Newer, more sophisticated instruments are changing the way we view the cornea. A review of the latest diagnostic tools that assess anterior corneal shape and integrity will help clinicians better understand the healthy cornea and what can be considered an abnormal reading. These new instruments help practitioners define disease and the changes in corneal shape and integrity it causes—all of which can affect vision.
The point spread function helps uncover corneal
abnormalities. Here, a cornea shows no distortion.

The Cornea Up Close

Before proceeding, it’s helpful to refresh our memories on the basic corneal anatomy and physiology we all learned in school so that we can better recognize when problems occur. The corneal layers, totaling an average of 540μm in thickness, include the epithelium, Bowman’s layer, stroma, Descemet’s membrane and endothelium.1-2 The stroma and epithelium make up the majority of the cornea’s tissue thickness.

The tear film, while a distinct entity, interacts with the corneal epithelium; one cannot exist without the other, and their interactions are an important consideration when diagnosing corneal irregularities.

Due to eyelid friction, the superior epithelium is thinner compared with the inferior region. Greater frictional forces are applied to the superior cornea as the upper lid reaches its maximum speed as it crosses the visual axis.3-7 The lid then skims across the inferior part of the cornea. Due to the anatomical difference between the nasal and temporal aspects of the cornea, the epithelium is thinner on the temporal side as the outer canthus is higher than the inner canthus. In addition, the temporal portion of the lid is higher than the nasal side.

A distorted point spread function, as seen here, indicates a
surface abnormality.

The organization of collagen fibrils in the cornea is critical to corneal shape and clarity. The preferred orientation of collagen fibrils in the normal cornea is along the vertical and horizontal meridians.8 There is also a regular increase in collagen mass from the center of the cornea toward the periphery.

The corneal endothelium—a monolayer of hexagonal cells that cover the posterior surface of the cornea—maintains the transparency of the corneal stroma by controlling corneal hydration.9 These specialized cells do not regenerate, so when cellular abnormalities occur, the corneal stroma swells, changing the collagen arrangement and affecting transparency.

Identifying Pathology
The relationship between epithelial and stromal thickness during an episode of edema and corneal desiccation can be monitored with OCT global pachymetry imaging.10 The maps of the epithelium, stroma and total corneal thickness are useful during routine screening to identify corneal abnormalities such as dry eye disease (DED) and ectasia.11 OCT imaging is also helpful in observing corneal intrusion with foreign bodies, surgical sutures, corneal dystrophies, infiltrates and corneal ulcerations. Finally, revealing the interaction of the epithelium and stroma also highlights the process of healing and can improve surgical outcomes when the cornea is involved.

The power map, this one showing astigmatism, is key to
understanding the changes in corneal shape.

The first stage of ectasia is the thinning of the stroma, although detection becomes difficult due to the corneal epithelium responding by becoming thicker, causing the total corneal thickness to remain unchanged. The only method of detecting the thickness of the epithelium and stroma using global pachymetry is with software that separates the layers—a feature that will become a modification on current anterior segment OCT devices as software improves. The epithelium becomes thicker over the depression and thinner over the elevations, smoothing over the corneal stromal irregularities and creating aberration-free visual acuity during the initial stages of the disease.12

As ectasia progresses, the epithelium begins to thin after the initial thickening stage, and the cornea distorts at the site of the stromal thinning. At the same time, the epithelium thins, forming a base encircling the area of stromal thinning giving support to the structure.13

In ectasia the collagen fibrils shift toward a preferred orientation of 20/160 degrees. There is also an increase in the irregularity of the scattering of the fibrils. The orientation of collagen fibrils inside the cone is altered considerably, while those in the periphery retain the preferred vertical/horizontal orientation.

Corneal topography assumes this change in collagen structure that affects the shape of the cornea.14 In Scheimpflug topography, a spinning mirror provides an enhanced depth of focus without distorting the image. Clinicians can image not only the curvature of the anterior cornea (as with placido-based topography), but also elevation of the anterior cornea, pachymetry and curvature of the posterior cornea. Indices such as center surround index, surface regularity index and standard deviation of the power quantify the change in corneal shape.

The most common index used with Scheimpflug topography is the Belin-Ambrosio Enhance Ectatic Display, which uses a modified best-fit sphere to classify the shape of the cornea. In a central 8mm zone, the thinnest part of the cornea is excluded (so that it does not skew the best-fit sphere). This enhanced best-fit sphere is compared to the standard best-fit sphere.15 If there is no pathology, those spheres will agree, but the difference between those spheres will be significant when ectasia is present. Studies have found that the Belin-Ambrosio index can predict risk of ectasia prior to refractive surgery.16,17 But, perhaps most impactful for optometrists, research suggests it can be extremely predictive for distinguishing a normal cornea from keratoconus or other non-inflammatory thinning disorders, such as pellucid marginal degeneration.18

The epithelium thickens peripherally, lending support at
the base of the stromal thinning.

Dry Eye
Corneas with DED have exhibited corneal epithelium thickness variation due to inflammation and desquamation of the cellular layer. During the initial stages of DED, the inflammatory processes and epithelium proliferation causes epithelium thickening. As the disease progresses, limbal stem cell atrophy results in epithelial thinning. Because superior and inferior stem cell population in the normal eye is greater in the superior and inferior cornea than the nasal and temporal regions, epithelial thickness change is more dramatic in the peripheral cornea than the central.19

As the tear film becomes more deficient and lubrication is reduced, greater frictional force upon the superior cornea results in an increase of cell loss. Research also shows tear deficient patients increase their blinking rate, causing even greater frictional force on the epithelium and additional cell loss and thinning.20 Investigators suggest long-term soft contact lens wearers also experience a thinning epithelium.21

Corneal Endotheliopathies
Since the endothelium is a 5μm monolayer, it is difficult to observe pathology without the use of a specular microscope.22 A specular microscope provides useful information when observing dystrophies and effects of contact lens wear. It is also helpful for ensuring the endothelium is functioning properly before presurgical intervention.

Normal cell loss occurs every year but can be exaggerated by uveitis, glaucoma, Fuchs’ dystrophy, contact lens wear and intraocular surgery.9 When cells die, they slough off the posterior surface of the cornea—compromising the endothelium mosaic and affecting function.

During contact lens wear and presurgical evaluations, visualizing the condition of the endothelial cellular arrangement is crucial to avoid potential damaging effects.23,24 Endothelial cell loss can render the cornea ineffective in controlling corneal hydration, resulting in pathological edema.

Contact lenses can induce endothelium change with high pleomorphism and polymegethism but also a decrease in endothelial cell density. Loss of endothelium cell density is correlated with length of time wearing contact lenses.23,24 The only method to observe changes in the corneal endothelium while wear contact lenses is with a specular microscope. This becomes important for future positive outcomes from ocular surgery such as cataract extraction and refractive surgery.

Patients might experience clinical signs of contact lens intolerance associates with hypoxia, especially while wearing large diameter scleral lenses or hybrid lenses. In addition to photophobia, contact lens intolerance, foggy, hazy or fluctuating vision, indicate the endothelium might be compromised. Any patient who exhibits signs of reduced vision after a few hours of wear without any other explanation should be examined with a specular microscope. Many of these patients are experiencing endotheliopathies.

Epithelium damage from corneal ulcer and foreign body.
Corneal Integrity
Corneal hysteresis is a measure of elasticity of the tissue and the ability of the cornea to dissipate energy when the shape is disrupted. The one commercially available device for measuring corneal hysteresis, the Ocular Response Analyzer (ORA, Reichert), records IOP as a puff of air indents the cornea and then as the cornea rebounds to its original shape.17 The difference in these two IOPs is recorded as corneal hysteresis (CH), which is actually a measure of corneal viscosity (how the cornea resists applied force).18 Clinical trials have used these two measurements to develop a constant for corneal thickness known as corneal resistance factor (CRF).25

Studies show CH and CRF are somewhat variable in healthy subjects, although there is a general trend toward greater CH as healthy patients age.26-28 When the cornea is thinned in either a pathological process such as keratoconus, or in a surgical process such as LASIK or LASEK, CH decreases.29 When the cornea is strengthened in corneal crosslinking, CH increases.30 Research shows eyes with pseudophakic bullous keratopathy have significantly reduced CH and CRF, which increase after DSAEK.31

Low CH is also associated with different forms of glaucoma, including primary open-angle, primary angle-closure, pseudoexfoliative and congenital.32 Because IOP measurements with Goldmann applanation tonometry may be different in patients with low CH and CRF, some researchers recommend glaucoma patients with low CH and CRF be treated more aggressively.32,33

Specular microscopy, as seen here, can help clinicians
observe changes in the corneal endothelium caused by
dystrophies and contact lens wear.

The Ins and Outs of Refraction
Patients come in every day with 20/20 vision, yet still discuss their inability to function at night or see clearly during the day—and the shape of the cornea is often the key.

The normal corneal curvature range is no more than 10D; anything greater than that suggests corneal shape abnormalities that can affect vision.34 If the power change created by the curvature across the cornea cannot be adequately corrected with spectacles due to the difference between the flattest and steepest curve, contact lenses (often rigid lenses) are indicated.

A combination autorefractor/keratometer can help clinicians uncover corneal shape and surface abnormalities useful for refractive and surgical outcomes.

Depending on the level of distortion seen on an autorefractor’s point spread function, two prescriptions may be necessary, and the power map is key to understanding why. As the power map changes from the apex of the cornea during dim illumination, the prescription will change during dilation.

The axial map measures the range of curvature distributed across the corneal surface. They are spherical biased and calculated from light rays projecting through the optical axis as a reference point. This smooths out the data, which can hide corneal abnormalities.

The instantaneous display or the tangential curvature map, best for understanding the true corneal shape and defining an ectatic cornea, does not use a reference axis and illustrates transitions in curvature with greater sensitivity.2,35

Diagnostic instruments help us identify corneal abnormalities within the ocular system by first defining the initial changes from the normal structure—far sooner than can be seen through a slit lamp. Armed with more knowledge of both normal and abnormal corneas, clinicians can readily identify the initial stages of disease and promptly institute treatment strategies.
Ultrasound vs. OCT
Although ultrasound pachymetry is still the standard for measuring corneal thickness, OCT pachymetry is rapidly taking its place. The inherent error in ultrasound’s hand-driven measurement is hard to overlook compared with a computer-driven tool. Research shows a statistically significant variance between ultrasound and OCT, with ultrasound measuring greater thickness compared with other techniques.1

1. Dutta D, Rao HL, Addepalli UK, Vaddavalli PK. Corneal thickness in keratoconus: comparing optical, ultrasound, and optical coherence tomography pachymetry. Ophthalmology. 2013;120(3):457-63. 
Dr. Davis is a cofounder of EyeVis Eye and Research Institute and is an adjunct faculty member at Southern California College of Optometry, Illinois College of Optometry, Pennsylvania College of Optometry at Salus University and University of Missouri at Saint Louis. Dr. Davis is a diplomate in the Corneal, Contact Lens and Refractive Technology section of the American Academy of Optometry and an inductee in National Academy Practice in Optometry.

Dr. Sonsino is a partner in a high-end specialty contact lens and anterior segment practice in Nashville, Tenn. He is a diplomate in the Cornea, Contact Lens, and Refractive Therapies Section of the AAO, chairman of the Cornea and Contact Lens Section of the American Optometric Association, a fellow of the Scleral Lens Education Society, board certified by the American Board of Optometry and the 2017 Gas Permeable Lens Institute practitioner of the year.   

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