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Purpose: To determine the impact of flap creation methods for sub-Bowman’s keratomileusis (SBK) on central Bowman’s layer thickness. Methods: SBK flaps were made by Moria microkeratome for 20 subjects and by femtosecond (FEMTO) laser for 21 subjects. Corneal sublayer thicknesses were measured by ultra-high resolution optical coherence tomography before SBK and at 1 day, 1 week, 2 weeks, and 1 month afterwards. Each subject was imaged twice on each visit. Thicknesses of central epithelium, Bowman’s layer, flap, and total cornea were calculated using a custom-made automated image processing algorithm. The repeatability of sublayer thickness measurements was tested by the intraclass correlation coefficient (ICC) and by the coefficient of repeatability (CoR) at 1 week post-SBK. Results: ICCs of the Moria and FEMTO groups were ≥0.959 and ≥0.961 respectively for all sublayer measurements. The segmentation CoRs were less than 6.78% and 5.63% respectively. For both groups, microdistortions were present in the epithelium and Bowman’s layer after SKB. The flap thickness of the Moria group was 9.8 μm (95% confidence interval: 4.8 – 14.8μm) thinner than the FEMTO group one day after SBK (independent samples t-test, P < 0.05). Bowman’s layer became thicker by 1.6 ± 1.1 μm and 1.7 ± 1.6 μm one day post-SBK for the Moria and FEMTO groups (repeated ANOVA, P < 0.05) and then remained stable. Corneal and sublayer thickness were similar between the two groups. Conclusions: Central Bowman’s layer thickness increased 1 day post-SBK. Flap creation by Moria microkeratome and femtosecond laser did not have significantly different impacts on Bowman’s layer thickness following SBK. Trial Registration: Chinese Clinical Trial Registry (ChiCTR) NO: [ABSTRACT FROM AUTHOR]

Purpose: Tumor-associated neutrophils (TAN) have been reported in a variety of malignancies. We conducted an up-to-date meta-analysis to evaluate the prognostic role of TAN in cancer. Method: Pubmed, Embase and web of science databases were searched for studies published up to April 2013. Pooled hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated. The impact of neutrophils localization and primary antibody were also assessed. Results: A total of 3946 patients with various solid tumors from 20 studies were included. High density of intratumoral neutrophils were independently associated with unfavorable survival; the pooled HRs were 1.68 (95%CI: 1.36–2.07, I2 = 55.8%, p<0.001) for recurrence-free survival (RFS)/disease-free survival (DFS), 3.36 (95%CI: 2.08–5.42, I2 = 0%, p<0.001) for cancer-specific survival (CSS) and 1.66 (95%CI: 1.37–2.01, I2 = 70.5%, p<0.001) for overall survival (OS). Peritumoral and stromal neutrophils were not statistically significantly associated with survival. When grouped by primary antibody, the pooled HRs were 1.80 (95%CI: 1.47–2.22, I2 = 67.7%, p<0.001) for CD66b, and 1.44 (95%CI: 0.90–2.30, I2 = 45.9%, p = 0.125) for CD15, suggesting that CD66b positive TAN might have a better prognostic value than CD15. Conclusion: High levels of intratumoral neutrophils are associated with unfavorable recurrence-free, cancer-specific and overall survival. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the repeatability, reproducibility, and agreement of thickness profile measurements of eight intra-retinal layers determined by an automated algorithm applied to optical coherence tomography (OCT) images from two different instruments. Methods: Twenty normal subjects (12 males, 8 females; 24 to 32 years old) were enrolled. Imaging was performed with a custom built ultra-high resolution OCT instrument (UHR-OCT, ∼3 µm resolution) and a commercial RTVue100 OCT (∼5 µm resolution) instrument. An automated algorithm was developed to segment the macular retina into eight layers and quantitate the thickness of each layer. The right eye of each subject was imaged two times by the first examiner using each instrument to assess intra-observer repeatability and once by the second examiner to assess inter-observer reproducibility. The intraclass correlation coefficient (ICC) and coefficients of repeatability and reproducibility (COR) were analyzed to evaluate the reliability. Results: The ICCs for the intra-observer repeatability and inter-observer reproducibility of both SD-OCT instruments were greater than 0.945 for the total retina and all intra-retinal layers, except the photoreceptor inner segments, which ranged from 0.051 to 0.643, and the outer segments, which ranged from 0.709 to 0.959. The CORs were less than 6.73% for the total retina and all intra-retinal layers. The total retinal thickness measured by the UHR-OCT was significantly thinner than that measured by the RTVue100. However, the ICC for agreement of the thickness profiles between UHR-OCT and RTVue OCT were greater than 0.80 except for the inner segment and outer segment layers. Conclusions: Thickness measurements of the intra-retinal layers determined by the automated algorithm are reliable when applied to images acquired by the UHR-OCT and RTVue100 instruments. [ABSTRACT FROM AUTHOR]

• A boundary-guided convolutional neural network (BG-CNN) was proposed to accurately and simultaneously segment different corneal layers and delineate their boundaries from OCT images. • Two network modules were defined based on the classical U-Net network by introducing three different convolutional blocks. • Experiment results on our collected OCT images demonstrated that the developed network achieved reasonable performance to identify corneal layers, as compared with several available networks. Accurate segmentation of corneal layers depicted on optical coherence tomography (OCT) images is very helpful for quantitatively assessing and diagnosing corneal diseases (e.g. , keratoconus and dry eye). In this study, we presented a novel boundary-guided convolutional neural network (CNN) architecture (BG-CNN) to simultaneously extract different corneal layers and delineate their boundaries. The developed BG-CNN architecture used three convolutional blocks to construct two network modules on the basis of the classical U-Net network. We trained and validated the network on a dataset consisting of 1,712 OCT images acquired on 121 subjects using a 10-fold cross-validation method. Our experiments showed an average dice similarity coefficient (DSC) of 0.9691, an intersection over union (IOU) of 0.9411, and a Hausdorff distance (HD) of 7.4423 pixels. Compared with several other classical networks, namely U-Net, Attention U-Net, Asymmetric U-Net, BiO-Net, CE-Net, CPFnte, M-Net, and Deeplabv3, on the same dataset, the developed network demonstrated a promising performance, suggesting its unique strength in segmenting corneal layers depicted on OCT images. [ABSTRACT FROM AUTHOR]

Purpose: To measure by ultralong scan depth optical coherence tomography (UL-OCT) dimensional changes in the anterior segment of human eyes during accommodation. Design: Evaluation of diagnostic test or technology. Participants: Forty-one right eyes of healthy subjects with a mean age of 34 years (range, 22–41 years) and a mean refraction of −2.5±2.6 diopters were imaged in 2 repeated measurements at minimal and maximal accommodations. Methods: A specially adapted and designed UL-OCT instrument was used to image from the front surface of the cornea to the back surface of the crystalline lens. Custom software corrected the optical distortion of the images and yielded the biometric measurements. The coefficient of repeatability and the intraclass correlation coefficient were calculated to evaluate the repeatability and reliability. Main Outcome Measures: Anterior segment parameters and associated repeatability and reliability upon accommodation. The dimensional results included central corneal thickness (CCT), anterior chamber depth and width (ACD, ACW), pupil diameter (PD), lens thickness (LT), anterior segment length (ASL = ACD + LT), lens central position (LCP = ACD + 1/2LT), and horizontal radii of the lens anterior and posterior surface curvatures (LAC, LPC). Results: Repeated measurements of each variable within each accommodative state did not differ significantly (P>0.05). The coefficients of repeatability (CORs) and intraclass correlation coefficients for CCT, ACW, ACD, LT, LCP, and ASL were excellent (1.2%– 3.59% and 0.998–0.877, respectively). They were higher for PD (18.90%–21.63% and 0.880–0.874, respectively) and moderate for LAC and LPC (34.86%–42.72% and 0.669–0.251, respectively) in the 2 accommodative states. Compared with minimal accommodation, PD, ACD, LAC, LPC, and LCP decreased and LT and ASL increased significantly at maximal accommodation (P<0.05), whereas CCT and ACW did not change (P>0.05). Conclusions: The UL-OCT measured changes in anterior segment dimensions during accommodation with good repeatability and reliability. During accommodation, the back surface of the lens became steeper as the lens moved forward. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. [Copyright &y& Elsevier]

Abstract: Purpose: To determine corneal biomechanical properties in patients with high myopia. Design: Observational study. Methods: High myopia patients (n =45, age: 37.0±12.6 years) with refractive errors of spherical equivalent (SE) greater than −9.00D were recruited in this study along with healthy subjects (n =90, age: 33.7±12.4 years) with refractive errors of SE ranging from 0D to −3.00D. Only the right eye was studied. Central corneal thickness (CCT) was measured by optical coherence tomography (OCT). Metrics of corneal biomechanical properties, including corneal hysteresis (CH) and corneal resistance factor (CRF), were measured with the Ocular Response Analyzer (ORA). The ORA also determined the values of intraocular pressure (IOPg) and corneal compensated IOP (IOPcc). Results: No significant differences of CCT and CRF were present between the two groups (P =.15 and 0.35 for CCT and CRF, respectively); however, CH in the high myope group was lower than that in the controls (P <.01). IOPg and IOPcc were both significantly higher in the high myopes compared to the controls. In both groups, there were significant correlations between CH and CCT and between CRF and CCT. CH was not significantly correlated with age in either the control group or the high myope group (P >.05). There was a significant correlation between CH and SE when the two groups were combined for analysis. Conclusion: CH, but not CRF, was significantly lower in high myopia patients compared to that in normal subjects. The results indicate that some compromised aspects of the biomechanical properties of cornea may exist in people with high myopia. [Copyright &y& Elsevier]

Purpose: To determine diurnal variation of tear menisci around upper and lower eyelids in normal subjects. Design: Prospective laboratory investigation. Methods: Twenty young healthy Chinese subjects (10 women and 10 men; mean age, 21.3 years; range, 20 to 26 years) with no history of contact lens wear or previously diagnosed dry eye were recruited. A custom-built, real-time anterior segment optical coherence tomography (OCT) instrument was used simultaneously to image the upper and lower tear menisci. Repeated measurements immediately after blinking were conducted on both eyes during a 24-hour period, including immediately before and after sleeping. Dimensional information of the tear menisci were obtained from the OCT images using custom software. Results: There were no significant differences between right and left menisci, nor were there any differences between females and males in the lower tear meniscus (P > .05, repeated-measurement analysis of variance [ANOVA]). Although the lower tear meniscus variables were correlated strongly with upper meniscus variables, the lower meniscus was significantly greater than the upper one. Significant diurnal variations (P < .05, repeated-measurement ANOVA) of all measured variables were observed during the study period. Tear menisci were significantly increased at eye opening after overnight sleep compared with the baseline before sleep at 10 pm (P < .001, post hoc tests). They remained elevated up to 10 minutes after eye opening (P < .001, post hoc tests). Conclusions: Real-time OCT can provide useful information regarding the dynamics of the tear system. Diurnal variation of the upper and lower tear menisci occur. [Copyright &y& Elsevier]

A decentered flattened Gaussian beam (DEFGB), is defined by a tensor method. The propagation formula for a DEFGB passing through an axially nonsymmetrical paraxial optical system is derived through vector integration. The derived formula can be reduced to the formula for a generalized decentered elliptical flattened Gaussian beam under certain condition. As an example application of the derived formula, the propagation characteristics of a DEFGB in free space are calculated and discussed. As another example we have studied the properties of superposition with radial array consisted by DEFGB. [Copyright &y& Elsevier]

Summary: The propagation of flattened Gaussian beams (FGBs) passing though misaligned optical systems with aperture has been studied in detail. The corresponding approximate equation has been derived, where the rectangular aperture function is expanded into a finite sum of complex Gaussian functions. Numerical examples are given to illustrate the application of the propagation equation and the properties of flattened Gaussian beams passing through a misaligned optical system with aperture are discussed. [Copyright &y& Elsevier]

Purpose: To generate a model that evaluates the presence and extent of peripheral anterior synechia (PAS) based on anterior segment optical coherence tomography (AS-OCT). Methods: The extent of PAS involvement in the eyes of patients with angle closure was assessed by indentation gonioscopy, and the part of non-PAS and PAS were assigned into two groups (NPAS and PAS). Anterior chamber angles were then imaged by AS-OCT with light-emitting diode (LED) irradiation directly into the pupils, leading to pupillary constriction and increasing anterior chamber angle width. Parameters including the angle opening distance at 750 μm anterior to the scleral spur (AOD750) and trabecular-iris space area at 750 μm anterior to the scleral spur (TISA750) were then obtained. The differences before and after LED irradiation of AOD750 and TISA750 were calculated and used to generate a PAS model based on binary logistic regression. Validation data were then tested. Results: A total of 258 AS-OCT images in 14 eyes were assigned to the modeling data, and 120 were assigned to the validation data. There were no differences in AOD750 and TISA750 in the dark between NPAS and PAS (PAOD750 = 0.258, PTISA750 = 0.486), whereas after LED light exposure, TISA750light was larger in NPAS than in PAS (P = 0.047). The light–dark differences of both parameters showed significant differences between the two groups (PAOD750dif = 0.019, PTISA750dif < 0.001). The area under the curve of the model performance was 0.841, and the overall correct rate was 80.8% based on the validation data. Conclusions: The present study demonstrates that the AS-OCT-based PAS model could be useful in the identifying of the presence of synechial angle closure and evaluating the extent of PAS in a single eye. [ABSTRACT FROM AUTHOR]

• A novel deep network – OCTD_Net – was proposed for early-stage DR classification using OCT images. • The network consisted of two independent networks to combine the deep features and layer information. • The proposed work is the first study that gives diagnostic suggestions for early DR detection using OCT images by visualizing deep features. Diabetic retinopathy (DR) is one of the leading causes of preventable blindness globally. Performing retinal examinations on all diabetic patients is an unmet need, and detection at an early stage can provide better control of the disease. The objective of this study is to provide an optical coherence tomography (OCT) image based diagnostic technology for automated early DR diagnosis, including at both grades 0 and 1. This work can help ophthalmologists with evaluation and treatment, reducing the rate of vision loss, and enabling timely and accurate diagnosis. In this work, we developed and evaluated a novel deep network – OCTD_Net, for early-stage DR detection. While one of the networks extracted features from the original OCT image, the other extracted retinal layer information. The accuracy, sensitivity and specificity was 0.92, 0.90 and 0.95, respectively. Our analysis of retinal layers and the features learned by the proposed network suggests that grade 1 DR patients present with significant changes in the thickness and reflection of certain retinal layers. However, grade 0 DR patients do not have such significant changes. The heatmaps of the trained network also suggest that patients with early DR showed different textures around the myoid and ellipsoid zones, inner nuclear layers, and photoreceptor outer segments, which should all receive dedicated attention for early DR diagnosis. [ABSTRACT FROM AUTHOR]

Myopia is a significant cause of visual impairment which may lead to many complications. However, the understanding of the mechanisms of myopia is still limited. In this paper, in order to investigate the development and the treatment of myopia, we analyzed the biological structure parameters of mice eyes, obtained from optical coherence tomography (OCT), and the optical performance of mice eyes calculated using ZEMAX software (ZEMAX Development Corporation, Kirkland, WA, USA) in which the optical model was built on the segment-by-segment optically corrected OCT 3D-images. Time-serial evaluation of three groups of mice eyes (form-deprivation myopia mice eyes, normal mice eyes, and atropine-treated myopia mice eyes) was performed. In addition to the biological structure parameters, imaging performance with the development of root-mean-square wavefront aberration at six filed angles was compared and analyzed. Results show that the biological structure parameters of the eye are closely related to the development of myopia. The peripheral defocus of the retina has a significant impact on inducing myopia, which verifies the new theory of myopia development. The delaying effect of atropine solution on myopia development is shown to verify the therapeutic effect of the medicine. This study provides technical support for the investigation of the myopia mechanism. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the centration and movement of soft contact lenses and to verify the repeatability of two repeated measurements of the lens centration and movement using ultra-long scan depth optical coherence tomography (UL-OCT). Methods. A 1-day Acuvue® Define™ lens was tested on both eyes of 10 subjects (5 males and 5 females; mean age, 31.6 years). The centration and blink-induced movement of the contact lens were measured using UL-OCT at 5 min and 30 min after insertion. The measurements were repeated once at each checkpoint. Results. Good repeatability was found in the lens centration and movement between the two repeated measurements at either checkpoint. The values of the lens movement were 0.457 ± 0.248 mm and 0.402 ± 0.229 mm at 5 min and decreased to 0.197 ± 0.065 mm and 0.211 ± 0.110 mm at 30 min after insertion for the right and left eyes, respectively (P<0.05). Conclusions. The custom-built UL-OCT presented good repeatability of centration and movement in Define lenses at 5 min and 30 min after insertion. Most of the lenses were centered temporal and inferior to the cornea during the first 30 min wearing period. Compared with 5 min after insertion, the lens was centered better and exhibited less movement at 30 min. [ABSTRACT FROM AUTHOR]

Purpose: To dynamically evaluate contact lens movement and ocular surface shape using ultrahigh-resolution and ultralong-scan-depth optical coherence tomography (OCT). Design: Clinical research study of a laboratory technique. Methods: Four different types of soft contact lenses were tested on the left eye of 10 subjects (6 male and 4 female). Lens edges at primary gaze and temporal and nasal gazes were imaged by ultrahigh-resolution OCT. Excursion lag was obtained as the distance between the lens edge at primary gaze and immediately after the eye was quickly turned either nasally or temporally. The inferior lens edges were imaged continuously to track vertical movements during blinking. Ultralong-scan-depth OCT provided quantifiable images of the ocular surface, and the contour was acquired using custom software. Results: Excursion lag at the horizontal meridian was 366 ± 134 μm at temporal gaze and 320 ± 137 μm at nasal gaze (P > .05). The lens uplift at the vertical meridian was 342 ± 155 μm after blinking. There were significant differences in horizontal lags and vertical movements among different lenses (P < .05). Horizontal lags were correlated with radii of curvatures and sagittal heights at 6-mm and 14-mm horizontal meridian (P < .05). The blink-induced lens uplift first lowered by 104 ± 8 μm, and then lifted 342 ± 155 μm after the blink. Conclusions: Ultrahigh-resolution and ultralong-scan-depth OCT can assess micrometer-scale lens movements and ocular surface contours. Both lens design and ocular surface shape affected lens movements. [Copyright &y& Elsevier]

Purpose: To measure corneal hysteresis (CH) in unilateral chronic primary angle-closure glaucoma (CPACG) patients to determine if it was affected by high intraocular pressure (IOP). Design: Prospective interventional case series. Methods: CH and Goldmann-correlated IOP (IOPg) were obtained with the Ocular Response Analyzer (Reichert Ophthalmic Instruments, Dephew, New York, USA) and central corneal thickness (CCT) was measured by optical coherence tomography. Baseline CH, IOPg, and CCT were measured in 40 CPACG eyes and compared to the fellow eyes and 40 normal controls. Reduction of IOPg in CPACG eyes was achieved medically, followed by trabeculectomy and peripheral iridectomy. Measurements were repeated at 2 and 4 weeks posttherapy. Results: IOPg decreased significantly from 31.55 ± 10.48 mm Hg (mean ± standard deviation) before therapy to 11.47 ± 4.71 mm Hg, and CH increased significantly from 6.83 ± 2.08 mm Hg to 9.22 ± 1.80 mm Hg at 2 weeks, with no further changes after that. However, the CH in the treated eyes remained significantly lower compared with that of fellow and normal eyes. Before treatment, CH was negatively correlated with IOPg; however, there was no correlation after treatment. CCT was not affected by the reduced IOPg in the CPACG eyes. Conclusions: CH was significantly lower in CPACG patients, and partial recovery occurred after successful IOP-lowering therapy. Alternations affecting corneal biomechanical properties appear to occur during glaucoma development. [Copyright &y& Elsevier]

Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) are two common retinal diseases for elder people that may ultimately cause irreversible blindness. Timely and accurate diagnosis is essential for the treatment of these diseases. In recent years, computer-aided diagnosis (CAD) has been deeply investigated and effectively used for rapid and early diagnosis. In this paper, we proposed a method of CAD using vision transformer to analyze optical coherence tomography (OCT) images and to automatically discriminate AMD, DME, and normal eyes. A classification accuracy of 99.69% was achieved. After the model pruning, the recognition time reached 0.010 s and the classification accuracy did not drop. Compared with the Convolutional Neural Network (CNN) image classification models (VGG16, Resnet50, Densenet121, and EfficientNet), vision transformer after pruning exhibited better recognition ability. Results show that vision transformer is an improved alternative to diagnose retinal diseases more accurately. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To demonstrate that high-resolution biometry is possible in mouse eyes in vivo, using real-time OCT with focal plane advancement by a stepper motor. Methods: OCT images of eyes were taken from nine 29-day-old C57BL/6 mice(18 eyes) on two consecutive days. A custom-built real-time OCT instrument with a stepper motor was used to advance the focal plane from the corneal apex to the retina along the ocular axis. The ocular dimensions were determined by advancement of the stepper motor as it displayed on the OCT scan images. Results: OCT images of the entire eye, including the cornea, anterior chamber, lens, vitreous chamber, and retina, were successfully obtained from both eyes of all mice. The measured average corneal thickness from 18 eyes at the age of 29 days was 90.8±4.6μm, anterior chamber depth 707.4±21.4μm, lens thickness 1558.7±18.0μm, vitreous chamber depth 707.4±21.4μm and retinal thickness was 186.9±15.1μm. Total axial length (from the corneal apex to the nerve fiber layer of the retina) was 3003.3±44.1μm. None of them were significantly different if measured on two consecutive days, and no significant differences were found between measurements in the left and right eyes. Conclusion: By focal plane advancement of a real-time OCT instrument through the mouse eye, highly repeatable measurements of the ocular dimensions were obtained. This novel method may be used to study small animal models of normal and abnormal eye development. [Copyright &y& Elsevier]

As the most common form of dementia, Alzheimer's disease (AD) is characterized by progressive cognitive impairments and constitutes a major social burden. Currently, the invasiveness and high costs of tests have limited the early detection and intervention of the disease. As a unique window of the brain, retinal changes can reflect the pathology of the brain. In this review, we summarize current understanding of retinal structures in AD, mild cognitive impairment (MCI) and preclinical AD, focusing on neurodegeneration and microvascular changes measured using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) technologies. The literature suggests that the impairment of retinal microvascular network and neural microstructure exists in AD, MCI and even preclinical AD. These findings provide valuable insights into a better understanding of disease pathogenesis and demonstrate that retinal changes are potential biomarkers for early diagnosis of AD and monitoring of disease progression. [ABSTRACT FROM AUTHOR]

Accurate segmentation of choroidal thickness (CT) and vasculature is important to better analyze and understand the choroid-related ocular diseases. In this paper, we proposed and implemented a novel and practical method based on the deep learning algorithms, residual U-Net, to segment and quantify the CT and vasculature automatically. With limited training data and validation data, the residual U-Net was capable of identifying the choroidal boundaries as precise as the manual segmentation compared with an experienced operator. Then, the trained deep learning algorithms was applied to 217 images and six choroidal relevant parameters were extracted, we found high intraclass correlation coefficients (ICC) of more than 0.964 between manual and automatic segmentation methods. The automatic method also achieved great reproducibility with ICC greater than 0.913, indicating good consistency of the automatic segmentation method. Our results suggested the deep learning algorithms can accurately and efficiently segment choroid boundaries, which will be helpful to quantify the CT and vasculature. [ABSTRACT FROM AUTHOR]

Introduction. Retinal structural and microvascular damages reflect damage to cerebral microvasculature and neurons. We aimed to investigate neovascular unit abnormalities among patients with large-artery atherosclerosis (LAA) or small-vessel occlusion (SAA) and control subjects. Methods. Twenty-eight LAA patients, forty-one SAA patients, and sixty-five age- and gender-matched controls were recruited. Based on optical coherence tomography angiography (OCTA), retinal capillary vessel density was assessed in the general and local sectors, and the thickness of individual retinal layer was extracted from retinal structural images. The differences between structural and microvascular were analyzed. Results. The superior peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly different among the three groups, and the LAA group had the thinnest thickness. Compared to the control group, the deep retinal capillary vessel density in other two stroke subgroups were significantly reduced in all regions except in the inferior region (P < 0.05), and the fractal dimension in C2 and C4 regions of deep retina was significantly lower in the LAA group (P < 0.05). Discussion. Compared with superficial microvascular network, deep microvascular network is more sensitive to ischemic stroke. In addition, we have demonstrated quadrant-specific pRNFL abnormalities in LAA and SAA patients. Superior quadrant pRNFL thickness differences between stroke subgroups may suggest that changes in retinal nerve fiber layer are more sensitive to subtype identification than changes in retinal microvascular structure. All in all, the alteration in retinal structural and microvascular may further elucidate the role of the neovascular unit in ischemic stroke, suggesting that the combination of these two indicators could be used for subtype identification to guide prognosis and establish a risk prediction model. [ABSTRACT FROM AUTHOR]

Introduction. Retinal structural and microvascular damages reflect damage to cerebral microvasculature and neurons. We aimed to investigate neovascular unit abnormalities among patients with large-artery atherosclerosis (LAA) or small-vessel occlusion (SAA) and control subjects. Methods. Twenty-eight LAA patients, forty-one SAA patients, and sixty-five age- and gender-matched controls were recruited. Based on optical coherence tomography angiography (OCTA), retinal capillary vessel density was assessed in the general and local sectors, and the thickness of individual retinal layer was extracted from retinal structural images. The differences between structural and microvascular were analyzed. Results. The superior peripapillary retinal nerve fiber layer (pRNFL) thickness was significantly different among the three groups, and the LAA group had the thinnest thickness. Compared to the control group, the deep retinal capillary vessel density in other two stroke subgroups were significantly reduced in all regions except in the inferior region (P < 0.05), and the fractal dimension in C2 and C4 regions of deep retina was significantly lower in the LAA group (P < 0.05). Discussion. Compared with superficial microvascular network, deep microvascular network is more sensitive to ischemic stroke. In addition, we have demonstrated quadrant-specific pRNFL abnormalities in LAA and SAA patients. Superior quadrant pRNFL thickness differences between stroke subgroups may suggest that changes in retinal nerve fiber layer are more sensitive to subtype identification than changes in retinal microvascular structure. All in all, the alteration in retinal structural and microvascular may further elucidate the role of the neovascular unit in ischemic stroke, suggesting that the combination of these two indicators could be used for subtype identification to guide prognosis and establish a risk prediction model. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relationships among retinal/choroidal thickness, retinal microvascular network and visual field in high myopia. Methods: This cross‐sectional study included a total of 62 subjects, comprising 31 eyes with high myopia and 31 eyes with emmetropia or low myopia. Optical coherence tomography was used to quantify the thickness of ganglion cell complex (GCC), inner nuclear layer and outer plexiform layer (INOPL), outer retinal layer (ORL) and choroid layer (ChL). Optical coherence tomography angiography was used to quantify the superficial vessel density (SVD) and deep vessel density (DVD). Retinal light sensitivity (RLS) was measured by microperimetry‐1 (MP1). The inner ring (1–1.75 mm), the outer ring (1.75–2.5 mm) and the whole ring (1–2.5 mm) around the macula were analysed and compared between the two groups. Pearson correlation analysis was performed to analyse the relationship among them. Results: In the highly myopic group, the thinning of retinal/choroidal thickness and the decrease in retinal vessel density and RLS were found when compared to the emmetropia or low myopia (p < 0.05). Decreased RLS was correlated with decreased ORL thickness (r = −0.469, p = 0.008) and choroid thickness (r = 0.398, p = 0.030). There was no correlation between retinal microvascular network parameters and RLS (p > 0.05), but DVD showed a negative correlation with ORL (r = −0.474, p = 0.007). Conclusion: Early visual field defects in highly myopic eyes may be influenced by the ORL loss and defect of choroidal circulation. The deep retinal microvascular network may have a compensatory action in the hypoxic setting of high myopia. [ABSTRACT FROM AUTHOR]

Objective: To investigate changes in retinal capillary density (RCD) that occur in Graves' ophthalmopathy (GO) and explore their association with the clinical manifestations for GO. Material and Methods: A total of 125 participants (93 GO patients and 32 normal subjects) were enrolled. All participants underwent ophthalmology and endocrinology examinations. Retinal microvasculature was imaged by spectral domain optical coherence tomographic angiography (OCT-A). The RCDs in the superficial and deep retinal capillary plexuses (SRCP and DRCP) were quantified by the custom software from the OCT-A images, which were divided into total annular zones (TAZ) and four quadrants. Multiple linear regression analysis was used to explore the associations between RCD and the relevant factors. Results: Significant reduction was seen in the TAZ zone in SRCP and DRCP of GO group (P <.05) when compared to the healthy subjects; significant differences remained after adjustment of vascular relevant factors. According to the univariate analysis, the relevant factors of higher IOP, larger proptosis, higher clinical activity scoring (CAS), thyroid stimulating hormone-receptor autoantibodies (TRAb), and 131I therapy were significantly associated with decreased RCDs in GO patients (P <.05). Multivariate linear regression analysis showed that CAS and TRAb were the most important relevant factors for decreased RCDs. Conclusions: The RCD of GO patients was significantly decreased compared to the healthy controls. The activity status and serum antibodies associated with GO were the relevant factors for reduced RCD. [ABSTRACT FROM AUTHOR]

Purpose. To determine conjunctival overlap over the edge of soft contact lens and to visualize the peripheral postlens tear film (PoLTF) underneath soft contact lenses using ultrahigh-resolution optical coherence tomography (UHR-OCT). Methods. Twenty participants (4 males and 16 females, 23.0 ± 3.7 years) were fitted with two different types of soft contact lenses randomly. The limbus with lens was imaged with the UHR-OCT at the horizontal meridian every two hours up to 6 hours during lens wear. The conjunctival overlap was ranked as the percentage of the edge covered by the conjunctiva. The frequency of occurrence for visualized peripheral PoLTF was determined. Results. The average conjunctival overlaps at insertion were 49% and 73% for galyfilcon A and balafilcon A lenses and increased significantly to 84% and 90% by 6 hours of lens wear (P<0.001). Lenses with rounded edges had more conjunctival overlap than the lenses with angled edges (P=0.014). There were significant decreases for PoLTF on the conjunctiva (P=0.014) and peripheral cornea (P=0.004) over the study period compared to insertion. The percentage of subjects with PoLTF on the conjunctiva (32.5%) and peripheral cornea (36%) were greater in subjects wearing balafilcon A lenses (P=0.017). Conclusions. Increased conjunctival overlap over the lens edges and reduced PoLTF underneath the peripheral region of soft contact lenses were shown during lens daily wear. The lens edge configuration may play a role in conjunctival response and peripheral PoLTF. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the repeatability and reproducibility of mapping the entire corneal thickness using spectral domain optical coherence tomography (SD-OCT). Methods: Thirty normal eyes, 30 post-laser in situ keratomileusis (LASIK) surgery eyes, and 30 keratoconus eyes were analyzed. A custom-built long scan depth SD-OCT device was used to obtain entire corneal images. Ten-millimeter-diameter corneal thickness maps were generated by an automated segmentation algorithm. Intraclass correlation coefficients of repeatability (ICC1) and reproducibility (ICC2), and coefficients of repeatability (CoR1) and reproducibility (CoR2), were calculated to quantify the precision and accuracy of corneal pachymetry measurements using the Bland-Altman method. Results: For SD-OCT measurements in healthy subjects, CoR1 and CoR2 were less than 5.00 and 5.53 μm. ICC1 and ICC2 were more than 0.997 and 0.996. For SD-OCT measurements in LASIK patients, CoR1 and CoR2 were less than 5.09 and 5.34 μm. ICC1 and ICC2 were more than 0.997 and 0.996. For SD-OCT measurements in keratoconus patients, CoR1 and CoR2 were less than 11.57 and 10.92 μm. ICC1 and ICC2 were more than 0.995 and 0.996. Conclusions: The measurements of corneal pachymetric mapping by long scan depth SD-OCT can be assessed over the entire corneal area with good repeatability and reproducibility. [ABSTRACT FROM AUTHOR]

Delivery of drugs, especially bioactive macromolecules such as proteins and nucleic acids, to the posterior segment is still a significant challenge for pharmaceutical scientists. In the present study, we developed an injectable thermosensitive polymeric hydrogel for sustained release of Avastin ® to treat posterior segment disorders. The payload of Avastin ® to poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) hydrogel did not influence its inherent sol–gel transition behavior, but shifted the sol–gel transition to a lower temperature. The resulting Avastin ® /PLGA-PEG-PLGA hydrogels had a porous structure (pore size, 100 ∼ 150 μm) as determined by scanning electron microcopy (SEM), facilitating sustained Avastin ® release over a period of up to 14 days in vitro . The PLGA-PEG-PLGA hydrogel was immediately formed in the vitreous humor after intravitreal injection, followed by slow clearance over an 8 week study period. The PLGA-PEG-PLGA hydrogel exhibited no apparent toxicity against retinal tissue, as indicated by the absence of inflammation, retinal necrosis, and stress responses, using optical coherence tomography (OCT) and histological/immunochemical analyses. Electrophysiology (ERG) examination also showed that the PLGA-PEG-PLGA hydrogel did not affect retinal function. In vivo pharmacokinetic studies indicated that the use of the PLGA-PEG-PLGA hydrogel greatly extended the release of Avastin ® over time in the vitreous humor and retina after intravitreal injection. Together, these results demonstrated that the PLGA-PEG-PLGA hydrogel was a promising candidate for ocular drug delivery of Avastin ® via intravitreal injection. [ABSTRACT FROM AUTHOR]

Purpose: To determine the biometry of anterior segment dimensions of the human eye on both horizontal and vertical meridians with extended scan depth optical coherence tomography (OCT) during accommodation. Methods: Twenty pre-presbyopic volunteers, aged between 24 and 30, were recruited. The ocular anterior segment of each subject was imaged using an extended scan depth OCT under non- and 3.0 diopters (D) of accommodative demands on both horizontal and vertical meridians. All the images were analyzed to yield the following parameters: pupil diameter (PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive measurements were performed to assess the repeatability and reproducibility of this OCT. They were evaluated by calculating the within-subject standard deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and the coefficient of repeatability/reproducibility (CoR). Results: There were no significant differences between two consecutive measurements on either horizontal or vertical meridians under both two different accommodative statuses (P>0.05). The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550) on the horizontal meridian under the non-accommodative status. In addition, the CoR for most of the parameters were excellent (0.004% to 4.89%). In all the parameters, only PD and PSC were found different between the horizontal and vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and PSC under accommodative status were significantly smaller than those under the non-accommodative status, except that the PSC at the vertical meridian did not change. In addition, LT was significantly increased when accommodation. Conclusion: The extended scan depth OCT successfully measured the dimensions of the anterior eye during accommodation with good repeatability and reproducibility on both horizontal and vertical meridians. The asymmetry of lens posterior surface and oval-shaped pupil were found during accommodation. [ABSTRACT FROM AUTHOR]

The retina provides a window to study the pathophysiology of cerebrovascular diseases. Pathological retinal microvascular changes may reflect microangiopathic processes in the brain. Recent advances in optical imaging techniques have enabled the imaging of the retinal microvasculature at the capillary level, and the generation of high-resolution, non-invasive capillary perfusion maps (nCPMs) with the Retinal Function Imager (RFI). However, the lack of quantitative analyses of the nCPMs may limit the wider application of the method in clinical research. The goal of this project was to demonstrate the feasibility of automated segmentation and fractal analysis of nCPMs. We took two nCPMs of each subject in a group of 6 healthy volunteers and used our segmentation algorithm to do the automated segmentation for monofractal and multifractal analyses. The monofractal dimension was 1.885±0.020, and the multifractal dimension was 1.876±0.010 (P =0.108). The coefficient of repeatability was 0.070 for monofractal analysis and 0.026 for multifractal analysis. This study demonstrated that the automatic segmentation of nCPMs is feasible for fractal analyses. Both monofractal and multifractal analyses yielded similar results. The quantitative analyses of microvasculature at the capillary level may open up a new era for studying microvascular diseases such as cerebral small vessel disease. [ABSTRACT FROM AUTHOR]

Purpose: To determine if corneal hysteresis (CH) was associated with increased central corneal thickness (CCT) induced by wearing soft contact lenses during eye closure. Design: A prospective laboratory investigation. Methods: CCT was measured with a modified optical coherence tomography (OCT), and CH was measured with a Reichert Ocular Response Analyzer (ORA) [Reichert Ophthalmic Instruments, Depew, New York, USA]. The ORA also determined values for intraocular pressure (IOP), corneal compensated IOP (IOPcc), and corneal resistance factor (CRF). One randomly selected eye of 20 non–contact lens wearers (four males and 16 females, age 19.7 ± 1.1 years) was patched during three hours of soft contact lens wear. Measurements were made before lens insertion, immediately upon removal, and every 20 minutes thereafter for 100 minutes. Results: Immediately after contact lens removal, CCT was increased by 13.1 ± 2.2% (mean ± SD) compared with baseline (post hoc, P = .001). After 100 minutes, it remained elevated by 2.4 ± 1.6% (post hoc, P = .001). However, there were no significant differences of CH at any time after lens wear (analysis of variance [ANOVA], P = .9). Immediately after lens removal, there were significant increases in IOP (post hoc, P = .003) and corneal resistance factor (CRF) (post-hoc, P = .015), but not in IOPcc (post hoc, P = .07). After lens wear, there were significant but weak correlations between the percentage change of CCT (CCT%) and IOP (r = 0.32, P = .001) and IOPcc (r = 0.29, P = .001). However, there was no significant correlation between CCT% and CH (r = 0.07, P = .458). Conclusion: CH as measured by ORA was not associated with corneal swelling induced by soft contact lens wear in this study group. [Copyright &y& Elsevier]

To determine the changes of the microvasculature and microstructure in the inner intra-retinal layers in systemic lupus erythematosus (SLE) patients without lupus retinopathy (LR). Thirty-two SLE patients (58 eyes) without LR (NLR), 14 patients (22 eyes) with LR and 50 healthy subjects (50 eyes) were enrolled. Spectral domain optical coherence tomography equipped with Angiovue was used to obtain three-dimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary plexuses (SRCP/DRCP) around the macula. Quantitative analyses were performed using a custom automated algorithm. Disease activity of patients was assessed using the SLE disease activity index (SLEDAI). Retinal capillary skeleton density of the SRCP in SLE patients without LR was significantly lower than the controls in almost all regions, which further decreased in the LR group (P <.05). No significant changes were evident in DRCP of the NLR group (P >.05). The inner retina in the LR group was significantly thinner than the controls in most regions, though there were only a few regions that were different between the NLR and the control groups (P <.05). There were significant differences of the SLEDAI scores between the two SLE groups. Significantly lower density in SRCP and regional thinning in inner retina were observed in the SLE patients without clinical fundus changes. OCT equipped with Angiovue might be useful in evaluating the microvascular and microstructural disorders of the inner retinal layers in SLE patients, which may contribute a quantitative approach to the early diagnosis and progression of LR. • Retinal microvasculature and microstructure were observed in SLE patients with and without lupus retinopathy. • General SRCP density decreasing and regional inner-retinal thinning were detected in SLE patients without lupus retinopathy. • OCT equipped with Angio may contribute a quantitative approach to the early diagnosis and progression of lupus retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of specific retinal sublayer thicknesses on optical coherence tomography (OCT) imaging with brain magnetic resonance imaging (MRI) markers using the Fazekas scale in hypertensive white matter hyperintensity (WMH) subjects. Methods: Eighty‐eight participants (32 healthy controls and 56 hypertensive white matter hyperintensity subjects) underwent retinal imaging using the OCT and MRI. A custom‐built algorithm was used to measure the thicknesses of the retinal nerve fiber layer (RNFL) and ganglion cell layer and inner plexiform layer (GCIP). Focal markers for white matter hyperintensities were assessed on MRI and graded using the Fazekas visual rating. Results: Hypertensive WMH showed significantly reduced (p <.05) RNFL and GCIP layers when compared to healthy controls, respectively. A significant correlation was found between the RNFL (ρ = −.246, p <.001) and GCIP (ρ = −.338, p <.001) of the total participants and the Fazekas score, respectively. Statistical differences were still significant (p <.05) when correlations were adjusted for intereye correlation, age, hypertension, smoking, body mass index, and diabetes. Among the cases of hypertensive WMH, higher Fazekas scores were significantly associated (p <.05) with the thinning of both the RNFL and GCIP layers after adjustment of age and other risk factors. Conclusions: Retinal degeneration in the RNFL and GCIP was independently associated with focal lesions in the white matter of the brain and deteriorates with the severity of the lesions. We suggest that imaging and measurement of the retinal sublayers using the OCT may provide evidence on neurodegeneration in WMH. [ABSTRACT FROM AUTHOR]

The structural characteristics of the outer retinal layers in primary open angle glaucoma (POAG) are still controversial, and these changes, along with those in the inner retinal layers, could have clinical and/or pathophysiological significance. A custom-built ultra-high resolution optical coherence tomography (UHR-OCT) combined with an automated segmentation algorithm can image and measure the eight intra-retinal layers. The purpose of this study is to determine the thickness characteristics of the macular intra-retinal layers, especially the outer layers, in POAG patients. Thirty-four POAG patients (56 eyes) and 33 normal subjects (63 eyes) were enrolled. Thickness profiles of the eight intra-retinal layers along a 6-mm length centred on the fovea at the horizontal and vertical meridians were obtained and the regional thicknesses were compared between two groups. The associations between the thicknesses of each intra-retinal layer and the macular visual field (VF) sensitivity were then analysed. POAG affected not only the inner retinal layers but also the photoreceptor layers and retinal pigment epithelium of the outer retina. However, the VF loss was correlated mainly with the damage of the inner retinal layers. UHR-OCT with automated algorithm is a useful tool in detecting microstructural changes of macula with respect to the progression of glaucoma. [ABSTRACT FROM AUTHOR]

Purpose: To measure the tear meniscus dynamics in aqueous tear deficiency dry eye patients using optical coherence tomography. Design: Clinical research study of a laboratory technique. Methods: Twenty-five aqueous tear deficiency dry eye patients and 30 healthy subjects were recruited. Upper and lower tear menisci of 1 randomly selected eye of each participant were imaged during normal and delayed blinking using optical coherence tomography. Measured parameters included upper tear meniscus height and volume, lower tear meniscus height and volume, the blink outcome defined as the meniscus volume change during blink action, and open eye outcome defined as the meniscus volume change during the open eye period. Results: During normal blinking, both tear meniscus height and volume before blink in dry eye patients were significantly smaller than those in healthy subjects, except for the upper tear meniscus volume. During normal blinking, the blink outcome and open eye outcome of lower tear meniscus were significantly smaller in dry eye patients compared with healthy subjects. During delayed blinking, the upper and lower tear menisci heights and volumes significantly increased in both groups. However, dry eye patients had smaller increases than healthy subjects. During delayed blinking, the open eye outcomes of upper and lower tear menisci were smaller in dry eye patients than healthy subjects. Conclusions: Dry eye patients seem to have reduced tear meniscus dynamics during normal blinking and smaller increases of meniscus volume during delayed blinking. Analysis of tear meniscus dynamics may provide more insight in the altered tear system in dry eye patients. [Copyright &y& Elsevier]