Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies.

Research in the development of ophthalmic drug formulations and innovative technologies over the past few decades has been directed at improving the penetration of medications delivered to the eye. Currently, approximately 90% of all ophthalmic drug formulations (e.g. liposomes, micelles) are applied as eye drops. The major challenge of topical eye drops is low bioavailability, need for frequent instillation due to the short half-life, poor drug solubility, and potential side effects. Recent research has been focused on improving topical drug delivery devices by increasing ocular residence time, overcoming physiological and anatomical barriers, and developing medical devices and drug formulations to increase the duration of action of the active drugs. Researchers have developed innovative technologies and formulations ranging from sub-micron to macroscopic size such as prodrugs, enhancers, mucus-penetrating particles (MPPs), therapeutic contact lenses, and collagen corneal shields. Another approach towards the development of effective topical drug delivery is embedding therapeutic formulations in microdevices designed for sustained release of the active drugs. The goal is to optimize the delivery of ophthalmic medications by achieving high drug concentration with prolonged duration of action that is convenient for patients to administer.

Clusterin from human clinical tear samples: Positive correlation between tear concentration and Schirmer strip test results.

PURPOSE: To investigate the relationship between tear concentration of the homeostatic protein clusterin (CLU) and dry eye signs and symptoms, and to characterize tear CLU protein. METHODS: Two independent studies were conducted, one in Tucson (44 subjects), the other in Los Angeles (52 subjects). A cohort study design was employed to enroll patients without regard to dry eye diagnosis. Dry eye signs and symptoms were assessed using clinical tests. Tear samples were collected by Schirmer strip, and also by micropipette at slit lamp when possible. CLU from both sample types was quantified by immunoassay. The relationship between CLU concentration and clinical test scores was determined by Pearson's correlation coefficient (for individual eyes) and multiple linear regression analysis (including both eyes). CLU was also evaluated biochemically by western blotting. RESULTS: In the Tucson cohort, a positive correlation was observed between tear CLU concentration and results of the Schirmer strip test, a measure of tear flow (p = 0.021 includes both eyes). This result was corroborated in the Los Angeles cohort (p = 0.013). The mean tear CLU concentration was 31 ±â€¯14 µg/mL (n = 18 subjects, 33 eyes; range = 7-48 µg/mL). CLU from clinical tear samples appeared biochemically similar to CLU from a non-clinical tear sample and from blood plasma. CONCLUSIONS: Results support the hypothesis that an optimal concentration of tear CLU is important for ocular surface health, and that this drops below the effective threshold in dry eye. Tear CLU measurement might identify patients that could benefit from supplementation. Information about concentration will aid development of therapeutic dosage parameters.