History Of Optic Neuritis Research Articles

Homonymous Hemiatrophy of Macular Ganglion Cell Layer as a Marker of Retrograde Neurodegeneration in Multiple Sclerosis-A Narrative Review.

Retrograde axonal neurodegeneration along the visual pathway-either direct or trans-synaptic-has already been demonstrated in multiple sclerosis (MS), as well as in compressive, vascular, or posttraumatic lesions of the visual pathway. Optical coherence tomography (OCT) can noninvasively track macular and optic nerve changes occurring as a result of this phenomenon. Our paper aimed to review the existing literature regarding hemimacular atrophic changes in the ganglion cell layer identified using OCT examination in MS patients without prior history of optic neuritis. Homonymous hemimacular atrophy has been described in post-chiasmal MS lesions, even in patients with normal visual field results. Temporal and nasal macular OCT evaluation should be performed separately in all MS patients, in addition to an optic nerve OCT evaluation and a visual field exam.

Evaluation of optical coherence tomography findings in patients with multiple sclerosis and glaucoma.

Glaucoma and multiple sclerosis (MS) can cause optic disc pathology and, in this way, affect optical coherence tomography (OCT) data. In this context, the objective of this study is to investigate the changes in the mean, quadrant, and sector data measured by OCT in glaucoma and MS patients. The sample of this prospective cohort study consisted of 42 MS patients (84 eyes), 34 Primary open-angle glaucomas patients (67 eyes), and 24 healthy control subjects (48 eyes). The MS group was divided into two groups according to the presence of a history of optic neuritis. Accordingly, those with a history of optic neuritis were included in the MS ON group, and those without a history of optic neuritis were included in the MS NON group. The differences between these groups in the mean, quadrant, and sector data related to the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) were evaluated. Superior nasal (SN), superior temporal (ST), inferior nasal (IN), and superior quadrant (SUP) values were significantly lower in the glaucoma group than in the MS group (p < 0.05). The mean superior GCC (GCC SUP) value was significantly lower in the MS ON group than in the glaucoma group (p < 0.05). On the other hand, SN, ST, inferior temporal (IT), IN, average RNFL (AVE RNFL), semi-average superior RNFL (SUP AVE RNFL), semi-average inferior RNFL (INF AVE RNFL), SUP, and inferior quadrant RNFL (INF) values were significantly lower in the glaucoma group than in the MS NON group (p < 0.05). RNFL and GCC parameters get thinner in MS and glaucoma patients. While the inferior and superior RNFL quadrants are more frequently affected in glaucoma patients, the affected quadrants vary according to the presence of a history of optic neuritis in MS patients. It is noteworthy that the GCC superior quadrant was thin in MS ON patients. The findings of this study indicate that OCT data may be valuable in the differential diagnosis of glaucoma and MS.

Unveiling the retinal secrets of neuromyelitis optica spectrum disorder

BackgroundVascular alterations are now recognized as important contributors to the pathophysiology of neuromyelitis optica spectrum disorder (NMOSD). This study aimed to use optical coherence tomography (OCT) and OCT-angiography (OCTA) to assess alterations in the retinal structure and microvasculature in patients with NMOSD, so we can understand pathophysiology of NMOSD, implicating this on disease activity, visual outcome and management on the future.MethodsA case–control study was conducted on 40 NMOSD patients with (NMOSD + ON) and without (NMOSD – ON) history of optic neuritis and 36 healthy subjects. The following data were assessed in NMOSD patients: clinical history, EDSS, and visual function testing. Both groups underwent spectral domain (SD)-OCT and OCTA.ResultsIn this study, NMOSD + ON patients had a statistically significant reduction in all SD-OCT parameters compared to healthy control. Regarding OCTA, there was a significant reduction in radial peripapillary capillary density (RPCD) in NMOSD + ON (P-value < 0.001) and some sectors of NMOSD–ON compared to healthy control. NMOSD + ON patients had significant differences in RPCD compared to those without (P-value < 0.001).ConclusionsHere we show that the advance of this study is that retinal microvascular alterations have been noticed in NMOSD–ON eyes, indicating that subclinical primary retinal vasculopathy and disease activity may occur in NMOSD before onset of ON and retinal atrophy. This may have implications on early detection of disease activity, early interference in management and prognostic tool to visual outcome in following the patients.

New insights in the pathogenic mechanism of multiple sclerosis: Is Epstein-Barr virus associated with optic nerve involvement?

There are no reports in the literature studying the possible relationship between Epstein-Barr virus (EBV) and optic nerve involvement in multiple sclerosis (MS). The aim of our study was to analyze the association between EBV antibodies titres and optical coherence tomography (OCT) and OCT angiography (OCTA) quantitative parameters. We conducted a retrospective study. The study included 98 eyes of 49 patients with MS. Years of MS duration, relapse count, history of optic neuritis (ON), and immunoglobulin (Ig) G antibodies to the EBV viral capsid antigen (VCA) were recorded from each patient. Also, OCT analysis (including retinal nerve fibre layer (RNFL) thickness and ganglion cell-inner plexiform layer (GCIPL) thickness) and OCTA analysis (including perfusion density (PD) and flux index (FI) of the radial peripapillary capillary plexus) were performed in each participant. No significant associations were observed between anti-EBV antibody levels and OCT or OCTA parameters (p > 0,05). Correlation analysis between OCT and OCTA measurements showed a significant positive correlation between RNFL thickness and GCIPL thickness with peripapillary PD and FI (p < 0,035). Subgroup analysis revealed a significant diminution of RNFL thickness, GCIPL thickness and peripapillary PD and FI (p < 0,05) in the ON group. We were unable to demonstrate a significant association between anti-EBV VCA IgG antibody titres and OCT or OCTA parameters. Nonetheless, further longitudinal studies are needed to explore the possible association of EBV with optic nerve involvement in MS.

Optical coherence tomography in multiple sclerosis.

Multiple sclerosis (MS) is a chronic neurodegenerative disease that damages myelinated fibers within the central nervous system. Data obtained using optical coherence tomography (OCT) have recently been identified as a potential biomarker for this disease. We aimed to measure circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using OCT and to compare the results in healthy participants with those of individuals having clinically definitive MS with and without a history of optic neuritis. This cross-sectional study recruited patients with clinically confirmed MS, with and without optic neuritis, and healthy individuals as a control group. We documented demographic characteristics, duration of MS, and time elapsed since the episode of optic neuritis. All participants underwent a thorough ocular examination and measurement of total, superior, and inferior cpRNFLT using swept-source OCT. In participants with MS, women outnumbered men in the subsets with (90%) and without (64%) optic neuritis. The control group comprised approximately similar numbers of men and women. There was a statistically significant difference in total, superior, and inferior cpRNFLT between study groups (all P < 0.001). Pairwise comparisons revealed significantly thinner total, superior, and inferior cpRNFLTs in patients having MS with and without (all P < 0.001) optic neuritis when compared with the controls. We found significantly higher total, superior, and inferior cpRNFLTs in women than in men (all P < 0.05). However, we found no significant correlation between total, superior, or inferior cpRNFLT and patient age, duration of MS, or time elapsed since the optic neuritis episode (all P > 0.05), except for a significant moderate inverse correlation between patient age and total cpRNFLT (r = - 0.41; P < 0.05), indicating a loss of total cpRNFLT with age. Patients with clinically confirmed MS, with or without optic neuritis, had a significantly decreased cpRNFLT compared to that of healthy individuals. There was a significant inverse correlation between age and total cpRNFLT and a difference in cpRNFLT between the sexes, indicating that age and sex may influence the measurement of cpRNFLT using OCT in patients with MS. As a screening tool, OCT should be used along with other existing diagnostic modalities for patients with definite or suspected MS. Further longitudinal studies including various classifications of MS with or without isolated episodes of optic neuritis, along with diagnostic accuracy studies, could provide more robust conclusions on the suitability of OCT as a biomarker of MS.

Retina hypoperfusion in multiple sclerosis: Is it only a consequence of atrophy?

Aims/Purpose: To study if there are vascular changes in patients with multiple sclerosis (MS) when compared healthy controls, analysing oct and OCT‐angiography findings (choroidal thickness and retinal vascular density) at the macular level.Methods: The study compared two groups (controls and patients) and it analysed whether there were statistically significant differences in the different parameters studied using OCT: choroidal thickness and in the vascular macular plexuses, using OCT‐angiography. Any patient has an optic neuritis history. It was also studied whether there was a statistically significant correlation between anatomical parameters (radial nerve fibre layer, RNFL and ganglion cell layer, GCL) and vascular parameters matching cases and controls by age and sex.Results: We found a statistically significant reduction in macular choroidal thickness in patients when compared to controls. The study of retinal vascular plexuses showed that the superficial and deep retinal vascular plexuses and the choriocapillaris plexus showed significantly lower vascular density in the patients group. Variations in anatomical parameters between anatomical parameters and in vascular parameters between vascular parameters pairing cases and controls show direct correlations. Regarding the correlation between the differences in anatomical versus vascular parameters, we only observed a low direct correlation between the difference in the papillary RFNL and that of the superficial macular vascular plexus between case and control group.Conclusions: The density of macular vascular plexus and choroidal thickness proved to be significantly lower in MS patients than in healthy subjects. To date, it is not known to what extent hypoperfusion in MS is a cause or consequence of the brain disease or whether it is a simply association. Vascular parameters could be used as useful markers in the diagnosis and follow‐up of MS.

Modern diagnostic potentials of studying structural and functional changes of the retina and the optic nerve in multiple sclerosis patients

Purpose: to study significant functional and structural changes in the retina and the intraocular section of the optic nerve in multiple sclerosis (MS) patients and analyze how they are interrelated with electrophysiological changes in the visual analyzer.Materials and methods. The study included 44 patients (88 eyes): group 1 (26 eyes) with MS duration ≤ 5 years and no history of optic neuritis (ON); group 2 (30 eyes) with MS duration from 6 to15 years and no history of ON; and group 3 (32 eyes) with MS duration ≤ 15 years with a history of ON. All patients underwent a complete ophthalmological examination and optical coherence tomography and had visually evoked potentials (VEP) and static automated perimetry registered.Results. A decrease in functional and structural parameters progressing with the duration of MS was revealed. In particular, best corrected visual acuity (BCVA) fell to 0.860 ± 0.075, the photosensitivity index MD maximally fell to -3.78 ± 0.95 dB, the strength of the P100 wave amplitude dropped to 7.84 ± 2.98 μV, the latency index of VEP rose to 124.21 ± 1.36 ms, the thickness of GCL + IPL fell to 65.69 ± 7.85 μm, and RNFL thickness averagely fell a low as to 80.25 ± 8.81 μm. When analyzing the topography of GCL + IPL decrease by sectors, the maximum value was revealed in the upper temporal segment (67.63 ± 7.89 μm). Sectoral changes in RNFL arranged in descending order of thickness showed the following sequence: lower upper nasal temporal. As the disease progressed, structural and functional changes were accompanied by an increase in the depth and a decrease in the thickness of the lamina cribrosa, with a maximum value revealed in the group with prior ON (239.00 ± 11.93 μm). Strong correlations were found in all study groups between (1) ave. GCL + IPL and ave. RNFL (r = 0.69; 0.64; 0.88, p &lt; 0.03), (2) ave. GCL+IPL and BCVA (r = 0.86; 0.75; 0.78, p &lt; 0.05), (3) MD and ave GCL + IPL (r = 0.52; 0.69; 0.71, p &lt; 0.03), and (4) MD and ave. RNFL (r = 0.67; 0.61; 0.66, p &lt; 0.05), as well as between the parameters of the lamina cribrosa and the markers under study.Conclusion. Significant functional and structural changes in the retina and the optic nerve were detected, correlating with the duration of the disease and with the clinical features of the course of multiple sclerosis. The presence of ON in history was accompanied by more pronounced changes, which can be considered as an important additional aggravating factor of the disease.

Topographical Correlation between Structural and Functional Impairment of the Macular Inner Retinal Layers in Multiple Sclerosis Eyes with a History of Optic Neuropathy.

We investigated the potential correlation between morphological and functional parameters describing the rarefaction and dysfunction of retinal ganglion cells (RGCs), located in the macula, in multiple sclerosis eyes with a history of optic neuritis (MS-ON). A total of 19 MS-ON eyes from 19 MS patients (mean age: 44.16 ± 4.66 years; 11 females and 8 males), with a mean disease duration of 10.06 ± 6.12 years and full recovery of visual acuity, and 30 age-similar (mean age: 45.09 ± 5.08 years) healthy eyes were submitted for ophthalmological evaluation using swept-source optical coherence tomography (SS-OCT) and multifocal photopic negative response (mfPhNR) to study the structural and functional features of localized RGCs. Both GCL+ thickness (via SS-OCT) and response amplitude density (RAD) (via mfPhNR) measurements were obtained from annular regions and ETDRS sectors. Morphological and electrophysiological data from the control and MS groups were compared by using an ANOVA test. GCL+ values were correlated with the corresponding RADs derived from almost superimposable areas using Pearson's tests (p < 0.01). In MS-ON eyes, the mean values of macular GCL+-T and mfPhNR RAD detected in all rings and ETDRS sectors were significantly reduced (p < 0.01) when compared with control ones. In addition, when plotting the GCL+-T and mfPhNR RAD individual data from MS-ON eyes, we found statistically significant linear correlations (p < 0.01) when considering responses from both rings and sectors. In conclusion, in MS-ON eyes, a topographical correlation between structural and functional impairment of macular RGCs occurs.

Cellular-Level Visualization of Retinal Pathology in Multiple Sclerosis With Adaptive Optics.

To apply adaptive optics-optical coherence tomography (AO-OCT) to quantify multiple sclerosis (MS)-induced changes in axonal bundles in the macular nerve fiber layer, ganglion cell somas, and macrophage-like cells at the vitreomacular interface. We used AO-OCT imaging in a pilot study of MS participants (n = 10), including those without and with a history of optic neuritis (ON, n = 4), and healthy volunteers (HV, n = 9) to reveal pathologic changes to inner retinal cells and structures affected by MS. We found that nerve fiber layer axonal bundles had 38% lower volume in MS participants (1.5 × 10-3 mm3) compared to HVs (2.4 × 10-3 mm3; P < 0.001). Retinal ganglion cell (RGC) density was 51% lower in MS participants (12.3 cells/mm2 × 1000) compared to HVs (25.0 cells/mm2 × 1000; P < 0.001). Spatial differences across the macula were observed in RGC density. RGC diameter was 15% higher in MS participants (11.7µm) compared to HVs (10.1µm; P < 0.001). A nonsignificant trend of higher density of macrophage-like cells in MS eyes was also observed. For all AO-OCT measures, outcomes were worse for MS participants with a history of ON compared to MS participants without a history of ON. AO-OCT measures were associated with key visual and physical disabilities in the MS cohort. Our findings demonstrate the utility of AO-OCT for highly sensitive and specific detection of neurodegenerative changes in MS. Moreover, the results shed light on the mechanisms that underpin specific neuronal pathology that occurs when MS attacks the retina. The new findings support the further development of AO-based biomarkers for MS.

Retinal clues for selective neuronal loss in multiple sclerosis.

The relationship between the cell body layer and the dendritic network layer of the retina and cognitive performance (CP) in MS patients has not been examined separately. The objective of this study is to predict cognitive impairment (CI) in RRMS patients and to examine the relationship between CP and ganglion cell layer (GCL), inner plexiform layer (IPL), and GCL divided by IPL (GCL/IPL). Ophthalmological evaluation, retinal segmentation, and Symbol Digit Modalities Test (SDMT) were performed on 102 RRMS patients and 54 healthy subjects. The relationships of GCL, IPL, and GCL/IPL with CP in eyes without a history of optic neuritis were investigated using Spearman's correlation. Models were created by accepting 1 standard deviation less of the SDMT mean of the control group as the limit for CI. The cutoff value of the GCL/IPL variable that could predict CI was calculated by ROC analysis, and the ability to accurately predict CI was tested with binary logistic regression. No correlation was found between OCT parameters and CP in healthy subjects. Correlation was found between GCL thickness and GCL/IPL variable and CP in RRMS patients (r=0.235, r=0.667 respectively). A GCL/IPL value of 1.255 was able to identify CI with 81.8% sensitivity and 75.9% specificity (AUC=0.844, LR=3.38) and predicted CI with 74.5% accuracy (Nagelkerke R2=0.439). In RRMS patients, the IPL thickness is unrelated to CP. Therewithal, the GCL/IPL-CP relationship is stronger than the GCL-CP relationship and GCL/IPL can predict CI.

Optical coherence tomography with voxel-based morphometry: a new tool to unveil focal retinal neurodegeneration in multiple sclerosis.

Neurodegeneration is the main contributor to disability accumulation in multiple sclerosis. Previous studies in neuro-ophthalmology have revealed that neurodegeneration in multiple sclerosis also affects the neuro-retina. Optical coherence tomography has been used to measure thinning of retinal layers, which correlates with several other markers for axonal/neuronal loss in multiple sclerosis. However, the existing analytical tools have limitations in terms of sensitivity and do not provide topographical information. In this study, we aim to evaluate whether voxel-based morphometry can increase sensitivity in detecting neuroaxonal degeneration in the retina and offer topographical information. A total of 131 people with multiple sclerosis (41 clinically isolated syndrome, 53 relapsing-remitting and 37 progressive multiple sclerosis) and 50 healthy subjects were included. Only eyes with normal global peripapillary retinal nerve fibre layer thickness and no history of optic neuritis were considered. Voxel-based morphometry and voxel-wise statistical comparisons were performed on the following: (i) patients at different disease stages and 2) patients who experienced the first demyelination attack without subclinical optic neuritis, assessed by visual evoked potentials. Standard parameters failed to discern any differences; however, voxel-based morphometry-optical coherence tomography successfully detected focal macular atrophy of retinal nerve fibre layer and ganglion cell/inner plexiform layer, along with thickening of inner nuclear layer in patients who experienced the first demyelination attack (disease duration = 4.2 months). Notably, the atrophy pattern of the ganglion cell/inner plexiform layer was comparable across disease phenotypes. In contrast, the retinal nerve fibre layer atrophy spread from the optic nerve head to the fovea as the disease evolved towards the progressive phase. Furthermore, for patients who experienced the first neurological episode, the severity of retinal nerve fibre layer atrophy at entry could predict a second attack. Our results demonstrate that voxel-based morphometry-optical coherence tomography exhibits greater sensitivity than standard parameters in detecting focal retinal atrophy, even at clinical presentation, in eyes with no history of optic neuritis and with normal latency of visual evoked potentials. Thinning of the ganglion cell/inner plexiform layer primarily concentrated in nasal perifovea in all disease phenotypes, indicating selective vulnerability of retinal ganglion cells and their perifoveal axons. Conversely, the degree of retinal nerve fibre layer thinning seems to be related to the clinical course of multiple sclerosis. The findings suggest bidirectional neurodegeneration in the visual pathway. Voxel-based morphometry-optical coherence tomography shows potential as a valuable tool for monitoring neurodegeneration on a patient level and evaluating the efficacy of novel neuroprotective treatments.

Delayed oculomotor response associates with optic neuritis in youth with demyelinating disorders

IntroductionImpairment in visual and cognitive functions occur in youth with demyelinating disorders such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Quantitative behavioral assessment using eye-tracking and pupillometry can provide functional metrics for important prognostic and clinically relevant information at the bedside. MethodsChildren and adolescents diagnosed with demyelinating disorders and healthy, age-matched controls completed an interleaved pro- and anti-saccade task using video-based eye-tracking and underwent spectral-domain optical coherence tomography examination for evaluation of retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Low-contrast visual acuity and Symbol Digit Modalities Test were performed for visual and cognitive functional assessments. We assessed saccade and pupil parameters including saccade reaction time, direction error rate, pupil response latency, peak constriction time, and peak constriction and dilation velocities. Generalized Estimating Equations were used to examine the association of eye-tracking parameters with optic neuritis history, structural metrics, and visual and cognitive scores. ResultsThe study included 36 demyelinating disorders patients, aged 8–18 yrs. (75% F; median = 15.22 yrs., SD = 2.8) and 34 age-matched controls (65% F; median = 15.26 yrs., SD = 2.3). Surprisingly, pro- and anti-saccade performance was comparable between patients and controls, whereas pupil control was altered in patients. Oculomotor latency measures were strongly associated with the number of optic neuritis episodes, including saccade reaction time, pupil response latency, and peak constriction time. Peak constriction time was associated with both retinal nerve fiber layer and ganglion cell inner plexiform layer thickness. Pupil response latency and peak constriction time were associated with visual acuity. Pupil velocity for both constriction and dilation was associated with Symbol Digit Modalities Test scores. ConclusionThe strong associations between oculomotor measures with history of optic neuritis, structural, visual, and cognitive assessments in these cohorts demonstrates that quantitative eye-tracking can be useful for probing demyelinating injury of the brain and optic nerve. Future studies should evaluate their utility in discriminating between demyelinating disorders and tracking disease progression.

Assessment of Outer Retina and Choroid Using Swept Source Optical Coherence Tomography and Angiography in Patients With Multiple Sclerosis.

For patients with multiple sclerosis (MS), both structure and microvasculature alterations in the inner retina have been investigated in several studies. However, little is known about the alterations in the outer retina and choroid. Hence, this study aimed to assess the outer retinal and choroidal changes in patients with MS with no history of optic neuritis (ON). Patients with MS and healthy control participants were enrolled in this cross-sectional study. Quantitative analyses were performed using swept source optical coherence tomography and swept source optical coherence tomography angiography images to assess outer retina thickness (ORT) and choroid thickness (CT), vessel density (VD) of choriocapillaris, and choroidal vascularity index (CVI), which were then compared between the groups. A total of 37 participants with MS (72 eyes) and 74 healthy control participants (148 eyes) were included in this study. Compared with healthy controls, patients with MS with no history of ON showed reduced VD of the choriocapillaris and CVI. There was no significant difference in ORT and CT between 2 groups. Meanwhile, in patients with MS, no correlation between OCTA parameters and expanded disability status scale score were found in this study. Our study indicates that patients with MS with no history of optical neuritis have reduced choriocapillaris vessel density and decreased choroidal vascularity index without detectable alteration in outer retina thickness and choroid thickness. The findings complement the outer retinal and choroidal component of MS, providing deeper insight into the pathophysiology of MS.

Pregnancy prevalence and outcomes after optic neuritis in South Korea

To compare pregnancy rates and complications in women with and without a history of optic neuritis (ON). A nationwide, population-based, retrospective study using data from the Korean National Health Claims from January 2011, to December 2017 was done. ON cohort (ON group) consisting of women aged 18 to 50 with a history of ON and 1:3 age-matched controls (control group) were compared for pregnancy and delivery rates using logistic regression after adjusting for possible confounders. Pregnancy-ON cohort (pregnancy-ON group), women aged 18 to 55 with a history of ON and pregnancy, and 1:3 age at pregnancy matched controls (pregnancy-control group) were analyzed for pregnancy complications using logistic regression after adjusting for covariates. ON group (n = 2516) showed decreased odds ratio (OR) for pregnancy [Adjusted OR2: 0.716, 95% confidence interval (CI): 0.626–0.820] and delivery (adjusted OR2: 0.647, 95% CI: 0.554–0.756) compared to controls (n = 7548). Pregnancy-ON group (n = 550) showed increased risk of delayed fetal growth (adjusted OR2: 9.867, 95% CI: 1.224–79.564), pre-eclampsia (adjusted OR2: 8.327, 95% CI: 2.911–23.819), preterm delivery (adjusted OR2: 3.914, 95% CI: 2.667–5.742), pregnancy and postpartum infection (adjusted OR1: 1.671, 95% CI: 1.296–2.154), diabetes in pregnancy (adjusted OR2: 1.365, 95% CI: 1.062–1.754) compared to pregnancy-control group (n = 1650). Our population-based cohort study suggests that history of ON is associated with decreased pregnancy and delivery rates. It may be a risk factor for various pregnancy complications.

Evaluation of microvascular changes in the retina and choriocapillaris in primary glaucoma and neuromyelitis optica spectrum disorder with optical coherence tomography angiography

BackgroundTo assess quantitatively the microvascular changes in the retina and choroid of healthy eyes, eyes of subjects with primary angle-closure glaucoma (PACG), primary open-angle glaucoma (POAG) and neuromyelitis optica spectrum disorder (NMOSD) using optical coherence tomography angiography (OCTA). MethodsA series of healthy individuals and subjects with PACG, POAG and NMOSD were recruited in this cross-sectional study. OCTA was performed to capture the optic nerve head and macula images and the vessel density (VD) and retinal nerve fiber layer (RNFL) thickness were quantified. The choriocapillary flow density (CFD) was calculated as the percentage of flow area to the whole selected area. ResultsA total of 68 PACG subjects, 25 POAG subjects, 51 NMOSD subjects and 37 healthy controls were enrolled. Significant decreases in peripapillary VD and RNFL thickness were observed in PACG (p < 0.001) and POAG (p < 0.001) eyes and also in NMOSD subjects with an optic neuritis history (p < 0.001) compared with healthy controls. Unaffected eyes in PACG and POAG subjects had lower baseline peripapillary VD than healthy controls (p = 0.002 and p = 0.011, respectively). PACG eyes showed a lower baseline CFD than POAG (p = 0.0027) and the CFD in early and advanced PACG eyes showed a significantly much more decrease than POAG (p = 0.002 and p < 0.001, respectively). ConclusionsThe peripapillary vessel density and RNFL thickness was reduced in glaucomatous and NMOSD eyes compared with healthy controls. PACG eyes showed a lower CFD than POAG and the distinct peripapillary and choriocapillaris microvasculature changes may be correlated to different PACG and POAG pathogenesis.

Diagnosis of multiple sclerosis using optical coherence tomography supported by artificial intelligence.

Current procedures for diagnosing multiple sclerosis (MS) present a series of limitations, making it critically important to identify new biomarkers. The aim of the study was to identify new biomarkers for the early diagnosis of MS using spectral-domain optical coherence tomography (OCT) and artificial intelligence. Spectral domain OCT was performed on 79 patients with relapsing-remitting multiple sclerosis (RRMS) (disease duration ≤ 2 years, no history of optic neuritis) and on 69 age-matched healthy controls using the posterior pole protocol that incorporates the anatomic Positioning System. Median retinal thickness values in both eyes and inter-eye difference in healthy controls and patients were evaluated by area under the receiver operating characteristic (AUROC) curve analysis in the foveal, parafoveal and perifoveal areas and in the overall area spanned by the three rings. The structures with the greatest discriminant capacity - retinal thickness and inter-eye difference - were used as inputs to a convolutional neural network to assess the diagnostic capability. Analysis of retinal thickness and inter-eye difference in RRMS patients revealed that greatest alteration occurred in the ganglion cell (GCL), inner plexiform (IPL), and inner retinal (IRL) layers. By using the average thickness of the GCL (AUROC=0.82) and the inter-eye difference in the IPL (AUROC=0.71) as inputs to a two-layer convolutional neural network, automatic diagnosis attained accuracy=0.87, sensitivity=0.82, and specificity=0.92. This study adds weight to the argument that neuroretinal structure analysis could be incorporated into the diagnostic criteria for MS.

Quantifying Retrograde Trans-Synaptic Degeneration of the Visual Pathway in Multiple Sclerosis. (S9.008)

<h3>Objective:</h3> To develop a method for quantifying retrograde trans-synaptic degeneration (rTSD) in multiple sclerosis (MS) and investigate its association with demographic characteristics and visual function. <h3>Background:</h3> Neurodegeneration occurs early in MS, contributes to irreversible clinical disability, and is poorly mitigated by currently available treatments. rTSD is a phenomenon in which injury to one neuroaxonal unit propagates retrogradely, amplifying neuronal loss from MS lesions. There are no effective ways of quantifying rTSD in the visual pathway and its impact on visual function has not been elucidated. <h3>Design/Methods:</h3> In this cross-sectional single-center study, patients with MS (pwMS) and non-MS controls underwent clinical, standard automated perimetry and optical coherence tomography assessments. Using customized retinal layer segmentation in nasal and temporal hemimacular sectors, we developed an rTSD-index, which compares ganglion cell hemimacular projections corresponding to each cerebral hemisphere, with positive values reflecting right-hemisphere driven rTSD and vice versa, and absolute rTSD-index (ArTSD) values indicating severity. <h3>Results:</h3> A total of 79 pwMS and 23 non-MS controls were included (average age 45±13 and 37±14, 67% and 61% female, respectively). On average, pwMS had higher ArTSD values (mean difference 1.5, p=0.02). Evidence of rTSD was detected in 13/79 (16%) pwMS and 0/23 non-MS controls at an ArTSD threshold of 3.5. In pwMS, longer disease duration was associated with increased ArTSD severity (β=0.9 for each decade of increased disease duration, p=0.03). For each 1 point increase in ArTSD value, there was on average a 0.1 dB worsening in corresponding visual hemifield function after excluding subjects with optic neuritis history (p=0.02). <h3>Conclusions:</h3> rTSD-index is a novel method to quantify rTSD of the visual pathway in MS, which occurs in 1 out of 6 pwMS, is associated with longer disease duration and subclinical visual field defects. Future studies investigating its association with clinical disability, MRI findings, and methods to mitigate it are needed. <b>Disclosure:</b> Mr. Manukyan has nothing to disclose. Miss Zabala has nothing to disclose. Ms. Locke has nothing to disclose. Dr. Guerrero has nothing to disclose. Dr. Kaisey has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Kaisey has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Kaisey has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Kaisey has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Eichhorn &amp; Eichhorn, LLP. The institution of Dr. Kaisey has received research support from NMSS. The institution of Dr. Kaisey has received research support from Race to Erase MS. Dr. Khodabakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bausch and Lomb. Dr. Khodabakhsh has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson and Johnson. Dr. Khodabakhsh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bausch and Lomb. Dr. Khodabakhsh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bausch and Lomb. The institution of Dr. Sicotte has received research support from Biogen. The institution of Dr. Sicotte has received research support from PCORI. The institution of Dr. Sicotte has received research support from NIH. The institution of Dr. Sicotte has received research support from NMSS. Dr. Sicotte has a non-compensated relationship as a National Medical Advisory Committee Chair with National MS Society that is relevant to AAN interests or activities. The institution of Dr. Sati has received research support from National Multiple Sclerosis Society. The institution of Dr. Sati has received research support from National Institutes of Health. Dr. Sati has received publishing royalties from a publication relating to health care. The institution of Dr. Al-Louzi has received research support from the National Multiple Sclerosis Society and American Brain Foundation.

Evaluation of transorbital sonography measures of optic nerve diameter in the context of global and regional brain volume in multiple sclerosis

Transorbital sonography (TOS) could be a swift and convenient method to detect the atrophy of the optic nerve, possibly providing a marker that might reflect other quantitative structural markers of multiple sclerosis (MS). Here we evaluate the utility of TOS as a complementary tool for assessing optic nerve atrophy, and investigate how TOS-derived measures correspond to volumetric brain markers in MS. We recruited 25 healthy controls (HC) and 45 patients with relapsing–remitting MS and performed B-mode ultrasonographic examination of the optic nerve. Patients additionally underwent MRI scans to obtain T1-weighted, FLAIR and STIR images. Optic nerve diameters (OND) were compared between HC, MS patients with and without history of optic neuritis (non-ON) using a mixed-effects ANOVA model. The relationship between within-subject-average OND and global and regional brain volumetric measures was investigated using FSL SIENAX, voxel-based morphometry and FSL FIRST. OND was significantly different between HC-MS (HC = 3.2 ± 0.4 mm, MS = 3 ± 0.4 mm; p < 0.019) and we found significant correlation between average OND and normalised whole brain (β = 0.42, p < 0.005), grey matter (β = 0.33, p < 0.035), white matter (β = 0.38, p < 0.012) and ventricular cerebrospinal fluid volume (β = − 0.36, p < 0.021) in the MS group. History of ON had no impact on the association between OND and volumetric data. In conclusion, OND is a promising surrogate marker in MS, that can be simply and reliably measured using TOS, and its derived measures correspond to brain volumetric measures. It should be further explored in larger and longitudinal studies.

Swept-Source Optical Coherence Tomography Thresholds in Differentiating Clinical Outcomes in a Real-World Cohort of Treatment-Naïve Multiple Sclerosis Patients

This study aimed to determine whether peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness thresholds for single-time-point swept-source optical coherence tomography (SS-OCT) measures can differentiate the clinical outcomes of treatment-naïve people with multiple sclerosis (pwMS). A total of 275 patients with the clinically isolated syndrome (n = 23), benign MS (n = 8), relapsing-remitting MS (n = 185), secondary progressive MS (n = 28), primary progressive MS (n = 31), and with no history of optic neuritis were included. The mean Expanded Disability Status Scale (EDSS) score was 3.0 ± 1.6. The cut-off values of pRNFL (87 µm and 88 µm) and GCIPL (70 µm) thicknesses have been adopted from previous studies using spectral-domain OCT. PwMS with pRNFL ≤87 µm and ≤88 µm had a longer disease duration, more advanced disability, and more frequently progressive MS variants compared to those with greater pRNFL thicknesses. In distinguishing pwMS with disability greater than or equal to the mean EDSS score (EDSS ≥ 3) from those with less severe disability, GCIPL thickness <70 µm had the highest sensitivity, while pRNFL thickness ≤87 µm had the greatest specificity. The optimal cut-off values differentiating patients with EDSS ≥ 3 from those with less severe disability was 63 µm for GCIPL thickness and 93.5 µm for pRNFL thickness. In conclusion, pRNFL and GCIPL thickness thresholds for single-time-point SS-OCT measurements may be helpful in differentiating the disability status of treatment-naïve pwMS.

Prognostic Role of Visual Evoked Potentials in Non-Neuritic Eyes at Multiple Sclerosis Diagnosis

Introduction: This study aimed to assess the prognostic role of visual evoked potentials (VEPs) of the non-neuritic eye at the diagnosis of multiple sclerosis (MS). Patients and methods: We enrolled 181 MS patients (62% females, mean age at diagnosis: 38 years, standard deviation: 12) at the time of the first diagnostic work-up, including VEPs. We collected P100 latency and N75-P100 amplitude of non-neuritic eyes at diagnosis, and then we calculated the mean values in 127 patients with no history of optic neuritis (ON) or considered the unaffected eye in the remaining. At last follow-up (minimum: one year), disability was evaluated according to MS Severity Score or MSSS (median: 2.44, range: 0.18-9.63). Statistical analysis included Mann-Whitney descriptive analysis, Spearman correlation for independent samples, and linear regression for significant predictors of MSSS. Results: 38/181 patients had P100 latency >115 ms, and 63/181 showed N75-P100 amplitude < 5 microV in the unaffected eyes at MS diagnosis. At last follow-up, MSSS correlated with P100 latency (rho = 0.21, p = 0.004) and N75-P100 amplitude (rho = 0.19, p = 0.009) collected at diagnosis. P100 latency (not N75-P100 amplitude) resulted in a predictor for disability over time (MSSS) in the regression model (along with age at onset, MS course, and disease-modifying treatments). Conclusions: Our study showed a prognostic value of VEPs in clinically unaffected eyes at MS diagnosis to predict future disability, independently from a history of ON.