Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ont.
Department of Family and Community Medicine, University of Toronto, Toronto, Ont.
Can J Ophthalmol. 2018 Aug;53(4):314-323. doi: 10.1016/j.jcjo.2017.10.040. Epub 2018 Jan 20.
The objective of this study was to evaluate systemic immunosuppression regimens used for patients undergoing ocular surface stem cell transplantation, including their benefits and adverse effects in the adjunctive management of limbal stem cell deficiency (LSCD). A systematic literature review was conducted using the MEDLINE and EMBASE databases (1980-2015). Data were collected on surgical intervention(s), type of immunosuppressive agent(s), duration of immunosuppression, percentage with stable ocular surface at last follow-up, mean follow-up time, and demographics. Data were also collected on adverse ocular and systemic outcomes. Sixteen reports met the inclusion criteria. There were no randomized controlled studies. Three studies were noncomparative prospective case series, whereas the majority were retrospective case series. Bilateral severe LSCD was the most common disease (50%), and keratolimbal allograft was the most common intervention (80%). Immunosuppressive regimens showed a progression from early studies using oral cyclosporine to later studies using combinations of mycophenolate mofetil and tacrolimus. Most studies included a course of high-dose systemic corticosteroids. For patients adherent to long-term systemic immunosuppression, stable ocular surface rates of 70%-80% at last follow-up were reported. Adverse effects included hypertension, diabetes mellitus, and biochemical abnormalities managed with pharmacotherapy or discontinuation of offending agents. There were no cases of mortality related to immunosuppression. However, the current literature does not elucidate which immunosuppressive regimen is most efficacious for different categories of LSCD or graft types. Evidence-based guidelines for systemic immunosuppression in limbal allograft therapy would benefit from randomized controlled and/or additional prospective studies. Long-term immunosuppression would benefit from close collaboration between ophthalmologists and transplant specialists to individualize treatments.
本研究旨在评估接受眼表干细胞移植的患者所使用的全身性免疫抑制方案，包括其在辅助治疗角膜缘干细胞缺乏症（LSCD）中的获益和不良反应。采用 MEDLINE 和 EMBASE 数据库（1980-2015 年）进行系统文献回顾。收集关于手术干预、免疫抑制剂类型、免疫抑制持续时间、末次随访时眼表稳定的百分比、平均随访时间和人口统计学数据。还收集了眼部和全身不良反应的数据。符合纳入标准的有 16 项研究。没有随机对照研究。有 3 项研究为非对照前瞻性病例系列研究，而多数为回顾性病例系列研究。双侧严重 LSCD 是最常见的疾病（50%），角膜缘同种异体移植是最常见的干预措施（80%）。免疫抑制方案显示出从早期使用口服环孢素到后期使用吗替麦考酚酯和他克莫司联合治疗的进展。大多数研究都包括一个疗程的高剂量全身皮质类固醇。对于长期坚持全身免疫抑制的患者，末次随访时眼表稳定率为 70%-80%。不良反应包括高血压、糖尿病和生化异常，通过药物治疗或停用致病药物来管理。没有因免疫抑制而导致的死亡病例。然而，目前的文献并不能阐明哪种免疫抑制方案对不同类型的 LSCD 或移植物类型最有效。在角膜缘同种异体移植治疗中，有必要制定基于循证的全身性免疫抑制指南，开展随机对照和/或前瞻性研究。长期免疫抑制需要眼科医生和移植专家密切合作，以实现个体化治疗。
