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MANAGING OPEN ANGLE GLAUCOMA

Fixed combinations (FC)
While monotherapy with a prostaglandin analogue is sufficient to achieve initial control in many individuals with
glaucoma, others may require additional intervention. Additional intervention may be necessary to attain a low
enough target pressure to reduce the risk for functional vision loss, particularly with increasing disease severity.
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Given that adherence to treatment decreases with each additional medication prescribed, the minimal number of
bottles used and drops administered to achieve target pressure is preferred.
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Prior to discussing a suggested pathway for treating open angle glaucoma, a discussion about fixed-combination
agents is warranted.

FC have a number of inherent benefits including: convenience of a single bottle over two, reduced number of eye
drops to increase the opportunity for better adherence to treatment, reduction in amount of preservative on the
ocular surface with fewer drops, and reduced washout potential with only one medication being administered at
any given time point. 330,355,356 Drawbacks of FC include the potential for higher dose of beta-blocker than required or
desired due to both the higher concentration (0.5%) in the combinations and the potential for multiple doses (when
the beta-blocker is combined with an alpha-agonist or a CAI, which require more than once-daily dosing). This may
be most important in those with pre-existing low blood pressure, especially nocturnal dips, but also in those with
previously undiagnosed heart block or breathing difficulties, and in children.

A systematic review and meta-analysis comparing the timolol/prostaglandin analogue FC to the unfixed admin-
istration found the latter to be more effective by 1-2mmHg. This may be due to the fact that when unfixed, the
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subjects received two doses of timolol compared to one with the FC, and may also have been related to the time of
dosing relative to IOP measurement in the studies. However, of interest is that the FC was better tolerated than its
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unfixed components administered separately.
Timolol 0.5% has been formulated with all three prostaglandin analogues (latanoprost 0.005%, travoprost 0.004%,
bimatoprost 0.03% (US)), the alpha agonist (brimonidine 0.2%), the CAIs (dorzolamide 2.0%, brinzolamide 1.0%),
and previously with other drugs such as pilocarpine 2%/4% (no longer available).

Analysis of mean diurnal IOP reductions showed good results for all of the following medications: 358

Category Fixed combination Reduction in IOP as per meta-analyses
travoprost / timolol 34.9%
PGA with timolol bimatoprost / timolol 34.2%
latanoprost / timolol 33.9%
brinzolamide / timolol 32.7%
CAI with timolol
dorzolamide / timolol 29.9%
Alpha agonist with timolol brimonidine / timolol 28.1%

The first FC agent formulated without a beta-blocker is brinzolamide/brimonidine and this FC agent appears to
demonstrate a similar response to the agents administered as an unfixed combination. More study of all of these
medications will further facilitate understanding of their use in the treatment of glaucoma.

Clinical Recommendation for IOP lowering with FC:
• Consider the pros and cons of FC medications in the management of each individual patient: in most
situations, the former will outweigh the latter.

TREATMENT ALGORITHM
The management of glaucoma must be individualized and thoughtful consideration given to all components of
diagnosis and treatment. This includes understanding each patient’s approach to coping with the disease in the
context of their larger life situations. However, a general approach may be taken to treatment of POAG, as described
in Figure 16.

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