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PHARMACEUTICAL UPDATE or
Everything You Wanted to Know
About Therapeutics, But Were Afraid
to Ask-Almost
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-SOMETHING FOR
EVERYONE
• BLEPHARITIS-MYTHS VS TRUTHS
• MANAGING OCULAR INFECTIONWHAT IS THE STANDARD OF CARE?
Ester is NOT your Jewish auntIt’s a new approach to disease
management
• It’s about time we had a
better anesthetic than
proparacaine
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
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
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.
• Amniotic membrane on a
scaffold ring
• Functions as a bandage lens
• Healing properties?
• COST = $900
• REIMBUSEMENT = $1,400
Prokera
SECOND: KEEP IT HEALED
• PEARL: Think Doxycycline (50mg BID)
• Watch out for smokers-Vitamin C (12gm/D
• SALT OINT, NOT SOLUTION
THIRD: If it don’t heal-POKE
IT WITH A SHARP STICK
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
Have you experienced any of the following during the last week:
All of the time
(4)
1
Eyes that are sensitive to light?
2
Eyes that feel gritty?
3
Painful or sore eyes?
4
Blurred vision?
5
Poor vision?
Most of the
time (3)
Half of the
time (2)
Some of
the time (1)
None of the time
(0)
SX
Have problems with your eyes limited you in performing any of the following during the last week:
All of the
time
6
Reading?
7
Driving at night?
8
Working with a computer or bank
machine (ATM)?
9
Watching TV?
Most of the
time
Half of the
time
Some of the
time
None of the
time
N/A
Activities
Have your eyes felt uncomfortable in any of the following situations during the last week:
All of the
time
10
Windy conditions?
11
Placed or areas with low humidity
(very dry)?
12
Areas that are air conditioned?
Most of the
time
Half of the
time
Some of the
time
Environment
None of the
time
N/A
OSDI Severity Grading
Severe
00 -12
0
10
13 -22 23 -32
20
33 -100
30
40
Normal
50
Score
Mild
60
Moderate
70
80
90
100
Severe
Total OSDI Score=
(Sum of Score for All Questions Answered) X (25)
(Total # of Questions Answered)
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.
Key(s) to managing dry eye?
• 2. FIND THE CAUSE:
• DRY EYE IS A COMPLEX DISEASE!
Drugs and Dry Eye
-A natural progression of disease-
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
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)
“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
Prevent Evaporation
• USE MAYONNAISE or
something like it
• Refresh ENDURA: OLD
• SOOTHE XP/Systane
Balance: NEW
Blepharitis: Know your
anterior from your posterior
OLD 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??!!
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.
DON’T TX KIDS LIKE
LITTLE ADULTS: Pediatric
conjunctivitis plays by different
rules
Don’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
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
The greatest resistance to the drug is
in which type of bacteria?
• 1. Gram positive
• 2. Gram negative
RESISTANT BACTERIA
• Methicillin resistant Staphylococcus
aureus
• Enterococcus Fecalis (group D
Streptococcus)
• Strep pneumoniae
• Haemophilus influenzae
• Aminoglycoside resistant
Pseudomonas
aeruginosa
• Beta lactamase producing Neisseria
• Atypical Mycobacteria
Fourth-Generation Fluoroquinolone
Chemical Structures
O
F
H3C
HN
O
COOH
N
OCH3
N
• 1.5 H2O
F
COOH
H
N
HN
OCH3
N
H
Gatifloxacin
Moxifloxacin
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
In adults-Viral
conjunctivitis is the #1
Cause of
Acute INFECTIOUS
Conjunctivitis@@@@
Viral Pathogens
• Adenoviral
• Herpes simplex
• Herpes zoster
TREATMENT OF BOTH
SYMPTOMS AND PREVENTION
OF INFLAMMATORY DAMAGE
•
•
•
•
Cool compresses and ASA
Lubrication
Decongestants
Steroids (infiltrates, membranes,
inflammation)@@@@
• Membrane removal
• Antibiotics?
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
Antiviral Agents
•
•
•
•
•
•
•
IDU
Vidarabine
Trifluridine
Ganciclovir
Acyclovir
Famcyclovir
Valcyclovir
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
Stromal H. simplexA 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
Herpes Zoster
• Commonly called
“shingles”
• Lesions “HONOR” the
mid-line
• Reoccurrence triggered by
decreased immunityMUST 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 antidepressantamitryptyline 25mg/day
• Neurontin
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@@@@
THE END
MANY THANKS-YOU MAKE
MY DAY