Purpose
To investigate the relationship between systemic and ocular sarcoidosis manifestations and immunologic biomarkers in tissue and peripheral blood. The study hypothesizes that indicators of both lymphocyte behavior and granuloma activity would exhibit a similar pattern of association with ocular and nonocular involvement.

Methods
A retrospective analysis was conducted on 59 sarcoidosis patients from two major Los Angeles medical systems, all of whom had biopsy-proven non-caseating granulomas and were examined by an Ophthalmology service. Tissue analysis involved immunohistochemistry and image analysis to quantify CD4 and CD8 T cell aggregates within native lymph node granuloma biopsies. Measurements taken during sarcoidosis workup included peripheral blood lymphocyte count and highest serum ACE levels. Ocular outcomes, such as diagnosis of uveitis, and systemic manifestations, such as bilateral hilar lymphadenopathy (BHL) and Scadding thoracic stage, were recorded.

Results
Lymph node granuloma CD4:CD8 ratio of patients with thoracic stage II disease (3.6) was higher than those with stage 0 and I (2.2) (p=0.011). Proportion of patients with BHL who had uveitis (10/38) trended higher than those without BHL who had uveitis (2/19) (p=0.301). Patients with uveitis exhibited significantly higher mean serum ACE levels (103 U/L) compared to non-uveitis cases (60 U/L) (p=0.041). Patients tended to not have concurrent elevated ACE levels and lymphopenia.

Conclusions
In this survey of biopsy-proven sarcoidosis, granuloma activity, as inferred by ACE levels, correlated with uveitis. Conversely, signs indicative of lymphocyte trafficking, particularly a higher CD4:CD8 ratio on biopsy, are associated with greater extent of thoracic disease. These results collectively suggest that distinct manifestations of systemic and ocular sarcoidosis may be driven by heterogeneous underlying immunological pathways.