Peer Review | July/Aug '17

Corneal Disparities

Variations by race, gender, and region exist.

Large population-based clinical registries such as the Intelligent Research in Sight (IRIS) are expanding resources that allow us to improve our understanding of eye disease and outcomes disparities. This article reviews the literature on racial and gender disparities in corneal disease and pathology to summarize current knowledge and clarify what has yet to be studied.

CORNEAL DYSTROPHY

The prevalence of corneal dystrophies varies by both gender and race. In a study by Musch et al,1 corneal dystrophies were found to be more common in women. Whites had a significantly higher percentage of anterior and endothelial corneal dystrophies, while blacks accounted for only 0.7% of those with granular dystrophy and 2.2% of those with anterior corneal dystrophy. Additionally, 2.2% of blacks in the study had anterior corneal dystrophy, while 5.4% had endothelial corneal dystrophy. Asians had significantly lower percentages of anterior and endothelial corneal dystrophies (1.6% and 2.0%, respectively). Hispanics composed 8.1% of enrollees without any corneal dystrophy. The authors do not discuss biological etiologies for these disparities, but they state that the registry reports only on insured patients, thereby underrepresenting blacks and overrepresenting whites.

Fuchs dystrophy diagnoses rates were slightly higher for white Medicare patients than for African Americans, even when adjusting for the lower rate that African Americans see ophthalmologists.2 Whites also had a 1.9-fold higher rate of endothelial or penetrating keratoplasty (PKP) compared with African Americans, which may suggest racial/ethnic differences in the manifestation and/or treatment of severe Fuchs dystrophy. A genetic variant predisposing patients to Fuchs dystrophy has been found mostly in US and European populations but is present in only a small percentage of Asian and Indian populations.3-8 Whether this is solely a genetic difference versus an environmental influence or an access to care issue requires further study.

CORNEAL ECTASIA

The prevalence of keratoconus differs significantly by ethnic group.9 Southeast Asians living in the English Midlands had a disease incidence between 4.4 to 9.2 times higher than whites.10-12 Arabs, Turks, and Kurds were found to have higher rates of keratoconus compared with Persians.13 Further, the age of onset of keratoconus is younger in Asians than in Caucasians.10-12,14

Studies on the regional prevalence of keratoconus have found that it is low in Northern Europe and the Urals in Russia9-11,15-19 and higher in Middle Eastern countries,13,20-25 India,26 and China.27 This raises the question of whether climate or sun exposure (ie, oxidative damage and ultraviolet light exposure) may influence keratoconus development.28

CORNEAL TRANSPLANTATION

Donor tissue. In the Cornea Donor Study, male donor gender (HR, 1.80; 95% CI, 1.06–3.05) and nonwhite corneal donors (HR, 1.72; 95% CI, 1.10–2.67) had increased rejection rates compared with female and white donors, respectively.29 However, a 1994 study by Maguire et al30 did not show a difference in outcome rates as a result of donor race. In addition, a 2013 study by Niziol et al29 did not show donor and recipient race mismatches to influence rejection risk. Corneal thickness, which predicts graft survival, is increased in white (non-Hispanic) donor races compared with nonwhite or Hispanic donors at 6 months to 5 years after PKP, which may be secondary to racial differences.31

The literature on the role of gender in graft rejection is conflicting. In a study of baseline factors of endothelial cell loss, female donors were associated with significantly higher endothelial cell density at 5-year follow-up (P = .04)32; this may be attributed to receptors for female hormones present in the corneal endothelium.32 The association was not statistically significant at 5 years for grafts that had not failed.32

Recipient demographics. In the Cornea Donor Study, being a female recipient was a risk factor for rejection at 5 years, but this risk did not remain significant at 10 years.33 In studies by Price et al34 and Sugar et al,35 recipient gender did not influence graft failure rates.

Nonwhite recipients had an increased failure hazard (HR, 4.95; 95% CI, 1.49–16.39).31 In the Cornea Donor Study, African American race (P = .11) was associated with trends in graft failure.36 Price et al34 found that African American race was associated with an increased risk of failure by rejection or endothelial decompensation after PKP. African Americans were twice as likely as whites and other races to experience graft failure.

In a study on risk factors for graft rejection in Descemet stripping endothelial keratoplasty, race was the principal risk factor that increased the relative risk of experiencing an initial rejection.37 African American graft recipients had a 4.8-fold increased relative risk compared with Caucasian recipients (P < .005). Gender was not a significant influencer.

Ezon et al38 had similar results for immunologic graft rejection in Descemet stripping automated endothelial keratoplasty. In an Asian population, primary graft failure was significantly associated with smaller graft.39 The smaller average anterior chamber depth (2.68 in Asian eyes) may explain the higher failure rate. The inferior wing of the folded graft is unable to unfold fully, impeded by the iris, which prevents extension of the donor tissue in these eyes.40

CONCLUSION

Current research on the disparities in corneal dystrophy rates and outcomes of corneal transplants shows variations by race, gender, and region. Samples were often smaller for nonwhite races, resulting in large confidence intervals and sometimes insufficient numbers to evaluate risk of failure separately for each group. This points to a need for targeted disparities research on risk factors for corneal disease and corneal transplant outcomes in order to discuss disease prognoses and true risks of procedures with patients.

1. Musch DC, Niziol LM, Stein JD, Kamyar RM, Sugar A. Prevalence of corneal dystrophies in the United States: estimates from claims data. Invest Ophthalmol Vis Sci. 2011;52(9):6959-6963.

2. Mahr MA, Baratz KH, Hodge DO, Erie JC. Racial/ethnic differences in rates of penetrating or endothelial keratoplasty for Fuchs endothelial corneal dystrophy among US Medicare beneficiaries. JAMA Ophthalmol. 2016;134(10):1178-1180.

3. Kuot A, Hewitt AW, Griggs K, et al. Association of TCF4 and CLU polymorphisms with Fuchs’ endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process. Eur J Hum Genet. 2012;20(6):632-638.

4. Nanda GG, Padhy B, Samal S, Das S, Alone DP. Genetic association of TCF4 intronic polymorphisms, CTG18.1 and rs17089887, with Fuchs’ endothelial corneal dystrophy in an Indian population. Invest Ophthalmol Vis Sci. 2014;55(11):7674-7680.

5. Riazuddin SA, McGlumphy EJ, Yeo WS, Wang J, Katsanis N, Gottsch JD. Replication of the TCF4 intronic variant in late-onset Fuchs corneal dystrophy and evidence of independence from the FCD2 locus. Invest Ophthalmol Vis Sci. 2011;52(5):2825-2829.

6. Wang KJ, Jhanji V, Chen J, et al. Association of transcription factor 4 (TCF4) and protein tyrosine phosphatase, receptor type G (PTPRG) with corneal dystrophies in southern Chinese. Ophthalmic Genet. 2014;35(3):138-141.

7. Wieben ED, Aleff RA, Eckloff BW, et al. Comprehensive assessment of genetic variants within TCF4 in Fuchs’ endothelial corneal dystrophy. Invest Ophthalmol Vis Sci. 2014;55(9):6101-6107.

8. Wieben ED, Aleff RA, Tosakulwong N, et al. A common trinucleotide repeat expansion within the transcription factor 4 (TCF4, E2-2) gene predicts Fuchs corneal dystrophy. PLoS One. 2012;7(11):e49083.

9. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. Biomed Res Int. 2015;2015:795738.

10. Pearson AR, Soneji B, Sarvananthan N, Sandford-Smith JH. Does ethnic origin influence the incidence or severity of keratoconus? Eye (Lond). 2000;14(4):625-628.

11. Georgiou T, Funnell CL, Cassels-Brown A, O’Conor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients. Eye (Lond). 2004;18(4):379-383.

12. Cozma I, Atherley C, James NJ. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asian and white patients. Eye (Lond). 2005;19(8):924-925; author reply 925-926.

13. Hashemi H, Khabazkhoob M, Fotouhi A. Topographic keratoconus is not rare in an Iranian population: the Tehran Eye Study. Ophthalmic Epidemiol. 2013;20(6):385-391.

14. Weed KH, MacEwen CJ, Giles T, Low J, McGhee CN. The Dundee University Scottish Keratoconus Study: demographics, corneal signs, associated diseases, and eye rubbing. Eye (Lond). 2008;22(4):534-541.

15. Ihalainen A. Clinical and epidemiological features of keratoconus genetic and external factors in the pathogenesis of the disease. Acta Ophthalmol. 1986;178:1-64.

16. Gorskova EN, Sevost’ianov EN. Epidemiology of keratoconus in the Urals [in Russian]. Vestn Oftalmol. 1998;114(4):38-40.

17. Nielsen K, Hjortdal J, Pihlmann M, Corydon TJ. Update on the keratoconus genetics. Acta Ophthalmol. 2013;91(2):106-113.

18. Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986;101(3):267-273.

19. Hofstetter HW. A keratoscopic survey of 13,395 eyes. Am J Optom Arch Am Acad Optom. 1959;36(1):3-11.

20. Millodot M, Shneor E, Albou S, Atlani E, Gordon-Shaag A. Prevalence and associated factors of keratoconus in Jerusalem: a cross-sectional study. Ophthalmic Epidemiol. 2011;18(2):91-97.

21. Shneor E, Millodot M, Gordon-Shaag A, et al. Prevalence of keratoconus amoung young Arab students in Israel. Int J Kerat Ect Cor Dis. 2014;3(1):9-14.

22. Assiri AA, Yousuf BI, Quantock AJ, Murphy PJ, Assiri AA. Incidence and severity of keratoconus in Asir province, Saudi Arabia. Br J Ophthalmol. 2005;89(11):1403-1406.

23. Ziaei H, Jafarinasab MR, Javadi MA, et al. Epidemiology of keratoconus in an Iranian population. Cornea. 2012;31(9):1044-1047.

24. Hashemi H, Beiranvand A, Khabazkhoob M, et al. Prevalence of keratoconus in a population-based study in Shahroud. Cornea. 2013;32(11):1441-1445.

25. Hashemi H, Khabazkhoob M, Yazdani N, et al. The prevalence of keratoconus in a young population in Mashhad, Iran. Ophthalmic Physiol Optics. 2014;34(5):519-527.

26. Jonas JB, Nangia V, Matin A, Kulkarni M, Bhojwani K. Prevalence and associations of keratoconus in rural Maharashtra in central India: the Central India Eye and Medical Study. Am J Ophthalmol. 2009;148(5):760-765.

27. Xu L, Wang YX, Guo Y, You QS, Jonas JB. Prevalence and associations of steep cornea/keratoconus in greater Beijing. The Beijing Eye Study. PLoS ONE. 2012;7(7).

28. Kenney MC, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Ant Eye. 2003;26(3):139-146.

29. Niziol LM, Musch DC, Gillespie BW, Marcotte LM, Sugar A. Long-term outcomes in patients who received a corneal graft for keratoconus between 1980 and 1986. Am J Ophthalmol. 2013;155(2):213-219.e3.

30. Maguire MG, Stark WJ, Gottsch JD, et al. Risk factors for corneal graft failure and rejection in the collaborative corneal transplantation studies. Collaborative Corneal Transplantation Studies Research Group. Ophthalmology. 1994;101(9):1536-1547.

31. Verdier DD, Sugar A, Baratz K, et al; Cornea Donor Study Investigator Group. Corneal thickness as a predictor of corneal transplant outcome. Cornea. 2013;32(6):729-736.

32. Lass JH, Beck RW, Benetz BA, et al; Cornea Donor Study Investigator Group. Baseline factors related to endothelial cell loss following penetrating keratoplasty. Arch Ophthalmol. 2011;129(9):1149-1154.

33. Dunn SP, Gal RL, Kollman C, et al; Writing Committee for the Cornea Donor Study Research Group. Corneal graft rejection 10 years after penetrating keratoplasty in the cornea donor study. Cornea. 2014;33(10):1003-1009.

34. Price MO, Thompson RW Jr, Price FW Jr. Risk factors for various causes of failure in initial corneal grafts. Arch Ophthalmol. 2003;121(8):1087-1092.

35. Sugar A, Tanner JP, Dontchev M, et al; Cornea Donor Study Investigator Group. Recipient risk factors for graft failure in the cornea donor study. Ophthalmology. 2009;116(6):1023-1028.

36. Sugar A, Gal RL, Kollman C, et al; Writing Committee for the Cornea Donor Study Research Group. Factors associated with corneal graft survival in the cornea donor study. JAMA Ophthalmol. 2015;133(3):246-254.

37. Price MO, Jordan CS, Moore G, Price FW Jr. Graft rejection episodes after Descemet stripping with endothelial keratoplasty: part two: the statistical analysis of probability and risk factors. Br J Ophthalmol. 2009;93(3):391-395.

38. Ezon I, Shih CY, Rosen LM, Suthar T, Udell IJ. Immunologic graft rejection in Descemet’s stripping endothelial keratoplasty and penetrating keratoplasty for endothelial disease. Ophthalmology. 2013;120(7):1360-1365.

39. Ang M, Htoon HM, Cajucom-Uy HY, Tan D, Mehta JS. Donor and surgical risk factors for primary graft failure following Descemet’s stripping automated endothelial keratoplasty in Asian eyes. Clin Ophthalmol. 2011;5:1503-1508.

40. Ivarsen A, Hjortdal J. Recipient corneal thickness and visual outcome after Descemet’s stripping automated endothelial keratoplasty. Br J Ophthalmol. 2014;98(1):30-34.

author
Cherie Fathy, MD
  • Resident, Beth Israel Deaconess Medical Center/Brockton Signature Hospital, Vanderbilt University School of Medicine, Nashville, Tennesse
  • Financial disclosure: None acknowledged
author
Zaina Al-Mohtaseb, MD | Section Editor
  • Assistant Professor of Ophthalmology and Associate Residency Program Director, Baylor College of Medicine, Houston, Texas
  • zaina@bcm.edu
  • Financial disclosure: None acknowledged

NEXT IN THIS ISSUE