Conjunctival Biopsy to Guide Treatment of Chronic Ocular Gvhd

Abstract 4491

The treatment of chronic ocular graft-versus-host disease (GVHD) is empirical, mainly due to the lack of knowledge of its pathogenesis. The goals of this study were to describe the histopathologic and immunophenotypic characteristics of conjunctival biopsies from patients with chronic ocular GVHD and to determine whether these findings can guide immunomodulation or palliative management strategies of GVHD associated dry eye disease.

A conjuctival biopsy was obtained in eleven patients who previously received an allogeneic hematopoietic stem cell transplant (HSCT) and presented with chronic GVHD and dry eye symptoms. Hematoxylin and eosin (H&E) and immunohistochemical staining of conjunctival biopsies were analyzed for presence of inflammatory cells (B and T cells), fibrosis, and apoptosis. All conjunctival biopsies showed the presence of keratosis and parakeratosis and 7/11 (64%) biopsies had evidence of conjunctival epithelial apoptosis. Immunohistochemistry demonstrated the presence of inflammatory cells in 72% (8/11). These cells were predominantly CD3+ T lymphocytes (54%), with a CD4:CD8 cell ratio of 1:1.7. No biopsies showed B cells. Fibrosis was noted in 54% of biopsies (6/11). Conjunctival apoptosis detected by caspase-3 antibody staining showed significant moderate positive correlation with goblet cell loss (r=0.6, p=0.04). Presence of inflammatory cells showed a stronger correlation with conjunctival apoptosis as compared with fibrosis (r=0.38 and 0.26 respectively), however both correlations were not significant (p<0.05).

A standard dry eye treatment regimen in chronic ocular GVHD remains to be determined, thus examining the histopathologic features may help guide a more focused management strategy. In this study conjunctival apoptosis was associated with significant goblet cell loss and it more frequently accompanied inflammation as compared to fibrosis. Aggressive topical immunomodulation may reduce inflammation and goblet cell loss in patients with conjunctival biopsies positive for apoptosis.