OCT in MOGAD
The quantitative and qualitative assessment of the retinal changes over time can be performed in close-to-cellular resolution using spectral domain optical coherence tomography (OCT) (23,115). Improvement of OCT techniques in the past decade has allowed the retina to be examined in greater detail. The unprecedented resolution of down to 3.9 µm enables measurement of retinal ganglion cell loss, evaluated by the combined macular ganglion cell layer and inner plexiform layers (mGCIPL) and their axons, as measured by the peripapillary retinal nerve fiber layer (pRNFL). These OCT metrics have been shown to correlate well with visual function and the damage that occurs in NMOSD and MS patients (116,117) Thus, OCT is a valuable tool for monitoring many neuro-ophthalmological and neurological conditions, including NMOSD and MOGAD (Figure 4) (68,118,119).
Acute ON in MOGAD is often bilateral and localised in the anterior optic nerve inducing severe and characteristic retinal edema (120). Initially covered by the edema, the neuroaxonal layers of the retina (pRNFL, mGCIPL) degenerate significantly in the following months (Figure 5) (23,69,115,120,121). These losses accumulate with each additional ON episode, which occur frequently in MOGAD (69,70). Therefore, although a single episode does not often lead to disastrous damage (122,123), the highly recurrent ON attacks accumulate with pRNFL and mGCIPL loss. This is comparable to patients with AQP4-IgG seropositive NMOSD, which is characterised by less frequent, but more damaging ON episodes (70). In comparison with MS, MOGAD patients are described as undergoing more severe retinal neurodegeneration after ON, however a final consensus on this topic has not been reached (115,122,124).
Further studies are warranted to investigate retinal neurodegeneration independent of ON in MOGAD. One study performed a first exploratory analysis in a small dataset recording pRNFL loss without associated GCIPL reduction (125). Apart from true retinal neurodegeneration, this could potentially be explained by a remission of attack-associated edema, which commonly affects the RNFL more than the ganglion cell layer (126). If the absence of ON-independent GCIPL loss is confirmed, this would not only stress the importance of ON attack-prevention in MOGAD but also allow a better separation from MS and AQP4-IgG seropositive NMOSD, which are both affected by ON-independent retinal neuroaxonal loss.
OCT data in paediatric MOGAD is scarce. The results in paediatric cohorts generally mirror those in adults with measurable post-ON swelling and associated reduction and thinning of the pRNFL (69,127). There are, however, conflicting reports concerning unilateral ON cases with subclinical involvement of the contralateral, clinically healthy eye, an area which would benefit from further research given the potential detrimental impact on the otherwise healthy eye (127,128).
In both paediatric and adult presentations, and notwithstanding the high relapse rates and severe neuroaxonal degeneration, high-contrast visual acuity is surprisingly preserved in MOGAD patients compared with AQP4-IgG seropositive NMOSD patients although both groups have comparable neuroaxonal loss (70,122,129–131). How visual acuity is preserved in MOGAD remains unclear, but data suggests an influence of a primary retinal astrocytopathy in AQP4-IgG seropositive NMOSD accumulating in additional retinal changes with functional consequences (Giegengack et al. in preparation ) (132). Nevertheless, MOGAD patients with their high prevalence of ON attacks, are at risk of irreversible visual impairment when deprived of a timely diagnosis and immunosuppression therapy.