Identifying Small-fiber Neuropathy of the Corneal Sub-Basal Nerve Plexus in Sjögren Syndrome Using In-Vivo Confocal Microscopy

Abstract

Purpose : Small fiber neuropathy is known to be associated with Sjögren Syndrome (SS) and in-vivo corneal confocal microscopy can identify features of a small fiber neuropathy. Here we performed a descriptive study to identify features of a short fiber neuropathy of the corneal sub-basal nerve plexus using in-vivo confocal microscopy in participants from the Sjögren’s International Collaborative Clinical Alliance (SICCA) returning for up to 15-year follow-up compared to healthy controls.

Methods : We recruited 14 participants from the SICCA, the largest SS cohort in the world and funded by the National Institutes of Health, and 22 healthy controls. Eleven participants met SS classification based on updated 2016 American College of Rheumatology/European League Against Rheumatism criteria. All participants underwent slit-lamp examination and in vivo confocal microscopy of the central cornea’s sub-basal nerve plexus centered about the central vortex to create a 30-image montage. Each image was analyzed with automated software (ACCmetrics, Manchester, United Kingdom) to produce seven nerve metrics. We performed t-tests to make comparisons of nerve metrics between SS (from SICCA cohort) and healthy controls (recruited from outside SICCA cohort) as well as SS and non-SS (both from SICCA cohort).

Results : Most nerve metrics were significantly lower in SS participants compared to healthy controls. Mean corneal nerve fiber density was found to be 3.5 mm/mm² in SS participants compared to 10.6 mm/mm² in healthy controls (95% CI: 0.48 to 6.46, p<0.001). Mean corneal nerve branch density was 2.7 main fiber branch points/mm² in SS participants compared to 15.2 in healthy controls (95% CI: -0.5 to 6.0, p=0.001). Mean corneal nerve fiber length was 4.3 mm/mm² in SS participants compared to 9.9 in healthy controls (95% CI: 2.6 to 6.1, p<0.001). When we compared SS (n=10) and non-SS (n=4) returning SICCA participants, mean nerve metrics were generally higher in those classified as non-SS, though these findings did not achieve statistical significance.

Conclusions : SS exhibits lower corneal nerve metrics compared to healthy controls. These findings suggest that a short fiber neuropathy can distinguish SS from healthy controls and may serve as a potential novel biomarker in identifying SS.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.