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.
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