Restless Legs Syndrome May Affect Retinal Nerve Fiber Layer Thickness

Inferior quadrant RNFL thinning in patients with multiple sclerosis and restless legs syndrome may indicate axonal loss and neurodegeneration.

Patients with relapsing remitting multiple sclerosis (RRMS) who have restless legs syndrome (RLS) may have a thinner peripapillary retinal nerve fiber layer (pRNFL) in the inferior quadrant than patients with RRMS and no RLS, according to findings published in Photodiagnosis and Photodynamic Therapy.

Patients with RRMS (N=75; eyes, 136; mean age, 37.53 years; 64% women), consisting of patients with RLS (n=20) and individuals without RLS (n=55) were recruited for the study between January and April 2022. Two neurologists evaluated patients for RLS using International Restless Legs Syndrome Study Group criteria. Participants self-reported fatigue symptoms using the fatigue severity scale and Epworth Sleepiness Scale assessments. 

All patients underwent comprehensive ophthalmic examinations including best corrected visual acuity assessment (BCVA), anterior segment analysis, and intraocular pressure (IOP) measurement. Optical coherence tomography (OCT) was used to measure pRNFL and macular ganglion cell-inner plexiform layer (MGCIPL) thicknesses. 

Participants in the  RLS cohort had the disorder for a mean 5.88 years (range, 1-18 years) and the mean RLS severity scale score was 25.7 points based on a scale from 0 to 40 (0, none; 40, very severe).

Following MS patients with OCT can help us get additional information on the neurodegenerative process in the retinal layers compatible with RLS.

Patients with RLS reported significantly higher fatigue severity scale scores (mean, 48.75 vs 36.7; P <.001) and Epworth Sleepiness Scale scores (mean, 7.44 vs 3.96; P <.001) compared with the patients without RLS, respectively.

No group differences in BCVA (P =.481), IOP (P =.351), or mean axial length (P =.282) were observed.

Similarly, OCT assessment revealed similar pRNFL, macular layer, and MGCIPL thicknesses, but patients with RLS had a thinner mean pRNFL in the inferior region compared with individuals who did not have RLS (104.5 vs 114.2 μm; P =.029).

Among the RLS cohort, expanded disability status scores, which evaluate ambulatory ability, correlated with mean (r, -0.563; P <.001), minimum (r, -0.586; P <.001), superior nasal (r, -0.617; P <.001), inferior nasal (r, -0.654; P <.001), superior (r, -0.546; P =.001), inferior temporal (r, -0.457; P =.005), superior temporal (r, -0.459; P =.005), and inferior (r, -0.421; P =.011) MGCIPL thicknesses.

“Patients with RLS had excessive daytime sleepiness, higher [expanded disability status] scores, a thinner pRNFL in the inferior quadrant, and presented with pronounced fatigue,” the study authors note. “Following MS patients with OCT can help us get additional information on the neurodegenerative process in the retinal layers compatible with RLS.”

The study was limited by a failure to include individuals with primer-progressive multiple sclerosis, small sample size, and the lack of a control arm.


Akmaz O, Koskderelioglu A, Eskut N, Sahan B, Kusbeci T. Restless legs syndrome in multiple sclerosis is related to retinal thinning. Photodiagnosis Photodyn Ther. Published online October 19, 2022. doi:10.1016/j.pdpdt.2022.103169