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The presence of plus disease is the primary indication for treatment of retinopathy of prematurity (ROP), but its diagnosis is subjective and prone to error. ROPtool is a semiautomated computer program that quantifies vascular tortuosity and dilation. Pictor is an FDA-approved, noncontact, handheld digital fundus camera. This pilot study evaluated ROPtool’s ability to analyze high-quality Pictor images of premature infants and its accuracy in diagnosing plus disease compared to clinical examination. In our small sample of images, ROPtool could trace and identify the presence of plus disease with high accuracy.

Structural retinal vascular characteristics, such as vessel calibers, tortuosity and bifurcation angles are increasingly quantified in an objective manner, slowly replacing subjective qualitative disease classification schemes. This paper provides an overview of the current methodologies and calculations used to compute retinal vessel tortuosity. We set out the different parameter calculations and provide an insight into the clinical applications, while critically reviewing its pitfalls and shortcomings.

The prevalence of Retinopathy of Prematurity (ROP) among preterm infants in the developing countries like India has increased many fold during the past decades. The main cause of this problem is lack of awareness among people, improper diagnostic methods, inter expert variability while screening etc. Treatment of ROP, one of the leading causes of childhood blindness is warranted based on the diagnosis of Plus disease. Comparison of tortuosity of blood vessels with a gold standard image was one of the common techniques used for its screening. Quantitative assessment of the disease includes evaluation of blood vessel tortuosity and vascular dilation in the retinal image. We present a semi-automated computer-based method for the assessment of Plus disease in ROP. This method involves initial preprocessing of the image followed by evaluation of tortuosity and width of retinal blood vessels. Based on the implemented work two image databases, EIARG2 and KIDROP were quantitatively classified as plus, pre-plus or normal case with high accuracy.

To identify any temporal trends in the diagnosis of plus disease in retinopathy of prematurity (ROP) by experts.Reliability analysis.ROP experts were recruited in 2007 and 2016 to classify 34 wide-field fundus images of ROP as plus, pre-plus, or normal, coded as "3," "2," and "1," respectively, in the database. The main outcome was the average calculated score for each image in each cohort. Secondary outcomes included correlation on the relative ordering of the images in 2016 vs 2007, interexpert agreement, and intraexpert agreement.The average score for each image was higher for 30 of 34 (88%) images in 2016 compared with 2007, influenced by fewer images classified as normal (P.01), a similar number of pre-plus (P = .52), and more classified as plus (P.01). The mean weighted kappa values in 2006 were 0.36 (range 0.21-0.60), compared with 0.22 (range 0-0.40) in 2016. There was good correlation between rankings of disease severity between the 2 cohorts (Spearman rank correlation ρ = 0.94), indicating near-perfect agreement on relative disease severity.Despite good agreement between cohorts on relative disease severity ranking, the higher average score and classifications for each image demonstrate that experts are diagnosing pre-plus and plus disease at earlier stages of disease severity in 2016, compared with 2007. This has implications for patient care, research, and teaching, and additional studies are needed to better understand this temporal trend in image-based plus disease diagnosis.

Background Retention rate, efficacy, and safety of abatacept (ABA) was compared between patients with rheumatoid arthritis receiving ABA as monotherapy to those in combination ABA + conventional synthetic DMARD (csDMARD). Methods The patients were obtained from the ORA registry. The retention rate was analysed in two ways: (1) therapeutic strategy retention, in which the addition of a csDMARD was considered to indicate failure of the monotherapy strategy; and (2) ABA retention, which was assessed by the discontinuation of ABA regardless of other treatment modifications. Efficacy and safety were compared between ABA initiated alone and ABA used in combination with a csDMARD. Results The retention rate at month 6 (M6) was evaluated in 569 patients. A significant difference was identified in the retention rate between the ABA monotherapy strategy and the ABA + csDMARD strategy (58.5 % [110/188] vs. 68 % [258/381], respectively, p = 0.031). No significant difference was identified in the ABA retention rate initiated either as a monotherapy or in combination with csDMARDs (75 % [142/188] vs. 76 % [291/381], respectively, p = 0.824). Data regarding ABA efficacy were available for 444 patients. There was no significant difference in the responder proportion after 6 months of treatment between ABA monotherapy and ABA + csDMARD treatment (60.2 % [88/146] vs. 60 % [179/298], respectively, p = 0.967). Conclusions This “real-life” analysis, which is relevant for bedside practice, emphasised the satisfactory efficacy and safety of ABA used in monotherapy, which provides an acceptable alternative when csDMARDs are undesirable.

Purpose: To review the incidence and risk factors for retinopathy of prematurity (ROP) King Faisal Specialist Hospital and King Abdulaziz University Hospital in Jeddah, Saudi Arabia. Material and methods: In this prospective cohort study, preterm infants who were admitted to a neonatal intensive care unit from 2012 to 2013 were evaluated for ROP. Inclusion criteria were, preterm infants with gestational age

Candidate genetic association studies have been found to have a low replication rate in the past. Here, we aimed to assess whether aspects of reported methodological characteristics in genetic association studies may be related to the magnitude of effects observed. An observational, literature-based investigation of 511 case-control studies of genetic association studies indexed in 2007, was undertaken. Meta-regression analyses were used to assess the relationship between 23 reported methodological characteristics and the magnitude of genetic associations. The 511 studies had been conducted in 52 countries and were published in 220 journals (median impact factor 5.1). The multivariate meta-regression model of methodological characteristics plus disease category accounted for 17.2 % of the between-study variance in the magnitude of the reported genetic associations. Our findings are consistent with the view that better conducted and better reported genetic association research may lead to less inflated results.

Purpose: To assess the long-term anatomic and visual outcomes and associated complications of lens-sparing vitrectomy (LSV) in infants with progressive posterior-type tractional retinal detachment (TRD) associated with stage 4A retinopathy of prematurity (ROP). Methods: In a retrospective case series, the medical records of consecutive patients who presented with progressive posterior-type stage 4A ROP and underwent LSV between 1999 and 2007 were reviewed. Retinal attachment status, visual acuity, and development of postoperative complications were assessed. Results: Eleven eyes of 9 patients were included. The mean follow-up period was 4.6 years. In 8 eyes (73%), plus disease was present at the time of LSV. In 3 eyes (27%), 2 (66%) without plus disease and 1 (13%) with plus disease, the retina remained reattached in the end, while 8 eyes (73%) had TRD on final examination. Two eyes with reattached retinas showed favorable visual acuity. In those eyes with detached retinas, 5 (68%) showed no light perception. When surgery for ROP was unsuccessful, development of cataract, corneal opac ity, or glaucoma was common. Conclusions: The long-term anatomic success rate of LSV for progressive posterior-type stage 4A ROP was low, especially in the presence of plus disease at the time of LSV. Anatomical reattachment is very important for preventing complications and gaining better visual outcomes.

Presence of plus disease in retinopathy of prematurity (ROP) is an important criterion for identifying ROP requiring treatment. Plus disease is defined by a standard published photograph selected more than 20 years ago by expert consensus. However, diagnosis of plus disease has been shown to be subjective and qualitative. Computer-based image analysis using quantitative methods has potential to improve the objectivity of plus disease diagnosis. The objective was to review the published literature involving computer-based image analysis for ROP diagnosis. The PubMed and Cochrane library databases were searched for the keywords “retinopathy of prematurity” AND “image analysis” AND/OR “plus disease.” Reference lists of retrieved articles were searched to identify additional relevant studies. All relevant English-language studies were reviewed. There are four main computer-based systems—ROPtool (area under the receiver operating characteristic curve [AUROC], plus tortuosity 0.95, plus dilation 0.87), RISA (AUROC, arteriolar TI 0.71, venular diameter 0.82), Vessel Map (AUROC, arteriolar dilation 0.75, venular dilation 0.96), and CAIAR (AUROC, arteriole tortuosity 0.92, venular dilation 0.91)—attempting to objectively analyze vessel tortuosity and dilation in plus disease in ROP. Some show promise for identification of plus disease using quantitative methods. This has potential to improve the diagnosis of plus disease and may contribute to the management of ROP using both traditional binocular indirect ophthalmoscopy and image-based telemedicine approaches.

Retinopathy of Prematurity (ROP) is the main cause of preventable blindness in premature babies. Currently, there is a shortage of trained ophthalmologists, which has resulted in an alarming increase in cases of vision loss and related complications. This study's aim was to determine the utility of examinations conducted by non-ophthalmologist physicians to assess posterior pole vessel abnormalities in eyes at risk for ROP.Non-ophthalmologist physicians (pediatrician and neonatologist) were trained to use an indirect ophthalmoscope to view the posterior pole of babies at risk for ROP. Examinations were conducted on both eyes of premature infants born before 35 weeks gestational age (GA) starting at the third week after birth and weekly thereafter. The presence of Plus disease was identified by the non-ophthalmologist and results compared to the clinical examination by a pediatric ophthalmologist experienced in ROP detection and treatment. Chi-square was used for proportions and the Mann Whitney U test for medians. Fagan's nomogram was determined for diagnostic usability. The Kappa index was used to rate inter-observer agreement.Results of 228 examinations performed on 150 premature infants were analyzed to determine the correlation of the non-ophthalmologist findings and the eye examination. For any vascular change in posterior pole diagnostic, findings were 87% and 87% accuracy for pediatrician and neonatologist, 82% and 83% sensitivity, 90% and 90% specificity respectively. There was no significant difference found in the detection of Plus disease for the examinations performed by the ophthalmologist compared to those performed by the non-ophthalmologist (P 0.05).After training in the use of an indirect ophthalmoscope, non-ophthalmologist physicians can reliably detect posterior pole retinal vessel changes for ROP diagnosis.

BackgroundPatients with high disease activity (HDA) relapsing-remitting MS are less likely to attain no evidence of disease activity (NEDA; no relapses, MRI activity or progression).ObjectivePost-hoc analysis to compare the proportion of patients with NEDA with cladribine tablets 3.5 mg/kg (CT3.5) vs placebo.MethodsPatients from CLARITY were retrospectively stratified using 2 definitions of HDA based on relapse history, prior treatment, and MRI characteristics: HRA (n=261) and HRA plus disease activity on treatment (HRA+DAT) [n=289]). Data for patients treated with CT3.5 or placebo who fulfilled these criteria and achieved NEDA status were compared over the 2 years using odds ratios (OR) and 95% CI.ResultsHRA subgroup: 76% of CT3.5-treated patients were relapse-free and 84% were T1 Gd+ lesion free vs 49% and 31%, respectively, for placebo. HRA+DAT subgroup: 77% of CT3.5-treated were relapse-free and 85% were T1 Gd+ lesion free vs 50% and 32%, respectively, for placebo. In the HRA and HRA+DAT subgroups, 43.2% and 43.7%, respectively, of CT3.5-treated patients were disease activity free compared with 8.7%, (OR: 8.02; 95% CI: 3.93 to 16.35; pConclusionsTreatment with CT3.5 significantly increased the proportion of HDA patients with NEDA vs placebo.Disclaimerhttp://medpub-poster.merckgroup.com/ABN2018DISC_NEDA.pdf

Importance Presence of plus disease in retinopathy of prematurity is the most critical element in identifying treatment-requiring disease. However, there is significant variability in plus disease diagnosis. In particular, plus disease has been defined as 2 or more quadrants of vascular abnormality, and it is not clear whether it is more reliably and accurately diagnosed by eye-based assessment of overall retinal appearance or by quadrant-based assessment combining grades of 4 individual quadrants. Objective To compare eye-based vs quadrant-based diagnosis of plus disease and to provide insight for ophthalmologists about the diagnostic process. Design, Setting, and Participants In this multicenter cohort study, we developed a database of 197 wide-angle retinal images from 141 preterm infants from neonatal intensive care units at 9 academic institutions (enrolled from July 2011 to December 2016). Each image was assigned a reference standard diagnosis based on consensus image-based and clinical diagnosis. Data analysis was performed from February 2017 to September 2017. Interventions Six graders independently diagnosed each of the 4 quadrants (cropped images) of the 197 eyes (quadrant-based diagnosis) as well as the entire image (eye-based diagnosis). Images were displayed individually, in random order. Quadrant-based diagnosis of plus disease was made when 2 or more quadrants were diagnosed as indicating plus disease by combining grades of individual quadrants post hoc. Main Outcomes and Measures Intragrader and intergrader reliability (absolute agreement and κ statistic) and accuracy compared with the reference standard diagnosis. Results Of the 141 included preterm infants, 65 (46.1%) were female and 116 (82.3%) white, and the mean (SD) gestational age was 27.0 (2.6) weeks. There was variable agreement between eye-based and quadrant-based diagnosis among the 6 graders (Cohen κ range, 0.32-0.75). Four graders showed underdiagnosis of plus disease with quadrant-based diagnosis compared with eye-based diagnosis (by McNemar test). Intergrader agreement of quadrant-based diagnosis was lower than that of eye-based diagnosis (Fleiss κ, 0.75 [95% CI, 0.71-0.78] vs 0.55 [95% CI, 0.51-0.59]). The accuracy of eye-based diagnosis compared with the reference standard diagnosis was substantial to near-perfect, whereas that of quadrant-based plus disease diagnosis was only moderate to substantial for each grader. Conclusions and Relevance Graders had lower reliability and accuracy using quadrant-based diagnosis combining grades of individual quadrants than with eye-based diagnosis, suggesting that eye-based diagnosis has advantages over quadrant-based diagnosis. This has implications for more precise definitions of plus disease regarding the criterion of 2 or more quadrants, clinical care, computer-based image analysis, and education for all ophthalmologists who manage retinopathy of prematurity.

IMPORTANCE: Presence of plus disease in retinopathy of prematurity is the most critical element in identifying treatment-requiring disease. However, there is significant variability in plus disease diagnosis. In particular, plus disease has been defined as 2 or more quadrants of vascular abnormality, and it is not clear whether it is more reliably and accurately diagnosed by eye-based assessment of overall retinal appearance or by quadrant-based assessment combining grades of 4 individual quadrants. OBJECTIVE: To compare eye-based vs quadrant-based diagnosis of plus disease and to provide insight for ophthalmologists about the diagnostic process. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter cohort study, we developed a database of 197 wide-angle retinal images from 141 preterm infants from neonatal intensive care units at 9 academic institutions (enrolled from July 2011 to December 2016). Each image was assigned a reference standard diagnosis based on consensus image-based and clinical diagnosis. Data analysis was performed from February 2017 to September 2017. INTERVENTIONS: Six graders independently diagnosed each of the 4 quadrants (cropped images) of the 197 eyes (quadrant-based diagnosis) as well as the entire image (eye-based diagnosis). Images were displayed individually, in random order. Quadrant-based diagnosis of plus disease was made when 2 or more quadrants were diagnosed as indicating plus disease by combining grades of individual quadrants post hoc. MAIN OUTCOMES AND MEASURES: Intragrader and intergrader reliability (absolute agreement and κ statistic) and accuracy compared with the reference standard diagnosis. RESULTS: Of the 141 included preterm infants, 65 (46.1%) were female and 116 (82.3%) white, and the mean (SD) gestational age was 27.0 (2.6) weeks. There was variable agreement between eye-based and quadrant-based diagnosis among the 6 graders (Cohen κ range, 0.32-0.75). Four graders showed underdiagnosis of plus disease with quadrant-based diagnosis compared with eye-based diagnosis (by McNemar test). Intergrader agreement of quadrant-based diagnosis was lower than that of eye-based diagnosis (Fleiss κ, 0.75 [95% CI, 0.71-0.78] vs 0.55 [95% CI, 0.51-0.59]). The accuracy of eye-based diagnosis compared with the reference standard diagnosis was substantial to near-perfect, whereas that of quadrant-based plus disease diagnosis was only moderate to substantial for each grader. CONCLUSIONS AND RELEVANCE: Graders had lower reliability and accuracy using quadrant-based diagnosis combining grades of individual quadrants than with eye-based diagnosis, suggesting that eye-based diagnosis has advantages over quadrant-based diagnosis. This has implications for more precise definitions of plus disease regarding the criterion of 2 or more quadrants, clinical care, computer-based image analysis, and education for all ophthalmologists who manage retinopathy of prematurity.

Objective To perform a descriptive analysis of the clinical and diagnostic implications of 123 I-IBZM SPECT in the patients studied in our center for movement disorders suggestive of Parkinson-Plus Disease (PP). Subjects and methods 123 I-IBZM SPECT was performed in 46 patients referred from the movement disorders consultation due to suspicion of PP. According to their symptoms, they were distributed into 3 groups: 35 patients had atypical symptoms (AS) for Parkinson's Disease, 2 showed no response to standard therapy (NR) and 9 presented both factors (AS, NR). The results of SPECT were only assessed qualitatively. Results The 123 I-IBZM supported the diagnosis of PP in 15(42.9%) out of the 35 patients with AS. The 123 I-IBZM was pathological in one of the two NR patients. Regarding the third group of patients (AS + NR), the 123 I-IBZM was pathological in 6 cases (66.7%). In 95.7% of our sample (44 patients), AS with or without NR was the main factor leading to suspicion of PP and the 123 I-IBZM was altered in only 47.7% (22 patients). Of these 22 cases, the final diagnosis was PP (with high positive predictive value) in 20(91%). Conclusion The study with 123 I-IBZM is useful in the clinical practice because it provides objective diagnostic information with implications for the treatment and prognosis of patients with suspicion of PP.

Plus disease is abnormal retinal vascular dilation and tortuosity, and it is now the primary indication for laser treatment in retinopathy of prematurity (ROP). ROPtool is a computer program that measures retinal arteriolar tortuosity. Our aim was to assess the accuracy of ROPtool's newly developed measurement of retinal vascular width (dilation).ROPtool was used to measure the width of 154 blood vessels in 20 high-quality RetCam images from 20 premature infants. ROPtool's accuracy was determined by comparing results with the mean grades of 2 authors who scored retinal vascular dilation using a 10-point scale.There was very good correlation (r = 0.80) between ROPtool's measurement of retinal vascular dilation and author judgment. Areas under receiver operating characteristics curves for identification of dilation sufficient for plus disease and for pre-plus disease were 0.93 and 0.90, respectively. At an optimal point on the receiver operating characteristics curve, ROPtool's sensitivity for diagnosing dilation sufficient for plus disease was 89% (24/27), and its specificity was 83% (106/127).In addition to measuring retinal vascular tortuosity, ROPtool now accurately measures retinal vascular width in high-quality RetCam images. Application of this technology has the potential to remove subjectivity from the assessment of plus disease.

Background Plus disease is the major criterion for laser treatment of retinopathy of prematurity. ROPtool is a computer program that traces retinal blood vessels and measures their tortuosity. Our objectives were to determine (1) whether examiners could accurately discriminate between arterioles and venules and (2) whether tortuosity sufficient for plus disease and pre-plus disease was assessed most accurately by considering arterioles, venules, or both. Methods One hundred retinal vessels were identified in 25 images randomly selected from 184 total images. Three pediatric ophthalmologists independently designated vessels as arteriole or venule. Seventy-seven images that had at least 1 traceable arteriole and venule in each quadrant were analyzed by ROPtool, and the results were compared with the consensus of 3 expert examiners. Receiver operating characteristics (ROC) curves were generated and areas under the curves calculated to quantify the diagnostic utility of ROPtool's assessment of tortuosity of arterioles, venules, and both. Results Three pediatric ophthalmologists agreed on the designation of arteriole or venule for 83 of 100 blood vessels. With the use of expert consensus as the reference standard, areas under the ROC curves for identification of tortuosity sufficient for plus disease were 0.91, 0.70, and 0.93 for arterioles, venules, and both, respectively. Areas under the ROC curves for identification of tortuosity sufficient for pre-plus disease were 0.91, 0.63, and 0.90 for arterioles, venules, and both, respectively. Conclusions When considering whether tortuosity is sufficient for plus or pre-plus disease, the assessment of either arterioles alone or of arterioles and venules together resulted in high diagnostic accuracy.

Purpose: “ROPtool” is a computer program that measures retinal blood vessel tortuosity. Our aim was to determine the feasibility and accuracy of analyzing images with ROPtool, which were obtained using video indirect ophthalmoscopy. Methods: Forty-five posterior pole still images captured from indirect ophthalmoscopy video clips were selected; 20 were selected for high quality and 25 were randomly selected. One of the authors (S.A.) used ROPtool to measure tortuosity for each quadrant of each image. Two of the authors (D.K.W. and S.F.F.) independently judged tortuosity on a 10-point scale, and their averaged grades were used as the reference standard. Results: Among randomly selected images, ROPtool was able to trace at least two major vessels in 43 of 100 quadrants (43%). Lighter fundus pigment color was associated with ROPtool's ability to analyze images (P = 0.004). When considering analyzable images only, ROPtool's sensitivity in detecting tortuosity sufficient for plus disease was 83% (5/6) and specificity was 90% (18/20). ROPtool's sensitivity for pre-plus tortuosity was 100% (9/9) and specificity was 71% (12/17). Conclusion: ROPtool is useful for analyzing video indirect ophthalmoscopy images only when applied to those with high quality. When analyzing these images, ROPtool has very good accuracy compared to consensus of experienced examiners.

Purpose Plus disease has become the major criterion for laser treatment in infants with retinopathy of prematurity (ROP), but its assessment is subjective. Our purpose was to compare quadrant-level and eye-level assessment of plus disease and pre-plus disease among 3 experienced ROP examiners and to report their rate of agreement. Methods One hundred eighty-one high-quality RetCam images from premature infants were graded by 3 of the authors. Dilation and tortuosity were judged separately using a scale of normal or sufficiently abnormal to meet criteria for pre-plus or plus disease. Results There was disagreement on the presence of plus disease for 18 images (10%), on tortuosity sufficient for plus disease (plus tortuosity) for 26 images (14%), and on dilation sufficient for plus disease (plus dilation) for 26 images (14%). Of 67 images judged to have pre-plus disease or worse, there was disagreement on the presence of plus disease for 18 images (27%), on plus tortuosity for 25 images (37%), and on plus dilation for 21 images (31%). For distinguishing plus or pre-plus disease from normal, there was disagreement on pre-plus tortuosity for 38 of 181 images (21%) and on pre-plus dilation for 58 of 181 images (32%). Conclusions Three experienced ROP examiners disagreed frequently on the diagnosis of plus or pre-plus disease when evaluating cropped clinical photographs of infants, many of which had borderline plus disease. Further study is required to determine the implications of these observations on clinical decision making.

These revised guidelines replace the previous guidelines on the screening of preterm infants for retinopathy of prematurity (ROP) that were published in 1999. Recently published research provided the impetus for this revision. These guidelines propose the following criteria for an efficient screening programme for the early detection and treament of ROP in Germany: Inclusion criteria for ROP screening: All preterm infants with a gestational age of less than 32 weeks (if gestational age is unknown; of > 1500 g birth weight) should be examined. In addition, all preterm infants with 32 - 36 weeks gestational age are included if postnatal oxygen was supplemented for more than 3 days. The first examination should be performed within the 5 th week of postnatal age (day 36 - 42), but not prior to 31 weeks gestational age. Indications for laser photocoagulation: in Zone I: 1. any stage with “plus disease”, 2. stage 3 without “plus disease.” In Zone II: stage 3 with extraretinal proliferations in 5 continuous or 8 cumulative clock hours in combination with “plus-disease”. In certain cases an earlier treatment may be indicated.

Purpose To measure accuracy of plus disease diagnosis by recognized experts in retinopathy of prematurity (ROP), and to conduct a pilot study examining performance of a computer-based image analysis system, Retinal Image multiScale Analysis (RISA). Methods Twenty-two ROP experts independently interpreted a set of 34 wide-angle retinal images for presence of plus disease. A reference standard diagnosis based on expert consensus was defined for each image. Images were analyzed by the computer-based system using individual and linear combinations of system parameters for arterioles and venules: integrated curvature (IC), diameter, and tortuosity index (TI). Sensitivity, specificity, and receiver operating characteristic areas under the curve (AUC) for plus disease diagnosis compared with the reference standard were determined for each expert, as well as for the computer-based system. Results Expert sensitivity ranged from 0.308 to 1.000, specificity ranged from 0.571 to 1.000, and AUC ranged from 0.784 to 1.000. Among individual computer system parameters, venular IC had highest AUC (0.853). Among all computer system parameters, the linear combination of arteriolar IC, arteriolar TI, venular IC, venular diameter, and venular TI had highest AUC (0.967), which was greater than that of 18 (81.8%) of 22 experts. Conclusions Accuracy of ROP experts for plus disease diagnosis is imperfect. A computer-based image analysis system has potential to diagnose plus disease with high accuracy. Further research involving RISA system parameter cut-off values from this study are required to fully validate performance of this computer-based system compared with that of human experts.

Objective To measure accuracy and reliability of the computer-based Retinal Image Multiscale Analysis (RISA) system compared with those of recognized retinopathy of prematurity (ROP) experts, for plus disease diagnosis. Design Evaluation of diagnostic test or technology. Participants Eleven recognized ROP experts and the RISA image analysis system interpreted a set of 20 wide-angle retinal photographs for presence of plus disease. Methods All experts used a secure Web site to review independently 20 images for presence of plus disease. Images were also analyzed by measuring individual computer-based system parameters (integrated curvature [IC], diameter, and tortuosity index) for arterioles and venules and by computing linear combinations and logical combinations of those parameters. Performance was compared with a reference standard, defined as the majority vote of experts. Main Outcome Measures Diagnostic accuracy was measured by calculating sensitivity, specificity, and receiver operating characteristic area under the curve (AUC) for plus disease diagnosis by each expert, and by each computer-based system parameter, compared with the reference standard. Diagnostic agreement was measured by calculating the mean κ value of each expert compared with all other experts and the mean κ value of each computer-based system parameter compared with all experts. Results Among the 11 experts, sensitivity ranged from 0.167 to 1.000, specificity ranged from 0.714 to 1.000, AUC ranged from 0.798 to 1.000, and mean κ compared with all other experts ranged from 0.288 to 0.689. Among individual computer system parameters, arteriolar IC had the highest diagnostic accuracy, with sensitivity of 1.000; specificity, 0.846; and AUC, 0.962. Arteriolar IC had the highest diagnostic agreement with experts, with a mean κ value of 0.578. Conclusions A computer-based image analysis system has the potential to perform comparably to recognized ROP experts for plus disease diagnosis.

Purpose The accurate diagnosis of plus disease is critical to optimize the timing of laser treatment. Unfortunately, it is highly subjective and error-prone. “ROPtool” is a computer program that automatically traces retinal blood vessels and measures their tortuosity and dilation. Our aims were to pilot ROPtool, determine its reliability and validity, and establish appropriate numerical thresholds for plus and pre-plus disease. Methods Twenty high-quality images of the posterior poles of premature infants were collected. Two of the authors (DKW and SFF) independently judged tortuosity and dilation separately as plus, pre-plus, or normal for each quadrant of each image. Disagreements were adjudicated, and the results were considered to be the standard for comparison to ROPtool. These two authors then separately used ROPtool to analyze the same 20 images. Results For determination of tortuosity sufficient for plus disease, ROPtool interuser agreement was 95% (19/20), compared with 90% (18/20) agreement by investigator judgment. Eye-level (2 MDs × 20 eyes) sensitivity of ROPtool in detecting tortuosity sufficient for plus disease averaged 95% (21/22) and specificity averaged 78% (14/18). Quadrant-level (2 MDs × 20 eyes × 4 quadrants) sensitivity averaged 85% (66/78) and specificity averaged 77% (63/82). A numeric threshold for pre-plus disease equal to 70% of the average tortuosity of the standard photograph of plus disease resulted in mean sensitivity of 89% (103/116) and mean specificity of 82% (36/44) in distinguishing quadrant-level tortuosity sufficient for pre-plus disease or worse from normal. Conclusions ROPtool can reduce subjectivity and thereby enhance the evaluation of plus and pre-plus disease.

The anatomic response to intravitreal bevacizumab injection in three patients with aggressive, posterior retinopathy of prematurity is described. In all cases, the worse eye was treated with a single intravitreal injection of 0.75 mg of bevacizumab as monotherapy or complementary to laser therapy. In 24 hours, all injected eyes showed regression of the tunica vasculosa lentis and iris vessel engorgement and disappearance of iris rigidity. In addition, plus disease and retinal proliferation began to regress. None of the eyes required additional treatment. Follow-up of up to 10 months showed good anatomic outcomes and no evidence of local or systemic adverse events. [Ophthalmic Surg Lasers Imaging 2007;38:233-237.] AUTHORS From the Pediatric Retina Department (ST, FEE, IP, GP), Ophthalmology Service, Hospital Fernando Fonseca, Lisbon; the Surgical Center of Coimbra (AT, IR, AST, RV), Coimbra; the Ophthalmology Department (PF), Centro Hospitalar de Lisboa, Zona Central, Hospital de S. José, Lisbon; Alfredo da Costa Maternity (AV), Lisbon; and the High Commissary for Portuguese Health (MCM), Lisbon, Portugal. Accepted for publication February 26, 2007. Presented at the World ROP Meeting, Vilnius, Lithuania, September 14-16, 2006. Abstract number 015. The authors thank Drs. Stephan Michels and Rike Michels for their support. Address correspondence to Susana Teixeira, MD, Pediatric Retina Department at the Service of Ophthalmology, Hospital Fernando Fonseca, R. João de Freitas Branco nº 21, 6º D, 1500-714 Lisboa, Portugal. E-mail: susanateixeira.oft@gmail.com.

Purpose To design software with a novel algorithm, which analyzes the tortuosity and vascular dilatation in fundal images of retinopathy of prematurity (ROP) patients with an acceptable accuracy for detecting plus disease. Methods Eighty-seven well-focused fundal images taken with RetCam were classified to three groups of plus, non-plus, and pre-plus by agreement between three ROP experts. Automated algorithms in this study were designed based on two methods: the curvature measure and distance transform for assessment of tortuosity and vascular dilatation, respectively as two major parameters of plus disease detection. Results Thirty-eight plus, 12 pre-plus, and 37 non-plus images, which were classified by three experts, were tested by an automated algorithm and software evaluated the correct grouping of images in comparison to expert voting with three different classifiers, k-nearest neighbor, support vector machine and multilayer perceptron network. The plus, pre-plus, and non-plus images were analyzed with 72.3%, 83.7%, and 84.4% accuracy, respectively. Conclusions The new automated algorithm used in this pilot scheme for diagnosis and screening of patients with plus ROP has acceptable accuracy. With more improvements, it may become particularly useful, especially in centers without a skilled person in the ROP field.

We appreciate the opportunity to respond to the insightfulcomments from Dr. Shapiro, Dr. Blair, and Mr. Garcia-Gonzalez. We agree that they have raised important points.Although many medical diagnoses are based on quantitativemeasurements,ophthalmicdiagnosisislargelybasedonqual-itative interpretationofvisualpatternsobservedduringexam-ination and recorded using photographs or even hand-drawnsketches.Theinternationalclassificationofretinopathyofpre-maturity (ICROP) has been extraordinarily useful by creatinga framework for disease classification based on discrete pa-rameters (e.g., zone, stage, plus disease) [1]. This universalclassification system has transformed ROP diagnosis frombeing purely qualitative and descriptive to being systematicand standardized and has created an infrastructure for im-proved clinical care and multi-center clinical trials [2, 3].However, asthe authors suggest,ROP diagnosis continuesto be subjective and qualitative, even with ICROP. We andothers have published studies showing that there is often sig-nificant disagreement, even among experts, regarding the di-agnosis of ROP parameters such as plus disease and zone[4–6]. In this current study, we showed that these inter-expert discrepancies extend to aggressive posterior ROP(AP-ROP) [7].On the one hand, we clearly agree with the authorsthat it would help to provide more guidance for prac-ticing ophthalmologists regarding the diagnosis of AP-ROP, plus disease, zone, and stage. We are developing awebsite (http://www.i-rop.com) that will provide a rangeof examples based on our previous studies in this area. WealsobelievetheremaybearoleforrevisedROPclassificationmethods that offer more guidance for ophthalmologists–perhaps by addressing issues such as Bpre-AP-ROP^,andbyprovidingmethodsforquantifyingvascularabnormalityusingcomputer-basedimageanalysis[8].Thatsaid,wealsofeelthatsome of what the authors are describing may reflect the factthat the practice of medicine may inevitably have some qual-itative, nuanced Bart^ that is difficult to capture using stan-dardized classification schemes such as ICROP [9].Wearegratefulthatthisstudyhasstimulatedsomeinterest,and hope to have opportunities to continue working with theauthors, along with other experts in the field, toward advanc-ing the science – as well as the art – of ROP care.

Purpose To evaluate inter-expert and intra-expert agreement on the diagnosis and treatment of retinopathy of prematurity (ROP). Design Prospective intra- and inter-rater reliability analysis. Methods In this multicenter study, 260 wide-field digital photographs of 52 patients were presented to 7 recognized ROP experts on 2 consecutive assessment days 8 weeks apart. Experts were asked to assess the patients for ROP stage, presence of plus disease, presence of aggressive posterior ROP, necessity for treatment, and suggested treatment. Agreement levels were measured with Fleiss' kappa and Cohen's kappa. Results Inter-expert agreement was fair for the ROP stage (κ = 0.24), plus disease (κ = 0.32), and aggressive posterior ROP (κ = 0.35); moderate for the necessity for treatment (κ = 0.41); and fair for the kind of treatment (κ = 0.38). Perfect inter-expert agreement was found in 9.6% of all patients for ROP stage 0–5, 45.1% for ≥ stage 2 ROP, 17.3% for plus disease, 57.7% for aggressive posterior ROP, and 25% for the necessity for treatment. Intra-expert agreement was higher than inter-expert agreement and was moderate for the ROP stage (κ = 0.56) and plus disease (κ = 0.51), moderate to substantial for aggressive posterior ROP (κ = 0.60), moderate for the necessity for treatment (κ = 0.47), and substantial for the kind of treatment (κ = 0.63). Conclusions ROP diagnosis and treatment decisions differ between experts and by 1 expert made on different days, indicating that the grading process is subjective and there is an observer bias when diagnosing ROP. These results could influence current practice in ROP assessment and training, and prompt further refinement of international ROP guidelines.

Importance 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. Objective 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. Design, Setting, and Participants 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. Exposure Digital retinal images. Main Outcomes and Measures Intragrader and intergrader variability and monitoring for temporal drift. Results 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. Conclusions and Relevance 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.

Retinopathy of prematurity (ROP) has been one of the issues about which the specialists have most argued but not compromised to that extent since its first definition. Restricted examination area of the eyes of the premature babies and difficulty of performing examination, and difficulty in achieving sufficient pupil dilatation have precluded the standardization of diagnosis and treatment. Plus disease, defined in 1980 has been used as an important indicator in the diagnosis and treatment of ROP. With a later revision, concepts such as preplus or threshold have been defined, and changes in posterior pole have gained much more importance. Desire of the ROP specialists in using technology towards the diagnosis of plus disease and consensus about the diagnosis has significantly increased in the last 10 years. In this article it was aimed to review the up-to-date studies about the diagnosis and treatment of ROP and plus disease.

Purpose: To study the efficacy of indirect diode laser photocoagulation and cryotherapy in prethreshold retinopathy of prematurity (ROP). Methods: Thirty-six eyes of 18 premature infants less than 34 weeks gestational age and/or less than 1600 g birth weight with prethreshold ROP were prospectively randomized to treatment with either indirect laser photocoagulation or cryotherapy. Prethreshold ROP was defined as any stage of ROP in zone I with plus disease; or stage 3 with three or more contiguous clock hours or five or more total clock hours of involvement of retina in zone II with plus disease but less than threshold disease. Regression of the ROP was assessed for a minimum period of 6 months. Results: Regression of ROP occurred in all 36 eyes (100%) in both groups. Conclusions: Excellent results are achieved if ROP is treated at the prethreshold stage with both indirect laser photocoagulation and cryotherapy. Although laser has definite advantages, cryotherapy can be considered as an alternative modality of treatment in developing countries due to economic reasons.

Background In some cases of retinopathy of prematurity (ROP), it difficult to determine with certainty whether plus disease is present or absent. We have developed a computer program that captures digital images from a video-indirect ophthalmoscope, identifies and traces the major posterior pole blood vessels, measures the dilation and tortuosity of each vessel, and calculates whether or not an eye has plus disease. Our purpose was to determine the accuracy of the computer program in comparison with two masked examiners. Methods A representative sample of posterior pole images from 20 premature infants, 10 normal and 10 representing various degrees of dilation and tortuosity, was extracted from our video database and analyzed by the computer program as well as by two masked examiners experienced in the diagnosis of ROP. The standard photograph from the Cryotherapy for ROP study, representing the minimum degree of dilation and tortuosity required for plus disease, was also digitized, analyzed, and used as a numeric comparison for the automated determination of plus disease. Results Of the five images determined to have plus disease by both examiners, four were calculated to have plus disease by the computer program (80% sensitivity). Of the 11 images without plus disease, 10 were calculated not to have plus disease by the computer program (91% specificity). Conclusions Our computer program has very good sensitivity and specificity compared with masked examiners’ determination of the presence or absence of plus disease. Automated analysis of dilation and tortuosity of posterior pole blood vessels has the potential to remove subjectivity from the determination of plus disease.

We report the effects of intravitreal ranibizumab as salvage therapy in an extremely low-birth-weight (ELBW) infant with rush type retinopathy of prematurity (ROP). This case was a girl of 23 weeks gestational age weighing 480 g at birth. At a postconceptual age of 33 weeks, she presented with zone 1, stage 3 ROP with plus disease. Despite intravitreal bevazucimab and laser photocoagulation, extraretinal fibrovascular proliferation persisted. Intravitreal 0.25 mg (0.025 ml) ranibizumab was injected OU. After treatment, extraretinal fibrovascular proliferation disappeared. Fundus examination showed flat retinas and normal vasculature in both eyes. She has been followed up for 2 years. Intravitreal ranibizumab injection seems effective and well tolerated as salvage therapy in an ELBW infant with rush type ROP. No short-term ocular or systemic side effects were identified. More cases and longer follow-up are mandatory.

Aggressive posterior retinopathy of prematurity is identified as a rare, rapidly progressing and severe form of retinopathy of prematurity (ROP). Here, we report the diagnosis and treatment of aggressive posterior retinopathy of prematurity (APROP) in two of the triplets born at low birth weight and small gestational age. A case concerning two triplets who were born at 31 weeks’ gestational age with low birth weight and reached bilateral threshold APROP was reported. The ROP of triplets A and B had the characteristic features of aggressive diseases, which were posterior location, prominence of plus disease and rapid progression. Low birth weight and small gestational age, multiple pregnancies, pregnancy-induced hypertension and older age of the mother might account for the presentations of APROP. These cases demonstrate the importance of early screening and diagnosis in APROP infants. Prompt and adequate laser photocoagulation with a large number of high-intensity closely performed spots and early retreatment could be effective and safe for preventing the progression of APROP with plus disease in zone 1 or 2 in premature triplets.

The subjective nature of clinical ophthalmology is perhaps nowhere more demonstrable than in the determination of plus disease and aggressive posterior retinopathy of prematurity (APROP) [1–3], in part because the clinical determination of plus disease and the number of vessels in zone 1 is often difficult to determine in a squirming infant. Even photographic screening to detect plus disease and aggressive posterior retinopathy of prematurity has its subjective features, as noted in the article entitled, “Aggressive posterior retinopathy of prematurity: Quantitative analysis of vascular features,” in this issue of Graefes’ Archives for Clinical and Experimental Ophthalmology. The determination of plus disease and number of clock-hours of vessels in zone 1 can predict a rapid course to severe retinopathy of prematurity (ROP), with retinal detachment and possible lifelong blindness. The higher the number of clock-hours of vessels in zone 1, the greater the likelihood of progressive disease. A standardized computerized method of detection of plus disease and exact sizing of zone 1 disease based on photographic imaging would be helpful in allowing the clinician to study the images carefully and provide more accurate management for the infant. In the study in this issue of von Graefes’ Archives, a single posterior pole picture was presented to readers. Does this really represent enough data, or would a montaged image of more of the retina with complete zone 1 determination at least give the readers more confidence of their opinion? It seems that more objective plus disease determination and rapidity of treatment would have a positive effect on the outcomes. The ability to use images from wide-angle cameras and computerized software to reach an objective determination of APROP and plus disease maymove ROP treatment forward in a global fashion [4, 5]. As ROP experts are in short supply worldwide, and the medical malpractice risk of ROP drives doctors further and further from ROP care in much of the world, such a determination with computerized aids may afford less experienced doctors a higher level of confidence to be able to supply accurate interpretation of ROP images. Although further validation studies are needed, the authors are to be congratulated for the excellent pilot study, which shows us the way for the future for ROP care. This type of photographic documentation and computer-linked vascular measurement can create a global standard of care that will revolutionize ROP management and reduce blindness for children that are at risk worldwide.

Changes in retinal vessel width can be indicative of the presence of several diseases, such as diabetic retinopathy, retinopathy of prematurity (ROP), and hypertension. Accurate detection and measurement of such changes could help in computer-aided diagnosis. An increase in venular thickness is a sign of plus disease, which warrants treatment of ROP. We present image processing methods for detection, tracking, and measurement of the width of the major temporal arcade (MTA), which is the thickest branch of the venular vessels, in retinal fundus images of preterm infants. The methods include the use of Gabor filters for the detection of the blood vessels, as well as morphological image processing for tracking and measurement of the width of the MTA. The results indicate a statistically significant difference in vessel width of normal cases as compared to cases diagnosed with plus disease (p = 0.015).

Objective.To evaluate whether patients with rheumatoid arthritis who did not respond sufficiently to tocilizumab (TCZ) plus disease-modifying antirheumatic drug (DMARD) treatment by Week 8 responded at later timepoints when continuing to take their original dose of TCZ.Methods.In this posthoc analysis of data from phase III randomized controlled trials of inadequate responders (IR) to DMARD or tumor necrosis factor-α inhibitors (anti-TNF), percentages of patients meeting early response criteria were calculated by randomized treatment arm (TCZ 4 mg/kg, 8 mg/kg, or placebo in combination with DMARD). Percentages of patients achieving certain disease activity thresholds at later timepoints were calculated for patients who had/had not achieved response by Week 8.Results.In DMARD-IR early nonresponders, 29.0%, 17.2%, and 3.7% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved 28-joint Disease Activity Score (DAS28) ≤ 3.2 by Week 24. Among anti-TNF-IR patients without early response, 26.5%, 8.5%, and 1.9% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved DAS28 ≤ 3.2 at Week 24.Conclusion.A substantial number of DMARD-IR patients taking TCZ 4 or 8 mg/kg and anti-TNF-IR patients taking TCZ 8 mg/kg who failed to respond by 8 weeks benefited from continued TCZ treatment in combination with DMARD. In contrast, the anti-TNF-IR patients without early responses who continued to take TCZ 4 mg/kg were unlikely to experience a cumulative benefit. ClinicalTrials.gov registration numbers: NCT00106548, NCT00106574, NCT00106535, NCT00106522.

BACKGROUND AND OBJECTIVE: Plus disease is the primary indication for retinopathy of prematurity (ROP) treatment, but in borderline cases ophthalmologists may struggle to judge whether it is present. ROPtool is a semi-automated computer program that objectively assesses plus disease by measuring retinal vascular tortuosity and width. This study determined ROPtool’s bedside diagnostic accuracy concurrent with ROP screening. PATIENTS AND METHODS: ROP screening examinations were recorded using Keeler video indirect ophthalmoscopy. A masked operator traced images in ROPtool at the bedside, comparing ROPtool’s plus diagnosis to the examiner’s clinical judgment. RESULTS: Four hundred sixty-four examinations (129 eyes of 65 infants) were performed. ROPtool’s sensitivity, specificity, and area under the receiver operating characteristic curve for plus diagnosis was 71% (CI: 38%–100%), 93% (CI: 89%–98%) and 0.87, and for pre-plus or worse was 68% (CI: 51%–85%), 82% (CI: 77%–86%) and 0.81, respectively. CONCLUSION: ROPtool can provide a real-time second opinion of plus disease at the bedside. Image enhancement technologies may further improve ROPtool’s diagnostic accuracy. [ Ophthalmic Surg Lasers Imaging Retina . 2014;45:542–548.]

138 premature infants born 1989–1991 have been examined by the ophthalmologist in Children's Hospital, University of Helsinki. The mean gestational age was 27.3 weeks and the mean birth weight 986 grams. Twenty-four cases of ROP were found. Seven of them got cryocoagulation treatment in both eyes for ROP 3 with plus disease. Only one child became blind. The risk to get ROP was 17.4% in the whole material and was highest among the most immature infants. The cryocoagulation treatment appeared an effective therapy to prevent blindness.

Introduction Serial digital photographic examinations have been combined into a video format, which shows development and evolution of the disease over time. This dynamic format has changed the teaching of retinopathy of prematurity (ROP) by illustrating the subtle changes in the temporal arcade angle and choroidal vascular pattern, which can be observed over time in these videos. Methods Consecutive weekly or biweekly images were obtained on the same infant and were captured using digital retinal photography (RetCam 120) and then archived on compact discs. Those infants that were most photographic and demonstrative of the evolution of ROP were selected for animation. The optic nerve vessels were aligned and image border blended into the previous image using a layer mask, thus creating an animation of consecutive images. Discussion The videos highlight the evolving features of ROP, such as development of arborized vessels posterior to the ridge, development of Stage 3 lesions, progression of plus disease, choroidal vascular changes accompanying the progression of ROP, dynamic changes in the temporal arcade angle, and regression of disease following last photocoagulation. Conclusions The documentation of this disease as it evolves and its presentation in video format, using digital retinal photographic technology, has allowed subtle anatomical changes to be visualized and potentially studied. This process highlights a new dimension of the dynamic nature of the disease for those involved in the care of an infant with ROP.

We present a patient with retinopathy of prematurity (ROP) who received panretinal photocoagulation (PRP), but in whom plus disease developed, likely secondary to a complicated cardiovascular history, including DiGeorge syndrome and tetralogy of Fallot. Interventional case report with clinical and angiographic correlation. Our patient had been born at 29 weeks and 2 days gestational age with a birthweight of 940 grams, tetralogy of Fallot, DiGeorge syndrome, and major aortopulmonary collaterals. Type 1 Early Treatment for Retinopathy of Prematurity ROP (zone 2, stage 2 with plus) developed, requiring PRP. Worsening plus disease developed and mild further PRP was performed. Despite this, plus disease persisted. We report plus disease even after appropriate PRP therapy for ROP. In this case, it is likely the patient's cardiovascular diseases that caused the persistent plus disease. Vascular tortuosity can be due to a number of different systemic disorders, so it is important to consider an infant's systemic conditions in the evaluation of ROP.

Background In retinopathy of prematurity (ROP), tortuosity of vessels near the posterior pole of the fundus is an important clinical sign, yet clinicians have difficulty estimating how tortuous the vessels are. Methods The authors have devised an objective, numeric index of retinal blood vessel tortuosity that is especially sensitive to the structural changes in vessels that occur in ROP, but it is not particularly sensitive to non-ROP changes. Computer software is used to calculate the index from fundus images; the quality of these images is typical of photographs or video-cassette frames that the authors record in the premature nursery. Results The index reliably segregates tortuous vessels from nontortuous ones and separates eyes that reach ROP treatment threshold from eyes that do not. Conclusions The index forms an objective measure of the ROP disease state. Its calculation requires only segments of vessels and thus, is potentially adaptable to imaging systems that automatically extract vessel portions from fundus images.

Purpose: To examine the impact of retinal field of view and magnification on interexpert reliability of plus disease diagnosis in retinopathy of prematurity. Methods: Fifteen wide-angle images from infants with retinopathy of prematurity were cropped and adjusted in magnification to create 2 additional image categories: medium angle (40°–50°) and narrow angle (20°–30°). These 45 images were uploaded to a Web-based system and interpreted independently by 13 experts of retinopathy of prematurity using a 3-level (plus, preplus, neither) and 2-level (plus, not plus) classification. Absolute agreement and kappa statistics were calculated to compare interexpert reliability. Results: In the 3-level classification, ≥70% experts agreed on the same diagnosis in 8 of the 15 wide-angle images (53%), but only in 3 of the 15 medium-angle (20%) and 3 of the 15 narrow-angle (20%) images. In the 2-level classification, ≥80% experts agreed on the same diagnosis in 11 of the 15 wide-angle images (73%), but only in 9 of the 15 medium-angle (60%) and 3 of the 15 narrow-angle (20%) images. Mean kappa of each expert compared with all other experts was 0.40 to 0.59 in 8 of 13 experts (62%) using wide-angle images, was 0 to 0.19 in 7 of 13 experts (54%) using medium-angle images, and was 0.20 to 0.39 in 9 of 13 experts (69%) using narrow-angle images. Conclusion: Interexpert agreement in plus disease diagnosis in wide-angle images is higher than from medium-angle and narrow-angle images. Plus disease is defined using a narrow-angle standard published photograph, yet this study suggests that peripheral findings also contribute to diagnosis.

Effective treatment for retinopathy of prematurity is based on good screening for ROP. This screening can be done either at the bedside or photographically and customarily involves screening in lower birth weight children. Screening should begin at approximately 31 weeks postmenstrual age and in our hands is continued until about 50 weeks. Screening looks for staging, zones, and plus disease, which can constitute high risk features originally described in the Cryo ROP Study, but more recently in the ETROP Study, which lead to approximately a failure rate of 9% of existing laser treatments.