Examining the Corneal Endothelium: Focus on Specular Microscopy

Examining the Corneal Endothelium: Focus on Specular Microscopy
Murat V. Kalayoglu, M.D., Ph.D.
Contributing Editor

A vast amount of information about the eye can be gathered through a slit-lamp exam conducted by an Ophthalmologist. Each layer of the cornea can be examined through a focused slit beam of light, and the light path can be angled and reflected off the iris to illuminate the endothelium. In doing so, the Ophthalmologist can single out the epithelium, stroma or endothelium for close examination. In this manner, a myriad of deposits on the endothelial layer can be picked up, including guttae that may indicate Fuchs’ corneal dystrophy, a Krukenberg’s spindle suggesting pigmentary dispersion syndrome and pigmentary glaucoma, and keratic precipitates (KP) that point towards uveitis. However, in addition to direct slit-lamp visualization of the endothelium, the Ophthalmologist also has access to specular microscopes that enable a magnified, direct view of the endothelium.

The corneal endothelium is a hexagonal cell monolayer that does not divide significantly. An infant’s endothelial cell count begins at 3500 – 4000 cells/mm2. As individuals age, the cell count declines; adults typically only have 2400 to 3200 cells/mm2 of endothelium. The endothelium’s chief function is to remove fluid from the corneal stroma, allowing the cornea to remain optically clear. Certain diseases that damage the corneal endothelium, such as Fuchs’ corneal dystrophy, lead to endothelial changes such as guttae and eventually lead to corneal edema. These individuals often require a corneal transplantation since endothelial cells do not regenerate significantly when damaged. Additional insults that can damage the corneal endothelium usually come from trauma; often, a long cataract case, especially when extracting a large mature cataract, may lead to endothelial damage and cell loss. Sometimes, patients with relatively few endothelial cell counts undergoing cataract surgery may require extended periods to resolve their corneal edema, chiefly because only a few endothelial cells are pumping fluid out of the stroma and into the anterior chamber. Younger patients are relatively much more likely to recover after traumatic insult to the endothelium because they tend to have many more endothelial cells compared with elderly individuals. In fact, otherwise healthy elderly individuals may have guttae that resemble those seen in Fuchs’ dystrophy, indicating a relatively decompensated endothelium due to age.

Specular microscopes have long been useful instruments to visualize the corneal endothelium. Early work by Vogt and Goldmann helped visualize endothelial cell patterns at low magnification. Vogt coined the word ‘Spiegelmikroskopie’ to describe the process, which translated to English as ‘specular microscopy’. In 1968, David Maurice developed the first high powered specular microscope to photograph endothelial cells ex vivo at 500x.

Today, Ophthalmologists, particularly corneal specialists, rely on specular microscopes to examine the corneal endothelium at a magnified level. Specular microscopy yields important information that guides the physician’s decision-making process when managing a corneal disorder. For example, specular microscopy enumerates the number of endothelial cells, allowing an objective assessment of the patient’s endothelium and helping reach a mutual decision on whether to proceed with transplantation. In addition, specular microscopy can help visualize the hexagonal layer of endothelial cells, magnifying specific damaged areas and deposits. Such techniques may be helpful when differentiating Fuchs’ dystrophy from posterior polymorphous membranous dystrophy (PPMD), in which the endothelium becomes multilayered and develops epithelioid features; in these instances, specular microscopy may be extremely helpful in establishing a diagnosis, since it can help distinguish the morphological features of these altered cells from the rest of the endothelium.

Additional features built into modern specular microscopes may include a capacity to also measure corneal thickness, and software algorithms that can determine the percentage of cells that show polymegathism and pleomorphism. Some specular microscopes also are able to capture video and pictures of the endothelium that may be useful when monitoring a patient for decompensation over extended periods. Both contact and non-contact specular microscopes are available.

New technologies such as corneal confocal microscopy are being developed to examine in detail each individual corneal layer, including the endothelium. Confocal microscopy offers several advantages, including the capacity to focus on a single depth to obtain clear images, and the ability to collect images from serial sections within a given thickness of tissue. However, emerging technologies are unlikely to replace specular microscopy given its relatively inexpensive method to yield a large amount of useful data.

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