Diagnosis and staging of ophthalmic manifestations of the graft-versus-host reaction after allogeneic hematopoietic stem cell transplantation

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Graft-versus-host reaction is a common complication of allogeneic hematopoietic stem cell transplantation. This condition develops in approximately 40–70% of patients. Its most common clinical manifestations include xerotic keratoconjunctivitis and cicatricial conjunctivitis. It is important to correctly diagnose and classify the ocular condition after surgery. Ocular graft-versus-host reaction can present as either classic acute or chronic form, acute form with late onset or with overlap syndrome. It may lead to severe ocular surface disease, which can significantly decrease the quality of life and restrict daily activities of patients. It is thus important to monitor the ocular condition closely since with early diagnosis of the condition and timely treatment start, risks of irreversible damage could be diminished. This article is dedicated to modern criteria of diagnosis and staging of ocular graft-versus-host reaction.

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About the authors

Natal’ya V. Chistyakova

R.M. Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Academician; I.P. Pavlov First St. Petersburg State Medical University

Author for correspondence.
Email: nchistik@mail.ru


Russian Federation, 6–8, L’va Tolstogo str., Saint Petersburg, 197022; Saint Petersburg


  1. Gratwohl A, Pasquini MC, Aljurf M, et al. One million haemopoietic stem-cell transplants: a retrospective observational study. The Lancet Haematol. 2015;2(3): e91–e100. doi: 10.1016/s2352-3026(15)00028-9
  2. Ogawa Y, Kim SK, Dana R, et al. International chronic ocular graft-vs-host-disease (GVHD) Consensus Group: Proposed Diagnostic Criteria for Chronic GVHD (Part I). Sci Rep. 2013;3(1):3419–3424. doi: 10.1038/srep03419
  3. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. The Lancet. 2009;373(9674):1550–1561. doi: 10.1016/s0140-6736(09)60237-3
  4. TASS [Internet]. Available from: https://tass.ru/obschestvo/6609236 (In Russ.)
  5. FORBES [Internet]. Available from: https://www.forbes.ru/obshchestvo/425733-zachem-rossii-centralnyy-registr-donorov-kostnogo-mozga
  6. Passweg JR, Baldomero H, Chabannon C, et al. The EBMT activity survey on hematopoietic-cell transplantation and cellular therapy 2018: CAR-T’s come into focus. European Society for Blood and Marrow Transplantation (EBMT) Bone Marrow Transplant. 2020;55(8):1604–1613. doi: 10.1038/s41409-020-0826-4
  7. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biol Blood Marrow Transplant. 2015;21(3):389–401. doi: 10.1016/j.bbmt.2014.12.035
  8. Schoemans HM, Lee SJ, Ferrara JL, et al. EBMT-NIH-CIBMTR Task Force position statement on standardized terminology and guidance for graft-versus-host disease assessment. Bone Marrow Transplant. 2018;53(11):1401–1415. doi: 10.1038/s41409-018-0204-7
  9. Mirza N, Zierhut M, Korn A, et al. Graft versus self against T-cell autoantigens is a mechanism of graft-host interaction. Proceedings of the National Academy of Sciences of the United States of America. 2016;113(48):13827–13832. doi: 10.1073/pnas.1609118113
  10. Baird K, Parletic SZ. Chronic graft versus host disease. Curr Opin Hematol. 2006;13(6):426–435. doi: 10.1097/01.moh.0000245689.47333.ff
  11. Tabbara K, Al-Ghamdi A, Al-Mohareb F, et al. Ocular findings following allogenic hematopoietic stem cell transplantation (HSCT). Ophthalmology. 2009;116(9):1624–1629. doi: 10.1016/j.ophtha.2009.04.054
  12. Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol. 1991;28:250–259.
  13. Flowers ME, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011;117(11):3214–3219. doi: 10.1182/blood-2010-08-302109
  14. Clift RA, Buckner CD, Appelbaum FR, et al. Long-term follow up of a randomized trial of two irradiation regimens for patients receiving allogeneic marrow transplants during first remission of acute myeloid leukemia. Blood. 1998;92(4):1455–1456. doi: 10.1182/blood.v92.4.1455.spll2_1455_1456
  15. Ferrara JLM, Reddy P. Pathophysiology of graft-versus-host disease. Semin hematol. 2006;43(1):3–10. doi: 10.1053/j.seminhematol.2005.09.001
  16. Shikari H, Antin JH, Dana R. Ocular graft-versus-host disease: a review. Survey of Ophthalmology. 2013;58(3):233–251. doi: 10.1016/j.survophthal.2012.08.004
  17. Uchino M, Ogawa Y, Kawai M, et al. Ocular complications in a child with acute graft-versus-host disease following cord blood stem cell transplantation: therapeutic challenges. Acta Ophthalmologica Scandinavica. 2006;84(4):545–548. doi: 10.1111/j.1600-0420.2006.00658.x
  18. Jacobs R, Tran U, Chen H, et al. Prevalence and risk factors associated with development of ocular GVHD defined by NIH consensus criteria. Bone Marrow Transplantation. 2012;47(11):1470–1473. doi: 10.1038/bmt.2012.56
  19. Jabs DA, Wingard J, Green WR, et al. The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease. Archives of Ophthalmology. 1989;107(9):1343–1348. doi: 10.1001/archopht.1989.01070020413046
  20. Jack M, Jack G, Sale GE, et al. Ocular manifestations of graft-v-host disease. Arch Ophthalmol. 1983;101(7):1080–1084. doi: 10.1001/archopht.1983.01040020082014
  21. Na KS, Yoo YS, Mok JW, et al. Incidence and risk factors for ocular GVHD after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplantation. 2015;50(11):1459–1464. doi: 10.1038/bmt.2015.187
  22. Qiu Y, Hong J, Peng R. Manifestation of Clinical Categories of Ocular Graft-versus-Host Disease. Journal of Ophthalmology. 2018;2018:6430953. doi: 10.1155/2018/6430953
  23. Lew J, Smith JA. Mucosal graft-vs-host disease. Oral Diseases. 2007;13(6):519–529. doi: 10.1111/j.1601-0825.2007.01412.x
  24. Quellmann S, Schwarzer G, Hübel K, et al. Corticosteroids in the prevention of graft-vs-host disease after allogeneic myeloablative stem cell transplantation: a systematic review and meta-analysis. Leukemia. 2008;22(9):1801–1803. doi: 10.1038/leu.2008.105
  25. Lin XH, Cavanagh HD. Ocular manifestations of graft-versus-host disease: 10 years’ experience. Clin Ophthalmol. 2015;9: 1209–1213. doi: 10.2147/opth.s84704
  26. Munir AZ, Aylward J. A review of ocular graft-versus-host disease. Optometry and Vision Science. 2017;94(5):545–555. doi: 10.1097/opx.0000000000001071
  27. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinic trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–956. doi: 10.1016/j.bbmt.2005.09.004
  28. Shulman HM, Kleiner D, Lee SJ, et al. Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinic trials in chronic graft-versus-host disease: II. Pathology Working Group report. Biol Blood Marrow Transplant. 2006;12(1):31–47. doi: 10.1016/j.bbmt.2005.10.023
  29. Couriel D, Caldera H, Champlin R, Komanduri K. Acute graft-versus-host disease: pathophysiology, clinical manifestations and management. Cancer. 2004;101(9):1936–1946. doi: 10.1002/cncr.20613
  30. Lee SJ, Klein JP, Barrett AJ, et al. Severity of chronic graft-versus-host disease: Association with treatment-related mortality and relapse. Blood. 2002;100(2):406–414. doi: 10.1182/blood.v100.2.406
  31. Ogawa Y, Kuwana M, Yamazaki K, et al. Periductal area as the primary site for T-cell activation in lacrimal gland chronic graft-versus-host disease. Invest Ophthalmol Vis Sci. 2003;44(5):1888–1896. doi: 10.1167/iovs.02–0699
  32. Ogawa Y, Yamazaki K, Kuwana M, et al. A significant role of stromal fibroblasts in rapidly progressive dry eye in patients with chronic GVHD. Invest Ophthalmol Vis Sci. 2001;42:111–119.
  33. Khanal S, Tomlinson A. Tear physiology in dry eye associated with chronic GVHD. Bone Marrow Trans. 2012;47(1):115–119. doi: 10.1038/bmt.2011.36
  34. Ban Y, Ogawa Y, Goto E, et al. Tear function and lipid layer alterations in dry eye patients with chronic graft-vs-host disease. Eye. 2009;23(1):202–208. doi: 10.1038/eye.2008.340
  35. Riley PA. Free radicals in biology: oxidative stress and the effects of ionizing radiation. Int J Radiat Biol. 1994;65(1):27–33. doi: 10.1080/09553009414550041
  36. Berchicci L, Iuliano L, Miserocchi E, et al. Tear osmolarity in ocular graft-versus-host disease. Cornea. 2014;33(12):1252–1256. doi: 10.1097/ico.0000000000000283
  37. Ogawa Y, Okamoto S, Wakui M, et al. Dry eye after hematopoietic stem cell transplantation. Br J Ophthalmol. 1999;83(10):1125–1130. doi: 10.1136/bjo.83.10.1125
  38. Westekemper H, Scholz SL, Thomasen H, et al. Ocular graft versus host disease: corneal complications. Der Ophthalmologe. 2017;114(8):697–702. doi: 10.1007/s00347-017-0488-9
  39. Adrean SD, Puklin JE. Perforated corneal ulcer with subsequent endophthalmitis in a patient with graft-versus-host disease. Cornea. 2007;26(1):107–108. doi: 10.1097/01.ico.0000240101.66652.36
  40. Mohammadpour M. Progressive corneal vascularization caused by graft-versus-host disease. Cornea. 2007;26(2):225–226. doi: 10.1097/01.ico.0000243956.22275.8c
  41. Yeh P, Hou Y, Lin WC, et al. Recurrent corneal perforation and acute calcareous corneal degeneration in chronic graft-versus-host disease. J Formos Med Assoc. 2006;105(4):334–339. doi: 10.1016/s0929-6646(09)60125-x
  42. Nassar A, Tabbara K, Aljurf M. Ocular manifestations of graft-versus-host disease. Saudi J Ophthalmol. 2013;27(3):215–222. doi: 10.1016/j.sjopt.2013.06.007
  43. Sun YC, Chai X, Inamoto Y, et al. Impact of chronic ocular graft-versus-host disease on quality of life. Biol Blood Marrow Transplantat. 2015;21(9):1687–1691. doi: 10.1016/j.bbmt.2015.05.020
  44. Saboo US, Amparo F, Abud TB, et al. Vision-related quality of life in patients with ocular graft-versus-host disease. Ophthalmology. 2015;122(8):1669–1674. doi: 10.1016/j.ophtha.2015.04.011
  45. Tatematsu Y, Ogawa Y, Abe T, et al. Grading criteria for chronic ocular graft-versus-host disease: comparing the NIH eye score, Japanese dry eye score, and DEWS2007 score. Sci Rep. 2014;22(4):6680. doi: 10.1038/srep06680
  46. Balaram M, Dana MR. Phacoemulsification in patients after allogeneic bone marrow transplantation. Ophthalmology. 2001;108(9):1682–1687. doi: 10.1016/s0161-6420(01)00675-3
  47. Auw-Haedrich C, Potsch C, Böhringer D, et al. Histological and immunohistochemical characterization of conjunctival graft vs host disease following haematopoietic stem cell transplantation. Graefe’s Arch Clin Exp Ophthalmol. 2007;245(7):1001–1007. doi: 10.1007/s00417-006-0448-6
  48. Moiseev IS, Dotsenko AA, Smirnova AG, et al. Long-term goals in the treatment of chronic graft-versus-host disease after matched allogeneic hematopoietic stem cell transplantation. Cellular Therapy and Transplantation. 2020;9(4):29–36. doi: 10.18620/ctt-1866-8836-2020-9-4-29-36
  49. 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. Bone Marrow Transplant. 2019;54(5):662–673. doi: 10.1038/s41409-018-0340-0

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Copyright (c) 2021 Chistyakova N.V.

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