Correlation of optical coherence tomography and histology in a laser-induced mouse retinal injury model

Understanding the origins of structural features observed in optical coherence tomography (OCT) is essential for improving interpretation of retinal biomarkers. We have developed a workflow to correlate in vivo OCT and OCT angiography with ex vivo histochemistry in a mouse model of laser-induced retinal injury. Adaptive optics OCT provided high-resolution volumetric imaging of lesions, while retinal tissues were subsequently cleared, stained, and imaged with confocal microscopy. A digital tissue-flattening procedure and a two-stage registration pipeline enabled mapping of confocal volumes to OCT datasets using the deep capillary plexus as a structural landmark. Across multiple lesions and animals, hyper-reflective foci (HRF) on OCT co-localised with IB4-positive structures, although inter-lesion variability in the degree of feature correspondence was observed. This framework provides an approach for validation of OCT features to enhance the biological interpretability of retinal imaging biomarkers.