David Yan

Three-month, randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy

ABSTRACT Objective: Fixed combinations of 0.2% brimonidine–0.5% timolol and 2% dorzolamide–0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine–timolol compared with dorzolamide–timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension. Study design and methods: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine–timolol BID or dorzolamide–timolol BID as monotherapy (n = 101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n = 79). Clinical trial registration: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov. Main outcome measures: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire. Results: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine–timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide–timolol (p = 0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine–timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide–timolol (p = 0.213). Patients on brimonidine–timolol reported less burning (p < 0.001), stinging (p < 0.001), and unusual taste (p < 0.001) than patients on dorzolamide–timolol. Conclusions: Fixed-combination brimonidine–timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide–timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine–timolol received higher ratings of ocular comfort than dorzolamide–timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine–timolol and dorzolamide–timolol during long-term treatment.

The role of episcleral venous pressure in glaucoma associated with Sturge-Weber syndrome

PURPOSE To evaluate the role of episcleral venous pressure (EVP) in the pathogenesis of glaucoma associated with Sturge-Weber syndrome (SWS). METHODS EVPs were determined prospectively using an episcleral venomanometer in 22 eyes of 11 patients aged 8-18 years with SWS with or without glaucoma. Pressure measurements in the glaucomatous eyes of patients with SWS were compared to those of patients with facial port wine marks but no glaucoma and to the contralateral uninvolved eye in both groups. RESULTS EVP in eyes with glaucoma (mean, 20.9 mm Hg) was significantly higher (P < 0.01) than EVP in contralateral uninvolved eyes (mean, 9.6 mm Hg). In patients with unilateral port wine mark and no glaucoma, EVP was normal for ipsilateral and contralateral eyes (mean, 8.6 mm Hg and 9.6 mm Hg, respectively). CONCLUSIONS Our data support the hypothesis that elevated EVP plays an important role in eyes with SWS glaucoma.

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma

AimThe aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG).MethodsOne eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy.ResultsSixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P<0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: −0.7 mm Hg, 95% confidence interval (CI): (−1.0, −0.3), P<0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (−1.0 mm Hg, 95% CI (−1.6,−0.5), P=0.001) and at 0200 (−0.9 mm Hg, 95% CI: (−1.4,−0.5), P=0.001). No significant difference existed for the other time points.ConclusionBoth the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.

Time-Dependent Finite-Volume Model of Thermoelectric Devices

Thermoelectric modules are an important alternative to heat engines in the harvesting of waste heat. Electrical-thermal analogs are often employed when studying heat conduction and this approach can be extended to develop a model for thermoelectric effects. In this article, the coupled thermoelectric partial differential equations are discretized using the finite-volume method; the discretization respects the coupling between the heat sink and the thermoelectric material. The new model is especially useful when an accurate picture of transients in a thermoelectric device is required. Results from the 1-D finite-volume model are shown to agree with experimental results as well as 3-D simulations using COMSOL.

An observational study of bimatoprost 0.01% in treatment-naïve patients with primary open angle glaucoma or ocular hypertension: the CLEAR trial

Background This study was designed to evaluate the occurrence and severity of ocular hyperemia in subjects with elevated intraocular pressure (IOP) due to primary open angle glaucoma (POAG) or ocular hypertension (OHT) following treatment with bimatoprost 0.01% in a real-world clinical setting. Methods This was an open-label, observational study conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% topically as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline and weeks 6 and 12 using a photographic five-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes only the subgroup of 522 subjects who were naïve to IOP-lowering medication prior to the study. Results After 12 weeks of treatment with bimatoprost 0.01%, hyperemia was graded as none-to-mild (grades 0, +0.5, or +1) for 93.3% of subjects and as moderate-to-severe (grades +2 or +3) for 6.7%. At weeks 6 and 12, most subjects (93.2% and 93.5%) had no change in hyperemia grade from baseline. IOP was reduced by 7.4 mmHg (29.8%) at week 6 and 7.7 mmHg (30.9%) at week 12 from baseline. Conclusion This real-world, observational study found that bimatoprost 0.01% instilled once daily reduced IOP by a mean of 30% from baseline without moderate or severe ocular hyperemia in 93% of treatment-naïve subjects with POAG or OHT.

Effect of Healon and Viscoat on outflow facility in human cadaver eyes

PURPOSE To compare the acute effects of Healon (sodium hyaluronate) and Viscoat (sodium chondroitin sulfate-sodium hyaluronate) on outflow facility in human cadaver eyes and determine which viscoelastic agent is least likely to cause an intraocular pressure (IOP) spike after cataract surgery. SETTING The Glaucoma Research Lab, University of Toronto, Ontario, Canada. METHODS In this prospective paired study, 15 pairs of human cadaver eyes were used. Following the construction of a 3.0 mm scleral tunnel, 0.25 cc of Healon was injected into the anterior chamber of 1 eye and 0.25 cc of Viscoat was injected into the contralateral eye. The viscoelastic agents were removed from both eyes in a standardized fashion and the scleral tunnels closed. The eyes were then perfused at a constant IOP of 8.0 mm Hg, corresponding to 16.0 mm Hg in vivo. Outflow facility (microL/minute [min]/mm Hg) was recorded every 15 minutes for 24 hours using standard methods. RESULTS Outflow facility in the Viscoat-treated eyes decreased appreciably for the first 3 hours, then recovered somewhat after 12 hours; facility in the Healon-treated eyes showed less of an overall decrease. Over the 24 hour perfusion period, mean outflow facility was 0.037 microL/min/mm Hg +/- 0.015 (SD) in the Viscoat-treated eyes and 0.060 +/- 0.012 microL/min/mm Hg in the Healon-treated eyes. Healon reduced outflow facility significantly less than Viscoat between 3.25 and 10.50 hours postoperatively (P < .05, 2-tailed t test). CONCLUSIONS Healon reduced outflow facility less than Viscoat between 3.25 and 10.50 hours postoperatively.

Theory of linear sweep voltammetry with diffuse charge: Unsupported electrolytes, thin films, and leaky membranes

Linear sweep and cyclic voltammetry techniques are important tools for electrochemists and have a variety of applications in engineering. Voltammetry has classically been treated with the Randles-Sevcik equation, which assumes an electroneutral supported electrolyte. In this paper, we provide a comprehensive mathematical theory of voltammetry in electrochemical cells with unsupported electrolytes and for other situations where diffuse charge effects play a role, and present analytical and simulated solutions of the time-dependent Poisson-Nernst-Planck equations with generalized Frumkin-Butler-Volmer boundary conditions for a 1:1 electrolyte and a simple reaction. Using these solutions, we construct theoretical and simulated current-voltage curves for liquid and solid thin films, membranes with fixed background charge, and cells with blocking electrodes. The full range of dimensionless parameters is considered, including the dimensionless Debye screening length (scaled to the electrode separation), Damkohler number (ratio of characteristic diffusion and reaction times), and dimensionless sweep rate (scaled to the thermal voltage per diffusion time). The analysis focuses on the coupling of Faradaic reactions and diffuse charge dynamics, although capacitive charging of the electrical double layers is also studied, for early time transients at reactive electrodes and for nonreactive blocking electrodes. Our work highlights cases where diffuse charge effects are important in the context of voltammetry, and illustrates which regimes can be approximated using simple analytical expressions and which require more careful consideration.

An observational study of bimatoprost 0.01% in patients on prior intraocular pressure-lowering therapy: the Canadian Lumigan ® RC Early Analysis Review (CLEAR) trial

Purpose To evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting. Subjects and methods This open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study. Results After 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from −2.3%±17.3% to −26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit. Conclusion This observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%–15% reduction in IOP.

Comparison of morning versus evening dosing and 24-h post-dose efficacy of travoprost compared with latanoprost in patients with open-angle glaucoma

ABSTRACT Objective: To compare the IOP-lowering efficacy of a.m.-dosed travoprost and latanoprost at 24-h post-dose. Research design and methods: Open-angle glaucoma patients not naïve to prostaglandin therapy and currently controlled on p.m.-dosed (2100) latanoprost (n = 21) or travoprost (n = 30) had baseline IOPs measured at 0900. In a randomized, single-masked, crossover design, patients received travoprost (Travatan†) or latanoprost (Xalatan‡) at 0900 for 4 weeks, then were crossed over to receive the second prostaglandin for another 4 weeks. Treatment IOP was measured at 0900 prior to morning dose at both 4 and 8 week visits. Patient dosing preference (a.m./p.m.) was surveyed on exit. Main outcome measure: Intraocular pressure (IOP). † Travatan is a registered trade name of Alcon Laboratories, Inc., Fort Worth, TX, USA ‡ Xalatan is a registered trade name of Pfizer, New York, NY, USA Results: The mean IOP in the first period when all patients were dosed in the evening was assessed 12 h after dosing at 09:00 and it was similar in the two treatment groups (mean ± standard deviation: 17.9 ± 2.7 mmHg for travoprost versus 17.7 ± 2.5 mmHg for latanoprost, p = 0.812). In the a.m.-dosing crossover comparison, the 24-h post-dose IOP was significantly lower ( p < 0.001) on travoprost (16.9 ± 3.1 mmHg) compared to latanoprost (18.6 ± 3.3 mmHg). In the exit survey, 51% of patients preferred a.m.-dosing. Conclusions: a.m.-dosed travoprost is superior to a.m.-dosed latanoprost by 1.7 mmHg at 24-h post-dose.

Characterizing Battery Behavior for Time-Dependent Currents

Batteries connected to the DC grid are exposed to a variety of currents. This paper presents measurements on a Ni-MH battery under different loading conditions and shows how a small signal circuit model can be used to explain the observations, establishing links between physical processes within the battery and elements in the model. At DC currents over 2 C, the impedance of the battery is not influenced by the ripple frequency, but rather by the higher temperatures. Results also show that the impact of the ripple frequency on modulation of the double layer charge is negligible at ripple frequencies exceeding 5 kHz. The amplitude of pulses that can be applied are shown to be governed by diffusion limits and the batterys state of charge.