Challenges and concepts in the diagnosis and management of ocular graft-versus-host disease

Abstract

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.

Keywords: diagnosis; dry eye; ocular graft-versus-host disease (GVHD); ocular surface inflammation; treatment.

Figure 1

Graft-versus-host disease may be due to self-reactive donor B cells (1), deficient deletion of autoreactive donor T cells in the thymus (2) or deficient deletion of autoreactive donor T cells in the lymph nodes (3). Especially antigen-presenting cell (APC) driven activation of donor T cells (4) but also B cells (5) lead to an inflammation of the ocular surface (6). Furthermore, activation of fibroblasts by APCs (e.g., dendritic cells) induces fibrosis of the lacrimal gland (7). (The figure was created with biorender.com.)

Figure 2

Findings in oGVHD: conjunctival hyperaemia and corneal staining (A), conjunctival scarring/fibrosis (B), conjunctival hyperaemia and symblepharon (C), filamentary keratitis (D), sterile corneal ulceration (E) and corneal melting with perforation (F).

Figure 3

The Oxford grading scheme differentiates 5 grades of corneal and conjunctival fluoresceine staining. Image adapted from Bron et al. (90).

Figure 4

The NEI grading for corneal and conjunctival staining of the ocular surface is a standardized grading system that is summed up by the grading of 0 to 3 of each sector. Image adapted from Lemp et al. (91).

Figure 5

Therapeutic interventions in eyes with oGVHD: silicone punctal plug (A), scleral lens (B), amniotic membrane transplantation (C), lamellar keratoplasty with loosening of the sutures (D), transpalpebral osteo-odonto-keratoprosthesis (E).