Tearfilm oriented dry eye therapy

In 2017 the Tear Film and Ocular Surface Society (TFOS) published the results of the second Dry Eye Workshop (DEWS II) in a number of consensus papers on the definition, diagnosis, pathophysiology and treatment of dry eyes. DEWS II defined dry eye as “a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.” The concept of disruption of tear film homeostasis is considered to be the unifying characteristic of dry eye disease (DED), which is then classified with respect to presence or absence of symptoms (symptomatic versus asymptomatic), and with respect to etiology (aqueous deficient versus evaporative dry eye). 


DEWS II suggests a staged treatment of dry eye in which ocular lubricants (artificial tears) play a central role, and are considered to replace or supplement the natural tear film without targeting the underlying pathophysiology of DED. Hyaluronan eye drops are offered as an option to increase tear viscosity and enhance lubrication due to their non-Newtonian shear-thinning properties.


Contrary to the DEWS II consensus, the Asia Dry Eye Society (ADES) restricts the definition of dry eye to patients having symptoms of either discomfort or visual disturbance. ADES recognizes that hyperosmolarity is not necessarily a precondition of dry eye, but frequently a consequence of reduced blinking frequency, e.g. in video display terminal (VDT) workers, and inflammation develops as a consequence in these patients. Coherently the ASED defines dry eye as a ‘multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage’.


The ASED classifies dry eye into three categories: aqueous deficient, increased evaporation and decreased wettability, recognizing that a compromised glycocalyx of the apical epithelial cells of the cornea will result in decreased water binding and lubricating properties of the ocular surface. Secretory as well as membrane bound mucins are believed to play a major role in tear film instability, and there is clinical evidence that this underlying mechanism may be ameliorated by topical secretagogues such as diquafasol and rebamipide eye drops. Out of this consideration the ASED developed a tear film oriented treatment (TFOT) strategy, where hyaluronan eye drops are indicated for the treatment of aqueous deficient dry eye, and secretagogue eye drops like 3% Diquafasol may be prescribed for all of the three dry eye categories.


Recently published clinical results seem to indicate that very high molecular weight hyaluronan (hylan A) eye drops do not only act as water binding lubricants, but may actively target the underlying pathophysiological mechanisms of ocular surface disease. 


0.15% hylan A eye drops (Comfort Shield®) provide in a dry eye stress model significantly better protection against the development of dry eye signs than 0.1% or 0.3% low molecular weight hyaluronic acid eye drops, as well as 3% Diquafasol eye drops. Moreover, 0.15% hylan A eye drops provide significantly better support in the recovery of physiological functions after dry eye stress, including amelioration of the inflammatory response. 


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