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Plasmodium parasites undergo development and replication within the hepatocytes before infecting the erythrocytes and initiating clinical malaria. Although type-I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers a pathway of lysosomal fusion with the parasitophorous vacuole (PV) to help clear Plasmodium . Second, guanylate-binding protein (GBP) 1 disruption of the PV activates caspase-1 inflammasome, inducing pyroptosis to remove the infected host cells. Remarkably, both human and mouse hepatocytes enlist these cell-autonomous immune programs to eliminate Plasmodium ; their pharmacologic or genetic inhibition led to profound malarial susceptibility, and are essential in vivo . In addition to identifying the IFN-I-mediated cell-autonomous immune circuits controlling Plasmodium infection in the hepatocytes, this study extends our understanding of how non-immune cells are integral to protective immunity against malaria.

A nearly 3-year-old boy on nightly dialysis presented emergently with sudden loss of vision. On examination, his visual acuity was light perception in the right eye and no light perception in the left eye. There was bilateral optic disk edema, diffuse pallor of posterior poles, and a cherry red spot in the left fundus. The patient was subsequently found to be hemodynamically unstable and admitted to the pediatric intensive care unit with presumed septic shock. Optical coherence tomography revealed paracentral acute middle maculopathy lesions in the right eye and diffusely thick retina in the left eye. Magnetic resonance imaging and magnetic resonance angiography of the brain and vessels did not reveal any acute findings. The patient's presentation was most consistent with bilateral nonarteritic ischemic optic neuropathy and unilateral central retinal artery occlusion. On repeat evaluation 9 months later, vision was largely unchanged., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Plasmodium parasites that cause malaria undergo asymptomatic development in the parenchymal cells of the liver, the hepatocytes, prior to infecting erythrocytes and causing clinical disease. Traditionally, hepatocytes have been perceived as passive bystanders that allow hepatotropic pathogens such as Plasmodium to develop relatively unchallenged. However, now there is emerging evidence suggesting that hepatocytes can mount robust cell-autonomous immune responses that target Plasmodium, limiting its progression to the blood and reducing the incidence and severity of clinical malaria. Here we discuss our current understanding of hepatocyte cell-intrinsic immune responses that target Plasmodium and how these pathways impact malaria., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The MAF gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the MAF variants in the C-terminal DNA-binding domain associated with non-syndromic congenital cataracts and describe a patient with a novel, disease-causing de novo missense variant. Published reports of C-terminal MAF variants and their associated congenital cataracts and ophthalmic findings were reviewed. The patient we present and his biological parents had genetic testing via a targeted gene panel followed by trio-based whole exome sequencing. A 4-year-old patient with a history of bilateral nuclear and cortical cataracts was found to have a novel, likely pathogenic de novo variant in MAF , NM_005360.5:c.922A>G (p.Lys308Glu). No syndromic findings or anterior segment abnormalities were identified. We report the novel missense variant, c.922A>G (p.Lys308Glu), in the C-terminal DNA-binding domain of MAF classified as likely pathogenic and associated with non-syndromic bilateral congenital cataracts.

Inflammasome-mediated caspase-1 activation facilitates innate immune control of Plasmodium in the liver, thereby limiting the incidence and severity of clinical malaria. However, caspase-1 processing occurs incompletely in both mouse and human hepatocytes and precludes the generation of mature IL-1β or IL-18, unlike in other cells. Why this is so or how it impacts Plasmodium control in the liver has remained unknown. We show that an inherently reduced expression of the inflammasome adaptor molecule apoptosis-associated specklike protein containing CARD (ASC) is responsible for the incomplete proteolytic processing of caspase-1 in murine hepatocytes. Transgenically enhancing ASC expression in hepatocytes enabled complete caspase-1 processing, enhanced pyroptotic cell death, maturation of the proinflammatory cytokines IL-1β and IL-18 that was otherwise absent, and better overall control of Plasmodium infection in the liver of mice. This, however, impeded the protection offered by live attenuated antimalarial vaccination. Tempering ASC expression in mouse macrophages, on the other hand, resulted in incomplete processing of caspase-1. Our work shows how caspase-1 activation and function in host cells are fundamentally defined by ASC expression and offers a potential new pathway to create better disease and vaccination outcomes by modifying the latter., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Purpose: Presumed ocular histoplasmosis syndrome (POHS) is a posterior segment disorder that is usually subclinical unless choroidal neovascular membrane (CNVM) develops. It is thought to be the sequela of a prior systemic infection with Histoplasma capsulatum , and evidence supporting this association is based on epidemiologic, animal, and few enucleation studies. Acute presentation of chorioretinal involvement during an initial histoplasmosis systemic infection in immunocompetent patients is rarely reported, presumably due to the usual lack of or minimal symptoms of both the systemic and ocular disease. We report on an immunocompetent male with choroidal lesions detected during disseminated histoplasmosis infection and characterize the lesions using multimodal imaging., Observations: A 17-year-old male presented when routine optometry screening detected two deep, yellowish-white lesions in the left fundus. Optical coherence tomography (OCT) imaging confirmed a choroidal mass with extension through Bruch's membrane into the subretinal space and a small amount of subretinal fluid. Fluorescein angiography was suggestive of CNVM. There were no clinical findings of intraocular inflammation, and the patient was initially lost to follow-up. Eight weeks after last follow-up, the patient presented to the emergency department with fatigue, mild respiratory symptoms, and abdominal pain for the last month. Imaging revealed a mediastinal mass with hilar extension and innumerable nodules throughout the lung and spleen. Serum Histoplasma IgM/IgG were positive, and biopsy of the mediastinal mass revealed Histoplasma organisms. The patient was treated with antifungals and discharged. The patient underwent an extensive immunologic evaluation while admitted, which did not reveal an underlying immunodeficiency. On last follow-up, the choroidal lesions were smaller and more consolidated, and the subretinal fluid had resolved., Conclusions and Importance: We present a patient with choroidal lesions in the setting of disseminated systemic histoplasmosis infection and characterize a lesion using multimodal imaging. The presentation of acute chorioretinal lesions in the setting of biopsy proven systemic Histoplasma infection supports H. capsulatum as the etiology of POHS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Purpose: To examine the association of childhood strabismus with functional limitation to identify particular domains of impairment., Methods: The authors analyzed 201 children ages 5 to 17 years with strabismus enrolled in the 1996-2015 Medical Expenditure Panel Surveys, representative annual surveys of the U.S., Population: Functional impairment was assessed using the Columbia Impairment Scale (CIS), a validated measure of behavioral and psychosocial functioning. A CIS score of 16 or greater defined clinically significant functional impairment. Multivariate regression models adjusted for age, sex, race, ethnicity, household income, geographic location, and insurance type were constructed to examine the association of strabismus diagnosis with overall impairment and individual domains of function., Results: Children diagnosed as having strabismus had higher rates of clinically significant functional impairment compared to those without strabismus (15.1% vs 9.1%, adjusted odds ratio [95% CI]: 1.82 [1.11 to 2.97], P = .02). Moreover, strabismus diagnosis was associated with higher rates of problems with getting along with their mother (1.70 [1.21 to 2.40], P = .003) and father (1.66 [1.16 to 2.38], P = .006), getting along with other children (1.67 [1.16 to 2.40], P = .006), behavior at home (1.94 [1.37 to 2.74], P = .0002), staying out of trouble (1.52 [1.04 to 2.23], P = .03), nervousness (1.49 [1.05 to 2.11], P = .02), and getting involved with sports and hobbies (1.55 [1.03 to 2.34], P = .04)., Conclusions: Childhood strabismus is associated with 1.8-fold greater odds of clinically significant functional impairment, with greater dysfunction in specific relationship and behavioral domains. Functional burden may be an important consideration in management decisions. [ J Pediatr Ophthalmol Strabismus . 2023;60(4):268-276.] .

Significance: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study., Purpose: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia., Methods: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism)., Results: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion)., Conclusions: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2023 American Academy of Optometry.)

Malaria is a deadly disease caused by the parasite Plasmodium and is transmitted through the bite of female Anopheles mosquitoes. The sporozoite stage of Plasmodium deposited by mosquitoes in the skin of vertebrate hosts undergoes a phase of mandatory development in the liver before initiating clinical malaria. We know little about the biology of Plasmodium development in the liver; access to the sporozoite stage and the ability to genetically modify such sporozoites are critical tools for studying the nature of Plasmodium infection and the resulting immune response in the liver. Here, we present a comprehensive protocol for the generation of transgenic Plasmodium berghei sporozoites. We genetically modify blood-stage P. berghei and use this form to infect Anopheles mosquitoes when they take a blood meal. After the transgenic parasites undergo development in the mosquitoes, we isolate the sporozoite stage of the parasite from the mosquito salivary glands for in vivo and in vitro experimentation. We demonstrate the validity of the protocol by generating sporozoites of a novel strain of P. berghei expressing the green fluorescent protein (GFP) subunit 11 (GFP11), and show how it could be used to investigate the biology of liver-stage malaria.

Background  Fellowship program Web sites are a crucial source of information for prospective pediatric ophthalmology applicants, especially in light of the restrictions on in-person interactions due to the coronavirus disease 2019 pandemic. Objective  This study examined all pediatric ophthalmology fellowship Web sites for availability and presented recruitment and training content. Methods  A full list of all pediatric ophthalmology and strabismus (POAS) fellowship programs were compiled from the Association of University Professors of Ophthalmology (AUPO) directory and the San Francisco Match (SFMatch) application listing. Each fellowship was queried by Google Internet search to identify the program's corresponding Web site. The content of Web sites was evaluated using 20 predetermined recruitment and training criteria. All data were collected in February 2022. Kruskal-Wallis and Mann-Whitney U tests were constructed to examine differences by geographic location, program size, number of teaching faculty, and affiliation with a top ophthalmology residency program. Results  There were 45 pediatric ophthalmology fellowships identified from the AUPO and SFMatch. All pediatric ophthalmology fellowships had an available program Web site. However, there was significant variability in content, and the average Web site had approximately half of the evaluated criteria. POAS Web sites reported a greater number of recruitment criteria than program training criteria. There were no differences by program size, number of faculty, affiliation with a top residency program, or geographic location in the number of observed criteria. Conclusions  This study provides data to drive efforts to improve pediatric ophthalmology fellowship Web sites. Pediatric ophthalmology fellowship Web sites are missing important information, and there are opportunities to improve program Web sites, regardless of program size, number of faculty, affiliation with a top residency, and geographic location. Informative, accurate Web sites may attract qualified candidates, and as a result, elevate the likelihood that interviewed candidates are well-suited to the program. As such, improvements to fellowship Web sites can streamline the application process and increase a program's success rate in the match., Competing Interests: Conflicts of Interest None., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Malaria, caused by Plasmodium parasites is a severe disease affecting millions of people around the world. Plasmodium undergoes obligatory development and replication in the hepatocytes, before initiating the life-threatening blood-stage of malaria. Although the natural immune responses impeding Plasmodium infection and development in the liver are key to controlling clinical malaria and transmission, those remain relatively unknown. Here we demonstrate that the DNA of Plasmodium parasites is sensed by cytosolic AIM2 (absent in melanoma 2) receptors in the infected hepatocytes, resulting in Caspase-1 activation. Remarkably, Caspase-1 was observed to undergo unconventional proteolytic processing in hepatocytes, resulting in the activation of the membrane pore-forming protein, Gasdermin D, but not inflammasome-associated proinflammatory cytokines. Nevertheless, this resulted in the elimination of Plasmodium -infected hepatocytes and the control of malaria infection in the liver. Our study uncovers a pathway of natural immunity critical for the control of malaria in the liver.

Malaria is a deadly disease caused by the parasite, Plasmodium , and impacts the lives of millions of people around the world. Following inoculation into mammalian hosts by infected mosquitoes, the sporozoite stage of Plasmodium undergoes obligate development in the liver before infecting erythrocytes and causing clinical malaria. The most promising vaccine candidates for malaria rely on the use of attenuated live sporozoites to induce protective immune responses. The scope of widespread testing or clinical use of such vaccines is limited by the absence of efficient, reliable, or transparent strategies for the long-term preservation of live sporozoites. Here we outline a method to cryopreserve the sporozoites of various human and murine Plasmodium species. We found that the structural integrity, viability, and in vivo or in vitro infectiousness were conserved in the recovered cryopreserved sporozoites. Cryopreservation using our approach also retained the transgenic properties of sporozoites and immunization with cryopreserved radiation attenuated sporozoites (RAS) elicited strong immune responses. Our work offers a reliable protocol for the long-term storage and recovery of human and murine Plasmodium sporozoites and lays the groundwork for the widespread use of live sporozoites for research and clinical applications.

Background: A fetal scalp electrode (FSE), first described by Edward Hon in 1967, is an intrapartum monitoring device embedded directly into the fetal scalp for an accurate measure of fetal heart rate. Though use of an FSE is generally safe, complications can occur from misplacement, including ophthalmic injury., Case Presentation: Patient was a 28-year-old G6P5006 who presented for induction of labor at 39 weeks due to asymptomatic bilateral pulmonary embolism. Concerning findings on external fetal monitoring led to placement of a fetal scalp electrode for close monitoring. Upon delivery, the neonate was noted to have the FSE embedded in the left upper eyelid. Ophthalmology was consulted and could not rule out ocular injury on external examination at the bedside. Examination under anesthesia in the operating room demonstrated no penetration of the ocular globe, and the eyelid laceration was sutured. The laceration was well-healing at one-week follow-up with no further complications., Conclusion: Facial or brow presentation during delivery is rare but may increase the risk for misplacement of an FSE. Ultrasound verification of vertex position is warranted immediately prior to placing an FSE for patients at higher risk of facial or brow presentation. Periorbital edema of neonates may protect against damage to deeper structures. However, Ophthalmology should be consulted to rule out ocular injury if the FSE is placed in the periocular region., (© 2022. The Author(s).)

Malaria is a devastating disease impacting over half of the world's population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, precluding the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire anti-malarial drugs and vaccine strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Cataract is an important cause of visual impairment in children. Data from a large pediatric cataract surgery registry can provide real-world estimates of visual outcomes and the 5-year cumulative incidence of adverse events., Objective: To assess visual acuity (VA), incidence of complications and additional eye operations, and refractive error outcomes 5 years after pediatric lensectomy among children younger than 13 years., Design, Setting, and Participants: This prospective cohort study used data from the Pediatric Eye Disease Investigator Group clinical research registry. From June 2012 to July 2015, 61 eye care practices in the US, Canada, and the UK enrolled children from birth to less than 13 years of age who had undergone lensectomy for any reason during the preceding 45 days. Data were collected from medical record reviews annually thereafter for 5 years until September 28, 2020., Exposures: Lensectomy with or without implantation of an intraocular lens (IOL)., Main Outcomes and Measures: Best-corrected VA and refractive error were measured from 4 to 6 years after the initial lensectomy. Cox proportional hazards regression was used to assess the 5-year incidence of glaucoma or glaucoma suspect and additional eye operations. Factors were evaluated separately for unilateral and bilateral aphakia and pseudophakia., Results: A total of 994 children (1268 eyes) undergoing bilateral or unilateral lensectomy were included (504 [51%] male; median age, 3.6 years; range, 2 weeks to 12.9 years). Five years after the initial lensectomy, the median VA among 701 eyes with available VA data (55%) was 20/63 (range, 20/40 to 20/100) in 182 of 316 bilateral aphakic eyes (58%), 20/32 (range, 20/25 to 20/50) in 209 of 386 bilateral pseudophakic eyes (54%), 20/200 (range, 20/50 to 20/618) in 124 of 202 unilateral aphakic eyes (61%), and 20/65 (range, 20/32 to 20/230) in 186 of 364 unilateral pseudophakic eyes (51%). The 5-year cumulative incidence of glaucoma or glaucoma suspect was 46% (95% CI, 28%-59%) in participants with bilateral aphakia, 7% (95% CI, 1%-12%) in those with bilateral pseudophakia, 25% (95% CI, 15%-34%) in those with unilateral aphakia, and 17% (95% CI, 5%-28%) in those with unilateral pseudophakia. The most common additional eye surgery was clearing the visual axis, with a 5-year cumulative incidence of 13% (95% CI, 8%-17%) in participants with bilateral aphakia, 33% (95% CI, 26%-39%) in those with bilateral pseudophakia, 11% (95% CI, 6%-15%) in those with unilateral aphakia, and 34% (95% CI, 28%-39%) in those with unilateral pseudophakia. The median 5-year change in spherical equivalent refractive error was -8.38 D (IQR, -11.38 D to -2.75 D) among 89 bilateral aphakic eyes, -1.63 D (IQR, -3.13 D to -0.25 D) among 130 bilateral pseudophakic eyes, -10.75 D (IQR, -20.50 D to -4.50 D) among 43 unilateral aphakic eyes, and -1.94 D (IQR, -3.25 D to -0.69 D) among 112 unilateral pseudophakic eyes., Conclusions and Relevance: In this cohort study, development of glaucoma or glaucoma suspect was common in children 5 years after lensectomy. Myopic shift was modest during the 5 years after placement of an intraocular lens, which should be factored into implant power selection. These results support frequent monitoring after pediatric cataract surgery to detect glaucoma, visual axis obscuration causing reduced vision, and refractive error.

Circulating memory CD8 T cell trafficking and protective capacity during liver-stage malaria infection remains undefined. We find that effector memory CD8 T cells (Tem) infiltrate the liver within 6 hours after malarial or bacterial infections and mediate pathogen clearance. Tem recruitment coincides with rapid transcriptional upregulation of inflammatory genes in Plasmodium-infected livers. Recruitment requires CD8 T cell-intrinsic LFA-1 expression and the presence of liver phagocytes. Rapid Tem liver infiltration is distinct from recruitment to other non-lymphoid tissues in that it occurs both in the absence of liver tissue resident memory "sensing-and-alarm" function and ∼42 hours earlier than in lung infection by influenza virus. These data demonstrate relevance for Tem in protection against malaria and provide generalizable mechanistic insights germane to control of liver infections., Competing Interests: Declarations of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Norrie disease is a rare X-linked recessive vitreoretinopathy. Variants of the NDP gene are associated with this condition. This case reports aims to demonstrate the variations of clinical presentations and exam findings of this disease., Observations: A retrospective chart review of the patient's ocular and systemic findings and imaging results was performed. The patient had received genetic testing, including mutational analysis of targeted genes associated with retrolental masses. The patient had a comprehensive eye exam for bilateral leukocoria, demonstrating large retrolental masses, anterior polar cataracts, stretched ciliary processes, and roving eye movements. B-scan ultrasonography and magnetic resonance imaging indicated total, funnel-shaped retinal detachments, which is a unique retinal configuration in Norrie disease. Genetic testing confirmed deletion of the coding region of all three exons in the NDP gene, which confirmed Norrie disease. He has not shown any extraocular involvement to date., Conclusions and Importance: This is a case demonstrating the association between deletion of the coding region NDP gene and Norrie disease. The phenotypical variation of this disease warrants further studies of genotype-phenotype correlations and mutations of the NDP gene., Competing Interests: The following authors have no financial disclosures: YZ, MJS, BKB, SK, MBM., (© 2021 The Authors.)

Aim: To investigate the impact of concussion on pupillary function in children by examining pupillometric parameters and assessing for differences in children reporting photosensitivity., Methods: Retrospective chart review was performed of pediatric patients referred for visual symptoms after concussion from 2017 to 2018 seen in a single academic outpatient clinic. Pupillometry data of 92 patients were included. Outcomes were compared to normative pediatric data from the same institution by 2-sample t tests. The association between photosensitivity and each outcome was assessed by use of linear mixed models with photosensitivity as a fixed effect and random patient effect., Results: Outcomes of 181 eyes in 92 concussion patients were averaged by patient and compared to normative values in scotopic conditions. Concussion patients had an average age of 13.8 ± 2.64 years. Average constriction velocity ( P = .0008), maximum constriction velocity ( P = .0012), and average dilation velocity ( P = .0034) were faster in concussion patients, whereas 75% recovery times ( P = .0027) was increased. Photosensitivity did not significantly affect measured pupillary responses., Conclusion: Dynamic pupillary responses may be increased in pediatric concussion. Pupillometry may provide insight into the complex pathophysiological changes underlying pediatric concussion.

CRISPR/Cas9 technology has revolutionized rapid and reliable gene editing in cells. Although many cell types have been subjected to CRISPR/Cas9-mediated gene editing, there is no evidence of success in genetic alteration of Ag-experienced memory CD8 T cells. In this study, we show that CRISPR/Cas9-mediated gene editing in memory CD8 T cells precludes their proliferation after Ag re-encounter in vivo. This defect is mediated by the proapoptotic transcription factor p53, a sensor of DNA damage. Temporarily inhibiting p53 function offers a window of opportunity for the memory CD8 T cells to repair the DNA damage, facilitating robust recall responses on Ag re-encounter. We demonstrate this by functionally altering memory CD8 T cells using CRISPR/Cas9-mediated targeted gene disruption under the aegis of p53siRNA in the mouse model. Our approach thus adapts the CRISPR/Cas9 technology for memory CD8 T cells to undertake gene editing in vivo, for the first time, to our knowledge., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Purpose: To present a pediatric case series in which the flanged intrascleral intraocular lens (IOL) fixation technique (Yamane technique) was used to correct aphakia., Methods: The surgical database of a single tertiary children's hospital was reviewed to identify all patients who underwent secondary IOL implantation by a single surgeon from May 2018 to January 2020. The medical records and operative reports of all patients operated on using the Yamane technique were reviewed retrospectively. Intra- and postoperative complications and pre- and postoperative vision and refraction were documented to assess outcomes., Results: A total of 12 eyes of 10 consecutive patients were included. Mean age at surgery was 10 ± 6 years. Indications for scleral fixation were ectopia lentis (secondary to Marfan syndrome [n = 3] or idiopathic [n = 1]), lens subluxation with intermittent pupillary block secondary to Weill- Marchesani syndrome (n = 2), early childhood lensectomy with insufficient residual capsular support (n = 5), and traumatic aphakia after an open globe (n = 1). Mean follow-up was 8 ± 5 months. No major intraoperative complications occurred. Postoperatively 1 patient required IOL repositioning 1 week after surgery. The location of one haptic was noted to be intrascleral but superficial in another patient, who did not require surgical intervention. The mean postoperative astigmatism was 2 ± 2 D. Good visual results were achieved in all eyes., Conclusions: With slight modifications, the Yamane technique can be adapted to the pediatric eye. This technique has significant surgical and anatomic advantages and provides stable IOL fixation. Visual outcomes and adverse events compare favorably with older techniques., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To evaluate the long-term visual outcomes of ab externo trabeculotomy for primary congenital glaucoma (PCG) at a single pediatric ophthalmology center., Methods: In this retrospective single-center case series, data from 63 eyes of 40 patients who underwent ab externo trabeculotomy between September 2006 and June 2018 were included. The data were analyzed for best corrected visual acuity (BCVA), stereopsis, and surgical success. Kaplan-Meier analysis was performed using the surgical success criteria defined as intraocular pressure (IOP) ≤ 21 mmHg and ≥ 20% below baseline without the need for additional glaucoma surgery., Results: BCVA at the time of diagnosis was 0.37 ± 0.48 logMAR, which changed to 0.51 ± 0.56 logMAR at the final follow-up ( P = 0.08). Twenty-five percent of patients had BCVA equal to or better than 20/40 at the final visit. The mean refraction at baseline was -4.78 ± 5.87 diopters, which changed to less myopic refraction of -2.90 ± 3.83 diopters at the final visit. Optical correction was prescribed in 66% of eyes at the final visit. The average final stereopsis was 395.33 sec of arc. The linear regression model showed a significant association between the surgery success rate and final BCVA as well as stereoacuity ( P -values: 0.04 and 0.03, respectively). Intraocular pressure (IOP) decreased significantly from 29.79 ± 7.67 mmHg at baseline to 16.13 ± 3.41 mmHg at the final follow-up ( P = 0.001)., Conclusion: Patients with PCG can achieve an acceptable visual acuity and stereoacuity, particularly in cases of timely intervention and close follow-up., Competing Interests: There are no conflicts of interest., (Copyright © 2020 Esfandiari et al.)

Malaria, caused by the protozoan Plasmodium, is a devastating disease with over 200 million new cases reported globally every year. Although immunization is arguably the best strategy to eliminate malaria, despite decades of research in this area we do not have an effective, clinically approved antimalarial vaccine. The current impetus in the field is to develop vaccines directed at the pre-erythrocytic developmental stages of Plasmodium , utilizing novel vaccination platforms. We here review the most promising pre-erythrocytic stage antimalarial vaccine candidates.

We present the case of a 4-year-old boy with acquired Brown syndrome of inflammatory origin. Without evidence of systemic inflammation, the disease typically resolves with oral steroids or nonsteroidal anti-inflammatory drugs. Refractory cases can be treated with local steroid injections or surgery. The present case of inflammatory Brown syndrome did not respond to conservative therapy, and parental concerns and wishes precluded more invasive treatments. Adalimumab was initiated and led to complete resolution of the disease., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Pupillary evaluation is a crucial element of physical exams. Noting size, reactivity, and consensual response is critical in assessing for optic nerve dysfunction. We aim to establish normative data for scotopic pupillary size and function in the pediatric population in a clinical setting., Methods: Pupillometry was obtained prospectively for consecutive, normal patients < 18 years old being evaluated by Lurie Children's Ophthalmology. Quantitative data included maximum (MAX) and minimum (MIN) diameters, constriction percentage (CON), latency (LAT), average (ACV) and maximum (MCV) constriction velocities, average dilation velocity (ADV), and 75% recovery time (T75). Iris color was noted as light, intermediate, or dark., Results: 196 eyes of 101 participants (42.6% male, ages 1-17 years, average age 10.3 years) were analyzed. Mean MAX was 6.6 mm (5.1-8.1 mm 95% CI); MIN was 4.7 mm (3.1-6.1 mm 95% CI); CON was 30% (17-42 95% CI); LAT was 230 milliseconds (160-300 ms 95% CI); ACV was 3.70 mm/sec (2.21-5.18 mm/sec 95% CI); and ADV was 0.88 mm/sec (0.38-1.38 mm/sec 95% CI). Age had a positive correlation with MAX, MIN, and CON. 84.2 and 95.8% of participants showed resting pupil asymmetry of ≤0.5 mm and ≤ 1.0 mm, respectively., Conclusions: Quantitative pupillometry can be a useful tool for screening pediatric patients. We sought to establish normative data in this group. We found males to have significantly greater MCV and CON than females (p < 0.05). Also, age had a positive correlation with MAX, MIN, and CON.

Pott's puffy tumor is a significant complication of frontal sinusitis that leads to frontal bone osteomyelitis and can be associated with frontal swelling, subperiosteal abscess, and intracranial abscess. It may be associated with antecedent trauma and typically presents in adolescents. Orbital involvement is rarely reported. We describe the case of a 15-year-old male who presented after blunt facial trauma with orbital hematoma and developed Pott's puffy tumor with orbital cellulitis and subperiosteal abscess. Management required a collaborative, multidisciplinary effort that yielded a good outcome.

Background : Congenital disorders of glycosylation (CDG) are a group of hereditary multisystem disorders characterized by hypoglycosylation of glycoproteins. CDG type I results in a defect in the assembly of lipid-linkedoligosaccharides or their transfer onto nascent glycoproteins. Ocular abnormalities are common in CDG, but there is no report of detailed ophthalmologic evaluation in patients with CDG type Ig in the literature. Materials and Methods : Retrospective chart review of a case of CDG type Ig with novel variant in the associated gene: ALG12. Results : In addition to typical systemic findings of CDG, our case was found to have exotropia, bilateralcataracts, and retinitis pigmentosa with extinguished electroretinography in photopic and scotopic conditions. Conclusions : We hope to extend the understanding of ALG12-related CDG type Ig with these ophthalmologic observations.

Precis: In this retrospective case series, both Baerveldt and Ahmed glaucoma drainage devices resulted in good long-term outcomes in eyes with pediatric glaucoma following cataract surgery (GFCS)., Background: The aim of this study was to describe the long-term safety and efficacy of primary glaucoma drainage device surgery in patients with pediatric GFCS., Methods: We retrospectively identified 28 eyes of 28 patients with GFCS that underwent tube shunt surgery with the Ahmed Glaucoma Valve or Baerveldt Glaucoma Implant. The primary outcome measure was a surgical failure, defined as intraocular pressure (IOP) >21 mm Hg or not reduced by 20% below baseline on 2 consecutive follow-up visits after 3 months, IOP <5 mm Hg on 2 consecutive follow-up visits after 3 months, and reoperation for glaucoma., Results: The mean duration between cataract removal and the diagnosis of glaucoma was 3.6±1.5 years. Kaplan-Meier survival curves indicated a mean time to failure of 41.9±2.1 months after drainage device surgery. The cumulative probability of failure at 1, 2, 3, and 4 years was 3.6%, 19%, 28%, and 28%. IOP was significantly decreased from 29.3±4.1 mm Hg preoperatively to 17.6±1.6 mm Hg at the final follow-up visit (P<0.001). The number of glaucoma medications at baseline was 3.1±0.6, which decreased to 2.1±0.7 at the final visit (P=0.001)., Conclusions: Glaucoma drainage device surgery results in good long-term outcomes in patients with GFCS.

Patients who survive sepsis experience long-term immunoparalysis characterized by numerical and/or functional lesions in innate and adaptive immunity that increase the host's susceptibility to secondary complications. The extent to which tumor development/growth is affected in sepsis survivors remains unknown. In this study, we show cecal ligation and puncture (CLP) surgery renders mice permissive to increased B16 melanoma growth weeks/months after sepsis induction. CD8 T cells provide partial protection in this model, and tumors from sepsis survivors had a reduced frequency of CD8 tumor-infiltrating lymphocytes (TILs) concomitant with an increased tumor burden. Interestingly, the postseptic environment reduced the number of CD8 TILs with high expression of activating/inhibitory receptors PD-1 and LAG-3 (denoted PD-1 hi ) that define a tumor-specific CD8 T cell subset that retain some functional capacity. Direct ex vivo analysis of CD8 TILs from CLP hosts showed decreased proliferation, IFN-γ production, and survival compared with sham counterparts. To increase the frequency and/or functional capacity of PD-1 hi CD8 TILs in tumor-bearing sepsis survivors, checkpoint blockade therapy using anti-PD-L1/anti-LAG-3 mAb was administered before or after the development of sepsis-induced lesions in CD8 TILs. Checkpoint blockade did not reduce tumor growth in CLP hosts when therapy was administered after PD-1 hi CD8 TILs had become reduced in frequency and/or function. However, early therapeutic intervention before lesions were observed significantly reduced tumor growth to levels seen in nonseptic hosts receiving therapy. Thus, sepsis-induced immunoparalysis is defined by diminished CD8 T cell-mediated antitumor immunity that can respond to timely checkpoint blockade, further emphasizing the importance of early cancer detection in hosts that survive sepsis., (Copyright © 2019 by The American Association of Immunologists, Inc.)

Purpose: To analyze the long-term results of ab externo trabeculotomy with a Harms trabeculotome at a single, tertiary care pediatric hospital., Methods: The medical records of pediatric patients operated on between September 2006 and June 2018 were reviewed retrospectively. Kaplan-Meier analysis was performed, with success defined as postoperative intraocular pressure (IOP) of ≤21 mm Hg, >20% reduction from preoperative IOP, and no need for further glaucoma surgery. Risk factors for failure were identified using Cox proportional hazards ratio., Results: A total of 63 eyes of 40 patients were included. The cumulative probability of success rate was 83% at 3 months, 76% at 6, 73% at 12, 72% at 18, and 65% at final visit. Presentation within 3 months of life was associated with a less favorable outcome. Thirty-five eyes (56%) underwent repeat trabeculotomy to treat a different area of the trabecular meshwork because of inadequately controlled IOP after the first session. Of those who needed another session of trabeculotomy, the final success rate was 60.2%. IOP significantly decreased from 29.79 ± 7.67 mm Hg at baseline to 16.13 ± 3.41 mm Hg by final follow-up (P = 0.001). Patients were followed for an average of 85.74 ± 32.95 months. IOP and success rates remained stable 18 months after surgery., Conclusions: In our patient cohort, ab externo trabeculotomy was associated with good long-term results. More extensive trabeculotomy (ie, more than one procedure) was associated with better long-term success rates., (Copyright © 2019 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Optic nerve aplasia (ONA) is a rare congenital anomaly with a limited number of published reports. A retrospective review was performed on seven patients with ONA seen during 2004-2017. Patient's ocular and extraocular manifestations, imaging findings, and clinical course were described. Magnetic resonance imaging (MRI) showed anomalies of the optic chiasm and tracts and other central nervous system involvement. In conclusion, in addition to thorough ophthalmic examinations, MRI is important in evaluating and diagnosing ONA. The patients need to be monitored for both ocular and extraocular concerns., (© 2019 Taylor & Francis Group, LLC.)

Immunity to malaria has been linked to the availability and function of helper CD4 + T cells, cytotoxic CD8 + T cells and γδ T cells that can respond to both the asymptomatic liver stage and the symptomatic blood stage of Plasmodium sp. infection. These T cell responses are also thought to be modulated by regulatory T cells. However, the precise mechanisms governing the development and function of Plasmodium-specific T cells and their capacity to form tissue-resident and long-lived memory populations are less well understood. The field has arrived at a point where the push for vaccines that exploit T cell-mediated immunity to malaria has made it imperative to define and reconcile the mechanisms that regulate the development and functions of Plasmodium-specific T cells. Here, we review our current understanding of the mechanisms by which T cell subsets orchestrate host resistance to Plasmodium infection on the basis of observational and mechanistic studies in humans, non-human primates and rodent models. We also examine the potential of new experimental strategies and human infection systems to inform a new generation of approaches to harness T cell responses against malaria.

Aim: To report a large series of children having Nd:YAG laser capsulotomy in the operating room using the lateral decubitus position., Methods: Medical records of children who underwent Nd:YAG laser capsulotomy in the operating room at Ann & Robert H. Lurie Children's Hospital of Chicago between September 2008 and April 2017 were reviewed. Induction of general anesthesia and intubation was performed in the supine position after which the patient was placed in lateral decubitus position. The Nd:YAG laser capsulotomy was performed using a standard protocol. At the completion of the procedure, the patient was turned back into the supine position and extubated., Results: This study included 87 eyes of 60 patients. Patient's age ranged from 1 to 18y (mean 6.4±4.1y). In most cases (84/87, 97%), the procedure was performed under general anesthesia. In all cases, good focus on the membrane was achieved, and the procedure was performed successfully. There were no intraoperative ocular or anesthesia-related complications., Conclusion: When performing Nd:YAG laser capsulotomy in the operating room, the lateral decubitus position allows an easy and safe approach without the risk of potentially devastating complications that have been associated with the previously described sitting and prone positions.

Plasmodium sporozoites inoculated by mosquitoes migrate to the liver and infect hepatocytes prior to release of merozoites that initiate symptomatic blood-stage malaria. Plasmodium parasites are thought to be restricted to hepatocytes throughout this obligate liver stage of development, and how liver-stage-expressed antigens prime productive CD8 T cell responses remains unknown. We found that a subset of liver-infiltrating monocyte-derived CD11c + cells co-expressing F4/80, CD103, CD207, and CSF1R acquired parasites during the liver stage of malaria, but only after initial hepatocyte infection. These CD11c + cells found in the infected liver and liver-draining lymph nodes exhibited transcriptionally and phenotypically enhanced antigen-presentation functions and primed protective CD8 T cell responses against Plasmodium liver-stage-restricted antigens. Our findings highlight a previously unrecognized aspect of Plasmodium biology and uncover the fundamental mechanism by which CD8 T cell responses are primed against liver-stage malaria antigens., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To report a case of OFCD associated with a de novo BCOR pathogenic variant and highlight the ocular findings and possible mechanisms., Methods: A retrospective chart review of the patient's ocular and systemic findings was performed. The patient underwent diagnostic whole exome sequencing (WES)., Results: The patient had a comprehensive eye exam in infancy demonstrating bilateral congenital cataracts consisting of posterior lenticonus with a posterior cortical opacity. She also had blepharoptosis with a hooded appearance and retinal pigment hypertrophy of the inferior retina bilaterally. Systemic findings include atrial septal defect, patent ductus arteriosus, congenital clubfoot, syndactyly, tethered cord, and laryngeal cleft. WES identified a de novo heterozygous R1136X pathogenic variant in the BCOR gene., Conclusion: The typical ocular manifestation of OFCD syndrome is congenital cataracts, which can have a significant impact on visual development and so should be considered in patients with multiple medical issues that may fit the diagnosis. A comprehensive eye exam in these patients is thus warranted.

Background: Marfan syndrome (MFS) is a genetic disorder that affects multiple organ systems, including the eye. The most common ocular manifestations include ectopia lentis and retinal detachment. The current literature qualitatively cites that MFS patients have miotic or "poorly dilating" pupils. This study was the first to quantitatively assess pupillary function in MFS patients., Materials and Methods: 57 eyes from 29 MFS patients, 36 eyes from 18 pediatric age- and gender-matched controls, and 44 eyes from 22 adult age-matched controls were measured in a clinic-based cross sectional study. Pupillometry data were measured in scotopic conditions using the handheld NeurOptics PLR-200™ Pupillometer (NeurOptics, Irvine, CA, USA). Data obtained with the pupillometer were maximum and minimum diameter, constriction percentage, latency, average and maximum constriction velocities, average dilation velocity, and 75% recovery time (T75)., Results: Pediatric patients with MFS had significantly slower average constriction velocity measurements (β = 0.65, p = 0.0003), maximum constriction velocity measurements (β = 0.51, p = 0.0150) and average dilation velocity measurements (β = -0.19, p = 0.0029) compared to control patients. In the adult cohort, results indicated significantly slower average dilation velocity measurements (β = -0.13, p = 0.0077) compared to controls., Conclusions: Our data highlight pupillary parameters within a population of MFS patients under scotopic conditions. Constriction and dilation velocities were slower in the pediatric MFS patients compared to age- and gender-matched controls, and dilation velocities were slower in the adult MFS patients compared to age-matched controls. These findings, for the first time, quantitatively demonstrated differences in pupillary function in patients with MFS.

Background: Previous studies of partially accommodative esotropia (PAET) have assessed factors requiring surgery and alignment outcomes. The purpose of the present study was to additionally evaluate stereoacuity in patients who required surgery for their nonaccommodative component., Methods: The medical records of consecutive patients with PAET who underwent bilateral medial rectus recession from April 1990 to July 2010 to treat the nonaccommodative component were reviewed retrospectively. Preoperative data included visual acuity, stereoacuity, cycloplegic refraction, deviation at distance and near, and age at surgery. The primary outcomes were stereoacuity and alignment., Results: A total of 84 patients were included. Stereopsis by the Titmus StereoTest was demonstrated in 51 (61%) by the final visit. The average follow-up time was 4.4 ± 2.8 years (range, 0.8-11.0 years). Fine stereopsis (100 arcsec or better) was appreciated in 29 patients (35%, 57% of those with stereopsis). Of those with residual esotropia, 11 (50%) demonstrated stereopsis, and 7 (32%) appreciated fine stereoacuity. No exotropic patient had stereopsis. There was a statistically significant correlation between age at time of surgery and stereopsis at 1 year (ρ = 0.233; P = 0.033) but not at the final visit (ρ = 0.106, P = 0.34). Of the 84 patients, 56 (67%) had a favorable alignment (within 10 Δ of orthotropia) at the final visit; 22 (26%) had residual esotropia; and 6 (7%) had consecutive exotropia., Conclusions: In this subset of esotropic patients who required surgery for their nonaccommodative component, favorable sensory outcomes can be achieved. Furthermore, favorable stereoacuity can be found even when there is a residual esodeviation., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Congenital lymphocytic choriomeningitis virus (LCMV) infection is associated with high mortality and morbidity. Although the number of cases reported in the literature has been increasing, it might still be clinically an underdiagnosed human fetal teratogen. We report 2 more cases of serologically proven congenital LCMV infection. One case presented with Aicardi-like syndrome features. Since congenital LCMV infection may mimic Aicardi syndrome, serologic testing should be considered in the workup of patients with Aicardi syndrome to rule out LCMV infection., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Central retinal artery occlusion (CRAO) is uncommon among children and young adults. Bilateral CRAO before the age of 18 years are extremely rare. We present a case of an idiopathic bilateral CRAO in a young healthy female., (Copyright © 2017 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Malaria, caused by the protozoan Plasmodium, is a devastating mosquito-borne disease with the potential to affect nearly half the world's population. Despite mounting substantial T and B cell responses, humans fail to efficiently control blood-stage malaria or develop sterilizing immunity to reinfections. Although forkhead box P3 (FOXP3) + CD4 + regulatory T (T reg ) cells form a part of these responses, their influence remains disputed and their mode of action is unknown. Here we show that T reg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (T FH )-B cell interactions in germinal centers. Mechanistically, T reg cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Targeting T reg cells or CTLA-4 in this precise window accelerated parasite clearance and generated species-transcending immunity to blood-stage malaria in mice. Our study uncovers a critical mechanism of immunosuppression associated with blood-stage malaria that delays parasite clearance and prevents development of potent adaptive immunity to reinfection. These data also reveal a temporally discrete and potentially therapeutically amenable functional role for T reg cells and CTLA-4 in limiting antimalarial immunity.

Activated CD8 + T cells differentiate into cytotoxic effector (T EFF ) cells that eliminate target cells. How T EFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in T EFF cells. Runx3-deficient CD8 + T EFF cells aberrantly upregulated genes characteristic of follicular helper T (T FH ) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the T FH program. Ablating Tcf7 in Runx3-deficient CD8 + T EFF cells prevented the upregulation of T FH genes and ameliorated their defective induction of cytotoxic genes. As such, Runx3-mediated Tcf7 repression coordinately enforced acquisition of cytotoxic functions and protected the cytotoxic lineage integrity by preventing T FH -lineage deviation.

Prostaglandin D2 (PGD 2 ), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD 2 signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression analyses indicated that PGD 2 /DP1 signaling is required for up-regulation of a putative inflammasome inhibitor, PYDC3, in CD11b + cells in the CNS of infected mice. Our results also demonstrated that, in addition to PGD 2 /DP1 signaling, type 1 IFN (IFN-I) signaling is required for PYDC3 expression. In the absence of Pydc3 up-regulation, IL-1β expression and, subsequently, mortality were increased in infected DP1 -/- mice. Notably, survival was enhanced by IL1 receptor blockade, indicating that the effects of the absence of DP1 signaling on clinical outcomes were mediated, at least in part, by inflammasomes. Using bone marrow-derived macrophages in vitro, we confirmed that PYDC3 expression is dependent upon DP1 signaling and that IFN priming is critical for PYDC3 up-regulation. In addition, Pydc3 silencing or overexpression augmented or diminished IL-1β secretion, respectively. Furthermore, DP1 signaling in human macrophages also resulted in the up-regulation of a putative functional analog, POP3, suggesting that PGD 2 similarly modulates inflammasomes in human cells. These findings demonstrate a previously undescribed role for prostaglandin signaling in preventing excessive inflammasome activation and, together with previously published results, suggest that eicosanoids and inflammasomes are reciprocally regulated., Competing Interests: The authors declare no conflict of interest.

Purpose: To report the distribution of macular and optic nerve topography in the eyes of individuals with Marfan syndrome aged 8-56 years using spectral domain optical coherence tomography (SD-OCT)., Methods: Thirty-three patients with Marfan syndrome underwent a full eye examination including slit-lamp biomicroscopy, indirect ophthalmoscopy, and axial length measurement; and SD-OCT measurements of the retinal nerve fiber layer (RNFL) and macular thickness., Results: For patients between the ages of 8 and 12 years, the average RNFL thickness is 98 ± 9 μm, the vertical cup to disc (C:D) ratio is 0.50 ± 0.10, the central subfield thickness (CST) is 274 ± 38 μm, and the macular volume is 10.3 ± 0.6 mm 3 . For patients between the ages of 13 and 17 years, the average RNFL is 86 ± 16 μm, the vertical C:D ratio is 0.35 ± 0.20, the CST is 259 ± 15 μm, and the macular volume is 10.1 ± 0.5 mm 3 . For patients 18 years or older, the average RNFL is 89 ± 12 μm, the vertical C:D ratio is 0.46 ± 0.18, the CST is 262 ± 20 μm, and the macular volume is 10.2 ± 0.4 mm 3 . When the average RNFL data are compared to a normative, age-adjusted database, 6 of 33 (18%) were thinner than the 5% limit., Conclusion: This study reports the distribution of SD-OCT data for patients with Marfan syndrome. Compared to a normative database, 18% of eyes with Marfan syndrome had RNFL thickness < 5% of the population.

T cells play a major role in control of both blood and liver stage of plasmodium infection. While immunization with certain attenuated whole-parasite vaccines that are attenuated at the liver stage of the infection induces protective T cell responses, even multiple exposures to natural infection in endemic areas do not lead to stable T cell memory or humoral immunity and sterilizing protection. One of the key differences between vaccination and natural exposure is the absence of blood stage during vaccination. Here we will discuss possible immunoregulatory strategies employed by blood stage of malaria leading to generation of severely compromised T cell and humoral immune responses and subsequent lack of sterilizing immunity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

As a result of the growing burden of tumors and chronic infections, manipulating CD8 T cell responses for clinical use has become an important goal for immunologists. In this article, we show that dendritic cell (DC) immunization coupled with relatively early (days 1-3) or late (days 4-6) administration of enhanced IL-2 signals increase peak effector CD8 T cell numbers, but only early IL-2 signals enhance memory numbers. IL-2 signals delivered at relatively late time points drive terminal differentiation and marked Bim-mediated contraction and do not increase memory T cell numbers. In contrast, early IL-2 signals induce effector cell metabolic profiles that are more conducive to memory formation. Of note, downregulation of CD80 and CD86 was observed on DCs in vivo following early IL-2 treatment. Mechanistically, early IL-2 treatment enhanced CTLA-4 expression on regulatory T cells, and CTLA-4 blockade alongside IL-2 treatment in vivo prevented the decrease in CD80 and CD86, supporting a cell-extrinsic role for CTLA-4 in downregulating B7 ligand expression on DCs. Finally, DC immunization followed by early IL-2 treatment and anti-CTLA-4 blockade resulted in lower memory CD8 T cell numbers compared with the DC+early IL-2 treatment group. These data suggest that curtailed signaling through the B7-CD28 costimulatory axis during CD8 T cell activation limits terminal differentiation and preserves memory CD8 T cell formation; thus, it should be considered in future T cell-vaccination strategies., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Despite decades of research, malaria remains a global health crisis. Current subunit vaccine approaches do not provide efficient long-term, sterilizing immunity against Plasmodium infections in humans. Conversely, whole parasite vaccinations with their larger array of target Ags have conferred long-lasting sterilizing protection to humans. Similar studies in rodent models of malaria reveal that CD8(+) T cells play a critical role in liver-stage immunity after whole parasite vaccination. However, it is unknown whether all CD8(+) T cell specificities elicited by whole parasite vaccination contribute to protection, an issue of great relevance for enhanced subunit vaccination. In this article, we show that robust CD8(+) T cell responses of similar phenotype are mounted after prime-boost immunization against Plasmodium berghei glideosome-associated protein 5041-48-, sporozoite-specific protein 20318-325-, thrombospondin-related adhesion protein (TRAP) 130-138-, or circumsporozoite protein (CSP) 252-260-derived epitopes in mice, but only CSP252-260- and TRAP130-138-specific CD8(+) T cells provide sterilizing immunity and reduce liver parasite burden after sporozoite challenge. Further, CD8(+) T cells specific to sporozoite surface-expressed CSP and TRAP proteins, but not intracellular glideosome-associated protein 50 and sporozoite-specific protein 20, efficiently recognize sporozoite-infected hepatocytes in vitro. These results suggest that: 1) protection-relevant antigenic targets, regardless of their immunogenic potential, must be efficiently presented by infected hepatocytes for CD8(+) T cells to eliminate liver-stage Plasmodium infection; and 2) proteins expressed on the surface of sporozoites may be good target Ags for protective CD8(+) T cells., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Background: Trypanosomosis or Surra, caused by the flagellated hemoprotozoan parasite Trypanosoma evansi, is a disease of economic importance through its wide prevalence in domestic livestock in tropical countries. In the absence of a protective vaccine, management of the disease relies on a few available chemotherapeutic agents. Although humoral immunity is the mainstay of resistance to T. evansi, the ability of the parasite to vary its immunodominant surface proteins to subvert the immune system has forced vaccine efforts to target a variety of invariant epitopes. Beta tubulin, an integral component of the trypanosome cytoskeleton, was therefore targeted using the recombinant form of the protein for immunization., Methods: The 1329 bp coding sequence of beta tubulin gene was PCR amplified and cloned in pQE-TriSystem expression vector. Recombinant beta tubulin was heterologously expressed in Escherichia coli as a 46 KDa fusion protein and used for immunization of mice. The Ig response was studied by ELISA, whereas the cytokine response was measured using a cytometric bead-based assay quantified by flow cytometry., Result: Immunization with recombinant beta (β)-tubulin protein induced a beta-tubulin specific humoral immune response of predominantly IgG2a isotype. Lethal challenge with T. evansi blood-form trypomastigotes post-immunization elicited a robust anamnestic response. An abundance of IFN-γ further confirmed the Th-1 bias of the protective response. We also observed extended survival and better control of the challenge infection in the immunized mice., Conclusions: A robust anamnestic response following challenge including a Th-1 serum cytokine profile coupled with increased survival is indicative of protective immunity in the immunized mice. These observations suggest that β-tubulin of T. evansi is a viable antigenic target for development of a vaccine against this important livestock pathogen.

Purpose: The purpose of this study was to characterize the clinical entity of dacryops infections through imaging with or without histopathology in the differential of ocular adnexal masses in the setting of infection., Methods: A retrospective chart review was performed on 5 patients seen at 1 clinical practice in which a complete ophthalmologic examination and imaging of the lesion had been obtained. Two of these patients additionally obtained surgical intervention with histopathologic examination., Results: The main lacrimal gland was involved in all 5 patients with dacryops infection presenting unilaterally. The average age of the patients was 44.6 years. Predisposing factors of eyelid margin disease, conjunctivitis, and contact lens usage were highlighted. CT provided useful information on the location and size of the lesion. Excision with or without marsupialization appears to prevent recurrence and provides a histopathologic diagnosis although spontaneous (or self-induced) drainage of the cyst in addition to antibiotic therapy can successfully manage the infection and cyst size, wherein affected individuals may not pursue further surgical management., Conclusions: Dacryops infection is a rare but important consideration in the differential of a mass lesion in the upper fornix associated with inflammation that may be confused with orbital cellulitis or abscess. Orbital imaging is helpful in delineating the extent of the lesion, whereas surgical excision with histopathology can confirm the diagnosis. The authors described 5 cases with this acute presentation and highlighted concomitant factors that may predispose certain patients to the development of infection.