Bruch's Membrane Opening Changes in Eyes With Myopic Macular Degeneration: AIER-SERI Adult High Myopia Study.

Purpose: The purpose of this study was to assess the choroidal thickness and the Bruch's membrane opening size and their relationship to visual acuity in eyes with myopic macular degeneration (MMD). Methods: This was a population-based, cross-sectional study. Patients over the age of 30 years with high myopia (spherical equivalent ≤-5 diopters [D]) were recruited. The eyes were grouped according to the International Meta-Analysis for Pathologic Myopia (META-PM) classification based on fundus photographs and diffuse atrophy was subdivided into peripapillary diffuse choroidal atrophy (PDCA) or macular diffuse choroidal atrophy (MDCA). Swept-source optical coherence tomography imaging was performed and then the subfoveal choroidal thickness (SFCT) and Bruch's membrane opening diameter (BMOD) were measured. Results: Of the 470 study participants recruited, 373 patients (691 eyes), with a mean age of 42.8 ± 7.2 years, were eligible for the study and included in the analysis. There was no significant difference in SFCT between MDCA and patchy atrophy (M3) groups (P = 1.000), and the BMOD enlarged significantly from no myopic macular lesions to M3 (the P values of multiple comparison tests were all <0.005). Simple linear regression analysis showed that BMOD correlated positively with age (P < 0.001) and axial length (P < 0.001). Multiple linear regression analysis showed that best corrected visual acuity (BCVA) was significantly correlated with age (P = 0.041), axial length (P = 0.001), and BMOD (P = 0.017), but not with SFCT (P = 0.231). Conclusions: The significant variation of BMOD among MMD groups and the correlation between BMOD and BCVA in MMD eyes suggest that BMOD may be an imaging biomarker for monitoring MMD.

In-vivo high-frequency quantitative ultrasound-derived parameters of the anterior sclera correlated with level of myopia and presence of staphyloma.

BACKGROUND: A high-frequency point-of-care (POC) ultrasound instrument was used to evaluate the microstructural and biomechanical properties of the anterior sclera in vivo using parameters computed from quantitative ultrasound (QUS) methods. METHODS: In this cross-sectional study, both eyes of 85 enrolled patients were scanned with the POC instrument and ultrasound data were processed to obtain QUS parameters. Pearson correlation and multi-linear regression were used to identify relationships between QUS parameters and refractive error (RE) or axial length. After categorising eyes based on RE, binary support vector machine (SVM) classifiers were trained using the QUS or ophthalmic parameters (anterior chamber depth, central corneal thickness, corneal power, and intraocular pressure) to classify each eye. Classifier performance was evaluated by computing the area under the receiver-operating characteristic curve (AUC). RESULTS: Individual QUS parameters correlated with RE and axial length (p < 0.05). Multi-linear regression revealed significant correlation between the set of QUS parameters and both RE (R = 0.49, p < 0.001) and axial length (R = 0.46, p = 0.001). Classifiers trained with QUS parameters achieved higher AUC (𝑝 = 0.06) for identifying myopic eyes (AUC = 0.71) compared to classifiers trained with ophthalmic parameters (AUC = 0.63). QUS-based classifiers attained the highest AUC when identifying highly myopic eyes (AUC = 0.77). CONCLUSIONS: QUS parameters correlate with progressing myopia and may be indicative of myopia-induced microstructural and biomechanical changes in the anterior sclera. These methods may provide critical clinical information complementary to standard ophthalmic measurements for predicting myopia progression and risk assessment for posterior staphyloma formation.

Comparison of manual and artificial intelligence-automated choroidal thickness segmentation of optical coherence tomography imaging in myopic adults.

BACKGROUND: Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems. METHODS: Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland-Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement. RESULTS: A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of - 26.7 µm (95% CI: - 29.7 to - 23.7, P < 0.001) and proportional bias of - 0.090 (P < 0.001). CONCLUSION: We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future.

The Spectrum of Relentless Placoid and Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE): Multimodal Imaging Analysis.

PURPOSE: To showcase the spectrum between APMPPE and relentless placoid utilizing ultra-widefield imaging findings of a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) progressing to relentless placoid chorioretinitis (RPC). METHODS: A 23-year-old Caucasian female presented with worsening vision in both eyes. Clinical examination and multimodal imaging modalities including fundus photos, fundus autofluorescence, fluorescein angiography (FA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography and angiography were utilized to diagnose APMPPE and clinically follow the patient. RESULTS: Clinical examination of the patient initially revealed posterior lesions consistent with APMPPE but subsequent multimodal images including ultra-widefield FA and ICGA revealed newer, more peripheral lesions more typical of RPC. CONCLUSION: When compared to standard multimodal imaging, ultra-widefield imaging is an effective tool to delineate nuances between APMPPE and RPC through identification of peripheral lesions, which may be of clinical importance when determining management and therapeutics for patients.

Efficient Combination Chemo-Sonodynamic Cancer Therapy Using Mitochondria-Targeting Sonosensitizer-Loaded Polysorbate-Based Micelles.

Sonodynamic therapy (SDT), utilizing ultrasound (US) and sonosensitizers, holds immense potential as a noninvasive and targeted treatment for a variety of deep-seated tumors. However, the clinical translation of SDT is hampered by several key limitations in sonosensitizers, especially their low aqueous stability and poor cellular uptake. In this study, non-ionic polysorbate (Tween 80, T80) was adopted to formulate effective nanocarriers for the safe and efficient delivery of sonosensitizers to cancer cells. Mitochondria-targeting triphenylphosphonium (TPP)-conjugated chlorin e6 (Ce6) sonosensitizer was loaded into T80-based micelles for efficient SDT. Pro-oxidant piperlongumine (PL) was co-encapsulated with TPP-conjugated Ce6 (T-Ce6) in T80 micelles to enable combination chemo-SDT. T80 micelles substantially enhanced the cellular internalization of T-Ce6. As a result, T80 micelles loaded with T-Ce6 and PL [T80(T-Ce6/PL)] significantly elevated intracellular reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells upon US exposure. Moreover, T-Ce6 exhibited selective accumulation within the mitochondria, leading to efficient cell death under US irradiation. Importantly, T80(T-Ce6/PL) micelles caused cancer-specific cell death by selectively triggering apoptosis in cancer cells through PL. This study demonstrated the feasibility of using T80(T-Ce6/PL) micelles for efficient and cancer-specific combination chemo-SDT.

Vocal fingerprinting reveals a substantially smaller global population of the Critically Endangered cao vit gibbon (Nomascus nasutus) than previously thought.

The cao vit gibbon (Nomascus nasutus) is one of the rarest primates on Earth and now only survives in a single forest patch of less than 5000 ha on the Vietnam-China border. Accurate monitoring of the last remaining population is critical to inform ongoing conservation interventions and track conservation success over time. However, traditional methods for monitoring gibbons, involving triangulation of groups from their songs, are inherently subjective and likely subject to considerable measurement errors. To overcome this, we aimed to use 'vocal fingerprinting' to distinguish the different singing males in the population. During the 2021 population survey, we complemented the traditional observations made by survey teams with a concurrent passive acoustic monitoring array. Counts of gibbon group sizes were also assisted with a UAV-mounted thermal camera. After identifying eight family groups in the acoustic data and incorporating long-term data, we estimate that the population was comprised of 74 individuals in 11 family groups, which is 38% smaller than previously thought. We have no evidence that the population has declined-indeed it appears to be growing, with new groups having formed in recent years-and the difference is instead due to double-counting of groups in previous surveys employing the triangulation method. Indeed, using spatially explicit capture-recapture modelling, we uncovered substantial measurement error in the bearings and distances from field teams. We also applied semi- and fully-automatic approaches to clustering the male calls into groups, finding no evidence that we had missed any males with the manual approach. Given the very small size of the population, conservation actions are now even more urgent, in particular habitat restoration to allow the population to expand. Our new population estimate now serves as a more robust basis for informing management actions and tracking conservation success over time.

Pathologic myopia in highly myopic patients with high axial anisomyopia.

PURPOSE: To determine prevalence of anisomyopia (axial length (AL) difference ≥2.5 mm) among high myopes ((HMs), defined by spherical equivalent of ≤6.0 diopters or AL ≥ 26.5 mm). To characterise the shorter anisomyopic eye (SAE) and evaluate if pathologic myopia (PM) in the longer anisomyopic eye (LAE) was associated with increased risk of PM in the SAE. METHODS: 1168 HMs were recruited from Singapore National Eye Centre clinic for this cross-sectional study. Biometry, fundus photography and swept-source optical coherence tomography were performed. Patients with high axial anisomyopia were identified. Structural characteristics and presence of PM were described. Stepwise multivariate regression explored associations between PM in the LAE and pathology in the SAE, controlling for confounding variables. RESULTS: Prevalence of anisomyopia was 15.8% (184 of 1168 patients). Anisomyopic patients (age 65.8±13.5 years) had mean AL of 30.6±2.0 mm and 26.2±2.3 mm in the LAE and SAE, respectively. 52.7% of SAEs had AL < 26.5 mm. Prevalence of myopic macular degeneration, macula-involving posterior staphyloma (PS), myopic traction maculopathy (MTM) and myopic choroidal neovascularisation (mCNV) in the SAE was 52.2%, 36.5%, 13.0% and 8.2%, respectively. Macular hole in the LAE was associated with increased risk of MTM in the SAE (OR=4.88, p=0.01). mCNV in the LAE was associated with mCNV in the SAE (OR=3.57, p=0.02). PS in the LAE was associated with PS in the SAE (OR=4.03, p<0.001). CONCLUSIONS: Even when controlled for AL, PM complications in the LAE predict similar PM complications in the SAE. Patients with high axial anisometropia with PM in the LAE should be monitored carefully for complications in the SAE.

ULTRA-WIDEFIELD IMAGING DETECTION RATE IN IDENTIFYING PERIPHERAL RETINAL TEARS IN SINGLE VERSUS MONTAGE OF PERIPHERAL STEERING.

PURPOSE: To compare the detection rate of orthogonal, directed peripheral steering, and automontaged images with ultra-widefield imaging and the factors influencing the ability to identify retinal breaks. DESIGN: Retrospective cohort study. METHODS: Three hundred and seventy-six treatment-naive eyes (349 patients) that underwent laser retinopexy for retinal breaks between 2015 and 2021 were included. Pretreatment ultra-widefield orthogonal, peripheral steering, and automontage were cross-referenced to scleral-depressed examination to determine whether images successfully visualized all retinal breaks. Total relative retinal area (RRA) visualized was divided by its optic disk area (pixels) to calculate relative retinal area. Potential associations were assessed by linear regression analysis. RESULTS: One hundred and sixty two eyes (154 patients) met inclusion criteria. Orthogonal, peripheral steering, and automontage images showed detection rates of 47.5%, 90.7%, and 80.0%, respectively. Relative retinal area increased from orthogonal versus montage by 34.7% ± 26.5% (mean ± SD), which increased the detection rate by 90.8% ( P = 0.006). In linear probability models, vertical meridian tears decreased probability of identification in orthogonal, peripheral steering, and automontage by -26.6%, -86.2%, and -68.7%, respectively ( P < 0.001), and horizontal meridian tears increased the probability by 62.2%, 92.9%, and 85.5%, respectively, ( P < 0.001). Tears posterior to the equator in orthogonal images increased the probability (91.4%, P < 0.001). Artifacts such as lids/lashes, reflection, and face guard decreased the probability in directed peripheral steering by -28.6%, -50.0%, and -66.7%, respectively, ( P = 0.020, P = 0.049, and P = 0.016). CONCLUSION: Using directed peripheral steering and automontage increases RRA and detection rate of identifying peripheral retinal breaks. Tears in horizontal meridians or posterior to the equator increase the probability of identification. Common ultra-widefield imaging artifacts can significantly limit the probability of identifying retinal tears.

Ultrasound Assessment of Gaze-induced Posterior Eyewall Deformation in Highly Myopic Eyes.

Purpose: To establish a quantitative metric of posterior eyewall deformability in different directions of gaze in highly myopic eyes with and without posterior staphyloma. Methods: A prospective study was performed on 53 highly myopic patients (106 eyes). Ultrasound scans were acquired in primary, up, downward, nasal, and temporal gazes. A validated intensity-based segmentation algorithm was used to quantify the posterior eyewall geometry on digitalized B-scan images. Posterior eyewall local curvature (K) and distance (L) to the transducer were calculated. The associations between directions of gaze, axial length (AL), and presence of staphyloma with the K and L parameters were assessed. Results: A total of 53 participants (106 eyes) were studied. Multivariate regression analysis demonstrated that, after accounting for longer AL, and presence of staphyloma, eccentric gaze was often independently associated with various K and L parameters. Specifically, downward gaze was associated with increased posterior eyewall concavity as reflected in the maximum of K (KMax) (ß = 0.050, P < 0.001) and absolute value of KMax (ß = 0.041, P = 0.011). Both downward gaze and upgaze were independently associated with increase in the derivative of absolute KMax (which is consistent with more apparent, steeper staphyloma ridges), local KMax (which detects KMax at smaller intervals), and Kstd (which represents likelihood of staphyloma presence) and decrease in maximum of L (which represents movement of the staphyloma apex) with all P < 0.05. The ß coefficients for downward gaze were consistently greater in magnitude compared with those in upgaze. After accounting for AL and presence of staphyloma, horizontal gazes were independently associated only with decrease in the standard deviation of L (which also represents likelihood of staphyloma presence) and maximum of L. Conclusions: Downward gaze results in a significant increase in posterior eyewall concavity in highly myopic eyes after accounting for AL and staphyloma presence. In comparison with downward gaze, upgaze resulted in a lower magnitude, but significant changes in staphyloma ridge steepness and the likelihood of staphyloma presence. Horizontal gazes seemed to be associated with less posterior eyewall geometric parameters. Studies are required to further assess the association between downward gaze during near work on posterior eyewall concavity and possible effects on myopia development and progression.

An effective and comprehensible method to detect and evaluate retinal damage due to diabetes complications.

The leading cause of vision loss globally is diabetic retinopathy. Researchers are making great efforts to automatically detect and diagnose correctly diabetic retinopathy. Diabetic retinopathy includes five stages: no diabetic retinopathy, mild diabetic retinopathy, moderate diabetic retinopathy, severe diabetic retinopathy and proliferative diabetic retinopathy. Recent studies have offered several multi-tasking deep learning models to detect and assess the level of diabetic retinopathy. However, the explanation for the assessment of disease severity of these models is limited, and only stops at showing lesions through images. These studies have not explained on what basis the appraisal of disease severity is based. In this article, we present a system for assessing and interpreting the five stages of diabetic retinopathy. The proposed system is built from internal models including a deep learning model that detects lesions and an explanatory model that assesses disease stage. The deep learning model that detects lesions uses the Mask R-CNN deep learning network to specify the location and shape of the lesion and classify the lesion types. This model is a combination of two networks: one used to detect hemorrhagic and exudative lesions, and one used to detect vascular lesions like aneurysm and proliferation. The explanatory model appraises disease severity based on the severity of each type of lesion and the association between types. The severity of the disease will be decided by the model based on the number of lesions, the density and the area of the lesions. The experimental results on real-world datasets show that our proposed method achieves high accuracy of assessing five stages of diabetic retinopathy comparable to existing state-of-the-art methods and is capable of explaining the causes of disease severity.

Brain endothelial cell-derived extracellular vesicles with a mitochondria-targeting photosensitizer effectively treat glioblastoma by hijacking the blood‒brain barrier.

Glioblastoma (GBM) is the most aggressive malignant brain tumor and has a high mortality rate. Photodynamic therapy (PDT) has emerged as a promising approach for the treatment of malignant brain tumors. However, the use of PDT for the treatment of GBM has been limited by its low blood‒brain barrier (BBB) permeability and lack of cancer-targeting ability. Herein, brain endothelial cell-derived extracellular vesicles (bEVs) were used as a biocompatible nanoplatform to transport photosensitizers into brain tumors across the BBB. To enhance PDT efficacy, the photosensitizer chlorin e6 (Ce6) was linked to mitochondria-targeting triphenylphosphonium (TPP) and entrapped into bEVs. TPP-conjugated Ce6 (TPP-Ce6) selectively accumulated in the mitochondria, which rendered brain tumor cells more susceptible to reactive oxygen species-induced apoptosis under light irradiation. Moreover, the encapsulation of TPP-Ce6 into bEVs markedly improved the aqueous stability and cellular internalization of TPP-Ce6, leading to significantly enhanced PDT efficacy in U87MG GBM cells. An in vivo biodistribution study using orthotopic GBM-xenografted mice showed that bEVs containing TPP-Ce6 [bEV(TPP-Ce6)] substantially accumulated in brain tumors after BBB penetration via transferrin receptor-mediated transcytosis. As such, bEV(TPP-Ce6)-mediated PDT considerably inhibited the growth of GBM without causing adverse systemic toxicity, suggesting that mitochondria are an effective target for photodynamic GBM therapy.

How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head.

Purpose: The purpose of this study was to assess optic nerve head (ONH) deformations following acute intraocular pressure (IOP) elevations and horizontal eye movements in control eyes, highly myopic (HM) eyes, HM eyes with glaucoma (HMG), and eyes with pathologic myopia (PM) alone or PM with staphyloma (PM + S). Methods: We studied 282 eyes, comprising of 99 controls (between +2.75 and -2.75 diopters), 51 HM (< -5 diopters), 35 HMG, 21 PM, and 75 PM + S eyes. For each eye, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze, (2) 20 degrees adduction, (3) 20 degrees abduction, and (4) primary gaze with acute IOP elevation (to ∼35 mm Hg) achieved through ophthalmodynamometry. We then computed IOP- and gaze-induced ONH displacements and effective strains. Effective strains were compared across groups. Results: Under IOP elevation, we found that HM eyes exhibited significantly lower strains (3.9 ± 2.4%) than PM eyes (6.9 ± 5.0%, P < 0.001), HMG eyes (4.7 ± 1.8%, P = 0.04), and PM + S eyes (7.0 ± 5.2%, P < 0.001). Under adduction, we found that HM eyes exhibited significantly lower strains (4.8% ± 2.7%) than PM + S eyes (6.0 ± 3.1%, P = 0.02). We also found that eyes with higher axial length were associated with higher strains. Conclusions: Our study revealed that eyes with HMG experienced significantly greater strains under IOP compared to eyes with HM. Furthermore, eyes with PM + S had the highest strains on the ONH of all groups.

Bioreducible exosomes encapsulating glycolysis inhibitors potentiate mitochondria-targeted sonodynamic cancer therapy via cancer-targeted drug release and cellular energy depletion.

Nanocarrier-assisted sonodynamic therapy (SDT) has shown great potential for the effective and targeted treatment of deep-seated tumors by overcoming the critical limitations of sonosensitizers. However, in vivo SDT using nanocarriers is still constrained by their intrinsic toxicity and nonspecific cargo release. In this study, we developed bioreducible exosomes for the safe and tumor-specific delivery of mitochondria-targeting sonosensitizers [triphenylphosphonium-conjugated chlorin e6 (T-Ce6)] and glycolysis inhibitors (FX11). Redox-cleavable diselenide linker-bearing lipids were embedded into exosomes to trigger drug release in response to overexpressed glutathione in the tumor microenvironment. Bioreducible exosomes facilitate the cytoplasmic release of their payload in the reducing environment of tumor cells. They significantly enhance drug release and sonodynamic effects when irradiated with ultrasound (US). The mitochondria-targeted accumulation of T-Ce6 efficiently damaged the mitochondria of the cells under US irradiation, accelerating apoptotic cell death. FX11 substantially inhibited cellular energy metabolism, potentiating the antitumor efficacy of mitochondria-targeted SDT. Bioreducible exosomes effectively suppressed tumor growth in mice without significant systemic toxicity, via a combination of mitochondria-targeted SDT and energy metabolism-targeted therapy. This study offers new insights into the use of dual stimuli-responsive exosomes encapsulating sonosensitizers for safe and targeted sonodynamic cancer therapy.

Predictive Factors of Mortality in Patients with Severe COVID-19 Treated in the Intensive Care Unit: A Single-Center Study in Vietnam.

INTRODUCTION: The fourth outbreak of COVID-19 with the delta variant in Vietnam was very fierce due to the limited availability of vaccines and the lack of healthcare resources. During that period, the high mortality of patients with severe and critical COVID-19 caused many concerns for the health system, especially the intensive care units. This study aimed to analyze the predictive factors of death and survival in patients with severe and critical COVID-19. METHODS: We conducted a cross-sectional and descriptive study on 151 patients with severe and critical COVID-19 hospitalized in the Intensive Care Unit of Binh Duong General Hospital. RESULTS: Common clinical symptoms of severe and critical COVID-19 included shortness of breath (97.4%), fatigue (89.4%), cough (76.8%), chest pain (47.7%), loss of smell (48.3%), loss of taste (39.1%), and headache (21.2%). The abnormal biochemical features were leukopenia (2.1%), anemia, thrombocytopenia (18%), hypoxia with low PaO2 (34.6%), hypocapnia with reduced PaCO2 (29.6%), and blood acidosis (18.4%). Common complications during hospitalization were septic shock (15.2%), cardiogenic shock (5.3%), and embolism (2.6%). The predictive factors of death were being female, age > 65 years, cardiovascular comorbidity, thrombocytopenia (< 137.109/l), and hypoxia at inclusion or after the first week or blood acidosis (pH < 7.28). The use of a high dose of corticosteroids reduced the mortality during the first 3 weeks of hospitalization but significantly increased risk of death after 3 and 4 weeks. CONCLUSIONS: Common clinical symptoms, laboratory features, and death-related complications of critical and severe COVID-19 patients were found in Vietnamese patients during the fourth wave of the COVID-19 pandemic. The results of this study provide new insight into the predictive factors of mortality for patients with severe and critical COVID-19.

Anatomical and Biomechanical Characteristics of Peroneus Longus Tendon: Applications in Knee Cruciate Ligament Reconstruction Surgery.

Introduction: The peroneus longus tendon is used in many orthopedic surgeries to regenerate the external ligaments of the knee. This study aims to evaluate some anatomical, biomechanical, and load-bearing properties of the peroneus longus tendon for use in cruciate ligament reconstruction. Materials and Methods: The study design is a cross-sectional description. The study subjects were 20 samples of the peroneus longus tendon from fresh carcasses. The leg is still intact, not crushed, is well preserved, and it has never been used in research. Results: The average length of the peroneus longus tendon was 29.25 ± 2.1 cm, and the average distance from the peroneus longus tendon to the deep peroneal nerve was 71.1 ± 8.63 mm. The peroneus longus tendon did not have an accessory ligament, the maximum tension of the peroneus longus tendon was 1170.4 ± 203 N, and the maximum length at break was 14.29 ± 3.88 mm. Conclusion: Removing the peroneus longus tendon will not affect the surrounding anatomical components. The maximum breaking force and the diameter of the peroneus longus tendon are similar to other graft materials, such as the hamstring tendon and patellar tendon.

Posterior scleral birefringence measured by triple-input polarization-sensitive imaging as a biomarker of myopia progression.

In myopic eyes, pathological remodelling of collagen in the posterior sclera has mostly been observed ex vivo. Here we report the development of triple-input polarization-sensitive optical coherence tomography (OCT) for measuring posterior scleral birefringence. In guinea pigs and humans, the technique offers superior imaging sensitivities and accuracies than dual-input polarization-sensitive OCT. In 8-week-long studies with young guinea pigs, scleral birefringence was positively correlated with spherical equivalent refractive errors and predicted the onset of myopia. In a cross-sectional study involving adult individuals, scleral birefringence was associated with myopia status and negatively correlated with refractive errors. Triple-input polarization-sensitive OCT may help establish posterior scleral birefringence as a non-invasive biomarker for assessing the progression of myopia.

Identifying Content for an Item Bank to Measure the Quality-of-Life Impact of Myopia Refractive Interventions.

Purpose: To report on the content generation and item refinement phases for a myopia refractive intervention-specific quality-of-life (QoL) item bank that will be operationalized using computerized adaptive testing. Methods: Myopia refractive intervention-specific QoL domains and items were generated from (1) a literature search of existing refractive-intervention QoL questionnaires; (2) semistructured interviews with myopic patients corrected using spectacles, contact lenses and/or refractive surgery (n = 32); (3) and myopia experts (n = 9) recruited from the Singapore National Eye Centre. After a thematic analysis, items were systematically refined and tested using cognitive interviews with 24 additional patients with corrected myopia. Results: Of the 32 participants with myopia interviewed (mean ± standard deviation age, 35.6 ± 9.0 years; 71.9% female; 78.1% Chinese), 12 (37.5%) wore spectacles, 7 (21.9%) used contact lenses, and 20 (62.5%) had undergone laser refractive surgery. Initially, 912 items within 7 independent QoL domains were identified. After refinement, 204 items were retained, including those relating to mobility challenges and work-related difficulties that are not well-represented in current refractive intervention-specific questionnaires. Conclusions: Through a rigorous item generation and selection process, we have developed a 204-item and 7-domain myopia refractive intervention-specific item bank that will now undergo rigorous psychometric testing to generate item calibrations for the validation of a novel computerized adaptive testing instrument designed for use in research and routine clinical practice. Translational Relevance: Once psychometrically validated and operationalized using computerized adaptive testing, this myopia refractive intervention-specific instrument will enable researchers and clinicians to quickly and comprehensively assess the impact of myopic refractive interventions across seven QoL domains.

High-frequency ultrasound point-of-care device to quantify myopia-induced microstructural changes in the anterior sclera.

PURPOSE: To develop a point-of-care (POC) device using high-frequency ultrasound (US) for evaluating microstructural changes in the anterior sclera associated with myopia. METHODS: The proposed POC device must satisfy four primary requirements for effective clinical use: the measurement component is handheld; the software must be simple and provide real-time feedback; patient safety and health data security requirements set forth by relevant governing bodies must be satisfied and the measurement data must have sufficient signal-to-noise ratio (SNR) and repeatability. Radiofrequency (RF) echo data acquired by the POC device will be processed using our quantitative US methods to characterise tissue microstructure and biomechanical properties. RESULTS: All stated requirements have been met in the developed POC device. The high-frequency transducer is housed in a custom, 3D-printed, pen-like holder that allows for easy measurements of the anterior sclera. Custom software provides a simple interface for data acquisition, real-time data display and secure data storage. Exposimetry measurements of the US pressure field indicate device compliance with United States Food and Drug Administration limits for ophthalmic US. In vivo measurements on a volunteer suggest the RF data SNR and acquisition consistency are suitable for quantitative analysis. CONCLUSIONS: A fully functioning POC device using high-frequency US has been created for evaluating the microstructure of the anterior sclera. Planned studies using the POC device to scan the eyes of myopia patients will help clarify how the anterior sclera microstructure may be affected by myopia. If effective, this portable, inexpensive and user-friendly system could be an important part of routine eye examinations.

Quadrant Asymmetry in Optical Coherence Tomography Angiography Metrics in Ischemic Versus Non-Ischemic Central Retinal Vein Occlusion Eyes.

Purpose: To determine whether quadrant asymmetry (QA) of optical coherence tomography angiography (OCTA) metrics differs between non-ischemic versus ischemic central retinal vein occlusion (CRVO). Methods: Fifty-eight eyes (21 non-ischemic, 10 ischemic CRVO, and 27 contralateral control eyes) underwent 3 × 3 mm spectral-domain OCTA scans with quantification of the superficial retinal layer vessel length density (VLD) and perfusion density (PD). QA, defined as the maximum-minus-minimum value among four parafoveal Early Treatment Diabetic Retinopathy Study (ETDRS) quadrants, was compared by linear regression including fixed effects for each eye. Results: Mean age was 73.6 ± 11.4 (range 39-88), 73.8 ± 12.4 (range 39-91) and 77.2 ± 9.83, (range 60-88); and QA was 3.46 ± 1.76, 3.14 ± 1.57, and 4.88 ± 2.42 for VLD and 0.072 ± 0.038, 0.062 ± 0.036, and 0.11 ± 0.056 for PD for control, non-ischemic, and ischemic, respectively. QA was significantly higher in ischemic (0.109 ± 0.056) than non-ischemic CRVO eyes (0.062 ± 0.036; P = 0.02) and control eyes for PD (0.072 ± 0.038; P = 0.03). QA was also greater in ischemic (4.875 ± 2.418) than non-ischemic CRVO (3.141 ± 1.572) for VLD (P = 0.04). In terms of identifying which particular quadrant is most affected by ischemia, multivariate regression analysis comparing intra-quadrant effect on the presence of ischemia versus non-ischemia showed no quadrant was significantly affected (P > 0.05 for all quadrants). Conclusions: Ischemic CRVO increases intraeye QA of OCTA metrics when compared to non-ischemic CRVO and control eyes. No specific ETDRS quadrant appears to be more affected. Translational Relevance: This work uses an intraeye method to delineate between ischemic and non-ischemic CRVO by OCTA imaging, overcoming inter-eye variables encountered in clinical care.

Applications of Genomics and Transcriptomics in Precision Medicine for Myopia Control or Prevention.

Myopia is a globally emerging concern accompanied by multiple medical and socio-economic burdens with no well-established causal treatment to control thus far. The study of the genomics and transcriptomics of myopia treatment is crucial to delineate disease pathways and provide valuable insights for the design of precise and effective therapeutics. A strong understanding of altered biochemical pathways and underlying pathogenesis leading to myopia may facilitate early diagnosis and treatment of myopia, ultimately leading to the development of more effective preventive and therapeutic measures. In this review, we summarize current data about the genomics and transcriptomics of myopia in human and animal models. We also discuss the potential applicability of these findings to precision medicine for myopia treatment.