Dynamic and Structural Retinal Microvascular Alterations After Radiation Exposure: Insights From a Large-Animal Model

Purpose: To investigate the effects of acute radiation exposure on retinal microvascular health using the New Zealand White Rabbit (NZWR) model, aiming to enhance understanding of vascular response to total body irradiation (TBI). Methods: This research involved two phases: a repeatability assessment of imaging metrics and evaluating changes after TBI. Advanced imaging modalities, including fluorescein angiography, laser speckle contrast imaging (LSCI), and optical coherence tomography, were used for characterizing the static and dynamic attributes of retinal blood flow. Results: In phase I, six NZWRs were imaged over 2 years to validate repeatability and reproducibility. Vessel density metrics derived from fluorescein angiography exhibited moderate to high reliability, with intraclass correlation coefficients of 0.69 to 0.71. Dynamic LSCI metrics, including blood flow velocity index and related parameters, demonstrated varying levels of repeatability, with the Resistivity Index showing the greatest consistency. In phase II, 11 NZWRs underwent imaging at baseline and at 7 longitudinal time points after TBI. There were significant changes in heart rate-adjusted LSCI metrics at various postradiation days compared with baseline measurements in different vascular areas. Conclusions: This study validates retinal imaging tools in the NZWR model and longitudinally assesses radiation-induced vascular changes. Our findings support the candidacy of the NZWR retina as a robust model for studying the short- and long-term effects of diseases, medical interventions, and harmful stimuli such as radiation on microvascular status, with potential applications in understanding systemic vascular conditions and neurodegenerative diseases.