Medical Treatment of Open-angle Glaucoma in 2011 Table 3: Summary of the Fixed Combination Drugs Commonly Used to Lower Intraocular Pressure4 Ingredient 1
Bimatoprost 0.03 % Latanoprost 0.005 % Travoprost 0.004 % Dorzolamide 2.0 % Brinzolamide 1.0 % Brimonidine 0.2 % Pilocarpine 2.0 % Pilocarpine 4.0 %
Ingredient 2 (Beta-receptor Blocker Component) Timolol 0.5 %
Timolol 0.5 % Timolol 0.5 % Timolol 0.5 % Timolol 0.5 % Timolol 0.5 % Timolol 0.5 % Timolol 0.5 %
IOP-lowering medications according to their mechanism of action, administration frequency and main side effects is given in Table 1. The IOP-lowering efficacies of the different drugs based on monotherapy data are presented in Table 2. When monotherapy (usually a prostaglandin analogue therapy or timolol) provides the expected IOP-lowering effect based on daytime phasing or a 24-hour diurnal IOP curve4,12
First Commercial Name in Europe First Launching Company
Ganfort Xalacom Duotrav Cosopt Azarga
Combigan Fotil
Fotil forte
Allergan Pfizer Alcon MSD
Alcon
Allergan Santen Santen
surface disease (OSD) and increases the frequency of OSD.13,14 BAK
is a detergent that destroys the lipid layer of the tear film, a process that increases evaporation of the aqueous layer. In addition, BAK has a dose-dependent toxic effect on the corneal, conjunctival and trabecular meshwork cells. This toxicity varies in different ophthalmic products according to the concentration.13,14
Such an apoptotic effect
and the individual target IOP range is reached, the treatment should be continued. If the IOP reduction does not exceed 15 % (and the patient is compliant to the therapy), a new monotherapy should be introduced (switching). No adjunctive medication is recommended in such cases because the eye is a non-responder to the first therapy.4
Setting a Combination Therapy
When a patient responds well to the initial monotherapy, but the target IOP is not reached with one medication, additional IOP reduction is necessary.4
drug-induced IOP reduction: •
• add a second drug concomitantly (unfixed combination); or
switch from the monotherapy to a fixed combination that contains the monotherapy drug plus one more ingredient (this option is limited in those countries where fixed-combination glaucoma drugs are not easily available).
Both approaches provide information on the additional IOP reduction provided by the adjunctive IOP-lowering drug. If the additional IOP reduction decreases IOP to the target range, the combination can be used long term. When available, a fixed combination of the two ingredients is preferred in the long run over the concomitant administration, since this reduces the number of daily instillations and total BAK exposure.4,13–15
If a third IOP-lowering drug is necessary,
the combination is unfixed (i.e., a combined medication that comprises a fixed combination and a different third drug).15
It is very important
to know that members of the same drug class must not be combined (thus two fixed combinations cannot be combined because all fixed combinations contain a beta-receptor blocker). This means that each ophthalmologist must know the ingredients in the medication prescribed. Another important issue is that the maximal daily dosage of a fixed combination is equal to the maximal daily dosage of the least frequently administered component of the fixed combination. The most commonly used fixed-combination glaucoma drugs are given in Table 3.
Intraocular Pressure Lowering Drops Preserved by Benzalkonium versus Those Not Preserved by Benzalkonium
For several decades, BAK chloride has been used widely to preserve ophthalmic products. However, it has also been known for decades that BAK worsens the signs and symptoms of dry eye or ocular
EUROPEAN OPHTHALMIC REVIEW There are two ways to increase the
gains importance during long-term exposure (glaucoma is a life-long disease) and worsens when multiple instillations are applied (unfixed combination therapy, unnecessary adjunctive medication). The subclinical inflammation caused by long-term use of BAK decreases the probability of successful filtering surgery because it stimulates the post-operative scarring process of the filtering bleb. Previously, it was thought that some toxic effects of BAK on the corneal epithelium (damaged integrity of the intercellular barrier) were beneficial for ocular drug penetration. Now it is clear that the IOP-lowering effect of timolol, certain prostaglandin analogues, timolol/dorzolamide fixed combination and certain prostaglandin/timolol fixed combinations is independent of the presence of BAK.16–19
In conclusion, when a
BAK-free or a non-BAK preserved alternative of an IOP-lowering drug is available, use of this formulation is recommended.
Compliance to the Prescribed Medication Several studies from all geographical regions are published on the poor compliance (adherence, persistence) of glaucoma patients.20–23
In
routine clinical practice, compliance needs to be monitored closely and supported with training and personal interactions with the patients. A decrease in the number of daily drug administration (i.e., the use of fixed combinations) is also beneficial. Fewer and less severe side effects are associated with better compliance. Thus, when a new therapy is set, the different types of side effects (individual molecule related, formulation related, drug-class related or BAK related) should be considered, based on the patient’s previous experience. The patient should always be involved as a partner in the evaluation of the treatment and his/her complaints (e.g., technical problems of opening the bottle or technical problems of the instillation) should be considered seriously when a long-term therapy is set. Each patient should be carefully instructed on the correct instillation technique, including avoidance of eye–bottle contact and blinking after instillation, use of punctual compression and the separation of different instillations by a five minute interval at least.
Laser and Surgical Treatment
Although the details of laser and surgical treatment of glaucoma are not subjects of the current review, it is important to understand that when a patient progresses despite an adequate IOP-lowering treatment, further intervention should not be postponed. The later the intervention is made, the more retinal ganglion cells that are lost and thus less visual function can be preserved. The longer the BAK
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