Ophthalmology – Persistent Fetal Vasculature (PFV)

Basics

Description

Persistent fetal vasculature (PFV) is a congenital developmental disorder caused by incomplete regression of the:

• Primary vitreous
• Hyaloid vascular system
• Tunica vasculosa lentis

The older term:

Persistent hyperplastic primary vitreous (PHPV)

has largely been replaced by PFV, because the abnormality may involve more than the primary vitreous alone.

PFV is usually:

• Unilateral
• Sporadic
• Associated with a smaller affected eye

It may cause:

• Leukocoria
• Cataract
• Retrolental fibrovascular tissue
• Retinal traction
• Retinal detachment
• Microphthalmia

Clinical Importance

The most important diagnostic issue is:

PFV must be distinguished from retinoblastoma.

Both may present in infancy with:

• Leukocoria
• Retrolental opacity
• Poor vision

Misdiagnosis can have major consequences.

Classification

PFV is divided into:

• Anterior PFV
• Posterior PFV
• Combined PFV

Combined disease is common.

Anterior PFV

Anterior findings may include:

• Retrolental fibrovascular membrane
• Posterior lens plaque
• Cataract
• Elongated ciliary processes
• Persistent tunica vasculosa lentis
• Shallow anterior chamber
• Microphthalmia

The retrolental membrane may exert traction on the:

• Ciliary processes
• Lens
• Iris

Posterior PFV

Posterior findings may include:

• Fibrovascular stalk from optic disc toward posterior lens
• Optic nerve hypoplasia
• Retinal folds
• Macular traction
• Retinal dysplasia
• Tractional retinal detachment
• Vitreous hemorrhage

Combined PFV

Combined PFV contains both:

• Anterior segment changes
• Posterior segment tractional abnormalities

Visual prognosis is generally worse than in isolated anterior PFV.

Epidemiology

PFV is rare.

Most cases are:

• Unilateral
• Sporadic

Bilateral disease is uncommon and should raise suspicion for:

• Genetic disease
• Syndromic retinal dysplasia
• Another diagnosis mimicking PFV

Embryology

The fetal hyaloid vascular system supplies the developing:

• Lens
• Primary vitreous

during early gestation.

It normally regresses before birth.

Remnants of this system can persist physiologically as:

• Mittendorf dot on the posterior lens capsule
• Bergmeister papilla at the optic disc
• Persistent hyaloid artery

PFV represents a much more extensive failure of involution.

Pathophysiology

Failure of normal fetal vascular regression produces persistent:

• Fibrovascular tissue
• Hyaloid vessels
• Primary vitreous

Subsequent contraction may cause:

• Lens distortion
• Ciliary process elongation
• Retinal traction
• Retinal folds
• Retinal detachment

Genetics

Most PFV is:

Sporadic

Rare familial and syndromic forms have been described.

Genes associated with PFV or PFV-like phenotypes include:

• ATOH7
• NDP
• FZD4
• LRP5
• PAX6

depending on phenotype.

Genetic evaluation is particularly appropriate when PFV is:

• Bilateral
• Associated with retinal dysplasia
• Accompanied by systemic abnormalities
• Present in multiple family members

Bilateral PFV

True bilateral PFV is unusual.

The differential should include:

• Norrie disease
• Familial exudative vitreoretinopathy
• Retinopathy of prematurity
• Incontinentia pigmenti
• Walker-Warburg spectrum
• Other developmental retinal disorders

Clinical Presentation

The classic presentation is:

Unilateral leukocoria in an infant with microphthalmia

Other presentations include:

• Strabismus
• Poor fixation
• Cataract
• Retrolental membrane
• Abnormal red reflex

History

Ask about:

• Abnormal red reflex
• Leukocoria
• Eye size asymmetry
• Strabismus
• Poor visual behavior
• Prematurity
• Oxygen treatment
• Family history of retinal disease
• Hearing impairment
• Developmental abnormalities

Microphthalmia

The affected eye is often:

Smaller than the fellow eye

This is a valuable clinical clue because retinoblastoma usually occurs in a:

• Normal-sized
• Sometimes enlarged

eye rather than a microphthalmic eye.

Anterior Segment Findings

Possible findings include:

• Shallow anterior chamber
• Cataract
• Posterior lens plaque
• Retrolental membrane
• Elongated ciliary processes
• Corectopia
• Poor pupillary dilation

Persistent anterior fetal vasculature may exert traction on the ciliary body.

Posterior Lens Appearance

The anterior lens may remain relatively clear while the posterior lens region shows:

• Fibrovascular plaque
• Membrane
• Cataract

A vascular stalk may attach to this posterior region.

Retrolental Fibrovascular Membrane

This may appear as:

• White
• Gray-white
• Vascularized

tissue behind the lens.

It contributes to the leukocoria.

Persistent Hyaloid Stalk

A classic posterior finding is:

Fibrovascular stalk extending from the optic disc toward the posterior lens

This corresponds to persistent fetal hyaloid tissue.

Posterior Segment Findings

May include:

• Optic disc hypoplasia
• Macular distortion
• Retinal fold
• Retinal dysplasia
• Tractional retinal detachment
• Vitreous hemorrhage

Retinal Fold

A retinal fold may extend:

• From the optic nerve
• Toward the peripheral retina or lens

and may substantially limit visual potential.

Retinal Dysplasia

Retinal dysplasia is an important determinant of visual prognosis.

Severe dysplasia may prevent useful vision even after technically successful surgery.

Diagnosis

Diagnosis is based on:

• Clinical examination
• Ocular ultrasound
• MRI when needed

The major diagnostic goal is to exclude:

Retinoblastoma

before proceeding with surgery.

Examination Under Anesthesia

In infants, examination under anesthesia may be required to adequately assess:

• Anterior segment
• Lens
• Peripheral retina
• Optic nerve
• Presence of retinal detachment

B-Scan Ultrasonography

B-scan is particularly useful when the fundus cannot be visualized.

It may demonstrate:

• Small globe
• Retrolental membrane
• Fibrovascular stalk
• Retinal detachment

A classic appearance is:

A stalk extending from posterior lens to optic disc

Calcification

A critical imaging distinction:

Retinoblastoma

Often demonstrates:

Intraocular calcification

PFV

Typically:

Does not contain calcification

However:

Absence of calcification does not completely exclude retinoblastoma.

Therefore imaging must be interpreted with the entire clinical picture.

MRI

MRI is preferred over CT when additional imaging is required because it:

• Avoids ionizing radiation
• Evaluates soft tissues better
• Helps distinguish PFV from noncalcified retinoblastoma
• Assesses optic nerve and brain

MRI Findings

Possible findings include:

• Microphthalmia
• Retrolental fibrovascular tissue
• Persistent hyaloid stalk
• Retinal detachment
• Abnormal lens morphology

CT

CT was historically used because of its ability to detect calcification.

However:

CT is no longer preferred routinely in infants when ultrasound and MRI can establish the diagnosis, because of ionizing radiation exposure.

OCT

In selected cooperative children or with handheld OCT, imaging may demonstrate:

• Retinal folds
• Macular traction
• Foveal distortion
• Outer retinal abnormalities

This may help estimate visual potential.

Fluorescein Angiography

Wide-field fluorescein angiography may occasionally help evaluate:

• Retinal vascular abnormalities
• Peripheral avascular retina
• Alternative diagnoses such as FEVR

It is not required in every classic unilateral case.

Visual Evoked Potentials

VEP has historically been used to estimate residual visual pathway function.

Its ability to predict postoperative visual outcome is limited.

Modern surgical decisions rely more heavily on:

• Ocular anatomy
• Macular status
• Optic nerve status
• Retinal attachment
• Clinical visual behavior

Differential Diagnosis

The most important differential is:

• Retinoblastoma

Other differentials include:

• Congenital cataract
• Norrie disease
• Familial exudative vitreoretinopathy
• Retinopathy of prematurity
• Incontinentia pigmenti
• Coats disease
• Ocular toxocariasis
• Coloboma
• Walker-Warburg spectrum
• Retinal dysplasia

PFV vs Retinoblastoma

PFV

Usually:

• Unilateral
• Microphthalmic eye
• Retrolental membrane
• Hyaloid stalk
• Elongated ciliary processes
• No calcification

Retinoblastoma

Typically:

• Intraocular retinal mass
• Calcification common
• Normal or enlarged globe
• Feeding vessels
• Possible vitreous or subretinal seeds

PFV vs Congenital Cataract

Congenital cataract may cause:

• Leukocoria
• Poor red reflex

but lacks:

• Hyaloid stalk
• Ciliary process traction
• Retinal folds
• Posterior fibrovascular membrane

unless associated with PFV.

PFV vs Norrie Disease

Norrie disease usually causes:

• Bilateral severe retinal dysplasia
• Pseudoglioma
• Retinal detachment

and may later cause:

• Sensorineural hearing loss
• Neurodevelopmental problems

Bilateral PFV-like disease should therefore prompt consideration of:

NDP-related disease

PFV vs FEVR

FEVR may produce:

• Peripheral avascular retina
• Retinal folds
• Traction
• Retinal detachment

Unlike classic unilateral PFV, FEVR is often:

• Bilateral
• Familial

although asymmetry can be marked.

Treatment Principles

Treatment depends on:

• PFV type
• Severity
• Visual potential
• Cataract
• Degree of traction
• Retinal status
• Age at presentation

Options include:

• Observation
• Surgery
• Amblyopia therapy

Observation

Observation may be appropriate for:

• Mild anterior PFV
• Clear visual axis
• Minimal traction
• Severe posterior disease with very poor visual potential
• Stable painless microphthalmic eye

Indications for Surgery

Consider surgery when there is:

• Visually significant cataract
• Visual-axis obstruction
• Progressive retrolental membrane
• Traction threatening the retina
• Retinal detachment amenable to repair
• Progressive secondary glaucoma
• Risk of painful phthisis

Surgical Goals

The major goals are:

• Clear the visual axis
• Release anterior-posterior traction
• Preserve retinal attachment
• Preserve globe anatomy
• Maximize amblyopia treatment potential

Anterior PFV Surgery

Typical procedures may include:

• Lensectomy
• Membranectomy
• Anterior vitrectomy

Care must be taken because the retrolental tissue can be:

Highly vascular

and intraoperative bleeding may occur.

Posterior / Combined PFV Surgery

May require:

• Pars plana or limbal vitrectomy
• Transection/removal of the fibrovascular stalk
• Membrane dissection
• Retinal reattachment procedures

These cases are technically challenging because:

• Retina may be dysplastic
• Tissue planes may be abnormal
• Bleeding risk is significant

Lens-Sparing Surgery

When the lens remains clear and anatomy allows, surgeons may attempt:

Lens-sparing vitrectomy

to reduce:

• Aphakia
• Anisometropia
• Amblyopia

However, this is feasible only in selected cases.

Intraocular Lens

Primary IOL implantation in PFV is individualized.

Factors include:

• Age
• Capsular support
• Eye size
• Degree of anterior segment abnormality

Many infants are initially managed with:

• Contact lens
• Aphakic spectacles

after lensectomy.

Amblyopia Treatment

Amblyopia is often a major limitation to visual recovery.

Treatment may include:

• Refractive correction
• Contact lens for aphakia
• Spectacles
• Patching of the better eye
• Atropine penalization in selected cases

Early and sustained amblyopia treatment is often as important as surgery.

Strabismus

Strabismus is common because of:

• Poor unilateral vision
• Anisometropia
• Structural retinal abnormalities

Surgery may later be considered for:

• Alignment
• Cosmesis
• Binocular function when possible

Glaucoma

Secondary glaucoma may develop from:

• Anterior segment dysgenesis
• Lens abnormalities
• Shallow anterior chamber
• Postsurgical changes

Monitor:

• IOP
• Corneal diameter
• Optic nerve
• Axial growth

Severe End-Stage Disease

Historically, some severely malformed eyes underwent enucleation.

Modern management is generally globe-preserving whenever the eye is:

• Comfortable
• Not suspicious for malignancy

Enucleation is uncommon and usually reserved for:

• Blind painful eye
• Severe disorganization
• Inability to exclude malignancy in exceptional cases

Follow-Up

All children require long-term follow-up whether treated surgically or observed.

Monitor:

• Visual acuity
• Refraction
• Amblyopia
• Strabismus
• Cataract
• Retinal status
• IOP
• Globe growth

Prognosis

Visual prognosis depends strongly on the subtype.

Anterior PFV Prognosis

Isolated anterior PFV generally has the:

Best visual prognosis

particularly when:

• Retina is attached
• Optic nerve and macula are relatively normal
• Visual axis is cleared early
• Amblyopia is treated aggressively

Useful visual acuity is possible.

Posterior PFV Prognosis

Posterior disease has a less favorable prognosis because of:

• Optic nerve hypoplasia
• Macular involvement
• Retinal folds
• Retinal dysplasia
• Retinal detachment

Combined PFV Prognosis

Combined disease generally has the poorest visual potential.

Nevertheless, modern surgery may sometimes achieve:

• Anatomical preservation
• Better-than-light-perception vision
• Improved functional vision

in selected patients.

Prognostic Factors

Poor visual prognosis is associated with:

• Severe posterior involvement
• Macular traction
• Optic nerve hypoplasia
• Retinal dysplasia
• Total retinal detachment
• Long-standing visual deprivation

Complications

Potential complications include:

• Cataract
• Amblyopia
• Anisometropia
• Strabismus
• Retinal detachment
• Vitreous hemorrhage
• Secondary glaucoma
• Corneal decompensation
• Phthisis bulbi
• Permanent visual loss

Ophthalmology Pearls

• Persistent fetal vasculature is the preferred term; PHPV is historical.
• PFV results from failure of regression of the fetal hyaloid vascular system and primary vitreous.
• It is typically unilateral, sporadic, and associated with microphthalmia.
• The classic finding is a fibrovascular stalk extending from the optic disc toward the posterior lens.
• Anterior PFV causes posterior lens plaque/cataract and elongated ciliary processes; posterior PFV causes retinal folds, traction, dysplasia, or detachment.
• The most important differential diagnosis is retinoblastoma.
• Calcification strongly favors retinoblastoma, but absence of calcification does not absolutely exclude it.
• Ultrasound plus MRI is usually preferred over CT in infants because MRI avoids radiation and better evaluates soft tissue.
• True bilateral PFV is unusual and should prompt consideration of Norrie disease, FEVR, ROP, or another inherited retinal disorder.
• Surgical goals are to clear the visual axis and release vitreoretinal traction, not simply remove a membrane.
• Anterior PFV has the best visual prognosis; posterior and combined PFV are limited by optic nerve, macular, and retinal dysplasia.
• Amblyopia and anisometropia frequently limit final vision even after technically successful surgery.