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Purpose: To benchmark the epidemiologic features of pediatric ocular surface inflammatory diseases (POSID)., Design: Retrospective cohort study., Participants: Patients 18 years of age or younger with a medical claim for a diagnosis of POSID in the Optum Labs Data Warehouse between 2007 and 2020., Methods: Patients with claims of blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), or vernal keratoconjunctivitis (VKC) were included. Those with less than 6 months of follow-up before the initial diagnosis of POSID were excluded. Odds ratios (ORs) were derived from multivariable logistic regression analyses evaluating the associations between epidemiologic variables and POSID development., Main Outcome Measures: The primary outcome was the estimated prevalence of POSID. Prevalence of POSID subtypes and changes in prevalence over time were also evaluated., Results: Two thousand one hundred sixty-eight patients with POSID were identified from 2018 through 2019, yielding an estimated prevalence of 3.32 per 10 000. The prevalence of POSID was higher among children between 5 and 10 years of age, male children, those of Asian descent, and those living in the Northeast and the West census regions of the United States. The prevalence (per 10 000) of BKC, HSK, and VKC in the same period were 0.59 (95% confidence interval [CI], 0.53-0.65), 0.74 (95% CI, 0.68-0.81), and 1.99 (95% CI, 1.88-2.10), respectively, and significant differences were found in terms of age, sex, racial, ethnic, and regional distributions among the diagnoses. Between 2008 through 2009 and 2018 through 2019, a significant increase in POSID was noted among Asians (from 6.26 [95% CI, 5.28-7.36] to 11.80 [95% CI, 10.40-13.34]) driven by changes in VKC. Multivariable analysis demonstrated that age older than 5 years (OR, 2.57-3.75; 95% CI, 2.17-4.34), male sex (OR, 1.38; 95% CI, 1.26-1.50), Asian descent (OR, 3.12; 95% CI, 2.70-3.60), and Black or African American descent (OR, 1.26; 95% CI, 1.02-1.55) were associated with POSID development., Conclusions: This study provides an estimated prevalence of POSID and its 3 common subtypes in the United States, with important epidemiologic differences among them., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To characterize visual outcomes in children screened for retinopathy of prematurity (ROP)., Design: Retrospective, interventional case series., Methods: Patients who received ROP screening examinations at UCLA Medical Centers and were followed with outpatient eye examinations at Stein Eye Institute and/or Doheny Eye Institute (Los Angeles, California) were included. Data were collected on birth characteristics, worst type of ROP, and ROP treatment. Adverse visual outcomes included myopia, strabismus, amblyopia, macular dragging, and optic atrophy. Snellen visual acuity was reported for children 4 years and older., Results: A total of 175 infants (350 eyes) were included for analysis (mean gestational age = 28.2 weeks and birth weight = 1059 g) from a screening population of 539 infants (1078 eyes, 32.4% follow-up) over a 9-year period. Fifteen eyes received primary anti-vascular endothelial growth factor (anti-VEGF) therapy, whereas 59 eyes received primary laser therapy. Primary anti-VEGF therapy, as compared with primary laser treatment, was associated with a decreased incidence of amblyopia (adjusted odds ratio [aOR] = 0.6-0.86, P < .0001) after controlling for gestational age and birth weight. The rates of optic atrophy (P = .79), strabismus (P = .98), and myopia (P = .93) were not different between anti-VEGF and laser treatment groups. Infants receiving anti-VEGF therapy had more posterior disease than laser-treated infants (P = .041). Infants receiving laser therapy were more likely to have severe myopia (aOR = 1.02-1.3, P = .023), amblyopia (aOR = 1.12-1.61, P = .002), and optic atrophy (aOR = 1.01-1.32, P = .045) than infants not treated., Conclusion: These findings add to the advantages of anti-VEGF treatment compared with primary laser treatment, particularly in posterior ROP., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Examine underrepresented minority (URM) recruitment and diversity education initiatives provided by residency programs in ophthalmology and other specialties, and identify means to support programs as they work to enhance diversity efforts., Design: Cross-sectional study., Setting: Multi-center survey of residency program leadership of the Association of University Professors of Ophthalmology, Johns Hopkins Medicine, University of Utah, and the University of California, Los Angeles., Participants: Residency program leadership (i.e., residency program directors and associate residency program directors) RESULTS: Our survey response rate was 34% (63/188); 56% percent of responses were from ophthalmology and 44% were from other specialties. Across all specialties, programs with a large number of clinical faculty and trainees were associated with having ≥1 URM resident in their program (p = 0.026 and p = 0.028, respectively). There was no significant difference between ophthalmology and other specialties with regard to the number of URM residents. Ninety-two percent of programs utilized strategies to recruit URM applicants. While certain strategies were more common for ophthalmology than other specialties, information sessions for URM students (62%) and a unique review of all URM residency applicants by a separate committee/person (46%) were most commonly used overall. Although 92% of residency program leadership believed it was highly important for health professionals to receive formal diversity training, only 54% of programs had a diversity education curriculum for both trainees and faculty, 11% had a curriculum for faculty only, and 3% had a curriculum for trainees only. Barriers to implementation of curricula included lack of faculty expertise (30%) and curricular time (30%)., Conclusions: An overwhelming majority of programs in our study utilized strategies to recruit URM applicants, but 22% had 0 URM residents in their program. To address the reported barriers to diversity education implementation, shared central resources/diversity education toolkits should be created to provide programs with needed support., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Among neonatal cardiomyopathies, primary endocardial fibroelastosis (pEFE) remains a mysterious disease of the endomyocardium that is poorly genetically characterized, affecting 1/5000 live births and accounting for 25% of the entire pediatric dilated cardiomyopathy (DCM) with a devastating course and grave prognosis. To investigate the potential genetic contribution to pEFE, we performed integrative genomic analysis, using whole exome sequencing (WES) and RNA-seq in a female infant with confirmed pathological diagnosis of pEFE. Within regions of homozygosity in the proband genome, WES analysis revealed novel parent-transmitted homozygous mutations affecting three genes with known roles in cilia assembly or function. Among them, a novel homozygous variant [c.1943delA] of uncertain significance in ALMS1 was prioritized for functional genomic and mechanistic analysis. Loss of function mutations of ALMS1 have been implicated in Alstrom syndrome (AS) [OMIM 203800], a rare recessive ciliopathy that has been associated with cardiomyopathy. The variant of interest results in a frameshift introducing a premature stop codon. RNA-seq of the proband's dermal fibroblasts confirmed the impact of the novel ALMS1 variant on RNA-seq reads and revealed dysregulated cellular signaling and function, including the induction of epithelial mesenchymal transition (EMT) and activation of TGFβ signaling. ALMS1 loss enhanced cellular migration in patient fibroblasts as well as neonatal cardiac fibroblasts, while ALMS1-depleted cardiomyocytes exhibited enhanced proliferation activity. Herein, we present the unique pathological features of pEFE compared to DCM and utilize integrated genomic analysis to elucidate the molecular impact of a novel mutation in ALMS1 gene in an AS case. Our report provides insights into pEFE etiology and suggests, for the first time to our knowledge, ciliopathy as a potential underlying mechanism for this poorly understood and incurable form of neonatal cardiomyopathy. KEY MESSAGE: Primary endocardial fibroelastosis (pEFE) is a rare form of neonatal cardiomyopathy that occurs in 1/5000 live births with significant consequences but unknown etiology. Integrated genomics analysis (whole exome sequencing and RNA sequencing) elucidates novel genetic contribution to pEFE etiology. In this case, the cardiac manifestation in Alstrom syndrome is pEFE. To our knowledge, this report provides the first evidence linking ciliopathy to pEFE etiology. Infants with pEFE should be examined for syndromic features of Alstrom syndrome. Our findings lead to a better understanding of the molecular mechanisms of pEFE, paving the way to potential diagnostic and therapeutic applications., (© 2021. The Author(s).)

Chinese ophthalmology residency training is continuously evolving with an emphasis on standardization. In this article, we assess the current status of ophthalmology residency training in China compared with that in the United States through analysis of literature review and onsite data collection. We comprehensively review various aspects of the residency training structure in China, including accreditation, resident selection, clinical and surgical curricula, research requirements, and evaluation. Our report demonstrates significant regional differences among training programs due to the lack of a national standard, resulting in varying competencies of graduating Chinese ophthalmology residents. The Chinese ophthalmology community is determined to improve the standardization process and quality of training for their ophthalmologists, an important goal that will facilitate international fellowship studies, exchange scholars, and research collaboration.

Purpose: To investigate self-administered, at-home use of a perceptual learning-based video game consisting of target detection of stimuli in different sizes, spatial frequency, orientation, and contrast as a potential dichoptic therapy to improve binocular function in amblyopic patients resistant to patching., Methods: Children (ages 8 to 18 years) with strabismic and/or anisometropic amblyopia were recruited from a single institution. All participants (n = 25) were prescribed 6 weeks of patching for 2 hours per day, and those whose visual acuity did not improve were randomized to binocular perceptual learning (n = 7), monocular perceptual learning (n = 8), or patching (n = 10) groups for 8 weeks in this prospective cohort study. After an 8-week long period of treatment cessation, during which participants stopped patching or perceptual learning, participants in the patching group were randomized to binocular or monocular perceptual learning training; those in the perceptual learning groups remained the same. Visual function was assessed by visual acuity, low contrast acuity, reading speed, stereoacuity, and binocularity; compliance was evaluated by exercise logs., Results: There were no significant improvements in visual function parameters, which did not vary by treatment group. However, some visual outcomes, such as binocular summation and reading speed, correlated positively with compliance to perceptual learning therapy., Conclusions: At-home, self-administered use of this perceptual learning-based video game-based visual training does not consistently add therapeutic benefit to those with amblyopia resistant to patching. Future investigation is required to determine whether methods to increase compliance will lead to more reliable outcomes. [J Pediatr Ophthalmol Strabismus. 2020;57(3):176-184.]., (Copyright 2020, SLACK Incorporated.)

There is a need to identify new and more effective treatments for posttraumatic stress disorder (PTSD). Allopregnanolone and its stereoisomer pregnanolone (together termed ALLO) are metabolites of progesterone that positively and allosterically modulate GABA effects at GABA A receptors, thereby reducing anxiety and depression. Previous research revealed that women with PTSD had low cerebrospinal fluid (CSF) ALLO levels and a low ratio of ALLO to the allopregnanolone precursor 5α-DHP, consistent with deficient activity of the ALLO synthetic enzyme 3α-hydroxysteroid dehydrogenase (3α-HSD). The current study examined ALLO and the ratio of ALLO to 5α-DHP in plasma at rest and in response to psychophysiological stressors in trauma-exposed, medication-free women with and without PTSD. Participants were examined twice in random order during the early follicular phase (eFP) and mid-luteal phase (mLP) of the menstrual cycle. Plasma neurosteroids were measured using gas chromatography-mass spectrometry. Results indicate that the ALLO to 5α-DHP ratio in plasma increases between the eFP and mLP. In addition, women with PTSD have a lower ratio of ALLO to 5α-DHP than trauma-exposed healthy women, as well as blunted increases in this ratio in response to a moderately stressful laboratory procedure, i.e., differential fear conditioning, across the menstrual cycle. Clinically feasible testing for 3α-HSD dysfunction is critical to translating this line of research into clinical care. Measurement of this ratio in plasma could facilitate patient stratification in clinical treatment trials, as well as precision medicine targeting of treatments that address ALLO synthesis deficits in women with PTSD., (Published by Elsevier Ltd.)

Few diseases blur the margins between their childhood and adult-onset varieties as much as optic neuritis. This report will review our state of knowledge of pediatric optic neuritis, as well as its relationship to the latest consensus definitions of neuroinflammatory disease. Current diagnostic and treatment options will be explored, as well as our potential to uncover an understanding of pediatric optic neuritis through systematic prospective studies. The risk of evolving multiple sclerosis is probably less than in adults, but pediatric optic neuritis is more likely to be an initial manifestation of acute disseminated encephalomyelitis. Steroids may hasten visual recovery, but they do not change visual outcome except in cases because of neuromyelitis optica. The role of puberty in modifying the presentation and risk associations is unknown. Prospective studies are required to resolve these diagnostic and management issues.

We describe a surgical technique to perform strabismus surgery in patients with a scleral buckle that allows for the use of adjustable sutures without removing or modifying the exoplant., (Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes., Design: Prospective, multicenter, observational case series., Participants: A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy., Testing: Magnetic resonance imaging (MRI) of the brain., Main Outcome Measures: Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment., Results: Among 109 patients enrolled in the study, 22 had cranial nerve III palsy, 25 had cranial nerve IV palsy, and 62 had cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5%; 95% confidence interval, 10.7-24.6). The presence of 1 or more vasculopathic risk factors (diabetes, hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, stroke, and smoking) was significantly associated with a presumed microvascular cause (P = 0.003, Fisher exact test). Vasculopathic risk factors were also present in 61% of patients (11/18) with other causes. In the group of patients who had vasculopathic risk factors only, with no other significant medical condition, 10% of patients (8/80) were found to have other causes, including midbrain infarction, neoplasms, inflammation, pituitary apoplexy, and giant cell arteritis (GCA). By excluding patients with third cranial nerve palsies and those with GCA, the incidence of other causes for isolated fourth and sixth cranial nerve palsies was 4.7% (3/64)., Conclusions: In our series of patients with acute isolated ocular motor nerve palsies, a substantial proportion of patients had other causes, including neoplasm, GCA, and brain stem infarction. Brain MRI and laboratory workup have a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Intracranial pressure (ICP) monitoring is an established clinical practice in managing patients with risk of acute ICP elevation although the clinically accepted way of measuring ICP remains invasive. However, the invasive nature of ICP measurement obviates its application in many clinical circumstances such as diagnosis of idiopathic intracranial hypertension (IH). We propose a noninvasive diagnostic tool for IH based on the morphological analysis of cerebral blood flow velocity waveforms. We mainly compare two types of IH detection methods: one based on the traditional supervised learning approach and the other based on the semisupervised learning approach. Our simulation results demonstrate that the predictive accuracy (area under the curve) of the semisupervised IH detection method can be as high as 92% while that of the supervised IH detection method is only around 82%. It should be noted that the predictive accuracy of the pulsatility index (PI)-based IH detection method is as low as 59%. Although the predictive accuracy is a widely used accuracy measurement, it does not consider clinical consequences of necessary and unnecessary treatments. For this reason, we have adopted the decision curve analysis to address this issue. The decision curve analysis results show that the semisupervised IH detection method is not only more accurate, but also clinically more useful than the supervised IH detection method or the PI-based IH detection method.

The development of fetal ocular gene transfer may be useful as a therapeutic tool for the prevention of retinal genetic disorders with congenital or early clinical manifestations. In this study we explored the neural progenitor transduction patterns of adeno-associated virus (AAV) vectors following delivery to the developing retina. Recombinant vectors with the same genome carrying the enhanced green fluorescent protein (EGFP) transgene packaged in capsids of differing serotypes (serotypes 1, 2, and 5, termed AAV2/1, AAV2/2, and AAV2/5, respectively) were created. Delivery of the AAV vectors during early retinal development resulted in efficient and stable transduction of retinal progenitors. Vector surface proteins and the developmental status of the retina profoundly affected viral tropism and transgene distribution. The procedure is not detrimental to retinal development and function and therefore provides a safe delivery vehicle for potential therapeutic applications and a means of assessing the mechanisms of retina development and disease.