Corneal Confocal Microscopy: a Surrogate Endpoint for Neurodegeneration in Clinical Trials


Corneal Confocal Microscopy: How It All Began?

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The optical principles of confocal microscopy were described by Minsky in 1955, who cited his rationale for developing this device “to better understand the interconnection of nerve cells’. The first functional microscopy was developed by Petran in 1960, but it was not until 1988 that Dilly demonstrated that device developed by Petran could be mounted horizontally and used to examine the human cornea in vivo. [This is a personal account, so please excuse my use of the ‘first person’ from here on]. In this presentation, I will describe how I became involved in using the first generation of commercially-available confocal microscopes. One of my earliest works with this instrument was to define the structure of the subbasal nerve plexus as seen with this device. By chance, I shared my thoughts on the application of this technique with my personal diabetes doctor, who happened to be Andrew Boulton. Andrew was very interested, but time-poor, so he arranged a meeting with Rayaz Malik, who was sceptical at first, but nevertheless agreed to run a small clinical trial to see if patients with diabetic peripheral neuropathy had a deficit in their corneal nerves. Thus began the translation of this modality from the ophthalmic to the diabetes research domain.