Persistent Fetal Vasculature

Persistent Fetal Vasculature (PFV), previously known as Persistent Hyperplastic Primary Vitreous (PHPV) is a rare developmental malformation of the eye characterized by the presence of a vascular membrane located behind the lens.  

ICD9 743.51  ICD10 Q14.0

Persistent hyperplastic primary vitreous accounts for 4.8% of childhood blindness and visual impairment in the United States. 

During embryonic development, the normal primary vitreous, which is composed of hyaloid vasculature and a fibrillary meshwork, appears during the first month of gestation and is replaced by a watery mass of loose collagen fibers and hyaluronic acid, called the secondary or adult vitreous. The primary vitreous progressively decreases in size and finally occupies only a small central space in the posterior chamber of the eye, which is called the hyaloid.
During the development of the human eye, spontaneous regression of the embryonic hyaloid artery occurs in-utero with the conversion of the primary vitreous to the secondary adult vitreous. 

The failure of regression of fetal vessels within the eye causes the congenital anomaly Persistent Fetal vasculature (PFV). This is a spectrum of congenital ocular abnormalities caused by the failure of in utero conversion of the primary vitreous to the secondary adult vitreous and regression of hyaloid vasculature.

PFV is the primary cause of leukocoria = “white pupil”, an abnormal pupillary reflex seen on mydriasis. It is the first sign of a range of serious intraocular disorders including cataract, retinoblastoma, Norrie disease and retrolental fibroplasia.

PFV is usually not associated with other systemic findings. However, some neurological abnormalities such as hemiparesis, ataxia, impaired coordination, hypotonia, spastic quadriplegia, microcephaly and deafness have been reported. PHPV is also associated with Aicardi syndrome: infantile spasm, agenesis of the corpus callosum and chorioretinal lacunae and with Walker-Warburg syndrome.1, 
Norrie disease is another condition characterized by X-linked recessive inheritance, bilateral persistent hyperplastic primary vitreous, and very early childhood leukocoria, deafness, mental retardation, and absence of retinal ganglion cells.4

Most cases of PFV are sporadic, but it can be inherited as an autosomal dominant or recessive trait. Recurrence risk is high in case of consanguinity or if the condition accompanies genetic syndromes at high recurrence. 

Visualization of vessels behind the lens is suggestive for the diagnosis. The most prominent sonographic findings include hyperechoic lenses (cataract) and a hyperechoic mass between the posterior surface of the lens and posterior wall of the eye, representing hyaloid artery persistence and retinal detachment.2
PFV is classically subdivided into three presentations: anterior, posterior and a combination of both forms. The purely anterior presentation of PFV is usually associated with cataract and glaucoma. The purely posterior presentation usually occurs in eyes with abnormalities confined to their posterior segments. The combination of both anterior and posterior forms is the most commonly seen. Postnatal diagnosis of PFV is usually confirmed by high-frequency ultrasonography, computed tomography or magnetic resonance imaging after clinical suspicion of the disorder.

The most commonly recognized clinical manifestation of PFV after birth is leukocoria (white lens). The differential diagnosis of PFV, especially anterior PFV, includes therefore those conditions that may also result in leukocoria. The most concerning is retinoblastoma, the most common intraocular tumor of childhood and this must be ruled-out in every case of PFV. Generally, PFV occurs in a microphthalmic eye, while retinoblastoma occurs in a normal-sized eye. Other causes of leukocoria are most commonly congenital cataracts or Coats’ Disease, however, the differential should also include astrocytic hamartomas (related to tuberous sclerosis), uveitis, toxocariasis, and retinopathy of prematurity. Classically, the genetic syndromes that may include PFV are Norrie’s disease, Trisomy 13, and the Walker-Warburg syndrome. When the eye in consideration has total retinal detachment and retrolental fibrous tissues suggestive of posterior PFV syndrome, familial exudative vitreoretinopathy, incontinentia pigmenti, ocular toxocariasis, and retinopathy of prematurity should be specially considered.  

In all cases when a cataract is seen or suspected, a careful examination of the eye chamber should be performed to exclude this anomaly. Also, a detailed examination of the fetal brain and of the whole fetal anatomy and a thorough family history should be carried out to exclude association with genetic syndromes.

The anomaly can become sonographically evident only late in pregnancy, therefore investigations should be repeated until the third trimester, before excluding the anomaly.

Persistent fetal vasculature can be a devastating developmental anomaly that remains an important cause of amblyopia and visual disabilities in children. The poor prognosis, without treatment, can also include recurrent intraocular hemorrhage and secondary glaucoma and eventually can require enucleation. 

Early surgical intervention is necessary to prevent progressive pathologic changes and to obtain the best visual results. With modern vitreoretinal techniques, aphakic rehabilitation, and aggressive amblyopic therapy, useful vision can be obtained in most  patients with both anterior and posterior persistent fetal vasculature.  Parental compliance is critical if visual improvement is to be seen in an individual with Persistent Fetal Vasculature.  Effective management of the anisometropic amblyopia requires motivated parents to ensure compliance with occlusive therapy, as well as parents willing to attend numerous visits to eye specialists.6

In cases with additional anomalies, the diagnosis of PFV suggests genetic syndromes which have poor prognoses and considerable recurrence potential, such as Aicardi or Walker-Warburg syndrome, an autosomal recessively inherited syndrome, characterized by congenital muscular dystrophy, hydrocephalus, hypoplasia of the cerebellar vermis, dysplasia of the cerebellar hemispheres, abnormal gyration, an absent or hypoplastic corpus callosum, encephalocele, and microphthalmia with ocular malformations, including persistent hyperplastic primary vitreous.
Also, in the presence of consanguinity and bilateral PFV, the suspicion of a genetic syndrome should arise. Owing to the high recurrence rate of some syndromes, prenatal genetic testing should be recommended for early intrauterine diagnosis in subsequent pregnancies.

1. Katorza E, Rosner M, Zalel Y, Gilboa Y, Achiron R. Prenatal ultrasonographic diagnosis of persistent hyperplastic primary vitreous. Ultrasound Obstet Gynecol. 2008;32(2):226-228. 
2. Esmer AC, Sivrikoz TS, Gulec EY, et al. Prenatal Diagnosis of Persistent Hyperplastic Primary Vitreous: Report of 2 Cases and Review of the Literature. J Ultrasound Med. 2016;35(10):2285-2291.
3. Smirniotopoulos JC, Bargallo N, Mafee MF. Differential diagnosis of leukokoria: radiologic-pathologic correlation. Radiographics 1994; 14: 1059–107
4. Marshman WE, Jan JE, Lyons CJ. Neurologic abnormalities associated with persistent hyperplastic primary vitreous. Can J Ophthalmol 1999; 34: 17– 22.
5.  Silbert M, Gurwood AS. Persistent hyperplastic primary vitreous. Clin Eye Vis Care. 2000;12(3-4):131-137.

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