Caring for Wounded Warriors with Vision and Hearing ...€¦ · eye movements to targets changing in resolution. • The successful outcome of this study will allow application of

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



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)




• 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


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


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


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


Two program announcements – II $1M, HD $250K




$13,766,396




visual system




1 Ocular and visual systems diagnostic capabilities and

assessment strategies



Two program announcements – TR $1M, HD $250K




$24,868,891






visual system

1 Rehabilitation strategies and quality of life measures




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


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


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.


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


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


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


Wearable Visual Aid as Treatment for

TBI Associated Visual Dysfunction

James Weiland, PhD University of Southern California


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.


2001 PRMRP 2 awards $1.3M

2002 PRMRP 1 award $1.6M




2008 DMRDP 4 awards $6.0M

2008 TSCRP 1 award $0.5M

2009 PH-TBI 2 awards $4.1M


2011 AFIRM 1 award $2.4M



2013 PH-TBI 1 award $0.3M

37 awards $48.2M

Other CDMRP Funded Vision


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


Thank You for Your Service!


Additional Hearing Slides


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


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


Sensory System

Investment of Active Projects


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


Diagnosis and Treatment of Blast-Induced Hearing Loss


Proposed Solution Timeline and Cost


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


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


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.

Documents

Caring for Wounded Warriors with Vision and Hearing ...€¦ · eye movements to targets changing in resolution. • The successful outcome of this study will allow application of