Fluocinolone Acetonide Implant for Uveitis: Dissecting Responder and Non-Responder Outcomes at a Tertiary Center.

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.

Multi-resolution X-ray phase-contrast and dark-field tomography of human cerebellum with near-field speckles.

In this study, we use synchrotron-based multi-modal X-ray tomography to examine human cerebellar tissue in three dimensions at two levels of spatial resolution (2.3 µm and 11.9 µm). We show that speckle-based imaging (SBI) produces results that are comparable to propagation-based imaging (PBI), a well-established phase-sensitive imaging method. The different SBI signals provide complementary information, which improves tissue differentiation. In particular, the dark-field signal aids in distinguishing tissues with similar average electron density but different microstructural variations. The setup's high resolution and the imaging technique's excellent phase sensitivity enabled the identification of different cellular layers and additionally, different cell types within these layers. We also correlated this high-resolution phase-contrast information with measured dark-field signal levels. These findings demonstrate the viability of SBI and the potential benefit of the dark-field modality for virtual histology of brain tissue.

Retinal blood flow velocities in infants with retinopathy of prematurity after intravitreal administration of bevacizumab.

BACKGROUND/OBJECTIVES: Progression of retinopathy of prematurity (ROP) is associated with increased retinal blood flow velocities. We investigated changes of central retinal arterial and venous blood flow after intravitreal administration of bevacizumab. SUBJECTS/METHODS: Prospective observational study using serial ultrasound Doppler imaging in preterm infants with bevacizumab-treated ROP. Eyes were examined 1 [0-2] days before injection (median [interquartile range]), and at three time points after injection (1 [1-2] days, 6 [3-8] days, and 17 [9-28] days). Preterm infants with ROP stage 2 displaying spontaneous regression served as controls. RESULTS: In 21 eyes of 12 infants with bevacizumab-treated ROP, peak arterial systolic velocity declined from 13.6 [11.0-16.3] cm/s prior to intravitreal bevacizumab to 11.2 [9.4-13.9] cm/s, 10.6 [9.2-13.3] cm/s and 9.3 [8.2-11.0] cm/s at discharge (p = .002). There was also a decline of the arterial velocity time integral (from 3.1 [2.3-3.9] cm to 2.9 [2.4-3.5], 2.7 [2.3-3.2] cm and 2.2 [2.0-2.7], p = .021) and mean velocity in the central retinal vein (from 4.5 [3.6-5.8] cm/s to 3.7 [2.6-4.1] cm/s, 3.5 [3.0-4.3] cm/s, and 3.2 [2.8-4.6] cm/s, p = .012). Arterial end-diastolic velocity and resistance index remained unchanged. Blood flow velocities in bevacizumab-treated eyes examined before injection were significantly higher than those measured in untreated eyes that ultimately showed spontaneous regression of ROP. Sequential examinations in these controls did not reveal any declines of retinal blood flow velocities. CONCLUSION: Increased retinal arterial and venous blood flow velocities in infants with threshold ROP decline following intravitreal bevacizumab injection.

Terabyte-scale supervised 3D training and benchmarking dataset of the mouse kidney.

The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks.

3D X-ray Histology for the Investigation of Temporal Lobe Epilepsy in a Mouse Model.

The most common form of epilepsy among adults is mesial temporal lobe epilepsy (mTLE), with seizures often originating in the hippocampus due to abnormal electrical activity. The gold standard for the histopathological analysis of mTLE is histology, which is a two-dimensional technique. To fill this gap, we propose complementary three-dimensional (3D) X-ray histology. Herein, we used synchrotron radiation-based phase-contrast microtomography with 1.6 µm-wide voxels for the post mortem visualization of tissue microstructure in an intrahippocampal-kainate mouse model for mTLE. We demonstrated that the 3D X-ray histology of unstained, unsectioned, paraffin-embedded brain hemispheres can identify hippocampal sclerosis through the loss of pyramidal neurons in the first and third regions of the Cornu ammonis as well as granule cell dispersion within the dentate gyrus. Morphology and density changes during epileptogenesis were quantified by segmentations from a deep convolutional neural network. Compared to control mice, the total dentate gyrus volume doubled and the granular layer volume quadrupled 21 days after injecting kainate. Subsequent sectioning of the same mouse brains allowed for benchmarking 3D X-ray histology against well-established histochemical and immunofluorescence stainings. Thus, 3D X-ray histology is a complementary neuroimaging tool to unlock the third dimension for the cellular-resolution histopathological analysis of mTLE.

Apochromatic X-ray focusing.

Achromatic doublets are combinations of two individual lenses designed to focus different wavelengths of light in the same position. Apochromatic optics are improved versions of the achromatic schemes which extend the wavelength range significantly. Both achromatic and apochromatic optics are well-established for visible light. However, X-ray achromatic lenses did not exist until very recently, and X-ray apochromatic lenses have never been experimentally demonstrated. Here, we create an X-ray apochromatic lens system using an appropriate combination of a Fresnel zone plate and a diverging compound refractive lens with a tuned separation distance. The energy-dependent performance of this apochromat was characterized at photon energies between 6.5 and 13.0 keV by ptychographic reconstruction of the focal spot and scanning transmission X-ray microscopy of a resolution test sample. The apochromat delivered a reconstructed focal spot size of 940 × 740 nm2. The apochromatic combination shows a four-fold improvement in the chromatic aberration correction range compared to an achromatic doublet configuration. Thus, apochromatic X-ray optics have the potential to increase the focal spot intensity for a wide variety of X-ray applications.

Zebrafish (Danio rerio) larvae as a predictive model to study gentamicin-induced structural alterations of the kidney.

Nephrotoxicity is an important drug safety aspect to be assessed during drug discovery and development. To study renal toxicity, in vitro cell-based assays are often used. Unfortunately, translating the results of such cell assays to vertebrates including human remains challenging. Therefore, we aim to evaluate whether zebrafish larvae (ZFL) could serve as a vertebrate screening model to detect gentamicin-induced changes of kidney glomeruli and proximal tubules. To validate the model, we compared the results of ZFL with those obtained from kidney biopsies of gentamicin-treated mice. We used transgenic zebrafish lines expressing enhanced green fluorescent proteins in the glomerulus to visualize glomerular damage. Synchrotron radiation-based computed tomography (SRµCT) is a label-free approach providing three-dimensional representations of renal structures with micrometre resolution. Clinically used gentamicin concentrations induce nephrotoxicity and affect glomerular and proximal tubular morphology. Findings were confirmed in mice and ZFL. There was a strong correlation between fluorescent signals in ZFL, SRµCT- derived descriptors of glomerular and proximal tubular morphology and the histological analysis of mouse kidney biopsies. A combination of SRµCT and confocal microscopy provides unprecedented insights into anatomical structures of the zebrafish kidney. Based on our findings, we suggest to use ZFL as a predictive vertebrate screening model to study drug-induced nephrotoxicity and to bridge the gap between cell culture-based test systems and experiments in mammals.

Ruminant inner ear shape records 35 million years of neutral evolution.

Extrinsic and intrinsic factors impact diversity. On deep-time scales, the extrinsic impact of climate and geology are crucial, but poorly understood. Here, we use the inner ear morphology of ruminant artiodactyls to test for a deep-time correlation between a low adaptive anatomical structure and both extrinsic and intrinsic variables. We apply geometric morphometric analyses in a phylogenetic frame to X-ray computed tomographic data from 191 ruminant species. Contrasting results across ruminant clades show that neutral evolutionary processes over time may strongly influence the evolution of inner ear morphology. Extant, ecologically diversified clades increase their evolutionary rate with decreasing Cenozoic global temperatures. Evolutionary rate peaks with the colonization of new continents. Simultaneously, ecologically restricted clades show declining or unchanged rates. These results suggest that both climate and paleogeography produced heterogeneous environments, which likely facilitated Cervidae and Bovidae diversification and exemplifies the effect of extrinsic and intrinsic factors on evolution in ruminants.

Three-dimensional analysis of aligner gaps and thickness distributions, using hard x-ray tomography with micrometer resolution.

Purpose: The morphology of a polymer aligner, designed according to an orthodontic treatment plan, determines clinical outcomes. A fundamental element of orthodontic tooth movement with aligner treatment is the fit of the aligner's surface to the individual teeth. Gaps between the aligner and teeth do occur because current aligner fabrication is not capable of completely reproducing the complex anatomy of the individual denture. Our study aims at a quantitative three-dimensional assessment of the fit between optically transparent aligners placed on a polymeric model of the upper dental arch for two thermofoil thicknesses at preselected thermoforming temperatures. Approach: Using an intraoral scan of a subject's upper dental arch, eight models were printed using a stereolithographic system. A series of eight NaturAligners® was manufactured with a pressure molding process, using thermofoils with thicknesses of 550 and 750 µ m and preselected process temperatures between 110°C and 210°C. These aligners placed on the corresponding models were imaged by an advanced micro computed tomography system. The aligners and the models were segmented to extract the gaps and aligners' local thicknesses as a function of the processing temperature for the two foil thicknesses. Results: The results indicate that the aligners show a better fit when the foils are processed at higher temperatures. Nevertheless, processing temperatures can be kept below 150°C, as the gain becomes negligible. Thermal processing reduces the average thickness of the aligners to 60% with respect to the planar starting foil. These thickness distributions demonstrate that the aligners are generally thicker on the occlusal surfaces of molars and premolars but thinner around the incisors and buccal as well as on oral surfaces. Conclusions: Hard x-ray tomography with micrometer resolution is a powerful technique employed to localize the gaps between aligners and teeth, and it also enables film thickness measurements after thermoforming. The thicker film on the occlusal surfaces is most welcome because of aligner abrasion during wear. The NaturAligner® surfaces consist of a 25 - µ m -thin cellulose layer, and thus the microplastics released via abrasion of less than this thickness are expected to be substantially less critical than for other commercially available, optically transparent aligners.

Special Section Guest Editorial: Hard X-Ray Tomography with Micrometer Resolution.

JMI guest editors introduce articles collected in the JMI Special Section on Hard X-Ray Tomography with Micrometer Resolution, a snapshot of this important niche area featured by hard x-ray tomography at the micrometer level.

Comparative hard x-ray tomography for virtual histology of zebrafish larva, human tooth cementum, and porcine nerve.

Purpose: Synchrotron radiation-based tomography yields microanatomical features in human and animal tissues without physical slicing. Recent advances in instrumentation have made laboratory-based phase tomography feasible. We compared the performance of three cutting-edge laboratory systems benchmarked by synchrotron radiation-based tomography for three specimens. As an additional criterion, the user-friendliness of the three microtomography systems was considered. Approach: The three tomography systems-SkyScan 2214 (Bruker-microCT, Kontich, Belgium), Exciscope prototype (Stockholm, Sweden), and Xradia 620 Versa (Zeiss, Oberkochen, Germany)-were given 36 h to measure three medically relevant specimens, namely, zebrafish larva, archaeological human tooth, and porcine nerve. The obtained datasets were registered to the benchmark synchrotron radiation-based tomography from the same specimens and selected ones to the SkyScan 1275 and phoenix nanotom m® laboratory systems to characterize development over the last decade. Results: Next-generation laboratory-based microtomography almost reached the quality achieved by synchrotron-radiation facilities with respect to spatial and density resolution, as indicated by the visualization of the medically relevant microanatomical features. The SkyScan 2214 system and the Exciscope prototype demonstrated the complementarity of phase information by imaging the eyes of the zebrafish larva. The 3 - µ m thin annual layers in the tooth cementum were identified using Xradia 620 Versa. Conclusions: SkyScan 2214 was the simplest system and was well-suited to visualizing the wealth of anatomical features in the zebrafish larva. Data from the Exciscope prototype with the high photon flux from the liquid metal source showed the spiral nature of the myelin sheaths in the porcine nerve. Xradia 620 Versa, with detector optics as typically installed for synchrotron tomography beamlines, enabled the three-dimensional visualization of the zebrafish larva with comparable quality to the synchrotron data and the annual layers in the tooth cementum.

Comparing efficacy and side effects of two systemic chemotherapy regimens for eye-preserving therapy in children with retinoblastoma.

BACKGROUND: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. METHODS: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. RESULTS: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank  < .001). The OES did not differ significantly between the two treatment groups (plogrank  = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank  < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank  < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years). CONCLUSIONS: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.

Virtual histology of an entire mouse brain from formalin fixation to paraffin embedding. Part 2: Volumetric strain fields and local contrast changes.

BACKGROUND: Fixation and embedding of post mortem brain tissue is a pre-requisite for both gold-standard conventional histology and X-ray virtual histology. This process alters the morphology and density of the brain microanatomy. NEW METHOD: To quantify these changes, we employed synchrotron radiation-based hard X-ray tomography with 3 µm voxel length to visualize the same mouse brain after fixation in 4% formalin, immersion in ethanol solutions (50%, 70%, 80%, 90%, and 100%), xylene, and finally after embedding in a paraffin block. The volumetric data were non-rigidly registered to the initial formalin-fixed state to align the microanatomy within the entire mouse brain. RESULTS: Volumetric strain fields were used to characterize local shrinkage, which was found to depend on the anatomical region and distance to external surface. X-ray contrast was altered and enhanced by preparation-induced inter-tissue density changes. The preparation step can be selected to highlight specific anatomical features. For example, fiber tract contrast is amplified in 100% ethanol. COMPARISON WITH EXISTING METHODS: Our method provides volumetric strain fields, unlike approaches based on feature-to-feature or volume measurements. Volumetric strain fields are produced by non-rigid registration, which is less labor-intensive and observer-dependent than volume change measurements based on manual segmentations. X-ray microtomography provides spatial resolution at least an order of magnitude higher than magnetic resonance microscopy, allowing for analysis of morphology and density changes within the brain's microanatomy. CONCLUSION: Our approach belongs to three-dimensional virtual histology with isotropic micrometer spatial resolution and therefore complements atlases based on a combination of magnetic resonance microscopy and optical micrographs of serial histological sections.

Virtual histology of an entire mouse brain from formalin fixation to paraffin embedding. Part 1: Data acquisition, anatomical feature segmentation, tracking global volume and density changes.

BACKGROUND: Micrometer-resolution neuroimaging with gold-standard conventional histology requires tissue fixation and embedding. The exchange of solvents for the creation of sectionable paraffin blocks modifies tissue density and generates non-uniform brain shrinkage. NEW METHOD: We employed synchrotron radiation-based X-ray microtomography for slicing- and label-free virtual histology of the mouse brain at different stages of the standard preparation protocol from formalin fixation via ascending ethanol solutions and xylene to paraffin embedding. Segmentation of anatomical regions allowed us to quantify non-uniform tissue shrinkage. Global and local changes in X-ray absorption gave insight into contrast enhancement for virtual histology. RESULTS: The volume of the entire mouse brain was 60%, 56%, and 40% of that in formalin for, respectively, 100% ethanol, xylene, and paraffin. The volume changes of anatomical regions such as the hippocampus, anterior commissure, and ventricles differ from the global volume change. X-ray absorption of the full brain decreased, while local absorption differences increased, resulting in enhanced contrast for virtual histology. These trends were also observed with laboratory microtomography measurements. COMPARISON WITH EXISTING METHODS: Microtomography provided sub-10 µm spatial resolution with sufficient density resolution to resolve anatomical structures at each step of the embedding protocol. The spatial resolution of conventional computed tomography and magnetic resonance microscopy is an order of magnitude lower and both do not match the contrast of microtomography over the entire embedding protocol. Unlike feature-to-feature or total volume measurements, our approach allows for calculation of volume change based on segmentation. CONCLUSION: We present isotropic micrometer-resolution imaging to quantify morphology and composition changes in a mouse brain during the standard histological preparation. The proposed method can be employed to identify the most appropriate embedding medium for anatomical feature visualization, to reveal the basis for the dramatic X-ray contrast enhancement observed in numerous embedded tissues, and to quantify morphological changes during tissue fixation and embedding.

Mechanistic Illustration: How Newly-Formed Blood Vessels Stopped by the Mineral Blocks of Bone Substitutes Can Be Avoided by Using Innovative Combined Therapeutics.

One major limitation for the vascularization of bone substitutes used for filling is the presence of mineral blocks. The newly-formed blood vessels are stopped or have to circumvent the mineral blocks, resulting in inefficient delivery of oxygen and nutrients to the implant. This leads to necrosis within the implant and to poor engraftment of the bone substitute. The aim of the present study is to provide a bone substitute currently used in the clinic with suitably guided vascularization properties. This therapeutic hybrid bone filling, containing a mineral and a polymeric component, is fortified with pro-angiogenic smart nano-therapeutics that allow the release of angiogenic molecules. Our data showed that the improved vasculature within the implant promoted new bone formation and that the newly-formed bone swapped the mineral blocks of the bone substitutes much more efficiently than in non-functionalized bone substitutes. Therefore, we demonstrated that our therapeutic bone substitute is an advanced therapeutical medicinal product, with great potential to recuperate and guide vascularization that is stopped by mineral blocks, and can improve the regeneration of critical-sized bone defects. We have also elucidated the mechanism to understand how the newly-formed vessels can no longer encounter mineral blocks and pursue their course of vasculature, giving our advanced therapeutical bone filling great potential to be used in many applications, by combining filling and nano-regenerative medicine that currently fall short because of problems related to the lack of oxygen and nutrients.

Accuracy of commercial intraoral scanners.

Purpose: In dental offices, there is a trend replacing conventional silicone impressions and plaster cast models by imaging data of intraoral scanners to map the denture and surrounding tissues. The aim of the study is the analysis of the accuracy of selected commercially available scanners. The accuracy is considered as the main drawback in comparison to the conventional approach. Approach: We evaluated the reproduction performance of five optical scanners by a direct comparison with high-resolution hard x-ray computed tomography data, all obtained from a polyetheretherketone model with similarity to a full-arch upper jaw. Results: Using the software GOM Inspect (GOM GmbH, Braunschweig, Germany), we could classify the intraoral scanners into two groups. The more accurate instruments gave rise to the following precision values: 35 µ m (TRIOS® 3, 3shape, Copenhagen, Denmark), 43 µ m (CS 3600, Carestream, Atlanta, Georgia), and 46 µ m (3M™ True Definition Scanner, 3M ESPE, St. Paul, Minnesota). The less precise systems yielded 93 µ m (Medit i500, Medit corp., Seongbuk-gu, South Korea) and 97 µ m (Emerald™, Planmeca Oy, Helsinki, Finland). Conclusions: The selected scanners are suitable for single crowns, small bridges, and separate quadrants prostheses. Scanners based on triangulation are hardly appropriate for full-arch prostheses. Besides precision, however, the choice of the scanner depends on scanning time, intraoral-camera size, and the user's learning curve. The developed protocol, which includes three-dimensional (3D) imaging and advanced computational tools for the registration with the design data, will be increasingly used in geometrical metrology by nondestructive procedures to perform dimensional measurements with micrometer precision and is capable for detailed 3D geometrical models reconstruction.

Behavior of SD-OCT Detectable Hyperreflective Foci in Diabetic Macular Edema Patients after Therapy with Anti-VEGF Agents and Dexamethasone Implants.

PURPOSE: Diabetic macular edema (DME) is the most common cause of blindness in the working-age population. Spectral-domain optical coherence tomography (SD-OCT) allows detection and monitoring of the edema and a detailed analysis of the retinal structure. Hyperreflective foci (HF) are small, circumscribed lesions on OCT, and their origin is yet to be determined. Our study was aimed to shed light on HF pathophysiology, by analyzing their number and location in DME patients at baseline and after therapy. METHODS: A prospective, observational study on 59 eyes of 51 DME patients who were treated with antivascular endothelial growth factor (VEGF) therapy (VEGF group, n = 40 eyes) or dexamethasone implant (DEX group, n = 19). HF and hard exudates (HE) were discriminated by their appearance on fundus photographs and their size on OCT. Quantity and location of HF and HE were analyzed at baseline and after therapy. RESULTS: DME decreased in 75% of patients in the VEGF (455.5 µm vs. 380.8 µm, p = 0.02) and in 95% of patients in the DEX group (471.6 µm vs. 381.9 µm, p = 0.007). The number of foci decreased in 62.5% of patients after anti-VEGF (130.6 vs. 111.1, p = 0.07) and in 68% of patients after dexamethasone injection ((123.4 vs. 94.9, p = 0.02) 5.1). A subgroup of 15% of eyes, all treated with anti-VEGF, showed accumulation of larger HF in outer retinal layers to visible HE during DME resolution, whereas smaller HF, found in all retinal layers, remained unchanged. There was a trend towards a dynamic shift of the foci from inner to outer retinal layers. CONCLUSION: The dynamic rearrangement of the small HF and their slightly greater reduction after anti-inflammatory therapy suggest inflammatory cells as their origin, whereas larger HF in the outer retinal layers correspond to microexudates. Furthermore, we found a more favourable outcome in patients with HF after treatment with dexamethasone implants compared to anti-VEGF agents.

Eye Tumors in Childhood as First Sign of Tumor Predisposition Syndromes: Insights from an Observational Study Conducted in Germany and Austria.

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in DICER1 was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality.

Reentry of endodontic access cavities: composite residue and loss of tooth substance.

The purpose of this study was to investigate the ability of dentists to remove composite fillings from endodontic access cavities using illumination from a conventional light source (CLS) versus the fluorescence-aided identification technique (FIT) in terms of completeness, selectivity and treatment duration. Therefore, two independent operators removed composite resin from six sets of root-filled incisors in a maxillary model under simulated clinical conditions using the CLS or FIT method (twelve teeth per operator and technique). The duration of treatment was recorded and before-after micro-CT scans were superimposed for volumetric assessment of treatment completeness and selectivity. Statistical significance was determined by t-testing and two-way ANOVA for operator comparison. Overall, there was no significant difference between FIT and CLS in terms of volume, height and area of composite residues (p=0.98 / p=0.75 / p=0.64) and regarding hard tissue loss in terms of volume, depth and area (p= 0.93 / p= 0.70 / p= 0.14). However, there was a significant difference between the two groups regarding treatment time (FIT= 428s, CLS=523s; p=0.023). Significant differences between operators regardless of method were found for volume, height and area of composite residues (p<0.05) and also for defect area (p=0.01) and time (p<0.001). Significant differences between operators including the method was only found for height of composites (p=0.037). It can be concluded, that composite remnants and tooth structure losses may occur after reentry of root-filled teeth regardless of the illumination method (conventional vs. fluorescence-aided) and operator, but preparation was less time-consuming with FIT.

Vascular findings in primarily affected and fellow eyes of middle-aged patients with Coats' disease using multimodal imaging.

AIMS: To investigate the retinal vascular structure and capillary anomalies of affected and fellow eyes of patients with unilateral Coats' disease using multimodal imaging. METHODS: Clinical investigation of both eyes of each patient with diagnosed Coats' disease using ultra-widefield (UWF) fundus imaging, including UWF fluorescein angiography (UWFFA), spectral domain optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). RESULTS: We analysed 38 eyes of 19 patients with unilateral Coats' disease and found that all fellow eyes (19/19; 100%) revealed vascular alterations, detected by UWFFA, predominantly located in the temporal periphery. Thereby, 89% of the fellow eyes (17/19) presented capillary bed abnormalities, that did not exceed the capillary level; 58% (11/19) presented tortuous abnormalities and 26% (5/19) presented microaneurysmatic abnormalities, exceeding the capillary level. If primarily affected eyes presented central Coats' specific vascular abnormalities, fellow eyes revealed tortuous vascular abnormalities twice as often (78% (7/9) vs 40% (4/10); P=0.096). In primarily affected eyes, a tendency towards larger foveal avascular zones was revealed, compared to fellow eyes (0.28±0.16 mm2 vs 0.20±0.10 mm2; P=0.123). CONCLUSION: The use of modern multimodal imaging allows the detection of even subtle vascular changes in fellow eyes of patients with Coats' disease. Coats' disease appears to be a bilateral ocular disease with a predominant manifestation in one eye of the affected patients.