Dry Eye Dx and Tx

Additional Implications of the Lacrimal Functional Unit

BY WILLIAM TOWNSEND, OD, FAAO

My October 2015 column discussed the lacrimal functional unit (LFU) as a comprehensive concept for addressing dry eye disease (DED). The “unit” includes the ocular surface (the cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal glands, and the afferent and efferent neural networks that interconnect these structures (Stern et al, 1998). The authors proposed that compromise of any portion of the LFU could impair support of the ocular surface and lead to a cascade of events that can ultimately impede reflexive tearing by the lacrimal glands.

Tear Osmolarity

The primary function of the LFU is to protect the ocular surface by sustaining homeostasis (Bron et al, 2014). Under normal conditions, it maintains tear osmolarity (Tosm) within the narrow range of 286.5 to 306.3 mOsm/L; these values are very comparable to human serum osmolality values (Versura et al, 2010). Failure to maintain normal Tosm is a common and diagnostic feature of both evaporative dry eye (EDE) and aqueous deficient dry eye (ADDE) (Bron et al, 2014). In dry eye states, Tosm is frequently elevated or asymmetric between the eyes, and the disparity increases with severity of the DED.

Tear film hyperosmolarity initiates ocular surface damage and induces inflammation, which represents a final common pathway of DED pathogenesis (Bron et al, 2014; Tuazon et al, 2015).The release of inflammatory cytokines has the potential to cause dysfunction of the lacrimal gland and to inhibit reflexive tearing in response to sensory nerve impulses (Stern et al, 1998). Loss of protective androgens may also be an initiating factor in DED development (Bron et al, 2014; Tuazon et al, 2015).

Inflammation

Hyperosmolarity is not the only initiating insult in DED; the dry, desiccating environment induced by medications or other external factors may promote the release of inflammatory cytokines from the lacrimal gland and the ocular surface, leading to chronic inflammation (Stern et al, 1998). It is therefore vital when evaluating suspected DED to know all medications that a patient is taking.

Proinflammatory mediators produced by activated lymphocytes are commonly found in the tears of dry eye patients. Cytokines inhibit the transmission in peripheral nerves, such as those innervating the lacrimal glands. This chain of events frequently leads to hyperosmolarity (Bron et al, 2014).

Therapeutic Agents

The concept of a LFU helps clinicians and researchers understand the multifaceted triggers and interactions that cause dry eye, thus providing a starting point for developing therapeutic agents (Stern et al, 1998). For example, the causal relationship between inflammation and dry eye resulted in the development of a topical immunomodulator, and similar inflammation-reducing agents are in development. Specific metabolites of omega-3 and omega-6 essential fatty acids also work to resolve inflammation (Duvall and Levy, 2015).

Androgens are protective of the lacrimal and meibomian glands. Understanding this facet of the LFU has led to the use of compounded testosterone and dehydroepiandrosterone (DHEA) for meibomian gland dysfunction and EDE (Truong et al, 2014). CLS

For references, please visit www.clspectrum.com/references and click on document #242.

Dr. Townsend practices in Canyon, Texas, and is an adjunct professor at the University of Houston College of Optometry. He is president of the Ocular Surface Society of Optometry and conducts research in ocular surface disease, lens care solutions, and medications. He is also a consultant or advisor to Alcon, Allergan, NovaBay, TearScience, TearLab, and Science Based Health. Contact him at drbilltownsend@gmail.com.