The Experts below are selected from a list of 12663 Experts worldwide ranked by ideXlab platform
Charles N J Mcghee - One of the best experts on this subject based on the ideXlab platform.
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fully automated montaging of laser scanning in vivo confocal microscopy images of the human corneal subbasal Nerve Plexus
Investigative Ophthalmology & Visual Science, 2012Co-Authors: Jason Turuwhenua, Dipika V Patel, Charles N J McgheeAbstract:PURPOSE: Creating wide-field montages of the human corneal subbasal Nerve Plexus using laser scanning in vivo confocal microscopy (IVCM) requires considerable expertise and remains highly labor intensive. A typical montage contains several hundred images to be quality checked and manually arranged. The purpose of this study was to develop and validate software for off-line montaging of IVCM images of the living human cornea. METHODS: The software was developed and tested using four large data sets of IVCM images from normal human corneas. Two of the data sets were used for calibration purposes, the remaining images served as a validation set. Techniques utilized included image binarization, clustering, key-point generation, and feature-based stitching. A range of tests involving computer processing and visual inspection were applied to audit and compare the automated montages with manually constructed montages. RESULTS: The original IVCM images (N = 2565) from four corneas were processed into image groups, reducing the number of effective images by 68% to 86%. Each data set contained a large primary grouping. A clustering strategy was used to reduce the total potential workload by 57%. Both programmatic and visual inspection confirmed the method was robust to errors, with a specificity of 100% (i.e., no falsely matched images). The time taken to complete the montage varied from 1.5 to 3 hours. METHODS: Computer-driven image stitching is a useful, effective, and time-saving tool for studies involving IVCM corneal Nerve imaging. Further research will extend and optimize these
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laser scanning in vivo confocal microscopy demonstrating significant alteration of human corneal Nerves following herpes zoster ophthalmicus
JAMA Neurology, 2010Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:60-YEAR-OLD WOMAN with herpes zoster ophthalmicus(HZO) of the right eye was treated with 800 mg ofacyclovir5timesperdayfor7days. Therewasnosignificantmedicalhis- tory. She developed reduced vision and ocular pain due to HZO disci- form keratouveitis (a central disc- like region of corneal edema with objective of the microscope was placedincontactwiththecorneaand thepatientwasaskedtofixateondis- tance targets arranged in a grid pat- tern to enable acquisition of mul- tipleconfocalimagesoverawidearea of cornea. Macromedia Freehand 10 (SanFrancisco,California)wasused to arrange images into wide-field montages of the subbasal Nerve Plexus. A montage of the left sub- basal Nerve Plexus demonstrated Nerve fiber bundles arranged in a ra- diatingpattern,convergingtoforma typical clockwise whorl, or vortex, pattern,andLangerhans(antigenpre- senting) cells were distributed throughout the imaged region (Figure 1). In contrast, a montage of the right subbasal Nerve Plexus could not be produced owing to the scarcity of subbasal Nerves. Indeed, only occasional nonbranching sub- basal Nerves were visible in the mid- peripheral cornea (Figure 2A) and most images of the right cornea con- sisted of a bare, Nerve-free Bowman layer (Figure 2B) with Langerhans cells (Figure 2C). COMMENT
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in vivo laser scanning confocal microscopy confirms that the human corneal sub basal Nerve Plexus is a highly dynamic structure
Investigative Ophthalmology & Visual Science, 2008Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:Purpose To add to findings in a prior study on the two-dimensional arrangement of the living human sub-basal corneal Nerve Plexus and determine whether it is a dynamic structure. Methods Laser scanning in vivo confocal microscopy was performed on the left cornea of a healthy subject who had been examined with the same methodology 2 years earlier. Examinations were performed once a week for 6 weeks with the purpose of producing a two-dimensional reconstruction map of the living human sub-basal corneal Nerve Plexus at each session. A two-dimensional graphics program was used to arrange and map images obtained at each session into confluent montages. Results The mean dimensions of the corneal areas mapped were 4.80 +/- 0.45 mm horizontally and 4.60 +/- 0.52 mm vertically. The Nerve branching patterns observed 2 years earlier did not correspond with those in any recent maps. Over the 6-week period, the sub-basal Nerve pattern appeared to migrate centripetally from the corneal periphery toward an inferocentral whorl. In the region of the whorl the Nerves altered their generally centripetal direction of migration, undergoing clockwise rotation. The centripetal rate of migration decreased with proximity to the center of the whorl (5.6 +/- 3.4 microm/wk at 13 microm from the whorl, 13.9 +/- 5.5 microm/wk at 333 microm from the whorl, and 25.9 +/- 8.6 microm/wk at 698 microm from the whorl). Conclusions This study provides strong evidence that the living human sub-basal corneal Nerve Plexus is a highly dynamic structure, with continuous centripetal movement of identifiable branch points of up to 26 microm/wk, creating dramatic pattern changes in the Plexus over a 6-week period.
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mapping the corneal sub basal Nerve Plexus in keratoconus by in vivo laser scanning confocal microscopy
Investigative Ophthalmology & Visual Science, 2006Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:PURPOSE To produce a two-dimensional reconstruction map of the living corneal sub-basal Nerve Plexus in keratoconus with in vivo confocal microscopy. METHODS Four eyes of four subjects with keratoconus were examined by slit lamp biomicroscopy, Orbscan II slit-scanning elevation topography (Bausch & Lomb Surgical, Rochester, NY), and laser scanning in vivo confocal microscopy with the Heidelberg Retina Tomograph II, Rostock Corneal Module (Heidelberg Engineering, Heidelberg, Germany). Subjects were asked to fixate on targets arranged in a grid to enable in vivo confocal microscopy of the cornea in a wide range of positions. RESULTS A mean of 402 +/- 57 images were obtained for each cornea, to create confluent montages. The mean dimensions of the corneal areas mapped were 6.60 +/- 0.70 mm horizontally and 5.91 +/- 0.72 mm vertically. All corneas exhibited abnormal sub-basal Nerve architecture compared with patterns previously observed in normal corneas. At the apex of the cone, a tortuous network of Nerve fiber bundles was noted, many of which formed closed loops. At the topographic base of the cone, Nerve fiber bundles appeared to follow the contour of the base, with many of the bundles running concentrically in this region. Central sub-basal Nerve density was significantly lower in keratoconus corneas (10,478 +/- 2,188 microm/mm2) compared with normal corneas (21,668 +/- 1,411 microm/mm2; Mann-Whitney; P < 0.01). CONCLUSIONS This is the first study to elucidate the overall distribution of sub-basal Nerves in the living central to midperipheral human cornea in keratoconus, using laser scanning in vivo confocal microscopy.
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mapping of the normal human corneal sub basal Nerve Plexus by in vivo laser scanning confocal microscopy
Investigative Ophthalmology & Visual Science, 2005Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:Purpose To produce a two-dimensional reconstruction map of the living human sub-basal corneal Nerve Plexus using in vivo confocal microscopy. Methods Laser scanning in vivo confocal microscopy was performed on three normal eyes of three healthy human subjects. Subjects were asked to fixate on targets arranged in a grid to enable examination of the cornea in a wide range of positions. Using the section mode, a mean of 573 +/- 176 images of the sub-basal Plexus were obtained for each subject. The data were arranged and images were mapped for each subject into confluent montages. Results Mean dimensions of the corneal areas mapped were 4.95 +/- 0.53 mm horizontally and 5.14 +/- 0.53 mm vertically. In all subjects, the sub-basal Nerve Plexus appeared to radiate toward a whorl-like complex centered 1 to 2 mm inferior to the corneal apex. Outside this area, the Nerve fiber bundles in the remainder of the cornea were arranged in a radiating pattern. Mean Nerve density was significantly higher in the inferocentral whorl region (25,249 +/- 616 microm/mm2) compared with the central cornea (21,668 +/- 1411 microm/mm2) (Mann-Whitney U test; P = 0.05). Conclusions This is the first study to elucidate the overall distribution of sub-basal Nerves in the healthy, live central to mid-peripheral human cornea by laser scanning in vivo confocal microscopy. The whorl pattern of the sub-basal Nerves is similar to that seen in the epithelium in corneal verticillata and may lend support to the theory that epithelial cells and Nerves migrate centripetally in tandem.
Oliver Stachs - One of the best experts on this subject based on the ideXlab platform.
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3d confocal laser scanning microscopy for large area imaging of the corneal subbasal Nerve Plexus
Scientific Reports, 2018Co-Authors: Stephan Allgeier, Sabine Peschel, Ralf Mikut, Klausmartin Reichert, Andreas Bartschat, Sebastian Bohn, Karsten Sperlich, Marcus Walckling, Veit Hagenmeyer, Oliver StachsAbstract:The capability of corneal confocal microscopy (CCM) to acquire high-resolution in vivo images of the densely innervated human cornea has gained considerable interest in using this non-invasive technique as an objective diagnostic tool for staging peripheral neuropathies. Morphological alterations of the corneal subbasal Nerve Plexus (SNP) assessed by CCM have been shown to correlate well with the progression of neuropathic diseases and even predict future-incident neuropathy. Since the field of view of single CCM images is insufficient for reliable characterisation of Nerve morphology, several image mosaicking techniques have been developed to facilitate the assessment of the SNP in large-area visualisations. Due to the limited depth of field of confocal microscopy, these approaches are highly sensitive to small deviations of the focus plane from the SNP layer. Our contribution proposes a new automated solution, combining guided eye movements for rapid expansion of the acquired SNP area and axial focus plane oscillations to guarantee complete imaging of the SNP. We present results of a feasibility study using the proposed setup to evaluate different oscillation settings. By comparing different image selection approaches, we show that automatic tissue classification algorithms are essential to create high-quality mosaic images from the acquired 3D datasets.
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local variability of parameters for characterization of the corneal subbasal Nerve Plexus
Current Eye Research, 2016Co-Authors: Karsten Winter, Rudolf F Guthoff, Patrick Scheibe, Bernd Kohler, Stephan Allgeier, Oliver StachsAbstract:AbstractPurpose: The corneal subbasal Nerve Plexus (SNP) offers high potential for early diagnosis of diabetic peripheral neuropathy. Changes in subbasal Nerve fibers can be assessed in vivo by confocal laser scanning microscopy (CLSM) and quantified using specific parameters. While current study results agree regarding parameter tendency, there are considerable differences in terms of absolute values. The present study set out to identify factors that might account for this high parameter variability.Materials and methods: In three healthy subjects, we used a novel method of software-based large-scale reconstruction that provided SNP images of the central cornea, decomposed the image areas into all possible image sections corresponding to the size of a single conventional CLSM image (0.16 mm2), and calculated a set of parameters for each image section. In order to carry out a large number of virtual examinations within the reconstructed image areas, an extensive simulation procedure (10,000 runs per imag...
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mosaicking the subbasal Nerve Plexus by guided eye movements
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Stephan Allgeier, Sabine Peschel, Oliver Stachs, S Maier, Ralf Mikut, Klausmartin Reichert, Bernd KohlerAbstract:PURPOSE A growing number of studies provide evidence that the morphology of the corneal subbasal Nerve Plexus (SNP), examined by corneal confocal microscopy (CCM), is a sensitive marker for diabetic peripheral neuropathy. However, it has been established that the field of view of a single CCM image (≈0.16 mm(2)) is insufficient for reliable assessment of corneal Nerve fiber morphology. The present work proposes a highly automated technique for imaging an extended area of the SNP and creating large-scale montages. METHODS A moving fixation target is presented on a small display in front of the nonexamined eye. By guiding the viewing direction of the subject in an expanding spiral pattern, the scanned corneal area is continuously expanded. Specialized software algorithms subsequently assemble a mosaic image from the acquired CCM image data. The proposed technique was applied in 12 healthy subjects. RESULTS Montage images of the SNP were successfully created from all examinations performed. The mean imaged SNP area was 9.86 mm(2) (range, 1.62-18.31 mm(2)). The mean CCM duration was 65.33 seconds (range, 14.58-142.58 seconds). CONCLUSIONS The key advances embodied in the proposed technique are its high degree of integration and automation (both for image acquisition and image processing) and the resulting short duration of CCM. By providing an easy-to-use tool for obtaining large-scale mosaic images of the SNP, this technique has the potential to facilitate larger clinical trials where SNP morphology is used as a surrogate marker for peripheral neuropathy.
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imaging and quantification of subbasal Nerve Plexus in healthy volunteers and diabetic patients with or without retinopathy
PLOS ONE, 2013Co-Authors: Andrey Zhivov, Karsten Winter, Marine Hovakimyan, Sabine Peschel, Volker Harder, Hanschristof Schober, Guenther Kundt, Simone Baltrusch, Rudolf F Guthoff, Oliver StachsAbstract:Background The alterations of subbasal Nerve Plexus (SBP) innervation and corneal sensation were estimated non-invasively and compared with the values in healthy volunteers. Additionally, this study addressed the relation of SBP changes to the retinal status, glycemic control and diabetes duration.
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image reconstruction of the subbasal Nerve Plexus with in vivo confocal microscopy
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Stephan Allgeier, Andrey Zhivov, Rudolf F Guthoff, S Maier, F Eberle, Bernd Koehler, Georg Bretthauer, Oliver StachsAbstract:PURPOSE. To overcome the anterior corneal mosaic (ACM) phenomenon in in vivo confocal laser scanning microscopy (CLSM) and to reconstruct undistorted images of the subbasal Nerve Plexus (SNP), facilitating morphometric analysis in the presence of ACM ridges. METHODS. CLSM was performed in five healthy volunteers. An original image processing algorithm based on phase correlation was used to analyze and reduce motion distortions in volume scan image sequences. Three-dimensional tracing of the SNP was performed to reconstruct images containing only the SNP layer, with Nerve fibers clearly visible even in ACM areas. RESULTS. Real-time mapping of the SNP revealed the presence of ridges with K-structures underneath them in all cases. The occurrence of K-structures correlated directly with development of ACM observed by slit lamp and resulted in massive deformation at the level of Bowman’s membrane, seriously interfering with examination of SNP structures. The average elevation of ACM ridges was 20.6 m (range, 8.7‐34.0 m). The novel method presented permitted reconstruction of the SNP layer in regions of ACM. CONCLUSIONS. The described method allows the precise analysis and elimination of motion artifacts in CLSM volume scans, in conjunction with the capability to reconstruct SNP structures even in the presence of severe ACM. The robustness and automation of the described algorithms require ongoing development, but this will provide a sound basis for extended studies of corneal Nerve regeneration or degeneration and for use in clinical practice. (Invest Ophthalmol Vis Sci. 2011;52: 5022‐5028) DOI:10.1167/iovs.10-6065
Dipika V Patel - One of the best experts on this subject based on the ideXlab platform.
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fully automated montaging of laser scanning in vivo confocal microscopy images of the human corneal subbasal Nerve Plexus
Investigative Ophthalmology & Visual Science, 2012Co-Authors: Jason Turuwhenua, Dipika V Patel, Charles N J McgheeAbstract:PURPOSE: Creating wide-field montages of the human corneal subbasal Nerve Plexus using laser scanning in vivo confocal microscopy (IVCM) requires considerable expertise and remains highly labor intensive. A typical montage contains several hundred images to be quality checked and manually arranged. The purpose of this study was to develop and validate software for off-line montaging of IVCM images of the living human cornea. METHODS: The software was developed and tested using four large data sets of IVCM images from normal human corneas. Two of the data sets were used for calibration purposes, the remaining images served as a validation set. Techniques utilized included image binarization, clustering, key-point generation, and feature-based stitching. A range of tests involving computer processing and visual inspection were applied to audit and compare the automated montages with manually constructed montages. RESULTS: The original IVCM images (N = 2565) from four corneas were processed into image groups, reducing the number of effective images by 68% to 86%. Each data set contained a large primary grouping. A clustering strategy was used to reduce the total potential workload by 57%. Both programmatic and visual inspection confirmed the method was robust to errors, with a specificity of 100% (i.e., no falsely matched images). The time taken to complete the montage varied from 1.5 to 3 hours. METHODS: Computer-driven image stitching is a useful, effective, and time-saving tool for studies involving IVCM corneal Nerve imaging. Further research will extend and optimize these
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laser scanning in vivo confocal microscopy demonstrating significant alteration of human corneal Nerves following herpes zoster ophthalmicus
JAMA Neurology, 2010Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:60-YEAR-OLD WOMAN with herpes zoster ophthalmicus(HZO) of the right eye was treated with 800 mg ofacyclovir5timesperdayfor7days. Therewasnosignificantmedicalhis- tory. She developed reduced vision and ocular pain due to HZO disci- form keratouveitis (a central disc- like region of corneal edema with objective of the microscope was placedincontactwiththecorneaand thepatientwasaskedtofixateondis- tance targets arranged in a grid pat- tern to enable acquisition of mul- tipleconfocalimagesoverawidearea of cornea. Macromedia Freehand 10 (SanFrancisco,California)wasused to arrange images into wide-field montages of the subbasal Nerve Plexus. A montage of the left sub- basal Nerve Plexus demonstrated Nerve fiber bundles arranged in a ra- diatingpattern,convergingtoforma typical clockwise whorl, or vortex, pattern,andLangerhans(antigenpre- senting) cells were distributed throughout the imaged region (Figure 1). In contrast, a montage of the right subbasal Nerve Plexus could not be produced owing to the scarcity of subbasal Nerves. Indeed, only occasional nonbranching sub- basal Nerves were visible in the mid- peripheral cornea (Figure 2A) and most images of the right cornea con- sisted of a bare, Nerve-free Bowman layer (Figure 2B) with Langerhans cells (Figure 2C). COMMENT
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in vivo laser scanning confocal microscopy confirms that the human corneal sub basal Nerve Plexus is a highly dynamic structure
Investigative Ophthalmology & Visual Science, 2008Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:Purpose To add to findings in a prior study on the two-dimensional arrangement of the living human sub-basal corneal Nerve Plexus and determine whether it is a dynamic structure. Methods Laser scanning in vivo confocal microscopy was performed on the left cornea of a healthy subject who had been examined with the same methodology 2 years earlier. Examinations were performed once a week for 6 weeks with the purpose of producing a two-dimensional reconstruction map of the living human sub-basal corneal Nerve Plexus at each session. A two-dimensional graphics program was used to arrange and map images obtained at each session into confluent montages. Results The mean dimensions of the corneal areas mapped were 4.80 +/- 0.45 mm horizontally and 4.60 +/- 0.52 mm vertically. The Nerve branching patterns observed 2 years earlier did not correspond with those in any recent maps. Over the 6-week period, the sub-basal Nerve pattern appeared to migrate centripetally from the corneal periphery toward an inferocentral whorl. In the region of the whorl the Nerves altered their generally centripetal direction of migration, undergoing clockwise rotation. The centripetal rate of migration decreased with proximity to the center of the whorl (5.6 +/- 3.4 microm/wk at 13 microm from the whorl, 13.9 +/- 5.5 microm/wk at 333 microm from the whorl, and 25.9 +/- 8.6 microm/wk at 698 microm from the whorl). Conclusions This study provides strong evidence that the living human sub-basal corneal Nerve Plexus is a highly dynamic structure, with continuous centripetal movement of identifiable branch points of up to 26 microm/wk, creating dramatic pattern changes in the Plexus over a 6-week period.
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mapping the corneal sub basal Nerve Plexus in keratoconus by in vivo laser scanning confocal microscopy
Investigative Ophthalmology & Visual Science, 2006Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:PURPOSE To produce a two-dimensional reconstruction map of the living corneal sub-basal Nerve Plexus in keratoconus with in vivo confocal microscopy. METHODS Four eyes of four subjects with keratoconus were examined by slit lamp biomicroscopy, Orbscan II slit-scanning elevation topography (Bausch & Lomb Surgical, Rochester, NY), and laser scanning in vivo confocal microscopy with the Heidelberg Retina Tomograph II, Rostock Corneal Module (Heidelberg Engineering, Heidelberg, Germany). Subjects were asked to fixate on targets arranged in a grid to enable in vivo confocal microscopy of the cornea in a wide range of positions. RESULTS A mean of 402 +/- 57 images were obtained for each cornea, to create confluent montages. The mean dimensions of the corneal areas mapped were 6.60 +/- 0.70 mm horizontally and 5.91 +/- 0.72 mm vertically. All corneas exhibited abnormal sub-basal Nerve architecture compared with patterns previously observed in normal corneas. At the apex of the cone, a tortuous network of Nerve fiber bundles was noted, many of which formed closed loops. At the topographic base of the cone, Nerve fiber bundles appeared to follow the contour of the base, with many of the bundles running concentrically in this region. Central sub-basal Nerve density was significantly lower in keratoconus corneas (10,478 +/- 2,188 microm/mm2) compared with normal corneas (21,668 +/- 1,411 microm/mm2; Mann-Whitney; P < 0.01). CONCLUSIONS This is the first study to elucidate the overall distribution of sub-basal Nerves in the living central to midperipheral human cornea in keratoconus, using laser scanning in vivo confocal microscopy.
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mapping of the normal human corneal sub basal Nerve Plexus by in vivo laser scanning confocal microscopy
Investigative Ophthalmology & Visual Science, 2005Co-Authors: Dipika V Patel, Charles N J McgheeAbstract:Purpose To produce a two-dimensional reconstruction map of the living human sub-basal corneal Nerve Plexus using in vivo confocal microscopy. Methods Laser scanning in vivo confocal microscopy was performed on three normal eyes of three healthy human subjects. Subjects were asked to fixate on targets arranged in a grid to enable examination of the cornea in a wide range of positions. Using the section mode, a mean of 573 +/- 176 images of the sub-basal Plexus were obtained for each subject. The data were arranged and images were mapped for each subject into confluent montages. Results Mean dimensions of the corneal areas mapped were 4.95 +/- 0.53 mm horizontally and 5.14 +/- 0.53 mm vertically. In all subjects, the sub-basal Nerve Plexus appeared to radiate toward a whorl-like complex centered 1 to 2 mm inferior to the corneal apex. Outside this area, the Nerve fiber bundles in the remainder of the cornea were arranged in a radiating pattern. Mean Nerve density was significantly higher in the inferocentral whorl region (25,249 +/- 616 microm/mm2) compared with the central cornea (21,668 +/- 1411 microm/mm2) (Mann-Whitney U test; P = 0.05). Conclusions This is the first study to elucidate the overall distribution of sub-basal Nerves in the healthy, live central to mid-peripheral human cornea by laser scanning in vivo confocal microscopy. The whorl pattern of the sub-basal Nerves is similar to that seen in the epithelium in corneal verticillata and may lend support to the theory that epithelial cells and Nerves migrate centripetally in tandem.
Nathan Efron - One of the best experts on this subject based on the ideXlab platform.
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fully automated semiautomated and manual morphometric analysis of corneal subbasal Nerve Plexus in individuals with and without diabetes
Cornea, 2014Co-Authors: Cirous Dehghani, Nicola Pritchard, Katie Edwards, Rayaz A Malik, Anthony W Russell, Nathan EfronAbstract:PURPOSE: The aim of the study was to determine the association, agreement, and detection capability of manual, semiautomated, and fully automated methods of corneal Nerve fiber length (CNFL) quantification of the human corneal subbasal Nerve Plexus (SNP). METHODS: Thirty-three participants with diabetes and 17 healthy controls underwent laser scanning corneal confocal microscopy. Eight central images of the SNP were selected for each participant and analyzed using manual (CCMetrics), semiautomated (NeuronJ), and fully automated (ACCMetrics) software to quantify the CNFL. RESULTS: For the entire cohort, mean CNFL values quantified by CCMetrics, NeuronJ, and ACCMetrics were 17.4 ± 4.3 mm/mm, 16.0 ± 3.9 mm/mm, and 16.5 ± 3.6 mm/mm, respectively (P < 0.01). CNFL quantified using CCMetrics was significantly higher than those obtained by NeuronJ and ACCMetrics (P < 0.05). The 3 methods were highly correlated (correlation coefficients 0.87-0.98, P < 0.01). The intraclass correlation coefficients were 0.87 for ACCMetrics versus NeuronJ and 0.86 for ACCMetrics versus CCMetrics. Bland-Altman plots showed good agreement between the manual, semiautomated, and fully automated analyses of CNFL. A small underestimation of CNFL was observed using ACCMetrics with increasing the amount of Nerve tissue. All 3 methods were able to detect CNFL depletion in diabetic participants (P < 0.05) and in those with peripheral neuropathy as defined by the Toronto criteria, compared with healthy controls (P < 0.05). CONCLUSIONS: Automated quantification of CNFL provides comparable neuropathy detection ability to manual and semiautomated methods. Because of its speed, objectivity, and consistency, fully automated analysis of CNFL might be advantageous in studies of diabetic neuropathy. Copyright
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morphometric stability of the corneal subbasal Nerve Plexus in healthy individuals a 3 year longitudinal study using corneal confocal microscopy
Faculty of Health; Institute of Health and Biomedical Innovation, 2014Co-Authors: Cirous Dehghani, Nicola Pritchard, Katie Edwards, Rayaz A Malik, Dimitrios Vagenas, Anthony W Russell, Nathan EfronAbstract:Purpose We examined the age-dependent alterations and longitudinal course of subbasal Nerve Plexus (SNP) morphology in healthy individuals. Methods Laser-scanning corneal confocal microscopy, ocular screening, and health and metabolic assessment were performed on 64 healthy participants at baseline and at 12-month intervals for 3 years. At each annual visit, eight central corneal images of the SNP were selected and analyzed using a fully-automated analysis system to quantify corneal Nerve fiber length (CNFL). Two linear mixed model approaches were fitted to examine the relationship between age and CNFL, and the longitudinal changes of CNFL over three years. Results At baseline, mean age was 51.9 ± 14.7 years. The cohort was sex balanced (χ2 = 0.56, P = 0.45). Age (t = 1.6, P = 0.12) and CNFL (t = -0.50, P = 0.62) did not differ between sexes. A total of 52 participants completed the 36-month visit and 49 participants completed all visits. Age had a significant effect on CNFL (F1,33 = 5.67, P = 0.02) with a linear decrease of 0.05 mm/mm2 in CNFL per one year increase in age. No significant change in CNFL was observed over the 36-month period (F1,55 = 0.69, P = 0.41). Conclusions The CNFL showed a stable course over a 36-month period in healthy individuals, although there was a slight linear reduction in CNFL with age. The findings of this study have implications for understanding the time-course of the effect of pathology and surgical or therapeutic interventions on the morphology of the SNP, and serves to confirm the suitability of CNFL as a screening/monitoring marker for peripheral neuropathies.
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wide field assessment of the human corneal subbasal Nerve Plexus in diabetic neuropathy using a novel mapping technique
Cornea, 2012Co-Authors: Katie Edwards, Nicola Pritchard, Rayaz A Malik, Anthony W Russell, Geoff P Sampson, Kevin Gosschalk, Nathan EfronAbstract:To develop a rapid optimized technique of wide-field imaging of the human corneal subbasal Nerve Plexus. A dynamic fixation target was developed and, coupled with semiautomated tiling software, a rapid method of capturing and montaging multiple corneal confocal microscopy images was created. To illustrate the utility of this technique, wide-field maps of the subbasal Nerve Plexus were produced in 2 participants with diabetes, 1 with and 1 without neuropathy. The technique produced montages of the central 3 mm of the subbasal corneal Nerve Plexus. The maps seem to show a general reduction in the number of Nerve fibers and branches in the diabetic participant with neuropathy compared with the individual without neuropathy. This novel technique will allow more routine and widespread use of subbasal Nerve Plexus mapping in clinical and research situations. The significant reduction in the time to image the corneal subbasal Nerve Plexus should expedite studies of larger groups of diabetic patients and those with other conditions affecting Nerve fibers. The inferior whorl and the surrounding areas may show the greatest loss of Nerve fibers in individuals with diabetic neuropathy, but this should be further investigated in a larger cohort.
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optimal image sample size for corneal Nerve morphometry
Optometry and Vision Science, 2012Co-Authors: Dimitrios Vagenas, Nicola Pritchard, Katie Edwards, Rayaz A Malik, Anthony W Russell, Geoff P Sampson, Ayda M Shahidi, Nathan EfronAbstract:Purpose Arbitrary numbers of corneal confocal microscopy images have been used for analysis of corneal subbasal Nerve parameters under the implicit assumption that these are a representative sample of the central corneal Nerve Plexus. The purpose of this study is to present a technique for quantifying the number of random central corneal images required to achieve an acceptable level of accuracy in the measurement of corneal Nerve fiber length and branch density. Methods Every possible combination of 2 to 16 images (where 16 was deemed the true mean) of the central corneal subbasal Nerve Plexus, not overlapping by more than 20%, were assessed for Nerve fiber length and branch density in 20 subjects with type 2 diabetes and varying degrees of functional Nerve deficit. Mean ratios were calculated to allow comparisons between and within subjects. Results In assessing Nerve branch density, eight randomly chosen images not overlapping by more than 20% produced an average that was within 30% of the true mean 95% of the time. A similar sampling strategy of five images was 13% within the true mean 80% of the time for corneal Nerve fiber length. Conclusions The “sample combination analysis” presented here can be used to determine the sample size required for a desired level of accuracy of quantification of corneal subbasal Nerve parameters. This technique may have applications in other biological sampling studies.
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repeatability of measuring corneal subbasal Nerve fiber length in individuals with type 2 diabetes
Eye & Contact Lens-science and Clinical Practice, 2010Co-Authors: Nathan Efron, Nicola Pritchard, Katie Edwards, Dimitrios Vagenas, Anthony W Russell, Geoff P Sampson, Ayda M Shahidi, Nicola Roper, Jim Graham, M A DabbahAbstract:Purpose: To analyze the repeatability of measuring Nerve fiber length (NFL) from images of the human corneal subbasal Nerve Plexus using semiautomated software. Methods: Images were captured from the corneas of 50 subjects with type 2 diabetes mellitus who showed varying severity of neuropathy, using the Heidelberg Retina Tomograph 3 with Rostock Corneal Module. Semiautomated Nerve analysis software was independently used by two observers to determine NFL from images of the subbasal Nerve Plexus. This procedure was undertaken on two occasions, 3 days apart. Results: The intraclass correlation coefficient values were 0.95 (95% confidence intervals: 0.92–0.97) for individual subjects and 0.95 (95% confidence intervals: 0.74–1.00) for observer. Bland-Altman plots of the NFL values indicated a reduced spread of data with lower NFL values. The overall spread of data was less for (a) the observer who was more experienced at analyzing Nerve fiber images and (b) the second measurement occasion. Conclusions: Semiautomated measurement of NFL in the subbasal Nerve fiber layer is highly repeatable. Repeatability can be enhanced by using more experienced observers. It may be possible to markedly improve repeatability when measuring this anatomic structure using fully automated image analysis software.
Stephan Allgeier - One of the best experts on this subject based on the ideXlab platform.
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3d confocal laser scanning microscopy for large area imaging of the corneal subbasal Nerve Plexus
Scientific Reports, 2018Co-Authors: Stephan Allgeier, Sabine Peschel, Ralf Mikut, Klausmartin Reichert, Andreas Bartschat, Sebastian Bohn, Karsten Sperlich, Marcus Walckling, Veit Hagenmeyer, Oliver StachsAbstract:The capability of corneal confocal microscopy (CCM) to acquire high-resolution in vivo images of the densely innervated human cornea has gained considerable interest in using this non-invasive technique as an objective diagnostic tool for staging peripheral neuropathies. Morphological alterations of the corneal subbasal Nerve Plexus (SNP) assessed by CCM have been shown to correlate well with the progression of neuropathic diseases and even predict future-incident neuropathy. Since the field of view of single CCM images is insufficient for reliable characterisation of Nerve morphology, several image mosaicking techniques have been developed to facilitate the assessment of the SNP in large-area visualisations. Due to the limited depth of field of confocal microscopy, these approaches are highly sensitive to small deviations of the focus plane from the SNP layer. Our contribution proposes a new automated solution, combining guided eye movements for rapid expansion of the acquired SNP area and axial focus plane oscillations to guarantee complete imaging of the SNP. We present results of a feasibility study using the proposed setup to evaluate different oscillation settings. By comparing different image selection approaches, we show that automatic tissue classification algorithms are essential to create high-quality mosaic images from the acquired 3D datasets.
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the corneal subbasal Nerve Plexus and thickness of the retinal layers in pediatric type 1 diabetes and matched controls
Scientific Reports, 2018Co-Authors: Aline Gotze, Karsten Winter, Sabine Peschel, Bernd Kohler, Stephan Allgeier, Sophie Von Keyserlingk, Ulrike Jacoby, Corinna Schreiver, Martin Rohlig, Anselm JunemannAbstract:Optical coherence tomography (OCT) of the retina and corneal confocal laser scanning microscopy (CLSM) of the subbasal Nerve Plexus (SBP) are noninvasive techniques for quantification of the ocular neurodegenerative changes in individuals with type 1 diabetes mellitus (T1DM). In adult T1DM patients these changes are hardly related to T1DM only. Instead, ageing and/or lifestyle associated comorbidities have to be considered as putative confounding variables. Therefore, we investigated pediatric T1DM patients (n = 28; 14.2 ± 2.51 y; duration of disease: 5.39 ± 4.16 y) without clinical signs of diabetic retina disease, neuropathy, vasculopathy or nephropathy and compared our findings with those obtained in healthy controls (n = 46; 14.8 ± 1.89 y). The SBP was characterized by the averaged length, thickness, and tortuosity of Nerve fibers as well as the number of branching and connecting points. OCT was used to determine the total thickness of the retina (ALL) and the thickness of each retinal layer. Both methods revealed signs of early neurodegenerative changes, e.g. thinning of distinct retinal layers at the pericentral ring and shortening of corneal Nerve fibers that are already present in pediatric T1DM patients. Standardization of instruments and algorithms are urgently required to enable uniform comparison between different groups and define normative values to introduce in the clinical setting.
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local variability of parameters for characterization of the corneal subbasal Nerve Plexus
Current Eye Research, 2016Co-Authors: Karsten Winter, Rudolf F Guthoff, Patrick Scheibe, Bernd Kohler, Stephan Allgeier, Oliver StachsAbstract:AbstractPurpose: The corneal subbasal Nerve Plexus (SNP) offers high potential for early diagnosis of diabetic peripheral neuropathy. Changes in subbasal Nerve fibers can be assessed in vivo by confocal laser scanning microscopy (CLSM) and quantified using specific parameters. While current study results agree regarding parameter tendency, there are considerable differences in terms of absolute values. The present study set out to identify factors that might account for this high parameter variability.Materials and methods: In three healthy subjects, we used a novel method of software-based large-scale reconstruction that provided SNP images of the central cornea, decomposed the image areas into all possible image sections corresponding to the size of a single conventional CLSM image (0.16 mm2), and calculated a set of parameters for each image section. In order to carry out a large number of virtual examinations within the reconstructed image areas, an extensive simulation procedure (10,000 runs per imag...
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mosaicking the subbasal Nerve Plexus by guided eye movements
Investigative Ophthalmology & Visual Science, 2014Co-Authors: Stephan Allgeier, Sabine Peschel, Oliver Stachs, S Maier, Ralf Mikut, Klausmartin Reichert, Bernd KohlerAbstract:PURPOSE A growing number of studies provide evidence that the morphology of the corneal subbasal Nerve Plexus (SNP), examined by corneal confocal microscopy (CCM), is a sensitive marker for diabetic peripheral neuropathy. However, it has been established that the field of view of a single CCM image (≈0.16 mm(2)) is insufficient for reliable assessment of corneal Nerve fiber morphology. The present work proposes a highly automated technique for imaging an extended area of the SNP and creating large-scale montages. METHODS A moving fixation target is presented on a small display in front of the nonexamined eye. By guiding the viewing direction of the subject in an expanding spiral pattern, the scanned corneal area is continuously expanded. Specialized software algorithms subsequently assemble a mosaic image from the acquired CCM image data. The proposed technique was applied in 12 healthy subjects. RESULTS Montage images of the SNP were successfully created from all examinations performed. The mean imaged SNP area was 9.86 mm(2) (range, 1.62-18.31 mm(2)). The mean CCM duration was 65.33 seconds (range, 14.58-142.58 seconds). CONCLUSIONS The key advances embodied in the proposed technique are its high degree of integration and automation (both for image acquisition and image processing) and the resulting short duration of CCM. By providing an easy-to-use tool for obtaining large-scale mosaic images of the SNP, this technique has the potential to facilitate larger clinical trials where SNP morphology is used as a surrogate marker for peripheral neuropathy.
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image reconstruction of the subbasal Nerve Plexus with in vivo confocal microscopy
Investigative Ophthalmology & Visual Science, 2011Co-Authors: Stephan Allgeier, Andrey Zhivov, Rudolf F Guthoff, S Maier, F Eberle, Bernd Koehler, Georg Bretthauer, Oliver StachsAbstract:PURPOSE. To overcome the anterior corneal mosaic (ACM) phenomenon in in vivo confocal laser scanning microscopy (CLSM) and to reconstruct undistorted images of the subbasal Nerve Plexus (SNP), facilitating morphometric analysis in the presence of ACM ridges. METHODS. CLSM was performed in five healthy volunteers. An original image processing algorithm based on phase correlation was used to analyze and reduce motion distortions in volume scan image sequences. Three-dimensional tracing of the SNP was performed to reconstruct images containing only the SNP layer, with Nerve fibers clearly visible even in ACM areas. RESULTS. Real-time mapping of the SNP revealed the presence of ridges with K-structures underneath them in all cases. The occurrence of K-structures correlated directly with development of ACM observed by slit lamp and resulted in massive deformation at the level of Bowman’s membrane, seriously interfering with examination of SNP structures. The average elevation of ACM ridges was 20.6 m (range, 8.7‐34.0 m). The novel method presented permitted reconstruction of the SNP layer in regions of ACM. CONCLUSIONS. The described method allows the precise analysis and elimination of motion artifacts in CLSM volume scans, in conjunction with the capability to reconstruct SNP structures even in the presence of severe ACM. The robustness and automation of the described algorithms require ongoing development, but this will provide a sound basis for extended studies of corneal Nerve regeneration or degeneration and for use in clinical practice. (Invest Ophthalmol Vis Sci. 2011;52: 5022‐5028) DOI:10.1167/iovs.10-6065
