Individual Prognostication of Disease Activity and Disability Worsening in Multiple Sclerosis With Retinal Layer Thickness z Scores.

BACKGROUND AND OBJECTIVES: Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted z scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS). METHODS: We established age-adjusted OCT reference data using generalized additive models for location, scale, and shape for peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses, involving 910 and 423 healthy eyes, respectively. Next, we transformed the retinal layer thickness of PwMS from 3 published studies into age-adjusted z scores (pRNFL-z and GCIP-z) based on the reference data. Finally, we investigated the association of pRNFL-z or GCIP-z as predictors with future confirmed disability worsening (Expanded Disability Status Scale score increase) or disease activity (failing of the no evidence of disease activity [NEDA-3] criteria) as outcomes. Cox proportional hazards models or logistic regression analyses were applied according to the original studies. Optimal cutoffs were identified using the Akaike information criterion as well as location with the log-rank and likelihood-ratio tests. RESULTS: In the first cohort (n = 863), 172 PwMS (24%) had disability worsening over a median observational period of 2.0 (interquartile range [IQR]:1.0-3.0) years. Low pRNFL-z (≤-2.04) were associated with an increased risk of disability worsening (adjusted hazard ratio (aHR) [95% CI] = 2.08 [1.47-2.95], p = 3.82e-5). In the second cohort (n = 170), logistic regression analyses revealed that lower pRNFL-z showed a higher likelihood for disability accumulation at the two-year follow-up (reciprocal odds ratio [95% CI] = 1.51[1.06-2.15], p = 0.03). In the third cohort (n = 78), 46 PwMS (59%) did not maintain the NEDA-3 status over a median follow-up of 2.0 (IQR: 1.9-2.1) years. PwMS with low GCIP-z (≤-1.03) had a higher risk of showing disease activity (aHR [95% CI] = 2.14 [1.03-4.43], p = 0.04). Compared with raw values with arbitrary cutoffs, applying the z score approach with optimal cutoffs showed better performance in discrimination and calibration (higher Harrell's concordance index and lower integrated Brier score). DISCUSSION: In conclusion, our work demonstrated reference cohort-based z scores that account for age, a major driver for disease progression in MS, to be a promising approach for creating OCT-derived measures useable across devices and toward individualized prognostication.

From progression to progress: The future of multiple sclerosis.

Significant advances have been made in the diagnosis and treatment of multiple sclerosis in recent years yet challenges remain. The current classification of MS phenotypes according to disease activity and progression, for example, does not adequately reflect the underlying pathophysiological mechanisms that may be acting in an individual with MS at different time points. Thus, there is a need for clinicians to transition to a management approach based on the underlying pathophysiological mechanisms that drive disability in MS. A Canadian expert panel convened in January 2023 to discuss priorities for clinical discovery and scientific exploration that would help advance the field. Five key areas of focus included: identifying a mechanism-based disease classification system; developing biomarkers (imaging, fluid, digital) to identify pathologic processes; implementing a data-driven approach to integrate genetic/environmental risk factors, clinical findings, imaging and biomarker data, and patient-reported outcomes to better characterize the many factors associated with disability progression; utilizing precision-based treatment strategies to target different disease processes; and potentially preventing disease through Epstein-Barr virus (EBV) vaccination, counselling about environmental risk factors (e.g. obesity, exercise, vitamin D/sun exposure, smoking) and other measures. Many of the tools needed to meet these needs are currently available. Further work is required to validate emerging biomarkers and tailor treatment strategies to the needs of individual patients. The hope is that a more complete view of the individual's pathobiology will enable clinicians to usher in an era of truly personalized medicine, in which more informed treatment decisions throughout the disease course achieve better long-term outcomes.

Patterns and utility of myelin oligodendrocyte glycoprotein (MOG) antibody testing in cerebrospinal fluid.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an idiopathic central nervous system (CNS) demyelinating disease gaining recognition with wider availability of cell-based assay (CBA) testing and recently published diagnostic criteria. However, uncertainty remains regarding the interpretation of antibody titers, particularly cerebrospinal fluid (CSF) MOG antibody titers. METHODS: All MOG IgG CBA results performed by the provincial MitogenDx laboratory in Alberta from July 2017 to July 2023 were retrieved. Chart review was performed in patients with both serum and CSF testing and ≥ 1 positive MOG antibody result. Demographics, antibody titers, clinical and imaging features, treatment, and diagnosis were analyzed based on serum/CSF status. RESULTS: Among 4494 MOG CBA assays, there were 413 CSF samples in 402 patients, and 268 patients had at least one associated serum sample. Mean time between CSF and serum testing was 20.9 days (range 0-870 days), most with testing within 30 days. Five of the 268 patients had serum positive/CSF positive MOG antibodies, 4 with acute disseminated encephalomyelitis and 1 with longitudinally extensive transverse myelitis. Twenty-three patients had serum positive/CSF negative MOG and 13/23 with optic neuritis. CSF MOG antibody positive patients were younger, and more likely to remain MOG seropositive versus CSF negative patients. No seronegative patient had MOG antibodies in CSF. CONCLUSIONS: In province-wide testing, CSF MOG antibodies were rare, only in MOG seropositive patients and none with optic neuritis. Our study does not support a clear role for CSF MOG antibody testing in the majority of patients, although further study is required.

Advantages and Pitfalls of the Use of Optical Coherence Tomography for Papilledema.

PURPOSE OF REVIEW: Papilledema refers to optic disc swelling caused by raised intracranial pressure. This syndrome arises from numerous potential causes, which may pose varying degrees of threat to patients. Manifestations of papilledema range from mild to severe, and early diagnosis is important to prevent vision loss and other deleterious outcomes. The purpose of this review is to highlight the role of optical coherence tomography (OCT) in the diagnosis and management of syndromes of raised intracranial pressure associated with papilledema. RECENT FINDINGS: Ophthalmoscopy is an unreliable skill for many clinicians. Optical coherence tomography is a non-invasive ocular imaging technique which may fill a current care gap, by facilitating detection of papilledema for those who cannot perform a detailed fundus examination. Optical coherence tomography may help confirm the presence of papilledema, by detecting subclinical peripapillary retinal nerve fiber layer (pRNFL) thickening that might otherwise be missed with ophthalmoscopy. Enhanced depth imaging (EDI) and swept source OCT techniques may identify optic disc drusen as cause of pseudo-papilledema. Macular ganglion cell inner plexiform layer (mGCIPL) values may provide early signs of neuroaxonal injury in patients with papilledema and inform management for patients with syndromes of raised intracranial pressure. There are well-established advantages and disadvantages of OCT that need to be fully understood to best utilize this method for the detection of papilledema. Overall, OCT may complement other existing tools by facilitating detection of papilledema and tracking response to therapies.  Moving forward, OCT findings may be included in deep learning models to diagnose papilledema.

Poorer subjective mental health among girls: Artefact or real? Examining whether interpretations of what shapes mental health vary by sex.

BACKGROUND: Despite reporting poorer self-rated mental health (SRMH) than boys, girls exhibit greater resilience and academic achievement, and less risk taking or death by suicide. Might this apparent paradox be an artefact arising from girls' and boys' different interpretations of the meaning of SRMH? We examined whether the indicator, SRMH, had a different meaning for girls and boys. METHODS: In 2021-2, we circulated social media invitations for youth age 13-18 to complete an online survey about their mental health, and which of 26 individual and social circumstances shaped that rating. All data were submitted anonymously with no link to IP addresses. After comparing weightings for each characteristic, factor analyses identified domains for the whole group and for girls and boys. RESULTS: Poor SRMH was reported by 47% of 506 girls and 27.8% of 216 boys. In general, circumstances considered important to this rating were similar for all, although boys focussed more on sense of identity, self-confidence, physical well-being, exercise, foods eaten and screen time, while girls paid more attention to having a boyfriend or girlfriend, comparisons with peers, and school performance. With factor analysis and common to boys and girls, domains of resilience, behavior/community, family, relationships with peers and future vision emerged. Girls' poorer SRMH did not arise from a more expansive interpretation of mental health. Instead, it may reflect perceived or real disadvantages in individual or social circumstances. Alternatively, girls' known greater resilience may propel lower SRMH which they use intuitively to motivate future achievement and avoid the complacency of thinking that 'all is well'. CONCLUSIONS: The relative similarity of attributes considered before rating one's mental health suggests validity of this subjective measure among girls and boys.

Neuro-ophthalmic manifestations of autoimmune disorders: diagnostic pearls & pitfalls.

PURPOSE OF REVIEW: The purpose of this review is to highlight a clinical-anatomical approach to localizing neuro-ophthalmic manifestations of associated autoimmune disorders. RECENT FINDINGS: Our understanding of autoimmune conditions has changed considerably over recent years, particularly with the emergence of novel autoantibodies. Cardinal neuro-ophthalmic signs and symptoms of antibody-mediated autoimmune disorders have been well characterized; knowledge thereof may be the first step towards an accurate diagnosis. SUMMARY: A thorough history, further refined by a comprehensive examination are cornerstones to disease localization in clinical medicine. Taken together, these essential steps both guide investigations and facilitate early recognition of autoimmune disorders. From a neuro-ophthalmic perspective, it is important to understand heralding signs and symptoms of autoimmune syndromes, avoid cognitive errors, and remain mindful of common diagnostic pitfalls to optimize care. VIDEO ABSTRACT: http://links.lww.com/COOP/A61.

Predictors of Long-Term Visual Acuity in a Modern Cohort of Patients With Acute Idiopathic and Multiple Sclerosis-Associated Optic Neuritis.

BACKGROUND: For patients with idiopathic or multiple sclerosis (MS)-associated optic neuritis (ON), the largest multicenter clinical trial (Optic Neuritis Treatment Trial [ONTT]) showed excellent visual outcomes and baseline high-contrast visual acuity (HCVA) was the only predictor of HCVA at 1 year. We aimed to evaluate predictors of long-term HCVA in a modern, real-world population of patients with ON and compare with previously published ONTT models. METHODS: We performed a retrospective, longitudinal, observational study at the University of Michigan and the University of Calgary evaluating 135 episodes of idiopathic or MS-associated ON in 118 patients diagnosed by a neuro-ophthalmologist within 30 days of onset (January 2011-June 2021). Primary outcome measured was HCVA (Snellen equivalents) at 6-18 months. Multiple linear regression models of 107 episodes from 93 patients assessed the association between HCVA at 6-18 months and age, sex, race, pain, optic disc swelling, symptoms (days), viral illness prodrome, MS status, high-dose glucocorticoid treatment, and baseline HCVA. RESULTS: Of the 135 acute episodes (109 Michigan and 26 Calgary), median age at presentation was 39 years (interquartile range [IQR], 31-49 years), 91 (67.4%) were women, 112 (83.0%) were non-Hispanic Caucasians, 101 (75.9%) had pain, 33 (24.4%) had disc edema, 8 (5.9%) had a viral prodrome, 66 (48.9%) had MS, and 62 (46.6%) were treated with glucocorticoids. The median (IQR) time between symptom onset and diagnosis was 6 days (range, 4-11 days). The median (IQR) HCVA at baseline and at 6-18 months were 20/50 (20/22, 20/200) and 20/20 (20/20, 20/27), respectively; 62 (45.9%) had better than 20/40 at baseline and 117 (86.7%) had better than 20/40 at 6-18 months. In linear regression models (n = 107 episodes in 93 patients with baseline HCVA better than CF), only baseline HCVA (ß = 0.076; P = 0.027) was associated with long-term HCVA. Regression coefficients were similar and within the 95% confidence interval of coefficients from published ONTT models. CONCLUSIONS: In a modern cohort of patients with idiopathic or MS-associated ON with baseline HCVA better than CF, long-term outcomes were good, and the only predictor was baseline HCVA. These findings were similar to prior analyses of ONTT data, and as a result, these are validated for use in conveying prognostic information about long-term HCVA outcomes.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): current understanding and challenges.

New diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have recently been proposed, distinguishing this syndrome from other inflammatory diseases of the central nervous system. Seropositivity status for MOG-IgG autoantibodies is important for diagnosing MOGAD, but only in the context of robust clinical characterization and cautious interpretation of neuroimaging. Over the last several years, access to cell-based assay (CBA) techniques has improved diagnostic accuracy, yet the positive predictive value of serum MOG-IgG values varies with the prevalence of MOGAD in any given patient population. For this reason, possible alternative diagnoses need to be considered, and low MOG-IgG titers need to be carefully weighted. In this review, cardinal clinical features of MOGAD are discussed. Key challenges to the current understanding of MOGAD are also highlighted, including uncertainty regarding the specificity and pathogenicity of MOG autoantibodies, the need to identify immunopathologic targets for future therapies, the quest to validate biomarkers that facilitate diagnosis and detect disease activity, and the importance of deciphering which patients with MOGAD require long-term immunotherapy.

Optic neuritis: current challenges in diagnosis and management.

PURPOSE OF REVIEW: The primary aim of this review is to describe the clinical course, salient imaging features, and relevant serological profiles of common optic neuritis (ON) subtypes. Key diagnostic challenges and treatment options will also be discussed. RECENT FINDINGS: ON is a broad term that describes an inflammatory optic nerve injury arising from a variety of potential causes. ON can occur sporadically, however there is particular concern for co-associated central nervous system (CNS) inflammatory syndromes including multiple sclerosis (MS), neuromyelitis optic spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD). The ON subtypes that often herald MS, NMOSD, and MOGAD differ with respect to serological antibody profile and neuroimaging characteristics, yet there is significant overlap in their clinical presentations. A discerning history and thorough examination are critical to rendering the correct diagnosis. SUMMARY: Optic neuritis subtypes vary with respect to their long-term prognosis and accordingly, require different acute treatment strategies. Moreover, delays in identifying MOGAD, and certainly NMOSD, can be highly detrimental because affected individuals are vulnerable to permanent vision loss and neurologic disability from relapses.

A qualitative description of barriers to visual rehabilitation experienced by stroke survivors with visual impairment in Alberta, Canada.

BACKGROUND: Post-stroke visual impairment (VI) is a common but under-recognized care challenge. Common manifestations of post-stroke VI include: diplopia, homonymous hemianopia, oscillopsia secondary to nystagmus, and visual inattention or neglect. In acute care settings, post-stroke VI recognition and treatment are often sub-optimal as emphasis is placed on survival. Stroke survivors with VI often face inconsistencies when accessing care out of hospital because variable availability and subsidization of visual rehabilitation. We sought to identify gaps in care experienced by stroke survivors with VI from stroke survivors' and care providers' perspectives. METHODS: We conducted a qualitative description study across 12 care sites in Alberta, Canada, using semi-structured interviews. Survivor interviews focused on the health system experience. Provider interviews discussed approaches to care, perceived gaps, and current resources. Interviews were audio-recorded and transcribed. Iterative content analysis was completed using NVivo 12. We promoted rigour through an audit trail, open-ended questions, thick description, and collaborative coding. RESULTS: We completed 50 interviews: 19 survivor interviews and 31 provider interviews. The majority of survivors were male (n = 14) and recruited from community settings (n = 16). Providers varied in profession and location within the care continuum. Two key themes emerged from the provider and survivor interviews pertaining to (a) facets of visual rehabilitation (sub-themes: access, resources, and multidisciplinary professional interaction); and (b) functioning with post-stroke VI (sub-themes: early experiences post-stroke and living with VI in the real world). CONCLUSIONS: The visual rehabilitation model needs to be optimized to ensure transparent inter-disciplinary communication and efficient referral pathways. Future research will focus on evaluating the effectiveness of post-stroke care from multiple perspectives in Alberta.

Sequential measurement of the neurosensory retina in hypertensive disorders of pregnancy: a model of microvascular injury in hypertensive emergency.

Optical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP.

Magnetization transfer saturation reveals subclinical optic nerve injury in pediatric-onset multiple sclerosis.

BACKGROUND: The presence of subclinical optic nerve (ON) injury in youth living with pediatric-onset MS has not been fully elucidated. Magnetization transfer saturation (MTsat) is an advanced magnetic resonance imaging (MRI) parameter sensitive to myelin density and microstructural integrity, which can be applied to the study of the ON. OBJECTIVE: The objective of this study was to investigate the presence of subclinical ON abnormalities in pediatric-onset MS by means of magnetization transfer saturation and evaluate their association with other structural and functional parameters of visual pathway integrity. METHODS: Eleven youth living with pediatric-onset MS (ylPOMS) and no previous history of optic neuritis and 18 controls underwent standardized brain MRI, optical coherence tomography (OCT), Magnetoencephalography (MEG)-Visual Evoked Potentials (VEPs), and visual battery. Data were analyzed with mixed effect models. RESULTS: While ON volume, OCT parameters, occipital MEG-VEPs outcomes, and visual function did not differ significantly between ylPOMS and controls, ylPOMS had lower MTsat in the supratentorial normal appearing white matter (-0.26 nU, p = 0.0023), and in both in the ON (-0.62 nU, p < 0.001) and in the normal appearing white matter of the optic radiation (-0.56 nU, p = 0.00071), with these being positively correlated (+0.57 nU, p = 0.00037). CONCLUSIONS: Subclinical microstructural injury affects the ON of ylPOMS. This may appear as MTsat changes before being detectable by other currently available testing.

Optic neuritis and autoimmune optic neuropathies: advances in diagnosis and treatment.

Optic neuritis is an inflammatory optic neuropathy that is commonly indicative of autoimmune neurological disorders including multiple sclerosis, myelin-oligodendrocyte glycoprotein antibody-associated disease, and neuromyelitis optica spectrum disorder. Early clinical recognition of optic neuritis is important in determining the potential aetiology, which has bearing on prognosis and treatment. Regaining high-contrast visual acuity is common in people with idiopathic optic neuritis and multiple sclerosis-associated optic neuritis; however, residual deficits in contrast sensitivity, binocular vision, and motion perception might impair vision-specific quality-of-life metrics. In contrast, recovery of visual acuity can be poorer and optic nerve atrophy more severe in individuals who are seropositive for antibodies to myelin oligodendrocyte glycoprotein, AQP4, and CRMP5 than in individuals with typical optic neuritis from idiopathic or multiple-sclerosis associated optic neuritis. Key clinical, imaging, and laboratory findings differentiate these disorders, allowing clinicians to focus their diagnostic studies and optimise acute and preventive treatments. Guided by early and accurate diagnosis of optic neuritis subtypes, the timely use of high-dose corticosteroids and, in some instances, plasmapheresis could prevent loss of high-contrast vision, improve contrast sensitivity, and preserve colour vision and visual fields. Advancements in our knowledge, diagnosis, and treatment of optic neuritis will ultimately improve our understanding of autoimmune neurological disorders, improve clinical trial design, and spearhead therapeutic innovation.

Barriers to Care for Poststroke Visual Deficits in Alberta, Canada.

Poststroke visual impairment (VI) negatively affects rehabilitation potential and quality of life for stroke survivors. In this cross-sectional observational study, stroke survivors and providers were surveyed to quantify perspectives regarding care for poststroke VI in Alberta, Canada (n = 46 survivors; n = 87 providers). Few patients (35%) felt prepared to cope with VI at the time of discharge from acute stroke and inpatient rehabilitation settings. Less than 25% of stroke survivors, and <16% of providers, felt referral processes were adequate. 95.2% of providers and 82% of stroke survivors advocated for a provincial clinical pathway to improve care quality for poststroke VI.

Diagnosis and classification of optic neuritis.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

Neuromyelitis Optica Spectrum Disorders.

PURPOSE OF REVIEW: This article reviews the cardinal clinical features, distinct immunopathology, current diagnostic criteria, relapse-related risk factors, emerging biomarkers, and evolving treatment strategies pertaining to neuromyelitis optica spectrum disorders (NMOSD). RECENT FINDINGS: The discovery of the pathogenic aquaporin-4 (AQP4)-IgG autoantibody and characterization of NMOSD as an autoimmune astrocytopathy have spearheaded the identification of key immunologic therapeutic targets in this disease, including but not limited to the complement system, the interleukin 6 (IL-6) receptor, and B cells. Accordingly, four recent randomized controlled trials have demonstrated the efficacy of three new NMOSD therapies, namely eculizumab, satralizumab, and inebilizumab. SUMMARY: Currently, NMOSD poses both diagnostic and treatment challenges. It is debated whether individuals who are seropositive for myelin oligodendrocyte glycoprotein (MOG)-IgG belong within the neuromyelitis optica spectrum. This discussion is fueled by disparities in treatment responses between patients who are AQP4-IgG seropositive and seronegative, suggesting different immunopathologic mechanisms may govern these conditions. As our understanding regarding the immune pathophysiology of NMOSD expands, emerging biomarkers, including serum neurofilament light chain and glial fibrillary acidic protein (GFAP), may facilitate earlier relapse detection and inform long-term treatment decisions. Future research focal points should include strategies to optimize relapse management, restorative treatments that augment neurologic recovery, and practical solutions that promote equitable access to approved therapies for all patients with NMOSD.

Machine learning classification of multiple sclerosis in children using optical coherence tomography.

BACKGROUND: In children, multiple sclerosis (MS) is the ultimate diagnosis in only 1/5 to 1/3 of cases after a first episode of central nervous system (CNS) demyelination. As the visual pathway is frequently affected in MS and other CNS demyelinating disorders (DDs), structural retinal imaging such as optical coherence tomography (OCT) can be used to differentiate MS. OBJECTIVE: This study aimed to investigate the utility of machine learning (ML) based on OCT features to identify distinct structural retinal features in children with DDs. METHODS: This study included 512 eyes from 187 (neyes = 374) children with demyelinating diseases and 69 (neyes = 138) controls. Input features of the analysis comprised of 24 auto-segmented OCT features. RESULTS: Random Forest classifier with recursive feature elimination yielded the highest predictive values and identified DDs with 75% and MS with 80% accuracy, while multiclass distinction between MS and monophasic DD was performed with 64% accuracy. A set of eight retinal features were identified as the most important features in this classification. CONCLUSION: This study demonstrates that ML based on OCT features can be used to support a diagnosis of MS in children.