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Research on the use of optical coherence tomography (OCT) in acute coronary syndrome (ACS) has increased in recent years. However, a comprehensive analysis of the trends and hotspots in OCT research is currently lacking. The objective of this study was to identify global trends in research on OCT in ACS from a bibliometric perspective and to provide researchers with new research hotspots. Relevant literature from 1998 to 2023 was retrieved from the Web of Science Core Collection. CiteSpace and VOSviewer software were used to collect and analyze publication trends in related fields. A total of 965 publications from 58 countries and 1389 institutions were included in the present study. We found that Japan produced the most publications (20.83%, 201), followed by the United States (19.90%, 192), and China (14.09%, 136). However, the United States has the highest total number of citations in this field. Harvard Medical School and Harbin Medical University had the highest numbers of publications and citations. The journal with the most publications was the International Journal of Cardiology. Plaque erosion, calcified nodules, and intracoronary imaging are the most recent research hotspots and frontiers. Our work summarizes 25 years of OCT research in the ACS, highlighting hotspots, key themes, and emerging frontiers to help guide future research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Optical coherence tomography (OCT) and OCT angiography (OCTA) are widely used in the diagnosis of ophthalmic diseases. This study aims to provide a comprehensive bibliometric analysis of ophthalmologic OCT and OCT angiography., Methods: We retrieved publications on ophthalmic OCT and OCTA from 2003 to 2022 from the Web of Science Core Collection and used bibliometric tools to analyze and visualize the distribution, trend, and hotspots., Results: In total, 20,817 articles written by 48,160 authors from 106 countries were selected. The number of publications has significantly increased. In the last two decades, the USA was the most productive country and received the highest citations. The most productive journal was Investigative Ophthalmology and Visual Science and received the highest number of citations. Moorfields Eye Hospital was the most productive institution. Bandello F published the most papers, while Spaide RF was the highest cited author. SPAIDE RF, 2011, AM J Ophthalmology was the most cited document. "OCT", "glaucoma" and "OCTA" were three hotspots in the last two decades. "Vessel density" and "deep learning" would be research hotspots in the future., Conclusion: The bibliometric analysis of ophthalmic OCT and OCTA research over the past two decades on keywords, authors, citations, hotspots and trends will provide global researchers with valuable information for future research and cooperation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: In order to analyze changes in retinal vessel flow after small incision lenticule extraction (SMILE)., Methods: A total of 32 patients (62 eyes) who underwent SMILE were enrolled in this prospective study. Optical parameters, including vessel density (VD), and perfusion density (PD) of foveal, parafoveal, and perifoveal regions, respectively, were measured before surgery and at 1 day, 1 week, 1 month, and 3 months postoperation. Preoperative parameters and surgical parameters were recorded., Results: Significant decreases in VD and PD on postoperative day 1 were detected in all quadrants, both in 3 mm and in 6 mm regions ( P < 0.001). One month after surgery, VD returned to preoperative levels. None of the preoperative and surgical parameters were significantly correlated with the VD and PD fluctuations (all P > 0.05) . Conclusion . VD may decrease significantly with regional disparity 1 day after SMILE while recovering at 1 month. Elevation of intraocular pressure due to suction may account for such changes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Qian Tan et al.)

Objectives: We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients., Methods: A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed., Results: Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology., Conclusion: Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The foveal avascular zone (FAZ) is a biomarker for quantifying diabetic macular ischemia (DMI), to automate the identification and quantification of the FAZ in DMI, using an improved U-Net convolutional neural network (CNN) and to establish a CNN model based on optical coherence tomography angiography (OCTA) images for the same purpose., Methods: The FAZ boundaries on the full-thickness retina of 6 × 6 mm en face OCTA images of DMI and normal eyes were manually marked. Seventy percent of OCTA images were used as the training set, and ten percent of these images were used as the validation set to train the improved U-Net CNN with two attention modules. Finally, twenty percent of the OCTA images were used as the test set to evaluate the accuracy of this model relative to that of the baseline U-Net model. This model was then applied to the public data set sFAZ to compare its effectiveness with existing models at identifying and quantifying the FAZ area., Results: This study included 110 OCTA images. The Dice score of the FAZ area predicted by the proposed method was 0.949, the Jaccard index was 0.912, and the area correlation coefficient was 0.996. The corresponding values for the baseline U-Net were 0.940, 0.898, and 0.995, respectively, and those based on the description data set sFAZ were 0.983, 0.968, and 0.950, respectively, which were better than those previously reported based on this data set., Conclusions: The improved U-Net CNN was more accurate at automatically measuring the FAZ area on the OCTA images than the traditional CNN. The present model may measure the DMI index more accurately, thereby assisting in the diagnosis and prognosis of retinal vascular diseases such as diabetic retinopathy., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Yongan Meng et al.)

Purpose: To evaluate the effectiveness of intravitreal bevacizumab treatment in patients with diabetic macular edema (DME) by assessing retinal changes using optical coherence tomography angiography (OCT-A)., Methods: This prospective study was performed in patients with treatment-naïve DME. The eyes of patients were imaged using a swept-source OCT system with a scan area of 6 × 6 mm. The DME patients with a central macular thickness (CMT) of ≥300  μ m received nine bevacizumab injections within 12 months. The demographic, systemic, and ocular parameters, including the best-corrected visual acuity (BCVA), CMT, microaneurysm (MA) count, and foveal avascular zone (FAZ) area in both superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as vessel density in SCP, were assessed in the patients. In addition, the response (good or poor) of the DME eyes to bevacizumab treatment and the final visual acuity (BCVA of 75 letters) were analyzed., Results: Seventy-seven eyes of DME patients were subjected to the final analysis. Bevacizumab treatment reduced CMT from 425.06  μ m (±77.15) to 350.25  μ m (±82.04) and improved BCVA by about 8.61 letters (from 64.73 to 73.34) in the patients. The mean number of MAs in SCP decreased from 3.51 ± 2.07 to 2.31 ± 1.15 ( p < 0.001) and in DCP from 17.12 ± 11.56 to 12.21 ± 6.99 ( p < 0.001), whereas the area of FAZ increased in SCP from 328.22 ± 131.38 to 399.70 ± 156.98 ( p < 0.001) and in DCP from 571.13 ± 396.01 to 665.89 ± 412.77 ( p = 0.001). The final BCVA letter score and CMT were statistically significant in both poor and good responders, as well as in BCVA < 75 and BCVA ≥ 75 groups., Conclusion: The fixed-regimen intravitreal bevacizumab therapy was effective in treating DME. Apart from noninvasive visualization of microvascular damage, OCT-A showed limited usefulness in predicting treatment response. Although the study showed that the number of MAs was significantly reduced during treatment, which is an OCT-A predictor of a good response to bevacizumab treatment at a 12-month visit, commonly observed artifacts may reduce the usefulness of OCT-A., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Magdalena Hunt et al.)

Objective: To investigate the optic nerve and macular parameters of children who recovered from COVID-19 compared with healthy children using optical coherence tomography (OCT)., Design: Cohort study., Setting: Hospital Clinico San Carlos, Madrid., Patients: Children between 6 and 18 years old who recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection and historical controls were included., Interventions: All patients underwent an ophthalmological examination, including macular and optic nerve OCT. Demographic data, medical history and COVID-19 symptoms were noted., Main Outcome Measures: Peripapillary retinal nerve fibre layer thickness, macular retinal nerve fibre layer thickness, macular ganglion cell layer thickness and retinal thickness., Results: 90 patients were included: 29 children who recovered from COVID-19 and 61 controls. Patients with COVID-19 presented an increase in global peripapillary retinal nerve fibre layer thickness (mean difference 7.7; 95% CI 3.4 to 12.1), temporal superior (mean difference 11.0; 95% CI 3.3 to 18.6), temporal inferior (mean difference 15.6; 95% CI 6.5 to 24.7) and nasal (mean difference 9.8; 95% CI 2.9 to 16.7) sectors. Macular retinal nerve fibre layer analysis showed decreased thickness in the nasal outer (p=0.011) and temporal inner (p=0.036) sectors in patients with COVID-19, while macular ganglion cell layer thickness increased in these sectors (p=0.001 and p=0.015, respectively). No differences in retinal thickness were noted., Conclusions: Children with recent history of COVID-19 present significant changes in peripapillary and macular OCT analyses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The formation of filtration blebs is the main drainage mechanism for reducing intraocular pressure after traditional incisional glaucoma surgery such as trabeculectomy and non-penetrating deep sclerotomy. Early and short-lasting blebs may also occur after canaloplasty. Bleb formation also plays an important role after the implantation of glaucoma drainage devices, including Minimally Invasive Glaucoma Surgery devices. Anterior segment optical coherence tomography (AS-OCT) is a rapid and non-invasive high-resolution imaging technique that has evolved in recent years to become a routine examination. Anterior segment optical coherence tomography (AS-OCT) provides key information in the assessment and follow-up of glaucoma surgery, especially in the assessment of filtration blebs. Thus, bleb morphology can be qualitatively classified into diffuse, cystic, encapsulated and flattened, and AS-OCT imaging can also provide several quantitative parameters of the bleb, such as total bleb height, bleb fluid-filled cavity height, bleb wall thickness, number of microcysts and trabeculectomy opening size. These parameters could have an impact on clinical management during follow-up because they may predict the success or failure of the surgery in the early and late postoperative periods. Additionally, they may also guide the procedures used to increase filtration and reduce intraocular pressure, such as bleb needling and laser suture lysis., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objectives: Drug-coated balloons (DCBs) have theoretical advantages over drug-eluting stents (DESs) to facilitate stent healing. We studied whether, in patients undergoing primary coronary interventions (pPCIs), a strategy of DCB after bare-metal stent improves early healing as determined by optical coherence tomography (OCT) compared with new-generation DES., Methods: pPCI patients were randomized (1:1) to treatment with new-generation sirolimus-eluting stents (DES group) or DCB-strategy. Vessel healing was assessed by OCT at 90 days., Results: Fifty-three patients were randomized (26 DES vs. 27 DCB). At 90 days, both strategies showed a low rate of uncovered struts (3.2 vs. 3.2%, P = 0.64) and a very high and similar rate of covered and apposed struts (96.6 vs. 96.1%, respectively; P = 0.58). However, DCB group had a significantly lower rate of major coronary evaginations (68 vs. 37%, P = 0.026), and more frequently developed a thin homogeneous neointimal layer (20 vs. 70.4%, P = 0.001) suggesting distinct superior healing at 3 months compared to DES., Conclusions: In pPCI both, sirolimus-DES and DCB-strategy, provide excellent strut coverage at 3 months. However, DCB ensures more advanced and optimal stent healing compared to sirolimus-DES. Further research is needed to determine whether, in patients undergoing pPCI, DCB offers superior long-term clinical and angiographic outcomes than new-generation DES (NCT03610347)., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Contemporary optical coherence tomography (OCT) findings in patients with acute coronary syndromes (ACS) are still subject of controversy. We sought to use OCT to evaluate plaque morphology and phenotype classification in patients with ACS., Methods: Using optical coherence tomography, culprit lesions were morphologically classified as plaque rupture, plaque erosion, calcified nodule, thin-cap fibroatheroma, thick-cap fibroatheroma (TCFA) or fibrotic, fibrocalcific or fibrolipidic plaque. Quantitative and qualitative analyses also included cholesterol crystals, neovascularization, spotty calcification and thrombus., Results: Of the 110 lesions imaged from June 2012 to April 2016, 54 (49%) were in patients with unstable angina (UA), 31 (28%) were in non-ST-elevation myocardial infarction (STEMI) patients and 25 (23%) were in STEMI patients. Compared with STEMI patients, patients with UA/non-STEMI were older and had more hypertension, hypercholesterolemia, known coronary artery disease, prior myocardial infarction and higher use of antiplatelet therapy. More patients with STEMI had lipidic arc >90% (36.6 versus 70.8%, P = 0.003), red and mixed thrombus (12.9 versus 28.0% and 7.1 versus 44.0%, respectively, all P < 0.001), plaque rupture (29.4 versus 76.0%, P < 0.001) and TCFA (57.1 versus 84.0%; P = 0.01). Predictors of plaque rupture were STEMI at presentation (odds ratio: 9.35, 95% confidence interval: 1.66-52.61, P = 0.01) and diabetes mellitus (odds ratio: 6.16, 95% confidence interval: 1.33-28.58, P = 0.02)., Conclusions: In this single-center study, the culprit lesion of patients with STEMI had more lipid, red and mixed thrombus, plaque rupture and TCFA versus patients with UA/non-STEMI. Clinical presentation may be driven by distinct pathophysiologic mechanisms in patients with ACS., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Age-related macular degeneration (AMD) is a progressive retinal disease, causing vision loss. A more detailed characterization of its atrophic form became possible thanks to the introduction of Optical Coherence Tomography (OCT). However, manual atrophy quantification in 3D retinal scans is a tedious task and prevents taking full advantage of the accurate retina depiction. In this study we developed a fully automated algorithm segmenting Retinal Pigment Epithelial and Outer Retinal Atrophy (RORA) in dry AMD on macular OCT. 62 SD-OCT scans from eyes with atrophic AMD (57 patients) were collected and split into train and test sets. The training set was used to develop a Convolutional Neural Network (CNN). The performance of the algorithm was established by cross validation and comparison to the test set with ground-truth annotated by two graders. Additionally, the effect of using retinal layer segmentation during training was investigated. The algorithm achieved mean Dice scores of 0.881 and 0.844, sensitivity of 0.850 and 0.915 and precision of 0.928 and 0.799 in comparison with Expert 1 and Expert 2, respectively. Using retinal layer segmentation improved the model performance. The proposed model identified RORA with performance matching human experts. It has a potential to rapidly identify atrophy with high consistency., (© 2021. The Author(s).)

Purpose: To compare posterior vitreous detachment (PVD) identification rate between clinical examination versus spectral domain optical coherence tomography in patients with retinal detachment (RD)., Methods: Data from the Primary Retinal Detachment Outcomes Study were used for this retrospective cross-sectional study of 506 patients. Spectral domain optical coherence tomography scans were reviewed to detect the separation of the posterior hyaloid face from the retina and the optic nerve on all 31 raster cuts of a 30 × 30 scan. Statistical analysis was performed to compare spectral domain optical coherence tomography-identified PVD with PVD identified on slit-lamp biomicroscopy., Results: There was a significant difference in the rate of PVD identification by clinical examination versus spectral domain optical coherence tomography in patients with RD. Clinical examination identified 51.58% of patients with PVD, whereas spectral domain optical coherence tomography identified 78.42% of patients with PVD. In patients with macula-on RD, 61.68% were found to have PVD on clinical examination versus 83.90% by imaging. Spectral domain optical coherence tomography identified larger number of PVD in patients with macula-off RD compared with clinical examination, 46.28% versus 75.43%, respectively. There was low agreement between the two methods (kappa score = 0.137). There was a significant difference in surgical procedure type chosen in those with versus without PVD., Conclusion: Knowledge about the posterior hyaloid anatomy is important before undergoing RD repair. Spectral domain optical coherence tomography can better identify PVD than clinical examination in patients with RD.

Purpose: To investigate any associations between cigarette smoking and retinal microvascular changes in diabetic patients without visible retinopathy., Design: Retrospective, cross-sectional study., Participants: 1099 eyes from 1099 diabetic patients with no clinical evidence of diabetic retinopathy (DR) were included in this study., Methods: Diabetic patients underwent optical coherence tomography angiography (OCTA) scanning at Zuckerberg San Francisco General Hospital and Trauma Center between April 2018 and September 2019. Patient demographic and clinical information was collected. Standard bivariate statistics and multivariate linear regression were performed., Main Outcome Measures: OCTA parameters included metrics related to the foveal avascular zone (FAZ; area, perimeter, circularity), perfusion density (PD; full, center, inner), and vessel length density (VLD; full, center, inner)., Results: The study population included 750 non-smokers and 349 smokers. FAZ perimeter was the only OCTA parameter that was significantly different between the two groups on uncontrolled analysis (P = 0.033). Multivariate regression analyses revealed significant associations between lower VLD full (β = -0.31, P = 0.048), lower VLD inner (β = -0.35, P = 0.046) and a history of smoking. No significant associations between cigarette smoking and either FAZ or PD were detected., Conclusions: Our results suggest that smoking is likely associated with deleterious changes in the retinal microvasculature of patients with a history of diabetes and no visible DR. Based on these findings, diabetic patients with a history of smoking may benefit from higher prioritization in terms of ophthalmic screening., Competing Interests: The authors have declared that no competing interests exist.

Abstract: We retrospectively compared the central corneal thickness (CCT) obtained by ultrasound pachymetry (USP; SP-3000, Tomey Corp., Nagoya, Japan), non-contact tonopachy (TP) (NT-530P, Nidek Co., Ltd., Gamagori, Japan), Pentacam HR (OCULUS Inc., Wetzlar, Germany), and RTVue optical coherence tomography (OCT) (Optovue Inc., Fremont, CA, USA) in 78 eyes of 78 healthy subjects with myopia. Agreement between the measurement methods was evaluated using 95% confidence intervals for the limits of agreement (LoA). The mean CCT values were 546.9 ± 34.7, 548.1 ± 33.5, 559.2 ± 34.0, and 547.2 ± 34.8 μm for USP, non-contact TP, Pentacam, and RTVue, respectively. The thickest and the thinnest mean CCT values corresponded to those obtained by Pentacam HR and USP, respectively. Plots of the differences against the means showed the best agreement between USP and RTVue (LoA, 10.14-10.70 μm), while the largest discrepancy was observed between RTVue and Pentacam systems (LoA, -25.47-1.44 μm). Our data showed that CCT measurements using these 4 instruments were well correlated. However, the results from Pentacam differed significantly from those of the other instruments., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To assess the current role of fluorescein angiography after the introduction of optical coherence tomography angiography in real-life clinical practice., Methods: This was a multicentric retrospective observational study to evaluate the number of fluorescein angiography and optical coherence tomography angiography procedures performed by different devices from January 2013 to December 2018. The centers involved were Centro Italiano Macula (Rome), and ophthalmology departments of University "G. D'Annunzio" Chieti-Pescara (Chieti) and "Azienda Ospedaliero Universitaria Careggi" (Florence)., Results: Out of 19,898 total fluorescein angiography procedures performed in the observation period, 3444 (17.3%) were in 2013, 3972 (19.9%) were in 2014, 3601 (18.1%) were in 2015, 3407 (17.2%) were in 2016, 3285 (16.5%) were in 2017, and 2189 (11%) were in 2018. Out of 7949 optical coherence tomography angiography procedures performed in the observation period, none were performed in 2013, 550 (6.9%) were in 2014, 908 (11.5%) were in 2015, 2098 (26.4%) were in 2016, 2090 (26.3%) were in 2017, and 2303 (28.9%) were in 2018., Conclusion: Fluorescein angiography procedures were performed less often after the introduction of optical coherence tomography angiography technology. The ease, speed, and safety of the optical coherence tomography angiography procedure in everyday clinical practice have facilitated more optical coherence tomography angiography application compared to fluorescein angiography in recent years. In the future, we will probably evaluate the different pathologies that still need an evaluation by fluorescein angiography.

Machine learning has greatly facilitated the analysis of medical data, while the internal operations usually remain intransparent. To better comprehend these opaque procedures, a convolutional neural network for optical coherence tomography image segmentation was enhanced with a Traceable Relevance Explainability (T-REX) technique. The proposed application was based on three components: ground truth generation by multiple graders, calculation of Hamming distances among graders and the machine learning algorithm, as well as a smart data visualization ('neural recording'). An overall average variability of 1.75% between the human graders and the algorithm was found, slightly minor to 2.02% among human graders. The ambiguity in ground truth had noteworthy impact on machine learning results, which could be visualized. The convolutional neural network balanced between graders and allowed for modifiable predictions dependent on the compartment. Using the proposed T-REX setup, machine learning processes could be rendered more transparent and understandable, possibly leading to optimized applications.

Optical coherence tomography (OCT) is a noninvasive cross-sectional imaging technology used to examine the retinal structure and pathology of the eye. Evaluating the thickness of the choroid using OCT images is of great interests for clinicians and researchers to monitor the choroidal thickness in many ocular diseases for diagnosis and management. However, manual segmentation and thickness profiling of choroid are time-consuming which lead to low efficiency in analyzing a large quantity of OCT images for swift treatment of patients. In this paper, an automatic segmentation approach based on convolutional neural network (CNN) classifier and l 2 - l q (0 < q < 1) fitter is presented to identify boundaries of the choroid and to generate thickness profile of the choroid from retinal OCT images. The method of detecting inner choroidal surface is motivated by its biological characteristics after light reflection, while the outer chorioscleral interface segmentation is transferred into a classification and fitting problem. The proposed method is tested in a data set of clinically obtained retinal OCT images with ground-truth marked by clinicians. Our numerical results demonstrate the effectiveness of the proposed approach to achieve stable and clinically accurate autosegmentation of the choroid., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Fang He et al.)

The purpose of this study was to introduce a new deep learning (DL) model for segmentation of the fovea avascular zone (FAZ) in en face optical coherence tomography angiography (OCTA) and compare the results with those of the device's built-in software and manual measurements in healthy subjects and diabetic patients. In this retrospective study, FAZ borders were delineated in the inner retinal slab of 3 × 3 enface OCTA images of 131 eyes of 88 diabetic patients and 32 eyes of 18 healthy subjects. To train a deep convolutional neural network (CNN) model, 126 enface OCTA images (104 eyes with diabetic retinopathy and 22 normal eyes) were used as training/validation dataset. Then, the accuracy of the model was evaluated using a dataset consisting of OCTA images of 10 normal eyes and 27 eyes with diabetic retinopathy. The CNN model was based on Detectron2, an open-source modular object detection library. In addition, automated FAZ measurements were conducted using the device's built-in commercial software, and manual FAZ delineation was performed using ImageJ software. Bland-Altman analysis was used to show 95% limit of agreement (95% LoA) between different methods. The mean dice similarity coefficient of the DL model was 0.94 ± 0.04 in the testing dataset. There was excellent agreement between automated, DL model and manual measurements of FAZ in healthy subjects (95% LoA of - 0.005 to 0.026 mm 2 between automated and manual measurement and 0.000 to 0.009 mm 2 between DL and manual FAZ area). In diabetic eyes, the agreement between DL and manual measurements was excellent (95% LoA of - 0.063 to 0.095), however, there was a poor agreement between the automated and manual method (95% LoA of - 0.186 to 0.331). The presence of diabetic macular edema and intraretinal cysts at the fovea were associated with erroneous FAZ measurements by the device's built-in software. In conclusion, the DL model showed an excellent accuracy in detection of FAZ border in enfaces OCTA images of both diabetic patients and healthy subjects. The DL and manual measurements outperformed the automated measurements of the built-in software.

Background Specific plaque phenotypes that predict a favorable response to statin therapy have not been systematically studied. This study aimed to identify optical coherence tomography predictors for a favorable vascular response to statin therapy. Methods and Results Patients who had serial optical coherence tomography imaging at baseline and at 6 months were included. Thin-cap area (defined as an area with fibrous cap thickness <200 μm) was measured using a 3-dimensional computer-aided algorithm, and changes in the thin-cap area at 6 months were calculated. A favorable vascular response was defined as the highest tertile in the degree of reduction of the thin-cap area. Macrophage index was defined as the product of the average macrophage arc and length of the lesion with macrophage infiltration. Layered plaque was defined as a plaque with 1 or more layers of different optical density. In 84 patients, 140 nonculprit lipid plaques were identified. In multivariable analysis, baseline thin-cap area (odds ratio [OR] 1.442; 95% CI, 1.024-2.031, P =0.036), macrophage index (OR, 1.031; 95% CI, 1.002-1.061, P =0.036), and layered plaque (OR, 2.767; 95% CI, 1.024-7.479, P =0.045) were identified as the significant predictors for a favorable vascular response. Favorable vascular response was associated with a decrease in the macrophage index. Conclusions Three optical coherence tomography predictors for a favorable vascular response to statin therapy have been identified: large thin-cap area, high macrophage index, and layered plaque. Favorable vascular response to statin was correlated with signs of decreased inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01110538.

An artificial stent implantation is one of the most effective ways to treat coronary artery diseases. It is vital in vascular medical imaging, such as intravascular optical coherence tomography (IVOCT), to be able to track the position of stents in blood vessels effectively. We trained two models, the "You Only Look Once" version 3 (YOLOv3) and the Region-based Fully Convolutional Network (R-FCN), to detect metal support struts in IVOCT, respectively. After rotating the original images in the training set for data augmentation, and modifying the scale of the conventional anchor box in both two algorithms to fit the size of the target strut, YOLOv3 and R-FCN achieved precision, recall, and AP all above 95% in 0.4 IoU threshold. And R-FCN performs better than YOLOv3 in all relevant indicators., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Xiaolu Jiang et al.)

Purpose: To analyze the individual value and the contribution of color fundus photography (CFP) and optical coherence tomography (OCT) in the screening of age-related macular degeneration (AMD) of an unselected population., Methods: CFP and OCT images of 15957 eyes of 8069 subjects older than 55 years, obtained during a population-based screening for AMD using a single diagnostic non-mydriatic imaging device, were analyzed by a blinded examiner. The two techniques were preliminary evaluated considering the dichotomous parameter "gradable/ungradable", then gradable images were classified. CFP were graded according to the standardized classification of AMD lesions. OCT images were also categorized considering the presence of signs of early/intermediate AMD, late AMD, or other retinal diseases. Another blinded operator re-graded 1978 randomly selected images (for both CFP and OCT), to assess test reproducibility., Results: Of the 15957 eyes, 8356 CFP (52.4%) and 15594 (97.7%) OCT scans were gradable. Moreover, most of the eyes with ungradable CFP (7339, 96.6%) were gradable at OCT. AMD signs were revealed in 7.4% of gradable CFP and in 10.4% of gradable OCT images. Moreover, at OCT, AMD signs were found in 1110 (6.9%) eyes whose CFP were ungradable or without AMD (847 and 263 eyes, respectively). The inter-operator agreement was good for the gradable versus ungradable parameter, and optimal for the AMD grading parameter of CFP. The agreement was optimal for all OCT parameters., Conclusions: OCT provided gradable images in almost all examined eyes, compared to limited CFP efficiency. Moreover, OCT images allowed to detect more AMD eyes compared to gradable photos. OCT imaging appears to significantly improve the power of AMD screening in a general, unselected population, compared to CFP alone., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The purpose of this tutorial is to provide visual scientists with various approaches for comparing two or more groups of data using parametric statistical tests, which require that the distribution of data within each group is normal (Gaussian). Non-parametric tests are used for inference when the sample data are not normally distributed or the sample is too small to assess its true distribution., Methods: Methods are reviewed using retinal thickness, as measured by optical coherence tomography (OCT), as an example for comparing two or more group means. The following parametric statistical approaches are presented for different situations: two-sample t-test, Analysis of Variance (ANOVA), paired t-test, and the analysis of repeated measures data using a linear mixed-effects model approach., Results: Analyzing differences between means using various approaches is demonstrated, and follow-up procedures to analyze pairwise differences between means when there are more than two comparison groups are discussed. The assumption of equal variance between groups and methods to test for equal variances are examined. Examples of repeated measures analysis for right and left eyes on subjects, across spatial segments within the same eye (e.g. quadrants of each retina), and over time are given., Conclusions: This tutorial outlines parametric inference tests for comparing means of two or more groups and discusses how to interpret the output from statistical software packages. Critical assumptions made by the tests and ways of checking these assumptions are discussed. Efficient study designs increase the likelihood of detecting differences between groups if such differences exist. Situations commonly encountered by vision scientists involve repeated measures from the same subject over time, measurements on both right and left eyes from the same subject, and measurements from different locations within the same eye. Repeated measurements are usually correlated, and the statistical analysis needs to account for the correlation. Doing this the right way helps to ensure rigor so that the results can be repeated and validated.

Background: Optical coherence tomography (OCT) can detect detailed plaque features in native coronary arteries. Stent struts cause shadows that partially obscure the vessel wall, but plaque features can still be seen. We investigated the impact of stent artefact on plaque quantification and whether the plaque behind struts is associated with microvascular dysfunction., Methods: Patients retrospectively recruited from two centres, underwent OCT pre- and post-stenting on the same vessel segment. Lipid (LA) and calcium (CA) were measured as arcs. Macrophages, microchannels and cholesterol crystals were counted. Subsequently, we determined whether stented plaque features were associated with reduced Thrombolysis in Myocardial Infarction (TIMI) flow grade in consecutive patients who underwent OCT post-stenting., Results: In 52 patients the lipid arc was similar pre- vs post-stent: median (55º [13º-93º] vs. 40º [18º-87°]; difference 1º [-7º to 16º], p = NS). Pre- and post-stent lipid were strongly correlated (r = 0.92, p < 0.001). In a further 128 patients those with reduced (TIMI ≤ II) vs normal flow post percutaneous coronary intervention (PCI) showed more plaque behind struts: lipid (89º [50º-139º] vs 62º [29º-88°]; p < 0.001); and calcium (24º [6º-45º] vs 7° [0º-34º]; p = 0.031). Multivariate logistic regression analysis showed that abnormal TIMI flow post-stenting was associated with diabetes (Odds ratio [OR] 2.87, CI 1.01-8.19, p = 0.048), LA (OR 1.29, 95% CI 1.14-1.38, p < 0.001) and CA (OR 1.26, CI 1.07-1.40, p = 0.005)., Conclusions: Plaque behind the struts can be accurately quantified using OCT. Furthermore, OCT plaque features in stented segments are associated with microvascular dysfunction post PCI., (Copyright © 2019 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

We evaluated the agreements in foveal avascular zone (FAZ) area and vessel density (VD) parameters (within the superficial capillary plexus region), between two widely used optical coherence tomography angiography machines. Participants who attended the Singapore Malay Eye Study III between 29th March and 6th August 2018, were enrolled in this study. Participants underwent fovea-centered 6×6-mm macular cube scan, using both AngioVue and Cirrus HDOCT machines. Scans were analyzed automatically using built-in review software of each machine. 177 eyes (95 participants) without retinal diseases were included for final analysis. Mean FAZ area was 0.38 ± 0.11 mm 2 and 0.30 ± 0.10 mm 2 , based on AngioVue and Cirrus HDOCT, respectively. Mean parafoveal VD was 0.50 ± 0.04 in Angiovue, and 0.43 ± 0.04 in Cirrus HDOCT. Cirrus HDOCT measurements were consistently lower than those by AngioVue, with a mean difference of -0.08 (95% limits of agreement [LOA], -0.30-0.13) mm 2 for FAZ area, and -0.07 (95% LOA, -0.17-0.03) for parafoveal VD. Intraclass correlation coefficients for FAZ area and parafoveal VD were 0.33 and 0.07, respectively. Our data suggest that agreements between AngioVue and Cirrus HDOCT machines were poor to fair, thus alternating use between these two machines may not be recommended especially for follow up evaluations.

Introduction: Non-invasive multimodal imaging, including optical coherence tomography angiography (OCTA), has demonstrated high sensitivity and specificity for the management of retinal diseases. Since the availability of OCTA in 2015, we have developed a policy of "as little fluorescein angiography as possible". In this study, we describe the rate of OCTA and fluorescein angiography (FA) performed and their indications., Methods: Retrospective descriptive single-centre study. Chart review of patients examined for retinal disorders by one medical retina specialist between January 2015 and June 2018., Results: 3487 patients were examined for a retinal disease. The charts of 651 of these patients (1170 eyes) were randomly selected for analysis (study group). The mean age in the study group was 72 years (60% female). Overall, OCTA and FA were performed in 49.4% and 6.5% of the studied eyes respectively. After the first year, the rate of FA decreased to 2%. The main indications for OCTA were age-related macular degeneration (AMD): 50%, central serous chorioretinopathy (CSC): 12% and retinal vascular occlusion: 10%. The most frequent indications for FA were AMD: 49%, diabetic retinopathy (DR): 18% and CSC: 14%. FA was performed in 16%, 11% and 10% of eyes diagnosed with DR, CSC and AMD respectively (P<0.05)., Conclusion: In routine practice, OCTA was performed in half of the eyes examined for a retinal disorder. The overall rate of FA was 6.5% and dropped to 2% after the first year of OCTA use. DR was the main disorder still requiring FA., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Line-field confocal optical coherence tomography (LC-OCT) is an imaging technique providing "optical biopsies" of the skin in real time and non-invasively. At a center optical wavelength of 1.3 µm, this innovative technology can be applied to dermo-cosmetic product development due to both high image resolution (~2 µm) and sufficient penetration (~0.5 mm). Nevertheless, the precise dermal area analyzed with LC-OCT has never been identified. In this study, the objective was to compare LC-OCT images with histological sections of the same area, in order to validate a new method for in vivo and non-invasive quantification of superficial dermis thickness. Once validated, this standardized and quantitative method was used to assess age-related changes of the superficial dermis., Materials and Methods: Ex vivo LC-OCT acquisitions and hematoxylin-eosin-safran staining were performed on a panel of four healthy Caucasian female volunteers. In vivo LC-OCT study of skin aging was performed on a panel of 37 healthy Caucasian female divided into five different age-groups., Results: Comparison with histological sections revealed that LC-OCT images allow the visualization and the quantification of the superficial portion of papillary dermis. Applied to different age-group of volunteers, LC-OCT images show a constant decrease in this superficial dermis thickness with age., Conclusions: In conclusion, we have introduced LC-OCT as a novel technique for in vivo and non-invasive evaluation of superficial dermis thickness. This approach could be used in the future to demonstrate visually and quantitatively the capacity of a dermo-cosmetic active ingredient to renormalize the structural properties of the dermis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Traditional coronary angiography (CA) as a main technique has been used to determine the coronary artery anatomy and guide percutaneous coronary intervention (PCI). We mainly focused on whether the new techniques could improve the patients' mortality, major adverse cardiovascular events (MACEs), and myocardial infarction., Methods: For the network meta-analysis, we searched the trials of different PCI guidances from MEDLINE, Current Contents Connect, Google Scholar, EMBASE, Cochrane Library, PubMed, Science Direct, and Web of Science. The last search date was December 10, 2018., Results: The analyses of all results found that there was no significant difference in mortality among the groups. Randomized clinical trials (RCT) analysis showed that intravascular ultrasound (IVUS)-guided PCI was significantly superior to CA, fractional flow reserve, instantaneous wave-free ratio, optical coherence tomography. However, CA, fractional flow reserve, instantaneous wave-free ratio, and optical coherence tomography showed no difference in reducing mortality. The analyses of all results found that there was no significant difference in the incidence of MACEs among the groups. RCTs analysis showed that IVUS-guided PCI was significantly superior to CA, but there was no significant difference among the other groups. The analyses of all results or RCTs showed that there was no significant difference in myocardial infarction incidence among the groups., Conclusion: IVUS-guided PCI is an effective method to decrease all-cause death MACEs.

Laser scanning based on Micro-Electro-Mechanical Systems (MEMS) scanners has become very attractive for biomedical endoscopic imaging, such as confocal microscopy or Optical Coherence Tomography (OCT). These scanners are required to be fast to achieve real-time image reconstruction while working at low actuation voltage to comply with medical standards. In this context, we report a 2-axis Micro-Electro-Mechanical Systems (MEMS) electrothermal micro-scannercapable of imaging large fields of view at high frame rates, e.g. from 10 to 80 frames per second. For this purpose, Lissajous scan parameters are chosen to provide the optimal image quality within the scanner capabilities and the sampling rate limit, resulting from the limited A-scan rate of typical swept-sources used for OCT. Images of 233 px × 203 px and 53 px × 53 px at 10 fps and 61 fps, respectively, are experimentally obtained and demonstrate the potential of this micro-scannerfor high definition and high frame rate endoscopic Lissajous imaging.

Spatiotemporal optical coherence (STOC) imaging is a new technique for suppressing coherent cross talk noise in Fourier-domain full-field optical coherence tomography (FD-FF-OCT). In STOC imaging, the time-varying inhomogeneous phase masks modulate the incident light to alter the interferometric signal. Resulting interference images are then processed as in standard FD-FF-OCT and averaged incoherently or coherently to produce cross-talk-free volumetric optical coherence tomography (OCT) images of the sample. Here, we show that coherent averaging is suitable when phase modulation is performed for both interferometer arms simultaneously. We explain the advantages of coherent over incoherent averaging. Specifically, we show that modulated signal, after coherent averaging, preserves lateral phase stability, enabling computational phase correction to compensate for geometrical aberrations. Ultimately, we employ it to correct for aberrations present in the image of the photoreceptor layer of the human retina that reveals otherwise invisible photoreceptor mosaics.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOP cc and corneal hysteresis with photoreceptor thickness.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Goals: To describe the distribution of the central corneal thickness (CCT) in the Tunisian population., Methods: A prospective descriptive study was performed in 201 right eyes of 201 randomly selected healthy Tunisian subjects without glaucoma. We measured the spherical error by autorefraction, the axial length using A-scan ultrasound biometry and the central corneal thickness using anterior segment optical coherence tomography (DRI TRITON OCT)., Results: We examined 201 eyes. The mean age was 47±13.5 years (18 to 77 years). The M/F sex ratio was at 0.46 (137 women and 64 men). The mean CCT was 508,1μm (standard deviation 31,5μm) and ranged from 440 to 600μm. In our population 43.8% had a CCT less than 500μm, and 89.1% had a CCT less than 550μm. No statistically significant correlation was observed between CCT and age, sex, spherical error or axial length., Conclusion: Central corneal thickness in the Caucasian Tunisian population is less than CCT in the European and Asian populations. CCT is independent of age, sex, spherical error or axial length. These results must be confirmed by larger multicentric studies., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

The optical attenuation coefficient (AC), an important tissue parameter that measures how quickly incident light is attenuated when passing through a medium, has been shown to enable quantitative analysis of tissue properties from optical coherence tomography (OCT) signals. Successful extraction of this parameter would facilitate tissue differentiation and enhance the diagnostic value of OCT. In this review, we discuss the physical and mathematical basis of AC extraction from OCT data, including current approaches used in modeling light scattering in tissue and in AC estimation. We also report on demonstrated clinical applications of the AC, such as for atherosclerotic tissue characterization, malignant lesion detection, and brain injury visualization. With current studies showing AC analysis as a promising technique, further efforts in the development of methods to accurately extract the AC and to explore its potential use for more extensive clinical applications are desired.

Background: Deep learning has the potential to transform health care; however, substantial expertise is required to train such models. We sought to evaluate the utility of automated deep learning software to develop medical image diagnostic classifiers by health-care professionals with no coding-and no deep learning-expertise., Methods: We used five publicly available open-source datasets: retinal fundus images (MESSIDOR); optical coherence tomography (OCT) images (Guangzhou Medical University and Shiley Eye Institute, version 3); images of skin lesions (Human Against Machine [HAM] 10000), and both paediatric and adult chest x-ray (CXR) images (Guangzhou Medical University and Shiley Eye Institute, version 3 and the National Institute of Health [NIH] dataset, respectively) to separately feed into a neural architecture search framework, hosted through Google Cloud AutoML, that automatically developed a deep learning architecture to classify common diseases. Sensitivity (recall), specificity, and positive predictive value (precision) were used to evaluate the diagnostic properties of the models. The discriminative performance was assessed using the area under the precision recall curve (AUPRC). In the case of the deep learning model developed on a subset of the HAM10000 dataset, we did external validation using the Edinburgh Dermofit Library dataset., Findings: Diagnostic properties and discriminative performance from internal validations were high in the binary classification tasks (sensitivity 73·3-97·0%; specificity 67-100%; AUPRC 0·87-1·00). In the multiple classification tasks, the diagnostic properties ranged from 38% to 100% for sensitivity and from 67% to 100% for specificity. The discriminative performance in terms of AUPRC ranged from 0·57 to 1·00 in the five automated deep learning models. In an external validation using the Edinburgh Dermofit Library dataset, the automated deep learning model showed an AUPRC of 0·47, with a sensitivity of 49% and a positive predictive value of 52%., Interpretation: All models, except the automated deep learning model trained on the multilabel classification task of the NIH CXR14 dataset, showed comparable discriminative performance and diagnostic properties to state-of-the-art performing deep learning algorithms. The performance in the external validation study was low. The quality of the open-access datasets (including insufficient information about patient flow and demographics) and the absence of measurement for precision, such as confidence intervals, constituted the major limitations of this study. The availability of automated deep learning platforms provide an opportunity for the medical community to enhance their understanding in model development and evaluation. Although the derivation of classification models without requiring a deep understanding of the mathematical, statistical, and programming principles is attractive, comparable performance to expertly designed models is limited to more elementary classification tasks. Furthermore, care should be placed in adhering to ethical principles when using these automated models to avoid discrimination and causing harm. Future studies should compare several application programming interfaces on thoroughly curated datasets., Funding: National Institute for Health Research and Moorfields Eye Charity., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Cutaneous blood flow plays a key role in numerous physiological and pathological processes and has significant potential to be used as a biomarker to diagnose skin diseases such as basal cell carcinoma (BCC). The determination of the lesion area and vascular parameters within it, such as vessel density, is essential for diagnosis, surgical treatment and follow-up procedures. Here, an automatic skin lesion area determination algorithm based on optical coherence tomography angiography (OCTA) images is presented for the first time. The blood vessels are segmented within the OCTA images and then skeletonized. Subsequently, the skeleton is searched over the volume and numerous quantitative vascular parameters are calculated. The vascular density is then used to segment the lesion area. The algorithm is tested on both nodular and superficial BCC, and comparing with dermatological and histological results, the proposed method provides an accurate, non-invasive, quantitative and automatic tool for BCC lesion area determination., (© 2019 The Authors. Journal of Biophotonics published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: To benchmark the human and machine performance of spectral-domain (SD) and swept-source (SS) optical coherence tomography (OCT) image segmentation, i.e., pixel-wise classification, for the compartments vitreous, retina, choroid, sclera., Methods: A convolutional neural network (CNN) was trained on OCT B-scan images annotated by a senior ground truth expert retina specialist to segment the posterior eye compartments. Independent benchmark data sets (30 SDOCT and 30 SSOCT) were manually segmented by three classes of graders with varying levels of ophthalmic proficiencies. Nine graders contributed to benchmark an additional 60 images in three consecutive runs. Inter-human and intra-human class agreement was measured and compared to the CNN results., Results: The CNN training data consisted of a total of 6210 manually segmented images derived from 2070 B-scans (1046 SDOCT and 1024 SSOCT; 630 C-Scans). The CNN segmentation revealed a high agreement with all grader groups. For all compartments and groups, the mean Intersection over Union (IOU) score of CNN compartmentalization versus group graders' compartmentalization was higher than the mean score for intra-grader group comparison., Conclusion: The proposed deep learning segmentation algorithm (CNN) for automated eye compartment segmentation in OCT B-scans (SDOCT and SSOCT) is on par with manual segmentations by human graders., Competing Interests: Authors BH, PK, SS are salaried employees of Supercomputing Systems, Zurich; this does not alter our adherence to PLOS ONE policies on sharing data and materials. Outside of the present study, the authors declare the following competing interests: PMM is a consultant at Zeiss Forum, Roche and holds intellectual properties for machine learning at MIMO AG, Berne, Switzerland. AYL has received funding from Novartis, Microsoft Corporation, NVIDIA Corporation and grant number from NEI: K23EY029246. CE and AT received a financial grant from the National Institute for Health Research (NIHR) Biomedical Research Centre, based at Moorfields Eye Hospital, and also from the NHS Foundation Trust and the UCL Institute of Ophthalmology. The views expressed in this article are those of the authors and not necessarily those of the National Eye Institute, NHS, the NIHR, or the Department of Health. AT is a consultant for Heidelberg Engineering and Optovue and has received research grant funding from Novartis and Bayer. CE is a consultant for Heidelberg Engineering and has received research grant funding from Novartis. MO has received travel and honorarium from Allergan. KF has received fellowship support from Alfred Vogt Stipendium and Schweizerischer Fonds zur Verhütung und Bekämpfung der Blindheit and has been an external consultant for DeepMind. JZ-V declares the following (where C: Consultant, S: Speaker; TG: Travel Grant, G: Research Grant, IP: Intellectual Properties): Alcon (C,S, TG, Alimera Sciences (C, S, TG), Allergan (C, S, TG, G), Bausch & Lomb (S, TG), Bayer (C,S, TG), Brill Pharma (C, S9, Novartis (S, TG), Topcon (S, TG, Zeiss (S). These do not alter our adherence to PLOS ONE policies on sharing data and materials.

Optical coherence tomography (OCT) based measurements of retinal layer thickness, such as the retinal nerve fibre layer (RNFL) and the ganglion cell with inner plexiform layer (GCIPL) are commonly employed for the diagnosis and monitoring of glaucoma. Previously, machine learning techniques have relied on segmentation-based imaging features such as the peripapillary RNFL thickness and the cup-to-disc ratio. Here, we propose a deep learning technique that classifies eyes as healthy or glaucomatous directly from raw, unsegmented OCT volumes of the optic nerve head (ONH) using a 3D Convolutional Neural Network (CNN). We compared the accuracy of this technique with various feature-based machine learning algorithms and demonstrated the superiority of the proposed deep learning based method. Logistic regression was found to be the best performing classical machine learning technique with an AUC of 0.89. In direct comparison, the deep learning approach achieved a substantially higher AUC of 0.94 with the additional advantage of providing insight into which regions of an OCT volume are important for glaucoma detection. Computing Class Activation Maps (CAM), we found that the CNN identified neuroretinal rim and optic disc cupping as well as the lamina cribrosa (LC) and its surrounding areas as the regions significantly associated with the glaucoma classification. These regions anatomically correspond to the well established and commonly used clinical markers for glaucoma diagnosis such as increased cup volume, cup diameter, and neuroretinal rim thinning at the superior and inferior segments., Competing Interests: Authors S.M., B.A, and R.G. are employed by IBM Research Australia. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To determine whether ultra-widefield (UWF) retinal imaging changes the staging or management of sickle cell retinopathy compared with clinical examination., Methods: Prospective, observational study including patients with sickle cell disease. All patients underwent dilated fundus examination by a fellowship-trained retina specialist, as well as UWF fundus photography (FF) and fluorescein angiography (FA). Sickle retinopathy stage and treatment recommendation per eye were determined after clinical examination, UWF-FF, and UWF-FA, respectively, and differences in retinopathy stage and treatment recommendation were compared., Results: A total of 70 eyes from 35 patients (17 women, 48.6%), mean age 30.4 years, were included. Sickle genotypes included 26 patients with sickle SS (74.3%), 7 SC (20.0%), and 2 β(+)thalassemia (5.7%). Based on examination, most eyes (42/70; 60.0%) had no visible retinopathy. Based on UWF-FF, about half of the eyes were found to be Goldberg Stage 2 or above (36/70; 51.4%). Based on UWF-FA, nearly all eyes were Goldberg Stage 2 or above (63/70; 90%). However, clinical examination reliably detected neovascularization, and in no case did the addition of UWF imaging change management relative to examination alone., Conclusion: Ultra-widefield imaging detects a higher stage of sickle cell retinopathy compared with clinical examination alone, but these differences may not be clinically significant.

Objectives: We aimed to compare the results of neointimal modification before drug-coated balloon (DCB) treatment with excimer laser coronary atherectomy (ELCA) plus scoring balloon predilation versus scoring balloon alone in patients presenting with in-stent restenosis (ISR)., Background: Treatment of ISR with ELCA typically results in superior acute gain by neointima debulking. However, the efficacy of combination therapy of ELCA and DCB remains unknown., Methods: A total of 42 patients (44 ISR lesions) undergoing DCB treatment with ELCA plus scoring balloon (ELCA group, n = 18) or scoring balloon alone (non-ELCA group, n = 24) were evaluated via serial assessment by optical coherence tomography (OCT) performed before, after intervention, and at 6 months., Results: Although there was significantly greater frequency of diffuse restenosis and percent diameter stenosis (%DS) after intervention in the ELCA group, comparable result was shown in %DS, late lumen loss, and binary angiographic restenosis at follow-up. On OCT analysis, a decreased tendency in the minimum lumen area and a significant decrease in the minimum stent area were observed in the ELCA group between 6-month follow-up and after intervention (-0.89 ± 1.36 mm 2 vs. -0.09 ± 1.25 mm 2 , p = 0.05, -0.49 ± 1.48 mm 2 vs. 0.28 ± 0.78 mm 2 , p = 0.03, respectively). The changes in the neointimal area were similar between the groups, and target lesion revascularization showed comparable rates at 1 year (11.1% vs. 11.4%, p = 0.85)., Conclusions: Despite greater %DS after intervention, ELCA before DCB had possible benefit for late angiographic and clinical outcome., Competing Interests: The authors have no associations with industry that could constitute conflicts of interest., (Copyright © 2019 Toru Miyazaki et al.)

Hydroxychloroquine (HCQ), an analog of chloroquine, is widely used in various rheumatologic and dermatologic disorders. However, it may cause severe retinopathy with long-term use. The guidelines proposed by the American Academy of Ophthalmology suggested a baseline fundus examination and an annual screening after 5 years by using automated visual fields (VF) plus spectral-domain optical coherence tomography (SD-OCT). Both multifocal electroretinogram (mfERG) and fundus autofluorescence (FAF) can also be used to improve the accuracy of diagnosis. The purpose of this study was to examine if the current HCQ screening practice in Taiwan was sufficient according to the guidelines to prevent severe macular complications.This study could remind every doctor to explain visual side effects thoroughly to every patient using HCQ, and refer patients for the ophthalmologic survey to eliminate potential visual impairment caused by this medicine.This nationwide population-based cohort study included all patients who started taking HCQ (n = 5826) from January 1, 1997, to December 31, 2007, in the Longitudinal Health Insurance Database 2000. The ICD codes used for HCQ retinopathy were 362.10, 362.55, 362.89, and 362.9. Patients previously diagnosed these retinal disorders were excluded. Demographic data including sex, age, diagnostic tools used, and the date of the initial diagnosis of the subsequent HCQ-related retinal disorder were collected. Patients were divided into 2 groups. The patients taking HCQ <5 years were defined as group 1, and >5 years as group 2. The risk of developing retinal diseases between these 2 groups was compared with a 2-sample t-test for continuous variables, and Fisher's exact test for discrete variables. Multiple logistic regressions were used for odds ratio calculation.The baseline examination ratio of the automated VF, SD-OCT scans, and multifocal electroretinograms (mfERGs) in the first 3 months were only 0.2% in both groups. The screening ratio of the 3 examination tools after 5 years were 1.1% in group 1 and 1.2% in group 2. 2.5% and 3.9% of patients developed a retinal disorder after HCQ use in group 1 and 2, respectively. The risk of developing retinal disorder was significantly higher in group 2 (relative risk = 1.53, P = .006). The odds ratio (OR) was also significantly higher in group 2 (1.67 with 95% cumulative incidence 1.20-2.30)The examination ratio according to the guidelines was very low in Taiwan. Thus, it is very important for doctors who prescribe HCQ to schedule both baseline and annual ophthalmology screening tests and inform patients of possible severe ocular complications, even in the patient taking HCQ <5 years. It is also important for ophthalmologists to review medical history carefully to find out the causes of retinotoxicity. Medications should be stopped, if possible when toxicity is recognized or strongly suspected.

Purpose: To describe prescriber reported scleral lens fitting and assessment strategies., Methods: The SCOPE (Scleral Lenses in Current Ophthalmic Practice Evaluation) study group designed and administered an IRB approved, electronic survey (REDCap) regarding current scleral lens fitting and assessment methods. The survey was distributed to attendees of the 2017 Global Specialty Lens Symposium., Results: 95 practitioners responded to the survey. Over half of the respondents, 58% (55/95) reported fitting scleral lenses for less than five years (new prescribers), and 42% (40/95) reported fitting scleral lenses for more than five years (experienced prescribers). There was a statistically significant difference between their initial use of technology (χ 2  = 21.117, p < 0.0005) in selection of a diagnostic lens. New prescribers consider base curve first (60%, 33/55), while experienced prescribers considered sagittal depth first (63%, 25/40) in their initial scleral lens selection. All of the experienced lens prescribers (100%, 39/39) reported estimating central clearance by comparing thickness of the post-lens tear reservoir to scleral lens thickness using a slit lamp beam at least some of the time, and 62% of new scleral lens prescribers (34/55; χ 2  = 19.175, p < 0.0005) reported doing so. All (100%, 40/40) experienced prescribers schedule scleral lens follow-ups at a specific time and assess conjunctival compression (100%, 40/40), conjunctival staining (100%, 39/39), and corneal staining (100%,40/40) after lens removal., Conclusions: Practitioners with varying backgrounds and experience have added sclerals to their lens inventories. However, definite guidelines for fitting have not been developed. The results of a survey are provided; demonstrating that among practitioners with greater than 5 years of scleral lens experience, a consensus has emerged for best practices. Strategies for lens evaluation, which may inform future efforts at generating scleral fitting standards are described., (Copyright © 2018 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)

Macular diseases, including neovascular age-related macular degeneration (nvAMD), are leading causes of irreversible blindness and visual impairment. One prominent feature of nvAMD is the detachment of the retinal pigment epithelium. The aim of this study is to implement an automated method for the segmentation of the pigment epithelial detachment (PED) using optical coherence tomography (OCT). OCT datasets from 8 patients with nvAMD were acquired during multiple sessions. At each session, 17 images with a resolution of 1020 × 640 pixels were obtained. The images were segmented using Gaussian filtering and template matching for the detection of the upper and lower border of the PED, respectively. The results of the method were compared with the ones obtained from the manual segmentation of the images by an expert. Four well-known metrics were used to evaluate the performance of the method with respect to the manual segmentation, resulting in high scores of consistency. Furthermore, the proposed method was also compared with four other well-known methods providing similar or superior performance.

Background and Objective: Accurate segmentation of the intra-retinal tissue layers in Optical Coherence Tomography (OCT) images plays an important role in the diagnosis and treatment of ocular diseases such as Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME). The existing energy minimization based methods employ multiple, manually handcrafted cost terms and often fail in the presence of pathologies. In this work, we eliminate the need to handcraft the energy by learning it from training images in an end-to-end manner. Our method can be easily adapted to pathologies by re-training it on an appropriate dataset., Methods: We propose a Conditional Random Field (CRF) framework for the joint multi-layer segmentation of OCT B-scans. The appearance of each retinal layer and boundary is modeled by two convolutional filter banks and the shape priors are modeled using Gaussian distributions. The total CRF energy is linearly parameterized to allow a joint, end-to-end training by employing the Structured Support Vector Machine formulation., Results: The proposed method outperformed three benchmark algorithms on four public datasets. The NORMAL-1 and NORMAL-2 datasets contain healthy OCT B-scans while the AMD-1 and DME-1 dataset contain B-scans of AMD and DME cases respectively. The proposed method achieved an average unsigned boundary localization error (U-BLE) of 1.52 pixels on NORMAL-1, 1.11 pixels on NORMAL-2 and 2.04 pixels on the combined NORMAL-1 and DME-1 dataset across the eight layer boundaries, outperforming the three benchmark methods in each case. The Dice coefficient was 0.87 on NORMAL-1, 0.89 on NORMAL-2 and 0.84 on the combined NORMAL-1 and DME-1 dataset across the seven retinal layers. On the combined NORMAL-1 and AMD-1 dataset, we achieved an average U-BLE of 1.86 pixels on the ILM, inner and outer RPE boundaries and a Dice of 0.98 for the ILM-RPE in region and 0.81 for the RPE layer., Conclusion: We have proposed a supervised CRF based method to jointly segment multiple tissue layers in OCT images. It can aid the ophthalmologists in the quantitative analysis of structural changes in the retinal tissue layers for clinical practice and large-scale clinical studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Coronary artery vasospasm (CS) can be identified as either a diffuse type or focal type; however, the difference in endothelial characteristics between these spasm types remains unclear. The features of coronary intima associated with diffuse spasm and focal spasm using coronary angioscopy (CAS) were evaluated and the optical coherence tomography (OCT) findings were compared., Methods: CAS and/or OCT observational analysis was performed in 55 patients (mean age: 61.4 years, 31 men) who had acetylcholine-provoked CS (diffuse CS, 31 patients; focal CS, 24 patients). The yellowness of the intima, presence of thrombus in CAS, and intimal characteristics based on the OCT results were evaluated., Results: CAS showed more atherosclerotic yellow plaques at the focal spasm segment than at the diffuse spasm segment (p=0.032). Moreover, there were more thrombi at the focal spasm segment (p=0.039). In addition, OCT results revealed that the intima area, maximum intima thickness, and lipid content in the focal CS group were larger than the diffuse CS group (4.22±1.67mm 2 vs. 3.45±2.36mm 2 ; 0.71±0.29mm vs. 0.53±0.30mm; 55.9% vs. 32.0%, p<0.001, respectively)., Conclusions: These results indicate that the presence of atherosclerotic plaques at the spasm site is likely to be related to the occurrence of a focal vasospasm. This may support the difference of features between focal CS and diffuse CS and contribute to precise treatment for each spasm type., (Copyright © 2018 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to identify the normative values of ganglion cell-inner plexiform layer (GCIPL) thickness in healthy Korean children using swept-source optical coherence tomography (SS-OCT) and to investigate the correlations of age, refractive error, axial length (AL), retinal nerve fiber layer (RNFL) thickness and cup-to-disc (C/D) ratio with GCIPL thickness. Children aged between 3 and 17 who had visited our pediatric ophthalmology clinic were enrolled. Each subject underwent full ophthalmic examinations including RNFL thickness, C/D ratio and GCIPL thickness measurement by SS-OCT as well as AL measurement by partial-coherence interferometry. A total of 254 eyes of 127 children were included. The mean average GCIPL thickness was 71.5 ± 5.35 μm; the thickest sector was the superonasal and the thinnest the inferior. According to multivariate regression analysis, average GCIPL thickness was significantly associated with spherical equivalent and RNFL thickness (P < 0.0001 for both): the higher the myopia or the thinner the RNFL thickness, the thinner the GCIPL thickness. In conclusion, this study provides an SS-OCT-based pediatric normative database of GCIPL thickness that can serve as a reference for early detection and follow-up of glaucoma and optic nerve diseases in children.

Anastomotic leakage is one of the most severe complications after esophageal resection with gastric tube reconstruction. Impaired perfusion of the gastric fundus is seen as the main contributing factor for this complication. Optical modalities show potential in recognizing compromised perfusion in real time, when ischemia is still reversible. This review provides an overview of optical techniques with the aim to evaluate the (1) quantitative measurement of change in perfusion in gastric tube reconstruction and (2) to test which parameters are the most predictive for anastomotic leakage.A Pubmed, MEDLINE, and Embase search was performed and articles on laser Doppler flowmetry (LDF), near-infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), fluorescence imaging (FI), sidestream darkfield microscopy (SDF), and optical coherence tomography (OCT) regarding blood flow in gastric tube surgery were reviewed. Two independent reviewers critically appraised articles and extracted the data: Primary outcome was quantitative measure of perfusion change; secondary outcome was successful prediction of necrosis or anastomotic leakage by measured perfusion parameters.Thirty-three articles (including 973 patients and 73 animals) were selected for data extraction, quality assessment, and risk of bias (QUADAS-2). LDF, NIRS, LSCI, and FI were investigated in gastric tube surgery; all had a medium level of evidence. IDEAL stage ranges from 1 to 3. Most articles were found on LDF (n = 12), which is able to measure perfusion in arbitrary perfusion units with a significant lower amount in tissue with necrosis development and on FI (n = 12). With FI blood flow routes could be observed and flow was qualitative evaluated in rapid, slow, or low flow. NIRS uses mucosal oxygen saturation and hemoglobin concentration as perfusion parameters. With LSCI, a decrease of perfusion units is observed toward the gastric fundus intraoperatively. The perfusion units (LDF, LSCI), although arbitrary and not absolute values, and low flow or length of demarcation to the anastomosis (FI) both seem predictive values for necrosis intraoperatively. SDF and OCT are able to measure microvascular flow, intraoperative prediction of necrosis is not yet described.Optical techniques aim to improve perfusion monitoring by real-time, high-resolution, and high-contrast measurements and could therefore be valuable in intraoperative perfusion mapping. LDF and LSCI use perfusion units, and are therefore subjective in interpretation. FI visualizes influx directly, but needs a quantitative parameter for interpretation during surgery.

Background: Although several previous studies have indicated that optical coherence tomography (OCT)-derived minimal lumen area (MLA) correlates with fractional flow reserve (FFR) severity, other morphologic criteria for functionally significant coronary stenosis assessed by FFR have not been fully elucidated. This study aimed to identify OCT-based morphological predictors of physiologically significant ischemia assessed by FFR in angiographically intermediate coronary lesions., Methods: We investigated 194 de novo intermediate coronary lesions in 178 patients with stable angina pectoris who underwent OCT imaging and FFR measurement. The lesions were divided into two groups according to an FFR threshold: ischemia group, FFR <0.75 (n=69) and non-ischemia group, FFR ≥0.75 (n=125). Clinical characteristics, angiographic, and OCT findings were compared between these two groups. Predictors of significant ischemia defined as FFR <0.75 were identified by logistic regression analyses., Results: Patient age, statin use, lesion in left anterior descending artery (LAD), OCT-derived MLA, and lipid volume index (LVI) (averaged lipid arc multiplied by lipid length) were independent predictors of FFR <0.75 in multivariate logistic regression analysis. Receiver operating characteristic analysis suggested that age <64 years old, OCT-derived MLA ≤1.39mm 2 , and LVI ≥733 are the best cut-off values for predicting FFR <0.75. Multiple logistic regression models, including the MLA combined with the LAD location, LVI, age, and statin use, provided superior predictive efficacy for physiologically significant ischemia compared with the model that only employed MLA., Conclusions: Information on OCT-derived LVI and lesion locations facilitates better identification of coronary lesions that cause ischemia than OCT-derived MLA analysis alone., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the repeatability of automatic measurements by a new anterior segment optical coherence tomographer (AS-OCT) combined with Placido topography and their agreement with those provided by 2 rotating Scheimpflug cameras., Setting: G.B. Bietti Foundation IRCCS, Rome, Italy., Design: Evaluation of a diagnostic test instrument., Methods: Unoperated eyes and eyes with previous myopic excimer laser surgery were analyzed. Three consecutive scans were acquired with an AS-OCT device (MS-39) and 1 with 2 rotating Scheimpflug cameras (Pentacam HR and Sirius). The following parameters were evaluated: simulated keratometry, posterior and total corneal power, total corneal astigmatism, corneal asphericity, thinnest corneal thickness, central epithelial thickness, corneal diameter, and aqueous depth. Repeatability was assessed using test-retest variability, the coefficient of variation (CoV), and the intraclass correlation coefficient; agreement was assessed by the 95% limits of agreement., Results: The study comprised 96 unoperated eyes and 43 eyes with previous myopic excimer laser surgery. High repeatability was achieved in both groups, as shown by a CoV less than 1.0% for most parameters. The repeatability of epithelial thickness was slightly lower than that of the whole corneal thickness, although the CoV was still good (1.87% in unoperated eyes; 3.28% in post-refractive surgery eyes). Moderate repeatability was found for total corneal astigmatism measurements, with a CoV greater than 20.0%. Agreement with Scheimpflug cameras was high for aqueous depth and thinnest corneal thickness and moderate for most other parameters., Conclusion: The high repeatability of automatic measurements by the new AS-OCT device supports its use in clinical practice., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Little is known regarding the association between chronological out-stent vessel remodeling and in-stent tissue characteristics of drug-eluting stent (DES) failure. We aimed to evaluate the relationship between serial vessel remodeling after DES implantation and neoatherosclerosis (NA) assessed by optical coherence tomography (OCT) in patients with DES failure., Methods: Forty-eight patients with late and very late stent failure after DES implantation, who underwent intravascular ultrasound (IVUS) at both the initial percutaneous coronary intervention and the time of stent failure and OCT imaging at the time of stent failure, were retrospectively investigated. NA on OCT was defined as neointimal formation with the presence of lipids or calcification inside the stents. Lesions were divided into two groups: those with NA and those without NA (NA: n=21; non-NA: n=27). From the serial IVUS examinations, external elastic membrane (EEM) volume and out-stent plaque volume were normalized by stent length and their changes were compared between the two groups., Results: The NA group showed older stent age [median, 5.1 years (IQR, 4.8-8.3) vs 1.4 years (IQR, 0.8-4.5); p<0.01] and more prevalent sirolimus-eluting stents (SES; 81.0% vs. 29.6%; p<0.01). IVUS findings of the NA group showed a greater serial increase in both normalized EEM volume and normalized out-stent plaque volume (OSPVI) [1.05 (0.41-1.90) vs. 0.11 (-0.64 to 0.80) mm 2 ; p<0.01; and 0.88 (0.57-1.98) vs. 0.12 (-0.41 to 0.78) mm 2 ; p<0.01]. On multivariate analysis, percentage change in OSPVI (OR, 1.07; 95% CI, 1.01-1.14; p=0.02) and SES (OR, 9.78; 95% CI, 2.20-43.40; p<0.01) remained independent predictors of NA., Conclusions: NA in late and very late DES failure was associated with out-stent positive vessel remodeling. In addition to SES, out-stent progressive positive remodeling may help predict NA in late and very late DES failure., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)