Referral-warranted Retinopathy Of Prematurity Research Articles

Multivariate Models to Diagnose Early Referral-Warranted Retinopathy of Prematurity With Handheld Optical Coherence Tomography.

The purpose of this study was to create multivariate models predicting early referral-warranted retinopathy of prematurity (ROP) using non-contact handheld spectral-domain optical coherence tomography (OCT) and demographic data. Between July 2015 and February 2018, infants ≤1500 grams birth weight or ≤30 weeks gestational age from 2 academic neonatal intensive care units were eligible for this study. Infants were excluded if they were too unstable to participate in ophthalmologic examination (2), had inadequate image quality (20), or received prior ROP treatment (2). Multivariate models were created using demographic variables and imaging findings to identify early referral-warranted ROP (referral-warranted ROP and/or pre-plus disease) by routine indirect ophthalmoscopy. A total of 167 imaging sessions of 71 infants (45% male infants, gestational age 28.2+/-2.8 weeks, and birth weight 995.6+/-292.0 grams) were included. Twelve of 71 infants (17%) developed early referral-warranted ROP. The area under the receiver operating characteristic curve (AUC) was 0.94 for the generalized linear mixed model (sensitivity = 95.5% and specificity = 80.7%) and 0.83 for the machine learning model (sensitivity = 91.7% and specificity = 77.8%). The strongest variables in both models were birth weight, image-based Vitreous Opacity Ratio (an estimate of opacity density), vessel elevation, and hyporeflective vessels. A model using only birth weight and gestational age yielded an AUC of 0.68 (sensitivity = 77.3% and specificity = 63.4%), and a model using only imaging biomarkers yielded 0.88 (sensitivity = 81.8% and specificity = 84.8%). A generalized linear mixed model containing handheld OCT biomarkers can identify early referral-warranted ROP. Machine learning produced a less optimal model. With further validation, this work may lead to a better-tolerated ROP screening tool.

Machine learning and logistic mixed model approach to create handheld optical coherence tomography models predicting referral-warranted retinopathy of prematurity

Machine learning and logistic mixed model approach to create handheld optical coherence tomography models predicting referral-warranted retinopathy of prematurity

Automated Explainable Multidimensional Deep Learning Platform of Retinal Images for Retinopathy of Prematurity Screening

A retinopathy of prematurity (ROP) diagnosis currently relies on indirect ophthalmoscopy assessed by experienced ophthalmologists. A deep learning algorithm based on retinal images may facilitate early detection and timely treatment of ROP to improve visual outcomes. To develop a retinal image-based, multidimensional, automated, deep learning platform for ROP screening and validate its performance accuracy. A total of 14 108 eyes of 8652 preterm infants who received ROP screening from 4 centers from November 4, 2010, to November 14, 2019, were included, and a total of 52 249 retinal images were randomly split into training, validation, and test sets. Four main dimensional independent classifiers were developed, including image quality, any stage of ROP, intraocular hemorrhage, and preplus/plus disease. Referral-warranted ROP was automatically generated by integrating the results of 4 classifiers at the image, eye, and patient levels. DeepSHAP, a method based on DeepLIFT and Shapley values (solution concepts in cooperative game theory), was adopted as the heat map technology to explain the predictions. The performance of the platform was further validated as compared with that of the experienced ROP experts. Data were analyzed from February 12, 2020, to June 24, 2020. A deep learning algorithm. The performance of each classifier included true negative, false positive, false negative, true positive, F1 score, sensitivity, specificity, receiver operating characteristic, area under curve (AUC), and Cohen unweighted κ. A total of 14 108 eyes of 8652 preterm infants (mean [SD] gestational age, 32.9 [3.1] weeks; 4818 boys [60.4%] of 7973 with known sex) received ROP screening. The performance of all classifiers achieved an F1 score of 0.718 to 0.981, a sensitivity of 0.918 to 0.982, a specificity of 0.949 to 0.992, and an AUC of 0.983 to 0.998, whereas that of the referral system achieved an F1 score of 0.898 to 0.956, a sensitivity of 0.981 to 0.986, a specificity of 0.939 to 0.974, and an AUC of 0.9901 to 0.9956. Fine-grained and class-discriminative heat maps were generated by DeepSHAP in real time. The platform achieved a Cohen unweighted κ of 0.86 to 0.98 compared with a Cohen κ of 0.93 to 0.98 by the ROP experts. In this diagnostic study, an automated ROP screening platform was able to identify and classify multidimensional pathologic lesions in the retinal images. This platform may be able to assist routine ROP screening in general and children hospitals.

Calculating Sensitivity, Specificity, and Predictive Values for Correlated Eye Data.

PurposeTo describe and demonstrate appropriate statistical approaches for estimating sensitivity, specificity, predictive values and their 95% confidence intervals (95% CI) for correlated eye data.MethodsWe described generalized estimating equations (GEE) and cluster bootstrap to account for inter-eye correlation and applied them for analyzing the data from a clinical study of telemedicine for the detection of retinopathy of prematurity (ROP).ResultsAmong 100 infants (200 eyes) selected for analysis, 20 infants had referral-warranted ROP (RW-ROP) in both eyes and 9 infants with RW-ROP only in one eye based on clinical eye examination. In the per-eye analysis that included both eyes of an infant, the image evaluation for RW-ROP had sensitivity of 83.7% and specificity of 86.8%. The 95% CI's from the naïve approach that ignored the inter-eye correlation were narrower than those of the GEE approach and cluster bootstrap for both sensitivity (width of 95% CI: 22.4% vs. 23.2% vs. 23.9%) and specificity (11.4% vs. 12.5% vs. 11.6%). The 95% CIs for sensitivity and specificity calculated from left eyes and right eyes separately were wider (35.2% and 30.8% respectively for sensitivity, 25.4% and 17.3% respectively for specificity). ConclusionsWhen an ocular test is performed in both eyes of some or all of the study subjects, the statistical analyses are best performed at the eye-level and account for the inter-eye correlation by using either the GEE or cluster bootstrap. Ignoring the inter-eye correlation results in 95% CIs that are inappropriately narrow and analyzing data from two eyes separately are not efficient.

Evaluation of a Remote Telemedicine Screening System for Severe Retinopathy of Prematurity.

To evaluate the validity of remote telemedicine screening for retinopathy of prematurity (ROP) in a population of at-risk preterm infants in Iowa and South Dakota. The medical records for all preterm infants screened for ROP at neonatal intensive care units (NICUs) in Sioux City, Iowa, and Sioux Falls, South Dakota, from September 1, 2017, to July 31, 2018, were retrospectively reviewed. The RetCam Shuttle (Natus Medical Inc., Pleasanton, CA) was used to capture retinal images, which were posted on a secure server for evaluation by a pediatric ophthalmologist. Infants with suspected ROP approaching the criteria for treatment with anti-vascular endothelial growth factor (VEGF) medications were transferred to the Children's Hospital and Medical Center NICU in Omaha, Nebraska, where a comprehensive examination was performed and treatment was administered when indicated. The remaining infants received an outpatient comprehensive examination by one of two pediatric ophthalmologists within 2 weeks of discharge. A total of 124 telemedicine examinations were performed on 35 infants during the study period. Remote telemedicine screening for referral-warranted ROP using the RetCam Shuttle had a sensitivity of 100%, specificity of 97%, positive predictive value of 66.7%, and negative predictive value of 100%. Of the three infants transferred for referral-warranted ROP, two required treatment with anti-VEGF medications. Good outcomes were noted in all cases, and no patients progressed beyond stage 3 ROP. Telemedicine screening reliably detected referral-warranted ROP in at-risk premature infants at two remote sites, with no poor outcomes during the 11-month period. These results demonstrate the validity and utility of remote telemedicine screening for ROP. [J Pediatr Ophthalmol Strabismus. 2019;56(3):157-161.].

The Accuracy of Digital Imaging in Diagnosis of Retinopathy of Prematurity in Iran: A Pilot Study.

Purpose:To evaluate sensitivity and specificity of digital retinal image reading in the diagnosis of referral-warranted retinopathy of prematurity (ROP).Methods:Infants referred to the ROP clinic underwent fundus examination through indirect ophthalmoscopy. Fundus photographs were acquired using RetCam (shuttle 2; Clarity medical systems, Pleasanton, CA, USA). Four retinal specialists who were blind to patients’ information reviewed the RetCam fundus photographs. By comparing the results of photographs’ readings with that of indirect ophthalmoscopy as the gold standard, the sensitivity and specificity of telescreening was determined.Results:A total of 147 treatment-naïve patients met the inclusion criteria and were enrolled in the study. Mean gestational age (GA) was 28.6 ± 2.0 weeks. Digital retinal imaging had sensitivity of 85% and specificity of 35% in detecting referral-warranted ROP in our study. Positive predictive value of digital photography was 80%, and negative predictive value was 43%.Conclusion:Digital photography for diagnosis of ROP may show good potential as a screening modality in developing countries. It can facilitate early diagnosis, prevent unnecessary referrals, and be implemented for investigational purpose. However, the overall study result did not provide evidence to propose digital photography as a substitute for indirect ophthalmoscopy in the diagnosis of ROP.

Asymmetry of Retinopathy of Prematurity Border in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study

To measure the location of the retinopathy of prematurity (ROP) border in a sample of premature infants developed ROP and to determine the location for predicting subsequent development of referral-warranted ROP (defined as stage 3 ROP, zone I ROP, or plus disease) or treated ROP. Secondary analysis of data from an observational cohort study, the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity study. Infants with birth weight (BW) of less than 1251 g with at least 1 examination and imaging session at 34 weeks postmenstrual age (PMA) or younger with ROP not meeting referral-warranted ROP and at least 1 subsequent examination at 36 weeks PMA or older. The 5-image set from the first imaging session for each eligible eye was mosaicked, and measurements of the ROP border were made using Image J. Measurements were compared among 3 groups of eyes with ROP: (1) those that never developed referral-warranted ROP or received treatment, (2) those that developed referral-warranted ROP but did not receive treatment, and (3) those that received treatment. Referral-warranted ROP and treated ROP. Three hundred seventeen eyes from 217 infants with mean BW of 755 g, mean gestational age (GA) of 25 weeks, and mean PMA of 33 weeks at first examination met study criteria. Of 211 eyes (66.6%) with sufficient-quality images for grading, 147 (69.7%) did not develop referral-warranted ROP or receive treatment, 36 (17.1%) developed referral-warranted ROP not requiring treatment, and 28 (13.3%) received treatment for ROP. Among all eyes, the disc-to-ROP border distance followed a consistent pattern, with nasal less than inferior less than superior less than temporal. In multivariate analysis adjusted by BW and GA, nasal ROP border distance was a significant predictor of the subsequent development of ROP that was treated (odds ratio, 0.86 for every 10-pixel increase in distance; P = 0.002). Retinopathy of prematurity is located asymmetrically around the optic disc and is closest to the optic disc nasally. Location of ROP nasally at first imaging is a significant predictor for subsequent development of ROP that was treated.

Single grading vs double grading with adjudication in the telemedicine approaches to evaluating acute-phase retinopathy of prematurity (e-ROP) study

To evaluate the sensitivity and specificity of single, independent, nonphysician trained reader (TR) gradings in the Telemedicine Approaches to Evaluating Acute-phase Retinopathy of Prematurity (e-ROP) study. Secondary analyses of image grading results from 1,235 infants of birth weights <1251g. Two of three TRs independently graded image sets; discrepancies were adjudicated by the reading center director (an ophthalmologist) to reach final grading. Sensitivity and specificity of each TR grading and final grading was calculated by comparing gradings to clinical examination results. Of 7,808 double graded image sets, TR1 graded 5,165; TR2, 3,787; and TR3, 6,664. Compared to final grading for referral warranted retinopathy of prematurity (RW-ROP), two TRs had relatively lower sensitivity (TR1, 75% vs 79% [P=0.03]; TR2, 73% vs 77% [P=0.02]) and specificity (TR1, 80% vs 83% [P<0.001]; TR2, 82% vs 83% [P=0.09]). TR3 had similar sensitivity (83% vs 83% [P=0.78]) and specificity (83% vs 84% [P=0.02]). Compared to final grading, TR1 had lower sensitivity for zone I ROP (47% vs 56% [P=0.04]) and stage ≥3 ROP (71% vs 77% [P=0.002]); TR2 had lower sensitivity for stage ≥3 ROP (69% vs 77% [P<0.001]) and lower specificity for all three components (P<0.001); TR3 had lower sensitivity for detecting plus disease (23% vs 35% [P<0.001]) and similar sensitivity for zone I ROP and stage ≥3 ROP. There is a small but significant decrease in the sensitivity and specificity for RW-ROP when single-reader grading is compared to double adjudicated grading.

Comparison of strategies for grading retinal images of premature infants for referral warranted retinopathy of prematurity

To determine the accuracy of identifying referral-warranted retinopathy of prematurity (RW-ROP, defined as any zone I ROP, stage 3 or worse, or plus disease) from retinal image sets using three grading protocols: a single optic disk-centered image, a set of 3 horizontal images, and a 5-image set. In this secondary analysis of images from the e-ROP study, a weighted sample of 250 image sets from 250 infants (125 with RW-ROP and 125 without RW-ROP) was randomly selected. The sensitivities and specificities for detecting RW-ROP and its components from a single disk center image, along with nasal and temporal retinal images, were calculated and compared with the e-ROP grading of RW-ROP of all 5 retinal images (disk center and nasal, temporal, superior, and inferior retinal images). RW-ROP was identified with a sensitivity of 11.2% (95% CI, 6.79%-17.9%) using a single disk center image, with a sensitivity of 70.4% (95% CI, 61.9%-77.9%) using 3 horizontal images, and a statistically higher sensitivity of 82.4% (95% CI, 75.0%-89.0%) using all 5 images (P=0.002). The specificities were 100%, 86.4%, and 90.4%, respectively. For grading using 3 horizontal images, sensitivity was 14.3% for plus disease, 25% for zone I ROP, and 71.2% for stage 3 or worse compared to 40.8%, 50%, and 79.8% for grading using 5-image sets, respectively. Both a single, disk-centered, posterior pole image and 3 horizontal images were less effective than a 5-image set in determining the presence of RW-ROP on qualitative grading by trained readers.

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.

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

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. Secondary data analysis from a prospective study. Preterm infants with birth weight (BW) ≤1250 g. 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. Retinal and vitreous hemorrhage. 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%). 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.

Impact of number and quality of retinal images in a telemedicine screening program for ROP: results from the e-ROP study

Telemedicine for the detection of retinopathy of prematurity (ROP) is becoming increasingly common; however, obtaining the required multiple retinal images from an infant can be challenging. This secondary analysis from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study evaluated the detection of referral-warranted ROP (RW-ROP) by trained readers when a full set of 5 retinal images could not be obtained. A total of 7,905 image sets from 1,257 infants in the study were evaluated. Retinal location of images and image quality were recorded. Sensitivity and specificity of RW-ROP detection by trained readers were calculated by comparing findings in incomplete image sets to the findings on standard eye examination. The majority of image sets contained all 5 retinal images (92.8%). The disk center view was the image most likely to be present and to be of acceptable image quality (96.8%). The nasal retina was the most difficult to obtain with acceptable image quality (83.4%). Sensitivity of detection of RW-ROP was 82.1% when 5 retinal images of acceptable quality were submitted for grading, 67.2% when 4 acceptable images were submitted, and 66.7% for 3 or fewer acceptable images (P = 0.02), with corresponding specificity of 82.2%, 89.0%, and 81.7% respectively (P < 0.0001). When images of any quality were evaluated, sensitivity was not increased (P = 0.74). The likelihood of detecting RW-ROP by telemedicine screening is decreased when a full set of retinal images is not obtained.

Analysis of Discrepancy Between Diagnostic Clinical Examination Findings and Corresponding Evaluation of Digital Images in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity Study

As effective treatments for potentially blinding retinopathy of prematurity (ROP) have been introduced, the importance of consistency in findings has increased, especially with the shift toward retinal imaging in infants at risk of ROP. To characterize discrepancies in findings of ROP between digital retinal image grading and examination results from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity study, conducted from May 2011 to October 2013. A poststudy consensus review of images was conducted by 4 experts, who examined discrepancies in findings between image grades by trained nonphysician readers and physician examination results in infants with referral-warranted ROP (RW-ROP). Images were obtained from 13 North American neonatal intensive care units from eyes of infants with birth weights less than 1251 g. For discrepancy categories with more than 100 cases, 40 were randomly selected; in total, 188 image sets were reviewed. Consensus evaluation of discrepant image and examination findings for RW-ROP components. Among 5350 image set pairs, there were 161 instances in which image grading did not detect RW-ROP noted on clinical examination (G-/E+) and 854 instances in which grading noted RW-ROP when the examination did not (G+/E-). Among the sample of G-/E+ cases, 18 of 32 reviews (56.3%) agreed with clinical examination findings that ROP was present in zone I and 18 of 40 (45.0%) agreed stage 3 ROP was present, but only 1 of 20 (5.0%) agreed plus disease was present. Among the sample of G+/E- cases, 36 of 40 reviews (90.0%) agreed with readers that zone I ROP was present, 23 of 40 (57.5%) agreed with readers that stage 3 ROP was present, and 4 of 16 (25.0%) agreed that plus disease was present. Based on the consensus review results of the sampled cases, we estimated that review would agree with clinical examination findings in 46.5% of the 161 G-/E+ cases (95% CI, 41.6-51.6) and agree with trained reader grading in 70.0% of the 854 G+/E- cases (95% CI, 67.3-72.8) for the presence of RW-ROP. This report highlights limitations and strengths of both the remote evaluation of fundus images and bedside clinical examination of infants at risk for ROP. These findings highlight the need for standardized approaches as ROP telemedicine becomes more widespread.

Impact of number and quality of retinal images in a telemedicine screening program for ROP: results from the e-ROP study

Telemedicine for the detection of retinopathy of prematurity (ROP) is becoming more common. However, obtaining multiple retinal images from an infant can be challenging. In this secondary analysis of data from the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) study, we evaluated the accuracy of detection of referral warranted ROP (RW-ROP) by trained readers when a full set of five retinal images could not be obtained.

Predictors for the development of referral-warranted retinopathy of prematurity in the telemedicine approaches to evaluating of acute-phase ROP (e-ROP) study

Predictors for the development of referral-warranted retinopathy of prematurity in the telemedicine approaches to evaluating of acute-phase ROP (e-ROP) study

Validated System for Centralized Grading of Retinopathy of Prematurity: Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study.

Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a reading center to evaluate retinal fundus images from infants at risk for retinopathy of prematurity (ROP). Details of certification for nonphysician trained readers (TRs) have not yet been described. To describe a centralized system for grading ROP digital images by TRs in the Telemedicine Approaches to Evaluating Acute-Phase Retinopathy of Prematurity (e-ROP) Study. Multicenter observational cohort study conducted from July 1, 2010, to June 30, 2014. The TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist reading center director. An ROP reading center was developed with standard hardware, secure Internet access, and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether referral-warranted ROP (RW-ROP; defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present in digital images from infants with birth weight less than 1251 g enrolled from May 25, 2011, through October 31, 2013. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the reading center director. Digital retinal images. Intragrader and intergrader variability and monitoring for temporal drift. Four TRs underwent rigorous training and certification. A total of 5520 image sets were double graded, with 24.5% requiring adjudication for at least 1 component of RW-ROP. For individual RW-ROP components, the adjudication rate was 3.9% for plus disease, 12.4% for zone I ROP, and 16.9% for stage 3 or worse ROP. The weighted κ for intergrader agreement (n = 80 image sets) was 0.72 (95% CI, 0.52-0.93) for RW-ROP, 0.57 (95% CI, 0.37-0.77) for plus disease, 0.43 (95% CI, 0.24-0.63) for zone I ROP, and 0.67 (95% CI, 0.47-0.88) for stage 3 or worse ROP. The weighted κ for grade-regrade agreement was 0.77 (95% CI, 0.57-0.97) for RW-ROP, 0.87 (95% CI, 0.67-1.00) for plus disease, 0.70 (95% CI, 0.51-0.90) for zone I ROP, and 0.77 (95% CI, 0.57-0.97) for stage 3 or worse ROP. These data suggest that the e-ROP system for training and certifying nonphysicians to grade ROP images under the supervision of a reading center director reliably detects potentially serious ROP with good intragrader and intergrader consistency and minimal temporal drift.

Validity of a telemedicine system for the evaluation of acute-phase retinopathy of prematurity.

The present strategy to identify infants needing treatment for retinopathy of prematurity (ROP) requires repeated examinations of at-risk infants by physicians. However, less than 10% ultimately require treatment. Retinal imaging by nonphysicians with remote image interpretation by nonphysicians may provide a more efficient strategy. To evaluate the validity of a telemedicine system to identify infants who have sufficiently severe ROP to require evaluation by an ophthalmologist. An observational study of premature infants starting at 32 weeks' postmenstrual age was conducted. This study involved 1257 infants with birth weight less than 1251 g in neonatal intensive care units in 13 North American centers enrolled from May 25, 2011, through October 31, 2013. Infants underwent regularly scheduled diagnostic examinations by an ophthalmologist and digital imaging by nonphysician staff using a wide-field digital camera. Ophthalmologists documented findings consistent with referral-warranted (RW) ROP (ie, zone I ROP, stage 3 ROP or worse, or plus disease). A standard 6-image set per eye was sent to a central server and graded by 2 trained, masked, nonphysician readers. A reading supervisor adjudicated disagreements. The validity of grading retinal image sets was based on the sensitivity and specificity for detecting RW-ROP compared with the criterion standard diagnostic examination. A total of 1257 infants (mean birth weight, 864 g; mean gestational age, 27 weeks) underwent a median of 3 sessions of examinations and imaging. Diagnostic examination identified characteristics of RW-ROP in 18.2% of eyes (19.4% of infants). Remote grading of images of an eye at a single session had sensitivity of 81.9% (95% CI, 77.4-85.6) and specificity of 90.1% (95% CI, 87.9-91.8). When both eyes were considered for the presence of RW-ROP, as would routinely be done in a screening, the sensitivity was 90.0% (95% CI, 85.4-93.5), with specificity of 87.0% (95% CI, 84.0-89.5), negative predictive value of 97.3%, and positive predictive value of 62.5% at the observed RW-ROP rate of 19.4%. When compared with the criterion standard diagnostic examination, these results provide strong support for the validity of remote evaluation by trained nonphysician readers of digital retinal images taken by trained nonphysician imagers from infants at risk for RW-ROP. clinicaltrials.gov Identifier:NCT01264276.

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.

Telemedicine detection of type 1 ROP in a distant neonatal intensive care unit

To demonstrate the feasibility of telemedicine screening for retinopathy of prematurity (ROP) by summarizing the results of our experience screening premature infants at a distant hospital in a rural location. Records of all premature infants remotely screened for ROP at a neonatal intensive care unit in Great Falls, Montana, from January 1, 2007 to June 30, 2011, were retrospectively reviewed. The RetCam II imaging system was used to capture retinal images, which were posted on a secure server for evaluation by one of two pediatric ophthalmologists. Infants suspected of having ROP approaching the criteria for laser treatment were transferred to a hospital, where a diagnostic examination was performed and treatment administered when indicated. All other infants received an outpatient diagnostic examination within 2 weeks of discharge. A total of 582 telemedicine examinations were performed on 137 infants during the study period. Of 13 infants transferred for referral-warranted ROP, 9 ultimately required laser treatment. Good outcomes were noted in all cases, with none progressing to stage 4 or 5 ROP. Telemedicine ROP screening detected patients at a remote site in need of laser treatment, allowing prompt transfer with no poor outcomes over a 4.5-year period. Our experience demonstrates the utility of remote screening for ROP.

Review of the Use of Digital Imaging in Retinopathy of Prematurity Screening

Retinopathy of prematurity (ROP) is a vision-threatening vasoproliferative condition of premature infants worldwide. As survival rates of younger and smaller infants improve, more babies are at risk for the development of ROP and blindness. Meanwhile, fewer ophthalmologists are available for bedside indirect ophthalmoscopy screening examinations. Remote digital imaging is a promising method with which to identify those infants with treatment-requiring or referral-warranted ROP quickly and accurately, and may help circumvent issues regarding the limited availability of ROP screening providers. The Retcam imaging system is the most common system for fundus photography, with which high-quality photographs can be obtained by trained non-physician personnel and evaluated by a remote expert. It has been shown to have high reliability and accuracy in detecting referral-warranted ROP, particularly at later postmenstrual ages. Additionally, the method is generally well received by parents and is highly cost-effective.