Table 3.

Studies reporting elevated levels of neutrophils at the ocular surface of patients with MGD associated with different clinical scenarios.

Author (year)	Study objective	Study findings
Sonawane et al. (2012) [93]	To determine the level of nucleases and their relation to eDNA and NET formation in ocular surface inflammation.	Increased eDNA strand length and amount in DED compared to controls, with co-localization of PMNs and elastase to the eDNA strands. Increased conjunctival TLR-9, MyD88, IFN-type 1, IL-6, and TNFα in DED compared to controls.
Reyes et al. (2018) [10]	To determine if inflammation has a role in MGD.	Increased quantities of neutrophils in MGD patient tear fluid samples strongly correlated with MGD clinical severity. Tear cytology of AKC and BKC patients revealed populations of leukocytes including neutrophils, eosinophils, and mononuclear cells.
Postnikoff et al. (2020) [94]	To describe the phenotype and activation pattern of closed-eye neutrophils in DED versus controls.	Tear neutrophils from DED patients had higher expression of CD66b and higher monocytes than controls. Elevated extracellular MMP-9 and neutrophil elastase.
Nair et al. (2021) [95]	To determine the proportion of immune cell subsets in the ocular surface wash samples of DED patients.	Flow cytometry revealed higher proportions of neutrophils, CD4, CD8 T-cells, and double-positive T-cells than controls. Higher neutrophil/NK ratio in evaporative and aqueous DED than in controls. Positive correlation of flow cytometry findings with clinical indices.
Mahajan et al. (2021) [65]	To investigate the pathogenesis of obstructive MGD in ocular surface inflammation.	Ocular discharge samples from patients with MGD show aggregated NETs and occlude meibomian gland orifices as shown via eyelid biopsy fluorescent confocal microscopy. Increased tear C5a, IL-6, IL-8, and IL-18. Levels of C5a and IL-8 correlated with tear deficiency.
Perez et al. (2023) [72]	To investigate the role of MGD in the pathogenesis of oGVHD.	Spectral flow cytometry on tear samples from oGVHD patients revealed a substantial cell population composed primarily of neutrophils, along with mononuclear, and CD4 cells compared with healthy controls.

Abbreviations: eDNA, extracellular DNA; NET, neutrophil extracellular trap; DED, dry eye disease; TLR-9, toll-like receptor 9; MyD88, mutant myeloid differentiation primary response 88; IFN, interferon; IL, interleukin; TNFα, tumor necrosis factor alpha; MGD, meibomian gland dysfunction; AKC, atopic keratoconjunctivitis; BKC, blepharokeratoconjunctivitis; CD, cluster of differentiation; MMP-9, matrix metalloproteinase 9; NK, natural killer cell; oGVHD, ocular graft-versus-host disease.

^*The study included “tear-deficient patients” with ocular cicatricial pemphigoid, oGVHD, and neurotrophic keratitis.