Abstract

Background: Retrograde trans-synaptic degeneration (TSD) following retro-chiasmal pathology, typically retro-geniculate in multiple sclerosis (MS), may manifest as homonymous hemi-macular atrophy (HHMA) of the ganglion cell/inner plexiform layer (GCIPL). Objective: To determine the frequency, association with clinical outcomes, and retinal and radiological features of HHMA in people with MS (PwMS). Methods: In this cross-sectional study, healthy controls (HC) and PwMS underwent retinal optical coherence tomography scanning. For quantitative identification of HHMA, a normalized asymmetry ratio was used, and its normative cutoffs were established from the HC. HHMA PwMS were propensity score matched 1:2 to non-HHMA PwMS. Mixed-effects linear regression models were used in analyses. Results: Based on normative data from 238 HC (466 eyes), 79 out of 942 PwMS exhibited HHMA (8.4%; 143 eyes). Compared to non-HHMA eyes from matched PwMS (158 PwMS; 308 eyes), HHMA eyes had lower average GCIPL (diff: −5.7 μm (95% CI −7.6 to −3.8); p < 0.001) but also inner nuclear layer (diff: −0.9 μm (95% CI −1.6 to −0.1); p = 0.02), and outer nuclear layer (diff: −1.9 μm (95% CI −3.4 to −0.4); p = 0.02) thicknesses; in further analyses, these differences were exclusive to the homonymous side of HHMA. HHMA participants also exhibited higher expanded disability status scale scores (diff: 0.5 (95% CI 0.1 to 0.9); p = 0.02), worse 100% and 2.5% visual acuity scores (diff: −3.2 (95% CI −4.1 to −1.0); p = 0.002, −5.4 (95% CI −7.5 to −3.5); p < 0.001), and higher frequency of microcystoid macular changes (10.1% vs. 3.2%; p = 0.03) compared to non-HHMA participants. Conclusions: HHMA, possibly as a marker of TSD, may signify higher disability in MS.