Abstract

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a neuro-immunological disorder that can cause optic neuritis (ON) and significant visual impairment. Our objective was to investigate clinical characteristics and visual outcomes in children with MOGAD-ON.Retrospective cohort study of MOG-IgG-positive children (onset age 18 years and younger) meeting 2023 international MOGAD panel criteria who presented with ON and received neuro-ophthalmic care between 2003 and 2023 at 3 academic centers in Northern California was conducted. We captured demographic and clinical characteristics, disease course, and presenting MOG-IgG titers through chart review. Ophthalmic metrics, including logarithmic minimum angle of resolution best-corrected visual acuity (logMAR BCVA), retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer thicknesses, and automated visual field mean deviation (AVF MD) at diagnosis, 1-month, 6-month, 1-year, and final (2+ years) visits, were obtained.This study included 49 ON-affected eyes of 29 patients (20 with bilateral involvement), with 19 (66%) being female. The median age at first diagnosis was 9 years (range 1-18). The median follow-up was 40 months (0-119). Age younger than 8 years at MOGAD onset was predictive of recurrent ON (β1=-1.61, P = 0.03). LogMAR BCVA improved from 1.4 at diagnosis to 0.2 at 1 month and 0.07 at the final visit (P < 0.0001). In total, 29 eyes (59%) of 22 patients (76%) achieved complete visual recovery (BCVA LogMAR 0). RNFL thickness decreased from mean 130 µm at diagnosis to 6 months (65 µm, P < 0.05). Average AVF MD improved from -12.8 dB at diagnosis to -5.4 dB at the final visit (P = 0.02). Higher presenting MOG-IgG titers were associated with worse presenting visual fields (r = -0.96, P = 0.04).Children with MOGAD-associated ON often return to normal visual acuity despite significant optic atrophy. Most RNFL thinning occurs in the first 6 months but continues beyond 2 years after MOGAD onset. Younger children were at greater risk of ON relapse. A prospective longitudinal study on pediatric MOGAD-ON is warranted to validate these findings and identify biomarkers for visual outcome prediction.

View details for DOI 10.1097/WNO.0000000000002516

View details for PubMedID 42606014

Abstract

FIREFISH was a multicentre, open-label, two-part, phase 2 trial that assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of risdiplam in children with type 1 spinal muscular atrophy and two SMN2 copies, aged 1-7 months at enrolment. Part 1 assessed safety and determined the dose for part 2. In part 2, treatment with risdiplam for 24 months resulted in continual improvements in motor function and achievement of developmental motor milestones. The aim of the 3-year open-label extension reported here was to assess long-term safety and efficacy of risdiplam.The 3-year extension of the FIREFISH trial was a multicentre, open-label study in 17 centres across 12 countries (in Asia, Europe, Brazil, and the USA). Children with a confirmed genetic diagnosis of spinal muscular atrophy and two copies of the SMN2 gene who had completed 2 years of risdiplam treatment were eligible to continue in the open-label extension study, during which risdiplam was administered once daily by oral syringe or feeding tube at the pivotal dose of 0·20 mg/kg for infants younger than 2 years, at 0·25 mg/kg for children aged 2 years and older with bodyweight below 20 kg, and at 5 mg for children aged 2 years and older with bodyweight of 20 kg or more. Adverse events were assessed as part of physical assessments every 13 weeks. More comprehensive assessments every 26 weeks included level of respiratory support and efficacy assessments of motor function in addition to safety and physical assessments. Outcomes assessed during the open-label extension study included adverse events, survival and event-free survival (defined as being alive with no permanent ventilation), growth measures, swallowing, feeding, and motor function. Motor function was assessed with the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), the gross motor subscale of the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), and the Hammersmith Infant Neurological Examination, Module 2 (HINE-2). For all children, safety data including adverse events, serious and non-serious adverse events of special interest; ophthalmology assessments; laboratory assessments; vital signs; ECGs; and other protocol-specified tests deemed critical to the safety evaluation of the study, were collected up to 30 days after the last dose. Survival and event-free survival are reported at year 5 for all enrolled children. Adverse events are reported at year 5 for all children who received at least one dose of risdiplam (safety population). All other efficacy endpoints are reported at year 5 for the population who received the pivotal dose. FIREFISH is registered with ClinicalTrials.gov, NCT02913482.Between Dec 23, 2016, and Nov 19, 2018, 62 children aged 1-7 months were enrolled in FIREFISH parts 1 and 2. After 2 years in the study (parts 1 and 2), 55 children continued risdiplam treatment into the open-label extension for a further 3 years. The study was completed on Dec 22, 2023, at which time 52 children (84%) had completed 5 years of risdiplam treatment. After 5 years of risdiplam treatment, 56 children (90%) were alive, and 50 (80%) were alive without the need for permanent ventilation. In the pivotal-dose population (n=58), 17 children (29%) did not require invasive or non-invasive respiratory support at year 5 and 13 (22%) did not require hospitalisations during the study. Upward trajectories for motor function responses were observed between years 1 and 5. The number of children who could sit without support for at least 5 s and 30 s was maintained during the 3-year extension, with 36 children (62%) and 34 children (59%), respectively, doing so by year 5. Similarly, for HINE-2, eight children (14%) reached the stable sit milestone and 26 (45%) met pivots at year 5. By year 5, four children (7%) could stand without support as assessed by both the BSID-III and HINE-2. No children could walk independently, but six (10%) met the HINE-2 cruising milestone. The mean HINE-2 total score increased from baseline (0·93 [90% CI 0·72-1·14]) to year 4 (14·22 [12·66-15·79]), remaining stable thereafter. Mean CHOP-INTEND scores increased from 22·47 at baseline (90% CI 20·97-23·96) and stabilised at around 50 at year 5, with scores of ≥40 for 38 children (66%), ≥50 for 29 children (50%), and ≥60 for 11 children (19%) at year 5. Most children maintained oral feeding (n=42; 72%) and swallowing (n=46; 79%) abilities, and growth was consistent with typical patterns seen in type 1 spinal muscular atrophy. Safety findings over 5 years were consistent with the results from the primary analysis. Most adverse events were mild or moderate. The most frequently reported adverse events were pyrexia (65% [n=40]), upper respiratory tract infection (63% [n=39]), and pneumonia (50% [n=31]). Pneumonia was the most frequently reported serious adverse event in 28 children (45%). No new safety findings were reported and no treatment-related events led to withdrawal from study treatment.Unlike the natural history of children with type 1 spinal muscular atrophy, after 5 years of risdiplam treatment, most children in FIREFISH were alive without needing permanent ventilation, were able to swallow and feed orally, and had reached motor milestones not typically observed in untreated patients. These results show long-term continuous efficacy and safety of risdiplam in children with type 1 spinal muscular atrophy.F Hoffmann-La Roche.

View details for DOI 10.1016/S2352-4642(26)00126-4

View details for PubMedID 42385757

View details for Web of Science ID 001879171400049

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

Pathogenic variants in the rhodopsin (RHO) gene are the most common cause of autosomal dominant retinitis pigmentosa leading to photoreceptor degeneration. Quantitative imaging using adaptive optics (AO) revealed irregularities in cone organization, even in relatively well-preserved retinal locations. At the leading disease front, rod density was disrupted to a greater extent than cones. Repeated longitudinal measurements demonstrate the possibility of using cone-based metrics for treatment trials to preserve photoreceptor structure.

View details for DOI 10.1038/s44385-026-00108-3

View details for PubMedID 42686920

View details for PubMedCentralID PMC13538484

View details for DOI 10.1364/BOE.608391

View details for Web of Science ID 001845505500024

Abstract

Here we present an adaptive optics scanning light ophthalmoscope with a square 1.5° full field of view, steerable within a 4° window. When imaging through a 7.72 mm diameter pupil, the instrument provides nominal diffraction-limited performance at the retinal conjugate over a 20 diopter (D) focus range centered at 1D of myopia and supports a 3 D source-detector vergence range for any combination of wavelengths between 450 and 1300 nm. The optical setup also provides nominal diffraction-limited imaging between the pupil conjugates of the wavefront sensor, deformable mirror, and eye, with distortion below 0.5% across the 3 D source-detector vergence range. The optical setup includes four pupil relays. The first three are telescopes formed by pairs of concave spherical mirrors tilted in a non-planar configuration. In these relays, the mirror-to-mirror spacing was held fixed, while the distances to the entrance and exit pupil planes were varied to mitigate aberrations in both pupil and retinal conjugates. The fourth relay comprises four spherical mirrors, two concave and two convex, tilted in a planar configuration. As-built instrument performance is demonstrated by imaging a telecentric model eye over a -6 to +8 D range (limited by deformable mirror stroke) and human photoreceptor mosaic imaging at 680 and 795 nm. The proposed relay forms are broadly applicable to adaptive optics ophthalmoscopes and imaging modalities, including fluorescence, spectroscopy, and optical coherence tomography.

View details for DOI 10.1364/BOE.608391

View details for PubMedID 42610141

View details for PubMedCentralID PMC13481075

Abstract

Heart failure is a major cause of morbidity and mortality worldwide, representing the end stage of cardiovascular diseases that induce pathological cardiac remodeling. At the cellular level, pathological remodeling includes myocyte hypertrophy and decreased survival, changes in myocyte metabolism and contractility, and interstitial myocardial fibrosis, all of which are controlled by a complex network of intracellular signaling pathways. At the outer nuclear envelope of the cardiomyocyte, A-kinase anchoring protein (AKAP) 6β (also known as mAKAPβ) organizes multimolecular signaling complexes called "signalosomes," which include over 25 different signaling enzymes and effector proteins that, in response to cAMP, calcium, and phosphoinositide second messengers, regulate gene expression. The AKAP6β scaffold also binds other scaffold proteins such as AKAP9, permitting higher-order interactions between signaling molecules at the nuclear envelope and adjacent Golgi apparatus. Together, these protein complexes present novel opportunities for compartmentalized inhibition of pathophysiological cardiac remodeling. Both basic molecular mechanisms and potential therapeutic approaches are considered, because this review highlights recent advances in the role of AKAP6 in coordinating compartmentalized signaling and the regulation of cardiomyocyte gene expression promoting heart failure. SIGNIFICANCE STATEMENT: Heart failure is a syndrome of major public health significance. Novel therapies for the treatment of cardiac disease are needed to improve patient quality of life, reduce symptoms, and manage comorbidities associated with heart disease. The A-kinase anchoring protein 6β signalosome has been shown to orchestrate multiple pathological signaling pathways in the cardiomyocyte that induce cardiac disease. Targeting this signalosome should comprise more specific therapeutics for heart failure with fewer side effects than those associated with current treatments.

View details for DOI 10.1016/j.molpha.2026.100145

View details for PubMedID 42727198

View details for DOI 10.1161/CIRCRESAHA.126.328631

View details for PubMedID 42096505

View details for PubMedCentralID PMC13155368

Abstract

The 2025 Cure Ocular Melanoma (CURE OM) Global Science Meeting took place in Amsterdam, The Netherlands on October 25th, 2025. Several promising drug candidates are in development; however, there is still an urgent need for better prevention, detection, and treatment of uveal melanoma. The purpose of this meeting was to promote international collaboration and idea exchange between scientists, industry, and patient advocates.

View details for DOI 10.1111/pcmr.70102

View details for PubMedID 42338188

Abstract

As optical coherence tomography (OCT) has enabled the identification of an expanding set of age-related macular degeneration (AMD) risk biomarkers and become central to routine clinical practice, there remains a need for a simplified grading scheme that allows physicians to communicate and synchronize AMD grading directly from standard OCT imaging rather than relying on traditional color fundus imaging. This study aims to establish a standardized OCT-based AMD classification that balances diagnostic accuracy with practicality for use across clinical and research settings.Spectral-domain OCT scans were independently graded by two retinal specialists following the newly proposed Stanford OCT-Based AMD Classification (SOAC). Discrepancies were adjudicated by a third independent retinal specialist. Inter-grader agreement was assessed using weighted kappa coefficients.Among the 109 eyes from 108 patients (mean age 79.61 ± 7.57 years; 41.7% men, 58.3% women), AMD staging based on SOAC was distributed as follows: normal aging in nine patients (8.3%), early AMD in 16 (14.7%), intermediate AMD in 32 (29.4%), neovascular AMD (nAMD) in 18 (16.5%), geographic atrophy (GA) in 20 (18.3%), and combined nAMD and GA in 14 (12.8%). The overall intergrader agreement demonstrated robust consistency, with a weighted kappa value of 0.95 (95% CI: 0.92-0.98), signifying excellent intergrader reliability and reinforcing the validity of SOAC.SOAC provides a standardized, OCT-based framework for AMD grading that demonstrates high intergrader agreement. By enabling consistent classification from commonly acquired OCT scans, SOAC supports reliable disease staging and facilitates integration across clinical studies and translational research. As imaging and molecular data continue to expand, SOAC can serve as a common OCT-based reference for phenotype refinement and longitudinal AMD studies.

View details for DOI 10.3928/23258160-20260409-02

View details for PubMedID 42165512

Abstract

Hunter syndrome (mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) mutations and is classically associated with multiple-organ-systems involvement. Ocular findings are usually reported in conjunction with systemic manifestations, and isolated ocular presentations have not been well characterized. Here, we report a novel hemizygous IDS variant in a patient who initially presented with isolated corneal and retinal pathology and was subsequently diagnosed with attenuated Hunter syndrome.Comprehensive ophthalmic and retinal evaluation was performed, including multimodal retinal imaging and full-field electroretinography, alongside genetic testing.A 44-year-old male with progressive nyctalopia demonstrated bilateral parafoveal and peripheral retinal depigmentation with central macular sparing on optical coherence tomography and a symmetric bull's-eye pattern on fundus autofluorescence. Visual field testing revealed bilateral ring scotomas, and full-field electroretinography showed subnormal rod-predominant responses. Pedigree analysis suggested X-linked inheritance. Genetic testing identified a novel hemizygous IDS variant (c.707A > G, p.Lys236Arg), and the diagnosis of Hunter syndrome was supported by markedly reduced IDS activity and elevated urinary glycosaminoglycans with increased heparan sulfate.A novel missense IDS mutation was identified in association with Hunter syndrome, highlighting the importance for ophthalmologists to consider MPS II in patients presenting with isolated retinopathy and the value of genetic diagnosis in revealing atypical systemic disease.

View details for DOI 10.1007/s10633-026-10104-y

View details for PubMedID 42033570

View details for PubMedCentralID 6238255

View details for DOI 10.1016/j.ophtha.2026.07.005

View details for PubMedID 42565765

Abstract

Retrospective identification of acute nonarteritic anterior ischemic optic neuropathy (NAION) cases is critical for research on risk factors. However, reliance on International Classification of Diseases (ICD) 10th edition coding for case identification has limited accuracy, and manual review of longitudinal electronic health records is time-intensive. The purpose of this study is to evaluate automated methods for retrospective identification of acute NAION cases using large language models (LLMs) that preserve patient privacy.Retrospective cross-sectional study.165 patients with ≥1 ICD-10 code for ischemic optic neuropathy (H47.01∗) in the electronic health record at an academic medical center.Five locally deployed LLM models (Mistral Small 3.1, Magistral Small, Gemma3, MedGemma, GPT-OSS 20B) were used to implement 4 approaches for acute NAION diagnostic classification using unstructured ophthalmology records (basic prompting, retrieval-augmented generation [RAG], 2-step agentic workflow, and 3-step agentic workflow). Ten percent of subjects were used for prompt refinement. Large language model/approach diagnostic classifications were compared against expert neuro-ophthalmologist diagnoses based on chart review.Positive predictive value (PPV) of LLM approaches for acute NAION case identification with expert chart review diagnosis serving as gold standard. Secondary outcomes included negative predictive value, sensitivity, specificity, accuracy, F1 score, and distribution of LLM/approach classifications.7/17 prompt refinement subjects and 58/148 testing subjects had acute NAION by expert chart review corresponding to PPV of 0.39 for ≥1 ICD code. Large language model approaches accurately identified 20 ± 12 (mean, standard deviation) acute NAION cases in the test set with PPV of 0.78 ± 0.16 and accuracy of 0.69 ± 0.06. The Mistral model using a 3-step agentic approach had the best-balanced performance (39 cases identified, 0.85 PPV, 0.82 accuracy, 0.75 F1 score).Privacy-preserving agentic LLM approaches can achieve high PPV for acute NAION case identification using unstructured ophthalmology longitudinal electronic health records. These results exceed the performance of using structured ICD codes to identify cases, offering a scalable, efficient method for case identification in retrospective research while maintaining patient confidentiality and local data control. This method has application for enhancing research efficiency and accuracy for studies on NAION risk factors, with potential applicability to other conditions requiring complex diagnostic review.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

View details for DOI 10.1016/j.xops.2026.101265

View details for PubMedID 42437116

View details for PubMedCentralID PMC13355692

Abstract

A 63-year-old man experienced progressive vision loss in his right eye over five years. Ophthalmologic examination showed right optic neuropathy with optic nerve pallor. Prior MRI findings of gadolinium enhancement near the prechiasmatic optic nerve had suggested acute optic neuritis. A repeat MRI revealed a dilated vascular structure compressing the optic nerve, confirmed by Time-of-Flight MRA as dolichoectatic ophthalmic artery. Compression-related optic neuropathy caused by a dolichoectatic ophthalmic artery can have similar appearance to acute optic neuritis on MRI. When the clinical history or course does not align with the initial diagnosis, it is important to reconsider the diagnosis.

View details for DOI 10.1080/01658107.2025.2526038

View details for PubMedID 42131160

View details for PubMedCentralID PMC13166200

Abstract

RNA therapies hold tremendous promise for treating genetic eye diseases. However, their development is limited by the lack of non-viral delivery platforms that can target specific ocular cell types. Here, we describe a charge-altering releasable transporter (CART) that delivers RNA selectively to the corneal endothelium, a non-regenerative cell layer whose dysfunction underlies several blinding conditions. We characterize the safety of CART-RNA nanoparticles in mice and show that they facilitate delivery of diverse RNA cargoes to the corneal endothelium, including circular RNA and CRISPR/Cas9. We verify that these nanoparticles can be redosed and apply them to achieve corneal gene editing. We further demonstrate CART transfection of corneal endothelial cells from a human donor in vitro and in a non-human primate in vivo, supporting the feasibility of clinical translation. Our findings establish CARTs as a platform for non-viral gene delivery to the eye, with the potential to treat corneal dystrophies and other vision disorders.

View details for DOI 10.1126/sciadv.ady8161

View details for PubMedID 42627922

Abstract

In embedded 3D bioprinting, biomaterial inks are extruded into sacrificial support baths to facilitate the fabrication of complex shapes, even from soft, liquid-like materials. Post-printing, the diffusion of small molecules into or out of the support bath can facilitate ink crosslinking to stabilize the printed structure. In these coupled reaction-diffusion systems, the rheological properties of the ink will change over time. Despite the importance of tuning the mechanical properties of these inks for biological applications, there are currently no methods to accurately predict ink stiffness over time throughout the crosslinking process. Here, we use a custom-developed magnetic stress rheometer to continuously monitor diffusion-driven crosslinking in situ. Our approach reveals how gelation kinetics depend on the thickness of the ink layer, and enables predictive estimation of mechanical evolution in these reaction-and diffusion-driven systems. With these insights, we fabricate specimens with predetermined mechanical properties and observe changes in cell phenotype as a response. These insights help inform the design of inks and timing of bioprinting protocols to achieve prints with desirable mechanical properties and further allow the fabrication of prints with patterned mechanical properties.

View details for DOI 10.1088/1758-5090/ae7ed3

View details for PubMedID 42309146

View details for DOI 10.1016/j.oret.2017.03.002

Abstract

To objectively quantify visuospatial selective and divided attention using steady-state visual evoked potentials (SSVEPs) in adults with persistent visual symptoms after mild traumatic brain injury (mTBI).Eighteen adults with mTBI (40-350 days post-mTBI) and 27 healthy controls participated. Frequency-tagged SSVEPs to eccentric flickering stimuli along with concurrent behavioral yes/no contrast-decrement-detection task were recorded under three cued covert spatial attention conditions: Selective Attention (SelAtt), Divided Attention (DivAtt), and Ignore. EEG epochs associated with eye fixation loss were excluded using two independent procedures: automated EEG artifact-rejection algorithms and concurrent EyeLink eye-tracking data.The mTBI group showed no significant change in task accuracy and complex-value SSVEP responses across attentional conditions (P > 0.05). In contrast, controls showed significant improvements in task accuracy (P < 0.001) and significant SSVEP modulations across conditions (P = 0.03), with stronger SSVEP during SelAtt compared with Ignore (P = 0.008). SelAtt SSVEPs in mTBI were significantly weaker than controls (P = 0.04). Unlike mTBI, control SSVEP amplitude and inter-trial phase coherence (ITPC) significantly increased across conditions (P = 0.02 and < 0.001, respectively). Both groups did not show any significant modulation in SSVEP phase across attentional conditions (P > 0.05). The significant ITPC-amplitude correlation within each group (P < 0.001) was associated with attention status, whereby SelAtt was associated with higher neural ITPC-amplitude response.These findings indicate impaired visuospatial selective attention in adults with persistent post-mTBI visual symptoms. Our results support neural synchronization theory on population-level neural correlates of attention and suggest impaired synchronization may underlie attention deficits in mTBI.SSVEP provides objective neurophysiological indices of attentional processing in mTBI.

View details for DOI 10.1016/j.clinph.2026.2112387

View details for PubMedID 42731193

View details for Web of Science ID 001878001700041

Abstract

To objectively investigate the effects of blur and disparity cues on accommodative response and microfluctuations (root mean square and low-frequency components), vergence, and pupillary responses to static targets in adolescents with persistent post-concussion symptoms.Thirty-one adolescents with concussions and 32 controls completed the study. Refractive states, eye position (vergence), and pupil size were measured simultaneously using photorefraction (50 Hz) while participants viewed near stimuli for 15 seconds at nine distances ranging from 100 to 25 cm under three viewing conditions: blur and disparity cues (binocular, cartoon movie), blur only (monocular, cartoon movie), and disparity only (binocular, difference of Gaussians target).Participants with concussions showed less accurate accommodative responses (greater accommodative lag) to targets at ≤33 cm than controls did when the targets provided both blur and disparity cues or blur cues only. When disparity-only cues were provided, no significant between-group differences in the accommodative responses were found, but accommodative microfluctuations in participants with concussion were significantly lower than controls at accommodative demands of ≥2.5 D (≤40 cm) for the root mean square and ≥2.25 D (≤44 cm) for low-frequency components. Vergence and pupillary responses were not significantly different between groups for any viewing conditions or demands.Accommodative response to static near targets was impaired in adolescents with persistent post-concussion symptoms when blur cues were provided. In contrast, vergence and pupillary response to static targets were not impacted at habitual near-viewing distances. This study provides mechanistic insights into accommodative dysfunction in concussion.

View details for DOI 10.1167/iovs.67.6.45

View details for PubMedID 42334145

View details for DOI 10.7554/eLife.104055.3.sa2

View details for Web of Science ID 001880077000001

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

To objectively quantify visuospatial selective and divided attention using steady-state visual evoked potentials (SSVEPs) in adults with persistent visual symptoms after mild traumatic brain injury (mTBI).Eighteen adults with mTBI (40-350 days post-mTBI) and 27 healthy controls participated. Frequency-tagged SSVEPs to eccentric flickering stimuli along with concurrent behavioral yes/no contrast-decrement-detection task were recorded under three cued covert spatial attention conditions: Selective Attention (SelAtt), Divided Attention (DivAtt), and Ignore. EEG epochs associated with eye fixation loss were excluded using two independent procedures: automated EEG artifact-rejection algorithms and concurrent EyeLink eye-tracking data.The mTBI group showed no significant change in task accuracy and complex-value SSVEP responses across attentional conditions (P > 0.05). In contrast, controls showed significant improvements in task accuracy (P < 0.001) and significant SSVEP modulations across conditions (P = 0.03), with stronger SSVEP during SelAtt compared with Ignore (P = 0.008). SelAtt SSVEPs in mTBI were significantly weaker than controls (P = 0.04). Unlike mTBI, control SSVEP amplitude and inter-trial phase coherence (ITPC) significantly increased across conditions (P = 0.02 and < 0.001, respectively). Both groups did not show any significant modulation in SSVEP phase across attentional conditions (P > 0.05). The significant ITPC-amplitude correlation within each group (P < 0.001) was associated with attention status, whereby SelAtt was associated with higher neural ITPC-amplitude response.These findings indicate impaired visuospatial selective attention in adults with persistent post-mTBI visual symptoms. Our results support neural synchronization theory on population-level neural correlates of attention and suggest impaired synchronization may underlie attention deficits in mTBI.SSVEP provides objective neurophysiological indices of attentional processing in mTBI.

View details for DOI 10.1016/j.clinph.2026.2112387

View details for PubMedID 42731193

View details for Web of Science ID 001880544000038

Abstract

An initial insult to an infant's developing brain can set off a chain reaction. This singular, damaging CNS event can cause subsequent injuries to the extrastriate cortex, which manifest later in childhood.

View details for DOI 10.1016/j.ophtha.2025.12.026

View details for PubMedID 41513103