Restasis® (Cyclosporine Ophthalmic Emulsion 0.05% – Allergan, Inc.) is an immunosuppressive agent when administered systemically. In patients whose tear production is decreased due to ocular inflammation associated with keratoconjunctivitis sicca (Dry Eye Disease – DED), cyclosporine emulsion is thought to act as a partial immunomodulator. Although the exact mechanism of action is not known, it is understood that dry eye is a disease in which ocular surface inflammation and hyperosmolarity may be linked in a perpetuating inflammatory cycle. Breaking this inflammation-osmolarity cycle would be a key component in treatment of DED.
Recently, we had participated in a referent value study on the general patient population for the TearLab Osmolarity System FDA 510(k) submission. Within that study, our site cataloged dry eye subjects who were being treated with Restasis. This gave us the opportunity to investigate the effect of Restasis on osmolarity, albeit from a more epidemiological approach than a longitudinal study.
It is well known that the average osmolarity of normal subjects is, on average 302 mOsms/L, having been reported in both the 2006 Tomlinson meta-analysis [Tomlinson A. et. al., IOVS 47(10): 2006] and more recently as the result of a TearLab sponsored 300-subject study [Sullivan BD. et. al. IOVS ePub (2010)]. Dry eye subjects typically have much higher tear film osmolarity than normal subjects, when the maximum value between the two eyes is used as a diagnostic indicator. Consistent with this observation, in the data analysis at our site 37 subjects were classified with dry eye disease, of which 20 subjects were on Restasis therapy. The 17 dry eye subjects not on Restasis therapy had a mean osmolarity of 316 ± 16.9, while the 20 subjects on Restasis therapy had a mean osmolarity of 310 ± 19.4. Two of the Restasis subjects had osmolarity values of 344 and 369 mOsms/L and were thus classified as “non-responders.” If the “non-responders” were removed from the Restasis data set, the mean osmolarity was reduced to a statistically significant 305 ± 11.1 (p<0.02, n=18).
Although this data represents a small pilot study, it does point to an interesting possibility that the inflammatory-osmolarity cycle may be broken using an immunosuppressive agent such as Restasis. Further study is recommended.
