Corneal nerve fiber loss as a marker of neuropathy in patients with Macular telangiectasia type 2

Abstract

Purpose : Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique that allows quantification of corneal nerve fibers (CNF) in vivo. CNF loss is associated with a range of peripheral neuropathies and central neurodegenerative diseases and has a diagnostic value comparable to skin biopsies measuring intraepidermal nerve fiber density.
Macular telangiectasia type 2 (MacTel) is a complex, neurodegenerative disease of the retina. Patients with MacTel display a particular metabolic phenotype, including increased levels of atypical sphingolipids (“deoxysphingolipids”) that have previously been linked to neuropathies. Whether patients with MacTel have evidence of neuropathy, which could be reliably diagnosed with CCM, has not yet been evaluated.

Methods : In a prospective, cross-sectional study, patients with a confirmed diagnosis of MacTel were recruited at 3 participating sites. Eligible patients completed a questionnaire on symptoms of neuropathy and underwent CCM, multimodal retinal imaging, and a fasted blood draw. Primary endpoints were CNF density (CNFD), length (CNFL) and branch density (CNBD) compared to a healthy, age- and gender-matched control cohort. Secondary endpoints included the correlation of CNF parameters with retinal disease severity and serum metabolites.

Results : 36 participants (72 eyes; mean age 59 years; 18 females) were included. CNFD (mean ± standard deviation: 21.0±6.4 vs 38.9±6.0 fibers/mm²), CNFL (16.3±5.4 vs 28.0±4.9 mm/mm²) and CNBD (57.9±31.0 vs 101.8±41.2 branches/mm²) were significantly lower in patients with MacTel as compared to healthy subjects (all p<0.0001). Differences remained highly significant when corrected for age, sex and diabetes status. The majority of patients reported symptoms of neuropathy, including muscle weakness (in 23 [64%] participants), autonomic (22 [61%]), and sensory symptoms (19 [53%]). CNF parameters were negatively correlated to retinal disease severity and serum deoxysphingolipid levels, albeit reaching only nominal significance.

Conclusions : Patients with MacTel show a loss of CNF, indicating small fiber neurodegeneration, which was associated with increased toxic lipid species and retinal neurodegeneration. Future studies are warranted to further characterize the type of neuropathy and determine if measures of CNF degeneration and regeneration could act as surrogate markers of therapeutic efficacy in patients with MacTel.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.