Introduction and Context
Glaucoma is a leading cause of irreversible vision loss worldwide. Clinicians rely on a combination of structural imaging (optical coherence tomography, OCT), visual field testing (standard automated perimetry, SAP), and clinical examination to detect and monitor glaucomatous optic neuropathy. Visual electrophysiology—objective tests that measure retinal and visual pathway function—has long been explored as a complementary approach to identify retinal ganglion cell (RGC) dysfunction earlier than perimetry or to clarify ambiguous cases.
In June 2026 the American Academy of Ophthalmology (AAO) published a focused evidence review: “Visual Electrophysiology for the Diagnosis of Glaucoma.” This report systematically evaluated contemporary literature (search through August 2025) and synthesized how electroretinography (ERG) variants and visual evoked potentials (VEP) perform for glaucoma diagnosis. The AAO panel concluded that electrophysiology shows promise but is not yet ready for routine clinical use. This article summarizes that report’s rationale, core recommendations, evidence strength, practical implications, and areas for future work.
Why this report was issued
– Clinical gap: Structural tests (OCT) detect RNFL thinning while functional tests (SAP) often lag, creating diagnostic uncertainty for early or preperimetric glaucoma. Objective electrophysiologic measures could, in theory, bridge structure–function discordance.
– New evidence: Since the previous syntheses, a spate of studies evaluated pattern electroretinography (PERG), the photopic negative response (PhNR) of the full-field ERG, multifocal VEP (mfVEP), and conventional VEP for glaucoma detection.
– Implementation uncertainty: Despite promising study results, adoption has been limited because of heterogeneous stimulation/analysis protocols, small studies, technical complexity, and lack of standardized reference ranges. The AAO convened a systematic review panel to judge readiness for clinical recommendation.
New Guideline Highlights (AAO 2026)
– Main conclusion: Visual electrophysiology tests are not recommended for routine glaucoma diagnosis at present.
– Selective use: Electrophysiology may be considered as an adjunct in specific clinical scenarios to augment structural and functional assessments.
– Test-specific findings:
– Pattern electroretinography (PERG): May detect early RGC dysfunction and help identify preperimetric glaucoma, especially when OCT shows RNFL thinning but SAP is normal.
– Photopic negative response (PhNR): Shows sensitivity to glaucomatous RGC loss with fewer fixation and media clarity requirements than PERG, making it attractive clinically.
– Visual evoked potentials (VEP/mfVEP): Can discriminate glaucoma from controls and may localize visual pathway deficits but are technically demanding and variable.
– Evidence grading: Of 20 studies synthesized, 0 were level I, 1 was level II, and 19 were level III (lower-level evidence; mostly observational studies, small cohorts).
Key takeaways for clinicians:
– Consider electrophysiology only as a complementary tool in select cases (see below).
– Do not replace OCT or perimetry with electrophysiology for routine diagnosis or monitoring.
– Be mindful of technical, logistical, and normative-data limitations that limit interpretability.
Updated Recommendations and Key Changes
Compared with prior practice (where electrophysiology was discussed but rarely integrated), the AAO report provides a more definitive position based on a systematic review of recent literature. Major changes include:
– Clearer stance against routine adoption due to insufficient high-level evidence and lack of standardization.
– Recognition of PhNR as an emerging, more clinically robust ERG metric compared with PERG in some contexts.
– Emphasis on mfVEP’s diagnostic potential but practical barriers (time, expertise, reproducibility) that hinder widespread use.
Why these updates: New studies through 2025 expanded experience with PhNR and mfVEP, but most lacked multicenter validation, consistent protocols, or adequate normative databases — limiting generalizability.
Topic-by-Topic Recommendations
Diagnostic role
– Recommendation: Do not routinely use electrophysiology (PERG, PhNR, VEP/mfVEP) as first-line diagnostic tests for glaucoma (AAO recommendation based on systematic review).
– Evidence context: Studies show discriminatory ability between glaucoma and controls, and PERG/PhNR often correlate with structural RNFL loss, but evidence is largely observational (levels II–III).
When to consider electrophysiology (select scenarios)
– Preperimetric glaucoma suspicion: When OCT demonstrates RNFL or ganglion cell–inner plexiform layer (GCIPL) thinning but SAP is normal, PERG or PhNR may add objective functional evidence of RGC dysfunction.
– Unreliable or nonrepeatable perimetry: When visual field testing is inconsistent or impossible (cognitive impairment, poor fixation), ERG-derived PhNR can provide objective assessment.
– Confounding media or fixation issues: PhNR (full-field) tolerates modest media opacity and less steady fixation better than PERG, making it preferable when fixation is poor.
– Disputed functional deficits: In cases of suspected nonorganic visual loss or when structure–function discordance persists, mfVEP or PERG might help clarify whether true visual pathway dysfunction exists.
Test selection, interpretation, and limitations
– PERG: Sensitive to macular RGC dysfunction and early glaucoma. Requires stable fixation and clear media. Standardized stimulation and reference ranges are variable between centers.
– PhNR (full-field ERG): Captures a cone-driven negative component reflecting RGC activity. Less dependent on fixation; might be better suited for broader clinical application; protocols require harmonization.
– mfVEP: Offers topographical mapping of visual pathway function and may detect localized defects corresponding to visual field loss. Technical complexity and susceptibility to noise are barriers.
Follow-up and monitoring
– Recommendation: Continue to use OCT and SAP as primary tools for longitudinal monitoring. Electrophysiology may be repeated in specialized centers where baseline abnormality was established and where changes might influence management.
Special populations
– Pediatric patients: Electrophysiology can be useful when perimetry is not feasible; however, normative pediatric databases and age-related changes must be respected.
– Media opacity or poor fixation: Prefer PhNR over PERG when fixation or media clarity is suboptimal.
Practical Implementation: What clinicians need to know
Barriers to routine clinical use:
– Lack of standardized stimulation/analysis protocols across devices and centers.
– Limited normative databases and variable reference ranges.
– Equipment cost and need for trained electrophysiology technicians and interpreting physicians.
– Time intensity for testing (mfVEP, PERG) and patient cooperation requirements.
If a practice chooses to use electrophysiology:
– Use ISCEV-compliant protocols where available and document deviations.
– Establish in-house or regional normative data that match patient demographics and equipment.
– Interpret electrophysiology results in the context of OCT, SAP, IOP, and clinical exam; do not make management decisions on electrophysiology alone.
Expert Commentary and Controversies
The AAO panel — composed of ophthalmic clinicians, electrophysiologists, and a methodologist — emphasized both optimism and caution. Paraphrased expert perspectives include:
– “Electrophysiology offers objective, physiologic assessment of RGC function that can complement structural imaging, particularly in ambiguous cases.” (panel sentiment)
– “However, the field needs multicenter, prospective studies and harmonized protocols before we can recommend routine adoption.” (consensus)
Areas of controversy and ongoing debate:
– Which metric is best? PERG has been studied longest for preperimetric changes; PhNR may be less sensitive to testing conditions and therefore more clinically feasible. Head-to-head multicenter comparisons are lacking.
– Standardization: Device manufacturers, clinical centers, and societies disagree on a single protocol. ISCEV standards provide a foundation for ERG/VEP testing, but disease-specific adaptations for glaucoma are not universally agreed.
Future research priorities identified by the panel:
– Prospective, multicenter trials comparing PERG, PhNR, mfVEP against longitudinal structural and functional outcomes.
– Development of standardized stimulation and analysis protocols with normative databases stratified by age and ocular media status.
– Evaluation of cost-effectiveness and impact on clinical decision-making when electrophysiology is added to current diagnostic pathways.
Practical Case Illustration
Case vignette: Sarah, a 62-year-old accountant, has unilateral RNFL thinning on OCT but two reliable normal SAP tests. IOP is borderline. How might electrophysiology be used?
– Application: In a center offering PhNR and PERG, the clinician orders PhNR given Sarah’s slightly unstable fixation and mild cataract. A reduced PhNR amplitude compared with age-matched norms provides objective evidence of RGC dysfunction, supporting a diagnosis of early glaucoma. Management is discussed in the context of all findings; electrophysiology supports, but does not dictate, starting IOP-lowering therapy.
Practical Implications for Practice
– Most general ophthalmology and glaucoma clinics should continue to rely primarily on OCT and SAP for diagnosis and monitoring.
– Tertiary centers and research programs should consider electrophysiology when: addressing structure–function discordance, evaluating patients unable to perform perimetry, or participating in studies to validate electrophysiologic biomarkers.
– Health systems contemplating investment in electrophysiology should weigh equipment/training costs against the current evidence base and local referral needs.
References
– Ou Y, Chopra V, Rosdahl JA, Richter GM, Knight OJ, Solá-Del Valle D, Takusagawa HL, Kim SJ, WuDunn D. Visual Electrophysiology for the Diagnosis of Glaucoma: A Report by the American Academy of Ophthalmology. Ophthalmology. 2026 Jun 12. PMID: 42287272. https://pubmed.ncbi.nlm.nih.gov/42287272/
– European Glaucoma Society. Terminology and Guidelines for Glaucoma, 5th Edition. Br J Ophthalmol. 2020;104(Suppl 1):1–169.
– McCulloch DL, Marmor MF, Brigell MG, et al. ISCEV Standard for full-field clinical electroretinography (2015 update). Documenta Ophthalmologica. 2015;130(1):1–12.
– Porciatti V. Electrophysiological assessment of retinal ganglion cell function. Prog Retin Eye Res. 2015;46:1–20. (Review on PERG/PhNR physiology and clinical relevance.)
Note: The AAO report synthesizes studies up to August 2025; clinicians should monitor for new randomized or multicenter validation studies that could alter recommendations.
Conclusions
The AAO 2026 report places visual electrophysiology in a supporting role for glaucoma diagnosis: promising and useful in select clinical situations but not yet ready to displace established structural and functional assessments. The path forward requires standardization, larger multicenter validation studies, and development of robust normative datasets. For now, electrophysiology is best applied judiciously in specialized centers and research settings, where it can contribute objective physiologic data to resolve challenging diagnostic dilemmas.
