Novel Scoring Criteria for the Evaluation of Ocular Graft-versus-Host Disease in a Preclinical Allogeneic Hematopoietic Stem Cell Transplantation Animal Model

- Employing an MHC-matched, minor transplantation antigen-mismatched allogeneic model of matched unrelated donor, we developed clinical scoring criterion identifying degrees of ocular pathology at both the ocular surface and adnexa
- The association of these clinical changes with the development of immune responses around the ocular adnexa is monitored in real time
- We report, for the first time, that these clinical and immune responses occur not only on the ocular surface, but they also heavily involve the lid margin region
- Studies facilitate a standardized analysis of the immunologic and pathologic findings in the eye that occurs in animal models of ocular graft-versus-host disease

Ocular complications occur after transplantation in 60% to 90% of chronic graft-versus-host disease (GVHD) patients and significantly impair vision-related quality of life. Ocular surface inflammation and dry eye disease are the most common manifestations of ocular GVHD. Ocular GVHD can be viewed as an excellent preclinical model that can be studied to understand the immune pathogenesis of this common and debilitating disease. A limitation of this is that only a few experimental models mimic the ocular complications after hematopoietic stem cell transplantation (HSCT) and have focused on the acute GVHD process. To address this issue, we used a preclinical animal model developed by our group where ocular involvement was preceded by systemic GVHD to gain insight regarding the contributing immune mechanisms. Employing this “matched unrelated donor” model enabled the development of clinical scoring criteria, which readily identified different degrees of ocular pathology at both the ocular surface and adnexa, dependent on the level of conditioning before HSCT. As far as we are aware, we report for the first time that these clinical and immune responses occur not only on the ocular surface, but they also heavily involve the lid margin region. In total, the present study reports a preclinical scoring model that can be applied to animal models as investigators look to further explore GVHD's immunologic effects at the level of the ocular surface and eyelid adnexa compartments. We speculate that future studies will use this clinical scoring index in combination with what is recognized histologically and correlated with serum biomarkers identified in chronic/ocular GVHD.