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Caring for Wounded Warriors with Vision
and Hearing Impairment
Overview of the Vision Research Program
Robert Read, MBA
CDMRP Program Manager
April 17, 2015
DEPARTMENT
OF DEFENSE
DEPARTMENT
OF THE ARMY ARMY
MEDICAL
COMMAND
MEDICAL
RESEARCH
AND
MATERIEL
COMMAND
CONGRESSIONALLY
DIRECTED MEDICAL
RESEARCH PROGRAMS
Congressionally Directed Medical
Research Programs (CDMRP)
U.S. Army Medical Research and Materiel Command 3
Since 1992, the CDMRP has…
● Administered over $8.7 billion in congressional
appropriations
● Processed more than 80,000 applications
● Provided over 12,400 grants to institutions world-wide
● Focused efforts on over 30 different research programs
Congressionally Directed Medical
Research Programs (CDMRP)
The CDMRP…
● Targets research as directed by Congress
● Employs a flexible science management model to accommodate rapid change
● Recruits and integrates consumer participation at all levels
● Uses an Institute of Medicine-recommended two tier review for technical merit
and mission relevance
● Supports the Office of the Assistant Secretary of Defense Health Affairs
(OASD[HA]), Defense Health Program (DHP), Defense Medical Research and
Development Program (DMRDP)
U.S. Army Medical Research and Materiel Command 4
Congressionally Directed Medical
Research Programs (CDMRP)
• Defense Medical R&D* • Peer Reviewed Orthopedic • Reconstructive Transplant* • Orthotics/Prosthetics Outcomes • Alcohol and Substance Abuse • Psychological Health/Traumatic Brain Injury* • Breast Cancer • Prostate Cancer • Peer Reviewed Cancer • Tuberous Sclerosis Complex • Amyotrophic Lateral Sclerosis • Bone Marrow Failure • Peer Reviewed Medical • Duchenne Muscular Dystrophy
• Joint Warfighter* • Military Burn • Spinal Cord Injury • Gulf War Illness • Vision • Ovarian Cancer • Lung Cancer • Autism • Alzheimer’s • Parkinson’s • Multiple Sclerosis • Neurofibromatosis
*CDMRP is assisting with the execution of a specified portion of these appropriation(s)
• Unique public/private
partnership
encompassing the
military, scientists,
disease survivors,
advocates, consumers,
and policy makers
• Support execution and
management of DHP
military medical
research
• Fund high-impact,
innovative medical
research to find cures,
reduce the incidence
of disease and injury,
improve survival, and
enhance the quality of
life for those affected
U.S. Army Medical Research and Materiel Command 5
VRP Funding Synopsis
Congressional
Appropriations
FY 09-12 FY13/14
FY15
$25M
$25M
$10M
94 Applications
33 Awards
? Applications
Anticipate 18 Awards
147 Applications
34 Awards
U.S. Army Medical Research and Materiel Command 6
Sensory Clinical Capability Gaps
Visual Capability Gaps
• Mitigation and treatment of traumatic
injuries, war-related injures, and diseases
to ocular structures and the visual system
• Mitigation and treatment of visual
dysfunction and associated with TBI
• Ocular and visual systems diagnostic
capabilities and assessment strategies
• Eye protection and vision loss prevention
strategies
• Vision rehabilitation strategies and
quality of life measures
• Epidemiological studies of military eye
trauma and TBI-related vision dysfunction
• Vision restoration
• Vision care education, training and
simulation
• War fighter vision readiness and
enhancement
Hearing and Balance Capability
Gaps
• Hearing Restoration
• Treatment of hearing loss
• Prevention and/or treatment of tinnitus
• Epidemiology and measurement tools
for hearing loss
• Prevention and Treatment of
vestibular dysfunction
U.S. Army Medical Research and Materiel Command 7
One program announcement – Maximum $2M per award
120 Pre-proposals Received
51 Selected for Full Proposal Submission
49 Submitted Full Proposals
$11,014,931
12 Investigators Selected for Funding
10 Mitigation and treatment of visual dysfunction
associated with traumatic brain injury (TBI)
1 Mitigation and treatment of traumatic injuries, war-
related injuries, and diseases to ocular structures and the
visual system
1 Vision restoration
2009/10 Peer Reviewed VRP
U.S. Army Medical Research and Materiel Command 8
Two program announcements – II $1M, HD $250K
151 Pre-proposals Received
48 Selected for Full Proposal Submission
45 Submitted Full Proposals
$13,766,396
21 Investigators Selected for Funding
7 Mitigation and treatment of traumatic injuries, war-
related injuries, and diseases to ocular structures and the
visual system
8 Mitigation and treatment of visual dysfunction
associated with traumatic brain injury (TBI)
5 Vision restoration
1 Ocular and visual systems diagnostic capabilities and
assessment strategies
2011/12 Peer Reviewed VRP
U.S. Army Medical Research and Materiel Command 9
Two program announcements – TR $1M, HD $250K
275 Pre-proposals Received
151 Selected for Full Proposal Submission
147 Submitted Full Proposals
$24,868,891
34 Investigators Selected for Funding
22 Mitigation and treatment of visual dysfunction
associated with traumatic brain injury (TBI)
5 Mitigation and treatment of traumatic injuries, war-
related injuries, and diseases to ocular structures and the
visual system
1 Rehabilitation strategies and quality of life measures
5 Vision restoration
2013/14 Peer Reviewed VRP
U.S. Army Medical Research and Materiel Command 10
Projects in Regards to Gaps
Gaps VRP1 VRP2 VRP3 Total
One 1 8 22 31
Two 10 7 5 22
Three 1 1
Five 1 1
Seven 1 5 6 12
Total 12 21 34 67
U.S. Army Medical Research and Materiel Command 11
Program Cycle
Release of
Program Announcement
Pre-Application
Receipt
Pre-Application
Screening
Invitation
to Submit Application
Receipt
Peer
Review
Programmatic
Review
Office of the
Assistant
Secretary of
Defense
(Health Affairs)
Approval
Award
Negotiations
By 30 September 2016
NSRAA Panels
Award Management
~ May 2015
~ July 2015
~ August 2015
~ October 2015
~ January 2016
~ November 2015
U.S. Army Medical Research and Materiel Command 12
Mechanism Focus
Supports both applied (preclinical) research and clinical trials addressing
specific focus areas:
Applied research is defined as work that refines concepts and ideas into
potential solutions with a view toward evaluating technical feasibility of
diagnostic and therapeutic techniques, clinical guidance, emerging
approaches and technologies, promising new products, and/or
pharmacologic agents.
A clinical trial is defined as a prospective accrual of human subjects where an
intervention (e.g., device, drug, biologic, surgical procedure, rehabilitative
modality, behavioral intervention, or other) is tested on a human subject for a
measurable outcome with respect to exploratory information, safety,
effectiveness, and/or efficacy. This outcome represents a direct effect on the
human subject of that intervention or interaction.
U.S. Army Medical Research and Materiel Command 13
Goal of Two-Tier Review Process
Peer Review
Panels
Programmatic
Review Panels
Partnership
To find scientifically meritorious proposals and
fund those that best fulfill program goals
• Criterion-based evaluation of full
proposal
• Determination of “absolute”
scientific merit
• Outcome: Written critique and
scores for individual criteria and
overall merit
• Comparison among proposals of high
scientific merit
• Determination of adherence to intent
and program relevance
• Outcome: Funding recommendations
No standing peer review panels
No contact between reviewers and
applicants
No “pay line” (portfolio balance)
Funds obligated up front; no out-year
budget commitments (but
milestones imposed)
No continuation funding
U.S. Army Medical Research and Materiel Command 14
Thermo-Responsive Reversibly Attachable
Patch for Temporary Intervention in Ocular Trauma
Mark Humayun, MD PhD University of Southern California
Study/Product Aim(s)
• A biocompatible, reversibly adhesive patch fabricated
from pNIPAM-on-parylene stubstrates that meets the most
significant safety and efficacy concerns for treatment of
combat-related ocular trauma.
• Device key features that would be useful in combat
scenario:
(1) Easily reversible upon cooling without damaging the
healing tissue.
(2) Ease-of-use, allowing sutureless wound closure
enabling treatment in lower tiered (2o or lower) care
centers.
Approach
Key challenges at this stage of development are: 1) sterilization effects on adhesion, 2) environmental effects (temperature during transport) on adhesion, 3) in vitro adhesion performance characterization and 4) preliminary biocompatibility. These four areas will be investigated in a stop-gate approach to assess whether this technology is viable to continue to sustained biocompatibility testing.
Goals/Milestones
CY12 Q4 Goal: – Fabrication, Quality Characterization, Exposure Test
Fabricate pNIPAM-parylene of different thicknesses (h=100nm, 400nm, 800m)
Perform baseline characterization (contact angle vs. T and FTIR)
Sterilize patches using either ETO sterilization or autoclave sterilization protocol
Extreme Thermal Exposure of Patches (120oF or -50oF for 168hrs)
Post-exposure characterization (Contact Angle vs. T and FTIR)
CY13 Goal – Performance Evaluation
Evaluate effect of sterilization and temperature protocols on adhesion
characteristics; Evaluate ease of use of patches
Initiate in vivo studies for scleral penetration closure and peritomy scarring
prevention.
CY14 Goal – Biocompatibility Assessment
Complete in vivo studies and analyze data for summary report
Accomplishments this quarter:
• 18 animals have completed the in vivo sclerotomy study using our
injector tool (left) and an interim statistical analysis of IOP results has
begun(right).
• 5 Animals have completed in vivo peritomy study and additional animals
are being scheduled for the rest of this study.
• Enucleated eyes are being prepared for histological analysis to evaluate
healing progression and tissue response to hydrogel material.
Loading port 1cc syringe Catheter tip
Reaction chamber
U.S. Army Medical Research and Materiel Command 15
Objective Methods to Test Visual Dysfunction in
the Presence of Cognitive Impairment
Randy Kardon, MD PhD University of Iowa
Problem, Hypothesis and Military Relevance
Activities FY 11 12 13
Implementation of novel product-ready
hardware solutions XXX
Testing in normal eyes XXX
Testing in eyes with retinal or optic nerve
damage XX
Testing in eyes with damage to primary
visual cortex XX XX
Optimize hardware systems and vision
testing protocols XXX XXX
• Addresses vision gap two: Models for Visual
Dysfunction Following Blast and Concussive Trauma.
• Specific areas of the visual pathway in the eye and brain can be
interrogated by a battery of visual stimuli designed to provide a
broad inventory of system-wide functioning after traumatic brain
injury.
• By applying these tests and validating them against standard
vision testing, patients and military personnel with visual
dysfunction can then be better diagnosed and characterized to
improve outcomes of therapeutic interventions.
• Objective is to use objective reflexes of the visual system to
diagnose vision deficits and ensure effective monitoring of their
treatment, when indicated.
• Aims: 1) In normal eyes, define range of values for pupil light
reflexes, evoked potentials and eye movements to targets
changing in resolution. 2) In eyes with damage to the retina or optic
nerve, define range of values for pupil light reflexes, evoked
potentials and eye movements to targets changing in resolution.
3) In eyes with damage to primary visual cortex (V1), define range
of values for perimetric pupil light reflexes, evoked potentials and
eye movements to targets changing in resolution.
• The successful outcome of this study will allow application of
objective tests to assess patients over a wider range of impaired
consciousness and cognitive dysfunction.
Smart Eye (head and eye movement
tracking system
Hand held puplilometer – resulting in a
new chromatic stimulus and pupil test
Proposed Solution
U.S. Army Medical Research and Materiel Command 16
Wearable Visual Aid as Treatment for
TBI Associated Visual Dysfunction
James Weiland, PhD University of Southern California
Problem, Hypothesis and Military Relevance
Activities FY 11 12 13 14
Optimize SLAM for wearable
system XXXX XXXX XXX X
Further develop neurally-
inspired attention algorithms XXXX XXXX XXX X
Implement wide field-of-view,
wide-dynamic range camera XXXX XXXX XXX X
Algorithm for system control
integrated with use interface XXXX XXXX XXX XXX
Test the portable system on
visually impaired volunteers XXXX XXXX XXX XXX
• Addresses vision gap seven: Regeneration and
Reconstruction of the Components of the Visual System
and Ocular Adnexa.
• A wearable system with advanced image sensors and
computer vision algorithms can provide the desired and
relevant information to individuals with TBI related injuries.
• The system will address major challenges encountered by
the blind, including detecting changes in elevation, guiding
safe street crossing, recognizing desired objects, and
orienting the user while navigating.
Proposed Solution • Optimize a simultaneous localization and mapping (SLAM)
algorithm for use in obstacle detection for visually impaired
individuals during ambulation;
• Further develop neurally-inspired attention algorithms that
detect important objects in an environment for use by visually
impaired individuals during search tasks;
• Implement a highly miniaturized prototype wide field-of-view,
wide-dynamic range camera for image capture in indoor and
outdoor environments;
• Develop an algorithm for overall system control and integration,
including functionality for a user interface and adaptation to
different tasks and environments, and integrate the camera and
all algorithms into a wearable system.
• Test the portable system on visually impaired human subjects.
U.S. Army Medical Research and Materiel Command 17
2001 PRMRP 2 awards $1.3M
2002 PRMRP 1 award $1.6M
2003 PRMRP 1 award $3.0M
2006 PRMRP 8 awards $7.5M
2008 PRMRP 6 awards $5.9M
2008 DMRDP 4 awards $6.0M
2008 TSCRP 1 award $0.5M
2009 PH-TBI 2 awards $4.1M
2010 DMRDP 7 awards $9.5M
2011 AFIRM 1 award $2.4M
2011 DMRDP 2 awards $4.7M
2012 PRMRP 1 award $1.4M
2013 PH-TBI 1 award $0.3M
37 awards $48.2M
Other CDMRP Funded Vision
U.S. Army Medical Research and Materiel Command 18
2001 PRMRP Gary Martinsen Russell McCally
2002 PRMRP Thomas Johnson
2003 PRMRP Darlene Dartt
2006 PRMRP Joe Rizzo Lu Chen Shelley Fried Kimberly Cockerham Michelle Callegan Balamurali Ambati Randy Kardon
De-Quan Li
2008 PRMRP Dean Li Joseph Sassani Kraig Bower Anthony Johnson Wolfgang Fink Irene Kochevar
2008 DRMRP Irene Kochevar Morgana Trexler Cathryn Sundback Anthony Johnson
2008 TSCRP Stephen Tsang
2009 PH-TBI Gang Luo Richard Hogle
2009/10 VRP Stacey Choi Kenneth Ciuffreda Colin Doherty Thao Nguyen Yury Petrov Uri Polat Richard Regueiro Tonia Rex
Gregory Schultz James Weiland Randy Kardon Nicholas Brecha
2010 DMRDP Richard Carvalho Gregory Liou Brian Lawrence Eli Peli Shigeo Tamiya Christopher Tyler Larry Benowitz
2011/12 VRP Eldon Geisert David Krizaj Mark Humayun Jena Steinle Andrew Hartwick Rajendra Kumar-Singh Cintia de Paiva
Andrew MacKay Shaomei Wang Jeffrey Goldberg Daniel Palanker Philip Troyk Sheila Nirenberg Michael Iuvone
Pavel Iserovich Kevin Park Walter Gray Brittany Coats Joseph Izatt Kenneth Ciuffreda James DeMar
2011 AFIRM Alexander Kiderman
2011 DMRDP Reza Dana Julie Haller
2012 PRMRP Stephen Plugfelder
2013 PH-TBI Alexander Kiderman
2013/14 VRP Joseph Brzezinski Alfredo Martinez Lora Likova Stephen Wong Cheryl Olman Shaochen Chen Kia Washington
William Jia Vijay Gorantla Jon Froehlich Derek Welsbie Samuel Fulcher Katherine Kajjar James Funderburgh
Jeffrey Mumm Douglas Dean James Akula Andrew Pieper Lu Chen Ali Djalilian Sanjoy Bhattachary Ricardo Carvalho
Sunil Chauhan Edward Chaum Joseph Ciolino Gere di Zerega David Kaplan Stephen Macknik Daniel Palanker Matthew Reilly
Lawrence Rizzolo Michael Steketee Morgana Trexler James DeMar
CDMRP & VRP Funded Vision Investigators
U.S. Army Medical Research and Materiel Command 19
Thank You for Your Service!
U.S. Army Medical Research and Materiel Command 20
Additional Hearing Slides
U.S. Army Medical Research and Materiel Command 21
Clinical & Rehabilitative
Medicine Research Program
To increase understanding of the CRM Vision
Research Portfolio.
Scope
The Vision Traumatic Injury Restoration and
Rehabilitation portfolio includes DoD efforts in the
areas of visual dysfunction associated with traumatic
injury, with a view ranging from basic research
through clinical development
Purpose
Restore/rehabilitate the vision of Service Members
post-traumatic injury by advancing medical
capabilities (improved methods, drugs, and devices)
through research and development
U.S. Army Medical Research and Materiel Command 22
To increase understanding of the CRM Hearing &
Balance Research Portfolio.
Scope
The Hearing and Balance Traumatic Injury Restoration
and Rehabilitation portfolio includes DoD efforts in the
areas of hearing and vestibular dysfunction associated
with traumatic injury, with a view ranging from basic
research through clinical development
Purpose
Restore/rehabilitate the hearing and balance of
Service Members post-traumatic injury by advancing
medical capabilities (improved methods, drugs, and
devices) through research and development
Clinical & Rehabilitative
Medicine Research Program
U.S. Army Medical Research and Materiel Command 23
Sensory System
Investment of Active Projects
U.S. Army Medical Research and Materiel Command 24
Sensory Clinical Capability Gaps
Visual Capability Gaps
• Mitigation and treatment of traumatic
injuries, war-related injures, and diseases
to ocular structures and the visual system
• Mitigation and treatment of visual
dysfunction and associated with TBI
• Ocular and visual systems diagnostic
capabilities and assessment strategies
• Eye protection and vision loss prevention
strategies
• Vision rehabilitation strategies and
quality of life measures
• Epidemiological studies of military eye
trauma and TBI-related vision dysfunction
• Vision restoration
• Vision care education, training and
simulation
• War fighter vision readiness and
enhancement
Hearing and Balance Capability
Gaps
• Hearing Restoration
• Treatment of hearing loss
• Prevention and/or treatment of tinnitus
• Epidemiology and measurement tools
for hearing loss
• Prevention and Treatment of
vestibular dysfunction
U.S. Army Medical Research and Materiel Command 25
Diagnosis and Treatment of Blast-Induced Hearing Loss
Problem, Hypothesis and Military Relevance
Proposed Solution Timeline and Cost
Activities FY 10 11 12
Aim 1a: Use our existing OCT device
to characterize the anatomic patterns
of damage after blast-injury in mice
Aim 1b: Develop endoscopic OCT
device for use in humans
Aim 2: Characterize the cellular,
molecular, and genetic patterns of
damage after blast-injury in mice
• Blast-induced hearing loss is common among active
military personnel.
• It produces a long-term disability that requires chronic
management through the Veterans Administration.
• Current treatments are limited to hearing aids.
• Hypothesis: Improved imaging of the ear and a detailed
understanding of the tissue, cellular, and genetic changes
that occur within the ear after blast injury will permit the
development novel and more effective treatments.
• Project: Rehabilitation; Task: Restoration and
Rehabilitation of Sensory System Traumatic Injury
• This proposal is designed to overcome current limitations
via two parallel and transformative specific aims.
• 1) To develop an endoscopic optical coherence
tomography (OCT) device to image the ear at high
resolution. This aim will result in a safe, non-invasive, and
portable device ready to be tested in humans.
• 2) To develop a mouse model of blast injury to
characterize the cellular damage and changes in gene
expression that occur after blast injury. This aim is
designed to identify molecular pathways of damage that
can be targeted by novel drugs.
• Collaborative research team: 1 clinician-scientist, 2
bioengineers, and 2 neuroscientists.
John S. Oghalai, MD Stanford University, Stanford, CA
(1) Novel Device to Image the Ear
after Blast Injury at High Resolution
(2) Cellular, Molecular, and Genetic
Characterization Studies to Identify
Novel Therapeutic Agents
U.S. Army Medical Research and Materiel Command 26
Assessing the impact of blast-related sensory impairment
on multisensory integration while maneuvering on foot
Douglas Brungart, Ph.D. The Henry M. Jackson Foundation
Study Aim(s) 1: To assess the multisensory integration ability of normal Service Members by
characterizing aurally-aided visual search (AAVS) performance as a function of visual
target acquisition time and auditory localization accuracy while SMs are physically in
stationary or moving conditions.
2: To assess the multisensory integration ability of Service Members with sensory
impairment by characterizing their aurally-aided visual search times in the stationary and
moving conditions and to compare their performance to that of unimpaired Service
Members with similar visual target acquisition times and auditory localization scores.
3. To determine the extent to which the aurally-aided visual search performance of
stationary and moving Service Members with sensory impairment can be predicted from
current clinical measures of neurological, sensory and vestibular function.
4. For those participants who proceed to the second phase of the study, to learn more
about the neurophysiological underpinnings of sensory integration disorder by comparing
results from virtual reality (Computer Assisted Rehabilitation Environment, CAREN) to an
experimental environment (Magnetoencephalography, MEG)
Approach The study will take an aurally-aided visual search paradigm that has been shown to be
effective for assessing audio-visual integration in stationary environments and port it to a moving platform that will greatly increase the sensory load and simulate dismounted combat operations.
Milestones and Goals
FY 13 Goals
Develop, build, and integrate spatial sound array in CAREN system (Done)
Obtain IRB Approval (Done)
FY14 Goals
Begin collecting AAVS data on control subjects (2 Completed)
Begin collecting AAVS data on impaired subjects
FY15 Goal
Develop a model of visual search time for normal and impaired subjects
Analyze and report results
Project Status: Green
All projected milestones have been met and current expenditures are under
projected budget.
Updated: 10/31/2014
Timeline and Cost
Activities FY 13 14 15
Recruit study personnel; implement spatial sound
array in CAREN; obtain IRB approval
Collect AAVS data on stationary and moving control
subjects
Collect AAVS data on stationary and moving
impaired subjects
Analyze and report results
The blue dots show the locations of the 64 loudspeakers used in the
experiment. These speakers are mounted on an aluminum scaffold behind the
fabric screen of the CAREN.
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