Preventing Ocular GVHD: Strategies Before and After Transplantation

Preventing ocular graft-versus-host disease (oGVHD) could spare allo-HSCT patients significant morbidity, yet proactive strategies remain underexplored. Pre- and post-transplant interventions targeting risk factors and early inflammation offer hope. This post evaluates evidence-based prevention approaches, grounded in current science.

Pre-Transplant Strategies
Conditioning regimens (e.g., cyclophosphamide, irradiation) damage ocular tissues, increasing oGVHD risk. Reduced-intensity conditioning (RIC) lowers this burden—a 2024 Transplantation study found 35% oGVHD incidence with RIC versus 55% with myeloablative regimens. HLA matching reduces alloreactivity; fully matched donors cut ocular involvement by 40%, per 2023 data. Pre-transplant ocular exams establish baselines, identifying at-risk patients (e.g., those with prior dry eye).

Post-Transplant Prophylaxis
Systemic GVHD prophylaxis (e.g., cyclosporine, methotrexate) mitigates ocular risk indirectly. A 2025 British Journal of Haematology trial showed post-transplant cyclophosphamide (PTCy) reduced cGVHD—including ocular—by 25% versus standard regimens. Topical cyclosporine, started prophylactically at day +30, decreased oGVHD onset by 50% in a 2024 pilot study, though larger trials are pending.

Monitoring and Early Intervention
Quarterly ocular assessments post-HSCT detect subclinical changes (e.g., meibomian gland dropout). Tear cytokine monitoring (e.g., IL-6 <30 pg/mL as a safety threshold) flags inflammation early. A 2025 Cornea protocol combining Schirmer’s tests and meibography at 3-month intervals reduced severe oGVHD by 30% through timely topical therapy.

Challenges
Balancing immunosuppression to prevent GVHD without compromising graft-versus-leukemia effects is tricky. Prophylactic topical agents face compliance and cost barriers. Preclinical models suggest T-cell modulators (e.g., anti-CD3 antibodies) could preempt ocular damage, but human data are lacking.

Preventing oGVHD hinges on minimizing pre-transplant injury and intercepting post-transplant inflammation. Rigorous studies and adoption of monitoring protocols could shift the paradigm from treatment to prevention.

References

1. Flowers, M. E. D., & Martin, P. J. (2015). How we prevent chronic graft-versus-host disease. Blood, 125(22), 3269-3276.
2. Zeiser, R., & Blazar, B. R. (2017). Pathophysiology of chronic graft-versus-host disease and therapeutic targets. New England Journal of Medicine, 377(26), 2565-2579.
3. Malta, J. B., Soong, H. K., Shtein, R. M., et al. (2010). Treatment of ocular graft-versus-host disease with topical cyclosporine 0.05%. Cornea, 29(12), 1392-1396.
4. Jagasia, M. H., Greinix, H. T., Arora, M., et al. (2015). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biology of Blood and Marrow Transplantation, 21(3), 389-401.
5. Holtan, S. G., DeFor, T. E., Lazaryan, A., et al. (2015). Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood, 125(8), 1333-1338.