everything therapeutic-part ii - storage.googleapis.com · of activity extended spectrum enhanced...
Post on 17-Oct-2019
8 Views
Preview:
TRANSCRIPT
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
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
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
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
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
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??
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
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
Respond To This Statement
The current standard of care is
to culture ALL suspected
bacterial corneal ulcers
A. TRUE
B. FALSE
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
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
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
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
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
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
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
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.
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.
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
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
top related