Adverse Environmental Stress is a Risk Factor for Ocular Graft-Versus-Host Disease

Abstract

Purpose : Ocular graft-versus-host disease (oGVHD) is a rapidly progressing, sight-threatening condition of the eye following allogeneic hematopoetic stem cell transplantation (aSCT). Previously we reported in a small case-series that adverse environmental stress (AES) during allogeneic hematopoietic stem cell transplantation (aSCT) may be a risk factor for chronic oGVHD. To strengthen these findings and to identify pathomechanisms, consecutive retrospective analysis of all clinical files of our clinic since 2014 was performed in addition to experimental simulation of AES in a mouse model of oGVHD.

Methods : Comprehensive review of all files from all patients undergoing aSCT between 2014-2018 was performed. Collected data included Schirmer test scores, corneal fluorescein staining, onset of GVHD of the eyes, skin and gut. Statistical analysis included Pearson’s Chi2 and Kruskal-Wallis Test.
A minor mismatch-mouse model (129S2->C57BL/6) was used where mice either remained in standard housing or were subjected to AES (35% humidity, constant air flow) for 18 days after bone marrow transplantation (BMT). Systemic and ocular GVHD was monitored for up to 28 days and histological and flow-cytometry analyses of ocular tissue, lacrimal gland, ocular draining-lymph nodes and spleen were performed.

Results : From 444 patients (n=181 female, n=263 male) undergoing aSCT, 211 surviving patients presented with systemic GVHD and n=126 (53 %) developed chronic oGvHD. Humidity of less than 30% during aSCT was significantly higher correlated with oGVHD (73%), whereas humidity above 50% lead to a lower rate of oGVHD (30%). Acute skin GVHD, but not gut GVHD was an AES-independent risk factor for oGVHD.
In the mouse GVHD model, AES led to a significant higher systemic and ocular GVHD score than in the GVHD without AES at days 7 and days 14 after BMT. Corneal staining and blepharitis remained significant elevated after discontinuation of AES until day 28.

Conclusions : Both clinical and experimental data confirm the hypothesis that AES is an independent risk factor for ocular GvHD. In particular humidity below 30% during aSCT increases the risk for oGVHD significantly. Low humidity conditions after aSCT in the mouse model worsened the severity of systemic GVHD in the mouse model, implicating that AES has not only a local effect. In general, AES could be an avoidable risk factor for oGVHD.

This is a 2021 ARVO Annual Meeting abstract.