Clinical and genetic profiling of fibromyalgia-associated dry eye: A multifactorial approach

Fibromyalgia syndrome (FM) is a chronic pain disorder affecting 3-6 % of the global population, often underdiagnosed and lacking specific diagnostic tests. Many patients also present with dry eye disease (DED), suggesting a possible link. This study explores the relationship between DED and FM-associated DED (FM-DED) by evaluating corneal nerve abnormalities using in vivo corneal confocal microscopy (IVCM), alongside gene expression and polymorphisms (COMT, MTHFR) related to inflammation.

The study included 113 participants: 81 patients (44 with DED, 37 with FM-DED) and 32 healthy controls (HC). Cell lines SK-OV-3, NCI-H1781, and NCI-H460 were included as controls. Clinical evaluations, IVCM, and genotyping of COMT Val158Met and MTHFR C677T from blood samples were conducted. Conjunctival gene expression was analyzed using an nCounter custom panel of 77 genes. Protein-Protein Interaction (PPI) network analysis identified key biological processes.

FM-DED patients showed significantly reduced corneal nerve density and increased Langerhans cells and microneuromas, with strong correlation with pain ((|ρ| > 0.7). Significant differences were observed in OSDI, NITBUT, TMH, and meibomian gland atrophy, but not in osmolarity or Schirmer I test. The GA genotype of COMT Val158Met was more frequent in FM-DED (60 %) and associated with severe cases. The CT genotype of MTHFR C677T was linked to increased corneal damage. Gene expression analysis showed immune-related gene overexpression (MUC1, IFITM1, PSMB8), with FM-DED-specific upregulation of PIGR and CEACAM6. PPI analysis highlighted lipopolysaccharide-mediated signaling.

Genetic polymorphisms and immune dysregulation contribute to FM-DED pathophysiology, supporting the need for differentiated diagnosis and targeted therapies.