CTC 2.18 Open-Angle Glaucoma PDF

PAMANTASAN NG LUNGSOD NG MAYNILA
College of Medicine
Department of Basic and Clinical Pharmacology, Toxicology, and Therapeutics
CLINICO-THERAPEUTIC CONFERENCE
CASE #18
PRIMARY OPEN-ANGLE GLAUCOMA
Submitted in Partial Fulfillment of the
Requirements in Medical Therapeutics
Date of Submission: August 29, 2014
THIRD YEAR SECTION A
CALAUNAN, Martin Joseph A.
Discussion of the Diagnosis

Epidemiology
Classifications of Open-Angle Glaucoma
Pathophysiology
ESNA of Cholinomimetics
ESNA of Alpha-Adrenergic Agonists
Compiler
LASCANO, Normilando V.
ESNA of Prostaglandin Analogues

ESNA of Drugs in p-Group and Selection of p-Drug
Sample Prescription
Non-Pharmacologic Management
PANGAN, Kimberly Anne M.
Therapeutic Objectives
ESNA Criteria
Overview of Drugs in Recommendation
ESNA of Beta-Adrenergic Antagonists
ESNA of Carbonic Anhydrase Inhibitors
THE CASE
R. V. J., a 48-year-old male businessman, came to the eye referral center for routine check-up and change of corrective lenses.
Tonometry exam revealed elevated value. He was subjected to gonioscopy examination which revealed normal result. His pupils
were dilated using a medicine for fundoscopic examination and revealed cup-to-disc ratio of 0.6 on the right and 0.8 on the left.
Visual field examination showed contracted peripheral fields. As an ophthalmologist, you highly considered open-angle
glaucoma.
SALIENT FEATURES
The salient features in this case are as follows: 48-year-old male, elevated value on tonometry exam, normal gonioscopy
examination, cup-to-disc ratio of 0.6 on the right eye and 0.8 on the left eye, and contracted peripheral fields on visual field
examination.
PRIMARY OPEN-ANGLE GLAUCOMA

INTRODUCTION
Glaucoma, colloquially known as the "silent stealer of
sight," is a clinical term referring to a variety of conditions
with the common feature of an optic neuropathy (i.e.,
glaucomatous optic neuropathy [GON]) characterized by a
distinctive loss of retinal nerve fibers and optic disc
changes (Canadian Ophthalmology Society, 2009).
Primary open-angle glaucoma (POAG) is a progressive,
chronic optic neuropathy in adults in which intraocular
presure (IOP) and other currently unknown factors
contribute to damage and in which, in the absence of other
identifiable causes, there is a characteristic acquired
atrophy of the optic nerve and loss of retinal ganglion cells
and their axons. This condition is associated with an open
anterior chamber angle on gonioscopy examination.
EPIDEMIOLOGY
Glaucoma is the second leading cause of blindness

worldwide, topped only by cataract. It is, however, the
leading cause of irreversible loss of vision. As of 2010, it
has affected at least 60 million people and caused
blindness in 8.4 million people. By the year 2020, almost
80 million people will have glaucoma, with 11.2 million
becoming bilaterally blind (Quigley and Broman, 2006).
These increases in the number of glaucoma and
glaucoma-associated blindness cases is possibly attributed
to an aging world population as glaucoma is a condition of
adult onset and commonly affects the older age group.
Open-angle glaucoma constitutes 74% or about threefourths of the worldwide cases. In Southeast Asia, about
2.1 million people have been diagnosed with open-angle
glaucoma as of 2010 and is expected to rise to 3 million by

2020.
Glaucoma is the third leading cause of bilateral blindness
in the Philippines, after cataract and refractive errors,
according to the Third National Survey on Blindness in the
Philippines by the Department of Health, conducted from
October 2001 to May 2002.
PREDISPOSING FACTORS
Intraocular pressure
Older age
African and Hispanic descent
Family history of glaucoma
Central corneal thickness
Low ocular perfusion pressures
Type 2 diabetes mellitus
Myopia
Migraine headache
Peripheral vasospasm
PATHOPHYSIOLOGY
The pathophysiology of glaucoma is believed to be

multifactorial. Several mechanisms are likely to underlie the
final common pathway of optic nerve dysfunction and
ganglion cell death (Choplin and Lundy, 2007). According
to various existing theories, factors like elevated intraocular
pressure (IOP) and vascular dysregulation primarily
contribute to the initial insult during glaucomatous atrophy
in the form of obstruction to axoplasmic flow within the
retinal ganglion cell axons at the lamina cribrosa, altered
optic nerve microcirculation at the level of lamina, and
changes in the laminar glial and connective tissue. The
factors leading to secondary insult include excitotoxic
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damage caused by glutamate or glycine released from

injured neurons and oxidative damage caused by overproduction of nitric oxide (NO) and other reactive oxygen
species. Whatever may be the primary and secondary
factors, the end result in glaucomatous eyes is the
dysfunction and death of RGCs leading to irreversible
visual loss, as a result of a complex interplay of multiple
factors rather than any one of them functioning individually
(Agarwal et al, 2009).
SYMPTOMATOLOGY
Majority of patients with primary open-angle glaucoma are
symptomatic even with the increased intraocular pressure.
They are typically only symptomatic in late disease, when
they may become aware of constricted visual field or
blurred vision. Occasionally, patients become aware of
earlier visual field defects when performing monocular
tasks (American Academy of Ophthalmology). Patients
may notice a gradual loss of peripheral vision, or "tunnel
vision" after loss of more than 40 percent of the nerve
fibers. Open-angle glaucoma usually is an incidental
finding during an adult eye evaluation performed for other
indications (Distelhorst and Hughes, 2003).
DIAGNOSIS AND WORK-UP
According to the Preferred Practice Pattern Guidelines of

the American Academy of Ophthalmology (2010), the
following are the clinical findings characteristics of primary
open-angle glaucoma:
Evidence of optic nerve damage from either, or both, of

the following:
Optic disc or retinal nerve fiber layer structural
abnormalities
Diffuse thinning, focal narrowing, or notching
of the optic disc rim, especially at the inferior
or superior poles
Documented, progressive thinning of the
neuroretinal rim with an associated increase in
cupping of the optic disc
Diffuse or localized abnormalities of the
peripapillary retinal nerve fiber layer, especially
at the inferior or superior poles
Disc rim or peripapillary retinal nerve fiber
layer hemorrhages
Optic disc neural rim asymmetry of the two
eyes consistent with loss of neural tissue
Reliable and reproducible visual field abnormality
considered a valid representation of the subject's
functional status
Visual field damage consistent with retinal
nerve fiber layer damage (e.g., nasal step,
arcuate field defect, or paracentral depression
in clusters of test sites)
Visual field loss in one hemifield that is
different from the other hemifield, i.e., across
the horizontal midline (in early/moderate
cases)
Absence of other known explanations
Adult onset
Open anterior chamber angles
Absence of other known explanations (i.e., secondary
glaucoma) for progressive glaucomatous optic nerve
change (e.g., pigment dispersion, pseudoexfoliation
[exfoliation syndrome], uveitis, trauma, and
corticosteroid use)
Primary open-angle glaucoma represents a spectrum of
disease in adults in which the susceptibility of the optic
nerve to damage varies among patients. Many POAG
patients present with elevated IOP, but a substantial
minority with otherwise characteristic POAG may not have
elevated IOP measurements. The vast majority of patients
with POAG have disc changes or disc and visual field
changes, but there are rare cases where there may be
early visual field changes before there are detectable
changes to the optic nerve (AAO, 2010).
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The comprehensive initial glaucoma evaluation (history and physical examination) includes all components of the comprehensive
adult medical eye evaluation in addition to, and with special attention to, those factors that specifically bear upon the diagnosis,
course, and treatment of primary open-angle glaucoma. The examination may require more than one visit. For instance, an
individual might be suspected of having glaucoma on one visit but may return for further evaluation to confirm the diagnosis,
including additional IOP measurements, gonioscopy, CCT determination, visual field assessment, and optic nerve head and
retinal nerve fiber layer evaluation and documentation (American Academy of Ophthalmology, 2010).
ELEMENTS OF OPHTHALMIC EVALUATION

HISTORY
VISUAL ACUITY
MEASUREMENT
PUPIL EXAMINATION
ANTERIOR SEGMENT
EXAMINATION
INTRAOCULAR
PRESSURE
MEASUREMENT
GONIOSCOPY
OPTIC NERVE HEAD AND

RETINAL NERVE FIBER
LAYER EXAMINATION
Ocular, family, and systemic history (e.g. asthma)

The severity and outcome of glaucoma in family members, including history of visual loss
from glaucoma, should be obtained during initial evaluation.
Review of pertinent records, with particular reference to:
Past IOP levels
Status of the optic nerve
Visual field
Current ocular and systemic medications (e.g. corticosteroids) and known local or systemic
intolerance to ocular or systemic medications
Ocular surgery
A history of LASIK or photorefractive keratectomy is associated with a falsely low IOP
measurement due to thinning of the cornea.
Cataract surgery may also lower the IOP compared with the presurgical baseline.
A history of prior glaucoma laser or incisional surgical procedures should be elicited.
Visual acuity with current correction (the power of the present correction recorded) at distance
and, when appropriate, at near should be measured. Refraction may be indicated to obtain the
best corrected visual acuity.
For reactivity and afferent pupillary defect
Slit-lamp biomicroscopic examination of the anterior segment can provide evidence of physical
findings associated with narrow angles, such as shallow peripheral anterior chamber depth and
crowded anterior chamber angle anatomy, corneal pathology, or a secondary mechanism for
elevated IOP such as pseudoexfoliation (exfoliation syndrome), pigment dispersion with
Krukenberg spindle and/or iris transillumination defects, iris and angle neovascularization, or
inflammation.
Intraocular pressure is measured in each eye, preferably by Goldmann applanation tonometry,
before gonioscopy or dilation of the pupil.
Recording time of day of IOP measurements may be helpful to assess diurnal variation.
Unrecognized fluctuations in IOP may lead to progression of POAG. Therefore, additional
measurements may be indicated, either at different hours of the day on the same day or
on different days.
Diagnosis of primary open-angle glaucoma requires careful evaluation of the anterior chamber
angle to exclude angle closure or secondary causes of IOP elevation, such as:
Angle recession
Pigment dispersion
Peripheral anterior synechiae
Angle neovascularization
Inflammatory precipitates
Provides valuable structural information about glaucomatous optic nerve damage
Visible structural alterations of the optic nerve head or retinal nerve fiber layer and
development of peripapillary choroidal atrophy frequently occur before visual field defects
can be detected.
Careful study of the optic disc neural rim for small hemorrhages is important, since these
hemorrhages often precede visual field loss and further optic nerve damage in patients
with glaucoma.
Preferred technique for optic nerve head and retinal nerve fiber layer evaluation involves
magnified stereoscopic visualization (as with the slit-lamp biomicroscope), preferably through a
dilated pupil. In some cases, direct ophthalmoscopy complements magnified stereoscopic
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visualization, providing additional information of optic nerve detail due to the greater
magnification of the direct ophthalmoscope. Red-free illumination of the posterior pole by
stereo-biomicroscopy with an indirect lens at the slit lamp, the direct ophthalmoscope, or with
digital red-free photography may aid in evaluating the retinal nerve fiber layer.
Examination of the fundus, through a dilated pupil whenever feasible, includes a search for
other abnormalities that may account for optic nerve changes and/or visual field defects (e.g.
optic nerve pallor, disc drusen, optic nerve pits, disc edema from central nervous system
disease, macular degeneration, retinovascular occlusion, and other retinal disease).
FUNDUS EXAMINATION
CENTRAL CORNEAL
THICKNESS
MEASUREMENT
Measurement of CCT aids the interpretation of IOP readings and helps to stratify patient risk
for ocular damage.
Overestimation of the real IOP may occur in eyes with corneas that are thicker than
average while underestimation of the real IOP tends to occur in eyes with corneas that are
thinner than average.
Automated static threshold perimetry is the preferred technique for evaluating the visual field.
The frequency doubling technology (FDT) method with the central 20-degree test program (C20) and short-wavelength automated perimetry (SWAP) with the central 24-degree test
program (24-2) are two of several alternative testing methods to screen for a defect before
conducting more definitive threshold testing. Visual field testing based on SWAP and FDT may
detect defects or progression of defects earlier than conventional white-on-white perimetry in
some patients.
Careful manual combined kinetic and static threshold testing (e.g., Goldmann visual fields) is
an acceptable alternative when patients cannot perform automated perimetry reliably or if it is
not available.
Repeat, confirmatory visual field examinations may be required for test results that are
unreliable or show a new glaucomatous defect before changing management. It is best to use
a consistent examination strategy for visual field testing.
The appearance of the optic nerve should be documented.
Color stereophotography is an accepted method for documenting optic nerve head
appearance. Computer-based image analysis of the optic nerve head and retinal nerve fiber
layer is an alternative for documentation of the optic nerve.
As improvements in these instruments continue, the capacity for them to help the clinician
diagnose glaucoma and identify progressive nerve damage becomes more reliable.
Stereoscopic disc photographs and computerized images of the nerve are distinctly different
methods for optic nerve documentation and analysis.
Each is complementary with regard to the information they provide the clinician who must
manage the patient. In the absence of these technologies, a nonstereoscopic photograph or a
drawing of the optic nerve head should be recorded, but these are less desirable alternatives to
stereophotography or computer-based imaging.
In patients with advanced glaucomatous optic neuropathy, there is limited benefit of using
stereophotography to identify progressive optic nerve change.
Three types of computer-based imaging devices currently available for glaucoma:
Confocal scanning laser ophthalmoscopy
Optical coherence tomography
Scanning laser polarimetry
Taken together, computer-based imaging devices for glaucoma provide useful, quantitative
information for the clinician when analyzed in conjunction with other relevant clinical
parameters. As device technology evolves (e.g., higher resolution spectral domain optical
coherence tomography), the diagnostic performance is expected to improve accordingly.
SUPPLEMENTAL OPHTHALMIC TESTING
VISUAL FIELD
EVALUATION
OPTIC NERVE HEAD AND

RETINAL FIBER LAYER
ANALYSIS
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EYE STAGING AND SETTING OF TARGET IOP
Canadian Ophthalmology Society glaucoma clinical practice guidelines (2009).
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TREATMENT ALGORITHM FOR PATIENTS WITH PRIMARY OPEN-ANGLE GLAUCOMA

American Academy of Ophthalmology Preferred Practice Pattern Guidelines (2010).
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THERAPEUTIC OPTIONS
PRINCIPLES. It is vital that treatment be tailored to the

needs of the individual patient in partnership with the
physician. Issues including compliance with therapy,
patient understanding of the disease, cost of treatment,
potential side-effects, and impact of therapy on the
patients quality of life should be explicitly incorporated into
the patients care plan. It is not sufficient to limit
discussions to intraocular pressure, visual field, and optic
nerve status; discussions about the implications of POAG
and its care need to be addressed with the patient (Choplin
and Lundy, 2007). Options for lowering IOP include the use
of topical or systemic medications, laser trabeculoplasty,
surgery to improve outflow facility, and cyclodestructive
laser to reduce aqueous production (COS, 2009).
According to the European Glaucoma Society guidelines
(2008), medical therapy should start with one drug. The
choice of management strategy must take into account
efficacy, safety, tolerability, quality of life, adherence and
cost. Prostaglandins or prostamides have been approved
as first line treatment for several years. They are
increasingly used as first choice treatment; the main
reasons are fewer installations (QD vs. BID), lack of
relevant systemic side effects, and IOP-lowering efficacy
(peak of >30%). Cost is the only downside. If the firstchoice monotherapy alone is not effective on IOP or not
tolerated, it is preferable to switch to any of the other
topical agents that can be initiated as monotherapy, If it is
well tolerated and effective, but not sufficient to reach the
target IOP, or there is evidence of progression and the
target IOP is being reconsidered, then adjunctive therapy in
the form of any other topical agent can be initiated (EGS,
2008).
First-choice treatment:
A drug that a physician prefers to use as initial IOP
lowering therapy.
First-line treatment:
A drug that has been approved by an official
controlling body (i.e. EMEA, CPMP or FDA) for
initial IOP lowering therapy.
INITIAL TREATMENT AND THERAPEUTICAL TRIAL.
Where practical, topical treatment is started in one eye first.
The differential IOP will give a better idea of the effect, with
less influence from diurnal variations. For some drugs, a
cross-over effect to the fellow eye must be taken into
account. Treatment is considered "effective" on the IOP
when the observed IOP lowering effect on the treated
patient is comparable to the published average effect for
the same compound on a similar population.
SWITCHING MONOTHERAPY AND ADJUNCTIVE

THERAPY. Monotherapy fails to achieve a satisfactory IOP
reduction in 40-75% of patients after more than 2 years of
therapy (EGS, 2008). The Ocular Hypertension Treatment
Trial showed that 40% of patients needed more than one
medication to achieve a 20% reduction in IOP (Schultz,
2010). In the event of monotherapy failure, replacement or
switching monotherapy should be attempted before adding
a second drug (EGS, 2008).
FIXED COMBINATIONS. There has been a substantial
increase in the use of fixed combinations of IOP-lowering
drugs for treatment of glaucoma in recent years. Fixeddose combinations of ophthalmic drugs (usually a betablocker as base drug and a prostaglandin analog, a
carbonic anhydrase inhibitor, brimonidine, or pilocarpine)
have been developed to simplify therapy and increase
patient compliance. In addition to making the treatments
simpler, patient costs might be cut if fewer bottles of
medicine were required for treatment (Schultz, 2010).
Some of the fixed combinations that are currently available
for lowering the IOP contain timolol and either CAI
dorzolamide or alpha agonist brimonidine or prostaglandin
analog, and the examples include Cosopt (timololdorzolamide), Combigan (timolol-brimonidine), Xalacom
(timolol-latanoprost),
Duotrav
(timolol-travoprost),
Ganfort (timolol-bimatoprost). Results from clinical
studies indicated that fixed combination was more
therapeutically effective than individual therapeutic agents
alone in lowering IOP. Fixed combinations provide a better
option for patients who need more than one drug to control
IOP, and hence they can be considered as important
adjuncts to the armamentarium of available therapies for
treating glaucoma (Balabathula, 2013).
How good as they may be, there are several difficulties to
consider before prescribing fixed combinations. First, there
is no dosing flexibility. For example, if a patient is doing
well with a QD beta-blocker therapy, this is not an option
with a fixed combination drug that is prescribed BID, such
as Cosopt or Combigan, and this can lead to overtreatment
with the beta-blocker. Second, the concentrations are fixed
and will thus lead to excessive treatment in some patients
who only require lower concentrations of individual drugs.
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PHARMACOLOGIC MANAGEMENT
THERAPEUTIC OBJECTIVES
Preserve the current visual function of the patient by reducing intra-ocular pressure
To compute for the target Intra-ocular pressure for each eye
To reduce the IOP of the left eye to 30% from baseline
To reduce the IOP of the right eye to at least 25% from baseline
Prevent further progression of visual defects
DRUGS UNDER CONSIDERATION

DRUG
PARASYMPATHOMIMETICS/CHOLINOMIMETICS
Pilocarpine hydrochloride (Isopto Carpine eye drops 2%)
15 ml container
ALPHA-2-ADRENERGIC AGONISTS
Brimonidine tartrate (Alphagan P ophthalmic solution 0.15%)
5 ml container
BETA-ADRENERGIC ANTAGONISTS
Betaxolol (Betoptic 0.5%)
5 ml container
Timolol (Celsus Timolol Maleate 0.5%)
5 ml container
CARBONIC ANHYDRASE INHIBITORS
Acetazolamide (Cetamid)
250 mg/tablet
#120 tablets
Dorzolamide HCl (Trusopt 2%)
5 ml container
PROSTAGLANDIN DERIVATIVES
Latanoprost (Xalatan ophthalmic solution 50 mcg/ml)
2.5 ml container
Travoprost (Travatan ophthalmic solution 0.004%)
2.5 ml container
Bimatoprost (Lumigan ophthalmic solution 0.03%)
3 ml
DOSE
NUMBER OF DAYS
1 drop per eye QID

1 drop in the affected eye/s TID
if monotherapy; BID if adjunctive
1 drop in the affected eye/s BID
1 drop in the affected eye/s BID
Take 1 tablet every 6 hours
everyday
Refill: every month
(as maintenance therapy)
1 drop in the affected eye/s TID
1 drop QD
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ESNA DISCUSSION
CRITERIA
EFFICACY
SAFETY
NECESSITY
AFFORDABILITY
Drug is able to effectively lower the intraocular pressure to target limits

Drug is able to reduce fluctuations in intraocular pressure during diurnal and inter-visit
periods
Drug has a long duration of action
Clinical trials/evidence showing better response rates
Drug has absent to minimal reversible side effects especially those that affect vision
Drug is not associated with or has no rare life-threatening ADRs which would require
discontinuation of use
Drug needs only "once-daily" dosing for better compliance
Drug has few drug-drug interactions or rare hypersensitivity reactions
Drug outweighs other treatment options
Drug is an effective stand-alone drug
Drug has no contraindication for use in relation to host factors
Drug has few reports of non-response
Total cost per month: 100.00-500.00 PhP
Total cost per month: >500.00-1000.00 PhP
Total cost per month: >2000.00 PhP
1 point
1 point
1 point
1 point
1 point
1 point
1 point
1 point
1 point
1 point
1 point
1 point
4 points
3 points
2 points
1 point
PILOCARPINE (PARASYMPATHOMIMETIC)
Parasympathomimetics increase aqueous outflow by action
on the trabecular meshwork through contraction of the
ciliary muscle. Stimulation of the longitudinal muscle of the
ciliary body (via the parasympathetic pathways mediated
by acetylcholine) increases traction on the scleral spur,
which in turn increases the tension on the trabecular
meshwork, resulting in increased outflow facility. This effect
on IOP may be achieved by direct stimulation of the
cholinergic receptors by drugs which mimic naturally
occurring acetylcholine (directly applied acetylcholine is
ineffective, because it is broken down by esterases in the
cornea) or by indirect stimulation with drugs that inhibit the
enzymatic breakdown of naturally occurring acetylcholine.
Pilocarpine, a direct-acting cholinergic agonist, is generally
better tolerated than the rest of the parasympathomimetics
and is considered the standard cholinergic agent for the
treatment of open-angle glaucoma (Brunton et al, 2008).
EFFICACY
EFFECTIVITY IN LOWERING IOP TO TARGET LIMITS.

Parasympathomimetic agents such as pilocarpine increase
aqueous outflow by action on the trabecular meshwork
through contraction of the ciliary muscle. Activation of the
constrictor pupillae muscle in these circumstances lowers
the intraocular pressure. Pilocarpine can reduce the
intraocular pressure by 20-25% (European Glaucoma

Society, 2008). In a study on comparative efficacy of
antiglaucoma medications using experimental models by
Gupta et al (2007), pilocarpine exhibited a maximum IOPlowering rate of 28.91%.
CONTROL OF IOP FLUCTUATIONS. The physiologic
diurnal IOP curve peaks at around noon and gradually
goes down toward the night. Ticho et al (1979) compared
the long-term effects of pilocarpine HCl 2% and Piloplex
wherein pilocarpine HCl 2% did not prevent the peaking of
IOP at the 12th hour and subsequent rises at the 15th and
21st hour, and the mean diurnal IOP was higher by 2.89
mm Hg with pilocarpine. However, a more recent study by
Bozorgi and Sarchahi (2011) on latanoprost and
pilocarpine using experimental models showed that
pilocarpine provided significant protection against the rise
in IOP induced by water loading (simulated ocular
hypertension).
DURATION OF ACTION. Pilocarpine (2% eye drops)
exerts its IOP-lowering effect within a few minutes (Brunton
et al, 2008) and has a relatively short duration of action of
6-7 hours (European Glaucoma Society and Canadian
Ophthalmologic Society).
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RESPONSE RATES. No literature specifically focusing on

the response rates with pilocarpine has been found. Ticho
et al (1979) reported that pilocarpine ophthalmic solutions,
even with increased pilocarpine concentration, have a
limited hypotensive effect on the increased intraocular
pressure.
SAFETY
SIDE EFFECTS. Pilocarpine is infrequently used

nowadays because the numerous side effects, especially
ocular side effects, significantly negate the therapeutic
usefulness of this drug. Cholinergic agonists can markedly
affect vision due to their effects on pupil size and ciliary
muscle tone. Stimulation of ocular cholinergic receptors
causes accommodative spasm with induced myopia due to
stimulation of the circular muscle of the ciliary body, and
miosis with decreased vision due to stimulation of the iris
sphincter. Prolonged use may result in conjunctival
hyperemia, pigment epithelial cysts of the iris sphincter,
inability to dilate the pupil due to fibrosis and posterior
synechiae, and uveitis due to breakdown of the bloodaqueous barrier (Choplin and Lundy, 2007). Cholinergic
agonists in general may exacerbate the following: severe
asthma, bronchial obstruction, acute cardiac failure or
recent myocardial infarction, active peptic ulcer,
gastrointestinal spasms, hyperthyroidism, urinary tract
obstruction, and parkinsonism (Netland, 2008).
Nevertheless, reports of adverse systemic effects from
miotics, such as pilocarpine, are rare (Everitt and Avorn,
1990). Systemic exposure to pilocarpine can prevented by
instructing patients to perform punctal occlusion after
topical administration.
DOSING AND COMPLIANCE. Because of the short action
of pilocarpine (2% eye drops) of 6-7 hours, pilocarpine is
administered on a QID basis which is an inconvenient
regimen to the patient and may result in poor compliance.
SIGNIFICANT DRUG-DRUG INTERACTIONS AND
HYPERSENSITIVITY REACTIONS. Although pilocarpine
causes ciliary muscle contraction which reduces
uveoscleral outflow (site of action of the prostaglandin
analogs), several studies have shown that pilocarpine does
not attenuate or antagonize the therapeutic effects of
prostaglandin analogs; the IOP reduction caused by
cholinergics may even be partially additive to that of the

uveoscleral outflow-enhancing prostaglandin derivative
latanoprost (Netland, 2008).
NECESSITY
DRUG AS FIRST-LINE TREATMENT AND AS

MONOTHERAPY. Pilocarpine, once a mainstay in
pharmacologic treatment of glaucoma, has been overtaken
by better drug groups such as beta-blockers and
prostaglandin derivatives as first-line therapies and has
been relegated as an adjunct to either a beta-blocker or a
prostaglandin derivative for the treatment of open-angle
glaucoma.
CONTRAINDICATION FOR USE IN RELATION TO HOST
FACTORS. There was no mention of host factors (e.g.
conditions in which pupilloconstriction will be undesirable
such as acute iritis) in the case that will make pilocarpine a
contraindication.
NON-RESPONSE. David, Livingston, and Luntz (1977) did
a study on long-term follow-up treated and untreated
glaucoma patients and reported that pilocarpine treatment
did not prevent glaucoma in about 10% of the treated
group and was not advantageous in patients whose mean
initial IOP was below 30 mm Hg. Meanwhile, Shroff (1982)
reported in his study that pilocarpine did not control the IOP
in 66% of the ocular hypertensive and open-angle
glaucoma subjects.
AFFORDABILITY
Pilocarpine is the most commonly used cholinergic and one

of the least expensive glaucoma medications (Choplin and
Lundy, 2007). It is available in the Philippines as Isopto
Carpine 2% eye drops and costs PhP 299.00 per 15 mL
container (MIMS, 2014). The dosing for Isopto Carpine 2%
eye drops is 1 drop per eye QID, so our patient's total
number of drops per day and per month will be 8 drops/day
and around 240 drops/month respectively. Assuming 1 mL
= 20 drops, 12 mL of the container will be consumed per
month; therefore, 1 container will be enough to meet the
240 drops/month requirement, costing PhP 299.00/month.
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EFFICACY
SAFETY
NECESSITY
AFFORDABILITY

Drug is able to reduce fluctuations in intraocular pressure during diurnal and intervisit periods
Drug needs only once-daily dosing for better compliance
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BRIMONIDINE (ALPHA-ADRENERGIC AGONIST)

Brimonidine, a selective alpha-adrenergic agonist and a
derivative of clonidine, primarily inhibits aqueous
production and secondarily increases aqueous outflow;
thus, it can be used to lower intraocular pressure in
patients with ocular hypertension or open-angle glaucoma
(Brunton et al, 2008). Furthermore, it appears to bind to
pre- and postsynaptic alpha-2 receptors. By binding to the
presynaptic receptors, the drugs reduce the amount of
neurotransmitter release from sympathetic nerve
stimulation and thereby lower IOP. By activating
postsynaptic alpha-2 receptors, these drugs stimulate the
G pathway, reducing cyclic AMP production and thereby
reducing aqueous humor production. Brimonidine is the
only clinically relevant alpha-adrenergic agonist for longterm treatment of glaucoma (Schultz, 2010).
EFFICACY
EFFECTIVITY IN LOWERING IOP TO TARGET LIMITS.

Alpha-adrenergic agonists reduce intraocular pressures by
20-25%, which is comparable to that of the beta-blockers
and parasympathomimetics, and can reach IOP reductions
of 27% as monotherapy (EGS, 2008). The efficacy of the
highly-selective alpha-2-adrenergic agonist brimonidine in
reducing intraocular pressure is similar to that of the betaadrenoceptor antagonist timolol (Brunton et al, 2008). A
study by Thomas et al (2003) on the efficacy and safety of
brimonidine in Indian eyes showed that only half of the
subjects on brimonidine had reduction rates of >25%.
RESPONSE RATES. Schuman et al (1997) conducted a

multicenter, double-masked, randomized, parallel-group,
active-controlled comparison clinical trial on brimonidine
bid for 1 year and reported that brimonidine-treated
subjects showed an overall mean peak reduction in
intraocular pressure (IOP) of 6.5 mm Hg as compared to
timolol-treated subjects showing a mean peak IOP
reduction of 6.1 mm Hg. Meanwhile, Joshi et al (2013) did
a prospective, open, randomized, comparative controlled
clinical trial on brimonidine and timolol and noted that the
mean IOP reduction in brimonidine (-5.5 mm Hg) is
comparable to that of timolol (-6.2 mm Hg).
CONTROL OF IOP FLUCTUATIONS. A cross-over, openlabel study by Thomas et al (2003) reported that
brimonidine, like latanoprost, also significantly reduces
diurnal fluctuations, albeit less than that of the latter. In the
study by Spaeth et al (2011), it was reported that
brimonidine decreased the short-term (daily) and long-term
(inter-visit) fluctuations by 18.9% and 11.3% respectively.
DURATION OF ACTION. Brimonidine peaks at 4-6 weeks,
and its duration of action ranges from 8 to 12 hours
(Parikh, 2008), longer than that of pilocarpine eye drops
but significantly shorter than beta-blockers or prostaglandin
analogs.
Page 12 of 29
RESPONSE RATES. Thomas et al (2003) reported in their

study that latanoprost had a higher mean IOP reduction
than brimonidine after 6 weeks; only 46.4% of the
brimonidine-treated patients attained an IOP reduction of at
least 25% and even less patients (28%) achieved at least
30% IOP reduction. On the other hand, a 3-month,
multicenter, double-masked, parallel-group, 4-visit study on
the efficacy and tolerability of brimonidine and latanoprost
in adults with open-angle glaucoma or ocular hypertension
(Dubiner et al, 2001) showed that at peak effect,
brimonidine BID was as effective as latanoprost QD in
lowering IOP. In treatment-naive patients, latanoprost was
associated with a significantly higher rate of nonresponse
(defined in the study as IOP reduction of less than 20%)
after 3 months of treatment compared with brimonidine,
and significantly more patients achieved clinical success
with brimonidine monotherapy than with latanoprost
monotherapy. Dubiner et al (2001) suggested that
brimonidine may be the more reliable choice for first-line
therapy of newly diagnosed open-angle glaucoma or ocular
hypertension.
SAFETY
SIDE EFFECTS. According to Schuman et al (1997),

brimonidine is well tolerated and has a low rate of allergic
response (more commonly, allergic blepharoconjunctivitis).
The lower incidence of the ocular adverse effects is due to
its greater alpha-2 selectivity, according to Apatachioae
and Chiselita (1999). Among the different preparation,
brimonidine 0.2% was more associated with ocular
allergies; brimonidine was formulated in concentrations of
0.15% and 0.1% to reduce the rate of allergy (Choplin and
Lundy, 2007). Brimonidine P 0.15% uses Purite instead of
benzalkonium chloride which has been known to cause
ocular allergies and fibrosis.
Brimonidine also has a neuroprotective effect, which is an
important feature in the new contexts of glaucoma
pathogenesis. However, brimonidine is associated with a
greater incidence of adverse local reactions than timolol. In
terms of systemic effects, it has no effects on
cardiopulmonary function. Serious systemic, especially
CNS, adverse effects are seen more in brimonidine-treated
children and more so in glaucoma-affected infants and
children below 2 years of age who are susceptible to lifethreatening adverse reactions such as CNS depression
and apnea brought about by the drug. This may be due to
brimonidine's ability to cross the blood-brain barrier.
Nevertheless, this is not very much applicable in our 48year-old patient.
DOSING AND COMPLIANCE. Brimonidine, although
commonly prescribed with a bid dosing, is best dosed
thrice daily as approved by the US FDA for round-the-clock
IOP control. As reported by Fedorchak et al (2014), 97% of
patients do not take it as prescribed because of such

regimen.
SIGNIFICANT DRUG-DRUG INTERACTIONS AND
HYPERSENSITIVITY
REACTIONS.
Brimonidine
significantly interacts with CNS depressants (alcohols,
barbiturates, opioids, sedatives, anesthetics, and tricyclics)
and may potentiate the depressive effects of the said drugs
(APGG and EGS). Ocular allergies e.g. allergic
conjunctivitis associated with brimonidine 0.2% are
significantly lessened with a formulation that has less
concentration of brimonidine (e.g. 1% or 1.5%).
NECESSITY
DRUG AS FIRST-LINE TREATMENT AND AS

MONOTHERAPY. Apatachioae and Chiselita (1999)
recommended brimonidine as first-line therapy in patients
who have contraindications to beta-blockers. Nevertheless,
numerous trials such as the one by Thomas et al (2003)
comparing brimonidine versus prostaglandin analogs have
significantly proven that the prostaglandin analogs hold a
clear advantage over the former as a treatment option
based on therapeutic parameters. Brimonidine is useful as
monotherapy (EGS, 2008). Investigators of a multicenter
open-label study on brimonidine (Abelson, 2001) reported
that brimonidine monotherapy is an efficacious and costeffective alternative to dual therapy for glaucoma and
ocular hypertension.
CONTRAINDICATIONS FOR USE IN RELATION TO
HOST FACTORS. Contraindications to brimonidine include
hypersensitivity to the drug or its components, infants and
children less than 2 years of age, and use of monoamine
oxidase inhibitors (EGS, 2008). As with all alpha-agonists,
this drug should be used with caution in patients with
cardiovascular disease (Brunton et al, 2008). However, our
patient did not have any of the above conditions which
would preclude brimonidine use, making it a suitable option
in our case.
NON-RESPONSE. Thomas et al (2003) reported that
39.3% of the brimonidine-treated eyes had IOP reduction
of less than 20% as compared to a 2% non-response rate
for latanoprost-treated eyes.
AFFORDABILITY
Brimonidine is available in the Philippines as Alphagan P

ophthalmic solution 0.15% and costs 905.75 PhP per 5 mL
container (MIMS, 2014). The dosing for this formulation is 1
drop in affected eye/s TID, so our patient's total number of
drops per day and per month will be 6 drops/day and
around 180 drops/month respectively. 9 mL of the
container will be consumed per month; therefore, it will take
2 containers of brimonidine to meet the 180 drops/month
requirement, costing PhP 1810.00/month.
Page 13 of 29
EFFICACY
SAFETY
NECESSITY
AFFORDABILITY

BRIMONIDINE (ALPHA-2-ADRENERGIC AGONIST)
0
1
0
1
1
1
0
1
0
1
1
1
4 points
3 points
2 points
1 point
3
3
2
10
Beta-blockers decrease intra-ocular pressure by reducing
aqueous humor production. They reach their peak effect
after 2 hours.
EFFICACY
CRITERION 1. DRUG IS ABLE TO EFFECTIVELY

LOWER THE INTRAOCULAR PRESSURE TO TARGET
LIMITS. For years, topical beta-blockers were the most
common first line of therapy for reducing intra-ocular
pressure. To decrease aqueous production, a nonspecific
beta-blocker eye drop such as levobunolol (Betagan) was,
until recently, the first drug class to be chosen. In a study
by Potocky and Vodrazkova, the influence of non-selective
betablockers (TIMOPTOL 0.5%, VISTAGAN 0.5%) and
selective betablocker (BETOPTIC 0.5%) on the intraocular
pressure, pulse frequency, systemic blood pressure and
lung capacity was evaluated. Authors concluded that all
three drugs reliably lowered intraocular pressure.
According to the European Glaucoma Society, beta
blockers have the ability to reduce intra-ocular pressure
from 20-25%. However central corneal thickness may have
an effect on the efficacy of the drug since thicker corneas
were shown to not respond as well to beta blocker therapy.
The advent of newer agents however, particularly
prostaglandin analogues, has given physicians and doctors
a wider variety of choices for both initial and adjunctive

medical therapy. But beta-blockers have been the gold
standard against which all new pressure lowering
medications are measured, and this is unlikely to change.
In the case, beta blockers would be sufficient to reduce the
intra-ocular pressure of the right eye to target limits
however it would not be enough for the left eye which
needs at least a 30% reduction from baseline. Because of
this, we do not give a point to beta-blockers for this
criterion.
CRITERION 2. DRUG IS ABLE TO REDUCE
FLUCTUATIONS IN INTRA-OCULAR PRESSURE
DURING DIURNAL AND INTER-VISIT PERIODS.
Elevated IOP is a known risk factor for glaucoma and for
progression of glaucoma; the higher a patient's IOP, the
greater the risk of progression. Increasingly, data suggest
that fluctuation in IOP throughout the day, even in the socalled "normal" range, may also be a risk factor for
progression. In a study conducted in 408 glaucoma
patients with low IOP, it was shown that even though IOP
was less than 18 mmHg at all times, patients whose
standard deviation was 2 mmHg or greater had a three
times greater risk of progression of damage (30- vs. 10percent risk) than those with deviations of less than 2
mmHg.
Page 14 of 29
These studies therefore affect the drugs we choose to treat

glaucoma. It is found out through studies that yesterday's
gold standard medical treatment, beta-blocker therapy,
does not control IOP at night, while some newer ocular
hypotensive medications control IOP throughout the 24hour cycle. We remember that the MOA of beta-blockers is
to reduce production of aqueous humor however during the
night there is a natural decrease of aqueous humor flow by
about 50%. This renders a drop that targets aqueous
production (i.e., beta blocker) less efficacious. Because of
this finding, we do not give a point for beta-blockers for this
criterion.
CRITERION 3. DRUG HAS A LONG DURATION OF
ACTION. Beta-blockers reach their peak action 2 hours
after instillation. To reach their maximum effect however
they need a few weeks to stabilize. The duration of action
of beta-blockers ranges from 12 to 24 hours. Comparing to
carbonic anhydrase inhibitors whose duration of action
usually lasts for only 8 to 18 hours, beta-blockers have a
longer duration. For this criterion, beta blockers get a point.
CRITERION 4. CLINICAL TRIALS/EVIDENCE SHOWING
BETTER RESPONSE RATES. In the Ocular Hypertension
Treatment Study (OHTS), there were no statistically
significant differences in IOP response to non-selective
beta blockers or prostaglandin analogues between selfidentified African-Americans and White Americans. Betablockers are not given a point under this criterion because
prostaglandin analogues show better response rates.
SAFETY
CRITERION 1. DRUG HAS ABSENT TO MINIMAL

REVERSIBLE SIDE EFFECTS ESPECIALLY THOSE
THAT AFFECT VISION. Ocular side effects for beta
blockers are uncommon. They include, epithelial
keratopathy, and slight reduction in corneal sensitivity.
Systemic side effects meanwhile include bradycardia,
arrhythmia, heart failure, syncope, bronchospasm and
airway obstruction. Systemic side effects can be minimized
by closing the eyes following application or using a
technique called punctal occlusion that prevents the drug
from entering the tear drainage duct and systemic
circulation. Although systemic side effects can be
prevented, the conditions enumerated are serious enough
to have beta-blockers lose a point for this criterion.
CRITERION 2. DRUG IS NOT ASSOCIATED WITH OR
HAS NO RARE LIFE-THREATENING ADRs WHICH
WOULD REQUIRE DISCONTINUATION OF USE.
Physicians should avoid using beta-blocker eye drops in
patients with reactive airway disease, cardiac conduction
defects, or heart failure. Systemic absorption of these eye
drops can cause bradycardia, bronchospasm, and even
fatalities from bronchospasm in patients with asthma and
heart conditions. If the physician is well-aware of the

possible complications of this drug, these systemic effects
can be effectively avoided. Also, based on a systemic
review on the different drugs for glaucoma, subjects on
timolol (beta-blocker) were seen to less likely drop out of
studies due to side effects than those on brimonidine
(alpha-adrenergic agonist), latanoprost (prostaglandin
analog), travoprost (prostaglandin analog), or betaxolol
(beta-blocker). Beta-blockers are given 1 point for this
criterion.
CRITERION 3. DRUG NEEDS ONLY ONCE-DAILY
DOSING FOR BETTER COMPLIANCE. Beta-blockers with
a duration of action lasting 12-24 hours usually requires a
daily dosing of once to twice a day. Levobunolol, a beta
blocker, often can be used "once-daily". Studies have
shown that dosing more than twice daily will not give any
further pressure lowering effect. Beta-blockers are given 1
point for this criterion.
CRITERION 4. DRUG HAS FEW DRUG-DRUG
INTERACTIONS OR RARE HYPERSENSITIVITY
REACTIONS. If the patient is already taking a systemic
beta blocker, the physician should consider using another
class of eye drops, because systemic beta-blocker therapy
may reduce the ocular hypotensive effects of beta-blocker
eye drops [Evidence level A, RCT].
Caution should be used in the co-administration of betablockers and oral and intravenous calcium antagonists
because of possible atrioventricular conduction
disturbances, left ventricular failure and hypotension.
Beta-blockers can also have a drug interaction with digitalis
and have an additive effect in prolonging conduction time.
An additive effect in producing hypotension and/or marked
bradycardia is also produced with catecholamine-depleting
drugs.
Beta-blockers are given a point under this criterion
because the case is assumed to be not taking any of the
aforementioned drugs.
NECESSITY
CRITERION
1. DRUG
OUTWEIGHS
OTHER
TREATMENT OPTIONS. Used in a variety of glaucoma
eye drops, beta-blockers were at one time the drugs of
choice in treating glaucoma. However, many glaucoma
specialists now report that prostaglandins have taken the
lead in recent years as a first-line therapy for glaucoma
(EyeWorld, January 2007).
It should be emphasized however that the emergence of
prostaglandins as first-line therapy has not eliminated other
options, such as beta-blockers. Beta-blockers are still a
viable option for glaucoma treatment and, in some cases,
Page 15 of 29
are the best therapy for some patients. Many glaucoma

patients will still end up using a beta-blocker at some point
in their treatment. They are good drugs just not the drug
used as first-line therapy anymore (Thimons, 2004).
Beta-blocker drugs do not get a point for this criterion.
CRITERION 2. DRUG IS AN EFFECTIVE STAND-ALONE
DRUG. Beta-blockers can be used as the only therapy for
primary open angle glaucoma. However, there are times
when monotherapy fails. When this happens, a
dorzolamide and timolol maleate combination (Cosopt) is
available to decrease aqueous production by two different
mechanisms in a single agent. Beta-blockers get a point for
this criterion.
CRITERION 3. DRUG HAS NO CONTRAINDICATION
FOR USE IN RELATION TO HOST FACTORS. Major
contraindications for the use of beta blockers are asthma,
history of obstructive pulmonary disease, sinus
bradycardia, heart block and cardiac failure. Since these
diseases were not given in the case, it is assumed that no
host factor is contraindicated for the use of beta blockers.
Beta-blockers get a point for this criterion.
CRITERIA 4. DRUG HAS FEW REPORTS OF NONRESPONSE. With longer-term use of timolol or
levobunolol, tachyphylaxis is not uncommon. In a
significant number of cases, the pressure responsiveness
decreases with continuous use. The timolol therapy is
associated with the phenomenon of short-term escape and
long term drift. In short-term escape, most patients
experience a good IOP reduction after the start of timolol
EFFICACY
SAFETY
NECESSITY
AFFORDABILITY
therapy, but the pressure rises after a few days to finally

level off after 3-4 weeks. One must therefore wait for at
least one month after starting timolol to determine its
efficacy. In long term drift, after about 1 year of timolol
therapy, few patients show a slow decline in pressure
responsiveness to timolol. Many of these will regain
responsiveness after a washout period.
Secondary analysis of phase three clinical trials comparing
twice daily treatment with 0.5% timolol versus .0005%
latanoprost daily demonstrated that 28% of patients treated
with timolol and 18% of those treated with latanoprost were
non-responders. Beta-blockers do not get a point for this
criterion.
AFFORDABILITY
Based on the website of MIMS, betaxolol and timolol are

both available in the Philippines. The drugs are usually
dispensed in 5 ml containers. The most expensive is
Betoptic which is available for 470 pesos per 5 ml
container. Other brands under timolol include Celsus
Timolol Maleate eye drops (320 PhP), Nyolol eye drops
.5% (550 PhP), and Oftan eye drops 5 mg/ml (392 PhP). If
we compute for the total expense for a month, considering
we distill 4 drops per day (2 for each eye) and that 1 ml has
20 drops. The most expensive which is Betoptic will have a
total of 564 PhP for one month, while the least expensive
which is Celsus Timolol Maleate will have a total of 384
PhP for a month. Considering this, beta-blockers are
considered affordable drugs and are given 4 points.

0
0
1
0
0
1
1
1
0
1
1
0
4 points
3 points
2 points
1 point
1
3
2
4
10
Page 16 of 29

The mode of action of carbonic anhydrase inhibitors in
lowering intra-ocular pressure is the reduction of aqueous
humor formation.
EFFICACY
CRITERION 1. DRUG IS ABLE TO EFFECTIVELY

LOWER THE INTRAOCULAR PRESSURE TO TARGET
LIMITS. Most of the available medications used to lower
intraocular pressure today come in the form of eye drops.
In keeping with that trend, when carbonic anhydrase
inhibitors (CAIs) are prescribed, they tend to be in topical
form. The shift away from oral carbonic anhydrase
inhibitors, such as acetazolamide and methazolamide, has
also been hastened by the development of potent classes
of topical drugs such as prostaglandin analogs and alpha
agonists. Often CAIs are overlooked when deciding how to
treat a patient. However, they can do a very effective job of
lowering IOP and keeping it at a safe level. Diamox
(acetazolamide) has been found to reduce aqueous flow
21-30% during the day and 24% at night. Data from the
European Glaucoma Society on the other hand observed
that CAIs can decrease IOP by 15-20%.
Dr. Todd Perkins of the University of Wisconsin also found
oral CAIs to be significantly more effective than topical
CAIs in many patients with a patient having an IOP of 40
mmHg drop to 25 mmHg. However not all the literature
agrees about the comparative value of oral vs. topical
CAIs; some studies have found the oral drugs to be more
effective than topical, while others have found little
difference.
Although effective, long-term use of CAIs is avoided
because of the potential for side effects. These drugs are
sometimes reserved for situations when a patient's
glaucoma is severe and also for short-term therapy.
Because these drugs can achieve a lowering of IOP by as
much as 30%, they are given a point for this criterion.
CRITERION 2. DRUG IS ABLE TO REDUCE
FLUCTUATIONS IN INTRAOCULAR PRESSURE
DURING DIURNAL AND INTER-VISIT PERIODS. Again,
according to Perkins, Diamox (acetazolamide) has been
found to reduce aqueous flow 21 to 30 percent during the
day and 24 percent at night which is an advantage over the
beta-blockers.
A study by Orzalesi, evaluated circadian IOP patterns in
patients taking several type of ocular hypotensive drugs
one of which was dorzolamide, a topical CAI. The study

found out that prostaglandins have the most consistent
coverage for 24 hours particularly in the nocturnal period.
As you can see in the figure below, dorzolamide did not
have much control in fluctuation of IOP, with
measurements of about 20 mmHg at 3 pm and 16 mmHg
at midnight. This might mean a better control of fluctuation
by oral CAIs than topical CAIs.
Even though prostaglandins are better controllers for IOP

fluctuations, CAIs were still able to provide control so they
are given a point for this criterion.
CRITERION 3. DRUG HAS A LONG DURATION OF
ACTION. Compared to other medications for open-angle
glaucoma, Carbonic Anhydrase Inhibitors have the shortest
duration of action leading to more frequent dosing. Oral
CAIs usually have a duration of 8-12 hours having 2-4
times daily intake. On the other hand, topical CAIs have a
slightly longer duration of action at 10-18 hours. Instillation
is usually 2-3 times daily. The CAIs do not get a point for
this criterion.
CRITERION 4. CLINICAL TRIALS/EVIDENCE SHOWING
BETTER RESPONSE RATES. According to Singh and
Shrivastava, the role of other contemporary classes of
glaucoma medications, including topical carbonic
anhydrase inhibitors, is limited for first-line use due to the
necessity of using these drugs more than twice a day and
because the quality of IOP lowering, even when dosed
three or four times a day, is not as desirable as that seen
with the prostaglandin analogs. CAIs do not get a point for
this criterion.
SAFETY
CRITERION 1. DRUG HAS ABSENT TO MINIMAL

REVERSIBLE SIDE EFFECTS ESPECIALLY THOSE
Page 17 of 29
THAT AFFECT VISION. One of the important factors

which limit the use of carbonic anhydrase inhibitors is their
capacity to produce systemic effects. Their side effect
profile tends to limit their use to situations involving acute
IOP elevation or chronically elevated IOP in a patient on
maximal topical agents prior to a more definitive procedure
to lower IOP (Canadian Opthalmological Society). Ocular
side effects can potentially include idiosyncratic
sulfonamide-related transient angle-closure, myopia and
choroidal thickening, but these are rare. Systemic effects
common with prolonged use include gastrointestinal upset,
paresthesias, diuresis, metabolic acidosis, malaise,
anorexia, metallic taste, tingling of fingers and potassium
depletion. CAIs are not given a point for this criterion.
CRITERION 2. DRUG IS NOT ASSOCIATED WITH OR
HAS NO RARE LIFE THREATENING ADRs WHICH
WOULD REQUIRE DISCONTINUATION OF USE.
Systemic carbonic anhydrase inhibitors may produce
adverse reactions common to all sulphonamide derivatives
like anaphylaxis, erythema multiforme, Stevens-Johnson
syndrome, bone marrow depression, pancytopenia,
thrombocytopenic purpura, haemolytic anemia and
agranulocytosis. Some of the above symptoms are
irreversible and lethal (European Glaucoma Society). CAIs
are not given a point under this criterion.
CRITERION 3. DRUG NEEDS ONLY "ONCE-DAILY"
DOSING FOR BETTER COMPLIANCE. Most of the oral or
topical carbonic anhydrase inhibitors need two to three
times daily dosing. This may decrease compliance to the
drug. CAIs are again not given a point in this criterion.
CRITERION 4. DRUG HAS FEW DRUG-DRUG
INTERACTIONS OR RARE HYPERSENSITIVITY
REACTIONS. Systemic CAIs should be used with caution
in patients on steroid and systemic hypertension diuretic
therapy because of the potential for developing
hypokalemia (European Glaucoma Society). Additive side
effects or increased toxicity have been reported for
systemic CAIs taken together with systemically
administered ciclosporin, digitalis, lithium, and aspirin
(increased toxicity). Systemic acetazolamide decreases the
effects of oral antidiabetics, and diminishes cholinesterase
activity. Stevens-Johnson syndrome also produces a
serious but rare hypersensitivity reaction. CAIs are not
given a point for this criterion.
NECESSITY
CRITERION
1. DRUG
OUTWEIGHS OTHER
TREATMENT OPTIONS. The short-term use of carbonic
anhydrase inhibitors to avoid systemic effects plus its
multiple daily dosing requirements puts CAIs at a

disadvantage as the preferred treatment option. CAIs are
not given a point for this criterion.
CRITERION 2. DRUG IS AN EFFECTIVE STAND-ALONE
DRUG. The topical carbonic anhydrase inhibitors,
dorzolamide and brinzolamide, often are used as
adjunctive therapy but rarely as initial therapy (Distelhorst,
2003). Systemic carbonic anhydrase inhibitors are the
reserved group of drugs given orally as an adjunct when
IOP is not controlled adequately with topical medication.
However, in another study by Serle and Rabinowitz,
dorzolamide, a topical CAI, is proven to be effective in
reducing IOP as a single-agent therapy. Thus, in some
patients dorzolamide may be used two or three times daily
as a first-line drug for the treatment of glaucoma. Because
of this, CAIs are given a point for this criterion.
CRITERION 3. DRUG HAS NO CONTRAINDICATION
FOR USE IN RELATION TO HOST FACTORS. According
to the European Glaucoma Society, topical CAIs are
contraindicated for patients with hypersensitivity reactions
for any of the drug components. On the other hand, major
contraindications for systemic CAIs include decreased
sodium and potassium levels, kidney and liver disease or
dysfunction, suprarenal gland failure and hyperchloremic
acidosis. All of these conditions are presumed to be absent
in the patient so CAIs are given a point in this criterion.
CRITERIA 4. DRUG HAS FEW REPORTS OF NONRESPONSE. No reports on non-response for carbonic
anhydrase inhibitors can be found. This may be attributed
to the use of CAIs only as last-line treatment for IOPs that
cannot be controlled by other topical drugs. In other words,
these drugs are reserved for situations when a patient's
glaucoma is severe. A point is given for CAIs in this
criterion.
AFFORDABILITY
A 5 ml container for dorzolamide (Trusopt) is 875.93 pesos.

Considering it is instilled 3 times a day, computation will
show that a patient will spend approximately 1577 PhP a
month. Brinzolamide (Azopt), another topical CAI is priced
at 942 PhP per 5 ml bottle. Considering it is instilled twice a
day, computation will that a patient will spend 1130.40 PhP
in a month. Acetazolamide (Cetamid) an oral CAI, comes in
packs of 100 pieces. Each piece is priced at 25 PhP. Thus,
if you take 4 tablets in one day, you spend 3000 pesos in
one month. Taking into consideration the availability of
cheaper topical CAIs, 2 point will be given for this drug
group.
Page 18 of 29
EFFICACY
SAFETY
NECESSITY
AFFORDABILITY

1
1
0
0
0
0
0
0
0
1
1
1
4 points
3 points
2 points
1 point
2
0
3
2
7
PROSTAGLANDIN ANALOGS
Prostaglandins reduce IOP by increasing outflow of
aqueous humor mostly by enhancing the uveoscleral
pathway. They have no effect on aqueous production. It is
believed that prostaglandins improve the uveoscleral
pathway by altering the ciliary body and scleral
architecture, making it more amenable to aqueous egress
through stimulation of collagenases and matrix
metalloproteinases, and the relaxation of ciliary muscle
bundles. The exact mechanism of action, however,
remains to be fully elucidated.
EFFICACY
EFFECTIVITY IN LOWERING IOP AND DURATION OF

ACTION. Currently, the only approach proven to be
efficient in preserving visual function is lowering the IOP.
Lowering the pre-treatment IOP by 25% or more has been
shown to inhibit progression of POAG. It is reasonable to
select an initial target pressure of at least 25% lower than
pre-treatment levels. However, in this case, it has been
established that the target IOP reduction from the baseline
is 25% for the right eye and 30% for the left eye.
Prostaglandins are the most potent topical agents for
lowering IOP. In a recent meta-analysis of articles
published up to 2003, prostaglandins had the highest peak
mean difference from baseline IOP compared with any
other class of topical anti-glaucoma agent. Their relative
change from mean baseline at peak was 31% to 33% and

at trough 28% to 29%. (Van der Valk, 2005).
As to the IOP lowering effectivity of prostaglandin analogs
during diurnal periods, there has been a study which was
conducted by Orzalesi, et. al. The results showed that the
drugs' effect was significantly greater during the daytime (9
am-9 pm) than during the night-time (midnight-6 am) with
all prostaglandin analogs. In 7 of 44 patients (16%),
nocturnal IOP was significantly higher than diurnal IOP,
both at baseline and under the 3 prostaglandin analogs.
Reduction of the intraocular pressure starts approximately
2-4 hours after the first administration with peak effect
reached within approximately 8-12 hours. Maximum IOP
lowering is often achieved 3 to 5 weeks from
commencement of treatment. Also, topical application of
prostaglandin analogs is recommended to be done in the
evening to reduce the early morning diurnal spike.
RESPONSE RATES TO TREATMENT. In a meta-analysis
study by Robert, the average mean percentage IOP
reduction values at 13 weeks showed that the
prostaglandin analogues generally provided better
response rates as evidenced by a greater percentage of
IOP reduction than the beta-blockers, achieving an
average mean IOP reduction 4.9 mmHg superior to that
produced by the beta-blockers.
Page 19 of 29
SAFETY
SIDE EFFECTS/ADVERSE DRUG REACTIONS.

According to the European Glaucoma Society, side effects
of prostaglandin analogs include cystoid macular edema,
conjunctival irritation, increased eyelash growth, periocular
hyperpigmentation, iris color change, uveitis, possible
herpes virus activation. In a study by Parrish, et.al., it has
been mentioned that although generally well tolerated,
prostaglandins do have local side effects and that
conjunctival hyperemia and irritation are the most common
of them. However, these side effects are easily managed
and are reversible. Conjunctival irritation caused by
application of prostaglandin analogs can be managed by
just washing the substance from the eye with water for 4-5
minutes.
EFFECTIVITY AS STAND-ALONE DRUG. As the

prostaglandin analogs and nonselective beta-blockers may
both be effective with OD dosing, fixed drug combination of
timolol 0.5% with each of the three frontline prostaglandin
analogs are commercially available. These have been
shown to have significantly more IOP lowering effect than
either drug used alone (Shah, 2011).
The European Glaucoma Society, on the other hand,
suggests that prostaglandin analogs, when used as standalone treatment, is capable of lowering the IOP up to 33%
from baseline. This lowering effect is enough since the
target is just 25% from the baseline. Satisfaction of the
recommended lowering effect suggests that prostaglandin
analogs are effective as stand-alone drugs.
DOSING AND COMPLIANCE. Better compliance to taking

medications is affected by the dosing procedures of the
drugs. Among the five families of anti-glaucoma agents,
only the prostaglandin analogs are administered "oncedaily".
According to the Asia-Pacific Glaucoma Guidelines, higher

targets, as in the cases in which there is a high suspicion of
visual loss, may require fixed-combination drugs, which
include timolol plus a prostaglandin analog, as mentioned
above.
DRUG-DRUG INTERACTIONS AND HYPERSENSITIVITY

REACTIONS. Topical preparations containing thiomersal
as preservative form a precipitate with latanoprost, and
hence must be instilled with a gap of at least 5 minutes
between the two (Shah, 2011). Clinical studies have
demonstrated additive effects of prostaglandins with all
other anti-glaucoma medications, including beta-blockers,
alpha-adrenergic medications, carbonic anhydrase
inhibitors and cholinergic agonists. As to hypersensitivity
reactions, it has been mentioned above that conjunctival
irritation is common among patients using prostaglandin
analogs. However, these hypersensitivity reactions may
easily be reversed.
CONTRAINDICATIONS. Contraindications for the use of

prostaglandin analogs include pregnancy, breast-feeding,
known cardiac or pulmonary conditions and uncontrolled
systemic diseases (Robert, 2010). These conditions were
not mentioned as present in our case which makes it safe
for prostaglandin analogs to be used.
NECESSITY
DRUG AS FIRST-LINE TREATMENT. Prostaglandins

rapidly replaced topical beta-blockers as first-line IOPlowering agents, mostly because of their potency, safe
systemic side-effect profile, and once-daily dosing.
(Higginbotham, 2002).
EFFICACY
SAFETY
AFFORDABILITY
COST FOR 1 MONTH DOSING. The following drugs are

the least expensive among the prostaglandin analogs
available in the Philippines:
Bimatoprost (0.03%) Lumigan P1,077.00/container (3
mL)
Latanoprost (0.005%) Xalatan P1,253.49/container (2.5
mL)
Travoprost (0.004%) Travatan P1,244.00/container (2.5
mL)
Each container may be used up to one month since they
are administered via one drop, "once-daily." A 2.5- or 3-mL
container contains 50-60 drops respectively, which is
enough for one month.

1
1
1
1
0
1
1
1
4
3
Page 20 of 29
NECESSITY
AFFORDABILITY

1
1
1
1
4 points
3 points
2 points
1 point
4
2
14
SUMMARY ESNA SCORES OF

DRUGS UNDER CONSIDERATION
BRIMONIDINE (ALPHA-2-ADRENERGIC AGONIST)
TOTAL
1
2
1
2
4
2
3
3
0
3
1
3
2
3
4
4
2
4
2
2
8
11
10
7
14
ESNA: PROSTAGLANDIN ANALOGS

LATANOPROST, TRAVOPROST, BIMATOPROST
PROSTAGLANDIN ANALOGS (LATANOPROST
AND TRAVOPROST)
These drugs are lipid structural derivatives and are
synthetic prostaglandin F2a analogues. They are actually
prodrugs and these arachidonic acid derivatives are
hydrolyzed by corneal esterases to a biologically active
free acid. The respective free acids then bind to to specific
PGF2 receptors in the trabecular meshwork and the ciliary
body in turn increasing the aqueous outflow through these
routes.
Latanoprost requires maintenance of cold chain prior to
uncapping of the bottle and, thereafter, has limited shelf life
of 44 days at room temperature. Travoprost has no such

considerations.
PROSTAMIDE (BIMATOPROST)
Bimatoprost is an active drug in contrast to latanoprost and
travoprost which, as described above, require activation by
corneal enzymes. Bimatoprost increase aqueous outflow
by increasing both trabecular outflow facility and
uveoscleral outflow. Bimatoprost acid is 3 to 10 times as
potent as latanoprost acid. Inspite of this, the
therapeutically used concentration of bimatoprost is 6 times
that of latanoprost. This is because of the slow conversion
of bimatoprost to bimatoprost acid.
Page 21 of 29
PROSTAGLANDIN ANALOGS AND

PROSTAMIDES
The recommended dosing regimen for these three drugs is
"once-daily" topical application preferably in the evening to
reduce the early morning diurnal spike. Studies have

shown that all the available classes of prostaglandins have
excellent 24-hour IOP control despite once a day dose,
making it extremely patient convenient.
CRITERIA
Efficacy
1 Drug is able to effectively lower the intraocular pressure to target limits
2 Drug is able to reduce fluctuations in intraocular pressure during diurnal and inter-visit periods
3 Drug has a long duration of action
4 Clinical trials/evidence showing better response rates
Safety
1 Drug has absent to minimal reversible side effects especially those that affect vision
2 Drug is not associated with or has no rare life-threatening ADRs which would require discontinuation
of use
3 Drug needs only "once-daily" dosing for better compliance
4 Drug has few drug-drug interactions or rare hypersensitivity reactions
Necessity
1 Drug outweighs other treatment options
2 Drug is an effective stand-alone drug
3 Drug has no contraindication for use in relation to host factors
4 Drug has few reports of non-response
Affordability
1 Total cost per month: 100.00-500.00 PhP
2 Total cost per month: >500.00-1000.00 PhP
3 Total cost per month: >1000.00-2000.00 PhP
4 Total cost per month: >2000.00 PhP
TOTAL
Legend:
L Latanoprost; T Travoprost; B - Bimatoprost
1
1
1
1
1
1
1
0
1
1
1
1
0
0
0
0
1
1
1
1
1
1
1
1
0
1
1
1
0
1
1
1
1
1
1
1
11
10
14
ESNA scores of each drug under prostaglandin derivatives.
LATANOPROST
Latanoprost lowers the IOP up to 33% from the baseline
(Van der Valk, 2005). In a commercial study by Pfizer, it
has been found out that latanoprost dosed "once-daily"
showed similar IOP reduction capacity with timolol, a betablocker, which is dosed twice daily. Patients with mean
baseline intraocular pressure of 24-25 mmHg who were
treated for 6 months in multi-center, randomized, controlled
trials demonstrated 6-8 mmHg reductions in intraocular
pressure. Reduction of the intraocular pressure starts
approximately 3 to 4 hours after administration and the
maximum effect is reached after 8 to 12 hours.
As to its safety, a study, still conducted by Pfizer, has
shown that one side effect of long-term use of latanoprost
is the pigmentation of the iris. Results showed that the
onset of noticeable increased iris pigmentation occurred
within the first year of treatment for the majority of the
patients who developed noticeable increased iris
pigmentation. Patients continued to show signs of
increasing iris pigmentation throughout the five years of the
study. With an increasing pigmentation of the iris, there is
also an increasing chance for visual loss. This is one of the

reasons why some latanoprost users discontinue the drug.
Latanoprost is preserved in benzalkonium chloride and it is
responsible for most of the hypersensitivity reactions to the
drug. Although human in-vivo studies have generated rare
reports of BAC induced IgE-mast cell type reactions, a
recent study demonstrated bronchoconstriction in
asthmatics when challenged with BAC suggesting a
nonspecific trigger (Lee, 2007). However, since the patient
in the case has no known asthma problem, this drug is not
contraindicated in relation to the patient.
TRAVOPROST
Travoprost lowers the IOP up to 31% from the baseline
(Van der Valk, 2005). Reduction of intraocular pressure
starts approximately 2 hours after administration of
travoprost. The maximum effect is observed 12 hours after
administration and is maintained throughout the day.
As to the safety profile of travoprost, since it is much similar
to latanoprost, the adverse drug reactions, drug-drug
Page 22 of 29
interactions and contraindications for both drugs are the

same.
Based on the guidelines provided by the European
Glaucoma Society, travoprost is only a second-line drug
indicating that it is prescribed for the reduction of elevated
intraocular pressure in patients with open-angle glaucoma
or ocular hypertension who are intolerant of other
intraocular pressure lowering medications or insufficiently
responsive (failed to achieve target IOP determined after
multiple measurements over time) to another intraocular
pressure-lowering medication.
BIMATOPROST
Bimatoprost has been proven to lower the IOP up to 31%
from the baseline (Van der Valk, 2005). A study by
Gandolfi, et. al. showed that Bimatoprost provided lower
mean pressures than latanoprost at every time point
throughout the 3-month period of the study and was
statistically superior in achieving low target pressures.
More patients reached low target pressures with
bimatoprost. Also, in a study by Cantor, et. al, they have
concluded that Bimatoprost provided greater mean IOP
reductions than travoprost. The result was taken after 6
months and the mean IOP reduction at 09:00 h was 7.1
mm Hg (27.9%) with bimatoprost and 5.7 mm Hg (23.3%)
with travoprost. At 13:00 h, mean IOP reduction was 5.9

mm Hg with bimatoprost (25.3%) and 5.2 mm Hg (22.4%)
with travoprost. At 16:00 h, the mean IOP reduction was
5.3 mm Hg (22.5%) with bimatoprost and 4.5 mm Hg
(18.9%) with travoprost.
Reduction of the intraocular pressure starts approximately
4 hours after the first administration with maximum effect
reached within approximately 8 to 12 hours. Bimatoprost
may be used concomitantly with other topical ophthalmic
drug products to lower intraocular pressure. If more than
one topical ophthalmic drug is being used, the drugs
should be administered at least five (5) minutes apart.
In clinical trials, the most frequent events associated with
the use of bimatoprost ophthalmic solutionoccurring in
approximately 15% to 45% of patients, in descending order
of incidence, included conjunctival hyperemia, growth of
eyelashes, and ocular pruritus. Approximately 3% of
patients discontinued therapy due to conjunctival
hyperemia. These side effects, however, are not lifethreatening and are reversible therefore, the safety of
bimatoprost as therapy to primary open-angle glaucoma is
still not in question.
SELECTING THE P-DRUG

Based on the above ESNA criteria of each drug under the category of prostaglandin analogs, bimatoprost acquired the highest
points. Aside from this, there are also other evidences which led to the selection of bimatoprost as the p-drug for the treatment of
primary open-angle glaucoma. Below is a meta-analysis of different studies comparing the IOP lowering ability of the three
prostaglandin drugs:
It has been noted that bimatoprost is the most effective of the three. This, along with a lower cost for medication, makes it the
prescribed drug for treatment of primary open-angle glaucoma.
Page 23 of 29
NON-PHARMACOLOGIC INTERVENTIONS
Surgery is indicated when glaucomatous optic neuropathy
worsens (or is expected to worsen) at any given level of
IOP and the patient is on maximum tolerated medical
therapy (MTMT).
MTMT varies considerably between individuals, and it may
consist of medicines from 1 or several classes (including a
beta-adrenergic antagonist, a prostaglandin agent, an
alpha-agonist, and a topical carbonic anhydrase inhibitor).
Some patients are observed to progress simply because
compliance with the medical regimen becomes too difficult
because of the following: high drug costs, inability to
remember the schedule of multiple medications, inability to
instill them in the eyes properly secondary to arthritis or
other incapacitation (especially common among elderly
patients or those with other chronic systemic conditions), or
intolerable ocular and systemic adverse effects.
LASER TRABECULOPLASTY
Argon Laser Trabeculoplasty
Argon Laser Trabeculoplasty (ALT) was introduced as a
treatment modality for open angle glaucoma because it has
been demonstrated that argon laser treatment of angle
structures could lower intraocular pressure (IOP) without
causing full-thickness openings through the trabecular
meshwork (TM) (Samples, 2011).
Two theories have been presented as to how this
procedure lowers the IOP. It is thought that (1) thermal
energy directed towards the TM causes focal scarring of
trabecular beams that constitute the TM, thereby opening
up space in adjacent structures (mechanical theory), or that
(2) inflammatory cytokines induce structural changes and
allow repopulation of the TM with dividing trabecular
epithelial cells from untreated areas, which are more
effective in phagocytosis and produce a different
composition of extracellular matrix with improved outflow
facility properties (biological theory).
Long-term studies such as that of Spaeth, et. al. have
shown that ALT maintains IOP control in 67-80% of eyes 1
year after the procedure and in 35-50% of eyes 5 years
after the procedure. ALT can be repeated, targeting the
reminder of the TM (typically half of the angle is treated
initially), but the effect to be expected is modest, especially
if the first treatment session had poor outcomes.
Selective Laser Trabeculoplasty
Selective Laser Trabeculoplasty (SLT) is basically the
same with ALT except only that it uses a lower power laser.
SLT protects trabecular meshwork against thermal or
coagulative effects by selectively targeting only the

pigmented cells and preserving surrounding tissue.
Several prospective and retrospective studies indicate that
SLT appears comparable to but not better than ALT in
lowering IOP (Van de Veire, 2006). Selective laser
trabeculoplasty also appears to be comparable in efficacy
to medical therapy with prostaglandin analogs, although in
one prospective study, SLT was only comparable to
latanoprost when 360 degrees of the trabecular meshwork
was treated. In this study, latanoprost had a better IOPlowering effect compared with 90 and 180 degrees of
treatment (Nagar, 2005).
INCISIONAL GLAUCOMA SURGERY

Trabeculectomy
Filtering surgery is effective in lowering IOP; it is generally
indicated when medicine or laser therapy is insufficient to
control disease and can be considered in selected cases
as initial therapy.
Filtering surgery provides an alternative path for the
escape of aqueous humor, and it often reduces IOP and
the need for medical treatment. Estimates of success rates
over time range from 31% to 56% in different populations
(Law, 2007).
While long-term control is often achieved, many patients
may require further therapy or a reoperation, which carries
a higher failure rate (Law, 2009). Furthermore, filtering
surgery increases the likelihood that phakic eyes may
undergo cataract surgery. In eyes that have undergone
previous cataract surgery involving the conjunctiva, the
success rate of initial glaucoma surgery is reduced (Hylton,
2003).
Aqueous Shunts
All aqueous shunts (also known as tube shunts,
glaucoma drainage devices, and setons) consist of a tube
that diverts aqueous humor to an end plate located in the
equatorial region of the eye. The primary resistance to flow
through these devices occurs across the fibrous capsule
that develops around the end plate. Aqueous shunts differ
in their design with respect to the size, shape, and material
from which the end plate is made. They may be further
subdivided into valved and nonvalved shunts, depending
on whether or not a valve mechanism is present to limit
flow through the shunt if the IOP becomes too low.
Aqueous shunts have traditionally been used to manage
medically uncontrolled glaucoma when trabeculectomy has
failed to control IOP or is deemed unlikely to succeed. This
Page 24 of 29
includes eyes with neovascular glaucoma, uveitic

glaucoma, extensive conjunctival scarring from previous
ocular surgery or cicatrizing diseases of the conjunctiva,
and congenital glaucoma in which angle surgery has failed.
However, the indications for using aqueous shunts have
been broadening, and these devices are being increasingly
utilized in the surgical management of glaucoma.
A systematic review concluded that aqueous shunts are

comparable with trabeculectomy for IOP control and
duration of benefit, that larger end-plate surface area
provides better IOP control, and that there appears to be
no advantage to the use of antifibrotic agents or systemic
corticosteroids as adjuncts to aqueous shunt procedures
(Minckler, 2008).
SAMPLE PRESCRIPTION
Bimatoprost 0.03%
(Lumigan)
3mL/container
#1 container
Sig: Instill one drop on the affected eye
"once-daily" in the evening.
Refill: None
Warning: Stop medication and seek consult
if the following occurs: eye itching, redness
and changes in color.
Page 25 of 29
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PAMANTASAN NG LUNGSOD NG MAYNILA

Department of Basic and Clinical Pharmacology, Toxicology, and Therapeutics

CALAUNAN, Martin Joseph A.

Discussion of the Diagnosis

ESNA of Prostaglandin Analogues

PANGAN, Kimberly Anne M.

PRIMARY OPEN-ANGLE GLAUCOMA

Glaucoma is the second leading cause of blindness

glaucoma as of 2010 and is expected to rise to 3 million by

The pathophysiology of glaucoma is believed to be

damage caused by glutamate or glycine released from

DIAGNOSIS AND WORK-UP

According to the Preferred Practice Pattern Guidelines of

Evidence of optic nerve damage from either, or both, of

ELEMENTS OF OPHTHALMIC EVALUATION

OPTIC NERVE HEAD AND

Ocular, family, and systemic history (e.g. asthma)

SUPPLEMENTAL OPHTHALMIC TESTING

OPTIC NERVE HEAD AND

EYE STAGING AND SETTING OF TARGET IOP

Canadian Ophthalmology Society glaucoma clinical practice guidelines (2009).

TREATMENT ALGORITHM FOR PATIENTS WITH PRIMARY OPEN-ANGLE GLAUCOMA

PRINCIPLES. It is vital that treatment be tailored to the

SWITCHING MONOTHERAPY AND ADJUNCTIVE

DRUGS UNDER CONSIDERATION

1 drop per eye QID

(as maintenance therapy)

1 drop in the affected eye/s TID

Drug is able to effectively lower the intraocular pressure to target limits

EFFECTIVITY IN LOWERING IOP TO TARGET LIMITS.

intraocular pressure by 20-25% (European Glaucoma

RESPONSE RATES. No literature specifically focusing on

SIDE EFFECTS. Pilocarpine is infrequently used

cholinergics may even be partially additive to that of the

DRUG AS FIRST-LINE TREATMENT AND AS

Pilocarpine is the most commonly used cholinergic and one

Drug is able to effectively lower the intraocular pressure to target limits

BRIMONIDINE (ALPHA-ADRENERGIC AGONIST)

EFFECTIVITY IN LOWERING IOP TO TARGET LIMITS.

RESPONSE RATES. Schuman et al (1997) conducted a

RESPONSE RATES. Thomas et al (2003) reported in their

SIDE EFFECTS. According to Schuman et al (1997),

patients do not take it as prescribed because of such

DRUG AS FIRST-LINE TREATMENT AND AS

Brimonidine is available in the Philippines as Alphagan P

Drug is able to effectively lower the intraocular pressure to target limits

BRIMONIDINE (ALPHA-2-ADRENERGIC AGONIST)

CRITERION 1. DRUG IS ABLE TO EFFECTIVELY

a wider variety of choices for both initial and adjunctive

These studies therefore affect the drugs we choose to treat

CRITERION 1. DRUG HAS ABSENT TO MINIMAL

heart conditions. If the physician is well-aware of the

are the best therapy for some patients. Many glaucoma

therapy, but the pressure rises after a few days to finally

Based on the website of MIMS, betaxolol and timolol are

Drug is able to effectively lower the intraocular pressure to target limits

CARBONIC ANHYDRASE INHIBITORS

CRITERION 1. DRUG IS ABLE TO EFFECTIVELY

one of which was dorzolamide, a topical CAI. The study

Even though prostaglandins are better controllers for IOP

CRITERION 1. DRUG HAS ABSENT TO MINIMAL

THAT AFFECT VISION. One of the important factors

multiple daily dosing requirements puts CAIs at a