Tiny Cup Attached to Eye Improves Drug Delivery for Retinal Diseases

Newswise — A new drug delivery system that uses a tiny silicone cup filled with any drug and sealed to the outer surface (episclera) of the eyeball may offer a more effective method for the sustained delivery of medicines for retinal and vitreous diseases, according to a new report by A. Linn Murphree, M.D, director of the Retinoblastoma Program in The Vision Center at Childrens Hospital Los Angeles. Dr. Murphree is also Professor of Ophthalmology and Pediatrics at the Keck School of Medicine of the University of Southern California and attending physician at the Doheny Eye Institute.

In his invited presentation, made July 30th, 2009 at the Association for Research in Vision and Ophthalmology (ARVO) Summer Eye Research Conference on Ophthalmic Drug Delivery Systems in Bethesda, MD, Dr. Murphree said the device, called an episcleral drug reservoir, holds the potential to fundamentally change how we deliver medications to the eye for diseases like macular degeneration, diabetic retinopathy, uveitis, endophthalmitis and retinoblastoma. Working much like an organ-specific transdermal skin patch, the tiny cup isolates the medication targeted to the eye from being absorbed into the blood stream. This new delivery system is a safe and non-invasive way to deliver effective doses of medications to the interior of the eye over long periods of time (weeks to months). Currently drops, periocular injections and intraocular injections are used to deliver medications to the eye but generally for short periods of time.

Dr. Murphree, who is a recipient of a National Institutes of Health RAID grant which provides funding for the development of procedures leading to clinical trials, believes the development of this type of delivery device represents a paradigm shift in the way physicians will deliver drugs to all organ systems in the future.

"The implantation of this kind of device on any organ and the ability to deliver medication to the affected organ, could be a huge advance in how we currently treat cancer," Dr. Murphree said. This work is done in conjunction with Ricardo Carvalho, M.D., Ph.D. and the company 3T Ophthalmics which is developing the drug delivery system.

The episcleral drug reservoir is inserted under the thin, filmy conjunctiva, or covering of the eyeball, to the sclera--the fibrous, protective outer layer of the eye. The tiny cup administers the drug slowly by passive diffusion through the sclera, where it reaches the retina and vitreous. The device is so small the patient should feel little or no discomfort and it does not hinder normal vision.

Currently, drugs for most retinal diseases are delivered either through an I.V. drip (i.e. systemically) or by an injection into the eyeball (i.e. intravitreal), both of which pose risks for the patient.

For example, chemotherapy for retinoblastoma, a cancer affecting one in 15,000 children, must now be given intravenously. This requires relatively large doses of the drug are needed to achieve a therapeutic concentration in the retina. The chemotherapy destroys the bone marrow and depresses the child's immune system, often leading to secondary infections.

Intravitreal injections using a syringe, often used to treat age-related macular degeneration, require frequent out-patient visits and can lead to vitreous hemorrhage and retinal detachment. Eye drops are also generally ineffective for retinal diseases because most medications are washed away or diluted before they have a chance to reach the retina, located at the back of the eye close to the brain.

"When we administer chemotherapy to an infant for retinoblastoma at The Vision Center, it is expensive and puts a great strain on the family, especially if they are from another state. Our preliminary research shows that once the cup is fitted, the child should be able go home for several weeks. Because the drug is being administered directly into the eye and not systemically, chemotherapy dosage levels will be much lower and the debilitating side effects will be reduced," said Dr. Murphree.

With preliminary testing complete, Dr. Murphree is currently developing a protocol for Phase I/II clinical trials in humans to take place over the coming year.

Founded in 1928 with 12,000 members currently, ARVO is one of the nation's largest organizations for research in vision and ophthalmology. For more information, see www.arvo.org.

The Vision Center at Childrens Hospital Los Angeles is an international referral center known for its family friendly environment of children afflicted with all forms of eye disease and provides a full range of inpatient and outpatient services. It is the largest pediatric ophthalmology program in the nation with multiple subspecialty programs that are considered to be among today's finest resources for diagnosis, treatment and research.

Founded in 1901, Childrens Hospital Los Angeles has been treating the most seriously ill and injured children in Los Angeles for more than a century, and it is acknowledged throughout the United States and around the world for its leadership in pediatric and adolescent health. Childrens Hospital is one of America's premier teaching hospitals, affiliated with the Keck School of Medicine of the University of Southern California since 1932. It is a national leader in pediatric research.

For more information, see www.TheVisionCenterAtCHLA.org.