Translational Vision Science & Technology

Purpose: To develop an interpretable automated pipeline for dome-shaped macula (DSM) detection and measurement from optical coherence tomography (OCT) B-scans. Methods: We analyzed one eye from each of 300 children aged 4-18 years in the Shanghai Child and Adolescent Large-scale Eye Study High Myopia (SCALE-HM) cohort (50 DSM-positive; 100 test eyes). A U-Net pretrained on OCTA-500 and fine-tuned on the development set segmented the retinal pigment epithelium (RPE) boundary. A geometric module located the apex, fitted a tangent-line baseline, and computed perpendicular height in physical coordinates. An eye was DSM-positive if any gradable B-scan had height >= 50 um. Two masked graders evaluated the test set; a third adjudicated disagreements. Results: The area under the receiver operating characteristic curve was 0.927 (95% confidence interval [CI], 0.850-0.986), sensitivity was 82.1% (95% CI, 64.4%-92.1%), and specificity was 100% (95% CI, 94.9%-100%) against the adjudicated reference. In concordant-positive eyes, automated height agreed with manual measurements (intraclass correlation coefficient, 0.949; mean absolute error, 6.9 um; bias, -5.7 um, versus Doctor A). Mean RPE-boundary error on pediatric test scans was 1.54 um. Conclusions: The pipeline may be considered a reliable and reproducible tool for automated DSM detection and height measurement on radial OCT, with each value traceable to landmarks on the source B-scan. External validation across populations, devices, and acquisition protocols is needed. Translational Relevance: The pipeline provides an objective and reproducible method to detect DSM and quantify dome height, width, and orientation across OCT meridians. Because each measurement can be verified on the source B-scan, it enables standardized DSM assessment.

Purpose: To evaluate the associations of the numerical AI-CO center index and visually classified central dark-area extent with Humphrey 10-2 mean deviation (MD). Methods: This single-center retrospective study included 320 eyes of 169 patients with AI-CO imaging, broad-field 24-2F or 30-2 testing, and 10-2 testing. Both visual field examinations were performed within 365 days before or after AI-CO imaging. Two ophthalmologists independently classified central dark-area extent into five Levels (0-4). Analyses assessed Spearman correlations, areas under the receiver operating characteristic curve (AUCs), distributions across final central dark-area Levels, and interrater reliability. Patient-cluster bootstrap confidence intervals and a one-eye-per-patient sensitivity analysis addressed inclusion of both eyes. Results: AI-CO center correlated with 10-2 MD (rho=0.829; 95% CI, 0.773-0.873). AUCs for 10-2 MD below -2, -6, and -12 dB were 0.902, 0.939, and 0.961, respectively. The numbers of eyes in Levels 0-4 were 66, 57, 94, 53, and 50; median 10-2 MD values were -0.59, -1.48, -3.54, -6.24, and -18.15 dB, respectively. Quadratic-weighted kappa was 0.970 (95% CI, 0.958-0.981). Sensitivity analyses yielded broadly similar findings. Conclusions: The numerical AI-CO center index and visually classified central dark-area extent were associated with central visual field damage. Assessing the extent of dark regions in the central image alongside the numerical index may provide useful information for interpreting central visual field status from the AI-CO display.

Purpose: To characterize the biomechanical response of the optic nerve head (ONH) in myopic versus non-myopic individuals with normal-tension glaucoma (NTG), and to evaluate the association between ONH strains and the rate of visual field (VF) progression. Design: Retrospective clinical cohort study. Participants: A total of 118 NTG eyes from 77 patients with [&ge;] 2 years of follow-up and 5 VF tests were enrolled, including 66 eyes with myopia and 52 eyes without. Methods: Each participant underwent three-dimensional (3D) optical coherence tomography (OCT) imaging of the ONH under three mechanical loading conditions: 20{degrees} adduction, 30{degrees} abduction and acute intraocular pressure (IOP) elevation by applying a 0.80 N force to the lower eyelid. Effective strains across the global ONH complex and within specific segmented tissues (pre-lamina, lamina cribrosa, choroid, and sclera) were quantified using a validated 3D strain-mapping algorithm. Results: Myopic NTG eyes exhibited significantly higher ONH strains compared to non-myopic eyes under acute IOP elevation (10.1{+/-}2.7% vs. 9.3{+/-}1.8%, P = 0.044) and abduction (9.2{+/-}2.3% vs. 8.4{+/-}2.1%, P = 0.048). In the non-myopic group, ONH strains varied significantly across conditions (P < 0.001), with adduction (9.9{+/-}2.0%) and acute IOP elevation (9.3{+/-}1.8%) eliciting greater strains than abduction (8.4{+/-}2.1%). These condition-dependent variations were less pronounced in the myopic group (10.1{+/-}2.7% vs. 9.8{+/-}2.7% vs. 9.2{+/-}2.3%, P = 0.07). Multivariable linear mixed-effects analysis revealed that in myopic NTG, higher ONH strains induced by adduction were significantly associated with faster MD decline (estimate: -0.139 dB/year per 1% increase, P = 0.03, adjusted for age, spherical equivalent and baseline perimetric mean defect). Conversely, larger strains during acute IOP elevation were associated with slower progression (estimate: 0.184 dB/year per 1% increase, P = 0.004). Tissue-specific analysis confirmed that adduction-induced strains in the choroid and pre-lamina tissue as well as IOP-induced strains across all ONH tissues were significantly correlated with the rate of perimetric progression in myopic eyes (all P < 0.05). Conclusions: In this cohort, greater adduction-induced ONH strain was associated with faster perimetric deterioration in myopic NTG. These findings support further investigation of gaze-related optic nerve traction as a potential non-IOP-related biomechanical factor in myopic NTG. Keywords: Normal tension glaucoma, Myopia, Optic nerve head, Ocular biomechanics, Visual field Progression, adduction.

Digital photography remains the gold standard for dermatological assessment, but reliance on standardized stationary image-capture systems limits trial scalability, whereas smartphones combined with computer vision artificial intelligence (AI) could enable hybrid and decentralized clinical trials (DCTs). This study assessed the facial feature grading of an AI-based system against expert panel consensus across three settings with decreasing acquisition control: Standard Studio Imaging (SSI), Clinic Smartphone Imaging (CSI), and Home Smartphone Imaging (HSI). Expert inter-rater reliability was good to excellent (median ICC 0.84-0.90), and the system showed high operator-independent test-retest repeatability across independently captured images (median ICC 0.97-0.98). Agreement with experts was maintained across all settings for macro-geometric features (ptosis {rho} = 0.74-0.81, nasolabial fold {rho} = 0.68-0.79) and for discrete pigmentation and inflammatory lesions (pigmented spot density {rho} = 0.62-0.76), declined for fine-texture features under uncontrolled acquisition (forehead wrinkles {rho} = 0.76 to 0.48), and remained limited for color-dependent features irrespective of setting. These findings support the AI-based system as an objective grading tool for a defined subset of facial endpoints in hybrid and DCTs in dermatology.

Published artificial intelligence for keratoconus is unproven in fellow eyes that topography and tomography call normal, the eyes where surgical decisions are made, although it reports near-perfect accuracy for early disease. In a registered systematic review of 573 studies (PROSPERO CRD420261441197), none of 2,035 claim-by-stratum units from 212 adjudicated studies established discrimination in these eyes. Most units (90.0%) answered a different question, never constructed the target population or certified its normality; external validation did not test label generation, and five systematic reviews did not assess it. In a public cohort, a frozen score yielded an area under the receiver operating characteristic curve of 0.996 against a same-eye index label and 0.549 against a contralateral proxy; its inputs reconstructed the label-generating index (r = 0.991), so accuracy there measured agreement with the index. Anchor-gap evaluation measures accuracy in these eyes against the contralateral clinical diagnosis.

Purpose: To understand the functional impact of macular atrophy (MA) and fibrosis in eyes with treated neovascular age-related macular degeneration (nAMD) based on deep visual sensitivity losses. Design: Cross-sectional study. Participants: One-hundred and nine eyes from 97 individuals with nAMD that had been treated for >=12 months without significant retinal fluid. Methods: All participants underwent defect-mapping microperimetry (DMP) testing - a strategy optimized to quantify the spatial extent of deep visual sensitivity losses through single 10 decibel stimuli presentations - where 208 locations were sampled in the central 8 degrees radius region. Participants also underwent color fundus photography, fundus autofluorescence and OCT imaging, which were co-registered and manually annotated for MA and fibrosis to determine their two-dimensional pointwise extent at individual test locations, and global extent in the corresponding region where DMP was performed. Main Outcome Measures: Pointwise association between the presence of MA and fibrosis with missing a stimulus on DMP and global association between the extent of MA and fibrosis with the proportion of locations missed (PLM) on DMP. Results: At a pointwise level, the presence of MA and fibrosis were independently associated with an increased likelihood of missing a stimulus on DMP (odds ratio = 42.5 and 2.5 respectively; P < 0.001 for both). However, at a global level, only an increasing extent of MA was associated with a significantly higher PLM on DMP (P < 0.001), but not fibrosis (P <= 0.227). MA extent explained a substantial proportion of the variance in the PLM (R2 = 0.97) and there was a very strong correlation between the two parameters ({rho} = 0.93). Conclusions: This study confirmed the expected functional impact of MA and fibrosis on DMP testing at a pointwise level. However, it showed at the global level that only the extent of MA, and not fibrosis, was independently associated with functional loss on DMP, and that there was a very strong structure-function correlation based on MA. These findings thus suggest that evaluating MA alone may be sufficient for capturing structural changes strongly associated with the global extent of deep visual sensitivity losses in those with treated nAMD.

Purpose: To compare continuous wavelet transform (CWT) and short-time Fourier transform (STFT) analyses of the oscillatory potentials (OPs) of the dark-adapted full-field electroretinogram (FFERG). Methods: FFERG recordings from Royal College of Surgeons (RCS) and healthy Brown Norway (BN) rats, wild-type and Atoh7 enhancer-knockout (KO) mice, and patients with diabetic retinopathy and healthy controls were analyzed with STFT and with CWT employing the real Morlet wavelet, after 60 Hz high-pass and sharp 60 Hz notch filtering. Time- and frequency-localized OP features were quantified and the methods compared on detection of transient OP signals. Both were additionally validated using synthetic OP-like bursts of known frequency embedded in each cohort's recorded noise. Results: CWT revealed distinct time-frequency patterns and disease-specific OP alterations across all rat, mouse, and human cohorts, with improved temporal localization and frequency resolution, whereas STFT merged transient features and was more susceptible to noise. CWT-derived dominant-frequency differences reached significance in all three models; the corresponding STFT difference reached significance only in rats (separate tests; methods not directly compared). In synthetic bursts, both methods recovered injected frequencies to within 1-2.5 Hz, but only CWT resolved two bursts separated by 15 ms. Conclusions: CWT employing the real Morlet wavelet provides a robust, physiologically relevant evaluation of OPs, with improved temporal localization and reduced spectral dispersion relative to STFT in clinical and experimental settings. Translational Relevance: CWT analysis may improve the characterization of inner retinal dysfunction by preserving transient OP time-frequency structure, as illustrated in preclinical rodent models and diabetic retinopathy patients.

Abstract Purpose To apply a mathematical model integrating vascular permeability, lesion transmural pressure, choroidal excess pressure, and wall stability to incomplete fluid response and massive submacular hemorrhage in neovascular age-related macular degeneration. Methods Permeability was calculated from aqueous vascular endothelial growth factor (VEGF). Windkessel gave usual lesion pressure from choriocapillaris pressure and high inflow from an arterial-level puncture pressure used as a working value. Choroidal excess pressure was calculated from choroidal thickness and a pachy index as increased outflow resistance. Exudative change used a revised Starling equation scaled to early central-retinal-thickness reduction, with 40-m threshold. A relative rupture-hazard index was calculated from Laplace wall stress and wall stability. VEGF, pressures, and that reduction were from the literature. Pressure was isolated from permeability and choroidal excess. Results In the model, raising lesion pressure from choroidal-excess lesion pressure to high inflow increased untreated exudative change from 150 to 760 m. Residual under saturation was 64 m as a lower-end reference (Monte Carlo 69 - 286 m; median, 170) and 90 m with high-hazard choroidal excess; both above 40 m. Reducing choroidal thickness in the thickened choroidal-excess state added 13 - 14 m, smaller than that residual. Lowering lesion pressure from high inflow to usual lesion pressure (21 to 10 mmHg) reduced the index to 0.64 of the high-hazard reference, and to 0.34 with wall stabilization. Conclusion Lesion transmural pressure due to high inflow left residual exudation even after permeability suppression with anti-VEGF. Fluid resolution on optical coherence tomography may not parallel a reduction in the rupture-hazard index, depending on wall stability.

Purpose To evaluate the safety, tolerability, and preliminary bioactivity of a single suprachoroidal injection of AXT107 (Gersizangitide), a multimodal integrin-disrupting peptide that acts on both the VEGFA pathway and angiopoietin-Tie2 pathway, in eyes with neovascular age-related macular degeneration (nAMD). Design Phase 1/2a, open-label, dose-escalation clinical trial. Participants Fifteen subjects with active nAMD, including 11 treatment-experienced partial responders to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and 4 treatment-naive subjects; 14 eyes met the protocol-specified baseline imaging criterion and were included in efficacy analyses. Methods Study eyes received a single suprachoroidal injection of AXT107 microparticles at doses of 0.125, 0.25, or 0.5 mg and were followed for 40 weeks. Protocol-specified rescue intravitreal anti-VEGF treatment was permitted from week 12 based on protocol-specified best-corrected visual acuity (BCVA) or central subfield thickness (CST) criteria; anti-VEGF treatment before Week 12 was investigator-initiated. Primary outcomes were ocular and systemic safety through week 40; secondary outcomes included change in CST, change in BCVA, and time to first protocol-specified rescue injection. Main Outcome Measures Incidence of ocular and systemic adverse events, intraocular pressure (IOP), CST, BCVA, and time to first protocol-specified rescue injection. Results Twenty subjects were screened and 15 enrolled across 4 U.S. sites; 3 eyes received 0.125 mg, 3 received 0.25 mg, and 9 received 0.5 mg of AXT107. No serious adverse events related to AXT107 occurred, and no cases of endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or clinically significant intraocular inflammation were observed through week 40. No clinically meaningful intraocular pressure (IOP) elevations occurred at any dose, and no subject required chronic IOP-lowering therapy. Among the 14 eligible eyes included in efficacy analyses, 2 eyes (01-04 and 01-05) completed 40 weeks without protocol-specified anti-VEGF rescue, and 1 eye (02-04) first received protocol-specified rescue at week 36. At the last on-treatment visit, BCVA changes ranged from +15 to -31 ETDRS letters; 3 eyes gained[&ge;]5 letters, 3 gained[&ge;]10 letters, and 1 gained[&ge;]15 letters. Among the 14 eligible eyes, anatomical improvements in CST were observed in at least 1 eye in each dose cohort. The most durable responses were seen in treatment-experienced eyes receiving 0.5 mg (median durability of 36 weeks), whereas treatment-naive 0.5-mg eyes showed more variable courses and generally earlier protocol-specified rescue in this small cohort. Conclusions In this first-in-human study, a single suprachoroidal injection of AXT107 up to 0.5 mg was well tolerated through Week 40, with no drug-related serious adverse events, no clinically significant intraocular inflammation, and no sustained IOP elevations. After a single suprachoroidal AXT107 injection, 2 eyes completed 40 weeks without protocol-specified rescue anti-VEGF treatment, and 1 additional eye received its first protocol-specified rescue treatment at Week 36. The exploratory observation that durability appeared greatest in treatment-experienced eyes supports further controlled study of AXT107, particularly in treatment-experienced nAMD populations.

Abstract Purpose: To use a minimally invasive lid treatment (MILT) utilizing Compressive Skin Contouring (CoCo) technology to compare patient- and surgeon-reported ecchymosis, edema, and incision appearance following MILT and traditional upper eyelid blepharoplasty (tBULB). Methods: Prospective, single-surgeon intra-patient study comparing MILT and tBULB in patients seen for bilateral blepharoplasty. Patients and the operating surgeon rated MILT and tBULB outcomes post-operatively on the day of surgery (T1) and at 2 months (T2) using surveys. Patient photographs taken 3 and 9 days post-operatively were blindly assessed by 3 independent surgeons to compare ecchymosis, edema, and incision appearance on the MILT and tBULB sides. Results: Seven patients participated in the study. At T1, 6/7 patients reported [&le;] ecchymosis and edema, and all patients reported better or equivalent incision appearance on the MILT side compared to the tBULB side. At T2, 6/7 of patients reported [&le;] edema; 4/7 reported < ecchymosis and better incision appearance on the MILT side. The surgeon reported < ecchymosis and [&le;] edema for 7/7 patients and better or equivalent incision appearance for 6/7 patients at T1; [&le;] ecchymosis and better or equivalent incision appearance for 7/7 and [&le;] edema for 6/7 patients at T2 on the MILT side. In the blinded evaluation, mean ecchymosis scores were lower, edema scores were lower or equivalent, and incision appearance was better for MILT vs. tBULB at days 3 and 9. Conclusions: In this intra-patient study, MILT outcomes compared favorably with tBULB, especially for ecchymosis and edema; two important aesthetic measures of patient perception.

Purpose: Electrical stimulation of the occipital cortex evokes visual percepts known as phosphenes. To date, most human studies have examined phosphenes elicited by large surface or depth electrodes. These differ considerably from the small penetrating intracortical microelectrodes capable of stimulating highly localized cortical populations that are the basis of current next-generation devices. Here, we provide a detailed characterization of phosphenes evoked by such intracortical microelectrodes. Methods: As part of the CORTIVIS clinical trial, a Utah Electrode Array with 100 penetrating electrodes was implanted in the early visual cortex of four blind volunteers. Participants completed drawing and description tasks in response to single-electrode stimulation. Two participants also performed forced-choice tasks to determine whether phosphenes elicited by different electrodes could be reliably discriminated. Results: Single-electrode stimulation reliably evoked phosphenes in all participants. Most percepts appeared in the contralateral visual field, although two participants reported near-midline ipsilateral percepts. Phosphenes ranged from simple dots to elongated, textured, circular, or otherwise idiosyncratic forms. One participant reported distinguishable phosphene colors, which depended on electrode and amplitude structure and varied across sessions. The two participants tested on forced-choice discrimination could successfully identify electrode-specific phosphenes across multiple sessions. Conclusions: Intracortical microstimulation of the human visual cortex produces phosphenes with diverse, electrode-specific appearances that are recognizable across repeated trials. These findings indicate that penetrating microelectrodes often evoke more structured percepts than simple points or blobs, providing foundational evidence that electrode-specific encoding strategies will be necessary in future visual prosthetic devices.

Objective. Temperature readings are routinely stratified by race and ethnicity, though significant group differences may reflect physiology, instrument noise, or categorization rather than biology. This study tests whether these categories partition facial infrared thermography measurements beyond individual variation and baseline device noise. Approach. A secondary analysis of thermography data (n = 951 adults) compares inner-canthus maximum (TCEmax) and full-face maximum (Tmax) temperatures across five administrative categories via one-way analysis of variance (ANOVA), mixed-effects modeling, Bland-Altman analysis against oral reference, and Monte Carlo sensitivity analysis. Main results. ANOVA returns significant group differences (p < 0.001; eta-squared = 0.04 for TCEmax, 0.03 for Tmax), but the total spread (0.2 to 0.3 degrees Celsius) is comparable to device accuracy and within-subject variability. Individual variation accounts for 95% of TCEmax variance, and adding simulated Gaussian noise to participant-level temperatures (sigma = 0.10 to 0.30 degrees Celsius) preserves the complete group-mean rank order in as few as 37.5% of iterations. Significance. Testing whether a group difference survives perturbation at the scale of instrument accuracy offers a check against treating significance alone as evidence of physiology. Here, observed group differences are small relative to measurement variability, and their physiological interpretation remains uncertain, with implications for clinical tools that treat administrative categories as biologically meaningful.

In fully-sighted individuals, pursuit and saccadic eye movements work together to foveate moving targets; pursuit attempts to match target velocity, while catch-up saccades re-align the fovea to the target if it deviates during pursuit. Although saccade-pursuit interactions are well understood in healthy individuals, much less is known about how these mechanisms adapt in the presence of central vision loss. Here, we simulated central vision loss in healthy young adults to examine plasticity in saccade-pursuit mechanisms and investigated whether and how catch-up saccades adapted over five days of visual tracking. Twenty-five fully sighted participants performed a task in which they pursued a moving target that stepped position randomly (designed to elicit catch-up saccades) while viewing with a gaze-contingent central scotoma. The scotoma was shaped like a bitten cookie to encourage use of a specific preferred retinal locus (PRL) corresponding to the peripheral location with the highest acuity. By the end of the five days of repetition, most participants showed catch-up saccade endpoints shifted towards the PRL rather than the fovea. On average, endpoints shifted 0.5 deg towards the PRL between days 1 and 5 (range=0.3-1.5 deg), with significant shifts in 13 of the 25 participants. Adaptation was asymmetric; shifts were largest when the target moved in the direction opposite the scotoma bite and smallest when it moved towards it. In summary, we observed adaptation of saccade-pursuit interactive mechanisms through the re-referencing of catch-up saccades from the fovea to PRL. These results provide a promising avenue for rehabilitation in central vision loss aimed at improving eye movements and encouraging PRL use. Ultimately, such an approach may enhance residual visual function and quality of life.

The chick embryo is a widely used vertebrate model for developmental biology, cardiovascular, and bioengineering research. We present an automated laser speckle contrast imaging (LSCI) platform for non-invasive, longitudinal, label-free imaging of the developing heart and extraembryonic vasculature of the chick embryo through the intact eggshell. The platform can detect blood vessels as small as 70 +/- 17 um in diameter and enable repeated imaging from day 0 to day 8 of incubation without disturbing normal embryonic development. It provides both structural (a map of growing extraembryonic blood vessels) and functional (blood flow dynamics and heart rate) information. Using this system, we generated the first continuous, non-invasive, time-lapse recordings of the early functioning chick heart and its extraembryonic vessels. Longitudinal imaging was performed on 15 embryos from different chicken breeds with eggshell colors white, brown and green. Analysis revealed slight variability in early cardiac and vascular morphogenesis across breeds and shell types and shows its potential for automated developmental staging. Finally, for the first time, the growing vasculature of the yolk sac and the chorioallantoic (CAM) membrane was imaged from day 4 to 8. The heart rate and growth of the extraembryonic blood vessels were quantified automatically during imaging.

Background and Objective: High-speed and high-resolution retinal imaging using adaptive optics line confocal ophthalmoscopy (AOLCO) resolves individual red blood cells (erythrocytes) flowing through the smallest retinal capillaries, but quantifying their velocity first requires removing linear and nonlinear distortions caused by eye motion that may result in a displacement of tens to hundreds of pixels between frames. We present a computational pipeline that stabilizes AOLCO capillary video and measures erythrocyte velocity in true physical units, delivered as an interactive 3D Slicer extension and a batch command-line tool sharing one analysis core. Methods: Our video analysis pipeline has four stages: preprocessing, registration, postprocessing, and velocity measurement. During preprocessing, illumination is corrected, and closed-eye frames are identified. During registration, each frame is aligned to a reference frame using affine and, when needed, B-Spline registration, initialized by our robust and fast (GPU-based) translation-registration algorithm to accommodate large eye movements (e.g., microsaccades). During postprocessing, adjacent registered frames are differenced to suppress stationary structures, and a 2D projection of the frame-difference video reveals the capillary network. During velocity measurement, an operator manually identifies capillary segments on the 2D projection image. Spatiotemporal images are then generated along these segments from the frame-difference video, and blood-flow velocity curves are obtained from these images using the Radon transform. Results: We validate the velocimetry of the pipeline against synthetic ground-truth flow data, and the experiments show that the velocimetry recovers the speed within an error of 4% The GPU-based translation registration algorithm aligns the large eye motions (~90 um per frame on average) and runs about 3.6 x (100 Hz) to 38 x (400 Hz) faster than the baseline method. Across the full cohort (2344 videos, 57 subjects, 30 Hz to 400 Hz), our registration approach improves structural similarity (SSIM) of the video frames on every acquisition from 0.73 to 0.86. The recovered blood flow velocities are physiologically plausible, of the same order as published AO measurements. Conclusions: Our computational pipeline enables AOLCO velocimetry on the capillary-level.

Ophthalmic decisions require probabilities tied to a clinical question, a candidate set and an operating policy. We present OphJev, an endpoint-aware System One framework that combines frozen image and text representations, candidate scoring, schema-specific calibration and selective generalist queries for fundus and OCT imaging. Across eight external resources, multiple representation families, three generalist sizes and three seeds, controlled interventions separate the effects of wording, supervision and computation. Schema-aware affine calibration lowers mean held-out Brier loss and selective risk in all eight primary image--text configurations. On HYGD, matched-supervision fusion raises AUROC from 0.772 to 0.798, while a separate gain-routing policy lowers Brier from 0.618 to 0.599 using at most 20\% logical generalist image calls. These effects demonstrate complementary decision-level capabilities rather than universal gains: external transfer and larger specialist banks remain cohort dependent. A retrospective text extension evaluates 1,996 clinical notes and 91 ophthalmic questions; validation-based calibration improves note probability scores, while a lexical control remains strong. OphJev provides an auditable decision framework; prospective clinical benefit remains unvalidated.

Achromatopsia (ACHM) is a rare autosomal recessive retinal disorder characterized by absent cone photoreceptor function from early life, leading to severe visual impairment. Mutations in genes involved in the cone phototransduction cascade frequently result in elevated cyclic guanosine monophosphate (cGMP) levels and activation of stress pathways, including endoplasmic reticulum (ER) stress and the unfolded protein response. Targeting common downstream mechanisms rather than individual mutations may provide a broadly applicable therapeutic strategy. Here, we investigated whether pharmacological inhibition of valosin-containing protein (VCP), a key regulator of ER and protein homeostasis, can prevent cone degeneration in the spontaneous cone photoreceptor function loss 1 (cpfl1) mouse model of ACHM. Organotypic culture of retinal explants from cpfl1 mice were treated with the selective VCP inhibitor ML240. Cone survival, cell death, opsin expression and localization were assessed by TUNEL assay, immunohistochemistry, and quantitative image analysis. ML240 treatment significantly increased cone density and improved cone opsin expression and trafficking to the outer segments (OSs) in cpfl1 explants compared to controls. Importantly, rhodopsin trafficking in rod photoreceptors was unaffected, indicating that VCP inhibition did not impair normal rod phototransduction. These findings demonstrate that VCP inhibition by ML240 effectively preserves cone photoreceptors and improves cone-specific functional markers in the cpfl1 model. Targeting VCP may represent a mutation-independent therapeutic strategy for preventing cone death in ACHM.

Background: Papillary thyroid microcarcinoma (PTMC, equal to or smaller than 1 cm) is increasingly diagnosed, and a subset behaves aggressively. Preoperative ultrasound (US) and fine needle aspiration (FNA) accuracy in this size range, particularly with multinodular disease, is poorly defined outside East Asian screening cohorts. Materials and Methods: We retrospectively analyzed 180 consecutive PTMC cases (2017 to 2026) with preoperative US and FNA and compared them with 191 benign thyroidectomy controls. ROC analysis identified an optimal size cutoff. We compared sensitivity, specificity, PPV, NPV, and accuracy across tumor-size subgroups, before/after 2023, and with/without dominant nodules (DNs) equal to or larger than 2 cm. Results: ROC analysis identified 5 mm as the optimal cutoff (AUC 0.80). FNA sensitivity was 44.4% overall, falling to 14.1% for tumors <5 mm versus 61.2% for [&ge;]5 mm, with specificity uniformly high (94.8%). US showed a similar pattern (sensitivity 23.4% vs. 64.7%) but lower specificity (69.6%), driven largely by calcification and Hashimoto's-related hypoechogenicity. Combined FNA+US improved sensitivity to 59.4%. DNs equal to or larger than 2 cm markedly reduced FNA true-positive rates (67.9% vs. 10.8%; OR 17.4). Excluding DN cases raised FNA sensitivity to 67%, NPV to 84.2%, and accuracy to 85.2%. Post-2023 experience significantly improved all metrics (sensitivity 34.4% to 54.4%). Conclusion: FNA and US sensitivity for PTMC decline sharply below 5 mm and in multinodular glands with dominant nodules, while specificity/PPV remain high. A 5 mm threshold, operator experience, and selective avoidance of FNA in dominant-nodule bearing multinodular goiters (favoring direct surgical referral) can meaningfully improve diagnostic performance and guide management.

Optical coherence tomography angiography (OCTA) has been extensively explored for the detection of pathological retinal changes arising in various ophthalmological diseases. Due to phase instability of conventional systems, most OCTA signal processing methods to date have relied on intensity-based averaging, despite the resulting lower contrast and dynamic range compared to coherent averaging approaches. In this work, we (1) present a novel computation pipeline that enables fully-coherent processing in any phase-stable or phase-unstable system, and (2) demonstrate the first angiography metric with integrated signal-to-noise ratio (SNR) correction and coherent spatiotemporal ensemble averaging effective in any OCT system. Our method does not rely on 2D en face projections or binarization to produce high-contrast en face views and it significantly enhances the contrast-to-noise ratio of computed OCTA volumes, particularly in regions with reduced SNR levels. Our OCTA volumes also have high cross-sectional quality, enabling the use of single-depth en face views and the localization of capillary paths in the axial dimension. We can now identify capillaries below the retinal pigment epithelium, near the lamina cribrosa in the optic cup, which was not previously possible due to low SNR. We also conducted an analysis of strategies for bias reduction in OCTA and developed the optimal method utilizing coherent spatiotemporal ensemble averaging. Because our method leverages coherent averaging across all dimensions, it provides flexibility in shaping the averaging kernel to target specific workflows. The value of this additional degree of freedom is illustrated in our vessel tracing investigations, in which the depth resolution was maximized by limiting coherent ensemble averaging to the two lateral dimensions even in presence of strong phase noise, enabling the identification of 3D features such as overlapping capillary paths.

Purpose: Post-marketing reports have associated faricimab, the first intravitreal bispecific antibody, with intraocular inflammation (IOI). Its inflammatory phenotype, temporal pattern and systemic safety relative to established anti-VEGF agents remain unclear. We compared faricimab, aflibercept and ranibizumab across three independent pharmacovigilance databases. Methods: We analysed FAERS reports from Q1 2022 to Q2 2026, with external validation in JADER (PMDA, Japan) and EudraVigilance. Reports were de-duplicated, restricted to primary-suspect reports, and a pre-specified list of 36 non-adverse-event preferred terms (PTs) was excluded. We computed reporting odds ratios (ROR), proportional reporting ratios and Bayesian information components, with Benjamini-Hochberg false discovery rate control. Head-to-head RORs were adjusted for demographic confounders by logistic regression. Time to onset (TTO) was modelled with Weibull distributions. Sensitivity analyses addressed masking and differential market duration. Signals were graded with a pre-specified bidirectional cross-database evidence framework (Confirmed, Consistent, Unconfirmed, Discordant). Results: Faricimab was reported more often for anterior-chamber and vitreal inflammation. Adjusted RORs (comparator versus faricimab, values <1 indicating faricimab excess) were 0.27 (95% CI 0.18-0.40) for iridocyclitis and 0.45 (0.35-0.58) for uveitis versus aflibercept, and 0.13 (0.06-0.24) and 0.12 (0.06-0.20) versus ranibizumab. All four PTs were Confirmed in JADER against both comparators; for iridocyclitis, RORs were 0.048 versus aflibercept and 0.109 versus ranibizumab. Faricimab IOI arose late (median TTO 100 days, IQR 31-182, versus 7 days for both comparators; P = 2.6E-14) and its Weibull onset distribution was markedly flatter (shape 0.81 versus {approx}0.42). In contrast, aflibercept predominated for endophthalmitis-spectrum events and intraocular pressure elevation, and ranibizumab for vitreous haemorrhage, the latter confirmed in JADER. Faricimab showed lower reporting across cardiac, nervous system, vascular and renal system organ classes, confirmed in EudraVigilance. An unadjusted FAERS death signal (ROR 3.16, aflibercept versus faricimab) attenuated after adjustment (aROR {approx}1.8) and was absent in outcome-based JADER analyses. Conclusions: Faricimab exhibits a reproducible, delayed-onset, anterior-predominant IOI phenotype alongside a comparatively favourable systemic safety profile. Clinicians should be aware that faricimab-associated IOI may arise weeks to months after injection. Prospective studies with exposure denominators are needed to quantify absolute risk.