Ophthalmological Diseases Research Articles

Mapping of choriocapillaris vascular density in young and aged healthy subjects.

To compare macular vascular density (VD) of the choriocapillaris (CC) between young and aged healthy individuals. A cross-sectional study was performed enrolling young and senior healthy individuals of Caucasian race and an axial length (AL) lower than 26 mm, and without systemic or ophthalmological diseases. CC VD was imaged with DRI Triton OCTA using a 6 × 6 mm macular analysis. Internal software delimited CC boundaries and gave colour pictures, which were analysed and codified into numbers, and a grid of 30 × 30 VD values was obtained. Two-dimension (2D) and three-dimension (3D) representations were created. 53 eyes of 53 young healthy individuals and 30 eyes of 30 senior healthy individuals were enrolled. Mean age was 27.17 ± 3.90 years, and 67.00 ± 7.41 years, respectively (p < 0.001). There were no differences in intraocular pressure (IOP) or AL (23.73 ± 0.79 mm, 23.18 ± 0.80 mm, respectively, p = 0.24). There were differences in foveal VD and in temporal perifoveal macula, but not in nasal perifoveal macula. Foveal VD was the highest in both groups. Foveal CC VD has been found to be considerably high with this method, and it is the area which most decreases with age. Nasal perifoveal VD is not reduced in older individuals. These outcomes are opposite to other studies using different methods but they are in line with previous histological findings.

Ophthalmic drugs: in vitro paraoxonase 1 inhibition and molecular docking studies.

Glaucoma is a neuropathy disorder and is generally treated by drugs. Allergic conjunctivitis is a common ophthalmologic disease. Paraoxonase 1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. PON1 is known for preventing atherosclerosis through lipid-modifying features, as well as which has decisive actions of antiapoptosis, anti-inflammatory, antithrombosis, and antiadhesion antioxidant activity properties. Thus, reducing the enzyme levels in hyperthyroidism, chronic renal failure, glaucoma, diabetes mellitus, and cardiovascular diseases is a significant risk. This study was tested some ophthalmic drugs used to treat the diseases, such as glaucoma and allergic conjunctivitis, mentioned above, travoprost, latanoprost, ketotifen, emedastine, and olopatadine, for their inhibition activities against PON1. These drugs displayed the potent inhibition effect with IC50 values ranging between 14.95 ± 0.15 and 299.60 ± 4.07 μM and KI constants ranging from 9.71 ± 2.63 to 261.50 ± 59.98 μM. Besides, the molecular docking analyses of the competitive inhibitors, travoprost, emedastine, and olopatadine, were performed to understand the binding interactions on the enzyme's binding site. According to both in vitro and in silico analysis results, travoprost had the most potent effect on PON1 enzyme activity.

An Effective and Robust Approach Based on R-CNN+LSTM Model and NCAR Feature Selection for Ophthalmological Disease Detection from Fundus Images.

Changes in and around anatomical structures such as blood vessels, optic disc, fovea, and macula can lead to ophthalmological diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration (AMD), myopia, hypertension, and cataracts. If these diseases are not diagnosed early, they may cause partial or complete loss of vision in patients. Fundus imaging is the primary method used to diagnose ophthalmologic diseases. In this study, a powerful R-CNN+LSTM-based approach is proposed that automatically detects eight different ophthalmologic diseases from fundus images. Deep features were extracted from fundus images with the proposed R-CNN+LSTM structure. Among the deep features extracted, those with high representative power were selected with an approach called NCAR, which is a multilevel feature selection algorithm. In the classification phase, the SVM algorithm, which is a powerful classifier, was used. The proposed approach is evaluated on the eight-class ODIR dataset. The accuracy (main metric), sensitivity, specificity, and precision metrics were used for the performance evaluation of the proposed approach. Besides, the performance of the proposed approach was compared with the existing approaches using the ODIR dataset.

Complementarity of Raman and Infrared spectroscopy for rapid characterization of fucoidan extracts

BackgroundFucoidans are sulfated polysaccharides from the cell-wall of brown algae. They have a wide range of applications in medicine, including regenerative medicine, ophthalmology, cancer, and autoimmune disease. Biological activity of fucoidans directly depends on their structure, which remains poorly understood. This is primarily because the polymeric nature of these molecules limits the use of nuclear magnetic resonance and mass spectrometry, classical tools of structural biology for their structural characterization. Raman and Infrared spectroscopies are non-invasive and non-destructive techniques that can be used to probe the structural organization of biological specimens. In this study, we investigate the potential of Raman and Infrared spectroscopy for structural analysis of several fucoidan extracts.ResultsOur results show that Infrared and Raman provide different but complimentary information about the structure of crude extracts of fucoidans, revealing the presence of minor impurities from co-extractants. We also found that at high extraction temperatures acidic conditions limit formation of melanoidins, while also yielding relatively high sulfate ester fucoidan. However, at high temperatures, water extraction may potentially result in formation of advanced glycation end products. Their presence could be problematic for fucoidan extracts intended for medicinal use, as advanced glycation end products have been linked to endocrine interruption mechanisms in vivo by crosslinking to and permanently altering extracellular matrix proteins.ConclusionRaman and Infrared can be used as complementary tools for rapid screening of crude fucoidan extracts, which can be a valuable tool for assessing impurities that remain after extraction.

Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death

Ultraviolet (UV) is one of the most energetic radiations in the solar spectrum that can result in various tissue injury disorders. Previous studies demonstrated that UVA, which represents 95% of incident photovoltaic radiation, induces corneal endothelial cells (CECs) death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor-interacting protein 3 kinase (RIPK3), a key signaling molecule of PCD, in UVA-induced injury using a short-term corneal endothelium (CE) culture model. UVA irradiation activated RIPK3 and mediated necroptosis both in mouse CE and primary human CECs (pHCECs). UVA irradiation was associated with upregulation of key necroptotic molecules (DAI, TRIF, and MLKL) that lie downstream of RIPK3. Moreover, RIPK3 inhibition or silencing in primary corneal endothelial cells suppresses UVA-induced cell death, along with downregulation of MLKL in pHCECs. In addition, genetic inhibition or knockout of RIPK3 in mice (RIPK3K51A and RIPK3−/− mice) similarly attenuates cell death and the levels of necroptosis in ex vivo UVA irradiation experiments. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced cell death in CE and indicate its potential as a future protective target.

The influence of dizziness on the quality of life in elderly

Vertigo is a common complaint in elderly, which has significant influence on the patients' quality of life. In many cases its background is complex, although, in some cases specific diagnosis can be made. Our study aimed to analyze the symptoms and quality of life of old-age vertiginous population. 36 patients (13 males, 23 females, mean age ± SD, 72.78 years ± 4.6) over 65 years, examined due to vertigo at our Neurotologic Department, were enrolled. A questionnaire including questions regarding the symptoms, risk factors, along with the Dizziness Handicap Inventory was used. Statistical analysis was carried out using IBM SPSS V24 software. Mann-Whitney U and chi square tests were used. Statistical significance was defined as p<0.05. Ménière's disease and central vestibular disorders were found as the most frequent diagnoses. Vertigo was the most tormenting symptom, which usually lasted for hours or days, and was defined as rotatory in 50%. Tinnitus, hearing loss and vegetative symptoms were also dominant. The most frequent comorbidities were musculoskeletal disorders, hypertension, ophthalmological diseases and psychiatric disorders. 77.8% of the patients have reported worsened quality of life, of which 30% was detected as severe. Based on the Dizziness Handicap Inventory, physical, functional and emotional scores showed similar results. Vertigo in elderly is important due to its influence on patients' quality of life. Besides comorbidities, the diagnosis of vestibular pathologies is of great importance. Therefore, therapy planning is possible, and patients' quality of life can be improved. Orv Hetil. 2021; 162(47): 1891-1896.

A transcriptome atlas of the mouse iris at single-cell resolution defines cell types and the genomic response to pupil dilation.

The iris controls the level of retinal illumination by controlling pupil diameter. It is a site of diverse ophthalmologic diseases and it is a potential source of cells for ocular auto-transplantation. The present study provides foundational data on the mouse iris based on single nucleus RNA sequencing. More specifically, this work has (1) defined all of the major cell types in the mouse iris and ciliary body, (2) led to the discovery of two types of iris stromal cells and two types of iris sphincter cells, (3) revealed the differences in cell type-specific transcriptomes in the resting vs. dilated states, and (4) identified and validated antibody and in situ hybridization probes that can be used to visualize the major iris cell types. By immunostaining for specific iris cell types, we have observed and quantified distortions in nuclear morphology associated with iris dilation and clarified the neural crest contribution to the iris by showing that Wnt1-Cre-expressing progenitors contribute to nearly all iris cell types, whereas Sox10-Cre-expressing progenitors contribute only to stromal cells. This work should be useful as a point of reference for investigations of iris development, disease, and pharmacology, for the isolation and propagation of defined iris cell types, and for iris cell engineering and transplantation.

Correlations among age, sex, axial length, and subfoveal choroidal thickness in the choriocapillaris structure analyzed using multiple en face image averaging optical coherence tomography angiography.

PurposeTo analyze the structure of the choriocapillaris in healthy eyes by using averaged en face images acquired using swept source optical coherence tomography angiography and to examine the changes in the macular profile in relation to age, sex, axial length, and choroidal thickness.MethodsThis prospective, cross-sectional study included 81 eyes of 81 subjects without ophthalmologic or systemic diseases who underwent a full ophthalmologic examination, including 3 × 3-mm macular optical coherence tomography angiography. Four to nine choriocapillaris en face images were registered and averaged. The averaged images were then binarized and analyzed.ResultsThe averaged choriocapillaris images showed a continuous capillary meshwork, whereas the unaveraged images had a granular appearance. The mean total area and size of flow voids were 0.99 ± 0.20 mm2 and 567.8 ± 201.5 μm2, respectively, and these values correlated positively with age (p = 0.002, R = 0.336 and p = 0.026, R = 0.247, respectively). Age-related gains in the mean total area and flow void size were 4.20 × 10−3 mm2 and 3.07 μm2 per year, respectively. However, the mean total area and flow void size had no significant correlation with axial length, subfoveal choroidal thickness, or sex.ConclusionsMultiple averaged en face swept source optical coherence tomography angiography is more effective than a single optical coherence tomography angiography scan for better visualizing the choriocapillaris. The total area and size of flow voids within a 3 × 3-mm macular area positively correlated with age. This technique can be useful for investigating the changes arising in macular diseases.

Update on the Management of Demodex Blepharitis

Demodex blepharitis is a common ophthalmologic disease that is often overlooked in the workup of blepharitis. Demodex infestation occurs in both symptomatic and asymptomatic individuals at similar rates; consequently, its role in the development of blepharitis has not been well elucidated. Two species have been confirmed to inhabit the human eyelid- Demodex folliculorum and Demodex brevis. These species differ in their preferred location of infestation, with D. folliculorum occupying the base of the eyelash and D. brevis inhabiting the meibomian glands, contributing to anterior and posterior Demodex blepharitis, respectively. A clinical index of suspicion must be developed from the history when blepharitis, conjunctivitis, or keratitis in adults and blepharoconjunctivitis or chalazia in children are resistant to treatment. The diagnosis can be strongly suspected by the presence of cylindrical dandruff at the base of the eyelash and confirmed by light microscopy of an epilated lash or by in vivo confocal microscopy. No cure is currently available. Management most frequently includes topical tea tree oil and its active ingredient terpinen-4-ol, both of which have produced good clinical outcomes. Topical tea tree oil is typically applied by a professional due to risk of toxicity. Several second-line treatment options have been studied, including ivermectin, metronidazole, selenium sulfide, microblepharoexfoliation, and lid hygiene. Novel, targeted therapies such as TP-03 (Tarsus Pharmaceuticals) are also currently being investigated in phase 2b/3 clinical trials. The purpose of this review purpose is to characterize Demodex blepharitis in detail, including its historical perspective and various classifications, and describe the latest diagnostic and management strategies.

Структурно-функциональные особенности центрального отдела сетчатки и совершенствование хирургического лечения больных с диабетическим макулярным отеком и эпиретинальной мембраной

Purpose. Improving the efficiency of surgical treatment of patients with diabetic macular edema and epiretinal membrane. Material and methods. Clinical studies were based on the analysis of morphological and functional parameters of the central retina. Patients with diffuse diabetic macular edema (DME) and epiretinal membrane (ERM) made up group A (main) of 96 people (96 eyes). Group B (control) included 22 patients (44 eyes) without ophthalmological diseases. Depending on the chosen method of surgical treatment, patients in group A were divided into three subgroups. Results. According to the data of optical coherence tomography, it was revealed that the average index of retinal thickness as a result of edema increased by 1.35 times (p=0.011) compared with group B. When conducting microperimetry in the macular zone in patients of group A, the total light sensitivity was reduced in 1.88 times compared with group B (p=0.028). Comparative analysis of long-term results of surgical treatment of patients with DMO and ERM showed that complex simultaneous vitrectomy and administration of an angiogenesis inhibitor is preferable compared to delayed administration of drugs, which is confirmed by a decrease in the total thickness of the retina in 78.3% of cases, preservation of the total photosensitivity of the central part of the retina on average, up to 15.3±3.24 dB, visual acuity - up to 0.51±0.22, no recurrence of edema in 63.4% of patients and the development of ERM - in 100% of cases. Conclusion. If the central thickness of the retina at the preoperative stage is less than 400 microns, it is possible to use a step-by-step method (vitrectomy + intravitreal administration of an angiogenesis inhibitor after 1 month). The use of the proposed one-step operation technique is preferable when the retina thickness is more than 400 microns. Vitrectomy with peeling of the internal limiting membrane in patients with cysts in the retinal edema zone with a diameter of more than 200 µm does not lead to a positive anatomical and functional result. Key words: diabetic macular edema, angiogenesis inhibitor, vitrectomy, microperimetry, epiretinal membrane.

Deep Att-ResGAN: A Retinal Vessel Segmentation Network for Color Fundus Images

Retinal vessel segmentation plays a significant role in the diagnosis and treatment of ophthalmological diseases. Recent studies have proved that deep learning can effectively segment the retinal vessel structure. However, the existing methods have difficulty in segmenting thin vessels, especially when the original image contains lesions. Based on generative adversarial network (GAN), this paper proposes a deep network with residual module and attention module (Deep Att-ResGAN). The network consists of four identical subnetworks. The output of each subnetwork is imported to the next subnetwork as contextual features that guide the segmentation. Firstly, the problems of the original image, namely, low contrast, uneven illumination, and data insufficiency, were solved through image enhancement and preprocessing. Next, an improved U-Net was adopted to serve as the generator, which stacks the residual and attention modules. These modules optimize the weight of the generator, and enhance the generalizability of the network. Further, the segmentation was refined iteratively by the discriminator, which contributes to the performance of vessel segmentation. Finally, comparative experiments were carried out on two public datasets: Digital Retinal Images for Vessel Extraction (DRIVE) and Structured Analysis of the Retina (STARE). The experimental results show that Deep Att-ResGAN outperformed the equivalent models like U-Net and GAN in most metrics. Our network achieved accuracy of 0.9565 and F1 of 0.829 on DRIVE, and accuracy of 0.9690 and F1 of 0.841 on STARE.

Development of Lutein-Containing Eye Drops for the Treatment of Dry Eye Syndrome.

Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of <5 μM lutein (L5) and <1% PVA (P1) maintained the cell viability at 80%. A real-time PCR showed that the inflamed human corneal epithelial cells (HCECs) cocultured with L5P1 had downregulated expression of inflammatory genes such as IL-1β, IL-6, and TNF-α. In a benzalkonium chloride- (BAC) induced DES mouse model, AT/L5P1 could repair damaged corneas, elevate tear secretion, increase the number of goblet cells, and inhibit the production of inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in the cornea. In conclusion, we demonstrate that lutein/PVA as eye drops could prolong the drug ocular retention time and effectively to decrease inflammation in DES mice. Therefore, lutein, obtained from eye drops, has a potential therapeutic role for DES.

Rapid discovery of potential ADR compounds from injection of total saponins from Panax notoginseng using data-independent acquisition untargeted metabolomics.

Injection of total saponins from Panax notoginseng (ISPN) is a modern preparation derived from traditional Chinese medicine (TCM) and is widely applied in the treatment of cardiovascular, cerebrovascular, ophthalmology, and endocrine system diseases. With the increase in the clinical application of ISPN, its adverse drug reactions (ADRs) and related safety issues have attracted much attention. In the present study, a data-independent acquisition (DIA) strategy was proposed to comprehensively characterize the saponins contained in ISPN based on the ultra-high-performance liquid chromatography/quadrupole-Orbitrap MS (UHPLC/Q-Orbitrap MS) platform. As many as 276 saponins were detected, and 250 compounds were identified or tentatively identified based on the retention times and MS/MS data. Furthermore, a metabolomic strategy was utilized to discover the discriminative saponins between normal and ADR batches. The results showed that six saponins, including ginsenoside Rh4, ginsenoside Rk3, ginsenoside Rg5, ginsenoside Rk1, ginsenoside Rg6, and 20(S)-ginsenoside Rh2, were significantly different between the two groups. According to cytotoxicity analysis and degranulation detection of RBL-2H3 cells, ginsenoside Rg5, ginsenoside Rk1, and 20(S)-ginsenoside Rh2 were considered the potential compounds responsible for clinical ADRs, ultimately. In addition, the quantitative analysis showed that the content of these three compounds in ISPN samples with ADRs was generally higher than that in samples without ADRs. This study demonstrated that it is advisable to screen out potential markers related to ADRs for developing the quality standard of ISPN by the integration of untargeted metabolomic analysis and cell biology study, and thus reduce its ADRs in the clinic.

Cortical Visual Impairments and Learning Disabilities.

Medical advances in neonatology have improved the survival rate of premature infants, as well as children who are born under difficult neurological conditions. As a result, the prevalence of cerebral dysfunctions, whether minimal or more severe, is increasing in all industrialized countries and in some developing nations. Whereas in the past, ophthalmological diseases were considered principally responsible for severe visual impairment, today, all recent epidemiological studies show that the primary cause of blindness and severe visual impairment in children in industrialized countries is now neurological, with lesions acquired around the time of birth currently comprising the commonest contributor. The resulting cortical or cerebral visual impairments (CVIs) have long been ignored, or have been confused either with other ophthalmological disorders causing low vision, or with a range of learning disabilities. We present here the deleterious consequences that CVI can have upon learning and social interaction, and how these can be given behavioral labels without the underlying visual causes being considered. We discuss the need to train and inform clinicians in the identification and diagnosis of CVI, and how to distinguish the diagnosis of CVI from amongst other visual disorders, including the specific learning disorders. This is important because the range of approaches needed to enhance the development of children with CVI is specific to each child’s unique visual needs, making incorrect labeling or diagnosis potentially detrimental to affected children because these needs are not met.

MF-Net: Multi-Scale Information Fusion Network for CNV Segmentation in Retinal OCT Images.

Choroid neovascularization (CNV) is one of the blinding ophthalmologic diseases. It is mainly caused by new blood vessels growing in choroid and penetrating Bruch's membrane. Accurate segmentation of CNV is essential for ophthalmologists to analyze the condition of the patient and specify treatment plan. Although many deep learning-based methods have achieved promising results in many medical image segmentation tasks, CNV segmentation in retinal optical coherence tomography (OCT) images is still very challenging as the blur boundary of CNV, large morphological differences, speckle noise, and other similar diseases interference. In addition, the lack of pixel-level annotation data is also one of the factors that affect the further improvement of CNV segmentation accuracy. To improve the accuracy of CNV segmentation, a novel multi-scale information fusion network (MF-Net) based on U-Shape architecture is proposed for CNV segmentation in retinal OCT images. A novel multi-scale adaptive-aware deformation module (MAD) is designed and inserted into the top of the encoder path, aiming at guiding the model to focus on multi-scale deformation of the targets, and aggregates the contextual information. Meanwhile, to improve the ability of the network to learn to supplement low-level local high-resolution semantic information to high-level feature maps, a novel semantics-details aggregation module (SDA) between encoder and decoder is proposed. In addition, to leverage unlabeled data to further improve the CNV segmentation, a semi-supervised version of MF-Net is designed based on pseudo-label data augmentation strategy, which can leverage unlabeled data to further improve CNV segmentation accuracy. Finally, comprehensive experiments are conducted to validate the performance of the proposed MF-Net and SemiMF-Net. The experiment results show that both proposed MF-Net and SemiMF-Net outperforms other state-of-the-art algorithms.

Truth of dare: The principles of storytelling in Ophthalmology services - review.

Storytelling has been long researched in literature and its benefits have been acknowledged. Recently, storytelling has widely been used in health care and has proved to be very helpful in health education. However, the impact of storytelling in several medical specialties has not been investigated. The aim of this paper was to highlight the benefits of using storytelling in Ophthalmology.As technology evolved, storytelling has been transformed into digital storytelling with more benefits for both health care consumers and health care providers. Apart from promoting a constant health education, digital storytelling offers the opportunity to raise the health care consumers’ awareness on a specific ophthalmologic disease, and identify proper methods to prevent it, as well as identify the risk factors accordingly.

Corneal endothelial cell density and morphology in ophthalmologically healthy young individuals in Japan: An observational study of 16842 eyes

We aimed to investigate the cell density and morphology of the corneal endothelium in ophthalmologically healthy young Japanese, given the lack of normative data in literature. This observational study included eyes without ophthalmologic diseases, besides refractive errors, examined between 1996 and 2015 at Miyata Eye Hospital. Eyes with a history of ophthalmologic diseases or contact lens usage were excluded. Correlation of corneal endothelial cell density (ECD), coefficient of variation (CV), appearance rate of hexagonal cells (6A), and cell area with age were examined. Multivariate linear regression analysis was performed to determine the predictors of corneal parameters. We included 16842 eyes of 8421 individuals (19.6 ± 8.7 years). ECD was 3109.0 ± 303.7 cells/mm2 and significantly reduced with age (p < 0.001). The ECD reduction rate was 0.42%/year in the total population. On multivariate analysis, age and sex were significantly correlated with ECD, CV, 6A, and cell area (all p < 0.001). ECD, 6A, CV, and cell area are significantly associated with age in healthy young Japanese individuals. Monitoring their corneal endothelium is essential to assess the risk of endothelial damage.

Uncertainty‐guided self‐ensembling model for semi‐supervised segmentation of multiclass retinal fluid in optical coherence tomography images

AbstractMacular edema is the accumulation of fluid leakage from retinal capillaries. Optical coherence tomography (OCT) images can show changes in the retinal tissue caused by ophthalmological diseases, such as fluid accumulation. Therefore, the segmentation of retinal fluid is important. Some methods based on image processing and machine learning often require large amounts of labeled data and rich domain knowledge. This study proposes a self‐ensembling semi‐supervised model based on uncertainty guidance, namely, UGNet. The model is trained end‐to‐end with a few labeled data and plenty of unlabeled data, and contains a teacher model and a student model with the same architecture. The two models consist of an encoder and three decoders, which are used to predict the probability map, contour map, and distance map. The segmentation result is the fusion result of the three maps generated by the student model. The selective kernel module (SKM) is embedded in the decoder to make the model adaptively adjust the receptive field according to the size of the fluid. The uncertainty of teacher model evaluation guides the student model to learn more reliable knowledge. The proposed method is trained and evaluated on the RETOUCH challenge dataset. The experimental results show that our method achieves better segmentation results than other start‐of‐the‐art methods.

DPN: detail-preserving network with high resolution representation for efficient segmentation of retinal vessels

Retinal vessels are important biomarkers for many ophthalmological and cardiovascular diseases. Hence, it is of great significance to develop automatic models for computer-aided diagnosis. Existing methods, such as U-Net follows the encoder-decoder pipeline, where detailed information is lost in the encoder in order to achieve a large field of view. Although spatial detailed information could be recovered partly in the decoder, while there is noise in the high-resolution feature maps of the encoder. And, we argue this encoder-decoder architecture is inefficient for vessel segmentation. In this paper, we present the detail-preserving network (DPN), which avoids the encoder-decoder pipeline. To preserve detailed information and learn structural information simultaneously, we designed the detail-preserving block (DP-Block). Further, we stacked eight DP-Blocks together to form the DPN. More importantly, there are no down-sampling operations among these blocks. Therefore, the DPN could maintain a high/full resolution during processing, avoiding the loss of detailed information. To illustrate the effectiveness of DPN, we conducted experiments over three public datasets. Experimental results show, compared to state-of-the-art methods, DPN shows competitive/better performance in terms of segmentation accuracy, segmentation speed, and model size. Specifically, (1) Our method achieves comparable segmentation performance on the DRIVE, CHASE_DB1, and HRF datasets. (2) The segmentation speed of DPN is over 20-160 $$\times$$ faster than other methods on the DRIVE dataset. (3) The number of parameters of DPN is around 120k, far less than all comparison methods.

Current status and future directions of clinical applications using iPS cells-focus on Japan.

Regenerative medicine using iPS cell technologies has progressed remarkably in recent years. In this review, we summarize these technologies and their clinical application. First, we discuss progress in the establishment of iPS cells, including the HLA-homo iPS cell stock project in Japan and the advancement of low antigenic iPS cells using genome-editing technology. Then, we describe iPS cell-based therapies in or approaching clinical application, including those for ophthalmological, neurological, cardiac, hematological, cartilage, and metabolic diseases. Next, we introduce disease models generated from patient iPS cells and successfully used to identify therapeutic agents for intractable diseases. Clinical medicine using iPS cells has advanced safely and effectively by making full use of current scientific standards, but tests on cell safety need to be further developed and validated. The next decades will see the further spread of iPS cell technology-based regenerative medicine.