anesthetic. However, after the filter-paper strips have been inserted into the inferior fornices, a cottontipped applicator is used to irritate the nasal mucosa. Wetting of less than 15 mm after 2 minutes is consistent with a defect in reflex secretion. Although an isolated abnormal result for any of these tests can be misleading, serially consistent results are highly suggestive. Schirmer testing is also useful in demonstrating to patients the presence of an ATD. An alternative to classic Schirmer strips is the phenol red–impregnated cotton thread test, which allows for quicker assessment of tear secretion but has not been fully validated.
Tear Composition Assays
Tear-film hyperosmolarity is highly suggestive of dry eye, as is a reduced level of tear lysozyme or lactoferrin. As our understanding of the tear film has increased, commercial assays to measure its various components have been developed. TearLab Osmolarity System (TearLab Corporation, San Diego, CA) measures tear-film osmolarity. The Touch Tear Lactoferrin MicroAssay (Touch Scientific, Inc, Raleigh, NC) measures the level of lactoferrin in tears. InflammaDry Detector (Rapid Pathogen Screening, Inc, Sarasota, FL) performs a microfiltration immunoassay for matrix metalloproteinase 9 (MMP-9), a product of the inflammatory cycle produced by distressed epithelial cells. Preliminary evidence suggests that tear osmolarity testing may be the best method for detection of dry eye.
Imaging Technologies
Noninvasive assessment of the TBUT can be made by using optical (eg, videokeratoscopic) imaging devices that can detect a break in the tear film. Wavefront sensing appears to be a useful objective method for evaluating sequential changes in visual performance related to tear-film dynamics. Anterior segment optical coherence tomography (OCT) has been used to measure the inferior tear meniscus and the tear film and its components.
Impression Cytology
Impression cytology is primarily a research tool that can allow for precise assessment of the ocular surface epithelium. Sheets of epithelial conjunctival or, in rare instances, corneal cells are harvested using a piece of filter paper. They can then be examined directly in morphological and histologic studies, or they may be processed as free cells for flow cytometry. The latter technique allows quantification of the expression of specific proteins (eg, cytokines, receptors) by the epithelial cells. Conjunctival impression cytology can be used to monitor the progression of ocular surface changes, beginning with decreased goblet cell density, followed by squamous metaplasia and, in later stages, keratinization.
Corneal Pachymetry
A corneal pachymeter measures corneal thickness, a sensitive indicator of endothelial physiology that correlates well with functional measurements. Optical pachymetry performed using a special device attached to the slit-lamp biomicroscope is somewhat imprecise and is rarely used today. Ultrasonic pachymetry, which is based on the speed of sound in the normal cornea (1640 m/sec), is both easier to
perform and more accurate. The applanating tip of the pachymeter must be perpendicular to the ocular surface because errors are induced by tilting. Scanning slit technology, Scheimpflug anterior segment imaging, OCT, and high-resolution ultrasonography are newer techniques that can be used to produce precise maps of the entire corneal thickness, including curvature (Fig 2-8).
Figure 2-8 Scheimpflug image map depicting multiple points of corneal thickness measurement (in micrometers). (Courtesy of
George J. Florakis, MD.)
The thinnest zone of the cornea is usually about 1.5 mm temporal to the geographic center, and the cornea becomes thicker in the paracentral zone and peripheral zone. The average central thickness of the normal human cornea is 540 μm. In the Ocular Hypertension Treatment Study, the average central corneal thickness was higher, at 573 ± 39 μm, but it was acknowledged that these numbers were
probably higher than those of the general population. Corneal thickness affects the measurement of intraocular pressure (IOP), with thicker corneas producing falsely higher IOP readings and thinner corneas falsely lower readings. However, Liu and Roberts demonstrated that the biomechanical properties of the cornea, particularly stiffness, may have a greater impact on IOP measurement errors than does corneal thickness or corneal curvature. Adjustment for corneal biomechanical properties may lead to a more accurate measurement of the IOP.
Pachymetry can also be used to assess corneal hydration and the function of the corneal endothelium in its dual role as a barrier to aqueous humor and as a metabolic pump. When functioning normally, the endothelial pump balances the leak rate to maintain the corneal stromal water content at 78% and the central corneal thickness at about 540 μm. Acute corneal edema is often the result of an altered barrier effect of the endothelium or epithelium. Chronic corneal edema is usually caused by an inadequate endothelial pump. Folds in the Descemet membrane are first seen when corneal thickness increases by 10% or more; epithelial edema occurs when corneal thickness exceeds 700 μm. Early signs of corneal edema evident on slit-lamp examination include patchy or diffuse haze of the epithelium, mild stromal thickening, faint but deep stromal wrinkles (WaiteBeetham lines), Descemet membrane folds, and a patchy or diffuse posterior collagenous layer. Stromal edema alters corneal transparency, but vision loss is most severe when epithelial microcysts or bullae occur. A central corneal thickness greater than 640 μm may indicate a higher risk for symptomatic corneal edema after intraocular surgery.
Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001;108(10):1779–1788.
Liu J, Roberts CJ. Influence of corneal biomechanical properties on intraocular pressure measurement: quantitative analysis. J Cataract Refract Surg. 2005;31(1):146–155.
Seitzman GD, Gottsch JD, Stark WJ. Cataract surgery in patients with Fuchs corneal dystrophy: expanding recommendations for cataract surgery without simultaneous keratoplasty. Ophthalmology. 2005;112(3):441–446.
Measurement of Corneal Biomechanics
The Ocular Response Analyzer (ORA; Reichert, Depew, NY) was the first commercially available instrument to allow in vivo clinical testing of a cornea’s direct biomechanical properties. The ORA uses a jet pulse of air to flatten the cornea and takes 2 measurements, capturing the increase in air pressure required for indention of the cornea, and the falling air pressure as the cornea returns to its original shape. Corneal hysteresis (CH) is the difference between these pressures. The corneal resistance factor (CRF) is derived from CH using a mathematical calculation to correlate with corneal thickness. These values have a normal distribution within the general population but are decreased in patients who have undergone LASIK or photorefractive keratectomy and in those who have corneal edema secondary to Fuchs dystrophy. However, because the ORA measures the viscous properties of the cornea and not the elastic properties, it is not a particularly effective device to use for screening refractive surgery patients for the risk of keratectasia or for documenting the increased stiffness associated with collagen crosslinking, aging, and diabetes mellitus.
Newer technologies for evaluating corneal biomechanics integrate dynamic corneal imaging instruments using Placido disk–based technology, the Scheimpflug camera system, or OCT, and allow more accurate measurement of the corneal deformation produced by the collimated air puffs. These devices can differentiate the elastic biomechanical properties of normal corneas from those of ectatic corneas and distinguish collagen crosslinking–treated corneas from pretreatment corneas, using variables such as the quantitative amplitude of inward deformation (greater in softer, ectatic