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Glaucoma
persistence are significant factors that can affect patient outcome. It to 2003 showed that, compared with any other class of topical
is important for physicians to consider these factors when selecting a antiglaucoma agent, prostaglandins were the most potent topical
medical therapy, while also stressing the importance of treatment agents for IOP lowering, with the highest peak mean difference from
adherence to their glaucoma patients. Non-adherence due to poor baseline IOP.
26
In addition to an enhanced IOP-lowering profile, the
ocular tolerability can lead to treatment failure because of inadequate systemic side effects common with β-blockers are largely absent in
IOP control. Glaucoma treatment should therefore be determined therapy with prostaglandins. Furthermore, unlike β-blockers,
with regard not only to IOP lowering, but also to minimisation of prostaglandins need only a single daily dose instead of twice-daily
systemic and ocular adverse events, while taking into account dosing. These factors – increased IOP potency, lack of systemic side
compliance as part of individualisation of patient care. effects and convenient dosing schedule – represent the main
advantages of using prostaglandins in lieu of topical β-blockers in
From β-blockers to Prostaglandin glaucoma therapy. Prostaglandins are generally well-tolerated,
Analogues and Beyond although there are some local side effects that are largely of only
Generally, initial treatment for lowering IOP is topical medical therapy cosmetic significance. Hyperpigmentation of the iris and periocular
with monotherapy as first choice. Several classes of antiglaucoma skin occurs quite commonly, in addition to lengthening of the
medication are currently available, including β-blockers, eyelashes. The most common side effect of prostaglandins relates to
prostaglandin analogues, alpha-2 adrenergic agonists, topical ocular tolerability – namely conjunctival hyperaemia,
27
which is
carbonic anhydrase inhibitors (CAIs) and parasympathomimetic tolerable if mild, but less so if moderate to severe.
Alpha-2 Adrenergic Agonists and
In the hypothetical situation where Carbonic Anhydrase Inhibitors
Alpha-2 adrenergic agonists decrease IOP levels by reducing
two different drugs are available with
aqueous humour production while increasing uveoscleral outflow,
28
similar intraocular pressure lowering while CAIs function by decreasing aqueous production.
29
Although
these drug classes are also indicated as first-line glaucoma
but different degrees of side effects,
treatments, they are limited by the number of associated adverse
it would make sense to use the drug effects. Possible side effects for alpha-2 adrenergic agonists include
allergic reaction, blurring, headache, fatigue, hypotension, insomnia,
with fewer side effects.
depression, syncope, dizziness and anxiety. Topical CAIs are
associated with blurred vision, irritation, dermatitis and bitter taste.
agonists. The latest European Glaucoma Society guidelines
recommend that the choice of initial monotherapy be based on Combination Therapy
physician preference.
4
In recent years prostaglandin analogues have Although the prostaglandin analogues have a strong IOP-lowering
emerged as first-line agents. Current data show that 40–75% of profile, many patients still require a multimodal approach with
glaucoma patients fail monotherapy after more than two years of multiple topical medications in order to achieve target pressure
treatment.
10,16
In these patients, combination therapy and/or further control;
10,16
patients are commonly treated primarily with a
adjunctive therapy is often considered. prostaglandin plus an additional drug in combination.
22,30–32
In some
cases where target IOP is still not achieved, the addition of a third
β-blockers drug may be considered. However, the use of multiple topical
β-adrenergic antagonists block the β-receptors in the ciliary body, treatments increases the risk of adverse effects and non-
thereby decreasing aqueous humour production. With over 30 adherence. The convenience of dosing in these multiple drug
years of clinical experience, the strengths of β-blockers, as well as regimens can be improved via fixed drug combinations, the most
their weaknesses, are well-established. Although able to lower IOP recent addition to the armamentarium of antiglaucoma drugs. The
effectively, these drugs have systemic effects on the circulation, simplicity of a single as opposed to multiple administration has
respiration and metabolism. Notably, owing to their systemic been shown to improve patient adherence.
33
Fixed combinations
absorption, β-blockers present concerns for patients with also prevent medication washout, which occurs when patients on
cardiopulmonary disease. They have been associated with multiple drugs apply their medications with too short an interval
congestive heart failure, bradycardia, arrhythmias, syncope, heart between drops, leading to a significant washout effect.
34
Moreover,
block and systemic hypotension.
17–22
β-blockade has also been in the event of needing to add a β-blocker to a prostaglandin-
shown to exacerbate asthma, reactive airway disease, chronic containing regimen, a once-daily fixed-dose combination product
obstructive pulmonary disease and bronchitis.
20,23–25
Worsening of would administer less β-blocker than a twice-daily regimen,
dry-eye syndrome, confusion and decreased libido have also been thereby reducing the rate or severity of adverse effects, as well as
observed.
25
Because a lot of patients with glaucoma are elderly, and the daily topical preservative load, without sacrificing efficacy.
35
many of them have cardiovascular, pulmonary or respiratory Several fixed-combination formulations are now available and all
problems, β-blockers have become less popular in recent years, contain a β-blocker as one component.
making way for the current most commonly used first-line agents:
prostaglandin analogues. Fixed-combination therapies are now widely used in glaucoma
therapy, particularly the combination of the prostaglandin analogue
Prostaglandin Analogues latanoprost and the β-blocker timolol, and that of the CAI
Prostaglandin analogues lower IOP by increasing uveoscleral and dorzolamide and timolol. The fixed combination of latanoprost/
conventional outflow. A meta-analysis of randomised clinical trials up timolol has been extensively studied, and has been shown to be
20 EUROPEAN OPHTHALMIC REVIEW