Ocular Involvement in Graft-versus-Host Disease

Abstract

In ocular graft-versus-host disease (GVHD), an inflammatory reaction occurs at the ocular surface after transplantation of allogeneic hematopoietic stem cells. Self-reactive T cells of the donor are particularly responsible for this. This can lead to a pronounced wetting disorder of the ocular surface, conjunctival hyperemia, and corneal ulceration up to perforation. The ocular GVHD is associated with a high degree of suffering, such as pain, photophobia, and reduction in visual acuity. This review provides an overview of typical ophthalmological findings, topical and systemic therapeutic approaches, and concomitant measures (e.g., scleral lenses, punctum plugs) and the appropriate management of complications.

Key words

graft-versus-host disease (GVHD) - allogeneic hematopoietic cell transplantation (HCT) - diagnosis - classification - therapy

Publikationsverlauf

Eingereicht: 06. November 2023

Angenommen: 21. November 2023

Artikel online veröffentlicht:
23. Januar 2024

• References/Literatur

• 1 Tappeiner C, Heiligenhaus A, Halter JP. et al. Challenges and concepts in the diagnosis and management of ocular graft-versus-host disease. Front Med (Lausanne) 2023; 10: 1133381 DOI: 10.3389/fmed.2023.1133381.
• 2 Wolff D, Radojcic V, Lafyatis R. et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report. Transplant Cell Ther 2021; 27: 817-835 DOI: 10.1016/j.jtct.2021.06.001.
• 3 Wolff D, Bertz H, Greinix H. et al. The treatment of chronic graft-versus-host disease: consensus recommendations of experts from Germany, Austria, and Switzerland. Dtsch Arztebl Int 2011; 108: 732-740 DOI: 10.3238/arztebl.2011.0732.
• 4 Shikari H, Amparo F, Saboo U. et al. Onset of ocular graft-versus-host disease symptoms after allogeneic hematopoietic stem cell transplantation. Cornea 2015; 34: 243-247 DOI: 10.1097/ICO.0000000000000340.
• 5 Filipovich AH, Weisdorf D, Pavletic S. 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 DOI: 10.1016/j.bbmt.2005.09.004.
• 6 Saboo US, Amparo F, Abud TB. et al. Vision-Related Quality of Life in Patients with Ocular Graft-versus-Host Disease. Ophthalmology 2015; 122: 1669-1674 DOI: 10.1016/j.ophtha.2015.04.011.
• 7 Sun YC, Chai X, Inamoto Y. et al. Impact of Ocular Chronic Graft-versus-Host Disease on Quality of Life. Biol Blood Marrow Transplant 2015; 21: 1687-1691 DOI: 10.1016/j.bbmt.2015.05.020.
• 8 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 (7 Suppl.): S19-S27 DOI: 10.1097/00003226-200310001-00004.
• 9 Ogawa Y, Okamoto S, Wakui M. et al. Dry eye after haematopoietic stem cell transplantation. Br J Ophthalmol 1999; 83: 1125-1130 DOI: 10.1136/bjo.83.10.1125.
• 10 Perez VL, Mousa HM, Soifer M. et al. Meibomian Gland Dysfunction: A Route of Ocular Graft-Versus-Host Disease Progression That Drives a Vicious Cycle of Ocular Surface Inflammatory Damage. Am J Ophthalmol 2022; 247: 42-60 DOI: 10.1016/j.ajo.2022.09.009.
• 11 Tung CI. Graft versus host disease: what should the oculoplastic surgeon know. Curr Opin Ophthalmol 2017; 28: 499-504 DOI: 10.1097/ICU.0000000000000400.
• 12 Saito T, Shinagawa K, Takenaka K. et al. Ocular manifestation of acute graft-versus-host disease after allogeneic peripheral blood stem cell transplantation. Int J Hematol 2002; 75: 332-334 DOI: 10.1007/BF02982052.
• 13 Trindade M, Rodrigues M, Pozzebon ME. et al. A plethora of ocular surface manifestations in a multidisciplinary ocular graft-versus-host disease unit. Sci Rep 2022; 12: 15926 DOI: 10.1038/s41598-022-19990-z.
• 14 Fahnehjelm KT, Törnquist AL, Winiarski J. Dry-eye syndrome after allogeneic stem-cell transplantation in children. Acta Ophthalmol 2008; 86: 253-258 DOI: 10.1111/j.1600-0420.2007.01120.x.
• 15 Pellegrini M, Bernabei F, Barbato F. et al. Incidence, Risk Factors and Complications of Ocular Graft-Versus-Host Disease Following Hematopoietic Stem Cell Transplantation. Am J Ophthalmol 2021; 227: 25-34 DOI: 10.1016/j.ajo.2021.02.022.
• 16 Xu Y, Wang YM, Sun ZT. et al. Corneal perforation associated with ocular graft-versus-host disease. Front Oncol 2022; 12: 962250 DOI: 10.3389/fonc.2022.962250.
• 17 Yoo YS, Na KS, Shin JA. et al. Posterior eye segment complications related to allogeneic hematopoietic stem cell transplantation. Retina 2017; 37: 135-143 DOI: 10.1097/IAE.0000000000001122.
• 18 Mirza N, Zierhut M, Korn A. et al. Graft versus self (GvS) against T-cell autoantigens is a mechanism of graft-host interaction. Proc Natl Acad Sci U S A 2016; 113: 13827-13832 DOI: 10.1073/pnas.1609118113.
• 19 Blecha C, Angstwurm K, Wolff D. et al. Retinal Involvement in a Patient with Cerebral Manifestation of Chronic Graft-Versus-Host-Disease. Oncol Res Treat 2015; 38: 532-534 DOI: 10.1159/000439490.
• 20 Inamoto Y, Petriček I, Burns L. et al. Non-Graft-versus-Host Disease Ocular Complications after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2019; 25: e145-e154 DOI: 10.1016/j.bbmt.2018.11.033.
• 21 Dietrich-Ntoukas T, Cursiefen C, Westekemper 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 DOI: 10.1097/ICO.0b013e318226bf97.
• 22 Blecha C, Wolff D, Holler B. et al. Verification of the new grading scale for ocular chronic graft-versus-host disease developed by the German-Austrian-Swiss consensus conference on chronic GVHD. Ann Hematol 2016; 95: 493-499 DOI: 10.1007/s00277-015-2575-9.
• 23 Ogawa Y, Dana R, Kim S. et al. Multicenter prospective validation study for international chronic ocular graft-versus-host disease consensus diagnostic criteria. Ocul Surf 2022; 26: 200-208 DOI: 10.1016/j.jtos.2022.09.002.
• 24 Nair S, Vanathi M, Mukhija R. et al. Update on ocular graft-versus-host disease. Indian J Ophthalmol 2021; 69: 1038-1050 DOI: 10.4103/ijo.IJO_2016_20.
• 25 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: 3419 DOI: 10.1038/srep03419.
• 26 Rapoport Y, Freeman T, Koyama T. et al. Validation of International Chronic Ocular Graft-Versus-Host Disease (GVHD) Group Diagnostic Criteria as a Chronic Ocular GVHD-Specific Metric. Cornea 2017; 36: 258-263 DOI: 10.1097/ICO.0000000000001109.
• 27 Singh RB, Yuksel E, Sinha S. et al. Prevalence of neurotrophic keratopathy in patients with chronic ocular graft-versus-host disease. Ocul Surf 2022; 26: 13-18 DOI: 10.1016/j.jtos.2022.07.001.
• 28 Alba-Linero C, Rodriguez Calvo de Mora M, Lavado Valenzuela R. et al. Ocular surface characterization after allogeneic stem cell transplantation: A prospective study in a referral center. Indian J Ophthalmol 2020; 68: 1556-1562 DOI: 10.4103/ijo.IJO_1865_19.
• 29 Berchicci L, Iuliano L, Miserocchi E. et al. Tear osmolarity in ocular graft-versus-host disease. Cornea 2014; 33: 1252-1256 DOI: 10.1097/ICO.0000000000000283.
• 30 Robin M, Liang H, Baudouin C. et al. In vivo Meibomian gland imaging techniques: A review of the literature. J Fr Ophtalmol 2020; 43: e123-e131 DOI: 10.1016/j.jfo.2019.11.003.
• 31 Berchicci L, Aragona E, Arrigo A. et al. Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease. J Ophthalmol 2021; 2021: 9958713 DOI: 10.1155/2021/9958713.
• 32 Gerber-Hollbach N, Plattner K, OʼLeary OE. et al. Tear Film Proteomics Reveal Important Differences Between Patients With and Without Ocular GvHD After Allogeneic Hematopoietic Cell Transplantation. Invest Ophthalmol Vis Sci 2018; 59: 3521-3530 DOI: 10.1167/iovs.18-24433.
• 33 Gehlsen U, Stern ME, Franklin J. et al. Desiccating Stress Significantly Increases the Risk for Chronic Ocular Graft-versus-Host-Disease. Transplant Cell Ther 2022; 28: 782.e1-782.e7 DOI: 10.1016/j.jtct.2022.07.027.
• 34 Deutsche Ophthalmologische Gesellschaft (DOG) und Berufsverband der Augenärzte Deutschlands e.V. (BVA). [Ocular Graft-Versus-Host Disease: Guidelines of the German Society of Ophthalmology (DOG) and the German Professional Association of Ophthalmologists (BVA)]. Ophthalmologie 2023; 120 (Suppl. 01) S50-S58 DOI: 10.1007/s00347-022-01781-6.
• 35 Yang J, Zhao W, Liao Y. et al. Ocular surface disease index questionnaire as a sensitive test for primary screening of chronic ocular graft-versus-host disease. Ann Transl Med 2022; 10: 855 DOI: 10.21037/atm-21-6946.
• 36 Dietrich-Ntoukas T, Steven P. [Ocular graft-versus-host disease]. Ophthalmologe 2015; 112: 1027-1038 DOI: 10.1007/s00347-015-0149-9.
• 37 Wang Y, Ogawa Y, Dogru 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 DOI: 10.1038/sj.bmt.1705900.
• 38 Ogawa Y, Okamoto S, Mori T. et al. Autologous serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Bone Marrow Transplant 2003; 31: 579-583 DOI: 10.1038/sj.bmt.1703862.
• 39 Chiang CC, Lin JM, Chen WL. et al. Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Cornea 2007; 26: 861-863 DOI: 10.1097/ICO.0b013e3180645cd7.
• 40 Bae SS, Iovieno A, Yeung SN. Outcomes of scleral lenses for dry eye disease in chronic ocular graft-versus-host disease. Cont Lens Anterior Eye 2023; 46: 101721 DOI: 10.1016/j.clae.2022.101721.
• 41 Magro L, Gauthier J, Richet M. et al. Scleral lenses for severe chronic GvHD-related keratoconjunctivitis sicca: a retrospective study by the SFGM-TC. Bone Marrow Transplant 2017; 52: 878-882 DOI: 10.1038/bmt.2017.9.
• 42 Inamoto Y, Sun YC, Flowers ME. et al. Bandage Soft Contact Lenses for Ocular Graft-versus-Host Disease. Biol Blood Marrow Transplant 2015; 21: 2002-2007 DOI: 10.1016/j.bbmt.2015.07.013.
• 43 Sabti S, Halter JP, Braun Fränkl BC. et al. Punctal occlusion is safe and efficient for the treatment of keratoconjunctivitis sicca in patients with ocular GvHD. Bone Marrow Transplant 2012; 47: 981-984 DOI: 10.1038/bmt.2011.205.
• 44 Yaguchi S, Ogawa Y, Kamoi M. et al. Surgical management of lacrimal punctal cauterization in chronic GVHD-related dry eye with recurrent punctal plug extrusion. Bone Marrow Transplant 2012; 47: 1465-1469 DOI: 10.1038/bmt.2012.50.
• 45 Peris-Martínez C, Menezo JL, Díaz-Llopis M. et al. Multilayer amniotic membrane transplantation in severe ocular graft versus host disease. Eur J Ophthalmol 2001; 11: 183-186 DOI: 10.1177/112067210101100215.
• 46 Yeh PT, Hou YC, Lin WC. et al. Recurrent corneal perforation and acute calcareous corneal degeneration in chronic graft-versus-host disease. J Formos Med Assoc 2006; 105: 334-339 DOI: 10.1016/s0929-6646(09)60125-x.
• 47 Adams GG, Kirkness CM, Lee JP. Botulinum toxin A induced protective ptosis. Eye (Lond) 1987; 1: 603-608 DOI: 10.1038/eye.1987.93.
• 48 Mohammadpour M, Maleki S, Hashemi H. et al. Recurrent Corneal Perforation due to Chronic Graft versus Host Disease; a Clinicopathologic Report. J Ophthalmic Vis Res 2016; 11: 108-111 DOI: 10.4103/2008-322X.180705.
• 49 Zhang CY, Farooq AV, Harocopos GJ. et al. Corneal perforation in ocular graft-versus-host disease. Am J Ophthalmol Case Rep 2021; 24: 101224 DOI: 10.1016/j.ajoc.2021.101224.
• 50 Plattner K, Goldblum D, Halter J. et al. Osteo-Odonto-Keratoprosthesis in Severe Ocular Graft versus Host Disease. Klin Monbl Augenheilkd 2017; 234: 455-456 DOI: 10.1055/s-0042-123148.
• 51 Teär Fahnehjelm K, Törnquist AL, Olsson M. et al. Cataract after allogeneic hematopoietic stem cell transplantation in childhood. Acta Paediatr 2016; 105: 82-89 DOI: 10.1111/apa.13173.
• 52 Gehlsen U, Faust C, Blecha C. et al. Outcomes and complications of cataract surgery in patients with chronic ocular graft-versus-host-disease – a multicenter, retrospective analysis. Graefes Arch Clin Exp Ophthalmol 2022; 260: 2613-2622 DOI: 10.1007/s00417-022-05613-w.
• 53 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: 389-401.e1 DOI: 10.1016/j.bbmt.2014.12.001.