Multiple Sclerosis Eyes Research Articles

Discrimination of multiple sclerosis using scanning laser ophthalmoscopy images with autoencoder-based feature extraction

ObjectiveOptical coherence tomography (OCT) investigations have revealed that the thickness of inner retinal layers becomes decreased in multiple sclerosis (MS) patients, compared to healthy control (HC) individuals. To date, a number of studies have applied machine learning to OCT thickness measurements, aiming to enable accurate and automated diagnosis of the disease. However, there have much less emphasis on other less common retinal imaging modalities, like infrared scanning laser ophthalmoscopy (IR-SLO), for classifying MS. IR-SLO uses laser light to capture high-resolution fundus images, often performed in conjunction with OCT to lock B-scans at a fixed position. MethodsWe incorporated two independent datasets of IR-SLO images from the Isfahan and Johns Hopkins centers, consisting of 164 MS and 150 HC images. A subject-wise data splitting approach was employed to ensure that there was no leakage between training and test datasets. Several state-of-the-art convolutional neural networks (CNNs), including VGG-16, VGG-19, ResNet-50, and InceptionV3, and a CNN with a custom architecture were employed. In the next step, we designed a convolutional autoencoder (CAE) to extract semantic features subsequently given as inputs to four conventional ML classifiers, including support vector machine (SVM), k-nearest neighbor (K-NN), random forest (RF), and multi-layer perceptron (MLP). ResultsThe custom CNN (85 % accuracy, 85 % sensitivity, 87 % specificity, 93 % area under the receiver operating characteristics [AUROC], and 94 % area under the precision-recall curve [AUPRC]) outperformed state-of-the-art models (84 % accuracy, 83 % sensitivity, 87 % specificity, 92 % AUROC, and 94 % AUPRC); however, utilizing a combination of the CAE and MLP yields even superior results (88 % accuracy, 86 % sensitivity, 91 % specificity, 94 % AUROC, and 95 % AUPRC). ConclusionsWe utilized IR-SLO images to differentiate between MS and HC eyes, with promising results achieved using a combination of CAE and MLP. Future multi-center studies involving more heterogenous data are necessary to assess the feasibility of integrating IR-SLO images into routine clinical practice.

Retinal small vessel pathology is associated with disease burden in multiple sclerosis

Background: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA). Objectives: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology. Methods: In this cross-sectional study, including 259 relapsing–remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools. Results: We identified a loss of small-sized vessels (diameter < 10 µm) in the superficial vascular complex in all MS eyes, irrespective of their optic neuritis (ON) history. This alteration was associated with MS disease burden and appears independent of retinal ganglion cell loss. In contrast, an observed reduction of medium-sized vessels (diameter 10–20 µm) was specific to eyes with a history of ON and was closely linked to ganglion cell atrophy. Conclusion: These findings suggest distinct atrophy patterns in retinal vessels in patients with MS. Further studies are necessary to investigate retinal vessel alterations and their underlying pathology in MS.

Evaluation of machine learning algorithms using OCT and OCT angiography for the diagnosis of multiple sclerosis

Aims/Purpose: We present a comprehensive evaluation of machine learning (ML) algorithms using Optical coherence tomography (OCT) and optical coherence tomography angiography (OCT‐A) for the diagnosis of Multiple sclerosis (MS).Methods: Prospective observational study using OCT volumes acquired with Cirrus HD‐OCT 5000 (Carl Zeiss, Meditec, Dublin, CA, EEUU) using the scanning protocols Optic Disc Cube 200 × 200 and Macular Cube 512 × 128, and OCT‐A macular volumes 175 × 350 with FOV 6 × 6 mm and OCT‐A of the Optic Nerve Head (ONH) with FOV 4.5 × 4.5 mm. The total data set consisted of 79 eyes of 40 patients with MS and 54 eyes of 27 control subjects. We evaluated classification algorithms such as Support Vector Machines, k‐Nearest Neighbour, Decision Trees, Random Forest, Extra Trees Classifier and Gaussian NB using data extracted from Ganglion Cell Analysis (8 parameters), Macular Thickness Analysis (7 parameters) and Optic Disc Analysis (5 parameters) from the OCT volumes and 5 parameters from the analysis of the macular OCT‐A volumes and 6 parameters from the analysis of the ONH. We studied all the ML algorithms considering three scenarios: OCT (20 parameters), OCT‐A (11 parameters), and OCT + OCT‐A (31 parameters). The models were trained using a 5‐fold cross‐validation strategy. We calculated the accuracy, F1‐score for each model and the area under the curve (AUC) was used to select the best ML algorithm. We applied SHAP (SHapley Additive exPlanations) to explain the output of the best ML model.Results: For the MS diagnosis, the best results were obtained for OCT with Gaussian NB (accuracy 0.865 ± 0.085, F1‐score 0.864 ± 0.086 and AUC 0.871 ± 0.081), for OCT‐A with Random Forest (accuracy 0.832 ± 0.032, F1‐score 0.832 ± 0.043 and AUC 0.831 ± 0.043) and for OCT + OCT‐A with Gaussian NB (accuracy 0.885 ± 0.028, F1‐score 0.886 ± 0.028 and AUC 0.891 ± 0.034). The input parameters with the highest contribution to the model's predictions were the minimum ganglion cell thickness and the temporal flow index in the ETDRS grid.Conclusions: This study highlights the efficacy of machine learning techniques in utilizing combined parameters from OCT and OCT‐A images of the macula and ONH tests to facilitate early diagnosis of MS. Moreover, it underscores the significance of ophthalmic examination in the comprehensive management 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.

Utility of optical coherence tomography in patients of central immune mediated demyelinating diseases - A prospective study.

Optical coherence tomography (OCT) is a non-invasive tool to measure thickness of various layers of retina. Recently, retinal nerve fibre layer (RNFL) and ganglion cell and inner plexiform layer (GCIP) thinning has been observed in OCT in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), This study compared OCT profile, along with visual acuity (VA), color vision (CV), contrast saturation (CS) and visual evoked potentials (VEP) in two main cohorts of MS and NMOSD and with controls, during acute episode of optic neuritis (ON), at 3 and 6months. We found that changes of ON were present in 75% of MS eyes and in 45% of NMOSD patients. Of these, subclinical involvement was present in 56.25% of MS eyes and only in 5% of NMOSD eyes suggesting frequent subclinical involvement in the former. Mean RNFL was 95.23±15.53 in MS and 66.14±43.73 in NMOSD after 6months of ON episode. Thinning of NQ and IQ was observed in NMOSD eyes in the immediate period after ON attack. At 6months relative sparing of RNFL in TQ was observed in NMOSD ON eyes and MS ON showed predilection for involvement of TQ.

Significant retinal microvascular impairments in multiple sclerosis assessed through optical coherence tomography angiography.

Multiple sclerosis (MS) is associated with different ocular disorders. This study aimed to investigate the retinal microvascular changes detected by optical coherence tomography angiography (OCTA) in eyes with MS with or without a history of optic neuritis (ON). A comprehensive literature search was conducted in the Web of Science, Embase, PubMed, and Cochrane Library databases on September 26, 2021 for articles focused on OCTA manifestations in the eyes of MS patients compared with healthy controls. RevMan Manager (v.5.4) and Stata (v.14.1) were used to analyze the main differences and publication risks. Weighted mean differences and 95% confidence intervals were calculated for continuous estimates. This study also included subgroup analysis between three groups: eyes with multiple sclerosis and with optic neuritis (MSON); eyes with multiple sclerosis and without optic neuritis (MSNON); and healthy controls. Thirteen studies with a total of 1803 eyes were identified, including 957 eyes with MS and 846 eyes of healthy controls. The vessel density of the MS eyes decreased significantly in most areas of the radial peripapillary capillary. A marked reduction in the macular superficial capillary plexus of MS eyes regardless of ON history was also confirmed. The results suggest that MS patients demonstrated significant retinal microvasculature impairment regardless of ON history, compared to healthy controls. Retinal vessel density attenuation detected by OCTA may serve as a reliable early marker of MS.

OCT retinal nerve fiber layer thickness differentiates acute optic neuritis from MOG antibody-associated disease and Multiple Sclerosis: RNFL thickening in acute optic neuritis from MOGAD vs MS

BackgroundOptic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities. MethodsThis was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS. ResultsSixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3–57.0) for the MOGAD group and 30.4 years (IQR: 25.7–38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116–212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93–113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74–0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17–105) and 7.5 µm (IQR: 1–18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening. ConclusionOCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials.

Choroidal Thickness in Multiple Sclerosis: An Optical Coherence Tomography Study.

Background and PurposeTo identify changes in the choroidal thickness (CT) in multiple sclerosis (MS) patients with and without optic neuritis (ON) using enhanced-depth-imaging optical coherence tomography (EDI-OCT).MethodsThis cross-sectional study included 96 eyes with MS and 28 eyes of healthy controls. All participants underwent an ophthalmologic examination and EDI-OCT scanning (Spectralis, Heidelberg Engineering, Germany) to assess the CT and the retinal nerve fiber layer (RNFL) thickness. MS patients were divided into two groups: 1) with and 2) without a history of ON. The CT was evaluated in the fovea and at six horizontal and six vertical points at 500, 1,000, and 1,500 µm from the fovea. Paired t-tests were used to compare the groups, and p-value<0.05 was considered as significant.ResultsAt all 13 measurements points, the CT was thicker in MS patients than in the healthy controls and was thinner in eyes with ON than in the contralateral eyes, but these differences were not statistically significant. However, the CT was always larger in all points in eyes with a history of ON than in the control eyes. The RNFL was significantly thinner (p<0.05) in both MS and ON eyes than in the control eyes.ConclusionsThe CT did not differ between MS and control eyes, but it was significantly larger in patients with a history of ON, in whom the RNFL was thinner. Further studies are necessary to establish the possible role of the choroid in MS.

Comparison of Visual Evoked Potentials in Patients Affected by Optic Neuritis From Multiple Sclerosis or Neuromyelitis Optica Spectrum Disorder.

To compare the visual evoked potentials (VEPs) of optic neuritis (ON) patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and controls. To evaluate correlations between VEP and optical coherence tomography (OCT), contrast sensitivity (CS), and automated perimetry. Fifty-five eyes with ON from 29 patients (MS = 14 and NMOSD = 15) and 57 eyes from 29 controls were evaluated using VEP, automated perimetry, CS, and optical coherence tomography. Three groups were analyzed: 1) MS eyes with history of ON (ON-MS), 2) NMOSD eyes with ON (ON-NMOSD), and 3) healthy controls. Groups were compared and associations between the parameters were tested. Compared to controls, ON-MS eyes showed significantly delayed N75 and P100 latencies when using a medium-sized stimulus (30'), and delayed P100 latency when using a large stimulus (1.5°), but similar amplitudes. Compared to controls, ON-NMOSD eyes showed significantly lower N75/P100 amplitudes (both stimulus sizes) and P100/N135 amplitudes (with the 30' stimulus), but latencies did not differ, except for a delayed P100 latency with the 30' stimulus. When comparing the 2 ON groups using the 1.5° stimulus, there was significant delay in P100 latency in ON-MS eyes and a reduction in N75/P100 amplitude in ON-NMOSD eyes. Peripapillary retinal nerve fiber layer, macular inner retinal layers, and CS measurements were significantly smaller in ON patients than in controls. A strong correlation was found between VEP parameters and inner retinal layer thickness in ON-NMOSD eyes. ON-MS eyes had normal amplitude and delayed VEP latency, whereas ON-NMOSD eyes displayed reduced amplitude and preserved latency when elicited by checkerboard stimulus with large 1.5° checks. Under such conditions, VEP may help distinguish resolved MS-related ON from resolved NMOSD-related ON.

Spectral-Domain Optical Coherence Tomography Assessment in Treatment-Naïve Patients with Clinically Isolated Syndrome and Different Multiple Sclerosis Types: Findings and Relationship with the Disability Status.

This study evaluates the peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular volume (TMV) using spectral-domain optical coherence tomography in treatment naïve patients with the clinically isolated syndrome (CIS) and different multiple sclerosis (MS) types. A total of 126 patients (15 CIS, 65 relapsing-remitting MS, 14 secondary progressive MS, 11 primary progressive MS, 21 benign MS) with or without optic neuritis (ON) history and 63 healthy age-similar controls were assessed. Concerning controls’ eyes, pRNFL thickness was significantly reduced in CIS-ON eyes (p < 0.01), while both TMV and pRNFL thickness was decreased in all MS eyes regardless of ON history (p < 0.01). Significant differences in pRNFL thickness and TMV between MS variants were observed for non-ON eyes (p < 0.01), with the lowest values in benign and secondary progressive disease type, respectively. The pRNFL thickness was inversely correlated with Expanded Disability Status Scale (EDSS) score in non-ON subgroups (p < 0.01), whereas TMV was inversely correlated with EDSS score in both ON and non-ON subgroups (p < 0.01). Concluding, pRNFL thinning confirms optic nerve damage in CIS-ON eyes and appears to be disproportionately high with respect to the disability status of benign MS patients. The values of TMV and pRNFL in non-ON eyes significantly correspond to MS course heterogeneity and patients’ disability than in ON eyes.

Differentiation between multiple sclerosis and neuromyelitis optica spectrum disorder using optical coherence tomography angiography

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) are autoimmune demyelinating diseases of distinct etiology presenting with optic neuritis (ON). This study aimed to identify the macular and peripapillary neurovascular alterations that may facilitate the differentiation between NMOSD and MS eyes using spectral-domain optical coherence tomography (OCT) and OCT angiography (OCTA). A total of 13 NMOSD patients and 40 MS patients were evaluated. After ON, the radial peripapillary capillary (RPC) vessel density was significantly decreased in the superior (S) and inferior (I) sectors in NMOSD compared with MS eyes, whereas in non-ON eyes, the temporal (T) sector of RPC was reduced in MS group. In the ON eyes, the retinal nerve fiber layer in the I and T quadrants was thinner in NMOSD than in MS. Regarding ON and non-ON eyes, the macular capillary plexuses, and the ganglion cell complex thickness did not differ between NMOSD and MS. The ratios, based on the disease-specific intra-eye RPC vessel density reduction pattern, were the best discriminants between NMOSD and MS, i.e., inferior to nasal (I/N) and I/T ratios for ON eyes, and S/T and N/T ratios for non-ON eyes. Our results show that the OCTA-based simple ratios may be useful in distinguishing NMOSD and MS patients.

OCT Variability Prevents Their Use as Robust Biomarkers in Multiple Sclerosis.

ObjectiveTo evaluate the agreement between the peripapillary retinal nerve fiber layer (pRNFL) and foveal thickness (FT) measurements among three different spectral domain-optical coherence tomography (SD-OCT) instruments in a sample of multiple sclerosis (MS) patients and a healthy age-matched control group.MethodsAn observational cross-sectional study with three groups: healthy subjects and MS patients w/w a previous clinical diagnosis of optic neuritis (ON) was conducted. The pRNFL and FT were measured using three different SD-OCT instruments (OCT PRIMUS 200 and OCT CIRRUS 500 SD-OCT [Carl Zeiss Meditec] and OCT 3D 2000 [Topcon]).ResultsTwenty eyes from 10 healthy subjects matched in age with MS patients without a previous history of eye disease and 62 MS eyes from 31 MS patients (29 eyes without history of ON and 33 eyes with history of ON) were enrolled. Healthy subjects and MS patients without ON did not show differences between the pRNFL and FT thickness (P>0.99) with any of the instruments. However, MS eyes with a previous episode of ON showed thinner pRNFL and FT (P<0.01). PRIMUS and CIRRUS OCT showed better agreement of the pRNLF and FT in both healthy and MS eyes. However, 3D OCT showed less agreement in the pRNFL measurement with CIRRUS in both healthy and MS eyes.InterpretationAlthough OCT is a valuable technology to improve MS patient assessment, differences between devices must be taken into account. It is necessary to create an international group that standardizes the measurement conditions and above all that provides reference bases for normal subjects.

Shortened Pattern Electroretinogram Latency and Impaired Autoregulatory Dynamics to Steady-State Stimuli in Patients With Multiple Sclerosis.

The steady-state pattern electroretinogram (PERG) is a sensitive measure of retinal ganglion cell (RGC) function that includes within-test progressive changes-adaptation-reflecting RGC autoregulatory dynamics. Comprehensive PERG assessment in patients with multiple sclerosis (MS) (with or without optic neuritis [ON]) may provide unique information about RGC dysfunction and its progression, as well as a comparison between functional loss and structural loss as measured by optical coherence tomography (OCT). The goal of this project was to measure steady-state PERG components and their associations with intraretinal layer thicknesses in MS. One hundred forty eyes of 70 patients with relapsing-remitting MS and 126 eyes of 63 age- and sex-matched healthy control subjects (HC) were investigated using a new-generation PERG method and ultrahigh-resolution OCT. Of MS eyes, there were 30 eyes with ON (MSON), 22 non-ON fellow eyes (MSFE), and 88 non-ON MS eyes (MSNON). PERG amplitude, phase (latency), and adaptation of amplitude and phase were measured and correlated with OCT-determined thicknesses of intraretinal layers. The average PERG amplitude in MSON eyes was significantly lower than MSFE (P = 0.007), MSNON (P = 0.002), and HC (P < 0.001). The PERG amplitude in MSFE eyes was also significantly lower than HC (P = 0.039). The PERG latency in MSON eyes was significantly shorter than in MSFE (P = 0.001), MSNON (P = 0.002), and HC (P < 0.001). The PERG latency in MSFE (P = 0.007) and MSNON (P = 0.002) was significantly shorter than in HC. However, no significant differences were found between MSFE and MSNON (P > 0.05). PERG adaptation of amplitude in MSON was significantly lower than that in MSNON (P = 0.039) and HC (P = 0.037). Both the amplitude and latency in the MS eyes were significantly correlated with the thicknesses of the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL). Shortened PERG latency and impaired autoregulatory dynamics occurred in MS, suggesting preferential dysfunction of small, slower RGC axons and decreased ability of RGC to autoregulate their gain in response to PERG stimulus. The established relations of PERG measurements with intraretinal thickness measurements suggested that PERG losses were primarily associated with GCIPL and mRNFL thinning.

Retinal Degeneration After First-Ever Optic Neuritis Helps Differentiate Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder.

Objective: Differentiation between neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) in the early phase is challenging but crucial for treatment and prognosis.Methods: We performed a prospective cross-sectional study to discriminate NMOSD from MS by evaluating retinal degeneration in optical coherence tomography (OCT) after a first-ever optic neuritis (ON) episode. Seventy-three NMOSD patients and 38 MS patients with ON at least 3 months prior were assessed by OCT, best-corrected visual acuity (VA), and 2.5% low-contrast VA. Multivariate linear regression models were used for comparisons. Receiver operating characteristic curves and Youden index were used for determining the discriminative value of retinal nerve fiber layer thickness (RNFL) and VA in distinguishing NMOSD from MS.Results: Among eyes with retinal degeneration after a first-ever ON episode (n = 93), NMOSD eyes (n = 60) presented thinner RNFL (p < 0.001) and worsened VA (p < 0.001) relative to MS eyes (n = 33). Furthermore, a RNFL thinner than 78.9 μm had a specificity of 93.9% for NMOSD; combined with a VA of <0.4 decimal, these characteristics provided 100% specificity for NMOSD.Conclusions: The first-ever ON eyes showed more severe retina degeneration in patients with NMOSD than MS, which could establish a cut-off of RNFL thickness and VA to distinguish NMOSD from MS in the early phase.

Assessment of the optic nerve and its arterial supply by ultrasound imaging in multiple sclerosis patients

BackgroundTransorbital sonography (TOS) has emerged as a promising assessment tool of the optic nerve and orbital arterial supply in multiple sclerosis (MS) patients.ObjectiveTo evaluate optic nerve diameter (OND), optic nerve sheath diameter (ONSD), and orbital hemodynamics using TOS in MS patients.MethodsForty MS patients and 28 matched healthy controls were included. Thirty-three eyes with previous optic neuritis (ON) and 47 eyes without previous ON of MS patients were examined. All subjects were submitted to assessment of OND, ONSD, and parameters of orbital hemodynamics using orbital ultrasound.ResultsOND and ONSD were smaller in MS eyes with previous ON than in controls. MS eyes with and without previous ON had statistically significant higher peak systolic and mean velocity of posterior ciliary arteries than the control eyes. Orbital blood flow velocities were negatively correlated with the duration of disease and Expanded Disability Status Scale (EDSS). A statistically significant decrease in blood flow velocities of the central retinal artery was detected in secondary progressive MS (SPMS) patients than in relapsing-remitting MS patients (RRMS).ConclusionTOS can be used as a feasible tool to detect optic atrophy in MS patients. MS patients may have abnormal retrobulbar hemodynamics compared to healthy controls.

Alterations in the retinal vasculature occur in multiple sclerosis and exhibit novel correlations with disability and visual function measures

Background: The retinal vasculature may be altered in multiple sclerosis (MS), potentially acting as a biomarker of disease processes. Objective: To compare retinal vascular plexus densities in people with MS (PwMS) and healthy controls (HCs), and examine correlations with visual function and global disability. Methods: In this cross-sectional study, 111 PwMS (201 eyes) and 50 HCs (97 eyes) underwent optical coherence tomography angiography (OCTA). Macular superficial vascular plexus (SVP) and deep vascular plexus (DVP) densities were quantified, and poor quality images were excluded according to an artifact-rating protocol. Results: Mean SVP density was 24.1% (SD = 5.5) in MS eyes (26.0% (SD = 4.7) in non-optic neuritis (ON) eyes vs. 21.7% (SD = 5.5) in ON eyes, p < 0.001), as compared to 29.2% (SD = 3.3) in HC eyes (p < 0.001 for all MS eyes and multiple sclerosis optic neuritis (MSON) eyes vs. HC eyes, p = 0.03 for MS non-ON eyes vs. HC eyes). DVP density did not differ between groups. In PwMS, lower SVP density was associated with higher levels of disability (expanded disability status scale (EDSS): R2 = 0.26, p = 0.004; multiple sclerosis functional composite (MSFC): R2 = 0.27, p = 0.03) and lower letter acuity scores (100% contrast: R2 = 0.29; 2.5% contrast: R2 = 0.40; 1.25% contrast: R2 = 0.31; p < 0.001 for all). Conclusions: Retinal SVP density measured by OCTA is reduced across MS eyes, and correlates with visual function, EDSS, and MSFC scores.

Visual Function and Disability Are Associated With Focal Thickness Reduction of the Ganglion Cell-Inner Plexiform Layer in Patients With Multiple Sclerosis.

PurposeThe purpose of this study was to visualize the topographic thickness patterns of the intraretinal layers and their associations with clinical manifestations in patients with multiple sclerosis (MS).MethodsNinety-four eyes of 47 relapsing-remitting MS patients without history of optic neuritis were imaged using optical coherence tomography and compared with 134 eyes of 67 healthy subjects. Volumetric data centered on the fovea were segmented to obtain the thickness maps of six intraretinal layers. The thickness measurements partitioned using the Early Treatment Diabetic Retinopathy Study (ETDRS) partition were correlated to the Expanded Disability State Scale (EDSS) and Sloan low contrast visual acuity (LCVA). The receiver-operating characteristics (ROC) curves were calculated to obtain the area under the ROC curves (AUCs).ResultsThe ganglion cell-inner plexiform layer (GCIPL) showed horseshoe-like thickness reduction profoundly at the nasal sector. The most profound thickness reduction zone (circular area, diameter = 1 mm) was located at 2 mm in the nasal sector and 0.4 mm inferior from the fovea, named the “M zone.” The thickness reduction of the M zone was −7.3 μm in MS eyes, which was the most profound alteration, compared to any ETDRS sectors. The AUC of the M zone was 0.75. The relationship between the thickness of the M zone and EDSS (r = −0.59, P < 0.001) or 2.5% LCVA (r = 0.51, P < 0.001) were ranked as the strongest relation compared to any ETDRS sectors.ConclusionsThis is the first study, to our knowledge, to visualize focal thickness alteration of GCIPL and reveal its relationship to visual function and disability in patients with MS without history of optic neuritis.

Ability of Swept-Source Optical Coherence Tomography to Detect Retinal and Choroidal Changes in Patients with Multiple Sclerosis.

Purpose To evaluate the ability of new swept-source (SS) optical coherence tomography (OCT) technology to detect changes in retinal and choroidal thickness in patients with multiple sclerosis (MS). Methods A total of 101 healthy and 97 MS eyes underwent retinal and choroidal assessment using SS Triton OCT (Topcon). Macular thickness and peripapillary data (retinal, ganglion cell layer (GCL+, GCL++) and retinal nerve fiber layer (RNFL) thickness) were analyzed, including choroidal thickness evaluation. Results Significant macular thinning was observed in all ETDRS areas (p < 0.001) in MS patients. Peripapillary retinal, RNFL, and GCL ++ thickness showed a significant reduction in patients in all sectors (p < 0.001) except in the nasal quadrant/sector (p > 0.05). GCL+ measurements were found to be reduced in the nasal (p=0.003), inferonasal (p=0.045), and temporal (p=0.001) sectors and total thickness (p < 0.001). Choroidal thickness was reduced in the outer macular ring in MS patients compared with controls (p=0.038). Conclusion New swept-source technology for OCT devices detects retinal thinning in MS patients, providing increased depth analysis of the choroid in these patients. MS patients present reduced retinal and choroidal thickness in the macular area and reduced peripapillary retinal, RNFL, and GCL thickness.

Microvascular blood flow velocities measured with a retinal function imager: inter-eye correlations in healthy controls and an exploration in multiple sclerosis

BackgroundThe retinal microcirculation has been studied in various diseases including multiple sclerosis (MS). However, inter-eye correlations and potential differences of the retinal blood flow velocity (BFV) remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV. The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls (HCs). Since prior studies raise the possibility of reduced BFV in MS eyes, a secondary aim was to compare retinal BFVs between MS eyes, grouped based on optic neuritis (ON) history and HC eyes.MethodsMacular arteriole and venule BFVs were determined using a retinal function imager (RFI) in both eyes of 20 HCs. One eye from a total of 38 MS patients comprising 13 eyes with ON (MSON) and 25 eyes without ON (MSNON) history were similarly imaged with RFI.ResultsOD (right) and OS (left) BFVs were not significantly different in arterioles (OD: 3.95 ± 0.59 mm/s; OS: 4.08 ± 0.60 mm/s, P = 0.10) or venules (OD: 3.11 ± 0.46 mm/s; OS: 3.23 ± 0.52 mm/s, P = 0.06) in HCs. Very strong inter-eye correlations were also found between arteriolar (r = 0.84, P < 0.001) and venular (r = 0.87, P < 0.001) BFVs in HCs. Arteriolar (3.48 ± 0.88 mm/s) and venular (2.75 ± 0.53 mm/s) BFVs in MSNON eyes were significantly lower than in HC eyes (P = 0.009 and P = 0.005, respectively). Similarly, arteriolar (3.59 ± 0.69 mm/s) and venular (2.80 ± 0.45 mm/s) BFVs in MSON eyes were also significantly lower than in HC eyes (P = 0.046 and P = 0.048, respectively). Arteriolar and venular BFVs in MSON and MSNON eyes did not differ from each other (P = 0.42 and P = 0.48, respectively).ConclusionsInter-eye arteriolar and venular BFVs do not differ significantly in HCs and are strongly correlated. Our findings support prior observations that arteriolar and venular BFVs may be reduced in MS eyes. Moreover, this seems to be the case in both MS eyes with and without a history of ON, raising the possibility of global blood flow alterations in MS. Future larger studies are needed to assess differences in BFVs between MSON and MSNON eyes.