Effect of castor oil emulsion eyedrops on tear film composition and stability☆
Introduction
Dry eye is defined as a disorder of the tear film due to a deficiency in aqueous tear production and/or increased evaporative loss that leads to irritation of the ocular surface and is associated with symptoms of discomfort [1].
The prevalence rates reported in the literature are highly dependent upon the selection criteria used to diagnose dry eye subjects. Estimates in the prevalence of dry eye syndrome ranged from 14.4% to 34.0% [2], [3], [4], [5], [6], [7], [8], [9] depending upon population biases and selection criteria. Additionally, an increased prevalence of dry eye with age [3], [6], in women [3], [6], [10] and in contact lens wearers with estimates from 43% to 50.1% [2], [3], [11] has also been observed.
Treatments have been formulated to either restore tear volume or to increase tear film stability hence reducing tear evaporation. The most commonly used treatment for dry eyes consists of topically applied artificial tears and lubricants in the forms of eyedrops, gel or ointments. In a 2000 study by Nelson et al. [12], 87% of dry eye patients were reported to have used medications for dry eye in the previous 3 months, 56% reported using lubricant drops and 40% using lubricant ointments. The main active agents in traditional artificial tears products are viscosity enhancing agents used in a range of concentrations, in preserved or unpreserved formulations. Such products have been used in practice to help in the relief of the symptoms present in mild dry eye conditions, with more viscous products dedicated to more pronounced symptoms [13], [14].
In the last few years, as a result of a better understanding of the complex aetiology of dry eye syndrome, more targeted, specialised treatments have emerged, either pharmacological compounds aimed at decreasing inflammation, improving lipid production and/or stimulating mucin and aqueous secretions from the ocular surface or treatments formulated to mimic the structure and function of natural tears.
A new emulsion eyedrop developed by Allergan, containing 1.25% castor oil stabilised within an aqueous demulcent formula, was initially used as a vehicle for cyclosporine ophthalmic emulsion 0.05% (Restasis®, Allergan), a pharmaceutical compound used to modulate inflammatory components in KCS and severe dry eye cases. It is available in the US in slightly modified form as an artificial tear emulsion (Refresh Endura®, Allergan). This artificial tear solution falls into the category of eyedrops with targeted efficacy, aiming at treating all three layers of the tear film. Upon release the oil is thought to interact with the superficial lipid layer stabilising the tear film and reducing tear film evaporation, while the aqueous demulcent enhances the aqueous and mucin layers [15].
Interestingly, in clinical studies of Restasis® cyclosporine ophthalmic emulsion, the castor oil vehicle alone was reported to reduce some signs and symptoms of dry eye [16], [17] and a pre-market study on the emulsion itself as an artificial tear on 73 mild to moderate dry eye subjects reported a significant increase in tear break-up time compared to baseline together with some improvements in signs and symptoms of dry eye after 90 days of usage [18].
Di Pascuale et al. [19] in a study on 5 normals and 10 aqueous tear deficient subjects reported a significant increase in tear lipid layer thickness and improved tear film spread time following the use of 1.25% castor oil emulsion eyedrop. Khanal et al. [20] measured reduced tear film evaporation with use of the 1.25% castor oil emulsion eyedrop, greater than that with a conventional aqueous drop. Further, Goto et al. [21] reported improved symptoms scores, increased tear break-up time and decreased tear evaporation after 2 weeks of six times daily treatment of homogenised castor oil compared to placebo for patients with non-inflamed obstructive meibomian gland dysfunction.
Castor oil eyedrops are lipid eyedrops which beneficial effects are thought to be associated with a modification of the lipid layer properties. The objectives of this pilot study were primarily to measure the prevalence of castor oil in the tear fluid over time and quantify the effects of the castor oil eyedrops on the tear film lipid layer of normal and dry eye subjects. A secondary objective was to quantify the initial effects of the emulsion eyedrop on ocular symptomatology.
Section snippets
Test products
The test product was an investigative formula of a new emulsion eyedrop containing a polar oil (castor oil) within a aqueous demulcent formula. The castor oil primarily consists of the triglyceride of ricinoleic acid. The demulcent aqueous phase consists of polysorbate 80 (demulcent and emulsifier), carbomer 1342 (gelling agent and emulsifier) and glycerin (demulcent and tonicity agent). The non-preserved formula was dispensed in unit-dose plastic ampoules. The modality of use of the test
Results
Fifteen subjects completed the study with no observed adverse events. The demographics of the population are presented in Table 1. Out of the fifteen subjects, ten subjects were classified as symptomatic according to the McMonnies questionnaire with an average score of 58.2 ranging from 40 to 88; the remaining five subjects were representative of normal asymptomatic patients with an average McMonnies score of 24.4 ranging from 16 to 34.
Conjunctival hyperaemia, rated using a 5-point scale, was
Discussion
The primary laboratory objective of this investigation was to measure the residence time of castor oil emulsion eyedrops in the tear film. Castor oil presence was detected up to 4 h after a single eyedrop instillation. The use of the emulsion eyedrop was also associated in some cases with a significant increase in the total volume of lipids presents in the tear film. Such increase was most marked for the triglycerides family at one and four hours post-instillation. However, overall due to the
Conclusion
This pilot study primarily measured the prevalence of castor oil in the tear fluid over time and quantified its effects on the tear film lipid layer of normal and dry eye subjects. Combined results for both normal and dry eye subjects showed that castor oil was detected up to 4 h after a single eyedrop instillation.
The volume of lipid present in the tear film, in particular triglycerides, increased significantly post-instillation suggesting that the castor oil eyedrop interacts with the tear
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The investigation was sponsored via a grant from Allergan Inc..