A combined ex vivo fundus imaging-histology protocol for clinicopathological validation of human donor eyes with limited medical history.

This study evaluated a combined ex vivo fundus imaging-histology protocol to improve accuracy of diagnosis in human donor eyes with limited medical history. Fifty-one formalin-fixed eyes from 32 donors underwent a standardised workflow comprising ex vivo fundus photography, selective spectral-domain optical coherence tomography (SD-OCT), and comprehensive histological examination. Medical/surgical retinal ophthalmologists independently reviewed imaging, while ophthalmic pathologists performed masked histological assessment. Diagnostic metrics were calculated using histology as the reference standard. Ex vivo imaging identified definitive pathology in 10 of 51 eyes (19.6%) and possible abnormalities in 4 eyes (7.8%). Histological analysis, however, revealed definitive pathology in 20 eyes (39.2%), detecting a broader range of diseases, including early age-related macular degeneration, hypertensive vasculopathy, and a rare choroidal tumour. Concordance was observed in 27 eyes (52.9%), mainly where no pathology was present. Significant discordance occurred in 24 eyes (47.1%), comprising 13 false negatives and 11 false positives (including misclassified pathology). Consequently, the sensitivity and specificity of ex vivo imaging for detecting pathology were 18.8% and 68.6%, respectively. While ex vivo imaging is a practical screening tool, imaging alone may miss or misclassify pathology due to postmortem artefacts and a lack of validated interpretive criteria. A combined imaging-histology approach validates the limited tissue available from eye-bank programs and maximises research value.