Choroidal-Derived Intraretinal Neovascularization Compensates for Diabetic Retinopathy Ischemia via Dual-Pathway Remodeling Post-Pan-Retinal Photocoagulation.

Abstract

To characterize pan-retinal photocoagulation (PRP)-induced hemodynamic alterations across retinal/choroidal layers and between the photocoagulated (PRP area) and nonphotocoagulated (NPRP area) areas in diabetic retinopathy (DR) using ultrawide-field swept-source optical coherence tomography angiography. Prospective longitudinal interventional study. Thirty-seven patients (44 eyes) with severe nonproliferative DR or proliferative DR. Participants underwent fovea-centered 24 mm × 20 mm UWF-SS OCTA at baseline and 3 months post-PRP. Vessel density (VD) was quantified in superficial (SCP), deep (DCP), full retinal, and choroidal capillary plexus (CCP), along with choroidal vascularity index (CVI) in Sattler's/Haller's layers. PRP and NPRP areas were manually segmented for regional comparative analysis. Changes in microvascular parameters (VD, CVI) across retinal/choroidal layers and between PRP/NPRP areas at 3-month follow-up. In NPRP areas, significant VD reductions were observed in the DCP (41.12% ± 4.57% to 38.49% ± 5.61%; P = .001), CCP (46.57% ± 3.80% to 42.66% ± 3.25%; P < .001), and full retinal capillary plexus (Δ = 1.65% ± 6.14%; P = .021), while SCP VD and CVI remained stable. In PRP areas, SCP VD significantly decreased (Δ = 1.22% ± 3.20%; P = .023) with concomitant CVI reduction across all quadrants (all P < .01). Notably, DCP and CCP VD showed no significant changes in PRP areas. Choroidal-derived intraretinal neovascularization (CDIRN) was identified at 72.5% (5085/7013) of photocoagulation scars. Ultrawide-field swept-source optical coherence tomography angiography reveals PRP's dual hemodynamic effects: (1) direct thermodamage evidenced by CVI reduction in the PRP areas, and (2) adaptive autoregulation shown by VD decreases in the NPRP DCP/CCP and PRP SCP. CDIRN formation at laser scars may functionally compensate for DCP/CCP perfusion loss in the PRP area, preserving VD. This dual pathway model (thermodamage + CDIRN-mediated compensation) advances our understanding of how PRP ameliorates retinal hypoxia without inducing ischemic injury.