LAUSR

BACKGROUND 5q Spinal Muscular Atrophy (SMA) is a progressive, inherited and severely disabling - yet treatable - motor neuron disease. Although treatment options have evolved in recent years, biomarkers for treatment monitoring and prognosis prediction remain elusive. Here, we investigated the utility of corneal confocal microscopy (CCM), a non-invasive imaging technique to quantify small corneal nerve fibres in vivo, as a diagnostic tool in adult SMA. METHODS In this cross-sectional study, 19 patients with SMA type 3 and 19 healthy controls underwent CCM to measure corneal nerve fibre density (CNFD), corneal nerve fibre length (CNFL), and corneal nerve branch density (CNBD) as well as corneal immune cell infiltration. Hammersmith Functional Motor Scale expanded (HFMSE) and Revised Upper Limb Module (RULM) scores and a six-minute walk test (6MWT) were conducted to explore any correlation between CCM findings and motor function. RESULTS Corneal nerve fibre parameters were decreased in SMA patients versus healthy controls (CNFD: p = 0.030; CNFL: p = 0.013; CNBD : p = 0.020) in absence of relevant immune cell infiltration. CNFD and CNFL correlated with HFMSE scores (CNFD: r = 0.492, p = 0.038; CNFL: r = 0.484, p = 0.042) and distance covered in the 6MWT (CNFD: r = 0.502, p = 0.042; CNFL: r = 0.553, p = 0.023). CONCLUSIONS CCM reveals sensory neurodegeneration in SMA, thereby supporting a multi-system view of the disorder. Subclinical small nerve fibre damage correlated with motor function. Thus, CCM may be ideally suited for treatment monitoring and prognosis.