Corneal Confocal Microscopy to Diagnose Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

Area of Science:

• Ophthalmology
• Neurology
• Medical Diagnostics

Background:

• Peripheral neuropathy (PN) is often diagnosed late or missed.
• Corneal confocal microscopy (CCM) measures corneal nerve fiber length (CNFL).
• CNFL shows potential for diagnosing diabetic and other peripheral neuropathies.

Purpose of the Study:

• To systematically review and meta-analyze studies on CNFL's diagnostic utility in peripheral neuropathies.
• To assess differences in CNFL between healthy controls and patients with sub-clinical or clinical PN.
• To evaluate the reliability of CNFL measurements in PN diagnosis.

Main Methods:

• Searched CENTRAL, Embase, and PubMed for peer-reviewed literature.
• Included gray literature from ProQuest Dissertations & Theses.
• Applied PRISMA guidelines for screening and data extraction; two authors worked independently.
• Analyzed CNFL using standardized mean difference and 95% confidence intervals.
• Performed sensitivity analysis to assess bias and model choice (random/fixed effects).

Main Results:

• Included 52 studies with 2995 participants across 34 conditions.
• Found significantly lower CNFL in clinical PN vs. healthy controls (SMD -1.12).
• Observed significantly lower CNFL in sub-clinical PN vs. healthy controls (SMD -0.78).
• Reported significantly lower CNFL in clinical PN vs. sub-clinical PN (SMD -0.93).
• Results remained significant after sensitivity analysis and regardless of the statistical model used.

Conclusions:

• CNFL measurement via CCM is a valuable diagnostic tool for peripheral neuropathies.
• This systematic review and meta-analysis supports CNFL's utility in PN diagnosis.
• CNFL provides a reliable biomarker for identifying neuropathic changes.