Retinal degeneration in MOG antibody Associated Disease (MOGAD): a longitudinal OCT study

Background and aims.Since in MOGAD(MOG antibody Associated Disease)data about prognostic meaning of MOG ab titres and retinal degeneration are still lacking, we analysed longitudinal dynamics of MOG antibodies and of GCL and RNFL thicknesses, acquired through OCT scans in a cohort of MOGAD patients. We compared GCL and RNFL thicknesses and dynamics between MOGAD patients and a cohort of multiple sclerosis(MS) patients. Methods.Prospective and retrospective interventistic monocentric study. MOGAD and MS patients referring to Mondino Foundation underwent periodic clinical and serological follow-up(FU)and OCT scans. Results.MOGAD cohort was made up of 16 patients, with mean age of 38 years, mean EDSS of 1.8, mean FU duration of 49 months. 8/16 patients showed a relapsing form of disease.MOG ab titres dynamics were similar between monophasic and relapsing patients. However, in 5/8 relapsing patients clinical relapse occurred in concomitance with increasing in MOGab titres. We didn’t find correlation between MOG antibody titres at baseline and mean GCL-RNFL thicknesses,and between MOG ab titres and OCT thicknesses variation rates. Patients were divided in groups according to history of optic neuritis(ON): MOG-ON+(N=11) and MOG-ON-(N=5). Mean MOG antibody titres at baseline were similar between groups, as baseline OCT thicknesses. We didn’t find differences in GCL-RNFL variation rates between groups.We didn’t find correlations between MOG dynamics and GCL-RNFL thinning rates considering eyes with and without ON. Considering whole cohort of MOGAD, we found association between annualized GCL variation rate and relapsing course of disease(p=0.01). This result also applied when splitting our cohort into MOG-ON+and MOG-ON-subgroups. Considering EDSS variation at FU, annualized CGL variation rate was higher in patients with disability progression(p=0.03). MS cohort was made up of 21 patients, with mean age of 34 years,mean EDSS of 1,mean FU duration of 40 months. Demographic features were similar between MOGAD and MS,except for baseline EDSS, which was higher in MOGAD and sex(F/M ratio was higher in RRMS cohort). Considering patients with ON, GCL-RNFL baseline thicknesses and thinning rates were similar between MOGAD and MS.Considering eyes without history of ON, we found a higher annualized GCL variation rate in MOGAD(p=0.03). This result applied when considering group of unaffected eyes(p=0.05), but didn’t apply when considering group of fellow eyes. Discussion and conclusions. Even if MOG ab titres dynamics didn’t differ between monophasic and relapsing patients, the occurrence of clinical relapses is preceded by an increasing in MOG ab titres. Thus, monitoring MOG-ab titres could have a prognostic utility. In MOGAD cohort, retinal degeneration was higher in relapsing patients, independently of the occurrence of ON. Thus, retinal degeneration could be accelerated by inflammatory events, independently of the district in which they occur. MOG ab titres didn’t correlate with retinal degeneration. Thus, monitoring MOG ab titres might not reflect severity of retinal degeneration, even in eyes with history of ON. All patients experiencing disability progression show increased MOG ab titres at FU and faster GCL thinning rates. As titres increased during relapses and retinal degeneration accelerates after inflammatory episodes, these data highlight the concept that retinal degeneration and disability progression could be result of recurrent relapses. Retinal degeneration is similar in MOGAD and MS eyes with ON as in fellow eyes. Thus, we could infer that retinal degeneration is independent of the triggering ON. Moreover, in fellow eyes, a similar physiopathological mechanism could occur. In eyes without ON retinal degeneration is higher in MOGAD than in MS.This data question if, even in MOGAD, a pure neurodegenerative process could exist thus considering that disability progression could not be caused only by clinical relapses.