Efficacy and safety of bimatoprost in glaucoma and ocular hypertension in non-responder patients

AIM: To establish the efficacy and safety of bimatoprost 0.03% monotherapy in glaucoma and ocular hypertension (OHT) patients with inadequate intraocular pressure (IOP)on current therapy. METHODS: Pre- and post-switch IOPs were analyzed for 59 consecutive patients who were switched from current therapy to bimatoprost monotherapy between 2011-2015. Demographic information, diagnosis, and any adverse events were recorded. Change in IOP post-pre switch was analyzed using a 2-sided Student''s paired t-test at the 5% significance level. RESULTS: There was a statistically significant mean reduction in IOP at the first follow up visit, which was maintained at subsequent follow up visits for patients regardless of diagnosis, or pre-switch treatment (P<0.001). Subgroup analysis also demonstrated a statistically significant mean reduction in IOP when looking at OHT patients only, as well as patients with any diagnosis switched from latanoprost monotherapy to bimatoprost monotherapy (P<0.001). CONCLUSION: This is the largest independent data set which supports switching glaucoma patients with poor response to current treatment onto bimatoprost monotherapy before considering other adjuvant medical or more invasive therapy.     

Effect of bimatoprost on ocular circulation in patients with open-angle glaucoma or ocular hypertension

Purpose To study the effect of bimatoprost 0.03% (Lumigan) on ocular hemodynamics in patients with open-angle glaucoma or ocular hypertension.Methods One randomly selected eye of each of 26 patients with open-angle glaucoma or ocular hypertension was enrolled. Each patient received a drop of bimatoprost 0.03% once daily for 1 month. The effect of bimatoprost on ocular circulation was assessed by color Doppler imaging (CDI), which measured peak systolic, end-diastolic blood flow velocities and resistance indices in the ophthalmic, posterior ciliary and central retinal arteries. Retrobulbar hemodynamics by CDI, intraocular pressure by Goldmann applanation tonometer, blood pressure by cuff, and heart rate by palpation were measured at baseline and at 1 month after bimatoprost treatment.Results Blood flow velocities and resistance indices in all retrobulbar vessels showed no statistically significant differences between baseline and bimatoprost condition (P>0.05). Bimatoprost lowered intraocular pressure significantly (P<0.001), with a mean change of 6.5 mmHg (27%) after 1 month of treatment. The systolic (P=0.38) and diastolic (P=0.74) blood pressures and pulse rate (P=0.94) did not show statistically significant differences during the study period.Conclusions The results of this study suggest that topical bimatoprost 0.03% significantly reduces intraocular pressure in patients with open-angle glaucoma or ocular hypertension. However, it does not have any effect on retrobulbar hemodynamics in open-angle glaucoma and ocular hypertension.The authors have no commercial or proprietary interest in any of the equipment and medication mentioned in this study     

Interaction of pilocarpine with latanoprost in patients with glaucoma and ocular hypertension.

PURPOSE: To study any interaction between pilocarpine and latanoprost when administered together, and to determine the optimal timing of dosage to maximize reduction of intraocular pressure (IOP). METHODS: Nineteen adult patients with either primary open-angle glaucoma or ocular hypertension participated in a single-center, prospective case study with masked observer. After a baseline measurement of IOP during treatment with latanoprost was obtained, initial treatment with pilocarpine three times daily was added without bedtime administration. This was followed by three different dose regimens in which pilocarpine was administered four times daily, altering the bedtime pilocarpine dose to precede the latanoprost dose by 1 hour, or to follow it by 10 minutes or 1 hour. Intraocular pressure was measured at 8:00 AM and 75 minutes after administration of the morning dose of pilocarpine. RESULTS: Comparison of IOP at 8:00 AM with baseline showed no significant change when pilocarpine was taken three times daily, or when pilocarpine was taken four times daily when the bedtime dose preceded administration of latanoprost by 1 hour. There were significant decreases in IOP versus baseline when the bedtime dose of pilocarpine was taken simultaneously with or 1 hour after administration of latanoprost. Application of pilocarpine immediately after the 8:00 AM IOP measurement revealed a significant additional decrease in pressure. There were no significant differences between dosage schedules in the magnitude of the additional reduction in IOP. CONCLUSION: The order and timing of administration of pilocarpine and latanoprost can significantly alter their ocular hypotensive activity. Pilocarpine is most effective when administered four times daily, and when the bedtime dose is administered 1 hour after administration of latanoprost.     

Two-year double-masked comparison of bimatoprost with timolol in patients with glaucoma or ocular hypertension

The object of this study was to compare the long term efficacy and safety of bimatoprost with timolol in patients with glaucoma or ocular hypertension. In a 12-month extension of two identically designed 1-year, multicenter, randomized, double-masked clinical trials, patients were treated topically with bimatoprost 0.03% QD (n=167), bimatoprost 0.03% BID (n=131), or timolol 0.5% BID (n=81). Main outcome measures were IOP at 8 am and 10 am and safety parameters. Bimatoprost QD provided significantly greater mean reduction from baseline IOP than did timolol at both measurements at each study visit (P< or =.001). At 10 am (peak timolol effect) at month 24, the mean reduction from baseline IOP was 7.8 mm Hg with bimatoprost QD and 4.6 mm Hg with timolol (P<.001). Patients treated with bimatoprost QD also sustained significantly lower mean IOP than timolol-treated patients at every follow-up visit throughout the 2-year study period (P< or =.006). At 10 am at month 24, a significantly greater proportion of bimatoprost QD than timolol patients achieved target pressures of < or =13-18 mm Hg (P< or =.010). Bimatoprost sustained an excellent safety profile during the second year of treatment. Most adverse events were mild, and there were no reports of increased iris pigmentation, uveitis, or CME. The incidence of hyperemia was significantly higher with bimatoprost QD (13.8%) than with timolol (2.5%) (P=.006). Mean reduction from baseline IOP with bimatoprost BID was not significantly different from that with timolol at month 24 at 10 am (P=.474). We conclude that bimatoprost QD provides superior IOP lowering to timolol, and is safe and well tolerated over 24 months of treatment.     

Effect of changing from concomitant timolol pilocarpine to bimatoprost monotherapy on ocular blood flow and IOP in primary chronic angle closure glaucoma.

The aim of the present prospective masked study was to assess the effect of bimatoprost monotherapy on ocular blood flow and intraocular pressure (IOP) in eyes of primary chronic angle closure glaucoma patients already on concomitant timolol and pilocarpine. Thirty two patients of bilateral primary chronic angle closure glaucoma (PCACG) on topical timolol 0.5% twice a day and pilocarpine 2% three times daily were switched over to bimatoprost 0.03% once daily in both eyes. Intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) were recorded before and after starting bimatoprost and were followed up every four weeks for three months. Bimatoprost had statistically significant (p < 0.05) mean IOP reduction from 19.3 +/- 6.6 to 13.5 +/- 4.5 mmHg (30.5%) and there was improvement from 858 +/- 260 to 1261 +/- 321 microL/min (46.8%) in mean pulsatile ocular blood flow (p < 0.05). Conjunctival hyperemia (32%) was the most common adverse effect of bimatoprost. Bimatoprost 0.03% monotherapy improved ocular blood flow and provided a better diurnal IOP control than concomitant timolol-pilocarpine in eyes with primary chronic angle closure glaucoma and was found to be well tolerated.     

Effect of bimatoprost on patients with primary open-angle glaucoma or ocular hypertension who are nonresponders to latanoprost

PURPOSE: To test the efficacy of bimatoprost 0.03% 2D for lowering intraocular pressure (IOP) in patients affected by primary open-angle glaucoma or ocular hypertension who did not respond to treatment with latanoprost 0.005% 2D. DESIGN: Prospective, randomized clinical trial with a cross over design (two 30-day treatment phases with a 30-day washout phase in between). PARTICIPANTS: Fifteen patients were enrolled. Random allocation to treatment to a single eye only of every subject. Eligibility criteria: (1) IOP > 22 mmHg in both eyes on current treatment (on three separate readings > 24 hours apart), (2) angle wide open in both eyes, (3) no pseudoexfoliation and/or pigment dispersion in either eye, (4) documented medical history consistent with < 10% IOP decrease in both eyes on 2-month treatment with latanoprost 0.005% every day. METHOD: The following variables were measured at each study visit: (1) IOP (Goldmann applanation tonometry, 5 readings, 8 AM, 12 noon, 4 PM, 8 PM, and 12 midnight); (2) visual acuity (Early Treatment of Diabetic Retinopathy Study chart, logarithm of the minimum angle of resolution); (3) estimate of conjunctival hyperemia based on 5 standard photographs (graded as "none," "trace," "mild," "moderate," and "severe"). MAIN OUTCOME MEASURE: IOP. RESULTS: IOP data (mean and standard deviation) were the following: baseline = 24.7 +/- 0.9 mmHg, after washout = 24.8 +/- 1.1 mmHg, after latanoprost phase = 24.1 +/- 0.9 mmHg, after bimatoprost phase = 18.1 +/- 1.7 mmHg. IOP on bimatoprost proved lower than both baseline (P < 0.0001) and latanoprost (P = 0.0001). Thirteen of 15 patients showed a > or =20% IOP decrease with bimatoprost treatment. None of the 15 patients showed a > or =20% decrease of IOP after 30 days of latanoprost treatment. No significant IOP changes were observed in the fellow untreated eye in each patient throughout the study. Trace-to-mild conjunctival hyperemia was recorded more often with bimatoprost phase (P = 0.035). CONCLUSIONS: Thirteen of 15 patients, who were nonresponders to latanoprost, 0.005%, 2D, were successfully treated with bimatoprost, 0.03%, 2D. Bimatoprost treatment was associated with a higher incidence of trace-to-mild conjunctival hyperemia than latanoprost.     

Psychophysical characterisation of early functional loss in glaucoma and ocular hypertension

AIM: The psychophysical evaluation of selective cell loss in early glaucoma and ocular hypertension. METHODS: Contrast sensitivity was measured for the detection of luminance modulated gratings at a range of spatial (0.5, 2, 8 c/deg) and temporal (0, 16 Hz) frequency combinations in three groups of age matched patients (primary open angle glaucoma, ocular hypertension, normal controls; n=16). Stimuli of 5 degrees were presented foveally and at 15 degrees along the nasal horizontal meridian under photopic conditions. RESULTS: Fovea: Compared to the normal group, the thresholds for the glaucoma patients were significantly elevated at all spatial and temporal frequencies (p<0.0001), but this reduction was not significantly different at any particular spatial or temporal frequency (p>0.1). There was no difference in contrast sensitivity between the normals and OHTs (p>0.10). Periphery: The thresholds of the glaucoma patients were elevated compared to the normal controls (p<0.01). The loss of sensitivity was slightly greater at the higher spatial frequencies for both stationary and flickering patterns but this did not reach significance (p=0.09). The contrast sensitivity in normal and OHT groups was not significantly different (p>0.10). CONCLUSIONS: In early glaucoma, the reduction in contrast sensitivity to stimuli which isolate the magnocellular pathway (0.5 c/deg, 16 Hz) was not significantly different compared with the reduction in contrast sensitivity to stimuli that isolate the parvocellular pathway. These findings are not consistent with the hypothesis that the magnocellular pathway is selectively damaged in early glaucoma.     

Intraocular pressure-lowering efficacy of bimatoprost 0.03% and travoprost 0.004% in patients with glaucoma or ocular hypertension

AIM: To evaluate the efficacies of bimatoprost and travoprost for lowering of intraocular pressure (IOP) for the treatment of glaucoma and ocular hypertension. METHODS: Prospective, randomised, investigator-blinded, parallel-group clinical trial. After completing a washout of all glaucoma drugs, patients (n = 157) were randomised to bimatoprost or travoprost for 6 months. Visits were at baseline, 1 week, and 1, 3 and 6 months. IOP was measured at 09:00 h at each visit and also at 13:00 and 16:00 h at baseline and at 3 and 6 months. RESULTS: No significant between-group differences were observed in IOP at baseline, at 09:00, 13:00 or 16:00 h (p> or =0.741). After 6 months, both drugs significantly reduced IOP at every time point (p< or =0.001). After 6 months, mean IOP reduction at 09:00 h was 7.1 mm Hg (27.9%) with bimatoprost (n = 76) and 5.7 mm Hg (23.3%) with travoprost (n = 81; p = 0.014). At 13:00 h, mean IOP reduction was 5.9 mm Hg with bimatoprost (25.3%) and 5.2 mm Hg (22.4%) with travoprost (p = 0.213). At 16:00 h, the mean IOP reduction was 5.3 mm Hg (22.5%) with bimatoprost and 4.5 mm Hg (18.9%; p = 0.207) with travoprost. Both study drugs were well tolerated, with ocular redness the most commonly reported adverse event in both treatment groups. CONCLUSIONS: Bimatoprost provided greater mean IOP reductions than travoprost.     

Pattern electroretinogram recorded by skin electrodes in early ocular hypertension and glaucoma

Diagnostic value of transient pattern electroretinogram (PERG), recorded by skin electrodes, was compared with Goldmann perimetry in cases of ocular hypertension and glaucoma. According to the assumption that the PERG mostly reflects activity of the retinal glanglion cells, and histological evidence that 30–50% atrophy of the retinal ganglion cells is necessary to cause defects in visual field, we wanted to assess if i) this method could be more sensitive in detecting early glaucomatous damage than routine Goldmann perimetry in eyes with normal or only borderline elevated intraocular pressure in the time of PERG recording (first group of patients), and ii) how the PERG amplitude corresponds to ganglion cell loss, expected in the eyes with already detectable initial glaucomatous visual field defects, according to Goldmann II/2 isopter, with normal or borderline elevated intraocular pressure in the time of PERG recording (second group).In the group with no visual field defects subnormal amplitude of the major positive component of the PERG, N1-P1, was detected in three of 30 eyes (10%), while in the group with initial visual field defects N1-P1 amplitude was subnormal in 6 of 11 eyes (54%).The amplitude of the major negative PERG component, P1-N2, was found normal in all eyes of the first group and subnormal in 5 eyes (45%) of the second group.Abbreviations PERG pattern electroretinogram - VFD visual field defect - IOP intraocular pressure     

PRRP abnormalities in glaucoma and ocular hypertension

The human-pattern reversal retinal potential (PRRP) is a bioelectrical response that reflects neural activity generated in the proximal retina. Visual diseases which affect the retinal ganglion cells and the optic nerve often produce significant reductions in the amplitude of the PRRP. PRRP amplitude reductions are frequently observed in patients with primary open-angle glaucoma (POAG). This investigation was designed to determine whether patients with ocular hypertension (OHT) who are at risk of developing POAG also exhibit PRRP amplitude reductions. High contrast (76%), rapidly counterphasing (16 rps), phase alternating checkerboard patterns (15-120 min checks) were used to elicit PRRPs from patients with POAG (n = 12) and OHT (n = 24), as well as age-matched visual normals (n = 11). The patients with OHT were selected to be either at high or low risk of developing POAG. The results indicate that PRRP amplitude reductions similar to those exhibited by POAG patients do occur in some OHT patients. However, many other ocular hypertensives, particularly those at low risk of developing POAG, do not exhibit PRRP abnormalities.