Betty Tung

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.

Prevalence of Myopia between 3 Months and 5 '/-- Years in Preterm Infants with and without Retinopathy of Prematurity

Purpose: The purpose of the study was to examine spherical equivalent refractive errors, especially myopia, at six ages between 3 months and 5’/, years post-term in preterm children with birth weights of less than 1251 g. Design: A cohort study. Participants: There were a total of 827 participants in the multicenter study of cryotherapy for retinopathy of prematurity (ROP). Approximately one third of the eyes did not develop ROP, whereas two thirds developed mildto-severe ROP. None of the eyes underwent ctyotherapy. Intervention: Refractive error was measured at 3 months, 1 year, and 5’/2 years after term due date at the five long-term follow-up centers. In most eyes, refractive error also was measured at 2, 3’/*, and 4’/* years. Main Outcome Measure: Myopia was defined as 0.25 diopter (D) or greater with high myopia as 5 D or greater. Results: The proportion of eyes with myopia in this preterm population was increased compared to published data on full-term children and was related to severity of both acute-phase and cicatricial-phase ROP. The percentage of eyes with myopia varied little across ages, ranging from 21.2% at 1 year to 15.7% at 4’1’~ years. The percentage of eyes with high myopia doubled from 1.8% to 3.9% between 3 months and 1 year and remained stable thereafter. The distribution of refractive errors in eyes with mild acute-phase ROP was similar to that of eyes with no ROP. In contrast, eyes with moderate or severe acute-phase ROP showed an increased prevalence of high myopia. The distribution of refractive errors changed between 3 months and 1 year with little change after 1 year. This pattern of refractive development differs from that of full-term infants. Birth weight, severity of ROP, and degree of myopia at 3 months predicted the presence of myopia and high myopia at 5’1, years of age. Conclusions: The distribution of refractive errors in preterm infants from age 3 months to 51/2 years varies with severity of acute-phase ROP and cicatricial disease. Changes in refractive error distribution occur primarily between 3 months and 1 year and involve a decrease in the proportion of eyes with hyperopia and an increase in the proportion with high degrees of myopia. Ophfhalmology 7998; 705:7292- 7300

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.

Outcome of Eyes Developing Retinal Detachment During the Early Treatment for Retinopathy of Prematurity Study (ETROP)

OBJECTIVE To describe the structural and visual outcomes at age 6 years of retinal detachment (RD) from retinopathy of prematurity (ROP) in the Early Treatment for Retinopathy of Prematurity (ETROP) study. METHODS Prospective multicenter nonrandomized series of infants with high-risk prethreshold ROP who developed an RD by 6 months corrected age treated with observation or vitreoretinal surgery. RESULTS Of 401 patients, 63 (89 eyes) experienced RD. Follow-up at age 6 years was available for 70 eyes (79%) of 49 surviving patients. The RDs were stage 4A in 28 eyes (40%), stage 4B in 14 (20%), stage 5 in 13 (19%), and not classified in 15 (21%). The macula was attached in 17 of 50 eyes (34%) after vitrectomy with or without scleral buckle, in 6 of 9 (67%) after scleral buckle only, and in 2 of 11 eyes (18%) observed. An attached macula at age 6 years after vitreoretinal surgery was present in 5 of 16 eyes (31%) with stage 4A, 6 of 10 (60%) with stage 4B, and 0 of 10 with stage 5. Favorable visual acuity (>20/200) was found in 6 of 70 eyes (9%); 5 had stage 4A, and 1 was not classified. CONCLUSIONS Macular attachment was achieved in approximately one-third of eyes with RD and favorable visual acuity in some eyes with stage 4A.

Grating visual acuity results in the early treatment for retinopathy of prematurity study

OBJECTIVE To compare grating (resolution) visual acuity at 6 years of age in eyes that received early treatment (ET) for high-risk prethreshold retinopathy of prematurity (ROP) with that in eyes that underwent conventional management (CM). METHODS In a randomized clinical trial, infants with bilateral, high-risk prethreshold ROP (n = 317) had one eye undergo ET and the other eye undergo CM, with treatment only if ROP progressed to threshold severity. For asymmetric cases (n = 84), the high-risk prethreshold eye was randomized to ET or CM. MAIN OUTCOME MEASURE Grating visual acuity measured at 6 years of age by masked testers using Teller acuity cards. RESULTS Monocular grating acuity results were obtained from 317 of 370 surviving children (85.6%). Analysis of grating acuity results for all study participants with high-risk prethreshold ROP showed no statistically significant overall benefit of ET (18.1% vs 22.8% unfavorable outcomes; P = .08). When the 6-year grating acuity results were analyzed according to a clinical algorithm (high-risk types 1 and 2 prethreshold ROP), a benefit was seen in type 1 eyes (16.4% vs 25.2%; P = .004) undergoing ET, but not in type 2 eyes (21.3% vs 15.9%; P = .29). CONCLUSION Early treatment of eyes with type 1 ROP improves grating acuity outcomes, but ET for eyes with type 2 ROP does not. APPLICATION TO CLINICAL MEDICINE: Type 1 eyes should be treated early; however, based on acuity results at 6 years of age, type 2 eyes should be cautiously monitored for progression to type 1 ROP. Trial Registration clinicaltrials.gov Identifier: NCT00027222.

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.

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.

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.

Visual Fields Measured with Double-arc Perimetry in Eyes with Threshold Retinopathy of Prematurity from the Cryotherapy for Retinopathy of Prematurity Trial

PURPOSE To measure monocular visual field extent in very-low birth weight children in whom severe (threshold) acute-phase retinopathy of prematurity (ROP) developed in one or both eyes, and who had random assignment of eyes to cryotherapy or no cryotherapy. A control group of very-low birth weight children in whom ROP did not develop also was tested. METHODS There were 78 children in the severe ROP group from 5 of 23 centers in the randomized trial of cryotherapy for ROP (CRYO-ROP). The comparison cohort consisted of 75 study participants in whom ROP did not develop. All subjects had birth weights of less than 1251 g. At the 5 1/2-year study examination, visual field size was measured using double-arc kinetic perimetry. Testers were masked to treatment status of each eye. Four meridia were tested: superotemporal (ST), inferotemporal (IT), inferonasal (IN), and superonasal (SN). Target size was 6 degrees. RESULTS When blind eyes were assigned a score of 0 degree, the no-ROP, treated, and control eyes had an average visual field extent of 62 degrees, 35 degrees, 27 degrees at ST; 73 degrees, 42 degrees, 35 degrees at IT; 51 degrees, 30 degrees, 21 degrees IN; and 50 degrees, 26 degrees, 22 degrees at SN, respectively. Among 25 children who had bilateral threshold ROP and measurable fields in each eye, values for treated and control eyes were 59 versus 62 at ST, 69 versus 80 at IT, 44 versus 49 at IN, and 41 versus 48 at SN, respectively. CONCLUSIONS Overall, visual fields in eyes that reached threshold ROP were smaller than those of eyes that did not develop ROP. When only pairs of sighted eyes were considered, visual fields in the treated eyes were 6.4 degrees smaller than those of control eyes. Therefore, it appears that a small loss of peripheral field occurs when cryotherapy prevents the development of retinal detachment.