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Introduction: Fixed dose combinations (FCs) represent a potentially valuable treatment strategy in glaucoma management. Fixed combinations not only improve adherence by reducing the medication burden, but also decrease the total amount of potentially deleterious preservatives an eye is exposed to., Areas Covered: We provide a critical review of selected evidence on both the safety and tolerability of presently available and emerging glaucoma FCs. There is convincing short-term safety and tolerability evidence on intraocular pressure (IOP)-lowering FCs compared to that of monotherapies and, to a lesser degree, to that of concomitant, equivalent combination therapies. In contrast, there is a scarcity of trials evaluating the long-term efficacy and safety of glaucoma FCs and no conclusive data on the reduction of adverse events with FCs., Expert Opinion: It is vital for clinicians to carefully weigh the efficacy, safety, tolerability, and adherence of IOP-lowering FCs. Given the number of currently available and emerging FC therapy options in glaucoma, as well as the complexities of incorporating them in the various combination therapy regimens, successful stepwise therapy remains often elusive.

Purpose: To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery., Patients and Methods: Children with primary pediatric glaucoma with postsurgical intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure., Results: A total of 37 patients (61 eyes) were analyzed. The mean age of the patients was 4.1 years (SD: 3.8). In total, 43 eyes were included in the efficacy analysis. A total of 33 eyes (76.7%; 95% confidence interval, 61.4-88.2) were considered responders: 19 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to central corneal thickness at the time of surgery and the age at the time of surgery. IOP reduction was 9.7 mm Hg (SD: 2.6) for latanoprost, 8.4 mm Hg (SD: 1.5) for the latanoprost/dorzolamide combination, and 9.3 mm Hg (SD: 2.5) for the dorzolamide monotherapy. None of the patients was withdrawn because of adverse events., Conclusions: Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children after surgery. Nonresponders were mainly patients with early presentation of the disease.

Introduction: To compare the effects of a preservative-free (PF) ophthalmic solution containing hyaluronic acid (HA) 0.4% and taurine (TAU) 0.5% with those of a PF ophthalmic solution containing HA 0.2% on ocular surface signs, symptoms, and morphological parameters in glaucoma patients under multiple long-term topical hypotensive therapy., Methods: Eligible patients underwent evaluation of ocular surface parameters by ocular surface disease index (OSDI) and glaucoma symptom scale (GSS) questionnaires, breakup time test (BUT), Schirmer I test, corneal and conjunctival staining (Oxford scale), and conjunctival in vivo confocal microscopy (Heidelberg Retina Tomograph 3, Heidelberg Engineering GmbH, Heidelberg, Germany). After the baseline visit, patients were randomized to use a PF ophthalmic solution containing HA 0.4% and TAU 0.5%, QID, in both eyes (group 1) or to use a PF ophthalmic solution containing HA 0.2%, QID (group 2) in addition to the ongoing preserved hypotensive treatment. Follow-up visits were scheduled at 30 and 90 days., Results: Thirty-nine eyes of 39 glaucoma patients were included in the study. At baseline, results of study tests of both groups were similar. After 90 days in group 1 the BUT (p = 0.01), the Oxford score (p = 0.03), the conjunctival goblet cells (CGC) density (p = 0.0005) ,and the two questionnaires score significantly improved (OSDI, p = 0.003; GSS, p = 0.003) compared to baseline values, while in group 2 all these parameters did not differ from baseline (BUT, p = 0.39; Oxford score, p = 0.54; CGC density, p = 0.33, OSDI p = 0.65, GSS, p = 0.25). The BUT and the CGC density were statistically different between groups both at 30 and 90 days (p = 0.04 and p = 0.04, respectively). The Schirmer I test did not statistically change after 90 days in both groups., Conclusions: The PF ophthalmic solution with HA 0.4% and TAU 0.5% seems to improve CGC density and reduce signs and symptoms of dry eye in glaucoma patients under long-term multiple preserved hypotensive therapy., Trial Registration: ClinicalTrials.gov identifier, NCT03480295.

Purpose: To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery., Patients and Methods: Children with primary pediatric glaucoma having postsurgical untreated intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure. The present article reports the 1-year analysis results., Results: A total of 35 patients (57 eyes) were analyzed. The mean age was 4.0 years (SD, 3.8). In total, 51 eyes were included in the efficacy analysis. In total, 43 eyes (84.3%; 95% confidence interval, 74.3-94.3) were considered responders: 29 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to the age at the time of surgery. IOP reduction was 8.7 mm Hg (SD, 2.2) for latanoprost, 7.5 mm Hg (SD, 1.4) for the latanoprost/dorzolamide combination, and 8.7 mm Hg (SD, 2.1) for the dorzolamide monotherapy. Only mild or moderate local adverse events were noted. None of the patients was withdrawn due to adverse events., Conclusion: Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children postsurgery. Nonresponders were mainly patients with early presentation of the disease.

Introduction: The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD)., Methods: Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period., Results: Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001)., Conclusions: In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy., Trial Registration: ClinicalTrials.gov (NCT02802137)., Funding: Santen.

Introduction: To investigate the efficacy of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery., Methods: Single arm, prospective, interventional multicenter study. Primary pediatric glaucoma patients younger than 13 years after a single surgical procedure with IOP between 22 and 26 mmHg were considered eligible. At baseline, patients were allocated to latanoprost monotherapy once daily. Depending on intraocular pressure (IOP) reduction at first visit, the patients were allocated to one of three groups: continuation of latanoprost monotherapy, addition of dorzolamide twice daily, or switch to dorzolamide three times daily. The same approach for allocation in medication groups was used in all subsequent visits. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered non-responders and withdrawn. Study treatment and patient follow-up will continue for 3 years or until treatment failure. The primary endpoint is the percentage of responders. Secondary endpoints are time to treatment failure and frequency of adverse events., Results: A total of 37 patients (69 eyes) were enrolled. The mean age was 4.0 ± 3.8 years, the female/male ratio was 1/1.7, and the majority of patients were Caucasian. Eighty percent of patients had bilateral glaucoma. Goniotomy was the most frequently performed surgery (38.6%), followed by trabeculotomy (22.8%), trabeculectomy (21.1%), and trabeculectomy plus trabeculotomy (17.5%). The baseline IOP was 23.6 ± 1.5 mmHg., Conclusion: The study population is representative of patients frequently encountered after the first surgery for primary pediatric glaucoma. The study will produce evidence on the medium-term efficacy of a defined pharmacological approach.

Purpose: The aim of the study was to evaluate the long-term 24-hour intraocular pressure (IOP) efficacy of travoprost monotherapy in primary open-angle glaucoma patients., Patients and Methods: A total of 36 previously untreated primary open-angle glaucoma patients were enrolled in this 5-year study. Patients underwent an untreated 24-hour IOP evaluation. Subsequently all patients were assigned to topical therapy with travoprost 0.004% eye-drops preserved with benzalkonium chloride (Travatan, Alcon Laboratories Inc., Fort Worth, TX) administered once in the evening (8:00 PM) in both eyes. All patients were then scheduled for a 24-hour IOP assessment approximately 12 months after the baseline visit. This schedule of follow-up was maintained for the whole duration of the trial. The predetermined range of target IOP reduction selected in this cohort of patients ranged between 20% and 30%., Results: A total of 34 patients completed all phases of the investigation. The mean survival time was 57.3±2.0 months and the cumulative survival rate was 0.82±0.6 at 60 months. Travoprost reduced the mean 24-hour IOP from 23.4±1.7 mm Hg at baseline to 16.8±2.4 mm Hg (28.4%), 16.8±2.5 mm Hg (28.1%), 16.8±2.4 mm Hg (28.5%), 16.7±2.5 mm Hg (28.6%), and 16.9±2.4 mm Hg (27.8%), respectively at the end of the first, second, third, fourth, and fifth year follow-up. No drug-related serious adverse events were registered during the study., Conclusions: The present study demonstrated the long-term 24-hour efficacy of travoprost for the treatment of primary open-angle glaucoma.

Purpose: To investigate the success (glaucoma control) of latanoprost therapy of primary congenital glaucoma (PCG) and factors affecting the long-term outcome., Methods: Patients with PCG treated with latanoprost were re-examined. At study visit and from clinical charts, we evaluated: intraocular pressure, length of glaucoma control with latanoprost, need of further medication or glaucoma surgery, systemic and topical side effects. Multivariate analysis was used to test factors related to the final outcome of the treatment., Results: Eighty-one eyes of 44 patients with PCG, and 42 eyes of 29 patients with previous glaucoma surgery, had received latanoprost therapy. In the first group, a success (glaucoma control by latanoprost therapy) was found in 24 eyes (29.6%), whereas 57 eyes (70.4%) had received surgery (45 eyes (55.6%) in the first year); among the eyes with previous surgery, a success was found in 12 eyes (28.6%), 13 eyes (31%) required an additional therapy, and 17 eyes (40.5%) had received further glaucoma surgery. No patient discontinued the treatment because of side effects. Factors related to the failure of the latanoprost treatment were: the high score of severity of glaucoma (P=0.014) and low age at PCG presentation (P=0.042)., Conclusions: Long-term treatment with latanoprost is effective in about 30% of the eyes; factors related to failure were severe glaucomatous alterations, and young age at PCG presentation.

Aim: To compare 24 h intraocular pressure (IOP) control obtained with preservative free (PF) tafluprost 0.0015% versus branded preservative containing latanoprost 0.005% administered as first choice monotherapy in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT)., Methods: This prospective, observer-masked, crossover study included consecutive newly diagnosed patients with POAG or OHT, and baseline IOP between 24 and 33 mm Hg. Qualifying patients underwent baseline untreated 24 h IOP monitoring in habitual positions, with Goldmann tonometry at times 10:00, 14:00, 18:00 and 22:00, and Perkins supine tonometry at times 02:00 and 06:00. They were then randomised to either latanoprost or tafluprost, administered in the evening, for 3 months and then switched to the opposite therapy for another 3 months. 24 h monitoring was repeated at the end of each treatment period., Results: 38 patients completed the study. Mean untreated 24 h IOP (24.9 mm Hg) was significantly reduced with both prostaglandins (p<0.001). Tafluprost demonstrated similar mean 24 h efficacy compared with latanoprost (17.8 vs 17.7 mm Hg; p=0.417). Latanoprost demonstrated significantly better 24 h trough IOP (15.9 vs 16.3 mm Hg; p=0.041) whereas tafluprost provided significantly lower 24 h IOP fluctuation (3.2 vs 3.8 mm Hg; p=0.008). No significant difference existed between the two prostaglandins for any adverse event., Conclusions: PF tafluprost achieved similar 24 h IOP reduction to branded latanoprost. The current study highlights the importance of complete assessment of efficacy over 24 h., Clinical Trials Registration: NCT01162603.

Purpose: To investigate the circadian and blood pressure (BP) reduction obtained with timolol maleate 0.5% solution administered twice daily versus timolol 0.1% in gel-forming carbomer administered in the morning in patients with primary open-angle glaucoma (POAG)., Methods: This investigator-masked, crossover study prospectively enrolled naive POAG patients not receiving systemic cardiovascular medications. Following a baseline evaluation, they were randomized to receive a timolol 0.5% solution or timolol 0.1% hydrogel for 2 months and then switched to the alternative medication for a further 2 months. Intraocular pressure (IOP) phasing (sitting Goldmann tonometry at 10 am, 2 pm, 6 pm, and 10 pm and supine Perkins tonometry at 2 am and 6 am) and ambulatory home BP monitoring were measured at baseline and after each treatment period., Results: On the basis of a prospective sample size estimate, 28 patients were analyzed. Mean 24-hour IOP decreased from 23.1 ± 0.7 mm Hg at baseline to 18.9 ± 0.6 mm Hg after timolol 0.5% and 18.9 ± 0.8 mm Hg after timolol 0.1% hydrogel (P < .001); both formulations also significantly decreased diurnal, nocturnal, and individual time point IOP in a statistically similar manner. Systolic and diastolic BP remained generally unaffected. The calculated diastolic ocular perfusion pressure was either unaffected or tended to increase with either medication., Conclusion: Both timolol formulations show similar and significant circadian efficacy and have minimal effects on BP and calculated diastolic ocular perfusion pressure.

Introduction: Glaucoma is the second leading cause of blindness globally, representing a significant public health concern. More than 60 million people are affected by glaucoma worldwide; as this population ages, the number is expected to increase. Glaucoma is a collection of heterogeneous diseases sharing common clinical characteristics. The goal of treatment is to prevent significant visual dysfunction through reduction of intraocular pressure (IOP)., Areas Covered: This is a review of the current literature about combination therapeutic regimens for the reduction of IOP, focusing on the risk : benefit profile of a fixed-combination therapy using travoprost and timolol., Expert Opinion: Since the debut of prostaglandin analogues in the 1990s, only modest innovation has occurred in glaucoma pharmacology. A growing body of research has established that the preservative benzalkonium chloride (BAK) might not be the benign contributor expected of excipient ingredients. Thus, BAK-free treatments were developed, with the goal of IOP reduction without furthering ocular surface disease symptoms. The BAK-free travoprost/timolol combination represents an important addition to glaucoma medication options and may fill an unmet need in this therapeutic arena.

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.

Purpose: To determine the direct costs of therapy over 5 years of a European monotherapy cohort begun on a prostaglandin (PTG) versus timolol in patients with primary open-angle glaucoma or ocular hypertension., Methods: A retrospective, multicenter, active-controlled, observational study. Data were abstracted for European patients treated as initial monotherapy in 1996 or afterward, with 5 years of available records., Results: This study included 271 patients (166 on a PTG and 105 on timolol at baseline). The average cost/month/patient over 5 years was $45.47±12.61 for PTG and $31.50±15.47 for timolol (P<0.001, based on German prices). After 5 years, although there was no difference in number of glaucoma medicines prescribed between groups (1.0 PTGs and 1.1 timolol, P=0.41), the timolol group demonstrated a higher intraocular pressure (17.7±2.9 vs. 16.5±3.0 mm Hg, P<0.001), more medication changes (P=0.01), greater incidence of glaucomatous progression (P=0.04), and less patients persistent on original monotherapy (P<0.001) than the PTG cohort., Conclusions: Patients originally on timolol monotherapy have a lower cost of care over 5 years than those started on a PTG. However, timolol patients during follow-up may demonstrate a higher intraocular pressure, more progression, more medication changes, and lower persistency of the original monotherapy.

Purpose: To evaluate the effect of the timolol-dorzolamide fixed combination (TDFC) and latanoprost 0.005% on 24-hour intraocular pressure (IOP), systolic (SBP) and diastolic (DBP) blood pressure, and diastolic ocular perfusion pressure (DOPP) in patients with primary open-angle glaucoma (POAG)., Methods: This was an institutional, randomized clinical trial. After a 24-hour assessment without treatment, 27 previously untreated patients with POAG were randomized to 6 weeks' treatment with twice-daily TDFC (8 AM and 8 PM) followed by once-daily latanoprost 0.005% (8 PM), or vice versa. One eye was analyzed per patient. The mean values of IOP, DBP, SBP, and DOPP (difference between DBP and IOP) were recorded at each time point, and the 24-hour data are the mean values of each patient's measurements over the 24-hour period. The differences between the values of the first treatment period and the baseline and the second treatment period and washout were calculated and analyzed by means of an analysis of variance model that tested the effects of sequence and treatment., Results: Both treatments significantly reduced 24-hour IOP (P < 0.0001), but TDFC led to lower 24-hour pressure (mean +/- SD: 15.4 +/- 1.9 vs. 16.7 +/- 1.7 mm Hg; P = 0.004). Latanoprost did not lead to any significant reduction in mean 24-hour SBP and DBP (SBP: P = 0.952; DBP: P = 0.831), but TDFC did (SBP and DBP: P < 0.0001). Both treatments significantly increased 24-hour DOPP (P < 0.0001), with no difference between the two medications (P = 0.09)., Conclusions: In previously untreated patients with POAG, TDFC, and latanoprost equally enhanced 24-hour DOPP: the former by counteracting the decrease in DBP with a substantial reduction in IOP and the latter by not affecting DBP and significantly reducing IOP. (isrctn.org number, ISRCTN67123277.).

Aim: To evaluate 24 h intraocular pressure (IOP) and blood pressure (BP) with bimatoprost or latanoprost in patients with normal-tension glaucoma., Design: Prospective, randomised, crossover, active-controlled, observer-masked study., Methods: After a 6-week medicine-free period, we randomised patients to either latanoprost or bimatoprost for 8 weeks and then to the opposite medicine for 8 weeks. At baseline, and at the end of each treatment period, we evaluated IOP and BP at 08:00 and then every 2 h over the 24 h day. Diastolic ocular perfusion pressure (DOPP) was calculated from the above parameters., Results: Forty completed patients had a 24 h untreated baseline IOP of 15.5 (2.3) mm Hg, and a DOPP of 59.2 (6.1) mm Hg. Both treatments lowered IOP at each time point (p<0.006), and over the 24 h curve (p<0.001, both medicines 13.1 mm Hg, 16% decrease). No difference existed between treatments in absolute IOP, at each time point, and over the 24 h curve (p>or=0.26). Additionally, no differences were found between treated 24 h systolic (p>or=0.29) and diastolic BP (p>or=0.12). The mean 24 h DOPP for latanoprost was increased from baseline (3%, p = 0.031) but not for bimatoprost (2%, p = 0.21). However, no difference in DOPP existed between treatments at any time point or over the 24 h curve (p>or=0.17). No difference was observed between treatments for any adverse event (p>0.05)., Conclusions: In patients with normal-tension glaucoma, both bimatoprost and latanoprost reduce the 24 h intraocular pressure from untreated baseline to a similar extent. Latanoprost is associated with slightly improved ocular diastolic perfusion pressure over 24 h but similar absolute perfusion levels to that of bimatoprost.

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.

Purpose: To determine the proportion of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH) who do not respond to latanoprost therapy., Methods: Three hundred forty consecutive patients with a new diagnosis of POAG or OH, or previously treated only with a beta-blocker and after an appropriate washout period, were treated with latanoprost for 1 month and then divided into three groups on the basis of the reduction in intraocular pressure (IOP): nonresponders (<15%), responders (> or =15% but <30%), and high-responders (> or =30%). To give a wide picture of the drug effect, eight different cut-off points were used to present data on distribution of mean IOP reductions. Only the nonresponders entered a randomized cross-over study investigating the efficacy of timolol, brimonidine, and pilocarpine., Results: IOP at baseline and after 1 month's latanoprost therapy was respectively 24.1+/-1.4 and 16.9+/-2.4 mm Hg, with a mean reduction in IOP of 29.9+/-4.2%. Nonresponders accounted for 4.1% of the patients and high-responders for 41.2%. The nonresponders showed a statistically significant reduction in IOP after brimonidine treatment (P=0.05), whereas the reduction after timolol and pilocarpine treatment was clinically relevant but not statistically significant., Conclusions: This multicenter prospective study found only 14 of 340 nonresponders to latanoprost. In the cross-over trial on nonresponders, IOP reduction reached statistical significance only after brimonidine, but their small number reduced its statistical power.