眼移植物抗宿主病临床表现及其治疗的研究进展

刚 陈(中国人民解放军南部战区总医院，中国)
亦笑 雷(中国人民解放军南部战区总医院，中国)
任萍 吴(中国人民解放军南部战区总医院，中国)
秀兰 邹(中国人民解放军南部战区总医院，中国)
翠翠 汤(中国人民解放军南部战区总医院，中国)
亮红 彭(中国人民解放军南部战区总医院，中国)

摘要

移植物抗宿主病是异体造血干细胞移植后常见的并发症，它影响包括眼睛在内的多个器官系统。这种疾病分为两种类型： 急性和慢性移植物抗宿主病。在慢性的移植物抗宿主病中，眼部表现作为一个常见的并发症，可能会涉及角膜、泪腺、结 膜和眼睑等部位，主要症状包括干眼症、结膜炎、角膜炎等病症，极端情况下可导致完全的视力丧失。目前针对移植物抗 宿主病，临床上尚无统一的治疗标准，医生使用人工泪液、糖皮质激素、自体血清滴眼液、局部环孢素、他克莫司、治疗 性镜片和手术等方式来进行治疗。论文旨在讨论移植物抗宿主病的最新进展，回顾和总结其的病理生理、临床表现和目前 的治疗方法。

关键词

眼移植物抗宿主病；临床表现；治疗

参考

Zhang, X.H., et al., The consensus from The Chinese Society of

Hematology on indications, conditioning regimens and donor

selection for allogeneic hematopoietic stem cell transplantation:

update[J]. Hematol Oncol,2021,14(1):145.

Wang, X., et al., Current status and prospects of hematopoietic stem cell

transplantation in China[J]. Chin Med J (Engl),2022,135(12):1394-1403.

Jagasia, M.H. National Institutes of Health Consensus Development

Project on Criteria for Clinical Trials in Chronic Graft-versusHost Disease: I. The 2014 Diagnosis and Staging Working Group

report[J]. Biol Blood Marrow Transplant,2015,21(3):389-401.

Shulman, H.M. Chronic graft-versus-host syndrome in man. A

long-term clinicopathologic study of 20 Seattle patients[J]. Am J

Med,1980,69(2):204-217.

Espana, E.M., et al., Graft versus host disease: clinical evaluation,

diagnosis and management[J]. Graefes Arch Clin Exp Ophthalm

ol,2013,251(5):1257-1266.

Abud, T.B. A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graftversus-Host Disease[J]. Ophthalmology,2016,123(7):1449-1457.

Azari, A.A. C.J. Rapuano, Autologous serum eye drops

for the treatment of ocular surface disease[J]. Eye Contact

Lens,2015,41(3):133-140.

Carreno-Galeano, J.T. A Review of Ocular Graft-versusHost Disease: Pathophysiology, Clinical Presentation and

Management[J]. Ocul Immunol Inflamm,2021,29(6):1190-1199.

Lee, S.M. Long-term effect of corneoscleral contact lenses

on refractory ocular surface diseases[J]. Cont Lens Anterior

Eye,2019,42(4):399-405.

Trounson, A. C. McDonald. Stem Cell Therapies in Clinical Trials:

Progress and Challenges[J]. Cell Stem Cell,2015,17(1): 11-22.

Ogawa, Y. A significant role of stromal fibroblasts in rapidly

progressive dry eye in patients with chronic GVHD[J]. Invest

Ophthalmol Vis Sci,2001,42(1):11-19.

Mukai, S. Novel Treatment of Chronic Graft-Versus-Host Disease

in Mice Using the ER Stress Reducer 4-Phenylbutyric Acid[J]. Sci

Rep, 2017(7):41939.

Yaguchi, S. Presence and physiologic function of the reninangiotensin system in mouse lacrimal gland[J]. Invest Ophthalmol

Vis Sci,2012,53(9):5416-5425.

Uchino, Y. Oxidative stress induced inflammation initiates functional

decline of tear production[J]. PLoS One, 2012,7(10):e45805.

Ogawa, Y. Dry eye after haematopoietic stem cell transplantation[J].

Br J Ophthalmol, 1999,83(10): 1125-1130.

Ban, Y. Morphologic evaluation of meibomian glands in

chronic graft-versus-host disease using in vivo laser confocal

microscopy[J]. Mol Vis, 2011(17):2533-2543.

Que, L., X. Zhang, M. Li. Single-Center Retrospective Study on

Meibomian Gland Loss in Patients With Ocular Chronic GraftVersus-Host Disease[J]. Eye Contact Lens,2018,44(Sl2):169-75.

Ogawa, Y., et al., International Chronic Ocular Graft-vs-HostDisease (GVHD) Consensus Group: proposed diagnostic criteria

for chronic GVHD (Part I)[J]. Sci Rep,2013(3):3419.

Mohammadpour, M. Progressive corneal vascularization caused by

graft-versus-host disease[J]. Cornea, 2007,26(2):225-226.

Mohammadpour, M., et al., Recurrent Corneal Perforation due to

Chronic Graft versus Host Disease; a Clinicopathologic Report[J].

Ophthalmic Vis Res,2016,11(1):108-111.

Kheirkhah, A., et al., Corneal Epithelial Immune Dendritic

Cell Alterations in Subtypes of Dry Eye Disease: A Pilot In

Vivo Confocal Microscopic Study[J]. Invest Ophthalmol Vis

Sci,2015,56(12):7179-7185.

Kheirkhah, A. In Vivo Confocal Microscopy in Dry Eye Disease

Associated With Chronic Graft-Versus-Host Disease[J]. Invest

Ophthalmol Vis Sci,2016,57(11):4686-4691.

He, J. In Vivo Confocal Microscopy Evaluation of Ocular Surface

with Graft-Versus-Host Disease-Related Dry Eye Disease[J]. Sci

Rep,2017,7(1):10720.

Herretes, S. Recruitment of Donor T Cells to the Eyes During

Ocular GVHD in Recipients of MHC-Matched Allogeneic

Hematopoietic Stem Cell Transplants[J]. Invest Ophthalmol Vis

Sci,2015,56(4):2348-2357.

Kusne, Y. Conjunctival subepithelial fibrosis and meibomian

gland atrophy in ocular graft-versus-host disease[J]. Ocul

Surf,2017,15(4):784-788.

Contreras-Ruiz, L. S. Masli, Immunomodulatory cross-talk

between conjunctival goblet cells and dendritic cells[J]. PLoS

One,2015,10(3):e0120284.

Shamloo, K. Local Renin-Angiotensin System Activation

and Myofibroblast Formation in Graft Versus Host DiseaseAssociated Conjunctival Fibrosis[J]. Invest Ophthalmol Vis

Sci,2021,62(13):10.

Hallberg, D. Conjunctival polyploid cells and donorderived myofibroblasts in ocular GvHD[J]. Bone Marrow

Transplant,2016,51(5):692-697.

Eberwein, P. Conjunctival epithelial cells with donor-derived

genome after human haematopoietic stem-cell transplantation[J].

Transplantation,2009,87(6):915-918.

Pflugfelder, S.C. Antiinflammatory therapy for dry eye[J]. Am

Ophthalmol,2004,137(2):337-342.

Dietrich-Ntoukas, T., et al., Diagnosis and treatment of ocular

chronic graft-versus-host disease: report from the GermanAustrian-Swiss Consensus Conference on Clinical Practice in

chronic GVHD[J]. Cornea, 2012,31(3):299-310.

Robinson, M.R., et al., Topical corticosteroid therapy for cicatricial

conjunctivitis associated with chronic graft-versus-host disease[J].

Bone Marrow Transplant,2004,33(10):1031-1035.

Duncan, N. C. Craddock, Optimizing the use of cyclosporin in

allogeneic stem cell transplantation[J]. Bone Marrow Transplant,

,38(3):169-174.

Wang, Y. Ocular surface and tear functions after topical cyclosporine

treatment in dry eye patients with chronic graft-versus-host disease[J].

Bone Marrow Transplant, 2008,41(3):293-302.

Thomson, A.W., C.A. Bonham, A. Zeevi, Mode of action of

tacrolimus (FK506): molecular and cellular mechanisms[J]. Ther

Drug Monit,1995,17(6):584-591.

Gupta, A. Transforming growth factor beta-1 and beta-2 in human

tear fluid[J]. Curr Eye Res, 1996,15(6):605-614.

Hwang, J. Comparison of clinical efficacies of autologous

serum eye drops in patients with primary and secondary Sjögren syndrome[J]. Cornea, 2014,33(7):663-667.

Kheirkhah, A. 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,2017,36(7):799-804.

Luo, Z.K. Efficacy and Safety of 1% Progesterone Gel to the

Forehead for Ocular Chronic Graft-versus-Host Disease[J].

Transplant Cell Ther, 2021,27(5):433e1-433e8.

Sosne, G., S.P. Dunn, C. Kim, Thymosin β4 significantly

improves signs and symptoms of severe dry eye in a phase 2

randomized trial[J]. Cornea,2015,34(5):491-496.

Inamoto, Y. Bandage Soft Contact Lenses for Ocular Graft-versusHost Disease[J]. Biol Blood Marrow Transplant, 2015,21(11):2002-

Chiu, G.B., C. Theophanous, J.A. Irvine, PROSE Treatment

in Atypical Ocular Graft-Versus-Host Disease[J]. Optom Vis

Sci,2016,93(11):1444-1448.

Shamloo, K. 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,2019,60(14):4511-

Yamane, M., et al., Long-Term Topical Diquafosol Tetrasodium

Treatment of Dry Eye Disease Caused by Chronic GraftVersus-Host Disease: A Retrospective Study[J]. Eye Contact

Lens,2018,44(S2):S215-S220.

Hessen, M. E.K. Akpek, Ocular graft-versus-host disease[J]. Curr

Opin Allergy Clin Immunol, 2012,12(5):540-547.

Carreno-Galeano, J.T. A Review of Ocular Graft-versusHost Disease Pathophysiology, Clinical Presentation and

Management[J]. Ocul Immunol Inflamm,2021(6).

Takano, Y. Dramatic healing of an allergic corneal ulcer

persistent for 6 months by amniotic membrane patching in

a patient with atopic keratoconjunctivitis: a case report[J].

Cornea,2004,23(7):723-725.

Tsubota, K. Surgical reconstruction of the ocular surface in

advanced ocular cicatricial pemphigoid and Stevens-Johnson

syndrome[J]. Am J Ophthalmol, 1996,122(1):38-52.

Ikarashi, H. Two case reports of continued progression of chronic

ocular graft-versus-host disease without concurrent systemic

comorbidities treated by amniotic membrane transplantation[J].

BMC Ophthalmol,2021,21(1):164.

Busin, M. Conjunctival and Limbal Transplantation From the

Same Living-Related Bone Marrow Donor to Patients With

Severe Ocular Graft-vs-Host Disease[J]. JAMA Ophthalm

ol,2017,135(10):1123-1125.

Ogawa, Y. Topical tranilast for treatment of the early stage of

mild dry eye associated with chronic GVHD[J]. Bone Marrow

Transplant,2010,45(3):565-569.

DOI: http://dx.doi.org/10.12345/yzlcyxzz.v7i5.17769