Region-specific ischemia, neovascularization and macular oedema in treatment-naïve proliferative diabetic retinopathy

Abstract Importance Region‐specific pathology in proliferative diabetic retinopathy enhances our understanding and management of this disease. Background To investigate non‐perfusion, neovascularization and macular oedema. Design A cross‐sectional, observational, non‐randomized study. Participants Consecutive 43 eyes of 27 treatment‐naïve patients. Methods Ultra‐widefield fluorescein angiography for studying specific zones, that is, far‐peripheral zone, mid‐peripheral zone and central retina (cr), and spectral‐domain optical coherence tomography for analysing thickness of macular layers. Main Outcome Measures Non‐perfusion index (NPI) and neovascularization index (NVI) in different zones, thickness of cr, retinal nerve fibre layer, ganglion cell layer (GCL), inner nuclear layer (INL) and outer plexiform layer in parafoveal regions. Results The NPI of far‐periphery and NVI of mid‐periphery were the highest by one‐way analysis of variance testing. Ischemic retina defined as high NPI in far‐periphery was significantly related to macular oedema via a binary classification approach ( P < 0.05). The ischemic retina was correlated with a decreased thickness of both retinal nerve fibre and GCL ( P < 0.05); macular oedema was correlated with increased INL thickness ( P < 0.0001). Conclusions and Relevance The region‐specific correlation of NPI of far‐periphery and NVI of mid‐periphery, but not with central retinal thickness, suggests different pathogeneses of neovascularization and macular oedema. Retinal nerve fibre layer and GCL, both biomarkers of diabetic retinal neuronopathy, are associated with retinal ischemia, but not with macular oedema, suggesting that diabetic microangiopathy and neuronopathy possess distinct pathogenic pathways. The strong correlation between macular oedema and INL indicates that intracellular oedema is a determining factor of diabetic macular oedema.