The National Eye Institute (NEI) funds vision research through its $707 million annual budget. Its Audacious Goal Initiative aims to regenerate neurons in the eye and visual system by focusing on photoreceptor loss, ganglion cell injury, and optic nerve regeneration. The NEI supports translational research through grants such as the NEI Translational Research Program and Small Business Grants. It also conducts intramural research including stem cell therapy and gene therapy clinical trials. The NEI commits $50 million annually to support large clinical trials through organizations like the Diabetic Retinopathy Clinical Research Network. It also trains students and clinicians in vision research through fellowship programs.

1. Ophthalmic Innovation 2016:
View from the National Eye Institute
Mala Dutta, Ph.D.
Lead, Office of Translational Research
National Eye Institute, NIH

2. NEI Operating Budget in FY2016:
$707 million1/
• NEI Research Project Grants: The biggest part of NEI budget.
• Non-dilutive funding:
Grantee keeps the IP (Bayh-Dole Act).
1/ Post HHS Secretary’s Transfer

3. The NEI Audacious Goal Initiative
“Regenerate neurons and neural connections in
the eye and visual system”
Three Focus areas of AGI
• photoreceptor loss
• ganglion cell injury
• optic nerve regeneration
• Addresses pathogenesis of many vision diseases and conditions.
AMD, Glaucoma, LHON, Retinal Degenerations, etc.
• Model for regenerative therapy beyond vision: CNS & spinal cord.
• Translate basic science of plasticity into effective treatments for strabismus,
amblyopia, and central visual processing.

4. The NEI Audacious Goal Initiative
Workshops to date:
•4 Experts Workshops (SfN & ARVO) / 2 Town Halls at ARVO
•2 white papers, next one in J. of Neuroscience
For more information please visit: nei.nih.gov/audacious
2 FOAs
•“Functional Imaging of the Visual
System”
o 5 awards, May 2015, ~$4M
total/yr. for 5 yrs.
•“Identifying Neural Regeneration
Factors in the Visual System”
o 6 awards, Sept 2016, ~$4M
total/yr. for 3 yrs.

5. Convergence of
initiatives
• The NEI Audacious Goals Initiative
 Catalyzing neuroregenerative medicine for vision
• The BRAIN Initiative at NIH-2014
 Providing new tools and technologies to understand and
modulate brain circuitry
• NIH Precision Medicine Initiative – 2015:
 Medical treatments of the future based on personal
genetic information
• NCATS Tissue Chip at NIH
 Developing 3-D platforms engineered to support living
human tissues and cells to improve drug screening

6. NEI Translational Research Program
(R24 Grants)
• Multidisciplinary and collaborative research projects
• $10M budget: 6-7 ongoing projects; $1.5M/year/ 5 years. Non
renewable grants
• Proof of concept Preclinical development IND/IDE
submission NEI U10/UG1 Clinical Vision Research Grant /R34
Clinical Study Development Grant.
• Current portfolio: small molecule photo switches for outer-
retinal blindness; gene therapy for a number of ocular disorders
(ABCA4-associated disorders, autosomal RP, and
achromotopsia); and microRNAs for potent anti-angiogenesis.
Program Director: Neeraj Agarwal, PhD. agarwalnee@nei.nih.gov
Success stories:
• Emory University: Nanoparticle preparation of chemotherapeutic agents
microneedles to inject drugs into suprachoroidal space Start-up Clearside Biomedical
• Univ of Miami: Leber Hereditary Optic Neuropathy (LHON) gene therapy product, AAV-
ND4 Phase 1 Clinical trial - follow-up U10 grant.

7. Small Business Grants (SBIR & STTR)
Program Director: Jerry Wujek, PhD, wujekjer@nei.nih.gov
Support small companies to transform innovative ideas into ophthalmic drugs,
medical instruments, or assistive devices that help people.
• $20 M/year, 70 small companies
• Regulatory Assistance Program
Success Stories:
• VisionQuest Biomedical, LLC: Telemedicine system for real-time, large scale eye
screening at sustainable cost.
• Photoswitch Biosciences: Small-molecule therapeutic photo-switch channel to restore
vision in retinal degenerative disease.
• Parion Sciences, Inc: Epithelial sodium channel antagonist to regulate salt & water
transport as a therapeutic for dry eye.

8. Cell and Gene Therapy in
Intramural Program
iPSC Stem Cell Therapy
• Use iPS cells to create RPE patch to treat AMD
•A major NEI intramural basic to clinical initiative
•IND for human trial in 2017/2018
•The leading NIH program for neural transplantation
Human Ocular Gene Therapy
X-Linked Retinoschisis (XLRS): Phase I / IIa.
•One of first NIH in vivo gene therapy programs
• Clinical trials with XLRS patients ongoing
X-Linked Retinitis Pigmentosa RPGR Gene Therapy
•Pre-Clinical Phase, murine animal model
•AAV-based therapeutic rescue

9. NEI commits nearly $50M in annual clinical trial support
NEI supported DRCR.net : rapid implementation of protocols for large-scale
clinical trials
•Prompt versus Deferred Panretinal Photocoagulation (PRP) with Intravitreal Ranibizumab
(Lucentis) with for Proliferative Diabetic Retinopathy (PDR)
• Phase III, prospective, multicenter randomized
• Results: Over 2 years, deferred w/Lucentis beneficial
• This trial marks the first major advance in PDR in 40 years
• A Comparative Effectiveness Study of Intravitreal Aflibercept, Bevacizumab and
Ranibizumab for Diabetic Macular Edema (DME)
• Safety and efficacy
• Results: Over 2 years, all 3 improved vision in DME when starting vision loss milder.
More advanced vision loss, Eylea clear advantage
• This study is critical for doctors and patients to make informed decisions in choosing
treatment for diabetic macular edema.
Extramural Clinical Trial Support

10. Nurturing Vision Research Talent
NEI trains students, fellows and clinicians
in vision research.
• Fellowship training in basic science and clinical
research engages graduate students,
baccalaureate fellows, postdoc fellows and
clinicians in vision research.
• Diversity in Vision Research and Ophthalmology
(DIVRO) recruits students from underrepresented
groups for summer internship program.

11. End of Slides
Ophthalmic Innovation 2015:
View from the National Eye Institute.
Paul A. Sieving, MD, PhD.