Conjunctival T Cell Profile in Allogeneic Hematopoietic Stem Cell Transplant Patients After Instilling Topical Cyclosporine-A 0.1% Cationic Emulsion

Overview

Journal Ophthalmol Ther

Specialty Ophthalmology

Date 2023 Mar 1

PMID 36856978

Authors

Louis Tong

Elizabeth Wen Ling Lim

Sharon Wan Jie Yeo

Aihua Hou

Yeh Ching Linn

Aloysius Ho

Hein Than

Jeffrey Kim Siang Quek

William Ying Khee Hwang

Francesca Lorraine Wei Inng Lim

Li Lim

Affiliations

Soon will be listed here.

Abstract

Introduction: To profile conjunctival T cell populations in allogeneic hematopoietic stem cell transplant (HSCT) patients after instillation of daily topical cyclosporine-A (CsA) 0.1% cationic emulsion (Ikervis), and to evaluate patients' tolerance to these eye drops.

Methods: Nineteen participants were prescribed Ikervis prophylaxis once daily to both eyes from 3-5 weeks pre-HSCT to 12 months post-HSCT. The outcome measure was conjunctival T cell proportions from flow cytometry after impression cytology. Covariates included visual acuity, intraocular pressure, slit lamp and fundal examination, dry eye (SPEED) and quality of life questionnaires, non-invasive keratograph tear break-up time (NIKBUT), conjunctival redness, meibography, lipid thickness, Schirmer test, tear cytokines, fluorescein staining, tear osmolarity, and meibomian gland expressibility.

Results: The conjunctival T cell analysis showed either stable or decreased proportions of conjunctival CD4 T cells at the last visit from baseline in compliant patients. CD4 proportions were increased in non-compliant patients and in the single patient who developed ocular graft-versus-host disease (GVHD). All patients were tolerant to Ikervis but 6/19 were not compliant. In the majority of patients, vision did not affect activities of daily living. Pre- and post-HSCT up to the last study visit, there was no statistically significant change in clinical covariates. Only one participant developed ocular GVHD at 9 months post-HSCT.

Conclusion: Superficial conjunctival T cell profile reflects compliance to daily topical Ikervis eye drops and clinical ocular surface parameters in allogenic HSCT patients. Tolerance is comparable to other formulations of topical CsA in the first 12 months.

Clinicaltrials:

Gov Identifier: NCT04636918. URL: https://clinicaltrials.gov/ct2/show/NCT04636918?cond=ocular+Graft+Versus+Host+Disease&cntry=SG&draw=2&rank=2 .

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References

Lemp M, Bron A, Baudouin C, Benitez Del Castillo J, Geffen D, Tauber J . Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol. 2011; 151(5):792-798.e1. DOI: 10.1016/j.ajo.2010.10.032. View

Hong J, Sun X, Wei A, Cui X, Li Y, Qian T . Assessment of tear film stability in dry eye with a newly developed keratograph. Cornea. 2012; 32(5):716-21. DOI: 10.1097/ICO.0b013e3182714425. View

Shikari H, Amparo F, Saboo U, Dana R . Onset of ocular graft-versus-host disease symptoms after allogeneic hematopoietic stem cell transplantation. Cornea. 2015; 34(3):243-7. PMC: 4318713. DOI: 10.1097/ICO.0000000000000340. View

Ogawa Y, Kuwana M, Yamazaki K, Mashima Y, Yamada M, Mori T . 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):1888-96. DOI: 10.1167/iovs.02-0699. View

Bose T, Lee R, Hou A, Tong L, Chandy K . Tissue resident memory T cells in the human conjunctiva and immune signatures in human dry eye disease. Sci Rep. 2017; 7:45312. PMC: 5366884. DOI: 10.1038/srep45312. View

Terry R, Schnider C, Holden B, Cornish R, Grant T, Sweeney D . CCLRU standards for success of daily and extended wear contact lenses. Optom Vis Sci. 1993; 70(3):234-43. DOI: 10.1097/00006324-199303000-00011. View

Massof R, McDonnell P . Latent dry eye disease state variable. Invest Ophthalmol Vis Sci. 2012; 53(4):1905-16. DOI: 10.1167/iovs.11-7768. View

Koh S, Ikeda C, Fujimoto H, Oie Y, Soma T, Maeda N . Regional Differences in Tear Film Stability and Meibomian Glands in Patients With Aqueous-Deficient Dry Eye. Eye Contact Lens. 2015; 42(4):250-5. DOI: 10.1097/ICL.0000000000000191. View

Ngo W, Situ P, Keir N, Korb D, Blackie C, Simpson T . Psychometric properties and validation of the Standard Patient Evaluation of Eye Dryness questionnaire. Cornea. 2013; 32(9):1204-10. DOI: 10.1097/ICO.0b013e318294b0c0. View

10.

Li L, Li Y, Zhu X, Wu B, Tang Z, Wen H . Conjunctiva Resident γδ T Cells Expressed High Level of IL-17A and Promoted the Severity of Dry Eye. Invest Ophthalmol Vis Sci. 2022; 63(12):13. PMC: 9652718. DOI: 10.1167/iovs.63.12.13. View

11.

Eckstein L, Van Quill K, Bui S, Uusitalo M, OBrien J . Cyclosporin a inhibits calcineurin/nuclear factor of activated T-cells signaling and induces apoptosis in retinoblastoma cells. Invest Ophthalmol Vis Sci. 2005; 46(3):782-90. DOI: 10.1167/iovs.04-1022. View

12.

Tong L, Beuerman R, Simonyi S, Hollander D, Stern M . Effects of Punctal Occlusion on Clinical Signs and Symptoms and on Tear Cytokine Levels in Patients with Dry Eye. Ocul Surf. 2016; 14(2):233-41. DOI: 10.1016/j.jtos.2015.12.004. View

13.

Arnous R, Arshad S, Sandgren K, Cunningham A, Carnt N, White A . Tissue resident memory T cells inhabit the deep human conjunctiva. Sci Rep. 2022; 12(1):6077. PMC: 9005529. DOI: 10.1038/s41598-022-09886-3. View

14.

Hingorani M, Metz D, Lightman S . Characterisation of the normal conjunctival leukocyte population. Exp Eye Res. 1997; 64(6):905-12. DOI: 10.1006/exer.1996.0280. View

15.

Filipovich A, Weisdorf D, Pavletic S, Socie G, Wingard J, Lee S . 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. DOI: 10.1016/j.bbmt.2005.09.004. View

16.

Paavonen T, Hayry P . Effect of cyclosporin A on T-dependent and T-independent immunoglobulin synthesis in vitro. Nature. 1980; 287(5782):542-4. DOI: 10.1038/287542a0. View

17.

Malta J, Soong H, Shtein R, Musch D, Rhoades W, Sugar A . Treatment of ocular graft-versus-host disease with topical cyclosporine 0.05%. Cornea. 2010; 29(12):1392-6. DOI: 10.1097/ICO.0b013e3181e456f0. View

18.

Cantu-Rodriguez O, Vazquez-Mellado A, Gonzalez-Trevino J, Martinez-Garza D, Gomez-De Leon A, Hawing-Zarate J . Cyclosporine A for the Prevention of Ocular Graft versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients Is Safe and Feasible. Acta Haematol. 2019; 143(5):425-431. DOI: 10.1159/000502405. View

19.

Chan J, Amankwah R, Robins R, Gray T, Dua H . Kinetics of immune cell migration at the human ocular surface. Br J Ophthalmol. 2008; 92(7):970-5. DOI: 10.1136/bjo.2007.131003. View

20.

Arita R, Itoh K, Inoue K, Amano S . Noncontact infrared meibography to document age-related changes of the meibomian glands in a normal population. Ophthalmology. 2008; 115(5):911-5. DOI: 10.1016/j.ophtha.2007.06.031. View