Orbital inflammatory disorders: new knowledge, future challenges.

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.

• Authors: Alon Kahana
• Journal: Current opinion in ophthalmology (Curr Opin Ophthalmol) Vol. 32 Issue 3 Pg. 255-261 (May 01 2021) ISSN: 1531-7021 [Electronic] United States
• PMID: 33606408 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

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

Topics

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