Wet macular degeneration occurs when abnormal blood vessels form and leak fluid or blood beneath the retina, causing permanent damage to the macula and central vision loss. At Wold Family Macular Degeneration Center we offer many clinical trials for treating wet AMD.

These studies involve administering injections of medication such as Lucentis (ranibizumab). Some may require lifelong, monthly treatments in order to maintain vision.

Long-Lasting Medications

Macular degeneration occurs when retinal pigment epithelial (RPE) cells in the macula begin to deteriorate, known as retinal pigment epithelial degeneration or AMD. By blocking or modulating various aspects of inflammation, new drugs may slow progression of dry AMD and improve vision; one such study being conducted at Wold Family Macular Degeneration Center evaluates an investigational drug called ASP7317 on patients suffering geographic atrophy associated with dry age-related macular degeneration.

Macular degeneration most frequently appears as dry form macular degeneration, consisting of yellow spots known as drusen which accumulate over time and gradually lead to central vision loss. Wet form macular degeneration involves abnormal blood vessels growing under the retina that leak fluid or blood, leading to rapid vision loss. The wet form is more severe and may result in rapid loss.

Researchers predict that new treatments for wet macular degeneration will soon become available. A combination treatment approach could potentially significantly lower vision loss rates by combining therapies that block VEGF, inhibit angiogenesis and treat choroidal neovascularization – two clinical trials are currently taking place at the Wold Family Macular Degeneration Research Center to test this theory.

At present, Lucentis is the sole anti-VEGF medication available for wet macular degeneration treatment, administered via subconjunctival injection once every month and has proven itself successful at significantly improving vision in many patients. Other studies are exploring other agents such as angiogenesis inhibitors or modulators which could provide additional benefit in wet AMD cases.

Casey Eye Institute, an internationally recognized leader in gene therapy research and practice, is conducting an upcoming clinical trial that combines surgery with gene-based therapy to offer promising solutions. Surgeons will replace or augment damaged genes associated with wet AMD; patients will also receive one injection of an investigational study drug ABP 938 that has yet to receive FDA approval; this comparison study will compare its safety and efficacy against that of Eylea(r).

Gene Therapy

Wet macular degeneration involves abnormal blood vessels forming beneath the retina, caused by growth factors like vascular endothelial growth factor (VEGF). Drugs designed to block these growth factors may help slow or stop their effects on leakage that leads to vision loss, while gene therapy involves implanting new genetic instructions into eye cells in order to produce proteins that treat this disease. Imaging technology makes the eye an ideal target for this treatment since its tissues can be isolated from rest of body, making imaging easy inside of eye.

Recombinant Adeno-Associated Viral (rAAV) vectors have repeatedly proven safe and effective at transferring genes into eye cells during clinical trials,1-8 the ADVM-022 study was one of the first uses of this technology in eye treatments; using an rAAV vector injection into one eye to deliver a gene that provides the code to make human CD59 soluble proteins that inhibit complement-mediated cell lysis thus keeping retinal cells alive.1-8

Results from this clinical trial demonstrate that the recombinant gene delivery system can significantly decrease the need for anti-VEGF injections. Patients receiving high doses experienced an annual reduction in injections by 98% while those in lower dose groups saw their injection frequency reduced by 81%.

Hemera Biosciences’ GT-005 gene therapy clinical trial provides another ocular gene therapy option. Using an AAV vector, this therapeutic modifies retinal cells so they produce more of the protein that protects against dry AMD. After receiving genetic modification treatment, these modified cells continue producing CFI permanently; making this gene therapy easy to administer via just one injection into each eye.

The ABBV-RGX-314 gene therapy study is another wet macular degeneration clinical trial employing this technology. RGX-314 is an experimental medication containing genetic instructions for producing anti-VEGF proteins. Once these genetically modified cells start producing it, RGX-314 should become easier to administer with one single injection rather than monthly ones. At UC Davis Health in early July, Dr. Yiu performed his inaugural gene therapy eye surgery as part of this research and will monitor this patient to see whether the gene therapy reduces his need for anti-VEGF injections.

Treat-and-Extend Regimens

Intravitreal injection of an anti-vascular endothelial growth factor (anti-VEGF) agent is currently the only proven therapy to improve and maintain visual acuity in wet macular degeneration. Wet macular degeneration occurs when abnormal blood vessels form under the retina, causing fluid leakage or hemorrhage which leads to vision loss; VEGF plays a key role in their development, leading to vision loss. There are currently four anti-VEGF drugs on the market – ranibizumab, Aflibercept, Bevacizumab, and Brolucizumab which reduce fluid and hemorrhage significantly but require monthly clinic visits due their fixed frequency dosing schedules for maintenance therapy due their fixed dosing schedules for maintenance therapy maintenance therapy maintenance therapy due their fixed frequency dosing schedules for maintenance therapy due their fixed dosing schedules for maintenance therapy maintenance therapy maintenance therapy maintenance therapy due their fixed dosing schedules.

Retinal specialists have devised a novel regimen called the treat-and-extend (TAE) approach in order to decrease clinic visits and treatment intervals required by patients. With this strategy, initial months of treatment are administered more frequently followed by longer dosing intervals – this strategy has proven more successful in producing improved results than fixed monthly dosing regimens or PRN regimes.

Recently, a large, multicenter randomized trial compared the efficacy of T&E treatment with traditional monthly regimen in treating treatment-naive neovascular AMD patients. After 24 months, vision outcomes were similar between groups while T&E group saw significantly fewer injections and visits overall than usual.

One resubmitted study evaluated the effectiveness of T&E regimens for non-AMD with persistent CNV, finding they could be maintained over time with reduced dosing over time. Furthermore, real world clinical practice allows patients to achieve an extended treatment interval of 16 weeks or more with Aflibercept.

These results demonstrate the power of T&E with reduced dosing frequency to provide effective visual outcomes without monthly clinic visits, something both patients and healthcare providers will appreciate. At RCSD, we are exploring other exciting approaches to slow macular degeneration progression such as long-acting molecules and gene therapy as possible solutions.

Genetic Screening

Genetic research is helping ophthalmologists better predict if a patient will develop the wet form of age-related macular degeneration, in which abnormal blood vessels in the retina cause permanent vision loss.1 Being able to identify patients at greater risk for wet AMD is critical, as this allows doctors to closely monitor them and possibly treat with FDA-approved drugs like Lucentis, Eylea, Macugen and Visudyne in combination with photodynamic therapy (PDT).

Anti-VEGF treatments work by blocking new blood vessel formation that contributes to wet macular degeneration. Treatment currently involves regular injections of these drugs into the eye; however, several gene therapies are in clinical trials that could offer patients one-and-done solutions, like RGX-314’s one-time application of anticomplement proteins and/or antiangiogenic proteins to the eye in order to inhibit new vessel growth and therefore slow progression of wet AMD.

Future generations may be able to use predictive genetic tests to assess an individual’s risk of wet AMD. Such tests identify mutations that contribute to disease development but do not exhibit symptoms at the time of testing2.2

Primary care physicians will increasingly be expected to advise their patients about the pros and cons of various genetic screening services and interpret test results. The success of genetic screening programs will largely depend on recruitment methods, education and counseling provided, testing schedules and predictive value as well as any interventions available for those screened3.3

Although genetic screening offers potential advantages, there are also fears that economic interests might lead to oversaturation of testing before its effectiveness, acceptability and cost-effectiveness have been verified. Furthermore, some people find being tested for conditions which have no direct bearing on their quality of life disconcerting; thus it is crucial that screening programs based on scientific evidence promote patient participation in such screening programs.