Persistent hyperplastic primary vitreous

Persistent hyperplastic primary vitreous (PHPV) is also referred to as persistent fetal vasculature (PFV) or persistent fetal vasculature syndrome (PFVS), OMIM 611308 (autosomal dominant PHPV) or OMIM 611311 (autosomal recessive PHPV).

It has previously been called persistent tunica vasculosa lentis, persistent posterior fetal fibrovascular sheath of the lens, congenital retinal septum, and ablatio falciformis congenita.


PHPV is a congenital anomaly of the eye that results following failure of embryological primary vitreous and hyaloid vasculature to regress. It is characterized by persistence of various portions of the primary vitreous (embryonic hyaloid vascular system) with hyperplasia of the associated embryonic connective tissue, and associated with microphthalmia, cataract and glaucoma.

PHPV was described by A. B. Reese in 1949. It belongs to the group of vitreoretinopathies.

PHPV is usually divided into three types:

  • Anterior PHPV: Anterior PHPV occurs when the remnant vascular stalk is seen attached to the back of the lens but no longer extends back to the optic nerve. The purely anterior PHPV is also known as persistent tunica vasculosa lentis and persistent posterior fetal fibrovascular sheath of the lens. This form is typically associated with cataract, glaucoma and retrolenticular membrane.
  • Posterior PHPV: In posterior PHPV the remnant vascular stalk is seen arising off the optic nerve but not reaching the lens, thus usually not causing cataract. Posterior PHPV may be associated with abnormal development of the retina, optic nerve and macula, vitreal stalk, vitreal membranes. The purely posterior presentation of PHPV is termed falciform retinal septum and ablatio falcicormis congentia.
  • A combination of anterior and posterior PHPV: A combination of anterior and posterior PHPV is the most commonly seen clinical presentation.

Epidemiology, onset & clinical features


Though the exact prevalence remains unknown, PHPV is considered to be not a very rare disease. The condition is usually unilateral and isolated (without associated systemic findings) in normal full-term infants. A study on childhood blindness and visual loss in the United States showed that PHPV accounts for about 5 % of all cases of blindness.


PHPV is typically found in full term infants. In majority of cases, the abnormality can be noted at birth or within the first few weeks of life.

Clinical features

The most common presenting signs are leukoria (white papillary reflex due to a dense retrolenticular membrane or cataractous lens), microphthalmia and cataract, but the clinical presentation may vary.

In more than 90 % of cases PHPV is unilateral. Microphthalmos is usually moderate, cornea is clear, anterior chamber is shallow. The lens may be clear or cataractic. The cataract may range from a tiny visually insignificant opacity to a widespread vascularised plaque on the back of the lens and varying degrees of opacity throughout the lens, including total white cataract. It may worsen with age. The iris may be normal or may show small notches at the margins of the pupilla.

Characteristic traction of the ciliary processes is sometimes visible in the periphery of the dilated pupil. Small eye, white papillary reflex and iridohyaloidal vessels seen over the anterior iris surface, papillary margin and posterior iris surface are the most important diagnostic parameters.

Occasionally, extensive intravitreal hemorrhage and retinal detachment are present. Visual acuity can be nearly normal, but in most cases of posterior PHPV it is 20/200 or less at diagnosis. Strabismus may be present at birth or develop shortly after in the postnatal period.

Complications of PHPV include glaucoma, intraocular hemorrhage, retinal detachment and phthisis bulbi.

Though the disease is typically isolated, it has also been reported in combination with other syndromes: trisomy 13, Norrie disease, Walker-Warburg syndrome, incontinentia pigmenti, cerebro-oculo-dysplasia-muscular dystrophy, fetal alcohol syndrome, neurofibromatosis 2, Axenfeld-Rieger syndrome.

Etiology and pathogenesis

During embryonic development of the eye, the compartment between the retina and crystalline lens contains a vascular system (hyaloid artery) that provides nutrients for the developing eye. The hyaloids vessels and the primary vitreous are supposed to regress in the third trimester of pregnancy.

PHPV may be due to a defect in the regression of the primary vitreous or in the formation of the secondary vitreous (that fills the developing second eye and is derived from the inner retinal cells starting in the 9th week of gestation) or to a combination of both. The persistent hyaloid vasculature and mesenchymal tissue from the embryonic primary vitreous in a microphthalmic eye leads to the clinical spectrum of PHPV. The exact cause and pathogenetical mechanisms, however, remain poorly understood.

In some patients with PHPV, mutations in the NDP gene have been identified. NDP mutations have been associated with a spectrum of pediatric retinal vitreopathies. Among them, Norrie disease represents the most severe phenotype, while PHPV together with X-linked familial exudative vitreoretinopathy (FEVR), Coats disease and retinopathy of prematurity (ROP) represent the less severe phenotypes.

The pathogenetic role of the NDP mutations in PHPV was supported by findings in Ndp knockout animal models that demonstrated failure of the primary hyaloid artery and associated structures to regress. One patient with bilateral PHPV was reported to have a mutation the NDP gene and the mother of this patient was confirmed to be a carrier.

Mode of inheritance & diagnosis

Mode of inheritance

The majority of PHPV cases occur sporadically. A few cases of familial occurrences have been reported in dizygotic twins, in two brothers, and in a mother and son. Autosomal dominant and autosomal recessive genetic forms of PHPV have been described.

PHPV in one eye is not considered a genetic disorder, therefore it should not be passed on by the affected children. However, genetic counseling should be offered to each family with affected child for specific information.


Diagnosis is based on comprehensive eye examination and confirmed by ultrasonography, computing tomography (CT) or magnetic resonance imaging (MRI). A cone-shaped retrolental density is a characteristic finding of PHPV on imaging studies.

Differential diagnosis

Retinoblastoma (that also typically presents with leukokoria and micropthalmos in the perinatal period) must be primarily concerned in the differential diagnosis of PHPV, as without treatment, most children with retinoblastoma develop life-threatening disease within 2 years.

PHPV is the second most common cause of leukokoria after retinoblastoma. Bilateral cases of PFVS can often be difficult to distinguish from Norrie disease or FEVR.

Other conditions that may easily be mistaken for PHPV include Coats disease, retinopathy of prematurity (ROP), microphthalmia, incontinentia pigmenti, congenital cataract, and ocular toxocariasis.

Diseases rarely confused with PHPV are coloboma of optic nerve, coloboma of posterior pole, uveitis, cataract, myelinated nerve fibers, juvenile xanthogranuloma, falciform retinal folds.

Management and prognosis


Today, the goals in treatment are saving the eye from the complications of untreated PHPV (mainly glaucoma and phthisis bulbi), saving of useful vision, and achieving acceptable cosmetic outcome.

When the cataract is significant, some authors suggest preventive lens extraction in the first few weeks of life. Lensectomy with or without anterior or total vitrectomy, and trabeculectomy are the surgical procedures that are performed depending on the clinical presentation. It should be noted however, that surgery for PHPV may be complicated by retinal detachment. Strict case selection is needed, as preoperative retinal or optic nerve abnormalities are particularly associated with poor outcomes.

Strabismus surgery may also be required though fusional potential is usually poor in these patients.

Visual rehabilitation (aphakic contact lens and amblyopia therapy) is possible with eyes that are fairly normal in structure after the lensectomy and membranectomy. In case of the numerous abnormalities of the posterior segment, visual rehabilitation may not be possible. In patients in whom surgery is not possible, the use of a cosmetic contact lens to give a black pupil is necessary. Enucleation of the blind eye may be indicated in case of intractable glaucoma and phthisis bulbi.


Visual prognosis is usually guarded as the disease is often progressive. Early surgery may result in relatively good visual results in selected patients.

The most important factor to predict the visual outcome in PHPV patients is whether or not the posterior pole is involved.

Treatment of posterior and combined anteroposterior PHPV usually has a less favorable outcome.


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Katia Marazova, MD, PhD, Prof. José Alain Sahel, MD, PhD and Dr Caroline Laurent-Coriat, MD, PhD

Disclaimer: This document contains information based on published scientific articles and is for educational purposes only. It is in no way intended as a substitute for qualified medical professional help, advice, diagnosis or treatment.