NAEC Meeting Minutes - June 16, 2016

National Advisory Eye Council (NAEC)
One Hundred Forty-third Meeting
June 16, 2016

The National Advisory Eye Council (NAEC) convened for its one hundred and forty-third meeting at 8:35 am on Thursday, June 16, 2016 at the T-Level Conference Center at 5635 Fishers Lane, Rockville, Maryland, 20852. Paul A. Sieving, MD, PhD, the Director of the National Eye Institute (NEI), presided as Chair of the Council, Anne E. Schaffner, PhD, as Interim Executive Secretary, and Michael A. Steinmetz, PhD, as Director of Extramural Science Programs. The meeting was open to the public from 08:35 am until 12:30 pm when the meeting was closed to the public for a session from 01:15 pm until 04:00 pm for the review of confidentiality and conflict of interest procedures and a review of grant and cooperative agreement applications.

Dr. Steven Bassnett
Dr. Laura Frishman
Dr. Thomas Glaser
Dr. Jane Gwiazda
Dr. Dennis Levi
Dr. Stephen McLeod
Dr. Louis Pasquale
Dr. Douglas Rhee
Dr. Sylvia Smith
Dr. Monica Vetter
Dr. Jayne Weiss
Dr. Rafael Yuste
Dr. Marco Zarbin, ex officio

Dr. Houmam Araj
Dr. Neeraj Agarwal
Mr. Joseph Balintfy
Dr. Sangeeta Bhargava
Dr. Steven Becker
Ms. Pamela Bobbitt
Ms. Sylvia Braxton
Dr. Hemin Chin
Ms. Monique Clark
Mr. Jay Colbert
Ms. Karen Colbert
Mr. William Darby
Ms. Kathryn DeMott
Ms. Linda Dingle
Ms. Courtney Dodson
Mr. Don Everett
Dr. Shefa Gordon
Dr. Thomas Greenwell
Dr. Brian Hoshaw
Dr. Jeanette Hosseini
Dr. Ellen S. Liberman
Dr. George McKie
Ms. Kathleen Moy
Mr. Chris Nee
Dr. Lisa Ann Neuhold
Dr. Steven Oversby
Dr. Gyan Prakash
Dr. Maryann Redford
Ms. Karen Robinson-Smith
Dr. Gale Saunders
Dr. Anne E. Schaffner
Dr. David Schneeweis
Dr. Eleanor Schron
Dr. Belinda Seto
Dr. Grace L. Shen
Dr. Paul A. Sheehy
Dr. Paul A. Sieving
Dr. Michael Steinmetz
Ms. Chantelle Stevenson
Dr. Dan Stimson
Mr. Gerod Thigpen
Mr. Brian Trent
Dr. Santa Tumminia
Dr. Cheri Wiggs
Dr. Jerome R. Wujek

Dr. Rajeev K Agarwal
Dr. Mary Custer, CSR
Dr. Sam Edwards, CSR
Dr. Nataliya Gordiyenko, CSR
Dr. Kristen Kramer, CSR
Dr. Peter Guthrie, CSR
Dr. Paek Lee, CSR
Dr. Kirk Thompson, CSR
Dr. Maqsood Wani, CSR

Scott Huber, AAO
Yoori Kim, Milken Institute
Mr. James Jorkasky, National Alliance for Eye and Vision Research (NAEVR)
Dr. Leonard Levine, McGill University
Ms. Alison Manson, AOA
Ms. Jo Olson, ARVO

08:35 am

Dr. Paul Sieving, NEI Director

Announced the appointment of four new Council Members (Drs. Thomas Glaser, Dennis Levi, Louis Pasquale, and Sylvia Smith).

NEI has restructured the Division of Extramural Research by creating two Divisions: the Division of Extramural Scientific Programs and the Division of Extramural Affairs, directed by Drs. Michael Steinmetz and Paul Sheehy, respectively.

Dr. Martha Flanders, whose portfolio will include Central Vision Processing, has joined the NEI and Dr. Eleanor Schron has retired.

Noted that NIH leadership has recently reiterated NIH’s interest in and commitment to basic research.

NEI sponsored workshops: One on mounting a challenge competition to develop retinal organoids which may speed research in retinal disorders; the challenge will be announced in the Fall. Two workshops were held in conjunction with ARVO focused on aspects of the Audacious Goals Initiative (summaries to be followed) and another will be held at the upcoming SfN.

NIH Clinical Center operation and governance has recently been reviewed and restructuring is ongoing. 

Postdoc salaries to be increased in response to the new Department of Labor standards.

Human Subject protections: Updating of the Federal-wide policy (the Common Rule) has been updated. 

Dr. Anne Schaffner, Interim Executive Secretary and Chief of Review, Division of Extramural Affairs

The Executive Secretary asked for comments and corrections to the January 2016 Council minutes. There were none, and the minutes were unanimously approved.

While funds are appropriated by Congress, the amount actually available to NEI is subject to numerous reductions and transfers (e.g. taps from DHHS or NIH OD). Current (FY16) operating level is $708M although further transfers are under consideration. FY17 budget is under development and at this time, both Senate and House versions are very preliminary. NEI’s budget has historically been distributed 86%/11% among Extramural and Intramural but ongoing changes in Clinical Center operations make it likely that the intramural share will increase. The overall FY17 budget request is unchanged from FY16.  Changes in costs (e.g. postdoc salaries) and taps (Clinical Center operations) will reduce the NEI success for competing research grants but it will remain significantly higher than the NIH success rate. 

Council Discussion: Council members discussed various strategies to increase success rate given fixed funds available. No final consensus was achieved.

Dr. Michael Steinmetz, Director of the Division of Extramural Scientific Programs

Launched in 2013 the BRAIN Initiative is a Public/Private Partnership aimed at revolutionizing our understanding of the human brain by accelerating the development and application of innovative technologies the human brain by accelerating the development and application of innovative technologies. Ten NIH Institutes and Centers participate with an overall contribution of $85 (FY15). To date, there have been 15 scientific initiatives resulting in 125 awards spanning 7 major thematic areas. In FY16 the thematic emphasis of the funding opportunities has moved from tool development toward the analysis of 1) circuits and 2) human and non-human tissues.  This trend will accelerate with the FY17 Funding Opportunity Announcements. 

Council Discussion: Dr. Yuste noted that the possible participation of the Department of Energy holds the prospect of tapping the extensive expertise and resources of the National Laboratories. Dr. Zarbin noted how the BRAIN Initiative is very complementary to the NEI Audacious Goals Initiative (AGI). Dr. Steinmetz noted that this has been recognized from the outset with the first BRAIN project is focused on the circuitry and operation of the retina and its connection to the brain. In this connection, the visual system has been the system studied in 40% of the first round of awards and 20% in the second round. Finally, Dr. Yuste noted the increasing international scope and prominence of the BRAIN Initiative.

Drs. Vetter and Hitchcock

Dr. Vetter noted that a challenge facing the AGI is that while humans have a limited ability to repair or replace retinal ganglion cells (RGCs), other species do it quite well. Ultimately we want to learn from those species in order to define a path towards RGC replacement in human disease. These strategies must address a number of aspects including: source, differentiation, integration, survival, connectivity, subtype, number, and function. While exogenous sources of RGCs have certain advantages, numerous challenges remain. Accordingly, endogenous sources merit continued consideration and this workshop considered gaps in our knowledge of and barriers to increasing our understanding of how cells intrinsic to the retina can replace RGCs. Discussion focused on 1) cell sources, 2) delivery and integration, and 3) outcome. The group recommended continued investigation of the mechanism(s) of RGC regeneration in multiple animal models and cell types, development of standardized criteria to allow comparisons across cell types and animal models, and development of tools by collaborative, multidisciplinary teams that focus on human diseases.

Council Discussion: It is not clear how predictive current animal models will be for more complex visual systems found in higher vertebrates.  Work on spinal cord injury may be informative in this context.

Dr. Leonard Levin

While we are yet at early stages, given the recurrent, multithreaded nature of developing therapies, it is important to include clinical considerations from the outset in the formulation and execution of the AGI strategy. Dr. Levine presented an overview and summary of a Town Hall meeting held at ARVO focused on these considerations that attracted many participants and elicited vigorous discussion.

Barriers to success include: 1) damaged neuronal circuitry in late stage disease, 2) damage to non-neuronal cells, 3) anti-regenerative responses (e.g. gliosis, fibrosis, tissue remodeling), 4) availability of appropriate animal models, and 5) the criteria for “success” in human patients (early results may well be small magnitude).

Important strategic choices include: 1) Resuscitation or Regeneration. While resuscitation may be easier to achieve, it may not be possible in late stage disease; 2) Candidate Disease. To a first approximation we can consider the broad groups diseases of the outer retina (photoreceptors or retinal pigment epithelium) or of the optic nerve (retinal ganglion cells). There are important features even within these groups that confer needs and opportunities that in turn drive the design of the clinical study both in terms of detecting an effect and patient safety. Broadly speaking these features include pattern of cellular loss and other anti-regenerative responses, early vs. late disease, genetic vs. acquired disease, acute vs. chronic disease, and unilateral vs. bilateral disease. Beyond the specific disease chosen there are important issues independent of trials in regenerative medicine regarding 1) how the previously discussed considerations apply to trial stage (safety vs. efficacy), 2) clinical endpoints (structural vs. clinical), 3) ethical recruitment, and 4) interactions with critical partners (industry and FDA).

In summary clinical trials to establish the success of regenerative therapies will require broad, thoughtful planning.

Council Discussion: Dr. Zarbin noted the value of including experts in clinical trial design in the planning groups.

Dr. McKie, Program Director, Division of Extramural Scientific Programs

Dr. McKie presented an overview of the NEI Cornea program along with highlights from three areas. The Cornea is the 3rd largest grant program comprising about 13% of extramural awards. Within the program there are eight broad areas (Tears, Infectious Diseases, Wound Healing, Stem Cells, Endothelial Disease, Corneal Transplants, Refraction, and Structural Malformations) although it should be noted that there is considerable overlap and cross cutting among these areas (e.g. Wound Healing and Stem Cells).

Dr. McKie then presented highlights from selected areas of current research on the cornea: 1) the protective function of the cornea (including simple barrier function, antimicrobial activities of tears and corneal epithelial cells), 2) using cutting edge technology to restore the refractive power of the cornea by adaptable contacts, and 3) studies of the protective function mediated by the nerves of the cornea (regulation of tears, production of trophic factors to maintain a healthy state).

Investigators are looking at how healthy eye prevents infection in relationship to why contact lens wearers get infection easily. Bacteria will stick to the healthy cornea if abraded but not invade the cornea unless the wound is deeper into the stroma. The healthy cornea fights is resilient to infection through tears, antimicrobial peptides, and acting as phagocytes to kill the bacteria. Recent work has found that pseudomonas aeruginosa (the most common cause of bacterial infections in patients who wear contact lenses) has developed a variety of ways to evade corneal defense mechanisms that may enable development of therapeutic countermeasures.

Methods to alter corneal refraction have been developed over course of centuries and currently available strategies include glasses, contacts, and refractive surgery. One exciting approach, supported by a NIH Director’s New Innovator Award and managed by NEI, is to develop an accommodative contact lens for the correction of presbyopia. Three engineering challenges need to be overcome: the accommodative ability of the lens using a hydrogel, developing an appropriately sized and renewable power supply, and ensuring that the electronics fit within the curved shape of a contact lens safely and comfortably.

The cornea nerves are supplied by the peripheral and central trigeminal sensory network. The sense mechanical, thermal, and chemical stimuli to elicit a pain response to withdraw the eye away from the stimulus. They provide protection to the eye through maintenance of the tears and the production of trophic factors to keep the cornea healthy.

Patients with corneal disease that is not currently treatable have two options, either a transplant or an artificial cornea. Advances in medicines, technique and surgical instrumentation have reduced the rate of complications for transplants but there remains room for improvement. Regardless of the complication rate, there are not enough cornea available for transplants due to increasing number of refractive surgeries and the aging population. This has led to the development of artificial corneas and two forms are currently available in the US.  A third form, developed by an NEI researcher, is currently awaiting FDA approval. This implant requires a less intrusive surgical approach (with fewer attendant complications and faster recovery) and has the ability to control for refractive power.

In summary, the cornea portfolio is a significant component of the NEI research program and it includes many exciting scientific opportunities and clinical needs.

Council Discussion: Council members noted that regeneration of corneal endothelium is an ongoing area of research.

Addressed the opportunities and challenges for the vision research community presented by “Big Data”. 

The Open Session adjourned at 12:30 PM.

These minutes were submitted for the approval of the Council; all corrections or notations were incorporated. We hereby certify that, to the best of our knowledge, the foregoing minutes and attachment(s) are accurate and complete.

Anne E Schaffner, Ph.D. 
Interim Executive Secretary
National Advisory Eye Council                                                                                                                                                                   
National Eye Institute

Paul A. Sieving, M.D., Ph.D.                                                                                   
Chairman, National Advisory Eye Council
Director, National Eye Institute