National Eye Institute

The National Advisory Eye Council (NAEC) convened for its one hundred and forty eighth meeting at 9:00 am on Thursday, January 18, 2018 at the T-Level Conference Center at 5635 Fishers Lane, Rockville, Maryland, 20852. Paul A. Sieving, M.D., Ph.D., the Director of the National Eye Institute (NEI), presided as Chair of the Council, Paul A. Sheehy, Ph.D., as Executive Secretary, and Michael A. Steinmetz, Ph.D., as Acting Deputy Director of NEI and Director of Extramural Science Programs. The meeting was open to the public from 08:30 am until 2:00 pm. The meeting was closed to the public from 2:30 pm until 4:00 pm for the reviews of confidentiality and conflict of interest procedures and grant and cooperative agreement applications.

Council Members Present:

Dr. Eduardo Alfonso
Dr. Steven Bassnett
Dr. Thomas Glaser
Dr. Jane Gwiazda
Dr. Dennis Levi
Dr. Carol Mason
Dr. Louis R. Pasquale
Dr. Douglas Rhee
Dr. Sylvia Smith (by teleconference)
Dr. Russell Van Gelder
Dr. Marco Zarbin

NEI Staff Present

Dr. Houmam Araj
Dr. Neeraj Agarwal
Dr. Sangeeta Bhargava
Dr. Steven Becker
Ms. Cindy Best
Dr. Kapil Bhatti
Ms. Pamela Bobbitt
Ms. Sylvia Braxton
Dr. Brian Brooks
Mr. Jay Colbett
Ms. Karen Colbett
Dr. Mary Francis Cotch
Ms. Ashley Dash
Ms. Linda Dingle
Ms. Kathryn DeMott
Ms. Comtney Dodson
Mr. Don Everett
Dr. Martha Flanders
Dr. Shefa Gordon
Dr. Thomas Greenwell
Mr. Dustin Hays
Dr. Brian Hoshaw
Dr. Ellen S. Libetman
Dr. Anna Mazzucco
Dr. George McKie
Dr. Sheldon Miller
Dr. Lisa Neuhold
Dr. John Prakash
Ms. Karen Robinson-Smith
Dr. Gale Saunders
Dr. Anne Schaffner
Dr. Paul A. Sheehy
Dr. Grace L. Shen
Dr. Paul A. Sieving
Dr. Michael Steinmetz
Mr. Brian Trent

Other NIH Staff Present:

Dr. Nataliya Gordiyenko, CSR
Ms. Melissa Trinchet
Dr. Santa Tumminia
Ms. Keturah Williams
Dr. Jerome R. Wujek
Dr. Kristin Kramer, CSR

Members of the General Public Present at the Open Session:

Mr. James Jorkasky, National Alliance for Eye and Vision Research
Ms. Allison Manson, American Optometric Association (AOA)

Open Session of the Meeting

08:30 am

Call to Order and Opening Remarks

Dr. Paul Sieving, NEI Director

Dr. Sieving welcomed the Council members and visitors. He then reviewed recent personnel changes at the Department of Health and Human Services and NEI. The nomination of Alex Azar as secretary of the U.S. Department of Health & Human Services (HHS) awaits confirmation by the Senate. Mr. Azar would fill the vacancy left by Dr. Tom Price, who resigned September 29, 2017. He was HHS general counsel from 2001-2005 and served as Deputy HHS Secretary (2005-2007) under HHS Secretary Mike Leavitt during the George W. Bush administration. Of note to NEI, his father, Alex Azar I, is a retired ophthalmologist from Maryland (Azar Eye Institute).

NEI Deputy Director Belinda Seto, Ph.D., has joined the NIH Office of the Director. In December 2017, she began serving as senior adviser to Dr. Lawrence Tabak, Principal NIH Deputy Director. She is finding ways to reinvent grants management as part of Reimagine HHS (an effort to improve efficiency and effectiveness across government). During her tenure at NEI, Dr. Seto transformed NEI IT from primarily a help desk service to an operation that includes data science, bioinformatics, and tools development. She also advocated for data sharing to enhance research advances through generation of hypothesis and enabling practices that reinforce rigor and reproducibility. Toward that goal she initiated the development of the NEI IT Commons as an infrastructure for data/tools sharing. The pilot phase of the NEI Commons has successfully disseminated transcriptomic data and molecular phenotypes of genetic eye diseases that resulted in protein conformational changes. I thank Dr. Seto for her service to NEI.

Dr. Michael Steinmetz, Ph.D., will serve as acting NEI Deputy Director until we can find a replacement. He is director of the NEI Division of Extramural Scientific Programs. Dr.

Steinmetz joined NEI in 2007 as director of the Strabismus, Amblyopia, and Visual Processing Program. He has been involved in several trans-NIH and government-wide committees, including the BRAIN Initiative, NIH Director's Pioneer Award and New Innovator Award, the NIH Blueprint committees and work groups, NIH and National Science Foundation Collaborative Research in Computational Neuroscience, and Department of Defense vision research and medical committees and centers. A nationwide search for a new Deputy Director will begin soon.

Wai T. Wong, M.D., Ph.D., a scientist in the NEI Intramural Research Program was recently tenured. Dr. Wong has headed the Unit on Neuron-Glia Interactions in Retinal Disease since 2007. He performed his residency in ophthalmology at the Scheie Eye Institute, U. Penn and joined NEI as a fellow in medical retina in 2005. His lab explores how microglia-resident immune cells in the retina-communicate and interact with other retinal cells and their role aging and retinal disease. His work spans basic, translational, and clinical vison science.

The FY 2018 federal budget is operating on a continuing resolution through January 22. Guidance from NEI Budget Officer Karen Colbert and HHS is pending.

Updates About Ongoing NEI and NIH Activities

Dr. Sieving

Report on Gender, Minority, and Child Inclusion in NEI Human Subjects Research—Don Everett will provide an update on NEI's compliance with the 1993 NIH Patient Inclusion Guidelines. Mr. Everett is group lead of the Collaborative Clinical Research Branch in DESP. Don will also summarize new requirements of the 21st Century Cures Act, which require NIH to convene a workshop on age groupings and age exclusions in clinical research, publish data on age of participants in NIH clinical research, including pediatric subgroups, and determine whether inclusion guidelines on age need revision.

A workshop, titled Inclusion Across the Lifespan Workshop, was held June 1-2, 2017 to discuss the challenges and barriers to including children and older adults in clinical trials and to identify strategies that would produce more age-inclusive clinical trials.

Report on the Age- Related Macular Degeneration Pathobiology Working Group—NEI supports a broad range of activities relevant to Age-Related Macular Degeneration (AMD) across our intramural and extramural programs. During the past 1.5 years, we have engaged a group of key scientists with AMD expertise to help focus our overall efforts. The AMD Pathobiology Working Group is a working group of the National Advisory Eye Council. Its purpose is to identify biological causes of AMD and develop hypotheses for clinical study, including clinical trials. Dr. Anna Mazzucco, Ph.D., will summarize recent work by the AMD Pathobiology Group. Dr. Mazzucco is a health science policy analyst in the NEI Office of the Director. Her presentation will foster a council discussion on how we can further leverage our AMD-related activities across the institute.

Update on NEI Clinical Trial and BRAIN Initiatives—Mike Steinmetz, director of the NEI Division of Extramural Scientific Programs, will provide an update on NIH clinical trials reforms. At the Oct. 2017 council meeting, Dr. Steinmetz summarized NIH's multi-faceted effort to enhance its stewardship over clinical trials. He will also provide a summary of recent BRAIN Initiative activities. 110 new BRAIN awards were made in FY 2017.

21st Century Cures Act—The 21st Century Cures Act was approved by Congress and signed by President Obama on December 13, 2016. The law provides critical tools and resources to advance biomedical research across the spectrum, from basic science to clinical trials. The 21st Century Cures Act established the NIH Innovation Account comprising four programs, two which directly affect NEI.

Precision Medicine Initiative—NIH' s All of Us Research Program asks for help in compiling research questions. Part of the Precision Medicine Initiative, the All of Us Research Program aims to build one of the largest, most diverse datasets of its kind for health research. It aims to enroll a million or more volunteers nationwide who will sign up to share their information over time.

Researchers will be able to access participants ' de-identified information for a variety of studies to learn more about the biological, behavioral, and environmental factors that influence health and disease. Their findings may lead to more individualized health care approaches in the future. The program is currently in beta testing, with a national launch anticipated in spring 2018.

They are currently asking for your input. You may provide research questions through February 9, 2018.

For more information, please visit https://allofus.nih.gov/researchpriorities.

Regenerative Medicine Innovation Project (RMIP) Workshop—21st Century Cures Act provides $30 million for regenerative medicine. The Regenerative Medicine Innovation Workshop took place Dec. 6-7, 2017, in Bethesda. The event explored the state of RM science involving adult stem cells and focused specifically on approaches to the development of safe and effective RM products. The event was chaired by Gary Gibbons (National Heart Lung and Blood Institute) and Peter Marks (FDA Center for Biologics Evaluation and Research).

The workshop addressed: 

  1. scientific areas poised for major transformative advances,
  2. critical gaps that must be addressed to enable significant innovation and rapid advancement of the field,
  3. specific issues related to product development and standards, regulatory science, and clinical applications,
  4. future directions and refinement of the Regenerative Medicine Innovation Project (RMIP), and
  5. development of an overarching strategy to further stimulate major transformative rather than incremental progress in the field.

NEI Program Planning—About every 5 years, NEI updates it program plan. The current plan, called Vision Research: Needs, Gaps, and Opportunities was published in 2012. NIH developed a strategic plan in 2015, as mandated by Congress. Congress also mandates 5-year planning by ICs. Today, Dr. Shefa Gordon will outline the process and ask for concept clearance to develop a new plan.

Dr. Gordon is acting director of the NEI Office of Program Planning and Analysis. He has helped NEI with the 2012 plan, analyzed our research portfolio for opportunities and gaps, reported to Congress on NEI research progress, and responded to congressional inquiries. Shefa will explain how NEI uses this planning exercise and the resulting document.

Scientific Presentation: The NEI Fundamental Retinal Neuroscience Program—Dr. Lisa Neuhold, Ph.D., will give an overview of the NEI Fundamental Retinal Neuroscience Program. Lisa serves as group leader of the Fundamental Retinal Processes Portfolio. She manages grants that focus on the basic biology and biochemistry of photoreceptors and retinal pigment epithelium, early development and differentiation of both animal and human stem cells, and transplantation of these retinal tissues.

Prior to joining NEI in 2008 Dr. Neuhold was a program director at the National Institute on Alcoholism and Alcohol Abuse, overseeing the Neurogenetics program.

Developing Therapies for Age-Related Macular Degeneration: From Bench Towards Bedside

Dr. Kapil Bharti, M.D., Ph.D., will summarize efforts in the NEI Intramural Research Program to develop a cell-based therapy for age-related macular degeneration. Dr. Bharti is a Stadtman Investigator in the NEI Unit on Ocular & Stem Cell Translational Research. The goal of the therapy is to rescue photoreceptors at risk of dying from loss of retinal pigment epithelium function. The therapy 's approach is to make sheets of retinal pigment epithelial cells from

patient-derived induced pluripotent stem cells and transplant these lab-grown tissues to patient retina. The project is on track to submit an investigational new drug application (IND) in spring 2018. It will be the first clinical trial of iPSC-derived tissues in the U.S.

Audacious Goals Initiative, New AGI funding—A new funding opportunity "Translation-Enabling Models to Evaluate Survival and Integration of Regenerated Neurons in the Visual System" RFA-EY-17-003 was announced December 7, 2017. Application due date is March 21, 2018 (revised).

This funding opportunity seeks to develop models that emulate critic al aspects of a human blinding disease that would be amenable to regenerative therapy. The model system might involve:

  1. Specific defects generated by transgenic gene insertion and/or deletion,
  2. Gene editing, chemical /physical means, and/or
  3. Other approaches to emulate characteristics of human disease or create defects amenable to cell-replacement therapy.

Desired research areas include:

  1. generating translation-enabling models of blinding retinal diseases that might be candidates for cell replacement therapy in humans,
  2. replacing retinal neurons using transplantation of stem cells or stem-cell derivatives,
  3. converting endogenous cell types into new retinal neurons, and,
    1. evaluating the anatomical and physiological integration over replacement cells into existing circuits.

The FOA strongly encourages using non-human primates or species with significant cone vision that are more representative of the anatomy and physiology of the human retina and establishment of research teams. The teams funded will convene and collaborate as a consortium and are expected to share data and technology. NEI will provide oversight of these projects in conjunction with an External Scientific Oversight Committee. These projects will complement ongoing AGI research, which includes 5 imaging projects and 6 discovery-based projects.

Discovery-based investigators meeting—Investigators working on AGI discovery-based projects met December 18, 2017. These six teams seek to identify biological factors that influence neural regeneration. The day-long meeting provided status reports presented to the External Scientific Oversight Committee (ESOC) from each of the 6 projects:

  1. Molecular discovery for optic nerve regeneration. Principal Investigators: Jeffrey L. Goldberg, M.D., Ph.D., Andrew D. Huberman, Ph.D., Stanford University, Palo Alto, California; Larry Benowitz, Ph.D., Harvard University, Cambridge, Massachusetts; Hollis Cline, Ph.D., Scripps Research Institute, La Jolla, California.
  2. Screening for molecules that promote photoreceptor synaptogenesis. Principal investigators: Donald J. Zack, M.D., Ph.D., Johns Hopkins University, Baltimore; David Gamm, M.D., Ph.D., University of Wisconsin, Madison.
  3. Evaluation of novel targets for retinal ganglion cell axon regeneration. Principal investigator: Stephen M. Strittmatter, M.D., Ph.D., Yale University, New Haven, Connecticut.
  4. Novel activators of regeneration in Muller glia. Principal investigators: Edward M. Levine, Ph.D., James G. Patton, Ph.D., David J. Calkins, Ph.D., Vanderbilt University School of Medicine, Nashville, Tennessee.
  5. Comparative transcriptomic and epigenomic analyses of Muller glia reprogramming. Principal investigators: David R. Hyde, Ph.D., University of Notre Dame, South Bend, Indiana; John D. Ash, Ph.D., University of Florida, Gainesville; Andy J. Fischer, Ph.D., Ohio State University, Columbus; Seth Blackshaw, Ph.D., and Jiang Qian, Ph.D., Johns Hopkins University, Baltimore.
  6. Novel targets to promote RGC axon regeneration: Insights from unique retinal ganglion cell cohorts. Principal investigators: Kevin Park, Ph.D., Vance Lemmon, Ph.D., Sanjoy Bhattacharya, Ph.D., University of Miami Miller School of Medicine.

The External Scientific Oversight Committee is comprised of Sally Temple, Ph.D. (Neural Stem Cell Institute), Mark Tzuszinski, Ph.D. (U.C. San Diego), Mike Dyer, Ph.D. (St. Jude's Children's Research Hospital), and Steve Finkbeiner, M.D., Ph.D. (Gladstone Institute of Neurological Disease).

ARVO 2018 AGI Town Hall—NEI AGI is making plans to host a town hall meeting at the 2018 ARVO annual meeting. The working title is "Bringing regenerative medicine therapies to the clinic".

NEI Steering Committee—We are searching for new AGI steering committee members. The AGI steering committee " assists the NEI with evaluating the scientific needs and obstacles to progress, prioritizing research opportunities in the context of the emerging science." The AGI charter prescribes 3 to 5 members. Tenns are 3 years and can be renewed. All three current members have served since August 2014.

NEI Organoid Challenge (3-D ROC)—We are nearing launch of phase two of the NEI 3-D Retina Organoid Challenge. 3-D ROC is an NEI federal Challenge prize competition to generate miniature, lab-grown human retinas. Phase 1 was launched May 1, 2017 with the goal to develop technology that will speed the discovery of treatments for retinal diseases. Such a tool will accomplish two main objectives:

  1. study how retinal cells interact under health and diseased conditions; and
  2. test potential therapies. There are two stages to the Challenge: ideation and development.

Ideation stage - Participants submitted ideas to improve current organoid systems or explain how new ideas or technology will advance protocols. The winner of the ideation stage was announced Sept. 28, 2017. Elin Lavik, Sc.D., is a professor of chemical, biochemical, and environmental engineering at the University of Maryland, Baltimore County. She and her team proposed building a retina by screen-pointing adult neural progenitor-derived retinal neurons in layers that mimic the structure of the human retina. The system is designed to be scalable, efficient, and reproducible, enabling high-throughput screening for drug testing. All the proposal abstracts are posted online. See the 3-D ROC website. ·

Development stage - Participants will develop functional retina organoid prototypes. The endpoint will be publication-quality data showing 3-D human retina organoid prototypes. Up to $1 M in prize money is available (in total) - multiple winners possible. Rules, how to register, and evaluation criteria are online at https://nei.nih.gov/3DROC.

NEI 50th Anniversary—NEI is celebrating its 50th anniversary in 2018.

We kicked the celebration off on November l 0, 2017, with a symposium titled Vision and the Brain, which was held in conjunction with the Society for Neuroscience annual meeting. A group of esteemed scientists provided an overview of our current state of knowledge:

  • Michael Goldberg, M.D., Columbia University
  • Dora Angelaki, Ph.D., Baylor College of Medicine Michele Basso, Ph.D., University California Los Angeles
  • Okihide Hikosaka, M.D., Ph.D., National Eye Institute
  • William Newsome, Ph.D., Stanford University
  • Marlene Cohen, Ph.D., University of Pittsburgh
  • Nicole Rust, Ph.D., University of Pennsylvania
  • Tony Movshon, Ph.D., New York University
  • Eric Kandel, M.D., Columbia University

Additional symposia on the NIH campus are scheduled for 2018:

  • Vision and Immunology on March 22nd
  • Vision Rehabilitation on June 29th
  • Future of Vision Research on October 18th

Other anniversary events—"NEI on Capitol Hill"- March 21, 2018, in the Rayburn Office Building. This 50th anniversary celebration will honor NEI and partner organizations. Congressman Pete Sessions (R-TX) will speak. The event is public and council members are encouraged to attend. You are invited!!! More details to come.

Information on the accomplishments made in vision research and eye health over the decades will be available in a variety of formats including: video series, small book about NEI, and a virtual reality experience.

Consideration of Proceeding Minutes and Future Dates

Dr. Paul Sheehy, Executive Secretary and Director, Division of Extramural Affairs

The Executive Secretary asked for comments and corrections to the October 2017 Council minutes. There were none, and the minutes were unanimously approved.

Dr. Sheehy asked Council members to review upcoming meeting dates and confirm their availability. He also noted that trans-NIH and the AGI Model Organisms RFAs will likely create the need for a virtual Council meeting in August of 2018 to allow awards to be made with fiscal year 2018 funds.

Budget Update

Ms. Karen Colbert, Budget Officer, Office of the Director

Ms. Colbert noted that NIH is under a Continuing Resolution effective through January 19th. We are proceeding conservatively, fully aware of the possibility of a lapse in funding.

Negotiation in Congress revolves around raising discretionary budget caps which are hard upper limits on how much Congress can spend on military and domestic programs. The Budget Control Act of 2011 placed dollar caps on discretionary spending for FY 2013 through FY 2021. There is no doubt that the President and Congress all want the caps raised but how those caps are raised is the sticking point. Republicans want larger increases for defense spending and Democrats want parity between defense and non-defense spending. Until the budget caps are set there can be no allocations to the Congressional sub-committees working on our funding bills.

The FY 2018 President's Budget Request contains policies and structural changes that if adopted, would significantly affect our operations and certainly the ability to fund some research priorities for both NIH and NEI. The House and Senate proposed substantially different budgets, showing continued support for the research priorities funded by NIH.

At this time of the year we typically report on how we ended the previous fiscal year and show how much funding went to specific activities - Competing grants, Non-competing grants, etc. Because 2017 data has not yet been reviewed by Congress, we are not able to share specifics about our spending. Nonetheless, we are confident that the final figures will show increases in all core activities. Of note, the increase in competing awards made in 2016 have our year commitments that create budget pressures in 2017 and consequently a slight decrease is possible.

When we talk about budget levels for a given fiscal year there are several different terms reflecting different budget levels. The Appropriation from Congress is subject to a variety of "taps" such that the Operating Level that we have available to fund research and other activities can be significantly less.

The distribution of funds among the major activities of the Institute (Extramural Research, Intramural Research and Management & Support) continue at traditional levels (85%, 11%, and 4%, respectively).

UPDATE: Report on Gender, Minority and Child Inclusion in NEI Human Subjects Research

Mr. Don Everett

By law, Council periodically receives a report regarding NEI's compliance with NIH participant inclusion guidelines. The NIH Revitalization Act of 1993, PLl 03-43 requires that:

  • Women and minorities be included in all clinical research studies unless there is a compelling rationale for exclusion
  • Phase III clinical trials be designed to permit analysis by sex/gender, race and ethnicity
  • NIH to support outreach efforts to recruit and retain women, minorities, and their subpopulations

The goal is to ensure individuals are included in clinical research in a manner appropriate to the scientific question under study.

The recent 21st Century Cures Act requires revision of policies and procedures regarding the Inclusion of Children, Women, and Minorities. To implement these requirements accordingly, NIH is revising its policies on inclusion of children (revised guidelines on age of participants in clinical research and data on age of participants) and inclusion of women and minorities (reporting of valid analyses by sex/gender and race/ethnicity in Clinicaltrials.gov for applicable NIH-defined Phase III clinical trials). NIH policy therefore requires that

  • Children (defined by the NIH as individuals <18 years) must be included in clinical research studies unless there are scientific or ethical reasons not to do so
  • The trial must be able to report participants by ethnic category (either Hispanic or Latino, or not Hispanic or Latino) and racial category (American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Other Pacific Islander, White, or more than 1 race).

NEI implementation strategies include activities to:

  • Highlight policy on website
  • Detail policy in all FOAs
  • Peer-review education/instruction
  • Train staff in new procedures
  • Document compliance in grant files
  • Maintain tracking system
  • Monitor analyses in Phase III trials
  • Collaborate with Offices of Research on Minority and Women' s Health to add special populations to clinical trials
  • Oversight by Program Director, Collaborative Clinical Research

Mr. Everett presented data showing that, to date, the distribution of participants in NEI awards closely tracks the US population with respect to gender, race and ethnicity for both Phase III trials and for non-Phase III trials.

Council Discussion: Council members noted that disorder-specific racial and ethnic incidence/prevalence are much more relevant comparators to consideration of participation and inclusion in NEI trials than overall national distributions. Mr. Everett noted that it is inherently problematic to repo1t overall representation since large trials will dominate the repo1ted distribution. For instance , NEI runs a study in Nepal (not included in this analysis) with 240,000 participants that would completely distort repo1ting in the racial category.

Council members also expressed concern that the requirement that children must be included has negative consequences for the power of the study and may be better addressed by retrospective study. Mr. Everett noted that these concerns apply to the other requirements as well.

UPDATE: An Overview of Age-Related Macular Degeneration Activities at the NEI

Dr. Anna Mazzucco

The purpose of the presentation was to present scope of NEI activities directed at probing the biology of Age-Related Macular Degeneration (AMO) as the basis for discussion by Council members. Dr. Mazzucco began by presenting a timeline of notable events in AMO research in the past two decades and highlighting several that had NEI support (including the AREDS study and the International AMO Genetics Consortium) as well as identifying new initiatives beginning this year (iPSC cell line generation and the AMO Ryan Initiative study).

As of today, AMD is the leading cause of vision loss among Americans 60 and older, and its prevalence is expected to double by 2050. AMD-associated genes have been identified, but their biological mechanisms and contributions to the disease process are not fully known. While VEGF treatment for wet AMD is widely used, other therapies are lacking, particularly for early­ stage disease and especially for dry AMD/ geographic atrophy. As such, there is a large effort directed at developing another approach to treat AMD.

Analysis of the current NEI AMO Extramural Portfolio identified 179 awards. In general, the work was more on wet AMO than dry or early stage disease. Most uses cell biological approaches in animal models, comparatively few use discovery approaches or high throughput screening. The topics most frequently studied are choroidal neovascularization, the inflammasome and immune signaling, and mitochondria/ROS.

In 2016 Dr. Sieving convened a Working Group of Council focused on AMD Pathobiology. Activities of the group to date include two in-person meetings with subsequent reports to Council; a white paper is in preparation that will address:

  • the Public health, economic burden and quality-of-life impact of the disease; provide a general overview of our current knowledge of AMO; and review our current knowledge of AMO and highlight major unsolved questions in AMD pathobiology, emphasizing those likely to be of clinical value.
  • approaches to address above gaps in knowledge (including "big data" and other ways to support patients and alleviate co-morbidities). They discuss resources needed to leverage such " big data" approaches (e.g. grant support and wider access to staged ocular tissue). They will also present examples of successes from other complex diseases where such approaches have been applied successfully.

The group has identified two big challenges: 1) We do not fully understand how genes and pathways implicated in AMD via genetic studies contribute to the disease process in cellular and temporal context; and 2) We need to diagnose and treat patients at earlier stages of disease. They make three recommendations: 1) develop functional and integrative approaches to put genes/pathways together; 2) provide access to high quality ocular tissue; and 3) develop biomarkers for early-stage changes that can be imaged in vivo in AMO patients.

In the area of ocular tissue access, NEI has supported the National Disease Research Interchange since 1990. On the order of 20 NEI-funded investigators per year use tissue from the NDRI and about 600 AMD samples have been distributed in last 5 years. We are currently exploring ways to improve quality (increased access and decreased post-mortem interval) and lower cost for investigators.

NEI convened the International AMD Genetics Consortium in June 2010 and August 2011 and continues to support their work. In 2015 the study identified 52 independently associated common and rare variants in 34 loci.

NEI's Extramural and Intramural Research Programs collectively support many clinical initiatives in AMO. The landmark clinical cohort study "Age-Related Eye Disease Study" is currently in a 10-year follow-on (AREDS2) to conduct genotype/phenotype analysis in a group of 1,000 patients. In a project in its initial stage, a second subset of patients will be chosen (based on known risk alleles) to be the source of iPSC cell lines that will be differentiated to Retinal Pigment Epithelia by the NEI Intramural Research Program. These cells will be available for distribution to vision and other research communities. Another IRP supported project expected to begin soon is the AMD Ryan Initiative Study (ARIS) led by Emily Chew, MD. ARIS has the goal of understanding clinical evolution of early AMD and reticular pseudodrusen. 600 patients 55 years and older (200 intermediate AMD, 200 Reticular pseudodrusen, and 200 controls) will be recruited and will have annual testing for 5 years. A variety of other treatment and natural history trials are also underway; one will be presented later today by Dr. Bharti. Finally, the NEI is supporting expansion of the Diabetic Retinopathy Clinical Research network to include AMD.

In summary, NEI supports a portfolio of efforts to address mechanisms, diagnosis, and prevention/therapy in AMD.

Council Discussion: Council asked for more information about the intended role for the Working Group. The Group is not intended to drive research but rather to identify emerging areas of consensus with respect to knowledge, animal models, research strategies, etc. Council noted the value for groups such as this in other areas of NEI's responsibilities and the potential value of adding expertise from multiple areas in such groups (e.g. in this case non-AMD)

Council members noted the key role of NEI in the advances to date and encouraged NEI to celebrate successes such as AREDS, Avastin, and others. They also supported increased efforts in 'big data’, developing new imaging approaches, and increasing access to and decreasing cost of high quality, well-characterized tissue. Several Council members reiterated that cost of tissue is a substantial impediment to research and that NEI is uniquely positioned to coordinate donors, medical facilities, repositories and consumers.

Another Council member recommended that NEI look to partner with philanthropies such as the Chan/Zuckerberg Neurodegeneration Challenge Network.

Break, 10:35-10:45
Open Session continued, 10:45 p.m. -12:45 p.m.

Last updated: June 10, 2020