Acute-phase Retinopathy Of Prematurity Research Articles

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study

BackgroundThere are no data on pharmacokinetics, pharmacodynamics, and immunogenicity of intravitreal aflibercept in preterm infants with retinopathy of prematurity (ROP). FIREFLEYE compared aflibercept 0.4 mg/eye and laser photocoagulation in infants with acute-phase ROP requiring treatment.MethodsInfants (gestational age ≤32 weeks or birthweight ≤1500 g) with treatment-requiring ROP in ≥1 eye were randomized 2:1 to receive aflibercept 0.4 mg or laser photocoagulation at baseline in this 24-week, randomized, open-label, noninferiority, phase 3 study. Endpoints include concentrations of free and adjusted bound aflibercept in plasma, pharmacokinetic/pharmacodynamic exploration of systemic anti-vascular endothelial growth factor effects, and immunogenicity.ResultsOf 113 treated infants, 75 received aflibercept 0.4 mg per eye at baseline (mean chronological age: 10.4 weeks), mostly bilaterally (71 infants), and with 1 injection/eye (120/146 eyes). Concentrations of free aflibercept were highly variable, with maximum concentration at day 1, declining thereafter. Plasma concentrations of adjusted bound (pharmacologically inactive) aflibercept increased from day 1 to week 4, decreasing up to week 24. Six infants experienced treatment-emergent serious adverse events within 30 days of treatment; aflibercept concentrations were within the range observed in other infants. There was no pattern between free and adjusted bound aflibercept concentrations and blood pressure changes up to week 4. A low-titer (1:30), non-neutralizing, treatment-emergent anti-drug antibody response was reported in 1 infant, though was not clinically relevant.Conclusions24-week data suggest intravitreal aflibercept for treatment of acute-phase ROP is not associated with clinically relevant effects on blood pressure, further systemic adverse events, or immunogenicity.ClinicalTrials.gov IdentifierNCT04004208.

Factors in Premature Infants Associated With Low Risk of Developing Retinopathy of Prematurity

Most premature infants will not develop retinopathy of prematurity (ROP) of clinical relevance, yet screening evaluations often continue beyond hospital discharge, even for those infants without ROP. To identify the characteristics of infants at low risk for ROP, for whom further postdischarge screening may be of limited value. This study took place in North American neonatal intensive care units where clinicians had expertise in ROP. Infants with birth weight less than 1251 g who were born at or transferred into an Telemedicine Approaches to Evaluating Acute-Phase ROP (e-ROP) study center were enrolled. The study included post hoc analysis of prospectively collected in-hospital ROP examination results among infants enrolled in the e-ROP study. We characterized infants without ROP and performed logistic regression on the subset of infants who were 27 to 33 weeks' gestational age to determine characteristics associated with the absence of ROP during all in-hospital examinations. The main measure was the absence of ROP prior to hospital discharge; the main outcome was treatment for ROP. A total of 1257 infants born at 22 to 35 weeks' gestation (median [interquartile range (IQR)], 26 [25-28] weeks) with birth weights less than 1251 g (median [IQR], 860 [690-1040] g) underwent 4113 ROP examinations between 31 and 47 weeks' postmenstrual age. Overall, 1153 examinations (38%) showed no ROP, and 456 infants (36%) did not have ROP prior to study center discharge or study end point. Among infants without ROP during examinations at 32 and 33 weeks' postmenstrual age, 16 (9.4%) and 14 (5.3%) subsequently underwent ROP treatment, respectively. At hospital discharge, there was no ROP in 59% of infants of 27 to 33 weeks' gestational age, compared with 15% of those who were less than 27 weeks' gestational age (difference, 44% [95% CI, 38.5%-48.1%]; P ≤ .001). With more than 85% follow-up among infants without ROP by 37 weeks' postmenstrual age, none (95% CI, 0%-0.98%) were treated for ROP. In multivariate analysis of infants born at 27 to 33 weeks' gestation, larger birth weight (OR, 4.1 [95% CI, 1.6-10.3]) and higher gestational age (OR, 4.0 [95% CI, 1.5-10.8]) were significantly associated with absence of ROP. These findings suggest that, for infants of 27 weeks' gestational age or greater and birth weights larger than 750 g, if no ROP has been detected by discharge at near-term postmenstrual age, then further ROP surveillance has limited value. Studies of all infants at risk are needed to develop more specific, objective criteria for termination of ROP surveillance and focus resources on infants at higher risk of ROP. ClinicalTrials.gov Identifier: NCT01264276.

Evidence-based schedule for retinopathy of prematurity (ROP) examinations

We sought to develop evidence-based recommendations for scheduling and termination of acute phase ROP examinations.

Follow-up to Age 4 Years of Treatment of Type 1 Retinopathy of Prematurity Intravitreal Bevacizumab Injection versus Laser: Fluorescein Angiographic Findings

To compare structural outcome at age 4 years of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in type 1 retinopathy of prematurity (ROP). Single, randomized, controlled trial. All inborn babies with type 1 zone 1 ROP at the Neonatal Intensive Care Unit of the Catholic University, Rome, from September 1, 2009, to March 31,2012. In 21 infants (42 eyes), 1 eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye underwent conventional laser photoablation. Digital retinal imaging and fluorescein angiography (FA) were performed at an average of 4 years after treatment in follow-up after these studies performed at treatment and 9 months. Fluorescein angiograms were examined by 2 experts to document retinal and choroidal findings. Among the 20 bevacizumab-treated eyes available at 4 years of age, all showed abnormalities at the periphery (avascular area, vessel leakage, shunts, abnormal vessel branching, and tangles) or the posterior pole (hyperfluorescent lesions, absence of foveal avascular zone). These lesions were not observed in the majority of the lasered eyes. Among the 19 laser-treated eyes, leakage was noted in 1 eye, shunts and tangles were noted in 3 eyes, and macular abnormalities were noted in 3 eyes. Fluorescein angiography has shown potentially serious and long-term ocular effects that arepresent more commonly after treatment with bevacizumab for acute-phase ROP than after laser.

Intereye Agreement of Retinopathy of Prematurity from Image Evaluation in the Telemedicine Approaches to Evaluating of Acute-Phase ROP (e-ROP) Study

To determine the symmetry on retinal image grading of fellow eyes for retinopathy of prematurity (ROP) features (stage, zone and plus disease) and severity, to provide the basis for the within subject comparison for ROP trials. Secondary analyses of data from the Telemedicine Approaches to Evaluating of Acute-Phase ROP (e-ROP) Study. Infants with birth weight less than 1251g. Infants underwent serial retinal imaging sessions in both eyes by certified imagers starting at 32-weeks postmenstrual age (PMA). Two trained non-physician readers graded each eye independently for ROP features in a 5 retinal-image set from each session. Discrepancies were adjudicated by a reading center supervisor. Readers were masked to all eye examination results, previous gradings of both eyes, current grading of the fellow eye, and demographic data. The inter-eye agreement assessed using percent exact agreement and weighted kappa (Kw ) for stage, zone, plus, referral-warranted ROP (RW-ROP, defined as presence of stage 3 or above, plus disease, or zone I ROP), and severity of ROP. Among 3918 image sessions in 1235 infants, the percent agreement (Kw ) between paired eyes was 75.3% (0.65) for stage of ROP, 82.3% (0.68) for zone of ROP, 78.7% (0.51) for plus disease, 84.7% (0.56) for RW-ROP, and 72.7% (0.63) for severity of ROP. Similar inter-eye agreements were found when considering ROP features at the first image session, at the last image session, at any image session. Based on image evaluations from all sessions, 412 (33.4%) infants had ROP stage 3 or above, 148 (12.0%) had zone I ROP, 70 (5.7%) had plus disease, and 419 (33.9%) had RW-ROP in one or both eyes; symmetrical findings were present in 71.4% for ROP stage 3 or above, 56.8% for zone I ROP, 50.0% for plus disease, and 73.7% for RW-ROP. Masked image evaluations by trained readers showed good inter-eye agreement in ROP characteristics, consistent with the high inter-eye agreement in ROP from clinical examinations by ophthalmologists in other studies. These data confirm that acute ROP is typically symmetrical and supports within subject comparison in ROP trials.

Risk Score for Predicting Treatment-Requiring Retinopathy of Prematurity (ROP) in the Telemedicine Approaches to Evaluating Acute-Phase ROP Study

To develop a risk score for predicting treatment-requiring retinopathy of prematurity (TR-ROP) in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study. Second analyses of an observational cohort study. Infants with birth weight (BW) <1251 g who had ≥1 imaging session by 34 weeks of postmenstrual age (PMA) and ≥1 subsequent retinopathy of prematurity (ROP) examination for determining TR-ROP by study-certified ophthalmologists. Nonphysician trained readers evaluated wide-field retinal image sets for characteristics of ROP, pre-plus/plus disease, and retinal hemorrhage. Risk score points for predicting TR-ROP were derived from the regression coefficients of significant predictors in a multivariate logistic regression model. TR-ROP. Eighty-five of 771 infants (11.0%) developed TR-ROP. In a multivariate model, significant predictors for TR-ROP were gestational age (GA) (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.7-18.9 for ≤25 vs. ≥28 weeks), need for respiratory support (OR, 7.0; 95% CI, 1.3-37.1 for high-frequency oscillatory ventilation vs. no respiratory support), slow weight gain (OR, 2.4; 95% CI, 1.2-4.6 for weight gain ≤12 g/day vs. >15 g/day), and image findings at the first image session including number of quadrants with pre-plus (OR, 3.8; 95% CI, 1.5-9.7 for 4 pre-plus quadrants vs. no pre-plus), stage and zone of ROP (OR, 4.7; 95% CI, 2.1-11.8 for stage 1-2 zone I, OR, 5.9; 95% CI, 2.1-16.6 for stage 3 zone I vs. no ROP), and presence of blot hemorrhage (OR, 3.1; 95% CI, 1.4-6.7). Image findings predicted TR-ROP better than GA (area under receiver operating characteristic curve [AUC]= 0.82 vs. 0.75, P= 0.03). The risk of TR-ROP steadily increased with higher risk score and predicted TR-ROP well (AUC= 0.88; 95% CI, 0.85-0.92). Risk score ≥3 points for predicting TR-ROP had a sensitivity of 98.8%, specificity of 40.1%, and positive and negative predictive values of 17.0% and 99.6%, respectively. Image characteristics at 34 PMA weeks or earlier independently predict TR-ROP. If externally validated in other infants, risk score, calculated from image findings, GA, weight gain, and respiratory support, enables early identification of infants in need of increased surveillance for TR-ROP.

Ensuring successful enrollment of premature babies into NICU-based clinical studies: lessons learned from the Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity (ROP)—e-ROP study

Ensuring successful enrollment of premature babies into NICU-based clinical studies: lessons learned from the Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity (ROP)—e-ROP study

Impact of retinopathy of prematurity on ocular structures and visual functions

The preterm baby may develop ophthalmic sequelae which can be due to prematurity per se, due to retinopathy of prematurity (ROP) or due to neurological damage. Focusing on the former...

Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity: Study Design

Purpose: Detecting sight-threatening retinopathy of prematurity (ROP) relies on a diagnostic examination (DE) performed by an experienced ophthalmologist. An alternative may be a telemedicine system where retinal images of at-risk infants are graded by readers to determine features of ROP indicating the need for a DE.Methods: The multicenter Telemedicine Approaches to Evaluating Acute-phase ROP (e-ROP) Study is a cohort study of 2000 infants with birth weights <1251 g. At each visit, ophthalmologists perform DEs and non-physician imagers obtain iris and five retinal images with the disc positioned in the center, right, left, up and down. Images are uploaded to a secure server for grading by non-physician readers for the detection of plus disease, stage 3 ROP and/or zone I disease, any of which indicates “referral-warranted ROP” (RW-ROP). Images from all infants with RW-ROP and a random sample of infants without RW-ROP (based on DEs) are selected for grading. Gradings are compared to DEs to determine the validity and evaluate reliability, feasibility, safety, and cost-effectiveness of the telemedicine system.Results: e-ROP is conducted in 12 Clinical Centers in the US and Canada with Study Headquarters, the Data Coordinating Center and the Image Reading Center in Philadelphia and the ROP Data Center in Oklahoma City. A total of 27 study center coordinators, 34 ophthalmologists, 26 imagers, and 4 readers have been certified. All study data are submitted using a secure web-based system.Conclusion: The design and findings of this study will be useful to conduct other ROP studies or evaluate telemedicine for other diseases.

Astigmatism Progression in the Early Treatment for Retinopathy of Prematurity Study to 6 Years of Age

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. Observational cohort study. 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. Eyes were randomized to receive laser photocoagulation at high-risk prethreshold ROP or to receive treatment only if threshold ROP developed. Astigmatism and high astigmatism at each study visit. 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). 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. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Atlas of Fluorescein Angiographic Findings in Eyes Undergoing Laser for Retinopathy of Prematurity

We sought to examine the clinical features of severe retinopathy of prematurity (ROP) using fluorescein angiography (FA). Retrospective case series of eyes with severe acute-phase ROP that underwent FA at the time of laser photocoagulation. We included 22 eyes of 11 infants that developed ROP stage 3 in zone 1 with plus disease, 8 eyes of 4 infants classified as ROP stage 3 in zone 1 without plus disease, and 21 eyes of 11 infants that developed ROP stage 3 in zone 2 with plus disease. All eyes underwent laser photocoagulation. A total of 51 sets of digital images including FA were obtained immediately before treatment. RetCam (Clarity, Pleasanton, CA) fundus images and video digital FAs were performed under general anesthesia right before laser treatment. A 10% solution of fluorescein was intravenously administered as a bolus at a dose of 0.1 ml/kg, followed by an isotonic saline flush. Fluorescein angiograms were examined retrospectively to catalog different retinal and choroidal findings In eyes with severe ROP, FA clearly shows extreme variability in both retinal circulation and choroidal filling pattern. Different patterns of vessels branching at the junction between vascular and avascular retina (V-Av junction) are noted. Posterior to the V-Av junction, hypoperfused retinal areas with or without hyperfluorescent "cotton-wool-like" or "popcorn-like" lesions due to dye leakage are documented by FA. Focal dilatation of capillaries, capillary tufts formations, and rosary-bead-like hyperfluorescent lesions inside the vessels were seen; sometimes all 3 are noted. Various macular abnormalities are noted including absence of foveal avascular area and significant exudative component. Fluorescein angiography was useful to distinguish the deceptively featureless zone 1 junction between the vascularized and nonvascularized retina. Further studies are needed to understand the role of vascular abnormalities observed in zone 1 vascularized retina.

Astigmatism in the Early Treatment for Retinopathy of Prematurity Study: Findings to 3 Years of Age

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. Randomized, controlled clinical trial. 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. 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. 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 ). 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. 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. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Visual Acuity at 10 Years in Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study Eyes

To describe recognition (letter) acuity at age 10 years in eyes with and without retinal residua of retinopathy of prematurity (ROP). 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. 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. 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.

The incidence of visually impaired children with retinopathy of prematurity and their concomitant disabilities.

To determine, in relation to two previous studies, the incidence of visual impairment (VI) caused by retinopathy of prematurity (ROP) in children born in the Netherlands between 1994 and 2000 and their associated nonvisual disabilities. From all institutes, schools, and ambulatory services for the partially sighted and blind, data on ROP infants born between 1994 and 2000 were retrieved. Apart from neonatal and ophthalmologic data, other data were gathered concerning the following concomitant disabilities: behavioral abnormalities, epilepsy, hearing deficit, developmental delay, and distinct neurological handicaps. Birth rate data were obtained from the Central Bureau of Statistics for the Netherlands. Data on 51 of 54 infants (94.4%) were studied. There was a statistically insignificant decrease in the incidence of visually impaired children caused by ROP in the period between 1994 and 2000 compared with the period between 1986 and 1994. Neonatal and ophthalmologic data of the infants were comparable for the study period and the previous period. The incidence of behavioral abnormalities in infants with ROP-related sequelae increased significantly in the study period compared with the previous one (46.9% v 21.8%, P <.05. The percentage of infants who received treatment for severe ROP did not change significantly (56.9% v 43.9% in the previous period). This study shows a statistically insignificant decrease in the number of infants with visual impairment caused by ROP in the Netherlands in the period between 1994 and 2000 as well as a significant increase in the incidence of behavioral abnormalities in these children. Still, 43.1% of the infants did not receive acute-phase ROP treatment.

The incidence of visually impaired children with retinopathy of prematurity and their concomitant disabilities

Purpose To determine, in relation to two previous studies, the incidence of visual impairment (VI) caused by retinopathy of prematurity (ROP) in children born in the Netherlands between 1994 and 2000 and their associated nonvisual disabilities. Methods From all institutes, schools, and ambulatory services for the partially sighted and blind, data on ROP infants born between 1994 and 2000 were retrieved. Apart from neonatal and ophthalmologic data, other data were gathered concerning the following concomitant disabilities: behavioral abnormalities, epilepsy, hearing deficit, developmental delay, and distinct neurological handicaps. Birth rate data were obtained from the Central Bureau of Statistics for the Netherlands. Results Data on 51 of 54 infants (94.4%) were studied. There was a statistically insignificant decrease in the incidence of visually impaired children caused by ROP in the period between 1994 and 2000 compared with the period between 1986 and 1994. Neonatal and ophthalmologic data of the infants were comparable for the study period and the previous period. The incidence of behavioral abnormalities in infants with ROP-related sequelae increased significantly in the study period compared with the previous one (46.9% v 21.8%, P < .05. The percentage of infants who received treatment for severe ROP did not change significantly (56.9% v 43.9% in the previous period). Conclusions This study shows a statistically insignificant decrease in the number of infants with visual impairment caused by ROP in the Netherlands in the period between 1994 and 2000 as well as a significant increase in the incidence of behavioral abnormalities in these children. Still, 43.1% of the infants did not receive acute-phase ROP treatment.

The rod photoreceptors in retinopathy of prematurity: an electroretinographic study.

To test the hypothesis that the more severe the acute phase retinopathy of prematurity (ROP) was in the preterm weeks, the more severely compromised is rod photoreceptor function after the ROP has resolved. Electroretinographic (ERG) responses were recorded from 25 dark-adapted children (ages 2.5 months' postterm to 14 years) categorized by maximum, acute phase ROP (None to Very Severe). From the ERG a-wave "S," a sensitivity parameter for the rod photoreceptor response, and R(mp3), the saturated amplitude of the rod photoreceptor response were calculated using a model of the activation of rod phototransduction. The patients' results were compared with those of healthy controls (n = 71). Among those in the None, Mild, Moderate, and Severe categories, both S and R(mp3) varied significantly with severity of acute phase ROP. In the Very Severe category, ERG responses were too attenuated to calculate S and R(mp3). The rod photoreceptors must be involved in ROP. The more severe the acute phase ROP, the more severe is the compromise of the processes involved in the activation of phototransduction in the rods.

Prevalence of myopia between 3 months and 5 [formula omitted] 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 1 2 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 mild-to-severe ROP. None of the eyes underwent cryotherapy. Intervention Refractive error was measured at 3 months, 1 year, and 5 1 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 1 2 , and 4 1 2 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 2 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 2 years of age. Conclusions The distribution of refractive errors in preterm infants from age 3 months to 5 1 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.

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

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. 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. 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. 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.