EVERYTHING

THERAPEUTIC-PART II

• Bruce Onofrey, OD, RPh, FAAO

• Professor, University of Houston

• UEI

Allergy, So What? What’s the

big Deal??

• Financially it IS a BIG DEAL!

• Billions of lost productivity

• Billions on treatments

• Lost revenue on CL fits

• Extra chair time

• Allergy is not a problem, it is an

opportunity

• Patients doctor shop to find someone that

has a strategy to control their SX

THE TRICK TO SUCCESSFUL

MANAGEMENT OF A CHRONIC

ILLNESS?

• THE PATIENT MUST KNOW THEY CAN’T

BE CURED

• THE DOCTOR MUST KNOW THAT THEY

CANNOT CURE THE PATIENT

• STAGE THE DISEASE

• PICK A TREATMENT THAT FITS THE

LEVEL OF DISEASE

• BE AGGRESSIVE WHEN NECCESSARY

So, What’s New?

• Better understanding of immune

mechanisms

• User friendly, “multi-tasking drugs”

• Safer, more effective therapy

• Better understanding of disease means

better patient counseling

THE MAJOR PLAYERS

1

• Histamine: Immediate

hypersensitivity

reaction; Itching,

swelling and hyperemia

• Primarily seen in

seasonal allergy

• No permanent tissue

damage-minimal

inflammation except in

extreme cases

THE MAJOR PLAYERS

2

• Eosinophils-Nasty little

WBC’s full of “ACID”

(Major basic protein)

• Attracted by release of

PAF (platelet activating

factor) and ECF

(Eosinophilic chemotactic

factor)

• Produce permanent tissue

changes seen in VKC and

GPC

EOSINOPHILIC TISSUE

CHANGES

ELVIS LIVES

DO YOU WANT STEROIDS

WITH THAT?!!!

Shield Ulcer

I thought Restasis was only for dry

eye• May have value in Vernal/AKC

(concentration)

• T cell modulating agent

• Equivocal results in studies

• Potential as a steroid sparing agent

THE MAJOR PLAYERS

3

• PRODUCTS OF ARACHADONIC

ACID DERIVED FROM THE MAST

CELL MEMBRANE

• PROSTAGLANDINS

• LEUKOTRIENES

• STIMULATE LATE PHASE T-CELL

RESPONSE SEEN IN AKC AND GPC

PROSTAGLANDIN AND

LEUKOTRIENE RESPONSES

OK, You Experts-Grade the GPC

Range is Grade 0-IV

• Two identical twins

• Multiple drug allergies, asthma and

acne

• Non-disposable CL’s-NOT disposable

• ONLY THREE YEARS OLD-per

mom-Child abuse???

• Nice brown tint to CL’s

• Same disease As 16th president

• What did they look like??I didn’t say 0-10

ASK YOURSELF THE

FOLLOWING QUESTIONS

• What am I treating-a histamine response

or an inflammatory response?

• What is the severity (stage ) of the

disease?

• What do I start treatment with and what

is the best maintenance therapy?

IT DOES IT ALL

-SAFELY?-

• Extremely effective

• Anti-inflammatory

• Cures everybody

• Fewer side-effects-

”soft steroid”

• How long do I use it

for??

• Maintenance drug??

ARE THERE TOPICALS

BESIDES THE EYE DROPS

YES OH HAIRY NOSED ONE

• Do what allergists do

• Nasal sprays before orals

• Mast cell inhibitors or long

acting steroids

• Safe

• Effective

• Synergistic with eye drops

• Safer than orals

Hey-I want to prescribe the big

guns- ORALS

Just hold your pants Dog

Breath

IF YOU MUST USE ORALS-

USE THE MOST FLEXIBLE

ONE

NOOOOOOOOOOOOOOO

Oral antihistamines should be avoided in

contact lens patient due to their_________

side-effects

• 1. Parasympathetic

• 2. Cholinergic

• 3. Parasympatholytic

• 4. Anticholinergic

• 5. Sympathetic

Oral antihistamines should be avoided in

contact lens patient due to their_________

side-effects• 1. Parasympathetic

• 2. Cholinergic

• 3.Parasympatholytic@@@@@

• 4. Anticholinergic@@@@@

• 5. SympatheticNever TX systemically

when topical therapy is

safer and more effective

Anticholinergic is a bad

word

Allegra

Indications/Dosage forms

• Indications:

• Seasonal allergy not responsive to topical

or nasal therapy

• Dosage forms:

• 60mg tablets-Adults BID

• Kids: 30mg tabs BID

• 180mg SR once daily for adults

• Zyrtec and Claritin: Adult dose = Kids

dose for 6 y/o and above@@@@

Allegra

• Non-sedating anti-histamine

• Good efficacy

• Minimal drug interactions

• No fatal interactions with erythromycin

or ketaconazole (Seldane and

Hismanyl)@@@@

• Dose can be titrated

How about ocular anaphylaxis?

Know your lipids

Singulair

• Leukotriene inhibitor

• No anticholinergic side-effects

• Safe in kids

• Once daily

• Lots of dosage forms:

• 4 and 5mg chewable tabs

• 4mg granules

• 10mg tablet

The Ideal Anti-infective

• Effective and selective

• Bacteriocidal

• Not destroyed by enzymes

• Rapid absorption

• No allergies

• Compatible with other drugs

• High therapeutic index

• Should not be toxic

It’s about time we had a

replacement for erythromycin

ointment

Clarithromycin for experimental Staphylococcus aureus keratitis.

Hume EB, Moreau JM, Conerly LL, Cannon BM, Dajcs JJ, Hill

JM, O'Callaghan RJ

Department of Microbiology, Immunology, and Parasitology, LSU

Medical Center, New Orleans, LA 70112, USA.

CONCLUSIONS: Clarithromycin proved to be an effective ocular

medication for the therapy of experimental S. aureus keratitis. The

effectiveness of clarithromycin in this model and its known

effectiveness for a variety of bacterial pathogens suggests a role for

this drug as a useful ocular antibiotic.

Azasite• Good theoretical activity

• Broad spectrum

• Bacteriocidal

• Needs enhanced vehicle for

increased contact with eye

• Occassional visual blur

• DOC for blepharitis

• Good for MRSA

DON’T TX KIDS LIKE

LITTLE ADULTS: Pediatric

conjunctivitis plays by different

rulesDon’t treat pediatric conjunctivitis without

first:

• Check history

• Check ears

• Check throat

• Check temperature

• Orals for conjunctivitis??

Hemophilus TX Options

• Amoxicillin

• 25-45mg/kg if

less than 40kg

• Macrolide

• Cephalosporin

“But Doctor, I’m Allergic to

Penicillin”

15 Y/O female presents with

mom-C/O red eye-Simple

Right??• Has seen one

nurse practitioner

• Has seen Two

Optometrists

• Tx with Ciloxan

• Tx with Tobradex

• Mom wonders

why nobody can

cure her daughter

Zithromax

Azithromcin• Broad spectrum activity

• 68 hour 1/2 life

• DOC in penicillin sensitive patients

• Effective in pediatric Hemophilus

• Mild-medium GI side effects

• Excellent compliance (5 day TX) (1 day

for chlamydia)

• Moderate cost

• Drug Interactions??

Pediatric dosing-azithromycin

• 5 day: 10mg/kg day 1, then 5mg/kg

• 3 day: 10mg/kg daily

• 1 day: 30mg/kg

In adults-Viral

conjunctivitis is the #1

Cause of

Acute INFECTIOUS

Conjunctivitis@@@@

Viral Pathogens

• Adenoviral

• Herpes simplex

• Herpes zoster

Adenoviral Signs

• Follicular conjunctivitis-

Variable most common in

lower fornix

• Mild to moderate chemosis

• Lid swelling with mild ptosis

• Lymphadenopathy in 66%

EKC SIGNS

• Papillary response of upper tarsal

conj.

• Subconj. Heme

• Pseudomembrane and conjunctival

scarring-Severe form

• Subepithelial infiltrates-Severe form

Is there a Cure for the

Common Cold of the

eye?• Spit and swish: Povidone 5%

ophthalmic solution

• Don’t spare the steroids

Herpes Simplex• Primary disease

• Recurrent disease

Conjunctivitis

Keratitis

• Stromal disease

• Kerato-uveitis

A TALE OF 3 ULCERS

BAD

WORSTER

BOING!!!!-POST-OP LASIK ULCER

ARE A DIFFERENT ANIMAL

WORSTEST

Respond To This Statement

The current standard of care is

to culture ALL suspected

bacterial corneal ulcers

A. TRUE

B. FALSE

What is The Standard of Care?

It’s whatever the expert witness

say’s it is!!

To test or not to test?Which Tests?

ARE ALL ULCERS TREATED THE SAME?

Culturing: The 1,2,3,4 Rule

• 1: Less than +1 anterior chamber RX

• 2: Less than 2 mm in size

• 3: At least 3mm from optic axis

• 4: Less than 1/4 depth of cornea

Differential DX of Infection

The Tests

• Cultures

• Diff-Quick

• Gram Stain

Gram Stain (FAST)• Differentiates bacteria by differences in

cell wall morphology@@@@

• Designates bacteria as Gram (+) or (-

)@@@@

Bacterial Ulcer Guidelines

• Always culture if you have the means

• Patients that get better never sue-those that don’t-DO

• Consider the 1-2-3-4 rule

• Fluoroquinolone mono-therapy is not fool-proof

• Grade the ulcer-Location, location, etc

• Step TX based on cultures

Antibiotic Pharmacology: The Next

Generation

ENGAGE

The “NEXT GENERATION”

fluoroquinolones are Miracle Drugs

GROWS HAIR!!!

• MAKES YOU

SMARTER

Evolution of the Quinolones

NalidixicAcid

Norfloxacin

Lomefloxacin

Ciprofloxacin

Ofloxacin

Sparfloxacin

Grepafloxacin

Levofloxacin

Gatifloxacin

Moxifloxacin

Limited spectrum

of activity

Extended spectrum

Enhanced activity against

Gram-negatives

Extended spectrum

Enhanced activity against

Gram-positives, streptococci,

anaerobes, atypical

mycobacteria

Improved pharmacokinetic

properties

H3

C N

C2H5

N

O

COOH

HN

N

F

N

O

COOH

NH3C-

N

F

CH3

N

O

COOH

O

N

H

OCH3

F

N

O

COOH

HN N

H

H

American Pharmaceutical Association; 2000.

Fourth-Generation Fluoroquinolone Chemical Structures

HN

OCH3

F

N

O

COOH

N

H

H

MoxifloxacinGatifloxacin

HNOCH3

F

N

O

COOH

NH3C

•1.5 H2O

Potency of Fluoroquinolones: MICs of 18

Fluoroquinolone-Resistant

Endophthalmitis Isolates*

Mather R, et al. Am J Ophthalmol. 2002;133:463-466.

0

10

20

30

40

50

60

70

Cip Ofx Lev Gat Mox

Med

ian

MIC

(µg

/mL

)

Coag-negStaphylococcusS aureus

Then and now-TX of Bacterial

keratitis

• Cephalexin 50mg/ml

• Tobramycin 13.5mg/cc

• These are fortified compounded meds

• Highly toxic and

• OBSOLETE

What percentage of all bacterial corneal

ulcers in a major study were successfully

treated with ciprofloxacin mono therapy?

• 1. 55%

• 2. 82%

• 3. 96%

• 4. 98%

• 5. 100%

What percentage of all bacterial corneal ulcers

in a major study were successfully treated with

ciprofloxacin mono therapy?

• 1. 55%

• 2. 82%@@@@

• 3. 96%

• 4. 98%

• 5. 100%

The greatest resistance to the drug is

in which type of bacteria?

• 1. Gram positive

• 2. Gram negative

which type of bacteria?

• 1. Gram positive@@@@

• 2. Gram negative

Sensitivity Profiles for Gram Positive Isolates

2001 (N=248) (Alvarez data, Bascom-Palmer)

67

66

64

90

32

67

100

88

0 20 40 60 80 100 120

penicillin

cefazolin

vancomycin

gentamicin

levofloxacin

ciprofloxacin

ofloxacin

trimethoprim

% sensitive

Reduced fluoroquinolone GR + activity

Gram-Positive Organisms

• 90% of ocular infections

S aureus

Staphylococcus epidermidis

Streptococcus pneumoniae

Coagulase-negative

staphylococci,Streptococcus

viridansLimberg M, Buggé C. Cornea. 1994;13:496-499.

The Latest MUST BE THE

GREATEST• Moxeza: Moxafloxacin

• Zymaxid: Gatafloxacin

• BUTTTTTTTTT:

• THEY DON’T WORK AGAINST MRSA

• Trust me-the trust 2 study states 15% efficacy against MRSA

For MRSA-Forget the

Fluoroquinolones

Back to the OLD Drugs

• Trimethoprim (not just for kids)

• Tobramycin

• Vancomycin

ANTIBIOTIC

RESISTANCE

RESISTANCE IS FUTILE

BACTERIA ARE SPEED

DATERS• Bacteria reproduce very quickly

• Eschericia coli can complete a life cycle in

30 minutes

Antibiotic ResistanceAPPEARANCE

DRUG INTRODUCTION OF RESISTANCE

Penicillin 1943 1946

Streptomycin 1945 1959

Tetracycline 1948 1953

Erythromycin 1952 1988

Vancomycin 1956 1988

Methicillin 1960 1961

Ampicillin 1961 1973

Cephalosporins 1964 late 1960’s

Selection favoring Resistance(1) Incomplete treatment: people fail to finish the full

course of their medication

- in the 1980’s, tuberculosis was almost wiped out w/

antibiotics

- in 1990’s, came back with a vengence, due to

resistant strains

- 25% of previously-treated tuberculosis patients

relapsed with drug

(2) Livestock doping: 50% of antibiotics used by

livestock farmers to increase yield of chicken, beef,

pork

Selection favoring Resistance(3) Mis-prescription: Mom demands antibiotics

for a cold

- widespread inappropriate use: up to 50% of

prescriptions are for viral infections that cannot

respond

(4) Gene transfer & multi-drug resistance

(a) genes encoding resistance accumulate on

plasmids

confer simultaneous resistance to

multiple drugs

(b) DNA is easily exchanged between bacteria

RESISTANT BACTERIA

• Methicillin resistant Staphylococcus aureus

• Enterococcus Fecalis (group DStreptococcus)

• Strep pneumoniae

• Haemophilus influenzae

• Aminoglycoside resistant Pseudomonas aeruginosa

• Beta lactamase producing Neisseria

• Atypical Mycobacteria

THE CORNEA “DREAM

TEAM”

CORNEAL INFLAMMATION

INFECTIOUS VS NON

DLK INFECTION

Survey #1 Survey #2 Survey #3

2001 2004 2008

8600 Surveys

RESPONSE:

56 docs reported

116 infections

Approx 340K

procedures

Incidence 1/3K

9129 Surveys

RESPONSE:

• 46 docs reported

48 infections

100K procedures

Incidence 1/2K

8500 Surveys

RESPONSE:

14 docs

reported

19 infections

21K procedures

Incidence 1/1K

Risk factors

• SURGERY

• EPITHELIAL DEFECTS

• EXCESSIVE SURGICAL

MANIPULATION

• INTEROPERATIVE

CONTAMINATION (ICE)

• DELAYED RE-EPITHLIALIZATION

• STEROIDS

Dominant Pathogens• 2001: Mycobacteria 48%

• 2004 GR (+) Staph/Strep sp

• 2008 MRSA 28%

2008

EARLY INFECTIONS (2 WEEKS POST-OP

STAPH (MRSA AND NON-MRSA}

STREP

LATE INFECTIONS ( > 2 WEEKS)

MYCO (NON-TB)

NOCARDIA

FUNGAL (NOTE, 9-19%!!) PRK AND STEROIDS!!

INCIDENCE BY PROCEDURE• % OF TOTAL PROCEDURES

• PRK 20%

• LASIK c KERATOME 50%

• LASIK/FEMPTOSEC. 28%

• 2.5 X > c PRK VS KERATOME

• 6 X > c PRK VS FEMPTOSEC

• 2.4 X > KERATOME VS FEMPTO

• PRK BADDDD

• FEMPTO GOOOOOD

MANAGEMENT• CULTURE CULTURE CULTURE

• SENSITIVITIES

• GRAM STAIN• LATE INFECTIONS R/O FUNGAL

TREATMENTONLY AFTER LIFTING FLAP, SCRAPING AND

CULTURING

EARLY1. Irrigate flap with

vancomycin 50mg/cc

2. 4th gen FQ Q 5MIN X 3 DOSES, THEN Q 30MIN ATC

3. ALT WITH VANCOMYCIN 50MG/CC Q 30MIN ATC

4. DOXY 100MG BID PO

LATE1. IRRIGATE FLAP WITH

AMIKACIN 50MG/CC OR CLARITHROMYCIN 10MG/CC OR AZITHROMYCIN 2MG/CC

2. 4TH GEN FQ Q 5MIN X 3, THEN Q 30MIN ATC

3. ALT WITH AMIKACIN 50MG/CC ATC

4. DOXY 100MG BID PO

5. MYCOPLASMA-4TH GEN FQ

6. R/O FUNGUS AND AMEOBIC

THE MOST IMPORTANT MEDS

FOR POST-OP CARE

• AMIKACIN-BETTER THAN

TOBRAMYCIN-THE 4TH GEN

AMINOGLYCOSIDE

• CLARITHROMYCIN

• VANCO FOR MRSA

Azithromycin injectable

• 500/X = 2mg/1cc

• 2X = 500

• X = 250CC solution

DON’T FORGET THE IMPORTANCE

OF PRE-OP INFECTION MGT

• Key point

– Avoid surgical procedures on infected tissues unless necessary

– Treat infections prior to performing a minor surgical procedure

• e.g. Treat blepharitis prior to performing refractive surgery

84

PRE-OP DISINFECTION

OPTIONS

• Designed to sterilize surfaces: Toxicity

and poor tissue penetration (ionic)

• Marked efficacy against many forms of

pathogens

• May be to toxic for use in eye unless

markedly diluted

• Hexachlorophine 3%

• Povidone Iodine 5-10%

85

Hexachlorophine

An excellent skin cleanser-Careful

around the eye

• Very sparing use for lid infection

• Not for blepharitis

• Short term

• Avoid getting in eye

AVENOVA 0.01% HYPOCHLOROUS ACID:

EVEN MORE GREEDY THAN MYLAN-THE

FOLKS THAT BROUGHT YOU THE $600 EPIPEN

• Sold as a prescription drug!?

• Let’s tap into the insurance

• Approximately $250.00 for

40ml/patient pays $60.00

• Great economics

1 GALLON-3.78 LITERS 0.046%

$24.98 ON AMAZON

• 0.046/0.01= 4.6 dilution factor

• 3,780ml X 4.6 = 17,388ml/40 =

• 435 (40ml) bottles of 0.01%

• = 24.98 /435 =

• 6 cents per 40ml

Better Choice: Ocusoft

Hypochlor 0.02%

• $24.00 per 12 oz

• No RX

• Double strength

• NO RIP-OFF TO

SYSTEM

YEEEEEECH

RATING DEMODEX

• 1 is mild, with CD present on fewer

than 5 lashes

• 2 is moderate, with CD present on 5-

9 lashes

• 3 is severe, with CD present on 10 or

more lashes.

Anterior blepharitis

92

Reducing Preoperative

Ocular Surface Flora

• Skin preparation

– Apply 5%-10%povidone-iodinescrub

• Conjunctival preparation

– Apply 5% povidone-iodinesolution1

– Apply a topical antibiotic2

1. Speaker MG, Menikoff JA. Ophthalmology. 1991;98:1769-1775.

2. Apt L, et al. Ophthalmology. 1989;96:289-292.

Photo courtesy of Michael E. Snyder, MD.

DR. ONOFREY-”CAN I GET

LASIK??!!!!!”

THE PHARMACOLOGY OF

GLAUCOMA-The New Paradigm

Evidence based medicine is in

What’s New in Glaucoma?

BOYS AND THEIR TOYS

THE TOYS-Our new (and

expensive) machines

OCT-

SEXY

GDX-

COOL

SWAP-

WOW

HAND HELD

PACHYMETER

WOW-WOW

NOW THAT’S COOL-

WOW-WOW-WOW** AND IT’S ALL MINE

We have all these nifty new drugs-

More on the drugs later

• Xalatan

• Lumigan

• Travatan Z

• Trusopt

• Azopt

• Cosopt

• Alphagan

• Combigan

BUTTTT….The REAL Advancement

isn’t technological ie drugs and

equipment, IT’s…IT’s…(WAIT FOR IT)

• KNOWLEDGE !!

• ie. INDIVIDUALIZED RISK

ASSESSMENT

The impact of clinical research on

current glaucoma management

• Who we treat and who we watch

• Initial drug selection/ maximizing drug combinations / max medical therapy

• How we (most accurately) assess disease progression

• The relationship between IOP and BP in GLC patients

• Evaluating and resolving similar studies with differing outcomes (sponsor bias?)

Topics to be covered

• Determining risk of developing glaucoma

• Determining risk of glaucoma progression

• Identification and prioritization of new

glaucoma risk factors

• New drug selection criteria

• WORLD PEACE-KUMBIYA

Live and die by studies-both good

and bad: Evidence based GLC

management

• OHTS

• EMGT

• AGIS

• ASRANI

• NTG

• LALES

• DPP

How have they altered our

approach to glaucoma?

A NEW standard of care?

The lawyers say yes

Significant Baseline Predictive Factorsfrom Multivariate Proportional Hazard Models

Age (decade)

Diabetes Mellitus

IOP (per mmHg)

CCT (per 40 µM decrease)

PSD (per 0.2 dB increase)

Horizontal C/D Ratio (per 0.1

increase)

Vertical C/D Ratio (per 0.1

increase)

1.22 (1.01, 1.49)

0.37 (0.15, 0.90)

1.10 (1.04, 1.17)

1.71 (1.40, 2.09)

1.27 (1.06, 1.52)

1.27 (1.14, 1.40)

1.32 (1.19, 1.47)

Hazard Ratio (95% CI)

0.0 1.0 2.0 3.0 4.0 5.0

I’m a clinician, so let’s talk patients

TWO Patients ( a priest and a lawyer) with

the same med HX walk into a bar

• 54 Y/O WT M presents for general exam/DM eye evaluation

• FM HX DM, HTN

• FM EYE HX-NEG

• Patient Med HX:

Type II DM X 5 Yrs-A1-C = 7

BP controlled with TX = 125/65

Lipitor for elevated lipids

• No allergies

Significant eye findings

• IOP’s: 26/24@

9AM

• C/D: 0.5/0.5 OU

• VF: 30-2

NML VF’s & Discs c elevated

IOP’s……TX??

Hold the thought

POAG Endpoints by Central Corneal Thickness

and Baseline IOP (mmHg) in Observation Group*

Baseline IOP (mmHg)

Central Corneal Thickness (microns)

* through 8 Nov 2001

< 23.75

>23.75 to < 25.75

>25.75

< 555 >555 to < 588 >588

17% 9% 2%

12% 10% 7%

36% 13% 6%

Vertical C/D Ratio

Central Corneal Thickness (microns)

* through 8 Nov 2001

< 0.30

>0.30 to <0.50

>0.50

< 555 >555 to < 588 >588

15% 1% 4%

26% 16% 4%

22% 16% 8%

POAG Endpoints by Central Corneal Thickness

and Baseline Vertical C/D Ratio in Observation Group*

Back to our ocular

hypertensive patient’- (s)

• Guy #1: Pachymetry = 595/600

• Risk of conversion to GLC in 5 years =

2 - 6% monitor

• Guy #2 Pachymetry = 495/501

• Risk = 17 – 36% TREAT

• OHTS Individualizes risk@@@@

EMGT-Early Manifest Glc Trial ( NEI and

Swedish Res. Council-Anders Hiejl 2002)

• 6 year study of TX VS non-TX of early glc

patients with IOP</= 30 and minimal VF defect

N = 255 TX: Betaxolol and ALT-AVG 25%

drop in IOP

• TX lowered risk of progression by 10%/mm

drop in IOP-

• TX lowered early damage seen in control group

• Risk increased with higher IOP, greater field

defects, exfoliation and recurrent disc heme

• First sign of progression VF-86%, Disc change

1%, Both 13% / NNT = 6

Risk factors for progression

• Treatment halved the risk of progression

• Risk lowered by 10% with each 1.0 mm of Hg reduction

from baseline to the first visit at 3 months

• First IOP at 3 months’ visit

• Progression occurred earlier (48 months) in untreated

versus treated group (66 months)

• Percent of patient follow-up visits with disc

hemorrhages was directly related to progression

OK, OK-The OHT’s and EMGT Study

proved that lowering IOP is important in

reducing the risk of:

1. Oc. Hypertensives developing GLC

2. Early GLC patients losing Vision (VF)

How low do we go?

<18

YOU GOT A BETTER NUMBER?

Lower IOP Stabilizes Glaucoma Progression

% of

Patients

100%

0%

20%

40%

60%

80%

12/13 14/15 16/17 18/19 20/21 22/23

Intraocular Pressure (mm Hg)

Glaucoma Stable Glaucoma Progressing

Additional Support (AGIS):“The AGIS data support the suggestive evidence from earlier studies

that achieving low levels of intraocular pressure slows the progression

of glaucomatous optic neuropathy”

Adapted from: Mao LK, et al. Am J Ophthalmol 1991;111:51-55.

(AGIS):7 Amer Jrl Ophthalmol 2000;130(4):429-440

Maximize patients with IOP 17

LALES Study

C/D Ratio as screening tool

• Los Angeles Latino Eye Study

• Comprehensive evaluation for predictors

of eye disease in this population

• 6,357 latinos over 40Y/O

• Vertical C/D > 0.6 cutoff for glc screening

• 92.3% sensitive for glc

• 95.3% specificity for glc

Both healthy eyes and eyes with glaucomatous changes showed

higher nocturnal supine IOP than diurnal sitting IOP

Supine IOP is higher than sitting IOP, regardless of time of day

Healthy habitual IOP

IOP Is Higher at Night (US)

IOP

(m

m H

g)

Glaucoma habitual IOP

3:30

AM

3:30

PM

5:30

PM

7:30

PM

9:30

PM

11:3

0 P

M

1:30

AM

5:30

AM

7:30

AM

9:30

AM

11:3

0A

M

1:30

PM

252423222120191817161514

26

Clock Time

n=24

Nocturnal

Supine

Diurnal SittingDiurnal SittingNocturnal

Supine

Diurnal SittingDiurnal Sitting

Clock Time

1:30

PM

IOP

(m

m H

g)

252423222120191817161514

26

3:30

AM

3:30

PM

5:30

PM

7:30

PM

9:30

PM

11:3

0 P

M

1:30

AM

5:30

AM

7:30

AM

9:30

AM

11:3

0 A

M

n=24

Liu et al. Invest Ophthalmol Vis Sci. 2003;44:1586-1590.

Ha

bit

ua

l IO

P (

mm

Hg

)

28

26

24

22

20

18

16

14

3:3

0 P

M

5:3

0 P

M

7:3

0 P

M

9:3

0 P

M

11

:30

PM

1:3

0 A

M

3:3

0 A

M

5:3

0 A

M

7:3

0 A

M

9:3

0 A

M

11

:30

AM

1:3

0 P

M

Clock Time

Sitting Supine Sitting

No treatment

Liu, Kripke, Weinreb. Am J Ophthalmol. 2004;138:389-395.

Timolol gel

No Nocturnal IOP Lowering with Timolol

17

18

19

20

21

22

23

24

25

9am 12pm 3pm 6pm 9pm 12am 3am 6am

Baseline Brimonidine 0.2%

IOP

(mm

Hg)

Brimonidine 0.2% minimally effective at night

Adapted from Orzalesi N, et al. Arch Ophthalmol 2003;121:453-457

- All IOP measurements taken in the sitting position

- Brimonidine dosing at 8am and 8pm

-2

-2.5

-3.9

-5

-4

-3

-2

-1

0

Ch

an

ge i

n I

OP

(m

m

Hg

)

Alpha Agonist Beta-Blockers CAI

O’Connor DJ, et al. Am J Ophthalmol. 2002;133:836-837.

P=

.006

TCAI: An Effective Adjunct to a

PGA

n = 25 n = 25n = 23

Prostaglandins-Wonder Drug!!

Yes, But…..

• Lowers IOP up to 33%

• Produces red eye and

darkens the iris

• HA, Herpes, CME,

IRITIS

• Watch out for

unpublished adverse

effects

CAI’s: Azopt VS Trusopt

• Remember your

pharmacokinetics!!!!

• Stinging solution VS no

sting suspension

• Equal efficacy and dosage

• Azopt is BID

• Trusopt is TID

• CAI’s best with

prostaglandins

A New Way to manage our

patients risk

Lower Diastolic,

Systolic, or

Mean Pressure

Reduces Perfusion

Pressure

Higher

IOP

Negatively Impacts

Perfusion Pressure

Perfusion Pressure

Is a Result of

A Delicate Balance

Between IOP

and Blood Pressure

Lower

Perfusion Pressure

Is Associated with

Increased Risk for

Open Angle GlaucomaLeske MC, et al. Ophthalmology 2007; 114,: 1965-72

Leske MC, et al. Ophthalmology 2008;115, 65-93.

Hayreh SS. Trans Am Acad Ophthalmol 1974;78:240-54

Ocular Perfusion Pressure and Glaucoma

Progression

Baseline Timolol Brimonidine Dorzolamide Latanoprost

Mean 24-

Hour IOP

(mm Hg)1

22.69 17.73 18.32 17.37 16.62

1. Quaranta L et al. Invest Ophthalmol Vis Sci. 2006;47:2917-2923.

IOP Results

Baseline Timolol Brimonidine Dorzolamide Latanoprost

Mean 24-

Hour

Diastolic

Ocular

Perfusion

Pressure

(mm Hg)1

50.7 53.0 46.2

Significant

reduction in

DOPP

(p < 0.0001)

55.9

Significant

improvement

in DOPP

(p < 0.0001)

56.4

Significant

improvement

in DOPP vs.

baseline

(p < 0.0001)

1. Quaranta L et al. Invest Ophthalmol Vis Sci. 2006;47:2917-2923.

2. Quigley HA, West SK, Rodriguez J, et al. Arch Ophthalmol. 2001;119:1819-26

Diastolic Ocular Perfusion

Pressure (DOPP) Results

* Reduction in DOPP is a risk factor for glaucoma progression2

REASONS FOR

TREATMENT FAILURE

• Adverse drug effects/

contraindications

• Too many drugs

• Efficacy (even at night)

THE NEW GLAUCOMA

PARADIGM• AVOID REDUCED

PERFUSION PRESSURE

• MUST WORK ON IOP

DURING SLEEP

• START WITH A

PROSTAGLANDIN

• ADD A CAI

• GET 3 FOR THE PRICE OF

(2) COSOPT OR COMBIGAN

THE END

MANY THANKS-YOU MAKE

MY DAY