Anterior Segment Changes in Prediabetes and Diabetes



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Purpose: It is well known there are many changes in the cornea due to type 2 diabetes mellitus (T2DM). These include decreased corneal nerve fiber density and delayed corneal wound healing. There is some evidence that these changes may start in prediabetes. This thesis aims to determine how the cornea is altered in prediabetes and early T2DM by specifically evaluating corneal nerve fiber density, corneal hysteresis, and central and peripheral epithelial differences between these groups.

Methods: Seventy subjects (aged 30–70 years) were recruited. Blood samples and body metrics were taken. Subjects were grouped as: healthy controls (hemoglobin A1c [HbA1c] <5.7%, n=22), prediabetes (5.7-6.4%, n=26), and T2DM (>6.4% or physician diagnosis, n=22). Central corneal subbasal nerve plexus was imaged using in vivo confocal microscopy (Heidelberg confocal microscope). Corneal nerve fiber density was measured. The corneal epithelium thickness and total central corneal thickness was measured centrally and peripherally (8 mm out; Avanti Ocular Coherence Tomographer). Corneal hysteresis values were acquired (Ocular Response Analyzer). Ocular surface symptoms were quantitated using the Ocular Surface Disease Index (OSDI) survey. Appropriate statistics were used for each analysis.

Results: Central corneal nerve fiber density was significantly lower in type 2 diabetes compared to prediabetes (p=0.045) and healthy controls (p=0.001). No differences were found in other corneal nerve fiber measures between groups. There was a significant association between HbA1c and corneal nerve fiber density (rho=-0.45, p=0.001) and body mass index (BMI; rho=-0.30, p=0.04). There was an increase in corneal hysteresis with HbA1c (p=0.02, R2=0.14). Corneal nerve fiber density and corneal epithelium thickness levels were not related (p=0.30). Only in the control subjects and those with prediabetes there was thinning of the peripheral epithelium with HbA1c (p=0.043), but not in T2DM. OSDI scores were correlated with HbA1c but not with structural health metrics in the cornea (p<0.03).

Conclusion: There are changes that occur in the cornea secondary to T2DM and prediabetes, such as corneal nerve fiber density, hysteresis values, and peripheral corneal epithelial thickness. These findings could be applied to the clinical setting to improve care in patients with prediabetes and T2DM.



Type 2 diabetes, T2dm, Confocal microscopy, Corneal nerve density, Prediabetes, Corneal hysteresis, Ocular response analyzer


Portions of this document appear in: Chao, Cecilia, Rachel Wang, Morgan Jones, Nicole Karson, Allison Jussel, Jennyffer Smith, Kathryn Richdale, and Wendy Harrison. "The relationship between corneal nerve density and hemoglobin A1c in patients with prediabetes and type 2 diabetes." Investigative Ophthalmology & Visual Science 61, no. 12 (2020): 26-26.