Ioannis N Petropoulos1, Georgios Ponirakis1, Maryam Ferdousi2, Shazli Azmi3, Alise Kalteniece2, Adnan Khan1, Hoda Gad1, Bilal Bashir4, Andrew Marshall5, Andrew J M Boulton3, Handrean Soran2, Rayaz A Malik6. 1. Research Division, Weill Cornell Medicine-Qatar, Doha, Qatar. 2. Faculty of Biology, Medicine and Health, University of Manchester, Cardiovascular Trials Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 3. Faculty of Biology, Medicine and Health, University of Manchester, Cardiovascular Trials Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom; Centre for Diabetes, Endocrinology and Metabolism, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 4. Centre for Diabetes, Endocrinology and Metabolism, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 5. Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom; Clinical Neurophysiology, The Walton Centre, Liverpool, United Kingdom; Division of Neuroscience and Experimental Psychology, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom. 6. Research Division, Weill Cornell Medicine-Qatar, Doha, Qatar; Faculty of Biology, Medicine and Health, University of Manchester, Cardiovascular Trials Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom. Electronic address: ram2045@qatar-med.cornell.edu.
Abstract
PURPOSE: Diagnosing early diabetic peripheral neuropathy remains a challenge due to deficiencies in currently advocated end points. The cornea is densely innervated with small sensory fibers, which are structurally and functionally comparable to intraepidermal nerve fibers. Corneal confocal microscopy is a method for rapid, noninvasive scanning of the living cornea with high resolution and magnification. METHODS: This narrative review presents the framework for the development of biomarkers and the literature on the use and adoption of corneal confocal microscopy as an objective, diagnostic biomarker in experimental and clinical studies of diabetic peripheral neuropathy. A search was performed on PubMed and Google Scholar based on the terms "corneal confocal microscopy," "diabetic neuropathy," "corneal sensitivity," and "clinical trials." FINDINGS: A substantial body of evidence underpins the thesis that corneal nerve loss predicts incident neuropathy and progresses with the severity of diabetic peripheral neuropathy. Corneal confocal microscopy also identifies early corneal nerve regeneration, strongly arguing for its inclusion as a surrogate end point in clinical trials of disease-modifying therapies. IMPLICATIONS: There are sufficient diagnostic and prospective validation studies to fulfill the US Food and Drug Administration criteria for a biomarker to support the inclusion of corneal confocal microscopy as a primary end point in clinical trials of disease-modifying therapies in diabetic neuropathy.
PURPOSE: Diagnosing early diabetic peripheral neuropathy remains a challenge due to deficiencies in currently advocated end points. The cornea is densely innervated with small sensory fibers, which are structurally and functionally comparable to intraepidermal nerve fibers. Corneal confocal microscopy is a method for rapid, noninvasive scanning of the living cornea with high resolution and magnification. METHODS: This narrative review presents the framework for the development of biomarkers and the literature on the use and adoption of corneal confocal microscopy as an objective, diagnostic biomarker in experimental and clinical studies of diabetic peripheral neuropathy. A search was performed on PubMed and Google Scholar based on the terms "corneal confocal microscopy," "diabetic neuropathy," "corneal sensitivity," and "clinical trials." FINDINGS: A substantial body of evidence underpins the thesis that corneal nerve loss predicts incident neuropathy and progresses with the severity of diabetic peripheral neuropathy. Corneal confocal microscopy also identifies early corneal nerve regeneration, strongly arguing for its inclusion as a surrogate end point in clinical trials of disease-modifying therapies. IMPLICATIONS: There are sufficient diagnostic and prospective validation studies to fulfill the US Food and Drug Administration criteria for a biomarker to support the inclusion of corneal confocal microscopy as a primary end point in clinical trials of disease-modifying therapies in diabetic neuropathy.
Authors: Frank G Preston; Yanda Meng; Jamie Burgess; Maryam Ferdousi; Shazli Azmi; Ioannis N Petropoulos; Stephen Kaye; Rayaz A Malik; Yalin Zheng; Uazman Alam Journal: Diabetologia Date: 2021-11-21 Impact factor: 10.122
Authors: George N Okoli; Rasheda Rabbani; Otto L T Lam; Nicole Askin; Tanya Horsley; Lorraine Bayliss; Ildiko Tiszovszky; John M Embil; Ahmed M Abou-Setta Journal: BMJ Open Diabetes Res Care Date: 2022-05