Abstract
We studied 172 patients for development of ocular graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT) from 2002 to 2009. Ocular GVHD was diagnosed in 60 patients (38%), with 27 (16%) being diagnosed at days 100 and 33 (23%) beyond day 100 for a 2-year cumulative incidence of 35% (95% confidence interval (CI), 28–43). The positive and negative predictive values of a Schirmer I test score (using ⩽5 mm as a cutoff) in predicting ocular GVHD (day 100) were 41 and 82%, respectively. In patients with ocular GVHD beyond day 100, extraocular manifestations of GVHD preceded the development of ocular GVHD in most patients (27 of 33, 81%). Prior acute skin GVHD (odds ratio 2.57, 95% CI 1.17–5.64, P=0.019) and male recipients of female donors (odds ratio 2.57, 95% CI 1.09–6.06, P=0.03) were independent risk factors for ocular GVHD. We recommend comprehensive ocular evaluation rather than a screening Schirmer's test to establish the diagnosis of ocular GVHD. Early diagnosis and preventive strategies in high-risk populations need to be studied in clinical trials to prevent devastating impact on quality of life in patients with prolonged ocular GVHD.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY et al. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood 2002; 100: 406–414.
Lee SJ, Vogelsang G, Gilman A, Weisdorf DJ, Pavletic S, Antin JH et al. A survey of diagnosis, management, and grading of chronic GVHD. Biol Blood Marrow Transplant 2002; 8: 32–39.
Lee SJ, Vogelsang G, Flowers ME . Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003; 9: 215–233.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11: 945–956.
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.
Kim SK . Update on ocular graft versus host disease. Curr Opin Ophthalmol 2006; 17: 344–348.
Hirst LW, Jabs DA, Tutschka PJ, Green WR, Santos GW . The eye in bone marrow transplantation. I. Clinical study. Arch Ophthalmol 1983; 101: 580–584.
Ogawa Y, Kuwana M . Dry eye as a major complication associated with chronic graft-versus-host disease after hematopoietic stem cell transplantation. Cornea 2003; 22: S19–S27.
Franklin RM, Kenyon KR, Tutschka PJ, Saral R, Green WR, Santos GW . Ocular manifestations of graft-vs-host disease. Ophthalmology 1983; 90: 4–13.
Jabs DA . Ocular complications of bone marrow transplantation. In: Pepose JS, Holland GN, Wilhelmus KR (eds). Ocular Infection and Immunity. Mosby, St Louis, 1996, pp 426–434.
Jabs DA, Hirst LW, Green WR, Tutschka PJ, Santos GW, Beschorner WE . The eye in bone marrow transplantation. II. Histopathology. Arch Ophthalmol 1983; 101: 585–590.
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: 1125–1130.
Pinschmidt NW . Evaluation of the Schirmer tear test. South Med J 1970; 63: 1256.
Nichols KK, Mitchell GL, Zadnik K . The repeatability of clinical measurements of dry eye. Cornea 2004; 23: 272–285.
Jagasia M, Giglia J, Chinratanalab W, Dixon S, Chen H, Frangoul H et al. Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria. Biol Blood Marrow Transplant 2007; 13: 1207–1215.
Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.
Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.
Dietrich-Ntoukas T, Cursiefen C, Westekemper H, Eberwein P, Reinhard T, Bertz H et al. Diagnosis and treatment of ocular chronic graft-versus-host disease: report from the German-Austrian-Swiss consensus conference on clinical practice in chronic GVHD. Cornea 2012; 31: 299–310.
Inamoto Y, Chai X, Kurland BF, Cutler C, Flowers ME, Palmer JM et al. Validation of measurement scales in ocular graft-versus-host disease. Ophthalmology 2011; 119: 487–493.
Kamoi M, Ogawa Y, Uchino M, Tatematsu Y, Mori T, Okamoto S et al. Donor-recipient gender difference affects severity of dry eye after hematopoietic stem cell transplantation. Eye (Lond) 2011; 25: 860–865.
Miklos DB, Kim HT, Miller KH, Guo L, Zorn E, Lee SJ et al. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood 2005; 105: 2973–2978.
Ochs LA, Miller WJ, Filipovich AH, Haake RJ, McGlave PB, Blazar BR et al. Predictive factors for chronic graft-versus-host disease after histocompatible sibling donor bone marrow transplantation. Bone Marrow Transplant 1994; 13: 455–460.
Remberger M, Kumlien G, Aschan J, Barkholt L, Hentschke P, Ljungman P et al. Risk factors for moderate-to-severe chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 674–682.
Kondo M, Kojima S, Horibe K, Kato K, Matsuyama T . Risk factors for chronic graft-versus-host disease after allogeneic stem cell transplantation in children. Bone Marrow Transplant 2001; 27: 727–730.
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: 758–763.
Jack MK, Jack GM, Sale GE, Shulman HM, Sullivan KM . Ocular manifestations of graft-v-host disease. Arch Ophthalmol 1983; 101: 1080–1084.
Lelli Jr GJ, Musch DC, Gupta A, Farjo QA, Nairus TM, Mian SI . Ophthalmic cyclosporine use in ocular GVHD. Cornea 2006; 25: 635–638.
Sabti S, Halter JP, Braun Frankl BC, Goldblum D . Punctal occlusion is safe and efficient for the treatment of keratoconjunctivitis sicca in patients with ocular GvHD. Bone Marrow Transplant 2012; 47: 981–984.
Murube J . Surgical treatment of dry eye. Orbit 2003; 22: 203–232.
Geerling G, Tost FH . Surgical occlusion of the lacrimal drainage system. Dev Ophthalmol 2008; 41: 213–229.
Takahide K, Parker PM, Wu M, Hwang WY, Carpenter PA, Moravec C et al. Use of fluid-ventilated, gas-permeable scleral lens for management of severe keratoconjunctivitis sicca secondary to chronic graft-versus-host disease. Biol Blood Marrow Transplant 2007; 13: 1016–1021.
Robinson MR, Lee SS, Rubin BI, Wayne AS, Pavletic SZ, Bishop MR et al. Topical corticosteroid therapy for cicatricial conjunctivitis associated with chronic graft-versus-host disease. Bone Marrow Transplant 2004; 33: 1031–1035.
Wang Y, Ogawa Y, Dogru M, Kawai M, Tatematsu Y, Uchino M et al. Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease. Bone Marrow Transplant 2008; 41: 293–302.
Acknowledgements
Author contributions: RJ, BNS and MJ designed the study, coordinated data analyses and wrote the manuscript. UT did ocular evaluation and contributed to the manuscript. HC did statistical analyses. CC, CL and LAV provided care to patients in long-term transplant clinic. AK, BGE, JPG and SGG contributed to the manuscript.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
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 Transplant 47, 1470–1473 (2012). https://doi.org/10.1038/bmt.2012.56
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2012.56
Keywords
This article is cited by
-
Long-term clinical outcomes and predictive factors in patients with chronic ocular graft-versus-host disease
Scientific Reports (2022)
-
Ocular graft-versus-host disease and dry eye disease after paediatric haematopoietic stem cell transplantation - incidence and risk factors
Bone Marrow Transplantation (2022)
-
Ocular Graft Versus Host Disease: Just a Severe Form of Dry Eye or Something More?
Current Ophthalmology Reports (2022)
-
Chronic ocular graft-versus-host disease after allogeneic haematopoietic stem cell transplantation in Denmark – factors associated with risks and rates in adults according to conditioning regimen
Bone Marrow Transplantation (2021)
-
Ocular surface indicators and biomarkers in chronic ocular graft-versus-host disease: a prospective cohort study
Bone Marrow Transplantation (2021)