Shape of the anterior cornea:Comparison of height data from 4 corneal topographers

<p>PURPOSE: To compare the ability of clinical corneal topographers to describe the shape of the anterior cornea for optical modeling.</p><p>SETTING: University Medical Center Groningen, Groningen, Netherlands.</p><p>DESIGN: Cross-sectional study.</p><p>METHODS: The anterior corneal shape of healthy subjects was assessed with 4 topographers (Atlas Placido disk, Galilei dual Scheimpflug, Orbscan scanning slit, Pentacam single Scheimpflug). Exported height data were fit with Zernike polynomials. Mean values with the standard deviation, interdevice variability, and test-retest variability were determined for the defocus Z(2,0), astigmatism Z(2,-2) and Z(2,2), coma Z(3,-1) and Z(3,1), and spherical aberration Z(4,0) coefficients for 5.5 mm and 8.0 mm diameters.</p><p>RESULTS: At 5.5 mm, the single Scheimpflug topographer showed the smallest coefficient of repeatability; 0.31 mu m for Z(2,0); 0.40 and 0.34 mu m for Z(2,-2) and Z(2,2), respectively; 0.15 and 0.11 mu m for Z(3,-1) and Z(3,1), respectively; and 0.08 mu m for Z(4,0); the other topographers showed up to 10 times larger coefficients of repeatability. The (unsigned) mean differences between the topographers were in the range of 0.20 to 1.21 mu m for Z(2,0); 0.02 to 0.31 mu m and 0.06 to 0.42 mu m for Z(2,-2) and Z(2,2), respectively; 0.03 to 0.18 mu m and 0.03 to 0.35 mu m for Z(3,-1) and Z(3,1), respectively; and 0.00 to 0.14 mu m for Z(4,0). The Placido-disk topographer and single Scheimpflug topographer data corresponded best. Similar trends were found at 8.0 mm.</p><p>CONCLUSION: Test-retest variability hampered a detailed description of the anterior corneal shape at the level of individual subjects; interdevice variability compromises the exchangeability of the devices.</p>

Development of a ciliary muscle-driven accommodating intraocular lens

PURPOSE: To develop a ciliary muscle-driven accommodating intraocular lens (IOL) that has a large and predictable range of variable power as a step toward spectacle independence. SETTING: Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, The Netherlands. METHODS: A concept IOL that has a rotating focus mechanism and a mechanical frame that can operate within the range of ciliary muscle contraction of a typical 60-year-old human eye was designed. Prototypes were made to test the IOL's mechanical performance in an enucleated pig's eye using a laboratory lens-stretching device that mimics the action of the human ciliary muscle. Changes in focal length during stretching were measured by laser-based ray tracing and a videocamera system. To rotate the 2 lenses in the IOL with variable optical power, a frame that allows the displacement and force of the ciliary muscle to be transferred by the capsular bag was designed. RESULTS: Ray tracing showed that the modulation transfer function (MTF) of the IOL in different accommodative states did not deviate to a great extent from the MTF of a monofocal IOL. During stretching experiments, the prototype IOL achieved 8.0 diopters of accommodation. CONCLUSIONS: Evaluation of an accommodating IOL that meets the requirements for a spectacle-independent solution to presbyopia showed that the mechanical and optical designs must be further optimized to improve optical quality and functionality

Targeting anti-apoptotic Bcl-2 by AT-101 to increase radiation efficacy: data from in vitro and clinical pharmacokinetic studies in head and neck cancer

BACKGROUND: Pro-survival Bcl-2 family members can promote cancer development and contribute to treatment resistance. Head and neck squamous cell carcinoma (HNSCC) is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. Inhibition of anti-apoptotic Bcl-2 family members therefore represents an appealing strategy to overcome resistance to anti-cancer therapies. The aim of this study was to evaluate combined effects of radiation and the pan-Bcl-2 inhibitor AT-101 in HNSCC in vitro. In addition, we determined human plasma levels of AT-101 obtained from a phase I/II trial, and compared these with the effective in vitro concentrations to substantiate therapeutic opportunities. METHODS: We examined the effect of AT-101, radiation and the combination on apoptosis induction and clonogenic survival in two HNSCC cell lines that express the target proteins. Apoptosis was assessed by bis-benzimide staining to detect morphological nuclear changes and/or by propidium iodide staining and flow-cytometry analysis to quantify sub-diploid apoptotic nuclei. The type of interaction between AT-101 and radiation was evaluated by calculating the Combination Index (CI) and by performing isobolographic analysis. For the pharmacokinetic analysis, plasma AT-101 levels were measured by HPLC in blood samples collected from patients enrolled in our clinical phase I/II study. These patients with locally advanced HNSCC were treated with standard cisplatin-based chemoradiotherapy and received dose-escalating oral AT-101 in a 2-weeks daily schedule every 3 weeks. RESULTS: In vitro results showed that AT-101 enhances radiation-induced apoptosis with CI’s below 1.0, indicating synergy. This effect was sequence-dependent. Clonogenic survival assays demonstrated a radiosensitizing effect with a DEF(37) of 1.3 at sub-apoptotic concentrations of AT-101. Pharmacokinetic analysis of patient blood samples taken between 30 min and 24 h after intake of AT-101 showed a dose-dependent increase in plasma concentration with peak levels up to 300–700 ng/ml between 1.5 and 2.5 h after intake. CONCLUSION: AT-101 is a competent enhancer of radiation-induced apoptosis in HNSCC in vitro. In addition, in vitro radiosensitization was observed at clinically attainable plasma levels. These finding support further evaluation of the combination of AT-101 with radiation in Bcl-2-overexpressing tumors