Small Fiber Neuropathy in Patients with Dry Eye Disease

Abstract Purpose: Small-fiber neuropathy (SFN) refers to a range of peripheral neuropathic conditions affecting small-caliber sensory and/or autonomic nerve fibers. This study aims to determine the prevalence and characteristics of SFN symptoms in patients with dry eye disease (DED). Design: Cross-sectional study at two academic eye centers Methods: 31 patients with DED and an Ocular Surface Disease Index (OSDI) greater than 13 were included. SFN symptoms were determined using the Small-Fiber Symptom Survey (SSS), a validated questionnaire, and positive symptoms were defined as having a score of 15.7 or higher (two standard deviations from the mean of healthy individuals without SFN). DED symptoms and ocular pain were assessed using the OSDI and the Ocular Pain Assessment Survey (OPAS), respectively. DED signs were assessed clinically and patient response to standard DED treatment was evaluated 6-12 months after the administration of the questionnaires. Results: The prevalence of SFN symptoms among DED patients was 77.4%. Positive correlations were found between SSS and OSDI (r=0.43, p=0.017), and between SSS and OPAS (r=0.62, p=0.0003). A negative correlation was observed between SFN symptoms and corneal fluorescein staining (CFS, r=-0.42, p=0.018) but not with tear break-up time or Schirmer’s test results. Despite more intense topical treatment and stable clinical signs of DED, patients with severe SFN symptoms (high SSS scores) had a less favorable subjective response to DED treatment, compared to those with low and moderate SSS scores. Conclusion: There is a high prevalence of SFN symptoms in patients with DED. SFN symptoms are strongly associated with ocular pain and DED symptoms and are negatively correlated with CFS. Patients with severe SFN symptoms have a less favorable subjective response to standard DED treatment, suggesting the presence of neuropathic conditions that warrant further neurological assessment.