Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis.

Purpose To determine if corneal subbasal nerve plexus (SBP) parameters derived from wide-area depth-corrected mosaic images are associated with type 2 diabetes. Methods One hundred sixty-three mosaics were produced from eyes of 82 subjects by laser-scanning in vivo confocal microscopy (IVCM). Subjects were of the same age, without (43 subjects) or with type 2 diabetes (39 subjects). Mosaic corneal nerve fiber length density (mCNFL) and apical whorl corneal nerve fiber length density (wCNFL) were quantified and related to the presence and duration of diabetes (short duration < 10 years and long duration ≥ 10 years). Results In mosaics with a mean size of 6 mm2 in subjects aged 69.1 ± 1.2 years, mCNFL in type 2 diabetes was reduced relative to nondiabetic subjects (13.1 ± 4.2 vs. 15.0 ± 3.2 mm/mm2, P = 0.018). Also reduced relative to nondiabetic subjects was mCNFL in both short-duration (14.0 ± 4.0 mm/mm2, 3.2 ± 3.9 years since diagnosis) and long-duration diabetes (12.7 ± 4.2 mm/mm2, 15.4 ± 4.2 years since diagnosis; ANOVA P = 0.023). Lower mCNFL was associated with presence of diabetes (P = 0.032) and increased hemoglobin A1c (HbA1c) levels (P = 0.047). By contrast, wCNFL was unaffected by diabetes or HbA1c (P > 0.05). Global SBP patterns revealed marked degeneration of secondary nerve fiber branches outside the whorl region in long-duration diabetes. Conclusions Wide-area mosaic images provide reference values for mCNFL and wCNFL and reveal a progressive degeneration of the SBP with increasing duration of type 2 diabetes.

[1]  P. Hossain,et al.  Early detection of diabetic peripheral neuropathy with corneal confocal microscopy , 2005, The Lancet.

[2]  Nathan Efron,et al.  Morphometric stability of the corneal subbasal nerve plexus in healthy individuals: a 3-year longitudinal study using corneal confocal microscopy. , 2014, Investigative ophthalmology & visual science.

[3]  Paolo Fogagnolo,et al.  Corneal subbasal nerves changes in patients with diabetic retinopathy: an in vivo confocal study. , 2009, Investigative ophthalmology & visual science.

[4]  Roni M. Shtein,et al.  Differential reduction in corneal nerve fiber length in patients with type 1 or type 2 diabetes mellitus. , 2014, Journal of diabetes and its complications.

[5]  N. Pritchard,et al.  Utility of Assessing Nerve Morphology in Central Cornea Versus Whorl Area for Diagnosing Diabetic Peripheral Neuropathy , 2015, Cornea.

[6]  Minshan Jiang,et al.  Corneal confocal microscopy for assessment of diabetic peripheral neuropathy: a meta-analysis , 2015, British Journal of Ophthalmology.

[7]  Pedram Hamrah,et al.  Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy. , 2015, Investigative ophthalmology & visual science.

[8]  Steven Orlov,et al.  Detection of Diabetic Sensorimotor Polyneuropathy by Corneal Confocal Microscopy in Type 1 Diabetes , 2012, Diabetes Care.

[9]  C. Marfurt,et al.  Anatomy of the human corneal innervation. , 2010, Experimental eye research.

[10]  Dipika V Patel,et al.  In Vivo Confocal Microscopy of Corneal Nerves: An Ocular Biomarker for Peripheral and Cardiac Autonomic Neuropathy in Type 1 Diabetes Mellitus. , 2015, Investigative ophthalmology & visual science.

[11]  Nathan Efron,et al.  Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark): study design and baseline characteristics. , 2014, Diabetes research and clinical practice.

[12]  M. Tsilimbaris,et al.  Correlation of Diabetic Retinopathy and Corneal Neuropathy Using Confocal Microscopy , 2012, Current eye research.

[13]  M. Roden,et al.  Early Detection of Nerve Fiber Loss by Corneal Confocal Microscopy and Skin Biopsy in Recently Diagnosed Type 2 Diabetes , 2014, Diabetes.

[14]  Akitoshi Yoshida,et al.  Imaging of the Corneal Subbasal Whorl-like Nerve Plexus: More Accurate Depiction of the Extent of Corneal Nerve Damage in Patients With Diabetes. , 2015, Investigative ophthalmology & visual science.

[15]  Nathan Efron,et al.  Wide-Field Assessment of the Human Corneal Subbasal Nerve Plexus in Diabetic Neuropathy Using a Novel Mapping Technique , 2012, Cornea.

[16]  H. Swarbrick,et al.  Changes in Corneal Subbasal Nerve Morphology and Sensitivity During Orthokeratology: Onset of Change. , 2017, The ocular surface.

[17]  M. Roden,et al.  Spatial analysis improves the detection of early corneal nerve fiber loss in patients with recently diagnosed type 2 diabetes , 2017, PloS one.

[18]  Nathan Efron,et al.  Corneal Confocal Microscopy Detects Early Nerve Regeneration in Diabetic Neuropathy After Simultaneous Pancreas and Kidney Transplantation , 2012, Diabetes.

[19]  R. Malik,et al.  The Inferior Whorl For Detecting Diabetic Peripheral Neuropathy Using Corneal Confocal Microscopy. , 2015, Investigative ophthalmology & visual science.

[20]  F. Varon Patients with diabetes. , 2009, Journal of the American Dental Association.

[21]  L. Dahlin,et al.  Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy , 2011, Diabetologia.

[22]  Asami Kawasaki,et al.  Corneal nerve fiber pathology in Japanese type 1 diabetic patients and its correlation with antecedent glycemic control and blood pressure , 2011, Journal of diabetes investigation.

[23]  Mehmet Orhan,et al.  Morphologic Alterations of Both the Stromal and Subbasal Nerves in the Corneas of Patients with Diabetes , 2006, Cornea.

[24]  Hyman A. Carrel,et al.  Decreased density of corneal basal epithelium and subbasal corneal nerve bundle changes in patients with diabetic retinopathy. , 2006, American journal of ophthalmology.

[25]  Cecilia Chao,et al.  Corneal Nerve Morphology, Sensitivity, and Tear Neuropeptides in Contact Lens Wear. , 2017, Optometry and vision science : official publication of the American Academy of Optometry.

[26]  P. Zimmet,et al.  Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[27]  A. Orszag,et al.  Reproducibility of in vivo corneal confocal microscopy as a novel screening test for early diabetic sensorimotor polyneuropathy , 2011, Diabetic medicine : a journal of the British Diabetic Association.

[28]  L. Weinehall,et al.  The Västerbotten Intervention Programme: background, design and implications , 2010, Global health action.

[29]  Nathan Efron,et al.  Corneal Confocal Microscopy Predicts 4-Year Incident Peripheral Neuropathy in Type 1 Diabetes , 2015, Diabetes Care.

[30]  G. Kundt,et al.  Imaging and Quantification of Subbasal Nerve Plexus in Healthy Volunteers and Diabetic Patients with or without Retinopathy , 2013, PloS one.

[31]  G. Bitirgen,et al.  Corneal nerve fibre damage precedes diabetic retinopathy in patients with Type 2 diabetes mellitus , 2014, Diabetic medicine : a journal of the British Diabetic Association.

[32]  Asami Kawasaki,et al.  Correlation between sudomotor function, sweat gland duct size and corneal nerve fiber pathology in patients with type 2 diabetes mellitus , 2013, Journal of diabetes investigation.

[33]  A. Boulton,et al.  Corneal Confocal Microscopy Detects Neuropathy in Subjects With Impaired Glucose Tolerance , 2014, Diabetes Care.

[34]  Alfons G H Kessels,et al.  New ophthalmologic imaging techniques for detection and monitoring of neurodegenerative changes in diabetes: a systematic review. , 2015, The lancet. Diabetes & endocrinology.

[35]  Elise M. Halpern,et al.  Structure-Function Relationship Between Corneal Nerves and Conventional Small-Fiber Tests in Type 1 Diabetes , 2013, Diabetes Care.

[36]  Alfredo Ruggeri,et al.  Standardized baseline human corneal subbasal nerve density for clinical investigations with laser-scanning in vivo confocal microscopy. , 2013, Investigative ophthalmology & visual science.

[37]  A. Boulton,et al.  Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes , 2015, Diabetes Care.

[38]  H. Swarbrick,et al.  Changes in corneal subbasal nerve morphology and sensitivity during orthokeratology: Recovery of change. , 2017, The ocular surface.