Ophthalmology – Persistent Hyperplastic Primary Vitreous / Persistent Fetal Vasculature

Basics

Description

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

• Hyaloid vascular system
• Primary vitreous
• Tunica vasculosa lentis

The older term persistent hyperplastic primary vitreous (PHPV) is now largely historical. PFV is preferred because the disorder may affect multiple structures beyond the primary vitreous, including the:

• Lens
• Ciliary body
• Retina
• Optic nerve
• Anterior chamber angle

PFV is usually:

• Unilateral
• Sporadic
• Present from birth
• Associated with a smaller affected eye

Severity ranges from a subtle persistent fetal remnant to severe retinal dysplasia and detachment.

Classification

PFV is classified as:

• Anterior PFV
• Posterior PFV
• Combined PFV

Combined anterior-posterior disease is common.

Anterior PFV

Anterior abnormalities may include:

• Persistent tunica vasculosa lentis
• Retrolental fibrovascular membrane
• Posterior lens plaque
• Cataract
• Elongated or centrally dragged ciliary processes
• Shallow anterior chamber
• Lens displacement
• Secondary angle closure
• Microcornea

Posterior PFV

Posterior disease may demonstrate:

• Persistent hyaloid artery
• Fibrovascular stalk from optic disc toward lens
• Bergmeister papilla
• Vitreous membranes
• Retinal fold
• Macular traction
• Retinal dysplasia
• Tractional retinal detachment
• Optic nerve hypoplasia or dysplasia

Embryology

The fetal hyaloid circulation supplies the developing lens and primary vitreous.

It normally undergoes regression before birth.

Normal remnants may include:

• Mittendorf dot on the posterior lens capsule
• Bergmeister papilla at the optic disc
• Occasionally a persistent hyaloid artery

PFV represents more extensive persistence with secondary fibrovascular contraction.

Pathophysiology

Failure of fetal vascular regression leaves:

• Persistent vessels
• Fibrous tissue
• Primary vitreous

Contraction of this tissue may pull on the:

• Lens
• Ciliary body
• Retina
• Optic disc

producing progressive structural distortion.

Epidemiology

PFV is uncommon.

The majority of cases are:

Unilateral and sporadic

Bilateral disease is unusual and should prompt consideration of an:

• Inherited retinal disorder
• Syndromic developmental disorder

Genetics

Most isolated PFV has no identifiable inherited cause.

Rare PFV or PFV-like phenotypes have been associated with genes including:

• ATOH7
• NDP
• FZD4
• LRP5
• TSPAN12
• PAX6

Genetic evaluation becomes particularly important in:

• Bilateral disease
• Familial disease
• Severe retinal dysplasia
• Systemic congenital abnormalities

Bilateral PFV – Important Principle

True bilateral isolated PFV is uncommon.

When both eyes show severe fibrovascular retinal abnormalities, consider:

• Norrie disease / NDP-related retinopathy
• Familial exudative vitreoretinopathy
• Retinopathy of prematurity
• Incontinentia pigmenti
• Walker-Warburg spectrum
• Other retinal dysplasia syndromes

NDP-Related Retinopathy

NDP-related disease may produce a severe congenital retinal phenotype resembling PFV.

The most severe form is:

Norrie disease

Typical features include:

• Bilateral retinal dysplasia
• Retinal detachment
• Pseudoglioma
• Severe congenital visual impairment

Associated systemic manifestations may include:

• Progressive sensorineural hearing loss
• Developmental or behavioral abnormalities

Familial Exudative Vitreoretinopathy

FEVR may produce:

• Peripheral avascular retina
• Neovascularization
• Fibrosis
• Retinal folds
• Tractional retinal detachment

It may be profoundly asymmetric, but bilateral peripheral vascular abnormalities often support FEVR over classic unilateral PFV.

Clinical Presentation

The classic presentation is:

Leukocoria in an infant with a microphthalmic eye

Other presentations include:

• Abnormal red reflex
• Cataract
• Strabismus
• Poor fixation
• Eye-size asymmetry

Microphthalmia

The affected eye is frequently:

Smaller than the fellow eye

This is an important diagnostic clue.

Retinoblastoma generally occurs in a normal-sized eye, whereas classic PFV often produces:

• Microphthalmia
• Microcornea

Anterior Segment Findings

Possible findings include:

• Microcornea
• Shallow anterior chamber
• Corneal clouding
• Persistent pupillary membrane
• Posterior cataract
• Retrolental membrane
• Ectropion uveae
• Lens subluxation
• Elongated ciliary processes

Iridohyaloid Vessels

Persistent fetal vessels may connect the:

• Iris
• Ciliary body
• Retrolental fibrovascular tissue

Contraction can cause:

• Centrally dragged ciliary processes
• Lens displacement
• Secondary angle closure

Mittendorf Dot

A Mittendorf dot is a benign remnant of the fetal hyaloid system located on the:

Posterior lens capsule

An isolated Mittendorf dot does not constitute severe PFV.

Posterior Segment Findings

Potential findings include:

• Persistent hyaloid artery
• Vitreous membranes
• Fibrovascular stalk
• Optic disc anomaly
• Retinal folds
• Macular distortion
• Retinal dysplasia
• Retinal detachment

Bergmeister Papilla

A Bergmeister papilla is a remnant of fetal tissue at the optic disc.

It may be:

• Small and clinically insignificant
• Associated with persistent vitreous tissue in more extensive PFV

Macular Abnormalities

Posterior PFV may produce:

• Macular traction
• Retinal fold crossing the macula
• Foveal distortion
• Absent or poorly developed foveal architecture

These substantially limit visual potential.

Optic Nerve Abnormalities

Associated findings may include:

• Optic nerve hypoplasia
• Optic nerve dysplasia
• Abnormal disc insertion of the fibrovascular stalk

These are important prognostic factors.

Diagnosis

Diagnosis is based on the combination of:

• Clinical examination
• Ocular imaging
• Characteristic anatomy

The most important diagnostic objective is:

Exclusion of retinoblastoma

Examination Under Anesthesia

Infants may require examination under anesthesia to evaluate:

• Cornea
• Anterior chamber
• Lens
• Ciliary processes
• Retina
• Optic nerve
• Degree of retinal detachment

B-Scan Ultrasonography

B-scan is especially useful when the fundus cannot be seen.

It may show:

• Microphthalmia
• Retrolental membrane
• Persistent hyaloid stalk
• Retinal fold
• Retinal detachment

A classic finding is:

A band or stalk extending from the posterior lens toward the optic disc.

Doppler Ultrasound

Color Doppler may occasionally demonstrate persistent blood flow within:

• Hyaloid vessels
• Fibrovascular stalk

particularly in younger infants.

MRI

MRI is preferred when cross-sectional imaging is needed.

It can demonstrate:

• Retrolental soft tissue
• Hyaloid stalk
• Retinal detachment
• Abnormal lens morphology
• Microphthalmia
• Optic nerve abnormalities

MRI is also useful when evaluating:

• CNS abnormalities
• Syndromic disease
• Possible noncalcified retinoblastoma

CT

CT historically played an important role because it detects:

Calcification

However, routine CT is now generally avoided in infants when ultrasound and MRI are adequate because of:

• Ionizing radiation

Calcification – Critical Pearl

PFV

Typically:

No intraocular calcification

Retinoblastoma

Commonly:

Calcified retinal mass

However:

Absence of calcification does not completely exclude retinoblastoma.

Fluorescein Angiography

Wide-field fluorescein angiography may be useful in selected patients to evaluate:

• Persistent fetal vessels
• Peripheral retinal vascularization
• FEVR-like abnormalities
• Fellow-eye vascular changes

It is not routinely required in classic unilateral PFV.

OCT

Handheld or conventional OCT may show:

• Vitreoretinal traction
• Macular fold
• Foveal distortion
• Retinal dysplasia
• Outer retinal abnormalities

It can help estimate visual potential and assist surgical planning.

Visual Evoked Potentials

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

Its predictive value is limited.

Modern prognosis is more strongly based on:

• Macular anatomy
• Optic nerve development
• Retinal attachment
• Clinical visual behavior

Differential Diagnosis

Important differential diagnoses include:

• Retinoblastoma
• Congenital cataract
• Norrie disease
• Familial exudative vitreoretinopathy
• Stage 5 retinopathy of prematurity
• Coats disease
• Incontinentia pigmenti
• Ocular toxocariasis
• Congenital retinal dysplasia
• Walker-Warburg spectrum
• Lens subluxation disorders

PFV vs Retinoblastoma

PFV

Usually:

• Unilateral
• Microphthalmic
• Retrolental fibrovascular membrane
• Persistent hyaloid stalk
• Elongated ciliary processes
• No calcification

Retinoblastoma

Usually shows:

• Retinal tumor mass
• Intraocular calcification
• Feeding vessels
• Vitreous or subretinal seeds
• Normal-sized or enlarged eye

PFV vs Retinopathy of Prematurity

Severe ROP usually occurs in:

• Premature infants
• Often bilaterally

End-stage disease may cause:

• Retrolental fibrosis
• Funnel retinal detachment
• Leukocoria

A history of extreme prematurity strongly favors ROP over isolated PFV.

PFV vs FEVR

FEVR favors:

• Bilateral peripheral avascular retina
• Family history
• Variable asymmetry
• Exudation or neovascularization

PFV favors:

• Unilateral microphthalmia
• Persistent hyaloid stalk
• Retrolental membrane
• Ciliary process traction

Treatment Principles

Treatment depends on:

• Severity
• Anterior vs posterior involvement
• Retinal status
• Macular anatomy
• Optic nerve development
• Visual potential
• Risk of progressive complications

Management ranges from:

• Observation
• Amblyopia treatment
• Anterior segment surgery
• Vitreoretinal surgery

Observation

Observation is reasonable for:

• Mild PFV
• Clear visual axis
• Stable retinal anatomy
• Minimal traction

It may also be appropriate for very severe disease with:

• Minimal visual potential
• Comfortable eye
• No progressive glaucoma or retinal complication

Surgical Indications

Surgery may be considered for:

• Visually significant cataract
• Visual-axis obstruction
• Progressive retrolental fibrosis
• Lens displacement
• Progressive retinal traction
• Retinal detachment
• Recurrent vitreous hemorrhage
• Secondary angle closure or glaucoma

Goals of Surgery

The aims are to:

• Clear the visual axis
• Release anterior-posterior traction
• Preserve retinal attachment
• Maintain a comfortable globe
• Maximize visual rehabilitation

Surgery should be individualized rather than performed solely because PFV is present.

Anterior PFV Surgery

Potential procedures include:

• Lensectomy
• Membranectomy
• Anterior vitrectomy

The retrolental tissue may remain vascular, so surgery can be complicated by:

Significant intraoperative hemorrhage

Posterior and Combined PFV Surgery

More severe cases may require:

• Vitrectomy
• Transection of the fibrovascular stalk
• Membrane dissection
• Retinal reattachment procedures

These operations can be technically difficult because of:

• Abnormal retinal anatomy
• Dysplastic retina
• Adherent fibrovascular tissue
• Bleeding risk

Lens-Sparing Vitrectomy

If the lens remains clear and posterior traction can be approached safely:

Lens-sparing vitrectomy

may be considered.

Preserving the lens can reduce:

• Aphakic anisometropia
• Optical rehabilitation burden
• Amblyopia

Aphakia Management

After infantile lensectomy, visual rehabilitation may require:

• Contact lens
• Aphakic spectacles
• Later IOL implantation in selected patients

Primary IOL implantation is individualized according to:

• Age
• Globe size
• Capsular support
• Anterior segment anatomy

Amblyopia

Even anatomically successful surgery may yield poor vision if amblyopia is not treated.

Management may include:

• Optimal refractive correction
• Contact lens correction
• Spectacles
• Patching of the better-seeing eye
• Atropine penalization in selected cases

Strabismus

Strabismus is common because of:

• Structural visual impairment
• Anisometropia
• Amblyopia

Surgery may later be performed for:

• Alignment
• Cosmesis
• Functional binocular goals when possible

Glaucoma

Secondary glaucoma can result from:

• Shallow anterior chamber
• Lens enlargement or displacement
• Angle abnormalities
• Postsurgical changes

Regular IOP surveillance is important.

Vitreous Hemorrhage

Persistent vascular tissue may bleed, causing:

• Recurrent vitreous hemorrhage
• Further visual deprivation

Persistent or severe hemorrhage may become an indication for vitrectomy.

Retinal Detachment

Tractional retinal detachment may:

• Remain stable
• Progress over time

Surgery is considered according to:

• Macular status
• Visual potential
• Severity of dysplasia
• Likelihood of anatomical success

Severe End-Stage Disease

Some eyes have such profound:

• Retinal dysplasia
• Optic nerve abnormalities
• Total detachment

that meaningful visual improvement is unlikely.

Management may then focus on:

• Comfort
• Globe preservation
• Cosmetic outcome

Enucleation is now uncommon unless:

• Eye becomes blind and painful
• Severe complications arise
• Malignancy cannot be excluded

Protective Eyewear

Children with profound unilateral visual impairment should use:

Impact-resistant protective spectacles

to protect the better-seeing eye.

Genetic Counseling

Genetic counseling is appropriate when there is:

• Bilateral disease
• Family history
• Associated developmental abnormalities
• Suspected NDP/FEVR-related disease

Follow-Up

All patients require ongoing ophthalmic follow-up.

Monitor:

• Visual acuity
• Refraction
• Amblyopia
• Strabismus
• Cataract
• Retinal traction
• Retinal detachment
• Vitreous hemorrhage
• IOP
• Globe growth

Prognosis

Visual prognosis is highly variable and depends more on:

Posterior segment anatomy

than on the anterior appearance alone.

Favorable Prognostic Features

Include:

• Isolated anterior PFV
• Attached retina
• Preserved macula
• Normal or near-normal optic nerve
• Early visual-axis clearance
• Successful amblyopia therapy

Poor Prognostic Features

Include:

• Combined PFV
• Optic nerve hypoplasia
• Macular dysplasia
• Retinal fold involving fixation
• Total retinal detachment
• Severe retinal dysplasia
• Long-standing visual deprivation

Anterior PFV Prognosis

Anterior PFV generally has the:

Best visual potential

particularly when the retina and optic nerve are relatively normal.

Posterior / Combined PFV Prognosis

These forms generally have worse visual outcomes because of:

• Retinal dysplasia
• Macular traction
• Optic nerve abnormalities
• Retinal detachment

Nevertheless, selected patients can achieve useful functional vision with modern surgery and aggressive amblyopia treatment.

Complications

Potential complications include:

• Cataract
• Corneal clouding
• Lens subluxation
• Angle closure
• Secondary glaucoma
• Recurrent vitreous hemorrhage
• Retinal traction
• Retinal detachment
• Amblyopia
• Strabismus
• Phthisis bulbi
• Permanent visual loss

Ophthalmology Pearls

• Persistent fetal vasculature is the preferred term; PHPV is an older, narrower term.
• PFV results from failure of regression of the fetal hyaloid vascular system and primary vitreous.
• The classic case is unilateral leukocoria in a microphthalmic infant.
• Classic anterior findings include microcornea, cataract, retrolental fibrovascular membrane, and elongated ciliary processes.
• Classic posterior findings include a fibrovascular stalk from the optic disc to the posterior lens, retinal folds, traction, and retinal detachment.
• Mittendorf dot and Bergmeister papilla are minor remnants of the same fetal vascular system and may occur without severe PFV.
• The most important diagnosis to exclude is retinoblastoma.
• Intraocular calcification strongly favors retinoblastoma, although absence of calcification does not completely rule it out.
• B-scan ultrasound and MRI are generally preferred to CT in infants.
• Bilateral PFV-like disease should prompt consideration of Norrie disease, FEVR, ROP, or another inherited retinal dysplasia.
• Surgical treatment aims to clear the visual axis and release traction, not simply remove the visible membrane.
• Posterior retinal and optic nerve abnormalities are the major determinants of final visual prognosis.
• Amblyopia can limit vision even after technically excellent surgery, making early optical rehabilitation essential.
• Children with severe unilateral loss should receive protective eyewear for the better-seeing eye.