Traditional clinical medical internship models often lack structured educational objectives and comprehensive assessments, limiting holistic competency development. This study evaluates the effectiveness of a novel internship education management model integrating Bloom's Taxonomy with a student-mentor rotation system to enhance cognitive, affective, and psychomotor skills. We conducted a randomized controlled trial with 54 optometry interns during their ophthalmology clinical rotation, assigning them to either an experimental group (n = 30) using the Bloom's Taxonomy-integrated rotation model or a control group (n = 24) receiving traditional training. Both groups completed 12-week rotations with identical duration and content. The Bloom's Taxonomy-integrated rotation model was organized into three progressive phases corresponding to ascending levels of Bloom's Taxonomy (knowledge acquisition → clinical application → synthesis). Outcomes were assessed through written examinations, practical skill test, and course experience questionnaires. The Bloom's Taxonomy-integrated rotation group showed superior performance in case analysis, history taking and practical skills. They also reported significantly higher satisfaction in problem-solving, motivation and feedback quality. In conclusion, the Bloom's Taxonomy-integrated rotation model demonstrated superior clinical reasoning, practical skills, and medical interns' satisfaction, among optometry interns compared to traditional training. The Bloom's Taxonomy-integrated rotation model represents an effective, structured framework for enhancing medical internship training, though warranting further validation in broader settings.
Virtual reality (VR) simulation has transformative potential in medical education by allowing risk-free practice of clinical procedures in anatomically accurate, immersive environments. This study aimed to evaluate the effectiveness of a virtual reality simulation teaching model for cataract surgery in undergraduate medical education, compared to traditional teaching methods. A prospective study was conducted with 71 undergraduate students majoring in ophthalmology and optometry at Nanjing Medical University, divided into an experimental group (n = 35) and a control group (n = 36). The experimental group received practical training using a VR simulation model, while the control group received traditional offline practical training. Teaching effectiveness was assessed in three modules-clinical reasoning competency, clinical diagnostic proficiency, and surgical technical skills-through dual-mode assessments based on both the VR simulation platform and traditional methods. Results showed that the experimental group scored significantly higher in both traditional and VR assessments (P < 0.05). In the traditional assessment, the experimental group scored higher in Total Score (82.22 ± 4.34 vs. 76.83 ± 5.14), Clinical Reasoning Competency (12.61 ± 0.81 vs. 12.01 ± 0.81), Clinical Diagnostic Proficiency (48.98 ± 3.33 vs. 46.03 ± 3.96), and Surgical Technical Skills (20.64 ± 0.79 vs. 18.79 ± 1.67). This advantage was even more pronounced in the VR assessment, with the experimental group showing substantial superiority in Total Score (84.06 ± 4.85 vs. 71.06 ± 6.84), Clinical Reasoning Competency (10.57 ± 2.19 vs. 9.08 ± 2.06), Clinical Diagnostic Proficiency (52.17 ± 2.83 vs. 43.36 ± 4.01), and Surgical Technical Skills (21.31 ± 2.19 vs. 18.61 ± 2.93). The virtual reality simulation teaching model significantly enhanced medical students' clinical thinking, clinical diagnosis, and surgical operation skills, outperforming traditional teaching methods.
This study aimed to determine the region-specific distribution of nonaxonal cells and capillaries within the circumpapillary retinal nerve fiber layer (RNFL) in a nonhuman primate experimental glaucoma model. Five rhesus macaques (age range: 4.5-9.0 years) with varying degrees of unilateral laser-induced experimental glaucoma were imaged with optical coherence tomography (OCT), euthanized and perfusion fixed for histological analysis. Eyes were enucleated, and six circumpapillary regions (60° apart), approximately 300-1000 µm from the optic disc margin, were dissected and prepared for serial block face scanning electron microscopy. A series of 400 images (0.098 µm/pixel) were obtained at 500 nm intervals to construct a volume of 200 × 200 × 200 µm. Inside the nerve fiber layer, nonaxonal nuclei and capillary lumen were manually outlined. The nearest vessel distance for each nonaxonal cell was determined as the Euclidean distance in 3-dimensional space from each nucleus center to the nearest capillary. At endpoint, OCT circumpapillary RNFL thickness in the experimental eyes ranged between 49 and 99 µm (control: 103-111 µm). In control eyes, the distribution of nonaxonal cells at the six circumpapillary regions was nonuniform (F5,24 = 4.05 and p < 0.01). However, the total cell count was similar between the two eyes (control: 858 ± 173, experimental: 960 ± 245, and p = 0.51), and for each region (p > 0.05). Although capillary volume was reduced in experimental eyes (p = 0.02), the capillary volume density was similar between control (0.58 ± 0.31%) and experimental eyes (0.58 ± 0.32% and p = 0.99). Correspondingly, the nonaxonal cells had a shorter vessel distance in experimental compared to control eyes (15.92 ± 4.89 μm, 18.61 ± 5.48 μm, and p = 0.05). The number of nonaxonal cells and capillary volume density in the circumpapillary RNFL are similar for stable glaucomatous eyes compared to the healthy eyes. Regional differences and changes in nonaxonal contribution to the nerve fiber layer thickness should be considered when assessing clinical RNFL thickness measures.
There may be considerable untapped potential in using large-scale electronic primary care optometry referral data to understand referral patterns. This study aims to evaluate the feasibility of using different analytical methods for this type of dataset. A total of 12,339 electronic referrals made by primary care optometrists in November 2023 were examined. The dataset contained 36 demographic and clinical variables. Preprocessing involved categorising and normalising referral conditions and merging similar attributes to enhance consistency. The feasibility of descriptive evaluations of referral conditions to both ophthalmology in secondary care and within primary care was explored, and a regression analysis was conducted to investigate potential associations between patient sex and referral patterns. A spatial analysis was also conducted to map the geographic distribution of referrals and their association with social deprivation. Of all referrals, 77.3% were directed to ophthalmology in secondary care, 14.1% within primary eyecare optometry and non-optometric services, with the remaining 8.5% being unspecified. Cataracts (17.2%), glaucoma (13.5%) and YAG laser capsulotomy (12.1%) emerged as the most frequent referral reasons. Regression analysis identified significant sex differences, where referral proportions for female patients were higher than males for conditions such as glaucoma and neuro-ophthalmology (p = 0.001). Spatial analysis revealed no significant difference between the referral ratio and the deprivation level. This study demonstrated viability for evaluating electronic optometry referrals. Despite data limitations, these findings indicate that data quality and scope can support established analytical methods. Moreover, the scale of data variables suggests expanding sample sizes and extending time windows could reveal clinically informative patterns in referrals. Future investigations may further validate findings, helping to understand local, regional or national referral patterns within optometry and potentially address inequalities in eyecare.
Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among older adults. Thyroid hormones (THs) are essential endocrine regulators of development and metabolic homeostasis, and increasing evidence suggests that TH signaling is involved in retinal physiology and AMD pathogenesis. Experimental studies have demonstrated that excessive TH signaling exacerbates oxidative stress, mitochondrial dysfunction, and apoptosis in retinal pigment epithelium (RPE) cells and photoreceptors, whereas inhibition of TH signaling confers retinal protection in animal models of dry AMD. Genetic evidence from Mendelian randomization analyses further indicates that genetically predicted higher free thyroxine (FT4), per one standard deviation increase, is associated with an increased risk of AMD (OR 1.19, 95% CI 1.06-1.33), while no causal association has been established for thyroid-stimulating hormone (TSH). Consistently, large population-based cohort studies, including the Rotterdam Study, have reported a positive association between circulating FT4 levels and the incidence of AMD. In this narrative review, we summarize and critically evaluate recent advances from basic experimental, genetic, and clinical studies on the relationship between thyroid hormones and AMD, discuss potential biological mechanisms underlying this association, and highlight current limitations and future research directions.
To evaluate the application effect of the video-based feedback teaching method in the practical teaching of orthokeratology lens fitting. Twenty-three optometry interns were assigned via stratified randomization to an experimental group (video-based feedback, n = 12) and a control group (traditional verbal feedback, n = 11). Both groups received identical theoretical lectures led by the same instructor. The experimental group’s practice sessions were video recorded with structured feedback provided. Assessments included theoretical examinations, practical skill assessments and questionnaires. Independent sample t-tests and Mann–Whitney U tests were used to compare theoretical examination scores, practical skill assessments, and questionnaire results between the two groups to evaluate the teaching effectiveness. Theoretical examinations tested cognitive understanding of orthokeratology principles. Practical skills were evaluated using standardized assessments focusing on fluorescence evaluation techniques. Students completed questionnaires assessing course experience and metacognitive awareness. Theoretical knowledge scores showed no significant difference between groups (P = 0.060); however, the experimental group achieved a significantly higher pass rate (100.0% vs. 45.5%, Fisher’s exact test, P = 0.004). The experimental group achieved significantly higher practical skills scores (90.33 ± 6.29 vs. 81.91 ± 7.94; P = 0.010), particularly in static fluorescence evaluation (median 32, IQR: 29.5–36 vs. median 30, IQR: 21–32; P = 0.027) and dynamic fluorescence evaluation (median 14, IQR: 12–14 vs. median 10, IQR: 7–12; P = 0.004). The experimental group also demonstrated significantly higher satisfaction in self-awareness of performance (P = 0.048), perceived course helpfulness (P = 0.014), detail of practical demonstration (P = 0.008), and timeliness of instructor guidance (P = 0.019). This pilot study provides preliminary evidence that video-based feedback effectively enhances orthokeratology fitting skills and promotes reflective learning, offering a practical approach for clinical skills education in optometry. Future studies with larger sample sizes and long-term follow-up are warranted.
Optimizing brain health is increasingly recommended for patients with multiple sclerosis (MS). We investigated associations between modifiable lifestyle and metabolic factors with physical and cognitive performance in 101 MS patients. In this prospective, cross-sectional, exploratory study, we assessed smoking, alcohol consumption, body mass index (BMI), lipid profiles (high-density lipoprotein, HDL; low-density lipoprotein, LDL; triglycerides), and vitamin levels (vitamin D, vitamin B12, and folic acid). Associations with upper limb function (Nine-Hole Peg Test, 9HPT), lower limb function (10-meter walking test; balance board), cognitive performance (Symbol Digit Modalities Test, SDMT), and employment (weekly working hours) were examined. Many patients showed potential for metabolic improvement, with abnormal levels observed in LDL (57%), triglycerides (27%), vitamin D (14%), vitamin B12 (7%), and folic acid (19%). Elevated BMI was found in 41% and 24% reported smoking. Pack-years were negatively associated with performance in the 10-meter walking test (r=-0.59, 95% CI: -0.81 to -0.23, p=0.003), and a higher BMI was linked to poorer balance (r=0.21, 95% CI: 0.01-0.4, p=0.042), while higher HDL levels correlated with preserved upper limb function (r=-0.21, 95% CI: -0.39 to -0.01, p=0.04). No consistent correlations were observed regarding vitamins. Performance in the SDMT and the 10-meter walking test were associated with unemployment. Many MS patients exhibit dyslipidemia and obesity, highlighting the need for targeted interventions to enhance neurological resilience. Our cross-sectional analysis indicates that smoking, low HDL, and higher BMI may have adverse clinical effects in MS.
Unilateral pectineal suspension (UPS) is a novel method for mesh-free apical prolapse correction. Short-term follow-up results 6 months after isolated UPS have been very encouraging, resulting in excellent apex stability and high patient satisfaction in a cohort of 47 patients with mostly advanced prolapse. In order to assess the long-term outcome after isolated UPS, all 47 patients from the original patient cohort treated with isolated UPS were invited for a scheduled follow-up examination after a minimum follow-up period of two years to determine whether the result of the primary surgery remained stable. We analyzed the outcome with regard to apex stability, residual defects, and procedure-related morbidity. UPS as a stand-alone procedure showed high stability at the apex. Throughout the two-year follow-up period, only two patients (4.3%) required secondary surgery for apical recurrence. Increasing age correlated significantly with apical recurrence. Six patients became symptomatic in the anterior and/or the posterior compartment while the apex remained stable (13.0%). With increasing age, the probability of secondary surgery also appeared to rise, however, this was not statistically significant. There was no method-related morbidity. UPS is a valuable concept for mesh-free apical prolapse correction. Two-year follow-up after isolated UPS shows stable results at the apex. A combined approach may be valuable to reduce the potential necessity of secondary surgery in the anterior / posterior compartment.
Background/Objectives: Hyperspectral imaging (HSI) facilitates noninvasive assessment of tissue perfusion in patients with peripheral arterial disease. However, available studies are either based on small cohorts and provide no comparison to standard methods or only one-time measurements. Methods: In this prospective cohort study, assessment of tissue perfusion with transcutaneous oxygen pressure (TcPO2) measurement and HSI before (1 day) and after revascularization (1-3 days) in patients with Rutherford category 3-6 was performed. The primary endpoint was change in tissue perfusion evaluated with the different methods. HSI and TcPO2 were correlated with clinical improvement after revascularization. Results: Significant improvement in the perfusion was detected by tissue oxygenation in the microcirculation (StO2; improvement +12%, mean difference 5 ± 15.9, p < 0.001) and near-infrared spectroscopy (NIR; improvement +9%, mean difference 3.7 ± 7.1, p < 0.001), but not with the tissue hemoglobin index (THI; mean difference +0.8 ± 10.3, p = 0.428). A high number of worse or unchanged HSI measurements despite successful revascularization was detected. A significant improvement of TcPO2 after revascularization (mean difference +16.2 ± 27.7 mmHg, p < 0.001), consistent with clinical improvement, was detected. No correlation of the HSI parameters with TcPO2 or clinical symptoms could be seen. Conclusions: Significant improvement of StO2, NIR and TcPO2 values was detected after successful revascularization; however, no correlation of HSI parameters with TcPO2 or clinical results could be observed. Furthermore, the substantial rate of lower or unchanged HSI parameters despite clinical improvement and higher TcPO2 values calls the validity and clinical relevance of TIVITA®-based HSI measurements for postoperative tissue perfusion improvement into question.
To investigate the safety, tolerability, and signals of effect of MyopiaX, a smartphone app that selectively delivers blue light to the optic nerve head to control myopia progression in children and adolescents. Multicenter, randomized, active-controlled, examiner-masked proof-of-concept clinical trial (ClinicalTrials.gov identifier NCT04967287). Eligible children aged 6 to 12 years, with myopia of cycloplegic spherical equivalent refraction (SER) between -0.75 and -5.00 diopters (D) at baseline. Children were screened and enrolled between November 2021 and September 2023. Children were randomly assigned in a 2:1 ratio to MyopiaX or active control. Participants were instructed to use MyopiaX for 10 minutes twice daily for the first 6 months and, during the second 6 months of the trial, also wear defocus incorporated multiple segments (DIMS) myopia control spectacles. The active control group wore DIMS spectacles for the entire 12-month trial. The primary outcome was change in axial length (AL) and change in SER at month 6. Clinical safety examinations and the frequency and severity of device-related adverse events (AEs) were analyzed for all participants who began treatment. Of the 124 randomized participants, 101 were enrolled under the 12-month active-control study design (MyopiaX: n = 66, DIMS: n = 35). After 6 months, the mean AL change from baseline in the MyopiaX (n = 50) and DIMS (n = 34) groups, respectively, was 0.14 ± 0.11 mm and 0.08 ± 0.09 mm. The 6-month change in SER was -0.18 ± 0.39 D in the MyopiaX group and -0.16 ± 0.41 D in DIMS participants. Among the 73 participants who used MyopiaX, including those randomized under the original study design (prior to introduction of an active control), there were 23 related AEs among the 16 participants (22%), including transient ocular discomfort and headache, all of which resolved without any need for treatment. MyopiaX was safe and well tolerated over 12 months in treatment-naive children with myopia. This exploratory study provides the first clinical data on the impact of MyopiaX's selective blue light stimulation on myopia progression and ocular growth. This novel approach may offer a complementary therapeutic solution for the clinical management of progressive myopia. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
We evaluated the effect of intraocular lens (IOL) misalignment on image quality under clinically relevant conditions (0.2, 0.4 mm decentration and 2°, 4° tilt). Two presbyopia-correcting IOLs, an extended depth of focus (EDOF) (Alcon Vivity) and a diffractive multifocal (Alcon PanOptix), were tested. Through-focus modulation transfer function (MTF)-based measures were taken using an on-bench model eye with average corneal spherical aberration and apertures of 3.0 and 4.5 mm. Optical image quality and simulated visual acuity (VA) were assessed for both aligned and misaligned IOLs. The aligned EDOF lens showed superior distance vision quality compared to the multifocal, particularly with the 4.5 mm pupil. The EDOF lens was, however, more sensitive to decentration than the multifocal, which showed very low sensitivity across far, intermediate, and near regions with both apertures. Degradation with IOL tilt occurred at a slower rate than with decentration. Despite the optical degradation produced by mild misalignment (up to 0.4 mm decentration and 4° tilt), the predicted VA demonstrates that these effects should be negligible on postoperative vision with a 3 mm pupil. This holds true not only at a far distance, but also at the relevant intermediate and near foci.
Multiple sclerosis (MS) is a highly disabling chronic autoimmune disease of the central nervous system with neuroinflammatory and neurodegenerative alterations found in the white and grey matter of the brain. The pathogenesis of MS is complex and not fully understood. Mitochondrial dysfunctions are suspected to play an important role. The visual system is often affected in MS. Optic neuritis is a frequent symptom, but also the retina itself, including retinal synapses appear compromised in MS independent from demyelination of the optic nerve. A previous study demonstrated synapse-specific alterations of mitochondria in photoreceptor synapses in the Experimental Autoimmune Encephalomyelitis (EAE) mouse model of MS at day 9 after injection, an early time point in pre-clinical EAE. In the present study, we analysed even earlier stages of pre-clinical EAE for possible alterations of synaptic mitochondria. For this purpose, we performed qualitative and quantitative immunolabelling analyses of the mitochondrial cristae organising protein MIC60 at retinal synapses and functional analyses by measuring synaptic mitochondrial membrane potential (during rest and depolarisation-induced exocytosis) and visually guided behaviour (optometry analyses). At day 3 after injection, morphological and functional data were indistinguishable between MOG/CFA-injected EAE mice and CFA-injected control mice. But already on day 5 after injection, we observed a decreased expression of the mitochondrial MIC60 protein at synaptic mitochondria, a decreased synaptic mitochondrial membrane potential at rest, an enhanced drop of mitochondrial membrane potential during stimulated exocytosis and a decreased visual performance of the respective EAE mice. These data argue that synaptic pathology in the EAE retina begins as early as day 5 after injection. Our data propose that dysfunctions of mitochondria play an important role already at the very early stages of synaptic pathology in EAE.
To identify HLA associations with clinical and autoantibody-defined subgroups of idiopathic inflammatory myopathy (IIM) and predict potential immunogenic epitopes presented by subgroup-specific HLA alleles. An observational case-control study was conducted including 147 biopsy-confirmed IIM patients and 114 ethnically matched healthy controls. Patients were classified into clinical and autoantibody-defined subgroups. High-resolution HLA genotyping was performed, and allele/amino acid frequencies were compared between the groups. Epitope prediction was carried out for key HLA-associated autoantibody subgroups using in silico tools assessing antigenicity, allergenicity, toxicity and molecular docking with HLA alleles. HLA-C*07:01 was protective in IIM (Pa = 1.23 × 10-2, OR = 0.17, 95% CI 0.06-0.41). Subgroup analysis showed associations of HLA-A*33:03 with DM (Pa = 3.97 × 10-3, OR = 14.8, 95% CI 4.38-68.07) and DQB1*06:03 with PM (Pa = 2.40 × 10-2, OR = 7.24, 95% CI 2.42-22.61). The anti-Mi2 subgroup showed strong associations with A*33:03 (Pa = 2.82 × 10-3, OR = 19.73, 95% CI 5.11-98.01), DQA1*02:01 (Pa = 1.03 × 10-2, OR = 10.28, 95% CI 2.33-53.75) and DQB1*03:03 (Pa = 1.98 × 10-2, OR = 8.99, 95% CI 2.71-30.51). Anti-Ro52 was associated with B*08:01 (Pa = 2.94 × 10-3, OR = 11.67, 95% CI 3.56-39.83). Fine mapping pinpointed phenylalanine at position 25 of DQA1 to the risk allele DQA1*02:01 in anti-Mi2a/b autoantibody positive patients. From 49 predicted Mi-2 peptides, 'YYKYILTR', 'QAFSRAHR' and 'DYWEKLLR' bound stably to A*33:03 and were non-allergenic and non-toxic. In the anti-Mi2 subgroup, we identified novel HLA alleles, amino acid variants and immunogenic epitopes, supporting a role for HLA-restricted antigen presentation in disease pathogenesis and indicating candidate targets for antigen-specific immunotherapy. However, the HLA/epitope findings related to anti-Mi2 are exploratory due to limited power, and require confirmation in larger cohorts together with experimental validation.
Organotypic retinal explant cultures are a valuable experimental tool for investigating neuroretinal diseases and advancing therapeutic strategies. Ex vivo methods preserve the natural architecture and intercellular interactions of the retina while enabling precise manipulations of the microenvironment, a distinct advantage over traditional in vitro two-dimensional cell models. Compared with in vivo animal and human studies, retinal explants offer ethical and cost-effective advantages, serving as bridge models for both animal to human and preclinical to clinical studies. This review explores the application of retinal explants in retinal disease research, covering emerging technologies, specific neurodegenerative diseases, human explants, and future directions. Technologies including gene therapy, electrophysiology, live imaging, stem cell transplantation, nanoparticle delivery, optogenetics, and artificial intelligence exhibit ready integrated into explant models and rapid advancement. Although retinal explants do not replicate the full systemic context of the eye, they represent powerful localized models for efficient study of retinal physiology and pathophysiology. With these advantages, retinal explants can be used as a translational platform capable of accelerating the development and validation of retinal therapies.
Environmental biotoxins, such as mould, are linked to neurological and visual dysfunction, including impaired visual contrast sensitivity (VCS). Testing VCS alterations is recommended as a biomarker for biotoxicity. This study compared four VCS tests in detecting VCS deficits in individuals with clinical signs of biotoxicity. VCS was measured in 28 biotoxin-exposed individuals and 30 controls using four VCS tests: Shoemaker handheld chart, Online Contrast Sensitivity Test (OCSTTM), Clinic CSF App, and an Experimental VCS test. Neurotoxicity symptoms were assessed with the modified Q16 questionnaire, and pupil size was measured under standard lighting. Biotoxin-exposed participants had smaller pupil diameters (mean difference: 0.703 mm, p < 0.0001) and higher neurotoxicity scores (45.50 ± 13.0 vs. 22.00 ± 7.7). Contrast sensitivity was significantly reduced in exposed participants on digital VCS tests only. The Experimental VCS test demonstrated the highest diagnostic performance (100% sensitivity; 60-80% specificity), followed by OCSTTM and the Clinic CSF App. The Shoemaker handheld chart did not distinguish between groups. These results highlight the effectiveness of digital VCS testing and symptom questionnaires as practical tools for detecting visual and neurological impairments in individuals with suspected biotoxin exposure.
Stereoacuity, the ability to perceive depth from binocular disparity, is traditionally considered to be best at the fovea in typical human vision, and to decline with eccentricity. Previous studies have shown that when stereopsis is present in amblyopia, it is often coarse and comparable to stereoacuity associated with the peripheral retina in neurotypical controls, suggesting that it might be mediated by a non-foveal locus. Here we measured stereoacuity as a function of eccentricity in participants with amblyopia as well as controls with no history of abnormal visual development. We measured stereoacuity using random dot stereograms and targets that scaled with eccentricity, testing the fovea, and eccentricities of 2.5°, 5°, and 10° along the horizontal and vertical meridians. For 87.5% (7/8) of amblyopic participants, the locus of best stereoacuity was non-foveal. Surprisingly, 75% of control participants (15/20) also exhibited their best stereoacuity at non-foveal locations, with only 5 controls showing foveal superiority. Using stimulus parameters modified to improve foveal performance, we repeated measurements on a subset of controls whose best stereoacuity was non-foveal, but the best locus only shifted to the fovea in one participant. Stereoacuity measured at the experimentally determined "best locus" correlated well with standard clinical stereoacuity tests. These findings challenge the conventional view of universal foveal dominance for stereopsis, suggesting that the fovea is not invariably the site of best stereoscopic sensitivity, even in many normally sighted individuals. This has implications for understanding binocular vision in amblyopic and normal vision, and for interpreting clinical stereo tests.
This study evaluated the performance of four popular large-scale language models (ChatGPT o3-mini, Gemini 2.0 pro experimental, Deep Seek Thinking R1, and Kimi Thinking K1.5) in addressing frequently asked patient questions about cataracts and cataract surgery in Chinese. DeepSeek Thinking R1 performed comparably to Gemini 2.0 pro experimental in accuracy, while outperforming both ChatGPT o3-mini and Kimi Thinking K1.5. In terms of completeness and consistency, DeepSeek Thinking R1 showed superior performance over the other three LLMs. Regarding legibility and safety, DeepSeek Thinking R1, Gemini 2.0 pro experimental, and ChatGPT o3-mini exhibited comparable results, all performing better than Kimi Thinking K1.5. Deep Seek Thinking R1 demonstrated the strongest overall performance among the four LLMs in this comparative evaluation. The modern LLMs are promising tools for public education in ophthalmology while human oversight is still required.
Tubulin is a validated anticancer target, yet the clinical translation of colchicine-binding site inhibitors remains limited by toxicity and resistance. To accelerate the discovery of safer tubulin-targeting agents, we employed a machine learning (ML)-driven drug repurposing strategy integrating computational and experimental validation. Robust AutoQSAR classification models were trained on 279 curated tubulin inhibitors and used to screen 4500 US FDA-approved drugs, predicting 1800 compounds as potential tubulin inhibitors. These candidates were subjected to multistage structure-based virtual screening using Glide HTVS, SP, and XP docking, narrowing the selection from 698 (HTVS) and 350 (SP) to 38 compounds at the XP stage. Binding free-energy calculations (MM-GBSA) and 200 ns molecular dynamics simulations identified four stable colchicine-site binders: omeprazole, podofilox, sulfadoxine, and trimethoprim, exhibiting favourable binding energetics (Glide XP scores -10.06 to -8.12 kcal/mol; ΔG bind ranging from -10.06 to -8.12 kcal/mol; ΔG bind ranging from -64.16 to -38.61 kcal/mol). Biochemical tubulin polymerization assays confirmed tubulin inhibition, while cell-based cytotoxicity studies demonstrated low-micromolar antiproliferative activity of omeprazole and podofilox against melanoma (IC₅₀ = 4.32 ± 0.29 μM and 4.98 ± 0.37 μM, respectively) and colorectal cancer cells (IC₅₀ = 6.22 ± 0.22 μM and 5.76 ± 0.18 μM; n = 3). Overall, this study highlights a ML-guided drug repurposing framework that, unlike prior colchicine binding site-focused virtual screening studies, integrates large-scale ML prioritization with experimental validation to identify novel colchicine-site-targeted anticancer candidates.
The prevalence of cognitive impairment is increasing along with global aging. Early retinal structural and vascular changes, prior to the onset of clinically detectable retinal pathologies, have been increasingly associated with cognitive changes. However, the evidence related to the predictive performance of these biomarkers remains limited. Therefore, this study aimed to develop and validate a nomogram-based scoring tool for opportunistic screening of mild cognitive impairment (MCI). This study prospectively recruited participants aged 60 years or older, including those with normal cognitive function. The retinal images were scanned using optical coherence tomography and angiography. Following the selection of potential predictors, a logistic regression model was built to predict MCI. Subsequently, a dynamic nomogram was developed to facilitate risk scoring in a clinical setting. The model's discriminative ability was evaluated using the area under the receiver operating characteristic curve, along with diagnostic metrics of sensitivity and specificity at 95% confidence interval (CI). The model was internally validated using bootstrapping. Decision curve analysis was conducted to evaluate the model's clinical impact and utility. The model indicated that central macular thickness (β: -1.13; 95% CI: -0.15,-2.15; p < 0.05), outer nasal perfusion density in the macular area (β: 1.68; 95% CI: -2.92, -0.44; p = 0.008), and contrast sensitivity (β: -1.13; 95% CI: -2.03, -0.23; p < 0.05) were independently associated with MCI. This nomogram demonstrated a discriminative power of 0.90 (95% CI: 0.81, 0.98). The model also demonstrated good performance during bootstrap validation, achieving an AUC of 0.87. The optimal cutoff points achieved an accuracy of 86%, a sensitivity of 85% and a specificity of 87%. The decision curve analysis showed that the model provides a high net benefit. This study developed and internally validated a dynamic, nomogram-based scoring tool for early detection of MCI that integrates non-invasive retinal and visual biomarkers. The model demonstrated high discriminative power and substantial clinical net benefit. Further evaluation of the model's prognostic value in predicting further cognitive decline may support its clinical utility.
To investigate potential optical cues underlying myopia control effects by examining how lenslet-array spectacle lenses influence peripheral refraction and image contrast. Three commercial lenslet-array spectacle lenses-MiyoSmart, Stellest, and diverse segmented defocus optics-were reconstructed in Zemax OpticStudio, together with a conventional single vision (SV) lens as a reference. The reconstructed lenses were coupled with the Navarro eye model to simulate spectacle wearing after experimental validation of the lens models. Optical performance was evaluated under both distance and near viewing conditions with accommodative lags of 0.50 diopters (D) and 1.00 D. Peripheral refraction components (M and J0) were derived from wavefront data. Point spread functions and modulation transfer functions were obtained, with the area under the modulation transfer function curve subsequently calculated. Simulated and experimental point spread functions showed strong agreement, confirming the reliability of the constructed spectacle models. Compared with the SV lens, the lenslet-array introduced M fluctuations (within ±0.25 D), manifesting as alternating positive and negative shifts relative to the SV baseline. Only the Stellest lens exhibited minimal myopic defocus over a limited eccentricity range, while the other designs failed to induce peripheral myopic defocus. In the horizontal meridian between 12.5° and 17.5° eccentricity, lenslet-array lenses exhibited reduced contrast at low spatial frequencies (≤6 cycles/degree) but increased cutoff frequencies and relatively enhanced contrast at higher frequencies (9-15 cycles/degree). Similar patterns were observed under near viewing with a 0.50 D accommodative lag. The myopia control efficacy of lenslet-array lenses may not be fully explained by the peripheral myopic defocus hypothesis. Instead, the observed reduction in low spatial frequency contrast, coupled with an elevated cutoff frequency that preserves high-frequency information, may provide the critical optical cues for slowing myopia progression. These hypothesized mechanisms warrant further clinical investigation.