Bruch Membrane Opening Minimum Rim Width in Neuromyelitis Optica

Optical coherence tomography (OCT) analyzes the neurodegeneration in neuromyelitis optica (NMO) and multiple sclerosis (MS) and quantifies optical atrophy. The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness are decreased, and this structural change is correlated with visual function of patients, including contrast vision and visual field deviation. The main objective of this study was to evaluate the Bruch membrane opening minimum rim width (BMO) of the patients with NMO

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Bruch Membrane Opening Minimum Rim Width in Neuromyelitis Optica Lorane Bechet, MD, Philippe Cabre, MD, PhD, Harold Merle, MD, PhD Background: Optical coherence tomography (OCT) analyzes the neurodegeneration in neuromyelitis optica (NMO) and multiple sclerosis (MS) and quantifies optical atrophy. The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness are decreased, and this structural change is correlated with visual function of patients, including contrast vision and visual field deviation. The main objective of this study was to evaluate the Bruch membrane opening minimum rim width (BMO) of the patients with NMO. Methods: We studied the thickness of the BMO by OCT, in patients with NMO (n = 25; 34 eyes), MS (n = 50; 70 eyes), and a control group (n = 51; 100 eyes). The study evaluated the structure–function relationship with the correlation between OCT and visual function: Visual acuity, Pelli– Robson score, Sloan 2.5 and 1.25, color vision, standard automated perimetry (SAP), and frequency-doubling technology perimetry (FDT). Results: The average thickness of BMO was significantly reduced in NMO and MS with or without a history of optic neuritis (ON). Significant thinning of the average, nasal, and inferonasal BMO in the absence of ON in NMO was found compared with controls (P = 0.022, 0.006, and 0.026, respectively). BMO was strongly correlated with Pelli– Robson score (P , 0.001), Sloan 2.5 (P , 0.001), and mean deviation of SAP and FDT (P = 0.004). The sectorial study found a high correlation between the BMO and the corresponding sector of the visual field. Conclusions: The BMO thickness is decreased after ON in NMO and MS. This study showed an improved ability of BMO over RNFL and GCL to detect infraclinical impairment in patients with NMO without a history of optic neuropathy. Like the RNFL and GCL, BMO is well correlated with visual function, including contrast vision and visual field deviation. Journal of Neuro-Ophthalmology 2022;42:e48–e55 doi: 10.1097/WNO.0000000000001297 © 2021 by North American Neuro-Ophthalmology Society Departments of Ophthalmology (LB, HM); and Neurology (PC), University Hospital of Martinique, Fort de France, France (French West Indies). The authors report no conflicts of interest. Address correspondence to Lorane Bechet, MD, Department of Ophthalmology, University Hospital of Martinique, Hôpital Pierre Zobda Quitman, BP 632, 97261 Fort de France Cedex, Martinique, France (French West Indies); E-mail: [e-mail] e48 N euromyelitis optica (NMO) and multiple sclerosis (MS) are demyelinating autoimmune diseases of the central nervous system. NMO is an astrocytopathy and the anti-aquaporin 4 (AQP4) antibody has an important role in pathophysiology with the involvement of humoral immunity (1,2). The prevalence varies according to country and ethnicity (3.9/100,000 in Olmsted County and 10/ 100,000 in Martinique) (3). NMO mainly affects women (70%–90%), and the average age of onset is 40 years. It is earlier in Afro-Caribbean patients with an average of 34 years (4,5). Optic neuritis (ON) is a manifestation found in both diseases, but severity and recovery are not the same. In NMO, the underlying ON is usually severe, unilateral or bilateral with rather posterior optic nerve involvement, and is associated with a profound visual impairment and an absence of spontaneous recovery, unlike MS. Differential diagnosis is usually made on the basis of paraclinical tests, such as AQP4 antibody assays and MRI. Availability and delay of results may delay diagnosis. Because the prognosis and treatment differ, developing markers to distinguish the 2 diseases early is of primary interest. Optical coherence tomography (OCT) is a noninvasive and reproducible examination that measures retinal degeneration. Several studies have shown that the decrease in macular and peripapillary retinal nerve fiber layer (RNFL) thickness is greater in NMO than in MS (6–8). Thinning was often correlated with the extent of impaired visual function (9,10). Bruch membrane opening minimum rim width (BMO) measures the thickness of the neuroretinal ring by detecting the smallest distance between the Bruch membrane termination and the internal limiting membrane. Primarily studied in glaucoma, BMO has been shown to be reproducible, efficient, and relevant in monitoring glaucoma at different stages of the disease (11–13). The BMO measures are correlated with loss of visual function and aging but unlike the RNFL are not related to ethnicity (14–18). With a longer acquisition time than the RNFL, BMO requires better compliance (19). Recently, Bechet et al: J Neuro-Ophthalmol 2022; 42: e48-e55 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Nguyen et al demonstrated a decrease in BMO for patients with MS, but the latter was less associated with visual function than measurement of ganglion cell layer (GCL) thickness (20). To the best of our knowledge, no studies of BMO have been performed in patients with NMO. The objective of our study is to measure BMO in patients with NMO and compare the results with patients with MS and controls. METHODS The study was conducted prospectively at the University Hospital of Martinique from January 2015 to November 2018. The study was approved by the University Hospital of Martinique Institutional Review Board. Patients’ and controls’ informed consent was obtained for inclusion. Patients Patients with NMO and MS included in the study were diagnosed by neurologists specialized in the management of demyelinating diseases. Diagnosis was based on the international criteria published in 2015 for NMO (21) and the 2010 revised McDonald criteria for MS (22). All the patients included were older than 18 years and attended at least one follow-up visit at the University Hospital of Martinique between January 2015 and November 2018. The inclusion did not require other clinical criteria or symptoms. However, patients with a relapse of ON less than 6 months old were excluded. Healthy controls were recruited from the University Hospital of Martinique and were matched for age (±1 year) and sex. Patients and healthy controls with a history of diabetes, uveitis, glaucoma, intraocular pressure greater than 21 mm Hg, trauma, ocular surgery, and neurological or retinal disease were excluded. Patients with a spherical refractive error of more than 6 diopters or more than 3 cylindrical diopters, with a visual field with a falsenegative, false-positive, or loss of fixation rate greater than 20% were also excluded. Information about the included patients was consolidated using a national database of patients with NMO and MS, the European Database for Multiple Sclerosis (23). The database comprises longitudinally collected clinical information at the University Hospital of Martinique (diagnosis date, duration of the disease, Expanded Disability Status Scale [EDSS], number and nature of relapses, etc.). Visual Function Visual acuity was measured using the Snellen scale (20/4,000 to 20/20) and the logarithmic scale of Early Treatment Diabetic Retinopathy Study (ETDRS). As for sensitivity to spatial contrast, the Sloan 2.5% and 1.25% charts and the Pelli–Robson test were collected. Exploration of color vision was performed with the Farnsworth 100Hue desaturated test. The score obtained according to the age of the patient was obtained using Verriest tables (24). Sensitivity to temporal contrasts was explored by frequencydoubling technology (FDT) perimetry (Carl Zeiss Humphrey, Dublin, CA). Standard automated static perimetry (SAP) was performed with the 24-2 SITA program (Humphrey Field Analyzer, Carl-Zeiss Meditec, Dublin, CA). The examination was considered reliable if the numbers of false-positives, false-negatives, and fixation losses were less than 20%. Optical Coherence Tomography The OCT examination was performed prospectively using Spectralis (SD-OCT, Heidelberg Engineering, Germany) by an ophthalmologist aware of the diagnosis. The measurement was performed without dilatation. BMO and RNFL were obtained with the optic nerve head-radial circle. After locating the center of the fovea and the center of the opening of the Bruch membrane, 24 B-radial scans separated by 15°, then 3 circles of 3.5, 4.1, and 4.7 mm diameter were performed. For the RNFL, the results of the 3.5-mm circle were collected. The analysis of the GCL was obtained from the posterior pole protocol. The results were presented in the form of a map divided into 9 sectors (a central part, 4 sectors at 3 mm, and 4 sectors at 6 mm). Only the central part and the sectors at 3 mm were considered. All scans were manually checked and modified in case of segmentation errors. This manual checking was performed during data collection by a second ophthalmologist blind to the diagnosis. The correlation between the different sectors of the visual field and the thickness of the BMO was FIG. 1. Structure–function map according to Garway-Heath et al (25). A. Sectors of the standard automated perimetry. B. Sectors of the OCT RNFL. C. SAP visual field test pattern and optic nerve head reference circle superimposed. OCT, optical coherence tomography; RNFL, retinal nerve fiber layer; SAP, standard automated perimetry. Bechet et al: J Neuro-Ophthalmol 2022; 42: e48-e55 e49 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. Selection of neuromyelitis optica and multiple sclerosis cases with OCT BMO. BMO, Bruch membrane opening examination; MS, multiple sclerosis; NMO, neuromyelitis optica; NMO-ON, patient with NMO with a history of optic neuritis; NMO-NON, patient with NMO without a history of optic neuritis; MS-ON, patient with MS with a history of optic neuritis; MSNON, patient with MS without a history of optic neuritis; OCT, optical coherence tomography. studied. The sector study was based on the Garway-Heath et al model (25). From illustrations of the nerve fiber layer of primates and taking into account the position of the optic nerve head (ONH) above the horizontal meridian, they have produced a clinically useful map that relates visual field test points to regions of ONH. Each sector of the SAP groups together the points of light sensitivity superimposed on the distribution and path of nerve fibers (Fig. 1, structure–function map according to Garway-Heath et al.). the Student test was used for mean comparisons. Spearman correlation coefficients (r) were used to examine the association between OCT-derived measures and visual function. The different OCT parameters were compared using the generalized estimating equation model with an exchangeable correlation structure to adjust for age, age of onset, number of relapses, and account for intereye dependency. The significance threshold used was P , 0.05. Statistics RESULTS Analyses were performed using R version 3.5.3 software (R Foundation for Statistical Computing, Vienna, Austria; 2011). Chi-square tests were performed for frequency comparisons; Seventy-seven patients with NMO or MS came for consultation and were included between January 2015 and November 2018 (Fig. 2). Twenty-seven patients (54 TABLE 1. Demographic and clinical characteristics of patients and controls NMO (34 Eyes) Age 48.09 ± 13.25 Female/male 29/5 ratio Age at onset 37.71 ± 13.61 Duration of 9.91 ± 6.71 disease EDSS 3.83 ± 2.44 No. of 1.97 ± 1.95 attacks/ eye Retrobulbar 14/34 optic neuritis Papillitis 5/34 MS (70 Eyes) NMO-ON (19 Eyes) MS-ON (15 Eyes) P* NMO-NON (15 Eyes) MS-NON (55 Eyes) P† Controls 45.09 ± 14.19 43.89 ± 14.47 40 ± 12.66 0.42 53.4 ± 9.52 46.47 ± 14.37 0.04 45.94 ± 13.93 58/12 16/3 12/3 0.82 13/2 46/9 0.41 43/8 31.40 ± 10.09 32.42 ± 13.11 27.46± 10.05 0.24 44.4 ± 11.41 32.51 ± 9.92 0.001 12.57 ± 10.80 10.90 ± 7.22 11.73 ± 8.40 0.76 8.67 ± 6.01 12.81 ± 11.45 0.18 — — 3.1 ± 12 0.614 ± 0.91 3.37 ± 2.31 2.84 ± 1.95 13/70 14/19 12/15 0.81 2/70 5/19 2/15 0.79 3.12 ± 2.35 — 0.1 — — — — — — — — — — — 3.04 ± 1.84 0.30 4.32 ± 2.56 1.73 ± 0.80 0.03 — *Comparison of the NMO-ON and MS-ON groups. † Comparison of the NMO-NON and MS-NON groups. EDSS, Expanded Disability Status Scale; MS-ON, patient with MS with a history of optic neuritis; MS-NON, patient with MS without a history of optic neuritis; NMO-ON, patient with NMO with a history of optic neuritis. e50 Bechet et al: J Neuro-Ophthalmol 2022; 42: e48-e55 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 2. Visual function of patients from the NMO-ON, NMO-NON, MS-ON, and MS-NON groups NMO-ON (19 Eyes) NMO-NON (15 Eyes) MS-ON (15 Eyes) MS-NON (55 Eyes) P (NMO-ON/MS-ON) P (NMO-NON/MS-NON) VA ETDRS Pelli–Robson Sloan 2.5 Sloan 1.25 100 Hue FDT MD FDT PSD SAP MD SAP PSD 20/25 ± 20/50 52.32 ± 29.94 1.19 ± 0.68 16.11 ± 14.88 4.42 ± 6.43 119.47 ± 87.14 24.88 ± 6.39 4.85 ± 1.95 28.33 ± 11.23 4.05 ± 3.84 20/20 ± 20/250 66.67 ± 15.73 1.61 ± 0.12 25.87 ± 11.34 9.73 ± 5.35 98.53 ± 60.76 21.02 ± 2.34 3.95 ± 1.16 20.62 ± 1.2 1.95 ± 1.38 20/25 ± 20/63 20/20 ± 20/200 68.13 ± 20.84 77.4 ± 17.06 1.37 ± 0.38 1.63 ± 0.13 15.87 ± 13.46 27.31 ± 9.56 2.4 ± 5.36 8.09 ± 6.93 178.4 ± 163.74 85.04 ± 69.62 22.55 ± 3.65 21.65 ± 3.05 5.55 ± 3.39 4.45 ± 1.79 23.43 ± 2.93 21.3 ± 2.37 3.07 ± 2.47 2.33 ± 2.14 0.335 0.247 0.741 0.277 0.111 0.142 0.636 0.139 0.615 0.052 0.915 0.001 0.474 0.538 0.415 0.508 0.154 0.206 0.507 0.522 ETDRS, Early Treatment Diabetic Retinopathy Study; FDT, frequency-doubling technology perimetry; MD, mean deviation; MS-ON, patient with MS with a history of optic neuritis; MS-NON, patient with MS without a history of optic neuritis; NMO-ON, patient with NMO with a history of optic neuritis; NMO-NON, patient with NMO without a history of optic neuritis; PSD, pattern SD; SAP, standard automated perimetry; VA, visual acuity. eyes) were diagnosed with NMO. Of these, 20 eyes were excluded (1 for hyaloid artery persistence, 2 for missing clinical data, and 17 for incomplete ocular data: 3 absence of visual function examination, 11 unreliable visual field, and 4 absence of color vision). Thirty-four NMO eyes were included, divided into 2 groups: 19 with a history of ON (NMO-ON) and 15 without a history of ON (NMONON). Fifty patients (100 eyes) were diagnosed with MS. Thirty eyes were excluded (10 for missing clinical data, 2 without BMO, and 18 for incomplete ocular data: 14 unreliable visual field, 1 absence of color vision, and 3 absence of SAP). Seventy MS eyes were included, divided into 2 groups: 15 with a history of ON (MS-ON) and 55 without a history of ON (MS-NON). Fifty-one controls were matched on age, sex, and corresponding eye. The demographic characteristics of the 4 groups and controls are summarized in Table 1. There were no differences in mean age, sex ratio, age of onset, duration of disease, and EDSS between the NMO and MS groups. The number of attacks per eye was greater in the NMO group, but the proportion of retrobulbar NO and papillitis was not different from the MS group. TABLE 3. Thickness of peripapillary retinal nerve fiber layer (RNFL), Bruch membrane opening minimum rim width (BMO), and ganglion cell layer (GCL) NMO-ON (19 Eyes) Mean Value RNFL average TS NS N NI TI T BMO average TS NS N NI TI T GCL average N S I T 71 82 92 65 91 102 43 252 226 303 282 307 268 175 31 31 33 33 28 ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 28 32 37 27 39 42 19 63 77 80 74 69 81 45 13 14 14 14 12 NMO-NON (15 Eyes) MS-ON (15 Eyes) MS-NON (55 Eyes) P Mean Value P Mean Value P Mean Value P Controls Mean Value ,0.001 ,0.001 ,0.001 0.002 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 100 ± 13 120 ± 26 128 ± 18 84 ± 14 120 ± 26 154 ± 22 66 ± 13 292 ± 44 286 ± 71 340 ± 58 303 ± 54 349 ± 50 328 ± 53 218 ± 45 46 ± 7 45 ± 9 48 ± 7 48 ± 7 43 ± 6 0.516 0.945 0.51 0.499 0.148 0.497 0.93 0.022 0.174 0.076 0.006 0.026 0.085 0.203 0.503 0.323 0.640 0.538 0.674 87 ± 18 109 ± 29 116 ± 24 76 ± 13 111 ± 30 128 ± 33 51 ± 16 303 ± 78 284 ± 85 351 ± 95 342 ± 94 369 ± 100 310 ± 84 209 ± 59 35 ± 11 35 ± 13 38 ± 12 35 ± 12 32 ± 12 ,0.001 0.063 0.012 ,0.001 0.019 0.010 ,0.001 0.044 0.034 0.026 0.108 0.032 0.023 0.168 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 98 ± 14 124 ± 25 120 ± 29 80 ± 14 80 ± 14 147 ± 27 64 ± 17 310 ± 60 308 ± 75 363 ± 84 330 ± 71 381 ± 79 335 ± 66 221 ± 52 46 ± 7 46 ± 9 48 ± 7 46 ± 8 42 ± 8 ,0.001 0.133 0.048 ,0.001 0.717 0.012 0.013 ,0.001 0.028 0.011 ,0.001 0.002 ,0.001 0.022 ,0.001 ,0.001 ,0.001 ,0.001 ,0.001 107 ± 11 127 ± 20 134 ± 25 93 ± 14 131 ± 26 158 ± 22 70 ± 9 352 ± 58 339 ± 63 404 ± 72 384 ± 72 427 ± 77 385 ± 67 245 ± 53 51 ± 6 52 ± 6 52 ± 6 52 ± 6 47 ± 7 P value indicates the difference between the data in the patients groups and the control group. BMO, Bruch membrane opening minimum rim width; GCL, ganglion cell layer; TS, superotemporal quadrant; NS, superonasal quadrant; N: nasal quadrant; NI, inferonasal quadrant; RNFL, retinal nerve fiber layer; TI, inferotemporal quadrant; T, temporal quadrant. Bechet et al: J Neuro-Ophthalmol 2022; 42: e48-e55 e51 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 4. Spearman correlation between the Bruch membrane opening minimum rim width (BMO) and the visual function parameters BMO NMO-MS Spearman P NMO Spearman P NMO-ON Spearman P NMO-NON Spearman P MS Spearman P MS-ON Spearman P MS-NON Spearman P VA Pelli– ETDRS Robson Sloan 2.5 Sloan 1.25 100 Hue FDT MD FDT PSD SAP MD SAP PSD RNFL r 0.279 0.004 0.251 0.542 0.488 0.01 ,0.001 ,0.001 0.299 20.225 0.002 0.024 r 0.401 0.021 0.241 0.623 0.169 ,0.001 0.47 0.005 0.232 20.026 0.578 20.726 0.607 20.366 0.740 0.712 0.187 0.891 ,0.001 ,0.001 ,0.001 0.033 ,0.001 ,0.001 r 0.605 0.006 0.512 0.822 0.025 ,0.001 0.719 0.001 0.378 20.009 0.111 0.975 0.651 20.774 0.003 ,0.001 0.658 20.421 0.785 0.840 0.002 0.073 ,0.001 ,0.001 r 0.101 0.73 0.408 0.132 0.11 20.248 20.096 0.696 0.373 0.734 0.434 20.642 0.106 0.01 0.599 20.257 0.796 0.018 0.354 ,0.001 r 0.185 0.128 0.135 0.516 0.473 0.267 ,0.001 ,0.001 0.334 20.301 0.005 0.012 0.142 0.25 0.191 20.072 0.718 0.571 0.115 0.554 ,0.001 ,0.001 r 0.332 0.227 0.166 0.553 0.498 0.059 0.553 0.033 0.521 20.443 0.047 0.098 0.682 20.636 0.005 0.011 r 0.07 0.613 0.146 0.503 0.287 ,0.001 0.396 0.003 0.264 20.149 20.053 0.052 0.278 0.709 0.109 0.699 0.283 20.279 0.004 0.004 GCL 0.103 0.409 0.031 0.827 0.317 20.156 0.693 0.605 0.001 0.114 ,0.001 ,0.001 0.561 20.625 0.029 0.013 0.052 0.706 0.732 0.002 0.409 0.130 0.677 0.006 0.13 0.699 0.509 0.345 ,0.001 ,0.001 BMO, Bruch membrane opening minimum rim width; ETDRS, Early Treatment Diabetic Retinopathy Study; FDT, frequency-doubling technology perimetry; GCL: ganglion cell layer; MD, mean deviation; NMO-MS: both patients with NMO and MS ; PSD, pattern SD; SAP, standard automated perimetry; RNFL, retinal nerve fiber layer; VA, visual acuity. Visual function was lower in the patients with NMO; however, there were no significant differences in visual acuity, contrast vision, color vision, and visual field between the NMO-ON and MS-ON groups (Table 2). In the absence of ON, the differences were also nonsignificant except for ETDRS visual acuity, which seemed lower in the NMO-NON group than that in the MS-NON group (66.67 ± 15.73 vs. 77.4 ± 17.06, P = 0.001). In the NMO-ON group, the mean and all sector values of BMO, RNFL, and GCL were significantly decreased compared with the controls (P , 0.001) (Table 3). Similarly, in the MS-ON group, there was a significant decrease in all values except for the upper temporal sector of RNFL FIG. 3. Correlation between BMO and RNFL of the NMO-MS group. BMO, Bruch membrane opening thickness; RNFL, retinal nerve fiber layer thickness. e52 Bechet et al: J Neuro-Ophthalmol 2022; 42: e48-e55 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 5. Spearman correlation between the sectors of Bruch membrane opening minimum rim width (BMO) and standard automated perimetry in the NMO groups MD r PSD P r Sup P r Intersup P r Temp P r BMO NMO 0.607 ,0.001 0.366 0.033 0.572 ,0.001 0.612 ,0.001 NMO-ON 0.658 0.002 0.421 0.073 0.652 0.002 0.643 0.003 NMO-NON 0.599 0.018 0.257 0.354 0.479 0.07 0.549 0.034 BMO TS NMO NMO-ON NMO-NON BMO NS NMO NMO-ON NMO-NON BMO N NMO NMO-ON NMO-NON BMO NI NMO 0.508 0.002 NMO-ON 0.579 0.009 NMO-NON 0.404 0.135 BMO TI NMO 0.601 ,0.001 NMO-ON 0.612 0.005 NMO-NON 0.540 0.038 BMO T NMO NMO-ON NMO-NON Central P r P Interinf r P Inf r P 0.508 ,0.001 0.678 ,0.001 0.679 ,0.001 0.604 ,0.001 0.507 0.027 0.766 ,0.001 0.708 ,0.001 0.729 ,0.001 0.601 0.018 0.517 0.048 0.661 0.007 0.389 0.152 0.717 ,0.001 0.733 ,0.001 0.703 0.003 0.581 ,0.001 0.710 ,0.001 0.435 0.105 0.434 0.543 0.493 0.010 0.016 0.062 0.596 ,0.001 0.569 0.011 0.378 0.165 BMO, Bruch membrane opening minimum rim width; Central, central sector of the SAP; Inf, inferior sector of the SAP; Interinf, interinferior sector of the SAP; Intersup, intersuperior sector of the SAP; MD, mean deviation; N, nasal quadrant; NI, inferonasal quadrant; NS, superonasal quadrant; PSD, pattern SD; SAP, standard automated perimetry; Sup, superior sector of the SAP; T, temporal quadrant; Temp, temporal sector of the SAP; TI, inferotemporal quadrant; TS, superotemporal quadrant. and the nasal and temporal sector of BMO (P = 0.108 and P = 0.168). Values for RNFL, BMO, and GCL were lower in the NMO-ON group than in the MS-ON group. In the group of patients with NMO without a history of ON (NMO-NON), RNFL and GCL were nonsignificantly decreased compared with the controls, whereas the mean BMO, the nasal, and lower nasal areas were significantly decreased (P = 0.022, P = 0.006, and P = 0.026, respectively). In the MS-NON group, RNFL, mean BMO, and mean GCL were all significantly decreased. In the group comprising both patients with NMO and MS, BMO was correlated with the results of tests exploring contrast vision: Pelli–Robson and Sloan 2.5, r = 0.542, P , 0.001 and r = 0.488, P , 0.001, respectively (Table 4). A better correlation was observed with MD of the FDT visual field or MD of the SAP than with visual acuity measurements (Snellen and ETDRS). A strong positive correlation was found with RNFL and GCL, r = 0.693, P , 0.001 and r = 0.605, P , 0.001, respectively (Fig. 3, correlation between BMO and RNFL of the NMO-MS group). A high correlation with RNFL and GCL was also observed when the NMO and MS groups were analyzed separately. Bechet et al: J Neuro-Ophthalmol 2022; 42: e48-e55 The average BMO was highly correlated with MD and with all the different areas of the visual field (Table 5). The sectoral study showed a high correlation between BMO and the corresponding sector of the visual field. CONCLUSIONS Supporting evidence from previous studies, a decrease in retinal nerve fiber thickness (BMO, RNFL, and GCL) in patients with a history of ON and in patients with MS without a history of ON was observed (7,9,10,26,27). Retinal nerve fiber layer damage in patients with ON was greater in the NMO group than in the MS group. These results illustrate the severity of ON during NMO and the need for prompt management. In contrast to MS lesions that combine demyelination and relative axonal preservation, NMO is characterized by axonal damage and lesions of necrosis, cavitation, and ischemia (9,28,29). The decrease in BMO in patients with a history of ON is consistent with results obtained by NGuyen et al (20). In the MS-NON group, RNFL, BMO, and GCL are decreased and the involvement is predominant in the temporal area, according to the literature (30–33). The decrease in retinal nerve fiber thickness is believed to be e53 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution independent of ON and reflects progressive axonal degeneration. In the NMO-NON group, only BMO was significantly decreased, similarly suggesting subclinical involvement. The results substantiate those obtained by Monteiro et al, Pisa et al, or Ratchford et al, who found a decrease in RNFL compared with a group of healthy subjects (9,28,34). Outteryck et al and Hu et al found that the decrease in RNFL was predominant in the lower sector (32,35). All these findings support the development of optic nerve damage independent of ON. They are believed to be the result of anterograde and retrograde bidirectional transsynaptic degeneration and not related to atrophy of the visual cortex V1 (36). BMO may be more sensitive than RNFL and GCL to detect these early lesions. A high correlation between BMO and visual function was observed, particularly with contrast vision, average FDT, and SAP deviation. This finding is consistent with other studies of retinal nerve fiber thickness that show a high correlation between RNFL, GCL, and visual function for both NMO and MS (10,27). To the best of our knowledge, this is the first study evaluating the correlation between BMO and different areas of the visual field during demyelinating diseases. A high correlation was found, as for RNFL and GCL in similar studies of patients with and without a history of ON (37,38). Essentially studied during glaucoma neuropathy, the correlation between BMO and MD is at least close to or sometimes better than the RNFL. Our study showed that BMO was decreased during NMO in patients with and without a history of ON. In patients without a history of ON, in contrast to RNFL and GCL, the decrease in BMO was significant. The BMO results correlated well with visual function, including contrast vision and mean visual field deviation (FDT and SAP). BMO was also well correlated with other measures of optic nerve fiber thickness, RNFL and GCL. As with RNFL and GCL, BMO allows during NMO to assess nerve fiber degeneration, particularly during severe ON. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: L. Bechet and H. Merle; b. Acquisition of data: L. Bechet, P. Cebre, and H. Merle; c. Analysis and interpretation of data: L. Bechet. Category 2: a. Drafting the article: L. Bechet and H. Merle; b. Revising it for intellectual content: L. Bechet and H. Merle. Category 3: a. Final approval of the completed article: L. Bechet, P. Cebre, and H. Merle. REFERENCES 1. 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