Extending Hui-Walter framework to correlated outcomes with application to diagnosis tests of an eye disease among premature infants.

Diagnostic accuracy, a measure of diagnostic tests for correctly identifying patients with or without a target disease, plays an important role in evidence-based medicine. Diagnostic accuracy of a new test ideally should be evaluated by comparing to a gold standard; however, in many medical applications it may be invasive, costly, or even unethical to obtain a gold standard for particular diseases. When the accuracy of a new candidate test under evaluation is assessed by comparison to an imperfect reference test, bias is expected to occur and result in either overestimates or underestimates of its true accuracy. In addition, diagnostic test studies often involve repeated measurements of the same patient, such as the paired eyes or multiple teeth, and generally lead to correlated and clustered data. Using the conventional statistical methods to estimate diagnostic accuracy can be biased by ignoring the within-cluster correlations. Despite numerous statistical approaches have been proposed to tackle this problem, the methodology to deal with correlated and clustered data in the absence of a gold standard is limited. In this article, we propose a method based on the composite likelihood function to derive simple and intuitive closed-form solutions for estimates of diagnostic accuracy, in terms of sensitivity and specificity. Through simulation studies, we illustrate the relative advantages of the proposed method over the existing methods that simply treat an imperfect reference test as a gold standard in correlated and clustered data. Compared with the existing methods, the proposed method can reduce not only substantial bias, but also the computational burden. Moreover, to demonstrate the utility of this approach, we apply the proposed method to the study of National-Eye-Institute-funded Telemedicine Approaches to Evaluating of Acute-Phase Retinopathy of Prematurity (e-ROP), for estimating accuracies of both the ophthalmologist examination and the image evaluation.

International Classification of Retinopathy of Prematurity, Third Edition.

PURPOSE: The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system. DESIGN: Review of evidence-based literature, along with expert consensus opinion. PARTICIPANTS: International ROP expert committee assembled in March 2019 representing 17 countries and comprising 14 pediatric ophthalmologists and 20 retinal specialists, as well as 12 women and 22 men. METHODS: The committee was initially divided into 3 subcommittees-acute phase, regression or reactivation, and imaging-each of which used iterative videoconferences and an online message board to identify key challenges and approaches. Subsequently, the entire committee used iterative videoconferences, 2 in-person multiday meetings, and an online message board to develop consensus on classification. MAIN OUTCOME MEASURES: Consensus statement. RESULTS: The ICROP3 retains current definitions such as zone (location of disease), stage (appearance of disease at the avascular-vascular junction), and circumferential extent of disease. Major updates in the ICROP3 include refined classification metrics (e.g., posterior zone II, notch, subcategorization of stage 5, and recognition that a continuous spectrum of vascular abnormality exists from normal to plus disease). Updates also include the definition of aggressive ROP to replace aggressive-posterior ROP because of increasing recognition that aggressive disease may occur in larger preterm infants and beyond the posterior retina, particularly in regions of the world with limited resources. ROP regression and reactivation are described in detail, with additional description of long-term sequelae. CONCLUSIONS: These principles may improve the quality and standardization of ROP care worldwide and may provide a foundation to improve research and clinical care.

Plus Disease in Telemedicine Approaches to Evaluating Acute-Phase ROP (e-ROP) Study: Characteristics, Predictors, and Accuracy of Image Grading.

PURPOSE: To describe characteristics and predictors of plus disease, and the accuracy of image grading for plus disease in the e-ROP Study. DESIGN: Secondary analyses of data from 13 North American centers. PARTICIPANTS: Premature infants with birth weight (BW) <1251 g. METHODS: Infants underwent regularly scheduled diagnostic examinations by ophthalmologists and digital imaging by trained imagers using a wide-field digital camera. Two masked nonphysician trained readers independently evaluated images for posterior pole abnormality (normal, preplus, plus), with discrepancies adjudicated by a reading supervisor. Logistic regression models were used to determine predictors for plus disease. The sensitivity and specificity of image grading for plus disease were calculated using the clinical examination finding as reference standard. MAIN OUTCOME MEASURES: Odds ratios (OR), sensitivity, and specificity. RESULTS: Among 1239 infants (mean BW 864 g, mean gestational age [GA] 27 weeks), 129 infants (10%) (226 eyes, 75% bilateral) had plus disease from clinical examination. When plus disease was first diagnosed in clinical examination at median postmenstrual age (PMA) of 36 weeks (range: 32-43 weeks), 94% to 96% of plus occurred in the superior or inferior temporal quadrant. Significant predictors for plus disease from multivariate analysis were as follows: GA (OR = 3.2 for ≤24 vs. ≥28 weeks, P = 0.004), race (OR = 2.4 for white vs. black, P = 0.01), respiratory support (OR = 7.1, P = 0.006), weight gain (OR = 1.5 for weight gain ≤12 vs. >18 g/day, P = 0.03), and image findings at the first image session, including presence of preplus/plus disease (OR = 2.7, P = 0.003), ROP stage (OR = 4.2 for stage 3 ROP vs. no ROP, P = 0.006), and blot hemorrhage (OR = 3.1, P = 0.003). These features predicted plus disease with an area under the receiver operating characteristic curve of 0.89 (95% confidence interval [CI]: 0.85-0.92). The image grading using preplus as the cut point had sensitivity of 94% (95% CI: 90%-97%) and specificity of 81% (95% CI: 79%-82%) for detecting plus disease in an eye. CONCLUSIONS: Among e-ROP infants, plus disease developed in 10% of infants at a median PMA of 37 weeks, with the majority being bilateral and mostly in the superior or inferior temporal quadrant. GA, race, respiratory support, postnatal weight gain, image findings of the posterior pole, and ROP predict development of plus disease. Nonphysician image grading can detect almost all plus disease with good specificity.

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

PURPOSE: 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). DESIGN: Single, randomized, controlled trial. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: Fluorescein angiograms were examined by 2 experts to document retinal and choroidal findings. RESULTS: 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. CONCLUSIONS: Fluorescein angiography has shown potentially serious and long-term ocular effects that are present more commonly after treatment with bevacizumab for acute-phase ROP than after laser.

Intraocular Hemorrhages and Retinopathy of Prematurity in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.

PURPOSE: To describe the clinical characteristics of intraocular hemorrhages (IOHs) in infants in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study and to evaluate their potential use for prediction of disease severity. DESIGN: Secondary data analysis from a prospective study. PARTICIPANTS: Preterm infants with birth weight (BW) ≤1250 g. METHODS: Infants underwent serial digital retinal imaging in both eyes starting at 32 weeks' postmenstrual age. Nonphysician trained readers (TRs) evaluated all image sets from eyes that ever had IOHs documented on image evaluation or eye examination for the presence, location, type, area, and relation of the IOH to the junction between vascularized and avascular retina. Associations of IOH with demographic and neonatal factors, and with the presence and severity of retinopathy of prematurity (ROP) were investigated by univariate and multivariate analyses. Sensitivity and specificity of the telemedicine system for detecting referral-warranted ROP (RW-ROP) were calculated with and without incorporating hemorrhage into the standardized grading protocol. MAIN OUTCOME MEASURES: Retinal and vitreous hemorrhage. RESULTS: Among 1239 infants (mean [standard deviation] BW = 864 [212] g; gestational age [GA] = 27 [2.2] weeks) who underwent an average of 3.2 imaging sessions, 22% had an IOH in an eye on at least 1 of the e-ROP visits. Classification of IOH was preretinal (57%), blot (57%), dot (38%), flame-shaped (16%), and vitreous (8%); most IOHs were unilateral (70%). The IOH resolved in 35% of eyes by the next imaging session and in the majority (76%) of cases by 8 weeks after initial detection. Presence of IOH was inversely associated with BW and GA and significantly associated (P < 0.0001) with the presence and severity of ROP (BW and GA adjusted odds ratios [ORs] of 2.46 for any ROP, 2.88 for stage 3, and 3.19 for RW-ROP). Incorporating IOH into the grading protocol minimally altered the sensitivity of the system (94% vs. 95%). CONCLUSIONS: Approximately 1 in 5 preterm infants examined had IOHs, generally unilateral. The presence of hemorrhage was directly correlated with both presence and severity of ROP and inversely correlated with BW and GA, although including hemorrhage in the grading algorithm only minimally improved the sensitivity of the telemedicine system to detect RW-ROP.

POSTNATAL SERUM INSULIN-LIKE GROWTH FACTOR I AND RETINOPATHY OF PREMATURITY.

PURPOSE: Low serum IGF-1 has been associated with development of severe ROP, but no U.S. studies have been reported. We sought to determine the relationship between postnatal serum IGF-1 levels and severe ROP in a racially diverse U.S. cohort. METHODS: Prospective cohort study of 74 infants with birth weight <1,251 g and a known ROP outcome at 3 Philadelphia hospitals. Weekly postnatal filter paper blood spot IGF-1 assays were measured through 42 weeks postmenstrual age. RESULTS: The cohort included 20 white, 45 black, 2 Asian, and 9 other infants; median gestational age was 27.6 weeks (range 23-33 weeks), and median birth weight was 975 g (range 490-1,250 g). During postmenstrual age Weeks 28 to 33, mean IGF-1 was 20.0 ng/mL (standard error 0.52) for no ROP (n = 46), 18.0 (0.49) for Stage 1 or 2 (n = 23), and 17.0 (0.70) for Stage 3 (n = 5, 2 lasered) (P = 0.003). Adjustment for birth weight and gestational age showed similar results. CONCLUSION: The presence and timing of an association between low postnatal serum IGF and ROP in a racially diverse U.S. sample were found to be consistent with those of European cohorts. This association provides the pathophysiological basis for growth-based predictive models, which could improve efficiency of ROP screening.

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

PURPOSE: 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. DESIGN: Second analyses of an observational cohort study. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: TR-ROP. RESULTS: 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. CONCLUSIONS: 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.

Changes in Course of Retinopathy of Prematurity from 1986 to 2013: Comparison of Three Studies in the United States.

PURPOSE: To compare infant and retinopathy of prematurity (ROP) characteristics from 3 clinical studies conducted over a 27-year period in the United States. DESIGN: Secondary analysis of results of 3 clinical studies. PARTICIPANTS: Infants with birth weight (BW) <1251 g. METHODS: Analysis of data from the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) and Early Treatment for Retinopathy of Prematurity (ETROP) trials and the primary data from the Telemedicine Approaches for the Evaluation of Acute-Phase Retinopathy of Prematurity (e-ROP) study. MAIN OUTCOME MEASURES: Infant characteristics and onset, severity, and time course of ROP. RESULTS: Across the 3 studies, mean (standard deviation) BW and mean gestational age (GA) decreased over time from CRYO-ROP (954 g [185 g], 27.9 weeks [2.2 weeks]) to ETROP (907 g [205 g], 27.4 weeks [2.2 weeks]) to e-ROP (864 g [212 g], 27.0 weeks [2.2 weeks]), with an increase in the percentage of infants enrolled weighing <750 g (15.8% CRYO, 24.9% ETROP, 33.4% e-ROP; P<0.0001). The percentage of infants who developed ROP varied only minimally (65.8% CRYO, 68.0% ETROP, 63.7% e-ROP; P = 0.003). Moderately severe ROP (defined as prethreshold or referral warranted) varied (17.8% CRYO, 12.3% ETROP, 19.4% e-ROP; P<0.0001), whereas the time of onset of any ROP did not vary (34.3 weeks CRYO, 34.1 weeks ETROP, 34.8 weeks e-ROP). CONCLUSIONS: The BW and GA of infants enrolled in ROP studies in the United States have decreased over the past 27 years, whereas ROP prevalence and onset of disease are stable.

Retinopathy of prematurity risk prediction for infants with birth weight less than 1251 grams.

OBJECTIVE: To predict retinopathy of prematurity (ROP) exam findings among infants with birth weight <1251 g from 32-40 weeks postmenstrual age (PMA). STUDY DESIGN: Secondary analysis of 3714 eye exams from 1239 infants. RESULTS: The likelihood of developing type 1 ROP by 40 weeks PMA varied by gestational age (GA) (P < .001), from 33% for ≤25 weeks, 10% for 26 or 27 weeks, 4% for 28 or 29 weeks, and none for ≥30 weeks. By 40 weeks PMA, 51% with GA ≤27 weeks still needed subsequent exams. Previous exam findings, GA, and PMA were predictive of the development of type 1 ROP (area under the curve, 0.78) or mature retina (area under the curve, 0.85). CONCLUSIONS: This analysis provides the opportunity for development of an ROP approach to estimate resource needs in the neonatal intensive care unit and to facilitate communication with families when planning discharge or transfer.

Vision screening for children 36 to <72 months: recommended practices.

PURPOSE: This article provides recommendations for screening children aged 36 to younger than 72 months for eye and visual system disorders. The recommendations were developed by the National Expert Panel to the National Center for Children's Vision and Eye Health, sponsored by Prevent Blindness, and funded by the Maternal and Child Health Bureau of the Health Resources and Services Administration, United States Department of Health and Human Services. The recommendations describe both best and acceptable practice standards. Targeted vision disorders for screening are primarily amblyopia, strabismus, significant refractive error, and associated risk factors. The recommended screening tests are intended for use by lay screeners, nurses, and other personnel who screen children in educational, community, public health, or primary health care settings. Characteristics of children who should be examined by an optometrist or ophthalmologist rather than undergo vision screening are also described. RESULTS: There are two current best practice vision screening methods for children aged 36 to younger than 72 months: (1) monocular visual acuity testing using single HOTV letters or LEA Symbols surrounded by crowding bars at a 5-ft (1.5 m) test distance, with the child responding by either matching or naming, or (2) instrument-based testing using the Retinomax autorefractor or the SureSight Vision Screener with the Vision in Preschoolers Study data software installed (version 2.24 or 2.25 set to minus cylinder form). Using the Plusoptix Photoscreener is acceptable practice, as is adding stereoacuity testing using the PASS (Preschool Assessment of Stereopsis with a Smile) stereotest as a supplemental procedure to visual acuity testing or autorefraction. CONCLUSIONS: The National Expert Panel recommends that children aged 36 to younger than 72 months be screened annually (best practice) or at least once (accepted minimum standard) using one of the best practice approaches. Technological updates will be maintained at http://nationalcenter.preventblindness.org.

Prevalence of vision disorders by racial and ethnic group among children participating in head start.

OBJECTIVE: To compare the prevalence of amblyopia, strabismus, and significant refractive error among African-American, American Indian, Asian, Hispanic, and non-Hispanic white preschoolers in the Vision In Preschoolers study. DESIGN: Multicenter, cross-sectional study. PARTICIPANTS: Three- to 5-year old preschoolers (n=4040) in Head Start from 5 geographically disparate areas of the United States. METHODS: All children who failed the mandatory Head Start screening and a sample of those who passed were enrolled. Study-certified pediatric optometrists and ophthalmologists performed comprehensive eye examinations including monocular distance visual acuity (VA), cover testing, and cycloplegic retinoscopy. Examination results were used to classify vision disorders, including amblyopia, strabismus, significant refractive errors, and unexplained reduced VA. Sampling weights were used to calculate prevalence rates, confidence intervals, and statistical tests for differences. MAIN OUTCOME MEASURES: Prevalence rates in each racial/ethnic group. RESULTS: Overall, 86.5% of children invited to participate were examined, including 2072 African-American, 343 American Indian (323 from Oklahoma), 145 Asian, 796 Hispanic, and 481 non-Hispanic white children. The prevalence of any vision disorder was 21.4% and was similar across groups (P=0.40), ranging from 17.9% (American Indian) to 23.3% (Hispanic). Prevalence of amblyopia was similar among all groups (P=0.07), ranging from 3.0% (Asian) to 5.4% (non-Hispanic white). Prevalence of strabismus also was similar (P=0.12), ranging from 1.0% (Asian) to 4.6% (non-Hispanic white). Prevalence of hyperopia >3.25 diopter (D) varied (P=0.007), with the lowest rate in Asians (5.5%) and highest in non-Hispanic whites (11.9%). Prevalence of anisometropia varied (P=0.009), with the lowest rate in Asians (2.7%) and highest in Hispanics (7.1%). Myopia >2.00 D was relatively uncommon (<2.0%) in all groups with the lowest rate in American Indians (0.2%) and highest rate in Asians (1.9%). Prevalence of astigmatism >1.50 D varied (P=0.01), with the lowest rate among American Indians (4.3%) and highest among Hispanics (11.1%). CONCLUSIONS: Among Head Start preschool children, the prevalence of amblyopia and strabismus was similar among 5 racial/ethnic groups. Prevalence of significant refractive errors, specifically hyperopia, astigmatism, and anisometropia, varied by group, with the highest rate of hyperopia in non-Hispanic whites, and the highest rates of astigmatism and anisometropia in Hispanics.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

PURPOSE: To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). DESIGN: Single randomized controlled trial. PARTICIPANTS: All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. METHODS: Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. MAIN OUTCOME MEASURES: Presence of retinal and choroidal abnormalities on FA at 9 months. RESULTS: Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. CONCLUSIONS: This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied.

Risk factors for amblyopia in the vision in preschoolers study.

OBJECTIVE: To evaluate risk factors for unilateral amblyopia and for bilateral amblyopia in the Vision in Preschoolers (VIP) study. DESIGN: Multicenter, cross-sectional study. PARTICIPANTS: Three- to 5-year-old Head Start preschoolers from 5 clinical centers, overrepresenting children with vision disorders. METHODS: All children underwent comprehensive eye examinations, including threshold visual acuity (VA), cover testing, and cycloplegic retinoscopy, performed by VIP-certified optometrists and ophthalmologists who were experienced in providing care to children. Monocular threshold VA was tested using a single-surround HOTV letter protocol without correction, and retested with full cycloplegic correction when retest criteria were met. Unilateral amblyopia was defined as an interocular difference in best-corrected VA of 2 lines or more. Bilateral amblyopia was defined as best-corrected VA in each eye worse than 20/50 for 3-year-olds and worse than 20/40 for 4- to 5-year-olds. MAIN OUTCOME MEASURES: Risk of amblyopia was summarized by the odds ratios and their 95% confidence intervals estimated from logistic regression models. RESULTS: In this enriched sample of Head Start children (n = 3869), 296 children (7.7%) had unilateral amblyopia, and 144 children (3.7%) had bilateral amblyopia. Presence of strabismus (P<0.0001) and greater magnitude of significant refractive errors (myopia, hyperopia, astigmatism, and anisometropia; P<0.00001 for each) were associated independently with an increased risk of unilateral amblyopia. Presence of strabismus, hyperopia of 2.0 diopters (D) or more, astigmatism of 1.0 D or more, or anisometropia of 0.5 D or more were present in 91% of children with unilateral amblyopia. Greater magnitude of astigmatism (P<0.0001) and bilateral hyperopia (P<0.0001) were associated independently with increased risk of bilateral amblyopia. Bilateral hyperopia of 3.0 D or more or astigmatism of 1.0 D or more were present in 76% of children with bilateral amblyopia. CONCLUSIONS: Strabismus and significant refractive errors were risk factors for unilateral amblyopia. Bilateral astigmatism and bilateral hyperopia were risk factors for bilateral amblyopia. Despite differences in selection of the study population, these results validated the findings from the Multi-Ethnic Pediatric Eye Disease Study and Baltimore Pediatric Eye Disease Study.

Risk factors for astigmatism in the Vision in Preschoolers Study.

PURPOSE: To determine demographic and refractive risk factors for astigmatism in the Vision in Preschoolers Study. METHODS: Three- to 5-year-old Head Start preschoolers (N = 4040) from five clinical centers underwent comprehensive eye examinations by study-certified optometrists and ophthalmologists, including monocular visual acuity testing, cover testing, and cycloplegic retinoscopy. Astigmatism was defined as the presence of greater than or equal to +1.5 diopters (D) cylinder in either eye, measured with cycloplegic refraction. The associations of risk factors with astigmatism were evaluated using the odds ratio (OR) and its 95% confidence interval (CI) from logistic regression models. RESULTS: Among 4040 Vision in Preschoolers Study participants overrepresenting children with vision disorders, 687 (17%) had astigmatism, and most (83.8%) had with-the-rule astigmatism. In multivariate analyses, African American (OR, 1.65; 95% CI, 1.22 to 2.24), Hispanic (OR, 2.25; 95% CI, 1.62 to 3.12), and Asian (OR, 1.76; 95% CI, 1.06 to 2.93) children were more likely to have astigmatism than non-Hispanic white children, whereas American Indian children were less likely to have astigmatism than Hispanic, African American, and Asian children (p < 0.0001). Refractive error was associated with astigmatism in a nonlinear manner, with an OR of 4.50 (95% CI, 3.00 to 6.76) for myopia (≤-1.0 D in spherical equivalent) and 1.55 (95% CI, 1.29 to 1.86) for hyperopia (≥+2.0 D) when compared with children without refractive error (>-1.0 D, <+2.0 D). There was a trend of an increasing percentage of astigmatism among older children (linear trend p = 0.06). The analysis for risk factors of with-the-rule astigmatism provided similar results. CONCLUSIONS: Among Head Start preschoolers, Hispanic, African American, and Asian race as well as myopic and hyperopic refractive error were associated with an increased risk of astigmatism, consistent with findings from the population-based Multi-ethnic Pediatric Eye Disease Study and the Baltimore Pediatric Eye Disease Study. American Indian children had lower risk of astigmatism.

Stereoacuity of preschool children with and without vision disorders.

PURPOSE: To evaluate associations between stereoacuity and presence, type, and severity of vision disorders in Head Start preschool children and determine testability and levels of stereoacuity by age in children without vision disorders. METHODS: Stereoacuity of children aged 3 to 5 years (n = 2898) participating in the Vision in Preschoolers (VIP) Study was evaluated using the Stereo Smile II test during a comprehensive vision examination. This test uses a two-alternative forced-choice paradigm with four stereoacuity levels (480 to 60 seconds of arc). Children were classified by the presence (n = 871) or absence (n = 2027) of VIP Study-targeted vision disorders (amblyopia, strabismus, significant refractive error, or unexplained reduced visual acuity), including type and severity. Median stereoacuity between groups and among severity levels of vision disorders was compared using Wilcoxon rank sum and Kruskal-Wallis tests. Testability and stereoacuity levels were determined for children without VIP Study-targeted disorders overall and by age. RESULTS: Children with VIP Study-targeted vision disorders had significantly worse median stereoacuity than that of children without vision disorders (120 vs. 60 seconds of arc, p < 0.001). Children with the most severe vision disorders had worse stereoacuity than that of children with milder disorders (median 480 vs. 120 seconds of arc, p < 0.001). Among children without vision disorders, testability was 99.6% overall, increasing with age to 100% for 5-year-olds (p = 0.002). Most of the children without vision disorders (88%) had stereoacuity at the two best disparities (60 or 120 seconds of arc); the percentage increasing with age (82% for 3-, 89% for 4-, and 92% for 5-year-olds; p < 0.001). CONCLUSIONS: The presence of any VIP Study-targeted vision disorder was associated with significantly worse stereoacuity in preschool children. Severe vision disorders were more likely associated with poorer stereopsis than milder or no vision disorders. Testability was excellent at all ages. These results support the validity of the Stereo Smile II for assessing random-dot stereoacuity in preschool children.

Intertester agreement in refractive error measurements.

PURPOSE: To determine the intertester agreement of refractive error measurements between lay and nurse screeners using the Retinomax Autorefractor and the SureSight Vision Screener. METHODS: Trained lay and nurse screeners measured refractive error in 1452 preschoolers (3 to 5 years old) using the Retinomax and the SureSight in a random order for screeners and instruments. Intertester agreement between lay and nurse screeners was assessed for sphere, cylinder, and spherical equivalent (SE) using the mean difference and the 95% limits of agreement. The mean intertester difference (lay minus nurse) was compared between groups defined based on the child's age, cycloplegic refractive error, and the reading's confidence number using analysis of variance. The limits of agreement were compared between groups using the Brown-Forsythe test. Intereye correlation was accounted for in all analyses. RESULTS: The mean intertester differences (95% limits of agreement) were -0.04 (-1.63, 1.54) diopter (D) sphere, 0.00 (-0.52, 0.51) D cylinder, and -0.04 (1.65, 1.56) D SE for the Retinomax and 0.05 (-1.48, 1.58) D sphere, 0.01 (-0.58, 0.60) D cylinder, and 0.06 (-1.45, 1.57) D SE for the SureSight. For either instrument, the mean intertester differences in sphere and SE did not differ by the child's age, cycloplegic refractive error, or the reading's confidence number. However, for both instruments, the limits of agreement were wider when eyes had significant refractive error or the reading's confidence number was below the manufacturer's recommended value. CONCLUSIONS: Among Head Start preschool children, trained lay and nurse screeners agree well in measuring refractive error using the Retinomax or the SureSight. Both instruments had similar intertester agreement in refractive error measurements independent of the child's age. Significant refractive error and a reading with low confidence number were associated with worse intertester agreement.

A practical method for reducing blindness due to retinopathy of prematurity in a developing country.

BACKGROUND: Retinopathy of prematurity (ROP) is a common cause of blindness in countries with rapidly developing systems of neonatal care. At present, detection and treatment programs are not widely available in many regions of middle- and low-income countries. SUBJECT POPULATION: Case series. METHODS: An analysis was undertaken to determine in which neonatal intensive care units (NICUs) in Peru babies blind from ROP had been cared for. Demographic and hospital information was gathered for children blind from ROP presenting before the age of 5 years. NICUs with a high likelihood of having ROP-blind children were offered training and equipment designed to improve neonatal care. RESULTS: Ninety-one children with ROP blindness were identified. Twenty-six percent were <1000 g at birth, and 17% had birth weights of >1500 g. Forty-six percent came from NICUs in Lima. Interventional workshops emphasizing neonatal care and oxygen administration have been conducted thus far in six of the 13 largest NICUs in Lima. The percentage of at-risk babies being examined has generally increased, whereas the percentage of babies requiring treatment decreased in three NICUs and increased slightly in two, and no preworkshop data were available in one. CONCLUSION: This report represents the initial results of an evidence-based approach to decreasing blindness from ROP in Peru. Workshops emphasizing neonatal care, especially targeting oxygen administration, provide methods for improving care of at-risk babies.