AEVR Highlights Latest in Clinical Practice and Research for Patients in its International Age-Related Macular Degeneration (AMD) Awareness Week 2021 Congressional Briefing

AEVR began its virtual Seventh Annual Emerging Vision Scientists (EVS) Day with the global International AMD Awareness Week 2021 Congressional Briefing, also held during Healthy Aging Month, that highlighted the latest advances in federally funded research at the National Eye Institute (NEI)—as well as that funded by private foundations and industry—which is resulting in new treatments used in clinical practice for AMD. A leading cause of blindness and low vision in the United States and the developed world, AMD destroys central vision through proliferation of new blood vessels (“wet” or neovascular AMD) or gradual breakdown of cells (“dry” AMD or geographic atrophy) in and around the light-sensitive retina. AMD vision loss makes it difficult to read, drive, and perform everyday tasks, thereby affecting productivity, independence, and quality of life. Although age is the primary non-modifiable risk factor for AMD, gender, race, and genetics can play a role. Smoking is the primary modifiable risk factor.    

Amir H. Kashani, MD, PhD (Wilmer Eye Institute/Johns Hopkins University)

Amir H. Kashani, MD, PhD, an Associate Professor of Ophthalmology in the Wilmer Eye Institute at Johns Hopkins University and an AEVR EVS in 2015, discussed the latest on clinical care of AMD patients—which is dependent on both the stage and form of the disease. Based on the NEI’s Age-Related Eye Disease Studies (AREDS/AREDS2), AMD is classified as Early, Intermediate, or Advanced, where all three stages can reflect the dry form of the disease and Advanced AMD also reflects the neovascular or wet form. As a result, dry AMD accounts for about 80-90 percent of incidence, while wet AMD accounts for 10 percent. Clinicians often diagnose the onset of AMD well before visual function is impaired using Optical Coherence Tomography (OCT) and OCT Angiography (OCTA), non-invasive imaging technologies that create three-dimensional images of the retina and can help clinicians detect near-cellular level changes in both the wet and dry forms of AMD before subjects have symptoms.    

Currently there are several Food and Drug Administration (FDA)-approved drug treatments for the wet form of AMD based on anti-Vascular Endothelial Growth Factor (VEGF) agents that inhibit abnormal blood vessel growth, minimize vision loss, and may improve vision in some cases. These drug therapies involve repeated monthly intravitreal injections, so researchers are looking to increase the “durability” of treatments by designing novel, long-lasting, reservoir-based drug delivery systems. Researchers are also studying potential new therapies in at least 27 ongoing clinical trials.

Although noting that there are currently no effective treatments for dry AMD, Dr. Kashani described his work as a Principal Investigator in an embryonic stem cell-based experimental therapy funded by the California Institute for Regenerative Medicine (CIRM). He showed how a single layer of stem cell-derived Retinal Pigment Epithelium (RPE) cells—which nurture photoreceptors in the retina—is grown on a substrate and then injected into the eye to “patch” RPE degenerated in dry AMD.            

Kapil Bharti, PhD (National Eye Institute)

Discussing dry AMD “patching” in even greater detail, Kapil Bharti, PhD, a Senior Investigator in the Ocular and Stem Cell Translational Research Unit at the NEI, described a current first-in-human clinical trial using an induced pluripotent stem cell (iPSC)-based therapy to treat dry AMD, for which he serves as Principal Investigator. The therapy takes a patient’s blood cells and converts them into iPS cells, which are then programmed to become RPE cells. Those RPE cells are then injected into the eye to shore up the health of remaining photoreceptors by replacing dying RPE with a patient’s own iPSC-derived RPE.  

Through graphics and videos Dr. Bharti demonstrated how, before they are transplanted, the iPSC-derived RPE cells are grown in tiny sheets one cell thick, replicating the natural structure within the eye. This monolayer of iPSC-derived RPE is grown on a biodegradable scaffold designed to promote the integration of the cells under the retina. A specifically designed surgical tool was built for the task of inserting the “patch” of cells under the retina. Proof-of-concept in the initial successful animal studies focused on the structural and functional assessment of the transplanted tissue and the RPE injury. For example, imaging studies confirmed that the lab-made cells had integrated within the animal eye, while electrical responses recorded from photoreceptors “rescued” by RPE patches were closer to normal, whereas photoreceptors treated with a control empty scaffold had died. 

Building upon this initial work, Dr. Bharti described other types of stem cell-derived tissues that may be needed at different stages of retinal disease or retinal injury to various structures in the eye—including the choroid, which is the vascular layer that provides nutrients to the RPE. He reported on his complementary DOD-funded research to develop an RPE patch, an RPE/choroid patch, or a retina/RPE/choroid patch, depending on the extent of blunt or blast injury that can lead to complex tears and tissue loss in the retina.

In concluding, he spoke about NEI’s AMD Integrative Biology Initiative for personalized medicine approaches to AMD treatments. Using a patient’s iPS cells, he can replicate the process of wet and dry AMD development “in a dish,” thereby studying the cellular mechanisms in detail. NEI’s goal is to combine datasets from a patient, including medical history, genetic information collected from past studies (e.g., AREDS, Genome-Wide Association Studies), and datasets from detailed cellular mechanism studies on patient-derived stem cells to then study through Artificial Intelligence (AI) applications disease risk, incidence, and progression.   

Matt Levine (American Macular Degeneration Foundation)

After the formal presentations, Matt Levine, American Macular Degeneration Foundation’s (AMDF) Director of Grants, Partnerships and Advocacy, moderated a discussion. In introductory comments, he emphasized the importance of private foundation funding for AMD research but noted that it reflects less than ten percent of the amount of federal funding for such research which is supported by the NEI.

In response to a question about earlier detection of AMD, Dr. Kashani again recognized the importance of advanced imaging technologies to diagnose disease, treat it before functional vision is lost, and monitor the effectiveness of treatments. In a question about the impact of COVID-19 pandemic clinical and laboratory slowdowns/shutdowns, Dr. Kashani recognized its impact on patient treatments and research and the growing importance of telehealth, while Dr. Bharti recognized that NIH labs are currently only at 50 percent operation and that, while the human iPS clinical trial for dry AMD received Institutional Review Board (IRB) approval to proceed in March 2020, he has lost more than a year of progress.