Ocular Sarcoidosis: Contemporary Insights and Future Directions.

Abstract

Background: Ocular sarcoidosis (OcSar) is a complex manifestation of systemic sarcoidosis that affects more than half of patients. Characterized by non-caseating granulomas, it can involve any ocular structure, from anterior uveitis to optic neuropathy. Its clinical heterogeneity has earned it the nickname "The Great Chameleon", as diagnosis often requires integration of ophthalmic, systemic, and laboratory findings.

Methods: A targeted literature search was conducted in PubMed for publications from the last five years on OcSar, including clinical studies, systematic reviews, and meta-analyses. Non-English articles, abstracts, and preprints were excluded. Forty-two relevant studies were analyzed to summarize current diagnostic and therapeutic strategies.

Results: Diagnosis is guided by the revised International Workshop on Ocular Sarcoidosis (IWOS-2019) and the Standardization of Uveitis Nomenclature (SUN) criteria. High-resolution computed tomography (HRCT) and positron emission tomography with 2-deoxy-2-fluoro-D-glucose (18F-FDG PET/CT) improve systemic assessment, while soluble interleukin-2 receptor (sIL-2R), angiotensin-converting enzyme (ACE), and lymphopenia support diagnostic accuracy. Enhanced depth imaging optical coherence tomography (EDI-OCT) identifies subclinical choroidal inflammation, and molecular markers such as dysregulated micro ribonucleic acids (microRNAs) and fatty acid-related gene signatures offer potential non-invasive diagnostic tools. The Ferning test also provides insight into tear film alterations associated with ocular sarcoidosis. Treatment progresses from corticosteroids to immunosuppressants (methotrexate, mycophenolate) and biologics (adalimumab, infliximab), with pars plana vitrectomy reserved for refractory or complicated cases.

Discussion: The evolving understanding of ocular sarcoidosis shows that conventional clinical evaluation alone is insufficient to capture the full spectrum of disease activity. Integrating structural imaging with tear-film analysis and molecular profiling not only enhances diagnostic confidence but also reveals previously underrecognized pathways of inflammation. These insights highlight the systemic nature of the disease and underscore the need to reassess monitoring strategies and therapeutic sequencing in light of emerging evidence.

Conclusion: Ocular sarcoidosis remains a diagnostic and therapeutic challenge due to its variability and risk of irreversible vision loss. Combining advanced imaging, molecular biomarkers, and targeted biologic therapies enables precision-based management, improving visual outcomes and patient quality of life.