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.

Augenbeteiligung bei Graft-versus-Host-Erkrankung

“…In schweren Fällen und bei Therapieresistenz mit persistierender inflammatorischer Aktivität oder akuter Exazerbation der okulären GVHD sind häufig auch Beginn oder Umstellung der Therapie mit krankheitsmodifizierenden Medikamenten (Disease Modifying Anti-Rheumatic Drugs; DMARDs) in enger Zusammenarbeit mit den behandelnden Kolleg*innen der Hämatoonkologie notwendig [1]. Kurzfristig muss häufig mit oralen Kortikosteroiden (initial 1 mg/kg Körpergewicht) behandelt werden, die dann schrittweise unter engmaschiger Kontrolle reduziert werden.…”

“…Kurzfristig muss häufig mit oralen Kortikosteroiden (initial 1 mg/kg Körpergewicht) behandelt werden, die dann schrittweise unter engmaschiger Kontrolle reduziert werden. Häufig werden steroidsparend auch Calcineurin-Inhibitoren (Ciclosporin A) oder Methotrexat eingesetzt [1]. Auch mTOR-Inhibitoren (Sirolimus) oder Proteosomen-Inhibitoren (Bortezomib), JAK-1/2-Inhibitoren (Ruxolitinib) oder ROCK-2-Inhibitoren (Belumosudil) können in therapierefraktären Fällen zum Einsatz kommen.…”

“…In severe cases and in treatment resistance with persistent inflammatory activity or acute exacerbation of ocular GVHD, initiation or conversion of treatment with disease-modifying anti-rheumatic drugs (DMARDs) in close collaboration with treating colleagues in hematology-oncology is often necessary [1]. In the short term, it is often necessary to treat patients with oral corticosteroids (initially 1 mg/kg body weight); these are then gradually reduced under close monitoring.…”

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DefinitionDie Graft-versus-Host-Erkrankung (Graft-versus-Host Disease, GVHD; "Spender-gegen-Empfänger-Reaktion") ist eine Multisystemerkrankung, die nach allogener hämatopoetischer Zelltrans-plantation (HCT) auftreten kann undneben nahezu allen anderen Organsystemenauch die Augen und deren Adnexe betreffen kann. Die GVHD ist durch eine immunologische Reaktion vor allem von Spenderlymphozyten gegen Gewebe des Empfängers bedingt [1]. Sie führt zu einer Gewebeschädigung mit teilweise irreversibler Fibrose, zu Immundefizienz und Immundysregulation [2].

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Graft-versus-host disease (GVHD) is a multisystem disease that can occur after allogeneic hematopoietic cell transplantation (HCT) andin addition to every other organ systemcan also af-fect the eyes and their adnexa. GVHD is caused by an immunological reaction primarily of donor lymphocytes against tissue of the recipient [1]. It leads to tissue damage with sometimes irreversible fibrosis, immunodeficiency, and immune dysregulation [2].

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