Fetal Vasculature Research Articles

Pediatric cataract surgery in congenital anterior segment dysmorphology: An overview

Abstract The purpose is to highlight the surgical modifications that are undertaken for a safe cataract surgery when associated with anterior segment dysmorphology. Surgical modifications that are undertaken in a case of congenital cataract complicated with congenital anterior segment dysmorphology such as microcornea, congenital corneal opacity, aniridia, anterior and posterior lenticonus of the lens, and persistent fetal vasculature are described. Careful preoperative assessment is crucial to anticipate and plan for intraoperative and postoperative challenges that may arise during cataract surgery in the presence of anterior segment dysmorphology. Surgical adjustments in cataract surgery when associated with anterior segment dysmorphology should be tailored to each individual case and the surgeon’s expertise.

Efficacy of intracameral mydriatics in pediatric lens surgery.

Introduction To evaluate the efficacy of intracameral administration of Mydrane® in children undergoing lens surgery. Methods We set up a single center prospective cohort trial including 40 consecutive patients between 8 weeks and 17 years old who were planned for lens surgery, including cataract, persistent fetal vasculature (PFV) or lens subluxation. We injected 0,1 ml of intracameral Mydrane at the beginning of surgery, no preoperative mydriatic eye drops were used. The aim of the study was to measure pupil size, and to monitor the evolution of the pupil size during surgery and the need for additional pupil expanding techniques. Results In 30 patients (75% (95%CI: 59 - 87%)), we did not need additional manipulations to obtain sufficient pupillary dilatation to perform the surgery and to implant an intraocular lens (IOL) following the bag-in-the-lens (BIL) technique. In the remaining 10 patients (25%), we saw an initiation of dilatation, but not to the required pupil diameter to continue the surgery without additional surgical maneuvers. The duration of surgery was significantly longer in the partial response group, reflecting the need for additional surgical steps. A significant relation between increase of pupillary diameter and age (P = 0.003), gender (P = 0.032) and horizontal corneal diameter (P < 0.001) could be shown. Even at baseline there is a larger pupil diameter in eyes with larger horizontal corneal diameters (p=0.039). No adverse events were observed during this study. Conclusion Intracameral administration of Mydrane resulted in some degree of dilatation in all eyes in this series, 75% of eyes did not need additional techniques to proceed with the surgery. Smaller pupils at baseline, younger age, male sex and small horizontal corneal diameter were related to a poorer response to Mydrane. The mydriasis persisted for the entire duration of the surgery, no ocular adverse events were observed during this study. This leads us to conclude that intracameral Mydrane is an effective and safe way to dilate the pupil in pediatric lens surgery.

Wagner Syndrome-like fundus presentation of atypical Persistent Fetal Vasculature.

To report the case of a woman with atypical Persistent fetal vasculature (PFV) accompanied by more typical findings of Wagner Syndrome. A 58-year-old woman complained about persistent flashes and floaters for more than 6 months. Multimodal retinal imaging showed Bergmeister papilla and a fibrous gray strand floating behind the macula in the right eye. Ultra-wide field retinography revealed a 270° paving-stone degeneration and a nasal circumferential vitreous veil in both eyes. Functional and genetic testing were negative for inherited retinal diseases. PFV spectrum confirms its heterogeneous presentation. We report an atypical adult PFV case in presence of retrolental and optic nerve head stalks, accompanied by extensive peripheral vitreoretinal degenerations. This case may expand the current understanding of PFV presentation in adulthood.

Persistent Vetal Vasculature-Vitreoretinal Surgery

Persistent fetal vasculature (PFV), previously known as persistent hyperplastic primary vitreous (PHPV), is a spectrum of congenital anomalies caused by complete or partial failure of the fetal hyaloid vasculature to regress. The severity of the disease may vary depending on the affected intraocular structures and anatomical variations. The outcomes of surgery depend on the type, location, extent, and severity of the disease. The aim of this review is to focus on surgical indications and techniques, and the prognosis of PFV in the current literature and our clinical experience.

Overlapping clinical features of persistent fetal vasculature and combined hamartoma of the retina and retinal pigment epithelium

PurposeTo investigate cases exhibiting overlapping features of persistent fetal vasculature (PFV) and combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) and to explore potential associations between these developmental ocular anomalies. MethodsThis retrospective, descriptive case series included 9 eyes of 8 patients aged 0-7 years with shared clinical features of PFV and CHRRPE. Diagnoses were established through clinical examination and intraoperative findings. ResultsAll eyes exhibited elevated pigmented retinal thickening, increased vascular tortuosity, and preretinal fibrotic/gliotic changes or epiretinal membranes. Macular involvement was observed in 56% of cases; peripapillary involvement, in 44%. Four eyes showed hyaloid stalklike fibrotic remnants extending from the lesion to the posterior lens surface, suggestive of PFV component; the other 5 harbored isolated CHRRPE. One patient presented with PFV in one eye and CHRPPE in the other. ConclusionsThis study reveals significant clinical overlap between PFV and CHRRPE, with some cases displaying features typically associated with the other condition. The presence of both diagnoses in the same patient further suggests a potential association between these entities. Further research, including molecular studies, is needed to explore this potential connection and deepen our understanding of ocular development.

Traumatic hyphema in a neonate: An unusual presentation

Subconjunctival hemorrhages following forceps delivery are common. However, their presence with hyphema is rare. This case report describes a full-term neonate who was initially examined for trauma and subconjunctival hemorrhage in both eyes with diffuse hyphema in right eye following forceps delivery. The anterior segment showed nondilating pupil with fine blood vessels on the iris in one eye along with tunica vasculosa lentis. B-scan showed a hyperechoic line in the vitreous suggestive of unilateral persistent fetal vasculature.

Placenta Extracellular Vesicles: Messengers Connecting Maternal and Fetal Systems.

The placenta operates during gestation as the primary communication organ between the mother and fetus. It is essential for gas, nutrient exchange, and fetal waste transfer. The placenta also produces a wide range of hormones and other factors that influence maternal physiology, including survival and activity of the corpus luteum of the ovary, but the means whereby the placenta shapes fetal development remain less clear, although the fetal brain is thought to be dependent upon the placenta for factors that play roles in its early differentiation and growth, giving rise to the term "placenta-brain axis". Placental hormones transit via the maternal and fetal vasculature, but smaller placental molecules require protection from fetal and maternal metabolism. Such biomolecules include small RNA, mRNA, peptides, lipids, and catecholamines that include serotonin and dopamine. These compounds presumably shuttle to maternal and fetal systems via protective extracellular vesicles (EVs). Placental EVs (pEVs) and their components, in particular miRNA (miRs), are known to play important roles in regulating maternal systems, such as immune, cardiovascular, and reproductive functions. A scant amount is known about how pEVs affect fetal cells and tissues. The composition of pEVs can be influenced by gestational diseases. This review will provide critical insight into the roles of pEVs as the intermediary link between maternal and fetal systems, the impact of maternal pathologies on pEV cargo contents, and how an understanding of biomolecular changes within pEVs in health and disease might be utilized to design early diagnostic and mitigation strategies to prevent gestational diseases and later offspring disorders.

The Red Reflex Test and Leukocoria in Childhood.

The red reflex test, performed using a direct ophthalmoscope, serves as a critical diagnostic tool in identifying various ocular conditions. These conditions encompass retinal anomalies (such as retinoblastoma, Coats disease, retinopathy of prematurity, familial exudative vitreoretinopathy, myelinated nerve fibers, ocular toxocariasis, ocular toxoplasmosis, retinochoroidal coloboma, astrocytic, and combined hamartoma), vitreous abnormalities (including persistent fetal vasculature), lens issues (like cataract), anterior chamber and corneal conditions (comprising dysgenesis of the anterior segment, congenital glaucoma, birth trauma), and tear film disturbances. During this examination, the presence of leukocoria, characterized by a white pupillary reflex, can suggest the presence of underlying conditions. Any suspicion of an abnormal red reflex test warrants immediate evaluation by a qualified ophthalmologist. This article primarily underscores the paramount importance of the red reflex examination, not only to identify potential sight-threateningbut also life-threatening conditions. It delves into the most common causes of leukocoria in childhood and offers insights into a comprehensive diagnostic approach. The target audience for this article includes pediatricians, primary care clinicians, and ophthalmologists, all of whom play a pivotal role in the early detection and intervention of these critical eye disorders.

Endoscopic Surgery for Congenital or Acquired Cataract Associated with Persistent Fetal Vasculature: A Case Series.

Persistent fetal vasculature (PFV) is a congenital malformation caused by a failure in regression of the primary vitreous and hyaloid vessels. An abnormal PFV occurs in the anterior and posterior segments of the eye. Surgery for PFV carries the risk of retinal detachment. We report four cases of cataracts associated with PFV, in which our novel surgical technique with an intraocular endoscope was safely performed. Lensectomy and vitrectomy were performed in cases 1, 3, and 4, while lensectomy, vitrectomy, and intraocular lens implantation using an endoscope were performed in case 2. In all cases, after lens removal, a slit at the posterior lens capsule was created to avoid the retrolental fibrovascular membrane using underwater electric coagulation. Moreover, the endoscope was inserted, by which the intraocular region was observed to determine the treatment method for the fibrovascular membrane and vitreous stalk. No additional surgeries were required for complications before or after any of the surgeries. Using an endoscope during cataract surgery associated with PFV, observing the vitreous stalk at high magnification and ensuring safe treatment were possible. Endoscopic surgery could be considered an effective method for treating PFV-associated cataracts.

Single-cell atlas of the human brain vasculature across development, adulthood and disease

A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood1. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell–cell interaction analyses predict substantial endothelial-to-perivascular cell ligand–receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.

Epigenetic regulation by hypoxia, N-acetylcysteine and hydrogen sulphide of the fetal vasculature in growth restricted offspring: A study in humans and chicken embryos.

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.

Accessory Right and Left Hepatic Arteries in a 69 year-old White Female Donor with a Duplicated Inferior Vena Cava: Anatomical and Surgical Significance

Hepatic artery variations are relatively common findings in patients with an array of findings that were categorized and quantified in the Michels classification system. Findings of an accessory right and left hepatic artery were found in a 69 year-old white female donor with a duplicated inferior vena cava during routine anatomical dissection (Michels type 7 variation). Research supports that the hepatic artery variations can be due to either failure of regression of ventral anastomosis between the dual aortas or failed regression of fetal hepatic blood flow. Given the concurrent development of the IVC and aortic branches during the fourth to seventh week of gestation, this patient’s duplicated IVC and abnormal CT and SMA anatomy are likely related, both a result of failure of regression of fetal vasculature. There are no known associated comorbidities with this vascular variation however it is clinically significant when undergoing any hepatobiliary surgical procedures and suggests an increased risk for hepatic ischemic events.

Genetics of bilateral pediatric cataract in the Israeli and Palestinian populations

PurposeBilateral pediatric cataract (BPC) is one of the most common causes of childhood visual impairment and blindness worldwide. A significant percentage of pediatric cataracts are caused by genetic alterations. We aim to characterize the set of genes and variants that cause BPC in the Israeli and Palestinian populations and to assess genotype-phenotype correlation.MethodsRetrospective study in a multidisciplinary center for visual impairment, located in a tertiary medical center. Medical charts of families who underwent genetic counseling because of BPC in a family member were reviewed. Clinical characteristics and genetic tests results were obtained from medical records of affected subjects.ResultsTwenty-two families (47 patients) underwent genetic counseling and completed genetic testing. Causative variants were identified in 18/22 (81.8%) of the families, including 3 novel variants. Genetic testing used included mainly panel for congenital cataracts and whole exome sequencing. Eleven families performed genetic testing with the intention of future pregnancy planning. Main causative genes identified were crystalline genes followed by transcription factor genes. BCOR gene variants were associated with persistent fetal vasculature (PFV) cataract in two of three families.ConclusionsCombined molecular techniques are useful in identifying variants causing pediatric cataracts and showed a high detection rate in our population. BCOR gene variants might be associated with PFV type of cataracts. The study of pathogenic variants may aid in family planning and prevention of pediatric cataracts in future pregnancies. Additionally, in certain cases, it assists in diagnosing non-suspected syndromic types of pediatric cataracts.

Pediatric Surgical Outcomes of Persistent Fetal Vasculature: A Five-Year Retrospective Study at a Tertiary Eye Center in Kazakhstan

Pediatric Surgical Outcomes of Persistent Fetal Vasculature: A Five-Year Retrospective Study at a Tertiary Eye Center in Kazakhstan

Revision of Initial Referral Diagnosis after Genotypic Confirmation of Familial Exudative Vitreoretinopathy

PurposeTo describe common referral diagnoses of FEVR (Familial Exudative Vitreoretinopathy) DesignRetrospective case series. SubjectsPatients with phenotypic FEVR evaluated by the pediatric retina service at Bascom Palmer Eye Institute from March 1, 2019 to May 31, 2023. MethodsA retrospective detailed review of history, imaging, and genetic testing was performed for all patients included in the study. Main Outcome MeasuresThe primary outcome measures included genetic evaluation, clinical imaging and characteristics. Secondary outcome measures were age and stage of disease at diagnosis. ResultsFifty-five patients with phenotypic and genetically confirmed FEVR were identified. Of these, the initial diagnosis was incorrect upon referral in 33 cases (60%). The referral diagnoses included Coats disease (n =2, 7%), toxoplasmosis (n=2, 7%), retinal detachment (n=6, 18%), persistent fetal vasculature (PFV) (n =5, 15%), suspected inherited retinal disease (n=2, 7%), myopia (n=3, 9%), retinopathy of prematurity (ROP) with preterm gestational age (n=7, 21%), and ROP at moderate to late preterm gestational age (n=6, 18%). The mean age at diagnosis was 8.78 years and 6.42 years for patients with revised diagnosis versus initial diagnosis of FEVR, respectively (p =0.4). There was no correlation between age of diagnosis and stage of disease (p =0.8). ConclusionsA high index of suspicion for FEVR must be maintained given the heterogeneity of phenotypes. Atypical cases of PFV, Coats disease, and ROP should prompt fluorescein angiography and genetic evaluation.

Pulmonary vasculature development in congenital diaphragmatic hernia: a novel automated quantitative imaging analysis.

Impaired fetal lung vasculature determines the degree of pulmonary hypertension in the congenital diaphragmatic hernia (CDH). This study aims to demonstrate the morphometric measurements that differ in pulmonary vessels of fetuses with CDH. Nitrofen-induced CDH Sprague-Dawley rat fetuses were scanned with microcomputed tomography. The analysis of the pulmonary vascular tree was performed with artificial intelligence. The number of segments in CDH was significantly lower than that in the control group on the left (U = 2.5, p = 0.004) and right (U = 0, p = 0.001) sides for order 1(O1), whereas there was a significant difference only on the right side for O2 and O3. The pooled element numbers in the control group obeyed Horton's law (R2 = 0.996 left and R2 = 0.811 right lungs), while the CDH group broke it. Connectivity matrices showed that the average number of elements of O1 springing from elements of O1 on the left side and the number of elements of O1 springing from elements of O3 on the right side were significantly lower in CDH samples. According to these findings, CDH not only reduced the amount of small order elements, but also destroyed the fractal structure of the pulmonary arterial trees.

Cannabidiol Exposure During Rat Pregnancy Leads to Labyrinth-Specific Vascular Defects in the Placenta and Reduced Fetal Growth.

Introduction: Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as "natural" and "safe" as it is non-intoxicating. In utero, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of Δ9-THC, there has been limited investigation into the impacts of in utero gestational CBD exposure on the placenta. Methods: This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat placentas from vehicle and CBD (3 mg/kg intraperitoneal injection) exposed pregnancies (E6.5-18.5). Results: The study revealed that pups from CBD-exposed pregnancies were 10% smaller, with the placentae displaying a decreased fetal blood space perimeter-to-area ratio. The transcriptomic analysis supported compromised angiogenesis and blood vessel formation with downregulated biological processes, including tube morphogenesis, angiogenesis, blood vessel morphogenesis, blood vessel development and vasculature development. Further, the CBD-exposed placentas displayed changed expression of glucose transporters (decreased GLUT1 and GR expression and increased GLUT3 expression). Transcriptomic analysis further revealed upregulated biological processes associated with metabolism. Finally, histological and transcriptomic analysis revealed altered cell populations within the placenta, specifically to syncytiotrophoblast layer II and endothelial cells. Conclusion: Together these results suggest that the structural changes in CDB-exposed placentae, including the altered expression of nutrient transporters and the changes to the placental fetal vasculature, may underlie the reduced fetal growth.

Persistent Fetal Vasculature with Pediatric Cataract, Microcornea, Sensory Exotropia and Mental Retardation: A Case Report

Introduction : Persistent Fetal Vasculature (PFV) is a congenital, nonhereditary ocular malformation that frequently involves the lens. PFV is most frequently unilateral. The classical presentation is leukocoria, microphthalmia, and cataract.&#x0D; Case Illustration : A 16-year-old boy patient with mental retardation, came with chief complaint blurred vision and white appearance on the RE, noticed for 1 month ago. Visual acuity of the RE was LPBP and the LE was 6/120. There was microcornea on both eyes with diameter 8 mm. Lens opacity and exotropia with XT 30 0 on the RE. IOP on both eyes was normal. Funduscopic on the RE was negative and LE there was tigroid retina. Ultrasonography of the RE was echogenic with minimal after movement and low to moderate spikes. Planning for this patient were RE lens extraction with IOL. After that evaluate for the posterior segment.&#x0D; Discussion : Progressive cataract formation often occurs, sometimes leading to a complete cataract. Strabismus associated with a unilateral cataract. The most important was differentiating PFV from retinoblastoma. In patients with poor view of the fundus, ultrasonography should be performed. Retinal or optic nerve abnormalities cannot be definitively ruled out, however, until the posterior pole can be visualized directly. The opacity in the affected eye should be cleared to allow visual development and to save the eye from complications of untreated PFV.&#x0D; Conclusion : It is important to obtain a detailed history of the child’s growth, development, systemic disorders, family history, and need further comprehensive examination and multidiscipline consultation to establish the diagnose.

PROFILE OF UNILATERAL CATARACT IN PEDIATRIC PATIENTS: A 3 YEAR RETROSPECTIVE STUDY

Introduction and Objective: Unilateral cataract presents from 19.6% to 55.5% of pediatric cataract. This condition is treatable, but delayed treatment may cause visual impairment. This study aims to understand characteristic of unilateral cataract in children. Methods: This study was descriptive review of patients aged 0-17 years old with unilateral cataract at Dr. Kariadi Hospital, Semarang. Data were collected from medical record of patients from January 2019 to December 2022. Results: Sixty patients were included in this study, 56.7% of whom were male and 43.3% were female. The mean age at presentation is 71.50 ± 48.34 months with whitish eye being the most common main complaint (65%), followed by blurred vision (35%) and squinting of eye (5%). Most of patients had congenital or infantile cataract (60%), followed by traumatic (36.6%), uveitis (1.7%) and iatrogenic (1.7%). Some of patients had microcornea (21.7%), persistent pupillary membrane (8.3%), retinopathy of prematurity (3.3%), persistent fetal vasculature (8.3%), nystagmus (8.3%), amblyopia (20%) and strabismus (40%), with exotropia being the most common type (33.3%). Most of patients did not have systemic disease (93.3%), but we found two patients had congenital rubella syndrome, one had congenital cytomegalovirus, one had down syndrome. Conclusion: Etiology of unilateral pediatric cataract mostly idiopathic followed by traumatic. Leukocoria was the most common complaint, followed by blurred vision and strabismus. In unilateral cataract, exotropia was more common type of strabismus.

Pediatric orbital lesions: ocular pathologies.

Orbital pathologies can be broadly classified as ocular, extra-ocular soft-tissue (non-neoplastic and neoplastic), osseous, and traumatic. In part 1 of this orbital series, the authors will discuss the differential diagnosis and key imaging features of pediatric ocular pathologies. These include congenital and developmental lesions (microphthalmos, anophthalmos, persistent fetal vasculature, coloboma, morning glory disc anomaly, retinopathy of prematurity, Coats disease), optic disc drusen, infective and inflammatory lesions (uveitis, toxocariasis, toxoplasmosis), and ocular neoplasms (retinoblastoma, retinal hamartoma, choroidal melanoma, choroidal nevus). This pictorial review provides a practical approach to the imaging work-up of these anomalies with a focus on ocular US as the first imaging modality and additional use of CT and/or MRI for the evaluation of intracranial abnormalities. The characteristic imaging features of the non-neoplastic mimics of retinoblastoma, such as persistent fetal vasculature and Coats disease, are also highlighted.