Structure-Function Relationship Between Handheld Photopic Negative Response and Macular GCIPL Thickness in Chronic Optic Neuropathy

Purpose To determine whether photopic negative response (PhNR) parameters obtained using a handheld electroretinography (ERG) device serve as quantitative indicators of retinal ganglion cell (RGC) function and residual optic nerve integrity in chronic unilateral non-glaucomatous optic neuropathy (ON). Methods In this retrospective observational study, 27 patients (54 eyes) with unilateral chronic ON were examined using handheld full-field photopic ERG (RETeval™, LKC Technologies) without pupil dilation or corneal electrodes. Nine ERG parameters, including the PhNR72 amplitude, PhNR minimum amplitude, P-ratio, and W-ratio were analyzed. Optical coherence tomography (OCT) – derived ganglion cell–inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses, and standard automated perimetry (SAP) indices were acquired on the same day. Linear mixed-effects models accounting for intereye correlation and false discovery rate (FDR) correction were used to assess structure–function relationships. Results ON eyes showed significantly reduced PhNR72 and PhNR minimum amplitudes, and lower P-ratio and W-ratio (all p < 0.01). In multivariable models, the W-ratio was independently associated with GCIPL thickness in the inferotemporal sector (β = 0.45; 95% CI, 0.22–0.68; FDR-adjusted p < 0.05), whereas no significant associations were found with RNFL thickness or SAP indices. Conclusions Handheld photopic ERG–derived PhNR parameters, particularly the W-ratio, selectively reflect RGC soma integrity represented by GCIPL thickness rather than axonal or field-level measures. Thus, portable ERG provides a practical functional biomarker complementary to OCT for evaluating the residual RGC function in chronic optic neuropathy.