There are many situations that confront the optometrist as
he/she decides whether to initiate therapy for ocular hypertension
(OHT) or glaucoma. For ocular hypertension, the decision process
is discussed in Chapter 5. In regard to glaucoma, when optic nerve
and/or visual field damage associated with glaucoma is recognized
and other causes of this loss are ruled out, therapy is in order. Before
therapy commences, a strategy is developed based upon the
stage of disease and IOP level, as well as other factors. A target intraocular
pressure (IOP) range is determined and a medication selected.
If therapy is not indicated, the patient is often classified as
a glaucoma suspect and followed once to twice per year, depending
upon the individual’s characteristics. The category of glaucoma suspect
includes individuals with ocular hypertension as well as suspicious
optic nerves or visual fields.
When medical therapy is initiated, the selection of the initial
agent usually is decided between two classes of drugs: prostaglandins (PGs) or topical beta-blockers. PGs have replaced
beta-adrenergic antagonists as the most commonly used agent for
initial therapy. This is due to their ability to reduce IOP efficiently
on a once-per-dosage schedule, without inducing serious side effects,
as well as their dampening IOP fluctuations that may occur
over a 24-hour period (diurnal curve). Beta-adrenergic antagonists
do not reduce IOP as effectively, especially when viewed over a 24-
hour period, and have some additional contraindications. Recent
information from several clinical trials has highlighted the need for
reduced target IOPs, further cementing PG’s role as first-line agents.
The initial medication selected is based upon its ability to reduce
IOP, its safety profile, tolerability and patient acceptance. The drug
needs to be matched to the patient. For example, a patient with a
history of anterior uveitis or macula edema would not be a good
candidate for PG therapy. Likewise, a patient with pulmonary disease
would not be a candidate for beta-adrenergic antagonist therapy.
Target IOPs must also be considered as a therapeutic agent is
selected. Target pressures refer to the range of IOP that we hope
will prevent further glaucomatous damage. A patient’s target IOP
may change over time, either as new knowledge becomes available,
indicating lower IOPs will be advantageous or if progression is confirmed.
Target IOPs are a best guess of what IOP will control the
condition. The best indicator to show that target IOP has been
achieved is when periodic optic nerve and visual field evaluations
reveal no change. If change is noted, additional reduction is necessary.
Target IOPs are based on the amount of damage present and
the highest IOP reading, with greater reduction required as damage
worsens. Recent clinical trials have provided evidence that lower
target IOPs are important, though no definitive study has shown
exactly what IOPs are optimal.
The Ocular Hypertension Treatment Study (OHTS), which had a
target IOP reduction of 20%, found that 4.4% of individuals in the
therapy group progressed. In a study of glaucoma patients, the Early
Manifest Glaucoma Trial (EMGT), in which the goal was 25% IOP
reduction, 45% of patients in the therapy group progressed over
time. The Collaborative Initial Glaucoma Treatment Study (CIGTS)
which had a similar group of patients with early glaucoma as the
EMGT, also monitored for progression. CIGTS found little change in
the group whose IOP was reduced 38%. In the Advanced Glaucoma
Intervention Study (AGIS), groups were broken down based on the
percentage of visits in which the IOP was reduced below 18mmHg.
One group with a mean IOP of 20.2mmHg showed significant deterioration,
while another group with a mean IOP of 12.3mmHg appeared
to be stable over an 8-year period. These studies, taken as
a group, do not provide proof that IOPs need to be reduced to the
low teens for all patients, but they do illustrate the need to reduce
IOPs to lower levels than previously thought.
The EMGT recognized that risk factors for glaucomatous progression
include higher IOP at the time of diagnosis, pseudoexfoliation,
bilateral disease, disc hemorrhages, older age and worse visual field
mean deviation. The AGIS found that an additional risk factor is
variation in IOP over a 24-hour period. This is a separate risk that
describes IOP fluctuation throughout the day, even when IOP is low
at certain time points. To recognize diurnal fluctuations, we should
record the time of each visit and schedule exams at varying times
during the day.
Often it is helpful to begin therapy with a monocular or unilateral
trial in which medication is begun in one eye for a few weeks,
with the contralateral eye serving as a control. The rationale is that
IOP, while often different between the two eyes, will rise and fall
over the day to a similar degree. Also, the response to a medication
should be similar in both eyes. Since non-responder rates vary from
8% to 25% depending on the class of medication, a monocular trial
is one way to ensure the medication is effective as well as determine
if side effects are occurring. Realini has questioned the use of
the monocular trial, in part because the IOP reduction in one eye
does not necessarily predict how the drug will perform in the other.
Moreover, monocular trials require at least one additional visit.
Nevertheless, many experts continue to recommend the monocular
trial, recognizing its limitations but also using it as a way to control
the initiation of a new drug.
At the outset of therapy, the patient needs to be educated in regard
to the optimal time for drop instillation(s) and potential side
effects. Also, it is important to demonstrate proper eyedrop instillation
technique and have the patient demonstrate that he/she
can properly instill the drops. If eyedrop instillation appears to be
a problem, there are devices to aid instillation. Also, a companion
or family member may aid in medication insertion. Finally, written
dosing schedules should be provided as reminders. The first followup
visit usually occurs 2 to 4 weeks after therapy commences. At
each visit, ask if any side effects have occurred and when the patient
last used the medication(s). Patient communication is discussed
in Chapter 10. Even when written schedules are provided,
some patients misunderstand how to use the medication. Questions
that should be addressed at every visit include whether the patient
is actually using the drug or if there are any problems or concerns.
The IOP is measured to assess whether the medication is effective
and pressure is at target level. If the drug is well-tolerated and effective,
then the patient is followed over time, watching for medication
side effects and/or progression. Patients are seen every 3 to
6 months depending on severity and type of disease. Ocular hypertensives
are monitored less often, and individuals with significant
loss, more often. Dilated optic nerve evaluation, imaging and visual
field testing should be performed at least yearly. Testing more
often is recommended in the first year after diagnosis, if a greater
degree of loss is present or a question of stability arises.
An important question that should be considered early in the
course of follow-up is the rate of change. If a patient is progressing
rapidly, we need to recognize this and modify our approach.
One way to measure rate of change is to perform perimetry on a 6-
month basis for the first 2 years. This is best done with SITA visual
fields and the Glaucoma Progression Analysis (GPA) software
tool. If the fields are unchanged, the interval between field testing
can be increased to yearly. Several fields are needed before a decision
can be reached regarding stability, but once 5 fields are available,
trends will emerge.
One challenge occurs when a patient does not respond or side effects
develop with the initial medication. If side effects occur, what
are they? Are they caused by the medication? May they be reduced
if a switch occurs within the same class of drugs? An intra-class switch may work if hyperemia develops with one PG. A more difficult
question is if the target IOP level is not reached with the initial
medication. In this case, the IOP response needs to be
evaluated. For example, if the IOP was very high and/or the damage
significant, leading to a target goal of 40% reduction, and the
drug provides 25% of the target reduction, then the medication appears
to be effective, but a second agent is needed. On the other
hand, if the reduction is 15% or less, the patient may be considered
a non-responder. Inadequate responses do occur and are not
often recognized, leading to unachieved target levels. We should
ask if progression may occur in 15 years at the present IOP level. It
may be then easier to appreciate the urgency of attempting to
achieve target IOP levels.
There are different reasons why the IOP may not have been reduced
with the initial agent, including lack of response or poor
compliance with the clinician faced with a decision of how to proceed.
Switching to a drug within the same class, such as going from
one PG to another (intra-class switches) is controversial, since it is
not proven that such switches work. Switch studies with PGs have
shown that the medication switched to always performs better.
However, one problem is that most switch studies have been conducted
over only short periods, usually about 30 days. The improved
efficacy may be due to the second drug’s greater response,
but other possible reasons for this reduction include improved compliance
or fluctuations in IOP (regression to the mean).
If the medication is effective but further reduction is needed, either
because the IOP is above the target goal or progression is identified,
the practitioner may choose an additional medication. If a
PG is the initial agent, the second agent may be a beta-blocker, alpha
agonist or topical CAI. A beta-blocker offers the convenience
of once-per-day use; thus the patient would take it in the morning
and take the PG at nighttime. When added to a PG, topical CAIs
may be more effective at lowering IOP than beta-blockers. But, topical
CAIs require twice-per-day dosage. If a patient is on a PG along
with a beta-blocker or topical CAI and further IOP reduction is
needed, then either of these drugs may be discontinued and a
fixed-combination agent containing timolol and dorzolamide
(Cosopt) begun. It is important to stress to patients taking two
medications that they should wait five minutes before instilling the
second agent to avoid washing the first from the eye. Also, remember
to instruct patients taking beta-blockers to close their eyes or
occlude their punctum for three minutes. This will reduce systemic
absorption, improve efficacy and reduce side effects. Argon or Selective
Laser Trabeculoplasty and filter surgery become options when
the patient is progressing or the IOP is above the target level, and
several medical options have been tried (see chapter 8).
In some cases, even with patients who respond well to initial
therapy, the IOP may slowly rise over time. Such increases could be
due to the glaucoma worsening, problems with compliance or the
development of tachyphylaxis. The two questions to ask are: Is the
drug effective, and is it being used? If the IOP is elevated, instill
the medication and measure the IOP several hours later. Also, observe
the patient’s drop instillation technique to determine if the
drug is getting into the eye. And finally, the reverse monocular trial
may be helpful to address whether tachyphylaxis has developed.
In this trial, the drug is temporarily discontinued in one eye and
continued in the other. If tolerance has developed, there will be little
change in the untreated eye’s IOP over the next several weeks.
However, a rising IOP proves the drug is effective and should be
continued, but an additional agent is necessary.
The management of ocular hypertension and glaucoma is an art
that requires the clinician to make an ongoing series of decisions
and adjustments over the patient’s lifetime to ensure the IOP remains
at acceptable levels and the condition does not worsen. Periodic
monitoring of the optic nerve and visual fields are also
necessary. The doctor needs to consider both the short and longterm
view to ensure occurs throughout the lifetime of their patient.
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