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Objective: To examine the effect of chronic demyelination in the optic nerve of patients with MS on progressive loss of retinal ganglion cell (RGC) axons., Methods: Progressive retinal nerve fiber layer (RNFL) loss, as measured by optical coherence tomography, was longitudinally examined in 51 patients with MS with a history of unilateral optic neuritis (ON) and 25 normal controls. Patients were examined annually with a median of 4-year follow-up. Pairwise intereye comparison was performed between ON and fellow non-ON (NON) eyes of patients with MS using the linear mixed-effects model and survival analysis. The latency asymmetry of multifocal visual evoked potential (mfVEP) was used to determine the level of demyelination in the optic nerve., Results: Although both ON and NON eyes demonstrate significantly faster loss of RGC axons compared with normal subjects, ON eyes with severe chronic demyelination show accelerated thinning in the RNFL in the temporal sector of the optic disc (temporal RNFL [tRNFL]) compared with fellow eyes (evidenced by both the linear mixed-effects model and survival analysis). Furthermore, progressive tRNFL thinning is associated with the degree of optic nerve demyelination and reflects the topography of pathology in the optic nerve. More rapid axonal loss in ON eyes is also functionally evidenced by mfVEP amplitude reduction, which correlates with the level of optic nerve demyelination., Conclusions: Although the effect of demyelination on axonal survival has been demonstrated in experimental studies, our results provide first clinically meaningful evidence that chronic demyelination is associated with progressive axonal loss in human MS., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: To assess differential patterns of axonal loss and demyelination in the optic nerve in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD)., Design: Cross-sectional study., Participants: One hundred ninety-two participants, including 136 MS patients (272 eyes), 19 NMOSD patients (38 eyes), and 37 healthy control participants (74 eyes)., Methods: All participants underwent spectral-domain OCT scans and multifocal visual evoked potential (mfVEP) recordings. High-resolution magnetic resonance imaging (MRI) with the diffusion protocol also was performed in all patients., Main Outcome Measures: Ganglion cell-inner plexiform layer (GCIPL) thickness and mfVEP amplitude and latency at 5 eccentricities; global and temporal retinal nerve fiber layer thickness., Results: In optic neuritis (ON) eyes, the NMOSD patients had more severe GCIPL loss (P < 0.001) and mfVEP amplitude reduction (P < 0.001) compared with MS patients, whereas in contrast, mfVEP latency delay was more evident in MS patients (P < 0.001). The NMOSD patients showed more morphologic and functional loss at the foveal to parafoveal region, whereas the MS patients showed evenly distributed damage at the macula. Correlation analysis demonstrated a strong structure-function (OCT-mfVEP) association in the NMOSD patients, which was only moderate in the MS patients. In non-ON (NON) eyes, the MS patients showed significantly thinner GCIPL than controls (P < 0.001), whereas no GCIPL loss was observed in NON eyes in NMOSD. In addition, a significant correlation was found between all OCT and mfVEP measures in MS patients, but not in NMOSD patients. MRI demonstrated significant lesional load in the optic radiation in MS compared to NMOSD eyes (P = 0.002), which was related to the above OCT and mfVEP changes in NON eyes., Conclusions: Our study demonstrated different patterns of ON damage in NMOSD and MS. In MS, the ON damage was less severe, with demyelination as the main pathologic component, whereas in NMOSD, axonal loss was more severe compared with myelin loss. The disproportional mfVEP amplitude and latency changes suggested predominant axonal damage within the anterior visual pathway as the main clinical feature of NMOSD, in contrast to MS, where demyelination spreads along the entire visual pathway., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Introduction: Visual evoked potential (VEP) latency prolongation and optic nerve lesion length after acute optic neuritis (ON) corresponds to the degree of demyelination, while subsequent recovery of latency may represent optic nerve remyelination. We aimed to investigate the relationship between multifocal VEP (mfVEP) latency and optic nerve lesion length after acute ON., Methods: Thirty acute ON patients were studied at 1, 3, 6 and 12 months using mfVEP and at 1 and 12 months with optic nerve MRI. LogMAR and low contrast visual acuity were documented. By one month, the mfVEP amplitude had recovered sufficiently for latency to be measured in 23 (76.7%) patients with seven patients having no recordable mfVEP in more than 66% of segments in at least one test. Only data from these 23 patients was analysed further., Results: Both latency and lesion length showed significant recovery during the follow-up period. Lesion length and mfVEP latency were highly correlated at 1 (r = 0.94, p = <0.0001) and 12 months (r = 0.75, p < 0.001). Both measures demonstrated a similar trend of recovery. Speed of latency recovery was faster in the early follow-up period while lesion length shortening remained relatively constant. At 1 month, latency delay was worse by 1.76 ms for additional 1mm of lesion length while at 12 months, 1mm of lesion length accounted for 1.94 ms of latency delay., Conclusion: A strong association between two putative measures of demyelination in early and chronic ON was found. Parallel recovery of both measures could reflect optic nerve remyelination.

Objective: To investigate the potential links between thinning of retinal ganglion cell axons in eyes of patients with multiple sclerosis (MS) without past optic neuritis (ON) and MS-related inflammatory damage of the posterior visual pathway., Methods: Temporal retinal nerve fiber layer (tRNFL) thickness was analyzed in eyes with no history of ON (NON) from 53 patients with relapsing-remitting MS. Fifty normal age- and sex-matched controls were examined with optical coherence tomography. Low-contrast visual acuity charts were used for functional assessment of vision. The optic tract (OT) and optic radiation (OR) were identified using probabilistic tractography, and volume of T2 fluid-attenuated inversion recovery lesions and diffusion tensor imaging (DTI) indices were measured within both structures. Cross-sectional diameter of the OT was also calculated., Results: tRNFL thickness was significantly reduced in NON eyes and was associated with reduced low-contrast visual acuity. Lesions within the OR were detected in the majority of patients. There was a significant correlation between thinning of the tRNFL and OR lesion volume (adjusted for non-OR lesion volume, age, sex, and disease duration). tRNFL thickness also correlated with OR DTI indices. No OT lesions were identified in any of the patients and no relationship between retinal nerve fiber layer loss and potential markers of OT lesions was found., Conclusion: The results demonstrate a strong tract-specific association between loss of tRNFL fibers and MS-related inflammation within OR., (© 2014 American Academy of Neurology.)

Purpose: The aim of the study was to test the hypothesis that latency delay of multifocal visual evoked potentials (mfVEP) in nonoptic neuritis (NON) eyes of multiple sclerosis (MS) patients is related to retrochiasmal demyelinating lesions., Methods: A total of 57 MS patients with no history of optic neuritis at least in one eye, and 25 age- and sex-matched healthy controls was enrolled. Probabilistic tractography was used to reconstruct optic radiation (OR) fibers. The MS lesion volume within and outside of OR was calculated. Diffusion tensor imaging (DTI) indices were measured along OR fibers. The relationship of the mfVEP latency with OR lesions and DTI indices was examined., Results: Average mfVEP latency in the MS cohort was significantly delayed compared to controls (P < 0.0001). Of the patients, 77% demonstrated OR lesions. Axial, radial, and mean diffusivity were significantly abnormal in MS patients (P < 0.001). Partial correlation demonstrated significant association between mfVEP latency delay and OR lesion load. There was also significant correlation between MfVEP latency and OR DTI. Subgroup analysis revealed significantly higher correlations in patients without a history of ON in either eye compared to the fellow eye of patients with previous ON., Conclusions: The findings of this study support our hypothesis that latency delay of the mfVEP in eyes of MS patients without previous ON is related to retrogenicular demyelinating lesions. Additionally, this study demonstrated that a previous episode of ON in the fellow eye may be a significant confounding factor, masking the relationship between the latency and OR lesions., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Background: Axonal loss is a major determinant of disability in multiple sclerosis (MS). While acute inflammatory demyelination is a principal cause of axonal transection and subsequent axonal degeneration in acute disease, the nature of chronic axonal loss is less well understood. In the current study, the relationship between degree of chronic demyelination and axonal degeneration was investigated using optic neuritis (ON) as a model., Method: 25 patients with a first episode of unilateral ON, good recovery of visual function and concurrent brain or spinal cord MRI lesions were enrolled. Axonal loss was assessed using change in retinal nerve fibre layer (RNFL) thickness between 1 and 3 years after ON. Optic nerve conduction was evaluated using latency of multifocal visual evoked potentials (mfVEP). The level of mfVEP latency delay at 12 and 36 months was considered indicative of the degree of permanent demyelination. Data from 25 age and gender matched normal controls were used for comparison., Results: RNFL thickness was significantly reduced in ON eyes at 12 months compared with controls but remained unchanged in fellow eyes. Average RNFL thickness demonstrated a small but significant reduction between 12 and 36 months for both ON and fellow eyes. Change in RNFL thickness between 12 and 36 months, however, did not correlate with the degree of mfVEP latency delay., Conclusion: The results, therefore, show no association between the degree of permanent optic nerve demyelination (as measured by latency delay) and progressive axonal degeneration, at least in the early stages of the disease. The fact that fellow eyes demonstrated a similar degree of progressive axonal loss supports this suggestion.

Optic neuritis provides an in vivo model to study demyelination. The effects of myelin loss and recovery can be measured by the latency of the multifocal visual evoked potentials. We investigated whether the extent of initial inflammatory demyelination in optic neuritis correlates with the remyelinating capacity of the optic nerve. Forty subjects with acute unilateral optic neuritis and good visual recovery underwent multifocal visual evoked potentials testing at 1, 3, 6 and 12 months. Average latency changes were analyzed. Extensive latency delay at baseline significantly improved over time with rate of recovery slowed down after 6 months. Magnitude of latency recovery was independent of initial latency delay. Latency recovery ranged from 7 to 17 ms across the whole patient cohort (average = 11.3 (3.1) ms) despite the fact that in a number of cases the baseline latency delay was more than 35-40 ms. Optic nerve lesions tend to remyelinate at a particular rate irrespective of the size of the initial demyelinated zone with smaller lesions accomplishing recovery more completely. The extent of the initial inflammatory demyelination is probably the single most important factor determining completeness of remyelination. The time period favorable to remyelination is likely to be within the first 6 months after the attack.

Objective: To investigate the relation between retinal nerve fiber layer (RNFL) thickness and latency and amplitude of multifocal visual-evoked potentials (mfVEPs) in the postacute stage of optic neuritis in patients with early or possible multiple sclerosis., Method: Thirty-two patients with clinical diagnosis of unilateral optic neuritis and magnetic resonance imaging lesions typical of demyelination and 25 control subjects underwent mfVEP and optical coherence tomography imaging., Results: Although there was significant reduction of RNFL thickness in the affected eyes (18.7%), a considerably larger decrease was observed for the amplitude of the mfVEPs (39.8%). Latency of the mfVEPs was also significantly delayed in optic neuritis eyes. In fellow eyes, the amplitude of mfVEPs was significantly reduced and the latency prolonged, but RNFL thickness remained unaltered. RNFL thickness correlated highly with the mfVEP amplitude (r = 0.90). There was also strong correlation between optical coherence tomography measure of axonal loss and mfVEP latency (r = -0.66)., Interpretation: Although our findings demonstrate strong associations between structural and functional measures of optic nerve integrity, the functional loss was more marked. This fact, together with amplitude and latency changes of the mfVEPs observed in clinically normal fellow eyes, may indicate greater sensitivity of mfVEPs in detecting optic nerve abnormality or the presence of widespread inflammation in the central nervous system, or both. The significant correlation of the mfVEP latency with RNFL thickness suggests a role for demyelination in promoting axonal loss.