Efficacy of topical dorzolamide 2% in diabetic cystoid macular edema

AIM: To study the effect of topical dorzolamide 2% on macular thickness reduction in diabetic cystoid macular edema (CME). METHODS: This was a prospective, non-randomized, open study including eyes with diabetic macular edema (DME). All eyes received topical dorzolamide 2% three times daily for one month. Changes in best-corrected visual acuity (BCVA), and central macular thickness (CMT) by optical coherence tomography) were evaluated at 1wk, 1, and 3mo post-treatment. RESULTS: Ninety-three eyes (84 patients) were included. Mean±SD (logMAR) BCVA improved significantly from 1.08±0.26 pretreatment to 0.66±0.24 at 1mo and 0.87±0.26 at 3mo post-treatment (P<0.001 both). The mean±SD CMT was significantly reduced from 535.27±97.4 μm at baseline to 357.43±125.8 μm at 1mo and 376.23±114.5 μm at 3mo post-treatment (P<0.001 both). No significant ocular or systemic side effects were recorded. CONCLUSION: Topical dorzolamide 2% results in significant improvement of mean BCVA and reduction of mean CMT at 3mo post-treatment. It can be used as an effective, affordable, and safe therapy for treatment of non-refractory diabetic CME.     

Dorzolamide induces vasodilatation in isolated pre-contracted bovine retinal arteries

The effect of the carbonic anhydrase inhibitor dorzolamide on vascular smooth muscle in pre-contracted bovine retinal arteries was examined. Ring segments of retinal arteries were placed in a small vessel myograph for measurement of contractile activity. The arteries were placed in a physiological saline solution. Vasoconstriction was induced by either 124 mM KCl (0.90 +/- 0.46 mN, n=34), 10(-4) M prostaglandin F2alpha (1.72 +/- 0.84 mN, n=10) or 10(-6) M norepinephrine (0.78 +/- 0.47 mN, n=6). Both KCl and prostaglandin F2alpha caused steady repeatable contractions but norepinephrine caused a single phasic contraction. The effect of the carbonic anhydrase inhibitor, dorzolamide on the vasoconstriction was examined. Dorzolamide, if added to the bath when the vasoconstriction had reached a maximum steady level, caused a highly significant relaxation (vasodilatation) of the arteries. This action of dorzolamide occurred irrespective of which agent was used to induce vasoconstriction. Similar results were obtained in experiments were Hepes buffer was used instead of CO2/bicarbonate buffer. The vasodilatation induced by dorzolamide was stable as long as the drug remained in the bath, and was reversible. These results show that dorzolamide causes a vasodilatation of retinal arteries, pre-contracted by three different mechanisms by direct action and presumably independent of changes in extracellular pH.     

Binding Affinity of Bunazosin,Dorzolamide, and Timolol to Synthetic Melanin

Purpose The purpose of this study was to compare the binding affinity of bunazosin and dorzolamide to synthetic melanin relative to that of timolol.Methods Synthetic melanin was prepared from dopa by the action of tyrosinase. Timolol, dorzolamide, and bunazosin were incubated separately at a concentration of 10^–4M in 2ml of 0.066M phosphate buffer containing 5mg of synthetic melanin. After centrifugation, the absorbance of each free drug in the supernatant was measured at its optimum wavelength. The percentage of each drug bound to melanin was calculated directly from the change in absorbance relative to the initial value.Results The increase in the binding rates of all three drugs seemed to reach a plateau after 30min. After incubating for 60min, the binding rate of timolol was 22.2% ± 4.9%, bunazosin 36.3% ± 2.5%, and dorzolamide 8.5% ± 1.9%. There were statistically significant differences between the binding rates of each drug.Conclusions Under our study conditions, the order of binding affinity of these ocular hypotensive agents to synthetic melanin seems to be as follows: bunazosin timolol dorzolamide. Jpn J Ophthalmol 2004;48:34–36 © Japanese Ophthalmological Society 2004     

Fixed combinations of dorzolamide-timolol and brimonidine-timolol in the management of glaucoma

Importance of the field: The emergence of fixed-combination drugs for the treatment of glaucoma has, to some extent, changed the medical management of glaucoma. The potential benefits of these drugs include a reduction in the total number of drops and preservatives instilled per day and improved patient comfort factors, which may contribute to better compliance. Combination medications may also improve therapeutic efficacy and play an important role in controlling medication cost. However, the fixed dosing may be a disadvantage in some cases.

Area covered in this review: This review describes the composition, pharmacokinetics, mode of action, efficacy, side effects, and safety profile of fixed-combination dorzolamide–timolol and fixed-combination brimonidine–timolol.

What the reader will gain: Understanding of the pros, cons, and safety profile of two FDA approved fixed-combination antiglaucoma medication.

Take home message: Fixed-combination medications may be a reasonable adjunct to prostaglandins if a large drop in the intraocular pressure (IOP) is desired and adding only one medication is unlikely to reach the target IOP range. Both mentioned drugs are effective in reducing the IOP and further clinical studies will help identify differences in efficacy between the two. The clinician must make an individualized assessment of the medication's risk-benefit profile for each patient.     

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma

Aim

The aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG).

Methods

One eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy.

Results

Sixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P<0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: −0.7 mm Hg, 95% confidence interval (CI): (−1.0, −0.3), P<0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (−1.0 mm Hg, 95% CI (−1.6,−0.5), P=0.001) and at 0200 (−0.9 mm Hg, 95% CI: (−1.4,−0.5), P=0.001). No significant difference existed for the other time points.

Conclusion

Both the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.     

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

AIM:To evaluate intraocular pressure (IOP)-lowering effect and ocular tolerability of brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer. Ocular discomfort (conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2^nd mo IOP measurements, and mean (%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.     

X-linked retinoschisis maculopathy treated with topical dorzolamide, and relationship to genotype

Purpose

To correlate the response of topical dorzolamide (Trusopt; Merck) in patients with X-linked retinoschisis (XLRS) with genotype.

Methods

We carried out a retrospective evaluation of four patients (seven eyes) with XLRS, treated with topical dorzolamide. The change in best-corrected visual acuity (VA) and central macular thickness (CMT; central 1 mm subfield thickness) from optical coherence tomography (OCT) was analysed over the follow-up period, using Student''s t-test. Each patient also had genetic analysis for mutations in the retinoschisisgene (RS1).

Results

The mean age at the start of treatment was 14.7±11 years, and mean follow-up duration was 21.7±7.7 months. Mean CMT at the final follow-up was significantly better than at baseline (291±123 vs352±119 μm, P=0.007); however, mean VA was worse (0.38±0.25 vs0.31±0.24 logMAR score, P=0.041). All four patients had a mutation in the RS1gene; there was no apparent association between the type of mutation and the response to topical dorzolamide.

Conclusion

Topical dorzolamide may have some effect in reducing central macular thickness in patients with XLRS, but this does not necessarily correlate with improvement in VA. In our case series, genotypic information did not predict the response to this treatment.     

Effect of latanoprost/timolol and dorzolamide/tiomolol on intraocular pressure after phacoemulsification surgery

AIM: To evalaute the effect of fixed-combination latanoprost 0.005%/timolol maleate 0.5% and dorzolamide hydrochloride 2%/timolol maleate 0.5% on postoperative intraocular pressure after phacoemulsification cataract surgery. METHODS: This study is a prospective, randomized, double-masked and placebo-controlled. The study included 90 eyes of 90 patients which were scheduled to have phacoemulsification surgery. Patients were randomly assigned preoperatively to 1 of 3 groups (30 eyes of 30 patients). Two hour before surgery, the patients received one drop latanoprost/timolol (group 1), dorzolamide/timolol (group 2) and placebo (group 3, control group). The IOPs were measured at preoperative and postoperative 4, 8, and 24 hours. RESULTS: The preoperative mean intraocular pressure was not statistically significant between both drug groups and control group. In group 1 and 2, the postoperative mean IOP [group1: (14.03±3.15)mmHg and group 2: (14.16±4.43)mmHg] at 24 hours were significantly lower than the control group [(16.93±3.70)mmHg, (P<0.05)]. In addition, the postoperative mean IOP of group 1 [(14.90±3.69)mmHg] at 8 hours was significantly lower than the control group [(17.70±3.89)mmHg, (P<0.05)], but there was no significant difference between group 2 [(16.16±5.23)mmHg] and control group at 8 hours (P>0.05). CONCLUSION: When compared with placebo, the use of preoperative fixed combination of latanoprost/ timolol and dorzolamide/timolol is an effective method for preventing intraocular pressure elevation in 24 hours after phacoemulsification surgery, but did not completely prevent IOP spikes.     

Additive effect of latanoprost and dorzolamide in patients with elevated intraocular pressure

Purpose : To evaluate the additive ocular hypotensive effect of latanoprost and dorzolamide in combination, on intraocular pressure reduction in patients with elevated intraocular pressure (IOP). Methods : Thirty patients with ocular hypertension or early capsular or primary open-angle glaucoma and elevated IOP were randomly assigned to two parallel treatment groups. The treatment period was twenty days. Fifteen patients (Group 1) received latanoprost once daily during the first ten days and, in addition, dorzolamide three times daily during the second ten days. Fifteen patients (Group 2) received dorzolamide three times daily during the first ten days and, in addition latanoprost, once daily during the second ten days. IOP was measured and conjunctival hyperemia was evaluated. Results : In Group 1, the mean IOP on day 0 was 26.8 mmHg; on day 10, 18.7 mmHg; and on day 20, 15.9 mmHg. In Group 2, the mean IOP on day 0 was 26.3 mmHg; on day 10, 21.2 mmHg; and on day 20, 16.1 mmHg. Both groups had clinically significant IOP- lowering effect on day 10 as compared with baseline day (30.2% and 19.4% respectively) (p < 0.01). When dorzolamide was added to latanoprost, the additional IOP reduction was 2.8 mmHg (15%) (p<0.01) compared with 5.1 mmHg (24.1%) (p<0.01when latanoprost was added to dorzolamide. No local serious adverse reactions were observed. A mild but statistically significant increase in conjunctival hyperemia was seen in latanoprost applied patients. Conclusions : The results showed that latanoprost and dorzolamide can be combined successfully to reduce IOP with their additive effects.