 or both eyes progressed to prethreshold ROP. Eyes that progressed to threshold ROP and were randomized to cryotherapy were excluded from this study, but control eyes that reached threshold ROP were included. The course of ROP for 1 prethreshold eye for each infant was tracked until the evaluation of its structural outcome at 3 months' postterm. Tables present structural outcome by selected risk characteristics. A multiple logistic risk model is used to summarize the combined effect of all of these known prognostic risk factors as they relate to structural outcome. RESULTS: Eyes were classified by predicted outcome into 10 risk categories, lowest to highest. Both the observed and predicted outcomes in each category showed an increasingly unfavorable outcome when viewed from lowest to highest risk. Prethreshold ROP eyes were then divided into 2 groups, high-risk, eyes (risk, 0.15-1.0) and low-risk eyes (risk, <0.15). High-risk eyes had an unfavorable outcome of 36% at 3 months' postterm; whereas, only 5% of the low-risk eyes had an unfavorable outcome. CONCLUSION: The model effectively identifies prethreshold ROP eyes that have a relatively high risk and eyes that have a lower risk of an unfavorable structural outcome at 3 months.

Health-related quality of life at age 10 years in very low-birth-weight children with and without threshold retinopathy of prematurity.

OBJECTIVE: To describe parental perspectives on health status and health-related quality of life (HRQL) at age 10 years in children with birth weights less than 1251 g who participated in the multicenter Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study. METHODS: In 244 participants in the randomized CRYO-ROP trial and 102 CRYO-ROP participants who did not develop ROP, the Health Utilities Index (HUI) system was used to characterize health status for the following 8 attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. Using a utility formula, HRQL was determined for each child on a scale from 0.0 (dead) to 1.00 (perfect health). RESULTS: The proportion of the ROP-randomized group with limitations in 4 attributes or more was 20.6% compared with 2.0% for the no-ROP group. Within the ROP-randomized group, the proportion of "sighted" children with limitations in 4 attributes or more was 6.4% vs 46.5% in the "blind/low vision" group. The median HRQL score for the ROP-randomized children was lower than for the no-ROP children (0.72 vs 0.97, P<.001); the median HRQL score for the sighted-randomized children was 0.87 vs 0.27 for the blind/low vision children (P<.001). CONCLUSIONS: Threshold ROP was associated with functional limitations in health attributes and reduction in HRQL scores at age 10 years. Furthermore, among children who developed threshold ROP, a greater reduction in HRQL scores was found among children with a poor visual outcome compared with those with better sight.

Evidence-based screening criteria for retinopathy of prematurity: natural history data from the CRYO-ROP and LIGHT-ROP studies.

BACKGROUND: The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) demonstrated the efficacy of treatment for threshold ROP and indicated the need for worldwide ROP screening. Previous guidelines for ROP screening have been largely based on clinical impression; we can now develop evidence-based screening recommendations. OBJECTIVE: To define the appropriate ages and retinal ophthalmoscopic signs that determine when to commence and conclude acute phase ROP screening. DESIGN: Analysis of data from 2 prospective randomized controlled trials: CRYO-ROP (January 1, 1986, to November 30, 1987) and Light Reduction in ROP (LIGHT-ROP) (July 1, 1995, to March 31, 1997). SETTING: Neonatal intensive care units in 23 study centers in the United States for CRYO-ROP and 3 centers for LIGHT-ROP. PATIENTS: Eyes were examined sequentially in 4099 infants with birth weight less than 1251 g (CRYO-ROP study) and in 361 infants with birth weight less than 1251 g and gestational age less than 31 weeks (LIGHT-ROP study). RESULTS: In 99% of infants, retinal conditions indicating a risk of poor outcome were not observed before 31 weeks' postmenstrual age or 4 weeks' chronologic age. Signs indicating that the risk of visual loss from ROP was minimal or had passed were the infant's attainment of 45 weeks' postmenstrual age without the development of prethreshold ROP or worse, progression of retinal vascularization into zone III without previous zone II ROP, and full vascularization. CONCLUSIONS: The initial eye examination should be conducted by 31 weeks' postmenstrual age or 4 weeks' chronologic age, whichever is later. Acute phase ROP screening can be discontinued when any of the 3 signs is present, indicating that the risk of visual loss from ROP is minimal or passed.

Clinical characteristics of children with severe visual impairment but favorable retinal structural outcomes from the Early Treatment for Retinopathy of Prematurity (ETROP) study.

PURPOSE: To describe visual function and associated characteristics at the 6-year examination in children enrolled in the Early Treatment for Retinopathy of Prematurity Study who had unfavorable visual outcomes despite favorable structural outcomes in one or both eyes. METHODS: The clinical examination records of children completing the 6-year follow-up examination were retrospectively reviewed. Eligible subjects were those with visual acuity of ≤20/200 in each eye (where recordable) and a normal fundus or straightening of the temporal retinal vessels with or without macular ectopia in at least one eye. Data regarding visual function, retinal structure, presence of nystagmus, optic atrophy, optic disk cupping, seizures/shunts, and Functional Independence Measure for Children (ie, WeeFIM: pediatric functional independence measure) developmental test scores were reviewed. RESULTS: Of 342 participants who completed the 6-year examination, 39 (11%) met inclusion criteria. Of these, 29 (74%) had normal retinal structure, 18 (46%) had optic atrophy, and 3 (8%) had increased cupping of the optic disk in at least one eye. Latent and/or manifest nystagmus occurred in 30 children (77%). The presence of nystagmus was not related to the presence of optic atrophy. Of the 39 children, 28 (72%) had a below-normal WeeFIM score. CONCLUSIONS: In 25 participants (7%) completing the 6-year examination, cortical visual impairment was considered the primary cause of visual loss. The remainder likely had components of both anterior and posterior visual pathway disease. Clinical synthesis of ocular anatomy and visual and neurologic function is required to determine the etiology of poor vision in these children.

Incidence of cataract development by 6 months' corrected age in the Early Treatment for Retinopathy of Prematurity study.

PURPOSE: To report the incidence of cataract development by 6 months' corrected age in preterm children who participated in the Early Treatment for Retinopathy of Prematurity study. METHODS: Infants who developed prethreshold retinopathy of prematurity (ROP) in one or both eyes and were determined by the RM-ROP2 model to have a high risk of poor structural outcome without treatment were randomized to receive early treatment (ET), defined as laser photocoagulation at high-risk prethreshold ROP, or to be conventionally managed (CM), receiving treatment only if threshold ROP developed. Data on eyes developing a cataract by 6 months' corrected age were analyzed. RESULTS: Of 401 randomized infants, 366 survived patients were followed, and 8 eyes of 7 patients (1.9%) developed cataracts by 6 months' corrected age. Among these patients, mean birth weight was 754 g, and mean gestational age was 25.7 weeks. Mean gestational age at treatment was 36.3 weeks for ET patients and 39.5 weeks for CM patients. Three ET eyes and 5 CM eyes developed a cataract. Of the CM eyes, 3 with and 2 without laser treatment developed a cataract. All 6 treated eyes had plus disease when treated. Three eyes had ROP in zone 1, whereas the other 3 had ROP in zone 2. All eyes were treated using a diode laser. CONCLUSIONS: By 6 months' corrected age, a small number of both ET and CM eyes developed cataracts following diode laser treatment for retinopathy of prematurity. Absence of obvious intraoperative complications does not preclude subsequent cataract development, which can occur without laser treatment.

Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity study: findings at 4 to 6 years of age.

PURPOSE: To report the prevalence of myopia and high myopia in children <6 years of age born preterm with birth weights <1251 g who developed high-risk prethreshold retinopathy of prematurity and who participated in the Early Treatment for Retinopathy of Prematurity trial. METHODS: Surviving children from the cohort of 401 participants who had developed high-risk prethreshold ROP in one or both eyes underwent cycloplegic retinoscopy at 6 and 9 months corrected age and yearly between 2 and 6 years postnatal age. Eyes were randomized to receive treatment at high-risk prethreshold ROP or conventional management with treatment only if threshold ROP developed. Myopia (spherical equivalent ≥0.25 D) or high myopia (≥5.00 D) in eyes at 4-, 5-, and 6-year examinations was reported. RESULTS: At ages 4, 5, and 6 years, there was no difference in the percentage of eyes with myopia (range, 64.8%-69.9%) and eyes with high myopia (range, 35.3%-39.4%) between earlier treated and conventionally managed eyes. CONCLUSIONS: Approximately two-thirds of eyes with high-risk prethreshold ROP during the neonatal period are likely to be myopic into the preschool and early school years. In addition, the increase in the proportion of eyes with high myopia that had been observed in both earlier-treated and conventionally managed eyes between ages 6 months and 3 years does not continue between ages 3 and 6 years.

Correlation of recognition visual acuity with posterior retinal structure in advanced retinopathy of prematurity.

OBJECTIVE To compare Early Treatment Diabetic Retinopathy Study visual acuity outcome with retinal structural outcome at the 6-year follow-up examination of infants randomized in the Early Treatment for Retinopathy of Prematurity study. METHODS We compared the results in 606 eyes of subjects in whom both functional (visual acuity) and retinal structural assessments were obtained at age 6 years. Visual acuity assessments were performed by masked testers, and retinal examinations were performed by certified ophthalmologists. MAIN OUTCOME MEASURES Visual acuity and retinal structure at age 6 years. RESULTS Concordant outcomes occurred in 462 eyes (76.2%): 402 eyes had favorable functional and structural outcomes and 60 eyes had unfavorable functional and structural outcomes. Discordant outcomes occurred in 92 eyes (15.2%): 86 eyes had unfavorable functional and favorable structural outcomes and 6 eyes had favorable functional and unfavorable structural outcomes. Of the 86 eyes with unfavorable functional and favorable structural outcomes, 43 had optic atrophy (23 eyes) and/or retinal abnormalities that were less severe than those considered to be unfavorable (32 eyes). In 52 eyes (8.6%), retinal structure could not be assessed or the visual acuity was untestable. CONCLUSION Posterior pole appearance correlates well with visual acuity in 6-year-old infants with a history of advanced retinopathy of prematurity. APPLICATION TO CLINICAL PRACTICE When the retinal structure is normal but visual acuity is poor in infants with a history of severe retinopathy of prematurity, other diagnoses such as optic atrophy and cortical visual impairment could at least partially account for the discrepancy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00027222.