Rate of response to latanoprost or timolol in patients with ocular hypertension or glaucoma

PURPOSE: This study determined the rate of response to latanoprost compared with timolol in patients with glaucoma or ocular hypertension, whether some patients convert from non-responders to responders after more prolonged therapy, and whether this conversion represents a delayed response or random fluctuation. METHODS: In a previously described, multicenter, randomized, double-masked, parallel group study, patients received either 0.005% latanoprost once daily (n = 128) or 0.5% timolol twice daily (n = 140) for 6 months. Intraocular pressure (IOP) was assessed at baseline and at 0.5, 1.5, 3, 4.5, and 6 months of treatment at 8 am on all visits, and also at noon and 4 pm at baseline and 6 months. Rate of response based on diurnal measurement at 6 months compared with baseline was assessed using several criteria for response. Eyes with an IOP reduction of less than 15% compared with baseline at 8 am arbitrarily were classified as non-responders at each of the 5 visits during treatment. Consistency of non-responder classifications for individual eyes was assessed. RESULTS: Mean IOP reduction was greater (P < 0.001) in latanoprost-versus timolol-treated patients throughout the course of therapy. A greater rate of response occurred in patients treated with latanoprost, and differences in response rates between the 2 drugs increased as the definitions of response became more stringent. A greater percentage of non-responders at any single visit were classified as responders at all other visits with latanoprost in comparison with timolol. CONCLUSIONS: Latanoprost produces a greater rate of response compared with timolol. A higher percentage of non-responders to latanoprost compared with timolol on any individual visit are responders on all other visits. Likewise, a higher proportion of patients who do not initially respond will become responders with continued treatment with latanoprost compared with timolol.     

Travoprost compared with latanoprost and timolol in patients with open-angle glaucoma or ocular hypertension

PURPOSE: This study evaluated the safety and intraocular pressure-lowering efficacy of two concentrations of travoprost (0.0015% and 0.004%) compared with latanoprost 0.005% and timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. METHODS: Eight hundred one patients with open-angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.0015%, travoprost 0.004%, latanoprost 0.005%, or timolol 0.5%. The efficacy and safety of travoprost (0.0015% and 0.004%) daily was compared with latanoprost daily and timolol twice daily for a period of 12 months. RESULTS: Travoprost was equal or superior to latanoprost and superior to timolol with mean intraocular pressure over visits and time of day ranging from 17.9 to 19.1 mm Hg (travoprost 0.0015%), 17.7 to 19.1 mm Hg (travoprost 0.004%), 18.5 to 19.2 mm Hg (latanoprost), and 19.4 to 20.3 mm Hg (timolol). For all visits pooled, the mean intraocular pressure at 4 PM for travoprost was 0.7 mm Hg (0.0015%, P =.0502) and 0.8 mm Hg (0.004%, P =.0191) lower than for latanoprost. Travoprost 0.004% was more effective than latanoprost and timolol in reducing intraocular pressure in black patients by up to 2.4 mm Hg (versus latanoprost) and 4.6 mm Hg (versus timolol). Based on a criterion of 30% or greater intraocular pressure reduction from diurnal baseline or intraocular pressure 17 mm Hg or less, travoprost 0.0015% and 0.004% had an overall response to treatment of 49.3% and 54.7%, respectively, compared with 49.6% for latanoprost and 39.0% for timolol. Iris pigmentation change was observed in 10 of 201 of patients (5.0%) receiving travoprost 0.0015%, six of 196 of patients (3.1%) receiving travoprost 0.004%, 10 of 194 of patients (5.2%) receiving latanoprost, and none of the patients receiving timolol (0 of 196). The average ocular hyperemia score was less than 1 on a scale of 0 to 3, indicating that on average patients experienced between none/trace and mild for all treatment groups. There were no serious, unexpected, related adverse events reported for any therapy. CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to latanoprost and superior to timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In addition, travoprost 0.004% is significantly better than either latanoprost or timolol in lowering intraocular pressure in black patients. Travoprost is safe and generally well tolerated in the studied patient population.     

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.     

Pneumatic trabeculoplasty vs latanoprost as adjunctive therapy to timolol in primary open-angle glaucoma or ocular hypertension

Purpose  To evaluate the efficacy and safety of pneumatic trabeculoplasty (PNT) compared with latanoprost 0.005%, in primary open-angle glaucoma (POAG) and ocular hypertension (OH) not controlled by timolol 0.5%. Procedures  In a randomized clinical study, 18 patients affected with primary open-angle glaucoma (POAG) or ocular hypertension (OH) with intraocular pressure (IOP) >20 mmHg after timolol 0.5% in one eye were treated with PNT; 18 control eyes received adjunctive therapy with latanoprost 0.005%. Visual acuity, IOP, visual field, biomicroscopy findings and fundus appearance were evaluated at each month. Patients with IOP >20 mmHg were excluded from the study. The study was continued until in one group no patients were left. Results  At 1 month, IOP had decreased significantly in both groups. In PNT-treated eyes the mean IOP decrease was 4.5 ± 1.8 mmHg (19.1 ± 7.8%) and in latanoprost-treated eyes was 6.6 ± 1.3 mmHg (28.2 ± 5.7%) (between two groups, P < 0.001). Eleven PNT-treated eyes (61%) and 17 latanoprost-treated eyes (94%) had an IOP reduction of more than 20% of baseline value (P = 0.049); two PNT-treated patients received additional therapy. At the following months, in the latanoprost group, IOP was stable: an IOP reduction of 20% or more was seen in 89% of the eyes. In some PNT-treated eyes IOP increased: at 2 months, an IOP reduction≥20% was seen in 50%, at 3 months in 33%, and at 4 months in 17% of the eyes. (between the two groups, respectively, P = 0.03, P = 0.002, P < 0.001). The number of eyes that required therapy increased progressively in the PNT group, and at 8 months all eyes had required therapy, whereas one latanoprost-treated eye had had additional therapy. After PNT, no patients had visual acuity reduction or intraocular inflammation; three eyes had subconjunctival hemorrhage and five eyes a hyperemia that regressed within 1 week. No posterior segment changes or visual field progression were detected in either groups. Conclusions  In eyes with glaucomatous damage that is not advanced, PNT can reduce the IOP in 60% of the eyes at 1 month, and in 33% of the eyes at 3 months, without significant side-effects. The indications, efficacy and safety of PNT retreatments remain to be investigated. IOP reduction is less and of shorter duration than that obtained by latanoprost adjunctive therapy. No financial relationship     

拉坦前列腺素与噻吗心安治疗原发性开角型青光眼和高眼压症对照研究

目的　以噻吗心安为对照,评估新型异丙酯前列腺素Ｆ２α的苯基替代衍生物拉坦前列腺素（ＰｈＸＡ４１）对于眼压升高病人的降眼压疗效和副作用。方法　３４ 例（６６ 只眼） 原发性开角型青光眼或高眼压症患者入选,随机分组,１７ 例（３２ 只眼）滴用０．０５ｇ·Ｌ－１ 拉坦前列腺素每天１ 次,１７ 例（３４ 只眼）滴用５ｇ·Ｌ－１ 噻吗心安每天２ 次,共治疗１２ｗｋ。结果　１２ｗｋ治疗期间,两种药物均能有效降低眼压（Ｐ＜ ０－０１） ,且效应持续。各次随访均显示,拉坦前腺素的降眼压效果显著优于噻吗心安（Ｐ＜ ０－０５）。１２ｍｏ 时,拉坦前列腺素组的眼压降低了９－５±３－１ｍ ｍＨｇ（３６－８ ％）（１ｍ ｍＨｇ＝ ０．１３３ｋＰａ） ,噻吗心安组降低了７－４±２－６ｍ ｍＨｇ（２９－６％ ）（ Ｐ＜ ０－０１）。拉坦前列腺素治疗后,少数病例发现角膜上皮点状脱落。噻吗心安组的平均心率减少４ 次·ｍｉｎ－１（Ｐ＜ ０－０５） 。结论　０ ．０５ｇ·Ｌ－１ 拉坦前列腺素每天１ 次与５ｇ·Ｌ－１ 噻吗心安每天２ 次相比,具有更强的降眼压作用,而且耐受性良好。因此,拉坦前列腺素将成为青光眼药物治疗的有效选择。     

Dorzolamide/timolol fixed combination versus latanoprost/timolol fixed combination in patients with primary open-angle glaucoma or ocular hypertension

PURPOSE: The efficacy of dorzolamide/timolol fixed combination (DTFC) versus latanoprost/timolol fixed combination (LTFC) in open-angle glaucoma or ocular hypertensive patients. METHODS: Patients were randomized to DTFC or LTFC for 6 weeks and switched to opposite treatment for Period 2. RESULTS: Thirty-two completed patients had a mean diurnal IOP of 19.5+/-3.2 mmHg for DTFC and 18.9+/-3.4 mmHg for LTFC (p=0.12), with no significant difference found between DTFC and LTFC at any timepoint following a Bonferroni correction (p>or=0.01). CONCLUSIONS: Patients treated with DTFC and LTFC have a statistically similar ocular hypotensive effect.     

Effect of dorzolamide timolol combination versus timolol 0.5% on ocular bloodflow in patients with primary open-angle glaucoma

PURPOSE: Addition of dorzolamide to timolol in primary open-angle glaucoma shows augmented reduction of intraocular pressure. It is unknown as yet if addition of dorzolamide will alter hemodynamics. METHODS: Fifteen patients with primary open-angle glaucoma were placed on a medication-dependent 1-week to 4-week washout that included maintenance on timolol. After washout, baseline measurements were taken (timolol). They were studied after a month on timolol or dorzolamide-timolol (Cosopt; Merck, Inc, Whitehouse Station, New Jersey), with the second drug preceded by another month of timolol maintenance and second baseline measurements. At each visit, visual function, intraocular pressure, and ocular hemodynamics were monitored, including indocyanine green and fluorescein angiography and color Doppler imaging. RESULTS: Cosopt significantly reduced intraocular pressure (14.7 to 13.4 mm Hg, P <.05) and increased arteriovenous passage time (superior temporal artery) of fluorescein dye (2.13 to 1.76 seconds, P =.01) but had no effect on visual function. CONCLUSIONS: When compared with timolol in primary open-angle glaucoma, Cosopt augments ocular tension reduction and reduces the amount of time required for blood to pass through the superior retinal vasculature.     

The efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in combination therapy with latanoprost, timolol, and dorzolamide.

PURPOSE: The aim of this study was evaluate the efficacy and ocular discomfort of substituting brinzolamide for dorzolamide in patients with glaucoma treated by latanoprost, timolol, and dorzolamide. METHODS: An 8-week, prospective, randomized, open-label, comparative study was performed in 58 patients with primary open-angle glaucoma treated by latanoprost, timolol, and dorzolamide. These patients were randomly enrolled into two groups: (1) dorzolamide three times daily was substituted with brinzolamide twice-daily (substituting group); and (2) dorzolamide three times daily was continued (control group). Intraocular pressure (IOP) was measured at baseline, 4, and 8 weeks after the enrollment. Subjective ocular discomfort (irritation and blurred vision) at the time of the instillation of the patient was noted with interview. RESULTS: The IOPs at baseline, 4 and 8 weeks after the enrollment were 17.7 +/- 2.7 mmHg, 17.5 +/- 2.6 mmHg, and 17.4 +/- 2.9 mmHg in the substituting group, and 18.0 +/- 2.5 mmHg, 17.8 +/- 2.5 mmHg, and 17.9 +/- 2.6 mmHg in the control group, respectively. There were no significant differences in IOP changes between the two groups (P = 0.74). In the substituting group, ocular irritation was decreased significantly (P = 0.0014) from 63% to 20%. The slight increase of blurred vision from 27% to 37% that occurred in the substituting group was not significant (P = 0.58). In the control group, neither ocular irritation (P = 0.58, from 68% to 57%) nor blurred vision (P = 0.99, from 25% to 21%) was changed. CONCLUSIONS: Substituting brinzolamide for dorzolamide maintained stable IOP with improvement in ocular comfort in patients with glaucoma.     

Effect of IOP on the visual field in ocular hypertension and glaucoma

The traditional opinion that increased intraocular pressure is the cause of glaucoma is controversial, probably mainly because of the fact that firm evidence for the value of pressure reduction is largely lacking. The present article reviews results from short term studies of visual fields before and after pressure reduction. It also reviews published and unpublished preliminary results from studies addressing the problem of whether the long term visual field prognosis, in glaucoma and inocular hypertension, is affected by pressure lowering therapy.There is no convincing agreement among results from modern studies using computerized perimetry indicating that acute lowering of the ocular tension results in an improvement of the glaucomatous visual field. Long-term result are equally conflicting, and often negative. We have noted from a preliminary analysis of our own masked, prospective study of patients with high risk ocular hypertension, that the same results may be interpreted in quite different ways.The results of available studies certainly indicate that pressure reduction does not automatically lead to clear and positive effects on the visual field. The studies have often been small, however, and have usually not had the power of detecting small effects of treatment. Also, pressure reduction has usually not been dramatic and many treated patients have maintained elevated pressure levels. Patients with very high pressures have not been included, and the effect of pressure reduction in this situation has therefore not been investigated at all. More controlled, prospective therapeutic studies are necessary and ethical. It seems particularly important to study the long-term effects of non-pharmacologically induced pressure reduction in patients with manifest field loss. It is necessary to make every effort to avoid bias not only in the design of such studies, but also in the interpretation of their results.     

latanoprost与噻吗心安治疗开角型青光眼及高眼压症的临床？…

验证ｌａｔａｎｏｐｒｏｓｔ对青光眼的治疗价值。方法对１２８例原发性开角型青光眼和高眼压症患者进行为期１２周的多中心、开放式,临床随机对照研究,观察其随眼压疗效和不良反应。分别应用０．００５％ｌａｔａｎｏｐｒｏｓｔ每日滴眼１次及０．５％噻吗心安每日滴眼２次。随访时间为治疗前、治疗后２、６及１２周、测量眼压并观察记录局部、全身不良反应。结果共入选１２８例（ｌａｔａｎｏｐｒｏｓｔ组６３例,噻吗心安组６５     

Comparison of the additive intraocular pressure-lowering effect of latanoprost and dorzolamide when added to timolol in patients with open-angle glaucoma or ocular hypertension: a randomized, open-label, multicenter study in Greece

PURPOSE: To compare the intraocular pressure-lowering effect of latanoprost with that of dorzolamide when added to timolol. PATIENTS AND METHODS: This randomized, open-label study with two parallel groups was conducted in five centers in Greece. The study enrolled 148 patients with inadequately controlled open-angle or pseudoexfoliation glaucoma (intraocular pressure of at least 22 mm Hg) or ocular hypertension (intraocular pressure of at least 27 mm Hg) who were receiving monotherapy with a beta-blocker or dual therapy in which one of the agents was a beta-blocker. The patients were switched to timolol 0.5% twice daily for 2 to 4 weeks (run-in period) before the start of the study (baseline). At baseline, the patients were randomized to receive latanoprost 0.005% once daily or dorzolamide 2% twice daily as add-on therapy to timolol. The intraocular pressure was recorded at 9:30 AM, 12:30 PM, and 3:30 PM at baseline and at 3 months. Safety was followed throughout the study. RESULTS: The diurnal intraocular pressure reduction was significant in both groups (P < 0.001). The mean intraocular pressure reduction from baseline was 32% for the latanoprost plus timolol group and 20% for the dorzolamide plus timolol group. The least square estimate of the mean diurnal intraocular pressure reduction after 3 months was -7.06 mm Hg in the latanoprost plus timolol group and -4.44 mm Hg in the dorzolamide plus timolol group (P < 0.001). Drugs administered in both treatment groups were well tolerated. CONCLUSION: This study clearly showed that the additive diurnal intraocular pressure-lowering effect of latanoprost is superior to that of dorzolamide in patients treated with timolol.     

Long-term effect of latanoprost/timolol fixed combination in patients with glaucoma or ocular hypertension: A prospective,observational, noninterventional study

Background  

Prospective, observational studies that enroll large numbers of patients with few exclusion criteria may better reflect actual ongoing clinical experience than randomized clinical trials. Our purpose was to obtain efficacy and safety information from a cohort of subjects exposed to latanoprost/timolol fixed combination (FC) for ≥18 months using a prospective, observational design.     

Comparison of the ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears added to timolol in glaucomatous monkey eyes

PURPOSE: To investigate the additive ocular hypotensive effect of brimonidine, dorzolamide, latanoprost, or artificial tears to timolol in monkey eyes with laser-induced unilateral glaucoma. METHODS: Eight monkeys were used and each animal received all four combinations of drugs in a randomized fashion during the study. The washout period between each combination was at least 2 weeks. Intraocular pressure (IOP) was measured at 8:30 AM, 11:00 AM, 1:00 PM, and 3:30 PM on day 1 (untreated baseline), day 2 (timolol treatment alone), and days 3 through 5 (combination therapy with two drugs). One drop of 0.5% timolol was topically applied at 3:45 PM on day 1 and at 8:45 AM and 3:45 PM on days 2 through 5. One drop of 0.2% brimonidine or 2% dorzolamide or artificial tears was added on day 2 at 4:00 PM and at 9:00 AM and 4:00 PM on days 3 through 5, or latanoprost was added at 9:00 AM on days 3 through 5. RESULTS: Compared with timolol alone, the maximal additive reduction in IOP which occurred on day 5 was 4.8 +/- 0.8 mm Hg (mean +/- standard error of the mean) with timolol plus brimonidine, 5.6 +/- 1.0 mm Hg with timolol plus dorzolamide, 4.3 +/- 1.0 mm Hg with timolol plus latanoprost, and 2.0 +/- 0.5 mm Hg with timolol plus artificial tears (P < 0.01). At all measurements, timolol plus brimonidine, timolol plus dorzolamide, and timolol plus latanoprost caused greater (P < 0.05) IOP reductions than did timolol plus artificial tears. The additive IOP-lowering effect was similar (P > 0.60) when comparing timolol plus brimonidine and timolol plus dorzolamide, timolol plus brimonidine and timolol plus latanoprost, timolol plus dorzolamide and timolol plus latanoprost at all measurements, but timolol plus dorzolamide caused a greater (P < 0.05) reduction of IOP than did timolol plus latanoprost at 0 hours on day 5. CONCLUSIONS: The addition of brimonidine, dorzolamide, or latanoprost to timolol caused similar additional reductions of IOP in glaucomatous monkey eyes.