Diabetes Link Found for Fuchs Corneal Endothelial Dystrophy

Researchers published the study covered in this summary on medRxiv as a preprint that has not yet been peer reviewed.

Key Takeaways

  • Diabetes, especially type 1 diabetes, may be a particularly important factor in the etiology of Fuchs endothelial corneal dystrophy (FECD) in findings from a case-control study of about 149.000 US military veterans.

  • Other apparently important etiologic factors for FECD are female sex, European ancestry, and increasing numbers of comorbidities in people who are age 65 and older.

Why This Matters

  • An estimated 4% of adults have FECD, making it a common corneal dystrophy and a leading indication for corneal transplantation in the United States.

  • The results suggest that in individuals with the “FECD phenotype” (people with an underlying susceptibility to developing FECD), diabetes and potentially other conditions that alter corneal physiology may increase the risk of onset, speed of onset, and progression of FECD.

  • The findings also suggest a central role for diabetes in the etiology of FECD. Further study of the relationship between diabetes and FECD may identify ways to slow FECD progression.

  • The algorithm the authors developed to identify cases of FECD could open the door to further FECD gene discovery.

Study Design

  • The researchers examined electronic health records (EHRs) from military veterans seen at three US Department of Veterans Affairs Medical Centers to develop an algorithm to identify FECD cases and controls using information in the electronic health records (EHR). Control individuals had no sign of corneal endothelial disease.

  • The researchers applied their validated algorithm to EHR data from a large national sample of veterans in the Million Veteran Program who were at least age 65 years to identify 2663 people with FECD and 146,659 controls.

Key Results

  • The final algorithm had a positive predictive value of 82% for FECD and a negative predictive value of 97%.

  • The researchers found a 1.78% prevalence of FECD: 2663 cases/149,322 total veterans assessed. This was somewhat lower than prior reports that FECD prevalence is approximately 4%.

  • Of these 2663 FECD cases, 2264 (85%) had European ancestry. Women comprised about 9% of the study cohort.

  • Women and individuals of European ancestry had significantly higher odds of being identified as FECD cases. After adjusting for age and ancestry, women had a 4.6-fold higher rate having FECD compared with men (P < .001). Non-European ancestry associated with a significantly lower risk for FECD (P < .001).

  • Those with FECD averaged 69.5 years old, significantly younger than the controls (mean age, 71.7 years).

  • The authors found diagnostic codes consistent with type 1 diabetes among the veterans with FECD twofold more often than in the controls, a significant difference. Type 2 diabetes was 1.25-fold more frequent among the FECD cases, also a significant difference. Obesity was 1.34-fold more common in the people with FECD, a significant difference.

  • After adjusting for age, sex, and ancestry, FECD cases were 1.2-fold more likely to have 1-3 comorbid conditions (based on their Charlson Comorbidity Index) than controls with no FECD.


  • The study relied on clinical coding, billing, and prescription data for case identification and used a specially designed algorithm to use these data to identify cases of FECD.

  • The study exclusively used data from older US veterans and the findings may not be generalizable to other populations.

  • Although the statistical model adjusted for age, sex, and genetic ancestry, other unaccounted-for confounders could have influenced the findings.


  • The study did not receive commercial funding.

  • None of the authors had financial disclosures.

This is a summary of a preprint research study , “Association between Fuchs Endothelial Corneal Dystrophy, Diabetes Mellitus and Multimorbidity” written by researchers from several US centers on medRxiv, provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.

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