“The cell never acts; it reacts.”
—Ernst Haeckel
A single layer of corneal endothelial cells covers the posterior surface of the Descemet membrane in a well-arranged mosaic pattern. These endothelial cells interdigitate and contain various junctional complexes. This interconnected cell layer provides a leaky barrier to aqueous humor and allows the transfer of small molecules and electrolytes between the endothelial cells. In humans, these cells are uniformly 5 μm in thickness and 20 μm in width and polygonal (mostly hexagonal) in shape.
The first direct visualization of the corneal endothelium was performed by Vogt in 1918.1 Using the slitlamp microscope, he demonstrated that the endothelial cell mosaic could be visualized in the axis of the reflected light. However, it was not until 1968 that David Maurice described the first laboratory specular microscope that could be used to study living corneas.2 Later, modifications to this made by Laing et al. and by Bourne and Kaufman allowed routine clinical examination and photography of the corneal endothelium.3,4 Specular microscopes have evolved from wide-field, contact microscopes to narrow-field, high-resolution noncontact devices.5,6 Currently, we are able to perform not only qualitative analysis but also detailed quantitative analysis of endothelial cells, including endothelial cell density (ECD) (measured as cells/mm2) mean cell area (measured as μm2/cell), coefficient of variation (CoV) (standard deviation of the cell areas/mean cell area), and pleomorphism (percentage of hexagonal cells). Previous studies have demonstrated that ECD decreases throughout life.7 This physiological attrition seems to happen rapidly from birth to the first few years of life, followed by a state of endothelial cell stability from ages 20 to 50 years, and a significant decrease after the age of 60 years with an average age-related loss of approximately 0.5% per year.8–10
The most common endothelial abnormality that the clinician encounters in clinical practice is corneal guttata. Guttata are excrescences of Descemet membrane that can be seen with specular microscopy much earlier than by slitlamp biomicroscopy. ECD alone is not the most sensitive measure of endothelial health because the endothelium can function even at low ECDs (<500 cells/mm2).11 Polymegethism (variation in the cell area as determined by CoV) and pleomorphism might be more sensitive measures of endothelial cell stress. The increased sensitivity of detailed morphometric analysis of the endothelium can be illustrated by the following example: If only 1 cell is lost in a cluster of 100 cells, the mean cell area would increase by a maximum of 1%, a statistically nondetectable difference. However, if a hexagonal cell is lost in a cluster of 100 cells, at least 2 cells (2%) or possibly up to 6 cells (6%) will show significant changes in cell patterns owing to repair mechanism, including cell stretch and slide. Therefore, cell loss not detectable by ECD measurements alone might be detectable by quantification of cellular polymegethism and pleomorphism.
A clear cornea with normal pachymetry is no assurance of a normal ECD or endothelial morphology. The ECD at which corneal edema occurs is highly variable but has been estimated to be between 300 and 700 cells per mm2.11,12 Assuming a cell loss in the range of 0 to 30% for any intraocular surgical procedure, a patient should have at least 1000 to 1200 cells per mm2 to safely undergo anterior segment surgery without the risk of endothelial decompensation.13
In this issue, Viberg and colleagues (page 961) report a registry-based cohort study on incidence of corneal transplantation in patients with corneal guttata. By pooling data from the Swedish National Cataract and Corneal Transplant Registry, they calculated the risk of corneal transplantation after phacoemulsification as 68.2 times higher for patients with corneal guttata than those without. The incidence rate for corneal transplantation after phacoemulsification was 88/10,000 person years in patients with guttata compared with 1.4/10,000 person years in patients without guttata. Although details of quantitative analysis of endothelium, nature of ophthalmic viscosurgical device, and energy parameters during phacoemulsification are not provided, this study provides useful global data. Dalby and colleagues (page 1030) report their results from a randomized clinical trial comparing endothelial cell loss after IOL exchange with retropupillary fixation of an iris claw lens compared with IOL repositioning by scleral suturing. At 2 years, both these procedures seemed safe in relation to corneal endothelial cell loss.
Routine specular microscopy should be a part of preoperative evaluation for any anterior segment intraocular surgical procedure because it helps the surgeon to objectively evaluate the state of the corneal endothelial cells. When the ECD is on the lower range, it behooves the surgeon to make certain that the patient understands the increased risk of postoperative corneal edema/decompensation.
REFERENCES
1. Vogt A. Die Sichtbarkeit des lebenden Hornhautendothesis. Ein Beitrog zur Methodik der Spaltampenmikroskopie. Grafes Arch Ophthalmol 1920;101:123–144
2. Maurice DM. Cellular membrane activity in the corneal endothelium of the intact eye. Experientia 1968;24:1094–1095
3. Laing RA, Sandstrom MM, Leibowitz HM. In vivo photomicrography of the corneal endothelium. Arch Ophthalmol 1975;93:143–145
4. Bourne WM, Kaufman HE. Specular microscopy of human corneal endothelium in vivo. Am J Ophthalmol 1976;81:319–323
5. Lohman LE, Rao GN, Aquavella JA. Optics and clinical applications of wide-field specular microscopy. Am J Ophthalmol 1981;92:43–48
6. Oblak E, Doughty MJ, Oblak L. A semi-automated assessment of cell size and shape in monolayers, with optional adjustment for the cell-cell border application to human corneal endothelium. Tissue Cell 2002;34:283–295
7. Abib FC, Barreto J Jr. Behavior of corneal endothelial cell density over a lifetime. J Cataract Refract Surg 2001;27:1574–1578
8. Nucci P, Brancato R, Mets MB, Shevell SK. Normal endothelial cell density range in childhood. Arch Ophthalmol 1990;108:247–248
9. Sherrad ES, Buckely RJ. Relocation of specific endothelial features with the clinical specular microscope. Br J Ophthalmol 1981;65:820–827
10. Bourne WM, Hodge DO, Nelson LR. Corneal endothelium five years after transplantation. Am J Ophthalmol 1994;118:185–196
11. Lass JH, Benetz BA, Gal RL, Kollman C, Raghinaru D, Dontchev M, Mannis MJ, Holland EJ, Chow C, McCoy K, Price FW Jr, Sugar A, Verdier DD, Beck RW; The Writing Committee for the Cornea Donor Study Research Group. Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: specular Microscopy Ancillary Study. Ophthalmology 2013;120:2428–2435
12. Mishima S. Clinical investigations on the cornel endothelium. Ophthalmology 1982;89:525–530
13. Corneal endothelial photography. American Academy of Ophthalmology. Ophthalmology 1991;98:1468
