Ophthalmology – Orbital Vascular Tumors and Malformations

Basics

Description

Orbital vascular lesions comprise a heterogeneous group of vascular tumors and vascular malformations involving the orbit, eyelids, and periocular tissues.

Modern terminology separates true vascular tumors from developmental vascular malformations.

Important orbital vascular lesions include:

• Infantile hemangioma
• Cavernous venous malformation — historically “cavernous hemangioma”
• Distensible venous malformation — historically “orbital varix”
• Lymphatic malformation
• Venolymphatic malformation
• Arteriovenous malformation (AVM)
• Solitary fibrous tumor (SFT) — historically including many lesions called hemangiopericytoma

This modern nomenclature is preferable because these lesions differ substantially in:

• Natural history
• Blood flow
• Imaging
• Treatment

Hemodynamic Classification

Orbital vascular malformations can also be considered according to flow characteristics.

No or Minimal Flow

• Lymphatic malformation

Low-Flow

• Venous malformation
• Venolymphatic malformation
• Cavernous venous malformation

High-Flow

• Arteriovenous malformation
• Arteriovenous fistula

Flow characteristics are important when planning:

• Imaging
• Embolization
• Sclerotherapy
• Surgery

Epidemiology

Vascular lesions represent an important proportion of orbital masses.

The typical age of presentation differs by lesion:

• Infantile hemangioma → infancy
• Lymphatic/venolymphatic malformation → childhood
• Distensible venous malformation → childhood to young adulthood
• Cavernous venous malformation → middle adulthood
• Solitary fibrous tumor → usually adulthood
• AVM → variable, often childhood or young adulthood but may present later

Infantile Hemangioma

Description

Infantile hemangioma is a benign vascular tumor of infancy characterized by:

1. Rapid postnatal proliferation
2. Plateau phase
3. Gradual spontaneous involution

It may involve:

• Eyelid
• Anterior orbit
• Deep orbit
• Combined superficial and deep tissues

Natural History of Infantile Hemangioma

Infantile hemangiomas are usually:

• Absent or subtle at birth
• Apparent within the first few weeks of life
• Rapidly proliferative during early infancy

Most growth occurs during approximately the first:

5–6 months of life

followed by stabilization and gradual involution over subsequent years.

Clinical Appearance

Superficial lesions classically appear:

• Bright red
• Lobulated
• “Strawberry-like”

Deep lesions may appear:

• Bluish
• Subcutaneous
• Poorly defined externally

Deep orbital lesions can produce:

• Proptosis
• Globe displacement
• Ptosis

Ophthalmic Importance of Infantile Hemangioma

Periocular hemangiomas may threaten vision through:

• Astigmatism
• Anisometropia
• Occlusion of visual axis
• Ptosis
• Strabismus
• Optic nerve compression in rare extensive lesions

The major pediatric concern is:

Amblyopia

Early refractive assessment is therefore essential.

PHACE Syndrome

Large segmental facial infantile hemangiomas, particularly involving the upper face, may be associated with:

PHACE syndrome

which includes:

• Posterior fossa abnormalities
• Hemangioma
• Arterial cerebrovascular anomalies
• Cardiac abnormalities/coarctation
• Eye abnormalities

Selected infants require:

• MRI/MRA
• Cardiac evaluation
• Multidisciplinary assessment

before systemic beta-blocker therapy.

Kasabach-Merritt Phenomenon

An important correction:

Kasabach-Merritt phenomenon is not a typical complication of ordinary infantile hemangioma.

It is classically associated with:

• Kaposiform hemangioendothelioma
• Tufted angioma

and involves:

• Severe thrombocytopenia
• Consumptive coagulopathy
• Platelet trapping

Pathology of Infantile Hemangioma

Histologically there is:

• Proliferation of capillary-sized vascular channels
• Benign endothelial cells

Infantile hemangiomas characteristically express:

GLUT1

This helps distinguish them from many vascular malformations.

Treatment of Infantile Hemangioma

Observation is appropriate when the lesion:

• Does not threaten vision
• Does not obstruct visual axis
• Does not induce significant astigmatism
• Does not cause major cosmetic or functional deformity

Propranolol

For vision-threatening or otherwise problematic infantile hemangioma:

Oral propranolol is the modern first-line systemic therapy.

It has largely replaced systemic corticosteroids.

It is especially useful for:

• Visual-axis obstruction
• Significant astigmatism
• Large periocular lesions
• Disfiguring lesions
• Rapid proliferation

Propranolol Safety

Before and during treatment consider:

• Cardiac history
• Heart rate
• Blood pressure
• Feeding status
• Risk of hypoglycemia
• Pulmonary disease

Important adverse effects include:

• Bradycardia
• Hypotension
• Bronchospasm
• Hypoglycemia
• Sleep disturbance

Infants should generally receive doses in association with regular feeding.

Topical Timolol

Topical beta-blocker therapy may be useful for:

• Small
• Superficial
• Thin infantile hemangiomas

It is less effective for large deep orbital lesions.

Corticosteroids

Systemic or intralesional corticosteroids are now used much less frequently because propranolol is usually more effective and better tolerated.

They may still have a role in selected patients when beta-blockers are:

• Contraindicated
• Ineffective

Other Hemangioma Treatments

Rarely considered options include:

• Laser therapy for selected superficial residual lesions
• Surgical excision
• Other systemic agents for highly refractory disease

Surgery is usually reserved for:

• Residual deformity
• Well-localized lesions
• Failure of medical treatment
• Diagnostic uncertainty

Cavernous Venous Malformation

Modern Terminology

The lesion historically called:

Cavernous hemangioma of the orbit

is now more appropriately termed:

Cavernous venous malformation (CVM)

It is not a true proliferative hemangioma.

Epidemiology

CVM is one of the most common benign orbital masses in adults.

Typical patient:

• Middle-aged adult
• Female predominance in many series

Clinical Presentation

Usually presents with:

Slowly progressive, painless unilateral proptosis

Other findings may include:

• Globe displacement
• Diplopia
• Optic nerve compression
• Choroidal folds
• Hyperopic shift

Sudden painful enlargement is unusual unless hemorrhage or thrombosis occurs.

Location

Most CVMs are:

Intraconal

often lateral to the optic nerve.

Because they are well circumscribed, they usually displace rather than infiltrate surrounding orbital structures.

Imaging of Cavernous Venous Malformation

CT

Typically demonstrates:

• Round or ovoid mass
• Well-circumscribed margins
• Intraconal location
• Homogeneous or progressively increasing enhancement

MRI

Usually shows:

• T1 iso- to hypointensity
• T2 hyperintensity
• Strong enhancement

A characteristic feature is:

Progressive contrast fill-in on delayed imaging

because of slow blood flow.

Treatment of Cavernous Venous Malformation

Observation is reasonable when:

• Small
• Asymptomatic
• Stable
• Not threatening the optic nerve

Surgical excision is considered for:

• Progressive proptosis
• Visual decline
• Optic nerve compression
• Diplopia
• Significant cosmetic deformity

Because most lesions are encapsulated, complete excision is often possible.

Distensible Venous Malformation / Orbital Varix

Description

An orbital varix is better understood as a:

Distensible venous malformation

consisting of abnormal thin-walled orbital veins that enlarge when venous pressure rises.

Clinical Presentation

Classic presentation:

Intermittent positional proptosis

which worsens with:

• Valsalva
• Coughing
• Straining
• Bending forward
• Jugular compression

The proptosis may disappear when the patient is upright and relaxed.

Complications of Venous Malformations

Potential complications include:

• Thrombosis
• Orbital hemorrhage
• Pain
• Acute proptosis
• Optic nerve compression

Long-standing lesions may cause:

• Orbital bone remodeling

Imaging of Venous Malformation

Dynamic imaging may be required.

CT or MRI can be performed with:

• Valsalva
• Dependent positioning

The lesion may be inconspicuous at rest and enlarge dramatically with venous pressure.

Imaging may demonstrate:

• Dilated venous channels
• Phleboliths
• Thrombosis

Treatment of Venous Malformation

Observation is appropriate for mild disease.

Intervention may be considered for:

• Visual compromise
• Recurrent thrombosis
• Pain
• Significant disfigurement
• Repeated hemorrhage

Options include:

• Surgical excision
• Sclerotherapy
• Endovascular approaches in selected anatomy

Management should be individualized because uncontrolled bleeding can occur.

Lymphatic Malformation

Modern Terminology

The lesion historically called:

Orbital lymphangioma

is now termed:

Lymphatic malformation

or, when both venous and lymphatic components are present:

Venolymphatic malformation

Pathophysiology

These are congenital developmental vascular malformations rather than true tumors.

They may cross normal anatomic boundaries because they are:

• Unencapsulated
• Multiloculated
• Infiltrative

They can involve:

• Eyelid
• Conjunctiva
• Orbit
• Face
• Intracranial regions

Clinical Presentation

Lesions may be present at birth but remain unnoticed until childhood.

They may suddenly enlarge following:

• Upper respiratory infection
• Hemorrhage
• Trauma

Acute Hemorrhage

Intralesional hemorrhage may produce:

• Sudden painful proptosis
• Eyelid swelling
• Motility restriction
• Optic nerve compression

Blood-filled cysts are sometimes called:

“Chocolate cysts”

Imaging of Lymphatic Malformation

MRI is particularly useful.

Typical features include:

• Multiloculated cystic lesion
• Irregular trans-spatial extension
• Minimal internal flow
• Fluid-fluid levels after hemorrhage

Different fluid levels reflect blood products of different ages.

Treatment of Lymphatic / Venolymphatic Malformation

Observation is appropriate if:

• Vision is unaffected
• Proptosis is mild
• There is no significant deformity

Treatment may be required for:

• Optic neuropathy
• Severe proptosis
• Exposure keratopathy
• Recurrent hemorrhage
• Significant disfigurement

Sclerotherapy

Image-guided sclerotherapy is now an important first-line intervention for many macrocystic lesions.

Agents may include, depending on specialist practice:

• Doxycycline
• Bleomycin
• Sodium tetradecyl sulfate
• Other sclerosants

Treatment is usually performed by an experienced:

• Interventional radiologist
• Orbital surgeon
• Multidisciplinary vascular anomalies team

Surgery for Lymphatic Malformation

Complete surgical excision is often difficult because lesions:

• Lack a capsule
• Infiltrate normal orbital tissues
• Cross anatomic compartments

Surgery may therefore involve:

• Debulking
• Removal of accessible cysts
• Treatment of vision-threatening components

Sirolimus

Systemic sirolimus may be useful in selected extensive or refractory venolymphatic malformations, particularly when lesions are:

• Multifocal
• Infiltrative
• Difficult to treat surgically

This usually requires specialist vascular-anomalies management.

Arteriovenous Malformation

Description

An orbital AVM consists of abnormal direct connections between:

• Arteries
• Veins

without an intervening normal capillary bed.

It is a:

High-flow vascular malformation

Clinical Findings

Possible features include:

• Pulsatile proptosis
• Periorbital swelling
• Conjunctival vascular dilation
• Bruit
• Thrill
• Orbital pain
• Elevated IOP
• Optic neuropathy

Some lesions enlarge during:

• Puberty
• Pregnancy
• Trauma

Imaging of AVM

Evaluation may include:

• CTA
• MRA
• Doppler imaging

However, definitive vascular characterization often requires:

Digital subtraction angiography

which identifies:

• Feeding arteries
• Nidus
• Draining veins

Treatment of AVM

Management usually requires a multidisciplinary neurovascular team.

Options include:

• Endovascular embolization
• Surgical excision after embolization
• Combined staged therapy

Simple surgical excision without vascular planning can result in catastrophic hemorrhage.

Solitary Fibrous Tumor

Modern Classification

Many lesions historically diagnosed as:

Hemangiopericytoma

are now classified within the spectrum of:

Solitary fibrous tumor (SFT)

Pathogenesis

SFTs characteristically demonstrate:

NAB2–STAT6 gene fusion

and strong nuclear:

STAT6 immunoreactivity

Clinical Presentation

Usually occurs in adults and presents with:

• Slowly progressive proptosis
• Globe displacement
• Diplopia
• Occasionally pain

These tumors are often:

• Well circumscribed
• Highly vascular

Imaging of Solitary Fibrous Tumor

CT or MRI may show:

• Well-defined lobulated mass
• Strong contrast enhancement
• Flow voids from vascularity

Some lesions may show:

• Infiltrative margins
• Bone remodeling

Pathology of Solitary Fibrous Tumor

Classic microscopic features include:

• Patternless spindle-cell architecture
• Collagenous stroma
• Branching “staghorn” vessels

Immunohistochemistry commonly shows:

• CD34
• Nuclear STAT6

Treatment of Solitary Fibrous Tumor

Primary treatment is:

Complete surgical excision

with negative margins when possible.

Radiotherapy may be considered for selected:

• Incompletely resected
• Recurrent
• Aggressive

tumors.

Prognosis of Solitary Fibrous Tumor

Most orbital SFTs behave indolently, but some can:

• Recur
• Invade locally
• Metastasize

Incomplete excision increases recurrence risk.

Importantly:

Incomplete excision does not itself cause malignant transformation.

Long-term surveillance is necessary because late recurrence may occur.

Associated Syndromes

PHACE

Associated with large segmental:

Infantile hemangiomas

Wyburn-Mason Syndrome

Associated with:

Retinal and intracranial arteriovenous malformations

and may involve orbital vascular abnormalities.

Blue Rubber Bleb Nevus Syndrome

Associated with multiple:

Venous malformations

especially involving:

• Skin
• Gastrointestinal tract

Orbital involvement is uncommon but possible.

Diagnosis

A complete orbital assessment should include:

• Visual acuity
• Pupils
• Color vision
• Visual fields when appropriate
• IOP
• Refraction in children
• Proptosis measurement
• Motility
• Globe displacement
• Slit-lamp examination
• Dilated fundus examination

Fundus Findings

Orbital vascular lesions may produce:

• Choroidal folds
• Optic disc edema
• Optic atrophy
• Venous congestion

depending on mass effect and vascular physiology.

Visual Complications

Visual loss may result from:

• Amblyopia
• Induced astigmatism
• Exposure keratopathy
• Optic nerve compression
• Elevated IOP
• Retinal or choroidal folds
• Orbital hemorrhage

Imaging Principles

MRI

Best for:

• Soft-tissue characterization
• Lymphatic/venolymphatic lesions
• Intracranial extension
• Optic nerve relationship

CT

Best for:

• Bone
• Phleboliths
• Calcification
• Acute hemorrhage in selected cases

Dynamic Imaging

Useful for:

• Distensible venous malformation

Angiography

Particularly important for:

• AVM
• Other high-flow lesions

Biopsy

Biopsy is generally not required for vascular malformations with characteristic imaging.

Avoid unnecessary needle biopsy of suspected high-flow vascular lesions because of:

Hemorrhage risk

Biopsy or excision is appropriate when:

• Diagnosis remains uncertain
• A true neoplasm is suspected
• Malignancy must be excluded

Differential Diagnosis

Important orbital mimics include:

• Thyroid eye disease
• Idiopathic orbital inflammation
• Optic nerve sheath meningioma
• Optic pathway glioma
• Rhabdomyosarcoma
• Lymphoma
• Metastatic tumor
• Dermoid cyst
• Lacrimal gland tumor
• Orbital cellulitis

Treatment Principles

Treatment is determined by:

• Lesion type
• Flow characteristics
• Age
• Visual threat
• Growth
• Cosmetic impact
• Surgical accessibility

Many lesions can be observed if they are:

• Stable
• Asymptomatic
• Not threatening vision

Indications for Treatment

Intervention is particularly appropriate when there is:

• Optic neuropathy
• Amblyopia risk
• Visual-axis obstruction
• Severe astigmatism
• Exposure keratopathy
• Significant proptosis
• Recurrent hemorrhage
• Pain
• Major cosmetic deformity

Follow-Up

Monitoring depends on lesion type.

Assess serially for:

• Visual acuity
• Amblyopia
• Refraction
• Proptosis
• Motility
• Optic nerve function
• Lesion growth
• Recurrent hemorrhage

Imaging is repeated when:

• Clinical findings change
• Growth is suspected
• Treatment response is being assessed

Prognosis

Prognosis varies markedly by lesion.

Infantile hemangioma

Usually excellent, especially when amblyopia is prevented.

Cavernous venous malformation

Excellent after complete excision when treatment is required.

Lymphatic/venolymphatic malformation

Often chronic and recurrent because of infiltrative anatomy.

Venous malformation

Usually benign but may cause recurrent positional symptoms, thrombosis, or hemorrhage.

AVM

Potentially serious because of high-flow vascular physiology and hemorrhage risk.

Solitary fibrous tumor

Usually favorable after complete excision, but requires long-term surveillance.

Complications

Potential complications include:

• Amblyopia
• Astigmatism
• Strabismus
• Ptosis
• Exposure keratopathy
• Optic neuropathy
• Visual field loss
• Elevated IOP
• Hemorrhage
• Thrombosis
• Recurrent proptosis
• Treatment-related bleeding
• Recurrence

Ophthalmology Pearls

• Modern terminology separates vascular tumors from vascular malformations.
• Infantile hemangioma is a true vascular tumor; propranolol is now the major first-line systemic treatment for vision-threatening lesions.
• The main ophthalmic danger from periocular infantile hemangioma is amblyopia from visual-axis obstruction or induced astigmatism.
• Kasabach-Merritt phenomenon is not typical of infantile hemangioma; think kaposiform hemangioendothelioma or tufted angioma.
• “Cavernous hemangioma” is better termed cavernous venous malformation and classically causes slowly progressive painless intraconal proptosis in adults.
• “Orbital varix” is a distensible venous malformation; proptosis characteristically increases with Valsalva or bending forward.
• “Lymphangioma” is better termed lymphatic or venolymphatic malformation.
• Fluid-fluid levels on MRI are classic for hemorrhage within lymphatic/venolymphatic malformations.
• Sclerotherapy is now an important treatment for many macrocystic lymphatic malformations; extensive refractory disease may sometimes require sirolimus.
• AVMs are high-flow lesions and often require angiography plus embolization before surgical treatment.
• “Hemangiopericytoma” of the orbit has largely been reclassified as solitary fibrous tumor, characterized by STAT6 nuclear positivity/NAB2–STAT6 fusion.
• Avoid biopsy of a suspected high-flow orbital vascular lesion without appropriate vascular imaging because of potentially severe hemorrhage.