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.

Longitudinal Changes in Choroidal Vascularity in Myopic and Non-Myopic Children.

Purpose: The purpose of this study was to evaluate longitudinal changes in choroidal vascular characteristics in childhood, and their relationship with eye growth and refractive error. Methods: Analysis of high-resolution optical coherence tomography (OCT) scans, collected over an 18-month period as part of the Role of Outdoor Activity in Myopia (ROAM) study, was conducted in 101 children (41 myopic, 60 non-myopic, age 10-15 years). OCT images were automatically analyzed and binarized using a deep learning software tool. The output was then used to compute changes in macular choroidal vascularity index (CVI), choroidal luminal, and stromal thickness over 18-months. Associations of these variables with refractive error and axial length were analyzed. Results: CVI decreased significantly, whereas luminal and stromal thickness increased significantly over 18 months (all P < 0.001). The magnitude of change was approximately double in stromal tissue compared to luminal tissue (luminal ß = 2.6 µm/year; 95% confidence interval [CI] = -1.0 to 4.1 µm/year; stromal ß = 5.2 µm/year; 95% CI = 4.0, 6.5 µm/year). A significant interaction between baseline axial length and change in CVI over time (P = 0.047) was observed, with a greater CVI reduction in those with shorter axial lengths. Significant associations were observed between the change in CVI, luminal thickness, stromal thickness, and change in axial length over time (all P < 0.05). Conclusions: Faster axial eye growth was associated with smaller reductions in CVI, and less increase in choroidal luminal and stromal thickness. The changes in choroidal vascularity, particularly in the stromal component, may thus be a marker for eye growth. Translational Relevance: This knowledge of the longitudinal changes in choroidal vascularity in childhood and their relationship with eye growth may assist clinicians in the future to better predict eye growth and myopia progression in childhood.

Attitudes towards transjugular intrahepatic portosystemic shunt (TIPS) in Australia: a national survey of TIPS centres.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a minimally invasive therapeutic option to treat the sequelae of portal hypertension. It is unclear whether current international recommendations are reflected in current clinical practice across Australia and the extent of variations in care. This study aimed to address this gap in knowledge and benchmark the current landscape of TIPS services in Australia against international guidelines. METHODS: We designed a 42-item questionnaire according to practice-based recommendations and standards of international guidelines to investigate current landscape of TIPS service across four key domains: (1) service provision, (2) patient selection and indications, (3) best procedure practice, and (4) postoperative care. RESULTS: Gastroenterologist/hepatologists from 23 major liver centres (67.6%) across Australia currently performing TIPS completed the questionnaire. Between 2017 and 2020, there were 456 elective TIPS insertions. Units offering TIPS service had a low median number of TIPS insertions (n=7 per annum). More than half of respondents (56.5%) did not have institutional clinical practice protocols. There was marked variation in practices across institutions in terms of TIPS indications and patient selection. Despite variations, the success rate of elective TIPS was high at 91.7% (79-100%), with 86.6% (29-100%) for rescue TIPS. There was significant variation in postoperative follow-up and care. CONCLUSION: Current TIPS practice in Australia varies significantly across institutions. There is a need for a national consensus clinical practice guidelines to improve access and minimise unwarranted variation. A national registry for TIPS could measure, monitor, and report on quality of clinical care and patient outcomes.

Increase in choroidal thickness after blue light stimulation of the blind spot in young adults.

BACKGROUND: Blue light activates melanopsin, a photopigment that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs). The axons of ipRGCs converge on the optic disc, which corresponds to the physiological blind spot in the visual field. Thus, a blue light stimulus aligned with the blind spot captures the ipRGCs axons at the optic disc. This study examined the potential changes in choroidal thickness and axial length associated with blue light stimulation of melanopsin-expressing ipRGCs at the blind spot. It was hypothesized that blue light stimulation at the blind spot in adults increases choroidal thickness. METHODS: The blind spots of both eyes of 10 emmetropes and 10 myopes, with a mean age of 28 ± 6 years (SD), were stimulated locally for 1-minute with blue flickering light with a 460 nm peak wavelength. Measurements of choroidal thickness and axial length were collected from the left eye before stimulation and over a 60-minute poststimulation period. At a similar time of day, choroidal thickness and axial length were measured under sham control condition in all participants, while a subset of 3 emmetropes and 3 myopes were measured after 1-minute of red flickering light stimulation of the blind spot with a peak wavelength of 620 nm. Linear mixed model analyses were performed to examine the light-induced changes in choroidal thickness and axial length over time and between refractive groups. RESULTS: Compared with sham control (2 ± 1 µm, n = 20) and red light (-1 ± 2 µm, n = 6) stimulation, subfoveal choroidal thickness increased within 60 min after blue light stimulation of the blind spot (7 ± 1 µm, n = 20; main effect of light, p < 0.001). Significant choroidal thickening after blue light stimulation occurred in emmetropes (10 ± 2 µm, p < 0.001) but not in myopes (4 ± 2 µm, p > 0.05). Choroidal thickening after blue light stimulation was greater in the fovea, diminishing in the parafoveal and perifoveal regions. There was no significant main effect of light, or light by refractive error interaction on the axial length after blind spot stimulation. CONCLUSIONS: These findings demonstrate that stimulating melanopsin-expressing axons of ipRGCs at the blind spot with blue light increases choroidal thickness in young adults. This has potential implications for regulating eye growth.

Choroidal Changes During and After Discontinuing Long-Term 0.01% Atropine Treatment for Myopia Control.

Purpose: Few studies have explored choroidal changes after cessation of myopia control. This study evaluated the choroidal thickness (ChT) and choroidal vascularity index (CVI) during and after discontinuing long-term low-concentration atropine eye drops use for myopia control. Methods: Children with progressive myopia (6-16 years; n = 153) were randomized to receive 0.01% atropine eye drops or a placebo (2:1 ratio) instilled daily over 2 years, followed by a 1-year washout (no eye drop use). Optical coherence tomography imaging of the choroid was conducted at the baseline, 2-year (end of treatment phase), and 3-year (end of washout phase) visits. The main outcome measure was the subfoveal ChT. Secondary measures include the CVI. Results: During the treatment phase, the subfoveal choroids in both treatment and control groups thickened by 12-14 µm (group difference P = 0.56). During the washout phase, the subfoveal choroids in the placebo group continued to thicken by 6.6 µm (95% confidence interval [CI] = 1.7 to 11.6), but those in the atropine group did not change (estimate = -0.04 µm; 95% CI = -3.2 to 3.1). Participants with good axial eye growth control had greater choroidal thickening than the fast-progressors during the treatment phase regardless of the treatment group (P < 0.001), but choroidal thickening in the atropine group's fast-progressors was not sustained after stopping eye drops. CVI decreased in both groups during the treatment phase, but increased in the placebo group after treatment cessation. Conclusions: On average, compared to placebo, 0.01% atropine eye drop treatment did not cause a differential rate of change in ChT during treatment, but abrupt cessation of long-term 0.01% atropine eye drops may disrupt normal choroidal thickening in children.

Using a human colonoid-derived monolayer to study bacteriophage translocation.

Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.