Comparative study of the pressure lowering efficacy and variations in the ocular pulse amplitude between fixed combinations of dorzolamide/timolol and brinzolamide/timolol

ObjectiveTo determine possible differences in the intraocular pressure (IOP) and ocular pulse amplitude (OPA) lowering capacity of the fixed drug combinations dorzolamide/timolol and brinzolamide/timolol.MethodsIn this cross-sectional study, one of the eyes of 25 healthy subjects was randomly assigned to treatment with dorzolamide/timolol and the other eye with brinzolamide/timolol. After instilling the drops, possible adverse effects (e.g., blurred vision, itching) were assessed in each eye. This assessment was repeated 30 minutes later. IOP and OPA were determined In each eye by dynamic contour tonometry at baseline and two hours following treatment.ResultsBoth fixed drug combinations significantly reduced IOP and OPA with no differences detected between treatment groups. Among the adverse effects recorded, itching was significantly greater in the first assessment in the eyes treated with dorzolamide/timolol (P = .011). This difference was no longer apparent in the second assessment.ConclusionsBoth fixed combinations were similarly effective in reducing intraocular pressure and ocular pulse amplitude. Adverse effects related to both treatments were mild and well-tolerated, though itching occurred most frequently in the eyes treated with dorzolamide/timolol.     

Evaluation of retinal haemodynamics and retinal function after application of dorzolamide, timolol and latanoprost in newly diagnosed open-angle glaucoma patients

PURPOSE: The purpose of this prospective, randomized, cross-over study was to investigate and compare the microcirculatory effects of timolol, dorzolamide and latanoprost in newly diagnosed primary open-angle glaucoma (POAG) patients. Haemodynamics were assessed using fluorescein angiography by means of a scanning laser ophthalmoscope (SLO). Visual function and visual field indices were evaluated during all drug treatment phases. METHODS: Fourteen patients with newly diagnosed POAG (age 55 +/- 7 years; 10 male, four female) were recruited for the study. At baseline examination, blood pressure, heart rate, intraocular pressure (IOP), SLO angiograms, and contrast sensitivity (CS) were analysed. Patients then randomly received timolol, dorzolamide or latanoprost treatment for 4 weeks. Patients then returned and all procedures were repeated and assessed. Arteriovenous passage times (AVPs), peripapillary arterial and venous diameters were assessed from SLO angiograms, using digital image processing. Calculated ocular perfusion pressure was determined for each treatment phase. RESULTS: Intraocular pressure was significantly lowered by each drug compared to baseline (p < 0.0001). Arteriovenous passage times were significantly shortened after dorzolamide application compared to baseline (p = 0.009), whereas neither timolol nor latanoprost treatment resulted in significant AVP changes. Peripapillary arterial and venous diameters, systolic and diastolic blood pressure, heart rate and ocular perfusion pressures were not significantly altered during any treatment phase. Contrast sensitivity testing at 6 cycles/degree (c.p.d.) revealed a significant rise after dorzolamide compared to timolol (p = 0.007). CONCLUSION: Our results suggest that dorzolamide treatment significantly shortened AVP times in newly diagnosed open-angle glaucoma patients, whereas timolol and latanoprost had no significant effect. Given that prolonged AVP times have been associated with disease progression in glaucoma; dorzolamide treatment may benefit optic nervehead preservation by increasing ocular perfusion.     

Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension

BACKGROUND: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. RESULTS: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol). CONCLUSIONS: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma.     

Topically administered timolol and dorzolamide reduce intraocular pressure and protect retinal ganglion cells in a rat experimental glaucoma model

AIMS: This study sought to elucidate the effects of timolol and dorzolamide on intraocular pressure (IOP) and retinal ganglion cell (RGC) death in an experimental model of glaucoma in rat. METHODS: Mild elevation of IOP was induced in rats by intracameral injection of India ink and subsequent laser trabecular photocoagulation. IOP was measured before the surgical procedures and weekly thereafter. Timolol (0.5%), timolol XE (0.5%), dorzolamide (1%), and artificial tears (vehicle) were topically applied daily. Retinal sections were prepared for histology to determine RGC number. RESULTS: Timolol, timolol XE, and dorzolamide induced a significant reduction in IOP (p<0.05) and counteracted the reduction in RGC number that occurred in vehicle treated glaucomatous eyes (p<0.05). The coefficient of correlation between RGC number and IOP was significant in the dorzolamide treated group (r = -0.908, p<0.005), but not in other groups (p>0.05). CONCLUSIONS: Both timolol formulation and dorzolamide reduced IOP and protected RGCs in a rat model of experimental glaucoma. It cannot be ruled out that timolol might protect RGCs by additional mechanisms other than simply lowering of IOP.     

Effects on aqueous flow of dorzolamide combined with either timolol or acetazolamide

PURPOSE: To determine the effect on aqueous flow of topical dorzolamide 2%, topical timolol 0.5%, or oral acetazolamide 250 mg when used alone or when dorzolamide is combined with either timolol or acetazolamide. METHODS: In 30 patients with ocular hypertension, aqueous flow and intraocular pressure (IOP) were determined at baseline and on the following combinations of drugs in a crossover design: (1) vehicle alone, (2) dorzolamide alone, (3) acetazolamide alone, (4) timolol alone, (5) dorzolamide + acetazolamide, and (6) dorzolamide + timolol. Treated eyes were compared with control eyes and comparisons were made between treatments. RESULTS: Compared with baseline, significant (P < 0.04) IOP reductions in the order of efficacy were: dorzolamide + timolol > dorzolamide + acetazolamide = acetazolamide = timolol > dorzolamide. Aqueous flow was reduced more by dorzolamide + timolol than by each drug alone (P < 0.04) and more by dorzolamide + acetazolamide than by dorzolamide alone (P < 0.04). CONCLUSION: The combination of dorzolamide and timolol demonstrated significant aqueous flow additivity and had greater IOP efficacy than the combination of dorzolamide and acetazolamide.     

Effects of topical hypotensive drugs on circadian IOP, blood pressure, and calculated diastolic ocular perfusion pressure in patients with glaucoma

PURPOSE: To compare the short-term effects of timolol 0.5%, brimonidine 0.2%, dorzolamide 2%, and latanoprost 0.005% on intraocular pressure (IOP), blood pressure (BP), and diastolic ocular perfusion pressure (DOPP), calculated as the difference between the diastolic blood pressure (DBP) and IOP. METHODS: According to a 4 x 4 Latin squares design for repeated measures, 27 untreated patients and patients with newly diagnosed primary open-angle glaucoma (POAG) were treated with timolol 0.5% at 8 AM and 8 PM; brimonidine 0.2% at 8 AM and 8 PM; dorzolamide 2% at 8 AM, 2 PM, and 8 PM; and latanoprost 0.005% at 8 PM. The duration of each treatment course was 6-weeks, with a 4-week washout between each treatment. IOP and BP were measured at baseline and at the end of each treatment period. IOP was measured every 2 hours throughout a 24-hour period. Sitting IOP was measured from 8 AM to 10 PM by Goldmann applanation tonometry. Supine IOP was assessed from 12 to 6 AM by means of a handheld electronic tonometer (TonoPen XL; Mentor, Norwell, MA). BP monitoring was performed by means of an automated portable device (TM-2430; A & D Co., Saitama, Japan). RESULTS: All the drugs tested decreased the IOP significantly at all time points in comparison with baseline pressure. The mean 24-hour IOP after latanoprost administration (16.62+/-0.98 mm Hg) was significantly lower than that after timolol, brimonidine, or dorzolamide (P=0.0001). During the 24-hour period, brimonidine induced a significant decrease in systolic BP (SBP) and DBP at all time points when compared with baseline measurements and with those after administration of the other drugs (P<0.0001). Timolol caused a significant decrease in DBP and SBP at all the 24-hour time points when compared with the baseline and with the dorzolamide- and latanoprost-induced changes (P<0.0001). The mean 24-hour DOPPs were 50.7+/-5.9 mm Hg at baseline, 53+/-5.5 mm Hg with timolol, 46.2+/-5.4 mm Hg with brimonidine, 55.9+/-4.6 mm Hg with dorzolamide, and 56.4+/-4.9 mm Hg with latanoprost. Brimonidine induced a significant decrease in the mean 24-hour DOPP compared with that at baseline (P<0.0001), whereas dorzolamide and latanoprost induced a significant increase (P<0.0001). CONCLUSIONS: Latanoprost seemed to induce a uniform reduction in IOP during the 24-hour period, although timolol was as effective as latanoprost during the daytime, and dorzolamide are as effective as latanoprost at night. SBP and DBP were significantly decreased by either timolol or brimonidine. In this study of patients with newly diagnosed POAG, only dorzolamide and latanoprost significantly increased mean 24-hour DOPP.     

Topical carbonic anhydrase inhibition increases ocular pulse amplitude in high tension primary open angle glaucoma

BACKGROUND—Ocular pulse amplitude (OPA) is reduced in normal tension primary open angle glaucoma (NTP) patients when compared with healthy age matched controls (CTL) while increased OPA appears to protect ocular hypertensive patients from visual field loss. If NTP is accompanied by vasospasm, as in roughly half of the primary open angle glaucoma (POAG) population (independent of intraocular pressure, IOP), calcium channel blockers increase OPA and thus stabilise visual fields in these patients. Current glaucoma drugs reduce IOP but do not activate (compromised) ocular perfusion.
METHODS—The influence of dorzolamide, a topical carbonic anhydrase inhibitor in standard dosage (three times daily, one eye) on OPA, IOP, blood pressure, and heart rate was investigated in a randomised, prospective, masked clinical trial assessing the acute effects of dorzolamide v placebo before and 2 days after application in 33 cataract patients with (n = 14) and without (n = 19) high tension POAG (HTP) who provided informed consent.
RESULTS—Following application of dorzolamide (D) IOP (mm Hg, mean (SEM)) in HTP_D (20.2 (0.5)/16.3 (0.5)) and in CTL_D (16.0 (0.5)/12.3 (0.5)) was highly significantly (p <0.001) reduced and was significantly (p<0.03) reduced in vehicle (V) treated eyes (HTP_V: 20.3 (0.4)/19.0 (0.4)) and CTL_V: 15.8 (0.4)/14.9 (0.3)) when compared with respective baseline measurements. OPA (mm Hg) in HTP_D (2.1 (0.1)/2.5 (0.1)) and CTL_D (2.2 (0.1)/2.6 (0.2)) eyes was significantly (p<0.05) increased and unaffected in vehicle treated eyes when compared with respective baseline measurements. Systemic perfusion variables were also unchanged.
CONCLUSION—Dorzolamide increased OPA in HTP and CTL. Drugs stimulating OPA may improve prognosis of POAGs.

Keywords: ocular pulse amplitude; primary open angle glaucoma; dorzolamide     

Comparison of the efficacy and safety of dorzolamide 2% when added to brimonidine 0.2% or timolol maleate 0.5% in patients with primary open-angle glaucoma.

OBJECTIVE: To determine the ocular hypotensive efficacy and safety of dorzolamide when added to brimonidine or timolol in patients with uncontrolled primary open-angle glaucoma (POAG). PATIENTS AND METHODS: This is a 1-year prospective open-label clinical trial of 48 consecutive POAG patients with inadequate intraocular pressure (IOP) control while using brimonidine 0.2% (23 patients) and timolol 0.5% (25 patients), 2 times daily. Patients were assigned to receive dorzolamide 2% as adjunctive therapy, added 3 times daily to brimonidine or timolol. IOP was measured on week 2, and months 3, 6, 9, and 12. RESULTS: A significant reduction in IOP from the baseline was observed after dorzolamide use in both groups at visits during that year (P < 0.001). Overall, mean IOP reduction was 5.6 +/- 1.9 mmHg with the brimonidine-dorzolamide combination, and 6.8 +/- 1.7 mmHg with timolol-dorzolamide after 1 year of treatment; the difference was significant (P = 0.029). No statistical differences existed between the groups for adverse events (P < 0.05). CONCLUSION: The addition of dorzolamide to brimonidine or timolol has significant IOP-lowering efficacy during 1 year in patients with POAG whose IOPs were inadequately controlled with brimonidine or timolol alone. The IOP-lowering effect of the timolol-dorzolamide combination at 1 year was more pronounced than brimonidine-dorzolamide. Both combinations were well-tolerated by the patients.     

Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or ocular hypertension

PURPOSE: To compare the around-the-clock intraocular pressure (IOP) reduction induced by timolol 0.5%, latanoprost 0.005%, and dorzolamide in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: In this crossover trial, 20 patients with POAG (n = 10) or OHT (n = 10) were treated with timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was randomized. All patients underwent measurements for four 24-hour tonometric curves: at baseline and after each 1-month period of treatment. The patients were admitted to the hospital, and IOP was measured by two well-trained evaluators masked to treatment assignment. Measurements were taken at 3, 6, and 9 AM and noon and at 3, 6, and 9 PM and midnight by handheld electronic tonometer (TonoPen XL; Bio-Rad, Glendale, CA) with the patient supine and sitting, and a Goldmann applanation tonometer (Haag-Streit, Bern, Switzerland) with the patient sitting at the slit lamp. Systemic blood pressure was recorded at the same times. The between-group differences were tested for significance by means of parametric analysis of variance. The circadian IOP curve of a small group of untreated healthy young subjects was also recorded using the same procedures. To compare the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for each subject were calculated. RESULTS: When Goldmann sitting values were considered, all the drugs significantly reduced IOP in comparison with baseline at all times, except for timolol at 3 AM. Latanoprost was more effective in lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM, and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight and 3 AM (P = 0.05). An ancillary finding of this study was that in the group of healthy subjects, the pattern of IOP curve was different that in patients with eye disease. CONCLUSIONS: Latanoprost seemed to lead to a fairly uniform circadian reduction in IOP, whereas timolol seemed to be less effective during the nighttime hours. Dorzolamide was less effective than latanoprost but led to a significant reduction in nocturnal IOP. The reason for the difference in the pattern of the IOP curve of healthy subjects is currently unknown and deserves further investigation.     

Comparison of the efficacy of the fixed-combination timolol/dorzolamide versus concomitant administration of timolol and dorzolamide.

The purpose of this study was to compare the efficacy of the fixed-combination solution of timolol 0.5%/dorzolamide 2% with the concomitant administration of its components, timolol 0.5% twice a day and dorzolamide 2% twice a day. Ninety-eight patients adequately controlled with a concomitant regimen of timolol and dorzolamide were switched to the fixed-combination regimen of the same components. Intraocular pressures at baseline and 4 weeks after the change in regimen were recorded. The mean baseline intraocular pressure (IOP) was 16.0 +/- 5.6 mmHg. Four weeks after the change in medication to the fixed-combination regimen, the mean IOP was 14.5 +/- 5.6 mmHg. The mean IOP change from baseline was -1.5 +/- 3.9 mmHg. The difference between the two treatment modalities was found to be statistically significant (p-value < 0.001). Eighty-one (83%) patients were considered successfully switched after 4 weeks of fixed-combination therapy, and seventeen eyes (17%) were deemed unsuccessful because a rise in IOP was detected. In conclusion, the fixed combination of timolol 0.5%/dorzolamide 2% twice a day provided equivalent or better intraocular pressure reduction in most patients who were successfully controlled on concomitant administration of its components, timolol and dorzolamide.     

Combined therapy of pilocarpine or latanoprost with timolol versus latanoprost monotherapy

Adjunctive intraocular pressure (IOP)-lowering therapy is widely used today, as one-third of all patients being treated for glaucoma need additional therapy to reach and maintain healthy IOPs. Timolol, latanoprost, and pilocarpine are three potent drugs that have been used in combination to reduce IOP. Timolol reduces the production rate of aqueous humor to achieve the IOP decrease. Latanoprost and pilocarpine both affect aqueous outflow, although by different mechanisms. The IOP efficacy of combined therapy with timolol and pilocarpine compared with timolol and latanoprost or with latanoprost alone has been investigated in three multicenter, randomized, clinical trials in Europe. This is a review of those published trials. In 2 of the 3 studies, the additional IOP lowering effect of latanoprost 0.005% administered once daily was compared with pilocarpine 2% administered 3 times daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension currently on monotherapy with timolol 0.5% twice daily. These 6-month studies found that the timolol and latanoprost combination reduced IOP more and was better tolerated with fewer side-effects than the timolol and pilocarpine combination. At 6 months, there was no evidence of long-term drift in IOP with timolol and latanoprost. This combined therapy provides an effective and safe option for lowering IOP in glaucoma patients. These results suggest that the timolol/latanoprost combination is preferable to the timolol/pilocarpine combination not only with regard to side effects but also to the magnitude of IOP reduction. Two of the 3 studies compared latanoprost monotherapy with timolol and pilocarpine combined therapy in patients with POAG, various other glaucomas, or ocular hypertension. Treatment was for 6 weeks or 6 months. In both studies, latanoprost was more effective and better tolerated than the combination of timolol and pilocarpine. These results suggest that latanoprost alone should be tried before the addition of pilocarpine to timolol therapy is considered. The convenience of daily administration of a single drop of latanoprost versus multiple drops of timolol and pilocarpine should improve patient compliance.     

Latanoprost versus combined therapy with timolol plus dorzolamide: IOP-lowering effect in open-angle glaucoma

PURPOSE: To compare the effect on intraocular pressure of latanoprost versus timolol plus dorzolamide in open-angle glaucoma. METHODS: Thirty-five patients with open-angle glaucoma were randomized, 18 to latanoprost once daily and 17 to timolol plus dorzolamide twice daily. Intraocular pressure and ocular side effects were recorded at baseline, and after 2 weeks and 3 months of treatment. RESULTS: Latanoprost reduced the intraocular pressure 1.09 and 1.58 mm Hg more than timolol plus dorzolamide after 2 weeks and 3 months of treatment, respectively. These differences were statistically significant (p<0.05) at the end of the study. After 3 months of treatment, 32.3% of the eyes in the latanoprost group reduced the intraocular pressure in 30% or more with respect to baseline, while 15.6% of the eyes in the timolol plus dorzolamide group achieved this reduction. CONCLUSIONS: Latanoprost administered once daily reduced the intraocular pressure at least as well as timolol plus dorzolamide twice daily in patients with open-angle glaucoma.     

A comparative analysis of the effects of the fixed combination of timolol and dorzolamide versus latanoprost plus timolol on ocular hemodynamics and visual function in patients with primary open-angle glaucoma.

AIMS: The aim of this study was to assess the effects of fixed combination of timolol and dorzolamide and latanoprost plus timolol on retinal, choroidal, and retrobulbar hemodynamics and visual function in primary open-angle glaucoma (OAG) subjects. METHODS: Sixteen (16) OAG patients (age, 63.5 +/- 10.8 years; 9 male) were evaluated in a randomized, crossover, double-blind study design after 4 weeks of treatment of latanoprost with timolol and fixed combination of timolol and dorzolamide. After randomization, 9 right eyes and 7 left eyes were included in the hemodynamic portion of the study. Measurements included: adverse events check, visual acuity, contrast sensitivity, blood pressure, heart rate, intraocular pressure (IOP), and fundus examination. Ocular blood flow was assessed using confocal scanning laser Doppler flowmetry, color Doppler imaging, and scanning laser ophthalmoscopy. RESULTS: Both therapies were effective at lowering IOP, whereas there was no statistically significant difference between latanoprost plus timolol and the fixed combination of timolol and dorzolamide (13.9% and 12.2% reduction, respectively; P = 0.5533). Fixed combination of timolol and dorzolamide significantly increased central retinal artery end diastolic blood flow velocity (P = 0.0168) and lowered resistance to flow (P = 0.0279). Temporal posterior ciliary artery peak systolic and end diastolic velocities were significantly increased with the fixed combination of timolol and dorzolamide (P = 0.0125 and 0.0238, respectively). Latanoprost plus timolol had no significant effects on ocular blood flow during 4 weeks of treatment. There were no statistically significant differences in adverse events, blood pressure, heart rate, visual acuity, contrast sensitivity scanning laser ophthalmoscopy, or Heidelberg Retinal Flowmeter for any treatment period. CONCLUSIONS: Fixed combination of timolol and dorzolamide therapy might increase blood flow in OAG patients while attaining a similar IOP reduction compared to latanoprost plus timolol. Visual function, however, was not different in this short-term comparison between the two treatments.     

Unoprostone as adjunctive therapy to timolol: a double masked randomised study versus brimonidine and dorzolamide

AIMS: To compare the safety and efficacy of unoprostone, brimonidine, and dorzolamide as adjunctive therapy to timolol in patients with primary open angle glaucoma or ocular hypertension. METHODS: This was a randomised, double masked, parallel group, multicentre (14) study. After using timolol maleate 0.5% monotherapy twice a day for 2 weeks, patients (n = 146) with an early morning intraocular pressure (IOP) between 22 and 28 mm Hg, inclusively, received unoprostone isopropyl 0.15% (n = 50), brimonidine tartrate 0.2% (n = 48), or dorzolamide hydrochloride 2.0% (n = 48) twice daily as adjunctive therapy to timolol maleate 0.5% for another 12 weeks. Safety was based on comprehensive ophthalmic examinations, adverse events, and vital signs. Efficacy was based on mean change from baseline in the 8 hour diurnal IOP at week 12. Baseline was defined as values obtained after 2 weeks of timolol monotherapy. RESULTS: Each drug was safe and well tolerated. Burning/stinging was the most common treatment emergent adverse event. No clinically relevant changes from baseline were observed for any ophthalmic examination or vital signs. At week 12, each adjunctive therapy produced statistically significant (p<0.001) reductions from timolol treated baseline in the mean 8 hour diurnal IOP (-2.7 mm Hg, unoprostone; -2.8 mm Hg, brimonidine; -3.1 mm Hg, dorzolamide). The extent of IOP reduction did not differ significantly between unoprostone and either brimonidine (p = 0.154) or dorzolamide (p = 0.101). CONCLUSION: Unoprostone was safe and well tolerated and provided a clinically and statistically significant additional reduction in IOP when added to stable monotherapy with timolol. Furthermore, unoprostone was not significantly different from brimonidine and dorzolamide as adjunctive therapy to timolol.     

Peak pulse blood volume and topical antiglaucoma drugs in rhesus monkeys with experimental open angle glaucoma

BACKGROUND: The present study was designed to investigate the effect of topical antiglaucoma drugs on Peak Pulse Blood Volume (PPBV; German abbreviation: PGBV) in cynomolgus monkey eyes without (CMNG; German abbreviation: RA-KTL) and with lasersurgically induced glaucoma (CMG; German abbreviation: RA-LHDG). METHODS: CMG unilaterally received 2-3 laser treatments so as to develop the lasered-eye glaucoma model. Intraocular pressure (IOP; German abbreviation: IOD) and Ocular Pulse Amplitude were measured and PPBV was determined until the glaucoma model had stabilized. Consecutively topical antiglaucoma drugs (epinephrine, paraaminoclonidine, pilocarpine, timolol) were investigated in 4-8 animals in CMNG and CMG eyes. RESULTS: IOP and PPBV were not significantly altered in CMNG. In the CMG eyes epinephrine and paraaminoclonidine did not significantly alter IOP or PPBV, whereas pilocarpine and timolol sig. (p < 0.01) reduced IOP and significantly (p < 0.05) increased PPBV. CONCLUSION: With respect to improved PPBV in the CMG eye the rank order of drug effectiveness is timolol > pilocarpine > paraaminoclonidine > epinephrine.     

The short-term IOP-lowering effect of brimonidine 0.2% and dorzolomide 2% combination in primary open-angle glaucoma

PURPOSE: To evaluate the ocular hypotensive effect of dorzolamide 2% in primary open-angle glaucoma (POAG) patients with intraocular pressure (IOP) of at least 22 mmHg despite ongoing twice daily treatment with brimonidine 0.2%. PATIENTS AND METHODS: Nineteen eyes of 19 patients with POAG and IOP >or= 22 mmHg, on twice daily brimonidine therapy, were included in the study. Intraocular pressure and adverse effects were recorded on days 2, 7, 14 and 30 after adding dorzolamide three times daily to the treatment. RESULTS: Mean pretreatment IOP was 27.6 +/- 2.2 mmHg. This decreased to 24.2 +/- 2.2 mmHg after a mean duration of 23.8 +/- 12.1 days. After dorzolamide was added to the treatment, mean IOP was 20.8 +/- 2.3 mmHg on day 2, 19.3 +/- 2.2 mmHg on day 7, 18.0 +/- 2.5 mmHg on day 14 and 17.2 +/- 2.3 mmHg on day 30. The differences between pre- and post-treatment IOP values were statistically significant (p < 0.0001, anova test). CONCLUSION: Dorzolamide administered three times daily has significant additive ocular hypotensive effect in POAG patients whose IOP is elevated despite ongoing treatment with brimonidine.     

A comparison of dorzolamide–timolol combination versus the concomitant drugs

PURPOSE: To compare the intraocular pressure (IOP) lowering effect of fixed combination dorzolamide 2% and timolol 0.5% therapy to that of concomitant administration of a topical beta-blocker and dorzolamide.METHODS: Seventy-four consecutive glaucoma patients were changed from a regimen including a topical beta-blocker and dorzolamide to the fixed combination dorzolamide–timolol in 1 eye, with the other eye used as the control. The average IOP readings before and 1 month after the change were compared.RESULTS: The mean baseline IOP in the entire study population was 19.4 ± 4.2 mm Hg in the study eyes and 16.9 ± 4.2 mm Hg in the control eyes. Four weeks after the medication change, the mean IOP was 17.3 ± 3.9 mm Hg in the study eyes (P < .001) and 16.1 ± 4.1 mm Hg in the control eyes (P = .02). The difference between the mean IOP change of 2.1 mm Hg in the study eyes and 0.8 mm Hg in the control eyes was found to be statistically significant (P = .01).CONCLUSION: These findings suggest that the fixed combination dorzolamide–timolol therapy achieves additional lowering of the intraocular pressure compared with the concomitant administration of a beta-blocker and dorzolamide.     

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.     

Timolol maleate 0.5% versus timolol maleate in gel forming solution 0.5% (Timolol GFS) in open angle glaucoma in India. Preliminary safety and efficacy study

PURPOSE: To compare the efficacy and safety profile of Timolol maleate 0.5% versus Timolol gel forming solution (GFS) 0.5% in open angle glaucoma in Indian eyes. METHODS: In a prospective crossover study 52 patients of open angle glaucoma, well controlled intraocular pressure (IOP) on 0.5% timolol maleate solution were switched over to timolol GFS once a day, after a washout period of one month. A diurnal IOP measurement was done after 6 weeks and compared with patients on timolol maleate 0.5% twice a day. In addition, side effects reported or observed were compared. RESULTS: Statistically significant difference was not observed in ocular hypotensive effect of the two treatment. The side-effects in both the treatment groups were similar except for higher incidence of blurring of vision in patients on timolol GFS. The compliance was better with timolol GFS, but was not statistically significant. CONCLUSION: The results of this study suggest that the more convenient 0.5% timolol in gel forming solution can be offered as an equally efficacious and well-tolerated alternative to twice daily 0.5% timolol solution in open angle glaucoma.