Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!

Dominick Maino, OD, MEd, FAAO, FCOVD-A
Moderator
Featuring the Best of AOA's 2016 Poster Presentations
Saturday, July 2nd 8-10AM
Current Clinical Case Reports and Research You
Should Incorporate into your Mode of Practice Now!

The Sunshine Act First Year Results: The Status of Optometry
Primary Author: Erik Mothersbaugh, OD
Residual peroxide levels after neutralization of two marketed one-step hydrogen peroxide
systems
Primary Author: Jessie Lemp, MS, DrPH
The Cat's Out of the Bag: Serial Analysis of Neuroretinitis Through Spectral Domain OCT and
Humphry Visual Field Assessment
Primary Author: Amy A. Puerto, OD
Safety and Efficacy of Latanoprostene Bunod for Lowering of Intraocular Pressure in Open-Angle
Glaucoma or Ocular Hypertension
Primary Author: Murray Fingeret, OD
Validation Study of Visual Objectives Biomarkers for Acute Mild Traumatic Brain Injury
Primary Author: José E. Capó-Aponte, OD, PhD
2016 AOA’s Best Presentations

Cochrane Reviews
http://www.cochrane.org/
… a global independent network of
researchers, professionals,
patients and people interested in
health…
Levels of
Research

Clinician’s View of Researchers

Researcher’s view of Clinicians

Poster Session
My Thanks to the AOA 2016 Abstract Review Committee
William McAllister, Elizabeth Wyles, Sunny Sanders,
Sarah Hinkley, Christine Allison, Jennifer Harthan, Aurora
Denial
176 posters submitted 50% of Posters accepted
Criteria for acceptance similar to those used by other well
respected organizations (clinical aspects emphasized)
Reasons for non-acceptance:
Did not follow instructions
Data does not support conclusions

Poster Session
Preview session on
Friday, July 1, 2016
(10:00am-6:00pm)
Interactive session on
Saturday, July 2, 2016
(11:00am-2:00pm)

Poster Session 2017
Please submit Case reports, Case series, Clinical research, etc. in all areas
of optometry for 2017 when the call for abstracts goes out!
Informational Posters Accepted (These also need to be well done and
cannot be a sales pitch for a particular product or service. This is NOT a
review of the literature.)
This Morning’s Presentation
The committee judged these posters to be notable and worthy to be
highlighted in this fashion
Questions welcome at the end of each of today’s presentations

The Sunshine Act First Year
Results: The Status of
Optometry
Erik Mothersbaugh, OD
Elizabeth Wyles, OD
Jordan Keith, OD

Brennan TA, et al. Health
industry practices that create
conflicts of interest. JAMA. 2006;
295: 429-433

69%
of Americans say that drug makers hold
too much sway over physicians
prescribing habits
2010 Consumer Reports National Research Center poll

Affordable Care Act: Section 6002
SUMMARY: This final rule will require applicable manufacturers of
drugs, devices, biologicals, or medical supplies covered by Medicare,
Medicaid or the Children’s Health Insurance Program (CHIP) to report
annually to the Secretary certain payments or transfers of value
provided to physicians or teaching hospitals (‘‘covered recipients’’). In
addition, applicable manufacturers and applicable group purchasing
organizations (GPOs) are required to report annually certain physician
ownership or investment interests. The Secretary is required to publish
applicable manufacturers’ and applicable GPOs’ submitted payment
and ownership information on a public Web site.

CMS Open Payments Database
• August 1, 2013: Industry required to start data capture
• December 31, 2013: End of first reporting period
• January 1, 2014: Beginning of second reporting period
• December 31, 2014: End of second reporting period

Chang, JS. The physician
payments sunshine act.
Ophthalmology 2015; 122(4):
656-661.

Design
• Retrospective data review
• Participants: Optometrists registered in CMS Open Payments
database
• Data collected: All general payments made to optometric
physicians between January 1, 2014 and December 31, 2014

What is considered a “general payment”?
• Cash or Cash Equivalent
• Consulting fees
• Speaking fees
• Honoraria
• Royalties
• In-Kind Items and Services
• Food and Beverage
• Travel and Lodging
• Education

What is NOT considered a “general
payment”?
• Ownership/Investment payments
• Research-related payments

Results: National
• Transactions: 165,035
• Optometric Physicians Accepting Payments: 36,426
• Total Payments: $18,289,817
• Average Transaction Value: $111
• Average Payment per Physician: $502

Results: National
• Range: $1 - $406,392
• Payments made to Top 10% of Payment Recipients:
$13,166,996
72% of the total $18.3 M went to physicians in the highest 10%

Results: State-by-State Comparison
States that Rank in Top 10 for both Total Payments and Average Payment per Provider
State Total Payment Rank Average Payment Rank
California 1st
8th
Florida 4th
9th
North Carolina 5th
3rd
Pennsylvania 3rd
5th
Utah 8th
1st

Results: State-by-State Comparison
States that Rank in Bottom 10 for both Total Payments and Average Payment per Provider
State Total Payment Rank Average Payment Rank
Alaska 45th
43rd
Delaware 48th
47th
Maine 47th
50th
Montana 49th
49th
New Mexico 44th
45th
North Dakota 43rd
41st
South Dakota 46th
48th

Do financial relationships with industry
influence physicians’ behavior?

“The present extent of physician-
industry interactions appears to affect
prescribing and professional behavior
and should be addressed at the level
of policy and education.”
Wazana A. JAMA 2000 Jan 19;283(3):373-80

“A minority of doctors (40%) thought
that industry involvement created a
conflict of interest but the majority of
doctors (86%) thought that it did not
create a bias in their own drug
selection.”
Rutledge et. Al. Pharmacoepidemiology and Drug
safety. 2003; 12: 663-667.

Conclusions
• Financial relationships with industry are widespread in the
profession of Optometry, with over 36,000 ODs participating.
• The majority of total dollars paid to Optometrists (72%) goes
to a relative minority of providers (10%).

“Guidelines establishing thresholds,
such as the arbitrary amount of $100,
are based on the belief that there is a
direct “dose response”—that the risk of
bias increases as the value of the gifted
item increases. There is no level,
however, below which it is guaranteed
that marketing wares have no effect on
the recipient.”
Katz, D. et al. All gifts large and small: Toward
an understanding of the ethics of
pharmaceutical industry gift-giving. The
American Journal of Bioethics; 3(3): 39-46.

Relationships with Industry
 Optometrists should avoid situations and activities
that would not be in the best interest of their
patients.
 Any financial and/or material incentive offered by
industry that creates an inappropriate influence on
an optometrist’s clinical judgment should be avoided
AOA Standards of Professional Conduct
Section E, Part 1-E – Non Patient Professional Relationships

Conflict of Interest
 The care of a patient should never be influenced by the self-interests of the
provider.
 Optometrists should avoid and/or remove themselves from any situation that
presents the potential for a conflict of interest where the optometrist’s self interests
are in conflict with the best interest of the patient
 Disclosure of all existing or potential conflicts of interest is the responsibility of the
optometrist and should be appropriately communicated to the patient
AOA Standards of Professional Conduct
Section B, Part 4-B – Nonmaleficence (“do no harm”)

References
• "Health Policy Brief: The Physician Payments Sunshine Act," Health Affairs, October 2, 2014.
• Lichter, PR. Debunking myths in physician-industry conflicts of interest. Ophthalmology 2008; 146(2): 159-171.
• Wazana A. Physicians and the pharmaceutical industry: Is a gift ever just a gift? JAMA 2000; 283: 373-380.
• Katz, D. et al. All gifts large and small: Toward an understanding of the ethics of pharmaceutical industry gift-giving. The American Journal of Bioethics;
3(3): 39-46.
• Epstein, AJ. et al. Does exposure to conflict of interest policies in psychiatry residency affect antidepressant prescribing? Medical Care; 51(2): 199-203.
• Austad, KE. et al. Association of marketing interactions with medical trainees’ knowledge about evidence-based prescribing: Results from a national
survey. JAMA Intern Med 2014; 174(8): 1283-1289.
• Segovis, CM. et al. If you feed them, they will come: A prospective study of the effects of complimentary food on attendance and physician attitudes at
medical grand rounds at an academic medical center. BMC Medical Education 2007; 7(22).
• Lichter, PR. Implications of the sunshine act – Revelations, loopholes, and impact. Ophthalmology 2015; 122(4): 653-655.
• Agrawal, SA. et al. The sunshine act – Effects on physicians. N Engl J Med 2013; 368(22): 2054-2057.
• Chang, JS. The physician payments sunshine act. Ophthalmology 2015; 122(4): 656-661.
• Brennan, TA. et al. Health industry practices that create conflicts of interest: A policy proposal for academic medical centers. JAMA 2006; 295(4): 429-
433.
• Rutledge P, et al. Do doctors rely on pharmaceutical industry funding to attend conferences and do they perceive that this creates a bias in their drug
selection? Results from a questionnaire survey. Pharmacoepidemiol Drug Safety 2003; 12: 663-667.
• Epstein AJ, et al. Does exposure to conflict of interest policies in psychiatry residency effect antidepressant prescribing? Med Care. 2003 February;
52(2): 199-203
• King M et al. Medical school gift restriction policies and physician prescribing of newly marketed psychotropic medications: difference-in-differences
analysis.

Questions?
1.)    How do the professions of
optometry and ophthalmology compare
with respect to these payments?
2.)    Why do you think so much of the
money goes to a relative few
physicians?
3.)    Have any optometry schools
instituted policies restricting industry
interaction?

The Sunshine Act First Year Results: The Status of Optometry
Primary Author:  Erik Mothersbaugh, OD
Residual peroxide levels after neutralization of two marketed one-step hydrogen peroxide
systems
Primary Author:  Jessie Lemp, MS, DrPH
The Cat's Out of the Bag: Serial Analysis of Neuroretinitis Through Spectral Domain OCT and
Humphry Visual Field Assessment
Primary Author:  Amy A. Puerto, OD
Safety and Efficacy of Latanoprostene Bunod for Lowering of Intraocular Pressure in Open-Angle
Glaucoma or Ocular Hypertension
Primary Author: Murray Fingeret, OD
Validation Study of Visual Objectives Biomarkers for Acute Mild Traumatic Brain Injury
Primary Author:  José E. Capó-Aponte, OD, PhD
2016 AOA’s Best Presentations

A Comparison of Residual Peroxide Profiles after
Neutralization of Two Marketed One-Step Hydrogen
Peroxide Systems
Jessie Lemp, MS, DrPH; Jami R. Kern, PhD;
Amanda Shows, BS; and Huagang Chen, MS
Alcon Laboratories, Inc.
Fort Worth, TX, USA
Jessie Lemp, Jami R. Kern, Amanda Shows, and Huagang Chen are employees of Alcon Laboratories, Inc.
44

Background
• Common one-step hydrogen peroxide lens disinfecting systems work by use of a 3%
H2O2 buffered solution, which is neutralized by a platinum catalyst disc during lens
storage.
• Clear Care®
(Alcon) brand 3% H2O2 systems recommend a 6-hour recommended storage time out to
100 cycles.
• PeroxiClear® (Bausch & Lomb) 3% H2O2, containing a platinum-modulating compound, recommends
a 4-hour storage time and a max of 35 cycles.
• Both the Clear Care® brands and PeroxiClear® have demonstrated similar, high levels of
disinfection efficacy.3,4
• Residual H2O2can remain after the disinfection cycle; if these levels are too high,
ocular discomfort can result.1,2
45
1. Paugh JR et al. Am J Optom Physiol Opt. 1988;65:91-98. 2. Mc
Nally J. CLAO J. 1990; Jan-Mar; 16 (suppl 1): S46-51. 3. Gabriel et al. Poster presented at BCLA Meeting,
Liverpool, UK May 29-31, 2015. 4. Cordero D et al. Poster presented at AAOpt Meeting, Seattle, WA Oct 22-27, 2013.

Purpose
•To compare the residual H2O2 profiles of Clear
Care Plus with HydraGlyde (CCP) and
PeroxiClear (PC) after neutralization in
laboratory-cycled cases and patient-used
cases.
46

Methods: (in vitro analysis)
• Neutralization rates of CCP and PC were evaluated.
• All cases (n=3/time point) were first cycled one time overnight.
• On the second cycle:
47
30
45
60
120
240
360
5
15
Minutes
An aliquot of product solution
recovered for the assay of
remaining H2O2 in parts per million
(ppm) using UV spectroscopy.
H202 levels determined by titration with potassium
permanganate

Method: (in vitro analysis)
• Residual H2O2 in the two systems was compared at room temperature through 100 neutralization cycles
without lenses.
• Each cup was filled with 10 mL of corresponding test solution (n=5/system), capped tightly, and allowed to
neutralize for the recommended storage time.
• At each test cycle, an aliquot of product solution recovered for the assay of remaining H2O2 (ppm) using UV
spectroscopy.
48
1..............15..............30..............45..............60..............75..............90.........100
@ 4hrs @ 6hrs
Cycles
Each non-test cycle lasted ≥4hrs or ≥6hrs respectively

Methods (ex vivo analysis)
Day 30
Used Cup
Day 30
Used Cup
Day 1-30
CCP
Day 30
Used Cup
Day 30
Used Cup
Day 1-30
PC
Day 1-30
PC
@ 4hrs @ 6hrs
An aliquot of product
solution recovered for the
assay of remaining H2O2 in
parts per million (ppm)
using UV spectroscopy.
Neutralization rates by way of testing residual H2O2 at 2, 3, and 4 hours of neutralization (CCP and PC)
and at 6 hours (CCP) were also determined using 10 randomly selected used cases per product.
10 mL of the appropriate solution (CCP or PC) was added to each used
case

50
Results (in vitro analysis)
• CCP had significantly lower residual H2O2 than PC at all tested neutralization time points up to 120 minutes
in unused cases (P < .05), with a trend towards lower residual H2O2 at 240 and 360 minutes (P < .10).
Neutralization Rates for CCP and PC over 6hrs (n = 3)

Results (in vitro analysis)
51
• Residual H2O2 concentrations of CCP were significantly lower than those of PC after neutralization cycles
of 1, 30, 60, and 90, corresponding to initial and 1, 2, and 3 months, respectively (P<.05).
Neutralization Profiles of CCP and PC at Manufacturer-Recommended Storage Time (n = 5)
Note: The Limit of Quantitation (LOQ) is 5 ppm. Data below 5 ppm are <LOQ. Values are mean ± SD.
*P< .05

Results (ex vivo analysis)
52
Mean Residual H2O2 for 30-Day Used CCP and PC Systems at Manufacturer-Recommended
Storage Times (n=130)
• In 30-day used cases, mean ± SD residual H2O2 for CCP and PC at neutralization time was 26.2 ± 41.17 and
229.7 ± 280.13, respectively (P<.001).

Results (ex vivo analysis)
53
Neutralization Rate Profiles for 30-Day Used CCP and PC Systems (n = 10)
• CCP had lower residual H2O2 than PC at 2, 3, and 4 hrs. (P<.05 at 2, 3 hrs.).
• Residual H2O2 was <100 ppm in the 30-day used CCP system by 3 hours of neutralization.
†
Not tested at 5 hr. ‡
PC not tested at 6 hr.

Results (safety analysis)
54
Ocular Adverse Events (Adverse Device Effects)
• There was a higher incidence of related adverse device effects (ADEs) in subjects using PC (11 ADEs in 5
subjects) than in those using CCP (2 ADEs in 1 subject).

Conclusions
• In both laboratory-cycled and patient-used cases, the
manufacturer-recommended 6-hour neutralization time of
CCP allows for more complete neutralization of H2O2 than the
4-hour neutralization time recommended with PC.
• Both the CCP and PC systems used by study subjects resulted
in higher residual H2O2 concentrations at neutralization time
compared to the systems cycled in the laboratory; however,
the relative increase was larger for PC.
55

Discussion
• Of the 30-day used lens cases collected, 98.5% of CCP and
20.0% of PC systems at recommended storage time showed
mean residual peroxide ≤ 100 ppm, the ocular detection
threshold.1
• Further research should be conducted to understand the clinical
implications of these findings.
• Given peroxide solutions are often recommended to sensitive
contact lens wearers, ECPs should consider these findings when
recommending a solution and educating their patients on proper
use.
56
1. Paugh JR, et al. Am J Optom Physiol Opt. 1988;65:91-98.

The Cat's Out of the Bag!
Serial Analysis of Neuroretinitis Through Spectral Domain OCT,
Fundus Photography, and Humphrey Visual Field Assessment
Amy Puerto, O.D.
Family Practice Resident
Bond-Wroten Eye Clinic
Hammond, Louisiana (New)

Financial Disclosure
I have no financial interest in any commercial or pharmaceutical entity
mentioned during this presentation.

Case Presentation
• Case Hx: Initial Visit
• New patient: 30-year-old Arab Male
• Presenting Complaint: Painless visual loss in his right
eye x 3 days, described as seeing a “blurry-gray spot”
near the center-right of his vision that had gotten
bigger.
• Ocular Hx:
• Wears spectacles/contact lenses denies history of eye
disease or eye surgeries
• Systemic Hx:
• Patient presented with concurrent history of fever,
fatigue, headaches, and chills x 1 week.
• Patient denied pain, parasthesia, numbness, motor
weakness or gait changes.
• Patient was not on any medications and denied smoking
and alcohol use.
• NKDA
• (+) Tylenol PRN
• Family Hx:
• Mother: (+) Diabetes, HTN
• Father: (+) Cardiovascular disease
• Examination:
• VA’s with CLs : 20/400 EF* OD, 20/20 OS
• Pupils: trace APD OD
• EOMs & Cover Test Unremarkable
• CVF Full OD, OS but patient reported
unable to “see” doctor’s left side of face
when performing test
• Color Vision: Ishihara 14/14 OD, OS**
• Red Cap Test: (+/?)**
• No lymphadenopathy
• BP: 113/76 Pulse: 60
• SLE:
• Anterior Segment: Unremarkable OD, OS
• Dilated Fundus Examination…
*EF- Eccentric Fixation

Fundus Presentation
Left EyeRight Eye

OCT Analysis-Retina
Left EyeRight Eye

Visual Field Analysis
Left EyeRight Eye

Review of Differential Diagnoses
1. Optic Neuritis assoc. MS
2. Ischemic Optic Neuropathy
NAION
AAION assoc. GCA
1. Papilledema
2. Retinal Vein Occlusion
3. Neuroretinitis

Assessment/Plan
Assessment:
• Neuroretinitis suspect Cat Scratch Disease etiology per Hx
Plan:
• Lab Work-up
• CBC w/ Diff, ESR, C-reactive Protein, and Bartonella Henselea Titer
• Rx’d doxycycline monohydrate 100mg p.o. BID x 30 days prophylactically
• Patient advised to RTC x 1 week for f/u with VF and OCT until resolution.
Time to be the CLINICIAN!
• Be systematic in your differentials and remember: “Common things
happen commonly.”
• Cost-effective laboratory testing and clinical observation can be used to properly
diagnose cases of optic nerve edema.

Assessment and Plan Cont’d
Lab Results Results Reference Range
WBC 21.4 3.4-10.8
Neutrophils 12.4 1.4-7.0
Lymphs 4.5 0.7-3.1
Monocytes 3 0.3-0.9
RBC 4.65 4.14-5.80
Platelets 265 150-379
ESR*6,7
18 mm/h 0-20mm/h
CRP 13m/L 0-7mg/L
Bartonella henselae Antibody IgG 1:1280 <1:320
Bartonella henselae Antibody IgM 1:200 <1:100
One Week Follow-up
• At one week f/u patient had confirmed labs
showing elevated WBC Count and a Positive
Bartonella titer.
• Patient VA’s remained at 20/400.
• Confirmed Diagnosis of Neuroretinitis
associated with Cat Scratch Disease.
• Cont. Doxy BID until medication is gone.

Cat Scratch Disease (CSD)
• Cat scratch disease (CSD) is a systemic infection caused by the bacteria Bartonella henselae,
with approximately 22,000 cases U.S./year. 1
• Patients contract the infection after being scratched, bitten, or licked by a cat and commonly report a
virus-like illness.
• Demographic: Persons of all ages and ethnicities, but is more often seen in pediatric
populations or those between the ages 30 and 40
• Ocular involvement occurs in ~10% of CSD cases1,2,5
:
• Parinaud's oculoglandular syndrome: granulomatous conjunctivitis with associated lymphadenopathy
• Focal chorioretinitis
• Neuroretinitis
• Positive Bartonella Henselae titer
• The condition tends to be self-limiting, for a period of eight to 12 weeks, though oral
doxycycline 100mg BID for two to four weeks is widely published as the primary treatment
choice to shorter the duration of symptoms. 3,4,5

Neuroretinitis
• Only 1% to 2% of patients with Cat Scratch Disease develop neuroretinitis!1,2
• Patient Symptoms5
:
• Preceding or concurrent flu-like illness*
• Decreased/blurry vision in one eye
• Decreased visual field in one eye…”spot missing in vision”
• red eye (in patients with POGS)
• Clinical Features:
• Disc swelling in the presence of an exudative macular star formation.1,3
• In cases of extreme disc edema, a neurosensory detachment may occur
• Disc edema usually precedes macular star formation by 2-4 weeks. 2,4
• APD may be present
• Lymphadenopathy (maybe subclinical)
• Enlarged blind spot on visual field testing
• While neuroretinitis associated with cat scratch disease is well documented in the literature, no
studies have visualized the sequential progression of retinal structures on OCT nor mapped a
patient’s visual field from disease onset to resolution. **

Review of Treatments
• Observation
• Antibiotic Approach
• Doxycycline
• Dosages
• Contraindications
• Side Effects
• Alternatives1,2
• Other therapies to be considered…
• For the ONH inflammation?
• For the Macular Edema?
• Should topical, oral, injections be considered?8,9

Week 1 & 2 Presentation
OCT Visual Field
One Week Later
Two Weeks
Later
VA’s: 20/200
VA’s: 20/400

The Progression Continues…
Weeks 3-5 Weeks 6-8
Week 3 VA’s:
20/100
Week 4 VA’s:
20/80
Week 5 VA’s:
20/60+
Week 6 VA’s:
20/40-
Week 7 VA’s:
20/25
Week 8 VA’s: 20/20-
2
Week 1 VA’s:
20/400
Week 8 VA’s: 20/20-
2

Visual Field Progression Analysis

Conclusion
• Neuroretinitis is an inflammatory optic neuropathy
characterized by optic disc edema and exudates within the
fovea in a macular star pattern.
• Cat scratch disease is the single most common cause of neuroretinitis.
• Bartonella Henselae Titer confirmative
• False negatives may be present in early disease progression
• OCT and VF analysis are valuable tools that can be used to
monitor disease resolution in cases of Neuroretinitis from Cat
Scratch Disease.
• Neuroretinitis generally has a good prognosis with
spontaneous improvement, but oral antibiotics appear to
hasten recover time.
• Changes in the foveal RPE tend to be permanent and residual “blind
spots” in the vision may persist.
• Having one episode of cat scratch disease usually makes patients
immune for the rest of their lives.1,5

Sources
1. Longmuir RA, Lee A. Cat-Scratch neuroretinitis (Ocular bartonellosis): 44-year-old female with non-specific "blurriness" of vision,
left eye (OS). EyeRounds.org. March 31, 2005. March 2016
2. Chappel, Michael. "Spotting Bartonella-Associated Uveitis." Review of Ophthalmology. Web. 21 Mar. 2011. March 2016.
3. Habot-Wilner, Z., D. Zur, M. Goldstein, D. Goldenberg, S. Shulman, A. Kesler, M. Giladi, and M. Neudorfer. "Macular Findings on
Optical Coherence Tomography in Cat-scratch Disease Neuroretinitis." Eye. Nature Publishing Group. Web. 25 Aug. 2011.February
2016.
4. Rob Foroozan. "What Is Neuroretinitis?" Healio: Medical News and Journals. Web. September 2014. Apr. 2016.
5. Ling, Jeanie. "Big Red ﬂags in Neuro-ophthalmology: Optic Disc Edema and the Presence of Subretinal Fluid." Neuro-
ophthalmology. Stanford. Can J Ophth: 48:1. Feb 2013. Web. Feb. 2016.
6. Harrison, Michael. "Erythrocyte Sedimentation Rate and C-reactive Protein." Aust Prescriber An Independent Review. Department
of the Interior. 38:93-4. 1 June 2015. Web. May 2016.
7. Feldman, M., B. Aziz, and GN Kang. "C-reactive Protein and Erythrocyte Sedimentation Rate Discordance: Frequency and Causes in
Adults." National Center for Biotechnology Information. U.S. National Library of Medicine. 161(1):37-43. 23 Aug. 2012. Web. May
2016.
8. Accorinti, Massimo. “Ocular Bartonellosis.” Int J Med Sci. 6(3):131-132; 19 March 2009. Web. May 2016
9. Purvin, Valerie, Nicholas Ranson, and Aki Kawasaki. "Idiopathic Recurrent Neuroretinitis." Arch Ophthalmol. JAMA Ophthalmology,
121(1):65-67; Jan. 2003. Web. May 2016.
10. Katz, Barrett. “The Dyschromatopsia of Optic Neuritis: A Descriptive Analysis of Data from the Optic Neuritis Treatment Trial.”
Transactions of the American Ophthalmological Society 93 (1995): 685–708. Print. May 2016.
11. Schneck, Marilyn, and Gunilla Haegerstrom. "Color Vision Defect Type and Spatial Vision In the Optic Neuritis Treatment Trial."
Investigative Ophthalmology & Visual Science 38.11 (1997): 2278-289. PubMed. Web. May 2016.

Integrated Safety and Efficacy of
Latanoprostene Bunod for Lowering of
Intraocular Pressure in Open Angle Glaucoma or
Ocular Hypertension
Murray Fingeret, OD
Chief of the Optometry Section
Dept. of Veterans Administration New York Harbor Health Care System
Clinical Professor
State University of New York College, College of Optometry
Jason Vittitow, PhD
Director, Clinical Affairs
Bausch + Lomb (New)

RELEVANT FINANCIAL DISCLOSURES
• Murray Fingeret, OD
Bausch + Lomb Consultant
• Jason Vittitow, PhD
Bausch + Lomb Employee
85
SPONSOR
Bausch + Lomb, 400 Somerset Corporate Blvd, Bridgewater, NJ
DISCLOSURE OF APPROVED USE:
This drug has not been approved by the U.S. Food and Drug Administration (FDA)

Nitric Oxide and Glaucoma
86
 Patients with primary open-angle glaucoma (POAG) have lower levels of NO synthase activity in the
trabecular meshwork (TM), Schlemm’s canal, and ciliary muscle and reduced NO metabolites in the
aqueous humor.1,2
 NO donors lower IOP in normal and POAG eyes.3-9
 A major site of action for NO donors is the TM/Schlemm’s canal.6-11
1. Nathanson JA, et al. Invest Ophthalmol Vis Sci 1995;36:1774-1784. 2. Galassi F, et al. Br J Ophthalmol 2004;88:757-60. 3. Wizemann AJ, et al. Am J Ophthalmol 1980;90:106-109.
4. Kotikoski H, et al. J Ocul Pharmacol Ther 2002;18:11-23. 5. Behar-Cohen FF, et al. Invest Ophthalmol Vis Sci 1996;37:1711-5. 6. Nathanson JA, et al. J Pharmacol Exp Ther
1992;260:956-965 7. Heyne GW, et al. Invest Ophthalmol Vis Sci 2013;54:5103-5110. 8. Schuman JS, et al. Exp Eye Res 1994;58:99-105. 9. Lei Y, et al. Invest Ophthalmol Vis Sci
2015;56:4891-8. 10. Becquet F, et al. Surv Ophthalmol 1997;42:71-82. 11. Cavet ME, et al. Invest Ophthalmol Vis Sci 2014;55:5005-15.

Latanoprostene Bunod (LBN):
An NO-donating Prostaglandin F2α
Analog
Latanoprost acid
1,4-Butanediol
NO
Krauss AH, et al. Exp Eye Res 2011;93:250-5
Butanediol mononitrate
Nitric oxide
HO
OH

LBN: A dual-acting IOP lowering agent
FP receptor
Latanoprost acid
Matrix metalloproteinases
Extracellular matrix
remodeling
Uveoscleral outflow
Reduced IOP
Nitric oxide
cGMP/PKG
Trabecular meshwork (TM)
cell relaxation
TM/Schlemm’s canal outflow
Soluble guanylyl cyclase
Lindsey JD et al. Invest Ophthalmol Vis Sci. 1997;38:2214-23
Schachtschabel U et al. Curr Opin Ophthalmol. 2000;11(2):112-5
Cavet ME et al. Invest Ophthalmol Vis Sci. 2014;55:5005-15

Pooled analysis of two Phase 3 studies
LBN 0.024% (QD) vs. timolol 0.5% (BID) in
OAG/OHT
89
Primary objective
Demonstrate non-inferiority of mean IOP reduction over 3 months of LBN
0.024% QD in the evening to timolol maleate 0.5% BID
Secondary objective Demonstrate the superiority of mean IOP reduction over 3 months of LBN
0.024% QD in the evening to timolol maleate 0.5% BID
Primary efficacy endpoint IOP measured at 8 AM, 12 PM, and 4 PM at Weeks 2 and 6 and at Month 3
Secondary efficacy endpoints
Proportion of subjects with IOP ≤ 18 mm Hg consistently at all 9 time points
Proportion of subjects with IOP reduction ≥ 25% from baseline consistently
at all 9 time points
Safety variables
Incidence of ocular and systemic adverse events
Ocular signs, BCVA, vital signs, investigator assessed conjunctival hyperemia

Inclusion Criteria and Demographics
90
Table 1. Subject Demographics
LBN 0.024% (N=562) Timolol 0.5% (N=269)
Age (Mean, SD) 64.9 (10.0) 63.7 (10.5)
Gender (n,%)
Male
Female
234 (41.6)
328 (58.4)
113 (42.0)
156 (58.0)
Race (n,%)
White
African American
Asian
Other
421 (74.9)
133 (23.7)
5 (0.9)
3 (0.5)
197 (73.2)
70 (26.0)
2 (0.7)
0
Treatment-Naïvea
(n,%)
Yes
No
165 (29.4)
397 (70.6)
68 (25.3)
201 (74.7)
a
Treatment-naïve = subjects who were not under treatment with IOP-lowering medication at screening and had no
documented IOP-lowering medication in their medical history 30 days prior to screening.
 Mean/median IOP ≥ 26 mm Hg at a minimum of 1 time point, ≥ 24 mm Hg at a minimum of 1
time point, and ≥ 22 mm Hg at 1 time point in the same eye
 Mean/median IOP ≤ 32 mm Hg in both eyes at all 3 measurement time points

Primary efficacy endpoint:
Mean IOP in the study eye (ITT population)
91
Bausch + Lomb, data on file.
 LBN-treated subjects had significantly greater IOP reductions with a mean diurnal decrease from baseline of 32.0%
at Month 3 vs. 27.6% for timolol-treated subjects
Week 6 Month 3Week 2
*
* *
*
* *
*
* *
*P<0.001 vs. timolol
Baseline IOP, mean (SD):
LBN = 26.7 (2.4) mm Hg
Timolol = 26.5 (2.3) mm
Hg

Secondary efficacy endpoint:
Mean IOP reduction by visit and time (ITT
population)
Week 2 Week 6 Month 3
8 AM 12 PM 4 PM 8 AM 12 PM 4 PM 8 AM 12 PM 4 PM
LBN Mean CFB (mm Hg) -8.7 -8.3 -7.6 -9.0 -8.6 -7.9 -9.0 -8.7 -8.0
Timolol Mean CFB (mm
Hg)
-7.7 -7.2 -6.7 -7.8 -7.5 -6.7 -7.7 -7.3 -6.6
Treatment Difference -1.1 -1.1 -1.0 -1.2 -1.1 -1.2 -1.2 -1.3 -1.4
Primary Objective NI NI NI NI NI NI NI NI NI
Secondary Objective P<0.001 for all time points
NI: Claimed if upper CI < 1.5 mm Hg at all time points and < 1.0 mm Hg for at least 5 of 9 time points.
Superiority: Claimed if upper CI < 0 mm Hg at all time points.
CFB = change from baseline
 LBN lowered IOP by 7.6-9.0 mm Hg (pooled studies) and 7.5-9.1 mm Hg (individual studies).
 IOP lowering exceeded that of timolol by >1 mm Hg at each time point.

Mean % IOP reduction at 3 months (ITT
population)
LS mean reduction from baseline in mean IOP
Mean IOP results use LOCF; no imputation applied to mean diurnal IOP

94
*P≤0.001 vs. timolol
CFB = change from baseline
 A greater proportion of subjects treated
with LBN 0.024% reached target IOP.
Response rates (ITT population)

Ocular TEAEs occurring in ≥ 1.0% of study eyes in
any treatment group (Safety population)
 The majority (>99.5%) of ocular TEAEs were mild or moderate in severity and occurred at a slightly higher
frequency with LBN.
 There were no non-ocular TEAEs occurring in ≥1.5% of subjects in any treatment group.
 Vital signs, ocular signs, and BCVA were comparable between treatment groups.
LBN 0.024% (N=560)
n (%)
Timolol 0.5% (N=270)
n (%)
≥1 ocular TEAE 104 (18.6) 34 (12.6)
≥1 treatment-related ocular TEAE 95 (17.0) 30 (11.1)
Eye Disorders
Conjunctival Hyperemia 33 (5.9) 3 (1.1)
Eye irritation 31 (5.5) 9 (3.3)
Eye pain 20 (3.6) 8 (3.0)
Ocular hyperemia 9 (1.6) 2 (0.7)
Dry eye 6 (1.1) 2 (0.7)
Foreign body sensation 6 (1.1) 0 (0.0)
Vision blurred 5 (0.9) 4 (1.5)
General disorders and instillation site reactions
Instillation site pain 7 (1.3) 2 (0.7)

Incidence of conjunctival hyperemia per
investigator assessment (Safety population)
96
Conjunctival Hyperemia (%)
LBN 0.024% Timolol 0.5%
Any
Moderate/
Severe Any
Moderate/
Severe
Baseline 38.8 4.3 41.1 3.3
Week 2 49.1 7.9 39.0 0.7
Week 6 47.5 9.7 36.1 3.4
Month 3 45.0 6.8 35.8 2.7
LBN = latanoprostene bunod
Data as observed
 Investigators reported similar rates of conjunctival hyperemia between treatment
groups, but with a greater proportion of subjects rated as having moderate/severe
hyperemia in the LBN group.

Summary and Conclusions
 LBN 0.024% QD in the evening was effective in reducing IOP in subjects with
OAG or OHT with significantly greater IOP-lowering activity compared to
timolol 0.5% BID.
• IOP lowering of 7.5 to 9.1 mm Hg from baseline.
• Statistically greater IOP lowering >1 mm Hg vs. timolol.
• Statistically greater proportion of subjects reached target IOP vs. timolol.
No significant safety findings during the 3 months of double-masked
treatment
• Safety findings consistent with PGAs

1. What were the efficacy findings
for the individual studies?
2. Efficacy vs. latanoprost
3. Why did subjects on Timolol do
so well?

Medical Research and Materiel CommandMedical Research and Materiel Command
U.S. Army Aeromedical Research LaboratoryU.S. Army Aeromedical Research Laboratory
Fort Rucker, AlabamaFort Rucker, Alabama
Validation Study of Visual Objectives Biomarkers for
Acute Mild Traumatic Brain Injury
LTC Jose E. Capó-Aponte, OD, PhD, FAAO
Department of Optometry
Womack Army Medical Center, Fort Bragg, NC
UNCLASSIFIED

Disclaimer
The views, opinions, and/or findings contained in this report are those of
the author(s) and should not be construed as an official Department of
the Army position, policy, or decision, unless so designated by other
official documentation.
The authors have no financial interest on any of the products included in this study.
UNCLASSIFIED
Funded by US Army Medical Research and Materiel Command (USAMRMC), FY13 Department of Defense Army Rapid Innovation Fund
Research Program of the Office of the Congressionally Directed Medical Research Programs (CDMRP). Award # W81XWH-14-C-0048.
2

UNCLASSIFIED
• The DOD reported that over 340,000 cases of traumatic brain injury (TBI) were confirmed since
2000, with mild TBI (mTBI) accounting for 82.5%.
• The diagnosis of mTBI has been a challenge for the military primarily because: lack of objective
assessment tools; overlap of symptoms in co-morbid conditions such as post-traumatic stress
disorder (PTSD); interpretation of signs and symptoms by healthcare providers relies on self-
reported symptoms from the injured Warfighters.
• Prompt and accurate diagnosis and management of mTBI generally increases an individual's
prognosis for neurological recovery and safe return to duty (RTD).
• Premature RTD places Warfighters at greater risk of disability if they suffer an additional
concussive trauma.
• Consequently, there is a quest for objective markers (e.g., protein, imaging, cognitive,
neurosensory) to objectively diagnose Warfighters with mTBI/concussion.
3
Introduction

UNCLASSIFIED
Gaps
• Lack of objective markers (e.g., protein, imaging, cognitive, neurosensory) to objectively diagnose Warfighters
with mTBI/concussion.
• Ideal tool must be: accurate, quick to perform, non-invasive, causes no discomfort or risk to patient, minimal
training, deployable, and low cost.
• Valid objective markers are particularly important in the field to assist deployed clinicians to make an accurate
determination of fit-for-duty (FFD)/RTD or evacuation.
Objectives
4
• Since approximately 30 areas of the brain, and 7 of the 12 cranial nerves deal with vision, it is not unexpected
that the patient with TBI may manifest a host of visual problems, such as pupillary deficit, visual processing
delays, and impaired oculomotor tracking and related oculomotor-based reading dysfunctions.
• This study investigates pupillometry, version (i.e., saccades) and vergence (i.e., convergence) eye movements
as potential biomarkers for acute mTBI.
• The study included 3 eye procedures and 1 visual symptoms questionnaire
• 10 min test battery.
Introduction

UNCLASSIFIED
• Case-Control Correlational
• 200 AD military personnel
– Age ranged from 19 to 44 years; Mean age 26.31±5.81 years
• 100 acute mTBI: 87 males & 13 females
– Medically documented mTBI/concussion during the acute phase (≤ 72 hrs)
» ≤ 30 min Loss of Consciousness
» ≤ 24 hrs Post-Traumatic Amnesia
» ≤ 24 hrs Alteration of Mental State
» Glasgow Coma Scale score (13 – 15)
» Normal structural brain imaging
• 100 age-matched Non-TBI; 79 males & 21 females
5
Methods: Design

UNCLASSIFIED
6
NeurOptics PLR-200
Hand-held, easy to use, quick, deployable, objective,
non-invasive, requires no specialized training and causes
no added discomfort or risk to the patient.
• Monocular Infrared pupillometer under
mesoscopic (dim) conditions (~3 cd/m²).
• Subject fixated with the non-tested eye on a
distance target (10 ft).
• Stimulus: 180 µW light for 185 msec.
• 8 pupillary light reflex (PLRs) were recorded
twice in the right eye and then twice in the
left, alternationg between eyes with an
interval of about 10 seconds between
recording.
Methods: Pupillometry

UNCLASSIFIED
7
1) Max. Pupil Diameter
2) Min. Pupil Diameter
3) % of Constriction
4) Constriction Latency
5) Avg. Constriction Velocity
6) Max. Constriction Velocity
7) Avg. Dilation Velocity
8) 75% Recovery of Dilation
Methods: Pupillometry

UNCLASSIFIED
8
• Near Point Rule was used to examine NPC
• 20/30 Snellen single letter stimulus.
• Repeated 2X
Methods: Near Point Convergence

UNCLASSIFIED
9
Figure A2. The King-Devick Card(s). The first card (top left) is the
demonstration card, and subsequent cards are test I, II and IIII,
respectively.
Eye movement/version test:
Subject is asked to read
numbers aloud while being
timed. Speed and accuracy is
emphasized.
Methods: King-Devick Test

UNCLASSIFIED
Convergence Insufficiency Symptoms Survey
• Score based on
scale:
 always (4)
 frequently (3)
 sometimes (2)
 rarely (1)
 never (0)
• Passing score ≤20
10
Methods: CISS

UNCLASSIFIED
11
Results: Maximum Diameter
OD: P = 0.121
C: 5.99±0.78
M: 5.88±0.95
OS: P = 0.171
C: 5.95±0.73
M: 5.78±0.98

UNCLASSIFIED
12
Results: Minimum Diameter
OD: P = 0.431
C: 4.05±0.66
M: 3.97±0.88
OS: P = 0.306
C: 3.99±0.62
M: 3.88±0.77

UNCLASSIFIED
Results: % of Constriction
OD: P = 0.188
C: 33.08±3.94
M: 32.30±4.68
OS: P = 0.719
C: 33.30±4.12
M: 33.09±4.79
13

UNCLASSIFIED
14
Results: Constriction Latency
OD: P = 0.259
C: 219.4±21.67
M: 215.9±22.17
OS: P = 0.108
C: 218.5±17.94
M: 213.8±22.45

UNCLASSIFIED
15
Results: Avg Constriction Velocity
OS: *P < 0.0001
C: 4.09±0.55
M: 3.68±0.79
OD: *P < 0.0001
C: 4.01±0.56
M: 3.63±0.77

UNCLASSIFIED
16
Results: Max Constriction Velocity
OD: P = 0.423
C: 5.27±0.73
M: 5.18±0.82
OS: P = 0.509
C: 5.37±0.70
M: 5.29±0.81

UNCLASSIFIED
17
Results: Avg Dilation Velocity
OS: *P < 0.0001
C: 0.97±0.22
M: 0.62±0.28
OD: *P < 0.0001
C: 0.91±0.22
M: 0.62±0.27

UNCLASSIFIED
18
Results: 75% Dilation Recovery Time
OS: *P < 0.0001
C: 2.54±0.66
M: 4.03±1.11
OD: *P < 0.0001
C: 2.65±0.63
M: 3.97±1.09

UNCLASSIFIED
19
*P < 0.0001
C: 8.18±2.15
M: 13.24±8.07
Results: Near Point of Convergence
(Objective + Subjective)

UNCLASSIFIED
(Subjective)
20
*P < 0.0001
C: 44.24±7.74
M: 59.20±19.06
Results: King-Devick Test

UNCLASSIFIED
21
*P < 0.0001
C: 8.82±7.42
M: 24.76±12.06
Results: CISS
(Subjective)

UNCLASSIFIED
– All methods proof effective tool to differentiate mTBI Vs. Controls.
• Objective component: PLR (i.e., ACV, ADV, T75%)
• Objective and Subjective component: NPC
• Subjective component: KD test
• Good correlation with CISS
– Easily performed by subjects, including mTBI
– Easily administered by technicians
– Faster (3 min) than conventional oculomotor examination (15 min)
– Provide tool to expedite mTBI diagnosis and management
• Delegate to technician/medics
– Future Direction
• Develop decision matrix to assist medical personnel make RTD decision
22
Discussion

UNCLASSIFIED
– Womack Army Medical Center (WAMC)
• Thomas A. Beltran
– Defense and Veterans Brain Injury Center / WAMC
• Dr. Wesley R. Cole
– The Geneva Foundation / WAMC
• Joseph Y. Dumayas
• Dr. Ashley Ballard
– US Army Aeromedical Laboratory
• LTC David V. Walsh
23
Acknowledgement

UNCLASSIFIED
Title and Classification
LTC Jose E. Capo-Aponte, O.D., Ph.D., F.A.A.O.
Visual Sciences Branch
WAMC
Department of Optometry
UNCLASSIFIED

UNCLASSIFIED
References
• 1. Defence and Veterans Brain Injury Center (DVBIC), DoD Worldwide Numbers for TBI. 2016. http://www.dvbic.org/dod-worldwide-numbers-tbi.
• 2. Marion, D.W., et al., Proceedings of the military mTBI Diagnostics Workshop, St. Pete Beach, August 2010. J Neurotrauma, 2011. 28(4): p. 517-26.
• 3. Schmid, K.E. and F.C. Tortella, The diagnosis of traumatic brain injury on the battlefield. Front Neurol, 2012. 3: p. 90.
• 4. Hoge, C.W., et al., Mild traumatic brain injury in U.S. Soldiers returning from Iraq. N Engl J Med, 2008. 358(5): p. 453-63.
• 5. Schneiderman, A.I., E.R. Braver, and H.K. Kang, Understanding sequelae of injury mechanisms and mild traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: persistent
postconcussive symptoms and posttraumatic stress disorder. Am J Epidemiol, 2008. 167(12): p. 1446-52.
• 6. Schmid, K.E. and F.C. Tortella, The diagnosis of traumatic brain injury on the battlefield. Front Neurol, 2012. 3: p. 90.
• 7. Katz, D.I. and M.P. Alexander, Traumatic brain injury. Predicting course of recovery and outcome for patients admitted to rehabilitation. Arch Neurol, 1994. 51(7): p. 661-70.
• 8.Novack, T.A., et al., Outcome after traumatic brain injury: pathway analysis of contributions from premorbid, injury severity, and recovery variables. Arch Phys Med Rehabil, 2001. 82(3): p. 300-5.
• 9. Povlishock, J.T. and D.I. Katz, Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil, 2005. 20(1): p. 76-94.
• 10. Khan, F., I.J. Baguley, and I.D. Cameron, 4: Rehabilitation after traumatic brain injury. Med J Aust, 2003. 178(6): p. 290-5.
• 11. Vandiver, V.L., J. Johnson, and C. Christofero-Snider, Supporting employment for adults with acquired brain injury: a conceptual model. J Head Trauma Rehabil, 2003. 18(5): p. 457-63.
• 12. Slobounov, S., et al., Differential rate of recovery in athletes after first and second concussion episodes. Neurosurgery, 2007. 61(2): p. 338-44; discussion 344.
• 13. Marion, D.W., et al., Proceedings of the military mTBI Diagnostics Workshop, St. Pete Beach, August 2010. J Neurotrauma, 2011. 28(4): p. 517-26.
• 14. Chesnut, R.M., et al., The localizing value of asymmetry in pupillary size in severe head injury: relation to lesion type and location. Neurosurgery, 1994. 34(5): p. 840-5; discussion 845-6.
25

UNCLASSIFIED
Questions?
• 1: Neuroptics also has a newer version of the monocular pupillometer called NPi-100 that
provides a Neurological pupil index (NPi) used in neurocritical patients as indication of brain
injury severity. Have you considered using the NPi-100 to determine if the patient has a mild
TBI/concussion?
2: Did you look at test-retest repeatability of the pupillometer?
• 3: Almost all articles examining the King-Devick as a side-line tool to determine if an athlete
sustained a concussion has a pre-game score to compare to post-injury score. Do you think a
pre-injury score is absolutely necessary to make an appropriate concussion assessment?
25

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