In addition to traditional testing methods for dry eye, including tear break-up time (TBUT), meibomian gland grading, ocular surface staining, and Schirmer testing, surgeons now have access to several ways to identify specific biomarkers of dry eye and enhance diagnostic capabilities with noninvasive measures. These tests—tear osmolarity, matrix metalloproteinase-9 (MMP-9) measurements, and quantitative imaging technologies—increase the likelihood of detecting dry eye accurately and reliably before a patient undergoes surgical intervention. In many cases, the tests can also be used to monitor the effects and usefulness of therapeutic regimens and identify patients who should not undergo surgical procedures that induce a refractive change, including LASIK and multifocal IOL implantation.
Just because newer tests are available does not mean that the traditional methods of dry eye diagnosis are obsolete, however. Rather, a combination of both modalities may be the best method for detection. The problem with using traditional methods of dry eye detection alone is that they are subjective. Therefore, not only can repetition of the same test produce different results, but also interpretation of results can vary between observers. On the other hand, novel methods of dry eye detection provide objective and reproducible measurements; however, the problem with using them exclusively is that they are still somewhat experimental, and studies in the literature are limited.
A REVIEW OF NOVEL METHODS
Tear osmolarity. In the presence of dry eye disease, a patient’s tear osmolarity is unstable and elevated above 316 mOsm/L.1,2 Hyperosmolarity is a global feature of dry eye, and the higher the osmolarity, the more severe the case. The TearLab Osmolarity System (TearLab Corp.) uses osmolarity measurements in 50-nL samples taken from the interior tear meniscus to identify aqueous deficient and evaporative dry eye disease in early, middle, and late stages.
According to company literature, the TearLab test performs analysis equally well as laboratory osmometers3 but is a quick, specific, and repeatable test. Tear osmolarity testing is variable over time, however, and analyses have shown a range of 10 to 15 mOsm/L among three consecutive measurements; occasional variation of up to 35 mOsm/L was also observed.4,5 Any difference greater than 8 mOsm/L between a patient’s two eyes is indicative of dry eye.
Because tear osmolarity often stabilizes and drops in response to improvement in dry eye,6 measurements taken after therapy is initiated are useful to quantify success of the management strategy.
MMP-9 measurements. As a nonspecific marker for inflammation, an elevated MMP-9 level (greater than 40 ng/mL) in a patient’s tears can be a signpost for dry eye disease. In one study, the MMP-9 levels found in tears correlated with categorical severity of tear dysfunction and severity of corneal fluorescein staining.7 In another, a high tear MMP-9 level was helpful to identify patients at risk for post-LASIK tear dysfunction.8
The InflammaDry test (Rapid Pathogen Screening) is an in-office test that measures MMP-9 levels in tear fluid collected from the inferior tarsus. It should be used in conjunction with patient history and clinical signs of dry eye disease to confirm diagnosis, and other inflammatory conditions such as corneal ulceration, allergic conjunctivitis, rosacea, and Sjögren syndrome must first be ruled out.
Interferometry. Although it is costly, another method of dry eye detection is tear film interferometry. Measurement of tear film lipids as they spread across the ocular surface is helpful to detect meibomian gland dysfunction (MGD), a common component of evaporative dry eye. A lipid diagnostic technology, the LipiView Ocular Surface Interferometer (TearScience), illuminates the tear film, measures the interference pattern of the reflected light, and records the data to determine the lipid layer thickness. If a thin lipid layer or an abnormal composition of tear film is identified, treatment for MGD is required.
Another TearScience product, the Meibomian Gland Evaluator, offers a cost-effective solution for MGD detection. The device can evaluate gland patency and lipid quality and guide decisions on the need for gland expression.
Tear and tear meniscus imaging. In its infancy as a dry eye detection method, optical coherence tomography (OCT) is being used to image the tear film and determine the tear meniscus height. Recent studies have shown that OCT can successfully document changes in the tear film after punctal occlusion and cyclosporine therapy.9,10 It has also been used to study the inferior and superior tear meniscus in dry eye.11 This noncontact method of dry eye detection does not require the use of dyes to stain the ocular surface. As a result, researchers postulate that reflex tearing is less likely with OCT compared with traditional assessments of tear film.
A more established diagnostic technique for dry eye evaluation is corneal topography. After Hartmann-Shack wavefront analysis was shown to correlate with clinical dry eye evaluations,12 special topography software for the Keratograph 5M (Oculus) was developed to characterize ocular dryness by measuring TBUT, performing interferometry and meibography, and assessing bulbar and limbal redness.
Finally, tear imaging using a system such as the Topographic Modeling System 2N (Tomey Corp.) can be used to establish a numerical TBUT. This device evaluates the focal changes in brightness of ring mires projected onto the cornea every second for 6 seconds.
With a variety of traditional and novel methods of dry eye detection now available, making a diagnosis before scheduling surgery can be more accurate than ever. The best dry eye work-ups combine the more traditional tests such as TBUT, meibomian gland grading, ocular surface staining, and Schirmer with one or more of the novel methods outlined above. These newer modalities are noninvasive and objective and can provide surgeons with additional information to aid in dry eye diagnosis.
- Lemp MA, Baudouin C, Baum J, et al. The definition and classification of dry eye disease: report of the definition and classification subcommittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5(2):75-92.
- Tomlinson A, Khanal S, Ramaesh K, et al. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci. 2006;47(10):4309-4315.
- http://www.tearlab.com/pdfs/TearLab%20Clinical%20Utility%20Guide.pdf. Accessed May 16, 2013.
- Khanal S, Millar T. Barriers to clinical uptake of tear osmolarity measurements. Br J Ophthalmol. 2012;96:341- 344.
- Eperjesi F, Aujla M, Bartlett H. Reproducibility and repeatability of the OcuSense TearLab osmometer. Graefes Arch Clin Ep Ophthalmol. 2012;250(8):1201-1205.
- Sullivan BD, Crews LA, Sönmez B, et al. Clinical utility of objective tests for dry eye disease: variability over time and implications for clinical trials and disease management. Cornea. 2012;31(9):1008-1009.
- Chotikavanich S, de Paiva CS, Li de Q, et al. Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome. Invest Ophthalmol Vis Sci. 2009;50:3203-3209.
- Sambursky R, O’Brien TP. MMP-9 and the perioperative management of LASIK surgery. Curr Opin Ophthalmol. 2011;22(4):294-303.
- Wang J, Shousa MA, Perez VL, et al. Ultra-high resolution optical coherence tomography for imaging the anterior segment of the eye. Ophthalmic Surg Lasers Imaging. 2011;42:S15-S27.
- Wang J, Cui L, Shen M, et al. Ultra-high resolution optical coherence tomography for monitoring tear meniscus volume in dry eye after topical cyclosporine treatment. Clin Ophthalmol. 2012;6:933-938.
- Shen M, Li J, Wang J, et al. Upper and lower tear menisci in the diagnosis of dry eye. Invest Ophthalmol Vis Sci. 2009;50:2722-2726.
- Cervino A, McDonald MB, Klyce SD. Shack-Hartmann pattern as aid in the diagnosis and evaluation of dry eye: a retrospective study. Poster presented at: the ARVO Annual Meeting; May 2002; Fort Lauderdale, Florida.