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	By Preeya K. Gupta, MD; Special to Ophthalmology Times

Hyperosmolarity and inflammation perpetuate the vicious cycle of dry eye, exacerbating the signs and symptoms of this chronic, progressive disease. (Image courtesy of Preeya K. Gupta, MD)Clinicians have long known that multiple factors influence tear film homeostasis. These factors were laid out very clearly in the “TFOS DEWS II pathophysiology report,” released by the Tear Film and Ocular Surface Society in July 2017.

	According to the report, hyperosmolarity is a core mechanism of dry eye disease. Its causes and effects, combined with those of inflammation, make up the vicious cycle that underpins the chronic, progressive nature of dry eye.

	Moving forward, our goal is to utilize this information to shape diagnostic testing for dry eye disease toward accurate, objective, early identification.

	No matter the cause of a patient’s dry eye disease, whether excessive evaporation or low production of aqueous, one result is a decrease in the relative volume of the aqueous component of the tear film, or hyperosmolarity.

	Surface epithelial cells sense the hyperosmolar environment and release inflammatory mediators, which cause cellular damage to the ocular surface, triggering heightened immune system activity. Inflammation and hyperosmolarity continue, perpetuating the vicious cycle of dry eye disease. Both mechanisms contribute to destabilization of the ocular surface and are exacerbated by the effects, continuing the cycle.

	Today, diagnostics are available to help us better understand the molecular impacts of the disease and identify them as they occur, and other technologies such as imaging modalities contribute more information to the patient’s complete diagnostic picture.

	As physicians, we tend to focus on obtaining a specific dry eye diagnosis.

		Does the patient have aqueous deficient or evaporative dry eye?

		Is the aqueous deficient dry eye caused by aging/hormonal changes, autoimmune disease, lacrimal obstruction, medications, refractive surgery, contact lens wear, or something else?

		In evaporative cases, does the patient have meibomian gland dysfunction, anterior blepharitis, vitamin A deficiency, or allergies, and are preservatives or contact lens wear exacerbating the problem?

		Is a combination of aqueous deficient and evaporative mechanisms at work?

	While there is value in understanding each patient’s disease state, for the practical purpose of diagnostic screening, we begin with objective point-of-care testing of tear osmolarity.

	The eye produces and maintains the tear film to create an optimal balance for lubrication, protection, and regulation of the ocular surface environment. I think of tear osmolarity testing as one of the “vital signs” that tell me how the tear film and ocular surface are functioning. All underlying causes of dry eye disease can influence osmolarity, so testing is informative, regardless of the cause.

	In 87% of cases, patients with a tear osmolarity test (TearLab Osmolarity Test, TearLab) that is positive for dry eye have the disease-the best predictive value of any test.

 The system requires a small tear sample, which the device processes for about 60 seconds.

When the osmolarity is 308 mOsm/L or higher, or if the differential between the eyes is 8 mOsm/L or greater, then I can tell my patients with great confidence that they have dry eye disease. Normal eyes have very little variation from day to day, but someone with dry eye disease could have a result of 290 mOsm/L one day and 330 mOsm/L the next.

	Integration of clinical examination with point-of-care testing is critical. If a patient has normal tear osmolarity but is symptomatic, I look for signs of ocular surface diseases unrelated to dry eye, such as anterior basement membrane dystrophy, allergic disease, or conjunctivochalasis. I often also perform inflammatory marker testing and meibography, and look at the results together to make the diagnosis.

	Because inflammation is a component of the vicious cycle, it is important to understand when a patient is at a clinically significant level of inflammation. In addition to examining patients for signs of inflammation, we can gather objective data using point-of-care testing. Testing is available for the inflammatory marker called MMP-9 (InflammaDry, Quidel).

	Understanding the degree of inflammation is helpful in terms of clinical decision making. If a patient has corneal or conjunctival staining and high MMP-9 levels, I might be more apt to prescribe topical steroids, lifitegrast (Xiidra, Shire), or cyclosporine (Restasis, Allergan).

	The combination of tear osmolarity and inflammatory marker testing can help to identify conditions masquerading as dry eye disease. If I see someone with normal osmolarity and elevated MMP-9, for example, I look for other causes of inflammation.

	Patients who test positive for hyperosmolarity or inflammatory markers often undergo more extensive testing, such as meibomian gland imaging, to tell us more about the nature of the patient’s disease, which guides the approach to treatment.

	1.  Bron AJ, de Paiva CS, Chauhan SK, et al. TFOS DEWS II pathophysiology report. 

	2.  Jacobi C, Jacobi A, Kruse FE, et al. Tear film osmolarity measurements in dry eye disease using electrical impedance technology. 

	Preeya K. Gupta, MD
	e: preeya.gupta@duke.edu
	Dr. Gupta is an associate professor of ophthalmology at Duke University Eye Center in Durham, NC, and clinical director of Duke Eye Center at Page Road, in Durham. Dr. Gupta did not indicate any proprietary interest relevant to the subject matter.

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