Photopic Negative Response in Pseudoexfoliation Syndrome and Pseudoexfoliative Glaucoma.

PRECIS: PhNR amplitudes and implicit times demonstrated graded functional impairment from controls to PXS and PXG, highlighting PhNR as a sensitive tool for detecting early inner retinal dysfunction and differentiating pseudoexfoliation stages. PURPOSE: To evaluate photopic negative response (PhNR) parameters across the pseudoexfoliation spectrum and determine whether PhNR can identify early retinal ganglion cell dysfunction in pseudoexfoliation syndrome (PXS) before the onset of pseudoexfoliative glaucoma (PXG). METHODS: This cross-sectional study included 93 eyes: 35 with PXG, 28 with PXS, and 30 healthy controls. PhNR was recorded using an extended ISCEV protocol with red-on-blue full-field electroretinography. PhNR peak-to-trough (PT) and baseline-to-trough (BT) amplitudes and implicit times were measured. Group comparisons, correlation analyses with visual field indices, and receiver operating characteristic (ROC) analyses were performed. RESULTS: PXG eyes exhibited significantly prolonged implicit times and reduced amplitudes in a-, b-, i-wave, and PhNR measures compared with both PXS and control eyes (all P<0.05). Compared with controls, PXS eyes showed significantly longer PhNR implicit times and reduced amplitudes, except for i-wave amplitude and PhNR BT amplitude, which were not significant (all P<0.05). In PXG eyes, PhNR implicit time correlated negatively with MD (r=-0.537, P=0.015) and VFI (r=-0.501, P=0.024), while PhNR PT amplitude correlated positively with VFI (r=0.591, P=0.006). ROC analysis indicated that PhNR PT amplitude as the strongest discriminator between PXG and controls (AUC=0.908, P<0.001). PhNR BT and PT amplitudes moderately differentiated PXG from PXS (AUC=0.699, P=0.011; AUC=0.664, P=0.028; respectively). CONCLUSION: PhNR effectively detected inner retinal dysfunction across the pseudoexfoliation spectrum and showed a progressive decrease from controls to PXS and PXG. PhNR may serve as a valuable adjunctive biomarker for risk stratification and early detection of glaucomatous transformation in PXS.