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Peer Review | Jul/Aug '14

Point-of-Care Diagnostic Tests for Ocular Surface Disease

Noninvasive technologies assessing the ocular surface via tear film stability, tear film height, and meibography are becoming evermore refined to aid in the diagnosis and management of dry eye disease (DED). It is, however, unlikely that these technologies will replace traditional dry eye tests because of the expense and current difficulties in reimbursement. In contrast, advanced point-of-care diagnostic tests are increasingly being integrated into clinical practice and may provide greater insight into the state of a patient’s ocular surface. 

Recently, Rob Sambursky, MD, and colleagues conducted a study (n=237) to determine the negative and positive agreement of a point-of-care matrix metalloproteinase-9 test, the InflammaDry (Rapid Pathogen Screening).1 The investigators compared the InflammaDry test with the clinical assessment of tear break-up time (TBUT), Schirmer testing, and corneal staining, both with and without the Ocular Surface Disease Index (OSDI), as a confirmatory test. They determined that if the OSDI is included in the definition for mild dry eye, the InflammaDry test has a total positive agreement of 81% and a negative agreement of 98%. If the OSDI is excluded from the definition of dry eye, InflammaDry demonstrates a positive agreement of 86% and a negative agreement of 97% against the clinical assessment. Thus, it was concluded that the InflammaDry test shows a high positive and negative agreement for confirming suspected DED.

In 2011,Michael Lemp, MD, and colleagues published data from a study (n=314) conducted to determine the clinical usefulness of tear osmolarity and commonly used objective tests to diagnose DED.2 Bilateral tear osmolarity, TBUT, corneal staining, conjunctival staining, Schirmer testing, and meibomian gland grading were performed. Diagnostic performance was measured against a composite index of objective measurements that classified patients as having normal, mild or moderate, or severe dry eye. Of the six tests performed, tear osmolarity was found to have superior diagnostic performance. The other tests exhibited either poor sensitivity (corneal staining, conjunctival staining, meibomian gland grading) or poor specificity (TBUT, Schirmer test). The investigators also found that intereye differences in osmolarity correlated with increasing disease severity. Based on these results, they concluded that tear osmolarity is the best single metric both to diagnose and classify DED.

Overall, tear osmolarity testing has been commercially available for several years longer than InflammaDry, which was more recently brought to market, increasing the number of publications on tear osmolarity. The TearLab osmometer also appears to be very inherently accurate at detecting the osmolarity of salt solutions.3

Tear osmolarity may be helpful in earlier detection and severity assessment of dry eye conditions, such as rheumatoid arthritis,4 membrane mucous pemphigoid,5 and DED associated with computer use.6 Tear osmolarity may also help guide a clinician down the decision tree of common symptomatologies, such as epiphora. Attas-Fox and colleagues7 demonstrated how tear osmolarity could provide better insight into which over-tearing patients have DED versus outflow problems.

Conversely, symptomatology can sometimes correlate poorly with objective ocular surface findings, particularly in older patients with a greater neurotrophic component. Tear osmolarity may be more effective at detecting DED in certain conditions, such as in patients with diabetes.8

As important as the initial diagnosis of the disease, time will tell how useful point-of-service tests are in tracking treatment progress and disease severity. There is little published on the use of these tests over multiple visits. Amparo and colleagues9 demonstrated that tear osmolarity did not show a significant correlation to changes in patient symptoms or corneal fluorescein staining. In contrast, Lee et al10 showed that tear osmolarity significantly improved in patients who were treated with topical 1% methylprednisolone drops. One last possible use for point-of-care testing may be in screening for potential DED, particularly in the preoperative assessment for corneal refractive or cataract surgeries.11

Ultimately, advanced diagnostic tests will be used in combination with certain traditional tests, such as a subjective symptom questionnaire (ie, OSDI) and biomicroscopic examination, and may effectively supplant more tedious and invasive traditional methods like Schirmer testing, in the diagnosis of DED. Time will provide greater insight as to what the best diagnostic combinations will be.

1. Sambursky R, Davitt WF 3rd, Friedberg M, Tauber S. Prospective, multicenter, clinical evaluation of point-of-care matrix metalloproteinase-9 test for confirming dry eye disease. Cornea. 2014;33(8):812-818.

2. Lemp MA, Bron AJ, Baudouin C, et al. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol. 2011;151(5):792-798.

3. Yoon D, Gadaria-Rathod N, Oh C, Asbell PA. Precision and accuracy of TearLab osmometer in measuring osmolarity of salt solutions. Curr Eye Res. 2014.

4. Türkyilmaz K, Küçükali Türkyilmaz A, Kurt A, Kurt EE, Sevim M, Oner V. Investigation of tear osmolarity in early rheumatoid arthritis: relation to disease activity. Can J Ophthalmol. 2013;48(4):235-239.

5. Miserocchi E, Iuliano L, Berchicci L, Bandello F, Modorati G. Tear film osmolarity in ocular mucous membrane pemphigoid. Cornea. 2014;33(7):668-672.

6. Fenga C, Aragona P, Di Nola C, Spinella R. Comparison of ocular surface disease index and tear osmolarity as markers of ocular surface dysfunction in video terminal display workers. Am J Ophthalmol. 2014;158(1):41-48

7. Attas-Fox L, Zhang AY, Fox BD, Arthurs BP. Evaluation of tearing in oculoplastics assisted by tear osmolarity measurement. Orbit. 2014;1-5.

8. Alves M, Reinach PS, Paula JS, et al. Comparison of diagnostic tests in distinct well-defined conditions related to dry eye disease. PLoS One. 2014;9(5):e97921.

9. Amparo F, Jin Y, Hamrah P, Schaumberg DA, Dana R. What is the value of incorporating tear osmolarity measurement in assessing patient response to therapy in dry eye disease? Am J Ophthalmol. 2014;157(1):69-77.

10. Lee JH, Min K, Kim SK, Kim EK, Kim TI. Inflammatory cytokine and osmolarity changes in the tears of dry eye patients treated with topical 1% methylprednisolone. Yonsei Med J. 2014;55(1):203-208.

11. Kaufman HE. The practical detection of mmp-9 diagnoses ocular surface disease and may help prevent its complications. Cornea. 2013;32(2):211-216.

Elizabeth Yeu, MD

Elizabeth Yeu, MD, is an Assistant Professor of Ophthalmology at Eastern Virginia Medical Schooland a Partner specializing in cornea, cataract, and refractive surgery at Virginia Eye Consultants in Norfolk, Virginia. She may be reached at eyeu@vec2020.com.