During the American Academy of Ophthalmology’s Retina Subspecialty Day in 2015, Peter K. Kaiser, MD, described six alternative methods being looked at for delivery of anti-VEGF drugs into the retinas of individuals experiencing choroidal neovascularization (CNV). Periodic intraocular injections are currently the only procedure for halting damaging blood vessel growth and leakage. Injections are expensive, time-consuming, and burdensome on the patients, so scientists are developing better ways to treat such blinding diseases as neovascular (wet) macular degeneration, diabetic macular edema, diabetic retinopathy, and myopic degeneration.
A biodegradable polymer, puts the drug into a polymer matrix by way of a biodegradable polymer that slowly releases the compound. “In the past,” said Dr. Kaiser, “emulsion technology was used to release particles, [but] the problem . . . is that the particles are variable in size, [and] size determines the release characteristics.” Improved polymer technology may make this a more effective method in the future.
Multilayer liposomes (phospholipids) are tiny bubbles (vesicles) in the body that are made of the same material as a cell membrane. Drugs can be stored in them. Then, as Dr. Kaiser explained, “as the lipid layer breaks down, the drug is released. By adjusting the phospholipid formulation, you can adjust release characteristics and duration of [the release].”
A Micropump can slowly release drugs into the eye as often as every hour over a period of 4 to 9 months. It is attached unseen to the side exterior of the eyeball, and it delivers drugs to the interior of the eyeball through a tube permanently inserted through the white covering of the eye. The reservoir is filled in the clinic and can be programmed wirelessly.
Similarly, Genentech is conducting trials with Lucentis, wherein a refillable port-delivery system releases the drug slowly over 3 to 4 months.
Gene therapy may be able to provide unlimited release of medications. An adenoviral-based vector containing the gene for human pigment epithelium-derived factor (PEDF) has shown evidence of being able to stop disease progression when injected directly into the eyes of patients with neovascular age-related macular degeneration.
Encapsulated cell technology (ECT) involves a semipermeable cylinder that has altered retinal pigment epithelial cells. A drug called ciliary neurotrophic factor (CNTF) is produced and released by a device into the vitreous of the patient’s eyes. The ECT acts like a miniature factory for production and distribution of the drug.
The choroid itself can act as a depot for medication. The choroid is the layer of the eye behind the retina containing blood vessels that nourish the inner cell layers. A microcatheter or microneedle can be used to inject drugs into the suprachoroidal space.
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“Intravitreal injections and sustained-release solid implants,” said Dr Kaiser, “are the most common techniques used at the present time. Advances will continue to occur, along with the development of new agents.”
Time will tell which of these delivery methods will prove to be most effective, but the day of the needle may be soon passing.
