Next-Generation Tools to Treat Abnormal New Ocular Blood Vessels

Yannis M. Paulus, M.D., has been awarded two grants to advance two novel technologies, each with the potential to revolutionize the treatment of a range of vision-threatening conditions.

A Nanoneedle Array for Long-Term, Sustained Intraocular Drug Delivery

National Institutes of Health/ National Eye Institute Research Project Grant (NEI R01)

The development of new blood vessels, or neovascularization, is a major cause of blindness worldwide. It occurs in conditions ranging from diabetes and macular degeneration to corneal diseases. Current treatments are suboptimal in that they can involve frequent, often monthly, injections inside the eye, which carry risks of infection, among other effects.

Recent attempts to design systems to deliver drugs through the corneal barrier, notably biodegradable ‘microneedles’, have proven problematic.

Dr. Paulus is collaborating with Dr. Chi Hwan Lee in the Weldon School of Biomedical Engineering at Purdue University to develop a novel platform technology that delivers long-term, sustained intraocular drugs through fully-miniaturized, slowlybiodegradable silicon ‘nanoneedles’ embedded on a water- soluble contact lens.

“Nanotechnology makes so many improvements possible,” explains Dr. Paulus. “Our nanoneedles are more than 30 times smaller than microneedles, and they degrade more than ten times more slowly, providing longer-lasting therapy. And the best part is that this is as simple as putting in a contact lens. The contact lens dissolves within 30 seconds, leaving nanoneedles embedded in the peripheral cornea for long-term, sustained drug delivery.”

The R01 grant (overseen by NEI Bioengineering and Technology Program Director Tony Gover, Ph.D.) will be used to evaluate nanoneedle platforms of different sizes, shapes, aspect ratios and porosities, and to compare the safety, efficacy, and side effects of silicon nanoneedles to the current anti- vascular endothelial growth factor and laser therapies.

“Our goal is a minimally-invasive platform for painless, sustained intraocular drug delivery,” Dr. Paulus says. “This idea has broad applications beyond corneal neovascularization, including the treatment of diabetic retinopathy, macular degeneration, infections, dry eyes, and glaucoma.”

Photo-Mediated Ultrasound Therapy to Remove Microscopic Blood Vessels

Alcon Research Institute Young Investigator Grant

Choroidal neovascularization, the development of new blood vessels in the choroid, is the leading cause of vision loss due to wet age-related macular degeneration (AMD).

Two main treatments are currently used: frequent (often monthly) injections of anti-vascular endothelial growth factor (anti-VEGF therapy) and laser photocoagulation. Both have considerable shortcomings.

Anti-VEGF therapy can result in serious complications like infection, bleeding, glaucoma, and cataracts. Moreover, despite repeated treatments, some patients end up with significant vision loss or blindness.

The current method of photocoagulation delivers a high dose of short duration laser energy. At that intensity, it can damage surrounding healthy cells, leading to serious side effects like retinal atrophy and loss of peripheral and night vision.

Dr. Paulus is part of a multidisciplinary team of researchers, including Drs. Xueding Wang and Xinmai Yang, that developed and patented a novel non-invasive alternative—photo-mediated ultrasound therapy, or PUT.

“PUT delivers synchronized nanosecond laser pulses and ultrasound bursts at unprecedented speed and significantly lower laser intensity,” explains Dr. Paulus. “That combination allows us to target micro vessels with a degree of precision not achieved with conventional photocoagulation, and with far less risk of damage to surrounding tissues.”

He will use the Alcon grant for studies comparing the effectiveness of PUT and anti-VEGF therapy—a vital next step in moving PUT closer to clinical application.

“PUT also has the potential to transform how we care for patients with other neovascular, oncologic, and dermatologic conditions.”