Vitreomacular Interface Abnormalities in Multiple Sclerosis; A Novel Signature of Disability
Hussein Moussa1, Grigorios Kalaitzidis2, Henrik Ehrhardt1, Olwen Murphy3, Eleni Vasileiou3, Gelareh Ahmadi1, Kathryn Fitzgerald4, Sahi Wuppukondur1, Sujata Rijal1, Scott Newsome3, Elias Sotirchos4, Peter Calabresi4, Amir Kashani1, Shiv Saidha1
1Johns Hopkins, 2Boston University Medical Center, 3Johns Hopkins Hospital, 4Johns Hopkins University
Objective:
To investigate the clinical (expanded disability status scale [EDSS] and visual function [VF]) measures, and retinal layer thickness differences between PwMS with (VMIA+) and without VMIAs (VMIA-).
Background:
Optical coherence tomography (OCT) allows high-resolution visualization of the retina, including vitreomacular interface abnormalities (VMIAs), such as epiretinal membranes. Correlations between blood-retinal barrier (BRB) dysfunction and VMIAs exist. Since BRB disruption may occur in multiple sclerosis (MS), elucidating VMIAs’ clinical relevance in people with MS (PwMS) is of interest, and remains largely unexplored.
Design/Methods:
In this cross-sectional study, 1463 PwMS (2926 eyes) underwent Cirrus HD-OCT imaging, with automated macular layer segmentation. VMIA presence was recorded. The VMIA+ and VMIA- groups were age and sex matched. EDSS, VF, and retinal layer thicknesses were analyzed using linear regression. Odds ratios (ORs) were estimated using logistic regression.
Results:
VMIAs were found in 95 PwMS (prevalence = 6.5%). The mean age and sex distribution of the VMIA+ (60.2 years, 72% female) and VMIA- (57.5 years, 79% female) cohorts were comparable. VMIA presence was associated with higher EDSS (difference 0.7, CI: 0.1-1.4, p=0.03), with the odds of having an EDSS>4 2.2 times higher in VMIA+, as compared to VMIA- (CI=1.21-4.16, p=0.01) PwMS. Inner nuclear layer (INL), outer nuclear layer (ONL), and retinal pigment epithelium (RPE) thicknesses were -0.98 µm (p=0.05), -2.84 µm(p=0.002) and -0.76 µm(p=0.001) respectively lower in the VMIA+ cohort. VF outcomes were similar between the groups.
Conclusions:
Our findings suggest VMIAs may identify an MS phenotype associated with greater disability, that is unrelated to visual dysfunction. Retinal inflammation disrupting BRB may activate Müller glia, potentially explaining why VMIA presence in PwMS correlate with greater disability. Müller glia in the INL and RPE cells may potentially migrate, possibly explaining INL and RPE thickness reductions in PwMS with VMIAs. Furthermore, disrupting the highly susceptible photoreceptors by VMIAs might reduce ONL thickness.