New developments in sustained release drug delivery for the treatment of intraocular disease
- National Eye Institute, National Institutes of Health, Bethesda, MD, USA
- Gisela Velez, MD, MPH, National Eye Institute, NIH, 10 Center Drive, Bldg 10, Rm 10N112, Bethesda, MD 20892, USA
Over the past 20 years, drug development has led to numerous medications with the potential to treat intraocular disease. These medications usually require systemic or frequent topical administration, which can limit the types of medications that can be used and the diseases that can be treated effectively.
Current methods of ocular drug delivery: limitations
Topical administration of medications can successfully treat a number of ocular diseases such as glaucoma, inflammation of the anterior segment or ocular surface, and external diseases of the eye. Nevertheless, topical delivery often fails to provide therapeutic levels in the vitreous cavity or posterior segment, and therefore is inadequate in the treatment of vitreoretinal diseases.
Drugs can often be delivered to the posterior segment by injection via the pars plana, as is the case, for example, with ganciclovir, foscarnet, and cidofovir. However, depending on the rate of clearance from the vitreous of a particular medication, large boluses and frequent administrations may be required to ensure therapeutic levels over an extended period of time. Frequent injections in clinical practice may not be practical for chronic diseases that can sometimes require multiple weekly administrations over months or years. In addition, multiple intraocular injections can lead to an increased likelihood of complications, such as vitreous haemorrhage, retinal detachment, and endophthalmitis.
The blood-ocular barrier is the main obstacle in the treatment of intraocular disease with systemic medications. Poor penetration of many drugs into the eye not only limits the number of medications available for the treatment of ocular diseases, but also limits the extent to which those available can be used without incurring serious systemic side effects. Medications, such as prednisone, cytotoxic agents for the treatment of intraocular inflammation, and antivirals for the treatment of cytomegalovirus (CMV) retinitis often cause severe side effects at the dosages needed to achieve their desired therapeutic effect. This is particularly problematic …
