Topical flunarizine reduces IOP and protects the retina against ischemia-excitotoxicity

PURPOSE: To determine whether topical application of flunarizine reduces intraocular pressure (IOP) and acts as a retinal neuroprotectant and to compare the effectiveness of flunarizine with betaxolol and nifedipine at reducing the influx of calcium and sodium. METHODS: Ischemia was delivered to the rabbit retina by raising the IOP. After 3 days, a flash electroretinogram (ERG) was recorded, and the retina processed for the localization of certain antigens. In the rat, N-methyl-D-aspartate (NMDA) was injected intravitreally, and 8 days later, the retinas were analyzed for the localization of Thy-1 or the relative amounts of mRNAs for antigens located to ganglion cells or photoreceptors. Rats and rabbits received topical flunarizine or vehicle before and after ischemia or NMDA. IOP was measured in rabbits after a single topical application of 2% flunarizine. Studies were conducted on isolated rat retinas, cortical cultures, and brain synaptosomes to compare the effectiveness of flunarizine with nifedipine and betaxolol at reducing the influx of calcium or sodium. RESULTS: Changes in rabbit retinal choline acetyltransferase and parvalbumin immunoreactivities and the b-wave of the ERG caused by ischemia-reperfusion were blunted by topical treatment with flunarizine. Similarly, NMDA induced reductions in Thy-1 immunoreactivity and mRNA for rat ganglion cell antigens (Thy-1 and neurofilament light form) were counteracted by topical application of flunarizine. Topical application of 2% flunarizine significantly lowered the IOP in rabbits over a period of 5 hours. Flunarizine was more effective than betaxolol and much stronger than nifedipine at attenuating veratridine-induced influx of sodium into synaptosomes. Nifedipine, flunarizine, and betaxolol all reduced the NMDA-induced influx of calcium into the isolated retina or cortical neurons, but betaxolol was the least effective. CONCLUSIONS: Topically applied flunarizine reduces IOP and attenuates injury to the whole of the retina, including the ganglion cells. The neuroprotective action of flunarizine is to reduce the influx of calcium and sodium into stressed neurons. The potent effect of flunarizine on sodium influx would be particularly protective to axons.     

Influence of topical betaxolol and timolol on visual field in Japanese open-angle glaucoma patients

PURPOSE: To assess the effects of topical betaxolol and timolol on the visual field in Japanese open-angle glaucoma (OAG) patients. METHODS: This study was a multicenter, 2-year, prospective, randomized and double-masked study. Tests using the Humphrey 30-2 perimeter program were conducted every 6 months and the data of 95 patients were analyzed using regression analysis. Estimated regression coefficients for mean deviation (MD), corrected pattern standard deviation (CPSD), and total deviation (TD) values clustered into 15 sectors were obtained for each treatment group. RESULTS: Estimated slopes (dB/year) for MD and CPSD showed no significant difference from zero in either group. However, in the betaxolol group, estimated slopes (dB/year) for two adjacent sectors in the inferior arcuate area were significantly positive (P =.0135,.0116) while in the timolol group, no significant difference from zero was seen in any of the sectors. IOP changes from baseline in the timolol group were greater than in the betaxolol group, although no statistical significance was seen at any of the examination times. CONCLUSION: MD and CPSD showed no significant change in either group. In the betaxolol group, however, a significant trend in improvement of visual field performance was seen in the inferior arcuate subfield. Timolol reduced IOP more effectively than betaxolol in OAG patients.     

Correlation of asymmetric glaucomatous visual field damage and water-drinking test response

PURPOSE: To determine whether there is a correlation between asymmetric glaucomatous visual field (VF) damage and water-drinking test (WDT) response. METHODS: A retrospective analysis was conducted of VF and WDT data from 101 patients with glaucoma in clinical therapy, who were receiving treatment with the same topical medication in both eyes, and asymmetric VF defect. Eyes were classified according to mean deviation (MD) into "better" and contralateral "worse" eyes. Maximum mean difference in basal IOP was 2 mm Hg between both eyes. The peak IOP and fluctuation obtained with the WDT were compared between both groups. For the statistical analysis, the Tukey post hoc multiple comparison test and paired t-test were used. RESULTS: Better and contralateral worse eyes presented mean MDs of -4.6 +/- 5.3 and -9.0 +/- 7.4 dB, respectively (P < 0.001). Mean basal IOPs were 13.9 +/- 3.3 and 13.9 +/- 3.1 mm Hg, respectively (P = 0.67). Mean maximum IOPs after water ingestion were 16.5 +/- 3.8 mm Hg in the group with less severe VF defect and 17.2 +/- 4.1 mm Hg in the contralateral group with worse visual fields (P < 0.001). Mean fluctuation (maximum IOP - minimum IOP after water ingestion) was 3.6 +/- 1.8 and 4.4 +/- 2.2 mm Hg (P < 0.001), respectively. CONCLUSION: Eyes with worse MDs presented higher IOP peaks and fluctuation after water ingestion. This study demonstrates a lower capacity of eyes with worse glaucomatous lesion to respond to a stimulus that leads to a transitory elevation of IOP.     

Influence of betaxolol and timolol on the venous tone in glaucoma patients

The aim of this study was the assessment of physiological venous reflexes in 40 glaucoma patients treated with topically applied timolol maleate 0.50% and betaxolol HCL 0.50%. They were divided into two groups of twenty each; one group being given timolol and the other betaxolol. The assessment of the venous tone was performed by testing venous reflexes. We found no statistically significant difference between timolol and betaxolol; however, when the influence of circulating catecholamines and the other vasoactive substances was excluded by suprasphygmatic insufflation of a pediatric cuff, a significant difference was found in the Valsalva's maneuver (125.5 ± 8.1 vs 85.0 ± 34.3 venoconstrictive units VCUs, p = 0.03).The IOP was significantly decreased in both treatment group, although the pressure reduction effect was more pronounced in the timolol group.Our study suggests that timolol and betaxolol have a slightly different mode of action on the venous side of circulation under topical medications. It is possible that the use of betaxolol topically may reducea systemic venoconstriction.     

Comparison of Clinical Characteristics and Progression Rates of Bilaterally and Unilaterally Progressing Glaucoma

Purpose

To compare the clinical characteristics of unilaterally progressing glaucoma (UPG) and simultaneously bilaterally progressing glaucoma (BPG) in medically treated cases.

Methods

Primary open angle glaucoma patients were classified as having UPG or BPG according to an assessment of optic disc and retinal nerve fiber layer photographs and visual field analysis. Risk factors including the presence of systemic diseases (hypertension, diabetes, cerebrovascular accident, migraine, and dyslipidema) were compared between the UPG and BPG groups. Baseline characteristics and pre- and post-treatment intraocular pressure (IOP) were compared between the progressing eye (PE) and the non-progressing eye (NPE) within the same patient in the UPG group and between the faster progressing eye and the slower progressing eye in the BPG group.

Results

Among 343 patients (average follow-up period of 4.2 years), 43 were categorized into the UPG group and 31 into the BPG group. The prevalence of all analyzed systemic diseases did not differ between the two groups. PEs in the UPG group had more severe pathology in terms of baseline visual field parameters than NPEs (mean deviation -6.9 ± 5.7 vs. -2.9 ± 3.9 dB, respectively; p < 0.001). However, baseline IOP, mean follow-up IOP, and other clinical characteristics were not significantly different between the PE and the NPE in the UPG group. The progression rate was significantly higher in the faster progressing eye in patients with BPG than in the PE for patients with UPG (-3.43 ± 3.27 vs. -0.70 ± 1.26 dB/yr, respectively; p = 0.014).

Conclusions

There were no significant differences in the prevalence of systemic diseases between the UPG and BPG groups. Simultaneously bilaterally progressing patients showed much faster progression rates than those with a unilaterally progressing eye.     

Effects of glaucoma medications on the cardiorespiratory and intraocular pressure status of newly diagnosed glaucoma patients

AIMS: To evaluate the short term cardiovascular, respiratory, and intraocular pressure (IOP) effects of four glaucoma medications in newly diagnosed glaucoma patients. METHODS: 141 newly diagnosed glaucoma patients were recruited and underwent a full ocular, cardiovascular, and respiratory examination, including an electrocardiogram (ECG) and spirometry. They were prescribed one of four topical glaucoma medications and reviewed 3 months later. One eye of each patient was randomly chosen for analysis, performed using analysis of variance and the chi(2) test. RESULTS: Latanoprost had the greatest mean IOP lowering effect in both the primary open angle glaucoma (POAG) (p = 0.005) and the "presumed" normal tension glaucoma (NTG) groups (p = 0.33), reducing the IOP by 8.9 mm Hg and 4.1 mm Hg respectively. Timolol was associated with lowered pulse rates and reductions in the spirometry measurements. 41% of patients using brimonidine complained of systemic side effects and over 55% of patients using betaxolol complained of ocular irritation. 28% of patients required an alteration in their glaucoma management. CONCLUSIONS: Latanoprost appears to be a useful primary treatment for glaucoma patients, in view of superior IOP control and a low incidence of local and systemic side effects. Timolol causes a reduction in measurements of respiratory function, a concern in view of the potential subclinical reversible airways disease in the elderly glaucoma population. Brimonidine is associated with substantial, unpredictable systemic side effects and betaxolol causes ocular irritation and weak IOP control. Spirometry is advised in all patients receiving topical beta blocker therapy to control their glaucoma.     

Effects of latanoprost and betaxolol on cardiovascular and respiratory status of newly diagnosed glaucoma patients

AIMS: To investigate the cardiovascular and respiratory effects of topical latanoprost 0.005% and topical betaxolol 0.25% monotherapy in newly diagnosed glaucoma patients. METHODS: Fortynewly diagnosed glaucoma patients were enrolled in this prospective, observer-masked, randomized, parallel study. Patients received either latanoprost 0.005% or betaxolol 0.25% for a duration of 3 months. Baseline evaluation included intraocular pressure (IOP) measurement and cardiorespiratory examinations including pulse rate, systolic and diastolic blood pressure measurements and spirometry. These measurements were repeated after 3 months. RESULTS: Both latanoprost and betaxolol reduced IOP significantly (p = 0.001). After 3 months of therapy, the mean pulse rate, systolic and diastolic blood pressure values of the betaxolol group were reduced (p = 0.027, p = 0.07 and p = 0.016, respectively). No significant changes occurred in the cardiovascular measurements of the latanoprost group (p > 0.05). There were no significant changes in any of the spirometric measurements tested for both groups (p > 0.05). CONCLUSION: Both latanoprost and betaxolol are safe concerning respiratory functions. Betaxolol may cause small changes in the cardiovascular system, suggesting that blood pressure and pulse rates should be checked before and in regular intervals after prescribing it for the elderly. Latanoprost seems to be a safe medication in view of absence of systemic cardiovascular and respiratory side effects.     

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.     

Effects of betaxolol and latanoprost on ocular blood flow and visual fields in patients with primary open-angle glaucoma

PURPOSE: To evaluate the effects of betaxolol and latanoprost on ocular blood flow and visual fields in patients with primary open-angle glaucoma (POAG) by means of an observer-masked, prospective clinical study. METHODS: Thirty-two patients with newly diagnosed POAG were included in the study. The patients were randomized into two groups. The first group was treated with betaxolol 0.50% twice daily and the second group with latanoprost 0.005% once daily. Baseline and posttreatment examinations on the first and third months of treatment included intraocular pressure (IOP) measurement, automated visual field testing, and ocular blood flow assessment. For evaluation of visual fields, mean defect and pattern standard deviation indices were used. Ocular blood flow was assessed by means of color Doppler imaging of the central retinal artery (CRA) and the temporal short posterior ciliary artery (PCA). For each vessel, peak systolic (PSV) and end-diastolic (EDV) blood flow velocities were measured and resistivity index (RI) calculated. RESULTS: After exclusion of one noncompliant patient, the study was completed with 31 eyes of 31 patients. Both drugs significantly reduced IOP (p<0.05). The mean IOP lowering effect of latanoprost was significantly higher than that of betaxolol (p=0.03). Visual field indices exhibited no significant changes in either group (p>0.05). There were no significant changes in PSV or EDV measurements of CRA or PCA in either group (p>0.05). RI decreased in both CRA and PCA with both drugs. The mean changes between baseline and 3 month blood flow measurements were not significantly different between betaxolol and latanoprost (p>0.05). CONCLUSIONS: Over a treatment period of 3 months, both betaxolol and latanoprost tended to improve ocular blood flow without one of them being superior to the other. The results suggest that the direct (non IOP-dependent) influence on ocular circulation is better for betaxolol than for latanoprost. In addition, neither drug caused significant generalized improvements in visual fields during this period.     

Betaxolol eye drops: A clinical trial of safety and efficacy

Objective: To study the cardiopulmonary safety and ocular hypotensive efficacy of topical betaxolol hydrochloride 0.5% (a selective beta-1 blocker) in patients with unacceptably elevated intraocular pressure (IOP) and respiratory dysfunction. Methods: Thirty-one patients with poor control of elevated IOP were selected on the basis of coexistent respiratory disease which could be exacerbated by beta-antagonist administration and/or who had past adverse reactions to topical timolol. Using an open-label design, the ophthalmic, cardiovascular and pulmonary parameters of these patients were measured before betaxolol therapy, for four hours immediately after the first administration of the drug, and after one, four and 12 weeks of therapy. The screening and 12-week examinations included a bronchial challenge with methacholine, a non-specific bronchoconstricting agent. Results: IOP reduction was significant at all time points measured after first instillation of betaxolol, with a mean maximum fall of 8.4 (SD, 3.2) mmHg (95% Cl -9.545 to -7.261) from a baseline mean IOP of 23.9 (SD, 3.8) mmHg. Over 12 weeks of therapy, the mean reduction from baseline in IOP was 3.9 (SD, 2.6) mmHg (95% Cl -4.908 to -2.988). After first instillation of betaxolol, mean arterial pressure (MAP) fell transiently to a mean maximum fall of 3.9 (SD, 9.3) mmHg (95% Cl -7.159 to -0.582), from a mean baseline MAP of 107.7 (SD, 9.4) mmHg. Heart rate did not change. There were no changes in any of the respiratory parameters measured: forced expiratory volume in one second, forced vital capacity and peak expiratory flow rate. Over 12 weeks of betaxolol therapy, there were no changes in any of the above systemic parameters and no change in mean bronchial reactivity as measured by methacholine challenge. Of the 31 patients, who included 13 patients with previous intolerance to timolol (a non-selective beta-antagonist), only one showed intolerance to betaxolol. Conclusions: Betaxolol appears to be an effective and well tolerated ocular hypotensive agent in a typical glaucoma population, which includes many patients with cardiopulmonary disease. Individual intolerance to betaxolol will continue to occur and care is always required when patients with cardiac or respiratory dysfunction are exposed to any beta-antagonist.     

Evaluation of visual field changes with retinal nerve fiber layer thickness in primary congenital glaucoma

Purpose:To evaluate visual field changes in primary congenital glaucoma (PCG) with retinal nerve fiber layer thickness on optical coherence tomography.Methods:In this cross-sectional, observational study, consecutive PCG children who underwent combined trabeculotomy with trabeculectomy and on regular follow-up were enrolled. All patients were aged over four years and co-operative for RNFL OCT and visual field examination. Perimetry was done on Humphrey visual field (HVF) analyzer using 30-2 and 10-2 SITA standard algorithms as appropriate. If a reliable automated perimetry was not feasible, kinetic perimetry was done. The following were noted at baseline and every follow-up: age, sex, visual acuity, intraocular pressure (IOP), cup–disc ratio (CDR), corneal diameters, refraction, any topical antiglaucoma medications, surgeries underwent, age at surgery and duration between surgery and final examination.Results:Forty-eight eyes of 34 children operated for PCG and 19 eyes of 17 controls were analyzed. A statistically significant thinner average RNFL thickness of 87.2 ± 28 μm was noted in PCG eyes as compared to controls with 100.6 ± 7.2 μm (P = 0.04). The mean cup–disc area ratio on OCT in PCG eyes was 0.43 ± 0.2 (0.02–0.93) and in control eyes was 0.23 ± 0.07 (0.1–0.4) (P < 0.001). On RNFL OCT, there was significant focal RNFL loss in temporal superior (P = 0.003), nasal inferior (P = 0.037) and temporal inferior (P < 0.001) quadrants compared to controls. Among PCG eyes, 20/48 eyes (41.7%), had definitive, reproducible glaucomatous VF defects. Mean baseline IOP in PCG eyes with VF defect was 28.7 ± 5.7 mmHg and in eyes with normal VF was 24.6 ± 5.9 mmHg (P = 0.03). On univariate regression analysis, higher baseline IOP was significantly associated with both RNFL loss (odds ratio (OR): −2.17) and VF defects (OR: 3.35). Fluctuation in follow-up IOP (OR: 3.33) was also significantly associated with the presence of VF defects. On multivariable regression analysis maximum, IOP was significantly associated with RNFL loss and VF defects.Conclusion:Peripapillary RNFL thickness could be used to identify PCG eyes having visual field loss and possibly poor visual function from PCG eyes without visual field defects. Baseline and follow-up IOP, significantly correlated with RNFL thickness in PCG eyes.     

Levobunolol and betaxolol. A double-masked controlled comparison of efficacy and safety in patients with elevated intraocular pressure

In a double-masked, randomized, controlled clinical trial, the authors evaluated the ocular hypotensive efficacy of twice-daily treatment with levobunolol (0.25 and 0.5%) and betaxolol (0.5%) in 85 patients with open-angle glaucoma or ocular hypertension. During the 3-month study, intraocular pressure (IOP) reductions in the two levobunolol groups were significantly greater than in the betaxolol group. From a mean baseline IOP of approximately 25 mmHg, overall mean reductions were 6.2 and 6.0 mmHg for the 0.25 and 0.5% levobunolol groups, respectively, and 3.7 mmHg for the betaxolol group. No clinically or statistically significant among-group differences were noted in the systemic safety variables evaluated. These data suggest that although all three treatments are effective, levobunolol provides a greater reduction in IOP than betaxolol.     

A comparison of the efficacy of betaxolol and timolol in ocular hypertension with or without adrenaline

Betaxolol hydrochloride, a selective beta:-adrenergic blocker, is claimed to be less likely to aggravate chronic obstructive airways disease than timolol maleate, a nonselective beta-blocker. It is not clear which drug is more effective in lowering intraocular pressure (IOP) and how each acts in combination with topical adrenaline. To assess this we conducted a randomised clinical trial on ocular hypertensive patients. Both betaxolol and timolol produced a significant fall in IOP though not in all patients. No significant difference was found between betaxolol and timolol. The addition of dipivefrin gave an additional fall in some eyes only. No significant difference was found between the addition of dipivefrin and adrenaline. Some fellow eyes had a fall in IOP when dipivefrin was added to timolol. It is important to assess the response carefully in each individual eye when using betaxolol or timolol or when adding additional medication.     

Results of the betaxolol versus placebo treatment trial in ocular hypertension

PURPOSE: To determine whether treatment with betaxolol can delay or prevent the conversion from ocular hypertension to early glaucoma on the basis of visual field criteria, by means of a prospective, randomised, placebo-controlled trial. METHODS: Three hundred and fifty-six ocular hypertensives were randomized to treatment with either betaxolol drops or placebo drops during the period 1992-1996. Each patient was followed prospectively with 4-monthly visits. Examination at each visit included visual field testing, intra-ocular pressure (IOP) measurement and optic disc imaging. Conversion to early glaucoma was defined on the basis of visual field change by AGIS criteria. An intent-to-treat analysis compared visual field conversion after 3 years in the treatment and placebo arms. Normal visual field survival analysis was also performed. The IOP characteristics of the two treatment groups were compared. RESULTS: Two hundred and fifty-five patients completed the study, which ended in 1998, with a range of follow-up of 2-6 years. Sixteen (13.2%) of 121 patients in the placebo group converted to glaucoma, compared with 12 (9.0%) of 134 patients in the betaxolol group. The intent-to-treat analysis demonstrated no evidence of any difference in conversion rates between the betaxolol and placebo groups after 3 years. Visual field survival analysis demonstrated no significant difference between the betaxolol and placebo groups. The betaxolol-treated group had significantly lower post-treatment IOP values. Converters had significantly higher pre- and post-treatment IOP values than non-converters. CONCLUSIONS: Betaxolol significantly lowered the IOP level compared with placebo. Conversion to glaucoma was found to be related to both the baseline and post-treatment IOP levels. However the intent-to-treat analysis did not demonstrate a statistically significant reduction in the conversion rate in the betaxolol-treated group.     

A comparison of the efficacy of betaxolol and timolol in ocular hypertension with or without adrenaline

Betaxolol hydrochloride, a selective beta 1-adrenergic blocker, is claimed to be less likely to aggravate chronic obstructive airways disease than timolol maleate, a nonselective beta-blocker. It is not clear which drug is more effective in lowering intraocular pressure (IOP) and how each acts in combination with topical adrenaline. To assess this we conducted a randomised clinical trial on ocular hypertensive patients. Both betaxolol and timolol produced a significant fall in IOP though not in all patients. No significant difference was found between betaxolol and timolol. The addition of dipivefrin gave an additional fall in some eyes only. No significant difference was found between the addition of dipivefrin and adrenaline. Some fellow eyes had a fall in IOP when dipivefrin was added to timolol. It is important to assess the response carefully in each individual eye when using betaxolol or timolol or when adding additional medication.     

Clinical efficacy of topical nipradilol and timolol on visual field performance in normal-tension glaucoma: a multicenter,randomized, double-masked comparative study

Purpose  To compare the effects of topical nipradilol and timolol on the visual field in Japanese normaltension glaucoma (NTG) patients. Methods  We enrolled 146 NTG patients. At baseline, age, intraocular pressure (IOP), and mean deviation (MD) by the Humphrey field analyzer were 47.6 (SD 8.5), 14.2 (1.7) mmHg, and −4.5 (3.0) dB. Seventy-two patients were randomly assigned to the 0.25% nipradilol group and 74 patients to the 0.5% timolol ophthalmic solution group twice daily for the 3-year study period. The Humphrey full-threshold 30-2 visual field test was performed every 6 months. The primary end point was the nonparametric O’Brien summary score (sum of the ranks of six slopes calculated from the average of the total deviation in each cluster) in each patient. The secondary analyses were differences in the MD slope, average of the total deviation in each cluster, the corrected pattern standard deviation (CPSD), and the time course of IOP. Results  No significant intergroup differences were found in baseline characteristics, or in the parameters of the primary and secondary analyses. In both groups, central superior clusters showed negative slopes and IOP decreased by about 1 mmHg from baseline. Conclusion  No significant difference in visual field performance or IOP reduction was seen between the nipradilol and timolol groups.     

Progression of visual field defects and visual loss in trabeculectomized eyes

Purpose To evaluate progression of visual field (VF) defects and development of visual impairment (low vision and blindness) after trabeculectomy.Methods We evaluated retrospectively 138 eyes of 138 consecutive patients over 40 years of age with primary open-angle glaucoma (POAG) or exfoliation glaucoma (EG) operated on by trabeculectomy without antimetabolites. The mean follow-up period was 3.5 years (range 2–5). In 83 eyes, pre- and postoperative VF measured by the same technique were compared to detect progression. Visual acuities (VA) were recorded as Snellen decimal notations. VA of <0.3 to 0.05 was defined as low vision and VA of <0.05 or VF constricted to less than 20° in diameter as blindness.Results In 34 (41%) of 83 eyes with comparable fields, VF defects progressed because of glaucoma. In logistic regression analysis, severity of preoperative VF loss (P=0.0047) and use of preoperative oral antiglaucomatous medication (P=0.047) correlated significantly with VF progression. In univariate analysis, also initial intraocular pressure (IOP) reduction after surgery (P=0.023) and IOP reduction from preoperative to last postoperative examination (P=0.036) were significantly smaller in eyes with VF progression. Defect progression did not, however, correlate significantly with the last IOP (P=0.58). Six eyes (4.3%) were blind due to glaucoma preoperatively and 14 eyes (10.1%) at the last follow-up. Visual impairment correlated with the severity of initial VF loss (P=0.008).Conclusions Progression of VF defects and development of visual impairment due to glaucoma was fairly common despite trabeculectomy. Both were associated with severity of initial VF defect. In this series, no significant correlation appeared between defect progression and the last IOP, but association between stability of VF and the amount of IOP reduction after surgery indicate that a lower target IOP level particularly in eyes with initially severe VF defect would, however, be needed.     

The one-month effects of topical betaxolol, dorzolamide and apraclonidine on ocular blood flow velocities in patients with newly diagnosed primary open-angle glaucoma

PURPOSE: This double-masked, prospective and randomized clinical trial was planned to investigate with color Doppler imaging the 1-month vascular effects of betaxolol, dorzolamide and apraclonidine treatment on patients with newly diagnosed primary open-angle glaucoma (POAG). METHODS: 22 consecutive patients with newly diagnosed POAG between the ages of 46 and 72 years were enrolled in this study. All patients were newly diagnosed cases and had not received any antiglaucoma medication before. Patients who had a systemic vascular disease (including systemic hypertension) or were taking beta-blockers, nitrates or calcium channel blockers were excluded from the study. The patients were randomly divided into three groups. Groups A and B contained 7 patients, group C contained 8 patients. Group A patients were treated with topical betaxolol, group B patients received topical dorzolamide eye drops, and group C patients were treated with topical apraclonidine eye drops. Peak systolic velocities (PSV), end-diastolic velocities (EDV) and resistive indices (RI) in the right ophthalmic arteries (OA), central retinal arteries (CRA) and posterior ciliary arteries (PCA) were measured at baseline by using color Doppler imaging on a masked basis. On days 15 and 30 of treatment, the same measurements were repeated. The inter- and intragroup results were compared statistically. RESULTS: Compared to pretreatment measurements, topical betaxolol therapy significantly decreased PSV only in the PCA and only on day 30 of treatment (p = 0.011). On days 15 and 30, dorzolamide decreased RI measurements in the PCA compared to pretreatment measurement (p = 0.013 and p = 0.011, respectively). Apraclonidine also decreased PSV in the OA on days 15 and 30 of treatment when compared to pretreatment values (p = 0.013 and p = 0.012, respectively). When 15-day measurements were compared between the groups, PSV in the OA were significantly higher in dorzolamide-treated patients compared to other groups (p = 0.01 and p = 0.011). On day 30 of treatment, PSV in the OA was also higher in the dorzolamide-treated group than the other groups (p = 0.012 and p = 0.01). Additionally, apraclonidine-treated patients had a significantly lower EDV in the OA than the other groups (p = 0.013 and p = 0.01). The RI in the OA was also significantly lower in the apraclonidine-treated group compared to the other groups (p = 0.01 and p = 0.011). CONCLUSION: Our study suggests that dorzolamide has the most advantageous 1-month effects on blood flow velocity in the retrobulbar arterial circulation of POAG patients. Betaxolol seems superior to apraclonidine in this regard. Our data may help the clinician when treating patients with POAG medically. Further studies using a larger population size may clarify our results.     

Canadian Glaucoma Study: 1. Study design, baseline characteristics, and preliminary analyses

Background: The Canadian Glaucoma Study is a multicentred, prospective longitudinal study designed to study a variety of systemic risk factors for the progression of open-angle glaucoma under a standardised interventional protocol for intraocular pressure (IOP) control.Methods: Newly or previously diagnosed patients with early to moderate open-angle glaucoma were recruited consecutively from 5 hospital-based university departments. Baseline parameters, including an assessment of peripheral vasospasm, haematologic, coagulation, and immunopathologic variables were obtained. Newly diagnosed patients were targeted for a ≥30% reduction in IOP, whereas previously diagnosed patients entered the study at a physician-defined target IOP. After baseline examinations, patients were followed at 4-month intervals with standard automated perimetry, short-wavelength automated perimetry, and confocal scanning laser tomography, and at 28-32-month intervals with stereo disc photography. If the patient had visual field progression with standard automated perimetry, a further ≥20% reduction in IOP was mandated. A standardized IOP treatment protocol, ranging from topical monotherapy to filtration surgery, was implemented.Results: A total of 258 patients (130 men and 128 women, median age 65.0 years) were enrolled. Baseline median values for visual acuity, visual field mean deviation, untreated IOP, and refractive error were 0.10 logMAR, −4.04 dB, 25.0 mm Hg, and 0.00 D, respectively. Approximately 30% of the patients were hypertensive, 16% had cardiovascular disease, 9% thyroid disease, 9% diabetes, 14% migraine, and 19% were smokers.The median follow-up was 5.3 years, with 148 (57.0%) and 51 (19.8%) patients completing ≥5 and ≥7 years follow-up, respectively. The cumulative visual field progression rate at 2,4,6, and 8 years was 11.3%, 21.5%, 33.1%, and 43.5%, respectively.Interpretation: We describe the study design and baseline patient characteristics of the Canadian Glaucoma Study and present some preliminary results. This long and close followup of a large group of patients will reveal the importance of several systemic factors for the progression of glaucoma.     

Effect of calcium channel blockers on intraocular pressure

We determined the effects of either topical or systemic calcium channel antagonists on rabbit intraocular pressure (IOP). Topical nifedipine, verapamil or diltiazem had no significant effect on IOP. Intravenous verapamil and nifedipine caused statistically significant reductions in IOP between 2 and 6 h after administration; the nifedipine response followed an increase in IOP at 30 min. Diltiazem, given 3 times daily for 3 days, caused no pressure change. In the rabbit, therefore, calcium channel antagonists have no effect when given topically, but do reduce IOP when given systemically.