Sustained release technologies for retinal diseases

Purpose: To develop a series of strategies for the preparation of implantable sustained release systems for delivery of agents to the vitreous and retina. Methods. The major emphasis was on the constraints and limitations imposed by the disease state itself. Closely aligned with this consideration was the likely outcome of present therapies. This determined both type of implant acceptable and the surgieal manipulations (complexity and frequency) potentially justified in the development of a treatment modality. Thus for a chronic, sight threatening disease with poor outcome from current therapy, implanting a device through a large scierai incision every 5 years may be reasonable. Similarly implanting a shorter duration device may also be reasonable in a patient population with a relatively short life expectancy. In such conditions, where chronic treatment requires tight control of the percentage of drug released per day, a biocrodible system is likely to have little benefit. For diseases requiring acute treatment, such tight control of release rates is unnecessary and bioerodible devices may have a place if the erosion does not cause untoward effects (such as inflammation). Results: Using these considerations implants have been developed giving long term (5 years plus) sustained release devices for cyclosporine (for chronic uveitis), mid term (1.5-2 year devices) sustained release for CMV retinitis and short term (2-3 months) sustained release for proliferative vitreorelinopathy. These systems have been found to be highly effective in animal models and rapid progression to clinical trials is anticipated. Conclusion: The systems described may be clinically effective but also will serve to further establish the ground rules for the development of more sophisticated devices. Preliminary efforts focusing on disease activated systems and biotechnology products are progressing.