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Bietti crystalline dystrophy (BCD) is an autosomal recessive inherited retinal disease (IRD) and its early precise diagnosis is much challenging. This study aims to diagnose BCD and classify the clinical stage based on ultra-wide-field (UWF) color fundus photographs (CFPs) via deep learning (DL). All CFPs were labeled as BCD, retinitis pigmentosa (RP) or normal, and the BCD patients were further divided into three stages. DL models ResNeXt, Wide ResNet, and ResNeSt were developed, and model performance was evaluated using accuracy and confusion matrix. Then the diagnostic interpretability was verified by the heatmaps. The models achieved good classification results. Our study established the largest BCD database of Chinese population. We developed a quick diagnosing method for BCD and evaluated the potential efficacy of an automatic diagnosis and grading DL algorithm based on UWF fundus photography in a Chinese cohort of BCD patients.

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Purpose: Primary surgery failure of macular holes causes poor visual acuity outcomes. Several studies indicate that small-medium idiopathic full-thickness macular holes (iFTMH) have consistent and high anatomical closure rates after vitrectomy and internal limiting membrane (ILM) peeling, regardless of iFTMH diameters. However, there is no systematic analysis examining the relationship between iFTMH diameters and anatomical closure rates. Methods: In this systematic review and meta-regression, we searched PubMed, Embase, and Web of Science databases on October 24th, 2022. We included studies regarding iFTMH, with ILM peeling/inverted flap technique, long-lasting gas tamponade, and face-down position after surgery. Univariable meta-regression with a restricted cubic spline model and component-plus-residual plot after covariables adjustment were used to explore non-linear association. Results: A total of 7257 participants from 19 randomized controlled trials and 49 observational studies were included in this meta-analysis. In ILM peeling group, every 100-µm increment in diameter was associated with a 3.8 % (95 % confidence interval [CI], 1.8%-5.7 %, P < 0.001) relatively lower anatomical closure rate. Yet, among studies using the inverted flap technique, baseline iFTMH diameter was not associated with a lower anatomical closure rate (0.2 %, 95%CI, -4.2 %-4.5 %, P > 0.9). The restricted cubic spline model and component-plus-residual plot controlling for age, sex, and symptom duration prior to surgery showed no evident non-linearity in both surgical techniques. Conclusions: The iFTMH diameter is linear and inversely associated with the anatomical closure rate after the ILM peeling technique, but not with the inverted flap technique. The present study supports the use of advanced techniques, e.g., inverted flap technique, in small-medium iFTMH to improve anatomical closure rates.

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PURPOSE: The aim of this study was to analyze the incidence of retinal vein occlusion (RVO) in patients with and without diabetes in the population and compare the influencing factors. METHOD: The community-based Kailuan Eye Study included 14,440 participants (9835 male, 4605 female) with a mean age of 54.0 ± 13.3 years (range, 20-110 years). They underwent a systemic and ophthalmologic examination. RVO were diagnosed on fundus photographs. RESULT: By matching for age and gender, we included a total of 2767 patients each with diabetes and non-diabetes. The prevalence of RVO among patients with and without diabetes was 1.5% and 0.8%, respectively. The prevalence of RVO was higher in patients with diabetes than in patients without diabetes in all age groups. Multifactorial regression analysis showed that only fasting blood glucose levels were significantly different between patients with RVO with or without DM. The occurrence of RVO in the group with diabetes was mainly associated with higher fasting glucose and systolic blood pressure; in the group without diabetes, RVO was mainly associated with higher diastolic blood pressure, Body Mass Index, and lower low-density lipoprotein cholesterol levels. CONCLUSION: We found that patients with diabetes have increased risks of RVO. In addition to blood pressure control, we recommend educating patients with diabetes about RVO, to prevent its subsequent occurrence.

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INTRODUCTION: Coronary microcirculation dysfunction (CMD) is prevalent in patients with coronary artery disease (CAD). Current therapies for CMD are focused on pharmacotherapy, non-pharmacological treatments such as enhanced external counterpulsation (EECP) have shown favourable results in patients with CAD. However, whether EECP can improve CMD remains unknown. This study is designed to evaluate the effectiveness of EECP on CMD in patients with CAD, and to assess the feasibility of conducting a multicentre randomised controlled trial. METHODS AND ANALYSIS: This study is a single-centre, outcome-assessor-blinded, parallel randomised controlled trial. A total of 110 participants with CAD will be included and randomly assigned to either the intervention group (EECP plus optimal medical therapy (OMT)) or the control group (OMT alone). EECP will be administered by operators for 60 min, 5 times per week for 7 weeks (35 times in total). Outcomes include patients' retention rates, the primary outcome and secondary outcomes. The primary outcome is the change in Myocardial Perfusion Reserve Index with cardiac MRI from baseline to the end of follow-up. The planned study duration is from 2024 to 2026. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Ethics Committee of the Eighth Affiliated Hospital, Sun Yat-sen University (ID: 2023-045-03). The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2300076231.

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PURPOSE: To evaluate efficacy and safety of efdamrofusp alfa compared with aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: Randomized, double-masked, multicenter, active-controlled, non-inferiority phase 2 study PARTICIPANTS: A total of 231 treatment-naïve and previously treated participants with active choroidal neovascularization secondary to nAMD were enrolled. METHODS: Eligible participants were randomized (1:1:1) to 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa or 2 mg aflibercept groups. Participants in all groups received three initial monthly loading doses, followed by treatment every 8 weeks with assessment every 4 weeks up to week 52. MAIN OUTCOME MEASURES: The primary endpoint was the mean BCVA change from baseline to week 36. The pre-specified noninferiority margin was set as -5 letters (80% CI). RESULTS: Each treatment group included 77 participants. The mean BCVA changes from baseline to week 36 for 2 mg efdamrofusp alfa, 4 mg efdamrofusp alfa and aflibercept groups were +10.6, +11.4, +12.0 letters, respectively; Least Squares (LS) mean difference were -1.4 (80% CI: -3.5 to 0.7) between 2 mg efdamrofusp alfa and aflibercept, and -0.6 (80% CI: -2.7 to 1.6) between 4 mg efdamrofusp alfa and aflibercept. Mean central retinal thickness changes were consistent across groups. Adverse event rate was comparable among the groups. CONCLUSIONS: Efdamrofusp alfa demonstrated noninferiority to aflibercept in BCVA improvement, accompanied by a similar safety profile.

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The lack of effective vaccines and the development of resistance to the current treatments highlight the urgent need for new anti-leishmanials. Sphingolipid metabolism has been proposed as a promising source of Leishmania-specific targets as these lipids are key structural components of the eukaryotic plasma membrane and are involved in distinct cellular events. Inositol phosphorylceramide (IPC) is the primary sphingolipid in the Leishmania species and is the product of a reaction mediated by IPC synthase (IPCS). The antihistamine clemastine fumarate has been identified as an inhibitor of IPCS in L. major and a potent anti-leishmanial in vivo. Here we sought to further examine the target of this compound in the more tractable species L. mexicana, using an approach combining genomic, proteomic, metabolomic and lipidomic technologies, with molecular and biochemical studies. While the data demonstrated that the response to clemastine fumarate was largely conserved, unexpected disturbances beyond sphingolipid metabolism were identified. Furthermore, while deletion of the gene encoding LmxIPCS had little impact in vitro, it did influence clemastine fumarate efficacy and, importantly, in vivo pathogenicity. Together, these data demonstrate that clemastine does inhibit LmxIPCS and cause associated metabolic disturbances, but its primary target may lie elsewhere.

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OBJECTIVES: The aim of this study was to explore inflammation of soft tissue around the upper third molar as a prevalent cause of limited mouth opening, identify the clinical and radiographic features, and summarize the therapeutic effectiveness of tooth extraction. MATERIALS AND METHODS: A retrospective analysis of data from 264 patients with limited mouth opening over the last five years was performed. RESULTS: Among the 264 patients, 24 (9.1%) had inflammation of the soft tissue around the upper third molar, which was the second most common cause of limited mouth opening. Twenty-one of the twenty-four affected patients, with an average mouth opening of 19.1 ± 7.6 mm, underwent upper third molar extraction. Gingival tenderness around the upper third molar or maxillary tuberosity mucosa was a characteristic clinical manifestation (p < 0.05). The characteristic features on maxillofacial CT included soft tissue swelling around the upper third molar and gap narrowing between the maxillary nodules and the mandibular ascending branch. Post extraction, the average mouth opening increased to 31.4 ± 4.9 mm (p < 0.05), and follow-up CT demonstrated regression of the inflammatory soft tissue around the upper third molar. CONCLUSIONS: Inflammation of soft tissue around the upper third molar is a common cause of limited mouth opening. Symptoms of pain associated with the upper third molar and distinctive findings on enhanced maxillofacial CT scans are crucial for diagnosis. Upper third molar extraction yields favorable therapeutic outcomes. CLINICAL RELEVANCE: Inflammation of the soft tissue around the maxillary third molar commonly causes limited mouth opening, but this phenomenon has long been overlooked. Clarifying this etiology can reduce the number of misdiagnosed patients with restricted mouth opening and enable more efficient treatment for patients.

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PURPOSE: Calculating the intraocular lens (IOL) in patients after corneal refractive surgery presents a challenge. Because an overestimation of corneal power in cases undergone this surgery leading to a subsequent under-correction of IOL power. However, recent advancements in technology have eliable measurement of total corneal power. The aim of this research was to assess the agreement in simulated keratometry (SimK) and total keratometry (TK) values between IOLMaster 700 and Pentacam AXL. METHODS: The study involved 99 patients (99 eyes) undergone small incision lenticule extraction (SMILE) surgery. Each patient underwent scans using IOL Master 700 and Pentacam AXL. The following parameters were recorded: SimK1, SimK2, Total K1 (TK1), and Total K2 (TK2) for IOLMaster 700; and SimK1, SimK2, True Net Power (TNP) K1, TNPK2, Total Corneal Refractive Power (TCRP) K1, and TCRP K2 for Pentacam AXL. Agreement between the two devices was evaluated using Bland-Altman plot, while paired t-test was utilized to compare any differences in the same parameter by both instruments. RESULTS: The results revealed a strong correlation between the two devices.Noticeable comparability was identified for all SimK variables. However, there were noticeable differences in TK measurements as well as TK1-TNPK1, TK2-TNP K2, TK1-TCRP K1, and TK2-TCRP K2 parameters when comparing the two devices. The IOLMaster 700 consistently measured steeper values than the Pentacam AXL, with significant and clinically relevant differences of 1.34, 1.37, 0.87, and 0.95 diopters, respectively. CONCLUSION: While there was a noticeable correlation between the IOLMaster 700 and Pentacam AXL in SimK measurements, a marked difference was noted in TK values. The two devices cannot be used interchangeably when quantifying TK values.

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BACKGROUND: Diabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes. METHODS: The Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed. RESULTS: This study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all). CONCLUSIONS: In this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

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PURPOSE: To compare the efficacy and safety between traditional lens fitting and computer-aided fitting methods for orthokeratology (OrthoK) in the Chinese population. METHODS: A multi-center, examiner-masked, randomized controlled study was conducted with a one-year follow-up period, enrolling 280 participants with spherical equivalent (SE) ranging from -0.5D to -4.0D. Participants were assigned to either the computer-aided orthokeratology fitting group (trial group) or the traditional lens fitting group (control group) using stratified randomization based on age (8 to 13 years, 13 to 18 years, and ≥ 18 years) to ensure a minimum of 30 cases in each sub-age group. Ocular examinations included visual acuity, objective and subjective refraction, corneal endothelial cell density, corneal topography, intraocular pressure, axial length, and ocular health assessment. Successful lens-correction was defined as the residual refraction with the OK lens, which should not exceed ± 0.5D, and/or an uncorrected visual acuity of no worse than 0.1 logMAR. Statistical analysis involves t-tests, analysis of variance, and Chi-squared tests. RESULTS: 215 subjects were included in the statistical analysis (109 in the trial group and 106 in the control group). In both groups, compared to baseline data, the uncorrected visual acuity (UCVA) improved significantly, with SE reduced and central corneal curvature flattened greatly after wearing OrthoK lens (P < 0.05 for all). Compared to the control group, the trial group exhibited a higher successful rate in correcting UCVA (93.6 % vs. 84.0 %, P = 0.03) and slightly better correction in refraction (77.1 % vs. 66.0 %, P = 0.07) at 1-month follow-up. However, no significant differences were observed in the axial length elongation, corneal changes, or the incidence of adverse events between the two groups. CONCLUSION: These findings indicate the higher efficiency and slightly better performance in correcting myopia and improving UCVA of computer-aided lens fitting approach compared to the traditional one, but similar outcomes in controlling axial elongation.

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AIM: To evaluate dry eye disease (DED) symptomatology and mental health status in different COVID-19 patients. METHODS: A cross-sectional observational design was used. Totally 123 eligible adults (46.34% of men, age range, 18-59y) with COVID-19 included in the study from August to November, 2022. Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) were used in this study. RESULTS: OSDI scores were 6.82 (1.25, 15.91) in asymptomatic carriers, 7.35 (2.50, 18.38) in mild cases, and 16.67 (4.43, 28.04) in recurrent cases, with 30.00%, 35.56%, and 57.89%, respectively evaluated as having DED symptoms (χ2=7.049, P=0.029). DEQ-5 score varied from 2.00 (0, 6.00) in asymptomatic carriers, 3.00 (0, 8.00) in mild cases, and 8.00 (5.00, 10.00) in recurrent cases, with 27.50%, 33.33%, and 55.26%, respectively assessed as having DED symptoms (χ2=8.532, P=0.014). The prevalence of clinical anxiety (50.00%) and depression (47.37%) symptoms were also significantly higher in patients with recurrent infection (χ2=24.541, P<0.001; χ2=30.871, P<0.001). Recurrent infection was a risk factor for high OSDI scores [odds ratio, 2.562; 95% confidence interval (CI), 1.631-7.979; P=0.033] and DEQ-5 scores (odds ratio, 3.353; 95%CI, 1.038-8.834; P=0.043), whereas having a fixed occupation was a protective factor for OSDI scores (odds ratio, 0.088; 95%CI, 0.022-0.360; P=0.001) and DEQ-5 scores (odds ratio, 0.126; 95%CI, 0.039-0.405; P=0.001). CONCLUSION: Patients with recurrent COVID-19 have more severe symptoms of DED, anxiety, and depression.

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Background: Ophthalmological screening for cytomegalovirus retinitis (CMVR) for HIV/AIDS patients is important to prevent lifelong blindness. Previous studies have shown good properties of automated CMVR screening using digital fundus images. However, the application of a deep learning (DL) system to CMVR with ultra-wide-field (UWF) fundus images has not been studied, and the feasibility and efficiency of this method are uncertain. Methods: In this study, we developed, internally validated, externally validated, and prospectively validated a DL system to detect AIDS-related from UWF fundus images from different clinical datasets. We independently used the InceptionResnetV2 network to develop and internally validate a DL system for identifying active CMVR, inactive CMVR, and non-CMVR in 6960 UWF fundus images from 862 AIDS patients and validated the system in a prospective and an external validation data set using the area under the curve (AUC), accuracy, sensitivity, and specificity. A heat map identified the most important area (lesions) used by the DL system for differentiating CMVR. Results: The DL system showed AUCs of 0.945 (95 % confidence interval [CI]: 0.929, 0.962), 0.964 (95 % CI: 0.870, 0.999) and 0.968 (95 % CI: 0.860, 1.000) for detecting active CMVR from non-CMVR and 0.923 (95 % CI: 0.908, 0.938), 0.902 (0.857, 0.948) and 0.884 (0.851, 0.917) for detecting active CMVR from non-CMVR in the internal cross-validation, external validation, and prospective validation, respectively. Deep learning performed promisingly in screening CMVR. It also showed the ability to differentiate active CMVR from non-CMVR and inactive CMVR as well as to identify active CMVR and inactive CMVR from non-CMVR (all AUCs in the three independent data sets >0.900). The heat maps successfully highlighted lesion locations. Conclusions: Our UWF fundus image-based DL system showed reliable performance for screening AIDS-related CMVR showing its potential for screening CMVR in HIV/AIDS patients, especially in the absence of ophthalmic resources.

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The signing of the Regional Comprehensive Economic Partnership agreement brings new opportunities for the development of international air transportation. Faced with fierce competition, it is worth studying how hub airports should enhance competitiveness, and how low-cost carriers and full-service carriers should optimize the RCEP international airline network layout for better development. Aiming at providing suggestions for the development of hub airports, low-cost and full-service carriers in the RCEP international airline network, this paper identifies the hub airports, analyzes the layout of the RCEP international airline network, and the multi-layered characteristics based on an improved contribution matrix using data from 2010 to 2019 collected from the Official Airline Guide (OAG). This method comprehensively considers attributes of hub airports and the multi-layered characteristics of the airports and routes. The layout analysis indicates that the RCEP international transportation market presents a more open environment for competition and cooperation where base carriers are often the biggest supporters of hub construction. The multi-layered characteristics analysis reveals that low-cost carriers contribute more towards opening up new RCEP routes than full-service carriers. It is advised that carriers newly entering the RCEP international aviation transportation market and low-cost carriers dedicate to establishing new routes around their hub airports to monopolize this market and enhance their market share, whilst full-service carriers consolidate existing routes and increase route density to achieve economic benefits.

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BACKGROUND: Inferior alveolar nerve (IAN) injury is one of the complications of impacted lower mandibular third molar (LM3) extraction. Given the unknown prognosis of IAN injuries and limited treatment options, it is critical to understand the risk factors of IAN injury before LM3 extraction. PURPOSE: The purpose of the study was to identify risk factors associated with IAN injury after LM3 extraction. STUDY DESIGN, SETTING, SAMPLE: This was a prospective cohort study including patients who underwent LM3 extraction from May to December 2021 at the authors' institution. Patients with systemic diseases, previous maxillofacial surgeries, or sensory abnormalities were excluded. PREDICTOR VARIABLE: The predictor variable is composed of several risk factors. The variables were grouped into four categories: demographic, radiographic, procedure-related, and surgeon experience. MAIN OUTCOME VARIABLE(S): The outcome variable was postoperative neurosensory disturbance coded as present or absent and was measured at 1-month (transient) and 1-year (permanent). COVARIATES: Not applicable. ANALYSES: The measurement data were represented by mean and standard deviation. The association of each variable with the presence of an IAN injury was tested by the χ2 test. Statistical significance was accepted at P < .05. RESULTS: The study sample consisted of 705 patients (37.0% male) with an average age of 28.51 ± 6.51 years. A total of 17/705 (2.4%) and 4/705 (0.57%) patients developed transient and permanent IAN injuries. The results demonstrated that the following factors were associated with higher rates of transient injury: use of chisels during surgeries (6.4%; 95% confidence interval (CI): 2.7 to 12.3; P = .02; relative risk (RR) = 11.4), LM3s located below the IAN canal (8.7%; 95% CI: 4.3 to 15.7; P < .01; RR = 7.3), compressed contact between LM3s and the IAN canal (36.4%; 95% CI: 12.3 to 78.2; P < .001; RR = 25.4), and not using corticosteroids after surgeries (3.8%; 95% CI: 1.9 to 6.5; P = .03; RR = 3.1). The only factor associated with permanent injury was compressed contact between LM3s and the IAN canal (18.2%; 95% CI: 2.2 to 62.3; P < .001; RR = 48.2). CONCLUSION AND RELEVANCE: Close proximity between LM3s and IAN canal and the use of chisels increase the risk of transient IAN injury. Corticosteroid treatment may promote nerve recovery. Compressed contact between LM3s and IAN canal is the only risk factor for permanent injury.

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