Activated Dendritic Cells in Dry Eye Linked to Systemic Immune Disorders

Middle age woman suffering eyestrain sitting on a couch at home
The study suggests that patients with dry eye symptoms who have systemic immune disorders have at least 2 “activated” dendritic cells in the central cornea.

Presence of at least 2 “activated” dendritic cells (aDCs) in central corneas may be a biomarker of a comorbid systemic immune disease in patients with dry eye (DE) symptoms, and topical anti-inflammatory therapy can reduce the number of aDCs, according to research published in The Ocular Surface.

To identify whether individuals with comorbid systemic immune conditions have DE, ophthalmologists typically need to manually count DCs, which are correlated with the lesser number of aDCs.

The investigators included 128 Miami Veterans Administrations Medical Center patients with DE symptoms, based on a score of at least 6 on the Dry Eye Questionnaire (DEQ-5), who had undergone an in vivo confocal microscopy (IVCM) scan between October 2018 and July 2020. They determined the corneal nerve fiber density, corneal nerve fiber length, corneal nerve branch density, corneal total branch density, corneal nerve fiber area, corneal nerve fiber width, corneal nerve fractal dimension. They identified “activated” DCs as the number per image of hyperreflective cells with at least 3 processes originating from the cell trunk that were at least the length of the cell body.

There was a mean of 5.67±7.5 DCs/image (35.4±46.9 cells/mm2) and 1.28±2.16 aDCs 5.67±7.5 DCs/image (35.4±46.9 cells/mm2) per image. Thirteen individuals were diagnosed with a systemic immune disease. The researchers conducted a receiver operator curve (ROC) analysis and determined the best aDC cut-off that identified whether individuals had a systemic immune disease was the presence of at least 2 aDC in the central cornea, with a sensitivity of 60% and a specificity of 77%.

Patients with systemic immune diseases were more likely (23.3%) to have at least 2 aDCs in their central cornea than those who did not have the diseases (7.5%) (P =.04), especially if they had secondary Sjogren syndrome (15.2% vs 3.2%, P =.03). 

Black patients (51.5%) were more likely than White patients (27.7%) to have at least 2 aDCs present (P =.02). Nerve fiber area and fractal dimension were higher in patients who had at least 2 aDCs compared with the group that had fewer than 2 aDCs (0.006±0.002 vs 0.007±0.004 mm2/mm2, P <.01 and 1.45±0.06 vs 1.47±0.04 mm2/mm2, P =.05, respectively).

Twelve patients who began topical anti-inflammatory therapy experienced a 78% decrease in ADCs in the central cornea, as seen on a repeat scan at least 3 months later.

Limitations of the study included limited generalizability to other populations, an activation status basis on morphology rather than specific markers, likely inclusion of patients with an undiagnosed systemic immune disease, and the lack of counting any aDCs that were positioned within the Z-axis.


Levine H, Hwang J, Dermer H, et al. Relationships between activated dendritic cells and dry eye symptoms and signs. Ocul Surf. 2021;21(7);186-192. doi:10.1016/j.jtos.2021.06.001