PHARMACEUTICAL UPDATE or

Everything You Wanted to Know

About Therapeutics, But Were Afraid

to Ask-PART I

Bruce E. Onofrey, R.Ph., O.D. FAAO

Professor, U. Houston

University Eye Institute

TODAYS MENU

• CHOOSING A BETTER ANESTHETIC

• DEALING WITH DEFECTS (EPITH)

• DRY EYE-ALL THE ANGLES

• BLEPHARITIS-MYTHS VS TRUTHS

• VIRAL EYE DISEASE-A CURE(s)

Ester is NOT your Jewish aunt-

It’s a new approach to disease

management

• It’s about time we had a

better anesthetic than

proparacaine

Proparacaine-A good anesthetic for

the central cornea, but not much else.

Problems:Efficacy

No limbal or

conjunctival

coverage

Allergy

Name the best AMIDE anesthetic for

LASIK, topical cataract surgery and

lacrimal procedures.

• 1. Proparacaine

• 2. Tetracaine

• 3. Lidocaine

• 4. Cocaine

• 5. Benoxinate

• THINK AMIDES, NOT ESTERS

YOU DON’T NEED A NEEDLE

TO USE LIDOCAINE IN THE

EYE

Topical Lidocaine is a BETTER

anesthetic

• BENEFITS:

• NO CROSS SENSITIVITY

• EFFICACY ON VASCULAR

TISSUE

• NO LOCAL METABOLISM

• LONGER LASTING

Available dosage forms

• 50cc bottle 4%-can be

autoclaved

• 3.5% ophthalmic gel

• No preservatives

Want less bleeding and longer

action-THINK SYNERGISM

1 (+) 1 = 3

Epithelial defects-no problemo

• Better

patching

• Bandage lenses

• Corneal

micropuncture

• Doxycycline??

• Steroids??

• Vitamin C

Clinical Pearl#2: Don’t try to

Patch Without It@@@@@

• Proper technique requires

that the patient NOT be

wrapped like a mummy

with tape.

• Do not attach tape to

nose, ears or glasses

• One touch technique

• Requires adhesive-

Tincture of benzoin cmpd.

The Magic Skin Glue

Use the right tape

Corneal Erosion

MANAGEMENT 2.0

FIRST: HEAL IT

Bandage CL

8.4 BC

Prokera • Amniotic membrane on a

scaffold ring

• Functions as a bandage lens

• Healing properties?

• COST = $900

• REIMBUSEMENT = $1,400

SECOND: KEEP IT HEALED

• PEARL: Think Doxycycline (50mg BID)

• Watch out for smokers-Vitamin C (1-

2gm/D

• SALT OINT, NOT SOLUTION

THIRD: If it don’t heal-POKE

IT WITH A SHARP STICK

PAIN MGT OPTIONS:

Oxycodone, The “BIG GUN”• With ASA = Percodan

• With APAP = Percocett

• Schedule II drug = High

abuse

• Vicodin now schedule ll

• Tramadol (Ultram)

• 50mg, up to 400mg

max/D

• Usual 1-2 tabs QID PO

That all fine and good butttt:

• My Patients a drug abuser

• My Patient’s allergic to opiates

• I CAN’T prescribe Narcotic agents

• I don’t want to prescribe narcotic agents

• My patient doesn’t want to use dope

• @@@@@@@@

+

Know your “ABC’s” of OSD

• A = ALLERGY

• B = BLEPHARITIS

• C = KERATO- CONJUNCTIVITIS SICCA

Management of Dry Eye

• How do YOU spell D-R-Y E-Y-E

• Ocular surface disease is a serious

business

• Chronic condition

• Multiple dry eye factors

• Mild to severe presentations

Key(s) to managing dry eye?

• 1. ASK and QUANTIFY (SX’s)

• DO YOU HAVE DRY EYE?

• HOW BAD IS IT?

OCULAR SURFACE DISEASE INDEX (OSDI)

3 question sets

First set: Symptoms

Second set: Function

Third set: Environment

Scaled from (0) to (4)

Allows us to quantify and objectify subjective

data

OCULAR SURFACE DISEASE INDEX (OSDI)Please Answer The Following Questions by Checking The Box That Best Represents Your Answer

All of the time

(4)Most of the

time (3)Half of the

time (2)Some of

the time (1)None of the time

(0)

1 Eyes that are sensitive to light?

2 Eyes that feel gritty?

3 Painful or sore eyes?

4 Blurred vision?

5 Poor vision?

Have problems with your eyes limited you in performing any of the following during the last week:

All of the

time

Most of the

time

Half of the

time

Some of the

time

None of the

time

N/A

6 Reading?

7 Driving at night?

8 Working with a computer or bank

machine (ATM)?

9 Watching TV?

Have your eyes felt uncomfortable in any of the following situations during the last week:

All of the

time

Most of the

time

Half of the

time

Some of the

time

None of the

time

N/A

10 Windy conditions?

11 Placed or areas with low humidity

(very dry)?

12 Areas that are air conditioned?

Have you experienced any of the following during the last week:

SX

Activities

Environment

OSDI Severity Grading

Miller, K.L., Mink, D.R., Mathias, S.D, & Walt, J.G. (2006). Estimating the minimal clinical important difference of the Ocular Surface Disease

Index®: Preliminary findings [Abstract]. Abstract obtained from www.isoqol.org/2006AbstractsBook.pdf.

Severe

Total OSDI Score=

(Sum of Score for All Questions Answered) X (25)

(Total # of Questions Answered)

Mild ModerateNormal Severe

0 10 20 30 40 50 60 70 80 90 100

Score

0-12 23-3213-220 33-100

Key(s) to managing dry eye?

• 2. FIND THE CAUSE:

• DRY EYE IS A COMPLEX DISEASE!

Aging

Dry Environment

Hormonal Changes

Contact Lens

Blepharitis

LASIK

Auto-immune

Disease

Anti-histamine use

Alcohol Use

Pollution

Computer

Use

Anti-depressants

Dry Eye CascadeABNORMAL TEAR FILM CAUSES

& CONTRIBUTORS

OBSERVABLE

PATHOPHYSIOLOGIES

Drugs and Dry Eye

-A natural progression of disease-

ACCUTANE USE = DRY

EYE@@@@

Hold off on the CL’s:

TX as OSD patient

Aging

Dry Environment

Hormonal Changes

Contact Lens

Blepharitis

LASIK

Auto-immune Disease

Anti-histamine use

Alcohol Use

Pollution

Computer

Use

Anti-depressants

Quaternary

Ammoniums

(i.e. BAK)

Dry Eye CascadeABNORMAL TEAR FILM CAUSES

& CONTRIBUTORS

OBSERVABLE

PATHOPHYSIOLOGIES

BAK

Key(s) to managing dry eye?

• 2. OBJECTIVELY STAGE THE

DISEASE (SIGNS)

Key(s) to managing dry eye?

• 3. SELECT THE PROPER TX

• ACUTE VS CHRONIC

• APPROPRIATE FOR TYPE

• STEP THERAPY

Step therapy of dry eye

• DROPS CANNOT HEAL A SICK CORNEA

• PUT AWAY THE FORCEPS

MRS JOHNSON, THIS WON’T

HURT A BIT!!

The Sjogrens patient

• Starts with a bad cornea and serious

aqueous deficiency

• Acute and chronic disease

• TX?

DRY EYE: THE NEW WAY

• Mucomimetic drop/bandage

CL?

• OMEGA 3 : DHA / EPA

• Anti-inflammatory: Steroid

induction/Cyclosporin

A/Xibrom?

• Punctal occlusion

• Evoxac (Sjogrens)

Restasis VS Steroids for OSD

“Doctor Onofrey, You changed

my life”

Oral meds for dry eye?

Evoxac: New and improved

pilocarpine@@@@

• Parasympathomimetic@@@@@

• Better tolerated

• 30mg TID

• No titration necessary-maybe

• NEVER in asthmatics

Scoper H. Simplex in K.sicca

Patient study

KWESTION?

DOES PUNCTAL

OCCLUSION OR

CYCLOSPORIN

PREVENT

RECURRENT

DISCIFORM

HERPES?

Results• Non-treated group: 6-7 months of disease/yr

• TX with EITHER thermal cautery or topical

cyclosporin: 1.1 months/yr of active disease

• TX with both: 0.8 months/yr

• Learning point:

• OSD patients with H. simplex require

aggressive management

• Topical cyclosporin A is safe and effective in

H. simplex patients

THE DRY AND THE

HIGH

Evidence-based Management Strategies for

Glaucoma Patients with Ocular Surface

Disease (OSD)

Prostaglandins

Compliance sucks

This brings us to Rule #1

• Glaucoma docs do not talk to ocular surface disease docs

• They mix like oil and water

• They have their own meetings

• Their own separate Societies

• Secret handshakes

• Glaucoma guys drink wine and martinis

• OSD guys drink scotch (Think Art Epstein) and beer

Ocular Surface Disease Prevalence Study (Fechner)

Purpose: To Determine The Prevalence of OSD Symptoms in Glaucoma Patients

Methods:

– 10 Sites

– 630 Glaucoma Patients:

• > 18 Years of Age

• Primary Open-Angle, Exfoliation, or Pigment Dispersion Glaucoma, or Ocular Hypertension in Both Eyes

• Treated With a Topical IOP-Lowering Medication

– Patients Completed an OSDI Survey While in The Office

Fechtner, R, Budenz, D, Godfrey D. Prevalence of ocular surface disease symptoms in glaucoma patients on IOP-lowering

medications. Poster presented at: annual meeting of the American Glaucoma Society ; March 8, 2008; Washington DC.

OSD Prevalence Study: Results

Ranking Normal Mild Moderate Severe

Patients 325 134 84 87

Percentage 51.6% 21.3% 13.3% 13.8%

48.4%

Fechtner, R, Budenz, D, Godfrey D. Prevalence of ocular surface disease symptoms in glaucoma patients on IOP-lowering

medications. Poster presented at: annual meeting of the American Glaucoma Society ; March 8, 2008; Washington DC.

OSDI Scores in Glaucoma Patients

CL patient with GLC

Wears daily disp. SCL’s: “I Never

had problems till I started GLC

TX” (with you)

- 8.00 myope

“I WOULD RATHER GO BLIND

THAN WEAR GLASSES” Cornea

too thin for lasik – Management??

COMPLIANCE?

CAN THEY COME IN THE

SAME PACKAGE?• GLAUCOMA

• OCULAR SURFACE DISEASE

Initial presentation

• 62 Y/O F with POAG

• (+) FM HX POAG (M & F)

• Pre Tx IOP’s 28/25 (ADJUSTED)

Pachymetry: 530/533

TBUT: 2-3 seconds, with scattered

SPK

SX: FB sensation with burning in PM

A TX SUCCESS?

Mrs Johnson, Your GLC drops

are working great

• Prostaglandin drops HS OU started:

• 1 month recheck adjusted IOP’s: 18/17 @

10AM (ADJ)

• BUTTTTTTTTTT:

“Dr. My eyes feel like they are

on fire!!”

THE HARD TRUTH• PRE-TREATMENT GLC PATIENTS

WITH OSD ALWAYS GET WORSE

WITH CHRONIC USE OF MOST GLC

MEDS

• TX OSD FIRST, THEN START GLC

TX

• MONITOR BOTH CONDITIONS

BAK = BUY ANOTHER KIND

New Options for your

OSD/GLC patients #1

Blepharitis: Know your

anterior from your posterior

LID DISEASE-THEOLD

MYTH’s

• Blepharitis is curable

• Staph exotoxins produce the

inflammation

• Ointments are the best TX

• SCRUB your troubles away

• Patient’s love complex expensive

treatments

• All tetracyclines are the same

• There is no substitute for tetracycline

What Causes Chronic Staph

Lid Inflammation?

Exotoxins Right??!!

Staph epidemidis DOES NOT

produce exotoxins, but it does

produce a complex organic

molecule:

OH-POO=POO

LIPIDS (+) LIPASE = FATTY ACIDS

(STAPH POO)

Step Therapy of Blepharitis

RESULTS: Doxycycline significantly decreased IL-1beta

bioactivity in the supernatants from LPS-treated corneal

epithelial cultures. These effects were comparable to those

induced by the corticosteroid, @@@@

CONCLUSIONS: Doxycycline can suppress the

steady state amounts of mRNA and protein of IL-beta

and decrease the bioactivity of this major

inflammatory cytokine. These data may partially

explain the clinically observed anti-inflammatory

properties of doxycycline. The observation that

doxycycline was equally potent as a corticosteroid,

combined with the relative absence of adverse effects,

makes it a potent drug for a wide spectrum of ocular

surface inflammatory diseases.

RESULTS: Doxycycline significantly decreased IL-1beta

bioactivity in the supernatants from LPS-treated corneal

epithelial cultures. These effects were comparable to those

induced by the corticosteroid,

CONCLUSIONS: Doxycycline can suppress the steady

state amounts of mRNA and protein of IL-beta and

decrease the bioactivity of this major inflammatory

cytokine. These data may partially explain the clinically

observed anti-inflammatory properties of doxycycline.

The observation that doxycycline was

equally potent as a corticosteroid,

combined with the relative absence of

adverse effects, makes it a potent drug for

a wide spectrum of ocular surface

inflammatory diseases.

Posterior blepharitis: Azithromycin vs

Doxycycline

• Dose:

• Doxycycline 100mg BID X 1 month

• Azithromycin 500mg/D X 3 DMeasure Type Primary

Measure Title Change of Blepharitis Symptoms Score

Measure Description Five main ocular symptoms of posterior blepharitis

(itching, foreign body sensation, dryness, burning, and lid

swelling) will be asked of each patient and graded at

baseline, and days 7, 31, 37 and 61 after treatment. For

each item there was a question with scale from zero to

three (zero for no symptom three for maximum symptom).

Therefore, maximum score for symptoms was 15 (worse

outcome) and minimum score for symptoms was zero

(better outcome). Finally, we reported a change in total

score calculated as the latest time point (61 days) minus

the earliest time point.

Time FrameChange from the baseline until 61 days after

treatment

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”

Bacterial Corneal Ulcers

What is the Standard of Care?

OPTIONS

• Fluoroquinolones

• Fortified agents

Ophthalmic Antibiotics:

Fluoroquinolones• The first safe broad-spectrum ophthalmic

agents

• Revolutionized treatment of severe corneal

infections

• Very low sensitization rate

• Excellent safety profile

• Comfortable

• No reports of systemic effects

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

The greatest resistance to the drug is

in 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

RESISTANT BACTERIA

• Methicillin resistant Staphylococcus aureus

• Enterococcus Fecalis (group DStreptococcus)

• Strep pneumoniae

• Haemophilus influenzae

• Aminoglycoside resistant Pseudomonas aeruginosa

• Beta lactamase producing Neisseria

• Atypical Mycobacteria

Laboratory Culture Report• Patient: Kerry Titus Age: 27

• Date: April 1, 2001 Source: Right cornea

• Time: 14:32 Physician: S. Kubrick

• Organism isolated: Staphylococcus aureus, coagulase-positive, methicillin-resistant

Drug Sensitivity Profile MIC

Interpretation

Cefazolin 8 Resistant

Oxacillin (methicillin) 30 Resistant

Amoxicillin/clavulanate potassium 6

Resistant

Ampicillin (injectable) 52 Resistant

Ciprofloxacin 8 Resistant

Vancomycin 1 Sensitive

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

Me

dia

n M

IC

(µg

/mL

)

Coag-neg

Staphylococcus

S aureus

Current Standard of Care

75

Current Standard of Care?

76

Fourth-Generation Fluoroquinolone

Chemical Structures

HN

OCH3

F

N

O

COOH

N

H

H

MoxifloxacinGatifloxacin

HNOCH3

F

N

O

COOH

NH3C

•1.5 H2O

The Latest

Besivance: NEW Molecule

Moxeza: Longer duration

Zymaxid: Higher concentration

Moxeza/Zymaxid

• Just released-no change in active

ingredient

• Zymaxid: Increased concentration

• Moxeza: Gel vehicle: BID for

conjunctivitis only (CHROME!)

NEW: The worlds FIRST

Chloro-fluoroquinolone!!!

• WHAT THE HECK IS THAT?

• BESIFLOXACIN (BESIVANCE)

Refractive Surgery and Bacterial

Keratitis

• Cornea is already

compromised

• Infection is under flap

• Stroma is greatly thinned

• Must be aggressive

• Vancomycin (+)

amikacin/fluoroquinolone

SO MANY RED EYESCRITICAL SKILL #1

THE DX

In adults-Viral

conjunctivitis is the #1

Cause of

Acute INFECTIOUS

Conjunctivitis@@@@

Viral Pathogens

• Adenoviral

• Herpes simplex

• Herpes zoster

THE TESTSOLD AND NEW

• Cool compresses and ASA

• Lubrication

• Decongestants

• Steroids (infiltrates, membranes,

inflammation)@@@@

• Membrane removal

• Antibiotics??

• NOOOOOOOO!!!!!

• A CURE?

TREATMENT OF BOTH

SYMPTOMS AND PREVENTION

OF INFLAMMATORY DAMAGE

CHILL OUTTHE PEOPLES

CHOICE

Is there a Cure for the

Common Cold of the

eye?• Spit and swish: Povidone 5%

ophthalmic solution

• Don’t spare the steroids

Is there a Cure for the

Common Cold of the eye?

NOT QUITE

• Spit and swish: Povidone 5%

ophthalmic solution

• Don’t spare the steroids

THE CURE?

Decrease infection from 18 to 7 days

Fewer complications

Tabbara K, Jarade E. Ganciclovir effects in adenoviral

keratoconjunctivitis. Invest Ophthalmol Vis Sci.

Currently in Animal Testing

• FORESIGHT PHARMACEUTICALS

Topical FST100 Dexamethasone 0.1%

Containing Povidone-Iodine 0.4% Reduced the

Clinical Signs and Infectious Viral Titers in a

Rabbit Model of Adenoviral Conjunctivitis

Herpes Simplex• Primary disease

• Recurrent disease

Conjunctivitis

Keratitis

• Stromal disease

• Kerato-uveitis

GONE

Antiviral Agents

• IDU

• Vidarabine

• Trifluridine

• Ganciclovir

• Acyclovir

• Famcyclovir

• Valcyclovir

The NEW Way to TX H.

Simplex

THE OLD:Trifluorothymidine

THE NEW: Ganciclovir

• Was drug of choice for topical

management of Herpes

• simplex ocular disease.

• Rapid absorption

• Toxicity occurs when

• used over 21 days

• Dosage-5-8X daily

• Viroptic 1%-7.5cc-Burroughs

Epithelial herpes is associated

with the (2) BIG “I”’s

• Inflammation and Infection

X

DO YOU WANT STEROIDS

WITH THAT?

IOP = 62/ (+) 3 C AND F

The drugsssssss

+ +

+

Stromal H. simplex-

A whole new ball game

• Mechanism is primarily

inflammation@@@@

• Stromal infiltrates are the

critical sign

• Balanced use of topical

steroid (FML) with anti-viral

cover@@@@

• Consider oral acyclovir at

this point in time

Tapering 1.0

Herpes simplex disciform

disease

Herpes Zoster• Commonly called

“shingles”

• Lesions “HONOR” the

mid-line

• Reoccurrence triggered by

decreased immunity-

MUST consider cause of

reoccurrence

Who gets Post-herpetic

Neuralgia@@@@

• Immunocompromised folk

• The elderly

• Best treatment is prophylactic TX

Manage Potential Post-herpetic

Neuralgia@@@@

• Oral acyclovir 800mg 5X daily

• Valacyclovir 1000mg TID

• Famcyclovir 500mg TID

• Low dose tricyclic antidepressant-

amitryptyline 25mg/day

• Neurontin

Chronic neural pain-A

different kind of animal

Neurontin: The New “Big Dog”

for chronic pain

• Huge dosage range: 100-5000mg/d

• Must start slow

• Must give enough

Narcotics and Zoster pain

• OK for short term ACUTE H. zoster

• Not best for late phase post-zoster

trigeminal neualgia

• Vicodin = Tylenol + hydrocodone works

well@@@@@

• Many side-effects = constipation,

drowsiness and nausea@@@@

DO YOU WANT STEROIDS

WITH THAT?

THE REST OF THE STORY

A REAL “DIZ-OSTER

Pavan-Langston et al performed polymerase chain

reaction studies on patient’s excised corneal tissue

and the response of patients to antiviral therapy.

They concluded that recurrent viral infection by

VZV may play a role in this late manifestation of the

disease, associated with MPK; thus, specific

antiviral therapy may be warranted in the treatment

of MPK. Specific antiviral therapy was not

consistently successful in all cases, but topical

trifluridine, vidarabine, and oral acyclovir were

individually used successfully in different cases.22

The use of newer topical and oral antivirals may

improve the general success rate of treatment.

The drugsssssss

+

+ +

HOW DO YOU TAPER YOUR ‘ROIDS?

Version 2.0

HOW ABOUT 1-2-3

1 2 3