Abstract

Hydrocephalus is a challenging neurosurgical condition due to nonspecific symptoms and complex brain-fluid pressure dynamics. Typically, the assessment of hydrocephalus in children requires radiographic or invasive pressure monitoring. There is usually a qualitative focus on the ventricular spaces even though stress and shear forces extend across the brain. Here, the authors present an MRI-based vector approach for voxelwise brain and ventricular deformation visualization and analysis.Twenty pediatric patients (mean age 7.7 years, range 6 months-18 years; 14 males) with acute, newly diagnosed hydrocephalus requiring surgical intervention for symptomatic relief were randomly identified after retrospective chart review. Selection criteria included acquisition of both pre- and posttherapy paired 3D T1-weighted volumetric MRI (3D T1-MRI) performed on 3T MRI systems. Both pre- and posttherapy 3D T1-MRI pairs were aligned using image registration, and subsequently, voxelwise nonlinear transformations were performed to derive two exemplary visualizations of compliance: 1) a whole-brain vector map projecting the resulting deformation field on baseline axial imaging; and 2) a 3D heat map projecting the volumetric changes along ventricular boundaries and the brain periphery.The patients underwent the following interventions for treatment of hydrocephalus: endoscopic third ventriculostomy (n = 6); external ventricular drain placement and/or tumor resection (n = 10); or ventriculoperitoneal shunt placement (n = 4). The mean time between pre- and postoperative imaging was 36.5 days. Following intervention, the ventricular volumes decreased significantly (mean pre- and posttherapy volumes of 151.9 cm3 and 82.0 cm3, respectively; p < 0.001, paired t-test). The largest degree of deformation vector changes occurred along the lateral ventricular spaces, relative to the genu and splenium. There was a significant correlation between change in deformation vector magnitudes within the cortical layer and age (p = 0.011, Pearson), as well as between the ventricle size and age (p = 0.014, Pearson), suggesting higher compliance among infants and younger children.This study highlights an approach for deformation analysis and vector mapping that may serve as a topographic visualizer for therapeutic interventions in patients with hydrocephalus. A future study that correlates the degree of cerebroventricular deformation or compliance with intracranial pressures could clarify the potential role of this technique in noninvasive pressure monitoring or in cases of noncompliant ventricles.

View details for DOI 10.3171/2024.6.PEDS24117

View details for PubMedID 39178478

View details for DOI 10.1016/j.jpeds.2024.114229

View details for PubMedID 39178940

View details for DOI 10.1093/neuonc/noae064.582

View details for Web of Science ID 001252720000219

Abstract

PURPOSE: To investigate retinal fluid features and ellipsoid zone (EZ) integrity dynamics on spectral-domain OCT (SD-OCT) in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept injection (IAI) in the VISTA-DME study.DESIGN: A post hoc subanalysis of a phase III, prospective clinical trial.PARTICIPANTS: Eyes received either IAI 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly doses (2q8).METHODS: All eyes from the VISTA Phase III study in the IAI groups imaged with the Cirrus HD-OCT system (Zeiss, Oberkochen, Germany) were included. The OCT macular cube datasets were evaluated using a novel software platform to generate retinal layer and fluid boundary lines that were manually corrected for assessment of change in EZ parameters and volumetric fluid parameters from baseline. The retinal fluid index (i.e., proportion of the retinal volume consisting of cystic fluid) was also calculated at each time point.MAIN OUTCOME MEASURES: The feasibility of volumetric assessment of higher-order OCT-based retinal parameters and its correlation with best-corrected visual acuity (BCVA).RESULTS: Overall, 106 eyes of 106 patients were included. Specifically, 52 eyes of 52 patients were included in the IAI 2q4 arm, and 54 eyes of 54 patients were included in the IAI 2q8 arm. Ellipsoid zone integrity metrics significantly improved from baseline to week 100, including central macular mean EZ to retinal pigment epithelium (RPE) thickness (2q4: 26.6 mum to 31.6 mum, P < 0.001; 2q8: 25.2 mum to 31.4 mum, P < 0.001). At week 100, central macular intraretinal fluid volume was reduced by >65% (P < 0.001) and central macular subretinal fluid volume was reduced by >99% in both arms (P < 0.001). Central macular retinal fluid index (RFI) significantly improved in both arms (2q4: 17.9% to 7.2%, P < 0.001; 2q8: 19.8% to 4.2%, P < 0.001). Central macular mean EZ-RPE thickness (i.e., a surrogate for photoreceptor outer segment length) and central RFI were independently correlated with BCVA at multiple follow-up visits.CONCLUSIONS: Intravitreal aflibercept injection resulted in significant improvement in EZ integrity and quantitative fluid metrics in both 2q4 and 2q8 arms and correlated with visual function.

View details for DOI 10.1016/j.oret.2019.06.010

View details for PubMedID 31473172

Abstract

Purpose: To report a case of presumed bilateral chorioretinitis secondary to alendronate therapy.Observations: A 71-year-old female presented to the clinic in July 2017 with six months history of difficulty in reading along with floaters in both eyes which were more severe in the right eye. Past medical and surgical history revealed a history of hypertension, gout, hyperthyroidism, osteoporosis, and humerus fracture. She was started on alendronate three months before developing ocular symptoms. On ocular examination, best corrected visual acuity was 20/30 in the right and 20/25 in the left eye. Slit-lamp examination demonstrated normal anterior chamber examination in both eyes. Dilated fundus examination revealed geographic chorioretinal lesions around the optic nerve head in both eyes, more extensively in the right eye; and superior and temporal to the macula in the right eye. Past ocular records in February 2015 did not reveal any such findings. Fundus autofluorescence demonstrated hyper-autofluorescence in the peripapillary lesions in both eyes. The lesion adjacent to the macula in right eye displayed mixed hyper and hypo-autofluorescence. Fluorescein angiography showed combined hyper- and hypo-fluorescence compatible with window defect, staining and blockage. However, no leakage was appreciated in the macula, peripapillary, and peripheral lesions in both eyes. Optical coherence tomography scan showed septate hyporeflective intraretinal spaces in the right eye.Conclusion and importance: The index report underscore the importance of considering alendronate as an etiologic cause of chorioretinitis, especially in subjects with atypical lesions developing after alendronate therapy. We, therefore, recommend discontinuation of this medication in subjects who develop chorioretinitis after employing this medication.

View details for PubMedID 30809598

Abstract

Purpose: To describe new cases of sclopetaria and evaluate the risk factors, management, and visual prognosis of all reported cases in the literature.Observations: We performed a retrospective, observational case series. This study included six cases (median age 23, interquartile range 33) of sclopetaria. Additionally, literature searches were conducted in the PubMed and Cochrane Library databases to uncover risk factors associated with all published cases of sclopetaria. Main outcome measure was best corrected visual acuity (BCVA) worse than 20/20. Sixty-seven cases (71 eyes) of sclopetaria have been reported, of which 59 cases (61 eyes) met inclusion criteria in this study. Most were young (median age 19.5 years) men (51/59, 88.1%). Thirty-seven eyes were observed while 24 underwent immediate surgery including six pars plana vitrectomies and three scleral buckles. Compared to initial presentation, BCVA improved in 31/48 (64.6%) eyes, remained stable in 12/48 eyes (25.0%), and worsened in 5/48 eyes (10.4%). Ten patients (16.4%) achieved a final BCVA of 20/20 with median follow up time of seven months. In a multivariate model, location of sclopetaria in the macula, temporal retina, or immediate orbital foreign body removal predicted poor final BCVA with an area under receiver operating characteristic curve of 0.767.Conclusions and importance: Traumatic chorioretinitis sclopetaria is rare, but reports have increased dramatically over the past two decades. While pars plana vitrectomy may be required for the management of retinal detachments and non-clearing vitreous hemorrhage, close observation is appropriate in most cases. Visual prognosis is poor with most patients attaining 20/200 vision or worse.

View details for PubMedID 30834355

Abstract

We explore camera-based pupil tracking using high-level programming in computing platforms with end-user discrete and integrated central processing units (CPUs) and graphics processing units (GPUs), seeking low calculation latencies previously achieved with specialized hardware and programming (Kowalski et al., [Biomed. Opt. Express12, 6496 (2021)10.1364/BOE.433766]. Various desktop and embedded computers were tested, some with two operating systems, using the traditional sequential pupil tracking paradigm, in which the processing of the camera image only starts after it is fully downloaded to the computer. The pupil tracking was demonstrated using two Scheimpflug optical setups, telecentric in both image and object spaces, with different optical magnifications and nominal diffraction-limited performance over an ∼18 mm full field of view illuminated with 940 nm light. Eye images from subjects with different iris and skin pigmentation captured at this wavelength suggest that the proposed pupil tracking does not suffer from ethnic bias. The optical axis of the setups is tilted at 45° to facilitate integration with other instruments without the need for beam splitting. Tracking with ∼0.9-4.4 µm precision and safe light levels was demonstrated using two complementary metal-oxide-semiconductor cameras with global shutter, operating at 438 and 1,045 fps with an ∼500 × 420 pixel region of interest (ROI), and at 633 and 1,897 fps with ∼315 × 280 pixel ROI. For these image sizes, the desktop computers achieved calculation times as low as 0.5 ms, while low-cost embedded computers delivered calculation times in the 0.8-1.3 ms range.

View details for DOI 10.1364/BOE.541421

View details for PubMedID 39679407

View details for PubMedCentralID PMC11640584

Abstract

Cone photoreceptor inner segments visualized in non-confocal split-detection adaptive optics scanning light ophthalmoscope (AOSLO) images appear as obliquely illuminated domes with bright and dark opposing regions. Previously, the pairing of these bright and dark regions for automated photoreceptor identification has necessitated complex algorithms. Here we demonstrate how the merging of split-detection images captured with a non-confocal quadrant light detection scheme allows automated cone identification using simple, open-source image processing tools, while also improving accuracy in both normal and pathologic retinas.

View details for DOI 10.1364/BOE.539001

View details for PubMedID 39553865

View details for PubMedCentralID PMC11563324

View details for DOI 10.1364/BOE.539001

View details for Web of Science ID 001332856400001

Abstract

Loss of retinal ganglion cells (RGCs) is central to the pathogenesis of optic neuropathies such as glaucoma. Increased RGC cAMP signaling is neuroprotective. We have shown that displacement of the cAMP-specific phosphodiesterase PDE4D3 from an RGC perinuclear compartment by expression of the modified PDE4D3 N-terminal peptide 4D3(E) increases perinuclear cAMP and protein kinase A activity in cultured neurons and in vivo RGC survival after optic nerve crush (ONC) injury. To explore mechanisms by which PDE4D3 displacement promotes neuroprotection, in this study mice intravitreally injected with an adeno-associated virus to express an mCherry-tagged 4D3(E) peptide were subjected to ONC injury and analyzed by single cell RNA-sequencing (scRNA-seq). 4D3(E)-mCherry expression was associated with an attenuation of injury-induced changes in gene expression, thereby supporting the hypothesis that enhanced perinuclear PKA signaling promotes neuroprotective RGC gene expression.

View details for DOI 10.1016/j.exer.2024.110017

View details for PubMedID 39097072

Abstract

Familial dilated cardiomyopathy is a prevalent cause of heart failure that results from the mutation of genes encoding proteins of diverse function. Despite modern therapy, dilated cardiomyopathy typically has a poor outcome and is the leading cause of cardiac transplantation. The phosphatase PP2A at cardiomyocyte perinuclear mAKAPβ signalosomes promotes pathological eccentric cardiac remodeling, as is characteristic of dilated cardiomyopathy. Displacement of PP2A from mAKAPβ, inhibiting PP2A function in that intracellular compartment, can be achieved by expression of a mAKAPβ-derived PP2A binding domain-derived peptide. To test whether PP2A anchoring disruption would be effective at preventing dilated cardiomyopathy-associated cardiac dysfunction, the adeno-associated virus gene therapy vector AAV9sc.PBD was devised to express the disrupting peptide in cardiomyocytes in vivo. Proof-of-concept is now provided that AAV9sc.PBD improves the cardiac structure and function of a cardiomyopathy mouse model involving transgenic expression of a mutant α-tropomyosin E54K Tpm1 allele, while AAV9sc.PBD has no effect on normal non-transgenic mice. At the cellular level, AAV9sc.PBD restores cardiomyocyte morphology and gene expression in the mutant Tpm1 mouse. As the mechanism of AAV9sc.PBD action suggests potential efficacy in dilated cardiomyopathy regardless of the underlying etiology, these data support the further testing of AAV9sc.PBD as a broad-based treatment for dilated cardiomyopathy.

View details for DOI 10.1016/j.omtm.2024.101233

View details for PubMedID 38572067

View details for PubMedCentralID PMC10988123

View details for Web of Science ID 001313316200208

Abstract

Dry age-related macular degeneration (AMD) has been historically managed with lifestyle modifications, monitoring for conversion to wet AMD, and vitamins. Recently there has been a flurry of research focused on discovering new targets to prevent worsening of dry AMD. In 2023, the US Food and Drug Administration approved the first two intravitreal complement inhibitors to slow the rate of geographic atrophy progression. However, serial intravitreal injections for a chronic progressive disease are burdensome for patients and have procedural risks. Therefore, there is significant research to discover novel oral medications to manage dry AMD. Several oral medications are currently in phase 2 and 3 clinical trials for dry AMD, whereas others have had recent readouts on their clinical trials and efficacy. The purpose of this review is to describe the therapeutic pathways currently being investigated and to provide an update on the clinical status of novel oral medications for the management of dry AMD. [Ophthalmic Surg Lasers Imaging Retina 2024;55:528-534.].

View details for DOI 10.3928/23258160-20240430-02

View details for Web of Science ID 001346253500008

View details for PubMedID 38917394

Abstract

We aim to present a case of disseminated fusariosis that occurred in the setting of immunosuppression and presented with bilateral endogenous endophthalmitis, along with a literature review of Fusarium endophthalmitis, highlighting management strategies.A 70-year-old male with acute myeloid leukemia who had recently undergone a bone marrow transplant noted bilateral floaters and decreased vision. He was found to have bilateral Fusarium endophthalmitis, with subsequent evidence of fungemia and fusariosis in his skin and joints. Despite aggressive local and systemic treatment, he succumbed to the disease. Endophthalmitis was initially stabilized with pars plana vitrectomy and intravitreal amphotericin and voriconazole until the patient transitioned to comfort measures. A review of 31 cases demonstrates that outcomes are poor and that the disease must be treated aggressively, often both systemically and surgically.This case highlights the recalcitrance of Fusarium bacteremia and Fusarium endophthalmitis.

View details for DOI 10.3390/vision8030044

View details for PubMedID 39051230

Abstract

Traumatic Brain Injury (TBI) induces neuroinflammatory response that can initiate epileptogenesis, which develops into epilepsy. Recently, we identified anti-convulsive effects of naltrexone, a mu-opioid receptor (MOR) antagonist, used to treat drug addiction. While blocking opioid receptors can reduce inflammation, it is unclear if post-TBI seizures can be prevented by blocking MORs. Here, we tested if naltrexone prevents neuroinflammation and/or seizures post-TBI. TBI was induced by a modified Marmarou Weight-Drop (WD) method on 4-week-old C57BL/6J male mice. Mice were placed in two groups: non-telemetry assessing the acute effects or in telemetry monitoring for interictal events and spontaneous seizures both following TBI and naltrexone. Molecular, histological and neuroimaging techniques were used to evaluate neuroinflammation, neurodegeneration and fiber track integrity at 8 days and 3 months post-TBI. Peripheral immune responses were assessed through serum chemokine/cytokine measurements. Our results show an increase in MOR expression, nitro-oxidative stress, mRNA expression of inflammatory cytokines, microgliosis, neurodegeneration, and white matter damage in the neocortex of TBI mice. Video-EEG revealed increased interictal events in TBI mice, with 71% mice developing post-traumatic seizures (PTS). Naltrexone treatment ameliorated neuroinflammation, neurodegeneration, reduced interictal events and prevented seizures in all TBI mice, which makes naltrexone a promising candidate against PTS, TBI-associated neuroinflammation and epileptogenesis in a WD model of TBI.

View details for DOI 10.1038/s41598-024-63942-8

View details for PubMedID 38867062

View details for PubMedCentralID 7301453

Abstract

This review article represents a collaborative effort across continents, bringing together the latest developments in neuro-ophthalmology with a focus on innovative diagnostic and therapeutic modalities that are shaping the future of the field. Among the most significant advancements is the rise of optical coherence tomography (OCT), now recognized as an indispensable tool in neuro-ophthalmological research, providing unparalleled insights into optic nerve and central nervous system pathologies. Gene therapy, particularly for conditions such as Leber's hereditary optic neuropathy, marks a new frontier in personalized medicine, offering hope for previously untreatable conditions. The article also examines the transformative role of telemedicine and artificial intelligence (AI) in clinical practice, which are revolutionizing patient care and enhancing diagnostic precision. Furthermore, it highlights the impact of novel serological biomarkers on the understanding and management of immune-mediated optic neuritis, and discusses the introduction of new therapeutic agents like Tocilizumab and Teprotumumab, which are redefining treatment paradigms. Collectively, these advancements reflect the profound influence of modern medicine on neuro-ophthalmology, paving the way for improved patient outcomes and fostering new avenues for research and clinical practice.

View details for DOI 10.4103/IJO.IJO_594_24

View details for PubMedID 39462921

View details for DOI 10.1001/jamaophthalmol.2024.4377

View details for PubMedID 39418056

View details for Web of Science ID 001324906900098

Abstract

Targeted drug delivery to the optic nerve head may be useful in the preclinical study and later clinical management of optic neuropathies, however, there are no FDA-approved drug delivery systems to achieve this. The purpose of this work was to develop an optic nerve head drug delivery technique.Different strategies to approach the optic nerve head were investigated, including standard intravitreal and retroorbital injections. A novel SupraChoroidal-to-Optic-NervE (SCONE) delivery was optimized by creating a sclerotomy and introducing a catheter into the suprachoroidal space. Under direct visualization, the catheter was guided to the optic nerve head. India ink was injected. The suprachoroidal approach was performed in New Zealand White rabbit eyes in vivo (25 animals total). Parameters, including microneedle size and design, catheter design, and catheter tip angle, were optimized ex vivo and in vivo.Out of the candidate optic nerve head approaches, intravitreal, retroorbital, and suprachoroidal approaches were able to localize India ink to within 2 mm of the optic nerve. The suprachoroidal approach was further investigated, and after optimization, was able to deposit India ink directly within the optic nerve head in up to 80% of attempts. In eyes with successful SCONE delivery, latency and amplitude of visual evoked potentials was not different than the naïve untreated eye.SCONE delivery can be used for targeted drug delivery to the optic nerve head of rabbits without measurable toxicity measured anatomically or functionally. Successful development of this system may yield novel opportunities to study optic nerve head-specific drug delivery in animal models, and paradigm-shifting management strategies for treating optic neuropathies.Here we demonstrate data on a new method for targeted delivery to the optic nerve head, addressing a significant unmet need in therapeutics for optic neuropathies.

View details for DOI 10.1080/10717544.2024.2379369

View details for PubMedID 39010743

View details for DOI 10.1001/jamaophthalmol.2024.4493

View details for PubMedID 39480408

View details for DOI 10.1016/j.oret.2017.03.002

Abstract

Concussed adolescents often report visual symptoms, especially for moving targets, but the mechanisms resulting in oculomotor deficits remain unclear. We objectively measured accommodative and vergence responses to a moving target in concussed adolescents and controls.Thirty-two symptomatic concussed participants (mean age, 14.4 ± 2.6 years; mean days since concussion, 107 days; range, 36-273 days) and 32 healthy controls (mean age, 12.7 ± 2.1 years) viewed a movie binocularly (closed-loop) and monocularly (vergence open-loop), as well as a Difference of Gaussians (DoG) target binocularly (accommodation open-loop). The movie or DoG target sinusoidally moved toward and away from participants at a 0.1-hertz (Hz) frequency at four separate stimulus amplitudes (1.50 diopters [D], 1.00 D, 0.50 D, 0.25 D) around a 2.50-D midpoint. Accommodation and vergence were continuously measured at 50 Hz using the PowerRef 3. Fourier analysis was used to assess the response amplitudes at the 0.1-Hz frequency. A 2 × 3 analysis of variance with the factors group (concussed, control) and viewing condition (binocular, monocular, DoG) was conducted on response amplitudes.Across groups, accommodative and vergence responses were significantly higher in binocular than monocular conditions (P < 0.001), but not DoG conditions. Compared to controls, concussed participants had significantly reduced monocular accommodative responses (P < 0.012; e.g., at 1.50 D, controls = 1.09 ± 0.47 D and concussed = 0.80 ± 0.36 D, P = 0.011). No group differences were observed for vergence responses in any viewing condition.Accommodative and vergence responses to the moving target were largely driven by disparity cues for both groups, with only minimal improvements in the presence of additional blur cues. Concussed participants showed reduced accommodative responses to a 0.1-Hz stimulus in monocular conditions, indicating mild accommodative deficits in the absence of disparity cues.

View details for DOI 10.1167/iovs.65.12.45

View details for PubMedID 39475939

View details for DOI 10.1097/OPX.0000000000002198

View details for PubMedID 39480127

Abstract

To assess the long-term stability of clinical measures of convergence (near point of convergence [NPC] and positive fusional vergence [PFV]) in participants enrolled in the Convergence Insufficiency Treatment Trial-Attention and Reading Trial (CITT-ART) who received 16 weeks of office-based vergence/accommodative therapy.A total of 310 children, 9-14 years old, with symptomatic convergence insufficiency were enrolled in CITT-ART. Some 270 completed both their 16-week primary outcome visit followed by a 1-year follow-up visit. Of those 270, 181 (67%) were randomised to the vergence/accommodative therapy. Of the 181 in the vergence/accommodative group, 121 (67%) reported not receiving any additional treatment after the 16-week primary outcome visit. The mean change in NPC, PFV and percentages of children classified by the predetermined success criteria of convergence (normal NPC [<6 cm] and/or improved by ≥4 cm; normal PFV [passing Sheard's criterion and base-out break >15Δ] and/or improved by ≥10Δ) were compared at the 16-week primary outcome visit and 1 year later.Of the 121 who returned for their 1-year follow-up visit, there was no significant change in mean adjusted NPC (reduction of -0.2 cm; 95% CI: -1.0 to 0.5 cm) at 1 year. There was a statistically significant decrease in mean-adjusted PFV (-4.7∆; 95% CI: -6.5 to -2.8Δ) at 1 year. There were similar percentages of participants classified as 'normal' (p = 0.30), 'normal and/or improved' (p > 0.50) and 'normal and improved' (p > 0.14) based on NPC and PFV at the 1-year visit compared with the 16-week primary outcome visit.The improvements in NPC and PFV following 16 weeks of vergence/accommodative therapy (with no reported additional treatment thereafter) in children with symptomatic convergence insufficiency persisted 1-year post-treatment.

View details for DOI 10.1111/opo.13378

View details for PubMedID 39141379

Abstract

Retinitis pigmentosa (RP) is a complex group of inherited retinal diseases characterized by progressive death of photoreceptor cells and eventual blindness. Pde6a, which encodes a cGMP-specific phosphodiesterase, is a crucial pathogenic gene for autosomal recessive RP (RP43); there is no effective therapy for this form of RP. The compact CRISPR/SaCas9 system, which can be packaged into a single adeno-associated virus, holds promise for simplifying effective gene therapy. Here, we demonstrated that all-in-one AAV-SaCas9-mediated Nrl gene inactivation can efficiently prevent retinal degeneration in a RP mouse model with Pde6anmf363/nmf363 mutation. We screened single guide RNAs (sgRNAs) capable of efficiently editing mouse Nrl gene in N2a cells and then achieved effective gene editing by using a single AAV to co-deliver SaCas9 and an optimal Nrl-sg2 into the mouse retina. Excitingly, in vivo inactivation of Nrl improved photoreceptor cell survival and rescued retinal function in treated Pde6a deficient mice. Thus, we showed that a practical, gene-independent method, AAV-SaCas9-mediated Nrl inactivation, holds promise for future therapeutic applications in patients with RP.

View details for DOI 10.1172/jci.insight.178159

View details for PubMedID 39499900

Abstract

There remain limited therapies to treat thyroid eye disease (TED) orbital fibrosis, highlighting the urgency to develop novel targets. Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts are important pathogenetic factor of TED. Endoplasmic reticulum (ER) stress may play a role in TED pathogenesis since it has been linked to liver, kidney, heart and lung fibrotic remodelling. We would evaluate the role of thioredoxin domain containing 5 (TXNDC5), a fibroblast-enriched ER protein, in TGF-β1-induced myofibroblast transdifferentiation from TED orbital fibroblasts.Orbital fibroblasts from patients with TED were treated with TGF-β1 to investigate ER stress-relative gene expression especially for TXNDC5. To determine if TXNDC5 is involved in TGF-β1-induced fibrosis, we transfected TED orbital fibroblasts by lentivirus with a small hairpin RNA of pLKO-TXNDC5 gene (shTXNDC5) to knockdown TXNDC5 protein expression levels. After transfection of shTXNDC5 in TED orbital fibroblast followed by TGF-β1 treatment, we analysed TGF-β1-induced fibrosis protein expression.We measured increased TXNDC5 gene and protein expression in primary TED orbital fibroblasts. TXNDC5 protein levels were increased in TED orbital fibroblasts under TGF-β1 stimulation (2.5, 5, 10 and 20 ng/mL). Moreover, TXNDC5 knockdown of attenuated TGFβ1 (5 ng/mL)-induced myofibroblast transdifferentiation and extracellular matrix protein upregulation whereas increasing TXNDC5 expression by a recombinant protein of TXNDC5 (rhTXNDC5) addition increased alpha smooth muscle actin, fibronectin and connective tissue growth factor protein expression.In conclusion, targeting TXNDC5 may be a novel therapeutic approach against TGF-β1-induced myofibroblast transdifferentiation in TED orbital fibroblasts.

View details for DOI 10.1136/bmjophth-2024-001693

View details for PubMedID 39721966

Abstract

Cannabis is the most used drug worldwide with an estimated 219 million users. This narrative review aims to explore the adverse effects and therapeutic applications of cannabis and cannabinoids on the eye, given its growing clinical and non-clinical uses. The current literature reports several adverse ocular effects of cannabis and cannabinoids, including eyelid tremor, ptosis, reduced corneal endothelial cell density, dry eyes, red eyes, and neuro-retinal dysfunction. Cannabinoids may transiently impair night vision, depth perception, binocular and monocular contrast sensitivity, and dynamic visual acuity. Cannabinoids are not currently considered a first-line treatment option for any ocular conditions. Δ-9-tetrahydrocannabinol been shown to result in short-term intraocular pressure reduction, but insufficient evidence to support its use in treating glaucoma exists. Potential therapeutic applications of cannabinoids include their use as a second-line agent for treatment-refractory blepharospasm, for dry eye disease given corneal anti-inflammatory properties, and for suppression of pendular nystagmus in individuals with multiple sclerosis, which all necessitate further research for informed clinical practices.

View details for DOI 10.2147/OPTH.S501494

View details for PubMedID 39629058

View details for PubMedCentralID PMC11613704

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

Recent evidence from small animal models and human electrophysiology suggests that the OFF-pathway is more vulnerable to glaucomatous insult than the ON-pathway. Thus, OFF-pathway based measurements of visual function may be useful in the diagnosis of Glaucoma. The steady-state visually evoked potential (SSVEP) can be used to non-invasively make such functional measurements. Here, we examine whether OFF- and ON-pathway biasing SSVEP measurements differently predict glaucoma diagnosis using a large cohort of 98 glaucoma patients and 71 controls. Using both a logistic regression with k-fold cross-validation and a random forest classifier, we show that OFF-pathway biasing features produce a small improvement in predictive accuracy over ON-pathway biasing features. However, despite our inclusion of many more response features and the retention of both participants' eyes, our classifier did not perform as well as previous reports that used the isolated-check VEP. This is likely a result of the relatively small amount of data we collected for each participant, but may also be explained by the absence of any train-test splitting in preexisting work. Nevertheless, our results support further exploration of the diagnostic potential of OFF-pathway biasing functional biomarkers for glaucoma.

View details for DOI 10.1101/2024.08.22.24312443

View details for PubMedID 39228700

View details for PubMedCentralID PMC11370506

Abstract

Musical engagement can be conceptualized through various activities, modes of listening and listener states. Recent research has reported that a state of focused engagement can be indexed by the inter-subject correlation (ISC) of audience responses to a shared naturalistic stimulus. While statistically significant ISC has been reported during music listening, we lack insight into the temporal dynamics of engagement over the course of musical works-such as those composed in the Western classical style-which involve the formulation of expectations that are realized or derailed at subsequent points of arrival. Here, we use the ISC of electroencephalographic (EEG) and continuous behavioural (CB) responses to investigate the time-varying dynamics of engagement with functional tonal music. From a sample of adult musicians who listened to a complete cello concerto movement, we found that ISC varied throughout the excerpt for both measures. In particular, significant EEG ISC was observed during periods of musical tension that built to climactic highpoints, while significant CB ISC corresponded more to declarative entrances and points of arrival. Moreover, we found that a control stimulus retaining envelope characteristics of the intact music, but little other temporal structure, also elicited significantly correlated EEG and CB responses, though to lesser extents than the original version. In sum, these findings shed light on the temporal dynamics of engagement during music listening and clarify specific aspects of musical engagement that may be indexed by each measure.

View details for DOI 10.1111/ejn.16324

View details for PubMedID 38626924

Abstract

Purpose: Our goal is to describe the contrast and blur sensitivity of multiple horizontal disparity subsystems and to relate them to the contrast and spatial sensitivities of their monocular inputs.Methods: Steady-state visual evoked potential (SSVEP) amplitudes were recorded in response to dynamic random dot stereograms (DRDSs) alternating at 2 Hz between zero disparity and varying magnitudes of crossed disparity for disparity plane and disparity grating stimuli. Half-image contrasts ranged between 2.5% and 80% and over a range of Gaussian blurs from 1.4 to 12 arcmin. Separate experiments measured contrast and blur sensitivity for the monocular half-images.Results: The first and second harmonics disparity responses were maximal for disparity gratings and for the disparity plane condition, respectively. The first harmonic of the disparity grating response was more affected by both contrast and blur than was the second harmonic of the disparity plane response, which had higher contrast sensitivity than the first harmonic.Conclusions: The corrugation frequency, contrast, and blur tuning of the first harmonic suggest that it reflects activity of neurons tuned to higher luminance spatial frequencies that are selective for relative disparity, whereas the second harmonic reflects the activity of neurons sensitive to absolute disparity that are driven by low monocular spatial frequencies.Translational Relevance: SSVEPs to DRDSs provide two objective neural measures of disparity processing, the first harmonic-whose stimulus preferences are similar to those of behavioral stereoacuity-and the second harmonic that represents an independent disparity-specific but not necessarily stereoscopic mechanism.

View details for DOI 10.1167/tvst.13.2.21

View details for PubMedID 38411970