Insights on Potential to Predict Clinical Outcomes in Optic Neuritis

Hesham Abboud, MD, PhD

Research shows that while idiopathic and multiple sclerosis (MS)-related optic neuritis (ON) is usually mild and self-limited, neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte antibody disease (MOGAD) cause more severe visual loss and may need more timely treatment.¹ Also, ON in patients with NMOSD often need treatment with plasma exchange (PLEX) while it is steroid-responsive in the other autoimmune diseases.² The final clinical phenotype of the ON is typically unknown at the time of the first presentation and thus having the ability to predict this, as well as identifying the etiology of an attack of ON, can allow for more treatment optimization for patients.

Recently published in the Journal of Neuroimmunology, findings from a retrospective study suggest that several factors at the time of initial presentation of ON are associated with specific clinical phenotypes and may help predict which neuroimmunological condition a patient will develop.3 The study aimed to determine final clinical phenotypes of either idiopathic ON, MS, NMOSD, MOGAD or secondary ON in a cohort of 64 patients who presented with an initial, isolated attack of ON.

After patients with MS, the final phenotypes identified were idiopathic ON (n = 14; 22%), MOGAD (n = 11; 17%), NMOSD (n = 10; 16%), and secondary ON (n = 7; 11%). Notably, older age, poor steroid responsiveness, and receiving PLEX were associated with NMOSD. Also, Black race, bilateral ON, papillitis on fundoscopy, and long-segment hyperintensity on orbital MRI were also associated with MOGAD. 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.

Senior author Hesham Abboud, MD, PhD, associate professor of neurology at Case Western Reserve University School of Medicine, had a recent conversation with NeurologyLive® to discuss how can early prediction of the clinical phenotype of ON can benefit presenting patients and their treatment course. He talked about the results regarding visual acuity as a predictor of clinical outcomes in ON and how the findings influence the treatment approach for patients with NMOSD. In addition, he shared his thoughts on what should be further investigated to improve predictive markers for ON. He also explained why race as a factor, particularly among African Americans, is important when considering ON in the context of MOGAD and NMOSD.

NeurologyLive: What were the main findings for this research on optic neuritis final phenotypes?

Hesham Abboud, MD, PhD: The main finding is that it is possible to predict the final clinical phenotype when evaluating a patient with a first-time optic neuritis attack. Before test results are back (which can take days to weeks depending on where you are), you can predict if your optic neuritis patient likely has an isolated one-time event or will develop MS, NMOSD, MOGAD, or neurosarcoidosis in the future. A careful evaluation of patient demographics, fundus exam, MRI findings, and response to treatment can aid in that determination.

Did any of the findings surprise you?

The most surprising finding was the fact that visual acuity was not predictive of the final clinical phenotype. It is widely acceptable that patients with severe visual loss are more likely to develop NMOSD or MOGAD as opposed to MS or idiopathic disease. However, we had some patients with MS and idiopathic optic neuritis in this cohort who suffered from severe visual loss. This resulted in visual acuity being not predictive of the clinical phenotype in our cohort, likely because of a referral bias as more severe cases –including those with MS and idiopathic disease- are typically referred to tertiary care centers like ours. Another surprising result was the fact that African Americans were more likely to have optic neuritis in the setting of MOGAD as opposed to other phenotypes including NMOSD in which African American race is typically prevalent.

What are the implications of these results for patients presenting these phenotypes?

The study has both therapeutic and prognostic implications. Based on early predictors, the clinician can decide whether to put patients on tapering corticosteroid treatment after acute therapy depending on their risk for early recurrences based on the predicted final phenotype. For example, patients with MS and idiopathic disease typically do not need oral taper after acute therapy while patients with MOGAD, NMOSD, and neurosarcoidosis typically need a long taper to offset early recurrences. In addition, using these early predictors, the clinician may be able to provide a more accurate prognosis to the patient including anticipated recovery and risk of future recurrence.

How does this data impact patients with NMOSD in terms of both diagnosis and treatment?

Patients with NMOSD are often steroid-resistant and most will require plasma exchange to achieve meaningful recovery after optic neuritis. The earlier the treatment, the better the outcome. Using the early predictors identified in our study could enable clinicians to identify potential patients with NMOSD even before their antibody results are available. Those patients can then be flagged for early plasma exchange treatment to minimize visual disability.

What are the next steps in terms of research and what should be further investigated in this area?

Studying larger cohorts in a prospective fashion can avoid the limitations of our study and shed more light on early predictors. Utilization of more advanced MRI and OCT techniques may also be valuable.

Transcript edited for clarity.

REFERENCES
1. Abel A, McClelland C, Lee MS. Critical review: Typical and atypical optic neuritis. Surv Ophthalmol. 2019;64(6):770-779. doi:10.1016/j.survophthal.2019.06.001
2. Kosiyakul P, Songwisit S, Ungprasert P, Siritho S, Prayoonwiwat N, Jitprapaikulsan J. Effect of plasma exchange in neuromyelitis optica spectrum disorder: A systematic review and meta-analysis. Ann Clin Transl Neurol. 2020;7(11):2094-2102. doi:10.1002/acn3.51203
3. Sarin S, Modak N, Sun R, et al. Predicting the final clinical phenotype after the first attack of optic neuritis. J Neuroimmunol. 2023;381:578130. doi:10.1016/j.jneuroim.2023.578130