Certain Factors May Assist in Predicting Clinical Phenotype Following Optic Neuritis


Factors such as older age, poor steroid responsiveness, and plasma exchange were associated with NMOSD phenotype, while normal or thinned retinal nerve fiber layer and short-segment hyperintensity were associated with idiopathic optic neuritis.

Hesham Abboud, MD, associate professor, Case Western Reserve University

Hesham Abboud, MD

New research has suggested that several factors at the time of initial presentation of optic neuritis (ON) are associated with specific clinical phenotypes, and may help predict which neuroimmunological condition a patient will develop. Ultimately, utilizing these early predictors in clinical practice could better inform prognosis and management decisions, the study investigators noted.

The trial aimed to determine final clinical phenotypes of either idiopathic ON, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte antibody disease (MOGAD) or secondary ON in a cohort of 64 individuals who presented with an initial, isolated attack of ON. Led by Hesham Abboud, MD, associate professor, Case Western Reserve University, univariate analyses on age, gender, race, laterality, visual acuity, relative afferent pulpillary defect, red desaturation, optical coherence tomography (OCT), fundoscopy, MRI, recovery, steroid response, need for plasma exchange (PLEX), and visual improvement were carried out to determine predictors of the final clinical phenotype.

Presented at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 31 to June 3, in Aurora, Colorado, the trial featured mostly females (78.1%), with an average age of onset of 41.3 (SD, 13.3) years and time to final diagnosis of 8.3 months. MS, the final phenotype in 22 individuals (34%), was associated with White race, unilateral ON, short segment hyperintensity on orbital MRI, and not receiving PLEX.

Following MS, the final phenotypes were idiopathic ON (n = 14; 22%), MOGAD (n = 11; 17%), NMOSD (n = 10; 16%), and secondary ON (n = 7; 11%). Findings showed that older age, poor steroid responsiveness, and receiving PLEX was associated with NMOSD, while Black race, bilateral ON, papillitis on fundoscopy, and long-segment hyperintensity on orbital MRI was associated with NMOSD. As for idiopathic ON, factors such as normal or thinned retinal nerve fiber layer on OCT and short-segment hyperintensity on orbital MRI were associated with final clinical phenotype. Of note, the initial visual acuity did not differentiate among final phenotypes at the time of initial presentation.

READ MORE: Arterial Stiffness Associated With Processing Speed in Multiple Sclerosis

Prior to this research, there were few studies that assessed multiple final phenotypes. One such study, a 3-year trial of Chinese patients, showed that average retinal nerve fiber layer thickness (RNFL) was similar between the MOGAD-ON and aquaporin-4-ON groups (63.41 [±13.39] and 59.40 [±11.46] um; P = .476), but both were thinner than the seronegative-ON group (74.06 [±11.14] P <.001). Macular ganglion cell-inner plexiform layer (GCIPL) revealed the same pattern. Despite RNFL and GCIPL thinning, the MOGAD-ON group’s outcome was as favorable as that of the seronegative-ON group, whereas the AQP4-ON group showed unsatisfactory results.

The Chinese-based study revealed that atypical ON, including MOGAD-ON and AQP4-ON, accoutns for more than half of all ON cases. The relapse rate of MOGAD-ON was as high as that of AQP4-ON, and more than one-quarter of patients in the latter group developed definitive neuromyelits optica after 3 years. "Therefore, testing for serum biomarkers such as MOG-Abs and AQP4-Abs is important when patients experience the first attack of ON, since the evaluation and treatment paradigms depend significantly on the serum status and phenotypes."

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1. Sarin S, Modak N, Sun R, et al. Predicting the final clinical phenotype after the first attack of optic neuritis. Presented at: 2023 CMSC Annual Meeting; May 31 to June 3; Aurora, CO. Abstract NID13
2. Feng C, Chen Q, Zhao G, et al. Clinical characteristics of optic neuritis phenotypes in a 3-year follow-up Chinese cohort. Sci Rep. 2021;11:14603
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