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Samuel A Cohen,1 Nikhita Yadlapalli,2 Jonathan D Tijerina,3 Chrisfouad R Alabiad,3 Jessica R Chang,4 Benyam Kinde,5 Nicholas R Mahoney,6 Kelsey A Roelofs,1 Julie A Woodward,7 Andrea L Kossler5 1Department of Ophthalmology, Stein Eye Institute at University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA; 2Department of Ophthalmology, FIU Herbert Wertheim College of Medicine, Miami, FL, USA; 3Department of Ophthalmology, Bascom Palmer Eye Institute at University of Miami Miller School of Medicine, Miami, FL, USA; 4Department of Ophthalmology, USC Roski Eye Institute at University of Southern California Keck School of Medicine, Los Angeles, CA, USA; 5Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, Palo Alto, CA, USA; 6Department of Ophthalmology, Wilmer Eye Institute at Johns Hopkins University School of Medicine, Baltimore, MD, USA; 7Department of Ophthalmology, Duke Eye Center at Duke University School of Medicine, Durham, NC, USACorrespondence: Andrea L Kossler, Department of Ophthalmology, Byers Eye Institute at Stanford University School of Medicine, 2452 Watson Court, Palo Alto, CA, USA, Email akossler@stanford.eduPurpose: To compare the accuracy and readability of responses to oculoplastics patient questions provided by Google and ChatGPT. Additionally, to assess the ability of ChatGPT to create customized patient education materials.Methods: We executed a Google search to identify the 3 most frequently asked patient questions (FAQs) related to 10 oculoplastics conditions. FAQs were entered into both the Google search engine and the ChatGPT tool and responses were recorded. Responses were graded for readability using five validated readability indices and for accuracy by six oculoplastics surgeons. ChatGPT was instructed to create patient education materials at various reading levels for 8 oculoplastics procedures. The accuracy and readability of ChatGPT-generated procedural explanations were assessed.Results: ChatGPT responses to patient FAQs were written at a significantly higher average grade level than Google responses (grade 15.6 vs 10.0, p < 0.001). ChatGPT responses (93% accuracy) were significantly more accurate (p < 0.001) than Google responses (78% accuracy) and were preferred by expert panelists (79%). ChatGPT accurately explained oculoplastics procedures at an above average reading level. When instructed to rewrite patient education materials at a lower reading level, grade level was reduced by approximately 4 (15.7 vs 11.7, respectively, p < 0.001) without sacrificing accuracy.Conclusion: ChatGPT has the potential to provide patients with accurate information regarding their oculoplastics conditions. ChatGPT may also be utilized by oculoplastic surgeons as an accurate tool to provide customizable patient education for patients with varying health literacy. A better understanding of oculoplastics conditions and procedures amongst patients can lead to informed eye care decisions.Keywords: oculoplastics, google, ChatGPT, readability, accuracy

Background: Understanding how periocular nonmelanoma skin cancer (NMSC) impacts quality of life (QoL) provides insight into the patient experience. Objective: To prospectively measure QoL of individuals with surgically treated periocular NMSC. Methods: Responses to the skin cancer index (SCI) and FACE-Q questionnaires were obtained at preoperative (PRE), postoperative week 1 (POW1), and postoperative month 3 (POM3) visits. Statistical analysis was performed using paired t -test and stepwise linear regression. Results: Forty-five patients participated in the study. Improved QoL as reflected in an increased mean difference of the total SCI score at PRE and POM3 visits (25.8, 95% confidence interval [CI 20.0 to 31.6]) and FACE-Q early life impact of treatment score at POW1 and POM3 visits (19.0, 95% CI [14.9 to 23.0), and a decreased mean difference of the FACE-Q adverse effects score at POW1 and POM3 visits (-1.3, 95% CI [-2.4 to -0.1]) was observed. Linear regression of the SCI and FACE-Q scores using demographic and clinical attributes revealed several predictors of postoperative QoL. Conclusions: Surgical management of periocular NMSC results in improved QoL, demonstrated at the final postoperative visit.

Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, αRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found an ectopic neuronal expression of Osteopontin (Spp1) in other RGCs subject to glaucomatous conditions. This contrasted with the Spp1 downregulation subject to axotomy. αRGC-specific Spp1 elimination led to significant αRGC loss, diminishing their resiliency. Spp1 overexpression led to robust neuroprotection of susceptible RGC subclasses under glaucomatous conditions. In contrast, Spp1 overexpression did not significantly protect RGCs subject to axotomy. Additionally, SPP1 marked adult human RGC subsets with large somata and SPP1 expression in the aqueous humor correlated with glaucoma severity. Our study reveals Spp1's role in mediating neuronal resiliency in glaucoma., Competing Interests: Declaration of interests D.S.W. is a founder of and consultant to Perceive Biotherapeutics., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Intraventricular meningiomas (IVMs) of the lateral ventricle are rare tumors that present surgical challenges because of their deep location. Visual field deficits (VFDs) are one risk associated with these tumors and their treatment. VFDs may be present preoperatively due to the tumor and mass effect (tumor VFDs) or may develop postoperatively due to the surgical approach (surgical VFDs). This institutional series aimed to review surgical outcomes following resection of IVMs, with a focus on VFDs., Methods: Patients who received IVM resection at one academic institution between the years 1996 and 2021 were retrospectively reviewed. Diffusion tensor imaging (DTI) reconstructions of the optic radiations around the tumor were performed from preoperative IVM imaging. The VFD course and resolution were documented., Results: Thirty-two adult patients underwent IVM resection, with gross-total resection in 30 patients (93.8%). Preoperatively, tumor VFDs were present in 6 patients, resolving after surgery in 5 patients. Five other patients (without preoperative VFD) had new persistent surgical VFDs postoperatively (5/32, 15.6%) that persisted to the most recent follow-up. Of the 5 patients with persistent surgical VFDs, 4 received a transtemporal approach and 1 received a transparietal approach, and all these deficits occurred prior to regular use of DTI in preoperative imaging., Conclusions: New surgical VFDs are a common neurological deficit after IVM resection. Preoperative DTI may demonstrate distortion of the optic radiations around the tumor, thus revealing safe operative corridors to prevent surgical VFDs.

The authors present a case of a non-traumatic, spontaneous subperiosteal orbital hematoma in a woman with a history of chronic pansinusitis and absence of midline nasal cavity structures due to chronic inhalational cocaine use. The patient underwent left orbitotomy and drainage of the lesion, showing mostly blood with a small amount of purulence that grew methicillin-resistant Staphylococcus aureus when cultured. The patient received 4 weeks of intravenous antibiotics in addition to functional endoscopic sinus surgery. At 1 month after surgery, her vision had returned to baseline, and proptosis was resolved. Fewer than 20 cases of subperiosteal orbital hematomas associated with chronic sinusitis have been reported. To the authors' knowledge, this is the first reported case of a subperiosteal orbital hematoma associated with cocaine-induced midline destructive lesions. Patient consent to obtain photographs was obtained and archived. All collection and evaluation of patient health information were compliant with the Health Insurance Portability and Accountability Act, and this report adheres to the Declaration of Helsinki., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Competing Interests: Conflict of Interest The authors have no conflict of interest to disclose.

Competing Interests: The authors have no financial or conflicts of interest to disclose.

Purpose: To report a case of microsporidia (Encephalitozoon hellem) keratoconjunctivitis acquired through avian transmission in an immunocompetent adult, diagnosed by metagenomic deep sequencing (MDS), and confirmed by polymerase chain reaction., Methods: A case report., Results: An 18-year-old woman was referred with unilateral keratoconjunctivitis unresponsive to topical and systemic therapy after exposure to birdcage debris. Slit-lamp examination of the left eye revealed a follicular papillary reaction of the palpebral conjunctiva and multiple corneal punctate epithelial opacities that stained minimally with fluorescein. In vivo confocal microscopy revealed bright double-walled structures and smaller bright round structures in the superficial epithelial debris and epithelium. Molecular diagnosis with MDS of E. hellem was confirmed by polymerase chain reaction. Clinical resolution and normalization of in vivo confocal microscopy was observed after a 6-week course of topical azithromycin. The patient elected a 3-week course of topical voriconazole 1% for definitive antimicrosporidial treatment, with no evidence of persistent infection 1 month later., Conclusions: Microsporidial (E. hellem) keratoconjunctivitis can occur through avian transmission in immunocompetent hosts. Topical azithromycin may be effective against this pathogen. MDS has utility in the diagnosis of atypical keratoconjunctivitis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

We describe a 4-year-old boy who presented with progressive right periorbital edema and proptosis, with no systemic symptoms, who was found to have B-lymphoblastic leukemia (B-ALL). Magnetic resonance imaging (MRI) showed an enhancing mass centered in the right superolateral extraconal orbit. Orbital biopsy was consistent with B-ALL (CD99, TdT, LCA cocktail, CD34, CD79, CD10, PAX5, MIB1 positive; CD3, CD20 negative). A subsequent bone marrow aspirate confirmed a diagnosis of B-ALL with 80% blasts by flow cytometry and haploid cytogenetic findings. The patient improved clinically after chemotherapy. There are seven cases previously reported in the literature with hematogenous orbital masses at initial presentation of childhood ALL, but all with systemic symptoms or an abnormal complete blood count (CBC) at presentation. Our case is the first report in which an orbital mass preceded detectable systemic or laboratory evidence of ALL. This patient highlights the importance of differentiating benign causes of eyelid swelling from malignant ones.

A healthy, asymptomatic woman was referred after incidental discovery of a right superior incongruous hemianopia. Magnetic resonance imaging disclosed a schizencephalic cleft passing through Meyer's loop of the left optic radiation. The lesion may have resulted from a focal vascular accident or disruption of cortical neurogenesis during gestation., (© 2020 Taylor & Francis Group, LLC.)

Purpose: Current sequencing strategies can genetically solve 55-60% of inherited retinal degeneration (IRD) cases, despite recent progress in sequencing. This can partially be attributed to elusive pathogenic variants (PVs) in known IRD genes, including copy-number variations (CNVs), which have been shown as major contributors to unsolved IRD cases., Methods: Five hundred IRD patients were analyzed with targeted next-generation sequencing (NGS). The NGS data were used to detect CNVs with ExomeDepth and gCNV and the results were compared with CNV detection with a single-nucleotide polymorphism (SNP) array. Likely causal CNV predictions were validated by quantitative polymerase chain reaction (qPCR)., Results: Likely disease-causing single-nucleotide variants (SNVs) and small indels were found in 55.6% of subjects. PVs in USH2A (11.6%), RPGR (4%), and EYS (4%) were the most common. Likely causal CNVs were found in an additional 8.8% of patients. Of the three CNV detection methods, gCNV showed the highest accuracy. Approximately 30% of unsolved subjects had a single likely PV in a recessive IRD gene., Conclusion: CNV detection using NGS-based algorithms is a reliable method that greatly increases the genetic diagnostic rate of IRDs. Experimentally validating CNVs helps estimate the rate at which IRDs might be solved by a CNV plus a more elusive variant.

Purpose: To perform a comprehensive analysis of characteristics of ophthalmology trials registered in ClinicalTrials.gov., Design: Cross-sectional study., Methods: All 4,203 ophthalmologic clinical trials registered on ClinicalTrials.gov between October 1, 2007, and April 30, 2018, were identified by using medical subject headings (MeSH). Disease condition terms were verified by manual review. Trial characteristics were assessed through frequency calculations. Hazard ratios and 95% confidence intervals were determined for characteristics associated with early discontinuation., Results: The majority of trials were multiarmed (73.6%), single-site (69.4%), randomized (64.8%), and had <100 enrollees (66.3%). A total of 33% used a data-monitoring committee (DMC), and 50.6% incorporated blinding. Other groups (51.6%) were funded by industry, whereas 2.6% were funded by the US National Institutes of Health (NIH). NIH trials were significantly more likely to address oncologic (NIH = 15.5%, Other = 3%, Industry = 1.5%; P < 0.001) or pediatric disease (NIH = 20.9%, Other = 5.9%, Industry = 1.4%; P < 0.001). Industry-sponsored trials (69.6% of phase 3 trials) were significantly more likely to be randomized (Industry = 68.7%, NIH = 58.9%, Other = 60.8%; P < 0.001) and blinded (Industry = 57.2%, NIH = 42.7%, Other = 43.5%; P < 0.001). A total of 359 trials (8.5%) were discontinued early, and 530 trials (12.6%) had unknown status. Trials were less likely to be discontinued if funded by sources other than industry (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55-0.95; P = 0.021) and/or had a DMC (HR, 0.71; 95% CI, 0.55-0.92; P = 0.010)., Conclusions: Ophthalmology trials in the past decade reveal heterogeneity across study funding sources. NIH trials were more likely to support historically underfunded subspecialties, whereas Industry trials were more likely to face early discontinuation. These trends emphasize the importance of carefully monitored and methodologically sound trials with deliberate funding allocation., (Published by Elsevier Inc.)

Mutations in the methyl-DNA-binding repressor protein MeCP2 cause the devastating neurodevelopmental disorder Rett syndrome. It has been challenging to understand how MeCP2 regulates transcription because MeCP2 binds broadly across the genome and MeCP2 mutations are associated with widespread small-magnitude changes in neuronal gene expression. We demonstrate here that MeCP2 represses nascent RNA transcription of highly methylated long genes in the brain through its interaction with the NCoR co-repressor complex. By measuring the rates of transcriptional initiation and elongation directly in the brain, we find that MeCP2 has no measurable effect on transcriptional elongation, but instead represses the rate at which Pol II initiates transcription of highly methylated long genes. These findings suggest a new model of MeCP2 function in which MeCP2 binds broadly across highly methylated regions of DNA, but acts at transcription start sites to attenuate transcriptional initiation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In mammals, the environment plays a critical role in promoting the final steps in neuronal development during the early postnatal period. While epigenetic factors are thought to contribute to this process, the underlying molecular mechanisms remain poorly understood. Here, we show that in the brain during early life, the DNA methyltransferase DNMT3A transiently binds across transcribed regions of lowly expressed genes, and its binding specifies the pattern of DNA methylation at CA sequences (mCA) within these genes. We find that DNMT3A occupancy and mCA deposition within the transcribed regions of genes is negatively regulated by gene transcription and may be modified by early-life experience. Once deposited, mCA is bound by the methyl-DNA-binding protein MECP2 and functions in a rheostat-like manner to fine-tune the cell-type-specific transcription of genes that are critical for brain function., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rett syndrome is a severe neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein gene (MECP2). MeCP2 is a methyl-cytosine binding protein that is proposed to function as a transcriptional repressor. However, multiple gene expression studies comparing wild-type and MeCP2-deficient neurons have failed to identify gene expression changes consistent with loss of a classical transcriptional repressor. Recent work suggests that one function of MeCP2 in neurons is to temper the expression of the longest genes in the genome by binding to methylated CA dinucleotides (mCA) within transcribed regions of these genes. Here we explore the mechanism of mCA and MeCP2 in fine tuning the expression of long genes. We find that mCA is not only highly enriched within the body of genes normally repressed by MeCP2, but also enriched within extended megabase-scale regions surrounding MeCP2-repressed genes. Whereas enrichment of mCA exists in a broad region around these genes, mCA together with mCG within gene bodies appears to be the primary driver of gene repression by MeCP2. Disruption of methylation at CA sites within the brain results in depletion of MeCP2 across genes that normally contain a high density of gene-body mCA. We further find that the degree of gene repression by MeCP2 is proportional to the total number of methylated cytosine MeCP2 binding sites across the body of a gene. These findings suggest a model in which MeCP2 tunes gene expression in neurons by binding within the transcribed regions of genes to impede the elongation of RNA polymerase., Competing Interests: The authors declare no conflict of interest.

Disruption of the MECP2 gene leads to Rett syndrome (RTT), a severe neurological disorder with features of autism. MECP2 encodes a methyl-DNA-binding protein that has been proposed to function as a transcriptional repressor, but despite numerous mouse studies examining neuronal gene expression in Mecp2 mutants, no clear model has emerged for how MeCP2 protein regulates transcription. Here we identify a genome-wide length-dependent increase in gene expression in MeCP2 mutant mouse models and human RTT brains. We present evidence that MeCP2 represses gene expression by binding to methylated CA sites within long genes, and that in neurons lacking MeCP2, decreasing the expression of long genes attenuates RTT-associated cellular deficits. In addition, we find that long genes as a population are enriched for neuronal functions and selectively expressed in the brain. These findings suggest that mutations in MeCP2 may cause neurological dysfunction by specifically disrupting long gene expression in the brain.

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.

Eukaryotic organisms age, yet detrimental age-associated traits are not passed on to progeny. How life span is reset from one generation to the next is not known. We show that in budding yeast resetting of life span occurs during gametogenesis. Gametes (spores) generated by aged cells show the same replicative potential as gametes generated by young cells. Age-associated damage is no longer detectable in mature gametes. Furthermore, transient induction of a transcription factor essential for later stages of gametogenesis extends the replicative life span of aged cells. Our results indicate that gamete formation brings about rejuvenation by eliminating age-induced cellular damage.

Ribonucleic acid structure determination by NMR spectroscopy relies primarily on local structural restraints provided by (1)H- (1)H NOEs and J-couplings. When employed loosely, these restraints are broadly compatible with A- and B-like helical geometries and give rise to calculated structures that are highly sensitive to the force fields employed during refinement. A survey of recently reported NMR structures reveals significant variations in helical parameters, particularly the major groove width. Although helical parameters observed in high-resolution X-ray crystal structures of isolated A-form RNA helices are sensitive to crystal packing effects, variations among the published X-ray structures are significantly smaller than those observed in NMR structures. Here we show that restraints derived from aromatic (1)H- (13)C residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) can overcome NMR restraint and force field deficiencies and afford structures with helical properties similar to those observed in high-resolution X-ray structures.

The California Egg Quality Assurance Program uses the delayed secondary enrichment culture method for detecting Salmonella Enteritidis in environmental drag swabs obtained from commercial layer complexes. The turnaround time for this method is variable and is dependent on the prevalence of Salmonella, level of the Salmonella identification, and capabilities of the performing laboratory. On a sample basis, a range of 4 to 8 days is required to identify a Salmonella sp. to the serogroup level. Additional time is required to serotype group D Salmonella isolates. A Salmonella Enteritidis-specific polymerase chain reaction (PCR) assay was developed for use on drag swabs and chick box papers, and had a turnaround time of 3-4 days. The delayed secondary enrichment culture method and the Salmonella Enteritidis-specific PCR assay were compared on 942 drag swab and 85 chick box paper samples submitted from 217 and 22 premises, respectively, as part of the California Egg Quality Assurance Program. The PCR assay identified 43 positive Salmonella Enteritidis samples from 22 premises, whereas the culture method identified 24 group D Salmonella-positive samples from 16 premises. There was a significant difference (P = 0.001) in the proportion of positive samples as determined by the two assays. Complete serotyping of the group D Salmonella-positive cultures confirmed Salmonella Enteritidis in all but one sample that was identified as Salmonella Jamaica and was negative by the PCR assay.