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Deep learning methods have enabled a fast, accurate and automated approach for retinal layer segmentation in posterior segment OCT images. Due to the success of semantic segmentation methods adopting the U-Net, a wide range of variants and improvements have been developed and applied to OCT segmentation. Unfortunately, the relative performance of these methods is difficult to ascertain for OCT retinal layer segmentation due to a lack of comprehensive comparative studies, and a lack of proper matching between networks in previous comparisons, as well as the use of different OCT datasets between studies. In this paper, a detailed and unbiased comparison is performed between eight U-Net architecture variants across four different OCT datasets from a range of different populations, ocular pathologies, acquisition parameters, instruments and segmentation tasks. The U-Net architecture variants evaluated include some which have not been previously explored for OCT segmentation. Using the Dice coefficient to evaluate segmentation performance, minimal differences were noted between most of the tested architectures across the four datasets. Using an extra convolutional layer per pooling block gave a small improvement in segmentation performance for all architectures across all four datasets. This finding highlights the importance of careful architecture comparison (e.g. ensuring networks are matched using an equivalent number of layers) to obtain a true and unbiased performance assessment of fully semantic models. Overall, this study demonstrates that the vanilla U-Net is sufficient for OCT retinal layer segmentation and that state-of-the-art methods and other architectural changes are potentially unnecessary for this particular task, especially given the associated increased complexity and slower speed for the marginal performance gains observed. Given the U-Net model and its variants represent one of the most commonly applied image segmentation methods, the consistent findings across several datasets here are likely to translate to many other OCT datasets and studies. This will provide significant value by saving time and cost in experimentation and model development as well as reduced inference time in practice by selecting simpler models.

The analysis of the choroid in the eye is crucial for our understanding of a range of ocular diseases and physiological processes. Optical coherence tomography (OCT) imaging provides the ability to capture highly detailed cross-sectional images of the choroid yet only a very limited number of commercial OCT instruments provide methods for automatic segmentation of choroidal tissue. Manual annotation of the choroidal boundaries is often performed but this is impractical due to the lengthy time taken to analyse large volumes of images. Therefore, there is a pressing need for reliable and accurate methods to automatically segment choroidal tissue boundaries in OCT images. In this work, a variety of patch-based and fully-convolutional deep learning methods are proposed to accurately determine the location of the choroidal boundaries of interest. The effect of network architecture, patch-size and contrast enhancement methods was tested to better understand the optimal architecture and approach to maximize performance. The results are compared with manual boundary segmentation used as a ground-truth, as well as with a standard image analysis technique. Results of total retinal layer segmentation are also presented for comparison purposes. The findings presented here demonstrate the benefit of deep learning methods for segmentation of the chorio-retinal boundary analysis in OCT images.

Knowledge of the normal in vivo thickness of the retina, and its individual layers in pediatric populations is important for diagnosing and monitoring retinal disorders, and for understanding the eye's normal development and the impact of eye growth and refractive error such as myopia (short-sightedness) upon retinal morphology. In this prospective, observational longitudinal study, total retinal thickness (and individual retinal layer thickness) and the changes in retinal morphology occurring over an 18-month period were examined in 101 children with a range of refractive errors. In childhood, the presence of myopia was associated with subtle but statistically significant (p<0.05) changes in the topographical thickness distribution of macular retinal thickness (and retinal layer thickness), characterised by a thinning of the parafoveal retina (and parafoveal or perifoveal thinning in most outer and inner retinal layers). The parafoveal retina was on average 6 μm thinner in myopic children. However, over 18 months, longitudinal changes in retinal thickness and individual layers were of small magnitude (average changes of less than 2 μm over 18 months), indicative of a high degree of stability in retinal morphology in healthy adolescent eyes, despite significant eye growth over this same period of time. This provides the first detailed longitudinal assessment of macula retinal layer morphology in adolescence, and delivers new normative data on expected changes in retinal structure over time and associated with myopia during this period of childhood development.

This prospective study investigated the magnitude and pattern of variation in choroidal optical coherence tomography angiography (OCT-A) indices every 4 h over 24 h in healthy young myopic (n = 24) and non-myopic (n = 20) adults. Choriocapillaris and deep choroid en-face images from macular OCT-A scans were analysed from each session to extract magnification-corrected vascular indices including choriocapillaris flow deficit number, size and density and deep choroid perfusion density in the sub-foveal, sub-parafoveal, and sub-perifoveal regions. Choroidal thickness was also obtained from structural OCT scans. Significant variations over 24 h (P < 0.05) were observed in most of the choroidal OCT-A indices excluding sub-perifoveal flow deficit number, with peaks observed between 2 to 6 AM. For myopes, peaks occurred significantly earlier (3–5 h), and the diurnal amplitude was significantly greater for sub-foveal flow deficit density (P = 0.02) and deep choroidal perfusion density (P = 0.03) compared with non-myopes. Choroidal thickness also showed significant diurnal changes (P < 0.05) with peaks between 2 to 4 AM. Significant correlations were found between diurnal amplitudes or acrophases of choroidal OCT-A indices and choroidal thickness, intraocular pressure, and systemic blood pressure. This provides the first comprehensive diurnal assessment of choroidal OCT-A indices over 24 h.

There is a paucity of knowledge regarding the normal in-vivo thickness of the choroid beyond the macula (~17°). In this study, the choroidal thickness of 27 healthy young adults was examined across the macular (the central 5 mm including the fovea, parafovea, and perifovea) and extra-macular (a 5–14 mm annulus including the near-periphery and periphery) regions using wide-field optical coherence tomography, and compared between emmetropes (n = 14) and myopes (n = 13). The choroid progressively thinned beyond the parafovea (350 ± 86 µm) towards the periphery (264 ± 44 µm), and was thickest superiorly (355 ± 76 µm) and thinnest nasally (290 ± 79 µm). Choroidal thickness also varied with refractive error; myopes exhibited a thinner choroid than emmetropes in the macular region (311 ± 88 vs. 383 ± 66 µm), however, this difference diminished towards the periphery (251 ± 48 vs. 277 ± 37 µm). Meridional variations in choroidal thickness were not different between myopes and emmetropes. In conclusion, the choroid was thickest within the perifovea; thinned substantially towards the periphery, and exhibited the minimum and maximum peripheral thinning superiorly and nasally across a 55° region respectively. Choroidal thinning associated with myopia was more pronounced in the macular than extra-macular regions.

Optical coherence tomography (OCT) of the posterior segment of the eye provides high-resolution cross-sectional images that allow visualization of individual layers of the posterior eye tissue (the retina and choroid), facilitating the diagnosis and monitoring of ocular diseases and abnormalities. The manual analysis of retinal OCT images is a time-consuming task; therefore, the development of automatic image analysis methods is important for both research and clinical applications. In recent years, deep learning methods have emerged as an alternative method to perform this segmentation task. A large number of the proposed segmentation methods in the literature focus on the use of encoder–decoder architectures, such as U-Net, while other architectural modalities have not received as much attention. In this study, the application of an instance segmentation method based on region proposal architecture, called the Mask R-CNN, is explored in depth in the context of retinal OCT image segmentation. The importance of adequate hyper-parameter selection is examined, and the performance is compared with commonly used techniques. The Mask R-CNN provides a suitable method for the segmentation of OCT images with low segmentation boundary errors and high Dice coefficients, with segmentation performance comparable with the commonly used U-Net method. The Mask R-CNN has the advantage of a simpler extraction of the boundary positions, especially avoiding the need for a time-consuming graph search method to extract boundaries, which reduces the inference time by 2.5 times compared to U-Net, while segmenting seven retinal layers.

ObjectiveVaccination against hepatitis B virus (HBV) confers protection from subsequent infection through immunological memory that is traditionally considered the domain of the adaptive immune system. This view has been challenged following the identification of antigen-specific memory natural killer cells (mNKs) in mice and non-human primates. While the presence of mNKs has been suggested in humans based on the expansion of NK cells following pathogen exposure, evidence regarding antigen-specificity is lacking. Here, we demonstrate the existence of HBV-specific mNKs in humans after vaccination and in chronic HBV infection.DesignNK cell responses were evaluated by flow cytometry and ELISA following challenge with HBV antigens in HBV vaccinated, non-vaccinated and chronic HBV-infected individuals.ResultsNK cells from vaccinated subjects demonstrated higher cytotoxic and proliferative responses against autologous hepatitis B surface antigen (HBsAg)-pulsed monocyte-derived dendritic cells (moDCs) compared with unvaccinated subjects. Moreover, NK cell lysis of HBsAg-pulsed moDCs was significantly higher than that of hepatitis B core antigen (HBcAg)-pulsed moDCs (non-vaccine antigen) or tumour necrosis factor α-activated moDCs in a NKG2D-dependent manner. The mNKs response was mediated by CD56dim NK cells coexpressing CD57, CD69 and KLRG1. Further, mNKs from chronic hepatitis B patients exhibited greater degranulation against HBcAg-pulsed moDCs compared with unvaccinated or vaccinated patients. Notably, mNK activity was negatively correlated with HBV DNA levels.ConclusionsOur data support the presence of a mature mNKs following HBV antigen exposure either through vaccination or infection. Harnessing these antigen specific, functionally active mNKs provides an opportunity to develop novel treatments targeting HBV in chronic infection.

The sclera and conjunctiva form part of the eye’s tough, protective outer coat, and play important roles in the eye’s mechanical protection and immune defence, as well as in determining the size and shape of the eye globe. Advances in ocular imaging technology now allow these tissues in the anterior eye to be imaged non-invasively and with high resolution, however there is a paucity of data examining the dimensions of these tissues in paediatric populations. In this study, we have used optical coherence tomography (OCT) imaging to examine the normal in vivo thickness profile of the anterior sclera and overlying conjunctiva in 111 healthy young participants, including a large proportion of paediatric subjects. We demonstrate that the thickness of the anterior sclera varies significantly with measurement location and meridian. Tissue thickness also varied significantly with age, with younger subjects exhibiting significantly thinner scleras and significantly greater conjunctival thickness. Males were also found to exhibit significantly greater scleral thickness. Refractive error however was not significantly associated with either scleral or conjunctival thickness in this population. These findings provide new data describing the normative dimensions of anterior eye tissues in children and the factors that can influence these dimensions in young populations.

Understanding normative retinal thickness characteristics is critical for diagnosis and monitoring of pathology, particularly in those predisposed to retinal disease. The macular retinal layer thickness of Australian Aboriginal and/or Torres Strait Islander children was examined using spectral-domain optical coherence tomography. High-resolution macular optical coherence tomography imaging was performed on 100 Aboriginal and/or Torres Strait Islander children and 150 non-Indigenous visually healthy children aged 4-18 years. The imaging protocol included a 6-line radial scan centred on the fovea. Images were segmented using semi-automated software to derive thickness of the total retina, inner and outer retina, and individual retinal layers across the macular region. Repeated measures ANOVAs examined variations in thickness associated with retinal region, age, gender and Indigenous status. Retinal thickness showed significant topographical variations (p < 0.01), being thinnest in the foveal zone, and thickest in the parafovea. The retina of Aboriginal and/or Torres Strait Islander children was significantly thinner than non-Indigenous children in the foveal (p < 0.001), parafoveal (p = 0.002), and perifoveal zones (p = 0.01), with the greatest difference in the foveal zone (mean difference: 14.2 μm). Inner retinal thickness was also thinner in Aboriginal and/or Torres Strait Islander children compared to non-Indigenous children in the parafoveal zone (p < 0.001), and outer retinal thickness was thinner in the foveal (p < 0.001) and perifoveal zone (p < 0.001). Retinal thickness was also significantly greater in males than females (p < 0.001) and showed a statistically significant positive association with age (p = 0.01). There are significant differences in macular retinal thickness between Aboriginal and/or Torres Strait Islander children and non-Indigenous children, which has implications for interpreting optical coherence tomography data and may relate to risk of macula disease in this population.

Purpose. To examine the interaction between a short period of hyperopic defocus and low-dose atropine upon the choroidal thickness and ocular biometrics of healthy myopic subjects. Methods. Twenty young adult myopic subjects had subfoveal choroidal thickness (ChT) and ocular biometry measurements taken before and 30 and 60 min following the introduction of optical blur (0.00 D and −3.00 D) combined with administration of 0.01% atropine or placebo. Each combination of optical blur and drug was tested on different days in a fixed order. Results. The choroid exhibited significant thinning after imposing hyperopic defocus combined with placebo (mean change of −11 ± 2 μm, p<0.001). The combination of hyperopic blur and 0.01% atropine led to a significantly smaller magnitude of subfoveal choroidal thinning (−4 ± 8 μm), compared to placebo and hyperopic defocus (p<0.01). Eyes treated with 0.01% atropine with no defocus exhibited a significant increase in ChT (+6 ± 2 μm, p<0.01). Axial length also underwent small but significant changes after treatment with hyperopic blur and placebo and 0.01% atropine alone (both p<0.01), but of opposite direction to the changes in choroidal thickness. However, the 0.01% atropine/hyperopic blur condition did not lead to a significant change in axial length compared to baseline (p>0.05). Conclusion. Low-dose atropine does inhibit the short-term effect of hyperopic blur on choroidal thickness and, when used alone, does cause a slight thickening of the choroid in young healthy myopic adults.