眼部移植物抗宿主病发生在超过一半的慢性移植物抗宿主病患者中,涉及眼表持续的炎症以及纤维化改变,最常见的表现为干燥性角膜结膜炎。严重的眼部移植物抗宿主病不但影响患者的工作和生活质量,同时也增加了其他眼部并发症的风险。慢性眼部移植物抗宿主病的治疗主要包括局部应用人工泪液、血清类制剂、抗炎药物等药物治疗,佩戴隐形眼镜、睑板腺按摩等物理治疗、封闭泪点、重建眼表等手术治疗。随着对眼部移植物抗宿主病发病机制的深入研究,许多新的治疗药物和治疗手段涌现临床。总结目前慢性眼部移植物抗宿主病在药物治疗、物理治疗、手术治疗方面的最新研究进展,将有助于为慢性眼部移植物抗宿主病的治疗带来更多选择和更新的研究思路。
More than half of the patients developed chronic graft-versus-host disease after accepting allogeneic hematopoietic stem cell transplantation suffer from ocular graft-versus-host disease. Ocular graft-versus-host disease involves persistent inflammation and fibrosis of the ocular surface and keratoconjunctivitis sicca is the most common symptom. Severe ocular graft-versus-host disease not only affects patients’ life quality, but also increases the risk of other ocular complications. The treatment of chronic ocular graft-versus-host disease mainly includes drug treatment, such as local application of artificial tears, serum eye drops and anti-inflammatory drugs; physical treatment, such as wearing contact lenses and meibomian gland massage; surgical treatment, such as punctal occlusion and reconstructing ocular surface. With the in-depth study of the pathogenesis of ocular graft-versus-host disease, many new therapeutic drugs and methods have emerged. Summarizing the latest research progress in drug, physical and surgical therapy of chronic ocular graft-versus-host disease will give us insights into treatment options and hot spot of research.
慢性移植物抗宿主病(chronic graft-versus-host disease,cGVHD)是骨髓移植后最具有破坏性并发症之一。移植物抗宿主病(graft-versus-host disease,GVHD)发生在10%~80%的造血干细胞移植(hematopoietic stem cell transplantation)受者中,而眼睛是人身体最脆弱的器官之一,有40%~60%接受HSCT的患者发生眼部GVHD,它主要影响泪腺、睑板腺、角膜和结膜等。cGVHD相关性干眼(dry eye associated with chronic graft-versus-host disease,cGVHD-DE)是眼部GVHD最多见的表现形式。cGVHD-DE的长期治疗因涉及多学科、多重结合治疗,至今仍然具有挑战性,其除了全身免疫抑制和眼部润滑剂外,通常还使用局部类固醇、环孢霉素和他克莫司滴眼液。针对中度和重度cGVHD-DE的治疗干预包括使用自体血清滴眼液和佩戴巩膜镜等,新兴起的治疗方案包括重链透明质酸 (heavy chain-hvaluronan/穿透素(pentraxin 3)结膜下注射、间充质基质细胞静脉注射、抑制纤维化药物等。
Chronic graft-versus-host disease (cGVHD) is one of the most devastating complications following bone marrow transplantation. GVHD develops in 10–80% of patients after hematopoietic stem cell transplantation (HSCT). The eye is one of the most vulnerable organs of the human body. Ocular GVHD occurs in 40–60% of patients with GVHD undergoing HSCT, and it mostly affects the lacrimal glands, meibomian glands, cornea, and conjunctiva. The most common form of ocular GVHD is dry eye disease (DED). The long-term treatment of cGVHD-related dry eye syndrome remains challenging and involves a multidisciplinary approach. Besides systemic immunosuppression and ocular lubricants, topical steroids, topical cyclosporine, and topical tacrolimus are commonly prescribed. Newer therapeutic interventions for moderate and severe cGVHD-related DED include using serum eye drops and scleral contact lenses. Emerging treatment options include subconjunctival injection of heavy chain-hyaluronan (HC-HA)/ pentraxin 3 (PTX3), intravenous injection of mesenchymal stromal cells, antifibrotic drugs, etc. This article reviews the mechanisms, clinical findings, and treatment of cGVHD-related dry eye syndrome.