Histopathologic and Immunophenotypic Characteristics of Conjunctival Biopsies in Chronic Graft Versus Host Disease

Abstract

Purpose: : To describe the histopathologic and immunophenotypic characteristics of conjunctival biopsies from patients with chronic ocular graft-versus-host-disease (GVHD). To determine whether histopathologic findings in conjunctival biopsies can guide immunomodulation or palliative management strategies of GVHD associated dry eye disease.

Methods: : Retrospective case series of patients with a history of allogeneic hematopoietic stem cell transplant (HSCT) with chronic GVHD and dry eye symptoms (n=11). 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.

Results: : All conjunctival biopsies (n=11) showed the presence of keratosis and parakeratosis. 64% (7/11) of the biopsies had evidence of conjunctival epithelial apoptosis. 72% (8/11) of the biopsies demonstrated inflammatory cells, predominantly the T lymphocytes; with CD3 positive T cells most frequently observed (54% of biopsies). No biopsies showed B cells. The ratio of the CD4:CD8 cells was 1:1.7. Fibrosis was noted in 54% of biopsies (6/11). Conjunctival apoptosis (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).

Conclusions: : 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.

Keywords: conjunctiva • apoptosis/cell death