Abstract
Dry eye disease (DED) is one of the most common ocular surface disorders characterised by a deficiency in quality and/or quantity of the tear fluid. Due to its multifactorial nature involving several inter-related underlying pathologies, it can rapidly accelerate to become a chronic refractory condition. Therefore, several therapeutic interventions are often simultaneously recommended to manage DED efficiently. Typically, artificial tear supplements are the first line of treatment, followed by topical application of medicated eyedrops. However, the bioavailability of topical eyedrops is generally low as the well-developed protective mechanisms of the eye ensure their rapid clearance from the precorneal space, thus limiting ocular penetration of the incorporated drug. Moreover, excipients commonly used in eyedrops can potentially exhibit ocular toxicity and further exacerbate the signs and symptoms of DED. Therefore, formulation development of topical eyedrops is rather challenging. This review highlights the challenges typically faced in eyedrop development, in particular, those intended for the management of DED. Firstly, various artificial tear supplements currently on the market, their mechanisms of action, as well as their application, are discussed. Furthermore, formulation strategies generally used to enhance ocular drug delivery, their advantages and limitations, as well as their application in commercially available DED eyedrops are described.
Highlights
Dry eye disease (DED) is one of the most prevalent ocular surface disorders affecting tens of millions of individuals globally [1]
DEWS II) reviewed the existing literature to achieve an international consensus on the current working knowledge of DED and defined it as “a multifactorial disease of the ocular surface characterised 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 aetiological roles” [2]
DED is often classified into two primary subtypes: aqueous tear-deficient dry eye (ADDE), characterised by inefficiency or inability of the lacrimal glands to produce tears, and evaporative dry eye (EDE), typically attributed to excessive evaporation of the tear fluid
Summary
Dry eye disease (DED) is one of the most prevalent ocular surface disorders affecting tens of millions of individuals globally [1]. DED is not sight-threatening in most patients, visual impairment associated with low spatial frequency and contrast sensitivity, increased glare, blurred vision and eye fatigue are frequently reported [3,4,5] In addition to these direct pathological manifestations, DED tends to compromise physical functioning, social interaction and general health and well-being of patients, resulting in a significant deterioration in their quality of life [6,7,8]. The efficacy of topically applied formulations is limited by the various protective mechanisms of the eye which reduce drug bioavailability, necessitating frequent eyedrop administration over prolonged periods This in turn is often associated with reduced patient compliance further limiting treatment efficacy. Formulations generally used in the management of DED to target the different underlying pathologies, their postulated benefits and their formulation characteristics are discussed
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