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Editors Selection IGR 18-1

Glaucoma and Systemic Diseases: Diabetes Mellitus and Glaucoma

Comment by Louis Pasquale on:

65884 Diabetes Pathology and Risk of Primary Open-Angle Glaucoma: Evaluating Causal Mechanisms by Using Genetic Information, Shen L; Walter S; Melles RB et al., American Journal of Epidemiology, 2016; 183: 147-155

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Considerable epidemiological evidence supports an adverse relation between type-2 diabetes (T2D) and primary open-angle glaucoma (POAG). Appropriately designed genetic studies can avert issues like reverse causation, detection bias and diabetes treatment effects that cast doubt about any relation between T2D and POAG because the genome is inherited from birth.

Appropriately designed genetic studies can avert issues like reverse causation, detection bias and diabetes treatment effects that cast doubt about any relation between T2D and POAG because the genome is inherited from birth

Shen et al. studied 69,685 participants in a large cohort nested in a Northern California health system subjected to high throughout genotyping. The authors used ICD-9 coding to capture POAG, normal tension glaucoma (NTG) and T2D status. Only validation for T2D case identification was performed and given the codes used to define POAG, some of the 3,554 cases captured likely represent individuals with and without reproducible visual field loss. The analysis is limited to Caucasians and it is not clear if the entire cohort was under ophthalmic surveillance. The authors composed polygenetic risk scores for T2D and confirmed that these panels were robustly associated with T2D. Furthermore, they reproduced the adverse relation between T2D and POAG. Next they showed the T2D genetic risk score was associated with a 2.5-fold increased risk of POAG, although the associations were attenuated and not statistically significant when adjusted for T2D status. Subsequently they stratified the T2D genetic biomarkers into the following categories based on their putative function: adiposity, pancreatic beta cell function, insulin regulation and other metabolic mechanisms. The pancreatic beta cell function genetic subpanel was associated with a 5-fold increased risk of POAG and these results remained significant when adjusted for T2D. No other subset of T2D genetic biomarkers was associated with POAG. Furthermore no association between any of the T2D genetic biomarker panels and NTG was found. While there is no clear biologic hypothesis linking pancreatic beta cell function and glaucoma, these results support a genetic link between T2D and POAG.

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