Purpose: Despite pharmacological advances, delivery of drugs to the posterior segment of the eye remains problematic. We investigated the ability of hydrogel contact lenses to deliver small-molecule steroids, as well as larger biological molecules to the posterior segment. Methods: Release characteristics of steroid-instilled lenses were studied in vitro. Drug delivery to the posterior segment of the eye was evaluated in a rabbit model, in which hydrogel contact lenses treated with diluted steroids (prednisolone or beclomethasone) were placed on rabbit corneas for four hours on days 1, 2, 5, 8 and 10. The amount of drug in plasma, posterior segment tissue and vitreous humour was measured with highperformance liquid chromatography-tandem mass spectrometry. In a further preliminary investigation, two rabbits were treated with ranibizumab. Results: The lenses released prednisolone and beclomethasone in saline over a six-hour period at a declining rate. Prednisolone was found in posterior segment tissue from six of six rabbits at concentrations ranging from 26.8 to 166 ng/g and in vitreous humour from two of six rabbits. Beclomethasone was detected in posterior segment tissue from three rabbits but was not found in the vitreous humour. Ranibizumab was detected in posterior segment tissue in a range from 0.19 ng/mL to 0.5183 ng/mL. Conclusions: Hydrogel contact lenses are a non-invasive, periocular drug delivery device capable of achieving measurable drug levels in posterior segment tissue.Submitted: 17 May 2010 Revised: 9 July 2010 Accepted for publication: 6 September 2010Key words: contact lens, drug delivery systems, high-performance liquid chromatography, hydrogels, mass spectrometry, passive diffusion/transport, ranibizumab Recent pharmacological advances have resulted in new drugs for the treatment of posterior segment ocular diseases. For example, inhibitors of vascular endothelial growth factor, a biological molecule closely linked to neovascularisation in the human eye, slow or stop the progression of age-related macular degeneration; [1][2][3] however, delivery of such drugs to the posterior segment of the eye remains problematic. To date, most have been delivered by intravitreal injection. This method provides rapid delivery of the drug to the vitreous humour and can achieve immediate therapeutic
212Clinical and Experimental Optometry © 2010 Optometrists Association Australia concentrations while avoiding systemic exposure; however, drugs are eliminated via first-order diffusion within a short time and thus, in most cases, repeated injections are necessary to maintain sustained delivery of the drug. 4,5 There are many risks associated with repeated intravitreal injections, including endophthalmitis, cataract formation, retinal detachment, haemorrhage and infection. 4,6 Less invasive approaches than intraocular drug delivery for the treatment of ocular diseases include topical application by means of eye drops or ointments, systemic delivery and periocular delivery through various sustained release device...
