Inner Retinal Layer Thinning May Predict Multiple Sclerosis Conversion


New data suggest that peripapillary retinal nerve fiber layer thinning may be an independent and novel risk factor for conversion to multiple sclerosis in those with RIS.

Dr Lilian Aly

Lilian Aly, MD, clinical scientist, Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich

Lilian Aly, MD

New study results suggest that for those who have radiologically isolated syndrome (RIS), the reduction or thinning of the peripapillary retinal nerve fiber layer (pRNFL) may increase the likelihood of conversion to multiple sclerosis (MS).1

In total, 8 participants with RIS converted to MS, all of whom showed a thinning of the pRNFL and the common ganglion cell and inner plexiform layer (GCIPL) at baseline and during follow‐up. Those with a pRNFL of ≤99 µm or a GCIPL of ≤1.99 mm3 displayed a 7.5-fold increased risk (95% CI, 1.9—29.9; P = .03) and 8.0‐fold increased risk (95% CI, 2.0—32.1; P = .02) for MS conversion, respectively, compared to individuals with higher measures.

After correction for other known risk factors, Cox proportional hazards regression revealed a hazard ratio (HR) of 1.08 for conversion to MS for each 1 µm decline in pRNFL. The additional Cox proportional hazard regression analysis did not reach significance for GCIPL volume, though the hazard for conversion to MS was 1.09 for each 0.02 mm³ decrease (P = .08; 95% CI, 0.989—1.220).

“Individuals with RIS are at increased risk of converting to MS. Early identification of later converters is crucial for optimal treatment decisions,” Lilian Aly, MD, clinical scientist in the Department of Neurology, Klinikum Rechts der Isar, Technical University of Munich, and colleagues wrote. “The purpose of this study was to assess the predictive potential of OCT measures in individuals with RIS regarding conversion to MS.”

Overall, the work included 2 sets of 36 individuals—those with RIS and healthy controls—from a pair of German MS centers, who had baseline optical coherence tomography (OCT) and clinical examination, longitudinally followed up to 6 years. In total, 52 eyes from 28 RIS individuals were used for longitudinal OCT analysis and follow-up OCT was available for 36 eyes in 18 healthy controls. Clinical follow‐up was a median of 46 months (interquartile range [IQR], 26—58).

READ MORE: Central Vein Sign: A Biomarker to Alleviate MS Misdiagnosis

When analyzing longitudinal changes in retinal architecture after baseline examination, those with RIS—irrespective of later conversion—showed a statistically significant annual loss in pRNFL thickness (-0.60 ±0.92 µm) compared to the control group (0.01 ±0.96 µm; P = .02), as well as GCIPL volume (RIS: -0.01 ±0.03 mm³; HC: 0.0 ± 0.02 mm³; P = .04). This effect, Aly and colleagues noted, was driven mostly by those who converted to MS, and no significant difference between controls and those with a sustained RIS diagnosis who did not convert was observed.

“Reduction of the pRNFL might be a novel and independent risk factor for conversion to MS in individuals with RIS. OCT might be useful for risk stratification and therapeutic decision‐making in individuals with RIS,” Aly and colleagues concluded.

Earlier this year, related work was conducted by Angeliki G. Filippatou, MD, neuroimmunology and neurological infections research fellow, Department of Neurology, Johns Hopkins University, and colleagues, which suggest that in the absence of overt metabolic comorbidities, body mass index (BMI) might be associated with accelerated rates of GCIPL atrophy in patients with MS.2

The data were from a 522-patient cohort, of which 9 were underweight and 153 were overweight in addition to 214 normal weight and 146 obese patients. Compared to patients with normal weight, those who were obese displayed significantly higher rates of GCIPL atrophy per year (obese: —0.57% per year [95% CI, –0.65 to 0.48]; normal weight: –0.42% per year [95% CI, –0.49 to –0.35]; P = .012). Additional analysis showed that each 1 kg/m2 higher BMI was associated with an accelerated GCIPL atrophy of —0.011% per year (95% CI, –0.019 to –0.004; P = .003). Notably, the GCIPL atrophy rate was not markedly different between overweight (—0.47% per year) and normal-weight patients (–0.42% per year; P = .41).


1. Aly L, Havla J, Lepennetier G, et al. Inner retinal layer thinning in radiologically isolated syndrome predicts conversion to multiple sclerosis. Eur J Neurol. Published online June 26, 2020. doi: 10.1111/ene.14416

2. Filippatou AG, Lambe J, Sotirchos ES, et al. Association of body mass index with longitudinal rates of retinal atrophy in multiple sclerosis. Mult Scler J. Published online April 16, 2020. doi: 10.1177/1352458519900942

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