Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy

The impact of changes in visual input on neuronal circuitry is complex and much of our knowledge on human brain plasticity of the visual systems comes from animal studies. Reinstating vision in a group of patients with low vision through retinal gene therapy creates a unique opportunity to dynamically study the underlying process responsible for brain plasticity. Historically, increases in the axonal myelination of the visual pathway has been the biomarker for brain plasticity. Here, we demonstrate that to reach the long-term effects of myelination increase, the human brain may undergo demyelination as part of a plasticity process. The maximum change in dendritic arborization of the primary visual cortex and the neurite density along the geniculostriate tracks occurred at three months (3MO) post intervention, in line with timing for the peak changes in postnatal synaptogenesis within the visual cortex reported in animal studies. The maximum change at 3MO for both the gray and white matter significantly correlated with patients' clinical responses to light stimulations called full field sensitivity threshold (FST). Our results shed a new light on the underlying process of brain plasticity by challenging the concept of increase myelination being the hallmark of brain plasticity and instead reinforcing the idea of signal speed optimization as a dynamic process for brain plasticity

Super-Resolution Reconstruction of Particleboard Images Based on Improved SRGAN

As an important forest product, particleboard can greatly save forestry resources and promote low-carbon development by reusing wood processing residues. The size of the entire particleboard is large, and there are problems with less image feature information and blurred defect outlines when obtaining the particleboard images. The super-resolution reconstruction technology can improve the quality of the particleboard surface images, making the defects clearer. In this study, the super-resolution dense attention generative adversarial network (SRDAGAN) model was improved to solve the problem that the super-resolution generative adversarial network (SRGAN) reconstructed image would produce artifacts and its performance needed to be improved. The Batch Normalization (BN) layer was removed, the convolutional block attention module (CBAM) was optimized to construct the dense block, and the dense blocks were constructed via a densely skip connection. Then, the corresponding 52,400 image blocks with high resolution and low resolution were trained, verified, and tested according to the ratio of 3:1:1. The model was comprehensively evaluated from the effect of image reconstruction and the three indexes of PSNR, SSIM, and LPIPS. It was found that compared with BICUBIC, SRGAN, and SWINIR, the PSNR index of SRDAGAN increased by 4.88 dB, 3.25 dB, and 2.68 dB, respectively; SSIM increased by 0.0507, 0.1122, and 0.0648, respectively; and LPIPS improved by 0.1948, 0.1065, and 0.0639, respectively. The reconstructed images not only had a clearer texture, but also had a more realistic expression of various features, and the performance of the model had been greatly improved. At the same time, this study also emphatically discussed the image reconstruction effect with defects. The result showed that the SRDAGAN proposed in this study can complete the super-resolution reconstruction of the particleboard images with high quality. In the future, it can also be further combined with defect detection for the actual production to improve the quality of forestry products and increase economic benefits

Effects of Ligand Modification and Protonation on Metal Oxime Hydrogen Evolution Electrocatalysts

The design of hydrogen-evolving electrocatalysts that operate at modest overpotentials is important for solar energy devices. The M^II/I reduction potential for metal diimine-dioxime and diglyoxime electrocatalysts is often related to the overpotential required for hydrogen evolution. Herein the impact of ligand modification and protonation on the M^II/I reduction potentials for cobalt, nickel, and iron diimine-dioxime and diglyoxime complexes is investigated with computational methods. The calculations are consistent with experimental data available for some of these complexes and additionally provide predictions for complexes that have not yet been synthesized. The calculated p<i>K</i>_a’s imply that ligand protonation is likely to occur at the O–H–O bridge but not at other ligand sites for these complexes. Moreover, the calculations imply that a ligand-protonated Co^III-hydride intermediate is formed along the H₂ production pathway for catalysts containing an O–H–O bridge in the presence of sufficiently strong acid. The calculated M^II/I reduction potentials indicate that the anodic shift due to protonation of the O–H–O bridge is greater than that due to replacing the O–H–O bridge with an O–BF₂–O bridge for cobalt and nickel but not for iron complexes. Experiments suggest degradation for complexes with two O–H–O bridges and alternative mechanisms for certain iron complexes with two O–BF₂–O bridges. Asymmetric cobalt, nickel, and strongly electron withdrawing substituted iron diimine-dioxime and diglyoxime complexes containing a single O–H–O bridge are proposed to be effective hydrogen evolution electrocatalysts with relatively low overpotentials in acetonitrile and water. These insights are important for the design of efficient aqueous-based hydrogen-evolving catalysts

Surgical Outcomes of Ahmed Glaucoma Valve Implantation with Postoperative Use of Prednisolone Acetate versus Difluprednate

To evaluate the effect of postoperative topical prednisolone acetate and difluprednate on surgical outcomes of Ahmed glaucoma valve (AGV) implantation. Retrospective, comparative case series. The study population consisted of 102 eyes of 90 patients, including 52 eyes that received 1% prednisolone acetate (Pred Forte [PF]; Allergan Inc) and 50 eyes that received 0.05% difluprednate (Durezol [DZ]; Novartis Inc). The medical records of consecutive patients who underwent AGV implantation at the University of California, San Francisco, were retrospectively reviewed. Patients in the PF group received 1% prednisolone acetate 6 to 8 times per day tapered over 5 to 6 months postoperatively, and patients in the DZ group received 0.05% difluprednate 4 times daily tapered over 4 months postoperatively. Intraocular pressure (IOP), number of glaucoma medications, visual acuity (VA), postoperative complications, and the rate of treatment success. At 1 year, the IOPs (mean ± standard deviation) were 12.4 ± 3.7 mmHg in the DZ group and 13.0 ± 4.0 mmHg in the PF group (P = 0.49). The numbers of glaucoma medications were 0.72 ± 0.71 in the DZ group and 1.09 ± 0.91 in the PF group (P = 0.04), with reductions from baseline of 2.5  ±  1.0 glaucoma medications in the DZ group and 1.8  ±  1.6 glaucoma medications in the PF group (P = 0.01). The logarithm of the minimum angle of resolution VAs (mean  ±  standard deviation) were 0.55 ± 0.80 in the DZ group and 0.59 ± 0.65 in the PF group after 1 year of follow-up (P = 0.81). The cumulative probabilities of success were 95.8% in the DZ group and 93.5% in the PF group at 1 year (P = 0.61). Postoperative complications occurred in 4 eyes (7.7%) in the DZ group and 6 eyes (12%) in the PF group (P = 0.52). After 1 year, postoperative treatment with 0.05% difluprednate after AGV implantation resulted in a similar IOP, with the use of fewer glaucoma medications, compared with postoperative treatment with 1% prednisolone acetate. The rates of treatment success and surgical complications were comparable between the 2 groups during the first year of follow-up

Dynamic structural remodeling of the human visual system prompted by bilateral retinal gene therapy

The impact of changes in visual input on neuronal circuitry is complex and much of our knowledge on human brain plasticity of the visual systems comes from animal studies. Reinstating vision in a group of patients with low vision through retinal gene therapy creates a unique opportunity to dynamically study the underlying process responsible for brain plasticity. Historically, increases in the axonal myelination of the visual pathway has been the biomarker for brain plasticity. Here, we demonstrate that to reach the long-term effects of myelination increase, the human brain may undergo demyelination as part of a plasticity process. The maximum change in dendritic arborization of the primary visual cortex and the neurite density along the geniculostriate tracks occurred at three months (3MO) post intervention, in line with timing for the peak changes in postnatal synaptogenesis within the visual cortex reported in animal studies. The maximum change at 3MO for both the gray and white matter significantly correlated with patients’ clinical responses to light stimulations called full field sensitivity threshold (FST). Our results shed a new light on the underlying process of brain plasticity by challenging the concept of increase myelination being the hallmark of brain plasticity and instead reinforcing the idea of signal speed optimization as a dynamic process for brain plasticity

Evaluation of Long-Term Visual Field Function in Patients Undergoing Glaucoma Drainage Device Implantation

To determine the change in global and regional Humphrey visual fields (VF) after glaucoma drainage device (GDD) implantation over a 3-year follow-up period. Retrospective interventional case series. Patients undergoing GDD placement from between 2010 and 2015 with reliable preoperative and yearly postoperative VF measurements were included. Clinical parameters were compared between preoperative and follow-up visits, including visual acuity, intraocular pressure (IOP), number of glaucoma medications, global VF metrics (mean deviation [MD]), pattern standard deviation (PSD), CIGTS (Collaborative Initial Glaucoma Treatment Study) score of total deviation probability (CIGTS_TDP) and pattern deviation probability (CIGTS_PDP), and regional metrics (regional total deviation (TD), regional pattern deviation (PD), and regional CIGTS_TDP and CIGTS_PDP). Multivariate regression analyses were performed to determine risk factors for VF worsening after GDD surgery. A total of 106 eyes from 95 patients were included. Mean IOP ± SD was reduced from 23.1 ± 8.5 mm Hg to 12.7 ± 3.1 mm Hg at 3-year follow-up (P < .001). MD, PSD, and global CIGTS_PDP showed no significant changes in follow-up, whereas global CIGTS_TDP showed mild progression from 10.7 to 12.8 at 3-year follow-up (P = .01). No regional metrics showed worsening at follow-up examinations. Defects in the superior hemifield were more common than in the inferior hemifield at baseline and follow-up examinations for all regional metrics. Pre-operative number of glaucoma medications was associated with worsening on CIGTS_TDP. Overall, GDD surgery is effective at stabilizing VF function over 3 years of follow-up. The superior hemifield is affected more than other regions. The number of pre-operative glaucoma medications is associated with mild VF progression, measured by CIGTS_TDP. •GDD implantation is increasingly used as primary procedure for uncontrolled glaucoma.•GDD implantation stabilizes both global and regional VF function over 3 years- Superior hemifield defects were more common than inferior at baseline and follow-ups.•Number of pre-operative glaucoma drops is associated with long-term VF progression

Age Associations with Dry Eye Clinical Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study

Purpose: To evaluate how increasing age is associated with dry eye disease (DED) signs and symptoms in the Dry Eye Assessment and Management (DREAM) study. This study was undertaken to better understand how DED signs and symptoms differ across decades of life with goals to help assess detection and treatment of DED. Design: Secondary analysis of the DREAM study. Subjects: One hundred twenty, 140, 185, and 90 participants aged < 50, 50 to 59, 60 to 69, and ≥ 70 years, respectively. Methods: We performed a secondary analysis of data from the DREAM study, a multicenter randomized clinical trial, to evaluate the effect of omega-3 fatty acid supplementation for the treatment of DED. At baseline, 6 months, and 12 months follow-up, participants underwent an assessment of DED symptoms and signs using Ocular Surface Disease Index, Brief Pain Inventory, tear break-up time (TBUT) (in seconds), Schirmer test with anesthesia (mm/5 minutes), conjunctival staining, corneal staining, meibomian gland dysfunction evaluation, and tear osmolarity (mOsm/l). Multivariable generalized linear regression models were used to compare DED symptoms and signs across the 4 age groups among all participants and by sex. Main Outcome Measures: Scores of DED symptoms, individual signs, and composite scores of DED signs. Results: Among 535 patients with DED, increasing age was significantly associated with worse TBUT (P = 0.01), corneal staining (P < 0.001), a composite severity score of DED signs (P = 0.007), and tear osmolarity (P = 0.001). Similar significant differences were found across 4 age groups of 334 women in TBUT, corneal staining score, composite severity score of DED signs, and tear osmolarity (all P < 0.05) but not in men. Conclusion: We found that corneal staining, TBUT, tear osmolarity, and a composite severity score of DED signs were significantly more severe with increasing age in women but not in men; worsening symptoms did not increase with increasing age. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article

Ocular examinations, findings, and toxicity in children taking vigabatrin

BackgroundThe antiepileptic medication vigabatrin has been associated with ocular toxicity, and close ophthalmic monitoring has been recommended; however, there is no clear consensus regarding the value and feasibility of such monitoring in children. We describe ophthalmic assessments in children in a real-world clinical setting, the incidence of vigabatrin-related ocular toxicity, and the utility of regular screening or ancillary testing in children taking vigabatrin.MethodsThe medical records of children taking vigabatrin with one or more ophthalmic assessments at Children's Hospital of Philadelphia or University of California, San Francisco, between May 2010 and May 2021, were reviewed retrospectively. Abnormalities on ophthalmic examination, visual field (VF), electroretinogram (ERG), and optical coherence tomography (OCT) were reviewed and categorized as attributable to vigabatrin, possibly attributable to vigabatrin, or not attributable to vigabatrin.ResultsA total of 1,281 assessments of 284 children (mean age, 2.09 years) were included. Of these, 283 (99.6%) had funduscopic examination(s), 37 (13.0%) had ERG, 19 (6.7%) had OCT, and 6 (2.1%) had formal VF. Rate of examinations and ERGs per child decreased over the 10-year study period. Two children (0.7%) had definite vigabatrin-related ocular toxicity, both identified on ERG. An additional 4 children (1.4%) had optic atrophy of unclear relation to vigabatrin, categorized as possible toxicity. The remaining 278 children did not have abnormal examination or testing findings attributable to vigabatrin.ConclusionsThe incidence of vigabatrin-related ocular toxicity in children was low in our cohort. Ocular and neurologic comorbidities and limited examinations in children make identification of such toxicity challenging and the value of screening is unclear