Impedimetric Biosensors for Detecting Vascular Endothelial Growth Factor (VEGF) Based on Poly(3,4-ethylene dioxythiophene) (PEDOT)/Gold Nanoparticle (Au NP) Composites

In advanced forms of diabetic retinopathy, retinal vascular occlusive disease and exudative age-related macular degeneration, vision loss is associated with elevated levels or extravasation of vascular endothelial-derived growth factor (VEGF) into the retina, vitreous, and anterior chamber of the eye. We hypothesize that point-of-care biosensors, capable of rapidly and precisely measuring VEGF levels within the eye will assist clinicians in assessing disease severity, and in establishing individualized dosing intervals for intraocular anti-VEGF injection therapy. An impedance biosensor based on a poly(3,4-ethylenedioxythiophene) (PEDOT)/gold nanoparticle (Au NP) composite was developed for detecting VEGF. PEDOT with Au NP was electrochemically deposited on three different medical electrode sensor designs: free-standing pads, screen printed dots, and interdigitated micro-strip electrodes. Anti-VEGF antibody was covalently immobilized on the surface of the polymer films through attachment to citrate-functionalized Au NPs, and the resulting composites were used to detect VEGF-165 by electrochemical impedance spectroscopy (EIS). The PEDOT-Au NP composite materials were characterized using optical microscopy, SEM/EDS, FIB, TEM, and STEM techniques. Among the different micro-electrodes, the interdigitated strip shape showed the best overall film stability and reproducibility. A linear relationship was established between the charge transfer resistance (Rct) and VEGF concentration. The detection limit of VEGF was found to be 0.5 pg/mL, with a correlation coefficient of 0.99 ± 0.064%. These results indicate that the proposed PEDOT/Au NP composites can be used in designing low-cost and accurate VEGF biosensors for applications such as clinical diagnosis of VEGF-mediated eye disease

Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma

Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC). Therefore, we assessed the role of anti-VEGF therapy in modifying DC function. We found that VEGF blockade results in a more mature DC phenotype in the brain, as demonstrated by an increase in the expression of the co-stimulatory molecules B7-1, B7-2, and MHC II. Furthermore, we observed reduced levels of the exhaustion markers PD-1 and Tim-3 on brain-infiltrating CD8 T cells, indicating improved functionality. Thus, anti-angiogenic therapy has the potential to be used in conjunction with and enhance immunotherapy for GBM

Worldwide Argus II implantation: recommendations to optimize patient outcomes

Abstract Background A position paper based on the collective experiences of Argus II Retinal Prosthesis System investigators to review strategies to optimize outcomes in patients with retinitis pigmentosa undergoing retinal prosthesis implantation. Methods Retinal surgeons, device programmers, and rehabilitation specialists from Europe, Canada, Middle East, and the United States were convened to the first international Argus II Investigator Meeting held in Ann Arbor, MI in March 2015. The recommendations from the collective experiences were collected. Factors associated with successful outcomes were determined. Results Factors leading to successful outcomes begin with appropriate patient selection, expectation counseling, and preoperative retinal assessment. Challenges to surgical implantation include presence of staphyloma and inadequate Tenon’s capsule or conjunctiva. Modified surgical technique may reduce risks of complications such as hypotony and conjunctival erosion. Rehabilitation efforts and correlation with validated outcome measures following implantation are critical. Conclusions Bringing together Argus II investigators allowed the identification of strategies to optimize patient outcomes. Establishing an on-line collaborative network will foster coordinated research efforts to advance outcome assessment and rehabilitation strategies.http://deepblue.lib.umich.edu/bitstream/2027.42/134581/1/12886_2016_Article_225.pd

A Comparative Study of Responses to Retina Questions from Either Experts, Expert-Edited Large Language Models, or Expert-Edited Large Language Models Alone

OBJECTIVE: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions. DESIGN: Randomized, masked multicenter study. PARTICIPANTS: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists. METHODS: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content). MAIN OUTCOME: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type. RESULTS: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy ( CONCLUSIONS: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article

Glutamate Stimulation of Retinal Ganglion Cells in Normal and S334ter-4 Rat Retinas: A Candidate for a Neurotransmitter-Based Retinal Prosthesis

Responses of retinal ganglion cells to locally applied glutamate were similar in normal and degenerated retinas and exhibited moderate to robust evoked responses that varied between cells, from moderate firing rates to high-frequency repetitive bursting. This article explores important parameters for a prototype neurotransmitter-based retinal prosthesis, including effective glutamate concentrations, monotonic dependence of responses on duration of ejection, and differential effects on different RGC types

Binocular Interference vs Diplopia in Patients With Epiretinal Membrane

This study evaluates associations with monocular eye closure in patients with epiretinal membrane and reports on binocular interference (closing 1 eye to improve visual quality). Importance Patients with epiretinal membrane (ERM) sometimes close 1 eye for improved vision, but associations have not been rigorously studied. Objective To evaluate associations with monocular eye closure in patients with ERM, and to report binocular interference (closing 1 eye to improve visual quality). Design, Setting, and Participants Retrospective medical record review of an adult strabismus clinic at a tertiary referral center. Patients with ERM referred from retina clinicians between June 2010 and October 2019 who completed the Adult Strabismus (AS)-20 questionnaire, including the question: "I cover or close one eye to see things better." Two groups were identified: (1) patients reporting eye closure sometimes or more, and (2) patients reporting no eye closure (as control patients). Main Outcomes and Measures Frequencies of (1) central-peripheral rivalry (CPR)-type diplopia (dragged fovea diplopia); (2) binocular interference (monocular eye closure but no diplopia or strabismus); and (3) other, associated with monocular eye closure. Visual acuity, metamorphopsia, aniseikonia, and AS-20 quality of life domain scores (self-perception, interactions, reading function, and general function) compared between binocular interference, CPR-type diplopia, and control patients. Results A total of 124 patients with ERM (58 of 124 were women [47%]; mean [SD] age, 70 [9] years) reported monocular eye closure. Associations were binocular interference in 36 (29%; 95% CI, 21%-38%), CPR-type diplopia in 34 (27%; 95% CI, 20%-36%), and other (primarily strabismus) in 54 (44%). Compared with control patients with ERM (n = 11), patients with ERM and binocular interference had worse quality of life on AS-20 reading function (95 vs 62; mean difference, 22 points; 95% CI, 7-27 points;P = .007) and general function (89 vs 68; mean difference, 23 points; 95% CI, 13-34 points;P = .01) domains. Compared with CPR-type diplopia, patients with binocular interference had poorer worst-eye visual acuity (median 0.50 vs 0.30 logMAR [20/63 vs 20/40]; mean difference, 0.13 logMAR; 95% CI, 0.00-0.25 logMAR [20/20 to 20/35];P = .03), and a larger interocular difference (0.46 vs 0.19 logMAR [20/58 vs 20/30]; mean difference, 0.15 logMAR; 95% CI, 0.03-0.28 logMAR [20/21 to 20/38];P = .004). Conclusions and Relevance Study findings suggest that binocular interference, manifesting as monocular eye closure (without diplopia or strabismus), is a distinct entity affecting quality of life in patients with epiretinal membrane. Question What features are associated with monocular eye closure in epiretinal membrane? Findings In this medical record review of patients with epiretinal membrane, monocular eye closure (sometimes or more; n = 124) was associated with binocular interference (reduced monocular vs binocular visual quality, no diplopia or strabismus) in 36 (29%), central-peripheral rivalry (CPR)-type diplopia in 34 (27%), and other (primarily strabismus) in 54 (44%). Patients with binocular interference were more likely to have reduced quality of life compared with epiretinal membrane patients who never close 1 eye. Meaning Study findings suggest binocular interference is a distinct entity and can be associated with epiretinal membrane.12 month embargo; published online 10 September 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Intravitreous Delivery of the Corticosteroid Fluocinolone Acetonide Attenuates Retinal Degeneration in S334ter-4 Rats

Retinal neuroinflammation has been identified in association with a number of retinal degenerative diseases, including retinitis pigmentosa and age-related macular degeneration. Low-dose intravitreal sustained-release fluocinolone acetonide dampened retinal neuroinflammation and was associated with preservation of photoreceptors and electroretinographic amplitudes in S334ter-4 rats

Retinitis pigmentosa associated with a mutation in BEST1

Purpose: There is only one prior report associating mutations in BEST1 with a diagnosis of retinitis pigmentosa (RP). The imaging studies presented in that report were more atypical of RP and shared features of autosomal recessive bestrophinopathy and autosomal dominant vitreoretinochoroidopathy. Here, we present a patient with a clinical phenotype consistent with classic features of RP. Observations: The patient in this report was diagnosed with simplex RP based on clinically-evident bone spicules with characteristic ERG and EOG findings. The patient had associated massive cystoid macular edema which resolved following a short course of oral acetazolamide. Genetic testing revealed that the patient carries a novel heterozygous deletion mutation in BEST1 which is not carried by either parent. While this suggests BEST1 is causative, the patient also inherited heterozygous copies of several mutations in other genes known to cause recessive retinal degenerative disease. Conclusions and Importance: How some mutations in BEST1 associate with peripheral retinal degeneration phenotypes, while others manifest as macular degeneration phenotypes is currently unknown. We speculate that RP due to BEST1 mutation requires mutations in other modifier genes