Vision and Vision-Related Measures in Progressive Multiple Sclerosis

Background: The aim was to compare the retinal nerve fibre layer (RNFL) thickness and visual evoked potentials (VEP) among eyes with multiple sclerosis (MS)‐associated optic neuritis, unaffected eyes of the same patients and eyes of disease‐free controls. Changes in RNFL thickness, visual acuity (VA) and VEP over time are evaluated in MS‐associated optic neuritis.Methods: Forty‐six eyes of 23 patients (six male and 17 female), who suffer from MS and were diagnosed with unilateral or bilateral optic neuritis, participated in the study. Forty eyes of 20 age‐ and gender‐matched controls were tested. VA measurement, optical coherence tomography and VEP were performed in all patients at presentation and at one, three and six months thereafter.Results: There was a statistically significant difference in VA between MS eyes with optic neuritis and controls (p < 0.0001), as well as between MS eyes with and without optic neuritis (p < 0.005). VA improved over time. Average RNFL thickness was reduced in MS eyes with or without optic neuritis in comparison to control eyes. This reduction in RNFL thickness was more marked over time. The amplitude of P100 was significantly decreased in MS eyes with optic neuritis in comparison to controls (p < 0.0001) and there was a statistically significant delay in peak time of P100 in MS eyes with optic neuritis versus the eyes of normal subjects (p < 0.0001), which improved over time.Conclusion: The present study suggests that there is a progressive decrease in RNFL over time in eyes with optic neuritis associated with MS. The amplitude and latency of P100 in VEP examination returned to normal ranges over time.

Should Spinal MRI Be Routinely Performed in Patients With Clinically Isolated Optic Neuritis?

BackgroundMultiple sclerosis (MS) is a common cause of neurological disabilities in adults and commonly affects the visual pathway. The objective of this study is to assess and compare the sensitivity of visual evoked potentials (VEP) and optical coherence tomography (OCT) as measures of early disability in ambulatory patients with MS.MethodsForty-four patients with MS with Expanded Disability Status Scale (EDSS) of ≤ 4.5 (ambulatory patients) and 14 healthy controls participated in this study. Patients were classified into 3 groups according to EDSS. Patients with EDSS of 0–1.5 formed the “No disability,” patients with EDSS of 2–3 formed the “Minimal to mild disability,” and finally patients with EDSS of 3.5–4.5 formed the “Moderate to significant disability” groups. N75/P100 amplitude, P100 latency, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer complex (GCLC) thickness were measured.ResultsPatients showed significantly lower N75/P100 amplitude, higher P100 latency, lower RNFL, and GCLC thicknesses compared to controls. However, there were non-significant changes in P100 latency, N75/P100 amplitude, and GCLC thickness among the 3 groups for both patients with and without history of optic neuritis (ON). On contrary, RNFL thickness was significantly different between the three groups for both patients with and without history of ON. Factorial ANOVA revealed non-significant disability × History of ON interaction.ConclusionCompared to VEP parameters, RNFL thickness was a sensitive correlate with the various degrees of early disability in fully ambulatory patients with MS whatever the history of ON.

Context: Retinal nerve fibre layer (RNFL) being unmyelinated, RNFL thickness (RNFLT) provides direct evidence of axonal loss in optic neuritis (ON) and may prove to be a valuable diagnostic and prognostic tool in the development of multiple sclerosis (MS). Aims: Assessment of RNFLT by OCT3 in patients with recent onset retrobulbar ON, comparison of obtained values based on presence or absence of the periventricular white matter lesion (PVWML) on magnetic resonance imaging (MRI), comparison with the RNFLT of a control group, and analysis of the obtained results. Settings and Design: Cross-sectional study. Materials and Methods: Eighteen patients with Statistical Analysis Used: ANOVA and Student's t test. Results: ON eyes in group B had thinnest RNFLT (average temporal = 39.75 μ), followed by group A (average temporal = 44.3 μ), and finally by group C (average temporal-OU = 80.78 μ). Conclusions: Our study shows that patients with ON, irrespective of detection of PVWML on MRI, have thinner RNFL compared to age-matched controls (P < 0.001). The average RNFLT values are lowest in patients with PVWML. The aspect of RNFL thinning in non-ON eyes should be further studied as a possible subclinical indicator of MS.

Background and ObjectivesTo investigate the long-term effect of permanent demyelination on axonal attrition by examining an association between intereye asymmetry of the multifocal visual evoked potential (mfVEP) latency delay and subsequent thinning of retinal ganglion cell axons in patients with a long-standing history of unilateral optic neuritis (ON).MethodsOnly patients with a significant degree of chronic demyelination (intereye latency asymmetry >5 ms) were included in this study. The level of optic nerve demyelination was estimated at baseline by the latency delay of mfVEP, while the degree of axonal loss was assessed by thinning of the retinal nerve fiber layer (RNFL) thickness between baseline and follow-up visits. Low-contrast visual acuity (LCVA) was also evaluated at baseline and follow-up. Patients were examined twice with an average interval of 6.1 ± 1.4 years.ResultsFrom 85 examined patients with multiple sclerosis, 28 satisfied inclusion criteria. Latency of the mfVEP was delayed, and RNFL thickness was reduced in ON eyes compared with fellow eyes at both visits. There was significant correlation between latency asymmetry and baseline or follow-up intereye RNFL thickness asymmetry. Intereye asymmetry of LCVA at baseline correlated with baseline latency asymmetry of mfVEP and baseline asymmetry of RNFL thickness. Latency of the mfVEP in ON eyes improved slightly during the follow-up period, whereas latency of the fellow eye remained stable. By contrast, RNFL thickness significantly declined in both ON and fellow eyes during the follow-up period. The rate of RNFL thinning in ON eyes, however, was more than 2 times faster compared with the fellow eyes (p < 0.001). Furthermore, baseline latency asymmetry significantly correlated with the rate of RNFL thinning in ON eyes during the follow-up (p < 0.001), explaining almost half of the variability of temporal RNFL progression. For each millisecond of latency delay (i.e., ∼0.5 mm of demyelination along the optic nerve), temporal RNFL thickness was annually reduced by 0.05%.DiscussionOur study provides clear in vivo evidence that chronic demyelination significantly accelerates axonal loss. However, because this process is slow and its effect is mild, long-term monitoring is required to establish and confidently measure the neurodegenerative consequences of demyelination.

BackgroundMultiple sclerosis (MS) is an autoimmune disease that attacks the central nervous system, with optic neuritis (ON) being a common early manifestation. Retinal nerve fiber layer (RNFL) thickness may be a biomarker of neuroaxonal damage in MS patients. We sought to evaluate changes in RNFL thickness over 4 years in Omani MS patients with or without ON in comparison to a healthy control group.MethodsThis retrospective case-control study involved 27 MS patients and 25 healthy controls. Optical coherence tomography was performed upon first diagnosis and at a four-year follow-up. Differences in mean RNFL thickness were calculated.ResultsA total of 51 eyes from the MS group and 50 eyes from the control group were evaluated. There was a significant reduction in mean RNFL thickness among MS patients with ON at follow-up (81.21 versus 72.14 μm; P = .003), whereas no significant RNFL thinning was observed among MS patients without ON. However, there was a significant reduction in RNFL thickness among MS patients compared to healthy controls (76.79 versus 93.72 μm; P = .009), regardless of ON presence/absence.ConclusionsAxonal damage was seen in the optic nerves of Omani MS patients. Moreover, there was a significant reduction in RNFL thickness among MS patients with ON as the disease progressed; however, while there was evidence of RNFL thinning in MS patients without ON, this difference lacked statistical significance. Evaluation of RNFL thickness may represent a useful biomarker for monitoring disease progression in MS and its association with ON.

PurposeCompare the retinal nerve fibre layer (RNFL) thickness in multiple sclerosis (MS) patients, with and without previous episodes of optic neuritis (ON), to disease‐free controls, using optical coherence tomography (OCT).MethodsThe RNFL was measured with a spectral domain OCT (Canon HS‐100) in 433 MS patients and in 70 controls. The MS eyes were sorted into three groups: MS non ON eyes (MSON−), MS ON eyes (MSON+) and the fellow eye of MS ON (MSON_fellow). One eye of each patient in the MSON‐group and in the control group was selected randomly for analysis.ResultsSeventy control eyes, 327 MSON‐ eyes, 106 MSON+ eyes and 106 MSON_fellow eyes were analysed in a linear regression adjusting for age. The average RNFL thickness was found to be statistically thinner in the MSON− group (88.2 ± 13.0 µm) compared to the controls (98.1 ± 9.0 µm; p &lt; 0.00).The average RNFL was thinner in the MSON+ group (77.3 ± 15.2 µm) compared to MSON− eyes and the controls (p &lt; 0.00). A paired t‐test showed a significant decrease in RNFL thickness in the MSON+ eyes compared to MSON_fellow.ConclusionsMultiple sclerosis causes RNFL loss. A mean reduction of ~10 µm was found in MS patients without history of ON and a mean reduction of 20 µm was found in MS patients with history of ON compared to healthy controls. This study showed that OCT is a useful tool that provides evidence of neural degeneration in MS patients, with or without the presence of ON.

To investigate the difference of retinal nerve fiber layer (RNFL) thickness and macular fovea thickness/volume between multiple sclerosis (MS) patients and healthy normal individuals using optical coherence tomography (OCT) and assess its association with visual field parameters. Thirty consecutive MS patients and 28 healthy controls were recruited in this prospective study. Comprehensive standardized ophthalmic examinations included visual acuity, cycloplegic refraction, intraocular pressure, gonioscopy, visual field, and RNFL thickness and macular fovea thickness/volume detection using Humphrey OCT. Mean values for the thickness of the peripapillary RNFL and macular volume were calculated. Associations between visual field parameters and RNFL thickness/macular volume were analyzed by Pearson correlation analysis. The RNFL thicknesses in each quadrant, the average macular thickness, and the average macular volume in MS patients were all less than those in healthy controls, with statistically significant differences. The RNFL thickness and macular fovea thickness/volume were greater in eyes without optic neuritis than in eyes with optic neuritis. The average visual field parameters had positive correlations with the RNFL thickness and negative correlations with macular parameters in MS patients. OCT measurements can effectively identify the nerve changes of MS patients, which provide more data for the diagnosis of MS.

Retinal alterations in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) remain unclear, especially the specific patterns and extent of microvascular change. This study aimed to compare these alterations and to develop logistic regression and machine learning models using combined retinal microvascular and structural metrics for disease differentiation. Patients with MS or NMOSD in clinically stable phases underwent swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Quantified OCTA metrics included density, perfusion, and microdensity of superficial and deep vascular complex (SVC, DVC), choroidal vascular, and stromal volumes (CVV, CSV). Structural OCT metrics included retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness. Logistic regression and machine learning models were developed for classification. The study enrolled 658 participants (167 MS patients, 221 NMOSD patients, and 270 age- and sex-matched healthy controls) with 1277 eyes. In optic neuritis (ON) eyes, NMOSD showed significantly lower SVC metrics than MS, whereas in non-ON eyes, MS exhibited more severe microvascular loss (most p < 0.017); correspondingly, EDSS-related SVC decline was steeper in ON eyes of NMOSD but steeper in non-ON eyes of MS (interaction p < 0.05 for most comparisons). The logistic regression model with microvascular metrics achieved an AUC of 0.900. Among machine learning classifiers, support vector machine performed best (AUC 0.912, accuracy 84.5%). Distinct retinal microvascular patterns differentiate NMOSD from MS and correlate with disability severity, especially considering ON history. OCTA-based models provide accurate, non-invasive differential diagnosis tools, highlighting microvascular integrity as a critical biomarker.

Longitudinal study of retinal nerve fiber layer thickness changes in a multiple sclerosis patients cohort: A long term 5 year follow-up

Aims/Background Pediatric acquired demyelinating disorders (ADS) include various monophasic and recurrent inflammatory conditions of the central nervous system (CNS). Optic neuritis (ON) is a demyelinating disease primarily affecting the optic nerve axons due to autoimmune inflammation. To investigate the clinical characteristics, ophthalmic manifestations, laboratory test results, and prognostic indicators of Chinese children and adolescents with ADS. Methods The clinical data of 57 patients with ADS treated in the Beijing Children's Hospital from March 2021 to December 2023, were retrospectively collected and analyzed. The primary outcomes include best-corrected visual acuity (BCVA) at onset, peripapillary retinal nerve fiber layers (RNFL) thickness, serum myelin oligodendrocyte glycoprotein (MOG) antibody level, aquaporin-4 (AQP4) antibody level, and final BCVA after hormone therapy. Results The analyses included 57 children and adolescents in the study, including 38 optic neuritis (ON), 12 neuromyelitis optica spectrum disorder (NMOSD), 5 acute disseminated encephalomyelitis (ADEM), and 2 multiple sclerosis (MS) patients. The median age of patients facing the initial attack of ON was 9 years (3-15 years), with 23 children and adolescents (40.4%) aged eight years or younger, and 37 patients (64.9%) were bilaterally affected. Half of the children and adolescents (15/30) were MOG-Ab seropositive, and 19.4% (6/31) were AQP4-Ab seropositive. Children and adolescents with NMOSD were more likely to have severe visual impairment at acute onset (p < 0.05), with 84.2% of them having low vision acuity (BCVA worse than 0.1), as compared with 64.9% in the ON group. The RNFL thickness of affected eye was thinner than unaffected eyes (median 72.0 μm vs. median 102.0 μm, p < 0.05). Patients with NMOSD exhibited lower RNFL thickness across all measured sectors compared to those with ON. Significant differences were noted in the average RNFL and in each specific region of the retina, including the temporal RNFL, nasal RNFL, nasal superior RNFL, nasal inferior RNFL, temporal superior RNFL, and temporal inferior RNFL (all p < 0.05). After the treatment with intravenous methylprednisolone, both patients with ON (52 eyes; 86.7%) or NMOSD (20 eyes; 90.9%) group had functional visual recovery (BCVA better or equal 0.4). Conclusion This study shows that Chinese children and adolescents with ADS present distinctive clinical features, including earlier onset and more bilateral involvement. Furthermore, NMOSD patients experience more severe visual acuity impairment and thinner peripapillary RNFL. All children and adolescents of ON or NMOSD respond well to methylprednisolone treatment.

To evaluate the association between the damage to the anterior and posterior visual pathway as evidence of the presence of retrograde and anterograde trans-synaptic degeneration in multiple sclerosis (MS). We performed a longitudinal evaluation on a cohort of 100 patients with MS, acquiring retinal optical coherence tomography to measure anterior visual pathway damage (peripapillary retinal nerve fiber layer [RNFL] thickness and macular volume) and 3T brain magnetic resonance imaging (MRI) for posterior visual pathway damage (volumetry and spectroscopy of visual cortex, lesion volume within optic radiations) at inclusion and after 1 year. Freesurfer and SPM8 software was used for MRI analysis. We evaluated the relationships between the damage in the anterior and posterior visual pathway by voxel-based morphometry (VBM), multiple linear regressions, and general linear models. VBM analysis showed that RNFL thinning was specifically associated with atrophy of the visual cortex and with lesions in optic radiations at study inclusion (p < 0.05). Visual cortex volume (β = +0.601, 95% confidence interval [CI] = +0.04 to +1.16), N-acetyl aspartate in visual cortex (β = +1.075, 95% CI = +0.190 to +1.961), and lesion volume within optic radiations (β = -2.551, 95% CI = -3.910 to -1.192) significantly influenced average RNFL thinning at study inclusion independently of other confounders, especially optic neuritis (ON). The model indicates that a decrease of 1cm(3) in visual cortex volume predicts a reduction of 0.6μm in RNFL thickness. This association was also observed after 1 year of follow-up. Patients with severe prior ON (adjusted difference = -3.01, 95% CI = -5.08 to -0.95) and mild prior ON (adjusted difference = -1.03, 95% CI = -3.02 to +0.95) had a lower adjusted mean visual cortex volume than patients without ON. Our results suggest the presence of trans-synaptic degeneration as a contributor to chronic axon damage in MS.

Optic neuritis (ON) is linked to multiple sclerosis (MS). The presence of white matter lesions on cerebral magnetic resonance imaging (MRI) predicts the risk of MS after ON with considerable accuracy. Oligoclonal bands (OCB) are present in 95 % of MS patients, and a lumbar puncture can also be valuable in the evaluation of patients with ON. We analyzed CSF findings in patients referred with ON in the context of MRI and visual evoked potential (VEP) pathology. We assessed the possible contributory role of a lumbar puncture and weigh this against disadvantages of the procedure. Between February 2003 and November 2011, 505 patients were referred by ophthalmologists to the Clinic of Optic Neuritis, Glostrup Hospital, University of Copenhagen. None had MS prior to referral. A total of 437 were included in the study, and all underwent MRI, a lumbar puncture and VEP. Patients with other organic causes of their symptoms and patients with >3 months between onset and tests were excluded. All files were reviewed retrospectively. CSF leukocytes and the IgG index were elevated in 33 and 41 %, respectively, and OCBs were detected in 61 % of patients. CSF abnormalities correlated strongly with VEP and MRI (p < 0.0001). Patients with normal VEP and MRI had a 96 % probability of a normal lumbar puncture. The contributory role of a lumbar puncture in the evaluation of ON seems negligible when patients have a normal VEP and MRI. We suggest that all patients should be evaluated with VEP and MRI before deciding on a lumbar puncture.

To evaluate the peripapillary retinal nerve fiber layer (RNFL) thickness with scanning laser polarimetry in patients with optic neuritis (ON) caused by multiple sclerosis. Peripapillary RNFL thickness was measured with a GDx VCC in 14 eyes of 13 patients with ON (nonrecurrent group), in 18 eyes of 11 patients with recurrent ON (recurrent group), and in 48 eyes of 48 healthy subjects (healthy group). The temporal, superior, nasal, inferior thickness (TSNIT) average, superior average, and inferior average of GDx VCC measurements were compared across the three groups. We calculated correlation coefficients between each of the three GDx VCC parameters and both the mean deviation (MD) of the Humphrey 30-2 full threshold visual field and the visual acuity (VA). The three parameters showed statistically significant differences across the three groups. There was no correlation between any of the three GDx VCC parameters and MD or VA in the nonrecurrent group, but there was significant correlation between each of the three GDx VCC parameters and MD in the recurrent group. ON caused morphological changes in the peripapillary RNFL, and recurrent ON aggravated the deterioration and caused diffuse rather than regional damage to the peripapillary RNFL.

RE-PERG is altered in presence of primary neuronal degeneration of retinal ganglion cells, both in glaucoma and other diseases. A previous study showed that in a model of retrograde degeneration (vascular dementia) RE-PERG was normal. In this study, we enrolled patients with pituitary adenoma (PA) to evaluate RE-PERG findings in another model of retrograde degeneration compared with healthy controls (HC). Based on the outcome of the present and our previous studies with RE-PERG, and reviewing the literature, we discuss the physiopathology of glaucoma. Twelve PA patients and 14 age-matched HC were recruited. All participants performed visual field (VF) test, retinal nerve fiber layer (RNFL) and ganglion cells complex (GCC) thickness measurement by means of optical coherence tomography (OCT), visual evoked potentials (VEPs) and RE-PERG, a non-invasive, fast steady-state pattern electroretinogram (SS-PERG) sampled in five consecutive blocks of 130 events. VEPs amplitude was significantly lower in PA with respect to HC (6.8±0.6 vs 7.4±0.6 µV; p=0.045). VEPs latency was higher in PA (123.2±5.8 vs 103.6±4.1 msec; p<0.01). As for VF, mean defect (MD) and pattern standard deviation (PSD) were higher in PA (-6.6±2.6 vs -0.01±1.02 dB; p<0.01 and 8.5±3.1 vs 1.5±0.3; p<0.01, respectively). RNFL thickness was lower in PA (88±8.1 vs 97±9.3 µ; p=0.01). There was no statistically significant difference between PA and HC for RE-PERG. There was a significant correlation among MD, PSD, VEPs amplitude, PERG amplitude and RNFL thickness in the PA group, whereas no correlation was found with SDPh, which remains as normal as in the HC group. Our findings confirm that RE-PERG is not altered in retrograde degeneration. Based on the outcome of the present and our previous studies about RE-PERG and glaucoma, we assume that in glaucoma a double mechanism of retinal ganglion cells degeneration, both retrograde and primary, can coexist.