March 2014
Volume 55, Issue 3
Research Highlight  |   March 2014
From the Bedside to the Bench and Back Again, With Corneal Confocal Microscopy
Investigative Ophthalmology & Visual Science March 2014, Vol.55, 1231. doi:
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      Rayaz A. Malik; From the Bedside to the Bench and Back Again, With Corneal Confocal Microscopy. Invest. Ophthalmol. Vis. Sci. 2014;55(3):1231.

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      © ARVO (1962-2015); The Authors (2016-present)

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In this issue of IOVS, Davidson and colleagues 1 apply a range of conventional techniques and the novel ophthalmic technique of corneal confocal microscopy (CCM) to phenotype nerve damage in an experimental model of prediabetes and type 2 diabetes. The key findings are that CCM allows a noninvasive demonstration of an early reduction in corneal innervation that correlates with a reduction in both corneal and intraepidermal nerve fiber density derived using invasive corneal and skin biopsy and conventional tissue histology. These abnormalities occur in parallel with a reduction in corneal sensitivity and conventionally accepted end points of thermal nociception latency and sensory nerve conduction velocity. These data build on the concept that CCM allows the rapid, noninvasive, and hence reiterative study of corneal nerves in a variety of animal species, 2 and in particular in the diagnosis and assessment of therapeutic efficacy in experimental diabetes 3,4 and patients with diabetic neuropathy. 5,6  
The current study exemplifies the bedside to bench, reverse translational approach, as CCM is predominantly used in clinical research and practice. In so doing it addresses why so many successful experimental therapies have failed to “cross the valley of death” and translate into therapies for our patients with diabetic neuropathy. 7 A key roadblock appears to be the lack of an adequate surrogate marker in clinical trials of diabetic neuropathy. Hence, CCM may “bridge the gap” as it detects and tracks early nerve damage and the response to therapeutic intervention in experimental diabetes 3,4 and in diabetic patients. 5,6 Of traditional “translational” value, that is, bench to bedside, Davidson and colleagues 1 also identify that the earliest corneal nerve damage is at the inferior whorl, providing important insights into the application of CCM in the diagnosis and assessment of therapeutic efficacy in patients with diabetic neuropathy. 
Davidson EP Coppey LJ Kardon RH Yorek MA. Differences and similarities in development of corneal nerve damage and peripheral neuropathy and in diet-induced obesity and type 2 diabetic rats. Invest Ophthalmol Vis Sci . 2014; 55: 1222–1230. [CrossRef] [PubMed]
Reichard M Hovakimyan M Wree A Comparative in vivo confocal microscopical study of the cornea anatomy of different laboratory animals. Curr Eye Res . 2010; 35: 1072–1080. [CrossRef] [PubMed]
Chen DK Frizzi KE Guemsey LS Ladt K Mizisin AP Calcutt NA. Repeated monitoring of corneal nerves by confocal microscopy as an index of peripheral neuropathy in type-1 diabetic rodents and the effects of topical insulin [published online ahead of print October 21, 2013]. J Peripher Nerv Syst . doi:10.1111/jns5.12044 .
Davidson EP Coppey LJ Yorek MA. Early loss of innervation of cornea epithelium in streptozotocin-induced type 1 diabetic rats: improvement with ilepatril treatment. Invest Ophthalmol Vis Sci . 2012; 53: 8067–8074. [CrossRef] [PubMed]
Petropoulos IN Alam U Fadavi H Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care . 2013; 36: 3646–3651. [CrossRef] [PubMed]
Tavakoli M Mitu-Pretorian M Petropoulos IN Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes . 2013; 62: 254–260. [CrossRef] [PubMed]
Butler D. Translational research: crossing the valley of death. Nature . 2008; 453: 840–842. [CrossRef] [PubMed]

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