Autoantibodies Against Trisulfated Heparin Disaccharide and Fibroblast Growth Factor Receptor-3 May Play a Role in the Pathogenesis of Neuropathic Corneal Pain

Abstract

Purpose: The aim of this study was to describe cases of patients with presumable dysimmune small-fiber neuropathy (SFN)-related neuropathic corneal pain (NCP), presenting with autoantibodies against trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor-3 (FGFR-3).

Methods: This study was a case series of 3 patients with NCP with positive anti-TS-HDS and/or anti-FGFR-3 autoantibodies and systemic SFN as confirmed by positive skin biopsy results.

Results: All 3 patients were women with a mean age of 34.3± 6.1 years. They suffered from moderate to severe persistent chronic ocular discomfort (10/10, 10/10, and 9/10 on a visual analogue scale, respectively). Although 1 patient suffered from ocular pain and photophobia alone, the other 2 patients experienced additional non-ocular pain. One of the patients had pain on her face and head, and 1 patient reported neck and lower back pain. Two patients had high anti-TS-HDS IgM titers, whereas 1 patient had both high anti-TS-HDS IgM and anti-FGFR-3 IgG titers. Skin biopsy confirmed the presence of SFN in all patients by demonstrating decreased intraepidermal nerve fiber density.

Conclusions: The presence of anti-TS-HDS and anti-FGFR-3 autoantibodies in patients with NCP with positive skin biopsy findings for SFN highlights the potential role of dysimmune SFN in the pathogenesis of this disease.

Figure 1.

Comparison of central corneal nerve densities and nerve fiber numbers between cases and healthy control group. A) The mean total nerve density was 10,279.0±1,542.9 μm/mm² in cases and 24,762.3±4,661.3 μm/mm² in healthy controls. B) The mean nerve fiber number was 5.8±1.0 fiber/frame in cases and 26.6±2.1 fiber/frame in healthy controls.

Figure 2.

In Vivo Laser Confocal Microscopy Images (HRT3/RCM, Heidelberg Engineering GmbH, Heidelberg, Germany). IVCM images demonstrated corneal nerves in a healthy eye (A) and extremely damaged corneal nerves and presence of microneuromas (white arrows) in, Case 2 (B), and Case 3 (C).

Figure 3.

In Vivo Laser Confocal Microscopy Images (HRT3/RCM, Heidelberg Engineering GmbH, Heidelberg, Germany). IVCM images demonstrated dendritiform cells (white arrows) in patient corneas; Case 1 (A), slightly increased DC density in Case 2 (B) and Case 3 (C).