Corneal confocal microscopy identifies early and definite diabetic cardiac autonomic neuropathy

Aims: To compare the diagnostic utility of corneal confocal microscopy (CCM) with that of gold-standard CARTs for identifying presence of cardiac autonomic neuropathy (CAN) in people with type 1 (T1D) and 2 diabetes (T2D).

Methods: This was a cross-sectional study conducted in UK (Manchester), enrolling 238 subjects with T1D and T2D and 37 subjects without diabetes.

Assessment of cardiovascular autonomic reflex tests (CART), deep-breathing – heart rate variability , E/I ratio and 30:15 ratio, was performed. Further, CCM was used to evaluate: corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL).

Subjects were divided in three groups: no CAN (n=37), subjects with early CAN (1 abnormal CART) (n=45) and definite CAN (≥2 abnormal CARTs) (n=156).

Results: Subjects with CAN were older compared to subjects without CAN. A progressive and significant reduction in small fiber parameters, CNFD, CNBD and CNFL, was observed with increased severity of CAN presence. CCM parameters showed a good performance in terms of diagnostic utility for both early and definite CAN, in particular CNFL showed the best area under the curve, sensitivity and specificity.

Conclusions: This cross-sectional study showed that CCM identifies CAN (both early and definite) in subjects with T1D and T2D with comparable sensitivity and specificity to CARTs, the gold standard tests.

Comments: This study confirms the potential use of CCM in detecting the presence of CAN in subjects with both T1D and T2D. Early identification of CAN is paramount to better managing subjects affected by it. CCM could be added to the clinical setting to assess people for the presence of neuropathy and stratify the risk over time. CCM could be useful in patients taking beta blockers, which could affect the results of some CARTs.

On the other hand, results should be confirmed in further studies in other populations, also stratifying subjects based on age to evaluate the accuracy of CCM in different age groups. 

More studies are needed to highlight the potential role of CCM in the prediction of CAN over time and to evaluate a combination of CCM parameters and CARTS to increase the performance for the tests recommended for the diagnosis of CAN.

Luca D'Onofrio

Reference: Azmi S, Ferdousi M, Kalteniece A, Petropoulos IN, Alam U, Ponirakis G, Asghar O, Marshall A, Boulton AJ, Efron N, Malik RA. Corneal confocal microscopy identifies early and definite diabetic cardiac autonomic neuropathy. Diabetes Res Clin Pract. 2025 Jun;224:112172. doi: 10.1016/j.diabres.2025.112172. Epub 2025 Apr 11. PMID: 40220793.

🔗 https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(25)00186-X/abstract