An OCT-based Structural Evaluation Framework for Laser-Induced Retinal Lesions in Mice and Exploratory Application Under ALDH2 Modulation

Laser-induced retinal injury models require structural assessments that capture lesion heterogeneity. We developed a five-dimensional optical coherence tomography (OCT) framework and explored its application under aldehyde dehydrogenase 2 (ALDH2) modulation. Following 532-nm left-eye photocoagulation, mice received dimethyl sulfoxide vehicle, Alda-1, or Daidzin intraperitoneally for seven days. OCT, fundus photography, and fluorescein angiography were performed 24 h after the final dose. The framework integrated morphologic classification, five-domain severity scoring, lesion geometry, layer-specific thickness and normalized area under the thickness-distance curve (AUC), and anatomically matched contralateral comparisons. Thirty-six lesions from nine mice were analyzed. Classification and scoring showed high interobserver agreement (κ = 0.839; intraclass correlation coefficient = 0.925). After Benjamini-Hochberg adjustment, severity score was the only tested outcome differing significantly among subtypes; eight of 45 structural correlations were significant. In 32 matched pairs, all six thickness comparisons showed significantly lower lesion-eye values. Correlations between local thickness and normalized AUC were significant after contralateral subtraction for outer retinal and outer nuclear layer measurements at the lesion level, whereas absolute correlations were nonsignificant; only the former remained significant at the mouse level. Alda-1 and Daidzin differed in subtype composition. Mouse-clustered models indicated lower scores, greater outer nuclear layer first-point thickness, and larger margin angles with Alda-1, but mouse-level comparisons were nonsignificant. Normalized AUC and its contralateral differences showed no significant treatment differences at either level. This framework integrates qualitative, semiquantitative, and quantitative assessments to characterize OCT-visible structural features in mouse retinal laser injury models.