A New Treatment for Diabetic Macular Edema

Approximately 28% of diabetics have ocular complications. Diabetic macular edema (DME) is one of the leading causes of blindness in the industrialized world and is caused by leaking of blood vessels. The 10-year rate of developing macular edema is 20% for type I diabetics and 25.4% for type II diabetics using insulin. Moreover, about half of patients with DME will lose 2 or more lines of vision within 2 years.

Studies have found that anti-inflammatory therapy with corticosteroids is superior to that of antiangiogenic therapy. Current therapy consists of repeated intravitreal corticosteroid injections or surgical implantation of corticosteroid-eluting retinal implants (e.g. dexamethasone-eluting implant known as Ozudex). The invasive nature of both intravitreal injections and implants can lead to complications and limits patient enthusiasm for such repeated procedures. Moreover, patients also develop steroid-induced increased intraocular pressure, but the drug cannot be removed once injected. Therefore, there is a large unmet need for a topical, non-invasive treatment for DME that can easily be discontinued if needed. Contact lens (CL) drug delivery has the potential to achieve this goal; however, providing sustained drug release from contact lenses has historically proven challenging. Moreover, it is unclear if topical delivery can provide therapeutic levels of dexamethasone to the retina.

We have developed an innovative drug-eluting therapeutic CL (TCL) that incorporates a thin drug-polymer film within the periphery of a standard CL (Fig. 1). In contrast to other TCL designs, our design enabled the release of large drug quantities in a controlled manner over the course of few weeks, while allowing unimpeded vision through the lens, and was composed of materials that are all FDA-approved for use on the eye. We have demonstrated sustained release of therapeutic amounts of an antibiotic (ciprofloxacin), an antifungal agent (econazole), a glaucoma medication (latanoprost), and a corticosteroid (dexamethasone) for up to a month in bench-top studies. In rabbits, a dexamethasone-eluting TCL demonstrated safety and sustained drug delivery to the retina and choroid at levels that far exceeded those of hourly drops. While it our preliminary data suggest that the TCL provides therapeutic drug levels to the retina, further research is needed to determine if the lenses are indeed as efficacious as intravitreal injections.

The underlying hypothesis of this application is that dexamethasone-eluting TCL can safely and effectively treat macular edema as much as the current standard of care, intravitreal corticosteroid injections.
Aim 1. Evaluate safety and drug flux of dexamethasone-eluting contact lenses in vivo. We will evaluate drug flux and biocompatibility in normal rabbit eyes.
Aim 2. Evaluate efficacy in an animal model of macular edema. We will compare the efficacy of dexamethasone-eluting contact lenses in a rabbit model that has leakage of the retinal vessels induced by intravitreal injection of VEGF A. We have preliminary data that demonstrates that intravitreal VEGF A results in statistically significantly greater fluorescein leakage after 2 days compared to baseline. Using fluorescein angiography, pathology, and evaluation by a fluorotron (provides quantitative analysis of fluorescein leakage), we will compare the following treatment groups:
1) Dexamethasone-eluting contact lens
2) Intravitreal dexamethasone injection
3) Hourly dexamethasone 0.1% drops (limited to 8 hours a day for humanitarian reasons)
4) No treatment

This proposed approach is both feasible and valuable. The TCL can deliver high drug concentrations to the target tissue (retina) and the device has been shown to be safe and effective in non-human primates. The TCL addresses a major compliance challenge with the current approach that requires intravitreal injections or surgical implantation of drug delivery devices.