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Posterior segment complications and the risk factors after allogeneic hematopoietic stem cell transplantation

Abstract

Purpose

To study the posterior segment complications (PSC) and the risk factors in patients after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

This cross-sectional, case-control study enroled 143 patients who received allogeneic HSCT. Comprehensive ocular examinations were performed to evaluate PSC and ocular Graft-versus-Host Disease (oGVHD). PSC was diagnosed based on the characteristic fundus findings and auxiliary examinations. Visual-evoked potential was examined in patients with unexplained visual loss and suspected visual pathway pathology (VPP). Ocular surface disease index, corneal fluorescein staining, conjunctival injection and Schirmer’s test were scored to diagnose oGVHD.

Results

PSC was detected in 36 (25.2%) patients, while 107 (74.8%) patients were not. Among them, 102 (71.3%) patients were diagnosed with oGVHD. The most common PSC included cytomegalovirus retinitis (13/143, 9.1%) and VPP (7/143, 4.9%). Central nervous system relapse of leukaemia was detected in four out of seven cases of VPP. Patients with PSC had worse visual acuity, lower prevalence and milder severity of oGVHD, and more donors from unrelated and human leucocyte antigen (HLA)-mismatch (all P < 0.05). PSC was associated with transplant from unrelated (OR = 6.494, 95% CI: 1.635–25.794, P = 0.008) and HLA-mismatched (OR = 7.193, 95% CI: 2.829–18.291, P < 0.001) donor but not with the occurrence of systemic GVHD or oGVHD.

Conclusions

PSC in post-HSCT patients was more common than previously noted, deserving the concern of ophthalmologists, especially in patients with unrelated or HLA-mismatched donors.

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Data availability

Data are available upon reasonable request from the authors.

References

  1. Copelan EA, Chojecki A, Lazarus HM, Avalos BR. Allogeneic hematopoietic cell transplantation; the current renaissance. Blood Rev. 2019;34:34–44.

    Article  CAS  PubMed  Google Scholar 

  2. Giannaccare G, Pellegrini M, Bernabei F, Scorcia V, Campos E. Ocular surface system alterations in ocular graft-versus-host disease: all the pieces of the complex puzzle. Graefes Arch Clin Exp Ophthalmol. 2019;257:1341–51.

    Article  PubMed  Google Scholar 

  3. Chung H, Kim KH, Kim JG, Lee SY, Yoon YH. Retinal complications in patients with solid organ or bone marrow transplantations. Transplantation. 2007;83:694–9.

    Article  PubMed  Google Scholar 

  4. Yoo YS, Na KS, Shin JA, Park YH, Lee JW. Posterior eye segment complications related to allogeneic hematopoietic stem cell transplantation. Retina. 2017;37:135–43.

    Article  CAS  PubMed  Google Scholar 

  5. Coskuncan NM, Jabs DA, Dunn JP, Haller JA, Green WR, Vogelsang GB, et al. The eye in bone marrow transplantation. VI. Retinal complications. Arch Ophthalmol. 1994;112:372–9.

    Article  CAS  PubMed  Google Scholar 

  6. Suh DW, Ruttum MS, Stuckenschneider BJ, Mieler WF, Kivlin JD. Ocular findings after bone marrow transplantation in a pediatric population. Ophthalmology. 1999;106:1564–70.

    Article  CAS  PubMed  Google Scholar 

  7. Moon SJ, Mieler WF. Retinal complications of bone marrow and solid organ transplantation. Curr Opin Ophthalmol. 2003;14:433–42.

    Article  PubMed  Google Scholar 

  8. Tabbara KF, Al-Ghamdi A, Al-Mohareb F, Ayas M, Chaudhri N, Al-Sharif F, et al. Ocular findings after allogeneic hematopoietic stem cell transplantation. Ophthalmology. 2009;116:1624–9.

    Article  PubMed  Google Scholar 

  9. Malerbi FK, Teixeira SH, Hirai LGG, Matsudo NH, Carneiro ABM. Retinal changes in solid organ and bone marrow transplantation patients. Einstein. 2017;15:123–9.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Crippa F, Corey L, Chuang EL, Sale G, Boeckh M. Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation. Clin Infect Dis. 2001;32:214–9.

    Article  CAS  PubMed  Google Scholar 

  11. Hiwarkar P, Gajdosova E, Qasim W, Worth A, Breuer J, Chiesa R, et al. Frequent occurrence of cytomegalovirus retinitis during immune reconstitution warrants regular ophthalmic screening in high-risk pediatric allogeneic hematopoietic stem cell transplant recipients. Clin Infect Dis. 2014;58:1700–6.

    Article  CAS  PubMed  Google Scholar 

  12. Ogawa Y, Okamoto S, Wakui M, Watanabe R, Yamada M, Yoshino M, et al. Dry eye after haematopoietic stem cell transplantation. Br J Ophthalmol. 1999;83:1125–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Atsuta Y, Suzuki R, Yamamoto K, Terakura S, Iida H, Kohno A, et al. Risk and prognostic factors for Japanese patients with chronic graft-versus-host disease after bone marrow transplantation. Bone Marrow Transplant. 2006;37:289–96.

    Article  CAS  PubMed  Google Scholar 

  14. Westeneng AC, Hettinga Y, Lokhorst H, Verdonck L, van Dorp S, Rothova A. Ocular graft-versus-host disease after allogeneic stem cell transplantation. Cornea. 2010;29:758–63.

    Article  PubMed  Google Scholar 

  15. Berchicci L, Rabiolo A, Marchese A, Iuliano L, Gigliotti C, Miserocchi E, et al. Ocular chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in an Italian referral center. Ocul Surf. 2018;16:314–21.

    Article  PubMed  Google Scholar 

  16. Ogawa Y, Kim SK, Dana R, Clayton J, Jain S, Rosenblatt MI, et al. International chronic ocular graft-vs-host-disease (GVHD) Consensus Group: proposed diagnostic criteria for chronic GVHD (Part I). Sci Rep. 2013;3:3419.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Flowers ME, Inamoto Y, Carpenter PA, Lee SJ, Kiem HP, Petersdorf EW, 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;117:3214–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Arnaout K, Patel N, Jain M, El-Amm J, Amro F, Tabbara IA. Complications of allogeneic hematopoietic stem cell transplantation. Cancer Investig. 2014;32:349–62.

    Article  Google Scholar 

  19. Amouzegar A, Dey BR, Spitzer TR. Peripheral blood or bone marrow stem cells? Practical considerations in hematopoietic stem cell transplantation. Transfus Med Rev. 2019;33:43–50.

    Article  PubMed  Google Scholar 

  20. Shinzato A, Tabuchi K, Atsuta Y, Inoue M, Inagaki J, Yabe H, et al. PBSCT is associated with poorer survival and increased chronic GvHD than BMT in Japanese paediatric patients with acute leukaemia and an HLA-matched sibling donor. Pediatr Blood Cancer. 2013;60:1513–9.

    Article  PubMed  Google Scholar 

  21. Stewart BL, Storer B, Storek J, Deeg HJ, Storb R, Hansen JA, et al. Duration of immunosuppressive treatment for chronic graft-versus-host disease. Blood. 2004;104:3501–6.

    Article  CAS  PubMed  Google Scholar 

  22. Larsson K, Lonnqvist B, Ringden O, Hedquist B, Ljungman P. CMV retinitis after allogeneic bone marrow transplantation: a report of five cases. Transpl Infect Dis. 2002;4:75–9.

    Article  PubMed  Google Scholar 

  23. Takenaka K, Gondo H, Tanimoto K, Nagafuji K, Fujisaki T, Mizuno S, et al. Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group. Bone Marrow Transpl. 1997;19:241–8.

    Article  CAS  Google Scholar 

  24. Xhaard A, Robin M, Scieux C, de Latour RP, Deplus S, Mazeron MC, et al. Increased incidence of cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation. Transplantation. 2007;83:80–3.

    Article  PubMed  Google Scholar 

  25. Yan CH, Wang Y, Mo XD, Sun YQ, Wang FR, Fu HX, et al. Incidence, risk factors, and outcomes of cytomegalovirus retinitis after haploidentical hematopoietic stem cell transplantation. Bone Marrow Transpl. 2020;55:1147–60.

    Article  CAS  Google Scholar 

  26. Jeon S, Lee WK, Lee Y, Lee DG, Lee JW. Risk factors for cytomegalovirus retinitis in patients with cytomegalovirus viremia after hematopoietic stem cell transplantation. Ophthalmology. 2012;119:1892–8.

    Article  PubMed  Google Scholar 

  27. Patel SA. Acute myeloid leukemia relapse presenting as complete monocular vision loss due to optic nerve involvement. Case Rep Hematol. 2016;2016:3794284.

    PubMed  PubMed Central  Google Scholar 

  28. Wong BJ, Berry JL. Acute lymphoblastic leukemia relapse presenting as optic nerve infiltration. JAMA Ophthalmol. 2017;135:e164656.

    Article  PubMed  Google Scholar 

  29. Shenoy SB, Karam T, Udupa K, Nayal B. Leukaemic infiltration of the optic nerve head: a rare site of initial relapse. BMJ Case Rep. 2016;2016:bcr2016217239.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Tornquist AL, Andersson T, Winiarski J, Gronlund MA, Fahnehjelm KT. Visual evoked potentials after hematopoietic allogeneic stem cell transplantation in childhood. Clin Neurophysiol Pract. 2017;2:67–71.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Russo A, Tomarchio S, Pero G, Consoli G, Marina R, Rizzari C, et al. Abnormal visual-evoked potentials in leukemic children after cranial radiation. Med Pediatr Oncol. 1985;13:313–7.

    Article  CAS  PubMed  Google Scholar 

  32. Kalinina Ayuso V, Hettinga Y, van der Does P, Boelens JJ, Rothova A, de Boer J. Ocular complications in children within 1 year after hematopoietic stem cell transplantation. JAMA Ophthalmol. 2013;131:470–5.

    Article  PubMed  Google Scholar 

  33. Gupta M, Bansal R, Beke N, Gupta A. Tacrolimus-induced unilateral ischaemic optic neuropathy in a non-transplant patient. BMJ Case Rep. 2012;2012:bcr2012006718.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Lake DB, Poole TR. Tacrolimus. Br J Ophthalmol 2003;87:121–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study is supported by grants from the National Natural Science Foundation of China (82070922, 82101133), and the High-level Hospital Construction Project of Guangdong Province (303020101).

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Contributions

All authors contributed to the study’s conception and design. Boyu Yang, Shaowen Wu, Shanshan Yu, Xiaoling Liang, and Qifa Liu performed the material preparation, data collection and analysis. Boyu Yang, Lingyi Liang and Fen Huang wrote the first draft of the manuscript, and all authors commented on previous versions. All authors read and approved the final manuscript.

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Correspondence to Fen Huang or Lingyi Liang.

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Yang, B., Wu, S., Yu, S. et al. Posterior segment complications and the risk factors after allogeneic hematopoietic stem cell transplantation. Eye 37, 1816–1821 (2023). https://doi.org/10.1038/s41433-022-02250-9

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