Review of Corneal Endothelial Specular Microscopy for FDA Clinical Trials of Refractive Procedures, Surgical Devices, and New Intraocular Drugs and Solutions

Abstract

Specular microscopy can provide a non-invasive morphological analysis of the corneal endothelial cell layer from subjects enrolled in clinical trials. The analysis provides a measure of the endothelial cell physiological reserve from aging, ocular surgical procedures, pharmaceutical exposure, and general health of the corneal endothelium. The purpose of this review is to discuss normal and stressed endothelial cell morphology, the techniques for determining the morphology parameters, and clinical trial applications.

Morphology of endothelial cells from different regions of the equine cornea

“…In order to increase the visibility of the cell boundary and thus allow a more reliable estimate of morphological parameters, alizarin red dye was used in this study. Poor recognition of cell borders can result in errors of omitting cells or double entering cells during the analysis (McCAREY et al, 2008). In the present study, the photographic magnification was large enough to allow accurate tracing of individual cells.…”

“…Studies reported in the literature concerning the comparison of endothelial density in the central and peripheral regions of the cornea by specular microscopy showed controversial results. In humans, rabbits and dogs, there was no significant difference in endothelial parameters between central and peripheral regions of healthy corneas (TAYLOR & HUNT, 1981;GWIN et al, 1982;McCAREY et al, 2008). However, AMANN et al (2003) concluded using specular microscopy and histological methods that human corneal endothelium has a higher density in peripheral regions compared with the central region.…”

“…Pleomorphism is the variation in cell shape represented by the percentage of hexagonal cells (LAING et al, 1979). Principal among the techniques used to study the corneal endothelium are specular microscopy and scanning electron microscopy (SEM) (PIGATTO et al, 2005a, PIGATTO et al, 2005bMcCAREY et al, 2008). Aside from these techniques, the analysis of the corneal endothelium using optical microscopy after cell staining with alizarin red has also been used (RODRIGUES et al, 2009 morphometric and morphological endothelial cell studies provided reference information for the investigation of clinical diseases, such as uveitis, glaucoma, and the effects of aging on different regions of the cornea.…”

In vivo confocal microscopy of the corneal endothelium: comparison of three morphometry methods after corneal transplantation

“…Cell analysis was first performed using the automated option on the NAVIS software without manual cell border correction, which is part of the Confoscan 4 package (version 3.6.6, Nidek Technologies). Following the automated analysis, a manual cell count was carried out, a technique similar to the 'frame method' described in a recent review by McCarey et al, 27 also available on the NAVIS system. This analysis was performed including cells overlapping the upper and left border of the ROI.…”

Corneal endothelial cell density and morphology in rabbits’ eyes using contact specular microscopy

“…Some studies evaluating animals of a unique age group have already been conducted and concluded that most cells have six sides (PIGATTO et al, 2004;PIGATTO et al, 2005a;PIGATTO et al, 2006;PIGATTO et al, 2008;IGATTO et al, 2009;TAMAYO-ARANGO et al, 2009;FRANZEN et al, 2010;ALBUQUERQUE et al, 2015;COYO et al, 2016). In humans with a healthy cornea, more than 60% of the corneal endothelium cells are six-sided (McCAREY et al, 2008). A decrease in the number of endothelial cells with six sides commonly occurs with aging (ALBUQUERQUE et al, 2015;COYO et al, 2016).…”