Repeatability of retinal and choroidal optical coherence tomography angiography indices in healthy children and young adults.

PURPOSE: To evaluate the repeatability of retinal and choroidal optical coherence tomography angiography (OCT-A) indices among healthy children and compare it to healthy young adults. METHODS: This prospective study captured 3 mm × 3 mm and 6 mm × 6 mm macular OCT-A scans including superficial and deep retinal layers, choriocapillaris and deep choroid over two visits, 1 week apart at approximately the same time of day, for 22 healthy adults (18-30 years) and 21 children (6-15 years). Magnification and projection-artefact corrected indices extracted using a custom image analysis program and individual biometry were compared between visits using Bland-Altman analysis and intraclass correlation (ICC). Retinal indices included foveal avascular zone metrics, perfusion and vessel density and choroidal indices included choriocapillaris flow deficit metrics and deep choroid perfusion density, in the foveal, parafoveal and perifoveal regions. Repeatability between adults and children was compared with F-test. RESULTS: Bland-Altman analysis showed that the mean differences between repeated OCT-A indices were not significantly different from zero for either of the zones, layers and scan sizes in the two age groups (p > 0.05) except for foveal vessel density and foveal avascular zone perimeter (p = 0.04 for both) of 6-mm-deep retinal layer scans. The ICC ranged between 0.67 and 0.99. Significantly higher variability between visits (p < 0.05) in the indices was noted among adults than children, especially for choroidal indices of larger scan size. CONCLUSION: The retinal and choroidal OCT-A indices in the foveal, parafoveal and perifoveal zones were repeatable in healthy children except for the foveal vessel density and foveal avascular zone perimeter of the 6-mm-deep retinal layer, which exhibited statistically borderline differences between visits. The adult group showed more variability between visits compared to children, especially in the larger scan size for choroidal OCT-A indices.

Hyperopia in schoolchildren: Investigating the impact on vision and determining appropriate methods for screening.

INTRODUCTION: Hyperopia is associated with reduced vision and educational outcomes in schoolchildren. This study explored the impact of clinically significant hyperopia (≥+2.00 D) on visual function in schoolchildren and compared the ability of different screening tests (alone and in combination) to detect this level of hyperopia. METHODS: Vision testing including monocular logMAR visual acuity (VA) measured to threshold (distance [DVA], near [NVA] and DVA through a plus lens [+2.50 D]), stereoacuity and cycloplegic autorefraction (tropicamide 1%) were undertaken on 263 schoolchildren (mean age: 11.76 years ± 3.38) in Queensland, Australia. Vision measures were compared between children with clinically significant hyperopia in at least one meridian (≥+2.00 D) and emmetropia/low hyperopia (>0.00 and <+2.00 D). Receiver operating curve (ROC) analysis was performed to identify optimal pass/fail criteria for each test and the diagnostic accuracy of individual and combinations of tests. RESULTS: Thirty-two children had clinically significant hyperopia and 225 had emmetropia/low hyperopia. DVA and NVA were worse (p < 0.01), while the difference in DVA through a plus lens was less in children with clinically significant hyperopia (p < 0.01). ROC analysis for individual tests resulted in areas under the curve (AUCs) ranging from 0.65 to 0.85. Combining screening tests revealed that failing one or more of the following tests was most effective for detecting hyperopia: DVA, NVA and difference in DVA through a plus lens, resulting in a sensitivity and specificity of 72% and 81%, respectively. CONCLUSION: Significant differences in visual function existed between schoolchildren with clinically significant hyperopia and emmetropia/low hyperopia. Combining measures of DVA and NVA and the difference in DVA through a plus lens demonstrated good discriminative ability for detecting clinically significant hyperopia in this population.

Central and peripheral choroidal thickness and eye length changes during accommodation.

PURPOSE: Eye length increases during accommodation, both on-axis and in the periphery. The aim of this study was to determine whether the peripheral choroid thins with accommodation and to determine the relationship with eye length changes measured at the same location. METHODS: Subjects included 53 young adults in good ocular and general health, with 19 emmetropes and 34 myopes. Measurements from the right eye were made for 0 D and 6 D accommodation stimuli for ±30° horizontal visual field/retinal locations in 10° steps. Valid eye length and choroidal thickness measurements were obtained for 37 and 47 participants, respectively, and both measures were taken for 31 participants. 2.5% phenylephrine was instilled to dilate the pupils. Participants turned their eyes, without head movement, to fixate targets and to make the target 'as clear as possible' during measurements. Correction was made for the influence of lens thickness changing at different peripheral angles. Choroidal thickness was measured with a spectral-domain-Optical Coherence Tomographer. For peripheral images, the internal cross target on the capture screen was moved from the centre to 17.25° nasal/temporal positions. RESULTS: In accordance with previous literature, eye length increased with accommodation. The greatest change (mean ± SD) of 41 ± 17 µm occurred at the centre, with a mean change across the locations of 33 µm. There were no significant differences between emmetropes and myopes. Choroidal thickness decreased with accommodation, with changes being about two-thirds of those occurring for eye length. The greatest change of -30 ± 1 µm occurred at the centre, with a mean change of -21 µm. Greater choroidal thinning occurred for myopes than for emmetropes (23 ± 11 vs. 17 ± 8 µm, p = 0.02). CONCLUSIONS: With accommodation, eye length increased and the choroid thinned, at both central and peripheral positions. Choroidal thinning accounted for approximately 60% of the eye length increase across the horizontal ±30°.

Higher order aberrations and retinal image quality during short-term accommodation in myopic and non-myopic children.

INTRODUCTION: Despite the known associations between near work and myopia, and retinal image quality and eye growth, accommodation-induced changes in higher order aberrations (HOA's) and retinal image quality in children with different refractive errors are poorly understood. METHODS: Ocular HOA's were measured using a Hartmann-Shack wavefront sensor (COAS-HD, Wavefront Sciences) in 18 myopic and 18 age- and sex-matched non-myopic children during short-term accommodation tasks (four demands of 0, 3, 6 and 9 D) presented using a Badal optometer. Eighth order Zernike polynomials were fitted across a 2.3 mm pupil diameter to determine refractive power vectors (M, J180 and J45 ) and the accommodation error, and a 4 mm pupil was used for HOA analyses. Retinal image quality was examined using the visual Strehl ratio based on the optical transfer function (VSOTF) for third to eighth radial orders only. RESULTS: Most refractive error group differences were observed for the 6 and 9 D demands. Myopic children underwent greater changes in with-the-rule astigmatism (J180 ), higher order and third order RMS values, primary vertical ( C 3 - 1 ) and horizontal coma ( C 3 1 ), and several other individual Zernike coefficients compared with non-myopic children (all refractive error group by demand interaction p-values of ≤0.02). Non-myopic children exhibited a greater negative shift in primary ( C 4 0 ) and positive shift in secondary spherical aberration ( C 6 0 ) (both refractive error group by demand interaction p-values of ≤0.002). The VSOTF degraded for the 6 and 9 D demands in both groups, but the myopic children underwent a greater mean (SE) reduction from 0 D of -0.274 (0.048) for the 9 D demand, compared with -0.131 (0.052) for the non-myopic children (p = 0.001). CONCLUSION: These results may have implications for the association between near work, accommodation and myopia development, particularly related to the use of short working distances during near tasks.

Feasibility of Integrating MEditatioN inTO heaRt Disease (the MENTOR Study): A Phase II Randomized Controlled Trial.

BACKGROUND: Comorbid depression and/or anxiety symptoms occur in 25% of patients attending cardiac rehabilitation (CR) programs and are associated with poorer prognosis. There is a need to evaluate psychological interventions, including meditation, that have potential to improve psychological health in CR programs. AIMS: The aim of this study was to determine the feasibility and acceptability of integrating a meditation intervention into an existing Australian CR program for the reduction of depression and anxiety symptoms. METHODS: This was a mixed-methods feasibility randomized controlled trial. Thirty-one patients with CVD and, at a minimum, mild depression and/or anxiety symptoms were randomized to meditation and standard CR or to standard CR alone. A 16-minute guided group meditation was delivered face-to-face once a week for 6 weeks, with daily self-guided meditation practice between sessions. Feasibility outcomes included screening, recruitment, and retention. Semistructured interviews of patients' (n = 10) and health professionals' (n = 18) perspectives of intervention participation and delivery were undertaken to assess acceptability. Between-group differences in depression, anxiety, stress, self-efficacy for mindfulness, and health status at 6 and 12 weeks were also assessed. RESULTS AND CONCLUSION: Meditation was considered feasible, with 83% (12/15) of the intervention group completing an average of 3.13 (SD, 2.56) out of 6 group meditation sessions and 5.28 (SD, 8.50) self-guided sessions. Meditation was considered acceptable by patients, clinicians, and health managers. Between-group differences in the number of CR sessions completed favored the intervention group in per-protocol analyses (intervention group vs control group, 12 vs 9 sessions; P = .014), which suggests that meditation may be useful to improve patients' adherence to exercise-based CR program.

PEMT Mediates Hepatitis C Virus-Induced Steatosis, Explains Genotype-Specific Phenotypes and Supports Virus Replication.

The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline (p < 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis.

OCT Retinal and Choroidal Layer Instance Segmentation Using Mask R-CNN.

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.

Hepatitis C Virus (HCV) Eradication With Interferon-Free Direct-Acting Antiviral-Based Therapy Results in KLRG1+ HCV-Specific Memory Natural Killer Cells.

Direct acting antiviral therapies rapidly clear chronic hepatitis C virus (HCV) infection and restore natural killer (NK) cell function. We investigated NK-cell memory formation following HCV clearance by examining NK-cell phenotype and responses from control and chronic HCV patients before and after therapy following sustained virologic response at 12 weeks post therapy (SVR12). NK-cell phenotype at SVR12 differed significantly from paired pretreatment samples, with an increase in maturation markers CD16, CD57, and KLRG1. HCV patients possessed stronger cytotoxic responses against HCV-infected cells as compared to healthy controls; a response that further increased following SVR12. The antigen-specific response was mediated by KLRG1+ NK cells, as demonstrated by increased degranulation and proliferation in response to HCV antigen only. Our data suggest that KLRG1+ HCV-specific memory NK cells develop following viral infection, providing insight into their role in HCV clearance and relevance with regard to vaccine design.

HBV vaccination and HBV infection induces HBV-specific natural killer cell memory.

OBJECTIVE: Vaccination 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. DESIGN: NK cell responses were evaluated by flow cytometry and ELISA following challenge with HBV antigens in HBV vaccinated, non-vaccinated and chronic HBV-infected individuals. RESULTS: NK 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. CONCLUSIONS: Our 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.

Immune-Checkpoint Inhibitors for Advanced Hepatocellular Carcinoma: A Synopsis of Response Rates.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. A first-line standard of care, sorafenib results in median overall survival of 12 months in patients with Child-Pugh class A disease and 6 months in patients with Child-Pugh class B disease with objective response rates (ORRs) not exceeding 19%. These low efficacy rates have driven research on alternative therapeutic options, particularly immune-checkpoint inhibitors (ICIs). We reviewed the response rates (estimated by RECIST 1.1 criteria) across patients with advanced HCC treated with ICIs in phase I-IV clinical trials published between December 2012 to December 2020; 17 reports were identified as eligible and included in the quantitative analysis. Within the selected studies, pembrolizumab + lenvatinib reached the highest absolute ORR (36%), with first-line atezolizumab + bevacizumab showing the second highest ORR (27.3%). With regard to second-line therapy, nivolumab + ipilimumab reached an ORR of 32%, and pembrolizumab alone resulted in an ORR of 17% among sorafenib-experienced patients with advanced HCC. In summary, current studies show high response rates of ICIs in patients with advanced HCC. Nonetheless, further studies are required in the second-line setting to further evaluate ICI therapeutic superiority. Finally, it is of particular interest to examine the therapeutic potential of ICIs for patients with decompensated liver disease (Child-Pugh class C), currently not eligible for any systemic therapy. IMPLICATIONS FOR PRACTICE: Immune-checkpoint inhibitors (ICIs) can provide high objective response rates (ORR, estimated with RECIST 1.1. criteria) when used as first-line treatment in advanced hepatocellular carcinoma, particularly pembrolizumab + lenvatinib (ORR 36%) or atezolizumab + bevacizumab (ORR 27.3%). In sorafenib-experienced patients, nivolumab + ipilimumab (ORR 32%) provided the highest ORR among ICI-based regimens. These findings emphasize high therapeutic potential of ICI-based therapies in patients with advanced hepatocellular carcinoma, although further studies are required to further validate and define their role in this context.

Anterior scleral thickness and shape changes with different levels of simulated convergence.

PURPOSE: Convergence plays a fundamental role in the performance of near visual tasks. We measured the effect of two levels of convergence on anterior scleral thickness and shape in emmetropes, low to moderate myopes and high myopes. METHODS: Forty-five healthy young adults aged between 18 and 35 years including 15 emmetropes, 15 low/moderate myopes, and 15 high myopes were recruited. Anterior segment optical coherence tomography and eye surface profilometry were used to evaluate the anterior scleral thickness (nasal only, n = 42) and shape (n = 40), before and during two visual tasks involving 9° and 18° convergence, in those participants with complete and reliable data. RESULTS: Convergence led to a thickening of the total anterior eye wall (5.9 ± 1.4 µm) and forward movement (10 ± 2 µm) of the nasal anterior scleral surface (both p < 0.001). Larger changes were found at 18° than at 9° convergence and in more peripheral nasal scleral regions. There was a significant association between total wall thickening and forward movement of the scleral surface. Refractive group was not a significant main effect, but there were significant interactions between refractive group and the thickness changes with convergence in different scleral regions. CONCLUSION: During convergence, the biomechanical forces acting on the eye lead to nasal anterior scleral thickening and forward movement of the nasal scleral surface.

Expansion of dysfunctional CD56-CD16+ NK cells in chronic hepatitis B patients.

BACKGROUND & AIMS: Natural killer (NK) cells are primary innate effector cells that play an important role in the control of human viral infections. During chronic viral infection, NK cells undergo significant changes in phenotype, function and subset distribution, including the appearance of CD56-CD16+ (CD56-) NK cells, previously identified in chronic human immunodeficiency virus (HIV) and hepatitis C virus infection. However, the presence of CD56- NK cells in the pathogenesis of chronic hepatitis B (CHB) remains unknown. METHODS: Phenotype and function of CD56- NK cells from patients with CHB (n = 28) were assessed using flow cytometry and in vitro stimulation with HBV antigen. RESULTS: CHB patients had a higher frequency of CD56- NK cells compared to healthy controls in peripheral blood (6.2% vs 1.4%, P < .0001). Compared to CD56+ NK cells, CD56- NK cells had increased expression of inhibitory receptors, and reduced expression of activating receptors, as measured by MFI and qPCR. CD56- NK cells were less responsive to target cell and cytokine stimulation compared to their CD56+ counterparts. In addition, CD56- NK cells demonstrated defective dendritic cells (DCs) interactions resulting in reduced DCs maturation, lower expression of NK CD69 and impaired capacity of NK cells to eliminate immature DCs in co-culture studies. Finally, frequency of CD56- NK cells was positively correlated with serum HBV DNA levels. CONCLUSION: Chronic HBV infection induces the expansion of highly dysfunctional of CD56- NK cells that likely contribute to inefficient innate and adaptive antiviral immune response in chronic HBV infection.

Repeatability of Anterior Eye Surface Topography Parameters from an Anterior Eye Surface Profilometer.

SIGNIFICANCE: Anterior eye shape measurements are important for clinical contact lens fitting. The detailed assessment of measurement repeatability using the Eye Surface Profiler (ESP; Eaglet Eye B.V., AP Houten, the Netherlands) allows for more reliable interpretation of eye surface topography measurements. PURPOSE: This study aimed to determine the repeatability of the ESP for anterior central corneal power and anterior eye surface height measurements. METHODS: A Badal optometer was mounted on the ESP to provide an external fixation target with appropriate accommodation control and refractive correction. Forty-five healthy young adults underwent two sessions of anterior eye measurements, separated by 20 minutes, using the ESP. In each session, three consecutive scans were captured. Sagittal height data were obtained from 8-mm central cornea and from 8- to 14-mm diameter (encompassing the corneal periphery and anterior sclera). Anterior corneal powers were determined from the central cornea. Intersessional and intrasessional repeatability values were determined as coefficients of repeatability and root mean square error differences. RESULTS: Sagittal height intersessional coefficients of repeatability for central nasal (5 µm) and central temporal (7 µm) were better than peripheral nasal (24 µm) and peripheral temporal (21 µm) regions. Sagittal height intrasessional coefficients of repeatability were 9, 8, 28, and 31 µm for central nasal, central temporal, peripheral nasal, and peripheral temporal regions, respectively. Intersessional coefficients of repeatability of mean sphere, 90/180° (J0) astigmatism, and oblique (J45) astigmatism were 0.67, 0.22, and 0.13 D, respectively, with corresponding intrasessional coefficients of repeatability of 1.27, 0.21, and 0.27 D. CONCLUSIONS: The modified measuring procedure for the ESP used in this study provides highly repeatable sagittal height measurements in the central cornea but is less repeatable in the corneal periphery and scleral region. Results of the current study can be considered when using ESP in the interpretation of anterior eye surface shape measurements and in contact lens fitting and design.

High Rates of Uncorrected Vision Conditions among Schoolchildren in Rural Queensland, Australia.

SIGNIFICANCE: This study is the first to report high rates of uncorrected vision conditions among Australian secondary schoolchildren living in a rural area and to comment on the rate of eye examinations undertaken on Australian Indigenous children. Uncorrected vision problems that continue throughout the school years have significant implications for children's quality of life and education. PURPOSE: This study aimed to investigate the prevalence of uncorrected vision conditions among Australian schoolchildren. METHODS: Participants included 280 students from rural primary and secondary schools (aged 4 to 18 years), of whom 40% identified as being of Aboriginal and/or Torres Strait Islander descent (Indigenous). All participants underwent an eye examination including measurements of monocular distance and near visual acuity, assessment of accommodative and vergence function, stereoacuity, color vision, and cycloplegic autorefraction. A parental questionnaire was used to determine whether the child had previously had his/her eyes examined. RESULTS: The overall prevalence of uncorrected vision conditions in this population was 35%. The odds of previously having had an eye examination were 2.3× higher for non-Indigenous compared with Indigenous children despite both groups exhibiting high rates of uncorrected vision conditions (Indigenous, 31 [29%]; non-Indigenous, 66 [40%]; χ21 = 3.24, P = .07). Of the children who had significant refractive error (Indigenous, 23 [21%]; non-Indigenous, 49 [30%]; χ21 = 2.70, P = .10), 82% were uncorrected, and only 39% of Indigenous children and 54% of non-Indigenous children had previously had an eye examination. CONCLUSIONS: These findings suggest that high rates of uncorrected vision conditions are present among Australian primary and secondary schoolchildren from a rural area and highlight that Indigenous children are much less likely to have had an eye examination. Understanding factors that affect the rate of eye examinations and compliance with spectacle correction must be addressed given the potential impact of these vision conditions.

Effects of brief periods of clear vision on the defocus-mediated changes in axial length and choroidal thickness of human eyes.

PURPOSE: To investigate the influence of brief, repeated periods of clear vision on the changes in axial length and choroidal thickness in response to short-term imposed defocus. METHODS: The right eye of 16 young adults was exposed to 60 min episodes of continuous and interrupted defocus conditions (+3 DS and -3 DS) over five separate sessions, with the left eye optimally corrected for distance. For interrupted defocus, 2 min episodes of clear vision were imposed before each 15 min episode of myopic or hyperopic defocus (2/15 min). For hyperopic defocus, the effect of frequency of clear vision exposure was also assessed by imposing 1 min of clear vision before each 7.5 min of defocus (1/7.5 min). The right eye axial length and choroidal thickness were measured before, during and after each defocus condition. RESULTS: After 60 min of continuous hyperopic defocus the eye elongated significantly by +9 ± 9 µm (p = 0.02). When exposed to interrupted (2/15 min) hyperopic defocus, axial elongation was significantly reduced by 77% compared to continuous hyperopic defocus (p = 0.03), with a final change of only +2 ± 10 µm relative to baseline. During interrupted (1/7.5 min) hyperopic defocus, axial elongation reduced slightly compared to continuous hyperopic defocus (+6 ± 8 µm relative to baseline, p = 0.12). For continuous myopic defocus, a reduction in axial length occurred but was not statistically significant (p > 0.05). A similar pattern of response was observed for choroidal thickness changes with continuous and interrupted (1/7.5 min) hyperopic defocus conditions. CONCLUSIONS: Brief periods of clear vision can diminish axial elongation and choroidal thinning induced by hyperopic defocus exposure in human eyes. If hyperopic defocus contributes to myopia progression in humans, then interruption with brief periods of clear vision could reduce its myopiagenic effects.

Effects of accommodation and simulated convergence on anterior scleral shape.

PURPOSE: The sclera plays an important role in the biomechanical stability of the eye. We aimed to examine if changes in the shape of the anterior sclera occur in response to accommodation and convergence. METHODS: Thirty-six healthy young adult participants aged between 18 and 30 years including 18 myopes (-0.5 to -4.0 D) and 18 emmetropes (+0.5 to -0.25 D) were recruited. Eye surface profilometry was used to evaluate the anterior eye surface shape before and during visual tasks involving accommodation (5.0 D demand), simulated convergence (9° demand) and their combination. The changes in the sagittal height and axial radius of curvature of the nasal (n = 25) and temporal (n = 31) corneal periphery and anterior sclera were analysed in those participants with complete and reliable data on these sides. RESULTS: Significant changes were confined to the nasal anterior scleral surface. A significant forward movement of the surface accompanied accommodation (mean change: 5 ± 2 µm), convergence (19 ± 6 µm), and their combination (16 ± 6 µm). There was flattening with convergence (0.092 ± 0.044 mm) and with the combination of accommodation and convergence (0.201 ± 0.071 mm). The changes in response to accommodation and convergence increased peripherally. Changes were not significantly different between low to moderate myopes and emmetropes. CONCLUSIONS: Accommodation and simulated convergence affect the nasal anterior scleral shape, with the greatest changes associated with convergence and being most evident in the more peripheral nasal scleral regions.

Changes in ocular biometry during short-term accommodation in children.

PURPOSE: Near work has been linked with myopia development; however, the underlying mechanism remains unclear. Small increases in axial length during accommodation have previously been reported in adults, and therefore, this study aimed to examine if accommodation-induced changes in ocular biometry also occur in school-aged children. METHODS: A range of ocular biometric measurements were captured during brief accommodation tasks at four demands (0, 3, 6, and 9 D), in a group of 87 non-myopic, school-aged children using a Badal optometer mounted to a non-contact optical biometer (Zeiss IOLMaster 700, https://www.zeiss.com/meditec/int/product-portfolio/optical-biometers/iolmaster-700.html). Reliable biometry measurements and active accommodation were observed for 76 participants who were included in the analysis. The average central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), anterior segment length (ASL), vitreous chamber depth (VCD), and axial length (AL) were determined for each accommodation demand. Raw measurements of AL and VCD were corrected to account for the effect of LT changes during accommodation. RESULTS: On average, AL increased with increasing levels of accommodation (p = 0.005). The mean (SEM, standard error of the mean) AL increase from 0 D to the 3, 6, and 9 D demands was 4 (1), 8 (1), and 15 (2) µm, respectively. All other biometric parameters, except CCT, changed significantly during accommodation. LT and ASL increased, and ACD and VCD decreased significantly with increasing accommodation (all p ≤ 0.02). A longer baseline AL was associated with greater levels of accommodation-induced axial elongation at the 9 D demand (p < 0.0001). CONCLUSIONS: AL increased significantly during accommodation in children, consistent with previous findings in adults up to a 6 D demand. AL continued to increase for higher levels of accommodation (9 D demand), which children may experience during near tasks. These findings provide further insights into potential mechanisms linking near work, axial elongation, and myopia development. However, no myopic children participated in this experiment; therefore, further research is required.

KLRG1+ natural killer cells exert a novel antifibrotic function in chronic hepatitis B.

BACKGROUND & AIMS: Natural killer (NK) cells are known to exert strong antiviral activity. Killer cell lectin-like receptor subfamily G member 1 (KLRG1) is expressed by terminally differentiated NK cells and KLRG1-expressing lymphocytes are known to expand following chronic viral infections. We aimed to elucidate the previously unknown role of KLRG1 in the pathogenesis of chronic hepatitis B (CHB). METHODS: KLRG1+ NK cells were taken from the blood and liver of healthy individuals and patients with CHB. The phenotype and function of these cells was assessed using flow cytometry and in vitro stimulation. RESULTS: Patients with CHB had a higher frequency of KLRG1+ NK cells compared to healthy controls (blood 13.4 vs. 2.3%, p <0.0001 and liver 23.4 vs. 2.6%, p <0.01). KLRG1+ NK cells were less responsive to K562 and cytokine stimulation, but demonstrated enhanced cytotoxicity (9.0 vs. 4.8%, p <0.05) and IFN-γ release (8.0 vs. 1.5%, p <0.05) via antibody dependent cellular cytotoxicity compared to their KLRG1- counterparts. KLRG1+ NK cells possessed a mature phenotype, demonstrating stronger cytolytic activity and IFN-γ secretion against hepatic stellate cells (HSCs) than KLRG1- NK cells. Moreover, KLRG1+ NK cells more effectively induced primary HSC apoptosis in a TRAIL-dependent manner. Increased KLRG1+ NK cell frequency in the liver and blood was associated with lower fibrosis stage (F0/F1) in patients with CHB. Finally, the expression of CD44, degranulation and IFN-γ production were all increased in KLRG1+ NK cells following stimulation with osteopontin, the CD44 ligand, suggesting that HSC-derived osteopontin may cause KLRG1+ NK cell activation. CONCLUSIONS: KLRG1+ NK cells likely play an antifibrotic role during the natural course of CHB infection. Harnessing this antifibrotic function may provide a novel therapeutic approach to treat liver fibrosis in patients with CHB. LAY SUMMARY: Individuals that are chronically infected with hepatitis B virus (HBV) possess an increased number of immune cells, called natural killer (NK) cells expressing the surface marker KLRG1 in the blood and liver. Here, we demonstrate that these specific NK cells are able to kill activated stellate cells in the liver. Because activated stellate cells contribute to liver scarring, i.e. fibrosis, and subsequent liver dysfunction in individuals with chronic HBV infection, KLRG1+ NK cells are a novel immune cell type that can limit liver scarring.

Daily axial length and choroidal thickness variations in young adults: Associations with light exposure and longitudinal axial length and choroid changes.

Evidence from animal studies suggests that the eye's natural diurnal rhythms can be disrupted by altering the light/dark cycle or during refractive error development. Although diurnal variations in axial length (AL) and choroidal thickness are well documented in human eyes, the relationship between ambient light exposure, refractive error progression and diurnal AL and choroidal thickness variations is not well understood. Therefore we examined the association between objective ambient light exposure and daily variations in AL and subfoveal choroidal thickness (SFCT), along with longer-term changes in AL and SFCT over 12 months. Thirty-four young adult emmetropes and myopes had their daily variations (measurements ~ every 3 h from 9 a.m. to 9 p.m.) in AL and SFCT assessed on a weekday and weekend in winter and then six months later in summer. Participants then returned six months later for a single measurement session to determine the longer-term change in AL and SFCT. Personal ambient light exposure was captured in winter and summer using wrist-worn light sensors (Actiwatch-2) worn for 14 days over the same period of time when the diurnal measurements were collected. Linear mixed model analyses revealed significant daily variations in AL and SFCT (each p < 0.05). The mean daily peak to trough difference (amplitude) in AL was significantly greater in myopes (0.020 mm; 95% CI: 0.014-0.026 mm) compared to emmetropes (0.010 mm; 95% CI: 0.005-0.015 mm) (p < 0.01), but the SFCT variations were not significantly different between the refractive groups (p = 0.45). Daily variations in AL were negatively associated with the daily SFCT variations (r = -0.603, p < 0.001). Correlation analyses indicated that the amplitude of daily AL variations was negatively associated with the daily time exposed to bright light (r = -0.511, p = 0.002) and positively associated with the longitudinal AL changes over 12 months (r = 0.381, p = 0.04). There was an inverse association between the longer-term changes in AL and SFCT (r = -0.352, p = 0.002). The daily ocular diurnal variations were not significantly different between weekdays and weekends, or between summer and winter (each p > 0.05). In summary, diurnal variations in AL were higher in amplitude in myopes compared to emmetropes and were also associated with longitudinal changes in AL. These findings suggest that diurnal variations may be associated with longer-term axial eye growth. Time spent in bright light also significantly influenced the amplitude of daily AL variations, with more time exposed to bright light associated with a smaller amplitude of diurnal AL change. Choroidal thickness exhibited an inverse association with the AL changes, implying a potential role for the choroid in eye growth.

Regional alterations in human choroidal thickness in response to short-term monocular hemifield myopic defocus.

PURPOSE: To examine the regional changes in human choroidal thickness following short-term exposure to hemifield myopic defocus using optical coherence tomography (OCT). METHODS: The central 26˚ visual field of the left eye of 25 healthy young adults (mean age 26 ± 5 years) was exposed to 60 min of clear vision (control session), +3 D full-field, +3 D superior retinal and +3 D inferior retinal myopic defocus, with the right eye occluded. Choroidal thickness across the central 5 mm (17°) macular region was examined before and after 60 min of defocus using a high-resolution, foveal centred vertical OCT line scan, with optical defocus simultaneously imposed using a Badal optometer and cold mirror system mounted on a Spectralis OCT device. RESULTS: Averaged across the central 5 mm macular area, choroidal thickness decreased by -4 ± 7 µm during the control session (p = 0.01), most likely due to the unique stimulus conditions of this study. The mean macular choroidal thickness increased during full-field (+2 ± 8 µm), inferior retinal (+3 ± 7 µm) and superior retinal myopic defocus (+5 ± 9 µm), representing a significant thickening of the choroid compared to the control session (all p < 0.05). The defocus induced changes in macular choroidal thickness differed between the superior and inferior hemiretinal regions (F2.26, 54.27  = 29.75, p < 0.001). When only the superior retina was exposed to myopic defocus, the choroid thickened in the superior region (+7 ± 8 µm, p < 0.001), but did not change significantly in the inferior region (+3 ± 9 µm, p = 0.12). When only the inferior retina was exposed to myopic defocus, the choroid thickened inferiorly (+4 ± 8 µm, p = 0.005), with no significant change observed in the superior region (+1 ± 8 µm, p = 0.46). CONCLUSIONS: These findings provide evidence supporting a local regional choroidal response to myopic defocus in the human eye, with hemifield myopic defocus leading to significant thickening of the choroid localised to the retinal region exposed to defocus. The novel finding of a localised response of the human choroid to hemifield myopic defocus, particularly in the superior hemiretina, may have important implications in optimising the optical design of myopia control interventions.