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      Intraobserver Repeatability of Automated versus Adjusted Optical Coherence Tomography Measurements in Patients with Neovascular Age-Related Macular Degeneration


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          Aim: To assess the intraobserver repeatability of automated versusadjusted optical coherence tomography (OCT) measurements in patients with neovascular age-related macular degeneration (NVAMD). Methods: Ten eyes with NVAMD from 10 consecutive patients underwent two OCT measurements within 5 days by a single operator. Automated and adjusted central 1-mm foveal thickness and automated and adjusted total macular volume were measured in each study eye. The term ‘adjusted’ refers to manually corrected values, in which the interface landmarks for measurements are selected by the operator using Stratus® scan profiling and custom software. Bland-Altman method and bootstrap comparison of intraclass correlations (ICCs) were used for repeatability analysis. Results: Bland-Altman comparison did not reveal any statistically significant difference in any parameter, when results at first and second examination were compared (p > 0.05), indicating that the repeated measurements are similar. Further analysis was conducted using the bootstrap comparison of ICCs. The difference between adjusted and automated foveal thickness ICCs (r = 0.945 and 0.635, respectively) was significant (p = 0.031), indicating higher repeatability for adjusted foveal thickness. The ICCs for adjusted and automated total macular volume (r = 0.873 and 0.863, respectively) showed no statistically significant difference (p = 0.881). Conclusion: The repeatability of adjusted retinal thickness measurements, in which the errors of retinal boundary detection by OCT analysis software is corrected by the operator using scan profiling, is found to be higher than that of automated ones in this small group of NVAMD patients when performed by a single experienced operator.

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          Most cited references6

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          Optical coherence tomography of the human retina.

          To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Research laboratory. Convenience sample of normal human subjects. Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10-microns depth resolution. Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.
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            Errors in retinal thickness measurements obtained by optical coherence tomography.

            To report the frequency and severity of optical coherence tomography (OCT) retinal thickness measurement errors and to describe parameters that predict these errors. Observational case series. Two hundred consecutive patients undergoing OCT imaging. One eye (primary) from each of 200 consecutive patients undergoing Stratus OCT imaging (Carl Zeiss Meditec, Dublin, CA) with radial lines or fast macular thickness-based acquisition protocols was selected for review by 2 graders. On each of the line scans, graders evaluated the position of the automated retinal boundary lines (inner retinal surface and retinal pigment epithelium band) used by the OCT machine for thickness calculations and graded the positioning on a 6-point subjective, categorical error scale to generate an error score. The presence of thickness errors was correlated with various parameters, including the analysis confidence assessment reported by the OCT software, disease diagnosis, retinal morphologic features, the foveal center thickness standard deviation (FCTSD), and the FCTSD-to-foveal center thickness (FCT) ratio. Average OCT retinal thickness error score. Errors of retinal boundary detection and thickness measurement were observed in 92% of eyes, but were severe in only 13.5% of eyes. The identification of an error or low analysis confidence by the OCT software was strongly associated with the severity of the retinal thickness errors. A higher FCTSD-to-FCT ratio and presence of subretinal fluid also were associated with more severe errors. Retinal cysts and a diagnosis of retinal vascular disease such as diabetic macular edema were less likely to be associated with significant errors. Retinal thickness measurement errors occur frequently with current OCT segmentation and analysis algorithms. Severe errors are more frequent in eyes with subretinal pathologic features, but generally are detected by the OCT software. A high FCTSD-to-FCT ratio (>0.1) also may alert the clinician to the possibility of thickness errors. Clinical studies, particularly those pertaining to subretinal diseases, should consider these errors when incorporating OCT imaging in the study design.
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              Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412.

              To evaluate the efficacy and safety of PKC412, an orally administered kinase inhibitor, in subjects with diabetic macular edema. This was a randomized (1:1:1:1), multicenter, double-masked, parallel-group study in which subjects (n = 141) received placebo or PKC412 (50, 100, or 150 mg/d) for up to 3 months. Subjects were 18 to 85 years of age and had retinal thickening that met predefined criteria and best corrected visual acuity of 55 letters or more. Efficacy was based on changes in retinal thickening measured by grading of fundus photographs and optical coherence tomography (OCT) and changes in visual acuity. Grading of fundus photographs showed a statistically significant decrease in the area of greatest retinal thickening in patients receiving 150 mg/d of PKC412 (P = 0.032). OCT demonstrated that the two higher doses of PKC412 caused a significant decrease in thickening in the region of greatest thickening and in the fovea (P < or = 039), with response in the high-dose group significantly different from that in the placebo group (difference = -66.69 micro m [95.2% CI: -128.57 to -4.81]; P = 0.030). Retinal volume for all locations also showed a significant decrease from baseline in the 100- and 150-mg/d PKC412 groups (P < or = 004), and the 150-mg/kg group showed significantly less retinal volume than the placebo group at 3 months (difference = -0.46 mm(3) [95.2% CI: -0.86-0.06]; P = 0.019). There was a small (4.36 letters), but significant (P = 0.007), improvement in visual acuity at 3 months compared with baseline in the 100-mg/d PKC412 group. Gastrointestinal side effects (diarrhea, nausea, and vomiting) were the most common adverse events attributed to the drug. Dose-related effects were observed for tolerability, glycemic control, and liver toxicity. Orally administered PKC412 at doses of 100 mg/d or higher may significantly reduce macular edema and improve visual acuity in diabetic subjects. However, concern regarding liver toxicity with systemic therapy makes local delivery an appealing approach.

                Author and article information

                S. Karger AG
                June 2007
                20 June 2007
                : 221
                : 4
                : 227-232
                aRetina Service, Wilmer Eye Institute, and bDepartment of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Md., USA; cDepartment of Ophthalmology, Pamukkale University School of Medicine, Denizli, Turkey
                101923 Ophthalmologica 2007;221:227–232
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                : 27 July 2006
                : 25 September 2006
                Page count
                Figures: 2, Tables: 2, References: 15, Pages: 6
                Original Paper

                Vision sciences,Ophthalmology & Optometry,Pathology
                Repeatability, automated vs. adjusted optical coherence tomography measurements,Neovascular age-related macular degeneration,Optical coherence tomography


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