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Dominick Maino, OD, MEd, FAAO, FCOVD-A
Moderator
Featuring the Best of AOA's 2016 Poster Presentations
Saturday, July 2nd ...
The Sunshine Act First Year Results: The Status of Optometry
Primary Author: Erik Mothersbaugh, OD
Residual peroxide level...
Cochrane Reviews
http://www.cochrane.org/
… a global independent network of 
researchers, professionals, 
patients and peo...
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,
Sar...
Poster Session
Preview session on
Friday, July 1, 2016
(10:00am-6:00pm)
Interactive session on
Saturday, July 2, 2016
(11:...
Poster Session 2017
Please submit Case reports, Case series, Clinical research, etc. in all areas
of optometry for 2017 wh...
The Sunshine Act First Year Results: The Status of Optometry
Primary Author: Erik Mothersbaugh, OD
Residual peroxide level...
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 Nation...
Affordable Care Act: Section 6002
SUMMARY:  This  final  rule  will  require  applicable  manufacturers  of 
drugs,  devic...
CMS Open Payments Database
• August 1, 2013: Industry required to start data capture
• December 31, 2013: End of first rep...
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...
What is considered a “general payment”?
• Cash or Cash Equivalent
• Consulting fees
• Speaking fees
• Honoraria
• Royaltie...
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...
Results: National
• Range: $1 - $406,392
• Payments made to Top 10% of Payment Recipients: 
$13,166,996
72% of the total $...
Results: State-by-State Comparison
States that Rank in Top 10 for both Total Payments and Average Payment per Provider
Sta...
Results: State-by-State Comparison
States that Rank in Bottom 10 for both Total Payments and Average Payment per Provider
...
Do financial relationships with industry
influence physicians’ behavior?
“The present extent of physician-
industry interactions appears to affect
prescribing and professional behavior
and should...
“A minority of doctors (40%) thought
that industry involvement created a
conflict of interest but the majority of
doctors ...
Conclusions
• Financial relationships with industry are widespread in the
profession of Optometry, with over 36,000 ODs pa...
“Guidelines establishing thresholds,
such as the arbitrary amount of $100,
are based on the belief that there is a
direct ...
Relationships with Industry
 Optometrists should avoid situations and activities
that would not be in the best interest o...
Conflict of Interest
 The care of a patient should never be influenced by the self-interests of the
provider.
 Optometri...
References
• "Health Policy Brief: The Physician Payments Sunshine Act," Health Affairs, October 2, 2014.
• Lichter, PR. D...
Questions ?
Questions?
1.)    How do the professions of 
optometry and ophthalmology compare 
with respect to these payments?
2.)    W...
The Sunshine Act First Year Results: The Status of Optometry 
Primary Author:  Erik Mothersbaugh, OD 
Residual peroxide le...
A Comparison of Residual Peroxide Profiles after
Neutralization of Two Marketed One-Step Hydrogen
Peroxide Systems
Jessie ...
Background
• Common one-step hydrogen peroxide lens disinfecting systems work by use of a 3%
H2O2 buffered solution, which...
Purpose
•To compare the residual H2O2 profiles of Clear
Care Plus with HydraGlyde (CCP) and
PeroxiClear (PC) after neutral...
Methods: (in vitro analysis)
• Neutralization rates of CCP and PC were evaluated.
• All cases (n=3/time point) were first ...
Method: (in vitro analysis)
• Residual H2O2 in the two systems was compared at room temperature through 100 neutralization...
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-...
50
Results (in vitro analysis)
• CCP had significantly lower residual H2O2 than PC at all tested neutralization time point...
Results (in vitro analysis)
51
• Residual H2O2 concentrations of CCP were significantly lower than those of PC after neutr...
Results (ex vivo analysis)
52
Mean Residual H2O2 for 30-Day Used CCP and PC Systems at Manufacturer-Recommended
Storage Ti...
Results (ex vivo analysis)
53
Neutralization Rate Profiles for 30-Day Used CCP and PC Systems (n = 10)
• CCP had lower res...
Results (safety analysis)
54
Ocular Adverse Events (Adverse Device Effects)
• There was a higher incidence of related adve...
Conclusions
• In both laboratory-cycled and patient-used cases, the
manufacturer-recommended 6-hour neutralization time of...
Discussion
• Of the 30-day used lens cases collected, 98.5% of CCP and
20.0% of PC systems at recommended storage time sho...
Questions ?
57
The Sunshine Act First Year Results: The Status of Optometry 
Primary Author:  Erik Mothersbaugh, OD 
Residual peroxide le...
The Cat's Out of the Bag!
Serial Analysis of Neuroretinitis Through Spectral Domain OCT,
Fundus Photography, and Humphrey ...
Financial Disclosure
I have no financial interest in any commercial or pharmaceutical entity
mentioned during this present...
Case Presentation
• Case Hx: Initial Visit
• New patient: 30-year-old Arab Male
• Presenting Complaint: Painless visual lo...
Fundus Presentation
Left EyeRight Eye
OCT Analysis-Retina
Left EyeRight Eye
OCT Analysis- Optic Nerve
Visual Field Analysis
Left EyeRight Eye
Review of Differential Diagnoses
1. Optic Neuritis assoc. MS
2. Ischemic Optic Neuropathy
NAION
AAION assoc. GCA
1. Papill...
Assessment/Plan
Assessment:
• Neuroretinitis suspect Cat Scratch Disease etiology per Hx
Plan:
• Lab Work-up
• CBC w/ Diff...
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...
Cat Scratch Disease (CSD)
• Cat scratch disease (CSD) is a systemic infection caused by the bacteria Bartonella henselae,
...
Neuroretinitis
• Only 1% to 2% of patients with Cat Scratch Disease develop neuroretinitis!1,2
• Patient Symptoms5
:
• Pre...
Review of Treatments
• Observation
• Antibiotic Approach
• Doxycycline
• Dosages
• Contraindications
• Side Effects
• Alte...
COLOR VISION10,11
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/...
ONH Progression
Visual Field Progression Analysis
What About That Fundus View?
Conclusion
• Neuroretinitis is an inflammatory optic neuropathy
characterized by optic disc edema and exudates within the
...
Sources
1. Longmuir RA, Lee A. Cat-Scratch neuroretinitis (Ocular bartonellosis): 44-year-old female with non-specific "bl...
Questions ?
Questions ?
The Sunshine Act First Year Results: The Status of Optometry
Primary Author: Erik Mothersbaugh, OD
Residual peroxide level...
Integrated Safety and Efficacy of
Latanoprostene Bunod for Lowering of
Intraocular Pressure in Open Angle Glaucoma or
Ocul...
RELEVANT FINANCIAL DISCLOSURES
• Murray Fingeret, OD
Bausch + Lomb Consultant
• Jason Vittitow, PhD
Bausch + Lomb Employee...
Nitric Oxide and Glaucoma
86
 Patients with primary open-angle glaucoma (POAG) have lower levels of NO synthase activity ...
Latanoprostene Bunod (LBN):
An NO-donating Prostaglandin F2α
Analog
Latanoprost acid
1,4-Butanediol
NO
Krauss AH, et al. E...
LBN: A dual-acting IOP lowering agent
FP receptor
Latanoprost acid
Matrix metalloproteinases
Extracellular matrix
remodeli...
Pooled analysis of two Phase 3 studies
LBN 0.024% (QD) vs. timolol 0.5% (BID) in
OAG/OHT
89
Primary objective
Demonstrate ...
Inclusion Criteria and Demographics
90
Table 1. Subject Demographics
LBN 0.024% (N=562) Timolol 0.5% (N=269)
Age (Mean, SD...
Primary efficacy endpoint:
Mean IOP in the study eye (ITT population)
91
Bausch + Lomb, data on file.
 LBN-treated subjec...
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...
Secondary efficacy endpoint:
Mean % IOP reduction at 3 months (ITT
population)
Bausch + Lomb, data on file.
LS mean reduct...
94
*P≤0.001 vs. timolol
CFB = change from baseline
Bausch + Lomb, data on file.
 A greater proportion of subjects treated...
Ocular TEAEs occurring in ≥ 1.0% of study eyes in
any treatment group (Safety population)
Bausch + Lomb, data on file.
 T...
Incidence of conjunctival hyperemia per
investigator assessment (Safety population)
96
Conjunctival Hyperemia (%)
LBN 0.02...
Summary and Conclusions
 LBN 0.024% QD in the evening was effective in reducing IOP in subjects with
OAG or OHT with sign...
Thank you!
Questions?
1. What were the efficacy findings
for the individual studies?
2. Efficacy vs. latanoprost
3. Why did subjects on Timolol ...
Medical Research and Materiel CommandMedical Research and Materiel Command
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Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!
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Current Clinical Case Reorts & Research You Should Incorporate into Your Mode of Practice Now!

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Dominick Maino, OD, MEd, FAAO, FCOVD-A
Moderator
Featuring the Best of AOA's 2016 Poster Presentations
Saturday, July 2nd 8-10AM

Five of the very best, clinically relevant posters were chosen to be given during the American Optometric Association meeting in Boston in 2016. These posters were chosen by the AOA Poster Committee (Dr. Dominick M. Maino, Chair).

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

  1. 1. 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! 
  2. 2. 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
  3. 3. Cochrane Reviews http://www.cochrane.org/ … a global independent network of  researchers, professionals,  patients and people interested in  health…  Levels of Research
  4. 4. Clinician’s View of Researchers
  5. 5. Researcher’s view of Clinicians
  6. 6. 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
  7. 7. Poster Session Preview session on Friday, July 1, 2016 (10:00am-6:00pm) Interactive session on Saturday, July 2, 2016 (11:00am-2:00pm)
  8. 8. 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
  9. 9. 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
  10. 10. The Sunshine Act First Year Results: The Status of Optometry Erik Mothersbaugh, OD Elizabeth Wyles, OD Jordan Keith, OD
  11. 11. Brennan TA, et al. Health industry practices that create conflicts of interest. JAMA. 2006; 295: 429-433
  12. 12. 69% of Americans say that drug makers hold  too much sway over physicians  prescribing habits 2010 Consumer Reports National Research Center poll
  13. 13. 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. 
  14. 14. 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
  15. 15. Chang, JS. The physician payments sunshine act. Ophthalmology 2015; 122(4): 656-661.
  16. 16. 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
  17. 17. 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
  18. 18. What is NOT considered a “general payment”? • Ownership/Investment payments • Research-related payments
  19. 19. 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
  20. 20. 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%
  21. 21. 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
  22. 22. 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
  23. 23. Do financial relationships with industry influence physicians’ behavior?
  24. 24. “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
  25. 25. “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.
  26. 26. 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%).
  27. 27. “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.
  28. 28. 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
  29. 29. 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”)
  30. 30. 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.
  31. 31. Questions ?
  32. 32. 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?
  33. 33. 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
  34. 34. 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
  35. 35. 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.
  36. 36. 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
  37. 37. 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
  38. 38. 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
  39. 39. 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
  40. 40. 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)
  41. 41. 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
  42. 42. 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).
  43. 43. 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.
  44. 44. 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).
  45. 45. 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
  46. 46. 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.
  47. 47. Questions ? 57
  48. 48. 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
  49. 49. 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)
  50. 50. Financial Disclosure I have no financial interest in any commercial or pharmaceutical entity mentioned during this presentation.
  51. 51. 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
  52. 52. Fundus Presentation Left EyeRight Eye
  53. 53. OCT Analysis-Retina Left EyeRight Eye
  54. 54. OCT Analysis- Optic Nerve
  55. 55. Visual Field Analysis Left EyeRight Eye
  56. 56. 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
  57. 57. 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.
  58. 58. 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.
  59. 59. 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
  60. 60. 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. **
  61. 61. 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
  62. 62. COLOR VISION10,11
  63. 63. Week 1 & 2 Presentation OCT Visual Field One Week Later Two Weeks Later VA’s: 20/200 VA’s: 20/400
  64. 64. 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
  65. 65. ONH Progression
  66. 66. Visual Field Progression Analysis
  67. 67. What About That Fundus View?
  68. 68. 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
  69. 69. 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.
  70. 70. Questions ?
  71. 71. Questions ?
  72. 72. 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
  73. 73. 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)
  74. 74. 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)
  75. 75. 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.
  76. 76. 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
  77. 77. 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
  78. 78. 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
  79. 79. 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
  80. 80. 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
  81. 81. 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 Bausch + Lomb, data on file.  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.
  82. 82. Secondary efficacy endpoint: Mean % IOP reduction at 3 months (ITT population) Bausch + Lomb, data on file. LS mean reduction from baseline in mean IOP Mean IOP results use LOCF; no imputation applied to mean diurnal IOP
  83. 83. 94 *P≤0.001 vs. timolol CFB = change from baseline Bausch + Lomb, data on file.  A greater proportion of subjects treated with LBN 0.024% reached target IOP. Secondary efficacy endpoint: Response rates (ITT population)
  84. 84. Ocular TEAEs occurring in ≥ 1.0% of study eyes in any treatment group (Safety population) Bausch + Lomb, data on file.  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)
  85. 85. 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. Bausch + Lomb, data on file.
  86. 86. 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
  87. 87. Thank you!
  88. 88. Questions?
  89. 89. 1. What were the efficacy findings for the individual studies? 2. Efficacy vs. latanoprost 3. Why did subjects on Timolol do so well?
  90. 90. 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
  91. 91. 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 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
  92. 92. 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 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
  93. 93. 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 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
  94. 94. 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 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
  95. 95. 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 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
  96. 96. 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 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
  97. 97. 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 UNCLASSIFIED 8 • Near Point Rule was used to examine NPC • 20/30 Snellen single letter stimulus. • Repeated 2X Methods: Near Point Convergence
  98. 98. 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 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
  99. 99. 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 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
  100. 100. 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 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
  101. 101. 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 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
  102. 102. 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 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
  103. 103. 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 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
  104. 104. 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 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
  105. 105. 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 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
  106. 106. 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 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
  107. 107. 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 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
  108. 108. 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 UNCLASSIFIED 19 *P < 0.0001 C: 8.18±2.15 M: 13.24±8.07 Results: Near Point of Convergence (Objective + Subjective)
  109. 109. 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 UNCLASSIFIED (Subjective) 20 *P < 0.0001 C: 44.24±7.74 M: 59.20±19.06 Results: King-Devick Test
  110. 110. 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 UNCLASSIFIED 21 *P < 0.0001 C: 8.82±7.42 M: 24.76±12.06 Results: CISS (Subjective)
  111. 111. 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 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
  112. 112. 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 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
  113. 113. 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 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
  114. 114. 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 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
  115. 115. 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 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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