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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D., Julinka Auta Fernandes

Overview

Visual evoked potentials (VEPs) and optical coherence tomography (OCT) are non-MRI paraclinical studies that can provide objective evidence of optic nerve involvement in a person being evaluated for multiple sclerosis (MS). The 2024 revisions of the McDonald diagnostic criteria, published in 2025, recognize the optic nerve as a fifth anatomical location for demonstrating dissemination in space; appropriately acquired and interpreted VEP or OCT abnormalities may be used to demonstrate this location when there is no better explanation for the finding.

Neither VEP nor OCT is specific for MS, establishes dissemination in time by itself, or should be used as a stand-alone diagnostic test. Results must be interpreted with the clinical presentation and the complete MS diagnostic evaluation, after exclusion of alternative ocular, retinal, optic-nerve, and post-chiasmal disorders.

Other Diagnostic Studies

Findings accepted for optic-nerve involvement

Study	Finding supporting optic-nerve involvement	Important qualification
Pattern-reversal VEP	Delayed absolute latency of the positive peak normally occurring approximately 100 milliseconds after stimulus reversal (P100) or an abnormally increased interocular P100 latency difference. Abnormality should be defined against age-appropriate, laboratory-specific healthy reference data; a value at least 2.5 standard deviations beyond the reference mean is generally used.	The waveform must be technically adequate and reproducible, and there must be no better explanation for the latency abnormality. P100 amplitude reduction alone is not the stated VEP criterion in the 2024 McDonald revisions.
OCT	An inter-eye difference of at least 6 µm in mean peripapillary retinal nerve fiber layer (pRNFL) thickness or at least 4 µm in macular ganglion cell and inner plexiform layer (GCIPL) thickness supports unilateral or asymmetric optic-nerve injury.	Validated acquisition and segmentation, rigorous quality control, and exclusion of ocular or retinal causes are required. Inter-eye thresholds have limited sensitivity for bilateral symmetric optic-nerve injury.

Visual evoked potentials

• VEPs record the occipital cortical electrical response to visual stimulation. In MS, demyelination of the anterior visual pathway typically produces delayed conduction, reflected by prolongation of the P100 peak latency. VEPs can demonstrate residual dysfunction after symptomatic optic neuritis and can reveal clinically silent optic-nerve involvement.
• A monocular pattern-reversal checkerboard VEP is the preferred standard test when visual acuity, fixation, and cooperation permit. The current International Society for Clinical Electrophysiology of Vision (ISCEV) standard specifies pattern-reversal recordings with large 1-degree and small 0.25-degree checks, standardized stimulus and recording conditions, an occipital recording electrode, and confirmation of waveform reproducibility.
• Both eyes should be tested separately. The report should provide the P100 latency for each eye, the interocular latency difference, the laboratory reference limits, and whether the response was reproducible. Amplitude and waveform morphology may be reported as additional information, but latency is the principal demyelination-sensitive measure used by the current diagnostic criteria.
• VEP may be particularly useful during the acute or subacute phase of optic neuritis, before retinal thinning is fully apparent on OCT. Latency can shorten over time with recovery or remyelination; therefore, a normal VEP does not exclude previous optic neuritis or MS.
• Potential confounders include uncorrected refractive error, poor fixation or attention, reduced visual acuity, cataract or other media opacity, amblyopia, retinal or macular disease, glaucoma, non-MS optic neuropathy, and post-chiasmal visual pathway lesions. Appropriate optical correction and a neuro-ophthalmic assessment are required when the history, examination, or test pattern is atypical.
• Pattern onset/offset or flash VEPs may be used under ISCEV standards when reliable pattern-reversal testing is not possible, including selected pediatric or poorly fixating patients. Their findings require age- and method-specific laboratory reference data and specialist interpretation; they should not be substituted uncritically for the pattern-reversal P100 criterion.

Optical coherence tomography

• OCT is a rapid, noninvasive retinal imaging study that quantifies neuroaxonal injury related to the optic nerve. The principal MS diagnostic measures are mean pRNFL thickness and macular GCIPL thickness in each eye.
• Under the 2024 McDonald revisions, a pRNFL inter-eye difference of at least 6 µm or a GCIPL inter-eye difference of at least 4 µm can provide objective evidence of unilateral or asymmetric optic-nerve involvement, provided that image quality is adequate and no better explanation exists.
• After acute optic neuritis, OCT intended to demonstrate prior neuroaxonal loss should generally be obtained at least 3 months after symptom onset. Acute optic-disc or pRNFL swelling and evolving retinal thinning can make earlier inter-eye comparisons misleading. GCIPL is less affected by optic-disc edema, but the diagnostic inter-eye thresholds should still be applied with attention to timing and the clinical context.
• OCT is most reliable for unilateral or asymmetric injury. A normal inter-eye difference does not exclude bilateral symmetric optic neuropathy, prior bilateral optic neuritis, or MS. Conversely, retinal thinning is not specific for MS and does not establish active inflammation or dissemination in time.
• Spectral-domain OCT or another platform with validated retinal-layer segmentation should be used. For longitudinal comparison, scans should preferably be obtained on the same device, with the same software version and scan protocol, because measurements are not automatically interchangeable among devices or segmentation algorithms.
• Scans should undergo systematic quality review. The obvious problems, signal strength, centration, algorithm failure, retinal pathology, illumination, and beam placement (OSCAR-IB) framework evaluates obvious acquisition problems, signal strength, centration, segmentation-algorithm failure, retinal pathology, illumination, and beam placement. Segmentation boundaries should be visually inspected and any manual correction documented.
• Acquisition and reporting should follow applicable Advised Protocol for OCT Study Terminology and Elements (APOSTEL) 2.0 elements, including the device and software, acquisition settings, scan protocol and measurement area, fundus image registration, post-acquisition selection, segmentation method and corrections, retinal-layer nomenclature, and quality-control exclusions.
• Potential confounders include glaucoma, retinal or macular disease, high refractive error or axial-length abnormalities, amblyopia, anomalous optic discs, media opacity, ocular trauma or surgery, diabetes, and other optic neuropathies. Automated segmentation errors and poor-quality scans must not be interpreted as evidence of optic-nerve involvement.

Minimum reporting elements

For a result intended to contribute to the MS diagnostic evaluation, the report should include:

• Clinical context: indication, eye-specific visual symptoms, history and date of optic neuritis, relevant ocular disease, and timing of the study relative to symptom onset.
• VEP: stimulus and recording protocol, monocular testing and optical correction, waveform reproducibility, P100 latency for each eye, interocular latency difference, laboratory- and age-specific reference limits, and technical or clinical confounders.
• OCT: device, software version, scan protocol, signal quality, centration and artifact assessment, segmentation review or correction, pRNFL and GCIPL values for both eyes, calculated inter-eye differences, and relevant ocular or retinal abnormalities.
• Interpretive conclusion: whether the study provides objective evidence of unilateral or asymmetric optic-nerve involvement under the current thresholds, whether an alternative explanation is present, and whether the study is limited or should be repeated.

Diagnostic limitations

• An abnormal VEP or OCT result demonstrates visual pathway or optic-nerve injury; it is not pathognomonic for MS. The finding can contribute one anatomical location toward dissemination in space only when the full current diagnostic criteria are otherwise appropriately applied and there is no better explanation.
• Neither study independently demonstrates dissemination in time, and neither should be used alone to confirm or exclude MS.
• Normal VEP and OCT results do not exclude MS. Discordant, borderline, bilateral, technically limited, or clinically atypical results should prompt review of test quality and consideration of repeat or complementary evaluation rather than automatic classification as an MS lesion.