Achieving physiologic restoration in dry eye

Take-home message: Tear osmolarity testing provides clinicians the opportunity to detect disease and select treatments to restore ocular surface health.

By Laura M. Periman, MD, Special to Ophthalmology Times

Dr. PerimanTear osmolarity excels as a predictive test for dry eye syndrome, with 89% of abnormal tests correlating with a positive diagnosis.¹

An energizing innovation for ophthalmologists long accustomed to frustration with the disconnect between signs and symptoms, the accuracy, objectivity, and speed of osmolarity testing makes it an exceptional tool for aiding the diagnosis of dry eye and tracking the success of treatment.

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Considered a biomarker for ocular surface health, normal tear osmolarity tests after treatment indicate improved functioning of the lacrimal functional unit (LFU).²

The power of osmolarity testing is greatest when appreciated as part of the larger diagnostic picture. Viewed alongside symptoms, inflammation (MMP-9) testing, and exam findings, tear osmolarity becomes a time-efficient and powerful way to characterize an individual patient’s ocular surface disease, as well as check progress and predict symptom relief over time.

What tear osmolarity tells us

What tear osmolarity tells us

A healthy tear film is held in excellent homeostatic control by the entire LFU. The LFU is comprised of afferent corneal nociceptor impulses, central nervous system integration, and efferent commands to the lacrimal gland, goblet cells, and meibomian glands to maintain a healthy tear balance, composition, and protection. Ocular surface disease inflammation is triggered by two core mechanisms: hyperosmolarity and desiccating stress.³

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Compensatory mechanisms pick up the pace; disease happens when these mechanisms are unable to recover homeostatic control. This aberrant activation of the innate defenses triggers the inflammation cascade, and as immunoregulatory control suffers, the cycle of inflammation becomes chronic and self-perpetuating.

One consequence of compromised homeostatic control of the ocular surface is an increase in osmolarity or osmolar variability between the eyes. Osmolarity testing gives a vital sign-like metric of ocular surface health and the eye’s ability to withstand additional stressors, such as those encountered in daily life or with surgery.

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An abnormal osmolarity test suggests the presence of a suboptimal ocular surface or an LFU in distress. Osmolarity changes may occur earlier than physical examination changes (staining). Early in dry eye disease progression, corneal nerve nociceptors send impulses to the brain that osmolarity is not optimal. The brain sends efferent commands to the lacrimal gland, goblet cells and meibomian glands.⁴

Clinically, patients may report significant discomfort, although no damage to the ocular surface is visible yet on exam. Osmolarity testing is helpful in an important subgroup on the dry eye disease spectrum – particularly hyperosmolar, early-stage patients. These cases often present as symptoms greater than traditional signs. The corneal nerves are firing in response to the osmolar nociceptive stimulus, but the physical signs have not yet manifested. Compensatory mechanisms engage, but eventually hybrid disease results.⁵

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The osmolarity test identifies the problem.

Instead of dismissing a patient’s complaints, physicians can get a number that verifies and quantifies what is happening to the tear film and the lacrimal functional unit. That very clear data point helps to characterize the patient’s problem, identify the location on the spectrum of disease development, and intervene appropriately.

The bonus: Because osmolarity testing allows for a diagnosis of dry eye much earlier in the disease process, patients still have significant functional reserves. It is possible not only to make them comfortable, but also to achieve physiologic restoration of the ocular surface and LFU.

Early diagnosis, treatment

Early diagnosis, treatment

Osmolarity values above 308 mOsms/L or an inter-eye variation greater than 8 mOsms/L is considered abnormal and characteristic of dry eye disease. ⁶

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I test tear osmolarity for dry eye referrals, dry eye exacerbations, and dry eye follow-up patients, as well as for general ophthalmology patients who have high scores on the Dry Eye Ocular Surface Disease Index (OSDI). MMP-9 testing (InflammaDry, RPS) is performed to detect inflammation. When these two tests and the exam point to dry eye, then it is necessary to characterize and treat the disease.

Once patients have begun treatment for dry eye disease, they are brought back after 6 weeks, when goblet cell density and immunoregulatory cytokines begin coming back online.⁷

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Osmolarity testing is essential for monitoring patients’ response to treatment over time. At regular visits, clinicians look at symptoms and patients’ response to therapy and compare tear osmolarity scores to baseline. Osmolarity scores have been found to improve before the symptoms improve,² which may be related to corneal nerve remodeling and nociceptor down regulation in response to treatment. It is very exciting to see scores improve over time because it suggests improved physiologic function of the LFU.

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More importantly, patients get excited about their scores. Patient fatigue is a challenge for anyone with a chronic disease, and objective data points that show progress are incredibly valuable as tools for encouraging and inspiring patients to keep up the good work. Patients feel encouraged as their eyes reach normal physiological range below 308 mOsms/L, without abnormal inter-eye variability.

Essential for general, surgical practices

Essential for general, surgical practices

Dry eye is more prevalent than realized and is significantly underdiagnosed. In a prospective, consecutive, observational study, researchers found that only 22% of patients came in with the diagnosis of dry eye, but in carefully examining the signs and symptoms, 80% of preoperative cataract patients had ITF level 2, 3, or 4 dry eye disease.⁸

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Additionally, 50% of patients had central corneal staining, which also can be problematic for preoperative testing and postoperative visual outcomes. Dry eye examination and diagnosis can take valuable time, and osmolarity testing is a time-efficient metric of ocular health status to evaluate in preoperative patients.

Importantly, dry eye diagnosis and treatment also have implications for surgical outcomes and postoperative wound healing. A compromised ocular surface can skew preoperative measurements.

As a study by Epitropoulos et al. showed, “Measurement of tear osmolarity at the time of cataract surgery planning can effectively identify patients with a higher likelihood of high unexpected refractive error resulting from inaccurate keratometry.”⁹

Vision performance starts with the tear film, and clinicians aim for excellent visual performance.

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However, all of our excellent cataract surgery technology and skill can go unnoticed if the patient’s visual performance and ocular comfort are impaired by dry eye.

Think of a top-line Porsche engine in a rusty, old, car frame. The technology and skill on the inside is not appreciated if the outside does not meet the same level of excellence. Physicians want patients to get the whole experience of high-visual performance.

Tear osmolarity testing

Additionally, because cataract and refractive surgery can take previously compensated dry eye patients and throw them over the cliff of exacerbated dry eye disease, patients deserve osmolarity testing and dry eye treatment before exposure to the surgical factors that can abruptly accelerate dry eye: nerve truncation, medication load and preservative load.

Tear osmolarity testing is a rapid and easy point-of-care cornerstone diagnostic technology that, with the addition of a history, MMP-9 testing and examination, reveals what lies behind a patient’s complaints-unveiling some factors behind the unhealthy ocular surface. It allows physicians to be more precise diagnosticians.

The osmolarity response to treatment is clinically satisfying. Patients love the idea that they are progressing toward restoration of the LFU system that nature designed. Osmolarity testing provides opportunity to detect disease and select treatments to restore ocular surface health.

More from Dr. Periman: Getting beyond the surface in ocular surface disease

References

1. Tomlinson A, Khanal S, Ramaesh K, Diaper C, McFadyen A. Tear film osmolarity: determination of a referent for dry eye diagnosis. Invest Ophthalmol Vis Sci. 2006;47:4309-4315.

2. Suzuki M, Massingale ML, Ye F et al. Tear Tear Osmolarity as a Biomarker for Dry Eye Disease Severity. Invest Ophthalmol Vis Sci. 2010;51:4557-4561.

3. DEWS Research Subcommittee. Research in Dry Eye: Report of the Research Subcommittee of the International Dry Eye WorkShop. Ocul Surf. 2007;5:179-193.

4. Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune disease. Int Rev Immunol. 2013;3:19–41.

5. Bron AJ, Yokoi N, Gaffney E, Tiffany JM. Predicted Phenotypes of Dry Eye: Proposed Consequences of Its Natural History. Ocul Surf. 2009;7:78-92.

6. Foulks GN, Lemp MA, Berg M, Bhola R, Sullivan BD. TearLab osmolarity as a biomarker for disease severity in mild-to-moderate dry eye disease. American Academy of Ophthalmology PO382, 2009.

7. Pflugfelder SC, De Paiva CS, Villarreal AL, Stern ME. Effects of sequential artificial tear and cyclosporine emulsion therapy on conjunctival goblet cell density and transforming growth factor-beta2 production. Cornea. 2008;2764-69.

8. Trattler W, Reilly C, Goldberg D, et al. Cataract and Dry Eye: Prospective Health Assessment of Cataract Patients’ Ocular Surface Study. Poster, American Society of Cataract and Refractive Surgery Annual Symposium and Congress. San Diego; March 2011.

9. Epitropoulos AT, Matossian C, Berdy GJ, Malhotra RP, Potvin R. Effect of tear osmolarity on repeatability of keratometry for cataract surgery planning. J Cataract Refract Surg. 2015;41:1672-1677.

Laura M. Periman, MD

E: lauraperiman@yahoo.com

Dr. Periman is in private practice at Redmond Eye Clinic, Redmond, WA. She is a speaker for Allergan, BioTissue, and Topcon, and a consultant for Allergan.