Alterations in clinical parameters in cicatrising conjunctivitis secondary to GvHD

Abstract

Cicatricial conjunctivitis is part of a well‐known complication of graft versus host disease (GVHD) resulting from the tissue fibrosis that affects different body organs. It results from inflammatory reactions determined by recognition of recipient antigens as foreign by donor cells. The main target tissues in ocular GVHD are the conjunctiva and the lacrimal gland, and conjunctival involvement is usually associated with more severe systemic disease. Clinical manifestations of cicatricial conjunctivitis includes conjunctival fibrosis, conjunctival shortening, conjunctival scarring and keratinization, and symblepharon and/or ankyloblepharon. Such scarring may even lead to cicatricial lagophthalmos, ectropion, entropion, and stenosis or closure of the lacrimal puncta. In fact, the degree of palpebral conjunctival changes has been used as a criterion to classify conjunctival involvement in chronic GVHD.Conjunctival epithelial cells and myofibroblasts may have donor origin, though with a very small proportion. These donor‐derived fibroblasts may play a role in the pathogenesis of conjunctival fibrosis. In addition, it has been shown that the ocular surface of patients with chronic GVHD may show epithelial‐mesenchymal transition, in which the epithelium may gain the mesenchymal phenotype and the ability to migrate into the subepithelial stroma, resulting in conjunctival fibrosis.Our group showed that a significant proportion of patients with ocular GHVD had subtarsal fibrosis, that was non evident in non‐GHVD dry eye disease (DED) patients, even with the same degree of clinical severity. Extent of involvement varied from one eye to another; on average, more than a quarter of the visible tarsal area was affected by the fibrosis. Such fibrosis was significantly associated with ocular surface epitheliopathy and conjunctival staining. In contrast, densities of epithelial and stromal immune cells in the conjunctiva were comparable between GVHD and non GVHD DED patients after adjustment for severity of DED. We also showed that spontaneous extrusion of punctal plugs occurs in a majority of ocular GVHD‐associated DED patients within 90 days of plug placement, and this lower retention rate of punctal plugs has been attributed to punctal subepithelial fibrosis.In all patients with ocular GVHD, the eye care provider should evaluate the presence of conjunctival fibrosis and associated ocular surface complications. If present, the therapeutic strategy should attempt to address this scarring process.