11TH ANNUAL INTERNATIONAL THINK TANK FOCUS:
New Methods of Drug Delivery to the Eye

For decades, glaucoma patients have been taking daily medication, most often in the form of eye drops to lower intraocular pressure (IOP), the main risk factor for the disease. Today, there are seven different classes of drugs used in treating glaucoma. Half of glaucoma patients use more than one drug, and for many the treatment involves trial and error to see what works best.

Now, researchers are looking at new ways to deliver drugs – ways that extend care, work more effectively (topical eye drops penetrate poorly because of tearing and dosage can be inconsistent), and don't require ongoing patient involvement. Non-compliance is a serious problem. Most glaucomas are chronic conditions that require continuing care and too many patients do not take their medications as prescribed by their physicians.

Are we approaching the end of the era of topical eye drops? What exactly is on the scientific research horizon as it relates to sustained release drug delivery systems that could control IOP and, down the road, protect the retinal ganglion cells which die in glaucoma and rescue damaged cells? Those questions were at the heart of The Glaucoma Foundation's Eleventh Annual Scientific Think Tank on "New Methods of Drug Delivery to the Eye in Relation to Neuroprotection, Regeneraion, and Treatment of Glaucoma."

As in previous years, the collaborative conference -- with some 30 participants from the United States, as well as from Germany, England and Israel -- provided a forum at which researchers across disciplines and laboratories could discuss ongoing research in various medical areas and the potential application of those ideas to glaucoma.

Concepts discussed at the Think Tank for future drug delivery systems (to the front of the eye?) ranged from those intended to be administered by a patient (a better way to achieve drug delivery that can be sustained for up to one week, for example some new form of a lens covering a part of the eye, with drug infused molecules dispersed in the lens material); procedures administered in a doctor’s office that can be sustained for several months (for example needleless injections of drugs or biomaterial inserts); and still others administered surgically (for example, intravitreal sustained release implants that would be retrived and replaced after an extended period of time).
Participants also discussed potential technologies for delivering materials to the posterior (back) of the eye, where the damage in glaucoma occurs -- for example, new therapies to deliver neurotrophic factors that nourish the cells and halt degeneration of the retinal ganglion cells that die in glaucoma.

What are some of the “smart” drug delivery systems being developed:

• Miniature implantable pumps that deliver fluid to the eye for an extended period.
  
• Injections that release drugs into the vitreous.
  
• Surgically-placed implants inside the eye that carry medication where it is needed and gradually release it.
  
• Electric current used to carry an ionized drug across tissue.
  
• Nanoparticles that incorporate conventional drugs and act as drug carriers.
  
• Transcleral drug delivery – injecting a drug that slowly diffuses into the eye through the white part of the eye.
  
• Stem cells that act as homing devices, delivering their drug payload where it is needed.
  
• Molecules which will carry genes inside the cells to internally synthesize a beneficial product.
  
• Neural progenitor cells that act as delivery vehicles for selected growth factors.
  
• Synthetic bubble-like molecules called liposomes that can carry drugs to cells or tissues.
  

Some alternative drug delivery systems are being applied to other diseases. Implants such as miniature insulin pumps, for example, and microstructures carrying chemotherapy drugs to target tissues have already improved countless lives. But, while many consider a sustained delivery system with minimal side effects – one that does not require patient involvement – a feasible goal for the next generation of glaucoma treatment, challenges still need to be addressed.

In the front of the eye, improving the biocompatibility of implantable medical devices so that the foreign body response that often follows transplants can be avoided remains a priority. Another challenge is the development of more adhesive biomaterials to help keep the drug in the eye. The inability of drugs to cross certain tissue layers in the eye and the need to overcome these barrier properties is another area that requires study.

Treating diseases of the back of the eye has been limited by the difficulty of delivering effective doses to target tissues – determining how much medication is needed and where in the back of the eye to target. Glaucoma poses special challenges as many different back of the eye locations are possible targets that may play a role in the degeneration of the retinal ganglion cells that cause the disease.

“The technologies exist,” says Dr. Robert Ritch, Chairman of the Think Tank and Medical Director of The Glaucoma Foundation. “Our hope is that our collaborative Think Tank, which has historically influenced how scientists direct their research, will help overcome the challenges that remain so that new drug systems will be available not only for controlling intraocular pressure, but for effectively delivering drugs and neuroprotective materials to targeted parts of the back of the eye where the damage in glaucoma occurs.”

Special thanks to the Eleventh Annual Think Tank organizers for their efforts that made this event so productive:
Robert Ritch, MD, Chairman
Terete Borrás, PhD
Henry F. Edelhauser, PhD
Julia E. Richards, PhD
Michael J. Young, PhD
Shuguang Zhang, PhD