Corneal Confocal Microscopy Can Help Monitor Diabetic Eye Disease

Mature doctor examining patient doing eyesight measurement in ophthalmology clinic
Research shows the technology demonstrates utility in measuring diabetic peripheral neuropathy progression.

Corneal confocal microscopy can be successfully utilized as a rapid, noninvasive measure to evaluate diabetic peripheral neuropathy progression, according to research published in Scientific Reports. 

Previous longitudinal studies of patients with diabetic neuropathy have only accounted for a short period of time and lacked detailed neuropathy phenotyping. However, the accurate quantification of diabetic peripheral neuropathy progression is important in identifying patients who will progress to foot ulceration, and to power clinical intervention trials. To mitigate this, researchers conducted a detailed study of neuropathy phenotyping to determine longitudinal utility of varying neuropathy measures in this patient population. 

Spanning 6.5 years, researchers compared changes in corneal confocal microscopy and intraepidermal nerve fiber density with the symptoms, signs, quantitative sensory testing, autonomic function, and neurophysiology in a cohort of 19 people with diabetes (52.2 years ± 14.7 years; diabetes duration, 26 years ± 13.8 years) and 19 healthy controls. 

Age, weight, and body mass index were similar between patients and controls and between patients at both baseline and follow-up. HbA1c was significantly higher in people with diabetes at baseline, but decreased significantly in this group at follow-up, while low-density lipoprotein cholesterol was significantly lower at baseline and decreased further at follow-up evaluation. 

The neuropathy symptom profile and neuropathy disability score were both significantly higher (P =.0005 and P <.0001, respectively) in patients at baseline compared with controls. In the study period, these measures increased significantly in the diabetes group per measurements at follow-up (P =.03 and P =.04, respectively). Measures of vibration perception threshold, cold perception threshold, corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length, as well as intraepidermal nerve fiber density, sural, and peroneal motor nerve conduction velocity all significantly decreased throughout the course of the study compared with controls. 

When the associations between changes in clinical and neuropathy measures were examined, worsening in corneal confocal microscopy in particular was associated with worsening diabetic neuropathy: change in corneal nerve fiber density correlated with change both cold perception threshold and expiration/inspiration ratio, while change in intraepidermal nerve fiber density correlated with change in corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length. 

Study limitations include the small number of patients available for assessment at follow-up. 

“[Corneal confocal microscopy] identifies progressive nerve damage despite improvement in glycemic control and LDL cholesterol,” the study says. “[Corneal confocal microscopy] is a rapid, noninvasive test to identify progression of neuropathy and may have greater utility than symptoms, signs, [quantitative sensory testing], and nerve conduction studies in longitudinal follow-up studies and clinical trials of [diabetic peripheral neuropathy].”


Dhage S, Ferdousi M, Adam S, et al. Corneal confocal microscopy identifies small fibre damage and progression of diabetic neuropathy. Sci Rep. 2021;11(1):1859. doi:10.1038/s41598-021-81302-8.