Interferometry for the Detection of Dry Eye

The human tear film is approximately 3 to 5 µm thick. When it comes to measuring the tear film—for the purpose of evaluating the presence of dysfunctional tear syndrome (DTS), commonly known as dry eye—we currently do not have a gold standard to detect abnormalities. Standard ocular coherence tomography (OCT) and confocal microscopy do not provide the necessary resolution to accurately measure the tear film. A new method of measurement, interferometry, may provide the first objective measurement of this important layer.

Noncontact confocal microscopy and OCT may be reliable methods to measure tear film thickness; however both have low resolution. Confocal microscopy only measures down to approximately 1 µm of the tear film when used in a noncontact fashion. The resolution is even lower in OCT, reaching only 3 µm. Alternatively, the noncontact interferometer (Figure 1) is able to measure down to 0.3 to 0.5 µm on the ocular surface, providing a good direct measurement of the tear film without the use of chemicals or dye that may induce reflex tearing. Interferometry provides measurements of aqueous and lipid layer thickness, thinning rate of the tear film, blink frequency, and the maximum interblink interval.

Clinical use of interferometry is possibly 2 to 5 years away. When it is introduced, this development has the potential to improve detection and treatment of dry eye disease. Advanced Medical Optics, Inc. (Santa Ana, California), is currently developing this technology. Its use will be especially relevant for refractive and cataract surgeons.

HOW DOES IT WORK?
Interferometry—the science of making measurements with coherent light—is not new. Using the principle of superposition, an interferometer combines two separate light beams, diagnosing their properties and studying the pattern of interference (Figure 2) when they traverse a medium. It is widely used in astronomy, fiber optics, metrology, oceanography, seismology, quantum mechanics, and plasma physics. A typical interferometer splits one single beam of light with a grating or partial mirror into two identical beams with the same wavelength. In the case of ophthalmic interferometry, the beams are reflected onto the anterior and posterior surfaces of a clear medium, such as the tear film. The beams are then recombined at the machine's detector, and the difference in the beam's path produces the diagnostic measurement.

In a nutshell, interferometry measures the interference between the beams reflected by the anterior and posterior surfaces. Measuring these two beams allows us to obtain measurements for the thickness of the different reflective media. We have been evaluating the use of interferometry to measure tear film thickness, including the different layers of the tear film (eg, lipid and aqueous layers). Previously, this has not been accurately done with any other instrument because of the lack of high resolution.

CURRENT STATUS
I have recently observed results of tear film interferometry with the latest prototype, and results have been striking. At this point, we are using the interferometer to detect normal and abnormal parameters for the tear film. We can see differences in the aqueous and lipid layers in patients. Interferometry enables us to detect that some patients have a thick aqueous layer and a thin lipid layer. At first glance, the surgeon may assume that this patient is not at risk for dry eye; however, despite a good total thickness of the tear film, the lipid layer does not constantly cover the surface of the eye, which likely correlates to an abnormal tear film breakup time.

The interferometer may be a more sensitive measurement of tear film breakup time compared with fluorescein tests. Fluorescein may grossly detect patients with mucin deficiencies using a chemical substance; however, the interferometer allows detection in real time and in a noncontact fashion of the behavior of specific layers both during and between blinks. Therefore, we know that although these patients may have thick lipid layers, it is probably not smooth over the whole tear film, causing it to break up in certain areas. Environmental changes affect the tear film thickness, and the interferometer may also be used to quantify these changes. For example, a recent Japanese study found changes in the tear films of smokers versus nonsmokers. The smokers had thinner lipid layers and shorter time of regional defects in the tear film.

IN THE FUTURE
We also plan on using interferometry to determine how the tear film changes with the application of lubricants or dry eye medications onto the ocular surface. These measurements are made in real time, meaning that we will be able to see the tear film immediately after the eye drops are instilled. More important, measurements can be followed over time to track how each lubricant or medication behaves in the eye, how the tear film reacts to the treatment, and how long a topical eye drop is effective. Interferometry may be a more sensitive and objective measurement compared with currently available tests, which do not completely correlate with DTS symptoms.

Ophthalmologists, especially anterior segment surgeons, can benefit from use of the interferometer. Many cataract patients who are evaluated preoperatively and have a good tear film may still develop symptoms of dry eye after surgery, including persistent foreign body sensations or visual degradation. Once interferometry is available, the surgeon will have a reliable way to measure the tear film preoperatively and obtain information that is vital for the patient's postoperative state. These patients could be treated preoperatively to avoid bad outcomes.

Interferometry is also potentially useful in refractive surgery. In the clinic, possibly 90% of patients have some problem with dry eye after corneal refractive surgery. Conversely, preoperative tear film status significantly affects refractive outcomes, in many cases causing a difference between the intended and obtained refraction. Patients with DTS tend to have more regression after LASIK compared with those who do not have DTS preoperatively. Interferometry can measure the pre- and postoperative tear film thickness and composition to find the most appropriate medication to avoid dry eye. This tool may be used to perform correlations between the target refraction and status of the tear film.

With interferometry, we have the potential to measure characteristics of the tear film that we previously could not measure with standard methods. Preoperatively, we can detect the tear film thickness and composition of the tear film as well as imbalance of tears in the hopes of avoiding dry eye.

Ashley Behrens, MD, is an Assistant Professor of Ophthalmology, specializing in cornea, cataract, and refractive surgery, at The Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Johns Hopkins Hospital. Dr. Behrens states that he has no financial interest in the products or companies mentioned. He may be reached at tel: +1 410 955 7450; fax: +1 443 442 2021; e-mail: abehrens@jhmi.edu.