Petropoulos IN, et al. Diabetes Metab J. 2018 Aug;42(4):255-269. https://doi.org/10.4093/dmj.2018.0056

Introduction: Corneal confocal microscopy (CCM) is a rapid non‐invasive ophthalmic imaging technique that identifies corneal nerve fiber damage. Small studies suggest that CCM could be used to assess patients with diabetic peripheral neuropathy (DPN).Aim: To undertake a systematic review and meta‐analysis assessing the diagnostic utility of CCM for sub‐clinical DPN (DPN⁻) and established DPN (DPN⁺).Data sources: Databases (PubMed, Embase, Central, ProQuest) were searched for studies using CCM in patients with diabetes up to April 2020.Study selection: Studies were included if they reported on at least one CCM parameter in patients with diabetes.Data extraction: Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and inferior whorl length (IWL) were compared between patients with diabetes with and without DPN and controls. Meta‐analysis was undertaken using RevMan V.5.3.Data synthesis: Thirty‐eight studies including ~4,000 participants were included in this meta‐analysis. There were significant reductions in CNFD, CNBD, CNFL, and IWL in DPN⁻ vs controls (P < 0.00001), DPN⁺ vs controls (P < 0.00001), and DPN⁺ vs DPN⁻ (P < 0.00001).Conclusion: This systematic review and meta‐analysis shows that CCM detects small nerve fiber loss in subclinical and clinical DPN and concludes that CCM has good diagnostic utility in DPN.

Introduction To assess the effect of exenatide and pioglitazone or basal-bolus insulin on diabetic peripheral neuropathy (DPN) in patients with poorly controlled type 2 diabetes (T2D). Research design and methods This is a substudy of the Qatar Study, an open-label, randomized controlled trial. 38 subjects with poorly controlled T2D were studied at baseline and 1-year follow-up and 18 control subjects were assessed at baseline only. A combination of exenatide (2 mg/week) and pioglitazone (30 mg/day) or glargine with aspart insulin were randomly assigned to patients to achieve an HbA1c <53 mmol/mol (<7%). DPN was assessed with corneal confocal microscopy (CCM), DN4, vibration perception and sudomotor function. Results Subjects with T2D had reduced corneal nerves, but other DPN measures were comparable with the control group. In the combination treatment arm (n=21), HbA1c decreased by 35.2 mmol/mol (3.8 %) (p<0.0001), body weight increased by 5.6 kg (p<0.0001), corneal nerve branch density increased (p<0.05), vibration perception worsened (p<0.05), and DN4 and sudomotor function showed no change. In the insulin treatment arm, HbA1c decreased by 28.7 mmol/mol (2.7 %) (p<0.0001), body weight increased by 4.6 kg (p<0.01), corneal nerve branch density and fiber length increased (p≤0.01), vibration perception improved (p<0.01), and DN4 and sudomotor function showed no change. There was no association between the change in CCM measures with change in HbA1c, weight or lipids. Conclusions Treatment with exenatide and pioglitazone or basal-bolus insulin results in corneal nerve regeneration, but no change in neuropathic symptoms or sudomotor function over 1 year.

Purpose: To evaluate whether corneal confocal microscopy (CCM) detects axonal degeneration and whether this is associated with retinal nerve fiber degeneration and clinical disability in patients with multiple sclerosis (MS). Methods: Twenty-five patients with MS and 25 healthy control subjects underwent CCM, optical coherence tomography (OCT), and assessment of neurological disability using the expanded disability status scale (EDSS) and MS severity score (MSSS). Results: In patients with MS compared with controls, there was a significant reduction in corneal nerve fiber density (CNFD), branch density (CNBD), and length (CNFL). There was no significant difference in CCM parameters between patients with optic neuritis (MS-ON) and without (MS-NON), or between relapsing-remitting (RRMS) and secondary-progressive MS (SPMS). There was significant thinning of the retinal nerve fiber layer (RNFL) in the global, temporal, temporal superior, and temporal inferior quadrants, with no difference between MS-ON and MS-NON. Patients with SPMS compared with RRMS had a significantly lower global, temporal superior, temporal inferior, nasal, and nasal superior RNFL. The EDSS and MSSS correlated significantly with CNBD, nasal, nasal superior, and nasal inferior RNFL and with CNBD and nasal inferior RNFL, respectively. Conclusions: CCM and OCT detect significant corneal and retinal nerve degeneration which relates to the severity of neurological deficits in patients with mild MS.