Abstract

To investigate the ability of flavoprotein fluorescence (FPF) imaging to quantify disease burden in optic disc drusen (ODD).Cross-sectional study.157 ODD eyes (94 participants, ages 7 - 89 years) and 69 control eyes (53 participants, ages 10 - 78 years).Comprehensive examination, visual function testing, and multimodal ophthalmic imaging. Statistical analysis was performed using parametric and nonparametric tests, ANOVA, and Spearman correlation.LogMAR, static perimetry mean deviation, optic disc and macular FPF, enhanced-depth imaging optical coherence tomography (EDI-OCT), OCT peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell complex (mGCC) thickness.Optic disc FPF signal corresponded with superficial and buried drusen visualized on 97 EDI-OCT B-scans. Compared with controls, ODD eyes have significantly elevated disc FPF (p < 0.0001) but no difference in macular FPF scores. Examination of age-related changes revealed stable disc FPF in controls over the first 7 decades of life. In contrast, ODD eyes exhibited elevated disc FPF within the first 2 decades of age, which increased over time and remained relatively plateaued after age 40. Sectoral analysis showed significantly elevated disc FPF in all quadrants in ODD compared with controls (p < 0.001). ODD eyes with visual field loss (mean deviation (MD < -2 dB) had significantly higher disc FPF and lower pRNFL and mGCC thicknesses compared with ODD eyes without visual field loss (MD ≥ -2 dB) (p < 0.001 for all). We found a nonlinear relationship between disc FPF and MD (RMSE = 4.4271, R² = 0.4504) and a negative correlation between disc FPF and pRNFL (r = -0.78) and mGCC thicknesses (r = -0.62). Disc FPF, pRNFL, and mGCC had high statistical power in segregating ODD eyes with and without visual field loss.Disc FPF is an objective imaging technique to quantify disease burden in ODD, reflecting a combination of drusen autofluorescence signal and metabolic stress from axonopathy. Disc FPF is correlated with structural and functional changes and has high predictive power of visual field loss in ODD, supporting its use as an outcome measure in prospective natural history and treatment studies in ODD.

View details for DOI 10.1016/j.ajo.2025.11.018

View details for PubMedID 41260483

Abstract

PURPOSE: To establish long-term reliability measures for vergence testing in a control population of adolescents.METHODS: Healthy participants between 12 and 17.5years with normal binocular vision were recruited from 10 clinical sites. Cover test, near point of convergence (NPC), positive and negative fusional vergences, vergence facility (12∆ base-out/3∆ base-in) and vergence jumps (using the Oculomotor Assessment Tool) were performed at the initial visit and repeated at 90days. The mean and standard deviation were calculated for the overall group for NPC, vergence facility and vergence jumps and by prism dioptre step value for PFV and NFV (1Delta or 2Delta if below 20∆ or 5Delta above 20∆). Agreement was assessed using Bland-Altman plots and 95% limits of agreement (LOA).RESULTS: Ninety-three participants (mean age 14.3±1.7years, 52% female) were enrolled and 91 (98%) completed the initial and 90-day outcome evaluation. The mean differences were significantly greater than zero for vergence facility (p<0.05) and the first and second 30s of vergence jumps (p<0.01). The 95% LOA were narrow for NPC (±2.5) and negative fusional vergence (±5.9), suggesting good repeatability. LOA were larger for positive fusional vergence (±17.8), vergence facility (±9.8) and vergence jumps (±16.2). Analysis of the positive fusional vergence data indicates that the different step sizes (1∆ or 2∆ vs. 5∆) in the horizontal prism bar contribute to considerably larger variability in these measures.CONCLUSIONS: In participants with normal binocular vision and no concussion history, good reliability yielded comparable results 90days apart for all vergence measures. The results provide values that can be used to interpret the effect of intervention for vergence disorders in clinical practice and research studies. An important outcome of this study is the understanding that 5∆ steps on the typical horizontal prism bar contribute to high variability in positive fusional vergence measures when findings are ≥20∆.

View details for DOI 10.1111/opo.70022

View details for PubMedID 41048201

View details for Web of Science ID 001603659901202

Abstract

Purpose: To evaluate risk factors associated with development of anti-adalimumab antibodies (AAA) in patients with non-infectious uveitis treated with adalimumab.Methods: A retrospective, cross-sectional, case-control study was done evaluating patients with non-infectious uveitis treated with adalimumab for at least 12 months and have undergone testing for AAA levels. Demographics, clinical characteristics, grading of ocular inflammation, and previous and concomitant immunomodulatory therapy were assessed. Univariate and multivariate analysis were done to estimate odds ratio (OR) with 95% confidence intervals for the various risk factors.Results: A total of 31 patients were included in the analysis, in which 12 patients who tested positive (Group 1) were matched with 19 patients who tested negative for AAA (Group 2). The groups differed significantly in terms of sex (female) (91.7% vs 52.6%, p=0.046), presence of systemic disease (91.7% vs 42.1%, p=0.008), and presence of anterior chamber inflammation at baseline (100% vs 63.2%, p=0.026). A history of interruption in anti-TNF therapy prior to starting or restarting adalimumab was found to have an increased odds for development of AAA (OR 16.89 [2.92, 107.11], p=0.008), as well as flare-ups (reactivation of disease) during adalimumab therapy (OR 6.77 [1.80, 61.80], p=0.027). Weekly dosing of adalimumab was shown to decrease odds of AAA development (OR 0.34 [0.02, 0.70], p=0.040), while concomitant anti-metabolite therapy was not shown to be a statistically significant protective factor (OR 2.22 [0.50, 9.96], p=0.148).Conclusions: History of interruption in anti-TNF therapy and flare during adalimumab were associated with development of AAA, while weekly dosing of adalimumab was protective against AAA. Identification of those with higher risk of developing AAA may guide in clinical decision making to optimize management for these patients.

View details for DOI 10.1016/j.heliyon.2024.e29313

View details for PubMedID 38694084

Abstract

To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic.Retrospective comparison of diagnostic approaches.Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by three uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc, Dunfermline, Scotland, UK), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering, Heidelberg, Germany) and UWFFA (Optos Plc, Dunfermline, Scotland, UK) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA, compared with Set 1.The mean age of the patients was 46.9±22.4 (range, 7-96) and 91 (57.6%) were female. With Set 1 alone, 138 (55.2%) eyes were found to have active disease; localization was anterior in 58 (42.0%) eyes, posterior in 53 (38.4%) eyes and anterior + posterior in 27 (19.6%) eyes. With Set 2, 169 eyes of 107 patients had active anterior, posterior or pan-uveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 (18.3%) eyes with active disease (p=0.006), and additional 31 (18.3%) eyes having disease in both anterior + posterior segments (p<0.001). Regarding the primary outcome, management was changed in 68 (27.4%) eyes in Set 2, compared to Set 1.Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared to clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of uveitis patients at the baseline visit.

View details for DOI 10.1016/j.ajo.2024.04.016

View details for PubMedID 38701875

Abstract

This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy.Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12.association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA).In both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters.Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO.

View details for DOI 10.1038/s41433-024-03015-2

View details for PubMedID 38622330

View details for PubMedCentralID 4176007

Abstract

Here, we propose optomechanical devices for steering anesthetized animals during retinal imaging and/or stimulation with stationary ophthalmoscopes. Simple operating procedures ensure that the entrance pupil of the eye remains centered on the exit pupil of the ophthalmoscope during steering, to avoid vignetting. The devices, built with commercially available manual linear stages and motorized rotating devices, can be used to capture image sequences for tiling, as is often done in microscopy. This automated steering system, demonstrated here in mice, is applicable to other animal species and imaging modalities, as well as explanted eyes. The use of these devices can reduce imaging time and retinal light exposure, both of which are important when using ophthalmoscopes with small fields of view, such as adaptive optics ophthalmoscopes, while also improving animal welfare.

View details for DOI 10.1364/BOE.582530

View details for PubMedID 41532121

Abstract

Advances in adaptive optics optical coherence tomography (AOOCT) have facilitated the three-dimensional assessment of structural and functional properties of individual retinal cells in the living human eye. However, even with diffraction-limited AOOCT systems, some cells in the living human retina can be difficult to resolve, especially when using near-infrared wavelengths of light (~1000 nm). We demonstrate that modifying the traditional AOOCT instrument design to enable annular illumination and sub-Airy disk detection results in improved imaging resolution beyond fundamental limits imposed by diffraction. We successfully applied this approach to in vivo human retinal imaging, achieving on average 36% improvement in lateral resolution beyond conventional imaging conditions, enabling improved visualization of the foveal cone and rod photoreceptor mosaics using AOOCT. These results demonstrate an effective strategy for improving lateral resolution in point-scanning AOOCT in a manner that is compatible with new and existing instruments.

View details for DOI 10.1038/s44172-025-00573-5

View details for PubMedID 41461899

Abstract

Here, we demonstrate a telecentric model eye for measuring scanning, sampling, and optical distortion in AO ophthalmoscopes across a 10-diopter focus range, seeking to improve the reproducibility of adaptive optics (AO) ophthalmoscopy biomarkers. The model eye lens provides diffraction-limited performance when imaging with 800 nm light over circular 2.0, 3.0, 4.6, and 9.2° fields of view through 8, 6, 4, and 2 mm diameter aperture stops, respectively. Measurements of double-pass wavefront aberrations using both model and real retinas show that the use of opal glass model retinas, rough model retina surfaces, and wavefront sensing beacon scanning mitigate first-pass aberrations. This is particularly important, as first-pass aberrations are often assumed but not always achieved in AO ophthalmoscopes. Using the model eye with custom distortion estimation algorithms, we recorded 0.06% non-isotropic scaling repeatability, 0.02° shear repeatability, 0.5% reproducibility for both metrics and a root-mean-square residual distortion of 0.1 pixels across the field of view and focus range.

View details for DOI 10.1364/BOE.565589

View details for PubMedID 40677819

View details for PubMedCentralID PMC12265597

Abstract

As the sole retinal output neurons, retinal ganglion cells (RGCs) transmit all visual information from the retina to the brain. RGCs do not regenerate, and effective therapies for promoting RGC survival and axon regeneration in glaucoma and other optic neuropathies comprise an unmet clinical need. Histone deacetylases (HDACs) are epigenetic modifiers that repress gene transcription. Here, we identify a role for HDAC4 in RGC neurodegeneration and axon regeneration.The role of HDAC4 in RGC neuroprotection and axon regeneration was studied in the mouse optic nerve crush (ONC) model for optic neuropathy by RGC transduction in vivo with adeno-associated virus vectors. RGC gene expression in vivo was studied by single cell RNA sequencing (scRNA-seq).A loss-of-function screen identified HDAC4 as essential for RGC survival after ONC injury. Expression of a nuclear-localized HDAC4 missense mutant (HDAC4 3SA) increased RGC survival and axon regeneration after ONC injury. Similar beneficial effects were conferred by an N-terminal fragment of HDAC4 (HDAC4 NT) that can constitutively repress gene expression. The scRNA-seq showed that 1 day after ONC injury, RGC transcriptomic profiles were altered such that HDAC4 NT and to a lesser degree the HDAC4 3SA mutant attenuated the gene expression changes associated with injury.Enhancement of HDAC4 activity promotes RGC survival and axon regeneration in a model of RGC injury, normalizing RGC gene expression toward the uninjured state. HDAC4 is thereby identified as a novel target in the development of therapeutics for RGC protection and restoration of visual function.

View details for DOI 10.1167/iovs.66.15.60

View details for PubMedID 41533933

View details for PubMedCentralID PMC12721432

Abstract

Genetic dilated cardiomyopathy (DCM) is a leading cause of heart failure. However, disease-modifying therapies remain limited. Metabolic dysfunction has emerged as a key driver of DCM pathogenesis, and impaired serine biosynthesis, catalyzed by the rate-limiting enzyme phosphoglycerate dehydrogenase (PHGDH), has recently been identified as a potential therapeutic target. Here, we evaluated the therapeutic potential of increasing serine biosynthesis through AAV9-mediated PHGDH gene augmentation in a transgenic TM54 mouse model of DCM with established pathology. Longitudinal echocardiography showed preserved systolic function and prevented ventricular dilatation in TM54 mice treated with AAV9-PHGDH compared to AAV9-GFP controls. Histological analysis revealed reduced myocardial fibrosis and cardiomyocyte hypertrophy in AAV9-PHGDH-treated TM54 hearts, indicating a reversal of pathological remodeling. Metabolic profiling, including targeted metabolomics and in vivo 13C-glucose tracing analysis, revealed that serine levels increased in hearts treated with AAV9-PHGDH, accompanied by decreases in glucose-derived pyruvate and lactate. At the same time, mitochondrial oxidative metabolism remained intact, indicating a shift of glycolytic carbon towards serine biosynthesis. Collectively, these findings show that enhancing cardiac serine synthesis through PHGDH gene augmentation therapy preserves contractile function and mitigates disease progression in vivo, suggesting a novel metabolic therapeutic strategy for DCM.

View details for DOI 10.1016/j.metabol.2025.156395

View details for PubMedID 40975489

Abstract

Our image classifier prognosticates future retinal tear/retinal detachment (RT/RD) likelihood from optical coherence tomography (OCT) while providing pixel-level explanations of clinical importance.RT/RD status (International Classification of Diseases, Ninth and Tenth Revision codes) and surgical status (Current Procedural Terminology codes) were determined for OCTs collected from the Stanford Research Repository. An image positive for future RT/RD-related surgery was defined as no RT/RD or surgery prior to the acquisition date and the acquisition date 90 days prior to RT/RD diagnosis or surgery. A negative image had no patient overlap with the positive class, had no RT/RD or surgery indication at any time, and was positive for plaquenil use without toxic maculopathy. A convolutional neural network, Inception-v4, was fine-tuned in a class-stratified fivefold fashion on the data set containing 433 negative patients (1027 images) and 343 positive patients (1027 images). Each fold contained a separate patient cohort. Heatmaps indicating a model's region of focus were generated using gradient-weighted class activation mapping to verify that the model's intuition was consistent with clinical knowledge.Performance metrics were collected by averaging across folds. For the test set, the model achieved an area under the receiver operating characteristic curve of 0.87, an average precision score of 0.85, and an accuracy of 0.78. Anatomy highlighted in heatmaps described macular biomarkers for RT/RD, including epiretinal membrane presence, vitreomacular traction, degree of myopic tilt, and choroidal thickness.The binary image classifier accurately identified future RT/RD development from OCTs.Our deep learning algorithm highlights biomarkers for patients at high risk for RT/RDs, providing a window for prophylactic treatment to prevent vision loss. .

View details for DOI 10.1167/tvst.14.11.18

View details for PubMedID 41247117

Abstract

Schirmer strips are widely regarded as the gold standard for tear fluid collection. However, their use presents several challenges for proteomic analysis. Here, we present a protocol for extracting tear proteins from Schirmer strips. We describe steps for acquisition and handling of strips, extraction buffer preparation, strip preparation, and protein extraction. This protocol is designed to improve protein yield and facilitate proteomic workflows and is adaptable for various protein-based studies, particularly in the context of ocular disease research and diagnostics.

View details for DOI 10.1016/j.xpro.2025.104146

View details for PubMedID 41108683

Abstract

In this article, we provide a brief overview of 3D bioprinting technologies and the types of cells employed in ophthalmic cell therapy. We then explore recent applications of 3D bioprinting in ophthalmic cell delivery systems.Cell therapy in ophthalmology is a promising treatment for various eye diseases, there exists some limitations of existing cell therapy strategies Such as cell loss, poor integration with Surrounding tissues, and the sustainability of long-term effects. In this regard, 3D bioprinting technology provides a beneficial method for developing highly biomimetic and reliable cell delivery systems for ophthalmic disease research. Recent advances have shown bioengineered tissues which replicate the microstructure of native tissues, personalized ophthalmic devices, and encapsulated cell-delivery systems. While still in the early stages of advancement, the development of cell delivery systems based on bioprinting technologies is indeed inspiring and has the potential to be applied to other ocular diseases.Cell therapy based on 3D bioprinting technology in ophthalmology has great potential in ophthalmic disease treatment as well as ocular tissue engineering and regenerative medicine.

View details for DOI 10.1007/s40135-025-00337-6

View details for PubMedID 41019312

View details for PubMedCentralID PMC12474738

Abstract

Severe optic neuritis (ON) is a common clinical manifestation in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and neuromyelitis optica spectrum disorder (NMOSD). Given distinct prognoses and often the necessity of early plasma exchange in NMOSD, prompt differentiation is crucial. In this study, we investigated the utility of optical coherence tomography (OCT) in differentiating between first acute NMOSD-ON and MOGAD-associated optic neuritis (MOGAD-ON), as well as specific factors associated with disc edema.In this retrospective multicenter study, 111 adult patients with MOGAD or aquaporin-4 antibody-positive NMOSD who experienced a first ON and underwent OCT within 2 weeks of symptom onset were included from 14 centers across 8 countries. Peripapillary retinal nerve fiber layer (pRNFL) thickness in µm was analyzed, including the average of both eyes in cases of bilateral manifestation.Eighty-three patients with MOGAD (51 women; 124 ON eyes; bilateral ON 48.2%) and 28 with NMOSD (24 women; 36 ON eyes; bilateral ON 21.4%) were enrolled. A significant increase in pRNFL thickness (>2SD), suggestive of disc edema, was observed in 73.4% of MOGAD-ON eyes and 11.1% of NMOSD-ON eyes (p < 0.001). The pRNFL thickness cutoff of 117.5 µm provided 92.9% specificity and 71.1% sensitivity in distinguishing between MOGAD-ON and NMOSD-ON (area under the curve = 0.838). There was no association between pRNFL thickening and MOG-IgG titer (high vs low), body mass index, or the delay between ON onset and OCT. Simultaneous bilateral MOGAD-ON was associated with significantly more pronounced pRNFL thickening.Acute-stage OCT contributes to the rapid and accurate differentiation between MOGAD-ON and NMOSD-ON prior to antibody confirmation, which can be critical for timely therapeutic decisions.

View details for DOI 10.1212/NXI.0000000000200531

View details for PubMedID 41499724

Abstract

BACKGROUND: High rates of mental health conditions have been reported among patients with idiopathic intracranial hypertension (IIH). Cognitive-behavioral therapy (CBT) has been suggested as a complementary treatment to help manage anxiety and headache pain in IIH. This study aims to assess the mental health of IIH patients through a psychiatric interview and to evaluate their suitability and interest in CBT.METHODS: Participants with IIH were recruited from Stanford Byers Eye Institute. Demographic and clinical characteristics were collected, and participants completed self-rated scales for depression (PHQ-9), anxiety (GAD-7), headaches (HIT-6), and disability (WHODAS-12). Diagnostic and Statistical Manual of Mental Disorders, 5th edition diagnoses, patient's suitability for CBT (SSCT scale), and preferred therapy focus were identified through a formal psychiatric interview.RESULTS: Fifty-three participants were enrolled and completed surveys, and 43 participants went on to have the psychiatric interview (mean age 38 years, 91% female). Among them, 76.7% had a GAD-7 score ≥5, indicating at least mild anxiety, and 76.7% of participants had a PHQ-9 score ≥5, indicating at least mild depression. In total, 81.4% of participants suffered from a mood, anxiety, or trauma- and stressor-related disorder. Participants who had received a venous stent or VP shunt had higher anxiety levels (average GAD-7 11.75 vs 6.52; P = 0.007); 81.4% were interested in CBT, and 83.7% were deemed good candidates for CBT (SSCT ≥ 30). Anxiety management most often emerged as their favored therapeutic focus.CONCLUSIONS: Our results confirm the high prevalence of mental health conditions and symptoms among patients with IIH. A majority of patients are interested in CBT, and many would likely benefit from this approach. CBT should therefore be considered in the therapeutic management of IIH. Further research is warranted to validate the efficacy of this intervention in this specific clinical population.

View details for DOI 10.1097/WNO.0000000000002449

View details for PubMedID 41568823

Abstract

To understand medication adherence and associated healthcare costs of patients with early Alzheimer's disease (AD).This retrospective cohort study used the Axon Registry® linked with claims data to examine medication adherence of U.S. patients with early AD (mild cognitive impairment [MCI] and mild dementia due to AD) from 2015 to 2022. Medication adherence was quantified by the proportion of days covered (PDC) over a one-year follow-up, and adherence rate was defined at a PDC ≥ 80%. Patient comorbidities and healthcare costs were described.Of 333 patients included, 213 (64%) were female with a median (IQR) age 79 (72-83) years. Patients had a mean (SD) of 2.3 (2.1) comorbidities and took a mean (SD) of 3.0 (1.5) medications. Weighted-average PDC across medications was 74.4% with 7 out of 10 medication classes having a medication adherence rate lower than 60%. DPP-4 inhibitors had the highest medication adherence rate (66.67% of patients), and memantine had the lowest (39.13% of patients). Annual median (IQR) medical and pharmacy costs per-patient were

View details for DOI 10.1007/s40135-025-00346-5

View details for Web of Science ID 001664492800001

Abstract

Artificial intelligence (AI)-aided diabetic retinopathy (DR) testing systems have been commercialized for 5 years, but adoption is still relatively limited. This article aims to summarize the evidence in clinical settings, describe the current state of adoption, and share themes of successful implementation.Evaluation of diagnostic test or technology.Ophthalmologists.We performed literature review and conducted interviews with ophthalmologists leading implementation of AI-aided DR testing programs at several academic health systems. The study focused on the 3 currently US Food and Drug Administration-cleared AI systems: LumineticsCore, EyeArt, and AEYE Diagnostic Screening (AEYE-DS), assessing their performance and strategies utilized by health systems to effectively implement this technology in clinics.Diagnostic accuracy data, ophthalmologist feedback.The literature review found 6 publications reporting diagnostic accuracy data of autonomous AI DR testing in primary care office settings, including 5 for LumineticsCore and 1 for EyeArt. Additional articles, of which 18 were selected for detailed review, addressed impact on patient adherence, health equity, and carbon footprint, as well as cost-effectiveness and workflow efficiency analyses. There were no studies comparing the systems on the same patients. In aggregate, adopters of the AI systems reported average nonmydriatic gradability of 49% to 75% (n = 5), sensitivity 87% to 100% (n = 3), and specificity 60% to 91% (n = 4). Based on public records at the time of writing, both LumineticsCore and EyeArt have >5 academic adopters in the United States. Limited information is available on AEYE-DS given recency of regulatory clearance. Elements of successful implementation include proper site selection, aligning AI tools with primary care clinic workflows, streamlining patient engagement and referrals, and ongoing training of staff. Health systems utilizing AI reported improved Healthcare Effectiveness Data and Information Set measures, health equity, productivity, and patient adherence to follow-up with ophthalmology.Artificial intelligence-aided diabetic eye examinations present a promising solution to facilitate early detection of DR, promote equitable access, and drive down system-level cost of care. Its successful implementation requires addressing technological, operational, and stakeholder engagement challenges. Our study underscores the potential of AI to revolutionize care delivery provided its adoption is strategically managed.The author has no/the authors have no proprietary or commercial interest in any materials discussed in this article.

View details for DOI 10.1016/j.xops.2025.100935

View details for PubMedID 41140908

View details for PubMedCentralID PMC12553049

Abstract

Gold nanobipyramids (GNBPs) were investigated as near-infrared contrast agents for optical coherence tomography (OCT) tracking of human corneal stromal stem cells (CSSCs). GNBPs with various longitudinal localized surface plasmon resonance peaks were synthesized, and the variant with a peak at 855 nm (GNBPs-1), closest to the central wavelength of the OCT system, exhibited optimal OCT signal enhancement. To improve stability and biocompatibility, GNBPs-1 were PEGylated. In vitro studies confirmed that PEGylated GNBPs were non-toxic to human CSSCs at concentrations up to 1.6 × 107 particles per cell. At a labeling concentration of 2 × 106 particles per cell, the OCT signal intensity increased by approximately threefold and remained detectable for at least 48 h. The OCT signal intensity and the number of detectable cells correlated closely with cell status upon GNBP-labeling, indicating enhanced tracking of intact transplanted cells. Ex vivo experiments using rabbit corneas demonstrated that GNBP-labeled CSSCs embedded in hydrogel exhibited significantly enhanced OCT contrast compared to unlabeled cells, with signal persistence for more than seven days. Overall, these results identify GNBPs as effective, non-toxic, and long-lasting OCT contrast agents for donor corneal stromal stem cell tracking, highlighting their potential for use in corneal regenerative therapies.

View details for DOI 10.1021/acsanm.5c04264

View details for PubMedID 41473342

View details for PubMedCentralID PMC12747316

View details for DOI 10.1016/j.oret.2017.03.002

Abstract

PURPOSE: To establish long-term reliability measures for vergence testing in a control population of adolescents.METHODS: Healthy participants between 12 and 17.5years with normal binocular vision were recruited from 10 clinical sites. Cover test, near point of convergence (NPC), positive and negative fusional vergences, vergence facility (12∆ base-out/3∆ base-in) and vergence jumps (using the Oculomotor Assessment Tool) were performed at the initial visit and repeated at 90days. The mean and standard deviation were calculated for the overall group for NPC, vergence facility and vergence jumps and by prism dioptre step value for PFV and NFV (1Delta or 2Delta if below 20∆ or 5Delta above 20∆). Agreement was assessed using Bland-Altman plots and 95% limits of agreement (LOA).RESULTS: Ninety-three participants (mean age 14.3±1.7years, 52% female) were enrolled and 91 (98%) completed the initial and 90-day outcome evaluation. The mean differences were significantly greater than zero for vergence facility (p<0.05) and the first and second 30s of vergence jumps (p<0.01). The 95% LOA were narrow for NPC (±2.5) and negative fusional vergence (±5.9), suggesting good repeatability. LOA were larger for positive fusional vergence (±17.8), vergence facility (±9.8) and vergence jumps (±16.2). Analysis of the positive fusional vergence data indicates that the different step sizes (1∆ or 2∆ vs. 5∆) in the horizontal prism bar contribute to considerably larger variability in these measures.CONCLUSIONS: In participants with normal binocular vision and no concussion history, good reliability yielded comparable results 90days apart for all vergence measures. The results provide values that can be used to interpret the effect of intervention for vergence disorders in clinical practice and research studies. An important outcome of this study is the understanding that 5∆ steps on the typical horizontal prism bar contribute to high variability in positive fusional vergence measures when findings are ≥20∆.

View details for DOI 10.1111/opo.70022

View details for PubMedID 41048201

Abstract

Oculomotor deficits in vergence and accommodation can arise in paediatric patients with persistent concussion symptoms, although the profile is not well established. This study aimed to describe the frequency of these deficits in persistently symptomatic concussed paediatric patients and identify effective screening tools.This was a prospective cohort study conducted at three clinical sites across the United States. Participants aged 8-18 years with diagnosed concussion were recruited within 9 months of injury through concussion clinics or referral to a vision provider. Participants without concussion were recruited through the local community and eye clinics. Clinical measures of ocular alignment, vergence and accommodation were collected. Group comparisons were assessed using Welch's t-test, Mann-Whitney U test and Fisher's exact test with Bonferroni correction. The diagnostic value of near point of convergence (NPC) and accommodative amplitude (AA) for identifying persistently symptomatic concussed participants was evaluated using logistic regression and receiver operating characteristic curve analysis.Seventy-one participants were recruited, including 34 concussed participants (mean age 14.3 [SD 2.4] years; 74% female, 26% male; median time since concussion 107 [IQR 80-118] days) and 32 controls (mean age, 12.7 [SD 2.1] years; 56% female, 44% male). Concussed participants scored significantly worse or had higher failure rates than controls on all vergence and accommodative tests (p < 0.05) except ocular alignment and monocular accommodative facility. Concussed participants had a higher frequency of diagnoses (vergence: 62% vs. 3%; accommodation: 76% vs. 3%; p < 0.001). NPC and AA were significant predictors for concussion in individual models (NPC: OR = 2.16 [95% CI: 1.52-3.61], p < 0.001, mean AUC [SD] = 0.88 [0.13]; AA: OR = 0.46 [95% CI: 0.29-0.64], p < 0.001, mean AUC [SD] = 0.88 [0.15]).The oculomotor profile of persistently symptomatic concussed paediatric participants shows a high frequency of vergence and accommodative deficits, for which NPC and AA are effective screening tools. Further investigation should examine oculomotor deficits in acutely concussed paediatric patients.

View details for DOI 10.1111/opo.70010

View details for PubMedID 40905935

Abstract

Children with uncorrected astigmatism are often assumed to accommodate to the circle of least confusion. However, empirical evidence in children without a history of refractive correction is lacking. This study found that most children accommodate toward the anterior focal plane, with both focal planes exhibiting a lag of accommodation.To examine accommodative responses by measuring refractive states of the eye during near viewing in children with uncorrected astigmatism without a history of refractive correction.Participants aged 3 to <10 years with no history of refractive correction monocularly viewed a 20/250 letter at a 3-D demand (33 cm) while accommodative responses were measured using open-field autorefraction. Responses were classified based on the focal plane closest to the stimulus: anterior or posterior focal plane, or circle of least confusion. Cycloplegic autorefraction was used to classify participants as having low astigmatism (≤1.50 D) or high astigmatism (>1.50 D). Participants were further subdivided as having hyperopia (≥2.00 D), myopia (≥0.75 D), or emmetropia (less than 0.75 D myopia and 2.00 D hyperopia) based on their spherical cycloplegic refractive error. Chi-square analyses and Fisher exact tests were used to assess the association between accommodative response and cycloplegic refractive error classification.Of the 352 participants, 316 (89.8%) had low astigmatism and 36 (10.2%) had high astigmatism. In both groups, significantly more participants were classified as being focused at the anterior focal plane (low: 98.7%; high: 83.3%) than the posterior focal plane (low: 0.6%; high: 0.0%) or circle of least confusion (low: 0.6%; high: 16.7%; p<0.001). Almost all nonhyperopic participants in the low astigmatism group (99.2%) and hyperopic participants irrespective of astigmatism magnitude (low: 100%; high: 95.2%) accommodated closer to the anterior focal plane with accommodative lags in both meridians. Most nonhyperopic participants with high astigmatism also accommodated to the anterior focal plane (66.7%) and a third to the circle of least confusion (33.3%).In contrast to the assumption that children with astigmatism accommodate to the circle of least confusion, our findings show that most children accommodated to the anterior focal plane during near-viewing tasks, with accommodative lags in both meridians.

View details for DOI 10.1097/OPX.0000000000002286

View details for PubMedID 40833971

Abstract

This study investigates the potential of matrine, a quinolizidine alkaloid, in regulating intraocular pressure (IOP) in normal and corticosteroid-induced ocular hypertension (OHT) mice.Wild-type C57BL/6 mice were randomly divided into normal and OHT groups. The OHT mouse model was established by periocular conjunctival fornix injections of dexamethasone-21-acetate (DEX). IOP was measured at 0.0, 0.5, 1.0, 3.0, and 6.0 hours after matrine treatment in both groups. Aqueous humor (AH) outflow facility was measured using our previously described/validated perfusion system. Anterior segment-optical coherence tomography was used to evaluate morphological changes in the anterior chamber following matrine treatment. Hematoxylin and eosin staining and immunofluorescence staining were used to investigate structural changes.Matrine treatment (50-200 µg/g) decreased the IOP in normal mice in a dose-dependent manner. AH outflow facility in normal mice elevated at 0.5 hours after matrine treatment (100 and 200 µg/g). Additionally, 100 µg/g matrine treatment increased the angle opening distance in the anterior chamber. In DEX-induced OHT mice, matrine (100 and 200 µg/g) reduced the elevated IOP and increased the AH outflow facility. Furthermore, 100 µg/g matrine treatment increased the angle opening distance compared with that of PBS-treated controls. However, matrine (100 µg/g) did not induce significant changes in trabecular meshwork gross morphology or the expression of cell contractility and extracellular matrix markers in OHT mice at 0.5 hours after treatment.Matrine decreased the IOP in the DEX-induced OHT mouse model, highlighting its potential as a therapeutic agent for managing glaucoma, particularly in corticosteroid-associated secondary cases.

View details for DOI 10.1167/iovs.66.11.18

View details for PubMedID 40772663

Abstract

Intraoperative floppy iris syndrome (IFIS)--characterized by iris blowing, prolapse, and progressive miosis during phacoemulsification surgery--poses significant challenges for eye surgeons. Despite being described almost 2 decades ago, its pathophysiology remains unclear. Initially, IFIS was thought to be a result of sympathetic signal blockage in the iris dilator muscle, since α-blockers such as tamsulosin were found to be a strong predisposing factor; however, many IFIS cases occur even in patients who discontinued α-blockers prior to cataract surgery. Several potential mechanisms through which α-blockers induces chronic changes in the iris - iris dilator atrophy, drug-melanin interaction, and loss of vascular tone - have been proposed as possible mechanisms. We address the prevailing theories on α-receptor-dependent mechanisms for IFIS and the current prophylactic measures undertaken to prevent IFIS-associated intraocular complications.

View details for DOI 10.1016/j.survophthal.2025.06.002

View details for PubMedID 40472999

Abstract

Visual impairment caused by retinal ganglion cell (RGC) axon damage or degeneration affects millions of individuals throughout the world. While some progress has been made in promoting long-distance RGC axon regrowth following injury, it remains unclear whether RGC axons can properly reconnect with their central targets to restore visual function. Additionally, the regenerative capacity of many RGC subtypes remains unknown in part due to a lack of available genetic tools. Here, we use a new mouse line that labels On direction-selective RGCs (oDSGCs) and characterize the survival and regenerative potential of these cells following optic nerve crush (ONC). In parallel, we use a previously characterized mouse line to answer these same questions for M1 intrinsically photosensitive RGCs (ipRGCs). We find that both M1 ipRGCs and oDSGCs are resilient to injury but do not display long-distance axon regrowth following Lin28a overexpression. Unexpectedly, we found that M1 ipRGC, but not oDSGC, intraretinal axons exhibit ectopic branching and are misaligned near the optic disc between one- and three-weeks following injury. Additionally, we observe that numerous ectopic presynaptic specializations associate with misguided ipRGC intraretinal axons. Taken together, these results reveal insights into the injury response of M1 ipRGCs and oDSGCs, providing a foundation for future efforts seeking to restore visual system function following injury.

View details for DOI 10.1016/j.expneurol.2022.114176

View details for PubMedID 35870522

Abstract

Early readers encounter thousands of printed words in children's books. The frequency with which they see each word shapes both neural and behavioral responses. Teachers also introduce novel written words through short, intensive learning experiences. Here we combined steady-state visual evoked potentials (SSVEP), corpus-based word frequency counts, and a novel two-week classroom "learning sprint" to examine and compare these two forms of experience-dependent plasticity. Cortical responses at 4 Hz to contrasts between real words of varying frequency (high: on average 1000 per million; medium: on average 200 per million) and pseudowords were sensitive to corpus-based frequency estimates-marking the first such finding using SSVEP. Strikingly, newly acquired low-frequency words (<1 per million)-taught in a child's own classroom versus counterbalanced words taught in two other classrooms-elicited cortical responses nearly identical to those evoked by high-frequency words versus pseudowords. Furthermore, 1 Hz responses to new vocabulary learning was linked to individual differences in reading skills, including word decoding and rapid automatic naming. Together, these findings highlight the causal impact of authentic instruction and the value of neuroscience-informed methods in education research.

View details for DOI 10.1038/s41539-025-00371-w

View details for PubMedID 41266420

View details for PubMedCentralID 9292610

Abstract

Progressive development of reading comprehension fluency from late childhood to early adolescence is remarkably linked to changes in the temporal dynamics of visual word recognition. EEG/ERP based measures of how an individual participant's cortical timing for visual word recognition change over development are limited by low reliability. We present a novel approach to this challenge that individually models cortical latency to visual word forms by extracting phase values from Steady-State Visual Evoked Potentials (SSVEPs) for each participant. The resulting precise and reliable timing information for neural signatures underlying visual word form processes help account for the development of fluent reading comprehension. Typically developing readers (n=68), aged 8-15 years, viewed streams of four-character stimuli presented at 3 Hz, which evoked large significant power spikes from every participant. Linear phase by frequency functions across harmonics at 3, 6, and 9 Hz were consistent with a delay model, indicating a mean latency of 170 ms. Subject-level latencies revealed (a) high internal consistency (r=.94); (b) stability across variations in character-level (letters, unfamiliar pseudo-characters) and word-form level (words, nonwords, pseudofont strings) manipulations; (c) a linear relationship with age; and most remarkably, (d) a strong relationship with individual variation in the fluency of reading comprehension, that was (e) mediated by word naming speed. Results suggest a promising new approach for investigating the neural basis of reading development across several levels of processes, with temporal precision at the individual level that holds translational significance for promoting population-level fluency in reading comprehension.

View details for DOI 10.1016/j.dcn.2025.101616

View details for PubMedID 41237489

Abstract

Ongoing experience is continuously processed in the context of past events. Divergence between current experience and memory-based predictions (i.e., a mnemonic prediction error; MPE) is theorized to be a signal for the hippocampus that encoding, as opposed to retrieval, should be prioritized. We asked how MPEs place demands on cognitive and neural resources beyond the hippocampus, and whether these demands differ as a function of prediction strength. We investigated these questions across two experiments, wherein we recorded scalp electroencephalography and/or pupillometry as 101 young human adults performed an associative memory task. Strong MPEs, more so than weak MPEs, increased physiological indices of cognitive control (frontal theta), attention (posterior alpha and pupil size), and arousal (pupil size). Trial-level pupil-linked MPE responses scaled with the amount of attention (posterior alpha) allocated during prediction generation. Finally, greater cognitive control (frontal theta) during strong MPEs promoted better learning of prediction violating (i.e., unexpected) stimuli. Collectively, these findings reveal how the mind and brain respond adaptively to violations of strong mnemonic predictions.

View details for DOI 10.1101/2025.10.02.680173

View details for PubMedID 41256715