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

AIM: The 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). METHODS: One 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. RESULTS: Sixty 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. CONCLUSION: Both the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.

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.

Study of regional deformation of the optic nerve head using scanning laser tomography.

PURPOSE: Previous studies have suggested that IOP-induced deformation of the optic nerve head (ONH) at the level of the lamina cribrosa may contribute to axonal damage in glaucomatous optic neuropathy. Our purpose was to introduce a novel enucleated eye model for characterizing acute IOP-induced changes in ONH topography, and to develop improved analytical methods for detection of regional topographic change in the ONH. METHODS: Using a specially designed experimental apparatus, enucleated human eyes were progressively pressurized to 5, 15, 30, and 50 mmHg. Seven topographic images of the optic disc were taken at each pressure by a scanning laser tomographer (Heidelberg Retina Tomograph-HRT). The dependence of ONH topography on IOP was quantified for the entire nerve using standard HRT indices of ONH topographic change. The supero-inferior and nasal-temporal hemifields were also analyzed. A new method of analysis was developed which computes the location of the point of maximum slope within a 10 degrees sector of the ONH, as well as the magnitude of this slope. This method, termed "Inflection Point Analysis," was designed to be robust to the potential artefacts of image translation, reference plane location, and the subjective determination of ONH limits. RESULTS: The results of three eyes are presented to illustrate the techniques. In our enucleated eye model, average ONH depth progressively increased with IOP, showing a maximum average posterior displacement of 36 microm as IOP was changed from 5 to 50 mmHg. Significant regional variability in ONH displacement was observed, which both Inflection Point Analysis and standard HRT parameters were able to detect. Inflection point analysis showed several advantages over standard HRT parameters: it was insensitive to artefacts due to tilt, was able to objectively delineate the boundary between the optic cup and neuroretinal rim, and was able to sensitively track changes in the location of this margin. CONCLUSIONS: Scanning laser tomography is capable of detecting regional variation in the deformation of the ONH in response to acute changes in IOP. Our enucleated eye model and Inflection Point Analysis are promising tools for basic studies of ONH deformation in response to IOP. More extensive studies of both enucleated and in vivo eyes are required to determine the potential of Inflection Point Analysis for studying and tracking the progression of glaucomatous optic neuropathy.

Deformation of the lamina cribrosa by elevated intraocular pressure.

The purpose of this study was to determine the mechanical response of the lamina cribrosa (LC) to elevated intraocular pressure (IOP) so as to identify possible mechanisms of optic nerve damage in early glaucoma. Ten pairs of normal human eyes were fixed after 24 hours' exposure to 50 mm Hg pressure (experimental eyes) or 5 mm Hg pressure (contralateral control eyes). Photomicrographs of the central region of the optic nerve head (ONH) were taken to examine the LC morphologically and to measure the dimensions of the LC. It was found that elevated IOP caused the LC to deflect posteriorly without affecting its thickness. The majority of the posterior displacement in the LC occurred near the periphery of the ONH. This shape change is consistent with a model of force distribution within the LC in which shear stresses are dominant; such stresses are maximal at the periphery and minimal at the centre of the ONH. These findings support a model in which mechanical forces, specifically shearing stresses within the peripheral lamina, play a direct role in the pathology of glaucomatous optic neuropathy.

Effects of hydrogen peroxide-induced oxidative damage on outflow facility and washout in pig eyes.

Previous studies show that hydrogen peroxide (H2O2) is present in the aqueous humor of many species and is capable of affecting outflow facility in animal model experiments. To study the hypothesis that oxidative damage to the outflow pathway may play a role in the pathogenesis of primary open-angle glaucoma, 3 mM H2O2 with 20 mM 3-aminotriazole and 1 mM carmustine (BCNU) in Dulbecco's phosphate-buffered saline (DPBS) was perfused into enucleated pig eyes at constant pressure. Baseline and experimental perfusions were done at two different pressures (7.5 and 30 mm Hg) to study the effect of pressure on the response to oxidative damage. Outflow facility in the baseline experiments (with DPBS only) was observed to increase nonlinearly with time during the perfusions, but could be linearized if plotted as a function of the volume perfused. Thus, a term "volumetric washout" (W) was introduced and defined as the fractional rate of change of outflow facility with respect to the volume perfused. This quantity was found to be independent of pressure in the baseline studies. Perfusion of H2O2 and inhibitors increased W at 7.5 mm Hg but decreased W at 30 mm Hg. These results indicate that oxidative damage increases outflow facility at normal pressure but decreases it at elevated pressure, suggesting that elevated pressure may increase the susceptibility of the outflow pathway to this form of insult.