Tear inflammatory cytokines and ocular surface changes in patients with active thyroid eye disease treated with high-dose intravenous glucocorticoids

J Endocrinol Invest. 2020 Jul;43(7):901-910. doi: 10.1007/s40618-019-01174-8. Epub 2020 Jan 11.

Abstract

Purpose: To evaluate high-dose intravenous glucocorticoid treatment on tear inflammatory cytokines and ocular surface parameters in patients with active TED. Correlations between tear inflammatory cytokines and clinical parameters were also investigated.

Methods: This prospective pilot study included 15 moderate-to-severe and active TED patients. Control group consist of 15 sex and age-matched healthy subjects. All TED patients were treated with high-dose intravenous methylprednisolone with cumulative dose of 4.5 g during the therapy subdivided into 12 weekly infusions. Tear concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-17A, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) were measured by multiplex bead analysis in TED patients at baseline and 12 weeks after treatment. Ocular surface disease index (OSDI), tear break-up time (TBUT), corneal fluorescent staining, and Schirmer's test were obtained from TED and controls.

Results: All baseline cytokine levels except for IL-17A were significantly elevated in active TED patients compared with controls. Concentrations of IL-1β, IL-6, IL-8, TNF-α, and VEGF were significantly decreased at 12 weeks compared with baseline. OSDI and TBUT showed significant improvement at 6 and 12 weeks. There were significant positive correlations between IL-6, IL-8, and CAS, and negative correlation was found between IL-6 level and TED duration before methylprednisolone treatment. The reduction of IL-6, IL-8, and VEGF were positive correlated with the reduction in CAS at 12 weeks.

Conclusions: High-dose glucocorticoids treatment improved ocular surface symptom, increased the tear film stability, and decreased tear inflammatory cytokines in active TED. The reduction of the inflammatory cytokines is consistent with the improvement of clinical parameters.

Keywords: Cytokines; Ocular surface; Tear; Thyroid eye disease.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Administration, Intravenous
  • Adult
  • Cytokines / analysis*
  • Cytokines / metabolism
  • Diagnostic Techniques, Ophthalmological
  • Dose-Response Relationship, Drug
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology
  • Graves Ophthalmopathy / diagnosis
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / metabolism
  • Graves Ophthalmopathy / pathology
  • Humans
  • Inflammation Mediators / analysis
  • Inflammation Mediators / metabolism
  • Male
  • Matched-Pair Analysis
  • Methylprednisolone / administration & dosage*
  • Methylprednisolone / pharmacology
  • Middle Aged
  • Ocular Physiological Phenomena* / drug effects
  • Pilot Projects
  • Surface Properties / drug effects
  • Tears / chemistry*
  • Tears / drug effects
  • Tears / metabolism
  • Treatment Outcome

Substances

  • Cytokines
  • Glucocorticoids
  • Inflammation Mediators
  • Methylprednisolone