WHAT YOU NEED TO KNOW ABOUT SPECULAR MICROSCOPY
FOR OPHTHALMIC MEDICAL DEVICE CLINICAL TRIALS

Specular microscopy is an essential part of the clinical evaluation of new implantable ophthalmic devices and pharmaceuticals. It is in sponsors’ interest to maintain a high level of control of equipment and data reading capability throughout the course of each and every clinical study. Failure to do so may result in what is perceived by reviewers to be an inadequate study and ultimately may jeopardize product approval schedules.

Medical device manufacturers often rely on clinical sites’ existing specular microscopes to meet their studies’ needs. This approach inherently results in questionable control over equipment standardization, operator training in image capture, storage and transfer, suitable inter-site transportation, equipment calibration, preventative maintenance, image quality, and reading uniformity.

The FDA has posted a draft proposed guidance to Industry applying to any ocular implant whose primary indication is the modification of the refractive power of a phakic eye to improve distance and/or near uncorrected visual acuity. This document also applies to any intraocular lens (IOL) intended for clear lens exchange. According to this draft guidance, "maintenance of endothelial cell counts is considered to be the primary safety endpoint for studies of refractive ophthalmic implants". "FDA’s main concern is the possibility of a chronic loss of endothelial cells, that, even at a low yearly rate could, over time, lead to corneal edema and decompensation".

A considerable amount of attention is given in the refractive guidance document and in a FDA document entitled "Phakic Intraocular Lenses - Clinical Topics for Ophthalmic Devices Panel Discussion (August 2, 2002)" to problems associated with data collection, image quality and data interpretation, with recommendations presented that strive to restore a measure of consistency and reliability to specular microscopy data collection during clinical evaluations of refractive implants:

• Non-contact specular microscopes are strongly recommended.
• The same model of specular microscope should be used at each site.
• Images should be stored on 35 mm slides, half-inch video, or in electronic format. Specular cameras that can record digitized images on disk or to email are preferable for ease of data transfer.
• Equipment calibration should be checked by the study monitor on at least a yearly basis. Calibration of the specular microscopes at the sites across the study should be performed by comparing cell density data from a standard set of images evaluated by each site.
• The study monitor should perform periodic validation of the study site’s methodology unless an automated camera is used.
• A reading center is advisable, although not required. However, if a reading center is not used, the person responsible for taking and accepting the images should be certified for ability to take high quality images, and be adequately trained in both endothelial cell photography and in the evaluation of the images. If possible, the same trained and certified technician/photographer should be used at each site throughout the study. A backup technician who is trained and certified should also be available.
• The technician/photographer should use a standardized counting method for the determination of cell density. Fixed-frame analysis, variable frame analysis, a center method, a corner method, or auto-count may be used.

Konan Clinical Group
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