Our experience of Restasis® use in patients with “dry eye” syndrome occurring against the context of graft versus host reaction after bone marrow allografting

Cover Page


Restasis® is the only ophthalmic medication containing cyclosporine A that is registered in the Russian Federation. According to prescribing information, it is indicated in keratoconjunctivitis sicca with decreased tear secretion. However, there are several similar conditions, in particular ophthalmic forms of graft versus host reaction, in which its use may be appropriate and of high practical interest. We observed 20 patients with ophthalmic forms of graft versus host reaction after bone marrow allografting. All patients were treated by Restasis® b.i.d., there were no side-effects. In one month of treatment tear breakup time test results improved, as well as the corneal epithelium status.

Sergey Yur'yevich Astakhov

Pavlov First State Medical University of Saint Petersburg

Email: astakhov73@mail.ru
MD, PhD, professor. Ophthalmology Department

Natal'ya Viktorovna Tkachenko

Pavlov First State Medical University of Saint Petersburg

Email: natalyatkachenko@yandex.ru
MD, PhD, assistant professor. Ophthalmology Department

Natalya Viktorovna Chistyakova

Pavlov First State Medical University of Saint Petersburg

Email: nchistik@mail.ru
Ophthalmology Department

  1. Бржеский В. В., АстаховЮ. С., Кузнецова Н. Ю. Заболевания слезного аппарата: пособие для практикующих врачей / Изд. 2, испр. и доп. СПб.: Изд-во Н-Л. 2009; 108.
  2. Бржеский В. В., Майчук Д. Ю. Новые возможности иммуносупрессивной терапии у больных с синдромом «сухого глаза». 2012; 1: 69-74.
  3. Кудряшова Ю. И. Современные подходы к терапии иммуноопосредованной формы синдрома «сухого глаза». Клиническая офтальмология. 2010; 1: 16-20.
  4. Милюдин Е. С., Золотарев А. В., Милюдин А. Е. Возможности местной иммуносупрессии при повторной кератопластике. Клиническая офтальмология. 2014; 3: 160-3.
  5. Aragona P., Tripodi G., Spinella R. et al. The effects of the topical administration of non-steroidal anti-inflammatory drugs on corneal epithelium and corneal sensitivity in normal subjects. Eye (Lond). 2000; 14 (Pt 2): Р. 206-10.
  6. Balaram M., Dana M. R. Phacoemulsification in patients after allogeneic bone marrow transplantation. Ophthalmology. 2001; 108 (9): 1682-7.
  7. Baudouin C., Aragona P., Messmer E. M. et al. Role of hyperosmolarity in the pathogenesis and management of dry eye disease: proceedings of the OCEAN groupmeeting. Ocul Surf. 2013; 11 (4): 246-58.
  8. Byun Y. S., Rho C. R., Cho K. et al. Cyclosporine 0.05 % ophthalmic emulsion for dry eye in Korea: a prospective, multicenter, open-label, surveillance study. Korean J Ophthalmol. 2011; 25 (6): 369-74.
  9. Chiang C. C., Lin J. M., Chen W. L. et al. Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Cornea. 2007; 26 (7): 861-3.
  10. Colón-Acevedo B., Rivera-Román L., Candelario N. et al. Ocular manifestations of acute graft versus host disease after allogeneic bone marrow transplant. Bol Asoc Med P R. 2014; 106 (2): 30-2.
  11. Couriel D., Carpenter P. A., Cutler C. et al. Ancillary therapy and supportive care of chronic graft-versus-host disease: national institutes of health consensus development project on criteria for clinical trials in chronic Graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group Report.Biol Blood Marrow Transplant. 2006; 12 (4): 375-96.
  12. Dastjerdi M. H., Hamrah P., Dana R. High-frequency topical cyclosporine 0.05 % in the treatment of severe dry eye refractory to twice-daily regimen. Cornea. 2009; 28 (10): 1091-6.
  13. De Paiva C. S., Corrales R. M., Villarreal A. L. et al. Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye. Exp Eye Res. 2006; 83: 526-35.
  14. Devec H., Kobak S. The efficacy of topical 0.05 % cyclosporine A in patients with dry eye disease associated with Sjögren's syndrome. Int Ophthalmol. 2014; 34 (5): 1043-8.
  15. Donnenfeld E. D., Solomon R., Roberts C. W. et al. Cyclosporine 0.05 % to improve visual outcomes after multifocal intraocular lens implantation. J Cataract Refract Surg. 2010; 36 (7): 1095-100.
  16. Filipovich A. H., 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 (12): 945-56.
  17. Gupta C., ChauhanA. Ophthalmic delivery of cyclosporine A by punctal plugs. J Control Release. 2011; 150 (1): 70-6.
  18. Gürdal C., Genç I., Saraç O. et al. Topical cyclosporine in thyroid orbitopathy-related dry eye: clinical findings, conjunctival epithelial apoptosis, and MMP-9 expression. Curr Eye Res. 2010; 35 (9): 771-7.
  19. Hessen M., Akpek E. K. Ocular graft-versus-host disease. CurrOpin Allergy ClinImmunol. 2012; 12 (5): 540-7.
  20. Igarashi T., Fujimoto C., Suzuki H. et al. Short-time exposure of hyperosmolarity triggers interleukin-6 expression in cornea epithelial cells. Cornea. 2014; 33 (12): 1342-7.
  21. Jabs D. A., Wingard J., Green W. R. et al. The eye in bone marrow transplantation. III. Conjunctival graft-vs-host disease. Arch Ophthalmol. 1989; 107 (9): 1343-8.
  22. 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. 2012; 47 (11): 1470-3.
  23. Jung J. W., Lee Y. J., Yoon S. C. et al. Long-term result of maintenance treatment with tacrolimus ointment in chronic oculargraft-versus-host disease. Am J Ophthalmol. 2015; 159 (3): 519-27.
  24. Kiang E., Tesavibul N., Yee R. et al. The use of topical cyclosporin A in ocular graft-versus-host-disease. Bone Marrow Transplant. 1998; 22 (2): 147-51.
  25. Kim S. K. Update on ocular graft versus host disease. Curr Opin Ophthalmol. 2006; 17 (4): 344-8.
  26. Kunert K. S., Tisdale A. S., Gipson I. K. Goblet cell numbers and epithelial proliferation in the conjunctiva of patients with dry eye syndrome treated with cyclosporine. Arch Ophthalmol 2002; 120 (3): 330-7.
  27. Kunert K. S., Tisdale A. S., Stern M. E. et al. Analysis of topical cyclosporine treatment of patients with dry eye syndrome: effect on conjunctival lymphocytes. Arch Ophthalmol. 2000; 118 (11): 1489-96.
  28. Kymionis G. D., Bouzoukis D. I., Diakonis V. F. et al. Treatment of chronic dry eye: focus on cyclosporine. Clin Ophthalmol. 2008; 2 (4): 829-36.
  29. Lelli G. J. Jr., Musch D. C., Gupta A. et al. Ophthalmic cyclosporine use in ocular GVHD. Cornea. 2006; 25 (6): 635-8.
  30. Luschmann C., Tessmar J., Schoeberl S. et al. Self-assembling colloidal system for the ocular administration of cyclosporine A. Cornea. 2014; 33 (1): 77-81.
  31. Marsh P., Pflugfelder S. C. Topical nonpreserved methylpresdnisolone therapy of keratoconjunctivits sicca in sjogren’s syndrome. Ophthalmology. 1999; 106: 811-6.
  32. McGhee C. N., Dean S., Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Saf. 2002; 25: 33-55.
  33. Mixon B., Mixon J., Isbey E. K. et al. Autologous serum eye drops for severe dry eye syndrome in a patient with chronic graft-versus-host disease: a case report.Int J Pharm Compd. 2014; 18 (5): 370-7.
  34. Ogawa Y., Kim S. K., Dana R. et al. International Chronic OcularGraft-vs-Host-Disease (GVHD) Consensus Group: proposed diagnostic criteria for chronic GVHD (Part I). Sci Rep. 2013; 3: 3419.
  35. Perry H. D., Doshi-Carnevale S., Donnenfeld E. D. et al. Efficacy of commercially available topical cyclosporine A 0.05 % in the treatment of meibomian gland dysfunction. Cornea. 2006; 25 (2): 171-5.
  36. Perry H. D., Solomon R., Donnenfeld E. D. et al. Evaluation of topical cyclosporine for the treatment of dry eye disease. Arch Ophthalmol. 2008; 126 (8): 1046-50.
  37. Pflugfelder S. C., Maskin S. L., Anderson B. et al. A randomized, double-masked, placebo-controlled, multicenter comparison of loteprednol etabonate ophthalmic suspension 0.5 %, and placebo for treatment of keratoconjunctivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004; 138: 444-57.
  38. Prabhasawat P., Tesavibul N., Karnchanachetanee C. et al. Efficacy of cyclosporine 0.05 % eye drops in Stevens Johnson syndrome with chronic dry eye. J Ocul Pharmacol Ther. 2013; 29 (3): 372-7.
  39. Reynolds S. A., KabatA. G. Therapeutic options for the management of early neurotrophickeratopathy: a case report and review. Optometry. 2006; 77 (10): 503-7.
  40. Riemens A., te Boome L., Imhof S. et al. Current insights into ocular graft-versus-host disease. Curr Opin Ophthalmol. 2010; 21 (6): 485-94.
  41. Roberts C. W., Carniglia P. E., Brazzo B. G. Comparison of topical cyclosporine, punctal occlusion, and a combination for the treatment of dry eye. Cornea. 2007; 26 (7): 805-9.
  42. Robinson M. R., Lee S. S., Rubin B. I. et al. Topical corticosteroid therapy for cicatricial conjunctivitis associated with chronic graft-versus-host disease. Bone Marrow Transplant. 2004; 33 (10): 1031-5.
  43. Russo P. A., Bouchard C. S., Galasso J. M. Extended-wear silicone hydrogel soft contact lenses in the management of moderate to severe dry eye signs and symptoms secondary to graft-versus-host disease. Eye Contact Lens. 2007; 33 (3): 144-7.
  44. Sahin A., Bozkurt B., Irkec M. Topical cyclosporine a in the treatment of superior limbic keratoconjunctivitis: a long-term follow-up. Cornea. 2008; 27 (2): 193-5.
  45. Sall K., Stevenson O. D., Mundorf T. K. et al. Two multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic emulsion in moderate to severe dry eye disease. CsA Phase 3 Study Group. Ophthalmology. 2000; 107 (4): 631-9.
  46. Schultz С. Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye. Ophthalmol Eye Dis. 2014; 6: 37-42.
  47. Shulman H. M., Sullivan K. M., Weiden P. L. et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980; 69 (2): 204-17.
  48. Smith J. A., Albeitz J. et al. Epidemiology DEWS Subcommittee. The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye Work Shop (2007) Ocul Surf. 2007; 5 (2): 93-107.
  49. Sosne G., Dunn S. P., Kim C. Thymosin β4 Significantly Improves Signs and Symptoms of Severe Dry Eye in a Phase 2 Randomized Trial. Cornea. 2015; 34 (5): 491-6.
  50. Steger B., Speicher L., Philipp W. et al. In vivo confocal microscopic characterisation of the cornea in chronic graft-versus-host disease related severe dry eye disease. Br J Ophthalmol. 2015; 99 (2): 160-5.
  51. Stern M. E., Gao J., Schwalb T. A. et al. Conjunctival T-cell subpopulations in Sjögren’s and non-Sjögren’s patients with dry eye. Invest Ophthalmol Vis Sci. 2002; 43: 2609-14.
  52. Stonecipher K. G., Chia J., Onyenwenyi A. et al. Health claims database study of cyclosporine ophthalmic emulsion treatment patterns in dry eye patients. Ther Clin Risk Manag. 2013; 9: 409-15.
  53. Su M. Y., Perry H. D., Barsam A. et al. The effect of decreasing the dosage of cyclosporine A 0.05 % on dry eye disease after 1 year of twice-daily therapy. Cornea. 2011; 30 (10): 1098-104.
  54. Ursea R., Purcell T. L., Tan B. U. et al. The effect of cyclosporine A (Restasis) on recovery of visual acuity following LASIK. J Refract Surg. 2008; 24 (5): 473-6.
  55. Vanathi M., Kashyap S., Khan R. et al. Ocular surface evaluation in allogenic hematopoietic stem cell transplantation patients. Eur J Ophthalmol. 2014; 24 (5): 655-66.
  56. Wu M. M., Yau G. S., Lee J. W. et al. Retrospective review on the use of topical cyclosporin a 0.05 % for paediatric allergic conjunctivitis in Hong Kong Chinese. Scientific World Journal. 2014; doi: 10.1155/2014/396987.
  57. YalcinTok O., Burcu Nurozler A., Ergun G. et al. Topical cyclosporine A in the prevention of pterygium recurrence. Ophthalmologica. 2008; 222 (6): 391-6.
  58. Zhou X. Q., Wei R. L. Topical cyclosporine A in the treatment of dry eye: a systematic review and meta-analysis. Cornea. 2014; 33 (7): 760-7.
  59. Ziaei M., ManzouriB. Topical cyclosporine in corneal transplantation. Cornea. 2015; 34 (1): 110-5.


Abstract - 491

PDF (Russian) - 320



Copyright (c) 2015 Astakhov S.Y., Tkachenko N.V., Chistyakova N.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies