Expanded array of diagnostic platforms target identification of dry eye disease
New point-of-care tests for diagnosing dry eye disease include technologies for analyzing tear composition, imaging the tear film, and collecting conjunctival cells.
By Cheryl Guttman Krader; Reviewed by Stephen C. Pflugfelder, MD
Houston- There are a variety of new diagnostic tests for dry eye and a number of reasons why clinicians should consider incorporating these technologies into practice, said Stephen C. Pflugfelder, MD, at the 2012 Cornea Subspecialty Day Meeting.
“The addition of certain tests appears to improve the ability to diagnose and classify tear dysfunction and may help identify patients with tear dysfunction who are poor candidates for LASIK or multifocal IOL surgery,” said Stephen C. Pflugfelder, MD, Professor and James and Margaret Elkins Chair, Department of Ophthalmology, Baylor College of Medicine, Houston, TX. “These tests may also prove valuable for guiding therapeutic decision making and for monitoring therapeutic efficiency.”
The new diagnostic technologies represent three categories: tests for evaluating tear composition, techniques for tear film imaging, and a method for sampling ocular surface cells for impression cytology.
The devices for measuring tear composition include one instrument that measures tear osmolarity (TearLab, TearLab) by sodium ion conductivity in a 50 nl sample collected from the inferior tear meniscus.
“It is well know that tear composition is altered in eyes with tear dysfunction due to lacrimal gland disease where there are reduced concentrations of factors secreted by the lacrimal glands and increased osmolarity,” Dr. Pflugfelder said. “However, osmolarity is also increased in aqueous sufficient dry eye conditions, such as meibomian gland dysfunction (MGD) and conjunctivochalasis.”
In a study where the device was used to measure tear osmolarity in 314 consecutive subjects classified as normal or with mild, moderate, or severe dry eye based on the Dry Eye Workshop composite severity score, a cutoff of 308 mOsm/L was the most sensitive threshold for discriminating between normal and mild subjects versus moderate and severe, whereas 315 mOsm/L had the greatest specificity.
In another study evaluating six different diagnostic tests, tear osmolarity showed the greatest correlation with the DEWS composite disease severity score. However, other researchers reported no differences in mean tear osmolarity comparing normal eyes and those with non-Sjogren’s syndrome aqueous tear deficiency or Sjogren’s syndrome aqueous tear deficiency, nor correlations between tear osmolarity and any other clinical tests.
“The value of this device may be to identify tear dysfunction, especially if osmolarity is consistently high,” Dr. Pflugfelder said.
He added results of other studies suggest it may be used to monitor ocular surface toxicity from chronic use of glaucoma drops with preservatives and to monitor the therapeutic effect of cyclosporine treatment.
A second device analyzing tear composition is a semiquantitative immunoassay that detects elevated levels (>40 ng/ml) of matrix metalloproteinase-9 (MMP9) in tear fluid (InflammaDry Detector, RPS). It is a single-use disposable assay and is approved in Europe and Canada but pending FDA approval. According to its manufacturer, the test has 85% sensitivity and 94% specificity for identifying dry eye diagnosed by “clinical truth.”
“Both the concentration and activity of this inflammatory protease have been shown to be increased in eyes with aqueous tear deficiency and MGD,” Dr. Pflugfelder explained. “Furthermore, elevated tear MMP9 activity correlates with a number of objective and subjective clinical parameters of tear dysfunction.”
The techniques for tear film imaging include a system that noninvasively analyzes tear stability (Tear Stability Analysis System, Tomey). A study evaluating its use found that the rate of increase of irregular points over 6 seconds was very low in normal eyes and progressively increased with severity level of dry eye.
Another tear film imaging unit noninvasively measures tear breakup time and location in reflected placido rings (Keratograph 5M, Oculus), The data are presented in a color-coded map. A third device using white light interferometry (LipiView, TearScience) provides data on the thickness and quality of lipid in the tear layer and is useful for diagnosing meibomian gland dysfunction, Dr. Pflugfelder said.
There are also two anterior segment-OCT platforms (Visante Omni, Carl Zeiss Meditec; RTVue, Optovue) that can be used for non-contact tear film imaging and to determine the inferior and superior tear meniscus height, width, and area. In addition, they calculate tear volume by extrapolation and are sensitive enough to detect tear meniscus debris.
Dr. Pflugfelder noted that in a study he conducted using anterior segment-OCT to image 128 consecutive patients with tear dysfunction, there was a strong negative correlation between the severity of corneal fluorescence staining and the tear meniscus height. Another study showed this technology was valuable for determining area of involvement in eyes with conjunctivochalasis.
A new point-of-care tool for performing conjunctival impressions collects cells on a high-affinity membrane that is applied to the bulbar conjunctival surface.
“Impression cytology has been used for decades to evaluate conjunctival epithelial morphology, measure goblet cell density, and determine expression of mucin, cytokine, and MMP genes, but it has generally been limited to academic centers,” Dr. Pflugfelder said. “This new technology is easy to use, requires no anesthesia, and the collected cells can be analyzed for proteins or gene expression.”
Stephen C. Pflugfelder, MD
Dr. Pflugfelder receives research support from and is a consultant for Allergan, Bausch + Lomb, and GSK. This article is adapted from Dr. Pflugfelder’s presentation during Cornea 2012 at the annual meeting of the American Academy of Ophthalmology.