Coats-Like Presentation of Familial Exudative Vitreoretinopathy Associated With a Novel LRP5 Variant.

This report describes a unique case of a Coats-like presentation of familial exudative vitreoretinopathy in an 11-year-old girl. The patient was originally referred for evaluation of presumed Coats disease and presented with telangiectatic vessels, perivascular exudates, diffuse peripheral exudation, and intraretinal hemorrhages. Clinical and angiographical findings were consistent with familial exudative vitreoretinopathy, while genetic testing identified variants of uncertain significance in two associated genes, LRP5 and ZNF408. In silico analysis predicts the LRP5 variant to be pathogenic. Retinal vasculopathies often have phenotypic overlap, warranting angiographic examination of both eyes and genetic testing to uncover the correct diagnosis and guide proper treatment. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

The journey of a generation: advances and promises in the study of primordial germ cell migration.

The germline provides the genetic and non-genetic information that passes from one generation to the next. Given this important role in species propagation, egg and sperm precursors, called primordial germ cells (PGCs), are one of the first cell types specified during embryogenesis. In fact, PGCs form well before the bipotential somatic gonad is specified. This common feature of germline development necessitates that PGCs migrate through many tissues to reach the somatic gonad. During their journey, PGCs must respond to select environmental cues while ignoring others in a dynamically developing embryo. The complex multi-tissue, combinatorial nature of PGC migration is an excellent model for understanding how cells navigate complex environments in vivo. Here, we discuss recent findings on the migratory path, the somatic cells that shepherd PGCs, the guidance cues somatic cells provide, and the PGC response to these cues to reach the gonad and establish the germline pool for future generations. We end by discussing the fate of wayward PGCs that fail to reach the gonad in diverse species. Collectively, this field is poised to yield important insights into emerging reproductive technologies.

Autoimmune Implications in a Patient with Graves' Hyperthyroidism, Pre-eclampsia with Severe Features, and Primary Aldosteronism.

Background and Objectives: Graves' disease (GD) and primary aldosteronism (PA) are two pathologies that can cause significant morbidity and mortality. GD is mediated by autoantibodies, and recent studies have shown autoantibody involvement in the pathophysiology behind both PA and pre-eclampsia. The coexistence of GD and PA, however, is reportedly rare. This report describes a unique case of Graves' hyperthyroidism and concomitant PA in a patient with a history of pre-eclampsia with severe features. Case Presentation: The patient presented at 17 weeks pregnancy with mild hyperthyroidism, negative TSH receptor antibodies, and a low level of thyroid-stimulating immunoglobulins (TSI). Her TSH became detectable with normal thyroid hormone levels, and therefore, no anti-thyroid medication was administered. At 34 weeks she developed pre-eclampsia with severe features, and a healthy child was delivered; her TSH returned to normal. Seven months after delivery, she presented emergently with severe hyperthyroidism, hypertensive crisis, and a serum potassium of 2.5 mmol/L. Her hypertension was uncontrolled on multiple anti-hypertensives. Both TSI and TSH receptor antibodies were negative. The aldosterone(ng/dL)/renin(ng/mL/h ratio was (13/0.06) = 216.7, and abdominal CT imaging demonstrated normal adrenal glands; thus, a diagnosis of PA was made. Her blood pressure was subsequently controlled with only spironolactone at 50 mg 2xday. Methimazole was started but discontinued because of an allergic reaction. Consequently, a thyroidectomy was performed, and pathology revealed Graves' disease. The patient remained well on levothyroxine at 125 mcg/day and spironolactone at 50 mg 2xday three months after the thyroidectomy. Conclusions: This patient manifested severe GD with antibodies undetectable by conventional TSI and TSH receptor assays and accelerated hypertension from PA simultaneously. These conditions were successfully treated separately by spironolactone and thyroidectomy. Autoimmune PA was considered likely given the clinical picture. The diagnosis of PA should be considered in hypertension with GD.

Removal of an infected pulmonary artery fibroelastoma disguised as a presentation of pulmonary embolism using a percutaneous suction thrombectomy device.

Papillary fibroelastoma (PFE) is a rare, often benign, tumor originating typically in the endocardium and valves, with a preference for the left side of the heart. Although PFEs can appear asymptomatic, in the setting of embolization, they can lead to stroke, acute limb ischemia, and/or mesenteric ischemia. Rarely, PFEs can originate from the pulmonary valve, with the potential for embolic showering into the pulmonary artery, leading to potential right-sided heart outflow obstruction. Treatment has been open surgery in most cases, although treatment of right-sided heart masses with extracorporeal circulatory support extraction systems have been described. Recently, large bore suction thrombectomy devices have become available, typically used for cases of venous thromboembolism. In the present report, we describe a case of a symptomatic infected PFE treated by percutaneous suction thrombectomy using the Inari FlowTriever system (Inari Medical).

Self-Reported Perceptions of Preparedness among Incoming Ophthalmology Residents.

Purpose The purpose of this study was to assess the self-perceived preparedness of incoming postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) ophthalmology interns/residents to carry out core competencies in ophthalmology. Methods An online survey was created using the Survey Monkey survey platform and distributed to all ophthalmology resident applicants to the Bascom Palmer Eye Institute from the 2021 to 2022 and 2022 to 2023 application cycles. The survey contained questions pertaining to demographics, prior ophthalmic experience, online resources that were used to prepare for ophthalmology, and self-perceived preparedness to carry out key clinical skills in ophthalmology. Results A total of 170 responses were obtained (16.1% response rate). Of those, 119 (70%) were incoming PGY1 interns and 51 (30%) were incoming PGY2 residents for the 2022 to 2023 academic year. Most respondents (90.6%, n = 154) reported that their ophthalmology residency was affiliated with an integrated ophthalmology intern year. Incoming PGY2s moderately agreed with the statement that they felt as prepared to see patients in ophthalmology as they do in other surgical subspecialties, whereas incoming PGY1s only mildly agreed with that statement ( p = 0.003). Both incoming PGY1s and PGY2s felt most prepared to obtain histories relating to basic ophthalmic complaints and felt least prepared to read and interpret ophthalmic imaging studies. The most popular online resources used by respondents in order of popularity were EyeGuru (35.2%, n = 60), EyeWiki (32.9%, n = 56), Tim Root/OphthoBook (26.5%, n = 45), American Academy of Ophthalmology (13.5%, n = 23), and EyeRounds/University of Iowa (13.5%, n = 23). Conclusion A major challenge in integrating ophthalmic education into the medical school curricula is the gradual shift toward shorter preclinical curricula. However, having a core foundation of ophthalmic knowledge is critical for incoming ophthalmology residents to be able to maximize their specialty-specific training. Integrated ophthalmology intern years likely play a significant role in the increased self-efficacy of incoming PGY2s compared with incoming PGY1s. Adopting nontraditional teaching methods like flipped classroom learning, utilizing online medical education resources, and continuing to increase ophthalmology exposure during PGY1 year may better prepare incoming PGY2s to operate independently in ophthalmology settings.

A Systematic Review of Digital Ophthalmoscopes in Medicine.

Purpose: Recent advances in telemedicine have led to increased use of digital ophthalmoscopes (DO) in clinical settings. This review aims to assess commercially available DOs, including smartphone (SP), desktop, and handheld ophthalmoscopes, and evaluate their applications. Methods: A literature review was performed by searching PubMed (pubmed.ncbi.nlm.nih.gov), Web of Science (webofknowledge.com), and Science Direct (sciencedirect.com). All English-language papers that resulted from the search terms "digital ophthalmoscope", "screening tool", "glaucoma screening", "diabetic retinopathy screening", "cataract screening", and "papilledema screening" were reviewed. Studies that contained randomized clinical trials with human participants between January 2010 and December 2020 were included. The Risk of Bias in Systematic Reviews (ROBIS) tool was used to assess the methodological quality of each included paper. Results: Of the 1307 studies identified, 35 met inclusion and exclusion criteria. The ROBIS tool determined that 29/35 studies (82.8%) had a low risk of bias, 3/35 (8.5%) had a moderate risk of bias, and 3/35 (8.5%) had a high risk of bias. Conclusion: The continued adoption of DOs remains uncertain because of concerns about the image quality for non-mydriatic eyes and the confidence in data captured from the device. Likewise, there is a lack of guidelines for the use of DOs, which makes it difficult for providers to determine the best device for their practice and to ensure appropriate use. Even so, DOs continue to gain acceptance as technology and practice integration improve, especially in underserved areas with limited access to ophthalmologists.

Proximal tibia triplane fracture with apophyseal avulsion.

Tibial tuberosity fractures occur in fewer than 1% of all paediatric fractures. We present this unusual case of an early adolescent football player who presented to the emergency department after sustaining an injury during a tackle. CT confirmed a tibial apophyseal fracture concurrent with a proximal tibial triplane fracture. The fracture was subsequently reduced operatively with cancellous cannulated screws. There are only 11 cases published in the literature of triplane fractures of the proximal tibia. Both other cases that involve a concurrent tibial tuberosity fracture with a triplane extension were sustained following a footballing injury. We therefore propose that forced knee flexion alongside a rotational component, common to football, may promote this rare fracture pattern. It is hoped that this case can be used to shed light on a possible mechanism and to guide future management.

The ophthalmology residency match: a new era.

PURPOSE OF REVIEW: The average number of applications per ophthalmology residency applicant continues to rise. The present article reviews the history and negative impacts of this trend, the dearth of effective solutions and the potential promise of preference signalling as an alternative strategy to address this and potentially improve match outcomes. RECENT FINDINGS: Application inflation adversely impacts applicants and programmes and undermines holistic review. Most recommendations to limit volume have been largely unsuccessful or undesirable. Preference signalling does not restrict applications. Early results from initial pilots in other specialties are promising. Signalling has the potential to facilitate holistic review, reduce interview hoarding and promote equitable distribution of interviews. SUMMARY: Preliminary data suggest preference signalling could be a useful strategy to address current issues with the Match. Building upon the blueprints and experiences of our colleagues, Ophthalmology should conduct its own investigation and consider a pilot project.

Endophthalmitis Associated With XEN Stent Implantation.

PURPOSE: The aim of this study is to report the clinical characteristics, causative organisms, and treatment outcomes in patients presenting with endophthalmitis related to XEN stent implants. DESIGN: Retrospective, noncomparative consecutive case series. METHODS: Clinical and microbiologic review was performed for 8 patients presenting to the Bascom Palmer Eye Institute Emergency Room between 2021 and 2022 with XEN stent-related endophthalmitis. Data collected included clinical characteristics of patients at presentation, organisms identified in ocular cultures, treatments received, and visual acuity at last follow-up. RESULTS: The current study included 8 eyes from 8 patients. All cases of endophthalmitis occurred >30 days after implantation of the XEN stent. At the time of presentation, there were external exposures of the XEN stent in 4 of 8 patients. Five of the 8 patients had positive intraocular cultures, all of which were variants of staphylococcus and streptococcus species. Management included intravitreal antibiotics in all patients, explantation of the XEN stent in 5 patients (62.5%), and pars plana vitrectomy in 6 patients (75%). At last follow-up, 6 of the 8 patients (75%) had a visual acuity of hand motion or worse. CONCLUSIONS: Endophthalmitis in the setting of XEN stents results in poor visual outcomes. The most common causative organisms are staphylococcus or streptococcus species. At time of diagnosis, prompt treatment with broad-spectrum intravitreal antibiotics is recommended. Consideration can be made to explant the XEN stent and perform early pars plana vitrectomy.

Cooperativity between H3.3K27M and PDGFRA poses multiple therapeutic vulnerabilities in human iPSC-derived diffuse midline glioma avatars.

Diffuse midline glioma (DMG) is a leading cause of brain tumor death in children. In addition to hallmark H3.3K27M mutations, significant subsets also harbor alterations of other genes, such as TP53 and PDGFRA. Despite the prevalence of H3.3K27M, the results of clinical trials in DMG have been mixed, possibly due to the lack of models recapitulating its genetic heterogeneity. To address this gap, we developed human iPSC-derived tumor models harboring TP53R248Q with or without heterozygous H3.3K27M and/or PDGFRAD842V overexpression. The combination of H3.3K27M and PDGFRAD842V resulted in more proliferative tumors when gene-edited neural progenitor (NP) cells were implanted into mouse brains compared to NP with either mutation alone. Transcriptomic comparison of tumors and their NP cells of origin identified conserved JAK/STAT pathway activation across genotypes as characteristic of malignant transformation. Conversely, integrated genome-wide epigenomic and transcriptomic analyses, as well as rational pharmacologic inhibition, revealed targetable vulnerabilities unique to the TP53R248Q; H3.3K27M; PDGFRAD842V tumors and related to their aggressive growth phenotype. These include AREG-mediated cell cycle control, altered metabolism, and vulnerability to combination ONC201/trametinib treatment. Taken together, these data suggest that cooperation between H3.3K27M and PDGFRA influences tumor biology, underscoring the need for better molecular stratification in DMG clinical trials.

Association between prostate size and glandular tissue volume of the peripheral zone via novel combined MRI and histopathology: possible pathophysiological implications on prostate cancer development.

PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent urologic diseases affecting elderly men. An inverse relationship between BPH/prostate size and PCa incidence is well documented in the current literature, but the precise mechanism is poorly understood. This study aims to investigate the effect of total prostate volume on total glandular tissue volume of the peripheral zone via a novel combination of magnetic resonance imaging (MRI) and histo-anatomical imaging. METHODS: 42 male patients between ages 53-79 years underwent both radical prostatectomy and pre-operative MRI scans. Prostate sizes ranged from 14.8-133.3cc. Quantitative measurements of surgical capsule thickness and glandular epithelial cell density within the peripheral zone (PZ) were obtained on histo-anatomical slides using computer-based imaging software. Quantitative prostatic zonal measurements were obtained from MRI scans. Combining MRI- and histopathology-obtained parameters allowed measurement of the total glandular tissue volume of the PZ (GVPZ). Statistical analysis was performed to identify associations between total prostate volume (TPV) and GVPZ. RESULTS: The Mann-Whitney U-test showed significant decreases in GVPZ in larger prostates when compared to smaller prostates. CONCLUSIONS: Combined MRI and histopathology techniques provide a novel method for accurate measuring of glandular tissue content within the prostatic PZ. The findings of this pilot study support the hypothesis of PZ compression by an expanding transition zone in large BPH prostates, leading to atrophy of PZ glandular tissue. As the majority of PCa originates in the PZ, this dynamic process may explain the protective effect of large BPH prostates against PCa development.

Smith-Lemli-Optiz syndrome: importance of ophthalmology referral and follow-up.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder caused by mutations in the 7-dehydrocholesterol reductase (DHCR7) gene, located on chromosomal region 11q13. This results in reduced cholesterol and increased 7-dehydrocholesterol (7DHC) levels. Accumulation of 7DHC in patients with SLOS can affect multiple organs and display a broad phenotypic expression. Ophthalmic abnormalities related to SLOS are variable but the most common is blepharoptosis. Over 50% of these patients present with self-injurious behavior, such as head banging, which can result in ocular complications and blindness. We report the first case of peripheral avascularity of the retina in a patient with SLOS. Physicians should be aware of the potential ocular complications associated with SLOS and confounding factors, such as prematurity, given that referral is usually delayed due to the lack of awareness of these potentially blinding associations. This case highlights the importance of early referral and continuous ophthalmologic follow-up in preventing further deterioration of visual development and complications that can lead to blindness.

Asymptomatic Rhegmatogenous Retinal Detachments: Outcomes in Patients without Initial Surgical Intervention.

OBJECTIVE: To report long-term outcomes of patients with asymptomatic retinal detachments (RDs) who did not undergo initial surgical intervention. DESIGN: Retrospective case series. METHODS: A retrospective chart review of patients diagnosed with asymptomatic RD. Patients with symptoms of photopsias or a visual field defect at presentation were excluded. PARTICIPANTS: Eighteen patients seen and evaluated at the Bascom Palmer Eye Institute between 2011 and 2021. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), presence or absence of progression of RD, and whether surgical intervention occurred during follow-up. RESULTS: The study group included 18 patients (20 eyes). The mean follow-up duration was 5.1 years (range, 0-30 years). Risk factors included myopia (95%), lattice retinal degeneration (60%), and pseudophakia (5%). Most asymptomatic RDs were located in the inferotemporal quadrant (80%), followed by the superotemporal (15%) and inferonasal (5%). No RDs were confined to the superonasal quadrant. The majority (80%) extended posterior to the equator and were ≤ 3 clock hours in size (65%). Five (25%) patients were previously treated with prophylactic laser demarcation. Final BCVA was 20/40 or better in 19 (95%) eyes and between 20/40 and 20/200 in 1 (5%) eye. During the follow-up, 2 (10%) patients exhibited progression of their asymptomatic RD and underwent surgical intervention. Retinal pathology in fellow eyes was previously diagnosed or identified during follow-up in 14 (78%) of 18 patients, of which 2 (11%) patients had bilateral asymptomatic RDs. CONCLUSIONS: Nonsurgical management with observation may be reasonable as an initial management strategy for asymptomatic patients with RDs in select cases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Attending Perceptions on the Use of Preference Signaling in the Ophthalmology Residency Application Process.

Objective This article characterizes perspectives of ophthalmologists involved in the residency selection process regarding the potential impact of preference signaling on the ophthalmology residency match. Methods An anonymous online questionnaire generated from SurveyMonkey was approved by the Association of University Professors of Ophthalmology (AUPO) Data Resource Committee for distribution to 391 individuals from the AUPO Departmental Chairs, Program Directors, and Directors of Medical Student Education email listservs in August 2022. Results A total of 96 (24.6%) ophthalmology faculty completed the questionnaire. The majority ( n = 76, 79.2%) agreed or strongly agreed that preference signaling should be implemented in the ophthalmology residency application system. Most respondents agreed or strongly agreed that preference signaling will allow for more holistic reviews of applications ( n = 55, 57.3%), agreed or strongly agreed that it will benefit applicants who do not have connections to home programs or faculty that can reach out to desired programs ( n = 81, 84.4%), and agreed or strongly agreed that it will improve the distribution of interviews to applicants ( n = 76, 79.2%). Participants agreed or strongly agreed that applicants who have signaled interest in their program will receive preference when offering interviews ( n = 59, 61.5%), and those signals will be used as a tiebreaker for similar applications ( n = 75, 78.1%). The majority of participants believed that the ideal number of preference signals' applicants should be given three to four signals ( n = 35, 36.0%) or five to six signals ( n = 29, 30.2%). Conclusion A majority of ophthalmology faculty surveyed support the integration of preference signaling into the ophthalmology residency match.

Outcomes in Patients with Suprachoroidal Hemorrhage After Anterior Segment Surgery.

Objective: The purpose of the current study is to report outcomes of suprachoroidal hemorrhage (SCH) after anterior segment surgery at a single institution, and to identify clinical features associated with visual prognosis. Methods and Analysis: Retrospective consecutive case series of patients with SCH occurring after anterior segment surgery. Results: The study includes 112 eyes of 112 patients between 2014 and 2020. There were 76 cases of non-appositional SCH versus 36 cases of appositional SCH. The mean presenting visual acuity for patients with non-appositional versus appositional SCH was 2.03 logMAR (SD 0.78) versus 2.39 logMAR (SD 0.43), respectively. Visual acuity outcomes generally remained poor at last follow-up: 64 (58%) patients had a visual acuity (VA) of ≤ 20/200, including 19 (17%) with light perception (LP), and 11 (10%) with no light perception (NLP). Regarding management of non-appositional versus appositional SCH, observation was selected in 46 (61%) vs 12 (33%), delayed drainage in 14 (18%) vs 15 (42%), delayed pars plana vitrectomy in 16 (21%) vs 13 (36%), and VA at last follow-up was 1.2 versus 1.86 logMAR (p=0.002). In patients that were observed, both appositional SCH (p=0.01) and duration of apposition (p=0.04) were correlated with worse outcome. Conclusion: Appositional SCH was associated with poorer visual outcomes compared to non-appositional SCH. Observation remains a reasonable management strategy for non-appositional SCH.