Marked infiltration of neutrophils at the upper palpebral conjunctiva in patients with chronic graft-versus-host disease

Purpose: Neutrophils may be involved in the local pathophysiology of chronic graft-versus-host disease (cGVHD). We evaluated neutrophil infiltration in cGVHD using conjunctival impression cytology (IC) and its clinical correlation with ocular surface status and neutrophil enzyme levels in tears. Methods: This cross-sectional observational study included 76 patients with cGVHD. The ocular surface was assessed for the tear break-up time, Schirmer I test, corneal and conjunctival staining score, meiboscore, and the ocular surface disease index questionnaire. Conjunctival IC was performed at the temporal, superior bulbar, and upper palpebral conjunctiva, and the number of neutrophils (cells/high power field [HPF]) was calculated. Neutrophil elastase (NE), myeloperoxidase (MPO), and matrix metalloperoxidase-8 and -9 levels in tear washes were measured in 20 patients. Results: The number of neutrophils was significantly greater at the upper palpebral conjunctiva (median [range], 16.5 [0 to 147] cells/HPF) than at the temporal and superior bulbar conjunctiva (0 [0 to 70] and 0 [0 to 105] cells/HPF; P < 0.0001). The number of neutrophils at the upper palpebral conjunctiva showed moderate correlations with the corneal staining score and the NE and MPO levels in tears (r = 0.668, 0.553, and 0.563, respectively; P < 0.0001, P = 0.014, and 0.012). Conclusions: Our results suggest that neutrophils at the upper palpebral conjunctiva associate with the clinical manifestations and inflammatory status of the ocular surface in cGVHD. Conjunctival neutrophils should be addressed when assessing the inflammatory activity of ocular cGVHD and exploring its pathogenesis.