综述
ENGLISH ABSTRACT
眼部移植物抗宿主病的治疗进展
王晶娆
张弘 [综述]
作者及单位信息
·
DOI: 10.3760/cma.j.cn115989-20200904-00627
Current and emerging strategies for ocular chronic graft-versus-host disease
Wang Jingrao
Zhang Hong
Authors Info & Affiliations
Wang Jingrao
Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
Zhang Hong
Department of Ophthalmology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
·
DOI: 10.3760/cma.j.cn115989-20200904-00627
0
0
0
0
0
0
PDF下载
APP内阅读
摘要

眼部移植物抗宿主病(GVHD)是异基因造血干细胞移植(HCT)术后的严重并发症,轻者可以表现为眼部不适,重者可以出现严重的致盲性并发症。目前对于该病的治疗通常是循序渐进的,首先局部应用人工泪液及免疫抑制剂治疗,当症状不能缓解时考虑加用泪点栓塞、自体血清滴眼液及角膜或巩膜接触镜治疗,单用局部治疗对于症状较轻的患者效果往往较好。若患者眼表炎症持续进展,常需加用全身免疫抑制治疗。对于出现严重角膜病变的患者则需要考虑手术治疗,但此时由于眼部GVHD患者眼表炎症的持续存在,预后常常较差。随着对该病发病机制认识的深入,多种新型治疗方法如促泌剂、JAK/SYK抑制剂、曲尼司特、利非格斯、肝素、siRNA治疗及干细胞治疗已投入临床研究及应用,并取得了较好的治疗效果,本文将对眼部GVHD的治疗进展进行综述,以期为临床工作及研究提供参考。

眼部移植物抗宿主病;免疫抑制;细胞治疗;治疗进展
ABSTRACT

Ocular graft-versus-host disease (GVHD) is a serious complication following hematopoietic cell transplantation (HCT). In mild cases, it can manifest as eye discomfort, while in severe cases, patients may suffer from vision loss.Ocular GVHD is often treated in a stepwise fashion, starting with artificial tears and immunosuppressive agents progressing to more aggressive interventions as needed.Topical therapy alone is often sufficient for patients with mild symptoms.If the ocular surface inflammation is still difficult to control, systemic immunosuppressive therapy is required.Patients with severe corneal disease should be considered for surgery, which often has a poor prognosis in the presence of ocular inflammation.With the deepening of the understanding of the pathogenesis of the disease, a variety of new therapies such as rebamipide, diquafosol, JAK/SYK inhibitors, tranilast, lifitegrast, heparin, siRNA therapy and stem cell therapy have been introduced into clinical research and application.This article reviews the current and emerging strategies for ocular GVHD to provide references for clinical practice and research.

Ocular graft-versus-host disease;Immunosuppressive therapy;Cell therapy;Emerging treatment
Zhang Hong, Email: nc.defudabe.umbrhgnohgnahz
引用本文

王晶娆,张弘. 眼部移植物抗宿主病的治疗进展[J]. 中华实验眼科杂志,2023,41(11):1130-1134.

DOI:10.3760/cma.j.cn115989-20200904-00627

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价
异基因造血干细胞移植(hematopoietic cell transplantation,HCT)是治疗多种血液系统疾病的有效手段,2019年中国进行了近万例HCT [ 1 ]。尽管HCT的疗效不断改善,移植物抗宿主病(graft-versus-host disease,GVHD)仍是主要的并发症和患者死亡的主要原因。根据临床特征的不同,GVHD可以分为急性和慢性2种,约12%~17%的急性GVHD患者会出现眼部表现,约60%~90%的慢性GVHD患者会出现眼部受累 [ 2 ]。眼部GVHD主要包括3个重要的病理学过程,即泪腺功能障碍、睑板腺功能障碍及角膜结膜炎症 [ 3 , 4 ]。HCT患者手术前的预处理方案引起广泛组织损伤、供体T细胞活化导致出现"细胞因子风暴"等是眼部急性GVHD的可能原因;眼部慢性GVHD的发病机制较为复杂,固有免疫与适应性免疫协同作用参与了组织炎症的维持及进展,并参与了纤维化的形成 [ 5 , 6 ]
虽然眼部GVHD通常不威胁生命,但会严重影响患者的生活质量,长期泪腺、角膜及睑板腺受累会使患者出现角膜溃疡、穿孔等致盲性并发症,因此及时完善的治疗对于改善患者的预后具有重要的作用。目前对于眼部GVHD的治疗主要依靠局部抗炎及对症治疗、全身免疫抑制治疗及手术治疗。近年来,多种新的治疗药物及方法也处于研究及应用阶段,本文对眼部GVHD的治疗及其进展进行综述。
试读结束,您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
中华医学会血液学分会干细胞应用学组中国异基因造血干细胞移植治疗血液系统疾病专家共识(Ⅲ)——急性移植物抗宿主病(2020年版)[J]中华血液学杂志 202041(7)∶529536. DOI: 10.3760/cma.j.issn.0253-2727.2020.07.001 .
返回引文位置Google Scholar
百度学术
万方数据
Stem Cell Application Group,Chinese Society of Hematology,Chinese Medical Association. Chinese consensus of allogeneic hematopoietic stem cell transplantation for hematological disease (Ⅲ) —acute graft-versus-host disease (2020)[J]Chin J Hematol 202041(7)∶529536. DOI: 10.3760/cma.j.issn.0253-2727.2020.07.001 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[2]
Giannaccare G Pellegrini M Bernabei F et al. Ocular surface system alterations in ocular graft-versus-host disease:all the pieces of the complex puzzle[J]Graefes Arch Clin Exp Ophthalmol 2019257(7)∶13411351. DOI: 10.1007/s00417-019-04301-6 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Inamoto Y Valdés-Sanz N Ogawa Y et al. Ocular graft-versus-host disease after hematopoietic cell transplantation:expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT[J]Bone Marrow Transplant 201954(5)∶662673. DOI: 10.1038/s41409-018-0340-0 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Kate A Singh S Das AV et al. Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease[J]Indian J Ophthalmol 202371(4)∶15381544. DOI: 10.4103/IJO.IJO_2820_22 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Shikari H Antin JH Dana R Ocular graft-versus-host disease:a review[J]Surv Ophthalmol 201358(3)∶233251. DOI: 10.1016/j.survophthal.2012.08.004 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Zeiser R Blazar BR . Pathophysiology of chronic graft-versus-host disease and therapeutic targets[J]N Engl J Med 2017377(26)∶25652579. DOI: 10.1056/NEJMra1703472 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Tong L Lim E Yeo S et al. Conjunctival T cell profile in allogeneic hematopoietic stem cell transplant patients after instilling topical cyclosporine-A 0.1%cationic emulsion[J]Ophthalmol Ther 202312(3)∶15471567. DOI: 10.1007/s40123-023-00686-0 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Lin X Cavanagh HD . Ocular manifestations of graft-versus-host disease:10 years ' experience [J]Clin Ophthalmol 2015912091213. DOI: 10.2147/OPTH.S84704 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Chun YH Beak JU Kim HS et al. Topical cyclosporine pretreatment of ocular surface in allogeneic hematopoietic stem cell transplant recipients[J]J Ocul Pharmacol Ther 201834(9)∶628632. DOI: 10.1089/jop.2018.0006 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Cantú-Rodríguez OG Vázquez-Mellado A González-Treviño JL et al. Cyclosporine A for the prevention of ocular graft versus host disease in allogeneic hematopoietic stem cell transplant recipients is safe and feasible[J]Acta Haematol 2020143(5)∶425431. DOI: 10.1159/000502405 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Gehlsen U Siebelmann S Steven P Tolerance and adherence to cationic 0.1%cyclosporine in ocular graft-versus-host disease[J]Ophthalmic Res 202164(1)∶7784. DOI: 10.1159/000509034 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
陆以腾周旭娇洪佳旭关注0.1% CsA阳离子乳剂在眼表免疫性疾病中的合理选择及应用[J]中华实验眼科杂志 202341(5)∶417420. DOI: 10.3760/cma.j.cn115989-20230331-00115 .
返回引文位置Google Scholar
百度学术
万方数据
Lu YT Zhou XJ Hong JX et al. Focusing on the rational application of 0.1%CsA cationic emulsion in ocular surface inflammatory disorder[J]Chin J Exp Ophthalmol 202341(5)∶417420. DOI: 10.3760/cma.j.cn115989-20230331-00115 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[13]
唐旭园夏建华吴琴. 0.1%他克莫司滴眼液治疗慢性移植物抗宿主病相关干眼症的疗效评价[J]中华眼视光学与视觉科学杂志 202022(3)∶172179. DOI: 10.3760/cma.j.cn115909-20191222-00339 .
返回引文位置Google Scholar
百度学术
万方数据
Tang XY Xia JH Wu Q et al. Evaluation of 0.1% tacrolimus eye drops in the treatment of dry eye patients caused by chronic graft-versus-host disease[J]Chin J Optom Ophthalmol Vis Sci 202022(3)∶172179. DOI: 10.3760/cma.j.cn115909-20191222-00339 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[14]
Abud TB Amparo F Saboo US et al. A clinical trial comparing the safety and efficacy of topical tacrolimus versus methylprednisolone in ocular graft-versus-host disease[J]Ophthalmology 2016123(7)∶14491457. DOI: 10.1016/j.ophtha.2016.02.044 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Munir SZ Aylward J A review of ocular graft-versus-host disease[J]Optom Vis Sci 201794(5)∶545555. DOI: 10.1097/OPX.0000000000001071 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Tung CI . Current approaches to treatment of ocular graft-versus-host disease[J]Int Ophthalmol Clin 201757(2)∶6588. DOI: 10.1097/IIO.0000000000000167 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Inamoto Y Sun YC Flowers ME et al. Bandage soft contact lenses for ocular graft-versus-host disease[J]Biol Blood Marrow Transplant 201521(11)∶20022007. DOI: 10.1016/j.bbmt.2015.07.013 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Magro L Gauthier J Richet M et al. Scleral lenses for severe chronic GvHD-related keratoconjunctivitis sicca:a retrospective study by the SFGM-TC[J]Bone Marrow Transplant 201752(6)∶878882. DOI: 10.1038/bmt.2017.9 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Lee SM Kim YJ Choi SH et al. Long-term effect of corneoscleral contact lenses on refractory ocular surface diseases[J]Cont Lens Anterior Eye 201942(4)∶399405. DOI: 10.1016/j.clae.2018.10.011 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Chhabra S Jerkins JH Conto JE et al. Lifitegrast ophthalmic solution for treatment of ocular chronic graft-versus-host disease[J]Leuk Lymphoma 202061(4)∶869874. DOI: 10.1080/10428194.2019.1695049 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Vegunta S Patel D Shen JF . Combination therapy of intense pulsed light therapy and meibomian gland expression (IPL/MGX) can improve dry eye symptoms and meibomian gland function in patients with refractory dry eye:a retrospective analysis[J]Cornea 201635(3)∶318322. DOI: 10.1097/ICO.0000000000000735 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Azari AA Karadag R Kanavi MR et al. Safety and efficacy of autologous serum eye drop for treatment of dry eyes in graft-versus-host disease[J]Cutan Ocul Toxicol 201736(2)∶152156. DOI: 10.1080/15569527.2016.1209770 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Inamoto Y Martin PJ Chai X et al. Clinical benefit of response in chronic graft-versus-host disease[J]Biol Blood Marrow Transplant 201218(10)∶15171524. DOI: 10.1016/j.bbmt.2012.05.016 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Olivieri J Manfredi L Postacchini L et al. Consensus recommendations for improvement of unmet clinical needs—the example of chr onic graft-versus-host disease:a systematic review and meta-analysis [J/OL]Lancet Haematol 20152(7)∶e297e305[2022-12-26]http://www.ncbi.nlm.nih.gov/pubmed/26688385. DOI: 10.1016/S2352-3026(15)00095-2 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Khoury HJ Langston AA Kota VK et al. Ruxolitinib:a steroid sparing agent in chronic graft-versus-host disease[J]Bone Marrow Transplant 201853(7)∶826831. DOI: 10.1038/s41409-017-0081-5 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Dietrich-Ntoukas T Cursiefen C Westekemper H et al. Diagnosis and treatment of ocular chronic graft-versus-host disease:report from the German-Austri an-Swiss Consensus Conference on Clinical Practice in chronic GVHD [J]Cornea 201231(3)∶299310. DOI: 10.1097/ICO.0b013e318226bf97 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Meller D Fuchsluger T Pauklin M et al. Ocular surface reconstruction in graft-versus-host disease with HLA-identical living-related allogeneic cultivated limbal epithelium after hematopoietic stem cell transplantation from the same donor[J]Cornea 200928(2)∶233236. DOI: 10.1097/ICO.0b013e31818526a6 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Busin M Giannaccare G Sapigni L et al. Conjunctival and limbal transplantation from the same living-related bone marrow donor to patients with severe ocular graft-vs-host disease[J]JAMA Ophthalmol 2017135(10)∶11231125. DOI: 10.1001/jamaophthalmol.2017.3204 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
He J Ogawa Y Mukai S et al. In vivo confocal microscopy evaluation of ocular surface with graft-versus-host disease-related dry eye disease [J/OL]Sci Rep 20177(1)∶10720[2022-12-28]http://www.ncbi.nlm.nih.gov/pubmed/28878217. DOI: 10.1038/s41598-017-10237-w .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Shamloo K Barbarino A Alfuraih S et al. Graft versus host disease-associated dry eye:role of ocular surface mucins and the effect of rebamipide,a mucin secretagogue[J]Invest Ophthalmol Vis Sci 201960(14)∶45114519. DOI: 10.1167/iovs.19-27843 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Yamane M Ogawa Y Fukui M et al. Long-term topical diquafosol tetrasodium treatment of dry eye disease caused by chronic graft-versus-host disease:a retrospective study[J]Eye Contact Lens 201844Suppl 2S215. S220DOI: 10.1097/ICL.0000000000000455 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Kheirkhah A Di Zazzo A Satitpitakul V et al. A pilot randomized trial on safety and efficacy of a novel topical combined inhibitor of janus kinase 1/3 and spleen tyrosine kinase for GVHD-associated ocular surface disease[J]Cornea 201736(7)∶799804. DOI: 10.1097/ICO.0000000000001206 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Ogawa Y Dogru M Uchino M et al. Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD[J]Bone Marrow Transplant 201045(3)∶565569. DOI: 10.1038/bmt.2009.173 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
An S Raju I Surenkhuu B et al. Neutrophil extracellular traps (NETs) contribute to pathological changes of ocular graft-vs.-host disease (oGVHD) dry eye:implications for novel biomarkers and therapeutic strategies[J]Ocul Surf 201917(3)∶589614. DOI: 10.1016/j.jtos.2019.03.010 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Yamane M Ogawa Y Mukai S et al. Functional role of lacrimal gland fibroblasts in a mouse model of chronic graft-versus-host disease[J]Cornea 201837(1)∶102108. DOI: 10.1097/ICO.0000000000001411 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Ohigashi H Hashimoto D Hayase E et al. Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD[J]Blood Adv 20193(7)∶10031010. DOI: 10.1182/bloodadvances.2018028431 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
Al-Jaibaji O Swioklo S Connon CJ . Mesenchymal stromal cells for ocular surface repair[J]Expert Opin Biol Ther 201919(7)∶643653. DOI: 10.1080/14712598.2019.1607836 .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Harrell CR Djonov V Volarevic V Therapeutic potential of mesenchymal stem cells in the treatment of ocular graft-versus-host disease[J/OL]Int J Mol Sci 202223(21)∶13254[2023-10-05]http://www.ncbi.nlm.nih.gov/pubmed/36362040. DOI: 10.3390/ijms232113254 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Martínez-Carrasco R Sánchez-Abarca LI Nieto-Gómez C et al. Subconjunctival injection of mesenchymal stromal cells protects the cornea in an experimental model of GVHD[J]Ocul Surf 201917(2)∶285294. DOI: 10.1016/j.jtos.2019.01.001 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
张弘,Email: nc.defudabe.umbrhgnohgnahz
B
所有作者均声明不存在利益冲突
C
国家自然科学基金项目 (81970776、81671844)
黑龙江省自然科学基金项目 (LH2020H039)
评论 (0条)
注册
登录
时间排序
暂无评论,发表第一条评论抢沙发
MedAI助手(体验版)
文档即答
智问智答
机器翻译
回答内容由人工智能生成,我社无法保证其准确性和完整性,该生成内容不代表我们的态度或观点,仅供参考。
生成快照
文献快照

你好,我可以帮助您更好的了解本文,请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持:

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号