Transcript Dermatologic Therapy

Using New Technology to Improve
Quality of Care & Profit
John A. McGreal Jr., O.D.
Missouri Eye Associates
McGreal Educational Institute
Excellence in Optometric Education
John A. McGreal Jr., O.D.
Missouri Eye Associates
 11710 Old Ballas Rd.
 St. Louis, MO. 63141
 314.569.2020
 314.569.1596 FAX
 [email protected]

JAM
Antaging
Calorie restriction (CR) – cutting normal calorie intake
by 1/3rd boosts animal lifespans by 30-40%
 Resveratrol – proven at Harvard & National Institute on
Aging to extend lifespan by 20%, slow aging process,
even with high calorie diet
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Studies in fruit flies, mice, fish, now humans
Present in red wine
Cardiovascular
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New Guidelines for Blood Cholesterol Treatment
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Heart disease is the number 1 killer in this country
65 million Americans should change life-style & diet (50)
36 million should take medications to lower cholesterol (13)
Many more patients are now candidates for drug treatment
than previous
many recent studies confirm a dramatic decrease in mortality
and morbidity associated with decreased cholesterol levels
Framingham Heart Study “risk calculator”
Cardiovascular
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National Cholesterol Education Program Adult
Treatment Panel (NCEP ATP-III) – lipid management in
USA is less than desirable
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<50% of even highest risk patients receive lipid lowering
treatment
1/3rd of treated patients achieve LDL goal
<20% of CHD patients achieve LDL goal
<50% of patients who are prescribed lipid lowering drugs are
still taking it six months later, 30-40% after 12 months
1 in 8 MI patients quit drugs only 1 month after discharge and
are 3 times more likely to die in the year after MI
New Cardiovascular Concepts
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>20 years old = lipoprotein profile
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Guidelines
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LDL, HDL, Triglycerides, total cholesterol, and BP
Total cholesterol
LDL
LDL (high risk)
HDL
<200
<130
<130
>35
<200 (175)
<130
<100 (70)
>40
Risk Factors
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Gender, age, smoking, high total cholesterol or LDL, low
HDL, HTN, family history premature heart disease, &
obesity
New Cardiovascular Concepts
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Risk Factors
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Diabetes now singled out as so potent risk factor and assumes
high risk category (same as for previous MI)
“metabolic syndrome” - new risk factor
 requires
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three or more of the following
abdominal obesity - 40 in men/35in women
low HDL -<40 men/<50 women
fasting triglycerides >150
HTN
fasting glucose >110
New Concepts – C reactive protein, apolipoproteins,
adiponectin protein, treat HDL & LDL together
Cholesterol Guidelines
More than half of the coronary artery disease in the
U.S. is attributable to abnormalities in the levels and
metabolism of plasma lipids and lipoproteins.
Diabetes, alcohol consumption, OCs, renal disease,
hepatitic disease, hypothyroidism can worsen
hypercholesterolemia or worsen underlying
hyperlipoproteinemia.
 LDL = total cholesterol – HDL – triglycerides / 5.
 Every 1% reduction in TC yields a 2% reduction in
CAD risk!
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Prehypertension
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New Guidelines for Blood Pressure Control
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JAMA 5.21.03 National Heart, Blood, Lung Institute
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45 million Americans have “prehypertension”
BP = 120-139/80-90
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Risks are MI, kidney failure, stroke, CHF
Many more patients are now candidates for drug treatment
than previous
Many recent studies confirm a dramatic decrease in mortality
and morbidity associated with decreased BP levels. Systolic
blood pressure is far more important risk factor > age 50.
Damage occurs at 115/75, with each 20/10 increase doubling
mortality!
Thrombolytics for MI
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Acute Coronary Syndromes
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Reteplace (Retavase)
Eptifibatide (Integrilin)
Tirofiban (Aggrastat)
ASA (Bayer) 325mg chewed STAT
Drug-eluting stents
Prevention
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ASA 81mg (only 1/3rd of 62 milllion at risk in US use ASA)
 Reduces 1st
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MI risk by 32%, 2nd MI risk by 20%
Caution in “vigorous” exercise which can contribute up to
17% of all sudden cardiac deaths
Diabetes Mellitus (DM)
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Diagnosis of DM
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Intermediate categories (“Prediabetes”) – not DM but at
substantial risk of developing type II DM and cardiovascular
disease in the future
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Fasting glucose >126mg/dl
Symptoms of diabetes and a random blood glucose of >200mg/dl
after a 75g oral glucose tolerance test
Impaired fasting glucose (IFG) - (110-126mg/dl)
Impaired glucose tolerance (IGT) – (140-200mg/dl)
Screening with fasting blood glucose – every 3 years
>45years, or sooner if additional risk factors
Treatment - Diabetes Mellitus
Education, control of multisystem complications
 Target HbA1c <7.0% (trending lower to 6.0-6.6%)
 Type I DM require 1.0U/kg/D insulin divided into
multiple doses, typically combining intermediate and
short acting insulins, given before morning and
evening meals or continuous subcutaneous insulin
infusion device
 Type II DM controlled with diet and exercise alone or
in combination with oral agents, insulin or
combinations of oral and insulin.
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Insulin Sensitizing Agents - DM
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Thiazolidinedione – these new insulin sensitizing drugs
allow dosages of insulin to be decreased and
combination therapy with oral agents to achieve better
glycemic control in pts with HA1c >8, on >30U of
insulin/day
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Troglitazone (Rezulin)
Rosiglitazone (Avandia) *
Pioglitazone (Actos) *
Repaglinide (Prandin)
New combination – Avandaryl qd
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Rosiglitazone (Avandia) & Glimepiride (Amaryl)
“Artificial Pancreas” for DM
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Paradigm system (Medtronic) – combination insulin
pump and glucose monitoring system
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Helps type 1 diabetics to avoid dangerous episodes of
hypoglycemia, reduce risks of death
Worn like a pager taped to the abdomen, continuously reads
blood sugar transmits data to pump which beeps or vibrates if
sugar drops to dangerous levels
 Avoids
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“dead in the bed syndrome” in young
Eliminates need for needle use to administer or test sugar
levels
$7,000. cost
Future Directions
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Insulin Eye Drops *****
Insulin nasal sprays – Exubera (Sanofi & Pfizer)
Diabetic Retinopathy Treatment – DRS & ETDRS established
photocoagulation as standard of care for retinopathy since 1974,
BUT….
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Fluocinolone acetonide implant (Envision TD/B&L)
Vascular endothelial growth factor (VEGF) studies in PDR and ARMD
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Lucentis (Genentech)
Macugen (Pfizer)
DPP-4 inhibitors – new class of diabetes medications
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Januvia (Merck) - type 2 DM highly effective !!
Galvus (Novartis) – (phase 3)
Blepharitis Therapy – Topical/Oral
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Cleeravue – M Convenience Kit
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Minocycline hydrochloride 50mg tablets
SteriLid Eyelid Cleanser (Advanced Vision Research)
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Foam container
60 tablets of antibiotic
StoneBridge Pharma, LLC
SteriLid Eyelid Cleanser (Advanced Vision Research)
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Linalool – naturally occurring liquid distilled from plant oils
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Found in many flowers and spice plants, tea tree oils
Outstanding kill – time data for eight eyelid organisms
Pump onto clean fingertips and apply directly to eyelids for 60 seconds
Recommended dosing is bid
Preoperative dosing should begin 3 days before surgery
Endophthalmitis Organism Library at
Mass Eye & Ear
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19 strains of S. epidermidis,
8 strains of S. aureus,
4 strains of Pseudomonas aeruginosa,
3 strains of methicillin-resistant S. aureus,
3 strains of S. warneri,
3 strains of Serratia marcescens
Blepharitis Therapy – Topical/Oral
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ALODOX Convenience Kit
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Doxycycline 20mg (low dose) tablets
 Below
antimicrobial level, safer for prolonged use
 Sustains collagenolytic activity, reducing inflammation
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Ocusoft Lid Scrub Plus (Cynacon/Ocusoft)
1
box of pre-moistened pads
 60 tablets of antibiotic
 1 bottle of 50ml Ocusoft Lid Scrub Original Formula
 Covered by most insurances as tier 3 co-pay
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$25.00 rebate
Assistance program through www.rxhope.com
Blepharitis Therapy – Topical/Oral
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ALODOX Convenience Kit
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Doxycycline 20mg (low dose) tablets
 Below
antimicrobial level, safer for prolonged use
 Sustains collagenolytic activity, reducing inflammation
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Ocusoft Lid Scrub Plus (Cynacon/Ocusoft)
1
box of pre-moistened pads
 60 tablets of antibiotic
 1 bottle of 50ml Ocusoft Lid Scrub Original Formula
 Covered by most insurances as tier 3 co-pay
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$25.00 rebate
Assistance program through www.rxhope.com
Blepharitis Therapy – Topical/Oral
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ALODOX Convenience Kit
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Doxycycline 20mg (low dose) tablets
 Below
antimicrobial level, safer for prolonged use
 Sustains collagenolytic activity, reducing inflammation
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Ocusoft Lid Scrub Plus (Cynacon/Ocusoft)
1
box of pre-moistened pads
 60 tablets of antibiotic
 1 bottle of 50ml Ocusoft Lid Scrub Original Formula
 Covered by most insurances as tier 3 co-pay
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$25.00 rebate
Assistance program through www.rxhope.com
Blepharitis Therapy – Topical/Oral

ALODOX Convenience Kit
–
Doxycycline 20mg (low dose) tablets
 Below
antimicrobial level, safer for prolonged use
 Sustains collagenolytic activity, reducing inflammation
–
Ocusoft Lid Scrub Plus (Cynacon/Ocusoft)
1
box of pre-moistened pads
 60 tablets of antibiotic
 1 bottle of 50ml Ocusoft Lid Scrub Original Formula
 Covered by most insurances as tier 3 co-pay
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$25.00 rebate
Assistance program through www.rxhope.com
Dermatologic Therapy - Topical
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Low Potency Corticosteroids
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Higher Potency Corticosteroids
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Betamethasone Valerate 0.1% (Valisone)
Triamcinolone 0.1%, 0.05% (Aristocort-A)
Mometasone 0.1% 15g/45g (Elocon)
Non-steroidal anti-inflammatory
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Hydrocortisone Cream 1.0% (Hytone)
Triamcinolone 0.025% (Aristocort-A)
Pimecrolimus 1% cream (Elidel)
Tacrolimus 1% (Protopic)
Antifungal
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Metronidazole 0.75% (MetroCream, Gel/Galderma)
Azelaic acid 15% gel / 15g (Finacea/Berlex) bid
Autologous Serum for PED
Tears contain EGF, vitamin A, TGF-B, fibronectin and
other cytokines…..all found in serum
 40ml of blood from venipuncture centrifuged for 5 min
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diluted to 20% by physiologic saline (empiric)/UV bottle
Dosed at 6-10 X/D with additional AFTs
Results
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43% healed within 2 wks, all within several months
Serum accelerates migration of corneal epithelial cells
Serum upregulates mucin expression of corneal epithelium
Amniotic Membrane
Transplantation (AMT)
Ocular surface reconstruction in SJS, severe dry eye,
and severe chemical burns
 Human amniotic membrane prepared from placenta of
elective cesarean section in seronegative (HIV, HepB
&C, syphilis)
 Facilitates epithelialization, reduces inflammation,
vascularization and scarring
 Limbal stem cell transplantation is needed in concert
with AMT in the most severe chemical burns
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RPS Adeno Detector™
Test Procedure
Assembling the Detector
1. Locate the Test Cassette
2. Assemble the detector by gently
placing the sampling pad of the
Sample Collector into the
sample transfer window of the
Test Cassette body.
3. Press firmly where indicated until
the detector is secure.
Transfer Window
Note: A double auditable click means the detector
is properly assembled, transferring the sample to the test strip.
RPS Adeno Detector™
Test Procedure
Running the Test
1. Open the buffer vial. Remove
the Protective Cap from the
Test Cassette. Do not allow
any portion of the detector
besides the absorbent tip to
touch the buffer vial.
2. Immerse the Assembled
Detector’s Absorbent Tip into
the buffer vial for 15 seconds.
RPS Adeno Detector™
Reading & Interpreting the Results
Positive Results:
The Results Line and Control Line are RED in the result window,
indicating that Adenovirus antigen is present.
Results Line
Control Line
Control Line
RPS Adeno Detector™
Reading & Interpreting the Results
Positive Results:
Note:
An uneven or incomplete test
line is due to an uneven
distribution of eye fluid on the
sample pad.
Even if the test line is faint in
color, incomplete over the width
of the test strip, or uneven in
color, it must be interpreted as
positive.
Results Line
RPS Adeno Detector™
Reading & Interpreting the Results
Invalid Results:
If the Control Line does not appear, the test must be interpreted
as invalid and discarded.
Note:
The Patient should be
re-tested with a new
RPS Adeno Detector
kit.
NO Control Line
Antiviral Therapy - Oral
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Acyclovir (Zovirax 200/400/800mg)
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Primary Herpes Simplex: 400mg- 5x/D x10D
Chronic Suppressive: 400mg bid qd
Varicella: 20mg/kg- 4x/D x 5D
Herpes Zoster: 800mg- 5x/D x 10D
Famciclovir (Famvir 500mg tid x 7D)
 Valacyclovir (Valtrex 1000mg tid x 7D)
 Vaccine for Zoster prevention
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Zoster Vaccine Live (Zostavax)
Levofloxacin
Fluoroquinolone
 Indications
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Action – DNA gyrase
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Conjunctivitis, injuries, pre and post operative care,
pneumonia, sinus, skin and skin structure, GI, GU
Prevents bacterial replication
Broadest spectrum, low toxicity, low resistance
Left stereoisomer of ofloxacin, therefore similar solubility and actions
Side effects – taste perversion
Available as
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Quixin 0.5%/1.5% (topical) – q2h x 4 days, then q4h for
conjunctivitis
Levaquin 500mg, Leva-pak 750mg, 25mg/ml q24h
Antimicrobial Therapy – 2008
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Expanded spectrum fluoroquinolones
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Levofloxacin 1.5% (IQUIX / Santen/Vistakon)
 Levofloxacin (L-stereoisomer of ofloxacin)
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Dual mechanism of action
Excellent solubility / penetration into cornea
– treatment of bacterial corneal ulcer
 Side effects are headache & taste disturbance 8-10%
 Dosage Day 1-3: q30m to 2 hrs while awake and every 46 hrs after retiring
 Dosage Day 4 through completion: q1-4h
 Supplied: 5ml white bottle with tan top
 Indication
Ophthalmic Azithromycin: AzaSite
AzaSite™ pairs DuraSite® drug delivery
technology with azithromycin (1.0%)
 Azithromycin has not been previously
used in ophthalmology
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A stable aqueous formulation is difficult
AzaSite™: A stable, easily delivered
formulation of azithromycin
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All the advantages of topical ophthalmic
delivery
Glaucoma Evolution
POAG
Diagnostics
Therapeutics
Future
Considerations
Glaucoma Evaluation is Transforming
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In the past, detection & management relied on
functional assessment
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Visual fields (white-on-white)
 Insensititve
for detecting early POAG
 High degree of variability
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Recently, structural change over time longitudinal
studies have validated the role of structural
imaging
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Are structural defects with normal functional tests
false positives or POAG?
JAM
Glaucoma Suspect
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CPT / ICD
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CPT / ICD
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99214 / Glaucoma Suspect (365.01) = $80.00
92020 / (365.01) = $25.00
76514 / (365.01) = $15.00
92250 / (365.01) = $70.00
92083 / (365.01) = $70.00
99213 or 92012 / (365.01) = $50.00 or $63.00
92235-RT, 92235-LT / (365.01) = $90.00
Total $400.00 or $413.00
Rx: Initiate or continue treatment or observe
Use V58.69 in addition to ICD code when changing medications
in a glaucoma patient
JAM
Gonioscopy
92020
Bilateral
 Requires documentation
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describe visible angle structures
No limitations to diagnostic groups in most states
 Fee
$25.71
JAM
Digital Gonioscopy
92020
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SL-OCT (Heidelberg)
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Integrated Slit lamp & digital gonioscopy system
Haag-Streit BD 900 slit lamp, OCT scanning unit
High resolution grey scale or false color reports
Fast, easy, non-contact OCT at any position
Stores data
Measures angle, angle opening distance, angle recess area,
trabecular iris contact length, trabecular iris space area
Measures pachymetry and biometry
JAM
TM
SL-OCT Hardware Features
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Non-contact
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Fast and easy to use
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Simultaneous
optical and OCT exam
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Color or gray-scale images
Limitations of Manual
Gonioscopy
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Patient discomfort – full globe contact
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Time consuming
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Subjective
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Requires considerable skill and experience
Statement of Assoc. of International Glaucoma Societies (AIGS)
3rd Global Consensus Meeting, May 2006
Computerized Corneal Topography
92025
Bilateral or unilateral
 Requires interpretation & report
 No limitations to diagnostic groups in most states
 Fee
$23.12- / $28.47
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JAM
92025 Corneal Topography
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ICD-9 Codes that Support Medical Necessity
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367.22* Irregular astigmatism
371.00 Corneal Opacity Unspecified
371.23 Bullous Keratopathy
371.50 Hereditary Corneal Dystrophy Unspecified
371.52 Other Anterior Corneal Dystrophy
371.57 Endothelial Corneal Dystrophy
371.60 Keratoconus Unspecified
371.61 Keratoconus Stable Condition
JAM
92025 Corneal Topography
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ICD-9 Codes that Support Medical Necessity
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371.62 Keratoconus Acute Hydrops
372.40 Pterygium Unspecified
996.51 Mechanical Complication Prosthetic Corneal Graft
V42.5 Cornea Replaced by Transplant
V45.61* Cataract Extraction Status
V45.69* Other States Following Surgery of Eye /Adnexa
*367.22 must be accompanied by V45.61 or V45.69
*V45.61 must be accompanied by 367.22
*V45.69 must be accompanied by 367.22
JAM
Special Anterior Segment Photography
92286
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With specular endothelial microscopy and cell count
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Ex: Konan specular microscope
Bilateral
 Not Bundled
 Requires Interpretation and report
 Fee
$101.04
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JAM
Special Anterior Segment Photography
92286
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364.00-364.04 iridocyclitits
364.10-364.11 chronic iridocyclitis
364.21 Fuch’s heterochromic iridocyclitis
364.22 glaucomatocyclitic crisis
364.23 lens induced iridocyclitis
364..24 VKH syndrome
364.51 essential iris atrophy
364.52 iridoschisis
364.53 pigmentary iris degeneration
364.54 pupillary margin degeneration
JAM
Special Anterior Segment Photography
92286
364.55 Miotic Cysts of pupil margin
 364.56-364.61 degenerative changes of anterior
structures
 366.21-23 Traumatic cataract
 366.32 cataract in inflammatory disorder
 366.33 cataract in ocular neovascularization
 371.20-24 corneal edemas
 371.32-33 folds or rupture in descemet’s membrane
 371.50, -.57,-.58, corneal dystrophy
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JAM
Special Anterior Segment Photography
92286
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371.82 corneal edema due to contact lens
379.31 aphakia
379.32 subluxation of lens
379.32 anterior displacement of lens
743.20-23 buphthalmos
906.5 late effect of burn of eye/face
940.2 alkaline burn of cornea/conj
940.3 acid burn of cornea/conj
940.4 other burn of cornea/conj
V42.5 cornea replaced by transplant
JAM
Special Anterior Segment Photography
92286
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996.51 mechanical complication of prosthetic corneal graft
996.60 infection/inflammation due to unspecified implant and
graft
996.69 complication of other implant or graft
998.89 complication of other transplanted organ
998.59 other postoperative infection
998.82 cataract fragments in eye following cataract surg
V53.1 fitting & adjusting specs or CL after intraocular surgery
JAM
B Scan Ultrasonaography
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Ocular ultrasound
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Ex: Accutome B Scan Plus
Unilateral
 Not Bundled
 Requires Interpretation and report
 Fee
$
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JAM
Accutome B Scan Plus
Model 24-6100
 Portable
 High definition
 0.015mm resolution (highest in industry)
 State-of-art probe design
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Plugs into any laptop or PC
2X full zoom
 Excellent software data analysis
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JAM
Pachymetry
76514
Bilateral
 Measurement of central corneal thickness (CCT) proven
by Ocular Hypertension Treatment Study (OHTS) to be
standard of care in diagnosis and management of
glaucoma, glaucoma suspect and ocular hypertension
 Also billable for keratoconus, corneal transplants,
cataracts with corneal dystrophies, guttata, edema
 Requires Interpretation & Report
 Fee
$11.92
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JAM
CCT Assessment
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Has become standard
Equipment widely available
– DGH was used in OHTS
– Low cost
Consider potential effect of
LASIK on IOP findings
Also billable for nonglaucoma ICD-9 codes
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Corneal edema, keratoconus
Reichert IOPac
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Portable, battery op.
Stores up to 1000 pats.
USB and infrared interface
Down load to PC and printer
 Detachable
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probe
Easily replaced if necessary
 Download
PDR into Palm
Pachymetry
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IOP correction by correlation to corneal thickness is NOT
POSSIBLE!
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A linear relationship does not exist!
Careful examination of regression analysis (scatter graph of IOP
relative to CCT) demonstrates huge bandwidth
Adjusting IOP by CCT instills a degree of accuracy into an
inaccurate measurement
It is possible to adjust the IOP in the WRONG direction
Barbados study of black patients shows no correlation of
CCT/IOP
“Trying to be more precise than this is not supported by the data
and may be harmful to patient care” Jamie Brandt, MD Dir
Glauc Src, UCD / OHTS investigator
JAM
Serial Tonometry
92100
Bilateral
 Requires Interpretation & Report
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Example: Angle closure glaucoma
multiple measurements over time
Fee
$55.91-
JAM
PASCAL at work:
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Slit lamp mounted
Technique similar to GAT
but…
Constant light pressure
No fluorescein
Self-calibrating
Battery operated
Pascal DCT
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Measures
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Ocular Pulse Amplitude
(OPA)
IOP
Quality (Q)
Heart Pulse (H)
Stores data
The PASCAL SensorTip
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Contour-matched concave tip
surface (7mm)
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Accurate for corneal radius 5.59.2mm and CCT 300-700
built-in pressure sensor (1.2mm)
transparent tip permits view of
cornea interface for centering and
control
Comparison of DCT With the GAT
 Univ.
Of Zurich
 228 eyes measure with DCT and GAT
 Compared IOP measurements
 Looked at effects of:
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CCT
Corneal curvature
Astigmatism
AC Depth
Axial length
 Intra-observer
and Inter-observer variability
DCT vs. GAT
DCT median difference: DCT +1.7mm higher than
GAT
 GAT: Affected by CCT, curvature, astigmatism, AC
depth and axial length
 DCT: NO EFFECT with any parameters
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DCT vs. GAT
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Intra-observer variability
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GAT 1.1mm
DCT 0.65mm
Inter-observer variability
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GAT 1.28mm
DCT 0.44mm
Kaufman et. al. IOVS 2004; 45:3118-3121
IOP Measurements Using DCT After
LASIK
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“Corneal ablation of 90.0+/-49.18microns reduced
IOP as measured by GAT by 3.0+/-mm. ..no
significant change in IOP was recorded by DCT(0.2MM)”
Kaufmann C, et al IOVS 2003; 44:9:3790-3794
Biomechanical Properties in Tonometry
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



Flatter corneas = lower IOP
Thinner corneas = Lower IOP
Softer corneas = lower IOP
Stiffer IOP = higher IOP
How accurate is Goldmann in thick, soft cornea?
How accurate is Goldmann in thin, stiff cornea?
Pascal DCT removes biomechanical properties from
measurements
Cannot correct IOP using thickness alone!
–
Linear correction factors of GAT will not accurately correct IOP
DCT in Ectatic Corneas
Study of 53 eyes at Will’s by Ozbek & Cohen
 Included eyes with keratoconus, Pellucid Marginal
Degeneration and penetrating keratoplasty

–
–
–
Topography = 54.7 X 43.6
CCT = 482
DCT = 16.1 / GAT = 14.3 / TP = 13.8
DCT were not different between PMD, KC, PK
 DCT were not affected by corneal steepening

Conclusions

“IOP measurements by DCT are highly concordant with
IOP readings obtained by GAT but do not vary in CCT
and have a lower intra- and inter-observer variability.
DCT seems to be an appropriate method of tonometry
for routine clinical use”
James Brandt, MD
Director Glaucoma Services
UC Davis
“Assuming that CCT can be used
as a correction factor for GAT is
a misinterpretation of the results
of OHTS… that couldn’t be
further from the truth. Adjusting
IOP based on CCT is attempting
to instill a degree of precision
into a flawed measurement. You
may actually correct in the
wrong direction. The issues
related to the most accurate
tonometry need to include the
material properties of the
cornea”
Ocular Pulse Amplitude (OPA)
 Amplitude
and shape of OPA are easily observed with DCT
 OPA is a function of
–
–
–
Vascular geometry & flexibility
Ocular rigidity
Systemic blood pressure
 Can
be used to assess ocular perfusion
 Data now suggests a correlation between OPA & Ocular
rigidity…and hence between OPA & risk of glaucoma
progression

A. Harris, PhD (Indiana University)
Latino Eye Study
How often is GAT significantly low?
 Median difference between DCT & GAT studied

>4.5mmHg = 10.6%
– >5.5mmHg = 4.4%
– >6.5mmHg = 2.5%
–
 Increased
IOP still most common factor
in optometric practice converting
normals to glaucoma suspects
IOP Measurements By DCT After LASIK
“Corneal ablation of 90.0 +/- 49.18u reduced IOP
as measured by GAT by 3.0mm...no significant
change in IOP was recorded by DCT (-0.2MM)”
 Clinically validated by manometric studies of
true intracameral pressure
 LASIK case volume in US is 7,401,400

–
GAT DOES NOT WORK!
Kaufmann C, et al IOVS 2003; 44:9:3790-3794
Case of “I Have A Peculiar Nerve”
45yowm CC: “OD wants R/O Papilledema”, Indistinct
optic discs, IOP 20-25 range, pach 637
 PH: Hodgkin’s disease, R hip replacement, 3 vessel
CABG, HTN, Hyperlipidemia
 FH: + POAG paternal aunt
 Meds: Darvocet,Amitryptilline, nitrate, isosorbide,
norvasc,toprol, plavix, lipitor, ASA
 VA 20/20 OU PERRL-APD
 IOP: 26/23
Pach: 639
 SLE: Nl OU
Fundus : As shown

What is the diagnosis?
1.
 2.
 3.
 4.
 5.

Normal optic nerves
Papilledema
Optic nerve drusen
Ocular histoplasmosis
Choroidal nevus
What tests are indicated?
1.
 2.
 3.
 4.
 5.

VF / Pach / SCODI / Stereo disc photos
MRI
MRI / VF
Histoplasmosis titres
IVFA / VF
Case of “I Have A Peculiar Nerve”

45yowm CC: “OD wants R/O Papilledema”,
 DCT
OD: 24.9 / OPA 4.4 / Q3
 DCT OS: 23.1 / OPA 3.8 / Q3
SLE: Nl OU Fundus : As prev
 VF OD: Superior and inferior nasal defects
 VF OS: minor changes
 SCODI: Confirms disc elevation limited to disc itself

Visual Field 9208x
Bilateral
 Requires Interpretation

–
–

separate report form
narrative in body of medical record, on date of service
Fee $43.88- (-81)
$57.37+ (-82)
$65.92- (-83)
JAM
Oculus Easy Field Perimeter
 Screening AND
Threshold
fields
 Color LCD-Display
 Fixation monitoring
–
CCD camera
 Stores
up to 40,000 exams
 Built-in printer
FDT Perimetry Abnormalities as
Predictors of Glaucomatous VF Loss

105 eyes of 105 glaucoma suspects
–
–
IOP 23mm+ or disc damage on photos
SAP VF normal
Baseline FDT obtained
 Mean follow-up 41 months

Medeiros FA, et al AJO 137:863-871, 2004
FDT as Predictor of VF Loss
16% (17 pats.) converted on SAP VF
 In pats. with abnl. FDT at baseline:

–
–

Probability of developing abnl. SAP:
30%
Pats. With NL FDT at baseline:
–
–
Probability of developing abnl. SAP:
4%
FDT as Predictor of VF Loss
Location of the FDT and SAP defects corresponded
in 14 of 17 patients
 FDT defects in 59% of the converters occurred as
much as 4 years before SAP

–
Mean: 21 months
However…..
Only 59% of SAP defects were previously
identified by abnl. FDT
 24% had SAP defects BEFORE FDT
 18% of converters NEVER developed FDT
defect
 24% of normal SAP’s showed abnl. FDT but
never developed abnl. SAP

–
False positives?
Other Important VF Studies
Paczka (2001) - found FDT better overall performance
in detecting damage than RNFL photographs
 Kondo (1998), Wu (2001) - In patients with SAP VFDs
restricted to 1 hemifield, FDT has shown to be able to
detect functional losses in the other hemifield
 Medeiros (2004) – functional defects in FDT predict
future defects on SAP

Other Important VF Studies

Kim (2007/AAO) – when SAP is normal, some patients
with VFD detected by FDT showed decreased NFL
thickness (OCT)
–
Provide evidence that coincident FDT & OCT abnormalities
may be an early sign of glaucoma
Visual Field Testing for Specific
Functions

Short wavelength autoperimetry (SWAP)
–

Frequency doubling technology (FDT)
–

Magnocellular ganglion cells
Motion automated perimetry (MAP)
–

Bistratified ganglion cell (9%) short-wavelength cones
Magnocellular ganglion cells (3%)
High pass resolution perimetry (HPRP)
–
Parvocellular ganglion cells
Visual Field Testing for Specific
Functions

Standard Autoperimetry (SAP)
–
–
–

Achromatic perimetry
Non-specific for ganglion cell type
Appreciable portion of nerve fibers lost before defect measured
Short wavelength autoperimetry (SWAP)
–
–
440nm, 1.6degree tartget @ 200ms yellow background
More sensitive by 3-5 years to early loss

–
UCD studied for over decade
Disadvantages – time consuming, variable, not bright enough to
threshold in advanced POAG
Visual Field Testing for Specific
Functions

Frequency doubling technology (FDT)
–
–
–
–
0.25 cycle/sec sinusoidal grating with 25Hz counterphase
flicker
View grating at low spatial frequency and high temporal rate
Percept is double frequency illusion attributable to subset of
magnocellular ganglion cells
Portable, fast, reproducible
Visual Field Testing for Specific
Functions

Motion automated perimetry (MAP)
–
–
–
–
Tests Magnocellular ganglion cells (3%)
Present random dot kinematogram with coherent motion on
uniform grey background in 14 locations
Computer controlled stimulus (1024x768), 30degree field, 7
frames in rapid succession (420ms), 20 dots/frame, in circular
7.3 degree angle, moving at 8 degree/sec
Superior to SAP in early detection, but time consuming and
high variability
Visual Field Testing for Specific
Functions

High pass resolution perimetry (HPRP)
–
–
–
–
–
Parvocellular ganglion cells system detection
Test presents spatially filtered rings, 50 test locations in
30degree field, 14 different ring sizes used @165 ms
6 minutes, easy
Very useful in following progression
Lacks standardization
A Comparison of Humphrey SITAStandard Perimetry With Both Screening
Oculus Easyfield Perimetry And With
Screening FDT

Seitzman,G.D., Robin,A.L., et al
–
Dept. of Oph., Johns Hopkins University
Objective

To determine the sensitivity and specificity of the
screening modes of the Oculus Easyfield Perimeter and
Frequency Doubling Testing when compared with SITA
standard threshold perimetry.
Methods

One hundred one subjects had the following perimetric
testing: Frequency Doubling Technology (screening
mode), Oculus Easyfield Perimetry (suprathreshold
mode), and Zeiss Humphrey SITA Standard C-24-2
threshold perimetry.
Results

The sensitivity and specificity of detecting any
glaucomatous visual field defect using an abnormal
Glaucoma Hemifield Testing criterion was 76% and
89% for the FDT and 86% and 98% of the Oculus
Perimeter, respectively.
Conclusions

Both smaller screening perimeters were relatively quick.
Although the Oculus was just 30 seconds slower than
the FDT, its increased sensitivity and specificity could
be much more cost effective in the treatment of
glaucoma.
Octopus 301 Perimeter
 Motorized
auto eye tracking
 100% fixation control
 Blazing fast speed
 Ergonomic design patient friendly
 Blue yellow testing in 3 min/eye
 Critical fusion testing
 One min screen
 Three min full threshold
 PeriTrend Analysis
 LAN ethernet
 800.787.5426
 www.haag-streit.com
Current Perimeters are Highly
Variable


After one abnormal visual
field test:
– 86% of patients test within
normal limits on next
exam
After two consecutive
abnormal test results:
– 66% of patient test within
normal limits on next
exam1
3.Keltner JL, et al. Arch Ophthalmol 2003; 121:643.
% Patients Returning to "Normal"
86%
66%
1
2
Number of Consecutive VF Tests
Heidelberg Edge Perimeter
New “Flicker Defined Form” Stimulus
 Overcomes limitations in Frequency Doubling
Technology
 True targeting of M-cell visual pathway
 Less test-retest variability
 Direct link to HRT optic disc assessment

Flicker Defined Form (FDF)
Targets M-cells
The magnocellular (M-cell) pathway is one of the three
main neural pathways from the retina to the primary
visual cortex
 M-cells may be the first to sustain damage in
glaucoma2,3
 There are fewer M-cells so selective testing can find
defect to all cells earlier4
 FDF selectively targets the M-cells which are sensitive
to high frequency and high contrast stimuli

5. Glovinsky et al. Retinal ganglion cell loss is size dependent in experimental glaucoma. IOVS. 1991;32:484-491
6. Kerrigan-Baumrind et al. The number of ganglion cells in glaucoma eyes… IOVS. 2000;41:741-748
7. Johnson CA. Psychophysical measurement of glaucomatous damage. Surv Ophthalmol. 2001;45:313-318
How is Flicker Defined Form (FDF)
Different ?

Frequency Doubling Technology is not as selective at
stimulating the M-cell pathway as previously thought5

Standard Automated Perimetry stimulates all retinal cells
(broadband stimulus)

FDF is more selective and targets the M-cell pathway

FDF studies show less test-retest variability
8..Quaid PT, Simpson TL and Flanagan JG. Frequency Doubling Illusion: Detection vs. Form Resolution. Optom Vis Sci. 82(1): 36-42, 2005.
HEP: The New Perimeter for
Glaucoma Management
New FDF stimulus for
early signs of glaucoma
 Less test-retest variability
for improved diagnosis
 Structure-Function Map
for combined assessment
 Network-ready
 Test types
– Contrast sensitivity
– Letter tests
– Driving test


Closing
Statements
Advances
in perimetry
are continuing
–

Customization for specific needs
–

SWAP allows early recognition, HPRP follows progression
SAP perimetry will continue to be preferred for established
glaucoma with VFDs
–

Early detection / established glaucoma / screening
Early VF loss is often selective, with specific types of axons
disturbed
–

Faster third generation algorithms reduce test time by 50%
Considerably improved methods of computer-assisted interpretations
of serial VFs
Screening methods will sacrifice sensitivity for specificity and
ease of use to detect the half of glaucoma patients who have
undiagnosed disease
–
Deployed in non-professional environments
Closing
Statements
 Perimetry is a robust method of examination, a cornerstone of





glaucoma management and will remain so
It will become more user and patient friendly
VF testing is easy to administer (technician)
VF instruments are not expensive
VF testing can still be performed in cataract patients
Computer-assisted analysis (ie Glaucoma Hemifield Test)
performs as well as trained observers and are extremely
specific
–
Asman Arch Ophthalmol 1992
Closing
Statements
 Standard SAP testing is not optimal
Combination testing of 2 or more modalities improves
detection
 Glaucomatous optic atrophy may precede currently
measurable functional loss in some
 Functional loss with specific tests may precede
detection of glaucoma disc changes on stereo
photograph review
 Most sensitive test may be different for each stage of
the disease

Fundus Photography
92250





Bilateral
Not Bundled
Stereo disc photography
Requires Interpretation
Fee $73.67+
JAM
Fundus Retinal Photos ROI






Synemed (Canon)
Cost $24,500.00
Lease $543.90
Breakeven 2 photos / wk
6 MP digital non-mydriatic
10 images / wk – lease =
$22,273.20 annual revenue
Extended Ophthalmoscopy
92225 / 92226
Unilateral
 Initial (-225) vs. Subsequent (-226)
 Implies detailed, extra ophthalmoscopy

–
document fundus lenses used
Modifiers RT /LT
 Requires retinal drawings & interpretation

–

sizes, colors and dimensions carrier specific
Fee
92225 ($22.23+)
92226 ($20.01+)
JAM
Scanning Computerized Ophthalmic
Diagnostic Imaging
92135
Unilateral
 Applies to glaucoma and retinal evaluations

–
–
–
–
Retinal Thickness Analyzer (RTA)
Heidelberg Retinal Topography (HRT3)
Humphrey Optical Coherence Tomography (OCT)
Laser Diagnostic Technology (GDX VCC)
Requires Interpretation & report
 Fee
$45.59
JAM
Scanning Laser
Covered Diagnosis List
362.85 retinal nerve fiber bundle defects 377.00-377.04
 364.22 glaucomatocyclitic crisis
Papilledema
 364.53 pigmentary iris degeneration
 364.73 goniosynechiae
 364.74 pupillary membranes
 364.77 recession of the angle
 365.00-365.9 glaucoma
 368.40-368.45 visual field defects
JAM
 377.9 unspecified disorder of optic nerve or pathways

Scanning Laser
92135

Moderate Damage - payable once or twice per year, not
with a field
–
Visual field examples
moderate reduction in retinal sensitivity
 temporal wedge

–
Optic Nerve examples
 enlarged
cup with sloped or pale rim
 focal notch
 rim/disc >0.1 but <0.2
 prominent lamina cribrosa
JAM
Scanning Laser
92135

Advanced Damage - rarely payable, fields more
valuable
–
Visual field examples
 loss
of central vision
 temporal island remains
 severe reduction in retinal sensitivity
 absolute defects to within 3 degrees of fixation
–
Optic Nerve examples
 rim
destroyed
 rim/disc ratio<0.1
JAM
GDx VCC







Image acquisition in less than
1 second
Uses internal fixation device
Compact, table-top design
Portable
Easiest to use
Comfortable, objective test for
patients
Easy interpretation
What’s NEW in the HRT3







OHTS Ancillary Study Results
GPS Glaucoma Probability Score
Enhanced Glaucoma Analysis
Enhanced Progression Software
Portable Design
More operator friendly
Choose from four packages
Top 5 Stereometric Parameters
Rim Area
 Rim Volume
 Cup Shape Measure
 Height Variation Contour
 Mean RNFL Thickness

DIAGNOSE: CUP, RIM & RNFL








Optic disc size measure and
“small”, “average” and
“large”
Parameters adjusted for disc
size
Largest normative database
Ethnic-selectable
OU asymmetry
RNFL normative data
Quality Indicator
Conclusion:
Complete Assessment
Monitor Change Over Time
 Baseline
–
compared to follow-up images
Absolute change calculated
 Progression
Change Probability Analysis
Pixel by pixel comparison
– Independent of reference plane
– No contour line is needed
–
 Progression Trend
–
Report
Normalized stereometric parameters graphically displayed
How Predictive is the HRT?
Regression Analysis – measures
rim area & adjusts for disc size
 40% of patients flagged at baseline as “outside of
 Moorfields
normal limits” by Moorfields Temporal Superior sector
analysis developed glaucoma.
 26% of patients flagged at baseline as “outside normal
limits” by Moorfields Global analysis developed
glaucoma
 90% of those with normal HRTs did not develop
glaucomatous damage over the next 5 years
Glaucoma Probability Score (GPS)
What if we could take the world’s leading glaucoma
experts and use their combined knowledge to help you
diagnose your patients?
 The Glaucoma Probability Score takes the first step in
this direction by applying machine learning to glaucoma
diagnostics.

GPS Advanced Artificial Intelligence
"Find a bug in a program, and fix it, and the program
will work today. Show the program how to find and
fix a bug, and the program will work forever."
- Oliver G. Selfridge, in AI's Greatest Trends and
Controversies
Glaucoma Probability Score
A new approach to optic disc analysis
 6 years in development
 Applies the latest in artificial intelligence to glaucoma
diagnostics – “Relevance Vector Machine”
 Produces an understandable indicator - probability of
disease
 Eliminates the need for contour lines or reference planes

GPS How It Works





Uses same HRT scan as in the past
Performs 3-dimensional shape
analysis
Relevance Vector Machine is
“trained” to look for glaucoma
Measures 5 key parameters
3 parameters represent cup shape and
2 represent RNFL
Healthy
Glaucomatous
Case of the “Ocular migraine?”
Age: 43yowm CC: “Flashes of light”
 HPI: 20mins / OU / once / 3L soda/Day / -HA, nausea,
vomiting / overweight
 Meds: synthroid
Allergy: none
 BVA: OU 20/20 Pupils: PERRL-APD
EOM: full
EXT: NL, CA auscultation Nl
 Pach: 528/532 SLE: Nl OU IOP 24/24,17/17
 VF: normal Optic N: OD 0.80 OS 0.65
 OcHx: Mother & brother susp ONH & Nl VFs

3-D Thickness Map

Thickness Map with
adjustable opacity

Can be rotated to
change perspective

Floor shows reflectance
image to help orient
user
Support Literature

Heidelberg Engineering website:
www.heidelbergengineering.com
–
–
–
–
Complete list of published articles on all products
Abstracts of published articles
Condensed summary of the supporting literature for main
topics of interest
Downloadable tutorials for all HE products
RTA
Early
Complete
& Reliable
Diagnostics
John A. McGreal Jr., O.D.
Optic Nerve Consult
27 yowf with optic atrophy
 HPI OD / 3w / mild /MVA 7 yrs ago / head
trauma, concussion, multiple fractures
 Meds: rhinocort, patanol, OCs
 OcROS: PAC, DSCLs
 BVA 20/20 OU
IOP: 18OU
Optic
nerve pallor OD

Assessment / Plan

Optic atrophy OD
–
–
–
Order RTA
Order VF
Order Fundus photo
Assessment / Plan

Optic atrophy OD with field defect
–
Order MRI of brain and orbit, R/O mass lesion of chiasm or
optic nerve, MS
Case of Black Out
32 yobf Transient loss of vision / OU /
painless / obese
 HA / constant / dull / AM worse /
cholesterol elevated
 Meds:Glucatrol, Wellbutrin
 VA 20/20 OU IOP: 17 OU
 Fundus: elevated ON heads OU, Mild nonproliferative DR


Papilledema
What
is the diagnosis?
Drusen of optic nerve
 Bilateral optic neuritis
 Ischemic optic neuropathy

Assessment / Plan
Order VF
 Order Fundus photo
 Order RTA
 Order BP

Assessment / Plan
Probable pseudotumor cerebri
 Must rule out mass lesion

–

Must confirm elevated CSF
–

MRI of brain and orbit
Lumbar puncture
Anomalous discs are diagnosis of exclusion
with burried drusen likely cause
Case of “Macular Hole”







21yowm CC: “have holes in my eye”, denied LASIK
HPI: OU / 1 mos duration / gradual loss / no pain
Meds: Atenolol, ASANKDA
BVA: 20/80 OD 20/100 OSPERRL No APD
EOM: Full
EXT: W&Q
SLE: nl, IOP: 13 OU
Fundus: as pictured
What is the diagnosis?
1.
 2.
 3.
 4.
 5.

Epiretinal membrane
Cilioretinal artery occlusion
Macular drusen
Macular hole – full thickness
Macular hole – partial thickness
What eye test would you order now?
1.
 2.
 3.
 4.

IVFA
Visual fields
RTA
ERG
What should you do now?
1. Take a refresher course in ophthalmoscopy
 2. ERG
 3. Retina consult
 4. Buy stock in scanning laser companies

What is the diagnosis?
1.
 2.
 3.
 4.
 5.

Epiretinal membrane
Cilioretinal artery occlusion
Macular degeneration – atrophic type
Cone dystrophy
Macular hole – partial thickness
Benefits of RTA







State of the art SCODI
New paradigm in glaucoma diagnosis
New paradigm in retina diagnosis
Improves clinical decision making
Improves quality of care
Generates additional revenue
Take advantage of unprecedented tax incentives
for new equipment
Optical Coherence Tomography OCT
Optical: Light-based
Coherence: property of light waves in which the
oscillations maintain a fixed relationship to
each other
Tomography: Cross-sectional imagery
How OCT works
Similar to ultrasound but uses light instead of
sound to image tissue
 Beam of light is directed into tissue and
reflections coming from different layers of the
tissue are received by a detector

Stratus OCT Software
 Macula
Thickness
Analysis
 RNFL Analysis
 ONH Analysis
RNFL analysis



Circular scanning around ONH
at a radius of 1. 73mm
Scan begins temporally
Three scans are acquired and
data is averaged
Optic nerve head analysis


Radial scanning across
optic nerve head
Six 4mm scans are taken
Optic Nerve Head Parameters

Volumetric Information
–

Dimensional
Information
–
–
–

Volume of Cup
Disk Area
Cup Area
Rim Area
Cup Disk Ratios
–
–
–
Horizontal
Vertical
Average
Ophthalmic Genetics

Researchers have identified genes for OAG
–
–
TIGR/Myocilin = juvenile OAG
OPTN (optineurin) = Primary OAG (NTG)

–


Optineurin may provide neuroprotection to optic N
CYP1B1 = Congenital glaucoma
Genetic testing will allow clinicians to determine if Pt is
predisposed to or affected with specific type of glaucoma, even
before symptoms appear
OcuGene (InSite Vision/Alimeda) – simple, in office test, 99%
accurate detection of TIGR (trabecular meshwork inducible
glucocorticoid response gene)
–
Positives may be treated more aggressively, earlier
Blood Flow Analysis
Paradigm/Dicon
 TonoPlus Tonograph

–
–
–
–
Pulsatile Ocular blood flow analysis
Identifies ocular ischemic syndromes
Reimbursable procedure
Small laptop size
Anti-Glaucoma Agents

Non-Selective B-Adrenergic Antagonists
–
–
–

Timolol (Timoptic 0.25%, 0.50%, XE, Istalol/Ista
Pharmaceuticals)
Levobunolol (Betagan 0.25%, 0.50%)
Metipranolol (Optipranolol 0.3%)
Selective B-Adrenergic Antagonists
–
–
–
Betaxolol (Betoptic-S 0.25%, 0.50%)
Levobetaxolol (Betaxon)
Carteolol (Ocupress 1.0%)
Anti-Glaucoma Therapy

Adrenergic Agonists
–
–
–
–
Dipivefrin (Propine 0.1%)
Epinephrine (Epinal,Eppy-N, Epifrin, Glaucon)
Apraclonidine (Iopidine 0.5%, 1.0%)
Brimonidine (Alphagan 0.2%, Alphagan P-0.1%, 0.15%) /
Timolol (Combigan)



41% less ocular allergy with Alphagan P vs Alphagan over 12 months
Only ophthalmic glaucoma drug without BAK
Cholinergic
–
Pilocarpine (Pilocar 0.50% - 8.0%, Pilogel 4%)
–
Carbachol (Carbachol 0.75%, 1.5%, 2.25%, 3%)
Echothiophate Iodide (0.03%, 0.06%, 0.125%, 0.25%)
–
Antiglaucoma - CAI

Topical
–
–
–

Dorzolamide (Trusopt)
Dorzolamide-Timolol (Cosopt)
Brinzolamide (Azopt)
Oral
–
–
–
Acetazolamide (Diamox)
Methazolamide (Neptazane, MZM)
Dichlorphenamide (Darinide)
Anti-Glaucoma Agents

Prostaglandin Analogue
–
–
–
–
–

Latanoprost (Xalatan 0.005%)
Bimatoprost (Lumigan 0.03%)
Travoprost (Travatan 0.004%/ Extravan with timolol 0.5%)
Travaprost (Travatan Z 0.004%) – No BAK
Unoprostone (Rescula 0.15%)
Pipeline
–
DE-085 (Santen) prostaglandin based; phase II
Profile of a Desirable Alternative IOP
Lowering Agent
BAK-free formulation
 Unsurpassed IOP-lowering efficacy
 Enduring IOP-lowering efficacy
 Well-tolerated
 Multi-dose bottle
 Same cost as current agents
 Anti-microbial activity meeting or exceeding
regulatory standards

G
Summary & Conclusion







Ocular Surface Disorder (OSD) has a significant presence in
the glaucoma population
OSD signs & symptoms are often under-appreciated by
doctors
Chronic, long term use of benzalkonium chloride (BAK)
contributes to OSD
Glaucoma patients are at an added risk of OSD
A BAK-free IOP-lowering medication is needed
Current BAK-free IOP-lowering alternatives have
significant limitations
TRAVATAN® Z Solution represents the first and only IOPlowering PGA medication without BAK
G
Low Tension Glaucoma


Compromised ocular blood flow
50% have a cause / find it / fix it
–
–
–
–
Past hx transfusions, bleed, hypovolemic
Medications: B-blockers, digoxin, digitalis
MRI: orbits & brain
R/O all cardiovascular causes of LTG


CBC/anemias, CA doppler, TEE, sleep studies, coagulaopathies (PTT), overly fit
(low BP)
Treatment
–
–
Decrease IOP, avoid B blockers, start with PG, bromonidine, CAIs last
resort
Ginko biloba 60mg/D: inc fluidity without affecting platelet
aggregation
Surgical Glaucoma Therapy
Argon Laser Trabeculoplasty (ALT, LTP)
 Selective Laser Trabeculoplasty (SLT)

–
–
–
–
Q switched Nd:YAG selectively targets pigmented
trabecular cells (increasing activity?)
Increases immune system by increasing monocytes &
macrophages in TM
Selective because it does not cause appreciable damage to
TM
50 confluent applications to 180 degrees @0.06mJ
 No
–
blanching or bubble phase needed
Addresses greatest roadblock = compliance with medical
therapy
Surgical Glaucoma Therapy
Trabeculectomy
 Trabeculectomy with surgical adjuncts

–
–

Indications
–
–
–
–

5 FU (lower risk eyes)
Mitomycin-C (MMC) – higher risk eyes
Maximum tolerated medical therapy
Progression of disease
Unable to instill medications
Secondary glaucomas (Neovascular glaucoma)
Consideration
–
–
–
–
Age, HTN, DM, Anticoagulants, Preop IOP, previous vitrectomy
Degree of visual impairment,
Lens status
Comorbidities
Surgical Glaucoma Therapy

Future directions
–
Newer antifibrinolytics
 CAT-12,
–
–
a monoclonal antibody to TGF-B2
Photodynamic therapy
Novel drug delivery systems
 Collagen
implants, bioerodable polymers, liposomes &
microspheres
–
Glaucoma drainage implants instead of filtering surgery
 Shunts
–
aqueous from AC tube through an episcleral plate
Ocular genetics
 Discover
genes, gene therapy, primary prevention of glaucoma
may become a reality
Glaucoma Pipeline
Extracellular Matrix metalloproteinases
 Oral neuroprotectants - Memantine (Nameda)
 Sustained release formulations
 Anecortave acetate (Retaane/Alcon) – ARVO 2006

–
–
–
–
Originally studied for ARMD
Steroid that actually LOWERS IOP
No cataract formation
25% decrease in IOP at six months after 1 juxtascleral
injection
Neurologic

Multiple Sclerosis
–
–
–
–
Glatiramer (Copaxone)
Interferon B-1b (Betaseron)
Interferon B-1a (Avonex)
Interferon B (Rufab)
effects – macular edema, CRVO, CRAO, CWS, optic
neuritis, papilledema
 Flu-like symptoms are common for 2 weeks
 Medications are given by injection
 Annual costs range from $12,000-$33,000/year
 Side
Neurologic

Optic Neuritis
–
Controlled High-Risk Avonex Multiple Sclerosis Study
(CHAMPS), Optic Neuritis Treatment Trial (ONTT)
 Initial
–
demylinating episode (like ON) treated with interferon
Conclusively showed that treatment with interferon slowed rate of
development of MS
 Do
not use oral steroids to treat ON
 Brain MRI obtained in all patients with ON
 If MRI abnormal IV/oral steroid regimen should be used
–
IV methylprednisolone 100mg q6h x 3d, followed by PO prednisone x 11
days
 Abnormal
MRI should be referred to neurologists for
consideration of interferon treatment
Neurologic

Optic Neuritis
–
–
–
–
–
Optic Neuritis Treatment Trial (ONTT)
Archives Ophthalmology 2003
Reported 10 year risk of developing MS is significantly
higher if there is a single brain lesion noted on MRI scan
at the time diagnosis (56% vs. 22%)
The overall 10 year risk is 38%
Male gender, no lesions on MRI and presence of disc
swelling places a patient at lower risk of developing MS
Neurologic / Psychiatric

Alzheimer’s Dementia – chronic, progressive
deterioration in global intellectual functioning. Familial
tendencies, associated with B- amyloid and organic
changes in the brain. 4.5 million Americans diagnosed
–
Research at Boston University
 2,581
patients
 79% reduction in risk of developing AD
 Statins reduce cholesterol by blocking enzyme HMG Co-A reductase
 Also interfere with production of B-amyloid
–
Current treatments target anticholinesterase, target amyloid
production and gamma secretase
Neurologic / Psychiatric

Alzheimer’s Dementia
–
–
–
–



Donepezil (Aricept)
Tacrine (Cognex)
Rivastigmine (Exelon)
Galantamine (Reminyl)
Experimental drugs with promise include Gleevec/Novartis
which targets proteins that regulate secretase, sage extract,
raloxifene, huperzin A (cholinesterase inhibitor, Chinese herb)
Combinations with Memantine (Namenda) are safe and effective
in moderate to severe AD
Regular exercise in midlife reduce risk of AD by 50% (Lancet
Neurol 2005)
–
20-30 minutes of exercise twice a week
Neurologic / Psychiatric

Alzheimer’s Dementia – 50% develop psychiatric and
behavioral symptoms
–
–
Anxiety, aggression/violent outbursts, paranoid thoughts
Treatment trials and “off-label” use of Depakote
 Inhibits
tangles and plaques
 May prevent psychiatric symptoms
–
Rule out UTI, thirst, hunger, pain, medication side effects
Neurologic / Psychiatric

Acute Ischemic Stroke
–
700,000/yr or one every 45 seconds
 500,000
–
–
new, 200,000 recurrent
164,000 deaths/yr, 3rd leading cause of deatths
Cost $56.8 billion in 2005
Risk factors – HTN, smoking, DM, artery diseases,
African-Americans twice prevalence
 Treatment

–
–
–
Alteplase (Activase)
Carotid artery stents – option in CA endarterctomy
Brain stents – Boston Scientific’s Wingspan
Theories on Aging and Eye Disease

Age related macular degeneration and cataracts are
associated with age
–
–
–
–
–
–
–

Leading causes of blindness worldwide
Elderly
Family history, gender, cardiovascular disease
Smoking – nicotine, benzopyrene, nickel, lead and arsenic
Light colored irides and hair
Exposure to UV radiation
Diet – saturated fat intake increases risk for AMD
Mechanisms – free radical damage, UV damage
AMD Risk Factors
Age > 60
 Race W>B
 Sex F>M
 HTN
 Smoking
 Nutrition
 Family History
 Fair complexion
 Cardiovascular disease

Neurologic

Multiple Sclerosis
–
–
–
–
Glatiramer (Copaxone)
Interferon B-1b (Betaseron)
Interferon B-1a (Avonex)
Interferon B (Rufab)
effects – macular edema, CRVO, CRAO, CWS, optic
neuritis, papilledema
 Flu-like symptoms are common for 2 weeks
 Medications are given by injection
 Annual costs range from $12,000-$33,000/year
 Side
Neurologic

Optic Neuritis
–
Controlled High-Risk Avonex Multiple Sclerosis Study
(CHAMPS), Optic Neuritis Treatment Trial (ONTT)
 Initial
–
demylinating episode (like ON) treated with interferon
Conclusively showed that treatment with interferon slowed rate of
development of MS
 Do
not use oral steroids to treat ON
 Brain MRI obtained in all patients with ON
 If MRI abnormal IV/oral steroid regimen should be used
–
IV methylprednisolone 100mg q6h x 3d, followed by PO prednisone x 11
days
 Abnormal
MRI should be referred to neurologists for
consideration of interferon treatment
Neurologic

Optic Neuritis
–
–
–
–
–
Optic Neuritis Treatment Trial (ONTT)
Archives Ophthalmology 2003
Reported 10 year risk of developing MS is significantly
higher if there is a single brain lesion noted on MRI scan
at the time diagnosis (56% vs. 22%)
The overall 10 year risk is 38%
Male gender, no lesions on MRI and presence of disc
swelling places a patient at lower risk of developing MS
Neurologic / Psychiatric

Alzheimer’s Dementia – chronic, progressive
deterioration in global intellectual functioning. Familial
tendencies, associated with B- amyloid and organic
changes in the brain. 4.5 million Americans diagnosed
–
Research at Boston University
 2,581
patients
 79% reduction in risk of developing AD
 Statins reduce cholesterol by blocking enzyme HMG Co-A reductase
 Also interfere with production of B-amyloid
–
Current treatments target anticholinesterase, target amyloid
production and gamma secretase
Neurologic / Psychiatric

Alzheimer’s Dementia
–
–
–
–



Donepezil (Aricept)
Tacrine (Cognex)
Rivastigmine (Exelon)
Galantamine (Reminyl)
Experimental drugs with promise include Gleevec/Novartis
which targets proteins that regulate secretase, sage extract,
raloxifene, huperzin A (cholinesterase inhibitor, Chinese herb)
Combinations with Memantine (Namenda) are safe and effective
in moderate to severe AD
Regular exercise in midlife reduce risk of AD by 50% (Lancet
Neurol 2005)
–
20-30 minutes of exercise twice a week
Neurologic / Psychiatric

Alzheimer’s Dementia – 50% develop psychiatric and
behavioral symptoms
–
–
Anxiety, aggression/violent outbursts, paranoid thoughts
Treatment trials and “off-label” use of Depakote
 Inhibits
tangles and plaques
 May prevent psychiatric symptoms
–
Rule out UTI, thirst, hunger, pain, medication side effects
Neurologic / Psychiatric

Acute Ischemic Stroke
–
700,000/yr or one every 45 seconds
 500,000
–
–
new, 200,000 recurrent
164,000 deaths/yr, 3rd leading cause of deatths
Cost $56.8 billion in 2005
Risk factors – HTN, smoking, DM, artery diseases,
African-Americans twice prevalence
 Treatment

–
–
–
Alteplase (Activase)
Carotid artery stents – option in CA endarterctomy
Brain stents – Boston Scientific’s Wingspan
Lung Cancer
Most caused by cigarette smoke (90%)
 25% of adult women smoke
 30% of high school women smoke
 13-22% of pregnant women smoke
 Cessation of smoking

–
–
–
–
–
Quit by 35 = 6-8 years of life expectancy
Quit by 44 = 6-7 years of life expectancy
Quit by 55 = 3-6 years of life expectancy
Quit by 65 = 1-4 years of life expectancy
55% decrease in heart attack after quitting for one year!
Smoking Cessation
1-7% chance of quitting without help
 Antidepressants

–

Bupropion (Wellbutrin/Zyban)
Nicotine replacement
–
–
–
–
–
Nicodern CQ Patch (Transdermal Nicotine 21mg, 14mg,
7mg steps over 10 weeks)
Nicorette Gum (2mg if <25 cigarettes/D, 4mg if >25
cigarettes/D)
Nicotrol Inhaler
Nicotrol Nasal Spray
Nicotrol Patch
Smoking Cessation

Best new option
–
Varenicline (Chantix/Pfizer)
 43.9%
quit vs 29.8% quit on bupropion
 Treatment is for 12 weeks, if successful take it 12 more weeks to
lessen chance of smoking again
 Blocks nicotine receptors in brain and stops “reward” associated
with smoking again
 Side effects – nausea is mild and tolerable but occurs at 32%, 3%
discontinued
Photodynamic Therapy for CNV

Intravenous infusion of photosensitiser
– Verteporfin (Visudyne/Novartis)
–

tin ethyl etiopurpurin (SnET2/Miravant)
Photoactivation - low level non- thermal 689nm light
within 15min after starting 10min IV infusion
–
50j/cm2 of NV lesion @ 600mW over 83secs
Photodynamic Therapy for CNV

Treatment spot =1000u larger than the Greatest
Linear Dimension (GLD)
–
–
–
allows a 500u border
established by IVFA & color photography
measure all classic & occult NV, blood +/- blocked
fluorescence, serous detachment of RPE
 maximum
spot size = 6400u
 recheck every 3 months & retreat if any CNV
–
Averages 3.4 treatments / year x 1 year
 avoid
exposure to bright light x 5 days
New for CNV

Intravitreal injection- (Pegaptanib / Macugen)

Selective VEGF antagonist for classic, occult, and mixed
forms on CNV
– Intravitreal injection every six weeks
– 70% lost <3 lines (27% treatment effect for loss of 3 lines
or more). Less effect in second year
– Complications include endophthalmitis, RD, cataract, IOP
spikes
Retrobulbar injection - Antecortave (Retaane /Alcon)
–
Intravitreal implant – (Fluocinolone / Retisert)
 Intravitreal implant – (Dexamethasone / Posurdex)

New FDA Approval for CNV
Vascular endothelial growth factor (VEGF/rhuFab V2,/
Lucentis / Avastin, Genentech)
–
–
–
–
–
–
Therapeutic antibody fragment that interferes/binds with
VEGF-A, a protein that plays a critical role in angiogenesis
Genentech renames rhuFab “Lucentis”
FDA approval for CNV in AMD
Proven efficacy in MARINA, ANCHOR, PIER & others
Intravitreal injection 0.5mg as 10mg/ml solution
Caution: Increased IOP, endophthalmitis, RD, cataract,
HTN, HA, thromboembolic events
New Ideas in AMD
Sub-subspecialty emerging in Retina
 Devices to measure Macular Pigment Optical Density

–
–

Macuscope
QuantifEye (ZeaVision)
Hyperacuity perimetry
–
Forsee PHP (Notal/MSS)
Zeaxanthin is considered important in supplementation
 Combination therapies more common in wet AMD

AMD Research on Genetics
Age related macular degeneration gene located
 Encodes for a protein called Compliment Factor H

–
–

Increases inflammatory proteins
Increases C-reactive protein
We now know a genetic component of the disease
exists!
Components of Ocular Supplements

Vitamins
–
–
–

Minerals
–
–
–

Zinc
Copper
Selenium
Macular pigments
–
–

Vitamin A as beta carotene
Vitamin C
Vitamin E
Lutein – macular carotinoid
Zeaxanthin – foveal carotenoid
Bioflavenoids
–
Ginko biloba – for AMD and glaucoma (blood flow) and memory
Treatment Modalities

Dietary Supplements
– TheraLife Eye & TheraLife Enhancer (TheraLife)
 Beta
carotene, bilberry, chrysanthemum, copper, fructus lycii,
Vitamin E & C, riboflavin (B2), selenium, semen cassiae, zinc
–
Hydrate Essential (Cynacon/Ocusoft)
 Essential
fatty acids - Flaxseed oil and bilberry extract
encapsulated in hydroxylated lecithin
–
HydroEye (Science Based Health)
 Blend
–
of omega fatty acids and nutrients
TheraTears Nutrition (Advanced Vision Research)
 EPA enriched
flaxseed oil & omega-3s
Nutritionals and OTC Vitamins



Ocuvite Lutein (B&L)
Ocuvite extra (B&L)
Ocuvite PreserVision (B&L)
–
–






AREDS NIH Study
2 tabs bid
ICAPS Lutein & Zeaxanthin Formula (Alcon)
ICAPS AREDS formula
ICAPS MV
I-Sense OcuShield (Akorn)
Maximize
EyePromise (ZeaVision)
Nutritionals
First degree relatives of ARM pts 2-4 times greater risk
of ARM compared to controls
 Twin studies show high levels of concordance of the
disease among monozygotic sibs
 Vitamin E may cause bleeding
 Vitamin D may be of benefit
 Diets high in omega-3 FAs are of benefit
 Control of weight, HTN & cholesterol is important
 Diet of green leafy vegetables increase lutein,
zeaxanthin which increase optical density of macular
pigment providing protective role

Measurement of Macular Pigment

Objective Techniques
–
–
–
–
–

Modified Fundus Cameras
Fundus Reflectence
Raman Spectroscopy
Autofluorescence Spectroscopy
Modified SLO
Subjective Techniques
–
–
HFP (Heterochromatic Flicker Photometry) (pschyophysical)
(Ability to detect a blue flickering light)
Is MPOD Related to AMD?
Three donor eye studies published, all show 30-50%
less pigment in AMD eyes vs controls
 Moran Eye Center (Bernstein) Raman method
 Manchester UK group HFP method found AMD patient
eyes had 50% lower MPOD
 Germans found 50% lower MPOD in dry AMD patient
eyes
 Dutch group did cross sectional prospective study using
reflectance and found no difference on MPOD in early
AMD

The AREDS I & II Formulations








AREDS (Age-Related Eye Disease Study)
Vitamin C: 500 mg*
Vitamin E: 400 IU*
Beta-carotene: 15 mg (May be listed on the label as “25,000 IU
vitamin A as beta-carotene) (eliminate!)
Zinc oxide: 80 mg (40 mg)
Copper: 2 mg (needed to prevent copper deficiency caused by
high dosage of zinc)
Lutein & Zeaxanthin 10 mg & 2 mg
Omega-3 fatty acids 1 gram
Nutritionals

EyePromise (ZeaVision)
–
Zeaxanthin 6mg
 in
–
–
–
–
–
–
–
–
the same 1:1 ratio as found in healthy macula
Lutein 6mg
Beta carotene – none
Vitamin C – 120mg
Vitamin E – 60 IU
Zinc – 15mg
Copper – none
Fish oil (omega-3) – 250mg
Alpha Lipoic acid – 10mg
Flaxseed Oil & Fish Oil
Flaxseed Oil thins meibomian gland oils and thickens
the oil layer, but does not suppress inflammation.
 Fish Oil suppresses inflammation, but does not thicken
the oil layer.
 Flaxseed Oil and Fish Oil work together synergistically
to stimulate tear and salivary gland secretion.

Special Flaxseed Oil, Special Fish Oil,
Special Vitamin E

Flaxseed oil (short-chain Omega-3s)
–

Fish oil (long-chain Omega-3s)
–

Organically grown, cold pressed, and ligand free.
Molecularly distilled/pharmaceutical grade.
Vitamin E
–
–
Includes just less than 200 IU of Vitamin E.
Includes gamma-tocopherol. Acts synergistically with DHA to
increase cellular resistance to apoptosis and suppress inflammation
TheraTears Nutrition
Vitamin E content
 Other Benefits of Vitamin E
–
–
–
–
Vitamin E prevents oxidation, maintaining the
integrity of the oils.
Long-term supplementation with omega- 3s
depletes serum levels of vitamin E.
Addition of vitamin E to TheraTears Nutrition
maintains serum levels of vitamin E.
Lacrimal-gland disease-based dry eye has
oxidative damage in the lacrimal gland and
depleted levels of vitamin E.
How Omega-3s Treat Dry Eye
Conclusions


Dietary deficiency of omega-3s
or imbalance of omega6:omega-3s can cause dry eye.
Flaxseed/Fish oil supplement
effective in treating dry eye and
dry mouth through
well-understood mechanisms of
action.
Visual Field 9208x
Bilateral
 Requires Interpretation

–
–
separate report form
narrative in body of medical record, on date of service
Fee $44.77- (-81) / $46.18
 Fee $58.29- (-82) / $59.09
 Fee $66.96- (-83) / $68.17

JAM
Why Is Early Diagnosis Important?
Earlier Diagnosis
Means Better
Final Visual Acuity
Lesion
size was a more
significant factor affecting
treatment benefit than either:

1. Lesion composition

2. Baseline visual acuity
TAP
and VIP Report 1, AJO, Sept., 2003
Average CNV Presentation

Average size:
–

Location:
–
–

80%
20%
Subfoveal
Extrafoveal
Initial Vision:
–
–
–
Olsen, TW Ophthalmology Feb. 2004
3300μ
20%
40%
40%
> 20/40
20/50 – 20/200
< 20/200
Inherent Faults of the Amsler Grid

Completion
–

Fixation
–

The Amsler Grid does not overcome
cortical completion
The Amsler Grid does not force
fixation
Crowding
–
Inhibition by neighboring peripheral
lines reduces detection
Foresee PHP™ Technology
Vernier Acuity
2 sec arc

The human ability to perceive
minute differences in the relative
spatial localization of two objects in
space

The brain is exceptionally sensitized
to the detection of small shifts in the
co-linear arrangement of
photoreceptors.
Hyperacuity

Snellen 20/15 Resolution
– 1minute of arc
– 0.017 degrees

Vernier Resolution
– Two seconds of arc
– 0.03 minutes of arc
– 0.00051 degrees
– The width of a pencil
viewed at 300 m !
The Future of AMD Monitoring
Foresee PHP™

Easy operation

Comfortable for patient

Noninvasive Rapid threshold test ~
5 min/eye

Automated results analysis

Generates visual field map of
disturbance patterns consistent with
the progression of AMD
Botulinum Toxins

Toxins type A to G
–
–

Blocks neuromuscular transmission by inhibiting the release
of presynaptic acetylcholine at peripheral neuromuscular
junctions
Local denervation produces paresis or paralysis with few
side effects, good duration of action
Approved for the treatment of focal muscle spastic
disorders and excessive muscle contractions, such as
dystonias, spasms, twitches, strabismus
Cosmetic Considerations

Nonsurgical treatments
–
–
–
Botox injections
Laser hair removal
Hyaluronic acid fillers

Restylane (Medicis)
–




Perlane (Thicker version waiting FDA approval)
Hyalform (Allergan)
Rejuvederm (Allergan)
Radiesse (Bioform Medical) – lasts twice as long
Surgical treatments – 12 million in 2005
–
–
–
Liposuction
Breast augmentation
Eyelid surgery
Thank you
McGreal Educational Institute
Missouri Eye Associates
Excellence in Optometric Education