Grid-Based Software for Quantification of Diabetic Retinal Nonperfusion on Ultra-Widefield Fluorescein Angiography

Background/Objectives: Fluorescein angiography (FA) is essential for diagnosing and managing diabetic retinopathy (DR) and other retinal vascular diseases and has recently demonstrated potential as a quantitative tool for disease staging. The advent of ultra-widefield (UWF) FA, allowing visualization of the peripheral retina, enhances this potential. Retinal hypoperfusion is a critical risk factor for proliferative DR, yet quantifying it reliably remains a challenge. Methods: This study evaluates the efficacy of the Michigan grid method, a software-based grading system, in detecting retinal hypoperfusion compared to the traditional freehand method. Retinal UWF fluorescein angiograms were obtained from 50 patients, including 10 with healthy retinae and 40 with non-proliferative DR. Two independent, masked graders quantified hypoperfusion in each image using two methods: freehand annotation and a new Michigan grid method. Results: Using the Michigan grid method, Grader 1 identified more ungradable segments, while Grader 2 identified more perfused and nonperfused segments. Cohen's weighted kappa indicated substantial agreement, which was slightly higher for the entire retina (0.711) compared to the central retinal area (0.686). The Michigan grid method shows comparable or slightly improved inter-rater reliability compared to the freehand method. Conclusions: This study demonstrates a new Michigan grid method for the evaluation of FA for hypoperfusion while highlighting ongoing challenges in achieving consistent and objective retinal nonperfusion assessment, underscoring the need for further refinement and the potential integration of automated approaches.