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Pundlik S, Shivshanker P, Luo G. Impact of Apps as Assistive Devices for Visually Impaired Persons. Annu Rev Vis Sci 2023;9:111-130.Abstract
The pervasiveness of mobile devices and other associated technologies has affected all aspects of our daily lives. People with visual impairments are no exception, as they increasingly tend to rely on mobile apps for assistance with various visual tasks in daily life. Compared to dedicated visual aids, mobile apps offer advantages such as affordability, versatility, portability, and ubiquity. We have surveyed hundreds of mobile apps of potential interest to people with vision impairments, either released as special assistive apps claiming to help in tasks such as text or object recognition (n = 68), digital accessibility (n = 84), navigation (n = 44), and remote sighted service (n = 4), among others, or marketed as general camera magnification apps that can be used for visual assistance (n = 77). While assistive apps as a whole received positive feedback from visually impaired users, as reported in various studies, evaluations of the usability of every app were typically limited to user reviews, which are often not scientifically informative. Rigorous evaluation studies on the effect of vision assistance apps on daily task performance and quality of life are relatively rare. Moreover, evaluation criteria are difficult to establish, given the heterogeneity of the visual tasks and visual needs of the users. In addition to surveying literature on vision assistance apps, this review discusses the feasibility and necessity of conducting scientific research to understand visual needs and methods to evaluate real-world benefits.
Yang M, Delcroix V, Lennikov A, Wang N, Makarenkova HP, Dartt DA. Genomic DNA activates the AIM2 inflammasome and STING pathways to induce inflammation in lacrimal gland myoepithelial cells. Ocul Surf 2023;Abstract
PURPOSE: Primary Sjögren's syndrome (pSS) is an autoimmune disease that mainly attacks the lacrimal glands causing severe aqueous-deficient dry eye. Clinical evidence indicates the DNA sensing mechanism in the pathogenesis of pSS. The purpose of the present study is to determine the pro-inflammatory effect of self-genomic DNA (gDNA) on myoepithelial cells (MECs), which along with acinar and ductal cells is a major cell type of the lacrimal gland. METHOD: MECs primary culture was acquired from female C57BL6J mice. Genomic DNA was extracted from the spleen of the same animal. The MECs were challenged with self-gDNA. The cytokine secretion was detected using supernatant by enzyme-linked immunosorbent assay (ELISA). The activation of inflammasomes was determined using FAM-FLICA. Cryosections of NOD.B10.H2b mouse model of pSS were obtained for immunofluorescence microscopy (IF), with Balb/C as control. RESULT: Treatment with gDNA activated AIM2 inflammasome assembly and function, leading to secretion of interleukin (IL)-1β and IL-18 in MECs. The stimulation of IL-1β secretion by gDNA appeared to be solely at the post-translational level, whereas IL-18 secretion was a combination of increased protein synthesis and post-translational modification. Genomic DNA also induced the activation of STimulators of INterferon Genes (STING), which correlated to the activation of STING in the lacrimal gland from the NOD.B10.H2b mouse. STING activation led to the secretion of IFN-β via Nuclear Factor-κB (NF-κB). The IFN-β further enhances the secretion of IL-1β. The contractility of MECs was disabled by treatment with gDNA or poly AnT, independent of the level of intracellular [Ca2+]. CONCLUSION: Self-gDNA induces a proinflammatory response in lacrimal gland MECs by activating both the AIM2 inflammasome and STING and thus may contribute to the pathogenesis of pSS.
Oke I, Hunter DG, Mantagos IS, Heidary G. The impact of the COVID-19 pandemic on the surgical volume of pediatric ophthalmology and strabismus fellows. J AAPOS 2023;27(5):305-307.Abstract
This study used data from the annual fellowship survey over 7 academic years (2014-15 to 2020-21) to describe the trends in surgical experience for pediatric ophthalmology and strabismus fellows and to quantify the impact of the COVID-19 pandemic on trainee surgical volume. The overall number of procedures performed by fellows in the primary surgeon role declined during the first academic year impacted by the pandemic but recovered in the second year. There was an increase in the number of intraocular cases performed per year during the 7-year study interval.
Zhao L, Wen Q, Nasrazadani D, Cheung NL, Weinert MC, Freedman SF, Silver J, Priestley YM, Congdon N, Prakalapakorn GS. Refractive Accuracy and Visual Outcome by Self-Refraction Using Adjustable-Focus Spectacles in Young Children: A Randomized Clinical Trial. JAMA Ophthalmol 2023;Abstract
IMPORTANCE: Uncorrected refractive error is the most common cause of vision impairment in children. Most children 12 years or older can achieve visual acuity (VA) of 20/25 or better by self-refraction using adjustable-focus spectacles, but data on younger children are lacking. OBJECTIVE: To assess refractive accuracy, corrected VA, and factors associated with not achieving VA of 20/25 or better among children aged 5 to 11 years performing self-refraction with Adspecs adjustable-focus spectacles (Adaptive Eyecare), compared with noncycloplegic autorefraction and cycloplegic refraction. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional noninferiority trial conducted from September 2, 2015, to December 14, 2017. The study setting was an academic pediatric eye clinic. Children aged 5 to 11 years with uncorrected VA of 20/40 or worse in 1 or both eyes and without systemic or ocular conditions preventing best-corrected VA of 20/25 or better were enrolled. Children who had best-corrected VA worse than 20/25 were excluded. Study data were analyzed from September 2017 to June 2023. EXPOSURES: Children were taught to self-refract with adjustable-focus spectacles. MAIN OUTCOMES AND MEASURES: Spherical equivalent refractive error (using self-refraction, noncycloplegic autorefraction, and cycloplegic refraction) and VA (uncorrected and using self-refraction, noncycloplegic autorefraction, and cycloplegic refraction) for study eyes were evaluated. Potential predictors of failure to achieve VA of 20/25 or better with self-refraction were assessed using logistic regression. RESULTS: A total of 127 consecutive children were enrolled. After exclusions, 112 children (median [IQR] age, 9.0 [8.0-10.3] years; 52 boys [46.4%]) were included in the study. Mean (SD) spherical equivalent refractive power was -2.00 (1.52) diopters (D) for self-refraction, -2.32 (1.43) D for noncycloplegic autorefraction, and -1.67 (1.49) D for cycloplegic refraction. Mean (SD) difference in refractive power between self-refraction and noncycloplegic autorefraction was 0.32 (1.11) D (97.5% 1-sided CI, 0.11 to ∞ D; P < .001) and between self-refraction and cycloplegic refraction was -0.33 (1.15) D (97.5% 1-sided CI, -0.54 to ∞ D; P = .77). The proportion of children with corrected VA of 20/25 or better was 79.5% (89 of 112) with self-refraction, 85.7% (96 of 112) with noncycloplegic autorefraction, and 79.5% (89 of 112) with cycloplegic refraction (self-refraction vs noncycloplegic autorefraction: McNemar P value = .27; self-refraction vs cycloplegic refraction: McNemar P value > .99). Those failing to achieve best-corrected VA of 20/25 or better with self-refraction had higher astigmatism (odds ratio [OR], 10.6; 95% CI, 3.1-36.4; P < .001) and younger age (OR, 1.5; 95% CI, 1.1-2.2; P = .02). CONCLUSIONS AND RELEVANCE: Self-refraction among children aged 5 to 11 years may result in more myopic power than cycloplegic refraction but not necessarily to a clinically relevant degree. Although the proportion of children achieving VA of 20/25 or better with self-refraction using adjustable-focus spectacles did not differ from cycloplegic refraction, it was less likely among younger children and those with higher astigmatism.
Ferreira Neto LC, Alves MS, Prichula J, Agnes G, de Oliveira TF, Trentin D, Merib J. An affordable and semiautomated approach as a novel strategy for the extraction of DNA using magnetic ionic liquids followed by real time-polymerase chain reaction. Anal Methods 2023;15(30):3752-3757.Abstract
This technical note describes a novel and straightforward experimental strategy for the extraction/capture of DNA using magnetic ionic liquid (MIL) followed by real time-polymerase chain reaction (qPCR) analysis. An affordable and low-cost magneto-based multiwell platform was first examined for capturing DNA allowing for simultaneous extractions that increased the analysis throughput of the experimental workflow. This configuration was composed of a series of neodymium rod magnets attached to a multiwell device in which a magneto-active extraction phase (MIL) was suspended for a single drop microextraction (SDME) approach. In this configuration, up to 32 extractions were able to be performed simultaneously, and DNA was successfully extracted from aqueous samples. Furthermore, as a proof-of-concept, this affordable and simple experimental strategy proved to be efficient for the extraction/capture of DNA from challenging samples such as whole blood without any pretreatment. This fact also consists of important feature compared to previous methodologies that required additional steps of sample preparation.
Xie L, Yin Y, Jayakar S, Kawaguchi R, Wang Q, Peterson S, Shi C, Turnes BL, Zhang Z, Oses-Prieto J, Li J, Burlingame A, Woolf CJ, Geschwind D, Rasband M, Benowitz LI. The oncomodulin receptor ArmC10 enables axon regeneration in mice after nerve injury and neurite outgrowth in human iPSC-derived sensory neurons. Sci Transl Med 2023;15(708):eadg6241.Abstract
Oncomodulin (Ocm) is a myeloid cell-derived growth factor that enables axon regeneration in mice and rats after optic nerve injury or peripheral nerve injury, yet the mechanisms underlying its activity are unknown. Using proximity biotinylation, coimmunoprecipitation, surface plasmon resonance, and ectopic expression, we have identified armadillo-repeat protein C10 (ArmC10) as a high-affinity receptor for Ocm. ArmC10 deletion suppressed inflammation-induced axon regeneration in the injured optic nerves of mice. ArmC10 deletion also suppressed the ability of lesioned sensory neurons to regenerate peripheral axons rapidly after a second injury and to regenerate their central axons after spinal cord injury in mice (the conditioning lesion effect). Conversely, Ocm acted through ArmC10 to accelerate optic nerve and peripheral nerve regeneration and to enable spinal cord axon regeneration in these mouse nerve injury models. We showed that ArmC10 is highly expressed in human-induced pluripotent stem cell-derived sensory neurons and that exposure to Ocm altered gene expression and enhanced neurite outgrowth. ArmC10 was also expressed in human monocytes, and Ocm increased the expression of immune modulatory genes in these cells. These findings suggest that Ocm acting through its receptor ArmC10 may be a useful therapeutic target for nerve repair and immune modulation.
Kurukuti NM, Nadeau M, Paschalis EI, Houston KE. An Adjustable Magnetic Levator Prosthesis for Customizable Eyelid Re-Animation in Severe Blepharoptosis: Design and Proof-of-Concept. Transl Vis Sci Technol 2023;12(8):11.Abstract
PURPOSE: Blepharoptosis is a common oculoplastic condition causing incomplete opening of the upper eyelid. Surgical approaches, the mainstay for correction, often fail to improve blink function. The purpose of this study was to develop a nonsurgical treatment option for severe ptosis that allows blink re-animation. METHODS: Magnetic force required to perform blink re-animation was characterized by evaluation of eye-opening and closing using inter-palpebral fissure (IPF) outcomes with various combinations of eyelid array and box magnets. Optimal size of the spectacle magnet that achieved forces required for optimal blink dynamics was selected using simulation. The adjustable magnetic levator prosthesis (aMLP) included an eyelid array magnet and an adjustable rotating spectacle magnet that allowed change in the magnetic direction, thus changing the net magnetic interactive force between the magnets. The clinical feasibility of aMLP in improving eye opening without limiting eye closing was evaluated in patients with ptosis through a proof-of-concept study using IPF and comfort outcomes. RESULTS: Optimal eye opening and closing was achieved by a magnet-array combination providing 45 grams of surface force (gF) in the tested ptosis population. The aMLP was able to modulate eye opening and closing with change in rotation of the spectacle magnet in two patients with ptotis. The best fitting of an aMLP improved IPF opening without limiting eye closing and with good comfort reported. CONCLUSIONS: Preliminary results suggest that the an aMLP can correct ptosis without adversely affecting blink function. Further evaluation in a larger patient population is warranted. TRANSLATIONAL RELEVANCE: A nonsurgical, proof of concept, adjustable magnetic treatment option for blink re-animation in patients with severe ptosis is presented.
Oke I, Gaier ED, Repka MX. Factors associated with visual acuity improvement with a binocular digital therapeutic for amblyopia. J AAPOS 2023;27(5):300-303.Abstract
We combined data from 121 amblyopic children enrolled in two prospective open-label pilot studies and a randomized trial of a binocular digital therapeutic to identify factors associated with positive response to amblyopia treatment. Visual acuity improved ≥1 line in 81% of participants after 12 weeks of therapy. Treatment response was not found to be associated with age, severity of amblyopia, or prior treatment status. Although these findings may suggest broad efficacy for this treatment approach, further investigation in larger cohorts is needed to identify factors associated with treatment response.
Jurkunas UV, Yin J, Johns LK, Li S, Negre H, Shaw KL, Samarakoon L, Ayala AR, Kheirkhah A, Katikireddy K, Gauthier A, Ong Tone S, Kaufman AR, Ellender S, Hernandez Rodriguez DE, Daley H, Dana R, Armant M, Ritz J. Cultivated autologous limbal epithelial cell (CALEC) transplantation: Development of manufacturing process and clinical evaluation of feasibility and safety. Sci Adv 2023;9(33):eadg6470.Abstract
To treat unilateral limbal stem cell (LSC) deficiency, we developed cultivated autologous limbal epithelial cells (CALEC) using an innovative xenobiotic-free, serum-free, antibiotic-free, two-step manufacturing process for LSC isolation and expansion onto human amniotic membrane with rigorous quality control in a good manufacturing practices facility. Limbal biopsies were used to generate CALEC constructs, and final grafts were evaluated by noninvasive scanning microscopy and tested for viability and sterility. Cultivated cells maintained epithelial cell phenotype with colony-forming and proliferative capacities. Analysis of LSC biomarkers showed preservation of "stemness." After preclinical development, a phase 1 clinical trial enrolled five patients with unilateral LSC deficiency. Four of these patients received CALEC transplants, establishing preliminary feasibility. Clinical case histories are reported, with no primary safety events. On the basis of these results, a second recruitment phase of the trial was opened to provide longer term safety and efficacy data on more patients.
Lu Y, Cui Y, Zhu Y, Lu ES, Zeng R, Garg I, Katz R, Le R, Wang JC, Vavvas DG, Husain D, Miller JW, Wu D, Miller JB. Quantitative Wide-Field Swept-Source Optical Coherence Tomography Angiography and Visual Outcomes in RAO. Clin Ophthalmol 2023;17:2505-2513.Abstract
PURPOSE: Retinal artery occlusion (RAO) is an ophthalmic emergency that can lead to poor visual outcomes and is associated with an increased risk of stroke and cardiovascular events. Wide-field swept-source OCT-A (WF SS-OCTA) can provide quick and non-invasive angiographic information with a wide field of view. Here, we looked for associations between OCT-A vascular imaging metrics and vision in RAO patients. METHODS: Patients with diagnoses of central (CRAO) or branched retinal artery occlusion (BRAO) were included. 6mm × 6mm Angio and 15mm × 15mm AngioPlex Montage OCT-A images were obtained for both eyes in each patient using Zeiss Plex Elite 9000 WF SS-OCTA device. Each 6mm × 6mm image was divided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Non-perfusion area (NPA) was manually measured using 15mm × 15mm images. A linear regression model was utilized to identify correlation between imaging metrics and vision. P-values less than 0.05 were considered as statistically significant. RESULTS: Twenty-five subjects were included. For RAO eyes, there was a statistically significant inverse correlation between retinal thickness as well as superficial capillary plexus (SCP) vessel density (VD) and vision. An inverse correlation was found between deep capillary plexus (DCP) VD and vision without statistical significance. There was a positive correlation between choroidal thickness as well as choroidal volume and vision without statistical significance. No significant correlation was found between the metrics and vision in contralateral eyes. For NPA and vision, no significant correlation was identified. CONCLUSION: This is the first study to investigate the utility of WF SS-OCTA in RAO and to demonstrate correlations between retinal vascular imaging metrics and visual outcomes. The results of this study provide a basis to understand the structural changes involved in vision in RAO and may guide management of RAO and prevention of cerebral stroke and cardiovascular accidents.
Moos WH, Faller DV, Glavas IP, Kanara I, Kodukula K, Pernokas J, Pernokas M, Pinkert CA, Powers WR, Sampani K, Steliou K, Vavvas DG. Epilepsy: Mitochondrial connections to the 'Sacred' disease. Mitochondrion 2023;72:84-101.Abstract
Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging. Diagnosis and monitoring of childhood epilepsy add to the need for non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms of epileptogenesis are not fully understood, evidence for mitochondrial involvement is substantial. Seizures affect 35%-60% of patients diagnosed with mitochondrial diseases. Mitochondrial dysfunction is pathophysiological in various epilepsies, including those of non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads to altered neuronal bioenergetics, metabolism and neurological complications, including seizures. Iron-dependent lipid peroxidation initiates ferroptosis, a cell death pathway that aligns with altered mitochondrial bioenergetics, metabolism and morphology found in neurodegenerative diseases (NDDs). Studies in mouse genetic models with seizure phenotypes where the function of an essential selenoprotein (GPX4) is targeted suggest roles for ferroptosis in epilepsy. GPX4 is pivotal in NDDs, where selenium protects interneurons from ferroptosis. Selenium is an essential central nervous system micronutrient and trace element. Low serum concentrations of selenium and other trace elements and minerals, including iron, are noted in diagnosing childhood epilepsy. Selenium supplements alleviate intractable seizures in children with reduced GPX activity. Copper and cuproptosis, like iron and ferroptosis, link to mitochondria and NDDs. Connecting these mechanistic pathways to selenoproteins provides new insights into treating seizures, pointing to using medicines including prodrugs of lipoic acid to treat epilepsy and to potential alternative therapeutic approaches including transcranial magnetic stimulation (transcranial), photobiomodulation and vagus nerve stimulation.
Liao XL, Li CQ, Ge QM, Tang L, Su T, Li QY, Pan YC, Shu HY, Zhang LJ, Shao Y. Investigation of Altered Spontaneous Brain Activity Patterns in Herpes Zoster Keratitis Using the Percent Amplitude of Fluctuation Method: A Resting-State Functional Magnetic Resonance Imaging Study. Neuropsychiatr Dis Treat 2023;19:1781-1789.Abstract
PURPOSE: The purpose of this study was to use the percent amplitude of fluctuation (PerAF) to study the changes in brain activity and nerve function of herpes zoster keratitis (HZK) patients. METHODS: We recruited 20 HZK patients and 20 healthy controls (HCs). Each of these groups included ten males and ten females and were matched in weight and age. All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI). The percent amplitude of fluctuation (PerAF) method was used for analysis and detected differences between the two groups in the neurological function of brain areas. We also applied the receiver operating characteristic (ROC) curve to analyze the two groups and did a correlation analysis between the PerAF value, anxiety and depression score, and visual acuity. RESULTS: The PerAF signal at the right putamen and right precentral gyrus was significantly higher in patients than in HCs. However, the PerAF value of the left inferior temporal was lower in patients than in HCs. In addition, the HZK patients' anxiety and depression score (HADS) and visual acuity (V.A.) Log MAR negatively correlated with the PerAF value at the left inferior temporal gyrus. CONCLUSION: HZK patients had some changes in brain regions, and the changes were also related to their mood and visual acuity. These findings might contribute to other studies on the potential pathological mechanism, disease development, prognosis, and brain function in HZK patients.
Baldwin GE, Gaier ED, Hennein LM. Isolated Sixth Nerve Palsy and COVID-19: A Recurrent Case in a 7-Month-Old Child and Analysis of Reported Cases. J Neuroophthalmol 2023;Abstract
BACKGROUND: With the SARS-CoV-2 pandemic (COVID-19), data on central and peripheral nervous system involvement, including those causing cranial nerve 6 (CN6) palsy, have been limited to case reports. To extract clinically relevant features of COVID-19-related CN6 palsy, we report on a recurrent pediatric case and analysis of reported cases associated with infection or immunization. METHODS: A PubMed search revealed 18 cases of isolated CN6 palsy in addition to the index case (n = 19). Clinical characteristics, workup, and temporal associations between systemic symptoms onset or vaccination, symptoms onset, and resolution were compiled and analyzed. RESULTS: The median age of CN6 onset was 43 years (interquartile range [IQR]: 28-52). Sixteen cases (84.2%) were associated with COVID-19 illness and 3 (15.8%) were associated with COVID-19 vaccination. Four cases (23.5%) had positive neuroimaging findings. The median latency from first COVID-19 symptoms or vaccination to onset of CN6 palsy was 6 days (IQR: 2.3-16), and the median time from onset to resolution was 30 days (IQR: 14-60). Latency to onset of CN6 palsy was significantly and directly associated with time to resolution (R2 = 0.401, P = 0.010). Patients who had a positive SARS-CoV-2 antibody test had significantly longer days from symptoms to onset (6.0 vs 24.5, P = 0.030), and patients with a positive SARS-CoV-2 polymerase chain reaction test had a significantly shorter time to resolution (17.50 vs 90, P = 0.042). CONCLUSIONS: Isolated CN6 palsy from COVID-19 is rare, can occur in infants as young as 7 months, and can be recurrent. Longer latency from systemic symptoms onset portends greater recovery times, and this relationship may reflect multiple mechanisms by which COVID-19 (and/or an immune response thereto) causes cranial neuropathies with direct clinical relevance.
Tao JP, Shen JF, Aakalu VK, Foster JA, Freitag SK, McCulley TJ, Vagefi RM, Kim SJ, Wladis EJ. Thermal Pulsation in the Management of Meibomian Gland Dysfunction and Dry Eye: A Report by the American Academy of Ophthalmology. Ophthalmology 2023;130(12):1336-1341.Abstract
PURPOSE: To review the literature to determine the efficacy and safety of thermal pulsation technologies in improving signs or symptoms of meibomian gland dysfunction (MGD) and dry eye compared with no therapy or with conventional warm compress therapy or eyelid hygiene. METHODS: A literature search was conducted in the PubMed database in June 2022 and again in March 2023 to identify all studies in the English language on the use of thermal pulsation to treat MGD or dry eye. The search yielded 59 citations, and 11 articles met all of the inclusion criteria. The panel methodologist then assigned a level of evidence rating for each study; 8 studies were rated level I evidence and 3 studies were rated level II evidence. RESULTS: All included studies evaluated a single 12-minute session using the LipiFlow automated thermal pulsation system (TearScience, Inc, or Johnson & Johnson). Improvements were detected in subjective and objective metrics of MGD or dry eye in patients within 1 to 12 months of thermal pulsation treatment compared with nontreatment. Most of the studies (9/11) reported greater efficacy with thermal pulsation than with standard warm compress therapy and eyelid hygiene. Four of these studies showed relevant industry conflicts of interest. Two of the 4 level I studies without direct industry participation concluded that thermal pulsation treatment was not significantly different from conventional hygiene or warm compress therapy control treatments (in symptoms in one of the studies and in objective findings in the second study). No serious adverse events were reported in any of the 11 studies. CONCLUSIONS: According to the current literature, a single thermal pulsation session may improve subjective or objective parameters of MGD and dry eye safely. However, industry support and participation were present in 4 of the 8 level I studies. The durability beyond several months and cost efficacy remain uncertain. Because the inclusion parameters of this assessment captured only the LipiFlow system, the conclusions are limited to that product. High-quality independent studies are needed to assess the long-term benefits of this intervention. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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