FDA-approved deep learning software application versus radiologists with different levels of expertise: detection of intracranial hemorrhage in a retrospective single-center study.

PURPOSE: To assess an FDA-approved and CE-certified deep learning (DL) software application compared to the performance of human radiologists in detecting intracranial hemorrhages (ICH). METHODS: Within a 20-week trial from January to May 2020, 2210 adult non-contrast head CT scans were performed in a single center and automatically analyzed by an artificial intelligence (AI) solution with workflow integration. After excluding 22 scans due to severe motion artifacts, images were retrospectively assessed for the presence of ICHs by a second-year resident and a certified radiologist under simulated time pressure. Disagreements were resolved by a subspecialized neuroradiologist serving as the reference standard. We calculated interrater agreement and diagnostic performance parameters, including the Breslow-Day and Cochran-Mantel-Haenszel tests. RESULTS: An ICH was present in 214 out of 2188 scans. The interrater agreement between the resident and the certified radiologist was very high (κ = 0.89) and even higher (κ = 0.93) between the resident and the reference standard. The software has delivered 64 false-positive and 68 false-negative results giving an overall sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 68.2%, 96.8%, 69.5%, 96.6%, and 94.0%, respectively. Corresponding values for the resident were 94.9%, 99.2%, 93.1%, 99.4%, and 98.8%. The accuracy of the DL application was inferior (p < 0.001) to that of both the resident and the certified neuroradiologist. CONCLUSION: A resident under time pressure outperformed an FDA-approved DL program in detecting ICH in CT scans. Our results underline the importance of thoughtful workflow integration and post-approval validation of AI applications in various clinical environments.

Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI.

Recent data suggest that multiple sclerosis white matter lesions surrounded by a rim of iron containing microglia, termed iron rim lesions, signify patients with more severe disease course and a propensity to develop progressive multiple sclerosis. So far, however, little is known regarding the dynamics of iron rim lesions over long-time follow-up. In a prospective longitudinal cohort study in 33 patients (17 females; 30 relapsing-remitting, three secondary progressive multiple sclerosis; median age 36.6 years (18.6-62.6), we characterized the evolution of iron rim lesions by MRI at 7 T with annual scanning. The longest follow-up was 7 years in a subgroup of eight patients. Median and mean observation period were 1 (0-7) and 2.9 (±2.6) years, respectively. Images were acquired using a fluid-attenuated inversion recovery sequence fused with iron-sensitive MRI phase data, termed FLAIR-SWI, as well as a magnetization prepared two rapid acquisition gradient echoes, termed MP2RAGE. Volumes and T1 relaxation times of lesions with and without iron rims were assessed by manual segmentation. The pathological substrates of periplaque signal changes outside the iron rims were corroborated by targeted histological analysis on 17 post-mortem cases (10 females; two relapsing-remitting, 13 secondary progressive and two primary progressive multiple sclerosis; median age 66 years (34-88), four of them with available post-mortem 7 T MRI data. We observed 16 nascent iron rim lesions, which mainly formed in relapsing-remitting multiple sclerosis. Iron rim lesion fraction was significantly higher in relapsing-remitting than progressive disease (17.8 versus 7.2%; P < 0.001). In secondary progressive multiple sclerosis only, iron rim lesions showed significantly different volume dynamics (P < 0.034) compared with non-rim lesions, which significantly shrank with time in both relapsing-remitting (P < 0.001) and secondary progressive multiple sclerosis (P < 0.004). The iron rims themselves gradually diminished with time (P < 0.008). Compared with relapsing-remitting multiple sclerosis, iron rim lesions in secondary progressive multiple sclerosis were significantly more destructive than non-iron rim lesions (P < 0.001), reflected by prolonged lesional T1 relaxation times and by progressively increasing changes ascribed to secondary axonal degeneration in the periplaque white matter. Our study for the first time shows that chronic active lesions in multiple sclerosis patients evolve over many years after their initial formation. The dynamics of iron rim lesions thus provide one explanation for progressive brain damage and disability accrual in patients. Their systematic recording might become useful as a tool for predicting disease progression and monitoring treatment in progressive multiple sclerosis.

Optimization of surgical parameters based on patient-specific models: Application to arcuate keratotomy.

PURPOSE: To determine surgical parameters for arcuate keratotomy by simulating the intervention with a patient-specific model. SETTING: University Eye Clinic Salzburg, Paracelsus Medical University, Austria, and Institute for Surgical Technology and Biomechanics, University of Bern, Switzerland. DESIGN: Computational modeling study. METHODS: A new approach to plan arcuate keratotomy based on personalized finite element simulations was developed. Using this numeric tool, an optimization algorithm was implemented to determine the incision parameters that best met the surgeon's requirements while preserving the orientation of the astigmatism. Virtual surgeries were performed on patients to compare the performance of the simulation-based approach with results based on the Lindstrom and Donnenfeld nomograms and with intrastromal interventions. RESULTS: Retrospective data on 28 patients showed that personalized simulation reproduced the surgically induced change in astigmatism (Pearson correlation = 0.8). Patient-specific simulation was used to examine strategies for arcuate interventions on 621 corneal topographies. The Lindstrom nomogram resulted in low postoperative astigmatism (mean 0.03 diopter [D] ± 0.3 [SD]) but frequent overcorrections (20%). The Donnenfeld nomogram and intrastromal incisions resulted in a small amount of overcorrection (1.5%) but a wider spread in astigmatism (mean 0.63 ± 0.35 D and 0.48 ± 0.50 D, respectively). In contrast, the new numeric parameter optimization approach led to postoperative astigmatism values (mean 0.40 ± 0.08 D, 0.20 ± 0.08 D, and 0.04 ± 0.13 D) that closely matched the target astigmatism (0.40 D, 0.20 D, and 0.00 D), respectively, while keeping the number of overcorrections low (<1.5%). CONCLUSION: Using numeric modeling to optimize surgical parameters for arcuate keratotomy led to more reliable postoperative astigmatism, limiting the risk for overcorrection.

Systemic exposure to intracameral vs topical mydriatic agents: in cataract surgery.

OBJECTIVE: The objective of this study was to compare systemic exposure to tropicamide/phenylephrine following intracameral or topical administration before cataract surgery. PATIENTS AND METHODS: Mydriatics exposure was calculated in patients randomized to intracameral fixed combination of mydriatics and anesthetic ([ICMA]: tropicamide 0.02%, phenylephrine 0.31%, and lidocaine 1%, N=271) or mydriatic eye drops ([EDs]: tropicamide 0.5% and phenylephrine 10%, N=283). Additional doses were permitted if required. Mydriatic plasma levels were determined by mass spectrometric HPLC in 15 patients per group before and after administration. RESULTS: Most ICMA patients (73.6%) received a single dose (200 µL) representing an exposure to tropicamide of 0.04 mg and phenylephrine of 0.62 mg. None of these patients received additional mydriatics. In the control group (three administrations), the exposure was 0.45 (11.3-fold higher than ICMA) and 10.2 (16.5-fold higher) mg. When additional ED was used in this group (9.2% of patients), it was 37.5-fold higher for tropicamide (10 drops, 1.5 mg) and 54.8-fold higher for phenylephrine (10 drops, 34 mg) than the recommended ICMA dose. Tropicamide plasma levels were not detectable at any time point in ICMA patients while it was detectable in all ED patients at 12 and 30 minutes. Phenylephrine was detectable in 14.3% of ICMA patients compared to all ED patients at least at one time point. More ED patients experienced a meaningful increase in blood pressure and/or heart rate (11.2% vs 6.0% of ICMA patients; P=0.03). CONCLUSION: Systemic exposure to tropicamide/phenylephrine was lower and cardiovascular (CV) effects were less frequent with ICMA. This could be of particular significance in patients at CV risk.

Osteo-odonto-, Tibial bone and Boston keratoprosthesis in clinically comparable cases of chemical injury and autoimmune disease.

PURPOSE: To compare anatomical and functional results between three types of keratoprosthesis (KPro) in chemical injury and autoimmune disease. METHODS: 70 clinically comparable cases were included as follows: Boston KPro Type 1 25 eyes, osteo-odonto-keratoprosthesis (OOKP) 23 eyes, Tibial bone KPro 22 eyes. Survival times for anatomical and functional success were evaluated with Kaplan-Meier estimations and Log-rank tests. KPro exchange was considered a complication, not as failure. RESULTS: Prosthesis retention in chemical injury group at 5 years was 86% for OOKP, 100% for Tibial bone KPro, and 65% for Boston KPro (p = 0.09), while in the autoimmune disease group it was 66% for Tibial bone KPro and 50% for Boston KPro (p = 0.19; OOKP only one case). Functional success in the chemical injury group at 5 years was 86% for OOKP, 84% for Tibial bone KPro and 71% for Boston KPro (p = 0.38), while in the autoimmune group, it was 44% for Tibial bone KPro and 15% for Boston KPro (p = 0.15; OOKP only one case). The post-operative complications in all groups were: retinal detachment, vitreous hemorrhage, endophthalmitis, retro-prosthetic membrane, uncontrolled glaucoma, the last two being more common in Boston KPro. CONCLUSIONS: For both diagnoses, chemical injury and autoimmune diseases, there was a tendency for better long-term anatomical and functional results with Tibial bone KPro followed by OOKP and Boston KPro Type 1. However, these results were not statistically significant.

Automatic segmentation and classification of breast lesions through identification of informative multiparametric PET/MRI features.

BACKGROUND: Multiparametric positron emission tomography/magnetic resonance imaging (mpPET/MRI) shows clinical potential for detection and classification of breast lesions. Yet, the contribution of features for computer-aided segmentation and diagnosis (CAD) need to be better understood. We proposed a data-driven machine learning approach for a CAD system combining dynamic contrast-enhanced (DCE)-MRI, diffusion-weighted imaging (DWI), and 18F-fluorodeoxyglucose (18F-FDG)-PET. METHODS: The CAD incorporated a random forest (RF) classifier combined with mpPET/MRI intensity-based features for lesion segmentation and shape features, kinetic and spatio-temporal texture features, for lesion classification. The CAD pipeline detected and segmented suspicious regions and classified lesions as benign or malignant. The inherent feature selection method of RF and alternatively the minimum-redundancy-maximum-relevance feature ranking method were used. RESULTS: In 34 patients, we report a detection rate of 10/12 (83.3%) and 22/22 (100%) for benign and malignant lesions, respectively, a Dice similarity coefficient of 0.665 for segmentation, and a classification performance with an area under the curve at receiver operating characteristics analysis of 0.978, a sensitivity of 0.946, and a specificity of 0.936. Segmentation but not classification performance of DCE-MRI improved with information from DWI and FDG-PET. Feature ranking revealed that kinetic and spatio-temporal texture features had the highest contribution for lesion classification. 18F-FDG-PET and morphologic features were less predictive. CONCLUSION: Our CAD enables the assessment of the relevance of mpPET/MRI features on segmentation and classification accuracy. It may aid as a novel computational tool for exploring different modalities/features and their contributions for the detection and classification of breast lesions.

Microvessels may Confound the "Swallow Tail Sign" in Normal Aged Midbrains: A Postmortem 7 T SW-MRI Study.

BACKGROUND AND PURPOSE: Susceptibility weighted imaging (SWI) plays a role in the differential diagnosis of Parkinson's disease, but lacks widespread acceptance in clinical routine. In a descriptive pilot study, we assessed hypointense microstructures of the normal substantia nigra pars compacta at ultrahigh-field strength for interpretation of the "swallow tail sign." METHODS: Magnetic resonance imaging at 7 Tesla was performed in five postmortem samples obtained from subjects not affected by Parkinson's disease. Susceptibility weighted images, including minimum intensity projections, were created followed by consensus assessment for microvascular confound. Histological workup in this case-control study included iron and myelin staining. Seven Tesla SWI images from the reference cohort of nine living subjects, all of which showed a positive "swallow tail sign" in their midbrains, were assessed visually. RESULTS: All specimens showed microvessels running through the dorsal pars compacta and along the caudolateral circumference of the red nucleus. Hypointense imaging patterns in the medial part of the "swallow tail" were due to susceptibility effects of iron deposits and microvessels. In eight out of nine control subjects, one or more microvessels were detected medial to the dorsolateral nigral hyperintensity or at least unilaterally in the medial part of the "swallow tail." One microvessel crossing nigrosome 1 was found in two in-vivo cases. CONCLUSION: Both iron deposits and microvessels contribute to the hyposignal surrounding nigrosome 1 in susceptibility weighted imaging of normal aged midbrains at ultrahigh-field strength. When assessing the substantia nigra for the presence or absence of the "swallow tail sign," intrinsic vessels may be a sporadic confounder.

The influence of brain iron and myelin on magnetic susceptibility and effective transverse relaxation - A biochemical and histological validation study.

Quantitative susceptibility mapping (QSM) and effective transverse relaxation rate (R2*) mapping are both highly sensitive to variations in brain iron content. Clinical Magnetic Resonance Imaging (MRI) studies report changes of susceptibilities and relaxation rates in various neurological diseases which are often equated with changes in regional brain iron content. However, these mentioned metrics lack specificity for iron, since they are also influenced by the presence of myelin. In this study, we assessed the extent to which QSM and R2* reflect iron concentration as well as histological iron and myelin intensities. Six unfixed human post-mortem brains were imaged in situ with a 7 T MRI scanner. After formalin fixation, the brains were sliced axially and punched. 671 tissue punches were subjected to ferrozine iron quantification. Subsequently, brain slices were embedded in paraffin, and histological double-hemispheric axial brain slices were stained for Luxol fast blue (myelin) and diaminobenzidine (DAB)-enhanced Turnbull blue (iron). 3331 regions of interest (ROIs) were drawn on the histological stainings to assess myelin and iron intensities, which were compared with MRI data in corresponding ROIs. QSM more closely reflected quantitative ferrozine iron values (r = 0.755 vs. 0.738), whereas R2* correlated better with iron staining intensities (r = 0.619 vs. 0.445). Myelin intensities correlated negatively with QSM (r = -0.352), indicating a diamagnetic effect of myelin on susceptibility. Myelin intensities were higher in the thalamus than in the basal ganglia. A significant relationship was nonetheless observed between quantitative iron values and QSM, confirming the applicability of the latter in this brain region for iron quantification.

Noise reduction in FLAIR2 images using total generalized variation, Gaussian and Wiener filtering.

PURPOSE: Multiplication of FLAIR and T2-weighted MRI scans results in images (called FLAIR2) with an improved contrast-to-noise ratio (CNR) for multiple sclerosis (MS) lesions but with a reduced signal-to-noise ratio (SNR). Denoising of these images may therefore further improve FLAIR2 image quality. The purpose of this work is to present a systematic investigation of FLAIR2 image denoising methods using Gaussian, Wiener and Total Generalized Variation (TGV) filtering approaches. MATERIALS AND METHODS: T2-weighted and FLAIR data of four MS patients were used. For CNR and SNR measurements, each scan was performed up to three times. TGV, Gaussian and Wiener filtering was applied to T2, FLAIR and the FLAIR2 data. FLAIR2 images were afterwards additionally created using all combinations of input data (native, filtered T2 and filtered FLAIR). SNR and CNR measurements were performed using the subtraction method for all FLAIR2 approaches (native and filtered input data) and for twenty MS lesions. Additionally, quantitative analysis of filtering based image blurring was performed on all data sets. RESULTS: FLAIR2 images denoised with TGV showed the highest SNR and CNR, while SNR values were similar for Gaussian and Wiener filtered images. The average CNR over 20 MS lesions within the native FLAIR2 (32.99) achieved an improvement to 91.17, 82.33 and 56.07 corresponding to TGV, Wiener and Gaussian filtering. FLAIR multiplied with T2.denoised showed no improvement, while FLAIR.denoised multiplied with T2 showed an increase by a factor of two to the native, not filtered FLAIR2. Blurring was most pronounced in Gaussian filtered images and similar in TGV and Wiener filtered images. CONCLUSION: FLAIR images filtered with Wiener or TGV multiplied with the unfiltered T2 results in FLAIR2 images with increased SNR and CNR and with minimal edge blurring.

Genetics in Keratoconus - What is New?

BACKGROUND: Keratoconus is characterized as a bilateral, progressive, non-inflammatory thinning of the cornea resulting in blurred vision due to irregular astigmatism. Keratoconus has a multifactorial etiology, with multiple genetic and environmental components contributing to the disease pathophysiology. Several genomic loci and genes have been identified that highlight the complex molecular etiology of this disease. CONCLUSION: The review focuses on current knowledge of these genetic risk factors associated with keratoconus.

Post Mortem Validation of MRI-Identified Veins on the Surface of the Cerebral Cortex as Potential Landmarks for Neurosurgery.

Background and Objective: Image-guided neurosurgery uses information from a wide spectrum of methods to inform the neurosurgeon's judgement about which tissue to resect and which to spare. Imaging data are registered to the patient's skull so that they correspond to the intraoperative macro- and microscopic view. The correspondence between imaging and optical systems breaks down during surgery, however, as a result of cerebro-spinal fluid drain age, tissue resection, and gravity-based brain shift. In this work we investigate whether a map of surface veins, automatically segmented from MRI, could serve as additional reference system. Methods: Gradient-echo based [Formula: see text]-weighted imaging was performed on two human cadavers heads using a 7 Tesla MRI scanner. Automatic vessel segmentation was performed using the Frangi vesselness filter, and surface renderings of vessels compared with photographs of the surface of the brain following craniotomy. Results: A high level of correspondence was established between vessel maps and the post autopsy photographs. Corresponding veins, including the prominent superior anastomotic veins, could be identified in all brain lobes. Conclusion: Automatic surface vessel segmentation is feasible and the high correspondence to post autopsy photographs indicates that they could be used as an additional reference system for image-guided neurosurgery in order to maintain the correspondence between imaging and optical systems.This has the advantage over a skull-based reference system that veins are clearly visible to the surgeon and move and deform with the underlying tissue, potentially making this surface net of landmarks robust to brain shift.

Local image variance of 7 Tesla SWI is a new technique for preoperative characterization of diffusely infiltrating gliomas: correlation with tumour grade and IDH1 mutational status.

OBJECTIVES: To investigate the value of local image variance (LIV) as a new technique for quantification of hypointense microvascular susceptibility-weighted imaging (SWI) structures at 7 Tesla for preoperative glioma characterization. METHODS: Adult patients with neuroradiologically suspected diffusely infiltrating gliomas were prospectively recruited and 7 Tesla SWI was performed in addition to standard imaging. After tumour segmentation, quantification of intratumoural SWI hypointensities was conducted by the SWI-LIV technique. Following surgery, the histopathological tumour grade and isocitrate dehydrogenase 1 (IDH1)-R132H mutational status was determined and SWI-LIV values were compared between low-grade gliomas (LGG) and high-grade gliomas (HGG), IDH1-R132H negative and positive tumours, as well as gliomas with significant and non-significant contrast-enhancement (CE) on MRI. RESULTS: In 30 patients, 9 LGG and 21 HGG were diagnosed. The calculation of SWI-LIV values was feasible in all tumours. Significantly higher mean SWI-LIV values were found in HGG compared to LGG (92.7 versus 30.8; p < 0.0001), IDH1-R132H negative compared to IDH1-R132H positive gliomas (109.9 versus 38.3; p < 0.0001) and tumours with significant CE compared to non-significant CE (120.1 versus 39.0; p < 0.0001). CONCLUSIONS: Our data indicate that 7 Tesla SWI-LIV might improve preoperative characterization of diffusely infiltrating gliomas and thus optimize patient management by quantification of hypointense microvascular structures. KEY POINTS: • 7 Tesla local image variance helps to quantify hypointense susceptibility-weighted imaging structures. • SWI-LIV is significantly increased in high-grade and IDH1-R132H negative gliomas. • SWI-LIV is a promising technique for improved preoperative glioma characterization. • Preoperative management of diffusely infiltrating gliomas will be optimized.

Combining phase images from array coils using a short echo time reference scan (COMPOSER).

PURPOSE: To develop a simple method for combining phase images from multichannel coils that does not require a reference coil and does not entail phase unwrapping, fitting or iterative procedures. THEORY AND METHODS: At very short echo time, the phase measured with each coil of an array approximates to the phase offset to which the image from that coil is subject. Subtracting this information from the phase of the scan of interest matches the phases from the coils, allowing them to be combined. The effectiveness of this approach is quantified in the brain, calf and breast with coils of diverse designs. RESULTS: The quality of phase matching between coil elements was close to 100% with all coils assessed even in regions of low signal. This method of phase combination was similar in effectiveness to the Roemer method (which needs a reference coil) and was superior to the rival reference-coil-free approaches tested. CONCLUSION: The proposed approach-COMbining Phase data using a Short Echo-time Reference scan (COMPOSER)-is a simple and effective approach to reconstructing phase images from multichannel coils. It requires little additional scan time, is compatible with parallel imaging and is applicable to all coils, independent of configuration. Magn Reson Med 77:318-327, 2017. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging.

In multiple sclerosis (MS), iron accumulates inside activated microglia/macrophages at edges of some chronic demyelinated lesions, forming rims. In susceptibility-based magnetic resonance imaging at 7 T, iron-laden microglia/macrophages induce a rim of decreased signal at lesion edges and have been associated with slowly expanding lesions. We aimed to determine (1) what lesion types and stages are associated with iron accumulation at their edges, (2) what cells at the lesion edges accumulate iron and what is their activation status, (3) how reliably can iron accumulation at the lesion edge be detected by 7 T magnetic resonance imaging (MRI), and (4) if lesions with rims enlarge over time in vivo, when compared to lesions without rims. Double-hemispheric brain sections of 28 MS cases were stained for iron, myelin, and microglia/macrophages. Prior to histology, 4 of these 28 cases were imaged at 7 T using post-mortem susceptibility-weighted imaging. In vivo, seven MS patients underwent annual neurological examinations and 7 T MRI for 3.5 years, using a fluid attenuated inversion recovery/susceptibility-weighted imaging fusion sequence. Pathologically, we found iron rims around slowly expanding and some inactive lesions but hardly around remyelinated shadow plaques. Iron in rims was mainly present in microglia/macrophages with a pro-inflammatory activation status, but only very rarely in astrocytes. Histological validation of post-mortem susceptibility-weighted imaging revealed a quantitative threshold of iron-laden microglia when a rim was visible. Slowly expanding lesions significantly exceeded this threshold, when compared with inactive lesions (p = 0.003). We show for the first time that rim lesions significantly expanded in vivo after 3.5 years, compared to lesions without rims (p = 0.003). Thus, slow expansion of MS lesions with rims, which reflects chronic lesion activity, may, in the future, become an MRI marker for disease activity in MS.

Visual, aberrometric, photic phenomena, and patient satisfaction after myopic wavefront-guided LASIK using a high-resolution aberrometer.

PURPOSE: The purpose of this study was to evaluate the visual, refractive, and aberrometric outcomes as well as the level of patient satisfaction and photic phenomena after myopic laser in situ keratomileusis (LASIK) surgery using wavefront-guided (WFG) ablations based on measurements obtained with a high-resolution aberrometer. PATIENTS AND METHODS: This study was a prospective analysis including 253 eyes of 127 patients (aged between 19 years and 54 years) undergoing WFG LASIK using the STAR S4 IR Excimer Laser System combined with the iDesign System and iFS Femtosecond Laser. Visual, refractive, and aberrometric outcomes during a 2-month follow-up as well as patient satisfaction and photic phenomena were evaluated by means of a questionnaire. RESULTS: A total of 85% (215/253) and 99% (251/253) of eyes achieved a postoperative (Postop) uncorrected distance visual acuity of 20/16 and 20/20, respectively, and all eyes achieved an uncorrected distance visual acuity of 20/25. Postop spherical equivalent values were within ±0.25 D and ±0.50 D in 97% and 100% of eyes, respectively. Likewise, manifest cylinder was <0.25 D in 97% (245/253) of eyes. A statistically significant reduction was found in the total root mean square (P<0.001) and in the level of primary spherical aberration (P=0.001). Postop difficulties related to vision were graded as minimal, with low levels of photic phenomena and high levels of patient satisfaction. The level of difficulty to perform daily activities and the level of glare perceived by patients while driving car were significantly decreased (P<0.001). CONCLUSION: WFG LASIK surgery using the technology evaluated is predictable and effective for the correction of myopia and leads to high levels of patient satisfaction.

Comparison of short-term refractive surgery outcomes after wavefront-guided versus non-wavefront-guided LASIK.

PURPOSE: To evaluate and compare visual and refractive outcomes after laser-assisted in situ keratomileusis (LASIK) surgery for the correction of myopia or myopic astigmatism using 3 different treatment protocols. METHODS: We included 736 eyes of 369 patients (age 18-62 years) divided into 3 groups: 235 eyes of 118 patients (MEL80 group) undergoing LASIK using optimized aspheric ablation profiles (MEL80 excimer laser; Carl Zeiss Meditec), 248 eyes of 124 patients (Wavescan group) undergoing wavefront-guided (WFG) LASIK (STAR S4IR excimer laser + Wavescan aberrometer; Abbott Medical Optics), and 253 eyes of 127 patients (iDesign group) undergoing WFG LASIK (STAR S4IR excimer laser + iDesign system; Abbott Medical Optics). Visual and refractive outcomes were evaluated 2 months after surgery. RESULTS: A total of 91% (215/235), 95% (237/248), and 99% (251/253) of eyes achieved a postoperative uncorrected distance visual acuity of 0.0 logMAR (≈20/20) in the MEL80, Wavescan, and iDesign groups, respectively. Postoperative spherical equivalent (SE) was within ±0.5 D in 95% (223/235), 98% (242/248), and 100% (253/253) of eyes in these same 3 groups, respectively. Likewise, manifest cylinder was below 0.50 D in 95% (223/235), 97% (241/248), and 100% (253/253) of eyes. Significant differences in postoperative SE and cylinder were found between the MEL80 and iDesign groups (p<0.05). CONCLUSIONS: All evaluated LASIK treatment protocols are predictable and effective for the correction of myopia. The treatment planned with a high resolution aberrometer obtained the best postoperative refractive outcomes.

Immunohistochemical Detection of CTGF in the Human Eye.

Purpose/Aim of the study: Connective tissue growth factor (CTGF) is a key player in the control of extracellular matrix remodeling, fibrosis, and angiogenesis. It is also involved in the modification of the trabecular meshwork, thus potentially modulating outflow facility and intraocular pressure (IOP). As a consequence, CTGF might be relevant for the development of elevated IOP, a major risk factor in glaucoma-pathogenesis. While comprehensive information on the origins of CTGF in the human eye is not available, the goal of this study is to identify ocular sources of CTGF using morphological methods. MATERIALS AND METHODS: Human donor eyes were prepared for immunohistochemical analysis of CTGF, α-smooth muscle-actin (ASMA), and CD31. Confocal laser scanning microscopy was used for documentation. RESULTS: In the cornea, CTGF-immunoreactivity (CTGF-IR) was detected in the epithelium, mainly in basal layers, stromal keratinocytes, and endothelial cells. Adjacent conjunctiva showed also CTGF-IR in epithelial cells. In the iris, both, the sphincter and dilator muscles displayed CGTF-IR, as did iris and ciliary body vessels, deriving at this location from the vascular endothelium, as detected with CD31, but not from vascular smooth muscle cells, as detected with ASMA. In the ciliary body, CTGF-IR was detected in smooth-muscle cells of the ciliary muscle and further in the non-pigmented epithelium. In the retina, CTGF-IR was detected in the NFL and weakly in the IPL/OPL. In the choroid, the choriocapillaris and blood vessels displayed CTGF-IR. Further, few cells in the optic nerve head and the lamina cribrosa were CTGF-positive. CONCLUSION: CTGF was detected in various structures of the human eye. Since CTGF has been also described in aqueous humor, the identified structures might be the sources of CTGF in the aqueous humor. By means of aqueous flow, CTGF is transported into the trabecular meshwork, where it could change outflow facility and therefore affecting IOP homeostasis.

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies.

The Ocular Surface and How It Can Influence the Outcomes of Keratoprosthesis.

Severe ocular diseases may result in partial or complete limbal cell deficiency. Besides conservative options, treatment options include conjunctival replacement procedures and limbal autografting. Limbal allografts are an option in patients with bilateral limbal cell deficiency. In many of these cases, a keratoprosthesis (KPro) is the last option to restore functional vision in patients with severe corneal blindness with no other options.

Suggested Guidelines for Reporting Keratoprosthesis Results: Consensus Opinion of the Cornea Society, Asia Cornea Society, EuCornea, PanCornea, and the KPRO Study Group.

PURPOSE: To propose a series of standardized guidelines for reporting keratoprosthesis (KPRO) results. METHODS: At the most recent KPRO Study Group Meeting (Barcelona, 2015), representatives of the 4 multinational corneal societies (Cornea Society, Asia Cornea Society, EuCornea, and PanCornea) and the KPRO Study Group agreed to propose consistent terminology for reporting KPRO results, especially in describing the length of follow-up and in the description of the KPRO itself. Consensus was reached for minimal reporting guidelines. RESULTS: The 4 multinational corneal societies and the KPRO Study Group agreed to standardized terminology for reporting the length of follow-up, preoperative diagnosis grouping, and data stratification based on the KPRO type used. CONCLUSIONS: Guidelines suggesting minimal reporting standards will assist in both data collection and reporting and will allow for better comparative analysis and pooling of the available data.