bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial intelligence in glaucoma: posterior segment optical coherence tomography
Authors: Gutierrez Alfredo , Chen Teresa C. 
Published: February 2023

Purpose of Review
To summarize the recent literature on deep learning (DL) model applications in glaucoma detection and surveillance using posterior segment optical coherence tomography (OCT) imaging.

Recent Findings
DL models use OCT derived parameters including retinal nerve fiber layer (RNFL) scans, macular scans, and optic nerve head (ONH) scans, as well as a combination of these parameters, to achieve high diagnostic accuracy in detecting glaucomatous optic neuropathy (GON). Although RNFL segmentation is the most widely used OCT parameter for glaucoma detection by ophthalmologists, newer DL models most commonly use a combination of parameters, which provide a more comprehensive approach. Compared to DL models for diagnosing glaucoma, DL models predicting glaucoma progression are less commonly studied but have also been developed.

Summary
DL models offer time-efficient, objective, and potential options in the management of glaucoma. Although artificial intelligence models have already been commercially accepted as diagnostic tools for other ophthalmic diseases, there is no commercially approved DL tool for the diagnosis of glaucoma, most likely in part due to the lack of a universal definition of glaucoma defined by OCT derived parameters alone (see Supplemental Digital Content 1 for video abstract, http://links.lww.com/COOP/A54).
Agreement of a Novel Artificial Intelligence Software With Optical Coherence Tomography and Manual Grading of the Optic Disc in Glaucoma
Authors: Shroff Sujani , Rao Divya P. , Savoy Florian M. , Shruthi S. , Hsu Chao-Kai , Pradhan Zia S. , Jayasree P.V. , Sivaraman Anand , Sengupta Sabyasachi , Shetty Rohit , Rao Harsha L. 
Published: February 2023

Précis:
The offline artificial intelligence (AI) on a smartphone-based fundus camera shows good agreement and correlation with the vertical cup-to-disc ratio (vCDR) from the spectral-domain optical coherence tomography (SD-OCT) and manual grading by experts.

Purpose:
The purpose of this study is to assess the agreement of vCDR measured by a new AI software from optic disc images obtained using a validated smartphone-based imaging device, with SD-OCT vCDR measurements, and manual grading by experts on a stereoscopic fundus camera.

Methods:
In a prospective, cross-sectional study, participants above 18 years (Glaucoma and normal) underwent a dilated fundus evaluation, followed by optic disc imaging including a 42-degree monoscopic disc-centered image (Remidio NM-FOP-10), a 30-degree stereoscopic disc-centered image (Kowa nonmyd WX-3D desktop fundus camera), and disc analysis (Cirrus SD-OCT). Remidio FOP images were analyzed for vCDR using the new AI software, and Kowa stereoscopic images were manually graded by 3 fellowship-trained glaucoma specialists.

Results:
We included 473 eyes of 244 participants. The vCDR values from the new AI software showed strong agreement with SD-OCT measurements [95% limits of agreement (LoA)=−0.13 to 0.16]. The agreement with SD-OCT was marginally better in eyes with higher vCDR (95% LoA=−0.15 to 0.12 for vCDR>0.8). Interclass correlation coefficient was 0.90 (95% CI, 0.88–0.91). The vCDR values from AI software showed a good correlation with the manual segmentation by experts (interclass correlation coefficient=0.89, 95% CI, 0.87–0.91) on stereoscopic images (95% LoA=−0.18 to 0.11) with agreement better for eyes with vCDR>0.8 (LoA=−0.12 to 0.08).

Conclusions:
The new AI software vCDR measurements had an excellent agreement and correlation with the SD-OCT and manual grading. The ability of the Medios AI to work offline, without requiring cloud-based inferencing, is an added advantage.
Effectiveness and Safety of XEN45 in Eyes With High Myopia and Open Angle Glaucoma
Authors: Fea Antonio , Sacchi Matteo , Franco Fabrizio , Laffi Gian Luca , Oddone Francesco , Costa Giacomo , Serino Federica , Giansanti Fabrizio 
Published: February 2023

Précis:
XEN45 implant was an effective and safe procedure in primary open angle glaucoma (OAG) eyes with high myopia. Although the hypotony incidence rate was relatively high, it resolved with medical therapy and was of short duration.

Purpose:
The purpose of this study is to evaluate the effectiveness and safety of the XEN45 stent in eyes with OAG and high myopia.

Design:
Retrospective and multicenter study.

Methods:
Consecutive OAG patients who underwent a XEN45, either alone or in combination with cataract surgery, and had a refractive error higher than −6 D and an axial length ≥26 mm. The primary endpoint was the mean intraocular pressure (IOP) lowering at the last follow-up visit.

Results:
Thirty-one eyes were included (96.8% with a primary OAG diagnosis). The mean refraction was −13.2±5.6 (range: −6.75 to−23.0) D. In the overall study sample, preoperative mean IOP (95% CI) was significantly lowered from 23.5 (20.5–26.4) mm Hg to 13.0 (12.2–13.8) mm Hg at the last follow-up visit, P<0.0001. At the last follow-up visit, 16 (57.1%) eyes achieved an IOP ≤14 mm Hg, 11 (68.9%) of them without treatment. The number of ocular hypotensive medications was significantly reduced from 3.0±1.1 drugs at preoperatively to 0.6±1.0 drugs at the last follow-up visit, P<0.0001. Median (95% CI) follow-up was 24.0 (12.0–24.0) months. Linear regression analysis showed a significant correlation between the preoperative refraction and the IOP lowering (r=0.43, P=0.0155). Needling procedure was performed in 11 eyes (39.3%) and hypotony (defined as an IOP <6 mm Hg) was observed in 8 eyes (28.6%) during the first postoperative day and remained for a week.

Conclusion:
Although the Xen implant effectively lowered IOP in highly myopic eyes with glaucoma, the incidence of hypotony was high, and in most cases, resolved within the first month with medical management and monitoring.
Teleglaucoma Using a New Smartphone-Based Tool for Visual Field Assessment
Authors: Grau Elisabeth , Andrae Stefan , Horn Folkert , Hohberger Bettina , Ring Matthias , Michelson Georg 
Published: February 2023

Précis:
COVID-19 underlines the importance of telemedical diagnostics. The smartphone-based campimetry (Sb-C) is a newly developed digital application allowing visual field testing using a head-mounted device and a smartphone. It enables visual field screening remotely from a clinic.

Background:
Sb-C is a newly developed tool for functional ophthalmic diagnosis. This study aimed to examine the comparability of the Sb-C and Octopus 900 to ensure ophthalmological care in times of social distancing.

Methods:
Total 93 eyes were included in the study. After an ophthalmological examination, the visual field was tested by the Octopus program G1 and by the smartphone-based campimeter. The Sb-C was performed using VR glasses and an iPhone 6. The software Sb-C was downloaded and installed as SmartCampiTracker app and is examining the 30-degree visual field with 59 test positions corresponding to the G pattern of Octopus G1. Sensitivities were recorded and saved on the app. In addition, test-retest reliability was tested on 6 ophthalmologically healthy participants.

Results:
The group comprised 48 women and 45 men (mean age: 62.52±12.2 y) including 19 controls, 17 patients with ocular hypertension, 11 preperimetric glaucomas, and 46 perimetric glaucomas. The mean sensitivity (MS) of all points of G1 perimetry was 23.13 dB (95% CI, 22.08–24.18). The MS of the Sb-C was 21.23 dB (95% CI, 20.37–22.08). The correlation between the mean MS measured by G1 perimetry and the Sb-C was strong (r=0.815, P<0.05). The test-retest reliability showed a correlation of r=0.591 (P<0.05).

Conclusions:
With some technical adjustments, the Sb-C shows promise for screening glaucoma and monitoring disease progression remotely from an ophthalmologic clinic.
Early Detection of Primary Open Angle, Angle Closure, and Normal Tension Glaucoma in an Asian Population Using Optical Coherence Tomography
Authors: Wu Chao-Wei , Chang Yue-Cune , Chen Hsin-Yi 
Published: February 2023

Précis:
Spectral-domain optical coherence tomography (SD-OCT) facilitates early glaucoma detection in the Chinese population in Taiwan. The best parameters for primary open angle glaucoma (POAG), primary angle closure glaucoma (PACG), normal tension glaucoma (NTG), and suspected glaucoma (GS) detection are temporal inferior Bruch’s membrane opening-minimum rim width (BMO-MRW), inner temporal macular ganglion cell layer (mGCL), temporal superior Circumpapillary retinal nerve fiber layer (cpRNFL), and mean global BMO-MRW, respectively.

Purpose:
We investigated the diagnostic capability of SD-OCT for different types of early glaucoma among the Chinese population in Taiwan.

Participants and Methods:
One eye each was assessed from 113 individuals with healthy eyes, 125 individuals with suspected glaucoma (GS), and 156 patients with early glaucoma (POAG, 87; PACG, 50; and NTG, 19). Circumpapillary (cp) RNFL thickness (global and sectoral), BMO-MRW, and macular parameters, including the macular RNFL (mRNFL), mGCL, and macular inner plexiform layer (mIPL), were assessed using SD-OCT. The areas under receiver operator characteristic curves (AUCs) were calculated to evaluate the diagnostic capacity of the parameters to differentiate between healthy and early glaucomatous eyes.

Results:
The parameters most suitable for detecting early POAG, PACG, NTG, and GS were temporal inferior BMO-MRW (AUC, 0.847), inner temporal mGCL (AUC, 0.770), temporal superior cpRNFL (AUC, 0.861), and mean global BMO-MRW (AUC, 0.768), respectively. Among the macular parameters, the mGCL exhibited the highest diagnostic capacity. The diagnostic capacity of the mGCL was lower than that of cpRNFL and BMO-MRW for POAG and NTG but not PACG. After adjusting for confounding variables in multivariable analysis, the AUC was determined to be 0.935 for POAG and 0.787 for GS.

Conclusion:
SD-OCT facilitates the detection of early POAG, PACG, and NTG. Using a combination of cpRNFL, BMO-MRW, and macular parameters may enhance their diagnostic capacities. Further studies are necessary to validate these findings.
Asymptomatic SARS-CoV-2 Infection by Age: A Global Systematic Review and Meta-analysis
Authors: Wang Bing , Andraweera Prabha , Elliott Salenna , Mohammed Hassen , Lassi Zohra , Twigger Ashley , Borgas Chloe , Gunasekera Shehani , Ladhani Shamez , Marshall Helen Siobhan 
Published: February 2023

Background:
Asymptomatic SARS-CoV-2 infections have raised concerns for public health policies to manage epidemics. This systematic review and meta-analysis aimed to estimate the age-specific proportion of asymptomatic SARS-CoV-2 infected persons globally by year of age.

Methods:
We searched PubMed, Embase, medRxiv and Google Scholar on September 10, 2020, and March 1, 2021. We included studies conducted during January to December 2020, before routine vaccination against COVID-19. Because we expected the relationship between the asymptomatic proportion and age to be nonlinear, multilevel mixed-effects logistic regression (QR decomposition) with a restricted cubic spline was used to model asymptomatic proportions as a function of age.

Results:
A total of 38 studies were included in the meta-analysis. In total, 6556 of 14,850 cases were reported as asymptomatic. The overall estimate of the proportion of people who became infected with SARS-CoV-2 and remained asymptomatic throughout infection was 44.1% (6556/14,850, 95% CI: 43.3%–45.0%). The predicted asymptomatic proportion peaked in children (36.2%, 95% CI: 26.0%–46.5%) at 13.5 years, gradually decreased by age and was lowest at 90.5 years of age (8.1%, 95% CI: 3.4%–12.7%).

Conclusions:
Given the high rates of asymptomatic carriage in adolescents and young adults and their active role in virus transmission in the community, heightened vigilance and public health strategies are needed among these individuals to prevent disease transmission.
COVID-19 Vaccine Reactogenicity and Vaccine Attitudes Among Children and Parents/Guardians After Multisystem Inflammatory Syndrome in Children or COVID-19 Hospitalization: September 2021—May 2022
Authors: Yousaf Anna R. , Kunkel Amber , Abrams Joseph Y. , Shah Ami B. , Hammett Teresa A. , Arnold Kathryn E. , Beltran Yajira L. , Laham Federico R. , Kao Carol M. , Hunstad David A. , Hussaini Laila , Baida Nadine , Salazar Luis , Perez Maria A. , Rostad Christina A. , Godfred-Cato Shana , Campbell Angela P. , Belay Ermias D. 
Published: February 2023

Background:
Multisystem inflammatory syndrome in children (MIS-C) is a multiorgan hyperinflammatory condition following SARS-CoV-2 infection. Data on COVID-19 vaccine adverse events and vaccine attitudes in children with prior MIS-C are limited. We described characteristics associated with COVID-19 vaccination, vaccine adverse events and vaccine attitudes in children with a history of MIS-C or COVID-19 and their parents/guardians.

Methods:
We enrolled children previously hospitalized for MIS-C or COVID-19 from 3 academic institutions. We abstracted charts and interviewed children and parents/guardians regarding vaccine adverse events and acceptability.

Results:
Of 163 vaccine-eligible children enrolled with a history of MIS-C and 70 with history of COVID-19, 51 (31%) and 34 (49%), respectively, received mRNA COVID-19 vaccine a median of 10 (Interquartile Range 6–13) months after hospital discharge. Among 20 children with MIS-C and parents/guardians who provided interviews, local injection site reaction of brief duration (mean 1.8 days) was most commonly reported; no children required medical care within 2 weeks postvaccination. Vaccine survey results of interviewed, vaccinated children and their parents/guardians: of 20 children with MIS-C and 15 children with COVID-19, 17 (85%) and 13 (87%), respectively, listed doctors in the top 3 most trusted sources for vaccine information; 13 (65%) and 9 (60%) discussed vaccination with their doctor.

Conclusions:
COVID-19 vaccination was well tolerated in children with prior MIS-C or COVID-19 participating in our investigation. Parents/guardians regarded their children’s doctors as a trusted source of information for COVID-19 vaccines, and most vaccinated children’s parents/guardians had discussed COVID-19 vaccination for their child with their doctor.
Phase I/II randomized, double-masked, placebo-controlled study of processed amniotic fluid drops after PRK
Authors: Ip Colin S. , Jones D. Kyle , Weinlander Eric , Gudgel Brett , Lin Amy , Yazdani Hina , Pierce Jan , Holubkov Richard , Jensen Hailey , Church Myrna , Mifflin Mark D. 
Published: February 2023

Purpose:
To evaluate the safety and efficacy of processed amniotic fluid (pAF) used postoperatively after photorefractive keratectomy (PRK).

Setting:
University of Utah, Moran Eye Center, Salt Lake City, Utah.

Design:
Randomized, double-masked, placebo-controlled prospective study.

Methods:
61 participants were randomized to receive either placebo or pAF drops, which were instilled 4 times per day for 1 week after PRK along with routine postoperative medications. The primary outcome measure was time to full re-epithelialization in days. Secondary measures included visual acuity at 30 days and postoperative pain scores during the first week.

Results:
There was no significant difference in time to re-epithelialization, with a median of 5 days for both groups. There were no difference in pain indicator scores during the first week and no difference in corneal staining scores at day 30 between the 2 groups. There were no adverse events.

Conclusions:
This pilot study evaluating the safety and efficacy of pAF as an additional postoperative topical medication for PRK demonstrated that pAF did not improve the rate of epithelial healing after PRK. pAF may be safely studied in other ocular conditions to determine its effect on epithelial healing.
Neuroendocrine mechanisms in oxaliplatin-induced hyperalgesic priming
Authors: Staurengo-Ferrari Larissa , Araldi Dionéia , Green Paul G. , Levine Jon D. 
Published: February 2023

Abstract
Stress plays a major role in the symptom burden of oncology patients and can exacerbate cancer chemotherapy-induced peripheral neuropathy (CIPN), a major adverse effect of many classes of chemotherapy. We explored the role of stress in the persistent phase of the pain induced by oxaliplatin. Oxaliplatin induced hyperalgesic priming, a model of the transition to chronic pain, as indicated by prolongation of hyperalgesia produced by prostaglandin E2, in male rats, which was markedly attenuated in adrenalectomized rats. A neonatal handling protocol that induces stress resilience in adult rats prevented oxaliplatin-induced hyperalgesic priming. To elucidate the role of the hypothalamic–pituitary–adrenal and sympathoadrenal neuroendocrine stress axes in oxaliplatin CIPN, we used intrathecally administered antisense oligodeoxynucleotides (ODNs) directed against mRNA for receptors mediating the effects of catecholamines and glucocorticoids, and their second messengers, to reduce their expression in nociceptors. Although oxaliplatin-induced hyperalgesic priming was attenuated by intrathecal administration of β2-adrenergic and glucocorticoid receptor antisense ODNs, oxaliplatin-induced hyperalgesia was only attenuated by β2-adrenergic receptor antisense. Administration of pertussis toxin, a nonselective inhibitor of Gαi/o proteins, attenuated hyperalgesic priming. Antisense ODNs for Gαi1 and Gαo also attenuated hyperalgesic priming. Furthermore, antisense for protein kinase C epsilon, a second messenger involved in type I hyperalgesic priming, also attenuated oxaliplatin-induced hyperalgesic priming. Inhibitors of second messengers involved in the maintenance of type I (cordycepin) and type II (SSU6656 and U0126) hyperalgesic priming both attenuated hyperalgesic priming. These experiments support a role for neuroendocrine stress axes in hyperalgesic priming, in male rats with oxaliplatin CIPN.
Targeting the vascular endothelial growth factor A/neuropilin 1 axis for relief of neuropathic pain
Authors: Stratton Harrison J. , Boinon Lisa , Gomez Kimberly , Martin Laurent , Duran Paz , Ran Dongzhi , Zhou Yuan , Luo Shizhen , Perez-Miller Samantha , Patek Marcel , Ibrahim Mohab M. , Patwardhan Amol , Moutal Aubin , Khanna Rajesh 
Published: February 2023

Abstract
Vascular endothelial growth factor A (VEGF-A) is a pronociceptive factor that causes neuronal sensitization and pain. We reported that blocking the interaction between the membrane receptor neuropilin 1 (NRP1) and VEGF-A–blocked VEGF-A–mediated sensory neuron hyperexcitability and reduced mechanical hypersensitivity in a rodent chronic neuropathic pain model. These findings identified the NRP1-VEGF-A signaling axis for therapeutic targeting of chronic pain. In an in-silico screening of approximately 480 K small molecules binding to the extracellular b1b2 pocket of NRP1, we identified 9 chemical series, with 6 compounds disrupting VEGF-A binding to NRP1. The small molecule with greatest efficacy, 4′-methyl-2′-morpholino-2-(phenylamino)-[4,5′-bipyrimidin]-6(1H)-one, designated NRP1-4, was selected for further evaluation. In cultured primary sensory neurons, VEGF-A enhanced excitability and decreased firing threshold, which was blocked by NRP1-4. In addition, NaV1.7 and CaV2.2 currents and membrane expression were potentiated by treatment with VEGF-A, and this potentiation was blocked by NRP1-4 cotreatment. Neuropilin 1-4 reduced VEGF-A–mediated increases in the frequency and amplitude of spontaneous excitatory postsynaptic currents in dorsal horn of the spinal cord. Neuropilin 1-4 did not bind to more than 300 G-protein-coupled receptors and receptors including human opioids receptors, indicating a favorable safety profile. In rats with spared nerve injury–induced neuropathic pain, intrathecal administration of NRP1-4 significantly attenuated mechanical allodynia. Intravenous treatment with NRP1-4 reversed both mechanical allodynia and thermal hyperalgesia in rats with L5/L6 spinal nerve ligation–induced neuropathic pain. Collectively, our findings show that NRP1-4 is a first-in-class compound targeting the NRP1-VEGF-A signaling axis to control voltage-gated ion channel function, neuronal excitability, and synaptic activity that curb chronic pain.
Lipoid Proteinosis Due to Homozygous Nonsense Mutation in Extracellular Matrix Protein 1 (ECM1) Gene in Three Pakistani Siblings
Authors: Tariq Hira , Jawad Shahbano , Aman Shahbaz , Saeed Anjum , Cheema Huma Arshad 
Published: February 2023

Introduction
Urbach–Wiethe disease (or lipoid proteinosis) is an autosomal recessive genetic disease. It is caused by a mutation in the extracellular matrix protein 1 gene (ECM1), resulting in deposition of hyaline material at the dermoepidermal junction of the skin, around blood vessels, and at multiple other sites.

Case presentation
The present report describes three siblings born to nonconsanguineous parents who presented with hoarseness, macroglossia, yellow waxy skin, beaded papules on the eyelids, atrophic scars, and recurrent skin infections. Histopathologic examination showed hyaline deposition at the interface between the dermis and epidermis and at the basal lamina of blood vessels. Exome sequencing revealed a homozygous nonsense variant in ECM1. This variant created a premature stop codon, leading to loss of function. Both parents were heterozygous for the same mutation.

Conclusion
This report is a useful addition to the current knowledge base regarding this phenotypically and genetically variable genodermatosis, which is rarely reported in Pakistan.
Local and systemic reactions associated with COVID-19 vaccines: logistic regression analysis
Authors: Lu Yu , He Chen-Lu , Jiang Guan 
Published: February 2023

Objective:
Universal vaccination is one of the most effective measures to control the COVID-19 epidemic. However, adverse reactions sometimes occur after vaccination. Therefore, we investigated the local and systemic adverse reactions associated with COVID-19 vaccines.

Methods:
We conducted a multicenter cross-sectional survey from 1 December 2021 to 28 February 2022 in Jiangsu, China to analyze skin and systemic reactions. We collected questionnaires from vaccination sites, communities, and hospitals. Participants could either complete an online survey using the WeChat-based survey program Questionnaire Star or complete a paper questionnaire. Individual participants remained anonymous both during and after data collection.

Results:
A total of 2136 participants successfully completed the survey. The most common symptoms were pain, swelling, and subcutaneous induration. Common systemic reactions were fatigue, muscle soreness, and dizziness and headache. The risk of reactions was associated with sex; age; history of allergy to vaccinations; history of eczema, dermatitis, or urticaria; and receiving the same type of vaccine from different manufacturers.

Conclusions:
Overall, our results indicated that many factors can influence the occurrence of local and systemic reactions associated with COVID-19 vaccines.