Previous studies have shown the fixed-combination brinzolamide-timolol eye drop to be significantly more effective than its individual components and noninferior to fixed-combination dorzolamide-timolol eye drops in lowering intraocular pressure.11
We suggest that although this crossover study was unidirectional and of limited size, it does demonstrate a different side effect profile for the two types of fixed-combination eye drops.
Stinging was significantly less and lasted for a shorter period of time with the brinzolamide-timolol eye drops, which is consistent with previous findings.12
Apart from any intrinsic differences in the two molecules which may alter the stinging profile of the two drugs, the pH of the eye drops containing brinzolamide is relatively more neutral than that of dorzolamide (pH 7.5 and pH 5.6, respectively). Furthermore, eye drops containing dorzolamide use sodium citrate as a buffer whereas none is present in the eye drops containing brinzolamide. All these differences seem to cause the brinzolamide-timolol eye drop to sting less.
Redness can be a problematic side effect of any antiglaucoma medication, and accordingly reduces compliance, but may also be a surrogate of general irritation and stinging. We found that fixed-combination eye drops containing brinzolamide or dorzolamide show a slight reduction in severity of redness, but of significantly shorter duration. Given that this represents another reduction in side effects, it should have the effect of increasing tolerability.7
Blurring of vision is a known side effect of brinzolamide,11
but studies have shown conflicting results when compared with dorzolamide. Stewart et al did not find any difference between the two drops.17
However, Silver found a higher incidence of visual blurring for brinzolamide than with dorzolamide, as did Manni et al and Mundorf et al.12
This increase in blurring of vision with the eye drop containing brinzolamide was also observed in our study, but does not seem to last any longer than the blurring caused by the eye drop containing dorzolamide. The increase in visual blurring is probably due to the viscosity of the eye drop, with the brinzolamide-timolol combination eye drop being much thicker than the dorzolamide-timolol eye drop. Indeed, seven of the 31 patients we interviewed stated that they found the brinzolamide-timolol eye drop difficult to apply due to its thickness. Also, one patient switched back to the dorzolamide preparation because of this application problem, even though she preferred the side effect profile of the brinzolamide eye drop.
Unfortunately absolute levels of blurring and the finite time for which the blurring persisted were not assessed in this study. Thus, no assumptions can be made regarding how blurring affects general daily activities using either type of eye drop. It could be that blurring persists long term and causes a significant reduction in ability to perform daily tasks, or it could be very transient and cause few problems. An answer to this question would help to make a more meaningful comparison of the side effect profiles of the two combination preparations.
Carbonic anhydrase inhibitors are known to cause dysgeusia. Initial studies by Silver showed a higher incidence of altered taste sensation with brinzolamide than with dorzolamide,16
although subsequent studies, including our study, showed no difference.12
There was no statistically significant difference between the overall comparison and likelihood of compliance with the fixed-combination brinzolamide-timolol and dorzolamide-timolol eye drops in this study. Previous studies have found a patient preference for the drop containing brinzolamide over the one containing dorzolamide.13
However, this and other studies show a reduction in stinging and redness at the cost of increased blurred vision. It is possible that the exchange of one side effect for another leaves the eye drops being equivalent overall. Interestingly, Jampel et al found that patients would pay more for an eye drop with reduced blurring but would not pay more for a reduction in any other side effect.19
This observation would suggest a preference for the dorzolamide combination overall, but this does not appear to be the case in this study.