1. Copyright restrictions may apply JAMA Ophthalmology Journal Club Slides: Influence of Mosaic Photographs on Retinopathy of Prematurity Patel SN, Klufas MA, Douglas CE, et al; i-ROP Research Consortium. Influence of computer-generated mosaic photographs on retinopathy of prematurity diagnosis and management. JAMA Ophthalmol. Published online September 29, 2016. doi:10.1001/jamaophthalmol.2016.3625

2. Copyright restrictions may apply Introduction Retinopathy of prematurity (ROP) is a vasoproliferative disease that affects the retinas of premature infants. Although disease management standards have been established by evidence-based trials, the availability of ophthalmologists to provide examinations by binocular indirect ophthalmoscopy remains an important barrier to ensuring appropriate ROP care. There has been a growing movement to elucidate the role and usefulness of digital imaging in ROP diagnosis and management, and retinal evaluation through telemedicine interpretation of digital images is becoming an increasingly important component of clinical care for ROP. Contact wide-field imaging systems, such as the RetCam (Clarity Medical Systems), can provide larger fields of view and have been adopted by the pediatric retina community to evaluate the eyes of infants at risk for ROP. Mosaic photographs of multiple individual images captured by the RetCam or a similar device may provide a larger field of view for evaluation compared with individual images captured by these camera systems.

3. Copyright restrictions may apply Design −In this prospective cohort study performed from July 12, 2011, to September 21, 2015, images were acquired from ROP screening at 8 academic institutions, and ROP experts interpreted 40 sets (20 sets with individual fundus photographs with ≥3 fields and 20 computer-generated mosaic photographs) of wide-angle retinal images from infants with ROP. All experts independently reviewed the 40 sets and provided a diagnosis and management plan for each set presented. −Within each image set, experts were asked to choose the zone (I, II, II- posterior, or III), stage (1, 2, 3, 4, or 5), plus (no, pre-plus, or plus), category (mild, type 2 ROP, pre-plus, or treatment-requiring ROP), management (observation, laser only, anti–vascular endothelial growth factor [VEGF] only, laser with anti-VEGF, or surgery), presence of aggressive posterior ROP (yes or no), image quality of the retinal images provided (adequate, somewhat adequate, or not adequate), and confidence (confident, somewhat confident, or not confident) in determining clinical diagnosis based on the retinal images provided. Methods

4. Copyright restrictions may apply Data Analysis ‫For each image set, a reference standard diagnosis (RSD) was determined by combining the clinical diagnosis as determined by indirect ophthalmoscopy with the image-based diagnosis from multiple experienced readers. With use of the RSD, the performance of individual experts was evaluated for each modality (multiple individual photographs and mosaic photographs). These results were then averaged to determine the sensitivity and specificity of each modality for detecting stage 1 disease or worse, stage 2 disease or worse, stage 3 disease or worse, zone I disease, disease in zone I or zone II, pre-plus disease or worse, plus disease or worse, mild ROP or worse, type 2 ROP or worse, and treatment-requiring ROP or not. The unweighted κ statistic was then calculated to measure chance-adjusted agreement for each head-to-head pairing of readers. These results were averaged to determine the mean unweighted κ for each reader in each category. Methods

5. Copyright restrictions may apply Accuracy of ROP Diagnosis by 9 ROP Experts Using Individual Color Fundus Photographs vs 1 Mosaic Photograph Results

6. Copyright restrictions may apply Results Unweighted Mean κ Statistics for Intergrader Agreement of ROP Diagnosis Among 9 ROP Experts Using Individual Color Fundus Images vs 1 Mosaic Photograph

7. Copyright restrictions may apply Results After viewing mosaic photographs, experts altered their choice of management in 42 of 180 responses (23.3%; 95% CI, 17.1%-29.5%). A total of 12 of 42 responses (28.6%; 95% CI, 14.9%-43.2%) changed from observation to laser treatment. Ten of 42 responses (23.8%; 95% CI, 10.9%- 36.7%) changed from observation to anti-VEGF therapy. Five of 42 responses (11.9%; 95% CI, 2.1%-21.7%) changed from laser treatment or anti-VEGF therapy to observation. After experts viewed mosaic photographs for each case, 169 of 180 responses (93.9%; 95% CI, 91.0%-97.4%) indicated that mosaic photographs provided additional clinically useful information for the management of the patient.

8. Copyright restrictions may apply Using a single mosaic photograph, compared to multiple individual photographs, may improve the accuracy of image-based diagnosis of clinically-significant ROP (plus disease and treatment-requiring ROP). Mosaic photographs, compared to multiple individual photographs, may improve intergrader agreement for image-based diagnosis of clinically significant ROP (plus disease, stage 3 or worse). When using a single mosaic photograph, compared to multiple individual photographs, a difference in the sensitivity or intergrader agreement of the image-based diagnosis of zone I was not detected. Comment

9. Copyright restrictions may apply Mosaic photography’s impact on plus disease diagnosis suggests that peripheral vessels may contain information that clinicians use diagnostically even though plus disease has historically been defined based on the posterior pole vessels. Mosaic photographs have the potential advantage of easier image modifications in the form of contrast, color, or tone enhancements to improve visualization of the retina. Mosaic photographs may have utility in improving the telemedical diagnosis of ROP. Comment

10. Copyright restrictions may apply If you have questions, please contact the corresponding author: –R. V. Paul Chan, MD, Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, 1855 W Taylor St, Chicago, IL 60612 (rvpchan@uic.edu). Funding/Support This study was supported by grants R01 EY019474 (Mss Jonas and Ostmo and Drs Chiang and Chan), P30EY010572 (Ms Ostmo and Dr Chiang), and NEI K12 EY021475 (Dr Chau) from the National Institutes of Health; The iNsight Foundation (Ms Jonas and Dr Chan); and unrestricted departmental funding from Research to Prevent Blindness Inc (Drs Patel, Chiang, and Chan and Mss Jonas and Ostmo). Conflict of Interest Disclosures All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Chau reported having a patent pending from work involved from grant K12 EY021475 from the National Eye Institute regarding a retinal imaging system that was not used in this work. Dr Chiang reported being an unpaid member of the Scientific Advisory Board for Clarity Medical Systems. Dr Chan reported being a member of the Scientific Advisory Board for Visunex Medical Systems. No other disclosures were reported. Contact Information