Inner Plexiform Layer Microstructure Is Altered in Multiple Sclerosis

In multiple sclerosis (MS), optical coherence tomography (OCT) is used to quantify retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning; however, thickness metrics may not capture microstructural alterations within the synapse-rich inner plexiform layer (IPL). The purpose of this study is to determine whether IPL microstructure differs in MS, whether abnormalities occur independently of optic neuritis and inner retinal thinning, and whether IPL metrics improve discrimination beyond thickness metrics.

Cross-sectional case-control study (49 MS [92 eyes], 59 controls [109 eyes]). IPL reflectivity was quantified from OCT. Mixed-effects models included RNFL/GCC adjustment; receiver operating characteristic curve assessed discrimination.

The percentage of IPL segments with an identifiable five-sublayer pattern was lower in MS (-20 percentage points; 95% confidence interval [CI], -25 to -13). MS eyes demonstrated higher outer hyporeflective sublayer intensity (0.15; 95% CI, 0.09 to 0.21) and lower middle hyperreflective-outer hyporeflective contrast (-0.13; 95% CI, -0.19 to -0.08). Findings persisted in non-optic neuritis eyes and after RNFL/GCC adjustment. The percentage of identifiable IPL segments discriminated MS from controls (area under the curve, 0.81; 95% CI, 0.73-0.90) exceeding RNFL/GCC.

IPL microstructure was altered in MS independent of optic neuritis and inner retinal thinning. Quantitative assessment of IPL microstructure may provide complementary structural information in MS.