Ocular graft-vs-host disease (GVHD) may accompany allogeneic-hematopoietic stem cell transplant (aHSCT) resulting in a decreased quality of life for those who undergo the procedure, according to research published in the American Journal of Ophthalmology. The systemic, inflammatory process is T cell-dependent and induces meibomian gland dysfunction (MGD).
Investigators used a murine model to induce ocular and systemic GVHD and perform a clinical assessment. Findings from the animal model were compared with human participants (n=57; 56% men; mean age, 53 years) using a retrospective chart review of patients with GVHD treated at a single center between 2017 and 2021.
In the murine model, mice received bone marrow transplant with (n=20) or without (n=20) T cells. At baseline, the 2 groups of mice had similar weights. At week 3, the mice injected with T cells developed progressive systemic disease, indicated by greater weight loss (74% vs 91% of baseline weight; P <.0001) and higher systemic disease score (mean, 6.75 vs 0.5; P <.0001) compared with those that were not injected with T cells. Tear production of the T cell recipients was significantly lower (P <.0001) and eyelid edema score was increased (P <.0001) compared with control mice. Receipt of T cells was associated with elevated CD45 cell (P =.021), polymorphonuclear neutrophil (P =.001), and CD8 cell (P =.04) counts and reduced CD4/CD8 ratio (P =.0004). Systemic GVHD score correlated with eyelid edema score (r, 0.38; P =.01).
In a subset analysis, the T cell recipients (n=15) had a higher MGD plugging score at day 21 compared with non-recipients (n=15; P <.0001). Noticeable MGD was observed in 93% of T cell recipient eyes, 47% of which had severe damage. Eyes with more severe atrophy had higher mean fluorescein green fluorescence index (P =.023).
The retroscopic analysis of human participants revealed that among patients with ocular GVHD, 96% had GVHD in at least one other organ. Skin (86%) was the most commonly affected organ, followed by gastrointestinal or oral involvement (61%).
Tears from patients with oGVHD had substantial neutrophil populations and 57% of these participants had a cell count of at least 100 CD45+ cells. Eyes without ocular GVHD did not not contain any identifiable immune cells, according to the report.
Meibography data was available for 89 eyes. Most eyes (97%) showed some MGD, 46% of which had moderate to severe MGD. A higher degree of MGD atrophy was associated with higher matrix metalloproteinase-9 (MMP-9) positivity (χ2, 4.05; P =.044) and lower tear breakup time (P =.0176).
“Our investigations in animal models and human patients highlighted the systemic inflammatory process driving an early T cell-driven bidirectional vicious cycle of disease progression that ultimately manifests in a robust form of inflammatory keratopathy,” according to the researchers. “Thus, future studies will be designed to test the role of MGD progression in ocular surface disease severity in oGVHD.”
Study limitations include a single center design and a retrospective nature in the patient cohort.
Disclosure: Multiple authors declared affiliations with biotech, pharmaceutical, and/or clinical research organizations. Please refer to the original article for a full list of disclosures
Perez VL, Mousa HM, Soifer M, et al. Meibomian gland dysfunction: a route of ocular graft-versus-host disease progression that drives a vicious cycle of ocular surface inflammatory damage. Am J Ophthalmol. Published online September 23, 2022. doi:10.1016/j.ajo.2022.09.009