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Paper text:
reduction of elevated intraocular pressure is the only established modifiable risk factor shown to reduce the risk of glaucoma - associated optic neuropathy.1,2 topical beta - adrenergic antagonists and carbonic anhydrase inhibitors are well accepted medical treatments for reducing production of aqueous humor.3,4 newer prostaglandin analogs reduce intraocular pressure by promoting uveoscleral aqueous outflow.46 however , the ocular hypertension treatment study showed that almost 40% of patients will require a combination of two or more medications to achieve a 20% reduction in intraocular pressure.1 complex drug regimens requiring the use of numerous bottles can reduce the therapeutic effect , and use of multiple bottles has also been shown to be a barrier to compliance.79 coadministration of drops may introduce a washout effect if not adequately spaced in time.10 similarly , eye drop tolerability will affect compliance and treatment outcomes.7 multiple - drop therapies have been formulated to address some of these compliance issues .
azarga ( alcon laboratories inc , fort worth , tx ) is a fixed combination of brinzolamide 1% + timolol 0.5% , and is effective in reducing intraocular pressure.11 in comparison , a fixed combination of brinzolamide 1% + timolol 0.5% is noninferior to a fixed combination of dorzolamide 2% + timolol 0.5% and achieved lower mean intraocular pressures at nine of 12 study visits.12 tolerability comparisons of these two fixed - combination eye drops seem to show a reduction in eye irritation using the brinzolamide formulation , but an increase in blurred vision.1215 in this study , we directly switched patients requiring multiple - drug treatments from a fixed combination of dorzolamide - timolol to brinzolamide - timolol and investigated the impact of this change on tolerability and compliance .
this study was performed at the glaucoma unit in the royal hallamshire hospital , sheffield , uk .
patients were switched from a fixed preparation of dorzolamide - timolol to brinzolamide - timolol . following the switch ,
patients were contacted by telephone and a number of questions were asked over a period of 426 weeks after changing eye drops .
one independent questioner read a preformed questionnaire to patients over the telephone ( figure 1 ) .
telephone consultations were initiated by confirming the patient details and that correct antiglaucoma treatment was concurrent .
a primary yes / no question was asked to confirm if a specific side effect had been experienced .
if a side effect was noted for either drug , a comparison of the two types of eye drop was made by asking patients to assign a numerical value ( 1 to 9 ) comparing the new ( brinzolamide - timolol ) and old ( dorzolamide - timolol ) drops .
thirty - one consecutive patients whose medication had been altered were contacted and questionnaires were successfully completed .
thirty - one consecutive patients ( 12 males and 19 females aged 4189 years ) successfully completed the questionnaire .
the data were analyzed for significant differences from the assumed mean of 5 using the t - test if the sample set was > 20 .
when the sample set was < 20 the wilcoxon signed - rank test was performed . a test for proportions
was used to compare the numbers of patients experiencing a specific side effect . the population varied in the percentages experiencing side effects , as shown in table 1 .
comparison of the percentages of side effects indicated less stinging but more blurring for brinzolamide - timolol compared with dorzolamide - timolol eye drops ( table 1 ) .
there were no differences in the proportions of patients who experienced altered taste or redness following instillation of the eye drops .
a comparison of the severity and chronicity of the side effects of the two types of fixed - combination eye drops is shown in table 2 .
the fixed combination of brinzolamide - timolol produced significantly less stinging and for a shorter amount of time than the dorzolamide - timolol eye drops ; it also produced less eye redness and for a significantly shorter amount of time .
however , the fixed combination of brinzolamide - timolol produced more blurring , although the length of time this was present was similar to that with dorzolamide - timolol .
no differences between the two eye drops were found for taste , overall impression , and likelihood of compliance .
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.11,12 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.1215 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.7,9 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.12,13,16 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 .
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.12,17,18 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.13,15 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 .
our study confirms the finding of other researchers pertaining to the side effect profiles of fixed combinations of brinzolamide - timolol and dorzolamide - timolol , ie , a reduction in stinging and redness but an increase in blurred vision .
the advantage of one eye drop over the other then becomes patient - specific , depending on which side effect they find more tolerable .
we suggest that both types of eye drop are acceptable and interchangeable choices for treating patients with glaucoma , but compliance may be an issue as a result of the specific side effects of one drop or the other .
backgroundthis study aimed to determine the impact of switching patients requiring multiple drug treatment from the dorzolamide - timolol fixed combination to the brinzolamide - timolol fixed combination and potential effects on tolerability and compliance.methodspatients were switched from dorzolamide - timolol to brinzolamide - timolol and questioned within a period of 426 weeks . 
 questions were asked to confirm if a specific side effect had been experienced , and then a numerical comparison between the two types of eye drop was made.resultsthirty-one consecutive patients ( 12 males and 19 females aged 4189 years ) successfully completed the questionnaire . 
 comparison of the severity and chronicity of the side effects of the two types of fixed - combination eye drops showed that brinzolamide - timolol caused significantly less stinging for a shorter amount of time than dorzolamide - timolol ; it also produced less eye redness for a significantly shorter amount of time . 
 brinzolamide - timolol produced more blurring , although the length of time this was present was similar to that for dorzolamide - timolol . 
 no differences between the two eye drops were found for taste , overall impression , and likelihood of compliance.conclusionour study confirms the findings of other researchers pertaining to the side effect profile of brinzolamide - timolol after switching from dorzolamide - timolol , which is a reduction in stinging but an increase in blurred vision . 
 the advantage of one eye drop over the other then becomes patient - specific , depending on which side effect they find most tolerable . 
 we suggest that both eye drops are acceptable choices in treating patients with glaucoma , and are interchangeable if compliance becomes an issue because of a specific side effect of one eye drop or the other .