Low GCIPL Thickness Associated With MS Disability Worsening

Angeliki G. Filippatou, MD

Data from a recent study published in Neurology suggest that lower baseline ganglion cell + inner plexiform layer (GCIPL) thickness on retinal spectral-domain optical coherence tomography (SD-OCT) is independently associated with long-term disability worsening in multiple sclerosis (MS).

Researchers found that an average baseline GCIPL thickness less than 70 µm was associated with a 4-fold increased odds of a meaningful expanded disability status scale (EDSS) score (adjusted odds ratio [aOR], 3.97 [95% CI, 1.24-12.70]; P = .02) as well as 3-fold increased odds of a 2.5% worsening of low-contrast visual acuity (LCVA; aOR, 2.93 [95% CI, 1.40-6.13]; P = .04).

“Our study provides robust evidence that SD-OCT assessment performed at a single time-point is independently associated with long-term disability worsening in people with MS. Lower baseline GCIPL thickness is associated with increased odds of meaningful EDSS worsening and LCVA worsening over a median of 10 years later in people with MS,” wrote first author Jeffrey Lambe, MD, Johns Hopkins Medicine, and colleagues

Lambe and colleagues, including Angeliki G. Filippatou, MD, analyzed data from 132 patients with MS treated at the Johns Hopkins MS center between September 2008 and March 2020. The patients had a mean age of 43 years, 106 had relapsing-remitting MS (RRMS), and the remaining 26 with primary or secondary progressive MS were grouped into a single progressive MS cohort. The median duration of follow-up was 10.4 years (standard deviation [SD], 0.9).

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The researchers found that patients with an average GCIPL thickness less than 70 µm were more likely to have a longer disease duration (mean, 10.9 years; SD, 8.9) than those with an average thickness of at least 70 µm (mean, 6.9 years; SD, 6.8; P = .007). These patients also constituted a greater proportion of follow-up on intermediate potency disease-modifying therapies (DMTs; 16%) than patients with an average thickness of at least 70 µm (9%; P <.001). No significant differences were seen in proportions in low-potency and high-potency DMTs.

Patients with an average baseline GCIPL thickness less than 70 µm also had lower baseline thicknesses of the peripapillary retinal nerve fiber layer (pRNFL), inner nuclear layer (INL), outer nuclear layer (ONL), and average macular thickness (AMT; all P <.001). These patients had lower binocular VA at 1.25% contrast (20.5 letters; SD, 9.7) than those with an average GCIPL thickness of at least 70 µm (26.4 letters; SD, 8.5; P = .015). 

Median baseline EDSS scores did not statistically differ between GCIPL thickness groups (P = .13), however, 14 of 45 patients (31%) with the lower thickness experienced EDSS worsening during follow-up compared to 7 of 72 patients (10%; P = .006) with the higher thickness. Patients with an average baseline GCIPL thickness of less than 70 µm had significantly greater annual increases in EDSS scores than those with thicker GCIPL (β, 0.06 [95% CI, 0.002-0.11]; P = .043).

Lambe and colleagues found that patients with RRMS specifically had even higher odds of meaningful EDSS worsening (n = 92; aOR, 6.19 [95% CI, 1.41-27.27]; P = .016). Other subgroups with higher odds of disability worsening were those with a disease duration of more than 9 years at baseline (n = 73; aOR, 14.42 [95% CI, 1.26-165.51]; P = .032) and those with a baseline EDSS score of at least 2 (n = 57; aOE, 8.58 [95% CI, 1.38-53.24]; P = .021). Altogether, patients with both RRMS and a disease duration of at least 9 years at baseline had the highest odds of disability worsening (aOR, 15.10 [95% CI, 1.60-142.83]; P = .018).

Patients with low thickness in both eyes had an over 5-fold increased risk of EDSS worsening (aOR, 5.03 [95% CI, 1.27-19.83]; P = .021) than patients with higher thickness in both eyes while patients that only had 1 eye with low thickness had no significant differences in outcomes from patients with GCIPL thickness of at least 70 µm in both eyes (aOR, 1.45 [95% CI, 0.18-11.34; P = .73).

The researchers also found that in patients with GCIPL thickness of less than 70 µm, each 1 µm higher baseline retinal layer thickness was associated with reduced odds of a 2.5% VA worsening of the GCIPL (aOR, 0.94 [95% CI, 0.89-0.99]; P = .022), ONL (aOR, 0.89 [95% CI, 0.83-0.95]; P = .001), AMT (aOR, 0.96 [95% CI, 0.94-0.99]; P = .006), and pRNFL (aOR, 0.96 [95% CI. 0.94-0.99]; P = .015).

A similar pattern was seen with 100% VA worsening and each 1 µm higher ONL (aOR, 0.92 [95% CI, 0.88-0.98]; P = .006) and AMT thickness (aOR, 0.97 [95% CI. 0.95-0.99]; P = .015). Retinal layer thickness was not found to be associated with 1.25% VA worsening.

Lambe and colleagues also found that each 1 µm lower baseline thickness was associated with lower annual percent change for the GCIPL (β = –0.015 [95% CI, –0.022 to –0.008]; P <.001), INL (β = –0.015 [95% CI, –0.027 to –0.003]; P = .012), ONL (β = –0.014 [95% CI, –0.022 to –0.005]; P = .002), AMT (β = –0.003 [95% CI, –0.004 to –0.002]; P <.001), and pRNFL (β = –0.013 [95% CI, –0.020 to –0.006]; P <.001).

“Our findings strongly support the utility of OCT measures as powerful surrogates of neurodegeneration, helping to predict clinically meaningful long-term outcomes in PwMS that may influence treatment decisions in the clinical setting," Lambe and colleagues concluded.

REFERENCE

Lambe J, Fitzgerald KC, Murphy OC, et al. Association of spectral-domain OCT with long-term disability worsening in multiple sclerosis. Neurology. Published online March 2, 2021. doi: 10.1212/WNL.0000000000011788