Ocular Allergy as a Risk Factor for Dry Eye in Adults and Children

Edoardo Villani; Giovanni Rabbiolo; Paolo Nucci


Curr Opin Allergy Clin Immunol. 2018;18(5):398-403. 

In This Article

Ocular Allergy and Ocular Surface Inflammation

Inflammation, including both innate immune response and adaptive response, is a key element of the DED vicious cycle. The acute response involves the mitogen-activated protein kinases and NF-κB signaling pathways, the generation of inflammatory cytokines as IL-1 and TNF-α, and the upregulation of matrix metalloproteinases (MMP) production by epithelial cells. The adaptive response is initiated by the activation and migration of resident antigen-presenting cells toward the regional draining lymphnodes, in which they stimulate naïve T cells (Th0), leading to the expansion of IL-17-γ and IFN-γ-secreting Th17 (Th17/1) cells.[18,27]

The conjunctival allergic inflammatory response is associated with IgE-mediated mast cell activation leading to the release of preformed mediators including histamine and proteases (acute phase). The subsequent de novo formation of chemokines and cytokines triggers a cascade of cellular and molecular events leading to the recruitment and activation of eosinophils and of Th2 and Th1 lymphocytes (late phase).[28]

The role of Th17 in ocular allergy is controversial. Some researches reported preliminary data suggesting increased tear levels of IL-17 in VKC[29] and in SAC and PAC.[30] However, this does not directly point to a role for Th17 cells as other cells, innate immune cells, are also IL-17 producers.[31] Moreover, Fukushima et al.,[32] in an experiment conducted on an animal model of allergic conjunctivitis, showed that wild type and IL-17−/− mice did not differ in conjunctival eosinophil infiltration.

Proteolytic enzymes, particularly MMP-9, play a key role in DED pathogenesis by disrupting intercellular epithelial tight junctions, leading to a breakdown of the ocular surface epithelial barrier.[18] MMP-9 has recently been proposed as one of the best DED severity biomarkers,[33] and as a diagnostic biomarker, assessable by a point-of-care immunoassay.[34]

Increased tears levels of MMP-1, MMP-2, and MMP-9, and increased ratio of MMPs to their tissue inhibitor have been well demonstrated in VKC and in a minority of patients with allergic conjunctivitis.[35,36] Significantly, in ocular allergy as in DED, MMP-9 showed a significant correlation with corneal epithelial damage.