Laminar Displacement and Prelaminar Tissue Thickness Change after Glaucoma Surgery Imaged with Optical Coherence Tomography

PURPOSE. To study changes in lamina cribrosa position and prelaminar tissue thickness (PTT) after surgical IOP reduction in glaucoma patients. METHODS. Twenty-two patients (mean age, 71.4 years) were imaged with spectral domain optical coherence tomography (SD-OCT; 24 radial B-scans centered on the optic nerve head [ONH]) before trabeculectomy or tube shunt implantation. Follow up images were acquired 1 week, 1 month, 3 months, and 6 months postsurgery. Bruch's membrane opening (BMO), the internal limiting membrane (ILM) and the anterior laminar surface (ALS) were segmented in each radial scan with custom software. Surfaces were fitted to the ILM and ALS with the extracted three-dimesional coordinates. PTT was the distance between the ILM and ALS, perpendicular to a BMO reference plane. Serial postsurgical laminar displacement (LD), relative to the BMO reference plane, and changes in PTT were measured. Positive values indicated anterior LD. RESULTS. Mean (SD) presurgery IOP was 18.1 (6.5) mm Hg, and reduced by 4.7 (5.5), 2.4 (7.7), 7.0 (6.2), and 6.8 (7.5) mm Hg at 1 week, 1 month, 3 months, and 6 months postsurgery, respectively. At the four postsurgery time points, there was significant anterior LD (1.8 [9.5], -1.1 [8.9], 8.8 [20.2], and 17.9 [25.8] mu m) and PTT increase (1.7 [13.3], 2.4 [11.9], 17.4 [13.7], and 13.9 [18.6] mu m). LD was greater in ONHs with larger BMO area (P = 0.01) and deeper ALS (P = 0.04); however, PTT was not associated with any of the tested independent variables. CONCLUSIONS. Both anterior LD and thickening of prelaminar tissue occur after surgical IOP reduction in patients with glaucoma. (Invest Ophthalmol Vis Sci. 2012;53:5819-5826) DOI:10.1167/iovs.12-992

Automated segmentation of the optic disc from stereo color photographs using physiologically plausible features. Investigative ophthalmology & visual science

PURPOSE. To evaluate a novel automated segmentation algorithm for cup-to-disc segmentation from stereo color photographs of patients with glaucoma for the measurement of glaucoma progression. METHODS. Stereo color photographs of the optic disc were obtained by using a fixed stereo-base fundus camera in 58 eyes of 58 patients with suspected or open-angle glaucoma. Manual planimetry was performed by three glaucoma faculty members to delineate a reference standard rim and cup segmentation of all stereo pairs and by three glaucoma fellows as well. Pixel feature classification was evaluated on the stereo pairs and corresponding reference standard, by using feature computation based on simulation of photoreceptor color opponency and visual cortex simple and complex cells. An optimal subset of 12 features was used to segment all pixels in all stereo pairs, and the percentage of pixels assigned the correct class and linear cup-to-disc ratio (LCDR) estimates of the glaucoma fellows and the algorithm were compared to the reference standard. RESULTS. The algorithm was able to assign cup, rim, and background correctly to 88% of all pixels. Correlations of the LCDR estimates of glaucoma fellows with those of the reference standard were 0.73 (95% CI, 0.58 -0.83), 0.81 (95% CI, 0.70 -0.89), and 0.86 (95% CI, 0.78 -0.91), respectively, whereas the correlation of the algorithm with the reference standard was 0.93 (95% CI, 0.89 -0.96; n ϭ 58). CONCLUSIONS. The pixel feature classification algorithm allows objective segmentation of the optic disc from conventional color stereo photographs automatically without human input. The performance of the disc segmentation and LCDR calculation of the algorithm was comparable to that of glaucoma fellows in training and is promising for objective evaluation of optic disc cupping. (Invest Ophthalmol Vis Sci

Rates of Change in the Visual Field and Optic Disc in Patients with Distinct Patterns of Glaucomatous Optic Disc Damage

Purpose: To investigate the rate of visual field and optic disc change in patients with distinct patterns of glaucomatous optic disc damage. Design: Prospective longitudinal study. Participants: A total of 131 patients with open-angle glaucoma with focal (n = 45), diffuse (n = 42), and sclerotic (n = 44) optic disc damage. Methods: Patients were examined every 4 months with standard automated perimetry (SAP, SITA Standard, 24-2 test, Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA) and confocal scanning laser tomography (CSLT, Heidelberg Retina Tomograph, Heidelberg Engineering GmbH, Heidelberg, Germany) for a period of 4 years. During this time, patients were treated according to a predefined protocol to achieve a target intraocular pressure (IOP). Rates of change were estimated by robust linear regression of visual field mean deviation (MD) and global optic disc neuroretinal rim area with follow-up time. Main Outcome Measures: Rates of change in MD and rim area. Results: Rates of visual field change in patients with focal optic disc damage (mean -0.34, standard deviation [SD] 0.69 dB/year) were faster than in patients with sclerotic (mean - 0.14, SD 0.77 dB/year) and diffuse (mean + 0.01, SD 0.37 dB/year) optic disc damage (P = 0.003, Kruskal-Wallis). Rates of optic disc change in patients with focal optic disc damage (mean - 11.70, SD 25.5 x 10(-3) mm(2)/year) were faster than in patients with diffuse (mean -9.16, SD 14.9 x 10(-3) mm(2)/year) and sclerotic (mean -0.45, SD 20.6 x 10(-3) mm(2)/year) optic disc damage, although the differences were not statistically significant (P = 0.11). Absolute IOP reduction from untreated levels was similar among the groups (P = 0.59). Conclusions: Patients with focal optic disc damage had faster rates of visual field change and a tendency toward faster rates of optic disc deterioration when compared with patients with diffuse and sclerotic optic disc damage, despite similar IOP reductions during follow-up. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 294-303 (C) 2012 by the American Academy of Ophthalmology.Canadian Institute of Health Research (MTN) [MOP200309]Canadian Institute of Health Research (MTN)Capes Foundation, Ministry of Educational of Brazil (ASCR)Capes Foundation, Ministry of Educational of Brazil (ASCR

Non-arteritic anterior ischemic and glaucomatous optic neuropathy: Implications for neuroretinal rim remodeling with disease severity.

PurposePost-acute non-arteritic ischemic optic neuropathy (NAION) and glaucomatous optic neuropathy (GON) can be difficult to differentiate clinically. Our objective was to identify optical coherence tomography (OCT) parameters to help differentiate these optic neuropathies.MethodsWe compared 12 eyes of 8 patients with NAION and 12 eyes of 12 patients with GON, matched for age and visual field mean deviation (MD). All patients underwent clinical assessment, automated perimetry (Humphrey Field Analyzer II; Carl Zeiss Meditec, Dublin, CA, USA), and OCT imaging (Spectralis OCT2; Heidelberg Engineering, Heidelberg, Germany) of the optic nerve head and macula. We derived the neuroretinal minimum rim width (MRW), peripapillary retinal nerve fibre layer (RNFL) thickness, central anterior lamina cribrosa depth, and macular retinal thickness.ResultsMRW was markedly thicker, both globally and in all sectors, in the NAION group compared to the GON group. There was no significant group difference in RFNL thickness, globally or in any sector, with the exception of the temporal sector that was thinner in the NAION group. The group difference in MRW increased with increasing visual field loss. Other differences observed included lamina cribrosa depth significantly greater in the GON group and significantly thinner central macular retinal layers in the NAION group. The ganglion cell layer was not significantly different between the groups.ConclusionsThe neuroretinal rim is altered in a dissimilar manner in NAION and GON and MRW is a clinically useful index for differentiating these two neuropathies. The fact that the difference in MRW between the two groups increased with disease severity suggests distinct remodelling patterns in response to differing insults with NAION and GON

Block and modified gating of cardiac calcium channel currents by terodiline

1. Terodiline, an anticholinergic/antispasmodic drug effective in the treatment of urinary incontinence, is presently restricted due to adverse side effects on cardiac function. To characterize its effects on cardiac L-type Ca(2+)-channel current carried by Ca(2+) (I(Ca,L)) and Ba(2+) (I(Ba,L)), concentrations ranging from 0.1 to 100 μM were applied to whole-cell-configured guinea-pig ventricular myocytes. 2. Although sub-micromolar concentrations of terodiline had no effect on I(Ca,L) at 0 mV, 100 μM drug reduced its amplitude to ca. 10% of pre-drug control. The estimated IC(50) (15.2 μM in K(+)-dialysed cells, 12.2 μM in Cs(+)-dialysed cells; 0.1 Hz pulsing rate) is eight times higher than reported for I(Ca,L) in bladder smooth muscle myocytes. 3. Terodiline affected I(Ca,L) in a use-dependent manner; block increased when the pulsing rate was increased from 0.1 to 2–3 Hz, and when holding potential was lowered from −43 mV. The drug accelerated the decay of I(Ca,L) at 0 mV in a concentration-dependent manner, and slowed the recovery of channels from inactivation. 4. Terodiline reduced peak I(Ba,L) more effectively than peak I(Ca,L), and markedly accelerated the rate of inactivation of the current. 5. The results are discussed in terms of mechanisms of Ca(2+) channel block and relation to the therapeutic and cardiotoxic effects of the drug

Differences in the effects of urinary incontinence agents S-oxybutynin and terodiline on cardiac K(+) currents and action potentials

1. The cardiac electrophysiological effects of S-oxybutynin, a single-enantiomer drug under evaluation for the management of urinary incontinence, have been investigated and compared with those of terodiline, an incontinence agent withdrawn following reports of QT lengthening and ventricular tachyarrhythmia. Membrane currents were recorded from whole-cell configured guinea-pig and rabbit ventricular myocytes, and action potentials were recorded from guinea-pig and rabbit papillary muscles. 2. L-type Ca(2+) current (I(Ca,L)), rapidly-activating K(+) current (I(Kr)) and slowly-activating K(+) current (I(Ks)) were unaffected by submicromolar S-oxybutynin and inhibited by higher concentrations; IC(50) values were 17.8 μM for I(Ca,L), 12 μM for I(Kr), and 41 μM for I(Ks). Terodiline IC(50) values were somewhat lower for I(Ca,L) (15.2 μM) and I(Ks) (30 μM), but 24 fold lower in the case of I(Kr) (0.5 μM). 3. The durations of action potentials in guinea-pig and rabbit papillary muscles driven at 1 Hz were unaffected or moderately shortened by 0.1–100 μM S-oxybutynin, but lengthened by terodiline. Terodiline (⩽10 μM) also depressed maximal upstroke velocity. 4. The action potential plateau shortened by an average of 23% when control rabbit papillary muscles were driven at 0.4 Hz instead of 1 Hz. Plateau shortening was significantly smaller in the presence of drugs (30 μM S-oxybutynin, 3 and 30 μM terodiline), suggesting that they suppress the transient outward current (I(to)) involved in rate-dependent shortening. In experiments on rabbit ventricular myocytes, 3 and 30 μM S-oxybutynin inhibited I(to) by 9±2% and 35±3%, respectively, whereas 3 and 30 μM terodiline inhibited the current by 31±3% and 87±3%, respectively. 5. The results indicate that S-oxybutynin has relatively weak non-specific effects on cardiac ion channels, and that clinically relevant submicromolar concentrations are unlikely to have terodiline-like proarrhythmic actions on the myocardium