Excellence in Optometric Education 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 jamod1@aol.com 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 Studies in fruit flies, mice, fish, now humans Present in red wine

Cardiovascular New Guidelines for Blood Cholesterol Treatment 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 National Cholesterol Education Program Adult Treatment Panel (NCEP ATP-III) – lipid management in USA is less than desirable <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 >20 years old = lipoprotein profile LDL, HDL, Triglycerides, total cholesterol, and BP Guidelines Total cholesterol <200 <200 (175) LDL <130 <130 LDL (high risk) <130 <100 (70) HDL >35 >40 Risk Factors Gender, age, smoking, high total cholesterol or LDL, low HDL, HTN, family history premature heart disease, & obesity

New Cardiovascular Concepts Risk Factors 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 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!

Prehypertension New Guidelines for Blood Pressure Control JAMA 5.21.03 National Heart, Blood, Lung Institute 45 million Americans have “prehypertension” BP = 120-139/80-90 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 Acute Coronary Syndromes Prevention Reteplace (Retavase) Eptifibatide (Integrilin) Tirofiban (Aggrastat) ASA (Bayer) 325mg chewed STAT Drug-eluting stents Prevention ASA 81mg (only 1/3rd of 62 milllion at risk in US use ASA) Reduces 1st 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) Diagnosis of DM Fasting glucose >126mg/dl Symptoms of diabetes and a random blood glucose of >200mg/dl after a 75g oral glucose tolerance test Intermediate categories (“Prediabetes”) – not DM but at substantial risk of developing type II DM and cardiovascular disease in the future 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.

Insulin Sensitizing Agents - DM 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 Troglitazone (Rezulin) Rosiglitazone (Avandia) * Pioglitazone (Actos) * Repaglinide (Prandin) New combination – Avandaryl qd Rosiglitazone (Avandia) & Glimepiride (Amaryl)

“Artificial Pancreas” for DM Paradigm system (Medtronic) – combination insulin pump and glucose monitoring system 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 “dead in the bed syndrome” in young Eliminates need for needle use to administer or test sugar levels $7,000. cost

Future Directions 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…. Fluocinolone acetonide implant (Envision TD/B&L) Vascular endothelial growth factor (VEGF) studies in PDR and ARMD Lucentis (Genentech) Macugen (Pfizer) DPP-4 inhibitors – new class of diabetes medications Januvia (Merck) - type 2 DM highly effective !! Galvus (Novartis) – (phase 3)

Blepharitis Therapy – Topical/Oral Cleeravue – M Convenience Kit Minocycline hydrochloride 50mg tablets SteriLid Eyelid Cleanser (Advanced Vision Research) Foam container 60 tablets of antibiotic StoneBridge Pharma, LLC Linalool – naturally occurring liquid distilled from plant oils 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 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 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 $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 $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 $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 $25.00 rebate Assistance program through www.rxhope.com

Dermatologic Therapy - Topical Low Potency Corticosteroids Hydrocortisone Cream 1.0% (Hytone) Triamcinolone 0.025% (Aristocort-A) Higher Potency Corticosteroids Betamethasone Valerate 0.1% (Valisone) Triamcinolone 0.1%, 0.05% (Aristocort-A) Mometasone 0.1% 15g/45g (Elocon) Non-steroidal anti-inflammatory Pimecrolimus 1% cream (Elidel) Tacrolimus 1% (Protopic) Antifungal 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 diluted to 20% by physiologic saline (empiric)/UV bottle Dosed at 6-10 X/D with additional AFTs Results 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

RPS Adeno Detector™ Test Procedure Assembling the Detector Locate the Test Cassette Assemble the detector by gently placing the sampling pad of the Sample Collector into the sample transfer window of the Test Cassette body. 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. 25

RPS Adeno Detector™ Test Procedure Running the Test 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. Immerse the Assembled Detector’s Absorbent Tip into the buffer vial for 15 seconds. 26

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 27

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 28

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 29

Antiviral Therapy - Oral Acyclovir (Zovirax 200/400/800mg) 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 Zoster Vaccine Live (Zostavax)

Levofloxacin Fluoroquinolone Indications Action – DNA gyrase Conjunctivitis, injuries, pre and post operative care, pneumonia, sinus, skin and skin structure, GI, GU Action – DNA gyrase Prevents bacterial replication Broadest spectrum, low toxicity, low resistance Left stereoisomer of ofloxacin, therefore similar solubility and actions Side effects – taste perversion Available as 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 Expanded spectrum fluoroquinolones Levofloxacin 1.5% (IQUIX / Santen/Vistakon) Levofloxacin (L-stereoisomer of ofloxacin) Dual mechanism of action Excellent solubility / penetration into cornea Indication – 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 4-6 hrs after retiring Dosage Day 4 through completion: q1-4h Supplied: 5ml white bottle with tan top

Ophthalmic Azithromycin: AzaSite AzaSite™ pairs DuraSite® drug delivery technology with azithromycin (1.0%) Azithromycin has not been previously used in ophthalmology A stable aqueous formulation is difficult AzaSite™: A stable, easily delivered formulation of azithromycin All the advantages of topical ophthalmic delivery Ophthalmic azithromycin, called AzaSite, pairs DuraSite drug delivery technology with azithromycin. Azithromycin has not been previously used in ophthalmology because a stable aqueous formulation is difficult to achieve. AzaSite is a stable, easily delivered formulation of azithromycin with all the advantages of topical ophthalmic delivery.

Glaucoma Evolution

Glaucoma Evaluation is Transforming In the past, detection & management relied on functional assessment Visual fields (white-on-white) Insensititve for detecting early POAG High degree of variability Recently, structural change over time longitudinal studies have validated the role of structural imaging Are structural defects with normal functional tests false positives or POAG? JAM

Glaucoma Suspect CPT / ICD 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 describe visible angle structures No limitations to diagnostic groups in most states Fee $25.71- JAM

Digital Gonioscopy 92020 SL-OCT (Heidelberg) 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

SL-OCTTM Hardware Features Non-contact Fast and easy to use Simultaneous optical and OCT exam Color or gray-scale images

Limitations of Manual Gonioscopy Patient discomfort – full globe contact Time consuming Subjective 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 JAM

92025 Corneal Topography ICD-9 Codes that Support Medical Necessity 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 ICD-9 Codes that Support Medical Necessity 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 With specular endothelial microscopy and cell count Ex: Konan specular microscope Bilateral Not Bundled Requires Interpretation and report Fee $101.04 JAM

Special Anterior Segment Photography 92286 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 JAM

Special Anterior Segment Photography 92286 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 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 Ocular ultrasound Ex: Accutome B Scan Plus Unilateral Not Bundled Requires Interpretation and report Fee $ JAM

Accutome B Scan Plus Model 24-6100 Portable High definition 0.015mm resolution (highest in industry) State-of-art probe design Plugs into any laptop or PC 2X full zoom Excellent software data analysis 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 JAM

CCT Assessment Has become standard Equipment widely available DGH was used in OHTS Low cost Consider potential effect of LASIK on IOP findings Also billable for non-glaucoma ICD-9 codes Corneal edema, keratoconus Given the strength of CCT in predicting the development of POAG in the OHTS, pachymetry should become a standard assessment for all patients with ocular hypertension. Devices suitable for office-based CCT measurement are currently available from several manufacturers. Keep in mind, too, that IOP measurements in patients whose corneas have been modified by LASIK may be artificially low.

Reichert IOPac Detachable probe Download PDR into Palm Portable, battery op. Stores up to 1000 pats. USB and infrared interface Down load to PC and printer Detachable probe Easily replaced if necessary Download PDR into Palm

Pachymetry IOP correction by correlation to corneal thickness is NOT POSSIBLE! 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 Example: Angle closure glaucoma multiple measurements over time Fee $55.91- JAM

PASCAL at work: Slit lamp mounted Technique similar to GAT but… Constant light pressure No fluorescein Self-calibrating Battery operated PASCAL mounted on the slitlamp‘s central axis. LCD displaying IOP and OPA (Ocular Pulse Amplitude), in mmHg. Quality factor „Q“ provides an assessment of the quality of the pulse curve segment used for computation. If a poor Q value is displayed, this would suggest to the user to perform a repeat measurement to verify the result obtained. Poor data may be obtained if the patient is not cooperative, or if the device is unable to establish proper contact with the cornea.

Pascal DCT Measures Stores data Ocular Pulse Amplitude (OPA) IOP Quality (Q) Heart Pulse (H) Stores data

The PASCAL SensorTip Contour-matched concave tip surface (7mm) Accurate for corneal radius 5.5-9.2mm and CCT 300-700 built-in pressure sensor (1.2mm) transparent tip permits view of cornea interface for centering and control (top) 3D drawing of the SensorTip, revealing the contoured, concave contact surface. The built-in pressure sensor appears as an opaque spot in the center of the contact surface. On the bottom of the tip, the electrical contacts which fit into the Main Unit‘s tip carrier can be seen. (bottom) View of the Cornea – SensorTip interface as seen through the slitlamp microscope at moderate magnification. In the center of the view, the pressure sensor obstructs the view of the iris. Around the opaque spot, the circular contact area can be seen nicely as a darker area in the color of the patient‘s iris. The surrounding area, where there is no contact with the cornea, apears lighter. In this picture, the conact area is not perfectly centered (it is displaced towards two o‘clock). However, it is sufficiently centered to provide a correct pressure reading.

Comparison of DCT With the GAT Univ. Of Zurich 228 eyes measure with DCT and GAT Compared IOP measurements Looked at effects of: 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

DCT vs. GAT Intra-observer variability Inter-observer variability GAT 1.1mm DCT 0.65mm Inter-observer variability GAT 1.28mm DCT 0.44mm Kaufman et. al. IOVS 2004; 45:3118-3121

IOP Measurements Using DCT After LASIK “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 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” This is a great quote for those in optometry that believe that adjusting IOP with CCT is some kind of standard. It isn’t. The only medical community you hear about this “standard” in is the OD community. The ophthalmology community does not look at it this way.

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. Normal optic nerves 2. Papilledema 3. Optic nerve drusen 4. Ocular histoplasmosis 5. Choroidal nevus

What tests are indicated? 1. VF / Pach / SCODI / Stereo disc photos 2. MRI 3. MRI / VF 4. Histoplasmosis titres 5. 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: 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) Bistratified ganglion cell (9%) short-wavelength cones Frequency doubling technology (FDT) Magnocellular ganglion cells Motion automated perimetry (MAP) 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 SITA-Standard 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.

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 Faster third generation algorithms reduce test time by 50% Customization for specific needs Early detection / established glaucoma / screening Early VF loss is often selective, with specific types of axons disturbed SWAP allows early recognition, HPRP follows progression SAP perimetry will continue to be preferred for established glaucoma with VFDs 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 377.9 unspecified disorder of optic nerve or pathways JAM

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? Moorfields Regression Analysis – measures rim area & adjusts for disc size 40% of patients flagged at baseline as “outside of 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 non-proliferative DR

What is the diagnosis? Papilledema 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 MRI of brain and orbit Must confirm elevated CSF 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, ASA NKDA BVA: 20/80 OD 20/100 OS PERRL No APD EOM: Full EXT: W&Q SLE: nl, IOP: 13 OU Fundus: as pictured

What is the diagnosis? 1. Epiretinal membrane 2. Cilioretinal artery occlusion 3. Macular drusen 4. Macular hole – full thickness 5. Macular hole – partial thickness

What eye test would you order now? 1. IVFA 2. Visual fields 3. RTA 4. 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. Epiretinal membrane 2. Cilioretinal artery occlusion 3. Macular degeneration – atrophic type 4. Cone dystrophy 5. 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 Volume of Cup Dimensional Information 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 Oral Dorzolamide (Trusopt) Dorzolamide-Timolol (Cosopt) Brinzolamide (Azopt) Oral Acetazolamide (Diamox) Methazolamide (Neptazane, MZM) Dichlorphenamide (Darinide)

Anti-Glaucoma Agents Prostaglandin Analogue Pipeline 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 A topical IOP-lowering medication with the above profile would be desirable. 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 IOP- lowering 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 5 FU (lower risk eyes) Mitomycin-C (MMC) – higher risk eyes Indications 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) Side 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

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) Side 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

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 Vitamin A as beta carotene Vitamin C Vitamin E Minerals Zinc Copper Selenium Macular pigments 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 Discuss zinc and beta carotene issues

Nutritionals EyePromise (ZeaVision) Zeaxanthin 6mg Lutein 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) Organically grown, cold pressed, and ligand free. Fish oil (long-chain Omega-3s) 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 omega-6: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 Early diagnosis is important since it has been established that the most significant predictor for treatment benefit is initial lesion size. This means that the earlier a lesion is diagnosed, the better the final visual outcome.

Average CNV Presentation Average size: 3300μ Location: 80% Subfoveal 20% Extrafoveal Initial Vision: 20% > 20/40 40% 20/50 – 20/200 40% < 20/200 Olsen, TW Ophthalmology Feb. 2004

Inherent Faults of the Amsler Grid Completion The Amsler Grid does not overcome cortical completion Fixation The Amsler Grid does not force fixation Crowding Inhibition by neighboring peripheral lines reduces detection

Foresee PHP™ Technology Vernier Acuity 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. 2 sec arc

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 ! Hyperacuity is the ability to describe localization; the human ability to localize an object with respect to other objects in space. For example, if we connect all the dots on the right with a virtual line, we can easily see that one of the dots is misaligned. How good is our ability to see such deviation? In the foveal area, it is about 3-6 sec of an arc - 10 times greater than the sensitivity of resolution. Format

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 Insert product-in-use shot again

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

Excellence in Optometric Education Thank you McGreal Educational Institute Missouri Eye Associates Excellence in Optometric Education