Ophthalmology – Periocular Infantile Hemangioma

Basics

Description

Infantile hemangioma (IH) is the preferred term for the lesion historically called:

• Capillary hemangioma
• Strawberry hemangioma
• Strawberry nevus

It is a benign vascular tumor of infancy characterized by:

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

Periocular IH may involve:

• Eyelid skin
• Subcutaneous tissues
• Orbit
• Conjunctiva
• Combination of superficial and deep tissues

The major ophthalmic concern is:

Amblyopia during the critical period of visual development.

Classification

Infantile hemangiomas are commonly classified as:

• Superficial
• Deep
• Combined

They may also be:

• Focal/localized
• Segmental
• Multifocal

Segmental facial lesions are particularly important because of their association with:

PHACE syndrome

Superficial Infantile Hemangioma

Typically appears as:

• Bright red
• Lobulated
• Raised
• Compressible

The classic appearance is often described as:

“Strawberry” hemangioma

Deep Infantile Hemangioma

Deep lesions involve:

• Subcutaneous tissue
• Orbit

They often appear:

• Bluish-purple
• Poorly defined externally
• Soft and compressible

Deep orbital lesions may cause:

• Proptosis
• Globe displacement
• Ptosis
• Astigmatism
• Strabismus

Epidemiology

Infantile hemangioma is the:

Most common benign vascular tumor of infancy

It occurs more frequently in:

• Girls
• Premature infants
• Low-birth-weight infants
• Multiple gestations

Periocular lesions represent a smaller subset of all infantile hemangiomas.

Risk Factors

Reported risk factors include:

• Prematurity
• Low birth weight
• Female sex
• Multiple gestation
• Advanced maternal age
• Placental abnormalities or procedures in some studies

Most cases are:

Sporadic

Pathophysiology

Infantile hemangioma is a true vascular tumor rather than a vascular malformation.

It demonstrates:

• Endothelial cell proliferation
• Increased angiogenic signaling
• Characteristic involution with maturation

Unlike vascular malformations, IH has a:

Proliferative phase followed by spontaneous regression.

Placental Hypothesis

Infantile hemangioma and placental microvasculature share several markers, leading to hypotheses involving:

• Placental-like endothelial cells
• Embolized placental cells
• Shared developmental pathways

However, a direct placental “metastasis” mechanism has not been definitively established.

Pathology

Histology demonstrates:

• Lobular proliferation of capillary-sized vessels
• Benign endothelial cells
• Closely packed vascular channels

A characteristic immunohistochemical marker is:

GLUT1 positivity

GLUT1 is useful in distinguishing infantile hemangioma from many vascular malformations.

Natural History

Most infantile hemangiomas are:

• Absent or subtle at birth
• Apparent within the first several weeks of life

Growth is most rapid during:

The first few months of life

Most proliferative growth occurs by approximately:

5 months of age

although deeper lesions may continue enlarging somewhat longer.

Involution

After the proliferative phase:

• Growth stabilizes
• Involution begins gradually

Regression occurs over:

Several years

Residual changes may include:

• Telangiectatic vessels
• Fibrofatty tissue
• Skin redundancy
• Pigmentary change
• Scarring after ulceration

Ophthalmic Importance

Periocular IH is particularly important because it can interfere with visual development.

Major visual complications include:

• Amblyopia
• Astigmatism
• Anisometropia
• Visual-axis occlusion
• Ptosis
• Strabismus

Amblyopia

Amblyopia may be:

Deprivation Amblyopia

From:

• Ptosis
• Eyelid mass blocking the pupil

Anisometropic / Astigmatic Amblyopia

From mechanical pressure on the globe causing:

• Corneal astigmatism
• Refractive asymmetry

Strabismic Amblyopia

From:

• Globe displacement
• Extraocular muscle involvement

Astigmatism

Mechanical pressure from an upper-eyelid or orbital lesion may deform the cornea and induce:

• Astigmatism
• Anisometropia

This may persist even after the hemangioma involutes.

Therefore:

Cycloplegic refraction is essential in periocular IH.

Strabismus

Strabismus may develop from:

• Globe displacement
• Motility restriction
• Visual deprivation
• Anisometropia

Proptosis

Deep orbital hemangiomas may cause:

• Axial or nonaxial proptosis
• Exposure keratopathy
• Optic nerve compression in severe cases

Clinical History

Parents often report:

• Small pink or red mark appearing shortly after birth
• Rapid enlargement over weeks
• Progressive eyelid swelling
• Partial occlusion of the eye

Deep lesions may present primarily with:

• Proptosis
• Bluish eyelid swelling

Examination

A complete pediatric ophthalmic examination should assess:

• Fixation behavior
• Age-appropriate visual acuity
• Pupils
• Ocular alignment
• Motility
• Degree of ptosis
• Pupillary occlusion
• Proptosis
• Corneal exposure
• Cycloplegic refraction
• Dilated fundus examination

Typical Lesion Appearance

Superficial lesions:

• Bright red
• Raised
• Lobulated
• Blanch partially with pressure

Deep lesions:

• Blue-purple
• Subcutaneous
• Compressible

Lesions may become more prominent with:

• Crying
• Dependent positioning
• Valsalva-like maneuvers

PHACE Syndrome

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

PHACE syndrome

The acronym refers to:

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

An S is often added for:

• Sternal defects
• Supraumbilical raphe

PHACE – Ocular Associations

Possible ocular abnormalities include:

• Microphthalmia
• Optic nerve hypoplasia
• Morning glory disc anomaly
• Peripapillary staphyloma
• Retinal vascular abnormalities
• Strabismus
• Congenital cataract
• Glaucoma
• Cranial nerve abnormalities

When to Consider PHACE Evaluation

Consider PHACE evaluation particularly in infants with:

Large segmental hemangioma of the face or scalp

Evaluation may include:

• MRI/MRA of brain and neck
• Cardiac examination
• Echocardiography
• Ophthalmic examination

Important Correction – Kasabach-Merritt Phenomenon

Kasabach-Merritt phenomenon is not associated with ordinary infantile hemangioma.

It is classically associated with:

• Kaposiform hemangioendothelioma
• Tufted angioma

and consists of:

• Severe thrombocytopenia
• Consumptive coagulopathy
• Platelet trapping

A child with an apparent “hemangioma” plus profound thrombocytopenia should therefore prompt reconsideration of the diagnosis.

Airway Hemangioma

Some infants with extensive facial or segmental hemangiomas may have:

• Subglottic
• Airway

hemangiomas.

Risk is especially associated with a:

Beard-distribution hemangioma

involving the:

• Chin
• Lower lip
• Mandibular region
• Anterior neck

Symptoms such as:

• Stridor
• Hoarse cry
• Respiratory distress

require urgent airway evaluation.

High-Output Cardiac Failure

Large or multifocal visceral hemangiomas, especially hepatic lesions, can rarely produce:

• High-output cardiac failure

through extensive vascular shunting.

Imaging

Most superficial periocular IH can be diagnosed clinically.

Imaging is useful when there is:

• Deep orbital involvement
• Proptosis
• Atypical presentation
• Diagnostic uncertainty
• Concern for PHACE
• Concern for another orbital mass

MRI

MRI with contrast is preferred for defining:

• Orbital extent
• Relationship to optic nerve
• Extraocular muscles
• Intracranial structures

Typical proliferative-phase findings include:

• Well-defined or lobulated lesion
• T1 iso- to hypointensity
• T2 hyperintensity
• Strong homogeneous enhancement
• Flow voids reflecting vascular channels

Ultrasound

Ultrasound with Doppler may demonstrate:

• Solid vascular mass
• High vascular density
• Increased internal blood flow

It can be useful when MRI is unnecessary or unavailable.

CT

CT can demonstrate:

• Enhancing soft-tissue mass
• Orbital extent

but is generally avoided when MRI or ultrasound can provide the needed information because of:

Ionizing radiation in infants.

Biopsy

Biopsy is rarely required in a classic infantile hemangioma.

Consider biopsy if:

• Clinical course is atypical
• Imaging is atypical
• Tumor does not behave like IH
• Malignancy is suspected

Differential Diagnosis

Important differentials include:

• Capillary malformation / port-wine stain
• Venous malformation
• Lymphatic/venolymphatic malformation
• Rhabdomyosarcoma
• Neuroblastoma
• Dermoid cyst
• Orbital teratoma
• Other vascular tumors

Infantile Hemangioma vs Port-Wine Stain

Infantile Hemangioma

• Usually appears after birth
• Proliferates rapidly
• Raised or mass-forming
• Eventually involutes

Port-Wine Stain

• Present at birth
• Flat
• Grows proportionately with child
• Does not spontaneously involute
• May occur in V1 distribution in Sturge-Weber syndrome

Infantile Hemangioma vs Vascular Malformation

Infantile Hemangioma

• Endothelial proliferation
• Rapid postnatal growth
• Spontaneous involution
• GLUT1 positive

Vascular Malformation

• Present from birth, though sometimes clinically occult
• Grows proportionately
• No proliferative/involution cycle
• Endothelial turnover usually normal

Rhabdomyosarcoma

Consider when there is:

• Rapidly progressive proptosis
• Orbital mass in an older infant or child
• No characteristic cutaneous hemangioma
• Atypical imaging

Unlike IH, rhabdomyosarcoma does not follow the classic:

Proliferation → involution

pattern.

Treatment Principles

Not every periocular infantile hemangioma requires treatment.

Observation is appropriate when the lesion:

• Does not obstruct the visual axis
• Does not induce significant astigmatism
• Does not cause strabismus
• Does not cause proptosis or optic nerve compromise
• Does not threaten skin integrity

Indications for Treatment

Treat when there is significant risk of:

• Amblyopia
• Visual-axis obstruction
• Progressive astigmatism
• Anisometropia
• Strabismus
• Exposure keratopathy
• Optic neuropathy
• Significant disfigurement
• Ulceration
• Airway compromise
• Other serious systemic involvement

First-Line Therapy – Oral Propranolol

Oral propranolol is the modern first-line systemic treatment for problematic infantile hemangioma.

It has largely replaced systemic corticosteroids.

Mechanisms of Propranolol

Proposed mechanisms include:

• Vasoconstriction
• Reduced VEGF signaling
• Reduced angiogenesis
• Induction of endothelial apoptosis

Clinical improvement can begin rapidly.

Propranolol Dosing

A commonly used target is approximately:

2–3 mg/kg/day

divided into:

• Twice-daily
• Occasionally three-times-daily dosing

according to formulation and protocol.

Treatment is individualized by:

• Pediatrics
• Dermatology
• Ophthalmology

Before Starting Propranolol

Assess:

• Cardiac history
• Heart rate
• Blood pressure
• Respiratory history
• Feeding pattern
• Risk of hypoglycemia

ECG or cardiology assessment is particularly appropriate when there is:

• Abnormal cardiac examination
• Bradycardia
• Arrhythmia history
• Relevant family cardiac history

Routine echocardiography is not required for every uncomplicated infant.

Propranolol Adverse Effects

Potential adverse effects include:

• Hypoglycemia
• Bradycardia
• Hypotension
• Bronchospasm
• Sleep disturbance
• Cold extremities

Preventing Hypoglycemia

Important parental instructions include:

• Give propranolol with or shortly after feeding
• Maintain regular feeding schedules
• Hold doses during prolonged fasting
• Hold treatment during significant vomiting or poor oral intake

Young infants are particularly vulnerable to:

Propranolol-associated hypoglycemia

PHACE and Propranolol

Propranolol is not absolutely contraindicated in PHACE.

However, severe cerebrovascular arterial abnormalities may theoretically increase ischemic risk if:

• Blood pressure falls abruptly

Therefore children with suspected PHACE may require:

• MRI/MRA
• Cardiac assessment
• Slow dose escalation
• Multidisciplinary management

Duration of Propranolol Therapy

Therapy often continues through much of the proliferative period, commonly until approximately:

• 12 months of age
• Sometimes longer for deep or recurrent lesions

Stopping too early can result in:

Rebound growth

Tapering practices vary.

Topical Timolol

Topical timolol may be useful for:

• Small
• Thin
• Superficial

infantile hemangiomas.

It is not adequate for:

• Large lesions
• Deep orbital lesions
• Vision-threatening bulky disease

Timolol Safety

Although topical, systemic absorption can occur.

Potential effects include:

• Bradycardia
• Hypotension
• Bronchospasm

Use particular caution in:

• Premature infants
• Large treatment surfaces
• Ulcerated skin

Corticosteroids

Systemic or intralesional corticosteroids were historically first-line therapy.

They are now generally reserved for:

• Propranolol contraindication
• Propranolol failure
• Selected refractory cases

Steroid Adverse Effects

Systemic corticosteroids may cause:

• Growth suppression
• Cushingoid appearance
• Hypertension
• Irritability
• Sleep disturbance
• Infection risk
• Adrenal suppression

Intralesional Steroids

Intralesional steroid injection is now used much less commonly.

Serious complications include:

• Central retinal artery occlusion
• Skin depigmentation
• Fat atrophy
• Necrosis
• Hemorrhage

Because of these risks, injection near the orbit requires great caution.

Laser Therapy

Laser is not usually first-line for a deep periocular hemangioma.

It may be helpful for:

• Residual superficial telangiectasia
• Selected ulcerated superficial lesions
• Residual cutaneous changes after involution

Pulsed-dye laser is generally preferred for superficial vascular skin changes.

Surgery

Surgical excision may be considered for:

• Well-localized lesions
• Persistent visual-axis obstruction
• Residual fibrofatty deformity
• Refractory disease
• Diagnostic uncertainty

Large diffuse orbital lesions are less amenable to complete excision.

Surgical Risks

Potential risks include:

• Significant bleeding
• Scarring
• Damage to orbital structures
• Eyelid deformity

Amblyopia Treatment

Hemangioma treatment alone is not enough if amblyopia has already developed.

Management may include:

• Cycloplegic refraction
• Spectacle correction
• Patching of the better eye
• Atropine penalization in selected cases

Follow-Up

Vision-threatening periocular IH requires frequent ophthalmic follow-up during infancy.

Monitor:

• Fixation and visual acuity
• Pupillary occlusion
• Cycloplegic refraction
• Astigmatism
• Anisometropia
• Strabismus
• Proptosis
• Corneal exposure
• Response to treatment

Frequency of Follow-Up

Young infants with significant lesions may require examination every:

Several weeks to a few months

depending on:

• Age
• Rate of growth
• Amblyopia risk
• Treatment response

Prognosis

Most infantile hemangiomas eventually undergo substantial:

Spontaneous involution

Overall prognosis is excellent when visual complications are identified early.

Visual outcome depends more on:

• Prevention of amblyopia
• Timely refractive correction
• Maintenance of a clear visual axis

than on the cosmetic size of the lesion alone.

Residual Changes

After involution, some children may retain:

• Telangiectasia
• Fibrofatty tissue
• Skin redundancy
• Pigment change
• Scarring

These may be addressed later with:

• Laser
• Plastic/oculoplastic surgery

if necessary.

Complications

Important complications include:

• Amblyopia
• Astigmatism
• Anisometropia
• Strabismus
• Ptosis
• Visual-axis obstruction
• Proptosis
• Exposure keratopathy
• Rare compressive optic neuropathy
• Ulceration
• Cutaneous scarring
• Residual deformity

Ophthalmology Pearls

• Infantile hemangioma is a benign vascular tumor, not a vascular malformation or simple hamartoma.
• It is usually absent or subtle at birth, then undergoes rapid proliferation during the first several months of life followed by gradual involution.
• The classic superficial lesion is a bright-red “strawberry” hemangioma; deep lesions may be bluish and cause proptosis.
• The most important ophthalmic complication is amblyopia, especially from ptosis, visual-axis occlusion, astigmatism, anisometropia, or strabismus.
• Perform cycloplegic refraction even when the visual axis appears relatively clear because induced astigmatism may be substantial.
• Oral propranolol is first-line systemic therapy for vision-threatening or otherwise problematic periocular IH.
• Give propranolol with feeds and withhold during significant fasting, vomiting, or poor intake to reduce hypoglycemia risk.
• Topical timolol is most useful for small, thin superficial lesions, not deep orbital disease.
• Large segmental facial hemangiomas should prompt consideration of PHACE syndrome.
• Kasabach-Merritt phenomenon is not a complication of ordinary infantile hemangioma; think kaposiform hemangioendothelioma or tufted angioma.
• Infantile hemangiomas are characteristically GLUT1 positive.
• Surgery and corticosteroids now have more selective roles because beta-blocker therapy has transformed management.

Classification Infantile hemangiomas are commonly classified as:  Superficial Deep Combined  They may also be:  Focal/localized Segmental Multifocal  Segmental facial lesions are particularly important because of their association with: PHACE syndrome

Superficial Infantile Hemangioma Typically appears as:  Bright red Lobulated Raised Compressible  The classic appearance is often described as: “Strawberry” hemangioma

Deep Infantile Hemangioma Deep lesions involve:  Subcutaneous tissue Orbit  They often appear:  Bluish-purple Poorly defined externally Soft and compressible  Deep orbital lesions may cause:  Proptosis Globe displacement Ptosis Astigmatism Strabismus

Epidemiology Infantile hemangioma is the: Most common benign vascular tumor of infancy It occurs more frequently in:  Girls Premature infants Low-birth-weight infants Multiple gestations  Periocular lesions represent a smaller subset of all infantile hemangiomas.

Risk Factors Reported risk factors include:  Prematurity Low birth weight Female sex Multiple gestation Advanced maternal age Placental abnormalities or procedures in some studies  Most cases are: Sporadic

Pathophysiology Infantile hemangioma is a true vascular tumor rather than a vascular malformation. It demonstrates:  Endothelial cell proliferation Increased angiogenic signaling Characteristic involution with maturation  Unlike vascular malformations, IH has a: Proliferative phase followed by spontaneous regression.

Placental Hypothesis Infantile hemangioma and placental microvasculature share several markers, leading to hypotheses involving:  Placental-like endothelial cells Embolized placental cells Shared developmental pathways  However, a direct placental “metastasis” mechanism has not been definitively established.

Pathology Histology demonstrates:  Lobular proliferation of capillary-sized vessels Benign endothelial cells Closely packed vascular channels  A characteristic immunohistochemical marker is: GLUT1 positivity GLUT1 is useful in distinguishing infantile hemangioma from many vascular malformations.

Natural History Most infantile hemangiomas are:  Absent or subtle at birth Apparent within the first several weeks of life  Growth is most rapid during: The first few months of life Most proliferative growth occurs by approximately: 5 months of age although deeper lesions may continue enlarging somewhat longer.

Involution After the proliferative phase:  Growth stabilizes Involution begins gradually  Regression occurs over: Several years Residual changes may include:  Telangiectatic vessels Fibrofatty tissue Skin redundancy Pigmentary change Scarring after ulceration

Ophthalmic Importance Periocular IH is particularly important because it can interfere with visual development. Major visual complications include:  Amblyopia Astigmatism Anisometropia Visual-axis occlusion Ptosis Strabismus

Amblyopia Amblyopia may be: Deprivation Amblyopia From:  Ptosis Eyelid mass blocking the pupil  Anisometropic / Astigmatic Amblyopia From mechanical pressure on the globe causing:  Corneal astigmatism Refractive asymmetry  Strabismic Amblyopia From:  Globe displacement Extraocular muscle involvement

Astigmatism Mechanical pressure from an upper-eyelid or orbital lesion may deform the cornea and induce:  Astigmatism Anisometropia  This may persist even after the hemangioma involutes. Therefore: Cycloplegic refraction is essential in periocular IH.

Strabismus Strabismus may develop from:  Globe displacement Motility restriction Visual deprivation Anisometropia

Proptosis Deep orbital hemangiomas may cause:  Axial or nonaxial proptosis Exposure keratopathy Optic nerve compression in severe cases

Clinical History Parents often report:  Small pink or red mark appearing shortly after birth Rapid enlargement over weeks Progressive eyelid swelling Partial occlusion of the eye  Deep lesions may present primarily with:  Proptosis Bluish eyelid swelling

Examination A complete pediatric ophthalmic examination should assess:  Fixation behavior Age-appropriate visual acuity Pupils Ocular alignment Motility Degree of ptosis Pupillary occlusion Proptosis Corneal exposure Cycloplegic refraction Dilated fundus examination

Typical Lesion Appearance Superficial lesions:  Bright red Raised Lobulated Blanch partially with pressure  Deep lesions:  Blue-purple Subcutaneous Compressible  Lesions may become more prominent with:  Crying Dependent positioning Valsalva-like maneuvers

PHACE Syndrome Large segmental facial hemangiomas, particularly involving the upper face, may be associated with: PHACE syndrome The acronym refers to:  Posterior fossa abnormalities Hemangioma Arterial cerebrovascular anomalies Cardiac abnormalities / coarctation Eye abnormalities  An S is often added for:  Sternal defects Supraumbilical raphe

PHACE – Ocular Associations Possible ocular abnormalities include:  Microphthalmia Optic nerve hypoplasia Morning glory disc anomaly Peripapillary staphyloma Retinal vascular abnormalities Strabismus Congenital cataract Glaucoma Cranial nerve abnormalities

When to Consider PHACE Evaluation Consider PHACE evaluation particularly in infants with: Large segmental hemangioma of the face or scalp Evaluation may include:  MRI/MRA of brain and neck Cardiac examination Echocardiography Ophthalmic examination

Important Correction – Kasabach-Merritt Phenomenon Kasabach-Merritt phenomenon is not associated with ordinary infantile hemangioma. It is classically associated with:  Kaposiform hemangioendothelioma Tufted angioma  and consists of:  Severe thrombocytopenia Consumptive coagulopathy Platelet trapping  A child with an apparent “hemangioma” plus profound thrombocytopenia should therefore prompt reconsideration of the diagnosis.

Airway Hemangioma Some infants with extensive facial or segmental hemangiomas may have:  Subglottic Airway  hemangiomas. Risk is especially associated with a: Beard-distribution hemangioma involving the:  Chin Lower lip Mandibular region Anterior neck  Symptoms such as:  Stridor Hoarse cry Respiratory distress  require urgent airway evaluation.

High-Output Cardiac Failure Large or multifocal visceral hemangiomas, especially hepatic lesions, can rarely produce:  High-output cardiac failure  through extensive vascular shunting.

Imaging Most superficial periocular IH can be diagnosed clinically. Imaging is useful when there is:  Deep orbital involvement Proptosis Atypical presentation Diagnostic uncertainty Concern for PHACE Concern for another orbital mass

MRI MRI with contrast is preferred for defining:  Orbital extent Relationship to optic nerve Extraocular muscles Intracranial structures  Typical proliferative-phase findings include:  Well-defined or lobulated lesion T1 iso- to hypointensity T2 hyperintensity Strong homogeneous enhancement Flow voids reflecting vascular channels

Ultrasound Ultrasound with Doppler may demonstrate:  Solid vascular mass High vascular density Increased internal blood flow  It can be useful when MRI is unnecessary or unavailable.

CT CT can demonstrate:  Enhancing soft-tissue mass Orbital extent  but is generally avoided when MRI or ultrasound can provide the needed information because of: Ionizing radiation in infants.

Biopsy Biopsy is rarely required in a classic infantile hemangioma. Consider biopsy if:  Clinical course is atypical Imaging is atypical Tumor does not behave like IH Malignancy is suspected

Differential Diagnosis Important differentials include:  Capillary malformation / port-wine stain Venous malformation Lymphatic/venolymphatic malformation Rhabdomyosarcoma Neuroblastoma Dermoid cyst Orbital teratoma Other vascular tumors

Infantile Hemangioma vs Port-Wine Stain Infantile Hemangioma  Usually appears after birth Proliferates rapidly Raised or mass-forming Eventually involutes  Port-Wine Stain  Present at birth Flat Grows proportionately with child Does not spontaneously involute May occur in V1 distribution in Sturge-Weber syndrome

Infantile Hemangioma vs Vascular Malformation Infantile Hemangioma  Endothelial proliferation Rapid postnatal growth Spontaneous involution GLUT1 positive  Vascular Malformation  Present from birth, though sometimes clinically occult Grows proportionately No proliferative/involution cycle Endothelial turnover usually normal

Rhabdomyosarcoma Consider when there is:  Rapidly progressive proptosis Orbital mass in an older infant or child No characteristic cutaneous hemangioma Atypical imaging  Unlike IH, rhabdomyosarcoma does not follow the classic: Proliferation → involution pattern.

Treatment Principles Not every periocular infantile hemangioma requires treatment. Observation is appropriate when the lesion:  Does not obstruct the visual axis Does not induce significant astigmatism Does not cause strabismus Does not cause proptosis or optic nerve compromise Does not threaten skin integrity

Indications for Treatment Treat when there is significant risk of:  Amblyopia Visual-axis obstruction Progressive astigmatism Anisometropia Strabismus Exposure keratopathy Optic neuropathy Significant disfigurement Ulceration Airway compromise Other serious systemic involvement

First-Line Therapy – Oral Propranolol Oral propranolol is the modern first-line systemic treatment for problematic infantile hemangioma. It has largely replaced systemic corticosteroids.

Mechanisms of Propranolol Proposed mechanisms include:  Vasoconstriction Reduced VEGF signaling Reduced angiogenesis Induction of endothelial apoptosis  Clinical improvement can begin rapidly.

Propranolol Dosing A commonly used target is approximately: 2–3 mg/kg/day divided into:  Twice-daily Occasionally three-times-daily dosing  according to formulation and protocol. Treatment is individualized by:  Pediatrics Dermatology Ophthalmology

Before Starting Propranolol Assess:  Cardiac history Heart rate Blood pressure Respiratory history Feeding pattern Risk of hypoglycemia  ECG or cardiology assessment is particularly appropriate when there is:  Abnormal cardiac examination Bradycardia Arrhythmia history Relevant family cardiac history  Routine echocardiography is not required for every uncomplicated infant.

Propranolol Adverse Effects Potential adverse effects include:  Hypoglycemia Bradycardia Hypotension Bronchospasm Sleep disturbance Cold extremities

Preventing Hypoglycemia Important parental instructions include:  Give propranolol with or shortly after feeding Maintain regular feeding schedules Hold doses during prolonged fasting Hold treatment during significant vomiting or poor oral intake  Young infants are particularly vulnerable to: Propranolol-associated hypoglycemia

PHACE and Propranolol Propranolol is not absolutely contraindicated in PHACE. However, severe cerebrovascular arterial abnormalities may theoretically increase ischemic risk if:  Blood pressure falls abruptly  Therefore children with suspected PHACE may require:  MRI/MRA Cardiac assessment Slow dose escalation Multidisciplinary management

Duration of Propranolol Therapy Therapy often continues through much of the proliferative period, commonly until approximately:  12 months of age Sometimes longer for deep or recurrent lesions  Stopping too early can result in: Rebound growth Tapering practices vary.

Topical Timolol Topical timolol may be useful for:  Small Thin Superficial  infantile hemangiomas. It is not adequate for:  Large lesions Deep orbital lesions Vision-threatening bulky disease

Timolol Safety Although topical, systemic absorption can occur. Potential effects include:  Bradycardia Hypotension Bronchospasm  Use particular caution in:  Premature infants Large treatment surfaces Ulcerated skin

Corticosteroids Systemic or intralesional corticosteroids were historically first-line therapy. They are now generally reserved for:  Propranolol contraindication Propranolol failure Selected refractory cases

Steroid Adverse Effects Systemic corticosteroids may cause:  Growth suppression Cushingoid appearance Hypertension Irritability Sleep disturbance Infection risk Adrenal suppression

Intralesional Steroids Intralesional steroid injection is now used much less commonly. Serious complications include:  Central retinal artery occlusion Skin depigmentation Fat atrophy Necrosis Hemorrhage  Because of these risks, injection near the orbit requires great caution.

Laser Therapy Laser is not usually first-line for a deep periocular hemangioma. It may be helpful for:  Residual superficial telangiectasia Selected ulcerated superficial lesions Residual cutaneous changes after involution  Pulsed-dye laser is generally preferred for superficial vascular skin changes.

Surgery Surgical excision may be considered for:  Well-localized lesions Persistent visual-axis obstruction Residual fibrofatty deformity Refractory disease Diagnostic uncertainty  Large diffuse orbital lesions are less amenable to complete excision.

Surgical Risks Potential risks include:  Significant bleeding Scarring Damage to orbital structures Eyelid deformity

Amblyopia Treatment Hemangioma treatment alone is not enough if amblyopia has already developed. Management may include:  Cycloplegic refraction Spectacle correction Patching of the better eye Atropine penalization in selected cases

Follow-Up Vision-threatening periocular IH requires frequent ophthalmic follow-up during infancy. Monitor:  Fixation and visual acuity Pupillary occlusion Cycloplegic refraction Astigmatism Anisometropia Strabismus Proptosis Corneal exposure Response to treatment

Frequency of Follow-Up Young infants with significant lesions may require examination every: Several weeks to a few months depending on:  Age Rate of growth Amblyopia risk Treatment response

Prognosis Most infantile hemangiomas eventually undergo substantial: Spontaneous involution Overall prognosis is excellent when visual complications are identified early. Visual outcome depends more on:  Prevention of amblyopia Timely refractive correction Maintenance of a clear visual axis  than on the cosmetic size of the lesion alone.

Residual Changes After involution, some children may retain:  Telangiectasia Fibrofatty tissue Skin redundancy Pigment change Scarring  These may be addressed later with:  Laser Plastic/oculoplastic surgery  if necessary.

Complications Important complications include:  Amblyopia Astigmatism Anisometropia Strabismus Ptosis Visual-axis obstruction Proptosis Exposure keratopathy Rare compressive optic neuropathy Ulceration Cutaneous scarring Residual deformity

Ophthalmology Pearls  Infantile hemangioma is a benign vascular tumor, not a vascular malformation or simple hamartoma. It is usually absent or subtle at birth, then undergoes rapid proliferation during the first several months of life followed by gradual involution. The classic superficial lesion is a bright-red “strawberry” hemangioma; deep lesions may be bluish and cause proptosis. The most important ophthalmic complication is amblyopia, especially from ptosis, visual-axis occlusion, astigmatism, anisometropia, or strabismus. Perform cycloplegic refraction even when the visual axis appears relatively clear because induced astigmatism may be substantial. Oral propranolol is first-line systemic therapy for vision-threatening or otherwise problematic periocular IH. Give propranolol with feeds and withhold during significant fasting, vomiting, or poor intake to reduce hypoglycemia risk. Topical timolol is most useful for small, thin superficial lesions, not deep orbital disease. Large segmental facial hemangiomas should prompt consideration of PHACE syndrome. Kasabach-Merritt phenomenon is not a complication of ordinary infantile hemangioma; think kaposiform hemangioendothelioma or tufted angioma. Infantile hemangiomas are characteristically GLUT1 positive. Surgery and corticosteroids now have more selective roles because beta-blocker therapy has transformed management.