Article ; Online: Orbital inflammatory disorders: new knowledge, future challenges.
Current opinion in ophthalmology
2021 Volume 32, Issue 3, Page(s) 255–261
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 ... ...
| 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. |
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| MeSH term(s) | 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 |
| Chemical Substances | Antibodies, Monoclonal, Humanized ; Cytokines ; IGF1R protein, human ; Receptors, Thyrotropin ; Receptor, IGF Type 1 (EC 2.7.10.1) ; teprotumumab (Y64GQ0KC0A) |
| Language | English |
| Publishing date | 2021-02-19 |
| Publishing country | United States |
| Document type | Journal Article ; Review |
| ZDB-ID | 1049383-9 |
| ISSN | 1531-7021 ; 1040-8738 |
| ISSN (online) | 1531-7021 |
| ISSN | 1040-8738 |
| DOI | 10.1097/ICU.0000000000000743 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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