SUSTAINED RELEASES INTRAOCULAR DRUG DELIVERY FOR DIABETIC MACULA EDEMA

Paul Ashton (Watertown)

Diabetic macular edema is presently managed by surgical procedures or laser therapy. Despite the best efforts however, hundreds of thousands of patients lose vision every year. One reason for this is the dearth of effective pharmacological treatments available for diseases of the back of the eye. Localized ocular delivery presents many unique problems that require a serious, concerted effort to overcome. Several strategies are now being developed to deliver drugs directly to the vitreous and retina. Such localized delivery enables agents to be used that would be ineffective or prohibitively toxic if given systemically. If successful, this approach has the potential to revolutionize patient care. Amongst the more promising developments are intraocular inserts designed to delivery drugs directly to the vitreous and retina.

The requirements of a delivery system reflect the severity and duration of a disease. For chronic progressive diseases such as diabetic retinopathy an ideal system should: (1) Be highly effective (2) Have a minimum duration of one year (3) Provide constant release over this time (4) Maintain steady, therapeutic drug levels in the eye while avoiding toxic peaks and sub therapeutic troughs (5) Avoid significant systemic exposure to the drug (6) Be safer and more effective than current therapies (7) Be simple to use and (8) Be cost effective. Vitrasert™, approved by the FDA for CMV retinitis, provides 6 - 8 months of constant release of ganciclovir drugs after implantation and is extremely effective in controlling CMV retinitis. Although Vitrasert fulfills many of the criteria listed above and is widely used for CMV, this insert is not ideal. The ideal system would provide sustained release for several years. We have now developed a system designed to be easily implanted into the eye and to provide constant drug release over 3 years.

Initial clinical trials have been performed in patients with severe diabetic macular edema. 6 patients received an implant releasing fluocinolone acetonide at 5 - 6 ug/day in their most severely affected eye. All patients had a rapid resolution of edema (as measured by fluoresceine angiography) and an improvement in visual acuity. This improvement has been stable for over the duration of follow-up while fellow, untreated eye have deteriorated. All eyes implanted with the high dose developed an elevated increase in IOP. One patient required a filter procedure and the others have been controllable with drops. Mulicenter trials using a low dose implant (0.5 ug/day) are ongoing.


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