Abstract
To evaluate the effect of donor-to-recipient sex mismatched (male donor corneas to female recipients) on the incidence of rejection episodes and failures up to 1 year after corneal transplantation. Prospective observational cohort study, with donor corneas randomly assigned and surgeons blind to the sex of donor. A unique eye bank retrieved and selected the donor corneas transplanted in 4 ophthalmic units in patients with clinical indication for primary or repeated keratoplasty for optical reasons, perforating or lamellar, either anterior or posterior. Rejection episode defined as any reversible or irreversible endothelial, epithelial or stromal sign, with or without development of corneal edema, and graft failure as a permanently cloudy graft or a regraft for any reason detected or acknowledged during a postoperative ophthalmic visit at any time up to 1 year after surgery were recorded.156 (28.6%) patients resulted donor-to-recipient gender mismatched for H-Y antigen (male donor to female recipient). During the 12 months follow-up, 83 (14.7%, 95% CI 12.0–17.9) grafts showed at least 1 rejection episode and 17 (3.2%, 95% CI 2.0–5.0) failed after immune rejection, among 54 (9.6%, 95% CI 7.4–12.3) grafts failed for all causes. No significant differences between matched and mismatched patients were found for cumulative incidence of both rejection episodes (15.2% and 13.5%) and graft failures following rejection (3.2% and 2.6%), respectively. Multivariable analyses showed that H-Y matching either is not a predictive factor for rejection or graft failure nor seems to influence incidence of failures on respect to patient’s risk category. The lack of influence of donor-to-recipient mismatched on the rate of rejections and graft failures resulting from this study do not support the adoption of donor-recipient matching in the allocation of corneas for transplantation.
Similar content being viewed by others
Data availability
Data and material are available for those who are entitled to access.
References
Armitage WJ, Winton HL, Jones MNA et al (2019a) Corneal transplant follow-up study II (CTFS II): a prospective clinical trial to determine the influence of HLA class II matching on corneal transplant rejection: baseline donor and recipient characteristics. Br J Ophthalmol 103:132–136
Armitage WJ, Goodchild C, Griffin MD et al (2019b) High-risk corneal transplantation: recent developments and future possibilities. Transplantation 103:2468–2478
Böhringer D, Spierings E, Enczmann J et al (2006) Matching of the minor histocompatibility antigen HLA-A1/H-Y may improve prognosis in corneal transplantation. Transplantation 82:1037–1041
Böhringer D, Böhringer S, Poxleitner K et al (2010) Long-term graft survival in penetrating keratoplasty: the biexponential model of chronic endothelial cell loss revisited. Cornea 29:1113–1117
Böhringer D, Grotejohann B, Ihorst G, Reinshagen H, Spierings E, Reinhard T (2018) Rejection prophylaxis in corneal transplant. Dtsch Arztebl Int 115:259–265
Bokhorst AG, Dorrepaal CA (2009) Allocation of corneas in Europe. In Bredehorn-Mayr T, Duncker G, Armitage WJ, eds. Eye Banking. Basel: Karger, vol 43, pp 87–96.
Borderie VM, Guilbert E, Touzeau O, Laroche L (2011) Graft rejection and graft failure after anterior lamellar versus penetrating keratoplasty. Am J Ophthalmol 151:1024–1029
Clayton JA, Davis AF (2015) Sex/gender disparities and women's eye health. Curr Eye Res 40:102–109
Dekaris I, Jones GLA, Gareiss-Lok A, Lok CD (2019) European Eye Bank Association Directory. 28th ed. January 2019
Di Zazzo A, Kheirkhah A, Abud TB, Goyal S, Dana R (2017) Management of high-risk corneal transplantation. Surv Ophthalmol 62:816–827
Eichwald EJ, Silmser CR, Wheeler N (1957) The genetics of skin grafting. Ann N Y Acad Sci 64:737–740
Feng MT, Price MO, Miller JM, Price FW Jr (2014) Air reinjection and endothelial cell density in Descemet membrane endothelial keratoplasty: five-year follow-up. J Cataract Refract Surg 40:1116–1121
Ge F, Huang T, Yuan S, Zhou Y, Gong W (2013) Gender issues in solid organ donation and transplantation. Ann Transplant 18:508–514
Guerra FP, Anshu A, Price MO, Giebel AW, Price FW (2011) Descemet's membrane endothelial keratoplasty: prospective study of 1-year visual outcomes, graft survival, and endothelial cell loss. Ophthalmology 118:2368–2373
Hopkinson CL, Romano V, Kaye RA et al (2017) The influence of donor and recipient gender incompatibility on corneal transplant rejection and failure. Am J Transplant 17:210–217
Hos D, Hos D, Tuac O, Schaub F et al (2017) Incidence and clinical course of immune reactions after Descemet membrane endothelial keratoplasty: retrospective analysis of 1000 consecutive eyes. Ophthalmology 124:512–518
Hos D, Matthaei M, Bock F et al (2019) Immune reactions after modern lamellar (DALK, DSAEK, DMEK) versus conventional penetrating corneal transplantation. Prog Retin Eye Res 73:100768. https://doi.org/10.1016/j.preteyeres.2019.07.001
Inoue K, Amano S, Oshika T, Tsuru T (2000) Histocompatibility Y antigen compatibility and allograft rejection in corneal transplantation. Eye (Lond) 14:201–205
Jordan CS, Price MO, Trespalacios R, Price FW Jr (2009) Graft rejection episodes after Descemet stripping with endothelial keratoplasty: part one: clinical signs and symptoms. Br J Ophthalmol 93:387–390
Kemna M, Albers E, Bradford MC et al (2016) Impact of donor-recipient sex match on long-term survival after heart transplantation in children: an analysis of 5797 pediatric heart transplants. Pediatr Transplant 20:249–255
Kim MJ, Kim JH, Jeon HS, Wee WR, Hyon JY (2018) Effect of histocompatibility y antigen matching on graft survival in primary penetrating keratoplasty. Cornea 37:33–38
Lai JC, Feng S, Roberts JP, Terrault NA (2011) Gender differences in liver donor quality are predictive of graft loss. Am J Transplant 11:296–302
Lakatos E (1988) Sample sizes based on the log-rank statistic in complex clinical trials. Biometrics 44:229–241
Larkin DF (2018) Letter to the Editor in response to Kim et al. Effect of histocompatibility Y antigen matching on graft survival in primary penetrating keratoplasty. Cornea 37:e19
Lass JH, Benetz BA, Gal RL et al (2013) Donor age and factors related to endothelial cell loss ten years after penetrating keratoplasty: specular microscopy ancillary study. Ophthalmology 120:2428–2435
Mannis MJ, Holland EJ, Gal RL et al (2013) The effect of donor age on penetrating keratoplasty for endothelial disease: graft survival after 10 years in the cornea donor study. Ophthalmology. https://doi.org/10.1016/j.ophtha.2013.08.026
Middleton D, Menchaca L, Rood H, Komerofsky R (2003) New allele frequency database: https://www.allelefrequencies.net. Tissue Antigens 61:403–407.
Niederkorn JY, Larkin DF (2010) Immune privilege of corneal allografts. Ocul Immunol Inflamm 18:162–171
Pierce RA, Field ED, den Haan JM et al (1999) The HLA-A*0101-restricted HY minor histocompatibility antigen originates from DFFRY and contains a cysteinylated cysteine residue as identified by a novel mass-spectrometric technique. J Immunol 163(12):6360–6364
Potapenko IO, Samolov B, Armitage MC, Byström B, Hjortdal J (2017) Donor endothelial cell count does not correlate with Descemet stripping automated endothelial keratoplasty transplant survival after 2 years of follow-up. Cornea 36:649–654
Price DA, Kelley M, Price FW Jr, Price MO (2018) Five-year graft survival of Descemet membrane endothelial keratoplasty (EK) versus Descemet stripping EK and the effect of donor sex matching. Ophthalmology 125:1508–1514
Reinhard T, Böhringer D, Enczmann J et al (2004) Improvement of graft prognosis in penetrating normal-risk keratoplasty by HLA class I and II matching. Eye 18:269–277
Scott DM (1995) Identification of a mouse male-specific transplantation antigen H-Y. Nature 376:695–698
Sullivan DA, Rocha EM, Aragona P et al (2017) TFOS DEWS II sex, gender, and hormones report. Ocul Surf 15:284–333
Tan JC, Wadia PP, Coram M et al (2008) H-Y antibody development associates with acute rejection in female patients with male kidney transplants. Transplantation 86:75–81
van Essen TH, Roelen DL, Williams KA, Jager MJ (2015) Matching for human leukocyte antigens (HLA) in corneal transplantation—to do or not to do. Prog Retin Eye Res 46:84–110
Völker-Dieben HJ, Claas FH, Schreuder GM et al (2000) Beneficial effect of HLA-DR matching on the survival of corneal allografts. Transplantation 70:640–648
Wagner H, Fink BA, Zadnik K (2008) Sex- and gender-based differences in healthy and diseased eyes. Optometry 79:636–652
Acknowledgements
The authors would like to thank Marianna Berton, MD, for the assistance in funding this project and for general encouragement and helpful hints along the way.
Funding
This research received an unconditional restricted funding by AMMI (Associazione Mogli Medici Italiani, The Italian Medical Doctors’ Partners Association) in the framework of the VII Call for Gender Medicine and Pharmacology Application—year 2018.
Author information
Authors and Affiliations
Contributions
AF: research design, participated in data analyses, writing of the paper. PG: data collection, database cleaning, manuscript revision. ACF: data analyses, manuscript revision. FB: surgery, patient evaluation and data collection. CM: surgery, patient evaluation and data collection. ER: surgery, patient evaluation and data collection. TB: patient evaluation and data collection. EP: surgery, patient evaluation and data collection. CM: patient evaluation and data collection. PV: surgery, patient evaluation and data collection. DP: manuscript revision. AF: research design, surgery, patient evaluation and data collection, final approval.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Ethics approval
It was obtained for the conduction of the study by the Ethic Committee.
Consent to participate
It was obtained from all the patients.
Consent for publication
It was obtained from all the patients.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Fasolo, A., Gallon, P., Frigo, A.C. et al. Gender medicine in corneal transplantation: influence of sex mismatch on rejection episodes and graft survival in a prospective cohort of patients. Cell Tissue Bank 22, 47–56 (2021). https://doi.org/10.1007/s10561-020-09864-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10561-020-09864-x