ACUTE- AND DELAYED-ONSET ENDOPHTHALMITIS AFTER OPEN GLOBE INJURIES: Clinical Features and Visual Acuity Outcomes.

PURPOSE: The purpose of the study was to report the clinical features and best-corrected visual acuity outcomes in patients with acute- and delayed-onset endophthalmitis after open globe injuries. METHODS: The study included a retrospective, comparative, consecutive case series of patients with endophthalmitis after open globe injury between January 2016 and October 2020 at the Bascom Palmer Eye Institute. RESULTS: Acute-onset endophthalmitis accounted for 16 of 20 cases (80%), and all cases were diagnosed at the initial examination. Delayed-onset endophthalmitis cases, occurring more than 2 weeks after injury, accounted for 4 of 20 cases (20%) and were because of Zone 1 wound leaks and infections. Factors associated with endophthalmitis included presence of a retained intraocular foreign body (11/20 [55%]) and delay of presentation >24 hours (15/20 [75%]) ( P < 0.001 and 0.002, respectively). The mean presenting best-corrected visual acuity was logMAR 1.64 (20/800), and the mean best-corrected visual acuity at the last follow-up was logMAR 1.22 (20/300). CONCLUSION: In patients with open globe injury-related endophthalmitis, visual acuity outcomes are generally poor. Despite intravitreal antibiotics at primary closure, delayed-onset endophthalmitis cases may develop in the setting of compromised Zone 1 wound integrity.

Atypical Presentations of Extraparenchymal Neurocysticercosis.

BACKGROUND: Neurocysticercosis (NCC) is the most common parasitic infection of the central nervous system and is typically diagnosed through visualization of the cysts in the cerebral parenchyma by neuro-imaging. However, neuro-imaging may not detect extraparenchymal neurocysticercosis (EPNCC), which is a rare manifestation of the disease involving the subarachnoid, meningeal, and intraventricular spaces. We report 2 cases of extraparenchymal neurocysticercosis, and discuss the diagnostic challenges and management of this entity. METHODS: Two cases were identified through clinical records. RESULTS: Both patients had an insidious onset with slow progression of disease, and presented with papilledema and cerebrospinal fluid (CSF) eosinophilia. One case was diagnosed with spinal cord biopsy. The other was diagnosed with CSF serology and next-generation sequencing-based pathogen analysis. Both patients were treated with ventriculoperitoneal shunt, systemic antiparasitic agents, and immunosuppression. CONCLUSIONS: EPNCC is less common than parenchymal NCC. A high level of clinical suspicion is required given its rarity, long incubation period, and slow progression. Diagnosis and treatment can be challenging and requires a multidisciplinary approach.

Matrix (factorization) reloaded: flexible methods for imputing genetic interactions with cross-species and side information.

MOTIVATION: Mapping genetic interactions (GIs) can reveal important insights into cellular function and has potential translational applications. There has been great progress in developing high-throughput experimental systems for measuring GIs (e.g. with double knockouts) as well as in defining computational methods for inferring (imputing) unknown interactions. However, existing computational methods for imputation have largely been developed for and applied in baker's yeast, even as experimental systems have begun to allow measurements in other contexts. Importantly, existing methods face a number of limitations in requiring specific side information and with respect to computational cost. Further, few have addressed how GIs can be imputed when data are scarce. RESULTS: In this article, we address these limitations by presenting a new imputation framework, called Extensible Matrix Factorization (EMF). EMF is a framework of composable models that flexibly exploit cross-species information in the form of GI data across multiple species, and arbitrary side information in the form of kernels (e.g. from protein-protein interaction networks). We perform a rigorous set of experiments on these models in matched GI datasets from baker's and fission yeast. These include the first such experiments on genome-scale GI datasets in multiple species in the same study. We find that EMF models that exploit side and cross-species information improve imputation, especially in data-scarce settings. Further, we show that EMF outperforms the state-of-the-art deep learning method, even when using strictly less data, and incurs orders of magnitude less computational cost. AVAILABILITY: Implementations of models and experiments are available at: https://github.com/lrgr/EMF. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Functional protein representations from biological networks enable diverse cross-species inference.

Transferring knowledge between species is key for many biological applications, but is complicated by divergent and convergent evolution. Many current approaches for this problem leverage sequence and interaction network data to transfer knowledge across species, exemplified by network alignment methods. While these techniques do well, they are limited in scope, creating metrics to address one specific problem or task. We take a different approach by creating an environment where multiple knowledge transfer tasks can be performed using the same protein representations. Specifically, our kernel-based method, MUNK, integrates sequence and network structure to create functional protein representations, embedding proteins from different species in the same vector space. First we show proteins in different species that are close in MUNK-space are functionally similar. Next, we use these representations to share knowledge of synthetic lethal interactions between species. Importantly, we find that the results using MUNK-representations are at least as accurate as existing algorithms for these tasks. Finally, we generalize the notion of a phenolog ('orthologous phenotype') to use functionally similar proteins (i.e. those with similar representations). We demonstrate the utility of this broadened notion by using it to identify known phenologs and novel non-obvious ones supported by current research.

The TOR signaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA.

Pseudouridine (Ψ) has been identified in various types of RNAs, including mRNA, rRNA, tRNA, snRNA, and many other noncoding RNAs. We have previously shown that RNA pseudouridylation, like DNA and protein modifications, can be induced by stress. For instance, growing yeast cells to saturation induces the formation of Ψ93 in U2 snRNA. Here, we further investigate this inducible RNA modification. We show that switching yeast cells from nutrient-rich medium to different nutrient-deprived media (including water) results in the formation of Ψ93 in U2 snRNA. Using gene deletion/conditional depletion as well as rapamycin treatment, we further show that the TOR signaling pathway, which controls cell entry into stationary phase, regulates Ψ93 formation. The RAS/cAMP signaling pathway, which parallels the TOR pathway, plays no role in this inducible modification.

FoxO1 Deacetylation Decreases Fatty Acid Oxidation in ß-Cells and Sustains Insulin Secretion in Diabetes.

Pancreatic ß-cell dysfunction contributes to onset and progression of type 2 diabetes. In this state ß-cells become metabolically inflexible, losing the ability to select between carbohydrates and lipids as substrates for mitochondrial oxidation. These changes lead to ß-cell dedifferentiation. We have proposed that FoxO proteins are activated through deacetylation-dependent nuclear translocation to forestall the progression of these abnormalities. However, how deacetylated FoxO exert their actions remains unclear. To address this question, we analyzed islet function in mice homozygous for knock-in alleles encoding deacetylated FoxO1 (6KR). Islets expressing 6KR mutant FoxO1 have enhanced insulin secretion in vivo and ex vivo and decreased fatty acid oxidation ex vivo Remarkably, the gene expression signature associated with FoxO1 deacetylation differs from wild type by only ∼2% of the >4000 genes regulated in response to re-feeding. But this narrow swath includes key genes required for ß-cell identity, lipid metabolism, and mitochondrial fatty acid and solute transport. The data support the notion that deacetylated FoxO1 protects ß-cell function by limiting mitochondrial lipid utilization and raise the possibility that inhibition of fatty acid oxidation in ß-cells is beneficial to diabetes treatment.

Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.

Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER)-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation. We discovered that ER from livers of obese mice exhibits a general reduction in protein synthesis, and comprehensive analysis of polysome-bound transcripts revealed extensive down-regulation of protein synthesis machinery, mitochondrial components, and bile acid metabolism in the obese translatome. Nutrient availability also plays an important but distinct role in remodeling the hepatic ER translatome in lean and obese mice. Fasting in obese mice partially reversed the overall translatomic differences between lean and obese nonfasted controls, whereas fasting of the lean mice mimicked many of the translatomic changes induced by the development of obesity. The strongest examples of such regulations were the reduction in Cyp7b1 and Slco1a1, molecules involved in bile acid metabolism. Exogenous expression of either gene significantly lowered plasma glucose levels, improved hepatic steatosis, but also caused cholestasis, indicating the fine balance bile acids play in regulating metabolism and health. Together, our work defines dynamic regulation of the liver translatome by obesity and nutrient availability, and it identifies a novel role for bile acid metabolism in the pathogenesis of metabolic abnormalities associated with obesity.

Efficacy and safety of hylan G-F 20 injection in treatment of knee osteoarthritis in Chinese patients: results of a prospective, multicentre, longitudinal study.

OBJECTIVE: To study the efficacy and safety of single intra-articular injection of 6-mL hylan G-F 20 in Chinese patients with symptomatic knee osteoarthritis. DESIGN: Prospective case series. SETTING: Six government hospitals in Hong Kong. PATIENTS: Patients with primary knee osteoarthritis were recruited from six government hospitals from 1 October 2010 to 31 May 2012. All patients received 6-mL intra-articular injection of hylan G-F 20. MAIN OUTCOME MEASURES: Pain visual analogue scale, functional visual analogue scale, and 5-point Likert scale on change of pain and function were assessed. Adverse events were checked. Radiographs were taken pre-injection and at 3 months and 1 year. RESULTS: A total of 110 knees of 95 patients with primary knee osteoarthritis were treated. The mean age of the patients was 62 (standard deviation, 9.8) years. All patients completed 1 year of follow-up. The mean pain visual analogue scale, functional visual analogue scale, and Likert value for pain and function showed statistically significant improvements at 6 weeks, 3 months, 6 months, and 1 year compared with the pre-injection values. No significant correlations were found between changes in visual analogue scale and age, body mass index, pre-injection radiological osteoarthritis severity, serum erythrocyte sedimentation rate, or C-reactive protein. Serial radiographs did not show any changes in the radiological severity of knee osteoarthritis. Overall, 16.4% of the patients experienced mild and self-limiting adverse events. CONCLUSION: Hylan G-F 20 is a safe and effective therapy to relieve pain and improve function for up to 1 year in Chinese patients with knee osteoarthritis.

Nurse-led orthopaedic clinic in total joint replacement.

OBJECTIVES: To introduce the practice of a nurse-led orthopaedic clinic for managing stable patients after total hip or knee replacement and to evaluate its efficacy. DESIGN: Case series. SETTING: A public hospital in Hong Kong. PATIENTS: Patients who had stable primary total knee replacement or total hip replacement done for longer than 2 years were managed in a nurse-led total joint replacement pilot clinic. RESULTS: From July 2012 to March 2014, 431 patients (including 317 with total knee replacement and 114 with total hip replacement) were handled, and 408 (94.7%) nurse assessments were independently performed. Six cases of prosthesis-related complications were diagnosed. One patient was hospitalised for prosthetic complications within 3 months after follow-up. The satisfaction rate was 100%. From November 2012 to April 2013, an advanced practice nurse, one resident specialist, and one associate consultant independently charted Knee Society Knee Score or Harris Hip Score for the patients attending preoperative assessment clinic to check the inter-observer reliability. Overall, 23 patients with 37 knees and 11 patients with 17 hips were examined. The mean correlation coefficient between assessments by the associate consultant and advanced practice nurse was 0.912 for Knee Society Knee Score, and 0.761 for Harris Hip Score. The advanced practice nurse could achieve better or equally good correlation with associate consultant when compared with the correlation between resident specialist and associate consultant (0.866 and 0.521 for Knee Society Knee Score and Harris Hip Score, respectively) and with international standard. CONCLUSION: Nurse-led total joint replacement clinic was safe, reliable, and well accepted by patients.

Fulgor: a fast and compact k-mer index for large-scale matching and color queries.

The problem of sequence identification or matching-determining the subset of reference sequences from a given collection that are likely to contain a short, queried nucleotide sequence-is relevant for many important tasks in Computational Biology, such as metagenomics and pangenome analysis. Due to the complex nature of such analyses and the large scale of the reference collections a resource-efficient solution to this problem is of utmost importance. This poses the threefold challenge of representing the reference collection with a data structure that is efficient to query, has light memory usage, and scales well to large collections. To solve this problem, we describe an efficient colored de Bruijn graph index, arising as the combination of a k-mer dictionary with a compressed inverted index. The proposed index takes full advantage of the fact that unitigs in the colored compacted de Bruijn graph are monochromatic (i.e., all k-mers in a unitig have the same set of references of origin, or color). Specifically, the unitigs are kept in the dictionary in color order, thereby allowing for the encoding of the map from k-mers to their colors in as little as 1 + o(1) bits per unitig. Hence, one color per unitig is stored in the index with almost no space/time overhead. By combining this property with simple but effective compression methods for integer lists, the index achieves very small space. We implement these methods in a tool called Fulgor, and conduct an extensive experimental analysis to demonstrate the improvement of our tool over previous solutions. For example, compared to Themisto-the strongest competitor in terms of index space vs. query time trade-off-Fulgor requires significantly less space (up to 43% less space for a collection of 150,000 Salmonella enterica genomes), is at least twice as fast for color queries, and is 2-6[Formula: see text] faster to construct.

Clinical Outcomes in Patients With Traumatic Dehiscence of Penetrating Keratoplasty Grafts.

PURPOSE: The purpose of this study was to report clinical characteristics and outcomes of surgical repair for patients with traumatic dehiscence of penetrating keratoplasty (PKP) grafts. METHODS: Retrospective, consecutive chart review of patients evaluated at Bascom Palmer Eye Institute between 2015 and 2020 with traumatic dehiscence of penetrating keratoplasty grafts. RESULTS: The study cohort consisted of 65 eyes of 65 patients. The mean age at presentation was 72 years (SD 18), with a male predominance (65%). The most common indications for PKP included keratoconus (42%), corneal scar (31%), and Fuchs corneal dystrophy (8%). Dehiscence occurred as a result of blunt trauma in 94% of cases, and the mean wound length was 6.4 clock hours (SD 2.4), with a predominance of inferior dehiscence. The mean presenting visual acuity (VA) was 2.45 logMAR (SD 0.41), and the mean final VA was 2.17 logMAR (SD 0.99). Graft failure occurred in 64% of patients, and 22% underwent repeat PKP. When stratified by indication for corneal transplantation (keratoconus vs. other), there was no significant difference in graft age at the time of rupture, final VA, rate of graft failure, or rate of repeat PKP. CONCLUSIONS: Traumatic dehiscence of corneal grafts remains a rare but serious subtype of ocular trauma with generally poor visual prognoses. Presenting VA along with severity of trauma and posterior segment involvement tend to be the worst prognostic factors in final visual outcome.

Foveal photoreceptor atrophy, persistent fetal vasculature, congenital cataracts, and microphthalmia in a pediatric patient with BCOR-associated oculo-facio-cardio-dental (OFCD) syndrome.

Purpose: To report a case of oculo-facio-cardio-dental (OFCD) syndrome secondary to a novel BCOR variant in a pediatric patient with congenital cataracts, microphthalmia, persistent fetal vasculature (PFV), focal chorioretinal hyperpigmentation, peripheral retinal avascularity, and foveal photoreceptor atrophy. Observations: A 3-month-old female patient was referred for bilateral congenital cataracts with microphthalmia. Her past medical history was significant for syndactyly of the toes, left bifid rib, atrial septal defect, patent ductus arteriosus, mitral regurgitation, pulmonary hypertension, anemia of prematurity, vesicoureteral reflux, and duodenal atresia. Examination under anesthesia revealed persistent fetal vasculature (PFV) with peripheral avascularity, foveal photoreceptor atrophy, and focal chorioretinal hyperpigmentation. A bilateral lensectomy with anterior vitrectomy and posterior capsulotomy were performed. Genetic testing identified a novel heterozygous pathogenic variant in the BCOR gene (c.1612C > T (p.Gln538Ter)), confirming a diagnosis of OFCD syndrome. Conclusions and importance: This case describes novel posterior segment findings in a patient with OFCD. A detailed examination of both anterior and posterior segments in combination with multimodal imaging should be performed in patients suspected of having OFCD, as this may be critical in determining visual potential and appropriate surgical management.

Meta-colored compacted de Bruijn graphs.

MOTIVATION: The colored compacted de Bruijn graph (c-dBG) has become a fundamental tool used across several areas of genomics and pangenomics. For example, it has been widely adopted by methods that perform read mapping or alignment, abundance estimation, and subsequent downstream analyses. These applications essentially regard the c-dBG as a map from k-mers to the set of references in which they appear. The c-dBG data structure should retrieve this set -- the color of the k-mer -- efficiently for any given k-mer, while using little memory. To aid retrieval, the colors are stored explicitly in the data structure and take considerable space for large reference collections, even when compressed. Reducing the space of the colors is therefore of utmost importance for large-scale sequence indexing. RESULTS: We describe the meta-colored compacted de Bruijn graph (Mac-dBG) -- a new colored de Bruijn graph data structure where colors are represented holistically, i.e., taking into account their redundancy across the whole collection being indexed, rather than individually as atomic integer lists. This allows the factorization and compression of common sub-patterns across colors. While optimizing the space of our data structure is NP-hard, we propose a simple heuristic algorithm that yields practically good solutions. Results show that the Mac-dBG data structure improves substantially over the best previous space/time trade-off, by providing remarkably better compression effectiveness for the same (or better) query efficiency. This improved space/time trade-off is robust across different datasets and query workloads. Code availability: A C++17 implementation of the Mac-dBG is publicly available on GitHub at: https://github.com/jermp/fulgor.

Fulgor: A fast and compact k-mer index for large-scale matching and color queries.

The problem of sequence identification or matching - determining the subset of references from a given collection that are likely to contain a query nucleotide sequence - is relevant for many important tasks in Computational Biology, such as metagenomics and pan-genome analysis. Due to the complex nature of such analyses and the large scale of the reference collections a resourceefficient solution to this problem is of utmost importance. The reference collection should therefore be pre-processed into an index for fast queries. This poses the threefold challenge of designing an index that is efficient to query, has light memory usage, and scales well to large collections. To solve this problem, we describe how recent advancements in associative, order-preserving, k-mer dictionaries can be combined with a compressed inverted index to implement a fast and compact colored de Bruijn graph data structure. This index takes full advantage of the fact that unitigs in the colored de Bruijn graph are monochromatic (all k-mers in a unitig have the same set of references of origin, or "color"), leveraging the order-preserving property of its dictionary. In fact, k-mers are kept in unitig order by the dictionary, thereby allowing for the encoding of the map from k-mers to their inverted lists in as little as 1+o(1) bits per unitig. Hence, one inverted list per unitig is stored in the index with almost no space/time overhead. By combining this property with simple but effective compression methods for inverted lists, the index achieves very small space. We implement these methods in a tool called Fulgor. Compared to Themisto, the prior state of the art, Fulgor indexes a heterogeneous collection of 30,691 bacterial genomes in 3.8× less space, a collection of 150,000 Salmonella enterica genomes in approximately 2× less space, is at least twice as fast for color queries, and is 2 - 6× faster to construct.

Evolving Use of Regional versus General Anesthesia for the Surgical Repair of Open Globe Injuries.

PURPOSE: The purpose of the current study is to report outcomes with the evolving use of regional anesthesia with monitored anesthesia care (RA-MAC) vs general anesthesia (GA) in the repair of open globe injuries. DESIGN: Retrospective, consecutive, comparative, nonrandomized clinical study. METHODS: The study includes 507 eyes of 507 patients with open globe injuries treated with either RA-MAC or GA at a tertiary referral center between 2015 and 2020. There was no predetermined protocol for selection of anesthesia method. However, based on experience and findings of prior research by this group, regional anesthesia with monitored anesthesia care was typically selected initially and changed to general anesthesia if warranted after evaluation of the patient and discussion with the surgeon. The main outcome measure was visual acuity at last follow-up. Results were compared to previously published study groups between 1995 and 2014. RESULTS: Primary closure of open globe injury was performed under RA-MAC anesthesia in 462 patients (91%) and under GA in 45 patients (9%). Zone 1, 2, and 3 injuries were recorded in 251, 170, and 86 patients, respectively. Zone 1 (96%, 240 of 251 patients) or zone 2 (92%, 156 of 170 patients) (P < .001) were more likely to be repaired under RA-MAC vs zone 3 injuries (76%, 65 of 86 patients). The improvement from presenting visual acuity was similar for the 2 anesthesia groups, 0.52 logMAR and 0.46 logMAR for RA-MAC and GA, respectively (P = .68, CI -0.3 to 0.2). The use of RA-MAC anesthesia for open globe injuries has increased at our institution from 64% in 1995-1999 to 91% in the present study, 2015-2020 (P < .00001). CONCLUSION: The current study demonstrates that with anesthesiologists experienced in ophthalmic regional anesthesia techniques, and appropriate case selection, RA-MAC can be safely used as an alternative to general anesthesia for open globe repair. Considerations when employing RA-MAC include a patient's ability to cooperate, position, and communicate for the duration of the globe repair.

Tree-based differential testing using inferential uncertainty for RNA-Seq.

Identifying differentially expressed transcripts poses a crucial yet challenging problem in transcriptomics. Substantial uncertainty is associated with the abundance estimates of certain transcripts which, if ignored, can lead to the exaggeration of false positives and, if included, may lead to reduced power. For a given set of RNA-Seq samples, TreeTerminus arranges transcripts in a hierarchical tree structure that encodes different layers of resolution for interpretation of the abundance of transcriptional groups, with uncertainty generally decreasing as one ascends the tree from the leaves. We introduce trenDi, which utilizes the tree structure from TreeTerminus for differential testing. The candidate nodes are determined in a data-driven manner to maximize the signal that can be extracted from the data while controlling for the uncertainty associated with estimating the transcript abundances. The identified candidate nodes can include transcripts and inner nodes, with no two nodes having an ancestor/descendant relationship. We evaluated our method on both simulated and experimental datasets, comparing its performance with other tree-based differential methods as well as with uncertainty-aware differential transcript/gene expression methods. Our method detects inner nodes that show a strong signal for differential expression, which would have been overlooked when analyzing the transcripts alone.

A patient with concurrent Axenfeld-Rieger and Stickler syndromes verified by molecular genetics.

Purpose: To report a case of Axenfeld-Rieger and Stickler Syndrome in a pediatric patient. Observations: A 3-month-old male was referred to the glaucoma clinic after he was noted to have elevated intraocular pressures in both eyes. His family history was notable for infantile glaucoma on his maternal side and retinal detachment on his paternal side. He was found to have anterior segment dysgenesis with iris strands, iridocorneal adhesions, and corectopia, as well as veil-like vitreous in both eyes. He required trabeculotomy, goniotomy, and multiple Baerveldt glaucoma implants in both eyes to achieve intraocular pressure control. Furthermore, the patient later developed macula-involving retinal detachments in both eyes, requiring pars plana vitrectomy with silicone oil tamponade. Genetic analysis confirmed heterozygous pathogenic variants in both the FOXC1 and COL2A1 genes, leading to the concurrent diagnoses of Axenfeld-Rieger and Stickler syndromes. Conclusions and importance: This is a rare case of a patient with concurrent Axenfeld-Rieger and Stickler syndromes. The severity of pathology in both the anterior and posterior segments required a collaborative multidisciplinary approach. In the diagnostic evaluation of congenital eye diseases, if there is strong family history of atypical findings for a given diagnosis, concurrent syndromes should be considered and ruled out. A comprehensive eye genetics panel may be a useful tool in these cases.

Peripheral Retinal Nonperfusion in Pediatric Patients with Optic Disc Hypoplasia.

PURPOSE: This study aims to report the association of optic nerve hypoplasia (ONH), peripheral retinal nonperfusion, and secondary complications in pediatric patients. DESIGN: Retrospective case series. METHODS: The study was conducted between January 2015 and January 2022 at the Bascom Palmer Eye Institute. Inclusion criteria were clinical diagnosis of optic disc hypoplasia, age <18 years, and a fluorescein angiography (FA) of acceptable quality. RESULTS: Seven patients (11 eyes) met inclusion criteria. Average age at presentation was 3.5 years (range 1 month-8 years) and the mean follow-up time was 34.28 months (range 2-87 months). Four patients (57.14%) showed bilateral optic disc hypoplasia. All eyes exhibited peripheral retina nonperfusion on FA, in which mild severity was found in 7 eyes (63.63%), moderate in 2 eyes (18.18%), severe in 1 eye (9.09%) and extreme in 1 eye (9.09%). Eight eyes (72.72%) showed evidence of 360 degrees of retinal nonperfusion. Two patients (18.18%) were diagnosed with concurrent retinal detachment that were deemed inoperable at the time of diagnosis. All cases were observed without intervention. None of the patients were observed to have complications during follow-up. CONCLUSION: Among pediatric patients with ONH, there appears to be a high rate of concurrent retinal nonperfusion. In these cases, FA is a helpful tool to detect peripheral nonperfusion. Retinal findings are subtle in some cases and may not be detectable in children with suboptimal imaging performed without examination under anesthesia.