Intraocular cetuximab: Safety and effect on axial elongation in young Guinea pigs with lens-induced myopization.

This study aimed to examine the intraocular tolerability of the epidermal growth factor receptor antibody cetuximab, when applied intravitreally, and its effect on axial elongation. Guinea pigs aged 2-3 weeks were subjected to bilateral plano glasses and bilateral lens-induced myopization (LIM) as a single procedure for group I (n = 8) and group II (n = 8), respectively. In the animals of group III (n = 8), group IV (n = 8), and group V (n = 8), the right eyes of the animals, in addition to LIM, received four weekly intravitreal injections of cetuximab (Erbitux®) in doses of 6.25 µg, 12.5 µg, and 25 µg, respectively. As controls, the left eyes, in addition to LIM, received corresponding intraocular injections of phosphate-buffered saline. The animals underwent regular ophthalmoscopic examinations and biometry for axial length measurements. With increasing doses of cetuximab, the inter-eye difference in axial elongation (at study end, left eyes minus right eyes) were significantly the smallest in group I (0.00 ± 0.02 mm) and group II (-0.01 ± 0.02 mm), they were larger in group III (0.04 ± 0.04 mm) and group IV (0.10 ± 0.03 mm), and they were the largest in group V (0.11 ± 0.01 mm). The inter-eye difference in axial elongation enlarged (P < 0.001) with the number of injections applied. Retinal thickness at the posterior pole (right eyes) was significantly thicker in group V than in group II (P < 0.01). The density of apoptotic cells (visualized by TUNEL-staining) did not vary significantly between any of the groups (all P > 0.05). The results suggest that intravitreal injections of cetuximab in young guinea pigs with LIM resulted in a reduction in axial elongation in a dose-dependent and number of treatment-dependent manner. Intraocular toxic effects, such as intraocular inflammation, retinal thinning, or an increased density of apoptotic cells in the retina, were not observed in association with the intravitreally applied cetuximab.

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study.

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.

Six-month binocular stereopsis recovery and its influencing factors in children with intermittent exotropia.

OBJECTIVE: To investigate the recovery of binocular stereopsis recovery and its influencing factors in children with intermittent exotropia after successful correction of eye position. METHODS: Prospective clinical study. A total of 178 patients, aged 9 ∼ 14 (10.8 ± 1.7) years, who were successfully corrected after intermittent exotropia surgery at the Beijing Tongren Hospital Affiliated to Capital Medical University from October 2023 to September 2023 were collected, the follow-up duration was six-month or longer. Paired t test, Pearson correlation analysis and multivariable linear regression analysis were used to probe preoperative clinical features that may predict the stereopsis six months after surgery. RESULTS: Six months after surgery, the angle of deviation of the patients met the orthotopic standard, and there was significant difference compared with that before surgery (distant: -2.7△±3.2△ vs. -30.5△±8.4△, t=-25.3, P < 0.001. Near:-3.7△±4.1△ vs. -33.7△±8.0△, t=-26.1, P < 0.001). Distant stereopsis (3.0 ± 0.6 vs. 3.9 ± 0.4, t = 4.9, P < 0.05) and near stereopsis (2.3 ± 0.5 vs. 2.6 ± 0.4, t = 3.8, P < 0.05) were both significantly improved compared with that of before surgery. 17% and 22% patients rebuilt normal distant stereopsis and normal near stereopsis, respectively. Preoperative distant stereopsis (r=-0.26, P = 0.004) and near stereopsis (r=-0.23, P = 0.011) was significantly negatively correlated with convergence reserve. Multivariable analysis showed that patients' age (ß = 0.003, p = 0.037), anisometropia (ß = 0.015, p = 0.043), and preoperative distant stereopsis (ß = 0.456, p < 0.001) were significantly associated with postoperative distant stereopsis. Patients' age (ß = 0.005, p = 0.044), anisometropia (ß = 0.127, p = 0.034), angle of deviation (ß=-0.230, p = 0.020), and preoperative near stereopsis (ß = 0.136, p < 0.001) were significantly associated with postoperative near stereopsis. CONCLUSION: IXT patients could get eye position fixed after surgery, about 20% patients benefited from stereopsis improvement. Patient's age, binocular anisometropia, angle of deviation and preoperative stereopsis were independent factors influencing postoperative stereopsis.

Lens-induced myopization and body weight in young guinea pigs.

BACKGROUND: To investigate the relationship between body weight and Axial length in guinea pigs. METHODS: Forty pigmented guinea pigs were randomly divided into two groups, namely control group and negative lens-induced myopization (LIM) group. After measuring the baseline axial length and body weight (BW), guinea pigs of LIM group received bilateral negative lens-induced myopization using - 10.0 diopters lenses. One week later, the lenses were removed and biometric and ophthalmoscopic examinations were repeated. RESULTS: Two groups of guinea pigs showed no statistical difference in initial body weight and eye axis length. Compared to the control group, the lens-induced group had a lower weight (P = 0.02) and a longer axial length (P < 0.01) at the end of study Neither at baseline nor at week 1 did AL correlate with BW in both groups (Control Baseline: r = 0.306, P = 0.19; Control Week1: r = 0.333, P = 0.15; LIM Baseline: r=-0.142, P = 0.55; LIM Week 1: r = 0.189, P = 0.42). Lens-induction had a significant effect on axial elongation (P < 0.01) while body weight had no impact on such aspect (P > 0.05). CONCLUSION: In guinea pigs of the same age, axial length was not correlated with body weight. Also, baseline body weight had no impact on natural axial length growth or lens-induced myopia. Lens-induction caused a significant reduction in body weight gain.

Risk Factors Associated With Inferior Alveolar Nerve Injury After Extraction of Impacted Lower Mandibular Third Molars: A Prospective Cohort Study.

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.

Total and simulated keratometry measurements using IOLMaster 700 and Pentacam AXL after small incision lenticule extraction.

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.

Vitamin D and myopia: a review.

Myopia is a worldwide public health problem of vision disorder caused by multiple factors, which has posed a huge socioeconomic burden, raising concerns about sight-threatening ocular complications. Vitamin D, as a kind of fat-soluble vitamin, related to time-spent-outdoors, has been considered by extensive studies to have potential relationship with myopia. We reviewed studies published in a decade which estimated the association of blood vitamin D status with myopia and summarized the universality and individuality of all research articles. Several research articles suggested the known environmental risk factors of myopia, including age, gender, ethnicity, education level, parental and school conditions, time-spent-outdoors, and sunlight exposure, and recent epidemiological studies demonstrate that increased vitamin D levels, by virtue of the extended outdoor time, may be an important modifiable factor and a protective effect that delay the progression of myopia in children and adolescents rather than in adults. The genetic studies have been conducted to get access to the evidence of gene polymorphism for explaining the association of serum vitamin D status and myopia, but the precise genetic interpretation of vitamin D and myopia remains unclear so far; on the other hand, the possible mechanisms are various like copolymerization mechanism, calcium homeostasis and imbalance of ciliary muscle function regulation, but nearly all of the investigators are inclined to remain skeptical. This article reviews the age-related epidemiological proofs, existent genetics correlations, possible underlying biological mechanisms and further values for the protective association between vitamin D and myopia, providing the possibility of prevention or postponement for myopia.

GCH1 Deficiency Activates Brain Innate Immune Response and Impairs Tyrosine Hydroxylase Homeostasis.

The Parkinson's disease (PD) risk gene GTP cyclohydrolase 1 (GCH1) catalyzes the rate-limiting step in tetrahydrobiopterin (BH4) synthesis, an essential cofactor in the synthesis of monoaminergic neurotransmitters. To investigate the mechanisms by which GCH1 deficiency may contribute to PD, we generated a loss of function zebrafish gch1 mutant (gch1-/-), using CRISPR/Cas technology. gch1-/- zebrafish develop marked monoaminergic neurotransmitter deficiencies by 5 d postfertilization (dpf), movement deficits by 8 dpf and lethality by 12 dpf. Tyrosine hydroxylase (Th) protein levels were markedly reduced without loss of ascending dopaminergic (DAergic) neurons. L-DOPA treatment of gch1-/- larvae improved survival without ameliorating the motor phenotype. RNAseq of gch1-/- larval brain tissue identified highly upregulated transcripts involved in innate immune response. Subsequent experiments provided morphologic and functional evidence of microglial activation in gch1-/- The results of our study suggest that GCH1 deficiency may unmask early, subclinical parkinsonism and only indirectly contribute to neuronal cell death via immune-mediated mechanisms. Our work highlights the importance of functional validation for genome-wide association studies (GWAS) risk factors and further emphasizes the important role of inflammation in the pathogenesis of PD.SIGNIFICANCE STATEMENT Genome-wide association studies have now identified at least 90 genetic risk factors for sporadic Parkinson's disease (PD). Zebrafish are an ideal tool to determine the mechanistic role of genome-wide association studies (GWAS) risk genes in a vertebrate animal model. The discovery of GTP cyclohydrolase 1 (GCH1) as a genetic risk factor for PD was counterintuitive, GCH1 is the rate-limiting enzyme in the synthesis of dopamine (DA), mutations had previously been described in the non-neurodegenerative movement disorder dopa-responsive dystonia (DRD). Rather than causing DAergic cell death (as previously hypothesized by others), we now demonstrate that GCH1 impairs tyrosine hydroxylase (Th) homeostasis and activates innate immune mechanisms in the brain and provide evidence of microglial activation and phagocytic activity.

Automatic retinoblastoma screening and surveillance using deep learning.

BACKGROUND: Retinoblastoma is the most common intraocular malignancy in childhood. With the advanced management strategy, the globe salvage and overall survival have significantly improved, which proposes subsequent challenges regarding long-term surveillance and offspring screening. This study aimed to apply a deep learning algorithm to reduce the burden of follow-up and offspring screening. METHODS: This cohort study includes retinoblastoma patients who visited Beijing Tongren Hospital from March 2018 to January 2022 for deep learning algorism development. Clinical-suspected and treated retinoblastoma patients from February 2022 to June 2022 were prospectively collected for prospective validation. Images from the posterior pole and peripheral retina were collected, and reference standards were made according to the consensus of the multidisciplinary management team. A deep learning algorithm was trained to identify "normal fundus", "stable retinoblastoma" in which specific treatment is not required, and "active retinoblastoma" in which specific treatment is required. The performance of each classifier included sensitivity, specificity, accuracy, and cost-utility. RESULTS: A total of 36,623 images were included for developing the Deep Learning Assistant for Retinoblastoma Monitoring (DLA-RB) algorithm. In internal fivefold cross-validation, DLA-RB achieved an area under curve (AUC) of 0.998 (95% confidence interval [CI] 0.986-1.000) in distinguishing normal fundus and active retinoblastoma, and 0.940 (95% CI 0.851-0.996) in distinguishing stable and active retinoblastoma. From February 2022 to June 2022, 139 eyes of 103 patients were prospectively collected. In identifying active retinoblastoma tumours from all clinical-suspected patients and active retinoblastoma from all treated retinoblastoma patients, the AUC of DLA-RB reached 0.991 (95% CI 0.970-1.000), and 0.962 (95% CI 0.915-1.000), respectively. The combination between ophthalmologists and DLA-RB significantly improved the accuracy of competent ophthalmologists and residents regarding both binary tasks. Cost-utility analysis revealed DLA-RB-based diagnosis mode is cost-effective in both retinoblastoma diagnosis and active retinoblastoma identification. CONCLUSIONS: DLA-RB achieved high accuracy and sensitivity in identifying active retinoblastoma from the normal and stable retinoblastoma fundus. It can be used to surveil the activity of retinoblastoma during follow-up and screen high-risk offspring. Compared with referral procedures to ophthalmologic centres, DLA-RB-based screening and surveillance is cost-effective and can be incorporated within telemedicine programs. CLINICAL TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov (NCT05308043).

Targeting non-muscle myosin II inhibits proliferative vitreoretinopathy through regulating epithelial-mesenchymal transition.

Proliferative vitreoretinopathy (PVR) is a common complication of rhegmatogenous retinal detachment, eventually leading to vision loss. To date, there are no effective drugs for the treatment of this disease. In this study, we investigated the effect of blebbistatin, a non-muscle myosin II inhibitor, on the ARPE-19 cell line and in a rabbit model of proliferative vitreoretinopathy. In vitro, we found that blebbistatin inhibited the epithelial-mesenchymal transition of retinal pigment epithelial (RPE) cells and inhibited the ability of RPE cells to migrate, proliferate, generate extracellular matrix, and affect contractility. In vivo the PVR model showed that blebbistatin significantly delayed PVR progression. It also partially prevents the loss of retinal function caused by PVR. Our results suggest that blebbistatin is a potential drug with clinical applications for the treatment of PVR.

Prognostic Value of the Radiomics-Based Model in the Disease-Free Survival of Pretreatment Uveal Melanoma: An Initial Result.

OBJECTIVE: The aim of this study was to develop a pretreatment magnetic resonance imaging (MRI)-based radiomics model for disease-free survival (DFS) prediction in patients with uveal melanoma (UM). METHODS: We randomly assigned 85 patients with UM into 2 cohorts: training (n = 60) and validation (n = 25). The radiomics model was built from significant features that were selected from the training cohort by applying a least absolute shrinkage and selection operator to pretreatment MRI scans. Least absolute shrinkage and selection operator regression and the Cox proportional hazard model were used to construct a radiomics score (rad-score). Patients were divided into a low- or a high-risk group based on the median of the rad-score. The Kaplan-Meier analysis was used to evaluate the association between the rad-score and DFS. A nomogram incorporating the rad-score and MRI features was plotted to individually estimate DFS. The model's discrimination power was assessed using the concordance index. RESULTS: The radiomics model with 15 optimal radiomics features based on MRI performed well in stratifying patients into the high- or a low-risk group of DFS in both the training and validation cohorts (log-rank test, P = 0.009 and P = 0.02, respectively). Age, basal diameter, and height were selected as significant clinical and MRI features. The nomogram showed good predictive performance with concordance indices of 0.741 (95% confidence interval, 0.637-0.845) and 0.912 (95% confidence interval, 0.847-0.977) in the training and validation cohorts, respectively. Calibration curves demonstrated good agreement. CONCLUSION: The developed clinical-radiomics model may be a powerful predictor of the DFS of patients with UM, thereby providing evidence for preoperative risk stratification.

Optoelectronic bio-synaptic plasticity on neotype kesterite memristor with switching ratio >104.

Optoelectronic memristors hold the most potential for realizing next-generation neuromorphic computation; however, memristive devices that can integrate excellent resistive switching and both electrical-/light-induced bio-synaptic behaviors are still challenging to develop. In this study, an artificial optoelectronic synapse is proposed and realized using a kesterite-based memristor with Cu2ZnSn(S,Se)4 (CZTSSe) as the switching material and Mo/Ag as the back/top electrode. Benefiting from unique electrical features and a bi-layered structure of CZTSSe, the memristor exhibits highly stable nonvolatile resistive switching with excellent spatial uniformity, concentrated Set/Reset voltage distribution (variation <0.08/0.02 V), high On/Off ratio (>104), and long retention time (>104 s). A possible mechanism of the switching behavior in such a device is proposed. Furthermore, these memristors successfully achieve essential bio-synaptic functions under both electrical and various visible light (470-655 nm) stimulations, including electrical-induced excitatory postsynaptic current, paired pulse facilitation, long-term potentiation, long-term depression, spike-timing-dependent plasticity, as well as light-stimulated short-/long-term plasticity and learning-forgetting-relearning process. As such, the proposed neotype kesterite-based memristor demonstrates significant potential in facilitating artificial optoelectronic synapses and enabling neuromorphic computation.

Neotype kuramite optoelectronic memristor for bio-synaptic plasticity simulations.

Memristive devices with both electrically and optically induced synaptic dynamic behaviors will be crucial to the accomplishment of brain-inspired neuromorphic computing systems, in which the resistive materials and device architectures are two of the most important cornerstones, but still under challenge. Herein, kuramite Cu3SnS4 is newly introduced into poly-methacrylate as the switching medium to construct memristive devices, and the expected high-performance bio-mimicry of diverse optoelectronic synaptic plasticity is demonstrated. In addition to the excellent basic performances, such as stable bipolar resistive switching with On/Off ratio of ∼486, Set/Reset voltage of ∼-0.88/+0.96 V, and good retention feature of up to 104 s, the new designs of memristors possess not only the multi-level controllable resistive-switching memory property but also the capability of mimicking optoelectronic synaptic plasticity, including electrically and visible/near-infrared light-induced excitatory postsynaptic currents, short-/long-term memory, spike-timing-dependent plasticity, long-term plasticity/depression, short-term plasticity, paired-pulse facilitation, and "learning-forgetting-learning" behavior as well. Predictably, as a new class of switching medium material, such proposed kuramite-based artificial optoelectronic synaptic device has great potential to be applied to construct neuromorphic architectures in simulating human brain functions.

The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis.

BACKGROUND: Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. METHODS: Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins' expression and localization was detected by western blot and immunofluorescence. RESULTS: NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes' transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. CONCLUSIONS: Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs' function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation.

Development and validation of medical record-based logistic regression and machine learning models to diagnose diabetic retinopathy.

PURPOSES: Many factors were reported to be associated with diabetic retinopathy (DR); however, their contributions remained unclear. We aimed to evaluate the prognostic and diagnostic accuracy of logistic regression and three machine learning models based on various medical records. METHODS: This was a cross-sectional study. We investigated the prevalence and associations of DR among 757 participants aged 40 years or older in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). We trained the models to predict if the participants had DR with 15 predictor variables. Area under the receiver operating characteristic (AUROC) and mean squared error (MSE) of each algorithm were compared in the external validation dataset using a replicate cohort from NHANES 2007-2008. RESULTS: Among the 757 participants, 53 (7.00%) subjects had DR, the mean (standard deviation, SD) age was 57.7 (13.04), and 78.0% were male (n = 42). Logistic regression revealed that female gender (OR = 4.130, 95% CI: 1.820-9.380; P < 0.05), HbA1c (OR = 1.665, 95% CI: 1.197-2.317; P < 0.05), serum creatine level (OR = 2.952, 95% CI: 1.274-6.851; P < 0.05), and eGFR level (OR = 1.009, 95% CI: 1.000-1.014, P < 0.05) increased the risk of DR. The average performance obtained from internal validation was similar in all models (AUROC ≥ 0.945), and k-nearest neighbors (KNN) had the highest value with an AUROC of 0.984. In external validation, they remained robust or with modest reductions in discrimination with AUROC still ≥ 0.902, and KNN also performed the best with an AUROC of 0.982. Both logistic regression and machine learning models had good performance in the clinical diagnosis of DR. CONCLUSIONS: This study highlights the utility of comparing traditional logistic regression to machine learning models. We found that logistic regression performed as well as optimized machine learning methods when classifying DR patients.

Prevalence and associated health and lifestyle factors of myopic maculopathy in northern China: the Kailuan eye study.

BACKGROUND: To evaluate the prevalence and associated health and lifestyle factors of myopic maculopathy (MM) in a northern Chinese industrial city. METHODS: The cross-sectional Kailuan Eye Study included subjects who participated in the longitudinal Kailuan Study in 2016. Ophthalmologic and general examinations were performed on all the participants. MM was graded based on fundus photographs using the International Photographic Classification and Grading System. The prevalence of MM was evaluated. Univariate and multiple logistic regression were adopted to evaluated risk factors of MM. RESULTS: The study included 8330 participants with gradable fundus photographs for MM and ocular biometry data. The prevalence of MM was 1.11% (93/8330; 95% confidence interval [CI] 0.89-1.33%). Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, and plus lesions were observed in 72 (0.9%), 15 (0.2%), 6 (0.007%), and 32 eyes (0.4%), respectively. MM was more common in eyes with longer axial length (OR 4.517; 95%CI 3.273 to 6.235) and in participants with hypertension (OR 3.460; 95%CI 1.152 to 10.391), and older age (OR 1.084; 95%CI 1.036 to 1.134). CONCLUSIONS: The MM was present in 1.11% of the northern Chinese individuals 21 years or older and the associate factors include longer axial length, older age, and hypertension.

Clinical Analysis of Primary Malignant Lacrimal Sac Tumors: A Case Series Study With a Comparison to the Previously Published Literature.

PURPOSE: To report management of a series of patients with primary malignant lacrimal sac tumors and to compare these results to the previously published literature. MATERIALS AND METHODS: A total of 27 patients with pathologically confirmed primary malignant lacrimal sac lesions were enrolled into this study. Pathological classifications, clinical characteristics, various treatment modalities and follow-up time, including tumor recurrence, were documented. The outcome measures included overall survival, progression-free survival, and median survival time. RESULTS: Among 27 eligible cases, 33.33% (9/27) of the tumor was non-Hodgkin B-cell lymphoma, and 33.33% (9/27) was squamous cell carcinoma; both were the most common tumor in this series, followed by adenocarcinoma 18.52% (5/27), then melanoma 7.41% (2/27). Treatment modalities included surgery, radiotherapy, and/or chemotherapy, the overall survival rate of 27 patients was 70.37%, with a median follow-up of 45 months (range: 7 mo-16 y), 8 patients had died from metastatic disease, but 13 patients remained without evidence of recurrent tumor. The 5-year overall survival and progression-free survival for all cases were 73.33% and 66.67%, respectively. The median survival time for 5 deceased patients with interstitial brachytherapy was 98 months, and 5-year survival rate was 60%. CONCLUSIONS: In this series, among primary malignant lacrimal sac tumors, the proportion of lymphoma had increased when compared with the previously published literature, and multidisciplinary therapy may lead to a good prognosis in the majority of patients with the tumors and patients may benefit more from interstitial brachytherapy than external beam radiotherapy.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

ALS-linked cytoplasmic FUS assemblies are compositionally different from physiological stress granules and sequester hnRNPA3, a novel modifier of FUS toxicity.

Formation of cytoplasmic RNA-protein structures called stress granules (SGs) is a highly conserved cellular response to stress. Abnormal metabolism of SGs may contribute to the pathogenesis of (neuro)degenerative diseases such as amyotrophic lateral sclerosis (ALS). Many SG proteins are affected by mutations causative of these conditions, including fused in sarcoma (FUS). Mutant FUS variants have high affinity to SGs and also spontaneously form de novo cytoplasmic RNA granules. Mutant FUS-containing assemblies (mFAs), often called "pathological SGs", are proposed to play a role in ALS-FUS pathogenesis. However, structural differences between mFAs and physiological SGs remain largely unknown therefore it is unclear whether mFAs can functionally substitute for SGs and how they affect cellular stress responses. Here we used affinity purification to isolate mFAs and physiological SGs and compare their protein composition. We found that proteins within mFAs form significantly more physical interactions than those in SGs however mFAs fail to recruit many factors involved in signal transduction. Furthermore, we found that proteasome subunits and certain nucleocytoplasmic transport factors are depleted from mFAs, whereas translation elongation, mRNA surveillance and splicing factors as well as mitochondrial proteins are enriched in mFAs, as compared to SGs. Validation experiments for a mFA-specific protein, hnRNPA3, confirmed its RNA-dependent interaction with FUS and its sequestration into FUS inclusions in cultured cells and in a FUS transgenic mouse model. Silencing of the Drosophila hnRNPA3 ortholog was deleterious and potentiated human FUS toxicity in the retina of transgenic flies. In conclusion, we show that SG-like structures formed by mutant FUS are structurally distinct from SGs, prone to persistence, likely cannot functionally replace SGs, and affect a spectrum of cellular pathways in stressed cells. Results of our study support a pathogenic role for cytoplasmic FUS assemblies in ALS-FUS.

Whole-exome sequencing identified genes known to be responsible for retinitis pigmentosa in 28 Chinese families.

Purpose: Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship. Method: In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations. Result: Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: USH2A, CYP4V2, PRPF31, RHO, RP1, CNGA1, CNGB1, EYS, PRPF3, RP2, RPGR, and TOPORS. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). USH2A (4/20, 20%) and CYP4V2 (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in USH2A1, USH2A2, PRPF31, RP2, TOPORS, CNGB1, and RPGR. Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in CYP4V2. Conclusion: Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. USH2A and CYP4V2 were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.