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MedicalPractice,
Management
of Glaucoma
Journal of Current Glaucoma
September-December
2009;3(3):13-17
Medical Management of Glaucoma
Tanuj Dada, Vivek Dave, Neha Mithal
Glaucoma Services, Dr RP Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
Essential Work-up before Initiating Therapy
Abstract: Primary open-angle glaucoma is a pressure sensitive,
progressive, chronic optic neuropathy characterized by acquired
atrophy of the optic nerve and loss of retinal ganglion cells and their
axons. Several well-designed clinical trials have clearly established
that lowering IOP is beneficial in slowing disease progression and
helped to establish a clear relationship between IOP control and
visual field preservation.
In addition one needs to address non-IOP dependant systemic
factors such as blood pressure, diabetes, sleep apnea, lipids and
vasospasm which can contribute to a worsening of glaucomatous
optic neuropathy. This article outlines the essential work-up and
follow-up protocol of POAG patients
Keywords: Pharmacotherapy of glaucoma, neuroprotection, target
IOP.
INTRODUCTION
Primary open-angle glaucoma is a pressure sensitive,
progressive, chronic optic neuropathy characterized by
acquired atrophy of the optic nerve and loss of retinal
ganglion cells and their axons. There are three major theories
regarding the pathogenesis of glaucoma: (1) Mechanical
(IOP related damage), (2) Vascular (decrease in blood supply
to optic nerve head) and (3) Biochemical (decrease in
neurotrophic factors/increased levels of neurotoxins) and
therefore the three possible therapeutic options would be to
(1) to decrease IOP, (2) to increase perfusion to the optic
nerve head and (3) provide neuroprotection to retinal ganglion
cells.1-3 As of today the only feasible option is to reduce
IOP by medical, laser or surgical therapy.4 Several welldesigned clinical trials have clearly established that lowering
IOP is beneficial in slowing disease progression and helped
to establish a clear relationship between IOP control and
visual field preservation.
In addition one needs to address non-IOP dependant
systemic factors such as blood pressure, diabetes, sleep
apnea, lipids and vasospasm which can contribute to a
worsening of glaucomatous optic neuropathy.
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Medical therapy once initiated will be life long and the
ophthalmologist must ensure that a correct diagnosis has
been made and rule out medical conditions which could be
adversely affected by glaucoma medications such as asthma,
heart block, antihypertensive treatment, hypotension,
diabetes, stroke, urinary stones, etc. Compliance to therapy,
affordability of treatment and family history should be
ascertained. In addition to routine ocular and systemic
history taking, an assessment of the impact of visual function
deterioration on activities of daily living should be done.
Diurnal IOP variation, gonioscopy, stereoscopic disk
evaluation/photographs and visual fields must be performed.
The diurnal IOP measurement also helps in determining the
timing of peak IOP spike in an individual patient and this
information is used for setting an appropriate timing of
glaucoma medication such that the peak IOP lowering effect
of the drug blunts the IOP spike.5-11 If baseline IOP is > 30
mm Hg, it is reconfirmed once and the patient should be
started on therapy without the need for performing a diurnal
IOP recording.
Glaucoma suspects require a case to case risk-to-benefit
analysis regarding when to begin treatment. The ocular
hypertension treatment study provides guidelines for risk
stratification. Therefore, one should be more aggressive in
treating patients who are older, have thinner corneas, higher
baseline IOP, and larger baseline cup: disk ratios. For those
patients who are similar to the OHTS cohort, a risk calculator
can be used to estimate their 5-year risk of developing
glaucoma.
Each treatment has its own inherent risks and benefits
which must be clearly discussed with the patient before
intiating therapy.
These include:
• Severity and type of glaucoma.
• Patient's compliance with treatment and his/he lifestyle.
Tanuj Dada et al
•
•
•
Affordability of therapy.
Patient's general health status and life expectancy.
Individual patient risk factors, family history and access
to health care delivery services.
Purpose of Initiating Glaucoma Therapy
Glaucoma therapy is aimed at preventing further
glaucomatous nerve damage. The basic goals of glaucoma
therapy are the following (Table 1).
Table 1: Goals of medical therapy for glaucoma
1. To achieve target IOP and reduce IOP fluctuations with minimal
possible medications.
2. To administer glaucoma medication which have the least side
effects on the quality of life of the patient.
3. To achieve this treatment at an affordable and sustainable cost
for the patient.
4. Monitor the structure and function of the optic nerve for further
damage and adjust the target IOP to a lower level if deterioration
occurs.
5. To treat non-IOP dependant systemic factors [systemic
hypertension, low diastolic perfusion pressures (diastolic blood
pressure minus IOP), diabetes, hyperlipidemia, vasospasm] which
may contribute to the development and worsening of
glaucomatous optic neuropathy.
6. To educate and involve the patient and his family in the
management of the disease process.
Antiglaucoma Medications
There are five classes of topical hypotensive medication:
prostaglandins, β-blockers, selective (α-2) adrenergic
agonists, carbonic anhydrase inhibitors (CAIs), and
cholinergics (Table 2).5
Systemic antiglaucoma medications include carbonic
anhydrase inhibitors like oral acetazolamide and
hyperosmotic agents like intravenous mannitol and oral
glycerol. Carbonic anhydrase inhibitors are contraindicated
in known allergy to sulfa drugs, acidosis, hyperkalemia,
renal failure. Known side effects are numbness, paresthesia,
nausea, depression, electrolyte disturbances and renal calculi.
Hyperosmotic agents are indicated in short-term treatment
of acute and marked elevation of IOP and for preoperative
preparation before intraocular surgery. They are
contraindicated in patients with anuria, severe dehydration,
uncontroled hypertension, pulmonary edema, cardiac
decompensation.
How to Set Target IOP?
Target IOP is defined as “A range of acceptable IOP levels
within which the progression of glaucomatous neuropathy
will be halted/retarded”. It is the specific level of pressure
that, if achieved, will prevent further Optic nerve damage
and is the IOP where the rate of loss of ganglion cell will
equal the age induced loss.12-15
The target IOP is dependant on several factors, the most
important being the severity of glaucomatous optic
neuropathy.
The following factors govern the setting of a target IOP
for an individual patient.14
• Optic nerve head and visual field damage
• Life expectancy
• IOP level at which damage occurred
• Rate of progression
• Family history
• Systemic diseases (Diabetes, HT, CAD, CVD).
There is no a way to determine the pressure below which
further optic nerve damage will be prevented in any particular
patient, therefore the initial target pressure is an estimate
towards the ultimate goal of protecting the optic nerve. The
target pressure is different among patients, and even in the
same patient it may require recalculation in the course of
the disease.
When initiating therapy, it is assumed that the measured
pretreatment pressure range resulted in optic nerve damage,
so, the initial target pressure selected is at least 20% lower
than the pretreatment IOP.
As a general guideline the IOP in any established case of
glaucoma should always be kept below 18 mm Hg. The
specific target IOP can be set by classifying the disease
based on severity of glaucomatous damage as follows:
Mild: Glaucomatous optic nerve abnormalities with normal
visual fields.
20% IOP reduction from baseline values, keep IOP <
18 mm Hg.
Moderate: Visual field abnormalities in one hemifield but
not within 5° of fixation.
30% IOP reduction, set IOP below 15 mm Hg.
Severe: Visual field abnormalities in either hemifields or field
loss within 5° of fixation. 50% IOP reduction, set IOP below
13 mm Hg.
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Medical Management of Glaucoma
Table 2: Summary of ocular hypotensive medications
Peak effect, washout
period
Drug
Mechanism of action
Efficacy
Local side effects
Systemic side effects
Prostaglandin
analogues:
latanoprost,
bimatoprost,
travoprost,
unoprostone
Increases uveo scleral
outflow by remodeling
the extracellular
matrix between the
ciliary musculature
Most efficacious of all
topical antiglaucoma
medications. Decrease
IOP about 30 to 35%
from baseline.
Worldwide the first
line drug
Conjunctival
hyperemia, stinging,
hypertrichosis,
trichomegaly,
periocular skin
pigmentation, uveitis,
cystoid macular edema
in pseudophakes and
aphakes
No known serious side 2 weeks, 6 weeks
effects. Some reports
of transient flu like
symptoms, joint pains
β -blockers: timolol,
betaxolol
(cardioselective),
levobunalol,
Act on β-adrenergic
receptor on the ciliary
body and decrease
aqueous production
Decrease IOP from 25 Ocular stinging, ocular Side effects common
to 30% from base line. hypesthesia,
on long-term
Efficacy decreases
epitheliopathy.
instillation.
over a period of time
Bradycardia, heart
called as long-term
block, bronchospasm,
tachyphylaxis
hyperglycemia,
depression, psychosis,
4 to 6 weeks,
4 to 6 weeks
α-adrenergic
agonists:
brimonidine,
apraclonidine
Act on alpha
adrenergic receptors
on ciliary vasculature
and decrease aqueous
production and also
increase uveo scleral
outflow
20 to 25% decrease in
IOP from base line.
Very efficacious as a
prophylaxis to
decrease postlaser
IOP spike
Follicular
conjunctivitis,
associated periocular
contact dermatitis,
blepharo
conjunctivitis, lid
retraction.
Brimonidine crosses
blood brain barrier to
cause systemic
hypotension and
drowsiness. It is thus
contraindicated in
children (< 6 years,
< 6 kg)
2 weeks, 2 weeks
Cholinergic
agonists:
pilocarpine
Increases trabecular
outflow
Decreases IOP by
20 to 25%
Headache, brow ache,
induced myopia,
miosis, conjunctival
hyperemia, iris cyst,
uveitis, cystoid
macular edema, retinal
detachment
Abdominal cramps,
sweating,
bronchospasm,
diarrhea
3 hours, 1 week
Carbonic anhydrase
inhibitors:
dorzolamide,
brinzolamide
Decreases aqueous
production by
inhibiting carbonic
anhydrase enzyme in
the ciliary processes
Decreases IOP by
20 to 25% from
baseline
Stinging and burning
sensation, corneal
decompensation in
Fuch's cornea and
postkeratoplasty eyes
Bitter taste in the
mouth, rarely drug
hypersensitivity
72 hours, 1 week
The adequacy of the target pressure is periodically
reassessed by comparing optic nerve status (quantitative
assessments of the disk and nerve fiber layer, and visual
field tests) with previous examinations. If progression
occurs at the set target pressure, the target IOP should be
lowered.12-18
How to Start Therapy?
Once the diagnosis of glaucoma has been confirmed, ocular
hypotensive medications can be started, starting with one
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drug at a time. Therapy is usually started in worse eye
(usually with higher IOP/more structural and functional
damage) first.5 This is known as the one eye therapeutic
trial. A drug with atleast 20% IOP lowering efficacy is chosen
as the first line therapy (usually a β-blocker or prostaglandin
analog). After the peak IOP reduction ability of that drug is
reached, diurnal variation of IOP (IOP reading at every 3
hours from early morning to late night, e.g. 7 am and
10 am, 1 pm, 4 pm, 7 pm, 10 pm) is evaluated to look for
Tanuj Dada et al
reduction in IOP and fluctuation. In eyes with ocular
hypertension—if a decision has been made to treat and in
cases with early glaucoma, topical β-blocker therapy may
be initiated as the first line therapy provided there are no
systemic contra-indications.5 Once there is moderate/severe
visual field damage, a prostagladin analog is preferred as it
is more likely to achieve desired target IOP. In eyes with
normal pressure glaucoma, prostaglandin analogs are the
preferred choice to start therapy and β-blockers should be
avoided as they are absorbed systemically and can lead to a
decrease in optic nerve head perfusion pressure. In eyes
with primary angle closure glaucoma, the first step is to do
a laser peripheral iridotomy, and then start with medical
therapy as mentioned above.5,17-21
The major reason for noncompliance is that glaucoma is a
chronic disease that requires lifetime therapy and is slowly
progressive, therefore, patients do not notice immediate
consequences if they do not comply with treatment.
Therefore a proper patient counseling about the disease
process, the rationale for treatment and how drugs act, and
the need of life long medication and follow-up cannot be
over emphasized. At each follow-up, the patient should be
questioned about possible systemic side effects which may
lead to a discontinuation of medication by the patient. It is
good to have printed cards for medication schedules,
demonstrate the eye drop administration technique and tailor
dosing schedule to daily events.22-25
When to Switch or Add Therapy?
The patient should be instructed to wash both hands, sit down
on a chair or lie in bed. If seated, the head is tilted slightly
backwards while gazing upward. The lower lid is gently pulled
down with the nondominant hand to form a small concavity
in which the drops will be placed. With dominant hand, the
dispenser is held above this concavity. The bottle should be
near enough to make sure that the drop will enter the eye and
far enough so as not to touch it (2 to 5 cm). Avoiding blinking
and the body of the bottle is pressed so that a single drop falls
into the eye. After application, lids should be kept closed (or
digital compression be applied to the punctum) for 1 to 2
minutes to minimize systemic absorption. The bottle cap
should be replaced and any excess fluid wiped from the skin,
especially when using prostaglandin medications that may
darken the skin color.25-29
If the drug achieves the desired target IOP, it is continued
and started in the second eye. If drug fails to reduce IOP
by at least 20% IOP from baseline or produces severe side
effects, we switch to another class of drugs. However, if
the first drug does reduce IOP more than 20% from baseline
but target IOP level is not reached, a second drug is added.
A time interval of at least 5 minutes should be given before
administering the second drop. In case IOP does not reach
target IOP by three topical antiglaucoma medications, laser/
filtering surgery should be considered.
Combination Therapy
If IOP is not at target with a single drug, a second drug is
added. These two drugs should have different mechanism
of action and the best combination is a prostaglandin analog
(which increases outflow) with a β-blocker (which
decreases inflow). Using combination eye drops with two
drugs in the same bottle is a good choice if more than one
drug is required as it decreases number of eye drops to be
instilled into the eye, decreases preservative induced
conjunctival toxicity and increases compliance. The most
important benefits of fixed-combination therapies are that
they provide equivalent IOP reductions with the potential
benefits of improved compliance, patient convenience, and
cost savings. Also, fewer drops per day mean decreased
exposure of the ocular surface to preservatives.
Improving Compliance
Noncompliance is a serious issue which leads to therapeutic
failure and progression of optic neuropathy. It has been
estimated that approximately 10% of all visual loss from
glaucoma can be attributed to nonadherence to therapy.
How to Instill Eye Drops?
Follow-up
In general a patient with established glaucoma should be
followed up every six months, however the frequency of
follow-up can be increased or decreased depending on the
severity of disease and whether there is any progression or
no over time. In stable patients with early disease, an yearly
follow-up may be adequate, while in advanced cases or
documented progression, a 3 to 4 monthly follow-up would
be advised.
In addition to treating the ocular condition, the ophthalmologist should also focus on educating the patient to adopt
a healthy life style and take care of any systemic disease
factors. Such measures include asking the patient to stop
smoking, wear a loose tie, regular exercise, decrease weight
if obese, and meditation to decrease the stress associated
with disease and improve the quality of life. For primary
prevention and early detection, a check-up of other family
members of the glaucoma patient is recommended.
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Medical Management of Glaucoma
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Tanuj Dada
([email protected])
“To put the world right in order, we must first put the nation in order; to put the nation in order, we
must first put the family in order; to put the family in order, we must first cultivate our personal life;
we must first set our hearts right.”
—Confucius
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