Mitra Tavakoli 1 , Maryam Ferdousi 1 , Ioannis N. Petropoulos 1 , Julie Morris 2 , Nicola Pritchard 3 , Andrey Zhivov 4 , Dan Ziegler 5 , 6 , Danièle Pacaud 7 , Kenneth Romanchuk 7 , Bruce A. Perkins 8 , Leif E. Lovblom 8 , Vera Bril 9 , J. Robinson Singleton 10 , Gordon Smith 10 , Andrew J.M. Boulton 1 , Nathan Efron 3 , Rayaz A. Malik , 1 , 11
29 January 2015
Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters.
A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis.
There was a significant linear age-dependent decrease in CNFD (−0.164 no./mm 2 per year for men, P < 0.01, and −0.161 no./mm 2 per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm 2 per year for men, P = 0.26, and −0.050 no./mm 2 per year for women, P = 0.78). CNFL decreased in men (−0.045 mm/mm 2 per year, P = 0.07) and women (−0.060 mm/mm 2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter.