A double-masked randomized comparison of the efficacy and safety of unoprostone with timolol and betaxolol in patients with primary open-angle glaucoma including pseudoexfoliation glaucoma or ocular hypertension. 6 month data.

PURPOSE: A long-term comparison of the ocular hypotensive efficacy and safety of unoprostone isopropyl 0.15% twice daily with that of timolol maleate 0.5% twice daily and betaxolol HCl 0.5% twice daily.DESIGN: This was a randomized, multicenter, double-masked, active-controlled 24-month clinical trial involving 27 centers in Europe and Israel. METHODS:The study population was composed of patients with primary open-angle glaucoma (including pseudoexfoliation) or ocular hypertension. After washout of antiglaucoma medications, intraocular pressure (IOP) was measured at 0, + 2, + 8, and + 12 hours. Patients were randomized in a 2:1:1 ratio to unoprostone, timolol, or betaxolol. Patients returned for examinations at 2 and 6 weeks and 3 and 6 months. RESULTS: 556 patients were randomized. Each drug produced a clinically and statistically (P <.001) significant reduction from baseline in 12-hour diurnal IOP at month 6 (- 4.3 mm Hg, unoprostone; - 5.8 mm Hg, timolol; - 4.9 mm Hg, betaxolol). Differences in adjusted treatment means between unoprostone and timolol and unoprostone and betaxolol were 1.57 mm Hg (95% CI: 1.00, 2.13) and 0.53 mm Hg (95% CI: - 0.03, 1.09), respectively. Unoprostone was clinically equivalent to betaxolol but did not have as great an IOP-lowering effect as timolol. Discontinued for inadequate control of IOP were 7%, 1%, and 4% of the patients for unoprostone, timolol, and betaxolol, respectively. There were no changes of note in visual acuity, pupil size, cup-to-disk ratio, visual fields, or iris color. Changes in heart rate and blood pressure were small, with no clinically significant differences between groups. CONCLUSIONS: Unoprostone provided a clinically significant IOP-lowering effect equivalent to betaxolol but not to timolol. The side effect profile of unoprostone appears to be comparable to other established IOP-lowering agents.     

Adverse reaction after use of latanoprost in Japanese glaucoma patients

PURPOSE: Although latanoprost has proven to have a strong hypotensive effect, some patients show adverse reactions such as eyelid pigmentation, iridial pigmentation, or hypertrichosis. We prospectively investigated these adverse reactions. SUBJECTS AND METHODS: One hundred and one Japanese glaucoma or ocular hypertension patients were included. Iridial, eyelid, and eyelash photographs were taken before and at 6 months after latanoprost treatment. Increased eyelid pigmentation, iridial pigmentation, eyelash pigmentation, vellus hair of the lid, and hypertrichosis were assessed from these photographs. The correlation between the incidence of these adverse reactions and the time of instillation, type of glaucoma, sex, age, or concomitantly used eye drops, and the overlap of these were evaluated. RESULTS: Increased pigmentation of the eyelid was found in 6 cases(5.9%), of the iris in 32 cases (31.7%), of the eyelashes in 29 cases (28.7%), vellus hair of the lid in 38 cases(37.6%), and hypertrichosis in 51 cases(50.5%). Pigmentation of the eyelid was more frequently observed in patients who used latanoprost concomitantly (16.7%) than in those who did not use anti-glaucomatous eye drops before latanoprost treatment (1.6%), or in those treated with latanoprost who had switched from other anti-glaucomatous eye drops (6.3%) (p= 0.03). CONCLUSIONS: The incidence of adverse reactions caused by latanoprost was higher in the eyelashes and iris than in the eyelid.     

Effects of Topically Instilled Bunazosin Hydrochloride and Other Ocular Hypotensive Drugs on Endothelin-1-induced Constriction in Rabbit Retinal Arteries

Purpose To compare the inhibitory effect of topically instilled bunazosin hydrochloride (bunazosin), a selective ₁-adrenoceptor antagonist, on the endothelin (ET)-1-induced vasoconstriction in rabbit retinal arteries with the effects of other ocular hypotensive drugs.Methods ET-1 was injected into the central part of the vitreous of both eyes of pigmented rabbits. Color fundus photographs were taken 5min before and 60min after the injection. The average diameters of the two major retinal arteries at the rim of the optic nerve head (ONH) were normalized with respect to ONH diameter. Fifty microliters of 0.01% bunazosin, or 0.12% isopropyl unoprostone (unoprostone), 1% dorzolamide hydrochloride (dorzolamide), 0.25% nipradilol, 0.5% betaxolol hydrochloride (betaxolol), or 0.5% timolol maleate (timolol) was instilled into one eye of each rabbit 60min before the ET-1 injection. The series of experiments was performed as masked tests.Results Bunazosin and unoprostone inhibited the ET-1-induced constriction of retinal arteries by 103% (P = 0.012 versus contralateral eyes) and 50% (P = 0.037), respectively. Dorzolamide, nipradilol, betaxolol, and timolol had no significant effects in this experiment.Conclusions Under our experimental conditions, bunazosin and unoprostone inhibited the ET-1-induced constriction. Hence, bunazosin and unoprostone may be clinically more effective against ET-1-related retinal diseases. Jpn J Ophthalmol 2004;48:465–469 © Japanese Ophthalmological Society 2004     

Measurement of iris color using computerized image analysis

PURPOSE: To develop a standardized method for measuring from iris photographs, light and dark segments of areas and densities of iris color. METHODS: Computerized image analysis was used to measure the iris photographs. The reproducibility of this method was studied in 30 normal eyes with three different colored irides, green-brown, blue-grey brown and yellow-brown. Three photographs were taken of each iris with a slit lamp camera at three different exposures at baseline. The photographs were repeated with exposure providing for the best reproducibility at 6.5 +/- 1.7 months as a first follow-up after baseline and 3.6 +/- 0.8 months following the first follow-up visit. At least one measurement was made for each photograph. RESULTS: The mean percent coefficient of variation (standard deviation of triplicate measurements/mean x 100) ranged from 1.0 to 4.1% for area and density measurements. Furthermore, the range of mean percent differences between baseline and follow-up visits ranged from 1.2 to 6.3%. CONCLUSION: We have developed a standardized method which appears suitable for measuring changes over time in iris color.     

Long-term efficacy and safety of combined topical antiglaucoma therapy--timolol & unoprostone vs. betaxolol & unoprostone

PURPOSE: To evaluate long-term efficacy and safety of treatment combining topical beta-blockers and isopropyl unoprostone in primary open-angle glaucoma and normal-tension glaucoma patients. METHODS: A prospective, open-label, parallel-group clinical comparison trial was performed to evaluate efficacy and safety of treatment combining 0.5% betaxolol and 0.12% isopropyl unoprostone (B&U) or 0.5% timolol and 0.12% isopropyl unoprostone (T&U). Forty eyes of 40 patients, which were matched in the aging and the stage of glaucomatous visual field defect, were studied. Twenty patients were treated with B&U and the other twenty patients with T&U twice daily for 24 months. Goldmann intraocular pressure(IOP), Humphrey automated perimetry, blood pressure, heart rate, and peak flow were done every six months in each group. RESULTS: In the B&U treatment group, mean IOP was 21.2 mmHg at baseline and 18.3 mmHg(p < 0.005) after 2 years, and in the T&U treatment group it was 21.1 mmHg at baseline and 17.9 mmHg (p < 0.001) after 2 years. The cases in which MD value decreased over 2 dB were one in the B&U treatment group and three in the T&U treatment group. The average MD value was significantly improved from -7.40 dB to -5.90 dB after 2 years with B&U treatment(p < 0.05), but there was no difference with the T&U treatment. None of the patients stopped combined therapy because of side effects, though heart rate was significantly reduced only in T&U treatment group. CONCLUSION: Both combined treatments were effective for IOP reduction in glaucoma patients, and the data from the B&U treatment group suggested that B&U was more effective in maintaining visual field than T&U.     

Changes in ocular surface caused by antiglaucomatous eyedrops: prospective, randomised study for the comparison of 0.5% timolol v 0. 12% unoprostone

AIM: To study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A beta blocker (0.5% timolol) and a novel prostaglandin F(2alpha) metabolite related drug (0.12% unoprostone) were examined in a prospective, randomised fashion. METHODS: 40 patients were randomly assigned to use either 0. 5% timolol (timolol group) or 0.12% unoprostone eyedrops (unoprostone group) twice a day for 24 weeks. In addition to routine ocular examinations, corneal epithelial integrity (vital staining tests, tear film break up time (BUT), anterior fluorometry, specular microscopy) and tear function (Schirmer's test, cotton thread test, tear clearance test (TCT)) were examined before and after the treatment. RESULTS: Both eyedrops caused significant reduction in intraocular pressure from the baseline levels. No significant changes were noted in corneal integrity in both groups, except a decrease in BUT at 20 weeks in the timolol group. The timolol group demonstrated significant decreases in Schirmer's test, tear clearance test, and tear function index (Schirmer's test value multiplied by clearance test); however, no such changes were noted in the unoprostone group. CONCLUSION: While unoprostone eyedrops caused no adverse effects on the corneal epithelial integrity and tear function, timolol caused significant impairments in tear production and turnover.     

Unoprostone isopropyl ester darkens iris color in pigmented rabbits with sympathetic denervation

PURPOSE: Unoprostone isopropyl ester (unoprostone) -induced iris color darkening was evaluated in a rabbit model using a cyclooxygenase inhibitor, an alpha(1)-adrenergic antagonist, and sympathetic denervation. MATERIALS AND METHODS: Dutch-belted rabbits were divided into five groups based on type of surgery and eyedrop treatment to both eyes: (1) sham surgery (n = 7); (2) bilateral superior cervical ganglionectomy (SCGx, n = 7); (3) SCGx plus flurbiprofen 0.03% (n = 7); (4) SCGx plus thymoxamine 0.5% (n = 6); and (5) SCGx plus flurbiprofen and thymoxamine (n = 6). All rabbits were treated with unoprostone 0.12% to one eye and its vehicle to the contralateral eye twice daily for 43 weeks after SCGx. Periodic color photographs of paired eyes were scored for difference in eye color. Iris melanin and aqueous humor protein were measured at week 43. RESULTS: Twenty-three of the 26 rabbits with bilateral SCGx and unilateral unoprostone treatment demonstrated a darker iris color on the unoprostone-treated side. The average scores (demonstrating difference in iris color) comparing photographs of treated versus control eyes in the four SCGx groups were higher than those in the sham surgery group (P < 0.03), and higher than at week 0 (P < 0.001). The group pretreated with flurbiprofen and thymoxamine had the highest score of all groups. The aqueous humor protein in unoprostone-treated eyes was higher (P < or = 0.0001) than in vehicle-treated eyes. The melanin content of irides of the denervated groups was higher (P < or = 0.01) in unoprostone-treated than in vehicle-treated eyes. CONCLUSION: Unoprostone produced iris color darkening in pigmented rabbit eyes with sympathetic denervation. Pretreatment with flurbiprofen and thymoxamine appeared to enhance this effect but this was not statistically demonstrated by the study.     

Inhibition of endothelin-1 and KCL-induced increase of [CA2+]i by antiglaucoma drugs in cultured A7r5 vascular smooth-muscle cells.

Over contraction of vascular smooth muscle may result in ischemia to ocular neuronal cells and deteriorate the glaucoma. The purpose of this study was to investigate the inhibitory effects of various commercial antiglaucoma drugs including brimonidine, dipivefrin, betaxolol, timolol, levobunolol, carteolol, brinzolamide, dorzolamide, unoprostone, latanoprost, pilocarpine, and preservative benzalkonium chloride on endothelin-1(ET-1) and KCl-induced increase of intracellular free Ca2+ ([Ca2+]i) in cultured rat A7r5 vascular smooth muscle cells. These drugs were diluted from original concentrations to 1/100, 1/1000, and 1/10000. [Ca2+]i mobility was analyzed by spectrofluorometry after loading with fura-2-AM. Betaxolol, timolol, levobunolol, and carteolol were found to inhibit KCl-induced release of [Ca2+]i in a dose-dependent manner. High concentrations of betaxolol, timolol, levobunolol, carteolol, and unoprostone also inhibited ET-1-induced increase of [Ca2+]i in A7r5 cells. However, ET-1- and KCl-induced increase of [Ca2+]i was not diminished by other drugs including brimonidine, dipivefrin, brinzolamide, dorzolamide, latanoprost, pilocarpine, and benzalkonium chloride. These results indicate that high concentrations of unoprostone and beta-adrenergic blocking agents including betaxolol, timolol, levobunolol, and carteolol may inhibit ET-1-induced increase of [Ca2+]i. The mechanism may be mediated by inhibition of extracellular calcium influx via blocking of L-type voltage-dependent Ca2+ channel in A7r5 cells.     

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

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

Travoprost compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension: meta-analysis of randomized controlled trials

BACKGROUND: It is still uncertain whether travoprost has comparable or better efficacy compared with other prostaglandin analogues or timolol in patients with open-angle glaucoma or ocular hypertension. The authors performed a meta-analysis of randomized controlled trials to evaluate the incidence of reported side-effects and intraocular pressure (IOP)-lowering effect of travoprost versus other prostaglandin analogues (latanaprost, bimatoprost, unoprostone) or timolol. METHODS: Systematic literature retrieval was conducted in Pubmed, EMBASE, Chinese Bio-medicine Database and Cochrane Controlled Trials Register to identify the potentially relevant randomized controlled trials. The statistical analysis was performed by RevMan 4.1 software that was provided by the Cochrane Collaboration. The outcome measures were the incidence of reported side-effects (hyperaemia, iris pigmentation, eyelash changes) and mean IOP pooled over treatment visits. RESULTS: In total, 12 articles involving 3048 patients with open-angle glaucoma or ocular hypertension were included in this meta-analysis. The combined results showed that travoprost 0.004% was more effective than timolol or travoprost 0.0015% in lowering IOP, but not more effective than bimatoprost or latanoprost. Travoprost 0.004% caused a higher percentage of hyperaemia than timolol, latanoprost, or travoprost 0.0015%. There was an increased incidence of pigmentation with travoprost than timolol. Travoprost 0.004% caused a higher percentage of eyelash changes than timolol, latanoprost, or travoprost 0.0015%. CONCLUSION: According to data available, travoprost is more effective than timolol in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Compared with other prostaglandin analogues, travoprost appears to be equivalent to bimatoprost and latanoprost. Although a limited number of local side-effects were reported, no serious treatment-related side-effects were reported.     

A controlled clinical trial of Dorzolamide: a single-centre subset of a multicentre study

Purpose: To assess the safety and intraocular pressure (IOP)-lowering activity of 2% dorzolamide (topical carbonic anhydrase inhibitor), compared to 0.5% timolol and 0.5% betaxolol eyedrops.
Methods: A parallel, masked, randomised one-year clinical trial was conducted in 16 patients with open-angle glaucoma or ocular hypertension, being a subset of a multicentre study which enrolled 523 subjects. Patients had IOP > 22 mmHg in one eye at baseline following washout of ocular hypotensive medications and were then randomised in a 3:l:l ratio to receive 2% dorzolamide thrice daily, 0.5% timolol twice daily or 0.5% betaxolol twice daily respectively. IOP was measured at Hour 2 (morning peak), Hour 5 and Hour 8 (afternoon trough for dorzolamide) at baseline, Weeks 2 and 4 and Months 2, 3, 6, 9 and 12.
Results: Topical dorzolamide 2% solution was well tolerated and safe. Mean IOP for dorzolamide at Hour 2 was 29.1 mmHg at baseline and 20.8 mmHg on treatment at one year, a 28.5% change. Mean IOP for dorzolamide at Hour 8 was 24.5 mmHg at baseline and 20.2 mmHg on treatment at one year, a 17.6% change. Comparable percent changes for timolol and betaxolol were 43.2/25.7 mmHg at Hour 2 and 21.9/13.5 mmHg at Hour 8 respectively.
Conclusions: Dozolamide 2% given thrice daily was well tolerated and safe, with a clinically significant effect on IOP comparable to betaxolol 0.5% twice daily, but not as great as timolol 0.5% twice daily.     

Brimonidine 0.2% vs unoprostone 0.15% both added to timolol maleate 0.5% given twice daily to patients with primary open-angle glaucoma or ocular hypertension

PURPOSE: To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily. METHODS: In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period. RESULTS: In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey. CONCLUSION: Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve.     

Effect of topical betablockers on human retinal vessels diameters

Purpose: To measure the effect of topicalbetaxolol 0.5% and timolol 0.5% on retinal vesselsdiameters by means of photographic enlargment.Methods: Thirteen glaucomatous patients(primary open angle glaucoma (POAG) and ocular hypertensive (OH)) were treatedtwice daily with betaxolol 0.5% for one year.These same patients were subsequently treated with timolol 0.5% during the following year. Fundus photographs were taken with Canoncamera 30 ° angle at baseline and two hours afterinstillation at 3, 6 and 12 months of treatment for each drug.The diameters of the superior and inferiortemporal vessels (arteries and veins) were measured at one and two discradii from the margin of the disc using photographicenlargment (× 66.7) of the right eye and were analysed under double masked fashion during the same session.Results: A significant increase of the meanarterial diameter (+ 7.4% p = 0.000 paired t) was found after 12months of betaxolol treatment, while no persistent further difference (+ 1.3% NS) was found after 12 months of timolol treatment.No modification was found in venous diameter.Conclusion: Betaxolol treatment isassociated with a beneficial effect on retinal arterieswidth whereas Timolol does not yield the same amplitude of benefit.     

Timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily to patients with primary open-angle glaucoma or ocular hypertension

OBJECTIVE: To compare the efficacy and safety of timolol 0.5%/dorzolamide 2% fixed combination vs timolol maleate 0.5% and unoprostone 0.15% given twice daily. DESIGN: Prospective multicenter, randomized, double-masked, crossover comparison study. METHODS: Primary open-angle glaucoma or ocular hypertension patients were randomly assigned to one of the treatment groups for a 6-week treatment period and then crossed over to the opposite treatment. Diurnal curve testing was performed at 8:00 AM, 10:00 AM, 4:00 PM, 6:00 PM, and 8:00 PM at baseline and the end of each treatment period. The run-in medicine was timolol twice daily for 28 days. RESULTS: Thirty-two patients completed this trial. The baseline trough pressure was 24.3 +/- 3.0 mm Hg, and the diurnal curve was 23.4 +/- 3.2 mm Hg. For the fixed combination the treatment trough pressure was 20.8 +/- 4.1 mm Hg and the diurnal curve was 19.6 +/- 3.6 mm Hg, whereas timolol and unoprostone concomitant therapy showed a treatment trough pressure of 20.1 +/- 4.5 mm Hg and a diurnal pressure of 19.8 +/- 4.1 mm Hg. There was no significant difference between treatment groups at any time point, for the diurnal curve, or in the extended reduction from baseline. There was no difference between treatment groups regarding ocular and systemic unsolicited or solicited adverse events. Burning, stinging, and conjunctival hyperemia were the adverse events most noted. There were no serious adverse events during this trial. CONCLUSIONS: This study suggests that both timolol/dorzolamide 2% fixed combination and concomitant timolol maleate 0.5% and unoprostone 0.15% therapy provide similar efficacy and safety throughout the daytime diurnal curve.     

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.     

The effects on the intraocular pressure and visual field resulting from a switch in the treatment from timolol to betaxolol.

Patients with primary open-angle glaucoma (POAG) were dosed twice-daily with 0.5% timolol maleate for 2 years, followed by 2 years of twice-daily dosing with 0.5% betaxolol hydrochloride. The changes in intraocular pressure (IOP) and effects on visual field by each treatment were monitored over this 4-year period. Both the timolol and betaxolol treatments controlled IOP. The mean MD (mean deviation in visual field) values at 24 months of the timolol treatment were -6.18 dB (decibels) and -5.32 dB. Mean MD baseline values following 24 months of the timolol treatment produced 2.31 dB and 0.95 dB reductions in sensitivity in the right and left eyes, and the reduction in the right eye was statistically significant (p < 0.01). The mean MD values after 24 months of the betaxolol treatment were -3.82 dB in the right eyes, an increase of 2.36 dB, and -4.05 dB in the left eyes, up by 1.28 dB. The results from this clinical trial demonstrated that betaxolol was superior over timolol in improving mean retinal sensitivity.     

Quantitative analysis of eyelash lengthening following topical latanoprost therapy

BACKGROUND: There have been several reports, mostly qualitative, of ocular side effects of latanoprost, including lengthening of eyelashes. We investigated changes in eyelash length in patients receiving topically administered latanoprost. METHODS: Seventeen patients (11 men and 6 women aged 63 to 80 years) with glaucoma or ocular hypertension were treated with latanoprost (one drop to one eye daily at bedtime). All had dark brown irises. At the start of treatment and after 2, 6 and 10 weeks of treatment, a single eyelash was removed from the centre of the upper eyelid of the treated and fellow (control) eyes and measured. Adverse events (defined as any undesirable event occurring in a subject, regardless of whether it was considered related to the latanoprost treatment) were monitored carefully. At each examination patients were asked whether they had any ocular or systemic symptoms. RESULTS: For the eyes treated with latanoprost, the mean eyelash length (and standard deviation) was 5.8 mm (0.7 mm) at baseline, 6.5 mm (0.6 mm) at 2 weeks, 6.5 mm (0.9 mm) at 6 weeks and 6.6 mm (0.7 mm) at 10 weeks (p < 0.001 for all differences from baseline). The corresponding values for the untreated eyes were 5.7 mm (0.7 mm), 5.8 mm (0.7 mm), 5.9 mm (0.7 mm) and 5.6 mm (0.7 mm); all differences were nonsignificant. INTERPRETATION: Latanoprost significantly increases eyelash length.     

Autoantibody against neuron-specific enolase found in glaucoma patients causes retinal dysfunction in vivo

PURPOSE: In our recent paper, we have reported the presence of serum autoantibody against neuron-specific enolase (NSE) in patients with glaucoma. The purpose of the present study was to investigate further the pathological effects of anti-NSE antibody on retina by comparing them with the effects induced by N-methyl-D-aspartate (NMDA). METHODS: Either a glaucoma patient's serum or purified anti-NSE antibody, or 10-40 mM NMDA was intravitreously administered into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs, such as timolol, betaxolol, nipradilol, and isopropyl unoprostone, and a calcium antagonist were also studied using these animal models. RESULTS: Electron microscopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50 kDa in Western blot analysis, and purified anti-NSE antibody induced retinal ganglion cell apoptosis in rat eyes. Functionally, these eyes showed a significant decrease in electroretinogram (ERG) responses and a remarkable decrease in rhodopsin phosphorylation reaction. These changes were comparable to the effects observed after the intravitreal administration of 20 mM NMDA. Co-administration of nipradilol, an alpha- and beta-blocker, with anti-NSE antibody or 20 mM NMDA caused marked recovery of the affected ERG responses within 2 weeks. In contrast, administration of timolol or betaxolol showed no recovery effect on the ERG responses. Among these drugs, only betaxolol showed a recovery effect on NMDA-induced decrease of rhodopsin phosphorylation. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phosphorylation reactions observed in rat eyes injected intravitreously with anti-NSE antibody or NMDA. These effects of nilvadipine were not changed by the addition of endothelin-1. In contrast, isopropyl unoprostone had no effect on these functions. CONCLUSION: These observations suggest that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo, similarly to NMDA.     

Changing antiglaucoma therapy from timolol to betaxolol: effect on ocular blood flow

The aim of the present study was to investigate the effect of a therapy change from timolol to betaxolol on ocular blood flow in patients with open-angle glaucoma. This randomized double-blind study comprised 34 consecutive patients with open-angle glaucoma, already treated with either timolol alone or in combination with other antiglaucoma agents. The patients were randomly allocated to receive either betaxolol (n = 17) or timolol (n = 17) instead of the present timolol drops. Additional antiglaucoma therapy remained unchanged. The retinal blood flow was assessed by scanning laser Doppler flowmetry and the pulsatile choroidal blood flow was assessed by laser interferometric measurement of fundus pulsation amplitude. Ocular blood flow measurement as well as systemic hemodynamic and intraocular pressure (IOP) measurements were performed at baseline and 1 week and 1 and 3 months after the therapy change. Visual field testing was performed at baseline and at 3 months. After 3 months of treatment with either timolol or betaxolol, neither the retinal nor the pulsatile choroidal blood flow were significantly altered. The power to detect a 9% change in pulsatile choroidal blood flow and a 20% change in retinal blood flow in the present study was 90%. The IOP was not significantly altered in either group. In contrast, visual fields slightly improved after betaxolol treatment compared to baseline (p = 0.047), but this effect was not significant versus timolol. Changing therapy from timolol to betaxolol has no effect on ocular blood flow in patients with open-angle glaucoma.     

Diversity of response of optic nerve head circulation to timolol maleate in gel-forming solution.

PURPOSE: This randomized, double-masked, placebo-controlled, two-period crossover study was conducted to investigate the effects of 0.5% timolol maleate in gel-forming solution on intraocular pressure (IOP) and blood circulation in the optic nerve head in patients with untreated ocular hypertension. METHODS: The effects of 0.5% timolol in gel-forming solution on IOP and optic nerve head capillary blood speed were studied in 12 patients with untreated ocular hypertension. Optic nerve capillary blood speed was measured using the laser Doppler technique before and at the end of each treatment period. RESULTS: In each patient, IOP decreased after treatment with timolol (mean decrease 16.8% versus placebo). Systemic blood pressure and pulse rate did not differ significantly after treatment with topical timolol from values after placebo. The mean change from baseline in Doppler broadening was 10.6% greater after treatment with timolol than after placebo. There was no significant change in mean Doppler broadening from baseline after treatment with either timolol or placebo. However, optic nerve head capillary blood speed increased in six patients, and was within the range of placebo response in six patients after treatment with timolol. Spearman correlation analysis of the baseline with Doppler broadening measurements after treatment showed a correlation for placebo but not for timolol. The percent change in Doppler broadening after timolol treatment was correlated with iris color. CONCLUSION: These results indicate that administration of timolol for 4 weeks reduces IOP in patients with ocular hypertension and generally does not change the blood circulation in the optic nerve head. Individual patients, however, showed variable changes in optic nerve head circulation after topical administration of timolol. Although the sample size was small, these changes in optic nerve head circulation were correlated with iris color.