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New frontiers of technology for treatment of eye diseases
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Contemporary health care is changing radically as emerging technologies use innovation and creativity to determine newer ways of managing complex problems. The pharmaceutical industry has been on the forefront of invention, creating novel drugs and drug delivery systems to treat myriad eye diseases. The current drug delivery approaches place a significant burden on patients and their families, with frequent dosing regimens and long-drawn treatment protocols. Also, the local and systemic side effects of some of these medications may lead to noncompliance with the treatment and ultimately to treatment failure.
As the number of patients requiring long-term medications is on the rise, there is an urgent need to develop novel ocular delivery systems. An ideal drug delivery system would achieve bioavailability of the drug at the target tissue for a prolonged time interval with minimal systemic side effects. It would have mechanisms incorporated to monitor the eye disease and be programmed to release the drug on demand. It would also be remotely controlled to administer precisely metered nano-doses. Such a device would be easy to insert and refillable and have a low cost. This would be groundbreaking.
Delivery devices
After the success of sustained-release drug delivery systems such as Retisert (fluocinolone acetonide intravitreal implant 0.59 mg, Bausch + Lomb) and Ozurdex (dexamethasone intravitreal implant 0.7 mg, Allergan), various drug delivery technologies are being developed to treat diseases of the eye. They are promising, but there are various obstacles to be surmounted.
Intravitreal inserts of brimonidine are being developed on the lines of the sustained-release dexamethasone PLGA platform for the management of geographic atrophy due to age-related macular degeneration and also as a neuroprotective modality in the management of glaucoma. Different tissue spaces to implant these reservoir-based drug delivery systems are also being explored. Subcutaneous, subconjunctival, intracanalicular, intracapsular and even suprachoroidal spaces have been looked at as potential sites for drug reservoirs.
A device that can be used for suprachoroidal drug delivery, the iTrack microcatheter (iScience Interventional), has been introduced commercially. The microcannula includes an optical fiber that helps to guide surgical insertion. Tetz et al reported the European experience with this device in a retrospective analysis. In 21 eyes with wet AMD unresponsive to conventional therapies, the microcatheter was used to deliver a combination of 4 mg bevacizumab and 4 mg triamcinolone to the submacular suprachoroidal space. The drug was delivered successfully and atraumatically in all cases, with no serious intraoperative or postoperative complications.
Another surgically implanted device, using encapsulated cell technology, is being developed by Neurotech. The device contains human retinal pigment epithelial cells genetically modified to secrete a drug. A semipermeable membrane allows the outward diffusion of drug and inward diffusion of nutrients for cell survival but protects the contents from immunological attack. Two such devices — NT-501, which secretes ciliary neurotrophic factor for the treatment of geographic atrophy in dry AMD, and NT-503, which secretes a VEGF receptor Fc fusion protein that is reportedly 20-fold more efficient in neutralizing VEGF than ranibizumab — for wet AMD are being evaluated.
Nano-ophthalmology
Nanomedicine in ophthalmology involves diagnosis, monitoring and treatment using biopharmaceuticals, implantable materials and implantable devices. Nanoparticles lend themselves beautifully as an ideal ocular drug carrier. Nanoparticles for drug delivery can be adjusted to modify numerous properties such as mucoadhesion, biocompatibility and biodegradability, thus enhancing drug permeation. In fact, nanobiotechnology can be used to render personalized treatment. Variation in the disease progression and response to treatment can be taken into consideration, and the pharmacogenetics and pharmacoproteomics can be modified to give specific treatment suited for the individual.
3-D printing of retinal cells
In a revolutionary breakthrough, Lorber and colleagues recently reported successfully printing retinal cells using an inkjet printer. The preliminary results provide proof of principle that an inkjet printer can be used to print two types of cells from the retina of adult rats: ganglion cells and glial cells. Their results showed that printed cells remained healthy and retained their ability to survive and grow in culture. This technology of making artificial retina grafts appears to be promising, but robust pre- and post-market scientific data are warranted to prove its efficacy in curing blindness.
References:
Jain KK. Med Princ Pract. 2008;doi:10.1159/000112961.
Lorber B, et al. Biofabrication. 2014;doi:10.1088/1758-5082/6/1/015001.
Tetz M, et al. Ophthalmologica. 2012;doi:10.1159/000336045.
For more information:
Dennis S.C. Lam, MD, FRCOphth, can be reached at State Key Laboratory in Ophthalmology, Sun Yat-Yen University, 54 South Xianlie Road, Guangzhou 510060, People’s Republic of China; +852-3997-3266; fax: +852-3996-8212; email: dennislam.gm@gmail.com.
Disclosure: The authors have no relevant financial disclosures.