Discussion

Our cohort of 30 patients with MOG-IgG ON demonstrated a female predominance and older age at presentation compared to typical ON. ^{Reference Beck16} Most patients were Caucasian. Just over half of patients reported eye pain or pain with eye movements and most cases were isolated without other neurological symptoms. Most patients had a normal MRI of the brain, consistent with international guidelines that suggest testing for MOG-IgG in patients with a normal brain MRI. ^{Reference Jarius, Paul and Aktas17} In patients with acute presentation, visual acuity was often worse than 20/200 with over one-fifth of these patients demonstrating incomplete recovery after treatment with high-dose corticosteroids and thus additionally treated with PLEX. Long-term immunosuppression was eventually initiated in 40% of patients and most demonstrated good final visual outcome with 20/30 average acuity at last follow-up.

The demographics of patients with MOG-IgG ON remain a topic of debate as previous studies included different patient populations and different geographic locations. Most patients in our cohort were female. Many previous studies have found a somewhat equal sex distribution, reporting a range between 47.9% and 63% females in their cohorts, with a few showing significant female predominance (Table 1). ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4–Reference Stiebel-Kalish, Lotan and Brody13} The highest reported percentages of women were 93.8% in a German study of 16 patients and 79% from in an Australian study of 19 patients. ^{Reference Ramanathan, Prelog and Barnes10,Reference Pache, Zimmermann and Mikolajczak11} No studies have shown a predominantly male cohort, with the highest reported percentage of males being 52.1% in a Korean cohort. ^{Reference Jang, Kim and Yun8} The age of onset of MOG-IgG ON can be variable as some studies have reported average onset in the second, ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4,Reference Ramanathan, Prelog and Barnes10} fourth, ^{Reference Chen, Flanagan and Jitprapaikulsan5,Reference Shor, Aboab and Maillart6,Reference Sepulveda, Armangue and Martinez-Hernandez9,Reference Pache, Zimmermann and Mikolajczak11,Reference Etemadifar, Abbasi, Salari, Etemadifar and Tavakoli12} or fifth decade of life. ^{Reference Ishikawa, Kezuka and Shikishima7,Reference Jang, Kim and Yun8,Reference Stiebel-Kalish, Lotan and Brody13} Our patients ranged in age from 16 to 77 with a mean age of 40.7 years, which is consistent with the previously reported notion that MOG-IgG ON can affect people across a wide range of ages. ^{Reference Chen and Tariq Bhatti2} This information is important as MOG-IgG ON should be kept in the differential diagnosis for all patients presenting with ON and age is not helpful in ruling out this condition.

Many studies reported bilateral eye involvement in around half of their cases of MOG-IgG ON, which is consistent with our cohort. ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4–Reference Shor, Aboab and Maillart6,Reference Stiebel-Kalish, Lotan and Brody13} The visual acuity of patients with acute presentations was significantly reduced, consistent with other studies reporting severe impairment of visual acuity at onset and nadir. ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4–Reference Ishikawa, Kezuka and Shikishima7,Reference Stiebel-Kalish, Lotan and Brody13} The MOG-IgG titer – whether low, medium, or high – did not seem to influence initial visual acuity. This supports the idea that the antibody titer does not influence the clinical phenotype. ^{Reference Chen and Tariq Bhatti2} Regarding optic disc appearance, our patients were less likely to have edema than patients in most other cohorts, which reported rates of edema as high as 86% to 100%. ^{Reference Chen, Flanagan and Jitprapaikulsan5,Reference Stiebel-Kalish, Lotan and Brody13} The higher proportion of optic disc pallor in our acute cases could largely be accounted for by the previous episodes of ON in these cases. Despite the poor vision at presentation, most patients had a good visual outcome and less than 5% of patients had a final visual acuity of 20/200 or worse, which has been reported to range from 6% to 14% of patients. ^{Reference Chen and Tariq Bhatti2,Reference Song, Zhou, Yang, Xu, Sun and Wei4,Reference Chen, Flanagan and Jitprapaikulsan5} The good final visual acuity was consistent with the preserved peripapillary OCT RNFL thickness in our group (72.15 um), which was better compared to previous reports from Germany (59 um) and China (68.7 um). ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4,Reference Pache, Zimmermann and Mikolajczak11}

Pain or pain with eye movements was common, headache was seen in a minority of individuals and neurological issues were infrequent in our patients. Pain is a frequent symptom reported in previous cohorts and can range from 75% to 86% of patients. ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4–Reference Ishikawa, Kezuka and Shikishima7} Headache occurrence has been reported to be as high as 50%. ^{Reference Asseyer, Hamblin and Messina18} Associated neurological symptoms were rare in our patients, but this may simply be a reflection of our patients being derived from neuro-ophthalmology practices. Transverse myelitis has been previously reported to be as high as 36% to 50% in previous cohorts of ON patients. ^{Reference Chen, Flanagan and Jitprapaikulsan5,Reference Pache, Zimmermann and Mikolajczak11} Perineural enhancement on MRI was common in our group of patients, consistent with previous literature that has reported this finding in 31.3%–52.0% of patients. ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4–Reference Shor, Aboab and Maillart6,Reference Jang, Kim and Yun8,Reference Etemadifar, Abbasi, Salari, Etemadifar and Tavakoli12} The rare optic chiasm (7.1%) and tract (3.6%) involvement are congruent with previous reports. ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4–Reference Shor, Aboab and Maillart6} The large majority of patients with MRI of the spine were normal and it was rare for patients to have abnormal spinal imaging when the brain was normal. Over 90% of our patients had a normal MRI of the brain, alerting the clinicians that normal brain MRI in patients presenting with ON should increase the suspicion for MOG-IgG associated disease.

There is a lack of consensus regarding optimal acute treatment for MOG-IgG ON attacks and long-term management to prevent additional attacks. ^{Reference Chen and Tariq Bhatti2} Intravenous methylprednisolone was the most used first-line agent for acute vision loss in our cohort, but prednisone 1250 mg was also used in a few cases. All but one patient had at least some improvement with high-dose corticosteroids, supporting this as a reasonable first-line treatment for acute MOG-IgG attacks. As demonstrated in our cohort, PLEX can be considered in patients who do not have significant improvement with high-dose corticosteroids, as this is an antibody-mediated disease. ^{Reference Chen and Tariq Bhatti2} No patients were given IVIG in our cohort, due to difficulty in accessing this agent in Ontario. Long-term immunosuppression was used in 40.0% of patients in our series. None of these patients had a relapse after being started on immunosuppressive therapy, supporting rituximab, mycophenolate mofetil, and azathioprine as reasonable chronic immunosuppressive agents in MOG-IgG ON. ^{Reference Chen and Tariq Bhatti2} Only 13.3% (4/30) of patients in our cohort had relapses after their initial visit, with one patient having more than one relapse. Other studies with established follow-up periods have reported relapses in at least 32% and up to 88% of their patients, making our relapse rate much lower. However, our follow-up time of 14.45 months was shorter than those studies, so it is possible that more patients in our cohort will have relapses in the future. ^{Reference Song, Zhou, Yang, Xu, Sun and Wei4–Reference Shor, Aboab and Maillart6,Reference Ramanathan, Prelog and Barnes10} A recent multicenter retrospective study found that the lowest annualized relapse rate was associated with maintenance IVIG therapy, but larger studies are needed to determine the comparative effectiveness of each. ^{Reference Chen, Flanagan and Bhatti19}

The strengths of our study include a relatively large cohort of MOG-IgG ON patients and captures the spectrum of disease presenting to neuro-ophthalmology clinics. Patients were evaluated with a comprehensive neuro-ophthalmic examination that included OCT and formal visual fields. Our study is limited in that it was retrospective in nature and follow-up time was limited, precluding strong conclusions on the effectiveness of long-term immunosuppression. We also may not have captured patients presenting with transverse myelitis or other neurological syndromes as they may have not been routinely referred to neuro-ophthalmology.

In conclusion, this study gives an initial overview of the spectrum of MOG-IgG ON in a group of Canadian patients. Our cohort was different from most previously reported cohorts in the following ways: older onset age; lower incidence of optic disc edema on presentation; lower rates of associated headache and neurological symptoms; less radiologic abnormalities; and lower relapse rates. Despite the poor visual acuity at presentation, most patients recover good visual function.