Design, Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and H2S Donors.

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H2S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H2S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H2S donors. The H2S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H2S by antiglaucoma H2S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds.

Application of topical betaxolol to cure superficial infantile hemangioma: A pilot study.

BACKGROUND: Beta-blockers have gradually become an attractive option for the treatment of infantile hemangiomas. Topical application is preferred to oral administration because of their potential systemic adverse effects. The aim of this study is to investigate the effect of betaxolol in treating superficial infantile hemangioma. METHODS: Seventy-four infants admitted to the First Affiliated Hospital of Xinjiang Medical University from 2018 to 2019 were observed and recorded. Variables such as color, size, tension, and thickness were recorded monthly and evaluated using visual analog scales. Multi-factor analysis of variance with repeated measurements and the non-parametric Kruskal-Wallis H test were used to compare clinical effectiveness across the different groups. RESULTS: After 6 months of treatment, 33.78% (25/74) showed excellent results, 55.41% (41/74) had good responses, 8.11% (6/74) had moderate responses, and 2.70% (2/74) had poor responses. Local discomfort and systemic complications were not found. There was no significant difference in gender and location of occurrence among groups (p > 0.05), and the effect of topical application of betaxolol was optimum in the children aged 0-3 months (p = 0.002). None of three age groups had statistically significant difference in heart rate and blood pressure after accepting treatment (1 month, p = 0.618; 4 months, p = 0.138; 6 months, p = 0.757). CONCLUSIONS: Our study showed that topical administration of betaxolol was effective and well tolerated for superficial infantile hemangiomas, particularly in the early proliferative stage. However, its safety and efficacy need further research.

The prophylactic effect of betaxolol 0.5% versus brimonidine 0.2% on IOP elevation after Nd:YAG laser posterior capsulotomy.

CLINICAL RELEVANCE: Posterior capsule opacification is a common late complication of cataract surgery. Posterior capsule opening with Nd:YAG laser, which is the standard treatment, may cause transient elevation of intraocular pressure (IOP). BACKGROUND: To evaluate the efficacy of betaxolol 0.|5% compared to brimonidine 0.2%, in prevention of intraocular pressure increase after Nd:YAG Laser posterior capsulotomy. METHODS: In a double masked randomised clinical trial, 38 eyes from 38 pseudophakic patients over 21 years of age who had significant posterior capsule opacification after phacoemulsification were randomly assigned to receive either betaxolol 0.|5% (18 eyes) or brimonidine 0.|2% (20 eyes) one hour before Nd:YAG Laser posterior capsulotomy.| Exclusion criteria were: glaucoma or history of glaucoma surgery, active uveitis, active ocular infection, pregnancy, unstable cardiovascular condition and severe asthma and lung diseases. Intraocular pressure was measured by Goldmann applanation tonometry, 1 hour before applying the laser and 4 hours after the laser application. RESULTS: There was no statistically significant difference between the two groups regarding the baseline mean IOP and the 4-hour post-laser mean IOP. There was a statistically significant decrease in the 4-hour post-laser mean IOP as compared to the baseline mean IOP in each group. The mean IOP change in the betaxolol group, was -2.39 ± 1.79 mm Hg and in the brimonidine group was -4.25 ± 2.20 mm Hg. The difference was statistically significant (P = 0.007). None of the patients experienced clinically significant IOP increase (≥5 mm Hg) in either group. CONCLUSION: Use of a single topical dose of betaxolol 0.5% and brimonidine 0.2%, 1 hour before laser treatment, can prevent significant acute IOP increase after Nd:YAG laser posterior capsulotomy, and betaxolol may provide a new alternative for prophylactic use.

Beta-Blockers for Pyogenic Granuloma: A Systematic Review of Case Reports, Case Series, and Clinical Trials

Pyogenic granuloma (PG) is an acquired vascular growth on the skin and mucous membranes. Even though PG is a benign tumor, treatment is required due to associated risk of ulceration and bleeding, cosmetic concerns, and the low likelihood of spontaneous regression. Treatment entails excisional surgery, cryotherapy, or electrocautery; recurrence however is a major problem. Beta-blockers became an attractive option for the treatment of vascular growths after it got approved for infantile hemangioma. PG was found to express beta adrenergic receptors, similarly to infantile hemangioma. Several publications have reported the use of oral and topical beta blockers such as timolol, propranolol, and betaxolol for the treatment of PG. In this study, we summarized the literature with regards to the effectiveness of topical beta blockers for the treatment of PG, and discussed all published case reports, case series, and open-label single arm trials. J Drugs Dermatol. 2019;18(10):1006-1010.

Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma.

BACKGROUND: To date, the rapid clearance from ocular surface has been a huge obstacle for using eye drops to treat glaucoma, since it has led to the short preocular residence time and low bioavailability. METHODS: The novel nanoparticles (NPs) were designed for topical ophthalmic controlled drug delivery system through intercalating the BH into the interlayer gallery of Na-montmorillonite (Na+Mt) and then further enchasing chitosan nanoparticles. The resulting nanoparticles had a positive charge (+29±0.18 mV) with an average diameter of 460±0.6 nm. RESULTS: In vitro study of drug release profiles suggested controlled release pattern. The irritation experiment analysis on both human immortalized cornea epithelial cell (iHCEC) and chorioallantoic membrane-trypan blue staining (CAM-TBS) showed good tolerance for ocular tissues. It was interestingly found that the nanoparticles could enter into iHCEC from the result of cellular uptake experiment measured by confocal layer scan microscopy (CLSM). Meanwhile, multilayered iHCEC was used to simulate the barrier of corneal epithelial cells for in vivo preocular retention capacity study, which suggested that BH-Mt/CS NPs could prolong the retention time in comparison with BH solution. The ocular pharmacokinetics studied by microdialysis sampling technique showed that AUC0-t and MRT0-t of BH-Mt/CS NPs were 1.99-fold and 1.75-fold higher than those of BH solution, indicating higher bioavailability. Moreover, the study of blood drug concentration, few researchers have reported, showed that low level drug could enter into blood, suggesting lower systematic side effect. Importantly, pharmacodynamics studies suggested that BH-Mt/CS NPs could make a significant decreased intraocular pressure on glaucomatous rabbits. CONCLUSION: Inspired by these advance of montmorillonite/chitosan nanoparticles, we envision that the BH-Mt/CS NPs will be a potential carrier for BH, opening up the possible applications in glaucoma therapy.

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier.

BACKGROUND: Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. MATERIALS AND METHODS: To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion-solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. RESULTS: Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. CONCLUSION: The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma.

Prevention of perioperative atrial fibrillation with betablockers in coronary surgery: betaxolol versus metoprolol.

In this study, we tried to compare the efficacy and safety of betaxolol vs. metoprolol immediately postoperatively in coronary artery bypass grafting (CABG) patients and to determine whether prophylaxy for atrial fibrillation (AF) with betaxolol could reduce hospitalization and economic costs after cardiac surgery. Our trial was open-label, randomized, multicentric enrolling 1352 coronary surgery patients randomized to receive betaxolol or metoprolol. The primary endpoints were the composites of 30-day mortality, in-hospital AF (safety endpoints), duration of hospitalization and immobilization, quality of life, and the above endpoint plus in-hospital embolic event, bradycardia, gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus safety endpoint). At the end of the study the incidence and probability of early postoperative AF with betaxolol was lower than with metoprolol in coronary surgery (P<0.0001). In the two study groups minor side effects were similar and no major complication was reported (P<0.001). Patient compliance was good and the general condition improved due to shortened hospitalization and immobilization with subsequent improvement in the psychological status, less arrhythmias and lack of significant side effects. In conclusion, because of its efficacy and safety, betaxolol was superior to metoprolol for the prevention of the early postoperative AF in coronary surgery.

Evidence for beta1-adrenergic receptor involvement in amygdalar corticotropin-releasing factor gene expression: implications for cocaine withdrawal.

We previously showed that betaxolol, a selective beta(1)-adrenergic receptor antagonist, administered during early phases of cocaine abstinence, ameliorated withdrawal-induced anxiety and blocked increases in amygdalar beta(1)-adrenergic receptor expression in rats. Here, we report the efficacy of betaxolol in reducing increases in gene expression of amygdalar corticotropin-releasing factor (CRF), a peptide known to be involved in mediating 'anxiety-like' behaviors during initial phases of cocaine abstinence. We also demonstrate attenuation of an amygdalar beta(1)-adrenergic receptor-mediated cell-signaling pathway following this treatment. Male rats were administered betaxolol at 24 and 44 h following chronic cocaine administration. Animals were euthanized at the 48-h time point and the amygdala was microdissected and processed for quantitative reverse transcriptase-polymerase chain reaction and/or western blot analysis. Results showed that betaxolol treatment during early cocaine withdrawal attenuated increases in amygdalar CRF gene expression and cyclic adenosine monophosphate-dependent protein kinase regulatory and catalytic subunit (nuclear fraction) protein expression. Our data also reveal that beta(1)-adrenergic receptors are on amygdalar neurons, which are immunoreactive for CRF. The present findings suggest that the efficacy of betaxolol treatment on cocaine withdrawal-induced anxiety may be related, in part, to its effect on amygdalar beta(1)-adrenergic receptor, modulation of its downstream cell-signaling elements and CRF gene expression.

Disc hemorrhages and treatment in the early manifest glaucoma trial.

PURPOSE: To evaluate the effect of intraocular pressure (IOP)-reducing treatment on the development of disc hemorrhages in patients with glaucoma. DESIGN: Prospective cohort study of patients in the Early Manifest Glaucoma Trial, followed up to 11 years (median = 8 years). PARTICIPANTS: Patients with newly detected glaucoma randomized to argon laser trabeculoplasty plus betaxolol (n = 129) or no initial treatment (n = 126), followed with tonometry, perimetry, and ophthalmoscopy every 3 months, and fundus photography every 6 months. METHODS: Logistic regression expressed as odds ratios (OR) and 95% confidence intervals (CIs), analysis of variance, and Cox time-dependent models, expressed as hazard ratios (HRs) and CIs. MAIN OUTCOME MEASURES: Presence (yes/no) and frequency of disc hemorrhages. RESULTS: Disc hemorrhages were identified in approximately 55% of all patients, whether by ophthalmoscopy or review of photographs. In analyses including data up to the time of progression, disc hemorrhages were equally common among treated and control patients: 51.2% versus 45.2%, respectively (P = 0.34), based on ophthalmoscopy, and 50.4% versus 44.4%, respectively (P = 0.34), based on photographs. Gender was the only factor related to the presence of disc hemorrhages detected by both ophthalmoscopy (OR = 0.48; CI, 0.26-0.88; P = 0.022) and photographs (OR = 0.64; CI, 0.38-1.09; P = 0.099) for male patients. The frequency of disc hemorrhages over time did not differ between treated and control patients: 8.4% versus 8.5%, respectively (P = 0.93), based on ophthalmoscopy, and 12.4% versus 11.2%, respectively (P = 0.36), based on photographs. Disc hemorrhages were significantly associated with time to progression (HR = 1.02; CI, 1.01-1.04), and there was no evidence of interaction between treatment group and disc hemorrhages. CONCLUSIONS: IOP-reducing treatment was unrelated to the presence or frequency of disc hemorrhages. The results may suggest that disc hemorrhages cannot be considered an indication of insufficient IOP-lowering treatment, and that glaucoma progression in eyes with disc hemorrhages cannot be totally halted by IOP reduction. The results also suggest that disc hemorrhages do not occur in all patients with glaucoma.

Benefits of a beta-blocker for intractable hemolysis due to paraprosthetic leakage.

We describe a 58-year-old man who was successfully treated with a beta-adrenergic receptor blocking agent for intractable hemolysis due to paraprosthetic leakage. After replacement of a mitral prosthetic valve with another mechanical valve, the patient suffered intractable intravascular hemolysis resulting from recurrent paraprosthetic leakage. With oral administration of a beta-adrenergic receptor blocker, betaxolol hydrochloride, for 3 months, the hemoglobin value increased from 9.7 g x dL(-1) to 12.4 g x dL(-1), although glutamic oxaloacetic transaminase and lactic dehydrogenase values remained elevated.

[Early Manifest Glaucoma Trial update 2004]. / "Early Manifest Glaucoma Trial" (EMGT) Update 2004.

Elevated intraocular pressure (IOP) represents one of the most important risk factors for developing glaucomatous optic neuropathy. The "Early Manifest Glaucoma Trial" (EMGT) was initiated to answer the question of how immediate IOD-lowering therapy affects the progression of early manifest glaucoma and which clinically relevant factors are important. The study compares 129 patients undergoing treatment with 126 patients receiving no IOP-lowering therapy. IOP remained virtually constant in the untreated group, while a reduction of 25% was achieved in the treatment group. The results of the EMGT indicate that glaucoma progression is influenced by higher initial IOP, pseudoexfoliation or bilateral glaucoma, poorer MD value, higher age, and marginal papillary hemorrhage. No clear conclusions can be drawn regarding the significance of cardiovascular risk factors.

Factors for progression and glaucoma treatment: the Early Manifest Glaucoma Trial.

PURPOSE OF REVIEW: This review summarizes factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of treatment. EMGT randomized patients with early glaucoma either to argon laser trabeculoplasty plus betaxolol (n = 129) or to no immediate treatment (n = 126) and followed them every 3 months. RECENT FINDINGS: Treated patients had delayed progression, as compared with controls. In Cox regression, EMGT treatment halved the risk of progression (hazard ratio = 0.50; 95% confidence interval: 0.35, 0.71). Risk decreased about 10% with each millimeter mercury of intraocular pressure (IOP) reduction from baseline; the higher (or lower) the IOP at follow-up, the higher (or lower) the risk. Baseline factors increasing progression were higher IOP, exfoliation, bilateral disease, worse perimetric mean deviation and older age; frequent disc hemorrhages at follow-up also increased risk. SUMMARY: EMGT treatment reduced progression risk in half, demonstrating the value of IOP lowering in early glaucoma. Age and indicators of disease severity also predicted progression.

Beneficial effects of betaxolol, a selective antagonist of beta-1 adrenoceptors, on exercise-induced myocardial ischemia in patients with coronary vasospasm.

Although beta-blockers can not be used for the treatment of vasospastic angina, the effect of beta-blockers with vasorelaxant property on coronary vasospasm remains uncertain. In this study, we evaluated the effect of betaxolol, a new beta-blocker with calcium antagonistic property, as an additional therapy on vasospastic angina (VSA) with anginal attacks on effort. We enrolled 12 patients with VSA and anginal attacks with ST segment depression during exercise stress test. All patients received 1.25-5 mg of betaxolol for 3 months. Treadmill exercise stress test and adenosine triphosphate stress thallium-201 myocardial scintigraphy were performed before and 3 months after the onset of the betaxolol treatment. The other drugs including calcium antagonists, nitrates and nicorandil were continued. No patients experienced the exacerbation of angina during the betaxolol treatment. Exercise time to chest pain (317.5+/-72.1-454.2+/-75.5 s, P<0.01) and maximal ST segment depression (1.67+/-0.67-1.16+/-0.46 mm, P<0.01) obtained by exercise stress test, the defect score (8.6+/-2.7-5.3+/-2.1, P<0.01), the extent score (14.8+/-5.8-8.8+/-4.6%, P<0.01), the severity score (17.5+/-7.3-11.3+/-5.2, P<0.01) and washout rate (31.4+/-5.6-37.6+/-5.0%, P<0.01) obtained by the scintigraphy were improved by betaxolol. Our results suggest that betaxolol increases regional myocardial blood flow and improves exercise capacity in patients with VSA. Betaxolol may become a drug for a new potential therapy for VSA.

Randomized clinical trial of topical betaxolol for persistent macular edema after vitrectomy and epiretinal membrane removal.

PURPOSE: To report the efficacy and safety of topical betaxolol for treatment of persistent macular edema. DESIGN: Randomized clinical trial. METHODS: Thirty-seven eyes (37 patients) with best-corrected visual acuity between 20/200 and 20/50 and macular edema that remained for 3 months after vitrectomy and removal of epiretinal membrane were prospectively, randomly assigned to receive betaxolol or placebo. Nineteen eyes of 19 patients received betaxolol twice daily, and 18 eyes of 18 patients received placebo as a randomized comparison group. The patients were followed up for 6 months. This study evaluated the effect of betaxolol on best-corrected visual acuity and area of macular edema, which was digitally measured on serial fluorescein angiogram. Calculations of mean best-corrected visual acuity were based on logarithm of the minimal angle of resolution (logMAR). To assess changes in area of edema, the initial (pretreatment) size of the edema was set to 100%, and all posttreatment measurements were normalized relative to the initial size. RESULTS: Mean best-corrected visual acuity at baseline was 0.216 (20 of 92.6) and 0.244 (20 of 82.0) in the treatment and control group, respectively. Mean area of macular edema was 2.271 +/- 1.629 mm(2) and 2.273 +/- 1.209 mm(2) in the treatment and control group; there was no significant difference. The visual acuity at 6 months after the start of the follow-up was 0.471 (20 of 42.5) in the treatment group and 0.236 (20 of 84.7) in the control group. Mean changes in logMAR of visual acuity for 3- and 6-month follow-up were -0.282 +/- 0.191 and -0.337 +/- 0.197 in the treatment group, and -0.016 +/- 0.186 and +0.015 +/- 0.267 in the control group; a significant difference was found (P <.0001; P <.0001). Areas of macular edema at 6 months after the start of the follow-up were 1.492 +/- 1.357 mm(2) in the treatment group and 2.125 +/- 1.434 mm(2)in the control group. Mean change in area of the edema for 6 months were 76.5% +/- 24.1% and 63.4% +/- 28.3% in the treatment group and 92.9% +/- 15.4% and 87.4% +/- 25.6% in the control group; treated patients showed a significantly larger reduction than untreated patients at each examination (P =.0193; P =.0102). No complication associated with treatment or placebo was found. CONCLUSIONS: Topical betaxolol appeared to have a favorable treatment effect in eyes with macular edema that remained after vitrectomy and removal of epiretinal membrane. Further investigation of more cases and longer follow-up are needed.

Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial.

OBJECTIVE: To assess factors for progression in the Early Manifest Glaucoma Trial (EMGT), including the effect of EMGT treatment. SETTING/PARTICIPANTS: Two hundred fifty-five open-angle glaucoma patients randomized to argon laser trabeculoplasty plus topical betaxolol or no immediate treatment (129 treated; 126 controls) and followed up every 3 months. METHODS: Progression was determined by perimetric and photographic optic disc criteria. Patient-based risk of progression was evaluated using Cox proportional hazard regression models and was expressed as hazard ratios (HR) with 95% confidence intervals (95% CI). RESULTS: After 6 years, 53% of patients progressed. In multivariate analyses, progression risk was halved by treatment (HR = 0.50; 95% CI, 0.35-0.71). Predictive baseline factors were higher intraocular pressure (IOP) (ie, the higher the baseline IOP, the higher the risk), exfoliation, and having both eyes eligible (each of the latter 2 factors doubled the risk), as well as worse mean deviation and older age. Progression risk decreased by about 10% with each millimeter of mercury of IOP reduction from baseline to the first follow-up visit (HR = 0.90 per millimeter of mercury decrease; 95% CI, 0.86-0.94). The first IOP at that visit (3 months' follow-up) was also related to progression (HR = 1.11 per millimeter of mercury higher; 95% CI, 1.06-1.17), as was the mean IOP at follow-up (HR = 1.13 per millimeter of mercury higher; 95% CI, 1.07-1.19). The percent of patient follow-up visits with disc hemorrhages was also related to progression (HR = 1.02 per percent higher; 95% CI, 1.01-1.03). No other factors were identified. CONCLUSIONS: Patients treated in the EMGT had half of the progression risk of control patients. The magnitude of initial IOP reduction was a major factor influencing outcome. Progression was also increased with higher baseline IOP, exfoliation, bilateral disease, worse mean deviation, and older age, as well as frequent disc hemorrhages during follow-up. Each higher (or lower) millimeter of mercury of IOP on follow-up was associated with an approximate 10% increased (or decreased) risk of progression.

Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial.

OBJECTIVE: To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma. DESIGN: Randomized clinical trial. PARTICIPANTS: Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, -4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible. INTERVENTIONS: Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter. MAIN OUTCOME MEASURES: Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as the same 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings. RESULTS: After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment (P =.002). CONCLUSIONS: The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.

Effect of treatment by medicine or surgery on intraocular pressure and pulsatile ocular blood flow in normal-pressure glaucoma.

PURPOSE: To study the effect of trabeculectomy and monotherapy with topical betaxolol, brimonidine and latanoprost on intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) in patients with normal-pressure glaucoma (NPG). METHODS: In this retrospective study NPG patients attending the glaucoma research unit at Moorfields Eye Hospital were reviewed. Patients treated by surgery or topical medication (betaxolol, brimonidine or latanoprost) who had pre- and post-treatment IOP and POBF measurements were studied. For those patients who were having treatment to both eyes, one eye was selected at random for analysis. RESULTS: A total of 147 patients were reviewed. Forty-three eyes were receiving betaxolol 0.5%, 58 eyes latanoprost 0.005%, 23 eyes brimonidine 0.2% and 23 eyes had undergone trabeculectomy surgery. There were more female than male patients in all four groups, and the groups were similar with regards age. Pre-treatment IOP and POBF values were similar among the groups ( P=0.27, P=0.08 respectively). Post-treatment IOP values tended to be lower than pre-treatment values for all four groups. All groups had an increased POBF except for betaxolol, where POBF decreased. CONCLUSION: Patients treated by trabeculectomy and those receiving topical latanoprost and brimonidine had lower IOP and higher POBF following treatment. The betaxolol-treated group, despite a slight decrease in IOP, had a decreased POBF. Lowering IOP by treatment may not necessarily be associated with an increase in POBF.

Levobetaxolol-induced Up-regulation of retinal bFGF and CNTF mRNAs and preservation of retinal function against a photic-induced retinopathy.

Betaxolol (racemic), a beta-adrenoceptor antagonist that is used to lower intraocular pressure in the treatment of glaucoma, has been shown to protect inner retina cells from various insults. To determine if such protection could be afforded to retinal photoreceptors and retinal pigment epithelial cells (RPE), levobetaxolol (S-betaxolol) was evaluated in a photic-induced retinopathy model. Rats were dosed (IP) with vehicle or levobetaxolol (10 and 20 mg kg(-1)) 48, 24 and 0 hr prior to exposure for 6 hr to fluorescent blue light. The electroretinogram (ERG) and retinal morphology were assessed after a 3 week recovery period. Evaluation of the ERG demonstrated significant protection of retinal function in levobetaxolol (20 mg kg(-1))-dosed rats compared to vehicle-dosed rats. Similarly, the RPE and outer nuclear layer were significantly thicker in levobetaxolol (20 mg kg(-1))-dosed rats compared to vehicle-dosed rats. To elucidate potential mechanism(s) of the neuroprotective activity of levobetaxolol, bFGF and CNTF mRNA levels in normal rat retinas were evaluated 12 hr after a single i.p. injection. Northern blot analysis of levobetaxolol treated retinas demonstrated a 10-fold up-regulation of bFGF and a two-fold up-regulation of CNTF mRNA levels, trophic factors that have been shown to inhibit retinal degeneration in a number of species. These studies suggest that levobetaxolol can be used as a novel neuroprotective agent to ameliorate retinopathy.