324-OR: Rapid Corneal Nerve Fibre Loss Predicts Neuropathy Progression in Diabetes: A Longitudinal Multinational Consortium Study
Authors: LEWIS EVAN J.H. , LOVBLOM LEIF ERIK , FERDOUSI MARYAM , JEZIORSKA MARIA , PACAUD DANIÈLE , PRITCHARD NICOLA , SHTEIN RONI M. , EFRON NATHAN , TAVAKOLI MITRA , BRIL VERA , MALIK RAYAZ A. , PERKINS BRUCE A. 
Published: June 2019

The measurement of corneal nerve fibre length (CNFL) by in vivo corneal confocal microscopy serves as a biomarker for the presence of diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the threshold for abnormal CNFL change, its prevalence in T1D and T2D, and if this biomarker could predict DSP progression. Data from 622 diabetes patients (424 T1D and 198 T2D) and 204 nondiabetic controls were examined as part of a 5-centre multinational consortium study. Patients had at least 1-year of follow-up data and were classified with Rapid CNFL (RCNFL) loss if the change in CNFL was beyond the 5thpercentile of the controls. Controls were 38±20 y, had a median of 3 follow-up visits over a median of 3.0 y, baseline CNFL of 16±4 mm/mm2, and a mean annual change in CNFL of -0.1%[90% CI, -5.9-5.0%]. RCNFL loss was defined by the 5th percentile value of -6% or greater loss. T1D patients were 40±19 y, had a median of 3 visits over a median of 4.4 y, baseline CNFL of 13.5±4.3 mm/mm2 and had a mean annual change in CNFL of -0.8%[90% CI, -14.0-9.9%]. T2D patients were 60±8 y, had a median of 3 visits over a median of 5.3 y, baseline CNFL of 13.8±4.4 mm/mm2 and a mean annual change in CNFL of -0.2%[90% CI, -14.1-14.3%]. Prevalence of RCNFL loss was similar between T1D (64(16.0%)) and T2D (37(19.4%), p=0.31). Baseline CNFL was not different between cases with RCNFL loss (14.3±4.2 mm/mm2) and diabetes controls (13.5±4.3 mm/mm2) (p=0.073). Cases were more likely to have DSP at baseline (47, (47%) vs. 144, (30%), p=0.001). During follow-up, CNFL decreased in cases (-3.5 mm/mm2[-5.7, -1.5] vs. 0.59 mm/mm2 [-1.3, 2.4], p&gt;0.001). Cases showed DSP progression measured by changes in sural nerve conduction velocity (0.0 m/s [-1.2, 2.4] vs. 0.2 m/s [-1.1, 5.0]. p=0.027) and peroneal conduction velocity (-1.1 m/s [-3.6, 0.9] vs. -0.6 [-2.8, 1.5], p=0.001) compared to diabetes controls. Rapid CNFL loss occurs in over 16% of diabetes patients and appears to predict those at highest risk for DSP progression.

Disclosure
E.J.H. Lewis: Board Member; Spouse/Partner; Nutarniq Corp. Employee; Self; Nutarniq Corp. L. Lovblom: None. M. Ferdousi: None. M. Jeziorska: None. D. Pacaud: Other Relationship; Self; Novo Nordisk A/S, Sandoz, TOLMAR. N. Pritchard: None. R.M. Shtein: None. N. Efron: None. M. Tavakoli: None. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alexion Pharmaceuticals, Inc., Alnylam, CSL Behring. Consultant; Self; Pfizer Inc. Research Support; Self; Baxter, Biogen, Grifols, UCB, Inc. R.A. Malik: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi.

Funding
National Institutes of Health (1DP3DK104386-01)