Persistência da vasculatura fetal diagnosticada pela ultrassonografia ­ Relato de caso / Vasculature persistence fetal diagnosed by ultrasound ­ case report

Contexto: A persistência da vasculatura fetal é uma malformação ocular rara em adultos, habitualmente unilateral, sendo uma condição não hereditária, com poucas manifestações sistêmicas e neurológicas. Descrição do caso: Homem de 45 anos queixando-se de dor no olho esquerdo, com pressão intraocular de 56 mmHg. A ultrassonografia do olho esquerdo demonstra aumento da ecogenicidade do cristalino inferindo catarata e redução da amplitude da câmara anterior, membrana posterior hiperecogênica no interior da câmara vítrea com intensa vascularização com fluxo arterial ao estudo com Doppler, caracterizando a persistência da vasculatura fetal. O paciente recebeu tratamento por três dias. Com a redução da pressão intraocular após esse período, realizou a cirurgia combinada de facoemulsificação com implante de lio e implante de tubo de Ahmed. Após o procedimento cirúrgico, o paciente não voltou a apresentar a sintomatologia. Discussão: Clinicamente, há duas condições de doença, dependendo da porção atingida do vítreo primário ­ as formas anterior e posterior. A persistência da vasculatura fetal não tratada frequentemente progride para phthisis bulbi ou enucleação devido a uma hemorragia intraocular recorrente e secundária ao glaucoma. Os esforços cirúrgicos têm o intuito de preservar a visão. Conclusão: Relatamos um caso de persistência da vasculatura fetal diagnosticado pela ultrassonografia e tratado cirurgicamente com sucesso devido ao alívio dos sintomas em olho esquerdo sem percepção luminosa.

Modulating EGFR-MTORC1-autophagy as a potential therapy for persistent fetal vasculature (PFV) disease.

Persistent fetal vasculature (PFV) is a human disease that results from failure of the fetal vasculature to regress normally. The regulatory mechanisms responsible for fetal vascular regression remain obscure, as does the underlying cause of regression failure. However, there are a few animal models that mimic the clinical manifestations of human PFV, which can be used to study different aspects of the disease. One such model is the Nuc1 rat model that arose from a spontaneous mutation in the Cryba1 (crystallin, beta 1) gene and exhibits complete failure of the hyaloid vasculature to regress. Our studies with the Nuc1 rat indicate that macroautophagy/autophagy, a process in eukaryotic cells for degrading dysfunctional components to ensure cellular homeostasis, is severely impaired in Nuc1 ocular astrocytes. Further, we show that CRYBA1 interacts with EGFR (epidermal growth factor receptor) and that loss of this interaction in Nuc1 astrocytes increases EGFR levels. Moreover, our data also show a reduction in EGFR degradation in Nuc1 astrocytes compared to control cells that leads to over-activation of the mechanistic target of rapamycin kinase complex 1 (MTORC1) pathway. The impaired EGFR-MTORC1-autophagy signaling in Nuc1 astrocytes triggers abnormal proliferation and migration. The abnormally migrating astrocytes ensheath the hyaloid artery, contributing to the pathogenesis of PFV in Nuc1, by adversely affecting the vascular remodeling processes essential to regression of the fetal vasculature. Herein, we demonstrate in vivo that gefitinib (EGFR inhibitor) can rescue the PFV phenotype in Nuc1 and may serve as a novel therapy for PFV disease by modulating the EGFR-MTORC1-autophagy pathway. ABBREVIATIONS: ACTB: actin, beta; CCND3: cyclin 3; CDK6: cyclin-dependent kinase 6; CHQ: chloroquine; COL4A1: collagen, type IV, alpha 1; CRYBA1: crystallin, beta A1; DAPI: 4'6-diamino-2-phenylindole; EGFR: epidermal growth factor receptor; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFAP: glial fibrillary growth factor; KDR: kinase insert domain protein receptor; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MKI67: antigen identified by monoclonal antibody Ki 67; MTORC1: mechanistic target of rapamycin kinase complex 1; PARP: poly (ADP-ribose) polymerase family; PCNA: proliferating cell nuclear antigen; PFV: persistent fetal vasculature; PHPV: persistent hyperplastic primary vitreous; RPE: retinal pigmented epithelium; RPS6: ribosomal protein S6; RPS6KB1: ribosomal protein S6 kinase, polypeptide 1; SQSTM1/p62: sequestome 1; TUBB: tubulin, beta; VCL: vinculin; VEGFA: vascular endothelial growth factor A; WT: wild type.

Regression of fetal vasculature and visual improvement in nonsurgical persistent hyperplastic primary vitreous: a case report.

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV) is a rare congenital developmental ocular disorder caused by incomplete regression of the embryonic hyaloid vasculature. Here we report a case of nonsurgical unilateral anterior PHPV that was managed by amblyopia treatment and resulted in an improvement of visual acuity and regression of the fetal vasculature. CASE PRESENTATION: A three-year-old girl was diagnosed with unilateral anterior PHPV in the left eye, manifested with posterior pole cataract, posterior capsule opacification, tunica vasculosa lentis, and a floating hyaloid artery connected to the retrolental mass. The plaque was not large enough to fill the pupil, and conservative management along with amblyopia treatment was conducted. Nineteen months later, the visual acuity in the affected eye improved from 20/100 to 20/50 with correction, and the fetal vasculature regressed gradually and finally into a nonperfusion ghost vessel. CONCLUSIONS: In PHPV-affected children, regression of the fetal vasculature may be observed, and conservative management and amblyopia treatment may be helpful for visual improvement.

A clinicopathological study of persistent fetal vasculature.

Purpose: To study the clinicopathological findings of Persistent Fetal Vasculature (PFV) in patients with congenital cataract and PFV. Methods: Six eyes with anterior or combined PFV with cataract underwent phacoaspiration with primary posterior capsulotomy with anterior vitrectomy with intraocular lens implantation followed by histopathological evaluation of the PFV stalk and membrane. Results: Four and two patients had combined and anterior PFV respectively. There was no postoperative hyphema, vitreous haemorrhage, glaucoma or retinal detachment in six months. Haematoxylin and eosin staining showed inflammatory cells predominantly with extramedullary hematopoeisis and vascularisation. Conclusion: We recommend IOL implantation in PFV, with early and aggressive amblyopia therapy.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IMAGING OF THE MACULA AND VITREOMACULAR INTERFACE IN PERSISTENT FETAL VASCULATURE SYNDROME WITH POSTERIOR INVOLVEMENT.

PURPOSE: To describe the microstructural features of the macula and vitreomacular interface in persistent fetal vasculature syndrome (PFVS) with posterior involvement managed with early vitrectomy or with observation, with functional correlation. METHODS: We retrospectively identified 45 consecutive pediatric patients with PFVS with posterior involvement treated from 2005 to 2016. The eyes that could be imaged with spectral domain optical coherence tomography were included, and images were correlated with best-corrected visual acuity. RESULTS: Thirty-eight imaging sessions were performed on 10 eyes from 9 patients, including 7 that had been managed with vitrectomy for PFVS-related tractional retinal detachment, and 3 that had been observed. Mean age of the patients who were imaged was 9.1 years and their average length of follow-up was 5.9 years. Best-corrected visual acuities of the eyes imaged ranged from 20/30 to count fingers, with mean best-corrected visual acuity 20/163. All eyes imaged had microstructural anomalies identified. The main anomalous features included posterior hyaloidal organization, vitreoretinal traction, vitreopapillary traction, diminished foveal contour, foveal displacement, and disruption of the ellipsoid zone. Posterior hyaloidal organization (P = 0.043), diminished foveal contour (P = 0.019), and disruption of the ellipsoid zone (P = 0.014) were associated with worse best-corrected visual acuity. CONCLUSION: Macular and vitreomacular interface anomalies were identified in all pediatric patients with posterior PFVS imaged with spectral domain optical coherence tomography. These microstructural findings, together with functional measures, may inform the diagnosis and management of PFVS with posterior involvement.

Clinical characteristics and treatment of 22 eyes of morning glory syndrome associated with persistent hyperplastic primary vitreous.

PURPOSE: To describe the clinical manifestations and treatment outcomes in a retrospective case series of morning glory syndrome (MGS) associated with persistent hyperplastic primary vitreous (PHPV). METHODS: The medical records of 85 eyes/74 patients referred for ophthalmology consultation diagnosed as MGS in our clinic were reviewed retrospectively. All patients underwent thorough ophthalmological examinations. 22 eyes of 19 patients diagnosed as having MGS associated with PHPV were included, accounting for 25.88% of all the MGS eyes. Clinical manifestations and management of these patients were documented. RESULTS: 15 patients (78.95%) were younger than 1 year old at the first diagnosis. Six eyes were associated with microphthalmia. 19 of 22 eyes (86.36%) had complications, including cataract (10 eyes), secondary glaucoma (8 eyes), corneal leucoma or oedema (8 eyes), retinal detachment (8 eyes), strabismus (3 eyes) and nystagmus (2 eyes). Treatment methods varied depending on the severity of the complications. Nine eyes with secondary glaucoma or cataract got lensectomy; three eyes underwent combined vitrectomy and lensectomy. Eight patients underwent cranial MRI/MR angiography or CT examination. Widened cerebral fissures of bilateral temporal lobes, abnormal dilated branch of middle cerebral artery in the left hemisphere and abnormal signal in the grey matter of frontal and occipital lobes were revealed respectively in three patients. CONCLUSIONS: Our study revealed the coexistence of PHPV in a significant percentage of patients with MGS, suggesting a potential common genetic link. Compared with MGS and PHPV alone, the combination of the two conditions manifested with higher incidence and more severe complications in younger patients. Close follow-up was recommended. Lensectomy and vitrectomy were beneficial in the management of the complications.

Hemorragia vítrea asociada a arteria hialoidea persistente / Vitreous haemorrhage associated with persistent hyaloid artery

Introducción: La hemorragia vítrea secundaria a una arteria hialoidea persistente (AHP) íntegra es una anomalía infrecuente. Caso clínico: Una mujer de 52 años presentó disminución de visión en su ojo ambliope. La biomicroscopia reveló una AHP rellena de sangre que se insertaba en la cristaloides posterior. En la oftalmoscopia se objetivó un hemovítreo leve. La tomografía de coherencia óptica (TCO) permitió analizar la estructura tubular de la AHP mostrando un interior hiporreflectivo. Sin embargo, el eco-doppler no detectó la presencia de flujo sanguíneo activo en su interior. Conclusiones: La realización de pruebas de imagen no invasivas que incluyen la TCO y el eco-doppler pueden ser útiles en el estudio de una hemorragia asociada a una AHP(AU)

Introduction: Haemorrhage from an entire persistent hyaloid artery (PHA) is an uncommon anomaly. Case report: A 52 year old female presented with blurred vision in her amblyopic eye. Biomicroscopy revealed a blood filled PHA which was inserted in the posterior crystalloid. Ophthalmoscopy showed a mild vitreous haemorrhage. A tubular structure showing a hypo-reflexivity inside the PHA was able to be analysed using optical coherence tomography (OCT). However, Doppler ultrasound did not detect the presence of active blood flow within it. Conclusions: The performance of non-invasive imaging tests such as the OCT and Doppler ultrasound may be useful in the study of vitreous haemorrhage associated with PHA(AU)

Persistent hyperplastic primary vitreous: congenital malformation of the eye.

Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature, is a rare congenital developmental malformation of the eye, caused by the failure of regression of the primary vitreous. It is divided into anterior and posterior types and is characterized by the presence of a vascular membrane located behind the lens. The condition can be of an isolated type or can occur with other ocular disorders. Most cases of PHPV are sporadic, but it can be inherited as an autosomal dominant or recessive trait. Inherited PHPV also occurs in several breeds of dogs and cats. In a limited number of cases, Norrie disease and FZD4 genes are found to be mutated in unilateral and bilateral PHPV. These genes when mutated also cause Norrie disease pseudoglioma and familial exudative vitreoretinopathy that share some of the clinical features with PHPV. Mice lacking arf and p53 tumour suppressor genes as well as Norrie disease pseudoglioma and LRP5 genes suggest that these genes are needed for hyaloid vascular regression. These experiments also indicate that abnormalities in normal apoptosis and defects in Wnt signalling pathway may be responsible for the pathogenesis of PHPV. Identification of other candidate genes in the future may provide a better understanding of the pathogenesis of the condition that may lead to a better therapeutic approach and better management.