Purpose To examine the impact of retinal field of view and magnification on inter-expert reliability of plus disease diagnosis in retinopathy of prematurity (ROP). Methods 15 wide-angle images from infants with ROP were cropped and adjusted in magnification to create two 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 ROP experts using a 3-level (plus, pre-plus, neither) and 2-level (plus, not plus) classification. Absolute agreement and kappa statistics were calculated to compare inter-expert reliability. Results In the 3-level classification, ≥70% experts agreed on the same diagnosis in 8/15 (53%) wide-angle images, but only in 3/15 (20%) medium-angle and 3/15 (20%) narrow-angle images. In the 2-level classification, ≥80% experts agreed on the same diagnosis in 11/15 (73%) wide-angle images, but only in 9/15 (60%) medium-angle and 3/15 (20%) narrow angle images. Mean kappa of each expert compared to all other experts was 0.40–0.59 in 8/13 (62%) experts using wide-angle images, was 0–0.19 in 7/13 (54%) experts using medium-angle images, and was 0.20–0.39 in 9/13 (69%) experts using narrow-angle images. Conclusions Inter-expert 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.

Purpose To review findings from the authors’ published studies involving telemedicine and image analysis for retinopathy of prematurity (ROP) diagnosis. Methods Twenty-two ROP experts interpreted a set of 34 wide-angle retinal images for presence of plus disease. For each image, a reference standard diagnosis was defined from expert consensus. A computer-based system was used to measure individual and linear combinations of image parameters for arteries and veins: integrated curvature (IC), diameter, and tortuosity index (TI). Sensitivity, specificity, and receiver operating characteristic areas under the curve (AUC) for plus disease diagnosis were determined for each expert. Sensitivity and specificity curves were calculated for the computer-based system by varying the diagnostic cutoffs for arterial IC and venous diameter. Individual vessels from the original 34 images were identified with particular diagnostic cutoffs, and combined into composite wide-angle images using graphics editing software. Results Expert sensitivity ranged from 0.308–1.000, specificity from 0.571–1.000, and AUC from 0.784 to 1.000. Among computer system parameters, one linear combination had AUC 0.967, which was greater than that of 18 of 22 (81.8%) experts. Composite computer-generated images were produced using the arterial IC and venous diameter values associated with 75% under-diagnosis of plus disease (ie, 25% sensitivity cutoff), 50% under-diagnosis of plus disease (ie, 50% sensitivity cutoff), and 25% under-diagnosis of plus disease (ie, 75% sensitivity cutoff). Conclusions Computer-based image analysis has the potential to diagnose severe ROP with comparable or better accuracy than experts, and could provide added value to telemedicine systems. Future quantitative definitions of plus disease might improve diagnostic objectivity.

The neurotoxic and gliotoxic effects of glutamate and several glutamate analogues were studied in isolated chick embryo retinas. To facilitate examination of initial pathological events, a short-term incubation system was developed and used for light microscopic and autoradiographic investigation. Low-dose, short-term glutamate treatment of 12-day retinas resulted in a glial-specific lesion in the Müller cells, characterized by extensive cellular edema; at higher concentrations and/or longer treatment times, neurotoxic as well as gliotoxic effects were seen. The early glial damage was identical in appearance to that seen after incubation with DL-alpha-aminoadipate and other reported gliotoxins. No evidence of a similar glial-specific action was seen after administration of kainic acid, although extensive neuronal degeneration did result. Incubation of retinas with tritiated glutamate (3H-glu) revealed a selective uptake of the label by Müller cells. Autoradiographic grains were localized over Müller foot processes at the inner limiting membrane, and by 30 minutes labeled the entire glial system. Prior treatment with neurotoxic levels of glutamate did not alter the autoradiographic localization to glial cells. Possible glial-neuronal interactions and their effect on cytotoxic patterns are discussed.