Orbital inflammatory disorders: new knowledge, future challenges

Curr Opin Ophthalmol. 2021 May 1;32(3):255-261. doi: 10.1097/ICU.0000000000000743.

Abstract

Purpose of review: This review aims to bring together recent advances in basic, translational and clinical research on the pathogenesis and treatment of orbital inflammatory conditions.

Recent findings: Basic science studies provide mechanistic insights into why the orbit is targeted for inflammation by autoimmune inflammatory disorders. Using Graves' disease as a test case reveals that endocrine pathways, such as the TSH and IGF1 receptor pathways play important roles in stimulating orbital inflammation. Furthermore, orbital tissues contain high concentrations of retinoids - byproducts of the visual pathway that diffuse across the sclera and can activate de novo transcription of inflammatory cytokines. Such cytokine expression places the orbit in a hyper-inflammatory 'resting' state, prone to respond to any additional systemic or local pro-inflammatory signals. The HIF2A--LOX pathway appears important for orbital tissue fibrosis. Lastly, bench-to-bedside studies of the IGF1R pathway have led to an FDA-approved drug, teprotumumab that represents a novel treatment approach for Graves' orbitopathy. Unfortunately, high drug costs and misplaced insurance company 'step-therapy' policies may block patients from receiving therapy that can protect vision and improve quality of life.

Summary: Improved understanding of orbital inflammatory conditions has led to a new drug and promises additional breakthroughs. Translational research is successful, but requires time, resources, and patience.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Cytokines / metabolism
  • Graves Ophthalmopathy / drug therapy
  • Graves Ophthalmopathy / etiology
  • Graves Ophthalmopathy / metabolism
  • Hashimoto Disease / drug therapy
  • Hashimoto Disease / etiology
  • Hashimoto Disease / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / etiology*
  • Inflammation / metabolism
  • Orbital Cellulitis / drug therapy
  • Orbital Cellulitis / etiology
  • Orbital Cellulitis / metabolism
  • Orbital Diseases / drug therapy
  • Orbital Diseases / etiology*
  • Orbital Diseases / metabolism
  • Orbital Myositis / drug therapy
  • Orbital Myositis / etiology
  • Orbital Myositis / metabolism
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Thyrotropin / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • IGF1R protein, human
  • Receptors, Thyrotropin
  • Receptor, IGF Type 1
  • teprotumumab