Understanding Disorganization of Retinal Layers and the (potential) role in staging and management of Diabetic Retinal Disease.

PURPOSE: Diabetic retinal disease (DRD) is increasingly recognized as a neurovascular disorder involving both microvascular and neurodegenerative damage. Optical coherence tomography (OCT) biomarkers such as disorganization of retinal inner layers (DRIL) and outer layers (DROL) serve as indicators of neuroretinal injury. This review examines their pathophysiology, clinical importance, and prognostic value. METHODS: A review of experimental and clinical evidence was conducted to evaluate the structural and functional implications of DRIL and DROL as seen on spectral domain OCT (SD-OCT) and OCT-Angiography (OCT-A). The associations between these biomarkers, neurovascular unit (NVU) dysfunction, diabetic macular ischemia (DMI), and visual outcomes were analyzed. RESULTS: DRIL reflects disruption of inner retinal layers involving bipolar, amacrine, horizontal, and Müller cells, associated with impaired synaptic organization and neuroglial dysfunction. It strongly correlates with DR severity and reduced vision, especially with DMI and capillary non-perfusion in the deep capillary plexus. DROL indicates more advanced outer retinal involvement, such as disruption of the ellipsoid zone and photoreceptors, indicative of disease progression. The extent and persistence of DRIL predict visual outcomes and treatment response, often better than traditional metrics. CONCLUSION: DRIL and DROL are key OCT biomarkers of neuroretinal damage, revealing NVU integrity. Their assessment enhances disease staging, prognosis, and treatment decisions, supporting a shift from a purely microvascular model to a neurovascular paradigm in DRD.