2016 summer seminar

SUMMER SEMINAR

July 13, 2016Ritz CharlesCarmel, IN

ALL ROADS LEAD TOEYE SPECIALISTS OF INDIANA

Robert Johnston O.D.

Ryan Gady O.D.

Glenn Kirk O.D. Zach Rossman O.D. Tessa Schlickbernd O.D. William Shultz M.D. Paul Walton M.D. Clark Springs M.D.

James Hunter O.D.

1901 North Meridian Street • Indianapolis, Indiana 462021950 West 86th Street • Indianapolis, Indiana 46260(317) 925-2200 • (800) 433-9766www.eyespecialistsofindiana.com

Indiana’s Original OptometricCo-Management Referral Center

Offering:•Experienceassociatedwithmorethan100,000

cataract procedures• Fleet vehicle statewide “door-to-door”

transportation service•Customizedcataractsurgery•Morethanthreedecadesofoptometriccontinuingeducationandsupport

•AAAHCaccreditedeyesurgerycenter

Brandon Sharp O.D.Craig Beyer D.O.

Thank You 2016 Corporate Sponsors

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Platinum Sponsor

8 – 9 am Continental Breakfast and Registration9 – 10 am Update on Age Related Macular DegenerationThis course will discuss the current treatment options for AMD, as well as some of the treatments in the pipeline. Topics such as the latest VEGF agents, genetic testing and new diagnostic equipment will be highlighted.Steven Ferrucci, O.D., Sepulveda, CA COPE 42196-PS, 1 Hour IOB and Legend Drug

10 am – 12 pm Posterior Segment Grand Rounds Including GlaucomaThis course will highlight some of the most common posterior segment etiologies, including glaucoma treatment and management, in a case analysis format. Topics may include choroidal nevi, CSR and retinal breaks.Steven Ferrucci, O.D., Sepulveda, CA COPE 41773-PS, 2 Hours IOB and Legend Drug

12 – 1 pm Lunch Included1 – 3 pm A Cornucopia of Corneal ConundrumsA multitude of pathologies may befall the cornea, with etiologies ranging from congenital to infectious to traumatic. This course reviews numerous corneal conundrums, focusing on detection, visual impact, prognosis and treatment in the optometric practice.Alan Kabat, O.D., Memphis, TN COPE 41701-AS, 2 Hours IOB and Legend Drug

3 – 4 pm Innovations in the Management of Ocular Surface Inflammation This lecture discusses several challenging inflammatory conditions of the ocular surface and some of the newest and more novel therapeutic measures designed to address these chronic or severe disorders. Included are several unique topical anti-inflammatory agents, as well as specialized amniotic membranes designed specifically for ophthalmic use.Alan Kabat, O.D., Memphis, TN COPE 41695-AS, 1 Hour IOB and Legend Drug

4 – 5 pm Fluorescein AngiographyThis course covers the basic principles associated with fluorescein angiography IVFA. The performance of the procedure and interpretation of the results are discussed. A discussion of various conditions as they relate to IVFA is included. Examples are CNVM, diabetic retinopathy, CME, and several others. An emphasis is also placed on alternative, less invasive technology, such as OCT that has replaced IVFA as the diagnostic procedure of choice in many conditions.Brad Sutton, O.D., Indianapolis, IN COPE 42150-IS, 1 hour IOB and Legend Drug CEE will not be offered at this event. Please visit and thank the exhibitors who support this event:

2016 Summer Seminar CE ScheduleWednesday, July 13, 2016 l Ritz Charles, Carmel, IN

We’re Back at the Sheraton...IOA Convention - April 21-23, 2017

Sheraton Indianapolis Hotel at Keystone Crossing Mark your calendar now!

IOA Board of Trustees

April 2016 - April 2017

Left to right: Christopher Browning, Treasurer; Greg Norman, Secretary; Damon Dierker, Central Trustee; Karon Nowakowski, President-Elect; Jeff Yocum, President; Nicole Bonham, Southwestern Trustee; Jeffrey Kirchner, West Central Trustee; Todd Niemeier, Immediate Past President; Paul Gill, Northeastern Trustee. Not pictured: Jeffrey Perotti, Southeastern Trustee; and James Stickel, Northwestern Trustee.

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Steven Ferrucci, ODSepulveda, CA

Update on Age Related Macular Degeneration

Posterior Segment Grand Rounds Including Glaucoma

Steven Ferrucci, OD, FAAOSepulveda, CA

Dr. Steven Ferrucci, a 1994 graduate of the New England College of Optometry, completed his Residency in Primary Care/Hospital Based/Geriatric Optometry at the Sepulveda VA Hospital in Sepulveda, CA. He is currently Chief of Optometry at the Sepulveda VA Ambulatory Care Center and Nursing Home. He is also the Residency Director at his site, and a Professor at the Southern California College of Optometry at Marshall B. Ketchum University.

Dr. Ferrucci has lectured extensively, with a special interest in Diabetes, Diabetic Eye Disease, Age-Related Macular Degeneration, and Fluorescein Angiography. He has also published several articles in optometric journals, including The New England Journal of Optometry, Optometry and Vision Science, Optometry: Journal of The AOA and Review of Optometry. Currently, he serves on the Editorial Board for both Review of Optometry and Optometry Times. He is an active member in the American Optometric Association and the California Optometric Association, as well as a fellow in both the American Academy of Optometry and the Optometric Retinal Society.

1

UPDATE ON AMD

STEVEN FERRUCCI, OD, FAAO CHIEF, OPTOMETRY SEPULVEDA VA

PROFESSOR, SCCO/MBKU

Disclosures

¥  Speakers bureau and/or Advisory Board for: –  Alcon –  Allergan –  B&L –  Heidelberg –  Macula Risk –  MacuLogix –  ThromboGenics –  Nicox

Introduction

¥  Exciting time to be interested in AMD ¥  Many new treatments now available for

AMD – Years ago, we had nothing at all to offer

patients with AMD ¥  Current Treatments ¥  Potential Treatments ¥  New Diagnostic Equipment

Dry AMD ¥  Currently mainstay treatment for Dry AMD

revolves around prevention of progression through vitamins, nutrition and lifestyle changes –  Rheophoresis, Laser, Anecortave Acetate did not

prove effective ¥  Early detection of conversion from dry to wet

may result in better treatment for patients

AREDS 2

¥  AREDS 2: Enrollment ended June 2008 with ≈4200 patients followed for six years –  Effect of lutein, zeaxanthin and omega 3 on AMD –  Effect of eliminating beta carotene on AMD –  Effect of reducing zinc on AMD –  Effect of supplements on cataracts –  Validate the AMD scale from original AREDS

¥  Results released May 5, 2013

AREDS2 Formulation ¥  Vitamin C (500 mg) ¥  Vitamin E (400 IU) ¥  Beta Carotene (15 mg) ¥  Lutein (10 mg)/Zeaxanthin (2 mg) ¥  Zinc (80 mg zinc oxide) ¥  Copper (2 mg cupric oxide) ¥  Omega-3 fatty acids (DHA/EPA)

2

Wet AMD

¥  Various agents currently being used as intravitreal injection –  Macugen® (pegatanib sodium) Dec 2004 –  Lucentis (ranibizumab) June 2006 –  Avastin (bevacizumab) Not FDA approved –  Eylea (aflibicert ) Nov 2011

Macugen® (pegatanib sodium)

¥  Anti-vasoactive endothelial growth factor (VEGF) aptamer –  Developed by OSI Pharmaceuticals, co-marketed with Pfizer –  Delivered by intravitreal injection

¥  FDA Approved December 2004 –  Commercially available February 2005

¥  VISION Study –  Intravitreous injections of 0.3 mg, 1.0 mg and 3.0 mg every 6

weeks for 48 weeks (8 injections) ¥  Loss of less than 15 letters 70% with tx vs 55% w/

o tx ¥  33% maintain or lost vision with tx vs 23% w/o tx

Macugen

¥  Macugen has been widely supplanted by newer agents – Most notably Lucentis and Avastin

¥  Must be injected every 6 weeks for 2 years – Eight to nine injections /year may be indicated – Cost: VA medication alone is $780. Most places

$1200 med plus fees

Lucentis (ranibizumab)

¥  Antibody fragment which blocks VEGF activity –  Less specific than Macugen, so perhaps more

efficacious

¥  Delivered by intravitreal injection ¥  Developed by Genentech and marketed

by Novartis ¥  FDA Approved June 30, 2006

Lucentis

¥  ANCHOR Study (classic CNVM) –  2 Year Phase 3 randomized study

¥  94% of pts treated with 0.3 mg had stable or improved vision vs 64% with Visudyne

¥  36% had gain of 15 letters or more ¥  Avg acuity gain was 11.3 letters vs 9.5 letters lost with Visudyne at

one year ¥  31% had VA of 20/40 or better vs only 3% with Visudyne

¥  MARINA Study (minimally classic/occult) –  95% of treated pts vs 62% of controls had less than 15 letter loss –  25% treated vs 4.6% of controls had 3 line gain –  At 2 yrs, 6.6 letter gain with tx vs 14.9 letters lost without

Lucentis

¥  Results were promising, with better results than Macugen – For first time, results showed an actual

increase in vision in treated vs untreated group

¥  Recommended injection: every 4-6 weeks for 2 yrs

¥  Cost: approx $2500 for medication alone

3

Lucentis

¥  Additional studies, PRONTO and PIER, looking at alternative dosing schedules – PRONTO: one injection/mos x 3. Then inject

based on clinical or OCT findings – PIER: one injection /mos x 3. Then inject q 6

months for 2 years ¥  Results were very similar to original

studies, especially with PRONTO

Avastin (bevacizumab)

¥  Drug currently FDA approved for the treatment of metastatic colorectal cancer and certain lung cancers (Genentech) –  Parent drug of Lucentis. Originally thought to be too large to

penetrate retina ¥  Currently widely used as treatment for CNVM due to its anti-VEGF

properties

Avastin

¥  First report of intravitreal injection in May 2005

¥  First case reports published in July 2005 ¥  Within 6 months, global acceptance and

widespread clinical use –  despite lack of large scale studies regarding efficacy,

safety and dosing

Avastin ¥  Major advantage is COST

–  $15-$50 per 0.3 ml injection ¥  1/40 cost of Lucentis

–  Approx $1k for Macugen/$2.5K for Lucentis ¥  Issue is there are no large prospective study to judge its efficacy and

safety –  Systemic concern is thrombolytic events

¥  Amount used in vitreous is 300-400 fold lower than that administered IV

¥  Some controversy remains but continues to be used widely

Avastin

¥  No studies yet to indicate proper dosing –  Most often, one injection/mos x 3 mos. –  Then repeat FA/OCT and evaluate for additional

treatments –  Also, no h/o MI or CVA within 6 mos

¥  Pt must be informed of its off-label use ¥  Dangers reported regarding compounding

Avastin vs. Lucentis What is the Treatment of Choice?

¥  Complications of Age-Related Macular Degeneration Treatment Trial (CATT) –  NEI/NIH sponsored trial –  First year results released May 1, 2011 NEJM

¥  1208 patients randomized –  Lucentis with 4 week dosing –  Avastin with 4 week dosing –  Lucentis with variable dosing (PRN) –  Avastin with variable dosing (PRN)

4

CATT: 1 yr results

¥  Equivalent effects on visual acuity with same administraKon – LucenKs monthly 8.5 leOers gained – AvasKn monthly 8.0 leOers gained – LucenKs PRN 6.8 leOers gained – AvasKn PRN 5.9 leOers gained

CATT: 1 yr results

¥  Central reKnal thickness: – Greater effect in LucenKs monthly group (196um decrease) than in other groups ¥  164 um AvasKn monthly ¥  168 LucenKs as needed ¥  152 AvasKn as needed

– Fluid on OCT ¥  At 4 weeks, no fluid in 27.5% of pts w/ LucenKs vs. 17.3% with AvasKn

¥  At 1 yr, no fluid in 43.7% LucenKs monthly 19.2% AvasKn PRN

CATT: 1 yr results

¥  Adverse effects – When dosing regimens combined, slightly more serious adverse events in Avastin group ¥  24.1% for Avastin ¥  19.0% for Lucentis ¥  Risk ratio 1.29 for avastin as compared to Lucentis

CATT: 1 yr summary

¥  Vision with LucenKs vs. AvasKn relaKvely equal over course of first year

¥  Some evidence of more effect with LucenKs on anatomical structure, ie more decrease in RT on OCT, but did NOT correlate with improved visual funcKon

¥  Some hint that less systemic events with LucenKs ¥  HUGE cost differenKal

– AvasKn wins most of the Kme, with select cases benefiKng from LucenKs

CATT: 1 yr results

¥  Average cost for first year treatment: – $23,400 for LucenKs monthly – $13, 800 for LucenKs PRN – $595 for AvasKn monthly – $385 for AvasKn PRN

CATT 2 yr Results ¥  At end of 2 years, both had similar effects on vision when the dosing

regimen was the same –  Mean gain in acuity, proportion gaining or losing 3 lines, % better than

20/40 all similar ¥  Mean gain slightly better for monthly vs. as needed, 2.4 letters ¥  Rates of death and thrombotic events similar ¥  Pts with serious systemic adverse effects higher with Avastin (39.9% vs.

31.7%)

5

CATT 2 yr results

¥  GA most in Lucentis monthly, but more in both monthly

¥  Less fluid at 1 and 2 yrs with Lucentis ¥  Led to 0.6 more injection with Avastin in second yr, 1.5 more over 2 yrs

Other studies

¥  MulKple other comparaKve studies have confirmed no clinically significant differences between AvasKn and LucenKs – CATT (US) –  IVAN (Great Britain) – MANTA (Austria) – GEFAL (France) – BRAMD (Netherlands) – LUCAS (Norway)

Eylea

View 1 –  95% of pts receiving 2 mg q 2 mos achieved maintenance of vision vs. 94% with LucenKs monthly

–  7.9 leOer mean improvement of vision (vs. 8.1 with LucenKs monthly)

Eylea

View 2

–  95% of pts receiving 2 mg q 2 mos achieved maintenance of vision vs. 94% with Lucentis monthly

–  8.9 letter mean improvement of vision (vs. 9.4 with Lucentis monthly)

Eylea

¥  Cost: Eylea ≈$1850/injection, with injection every 2 months – Therefore ½ of Lucentis montlhy

¥  Second year study will evaluate use PRN

Eylea

¥  Second year results (unpublished) found virtually similar results when Eylea vs . Lucentis used as needed – Elyea 4.2 injections for the year – Lucentis 4.7

6

Is AMD in our DNA?

¥  AMD is a geneKc disease with known markers accounKng for at least 70% of the populaKon aOributable risk

¥  Other 30% is environmental/lifestyle ¥  Risk factors

– Non-‐modifiable: age, race, gender – Modifiable: Smoking, increased BMI, poor diet/nutriKon, UV exposure

AMD is a GeneKc Disease

Those with stronger genetic risk develop more advanced disease earlier in life.

Major genetic factors

¥  CFH –  Single most important geneKc component –  CFH Y402H

¥  ARMS2/HTRA1 –  Second most important gene in AMD

¥  C3 – Another component of the complement system

¥  ND2 – Mitochondrial oxidaKve phosphorylaKon molecule

¥  Others

Genetic Factors and Risk: More than additive!

¥  Former Smokers: 1.29x ¥  Current Smokers: 2.4X ¥  Non-Smoker and CFH,Y402H: 7.6X ¥  Current smoker and CFH,Y420H: 34X

AMD GeneKc TesKng

Macula Risk NXG

IdenKfies AMD paKents who may progress to vision loss within:

¥  2 years ¥  5 years ¥  10 years

Cheek Swab

Clinical ValidaKon March 2012 IOVS

ProspecKve Assessment of GeneKc Effects on Progression to Different Stages of Age-‐Related Macular

DegeneraKon Using MulKstate Markov Models Yi Yu, Robyn Reynolds, Bernard Rosner, Mark J. Daly,

and Johanna M. Seddon InvesKgaKve Ophthalmology & Visual Science, March 2012, Vol. 53, No. 3

2560 Caucasians

Average Follow up = 10.3 years 5 year predicKve power = 0.883 ‘C’ StaKsKc Score 10 year predicKve power = 0.895 ‘C’ StaKsKc Score

SensiKvity & Specificity > 80% Macula Risk NXG

7

Primary Eye Care Protocol

Recommended pracKce protocol developed by the Macula Risk Optometry Advisory Board: L. Alexander, D. Cunningham, M. Dunbar, S. Ferrucci, J. Gerson, P. Karpecki, G. Morgan, D. Nelson, J. Rumpakis, J. Schaeffer, L. Semes, D. Shechtman, J. Sherman, K. Smick

AutoGenomics

¥  Developer of automated mulKplexed DNA with more than 50 applicaKons currently –  InfecKous disease, women’s health, oncology

¥  Currently developing and AMD panel looking at over 20 geneKc variants – CFH – ARMS2 – C2, C3 – TIMP 3, etc.

GeneKcs and Treatment

¥  Ophth 2013 Hagstrom (843 pts) –  37% higher risk for additional Lucentis if

Y402H CFH –  CFH TT/TC treated with Avastin had increase in

vision with 53.7 % improved vs. only 10.5% if CC genotype

¥  Ophth Nov 2010 Smailhodzic et al


¥  Ophth Nov 2012 Smailhodzic et al – If no high risk ARMs 2 /CFH alleles,

mean a VA improvement of 10 letters – No VA improvement if 4 High risk CFH

and ARMS 2 alleles – If 6 high risk alleles, lost of 10 letters – Patients with high risk alleles were on

average 5.2 years younger than those with less high risk alleles


¥  Br J Ophthalmol June 2015 Hu et al – Meta Analysis looking at response to anK-‐VEGF treatment in wet AMD

–  12 carKcles, 2389 cases –  A69S gene in ARMS 2 shown to predict anK-‐angiogenic response in an East Asian polulaKon

–  Not found to be predicKve in Caucasian subgroups

GeneKc Treatment

¥  If defecKve gene responsible for abnormal VEGF expression can be localized, perhaps a replacement, or fixer gene can be injected into the eye ONE TIME!

– Genzyme – Avalanche Biotechnologies – Oxford BioMedica – ForSight Labs – NeuroTech

8

Avalanche Biotechnologies: AAV2 ¥  Viral vector harboring a gene that encodes a protein (sFLT-‐1/VEGFR-‐1) for the treatment of Wet AMD

¥  8 eyes with wet AMD –  Injected with LucenKs, then AAVs, then 2nd LucenKs –  5/6 with AAV2 gained +8.7 leOers (low dose) or +6.3 ( high dose) –  -‐3.5 leOers in control –  Only 2/6 needed addiKonal injecKon in first year

¥  2a study in Australia underway (32 pts) ¥  2b Enrolling in US late 2015

Summary

¥  Knowledge of genetic risk is important ¥  Increased counseling for patients at high risk

¥ Know which pts need to be examined more frequently

¥ Sooner vitamin supplementation ¥ May have implications regarding treatment

¥ May lead to new treatments

Potential Therapies ¥  Currently, there are ≈ 1143 studies

evaluating AMD, both Wet and Dry – www.clinicaltrials.gov (February, 2015)

¥  Exciting time to be involved, with many possible therapies out there that may prove useful for our AMD patients

PotenKal Therapies

¥  BeOer Efficacy –  BeOer drug –  Different Mechanism

¥  Reduced administraKon ¥  Different delivery System

–  Eye drops –  Oral –  Others

¥  Earlier Diagnosis

FoVista

¥  AnK-‐PDGF agent ¥  Theory is that when used in conjuncKon with anK-‐VEGF agents, will have a beOer effect due to synergisKc effect

¥  Ophthotech –  Currently in stage 2b studies

FoVista

¥  IniKal phase 1 trial to show safety –  59 % had improvement of three lines or more

¥  Phase 2b study: 449 paKents –  Fovista/LucenKs combinaKon gained 10.6 leOers at 24 weeks, vs. 6.5 with LucenKs alone ¥  62% addiKonal benefit ¥  First study to show results BETTER THAN LucenKs

9

Abicipar Pegol

¥  Vegf-‐ DARPin: Designed Ankyrin Repeat Protein – Allergan

¥  Binds VEGF A with higher affinity ¥  Longer half life

–  PotenKal to last 12 weeks ¥  Phase II Trials: 25 pts

–  at 20 weeks, mean VA improvement ¥  Abicipar Pegol 2mg: 9.0 leOers ¥  Abicipar Pegol 1 mg: 7.1 leOers ¥  LucenKs: 4.7 leOers

ESBA 1008

¥  Single chain anKbody fragment (scFv) ¥  Smaller than current agents, yet potenKally longer duraKon

¥  Alcon/NovarKs ¥  Phase II study: 194 paKents

– ESBA 1008 0.5, 3, 4.5, or 6 mg vs. o.5 mg LucenKs – At 1 mos, mean VA improvement

¥  6 mg ESBA 1008: 10.4 leOers ¥  O.5 mg LucenKs: 6.5 leOers

ESBA 1008 ¥  Now Renamed RTH258 ¥  Phase 2 study

–  6 mg of RTH258 vs. 2 mg Eylea in 90 eyes –  “Promising visual acuity gains that were non-‐inferior to Eylea”

– Well tolerated, no adverse events –  Perhaps a prolonged duraKon of acKon, potenKally reduced treatment burden

¥  Two phase 3 trials will look at RTH258 in about 1700 pts every 3 months

Replenish®

¥  Replenish® drug delivery pump by Alcon/NovarKs

¥  Fully programmable, refillable pump ¥  Rechargeable to support chronic use ¥  Applicable to back of eye disorders ¥  May prove alternaKve to injecKons ¥  Looking at with ESBA 1008 Proof of concept

VEGF Eye Drops ¥  ATG3: a topical eye drop for treatment of wet ARMD

–  Phase II trial will enroll 330 pts to receive two concentrations of ATG3 bid vs placebo for 48 weeks

¥  GATE Study by Alcon –  Phase III study evaluating AL-8309B as topical ocular treatment

for geographic atrophy secondary to ARMD ¥  Pazopanib

–  FDA approved for renal cell carcinoma –  Treatment for wet ARMD

¥  OT-551 –  Anti-angiogenic drop being investigated for GA –  Recent study showed ineffective

Squalamine

¥  Eye drop derived from shark fin that has shown to have AnK-‐VEGF, AnK-‐PDGF, and AnK-‐bFGF properKes

¥  Phase 11 trials –  LucenKs PRN plus Squalamine bid had increased BCVA vs LucenKs alone ¥  48.3% vs. 21.2% had >15 leOers gain ¥  10.4 mean gain vs. 6.3 gain

–  Primary endpoint of reduced frequency of injecKons not met ¥  6.2 vs. 6.4 over study

¥  Phase III enrolling –  Looking at visual acuity gains over 6 mos

10

NRTI’s – HIV drugs, Nucleoside Reverse TranscripKon Inhibitors (NRTIs), found to block inflammaKon

–  Stavudine and zodovudine prevented GA in a mouse study

¥  Prevented GA progression in 5/6 mice administered orally daily vs. 0/6 control

¥  Prevented GA in 8/9 mice received twice daily abdominal injecKons vs. 0/8 control

–  Two addiKonal trails under way: one oral and one intravitreal injecKon

Oral FenreKnide ¥  Oral medicaKon being invesKgated for the treatment of GA – Theory is that the medication prevents

delivery of retinol to the eye, a precursor of lipofuscin, which reduces retinol derived metabolites (A2E) that are toxic to the RPE and photoreceptors

– Has been studied for a few years – Given FDA fast track in 2009 after early

studies

Oral FenreKnide: update ¥  100 and 300 mg orally in 246 pts with GA

at 30 sites in US for 2 years ¥  Mean reducKon on o.33 mm2 in yearly growth rate vs. placebo

¥  1.70 mm2 /yr vs. 2.03 mm2 per year ¥  Reduced rate of conversion of CNVM by 45%

– Encouraging results further study indicated

Copaxone

¥  Copaxone (glatiramer acetate) is a immunomodulary substance which has been proven to be safe and effective in treating neurodegenerative disease, such as MS

¥  Phase II study will investigate if a weekly vaccination can stop the progression as well as conversion of dry to wet ARMD – New York Eye and Ear Infirmary

CNTF

¥  Ciliary neurotrophic factor (CNTF) intraocular implant, NT-‐501 –  Recent study of paKents with GA

¥  Awer 12 mos, 96.3% of high-‐dose group had stable vision vs. 75% with sham

¥  Also showed increase in reKnal thickness in treated group at 12 months

Stem Cells

¥  Stem cells: Transplantation of fetal RPE cells has been performed in pts with CNVM and GA – American Journal of Ophthalmology, August

2008 ¥  10 patients (6 RP, 4 ARMD) with VA 20/200 or

worse received RPE tissue ¥  7/10 had improved vision

– Promising results, but many researchers feel widespread use may be decades away

11

AdaptDx ¥  Measures the rate of recovery of scotopic

sensitivity after photo-bleaching as a diagnostic measure of AMD

¥  Not currently FDA approved for AMD ¥  Approved as a dark adaptometer only ¥  18 clinical studies and trials ¥  Over 1300 patients ¥  Commercially available late 2012

¥  Decreased dark adaptation may precede clinical findings by as much as 4 years

¥  MacuLogix

Adapt DX

¥  Studies indicate dark adaptation is very sensitive for AMD diagnosis, more than other standard test – Dark adaptation 85% sensitivity – Snellen acuity 25% – Contrast sensitivity 25% – Photopic visual field 25% – Scotopic visual field 20%

Fundus Autofluorescence (FAF) Imaging

¥  Non-invasive technique which utilizes fluorescent properties of lipofuscin to study the health and viability of RPE/photoreceptor complex

¥  In AMD, may help differentiate from similar entities

¥  FAF variation may precede retinal changes, and may be prognostic for those patients that will continue to develop vision loss

AREDS 2 home study

¥  1520 pt with at least one large drusen and VA 20/60 beOer – 763 with home monitoring, 51 CNVM detected – 757 standard monitoring, 31 CNVM detected

¥  4 leOers lost with device vs. 9 without ¥  94% had beOer than 2040 with device vs. 87% without

5/5/16

1

Posterior Segment Grand Rounds (including Glaucoma)

Steven Ferrucci, OD, FAAO Chief, Optometry Sepulveda VA

Professor, SCCO/MBKU

Disclosure Statement

¥  Speakers bureau/Advisory Board –  Allergan –  Alcon –  B&L –  Centervue –  Heidelberg –  Macula Risk –  MacuLogix –  Nicox –  Science Based Health –  ThromboGenics

CHRPE ¥  Unifocal lesion typically appear as flat, pigmented round lesions

with distinct margins ¥  Color ranges from light brown to jet black, depending upon

amount of melanin ¥  Often have areas of chorioretinal atrophy within the lesion that

appear window like and allow a clear view of the underlying choroid (lacunae)

CHRPE

¥  Typical size is 2-‐6 mm, but may be smaller or as large as 14 DD (21 mm)

¥  Can be located anywhere within the fundus, but about 70% in temporal half of fundus

¥  No apparent racial predisposiWon, although reported more in Caucasians

¥  May be present at birth, with reports in as young as 3 months old

CHRPE

¥  Lesions are almost always stable in size, but color may

change. –  Very rare instances of enlargement with time

¥  Typically asymptomatic, and found on routine exam, but large lesions have been shown to have VF defects

CHRPE

¥  Can also appear as mulWfocal CHRPE – From 3 to 30 lesions, 0.1 to 3.0 mm in size

¥  Benign, staWonary and unilateral in 85% of the cases

¥  O[en called bear tracks

5/5/16

2

Gardner’s Syndrome

¥  Multifocal CHRPE have been associated with Gardner’s Syndrome –  Familial condition of colonic polyps that may be precursor to

colon cancer –  However, these lesions are bilateral, have more irregular

borders, and are often scattered throughout the fundus

CHRPE ¥  DeferenWal includes nevi and choroidal melanoma

–  Nevi: nevi are rarely jet black and tend to have more indisWnct borders –  Melanomas tend to be greater than 2mm in thickness, where CHRPE

are flat

¥  B-‐scan, serial photos and frequent monitoring of assistance

Nevus

¥  Common, benign tumor of the posterior fundus ¥  Typically slate –gray or brown in color, with somewhat

indistinct borders –  Often have overlying drusen, which signify chronicity of

lesion

¥  Vary in size from 1/3 DD to as much as 7 DD –  Flat or minimally elevated, < 2mm

Nevus

¥  Very common, with prevalence ranging from 0.2% up to 32% of patients

¥  More common in Caucasian population ¥  Asymptomatic, and usually found on routine exams ¥  Management consists of serial photography and

frequent follow-up, with ultrasound if needed for more suspicious lesions

Nevus

¥  TFSOM: To Find Small Ocular Melanomas –  T: Thickness: lesions > 2 mm –  F: Fluid: any subretinal fluid suggestive of RD –  S: Symptoms of photopsia or vision loss –  O: Orange pigment overlying the lesion –  M: Margin touching the optic nerve head

¥  No factor= 3% risk of converting to melanoma in 5 yrs ¥  1 factor=8% risk ¥  2 or more factors =50% risk

VMT: Vitreomacular Traction ¥  VMT syndrome is characterized by a partial

detachment of the posterior detachment with persistent adherence to the macula –  Can lead to CME, ERM, and macular hole formation

¥  Once thought to be relatively rare, with advent of OCT now being seen more and more –  In one study, 8% of pts were thought to have VMT by

clinical observation only, but 30% by OCT

5/5/16

3

VAST STUDY

¥  2,179 eyes, 1,120 asymptomaWc pts>40 years of age –  Mean age 59 –  57% female –  57% hyperopes, 35% myopes, 8% emmetropes

¥  VMA in 31% of eyes –  Peak age 50-‐59 –  Less common in AA and HA

VMA vs. VMT: Duker

VMA ¥  Evidence of vitreous cortex

detachment from reWnal service

¥  Afachment of vitreous within 3 mm of fovea

¥  No detectable change in foveal contour or underlying 7ssues

¥  Focal: <1500 um ¥  Broad: >1500 um

VMT ¥  Evidence of vitreous cortex

detachment from reWnal service

¥  Afachment of vitreous within 3 mm of fovea

¥  Distor7on of foveal surface, intrare7nal structural changes, and/or eleva7on of fovea, but no full thickness interrup7on of re7nal layers

VMT ¥  More commonly encountered in older

women – Can occur in either sex, and age, no

apparent racial predilection ¥  Aphakia and pseudophakia are protective,

as these patient typically have a complete PVD

¥  Pts may report decreased vision, metamorphopsia and photopsia

VMT ¥  Clinically, very hard to diagnose

–  PVD with adherence to macular area –  Can present as macular surface wrinkling/

striae , similar to ERM, or loss of foveal reflex –  May also note a thickened posterior hyaloid

membrane –  Retinal blood vessel distortion straightening may

be present –  Retinal thickening /macular edema may be

associated

– OCT IS THE KEY!!!!

VMT

¥  Natural progression of disease is rather variable – Slow progression possible with near

normal acuity – Approx 10% will have spontaneous PVD

and resolution ¥  Therefore, close monitoring my be advised

for some patients

VMT ¥  In patients with poor vision, or

symptomatic, a pars planar vitrectomy (PPV) may be considered – Duration, severity should also be

considered ¥  Literature repots up to a 75% success rate

and improvement of vision following PPV

5/5/16

4

Jetrea (Ocriplasmin)

¥  Intravitreal injecWon of thrombolyWc agent that causes lysis of vitreous –  Pharmacologic vitrectomy

¥  FDA approved October 2012 for treatment of symptomaWc vitreomacular adhesion

¥  Two phase 3 trails –  26.5% of pts had resoluWon of VMA vs. 10.1% with placebo –  Minimal adverse effects –  0.125 mg (0.1 ml) injecWon

¥  Available January 2013 ¥  Cost?

Epi-retinal Membrane

¥  AKA macular pucker, cellophane maculopathy ¥  Can be secondary to peripheral retinal

disease, such as detachment or tear; a retinal vascular disease such as BRVO; inflammation; trauma or idiopathic

¥  Idiopathic tend to be more mild and non-progressive vs. those after retinal tear


¥  VA can range from 20/20 to 20/200 or worse – Studies show > 5% have worse than 20/200

¥  Often metamorphopsia is only complaint with idiopathic ERM

¥  Fewer than 20% of cases are bilateral ¥  Surgical removal is considered if severe vision

loss or distortion


¥  Consider surgery if: – VA 20/40 or worse – Symptomatic – Visual need of patient

¥  Make sure you have an experienced surgeon!!

Central Serous ReWnopathy

¥  Common disorder of unknown etiology which typically affects men between age 20 and 45 – Males to females 10:1

¥  Serous detachment of neurosensory retina due to leakage from small defect in RPE


¥  Pt typically presents with fairly recent onset of blurred VA in one eye with a scotoma, micropsia, or metamorphopsia –  VA typically 20/30-20/70 – Often correctable with low hyperopic RX – Unilateral in 70% of cases

5/5/16

5


¥  Appears as a shallow round or oval elevation of the sensory retina often outlined by a glistening reflex

¥  FA is helpful in providing definitive diagnosis – Classic Smoke stack appearance

(occasionally) – Ink-blot appearance

¥  OCT shows marked elevation

CSR: Risk Factors ¥  Male > Female 10:1 ¥  Age: Peak 20-‐45 ¥  Type A personality ¥  Stress ¥  Pregnancy

¥  Steroid use –  Oral –  Topical? –  InjecWon?

¥  Choroidal Thickness? ¥  GeneWcs? ¥  Viagra?


¥  80-‐90% of pts will undergo spontaneous resoluWon and return to normal (or near normal) VA within 1-‐6 mos. – >60% resolve back to 20/20 – Rare to have vision remain < 20/40

¥  Approx 40% will get recurrence ¥  CNVM is VERY rare occurrence, but possible


¥  No known medical therapy has been proven effecWve –  Topical steroids, NSAIDs etc

¥  Localized photocoagulaWon may be of some benefit, but only if

¥  DuraWon at least 4 months ¥  VA in other eye is reduced from other afacks ¥  Recurrent CSR has already reduced VA in that eye ¥  Pt is intolerant of vision and willing to take risk

¥  PDT suggested in some cases ¥  AvasWn? ¥  Behavior modificaWon?

Treatment

¥  ObservaWon ¥  PDT ¥  AnW-‐VEGF ¥  AnW-‐corWcosteroids

–  Rifampin –  Mifepristone –  Ketoconazole –  Spironolactone/

eplerenone –  Finasteride

¥  Acetazolamide ¥  Aspirin ¥  Metoprolol ¥  H.pylori treatment ¥  Methotrexate ¥  Behavior ModificaWon!

EvoluWon in Primary Therapy

¥  Over the past 12+ years, clinicians have switched from topical B-‐blockers to prostaglandin agents –  Prostaglandin analogues

¥  Superior efficacy -‐ 30-‐35% reducWon (or more!) ¥  Systemic safety ¥  Diurnal control of IOP ¥  Convenience / enhanced compliance ¥  RelaWvely few side effects

5/5/16

6

Prostaglandins

¥  Latanoprost (Xalatan) Pharmacia-‐ Aug 1996 ¥  Unoprostone (Rescula) NovarWs-‐ Sept 2000 ¥  Brimatoprost (Lumigan) Allergan-‐ March 2001 ¥  Travoprost (Travatan) Alcon-‐ March 2001 ¥  Generic latanoprost-‐ March 2011 ¥  Tafluprost (Zioptan) Merck-‐Feb 2012

Prostaglandin: pros

¥  Very few systemic side effects ¥  Once daily administraWon ¥  Long acWon with flafening of diurnal curve ¥  Few drug/drug interacWons

Prostaglandins: cons

¥  Mild hyperemia –  Subsides over Wme, 2 weeks or less –  While 35-‐50% do reports some level of hyperemia, only

3% disconWnued due to hyperemia

¥  Eyelash growth: low incidence 0.8% ¥  Iris color change: benign, cosmeWc change

–  2-‐3%

Prostaglandins: cons

¥  CME ¥  IriWs

–  Avoid in paWents with h/o iriWs, as can precipitate afack –  Consider d/c while in post-‐op cataract period

¥  Re-‐acWvaWon of HSV ¥  Non-‐response: 8-‐9%

–  Similar or befer than virtually all other classes

Generic Latanoprost

¥  March, 2011 ¥  Several companies

–  Apotex, Inc. –  Mylan PharmaceuWcals, Inc. –  B&L PharmaceuWcals –  Greenstone, Ltd. –  Falcon PharmaceuWcals

Generic Latanoprost ¥  Few studies indicate if equivalent ¥  Indian J of Ophth 2007 Study

–  Xalatan group had slightly lower IOP reducWon than generic, 38% vs. 25%

–  If switched from generic to trade, just under 1 mm decrease (16.98 to 16.09)

–  If switched from trade to generic IOP rose just over 1 pt (14.29 to 15.36)

–  Adverse effects: iniWal, 8/11 in trade name vs. 16/18 in generic; 11/11 switched to generic vs. only 6 of 18

5/5/16

7

Generic Latanoprost

¥  Pt switched from brand name to generic PG actually showed increased adherence over the next 18 mos –  8427 POAG pts –  28% less likely to have increased adherence if kept on

brand name –  39% more likely to demonstrate reduced adherence

than pts switched to generic ¥  Stein et al, Impact of the IntroducWon of generic

Latanoprost on Glaucoma MedicaWon Adherence, Ophth 2015; 122:738-‐747.

Generic Latanoprost

¥  Bofom line: –  Fairly similar IOP response –  Maybe more adverse reacWon in generic –  Generics may need extra counseling etc. –  Have back for IOP change a[er switch?

¥  Cost: –  $104.99 for 2.5 ml for trade vs. $22.99 for generic

¥  Travatan-‐z and Lumigan: March 2014

Zioptan (tafluprost 0.0015%)

¥  FDA approved Feb 13th, 2012 ¥  First preservaWve-‐free PG ¥  Indicated for reducing elevated IOP in paWents with

open-‐angle glaucoma or ocular hypertension

Zioptan (tafluprost 0.0015%) ¥  FDA approval based on 5 clinical studies of 905 pts

–  IOP lowered 6-‐8 mm at 3 mos, 5-‐8 mm at 6 mos in pts with baseline IOP of 23 to 26 mm

¥  Dosed once daily in the evening ¥  Cost: ≈ $97 for 30-‐day supply

Zioptan (tafluprost 0.0015%) ¥  Side effects:

–  Increased length, color, thickness and shape of lashes –  Usually reversible upon d/c –  Increased iris pigmentaWon –  Redness of eyes

Beta Blockers: pros

¥  Long, proven track record ¥  Few ocular side effects ¥  RelaWvely inexpensive

–  MulWple generics

5/5/16

8

Beta Blockers: cons

¥  Long term dri[ –  A[er 2 years – nearly 50% change therapy

¥  Systemic side effects: –  Breathing issues, pulse rate, depression, decreased libido,

cauWon in diabeWcs etc, etc.

¥  BID administraWon ¥  Many drug/drug issues

–  Systemic b-‐blockers, cardiac meds (digitalis, CA channel blockers)

IOP Control with Beta Blockers

¥  Clinical trials – adding prostaglandin to Wmolol monotherapy – 25% further IOP reducWon

¥  Switching from Wmolol to prostaglandin – similar IOP reducWon –  Approximately 23%

NOTES:

Alan Kabat, ODMemphis, TN

A Cornucopia of Corneal Conundrums

Innovations in the Management of Ocular Surface Inflammation

Alan Kabat, OD, FAAOMemphis, TN

Dr. Alan Kabat is an honors graduate of Rutgers University and the Pennsylvania College of Optometry. He completed his optometric residency training at John F. Kennedy Memorial Hospital in Philadelphia. Following his education and several years in practice, Dr. Kabat joined the faculty at Nova Southeastern University College of Optometry in Fort Lauderdale, Florida. During his 20 years at NSU, he served as Director of Residency Programs, Chief of the Primary Care Service at The Eye Institute and also Director of the Dry Eye & Ocular Surface Disease Service at The Eye Institute. In 2013, Dr. Kabat joined Southern College of Optometry in Memphis, Tennessee, where he currently holds the rank of Professor. In addition to teaching several classes, seminars and laboratories, he serves as Attending Physician in the Advanced Care Ocular Disease Service and Clinical Care Consultant at TearWell Advanced Dry Eye Treatment Center.

Dr. Kabat has built a reputation of clinical excellence and distinguished service in the area of optometric education. He is an internationally recognized expert in ocular disease management, with a primary interest in dry eye disease and related disorders of the ocular surface. Dr. Kabat has published close to 250 papers, book chapters and review articles in the optometric literature. Additionally, Dr. Kabat lectures regularly at optometric educational conferences in the United States and abroad, having been invited to such diverse venues as Hawaii, Ontario, Quebec, Belize, Bermuda, Colombia, Great Britain, South Africa and Australia.

Financial Disclosure: During the 12 months preceding this event, Dr. Kabat has served as consultant to, and/or received research support and/or speaking honoraria from the following: Bio-Tissue, BlephEx, Ocusoft, Shire and ThermiAesthetics.

A Cornucopia of Corneal Conundrums Alan G. Kabat, OD, FAAO

July 13, 2016 1

Alan G. Kabat, OD, FAAO Memphis, Tennessee

All views in this talk, including off-label (non-USFDA approved) use of medications, are solely those of the presenter. The presenter has served as consultant to, and/or received research support

and/or speaking honoraria within the past 12 months from the following:

Associate Clinical Editor

Editorial Review/Advisory Board:

Dr. Kabat is a faculty member at the Southern College of Optometry (SCO). SCO does not endorse any particular product; any endorsements or recommendations in this presentation are those of the presenter alone. TearWell Is a registered trademark of SCO.

A Note About the Notes

These notes are for reference only. The entities discussed herein may or MAY NOT be

covered during the lecture, depending upon time. This presentation will be delivered in a “grand-rounds”

style format, highlighted by cases. You are encouraged to follow the LECTURE and test your

clinical acumen as cases are presented. Additionally, you are encouraged to engage in the discussion

and share your clinical experience and opinions. If you would like a copy of the FINAL presentation, email

me after the lecture at [email protected] and I will be happy to share it with you.

Epithelial Basement Membrane Disease

Varied nomenclature EBMD, ABMD Cogan’s dystrophy, “map-dot-fingerprint” dystrophy

Typically asymptomatic Non-specific complaints include blurred vision,

“ghosting” (i.e. monocular diplopia), or glare. Less commonly, photophobia or foreign body sensation

Advanced cases of may predispose toward recurrent corneal erosion

Pathophysiology

Not a “true” dystrophy; classified as a form of corneal degeneration.1

Basement membrane becomes hypertrophied and misdirected; basal cells manufacture aberrant projections that protrude from an abnormally thickened basement membrane.

1. Payant JA. Eggenberger LR. Wood TO. Electron microscopic findings in corneal epithelial basement membrane degeneration. Cornea 1991; 10(5):390-4.


July 13, 2016 2

Salzmann’s Nodular Degeneration

Typically asymptomatic Non-specific complaints include blurry vision, especially

if the nodules are situated on or near the visual axis Less commonly, burning, photophobia or FB sensation

Appears clinically as one or more round to oval, bluish-white subepithelial corneal nodules Often arranged in a semi-circular fashion Usually mid-peripheral; can be central or peripheral Usually bilateral; more common in women

Advanced cases of may predispose toward recurrent corneal erosion

Pathophysiology

Associated with chronic ocular surface inflammation Etiologies include phlyctenule,

MGD, VKC, trachoma, interstitial keratitis, EBMD, rigid lens wear, keratoconus, filamentary keratitis, chemical trauma, and incisional surgery

Provokes histopathologic changes at Bowman’s layer; nodules represent hyaline plaque formation between epithelium and Bowman’s layer

Papanikolaou T, Goel S, Jayamanne DG, et al. Familial pattern of Salzmann-type nodular corneal degeneration--a four generation series. Br J Ophthalmol. 2010 Nov;94(11):1543.

Management

For asymptomatic patients with EBMD, only supportive therapy is necessary FreshKote

Corticosteroids (and other NSAIDs) may suppress discomfort, but are not a viable long-term solution

Ultimately, surgical keratectomy or PTK may be required for EBMD and/or Salzmann’s Course dictated by acuity & symptoms

FreshKote

Now OTC High “oncotic pressure” Utilizes colloidal (vs. ionic) osmolality Purportedly reduces epithelial edema Re-establishes integrity of epithelium Reduces microcystic edema & prevents recurrent damage

“Amisol® Clear” A proprietary phospholipid agent; improves lubricity

and helps stabilize the tear film

Focus Laboratories North Little Rock, AR

Filamentary Keratitis

Soluble mucins in tear film precipitate and accumulate into long strands

These in turn bind to defects on corneal surface, resulting in painful episodes

Most commonly associated with dry eye; other etiologies include: superior limbic keratoconjunctivitis prolonged patching after ocular surgery herpetic keratitis recurrent corneal erosion neurotrophic keratitis


July 13, 2016 3

Corneal inflammation

induces epithelial damage

Compromised epithelial cells

become desquamated

Inflammatory stimuli induce excess mucus

production

Epithelial cells and mucin

bind to form filaments

Filaments adhere to the cornea, causing discomfort

Blinking stimulates filamentary traction and

corneal microtrauma

Filamentary Keratitis: Management

Physical removal with forceps (anesthesia) Lubrication therapy Lipid-restorative artificial tears!

Greiner JV, Korb DR, Kabat AG, et al. Successful treatment of chronic idiopathic recurrent filamentary keratopathy using a topical oil-in-water emulsion: A report of 5 cases. Poster presented at the 25th Biennial Cornea Research Conference. Boston, MA: October 11-13, 2007.

Filamentary Keratitis: Management

Bandage contact lens ProKera

‡

ADDRESS THE UNDERLYING CAUSE! Corticosteroids…? Cyclosporine A…?

More recalcitrant cases may require a mucolytic agent (acetylcysteine 5-10% sol’n)

‡ Suri K, Kosker M, Raber IM, et al. Sutureless amniotic membrane ProKera for ocular surface disorders: short-term results. Eye Contact Lens. 2013 Sep;39(5):341-7.

Granular Dystrophy

Most common stromal corneal dystrophy seen in clinical practice

Bilateral; affects the central cornea Discrete corneal deposits non-uniform in size resemble snowflakes or breadcrumbs

Symptoms usually begin in 30’s – 40’s Visual acuity diminishes over time with density of

deposits; late stages: 20/200 or worse Varying degrees of ocular irritation

Propensity toward recurrent epithelial erosion


July 13, 2016 4

Pathophysiology

Autosomal dominant inheritance pattern with complete penetrance

Degenerative changes to epithelial cells and/or keratocytes

Deposits composed of hyaline material

Epithelial basement membrane and Bowman’s layer are also altered May lead to recurrent

erosion

Management:

Lubrication therapy for early, symptomatic stages

PKP or lamellar keratoplasty when significant visual compromise ensues

Phototherapeutic keratectomy (PTK) has been used to restore vision in moderately advanced cases*

Treat recurrent erosions appropriately

* Nassaralla BA, Garbus J, McDonnell PJ. Phototherapeutic keratectomy for granular and lattice corneal dystrophies at 1.5 to 4 years. J Refract Surg 1996; 12(7):795-800.

Photos courtesy of Louise Sclafani, OD

Recurrent Corneal Erosion

History, History, History! Pain on awakening Previous corneal trauma (usually) Previous episodes of RCE

Etiology: Improperly treated initial

corneal trauma, abrasion, or foreign body removal

Certain corneal dystrophies

Acute management: LUBRICATION!! Hyperosmotics? Bandage?

Additional Treatment for RCE

Anterior Stromal Puncture (ASP)

Theory… Requires special ASP

needle (Storz) or bent 25-g needle Images courtesy of: Casser L, Fingeret M, Woodcome HT. Atlas

of Primary Eyecare Procedures, 2nd Edition.

Photo courtesy of Carl Spear, OD, FAAO

Post ASP

Cycloplegic Antibiotic NSAID Pressure Patch? Bandage CL? Oral tetracycline?

Long Term Hyperosmotics Lubrication therapy


July 13, 2016 5

Fungal Keratitis: Risk Factors

Ocular trauma – particularly if organic vegetative matter is involved

Agricultural and tropical environments Topical steroid therapy

Ocular or systemic immunosuppressive diseases Altered epithelial barrier increases the threat

Fungal Pathogens

Molds (filamentary fungi) Septate - most common cause of fungal keratitis e.g. Aspergillus, Fusarium

Non-septate e.g. Mucor, Zygomycota

Yeasts e.g. Candida, Cryptococcus

Non-septate filamentary fungi are responsible for orbital disease, but rarely infect the cornea.

The vast majority of fungal keratitis is caused by Fusarium, Aspergillus and Candida.

Fungal Keratitis: Presentation

Initially presents with a feathery, branching pattern Cornea becomes rough, dull & gray with heaping of

epithelium Severe anterior uveitis is typical

The “classic” feathery appearance disappears after a few weeks, and the fungal keratitis begins to resemble advanced bacterial keratitis. Misdiagnosis at this point is likely.

“Feathery” edges associated with fungal hyphae.

Hypopyon uveitis, Endothelial “plaque"

Hypopyon uveitis, “Satellite” infiltrates


July 13, 2016 6

Fungal Keratitis: Diagnosis

Elevated suspicion in cases of: Severe, atypical or recalcitrant ulceration Ulcers non-responsive to conventional therapy Positive history of trauma and/or contact lenses

Diagnostic testing = corneal scrapings Gram or Giemsa staining Cultures (at least 2 weeks for growth) Sabouraud agar plates

Fungal Keratitis: Management

Polyene antibiotics nystatin, amphotericin B, natamycin

Pyrimidine analogs flucytosine

Imidazoles clortrimazole, miconozole,

econazole, ketoconazole

Triazoles fluconazole, itraconazole

Silver sulfadiazine

Unfortunately, there is no “magic bullet” for

fungal keratitis. Usually it requires

multiple medications & prolonged therapy.

Fungal Keratitis: Clinical Pearls

DO suspect atypical pathogens in unusual, recalcitrant or aggressive cases of keratitis Vegetative injury is significant risk factor

DO obtain (or refer for) cultures DO refer keratitis cases that are

outside of your “comfort zone”

DON’T initiate steroids if diagnosis is uncertain This INCLUDES combinations drugs like TobraDex! 24-hour empirical therapy… then reassess

Marginal Keratitis: Etiology

Bacterial antigens or exotoxins

Solution or drug hypersensitivity

Debris under lenses

Systemic autoimmune disorders

Ulcers vs. Infiltrates

Ulcers 1-to-1 staining-to-defect

ratio Attendant uveitis Solitary lesion Generalized injection Central Severe pain

Infiltrates Infiltrate larger than area

of staining No A/C reaction May be multiple Sectorial injection Peripheral ( & )

Mild - moderate pain

Sweeney DF, Jalbert I, Covey M, et al. Clinical characterization of corneal infiltrative events observed with soft contact lens wear. Cornea 2003; 22(5):435-42.


July 13, 2016 7

“Marginal Keratitis”: Management

Reduce wearing time Discontinue lens wear until inflammation resolves Usually 3-7 days

Liberal use of non-preserved lubricants

Steroid/antibiotic drops help speed resolution Typically QID x one week Still somewhat controversial globally but

standard of care in U.S.

Bacterial Keratitis: Signs & Symptoms

SYMPTOMS: pain, photophobia, lacrimation blurred vision

SIGNS: conjunctival, episcleral injection severe anterior chamber reaction corneal infiltrate with overlying epithelial erosion mild mucopurulent discharge corneal edema & reduced visual acuity extended contact lens wear, corneal trauma

Bacterial Keratitis: Management

Significant risk of permanent visual loss - treatment must be prompt and aggressive.

Cultures…? 1, 2, 3 Rule defines “potentially sight threatening” ulcers: Anterior chamber reaction 1+ (10 cells in 1 mm

beam) Dense infiltrate 2 mm in size (greatest linear dimension) Edge of infiltrate 3 mm from center of the cornea

Immuno-compromised or post-surgical patients

Vital MC, Belloso M, Prager TC, Lanier JD. Classifying the severity of corneal ulcers by using the "1, 2, 3" rule. Cornea. 2007 Jan;26(1):16-20.

Bacterial Keratitis: Management

Broad spectrum antibiosis - empirical therapy *Loading dose* and frequent administration,

consistent with severity of ulceration Fluoroquinolones: Ciloxan, Ocuflox, IQUIX “off label” – Vigamox1, Zymar1,2

Fortified aminoglycosides and/or cephalosporins Also NOT FDA approved

1. Constantinou M, Daniell M, Snibson GR, et al. Clinical efficacy of moxifloxacin in the treatment of bacterial keratitis: a randomized clinical trial. Ophthalmology 2007 Sep;114(9):1622-9.

2. Shah VM, Tandon R, Satpathy G, et al. Randomized clinical study for comparative evaluation of fourth-generation fluoroquinolones with the combination of fortified antibiotics in the treatment of bacterial corneal ulcers. Cornea. 2010 Jul;29(7):751-7.

Shah VM, Tandon R, Satpathy G, et al. Randomized clinical study for comparative evaluation of fourth-generation fluoroquinolones with the combination of fortified antibiotics in the treatment of bacterial corneal ulcers. Cornea. 2010 Jul;29(7):751-7.

Conclusion: The study failed to find a

difference in the efficacy of monotherapy with fourth-

generation fluoroquinolones in the treatment of bacterial corneal ulcers of 2–8 mm

size when compared with combination therapy of

fortified antibiotics.


July 13, 2016 8

Bacterial Keratitis: Adjunctive Therapy

CYCLOPLEGICS Must have significant potency to penetrate

compromised epithelium Atropine 1% MAYBE homatropine; NEVER cyclopentolate!

CORTICOSTEROIDS When to initiate therapy?? Potency is paramount for short-term use

The Role of Corticosteroids in Bacterial Infection

Under ideal conditions, antibiotics rapidly eradicate bacterial pathogens

Inflammatory cascade is the body’s natural defense against invasion… inflammatory “momentum” persists after pathogen is removed

White cells and their by-products (cytokines, proteases, etc.) impact bodily tissues in a negative way – autoimmune disease

Suppression of the immune response is crucial to prevent additional tissue damage

SCUT Steroids for Corneal Ulcers Trial SCUT-1: Study Design

Single center, double-masked, placebo-controlled clinical trial

42 patients with culture-confirmed bacterial keratitis All patients received topical moxifloxacin 0.5% Randomized to either topical prednisolone phosphate

1% or placebo

Outcome measures: BCVA @ 3 months, time to complete reepithelialization, infiltrate/scar size.

SCUT-1: Results

Compared to placebo, the steroid group reepithelialized more slowly.

There was no significant difference in BCVA or infiltrate/scar size at 3 weeks or 3 months.

To have 80% power to detect a 2-line difference in acuity, 360 cases would be required.

“To assess the effect of steroids on acuity, a larger trial is warranted and feasible.”

SCUT-2: Study Design

Multicenter, double-masked, placebo-controlled clinical trial

500 patients with culture-confirmed bacterial keratitis All patients received topical moxifloxacin 0.5% Randomized to either topical prednisolone phosphate 1% or

placebo

Outcome measures: BCVA @ 3 months, time to complete reepithelialization, infiltrate/scar size and perforation.


July 13, 2016 9

SCUT-2: Results

Conclusions: “We found no overall difference in 3-month BCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers.”

Application to Clinical Practice: “Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers.”

Shortcomings of SCUT

Corticosteroid regimen was too conservative. Prednisolone sodium phosphate 1% QID X 1 wk, then BID X 1 wk, then QD X 1 wk Initiated 48 hours after moxifloxacin therapy


Considerations were not made for subjective measures such as: Patient comfort & QOL Functional visual recovery time How quickly did vision improve in the steroid group vs. the

placebo group? “At 3 weeks, corticosteroid treated patients had a 0.024

better logMAR acuity (approximately one-fourth of a line)…”


A MINOR footnote:

“Corticosteroid treatment was associated with a benefit in visual acuity compared with placebo in the subgroups with the worst visual acuity and central ulcer location at baseline. These subgroup analyses suggest that patients with severe ulcers, who have the most to gain in terms of visual acuity, may benefit from the use of corticosteroids as adjunctive therapy.”

An alternative to topical steroids? What is ProKera ?

ProKera represents biologic therapy via the use of active, cryopreserved amniotic membrane. ProKera is the only self-retaining amniotic membrane

available to eye care physicians.

Unique properties of amniotic membranes: Reduce inflammation Promote regenerative (i.e. scarless) healing Inhibit the angiogenic process Ameliorate pain

Deleterious effects of corticosteroids (e.g. delayed wound healing, increased IOP, cataractogenesis) are NOT encountered with amniotic membranes.


July 13, 2016 10

61-year-old CL wearer

Patient presents with appearance above; BVA 20/800 Corneal scraping and culture reveal Staph. aureus Initiate fortified antibiotics QID, insert ProKera After 2 weeks, inflammation reduced, epithelial defect completely healed and BVA

20/25 (below)

Case and im

ages courtesy of Sheffer C.G

. Tseng, MD

, Miam

i, Florida

Epithelial ingrowth

Represents epithelial proliferation between flap and stroma

Usually appears within the first several months post-op More common after enhancement

May cause discomfort, visual distortion, glare, reduced VA and even flap melt

Peripheral ingrowth

Central ingrowth

Pathophysiology

Poor flap adhesion allows epithelial cells to grow into flap interface.

Invading cells may become ischemic or necrotic Collagenase and protease

enzymes are released by necrotic cells

Potentially leads to scarring, fibrosis and keratolysis of surrounding stromal elements

Removal Criterion for Ingrowth

Treat in cases of: Chronic FB sensation Prescription change Visual axis

encroachment with glare symptoms

Evidence of rolling edge or melt


July 13, 2016 11

Video of ingrowth removal

Video courtesy of Cory Lessner, MD pristineflap.com

Corneal Laceration

PAIN, decreased vision Deeper than abrasion; may be smaller, linear + Seidel’s sign; additionally, may see hyphema,

A/C rxn, flattened A/C (relative) with air bubbles Iris prolapse possible IOP is low…

DO NOT perform tonometry!

Corneal Laceration: Management

Photodocument (for clinicolegal purposes), then

LESS is MORE! MINIMAL manipulation of the globe! Avoid topical medications! Shield the eye but DO NOT PATCH! N.P.O. Refer IMMEDIATELY for surgical repair Finding someone to handle this may be more difficult

than you think…!

Corneal Laceration

Pre-treatment Post-treatment Questions? Email me at: [email protected]

1

Innovations in the Management of Ocular Surface InflammationAlan G. Kabat, OD, FAAO

July 13, 2016

ALAN G. KABAT, OD, FAAOMEMPHIS, TENNESSEE

All views in this talk, including off-label (non-USFDA approved) use of medications, are solely those of the presenter. The presenter has served as consultant to, and/or received research support

and/or speaking honoraria within the past 12 months from the following:

Associate Clinical Editor

Editorial Review/Advisory Board:

Dr. Kabat is a faculty member at the Southern College of Optometry (SCO). SCO does not endorse any particular product; any endorsements or recommendations in this presentation are those of the presenter alone. TearWell Is a registered trademark of SCO.

Understanding Inflammation

From the Latin , “to ignite” A self-protective immune response involving host

cells, blood vessels and proteinso Chemical are mediators produced by damaged host cellso These in turn recruit immune cells to address damage

Goals:1. Isolation and elimination of harmful stimuli2. Removal of pathogens, irritants and damaged/dead tissue3. Initiate the process of repair (healing)

In nature, inflammation is intended to be an ACUTEand self-limited response. However, when inflammation is persistent and CHRONIC, collateral damage to healthy tissue may ensue.

Results from:o Infection

o Physical Trauma

o Chemical Trauma

o Tissue Necrosis

o Foreign Bodies

o Immune Complexes

Results from:o Persistent Infection

o Prolonged Exposure to Insult

o Auto-immunity

Cardinal Signs of Inflammation

CALOR RUBOR TUMOR DOLOR FUNCTIO LAESA

Rapid onset Short duration (days/weeks) Fundamental cells:

o Neutrophilso Macrophages

Primary mediators:o Serotonino Histamineo Prostaglandinso Thromboxane

Tissue response:o Fluid exudationo Edema

2


July 13, 2016

Arachidonic Acid Metabolism

CELL-DERIVED INFLAMMATORY MEDIATORS

Insidious / delayed onset Long duration (months/years) Fundamental Cells

o Lymphocytes (T- and B-cells)o Fibroblasts o Macrophages

Primary mediators:o IFN-γo TNF-αo Reactive oxygen specieso Hydrolyzing enzymes

Tissue response:o Angiogenesiso Fibrosis

Addressing Acute Inflammation

CELL-DERIVED INFLAMMATORY MEDIATORS

3


July 13, 2016

NSAIDs Prototype: Aspirin Mechanism: Block the COX enzymes and reduce

prostaglandin synthesis Indications: Used primarily to treat inflammation,

mild to moderate pain, and fever

NSAIDs Ophthalmic indications: Reduction of pain and

inflammation associated with incisional ocular surgery (e.g. cataract, LASIK, etc.)

First in class: OCUFEN® ( ) flurbiprofen sodium 0.03% Allergan

Newest addition: BROMSITE®

bromfenac sodium 0.075% Sun Pharma

Evolution of bromfenac sodium

Initial FDA approval:March 24, 2005

BID dosing

Labeling revision:October 16, 2010

QD dosing

Reformulation:April 5, 2013QD dosing

ISV-101

ISV-303

Initial FDA approval:April 11, 2016

BID dosing

R&D

R&D

Clinical benefits:

Halogenation of bromfenac with bromine is believed to impart increased potency and penetration into ocular tissues

pH is 7.8… more physiologically neutral than XIBROM® or BROMDAY® (both 8.3)

Makes the molecule more lipophilic and further improves penetration

Preserved with a very low concentration (0.005%) of BAK

Convenient once daily dosing

?

?

?

?

Clinical Utility of NSAIDs

On-label Prevention of post-operative inflammation

and pain for cataract and/or refractive surgery

Seasonal allergic conjunctivitis

Off-label Prevention / management of CME following

surgery Management of ocular pain secondary to

corneal trauma, e.g. Corneal abrasions Recurrent corneal erosion Corneal burns (thermal & UV) and chemical

keratitis

4


July 13, 2016

Corticosteroids Prototype: Cortisone, hydrocortisone Mechanism: Primarily block phospholipase A2 enzyme

and imparts anti-inflammatory effects by: 1. stabilizing lysosomal membranes2. decreasing the release of inflammation-causing lysozymes 3. decreasing capillary permeability which prevents loss of

plasma protein into tissues

Indications: Used in the management of pain and/or inflammation, for example in arthritis, temporal arteritis, dermatitis, allergic reactions, asthma, hepatitis, systemic lupus erythematosus, inflammatory bowel disease and sarcoidosis.

Corticosteroids

Ophthalmic indications: For the treatment of corticosteroid-responsive inflammation of the ocular tissues, including the conjunctiva, cornea, iris and ciliary body; may carry specific indications for post-operative inflammation or endogenous uveitis.

First in class: HYDROCORTONE®

(hydrocortisone acetate 1.5%, Merck) in Newest additions:

DUREZOL® (difluprednate 0.05% emulsion, Alcon)

LOTEMAX® (loteprednol etabonate 0.5% gel, B+L)

Exogenous inflammation Traumatic Iatrogenic (i.e. surgical)

Endogenous inflammation Idiopathic or systemic-associated

(e.g. uveitis, episcleritis, scleritis) Infectious

(with concurrent anti-microbial therapy) Allergic eye disease Dry eye diseaseMiscellaneous

Thygeson’s Posner-Schlossman syndrome Interstitial keratitis

Clinical Utility of Corticosteroids Potential Clinical ConcernsNSAIDs

Local irritant effects: Conjunctival hyperemia Burning Stinging Corneal anesthesia

Indolent corneal ulceration

Full-thickness corneal melts

Corticosteroids Delayed wound healing

Secondary infection

Elevation of intraocular pressure

Cataractogenesis

Corneal melts

Central serous chorioretinopathy?

Addressing Chronic Inflammation:

Targeting T-cellsRestasis

Cyclosporine 0.05% emulsion

Allergan (Irvine, CA)

FDA approval: 12-23-2002 BID dosing

“… did not increase tear production in patients using anti-inflammatory eye drops or tear duct plugs.”

11-15-2015: submitted a Prior Approval Supplement (PAS) for RESTASIS® Multi-Dose Preservative-Free (MDPF).

5


July 13, 2016

Cyclosporine A - MOA

Calcineurin inhibitor

Blocks transcription of cytokine genes in activated T-cells

Ultimately blocks production of IL-2 Diminishes

subsequent T-cell proliferation and activation

“… its precise mechanism of action in dry eye is unknown.”

Lifitegrast 5%

Not yet FDA-approved! Described as an:

“Integrin antagonist” “ICAM-1 decoy”

“LFA-1 mimic”

Activation and migration of free lymphocytes to the ocular surface are key steps in the inflammatory process associated with dry eye disease

This process is initiated and influenced by the binding of the T-cell integrin lymphocyte function antigen-1 (LFA-1) to intercellular adhesion molecule-1 (ICAM-1).

Lifitegrast acts as an ICAM-1 decoy; it prevents the binding of LFA-1 with ICAM-1 on the inflamed epithelial cell surface.

Activation and homing of T-cells is prevented.

The cycle of T-cell mediated inflammation on the ocular surface is broken.

Lifitegrast - MOA

1. Expression2. Recruitment

3. Activation4. Release

Prospect ive, double -masked, placebo -cont ro lled, paral lel arm, mul t icenter t r ia l

n = 588 adul ts wi th dr y eye disease randomized 1:1 5% lifitegrast or placebo BID X 84 days

Primar y endpoints - mean Δ from basel ine : SIGN - Inferior Corneal Staining Score (ICSS) SYMPTOM - Visual-Related function sub-score of

the Ocular Surface Disease Index (VR-OSDI)

Resul ts: For ICSS, p = 0.0007 * For VR-OSDI, p = 0.7894 No serious ocular adverse events Significant improvement noted in secondary

endpoints of ocular discomfort (p = 0.0273) and eye dryness (p = 0.0291)

OPUS-1S H E P PA R D J D , T O R K I L D S E N G L , L O N S DA L E J D , E T A L . L I F I T E G R A S T O P H T H A L M I C S O L U T I O N 5 . 0 % F O R T R E AT M E N T O F D R Y E Y E D I S E A S E : R E S U LT S O F T H E O P U S - 1

P H A S E 3 S T U D Y. O P H T H A L M O LO GY. 2 0 1 4 F E B ; 1 21 ( 2 ) : 47 5 - 8 3 .

OPUS-2TA U B E R J , K A R P E C K I P, L A T K A N Y R , E T A L . L I F I T E G R A S T O P H T H A L M I C S O L U T I O N 5 . 0 % V E R S U S P L A C E B O F O R T R E A T M E N T O F D R Y E Y E D I S E A S E : R E S U LT S O F T H E

R A N D O M I Z E D P H A S E I I I O P U S - 2 S T U D Y. O P H T H A L M O LO GY. 2 0 1 5 S E P 1 0 . [ E P U B A H E A D O F P R I N T ]

Mult icenter, prospective, double -masked, p lacebo-controlled c l in ical t r ia l

n = 71 8 adults with dry eye disease randomized 1:1 after 14-day placebo run-in 5% lifitegrast or placebo BID X 84 days

Primary endpoints - mean Δ from baseline : SIGN - Inferior Corneal Staining Score (ICSS) SYMPTOM - Eye Dryness Score (EDS)

Results: For ICSS, p = 0.6186 For EDS, p = 0.0001 * No serious ocular adverse events Significant improvement noted in secondary

endpoints of ocular discomfort (p = 0.0005) and eye discomfort (p < 0.0001)

Potential Clinical ConcernsRestasis

One of the safest, chronic-use ophthalmic drugs available

Stinging upon instillation: 17% (10%)

Delayed onset of action

Lifitegrast Safety record unknown

Good safety in Phase II, III

Notable adverse reactions: Discomfort upon instillation: 18%

(14%) Dysgeusia (taste alteration): 14%

6


July 13, 2016

What is theAmniotic Membrane? The innermost, avascular lining of the placenta Shares the same cell origin as the fetus

Contains anti-inflammatory cytokines and growth factors

Extracellular matrix components found in amniotic membrane regulate and promote regenerative tissue processes1,2,3

Key components: Heavy chain-hyaluronic acid Proteoglycans Growth factors Collagens Fibronectin Laminin

Amniotic Membrane Components

1. Rinastiti M, et al. Int J Oral Maxillofac Surg. 2006;35:247-251. 2. Jin CZ, et al. Tissue Eng. 2007;13:693-702. 3. Niknejad H, et al. Eur Cell Mater. 2008;15:88-99. 4. He H, et al. J Biol Chem. 2009;284:20136-20146. 5. Data on file, Bio-Tissue, Inc., 2012. 6. Hopkinson A, et al. Invest Ophthalmol Vis Sci. 2006;47:4316-4322.

Slide courtesy of Sheffer C.G. Tseng, MD, PhDOcular Surface Education & Research Foundation (OSREF)

Key functions: Inhibits pro-inflammatory cells 4,5

Suppresses T-cell activation Dose-dependently inhibits giant

Promotes regenerative healing 6

• Correlates with amniotic membrane presence • Allows for healing without scar formation

Fetal regenerative healing capabilities

Same child at 3 months

Same child at 18 months

Giant neck massFetal surgery at 26 weeks performed in uteroMass removed leaving little natural anatomy

1. Armstrong et al., Wound Rep Reg 1993; 2. Adzick and Lorenz, An of Surg 2004; 3. Larson et al., PRS 2010.

Slide courtesy of Sheffer C.G. Tseng, MD, PhDOcular Surface Education & Research Foundation (OSREF)

Mechanism of Action:Proposed theories

Biological bandage Substrate (basement membrane) transplant Promoter of epithelialization Carrier for ex vivo expansion of corneal epithelial

cells Suppressor of inflammation* Inhibitor of scarring* Inhibitor of angiogenesis* Anti-microbial agent*

Dua HS, Gomes JA, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49(1):51-77.

Amniotic Membranes

First in class: AMNIOGRAFT® (BioTissue) in Newest additions:

AMBIODISK® (IOP Ophthalmics) PROKERA®, including line extension items

PROKERA® Slim & PROKERA® PLUS (BioTissue) BIODOPTIX® (BioD)

7


July 13, 2016

Amniotic Membranes

Late to the Party… aril (Seed Biotech)

AmnioTek-C (IOP Ophthalmics)

ReNovo-AT-O (RegenMed Group)

VisiDisc Thin & VisiDisc Thick (Skye Biologics)

AlphaVision (Amniotic Therapies)

Clinical Utility of Amniotic Membranes

CORNEA

Limbal stem cell deficiency Pseudophakic bullous

keratopathy Persistent corneal epithelial

defects and perforations Infectious keratitis

Neurotrophic keratitis Chemical burns

CONJUNCTIVA

Pterygium surgery Conjunctivochalasis surgery Tumor excision and

reconstruction Symblepharon prevention

Chemical burns

Stevens-Johnson syndrome

Glaucoma filtering surgery

Questions? Email me at: [email protected]

Brad Sutton, ODIndianapolis, IN

Fluorescein Angiography

Brad Sutton, OD, FAAOIndianapolis, IN

Dr. Brad Sutton is a Clinical Professor at the Indiana University School of Optometry and is the Chief of Service at the Indianapolis Eye Care Center. Dr. Sutton’s main areas of clinical interest include ocular disease and surgical co-management. He has given approximately 300 continuing education lectures on topics related to ocular disease at the local, state, national, and international level, and has published extensively. Dr. Sutton was named the Young Optometrist of the Year for the state of Tennessee in 1997-1998 and received the same award (President’s Citation) for the state of Indiana in 2001. He is also currently the President of the Optometric Retina Society.

1

Fluorescein Angiography

Brad Sutton, O.D.,F.A.A.O.

IU School of Optometry

Indianapolis Eye Care Center

Financial disclosures

None

When do we do it?Not as much as we used to! OCT technology, including OCT angiographyOCT angio: amazing images of blood vessels, but can’t show leakage

OCT angiography

Image: Oct.optovue.com

OCT Angiography

Image: oct.optovue.com

When is it better than OCT?

Evaluating surface neovascularization……..is it neo or is it not? Nonperfusion.In some instances, it is better with SRNVM (active or not)PED with no obvious SRNVM on OCTSome choroidal pathology (ICG)Coat’s / MT (which vessels are leaking)

2

What is it?

Sodium fluorescein is an inert dye that is yellow-orange in color. 10% and 25% strengths Absorbs wavelengths in the blue range and fluoresces at 520-530 nm.When injected intravenously, the dye leaks from all vessels except those in the central nervous system including the retina

How does it work?

Around 80% of the dye binds to plasma proteins such as albumin leaving 20% free to fluoresceWhen performing the angiogram, a blue exciter filter in front of the flash excites the dye causing it to fluoresce at a green-yellow wavelength

How do we do it?Always obtain informed consent first!Seat patient at the retinal cameraBegin by taking a color photo of each fundus

How do we do it

Locate an acceptable vein. The anticubital space is preferred but the back of the hand and rarely others can be usedClean the site with alcohol pad

Tourniquet

Apply a tourniquet downstream to the injection site.With a vein, “downstream” is toward the heart

How do we do it?Enter vein at about a 30 degree angle. After seeing blood flow into tubing confirming that a vein has been “hit”, inject 5ml of 10 % (3ml of 25%) dye into the vein at a rate of 1ml per secondEmpty tubing vs. saline vs 10% dyeInjecting too quickly causes nausea, too slowly results in poor early picturesStart timer when the injection begins

3

IV technique No good!

Fluorescein Dye Fluorescein Dye

Can see blood return with 10% dye, harder with 25%

How do we do it?Begin taking photos at the first sign of fluorescence (standard arm to retina transit time is 10-15 seconds)Take one shot per second for the first 10 seconds or so then shoot areas of interestTake several photos at the mid-phase, approximately 1 ½ to 2 minutes post injectionRemove the butterfly infusion (which had been taped to the patients arm) and apply a band aid

How do we do it?

Shoot several shots during the late phase 8-10 minutes after injection

4

What can go wrong?Side effects are usually mild but serious reactions can occur (must always have a crash cart available with epi-pen)Contraindications include a known sensitivity to fluorescein contrast dye, pregnancy, and lactation

What can go wrong?Yellowing of the skin and urine always occurs. Urine can remain orange for over 24 hoursNausea and vomiting happen in approximately 15% of patients. Conveniently, this often occurs around the time of the mid-phase so the test can be completed after it passes! The sensation usually passes very rapidly and actual vomiting occurs far less frequently than nausea

What can go wrong?

Extravasation of the dye is painful, and can lead to tissue necrosis in 1-2% of casesHives are possible and severe anaphylactic responses occur in approximately .05% of patientsThe reported death rate associated with IVFA is approximately .00045%

What’s normal?

The choriocapillaris has fenestrations which allow the dye to leak into the extravascular spaceThe RPE serves as a barrier to prevent this dye from leaking forward and also limits its visibilityNormal retinal vessels do not leak dye

What’s normal

The angiogram progresses through many stages#1: Choroidal flush. The choroid takes on a patchy, flushed appearance as dye enters the eye. This is blocked in the macula due to increased pigment#2: Arterial phase: Dye rapidly fills the retinal arteries. This phase is over in a few seconds

What’s normal

#3: Arteriovenous phase. After the retinal arteries fill the veins begin to fill. Initially this filling is along the walls of the veins ( laminar flow ) due to the rapid movement of RBC’s in the central lumen. This phase lasts until the lumen fills entirely and typically covers only 5-10 seconds.

5

What’s normal?

#4 Venous phase. Arteries and veins are of equal intensity.#5 Late Venous phase. The intensity in the veins is greater than that in the arteries#6 Recirculation phase. Fluorescence progressively lessens as dye leaves the system

What’s normal

#7 Late phase. Occurs 5-10 minutes after injection. Arteries and veins are essentially void of dye and the choroidal flush is minimal.Optic nerve head will still show fluorescence.In thirty minutes all traces of dye will be gone from the eye.

6

What’s not normal?

Abnormalities can be broken down into two main categories: hypofluorescence and hyperfluorescenceIncreased vein to eye filling time can be indicative of a systemic vascular abnormality or occlusionHypofluorescence is the result of either a filling defect or blockage


A filling defect is the result of capillary non-perfusion ( diabetes, post vein occlusion ) or a blockage such as an arterial embolus or sickle cell induced clot. Arteriosclerosis can also result in a lack of fillingHypofluorescence due to blockage is the result of some entity blocking the background fluorescence of the choroidal flush or obscuring the retinal vasculature


Examples include pre-retinal, intra-retinal, and sub-retinal hemorrhages as well as exudates, pigment, and masses.Hyperfluorescence is the result of either loss of normal blockage of the background flush or leakage from abnormal vessels


Window defects, atrophy and chorioretinal scars can lead to loss of the RPE and hyperfluorescence due to lack of blockingHyperfluorescence from leakage occurs with neovascularization, microanyeurysms, edema, and compromised vessels

7


Staining occurs normally with the borders of the optic nerve head and with the sclera. Druse will also stain

8

OCT CME

Sickle Cell Sea fans

9

SRNVM

Choroidal folds OCT

10

PED PED comparison

Coat’s disease: Images courtesy Dr. Dan Neeley Coat’s IVFA

Coat’s IVFA IRVAN

11

Collaterals Collaterals late

OCT ONH Drusen

ONH Drusen : B-Scan FAF ONH Drusen

12

Metastatic tumors What is ICG

Indocyanine green is a water soluble dye that leaks less freely from choroidal vasculature than Fluoresecein dye doesThe RPE blocks less of the emitted wavelength than with fluorescein, making ICG preferred for choroidal pathology98% binds to plasma proteins

What is ICG?

Inject into arm vein like fluorescein but test takes longer. Mid-phase is about 10 minutes after injection, late about 25Contraindications include pregnancy and lactation, known hypersensitivity, and allergy to iodine or shellfish

When do we use it?

Choroidal pathology such as SRNVM’s, AMPPE, angioid streaks, MEWDS, PCV, etc.

Image:retinagallery.com

ICG / FA Image : Youtube APMPPE OD FAF

13

APMPPE 3 week FU on oral steroids FAF PCV

ICG: PCVImage:

Strathfieldretina.com

The end!

Thank You I-Care PAC Contributors

January 1, 2015 - December 31, 2015

Thank You I-Care PAC Contributors January 1, 2015 –December 31, 2015

William G. Ahlfeld, OD Michael C. Ashman, OD Wynde Ashman, OD Jennifer R. Bailey, OD Max E. Bailey, OD James C. Bigham, OD Scott D. Bixler, OD David R. Britzke, OD Christopher J. Browning, OD Michael W. Brumit, OD E. Cy Burkhart, OD Frank L. Burton, OD Colin C. Christie, OD Conway S. Cox, OD David L. Cripe, OD Sara F. Cubenas, OD Timothy J. DeBoer, OD Kelly P. Dice, OD D. Barry Downing, OD Walter H. Egenmaier, OD Russell P. Elliott, OD Bradley A. Farlow, OD Linda L. Fischer, OD Linda A. Frechette, OD David A. Fullenkamp, OD Jeremy S. Gard, OD Nicholas J. Garn, OD Katherine R. Garringer, OD Joshua D. Greenlee, OD Beth Groninger, OD Ryan C. Gustus, OD James L. Haines, OD Mark S. Harris, OD Troy Hockemeyer, OD Andrew D. Hoffman, OD Richard M. Hoffman, OD Steven E. Holbrook, OD J. Jeffrey Hughes, OD Donald H. Hulsey, OD Sarah A. Huseman, OD Jeffrey D. Irvin, OD William H. Jones Jr., OD Zubair A. Khan, OD Monica Kalia, OD Kyle W. King, OD Jeffrey E. Kirchner, OD Robert W. Kirkpatrick, OD Marjorie J. Knotts, OD Jennifer L. Kohn, OD Caterina A. Komyatte, OD Scott E. Lehman, OD $100.00 - $499 = FALCON $500.00 - $999 = HAWK $1000.00 + = EAGLE

Steven A. Levin, OD Jerry W. Logan, OD Stacy L. Lowdermilk, OD Ann Madden, OD Lance E. Malott, OD Andrew F. Mansueto, OD Ronald T. McDaniel, OD John D. McKenna, OD Barbara Marvel McNutt, JD Matthew D. Mitchell, OD Douglas C. Morrow, OD Rebecca L. Moser, OD Robert W. Moses, OD Kim E. Moyer, OD Todd E. Niemeier, OD Philip G. Nix, OD Gregory D. Norman, OD Karon K. Nowakowski, OD Lori Obenauf Di-Gregory, OD John J. Offerle, OD Candice Olund, OD Nathaniel P. Pelsor, OD Jeffrey D. Perotti, OD Merle K. Pickel Jr., OD Whitney R. Purtzer, OD Kirstin Rhinehart, OD Linnea Robbins-Winters, OD Zachary C. Rossman, OD R. Alan Roush, OD Steven R. Rutan, OD Steven F. Sampson, OD Richard J. Schamerloh, OD Leo Semes, OD, FAAO Steven L. Seward, OD Thomas E. Smith, OD Anna Stegemiller, OD Bryan K. Stephens, O.D Gail F. Stewart, OD James B. Stewart, OD James S. Stickel, OD Dalia A. Tawfeek, OD Brandon N. Terry, OD Christopher C. Wehrle, OD David J. Weigel, OD Thomas E. Welage, OD Kevin Whiteleather, OD Laura K. Windsor, OD Richard L. Windsor, OD Kevin A. Yaryan, OD Jeffrey J. Yocum, OD James M. Zieba, JD

FOCUSED FUNDRAISERS Grey P. Baals, OD James C. Bigham, OD Charles Brizius, OD Christopher J. Browning, OD Lindsay J. Culver, OD Mona R. Dewart, OD Daniel D. Diedrich, OD Damon Dierker, OD Walter H. Egenmaier, OD Patrice C. Ellingson, OD Randall A. Faunce, OD William R. Fawcett, OD Todd J. Fettig, OD Craig A. Ford, OD Nicholas J. Garn, OD Gregory L. Garner, OD Paul A. Gill, OD Allison L. Good, OD James L. Haines, OD Ryan J. Heady, OD Polly E. Hendricks, OD Doug Herrick, OD Nathan T. Hoover, OD R A. Hopper Jr., OD James E. Hunter, OD Jeffrey D. Irvin, OD John A. Jones, OD

Robert W. Kirkpatrick, OD Marjorie J. Knotts, OD J. Thomas Lisle, OD Perry Lopez, OD Timothy L. Masden, OD Eugene J. McGarvey III, OD John D. McKenna, OD Scott A. Miller, OD Darren L. Minnich, OD Douglas C. Morrow, OD Todd E. Niemeier, OD Ronald K. Norlund, OD Gregory D. Norman, OD Karon K. Nowakowski, OD Jeffrey D. Perotti, OD Zachary C. Rossman, OD Heather R. Russ, OD James S. Stickel, OD Brad M. Sutton, OD Thomas O. Troutman, OD Bruce L. Trump, OD Nathan D. Trump, OD Stephan A. VanCleve, OD David M. Wilson, OD Laura K. Windsor, OD Richard L. Windsor, OD Jeffrey J. Yocum, OD

I-Care PAC Contributors This Year--January 1 - June 17, 2016William G. Ahlfeld, O.D.Nicole R. Albright, O.D.Chris Browning, O.D.E. Cy Burkhart, O.D.Conway Stewart Cox, O.D.David L. Cripe, O.D.Eric E. Dale, O.D.Timothy J. De Boer, O.D.Walter H. Egenmaier, O.D.Linda Louise Fischer, O.D.David A. Fullenkamp, O.D.Nicholas J. Garn, O.D.Paul A. Gill, O.D.Joshua D. Greenlee, O.D.James L. Haines, O.D.Steven A. Hitzeman, O.D.J. Jeffrey Hughes, O.D.William H. Jones Jr., O.D.Zubair A. Khan, O.D.Kyle W. King, O.D.Jeffrey E. Kirchner, O.D.Marjorie J. Knotts, O.D.Jennifer L. Kohn, O.D.

Rajender Macha, O.D.Andrew F. Mansueto, O.D.John D. McKenna, O.D.Barbara McNutt, J.D.Darren L. Minnich, O.D.Douglas C. Morrow, O.D.Todd E. Niemeier, O.D.Gregory D. Norman, O.D.Karon K. Nowakowski, O.D.Merle K. Pickel Jr., O.D.Whitney R. Purtzer, O.D.Mitchell S. Reinholt, O.D.Zachary C. Rossman, OD.Steven R. Rutan, O.D.Thomas E. Smith, O.D.James I. Sowders, O.D.James S. Stickel, O.D.David J. Weigel, O.D.Thomas E. Welage, O.D.Laura K. Windsor, O.D.Richard L. Windsor, O.D.Jeffrey J. Yocum, O.D.

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Macular Degeneration is

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