Photopic negative response (PhNR) of the full-field electroretinogram as a biomarker of retinal ganglion cell loss in glaucoma: a systematic review and meta-analysis.

PURPOSE: The photopic negative response (PhNR) of the full-field electroretinogram reflects retinal ganglion cell (RGC) function and is reduced in glaucoma, yet no quantitative synthesis of PhNR amplitude data across glaucoma studies exists. METHODS: PubMed, Embase, Web of Science, Scopus, and Cochrane Central were searched from inception to February 2025 for studies reporting full-field PhNR amplitude in glaucoma patients versus healthy controls. Random-effects meta-analysis (DerSimonian-Laird) was performed. Subgroup analyses examined glaucoma subtype (POAG, NTG, OHT/suspect), disease severity, and recording methodology. Meta-regression assessed intraocular pressure (IOP) as a moderator. Publication bias was evaluated by Egger and Begg tests. Quality was assessed using the Newcastle-Ottawa Scale. RESULTS: Twenty-eight studies (2847 eyes: 1624 glaucoma, 1223 controls) met inclusion criteria. Glaucoma patients demonstrated significantly reduced PhNR amplitude versus controls (pooled standardized mean difference [SMD] = - 37.82 μV, 95% CI - 40.14 to - 35.50, p < 0.001; I2 = 58.4%). Reduction was proportional to disease severity: early glaucoma (SMD = - 21.0 μV), moderate (- 38.4 μV), and advanced (- 56.5 μV). NTG showed significant but smaller reduction (SMD = - 25.4 μV, p < 0.001) than POAG (- 38.1 μV). Meta-regression demonstrated a significant association between IOP and PhNR reduction (β = - 2.1 μV per mmHg, p < 0.001). No significant publication bias was detected (Egger p = 0.084). CONCLUSIONS: PhNR amplitude is a sensitive, non-invasive electroretinographic biomarker of RGC loss in glaucoma, reduced proportionally to disease severity and IOP. These findings support incorporation of PhNR into glaucoma electrophysiological assessment protocols. PROSPERO: CRD420261487121.