Ophthalmology – Peripheral Corneal Ulcers / Peripheral Ulcerative Keratitis

Basics

Description

Peripheral ulcerative keratitis (PUK) is a potentially vision- and globe-threatening inflammatory disorder characterized by:

• Peripheral corneal epithelial defect
• Stromal inflammation
• Progressive stromal thinning or “melting”

It occurs within the peripheral cornea adjacent to the limbus, where the cornea is exposed to:

• Limbal blood vessels
• Immune complexes
• Complement
• Inflammatory cells

PUK may be:

• Immune-mediated
• Infectious
• Postoperative or post-traumatic

The most clinically important form is immune-mediated PUK associated with systemic vasculitis.

Clinical Importance

PUK can progress rapidly to:

• Severe stromal thinning
• Descemetocele
• Corneal perforation
• Permanent visual loss

When associated with systemic vasculitis, it may also signal:

Potentially life-threatening systemic disease

Therefore severe or progressive PUK requires urgent:

• Corneal evaluation
• Infectious exclusion
• Systemic investigation
• Rheumatologic collaboration

Peripheral Cornea and Immunology

The peripheral cornea is particularly susceptible to immune injury because of its proximity to the:

Limbal vascular arcade

Immune complexes and inflammatory mediators can enter the peripheral cornea and activate:

• Complement
• Neutrophils
• Macrophages
• Matrix metalloproteinases

leading to:

Collagen degradation and stromal melt

Etiology

Immune-Mediated

Important causes include:

• Rheumatoid arthritis
• Granulomatosis with polyangiitis (GPA)
• Polyarteritis nodosa
• Systemic lupus erythematosus
• Relapsing polychondritis
• Inflammatory bowel disease
• Other systemic vasculitides

Rheumatoid Arthritis

RA is one of the most common systemic associations.

PUK often occurs in patients with:

• Long-standing
• Seropositive
• Severe systemic disease

However:

Ocular severity does not necessarily parallel joint activity.

A patient with apparently quiet arthritis may still develop severe corneal vasculitis.

Granulomatosis With Polyangiitis

Formerly called:

Wegener granulomatosis

GPA-associated PUK may occur with:

• Necrotizing scleritis
• Orbital inflammation
• Pulmonary disease
• Renal disease

This combination should be treated as a systemic vasculitic emergency.

Infectious Peripheral Ulceration

Infectious keratitis must always be excluded.

Potential organisms include:

Bacterial

• Staphylococcus
• Streptococcus
• Pseudomonas
• Moraxella
• Neisseria gonorrhoeae

Fungal

• Fusarium
• Aspergillus
• Candida
• Other fungi depending on exposure

Viral

• Herpes simplex
• Herpes zoster

Important Principle

Do not assume that a peripheral ulcer in a patient with rheumatoid arthritis is sterile.

Immune-mediated patients may simultaneously develop:

• Bacterial keratitis
• HSV keratitis
• Fungal infection

particularly if they are immunosuppressed.

Risk Factors

Important risk factors include:

• Rheumatoid arthritis
• Systemic vasculitis
• Autoimmune disease
• Previous ocular surgery
• Trauma
• Severe dry eye
• Exposure keratopathy
• Lagophthalmos
• Immunosuppression
• Contact lens use
• Ocular surface disease

Postoperative PUK

PUK may occur after ocular surgery, including:

• Cataract surgery
• Corneal surgery
• Scleral surgery

In predisposed patients, surgery may trigger:

Aberrant immune activation against corneal antigens

Pathophysiology

Immune-mediated disease involves:

1. Immune complex deposition around limbal vessels
2. Complement activation
3. Recruitment of inflammatory cells
4. Release of proteases and collagenases
5. Stromal collagen destruction
6. Progressive corneal thinning

Matrix metalloproteinases contribute substantially to:

Corneal melting

Association With Scleritis

PUK may occur with:

Necrotizing anterior scleritis

This strongly suggests:

• Severe systemic autoimmune disease
• Systemic vasculitis

and generally requires aggressive systemic immunosuppression.

History

Patients commonly present with:

• Red eye
• Severe pain
• Photophobia
• Tearing
• Foreign-body sensation
• Reduced vision

Pain may be particularly severe when:

Scleritis accompanies PUK

Systemic History

Ask about:

• Rheumatoid arthritis
• Sinus disease
• Hemoptysis
• Cough
• Dyspnea
• Hematuria
• Renal disease
• Skin rash
• Joint pain
• Oral ulcers
• Neurologic symptoms

These may indicate systemic vasculitis.

Infectious History

Ask about:

• Trauma
• Vegetable matter injury
• Contact lens use
• Recent ocular surgery
• Lagophthalmos
• Hospitalization
• Immunosuppression
• Previous HSV or HZO

Physical Examination

Typical PUK demonstrates:

• Peripheral epithelial defect
• Adjacent stromal infiltrate
• Stromal thinning
• Limbal inflammation

The lesion may extend:

• Circumferentially
• Centrally

Corneal Melt

Progressive stromal destruction may produce:

• Marked thinning
• Descemetocele
• Microperforation
• Frank perforation

The central edge may appear:

• Undermined
• Steep
• Actively melting

Corneal Epithelial Defect

True PUK generally has an:

Overlying epithelial defect

If the epithelium remains intact, consider alternative diagnoses such as:

• Marginal keratitis
• Peripheral stromal inflammation

rather than classic ulcerative keratitis.

Associated Scleritis

Look carefully for:

• Deep scleral injection
• Violaceous hue
• Severe tenderness
• Areas of scleral necrosis

Necrotizing scleritis with PUK is particularly concerning for systemic vasculitis.

Infectious Keratitis Findings

Features suggesting infection include:

• Dense focal stromal infiltrate
• Purulent discharge
• Significant anterior chamber reaction
• Hypopyon
• Rapid progression
• Satellite lesions in fungal disease
• Contact lens or trauma history

Herpetic Peripheral Keratitis

HSV or HZO may produce:

• Peripheral epithelial disease
• Stromal infiltrates
• Corneal thinning
• Reduced corneal sensation

However, corneal hypoesthesia may not always be obvious.

Herpetic disease must be excluded before escalating immunosuppression.

Gonococcal Keratitis

Neisseria gonorrhoeae can penetrate intact corneal epithelium and cause:

• Rapid stromal destruction
• Hyperpurulent discharge
• Perforation

This is an ophthalmic emergency requiring:

Immediate systemic and topical antimicrobial treatment

Diagnostic Approach

The main diagnostic questions are:

1. Is this infectious or sterile?
2. Is there associated scleritis?
3. Is there underlying systemic vasculitis?
4. Is the cornea at risk of perforation?

Corneal Scraping

Perform corneal scraping when there is:

• Epithelial defect with infiltrate
• Significant suppuration
• Rapid progression
• Atypical appearance
• Immunosuppression
• Concern for bacterial or fungal infection

Tests may include:

• Gram stain
• Culture
• Fungal stain/culture

HSV Testing

HSV PCR may be useful when:

• Clinical suspicion is high
• Presentation is atypical
• Diagnosis remains uncertain

It is not routinely required for classic cases.

Systemic Laboratory Evaluation

In unexplained or suspected immune-mediated PUK, consider:

• CBC
• ESR
• CRP
• Renal function
• Urinalysis

Autoimmune testing may include:

• Rheumatoid factor
• Anti-CCP antibodies
• ANCA
• PR3-ANCA
• MPO-ANCA
• ANA
• Complement levels when indicated

Infectious Screening Before Immunosuppression

Depending on context and planned therapy, consider:

• Syphilis serology
• Tuberculosis screening
• Hepatitis B
• Hepatitis C
• HIV

especially before major systemic immunosuppression or biologic therapy.

Urinalysis

Urinalysis is particularly important when GPA is suspected.

Look for:

• Hematuria
• Proteinuria
• Cellular casts

which may indicate:

Glomerulonephritis

Chest Imaging

Chest radiography or CT may be appropriate when there is concern for:

• GPA
• Sarcoidosis
• Tuberculosis
• Systemic vasculitis

Biopsy

Systemic tissue biopsy may occasionally be required to establish:

• GPA
• Other vasculitic disease

Potential sites include:

• Kidney
• Lung
• Upper respiratory tract

depending on clinical disease.

Anterior Segment OCT

AS-OCT is useful for documenting:

• Location of thinning
• Residual stromal thickness
• Progression
• Response to treatment

It is particularly helpful in severe or impending perforation.

Differential Diagnosis

Important differentials include:

• Infectious keratitis
• Marginal keratitis
• Mooren ulcer
• Terrien marginal degeneration
• Pellucid marginal degeneration
• Dellen
• Neurotrophic keratopathy
• Exposure keratopathy
• HSV/HZO keratitis

Mooren Ulcer

Mooren ulcer is a painful progressive peripheral ulcerative keratitis occurring:

• Without associated scleritis
• Without identifiable systemic vasculitic disease
• After infectious and systemic causes have been excluded

It is therefore largely a:

Diagnosis of exclusion

Mooren Ulcer Features

Typical findings include:

• Severe pain
• Peripheral crescentic ulcer
• Undermined central edge
• Circumferential progression
• Later central progression

Scleral involvement argues against classic Mooren ulcer.

Marginal Keratitis

Staphylococcal marginal keratitis usually shows:

• Peripheral infiltrates
• Clear interval between infiltrate and limbus
• Associated blepharitis

It is generally less destructive than PUK.

Terrien Marginal Degeneration

Terrien degeneration is usually:

• Painless
• Noninflammatory
• Slowly progressive

with:

• Peripheral thinning
• Lipid deposition
• Intact epithelium

This contrasts with painful inflammatory PUK.

Treatment Principles

Management has three simultaneous goals:

1. Exclude and treat infection
2. Suppress destructive inflammation
3. Preserve globe integrity

Immune-Mediated PUK

Severe immune-mediated PUK generally requires:

Systemic immunosuppression

Topical treatment alone is insufficient.

Systemic Corticosteroids

High-dose systemic corticosteroids may be used for rapid control of severe inflammation.

However:

Steroids are usually a bridge rather than definitive long-term therapy

because steroid-sparing immunosuppression is often required.

Immunosuppressive Therapy

Treatment depends on the underlying systemic disorder.

Agents may include:

• Methotrexate
• Mycophenolate mofetil
• Azathioprine
• Cyclophosphamide
• Rituximab

GPA-Associated PUK

Severe GPA-related ocular disease may require induction therapy with:

• Rituximab
• Cyclophosphamide

usually combined initially with systemic corticosteroids.

Management should be coordinated urgently with:

Rheumatology

Rheumatoid Arthritis-Associated PUK

Systemic treatment may involve:

• Methotrexate
• Mycophenolate
• Biologic therapy
• Rituximab
• Other disease-modifying agents

depending on systemic disease and severity.

Biologic Therapy

Refractory disease may respond to biologic agents such as:

• Rituximab
• Anti-TNF therapy in selected conditions

Choice depends on:

• Underlying systemic disease
• Previous treatment
• Infectious risk

Topical Corticosteroids

Topical corticosteroids require caution.

They may reduce inflammation but can also:

• Delay epithelial healing
• Promote collagenolysis
• Worsen undiagnosed infection

Therefore:

Do not use topical steroids indiscriminately in an actively melting peripheral ulcer.

They may be considered after infection is excluded and systemic inflammation is being appropriately treated.

Topical Lubrication

Use aggressive ocular-surface support with:

• Preservative-free artificial tears
• Lubricating ointment

Treat associated:

• Dry eye
• Exposure
• Blepharitis

Oral Doxycycline

Doxycycline may be used as an adjunct because it inhibits:

Matrix metalloproteinases

and may reduce corneal collagenolysis.

It is not being used primarily for its antimicrobial effect in sterile PUK.

Vitamin C

Oral vitamin C may be used as an adjunct because it supports:

• Collagen synthesis
• Stromal healing

It is supportive rather than definitive therapy.

Infectious Bacterial Ulcer

Treatment may include:

• Intensive topical fluoroquinolone
• Fortified antibiotics for severe disease

Choice depends on:

• Size
• Depth
• Location
• Gram stain
• Culture

Fungal Keratitis

Treatment depends on organism.

Common options include:

• Natamycin for filamentous fungi
• Amphotericin B for selected yeasts
• Voriconazole in selected cases

Treatment should be culture-guided when possible.

Herpetic Disease

HSV or HZO may require:

• Systemic antiviral therapy
• Topical antiviral therapy in appropriate epithelial HSV disease

Topical steroids should only be used in selected stromal disease under:

Antiviral cover

Corneal Perforation

Impending or actual perforation is an emergency.

Treatment depends on:

• Size
• Location
• Activity of inflammation
• Presence of infection

Cyanoacrylate Tissue Adhesive

For small focal perforations, cyanoacrylate glue may provide:

Temporary tectonic support

often with a bandage contact lens placed over the glue.

Bandage Contact Lens

A bandage lens may help protect:

• Tissue adhesive
• Small epithelial defects

However, caution is required in active infection because contact lenses may increase microbial risk.

Lamellar Keratoplasty

Peripheral lamellar or patch grafting may be required for:

• Severe thinning
• Larger peripheral perforation
• Failure of tissue adhesive

Penetrating Keratoplasty

Full-thickness grafting may be required for:

• Large perforation
• Central involvement
• Extensive structural failure

Outcomes are poorer when surgery is performed during:

Active uncontrolled inflammation

so systemic disease control remains critical.

Conjunctival Resection

Adjacent conjunctival resection was historically used to reduce delivery of:

• Inflammatory cells
• Immune complexes

to the peripheral cornea.

It now has a much more limited role because modern systemic immunosuppression and other therapies are generally preferred.

Tarsorrhaphy

Partial tarsorrhaphy may be useful when significant:

• Lagophthalmos
• Exposure keratopathy

contributes to peripheral thinning.

Dry Eye Management

Treat aggressively with:

• Preservative-free lubrication
• Ointment
• Punctal occlusion in selected patients
• Moisture protection
• Eyelid closure procedures when needed

Follow-Up

Active PUK may require examination:

Daily or every few days

depending on severity.

Monitor:

• Epithelial defect size
• Stromal thinning
• Infiltrate
• Anterior chamber inflammation
• Scleritis
• Signs of impending perforation

Rheumatologic Follow-Up

Immune-mediated disease requires close co-management with:

• Rheumatology
• Internal medicine

because controlling systemic vasculitis may:

• Preserve the eye
• Reduce systemic morbidity
• Improve survival

Prognosis

Prognosis depends on:

• Cause
• Speed of diagnosis
• Degree of stromal thinning
• Scleral involvement
• Infection
• Systemic disease control

Early aggressive therapy can preserve:

• Globe integrity
• Useful vision

Visual Loss

Vision may be reduced by:

• Corneal scarring
• Irregular astigmatism
• Central extension
• Perforation
• Surgical graft complications

Complications

Major complications include:

• Corneal melt
• Descemetocele
• Corneal perforation
• Severe scarring
• Irregular astigmatism
• Secondary infection
• Recurrent ulceration
• Necrotizing scleritis
• Permanent visual loss

Ophthalmology Pearls

• PUK is a peripheral corneal epithelial defect with stromal inflammation and progressive thinning.
• Always distinguish infectious keratitis from immune-mediated PUK before escalating corticosteroids or systemic immunosuppression.
• The strongest systemic associations include rheumatoid arthritis and granulomatosis with polyangiitis.
• PUK plus necrotizing scleritis should raise major concern for severe systemic vasculitis.
• Ocular PUK may be severe even when the patient’s systemic autoimmune disease appears clinically quiet.
• Urinalysis, renal function, ANCA, RF/anti-CCP, and inflammatory markers are important when systemic vasculitis is suspected.
• True PUK usually has an epithelial defect; peripheral stromal inflammation with intact epithelium should broaden the differential.
• Mooren ulcer is a diagnosis of exclusion and classically lacks associated scleritis or systemic vasculitis.
• Systemic immunosuppression is the cornerstone of treatment for severe autoimmune PUK; topical therapy alone is inadequate.
• Rituximab or cyclophosphamide may be required for severe GPA-associated disease.
• Oral doxycycline can be useful as an adjunct because of its anti-collagenase/MMP-inhibiting effect.
• Small perforations may be managed temporarily with cyanoacrylate glue, while larger defects may require tectonic keratoplasty.
• Peripheral ulcerative keratitis can be a marker of life-threatening systemic vasculitis, so treatment may improve not only vision but overall survival.

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.

Ophthalmology – Pediculosis Ciliaris (Phthiriasis Palpebrarum)

Basics

Description

Pediculosis ciliaris, also called phthiriasis palpebrarum, is infestation of the:

• Eyelashes
• Eyelid margins
• Occasionally eyebrows

by the pubic or crab louse:

Phthirus pubis

It typically causes:

• Intense eyelid pruritus
• Burning
• Chronic blepharitis
• Conjunctival irritation

Because the lice and nits may be subtle, the condition can be mistaken for ordinary blepharitis.

Synonyms

Terms include:

• Pediculosis ciliaris
• Phthiriasis palpebrarum
• Phthirus pubis infestation
• Pubic lice
• Crab lice

Transmission

P. pubis is most commonly transmitted through:

• Close physical or sexual contact

Eyelash infestation may occur through:

• Hand transfer from another body site
• Close face-to-face contact
• Contaminated bedding or clothing, less commonly

Fomite transmission is possible but generally less important than direct close contact.

Pediatric Considerations

Identification of pubic lice on a child’s eyelashes requires:

Careful safeguarding assessment

because sexual transmission or abuse must be considered.

However, ocular infestation does not by itself prove sexual abuse, since nonsexual transmission can occur.

Evaluation should include:

• Detailed history
• Examination for infestation elsewhere
• Assessment for other injuries or concerning findings
• Consideration of STI testing when appropriate
• Involvement of pediatric safeguarding/child-protection professionals according to local law and clinical circumstances

Epidemiology

Pubic lice occur worldwide.

They can affect:

• Adolescents
• Adults
• Children

There is no important sex predilection.

Ocular infestation is much less common than genital infestation.

Risk Factors

Risk factors include:

• Close contact with an infested individual
• Multiple sexual partners
• Shared bedding or clothing
• Household exposure
• Crowded living conditions

Poor hygiene is not required for infestation and should not be assumed.

Organism

Phthirus pubis is:

• Short
• Broad
• Crab-like
• Approximately 1–2 mm in size

It possesses prominent claws adapted for gripping coarse hair.

Life Cycle

The life cycle includes:

1. Egg / nit
2. Nymph
3. Adult louse

Nits are firmly cemented to hair shafts.

Adult lice feed repeatedly on:

Human blood

and cannot survive for long away from the host.

Pathophysiology

The louse attaches to hair and feeds by piercing the skin.

Symptoms result from:

• Mechanical irritation
• Local inflammatory response
• Hypersensitivity to louse saliva
• Excoriation from scratching

Associated Ocular Disease

Ocular infestation may cause:

• Blepharitis
• Blepharoconjunctivitis
• Follicular conjunctivitis
• Eyelid edema
• Excoriation
• Secondary bacterial infection

History

Typical complaints include:

• Intense eyelid itching
• Burning
• Foreign-body sensation
• Red eye
• Chronic “blepharitis” not responding to routine therapy

Symptoms may be worse:

• At night

Ask about:

• Pruritus elsewhere on the body
• Genital itching
• Household contacts
• Sexual contacts when age-appropriate
• Previous unsuccessful blepharitis treatment

Physical Examination

Slit-lamp examination may directly demonstrate:

• Adult lice
• Nymphs
• Nits

Look carefully at:

• Lash bases
• Lash shafts
• Eyelid skin
• Eyebrows

Appearance of Lice

Adult lice may appear as:

• Brown-gray
• Translucent
• Small mobile bodies

They may be difficult to see because they remain close to the lid margin.

Movement under magnification can confirm the diagnosis.

Appearance of Nits

Nits appear as:

• Small
• Oval
• White-gray or translucent structures

firmly attached to:

Eyelash shafts

Unlike ordinary debris, they cannot be easily brushed away.

Eyelid Findings

Other findings may include:

• Crusting
• Excoriation
• Blood-tinged debris
• Eyelid erythema
• Eyelid edema

Severe infestations may produce significant inflammatory swelling.

Conjunctival Findings

Possible findings include:

• Conjunctival injection
• Follicular conjunctivitis
• Irritation
• Tearing

Maculae Ceruleae

Occasionally, painless:

Blue-gray macules

may occur around affected skin.

These are called:

Maculae ceruleae

and are thought to result from altered blood pigments at louse feeding sites.

Papular Reaction

Small erythematous papules may occur at feeding sites because of:

• Local hypersensitivity
• Inflammation

Lymphadenopathy

Reactive:

• Preauricular
• Submandibular

lymphadenopathy may occasionally occur.

Diagnosis

Diagnosis is usually clinical and made by:

Direct visualization of lice or nits on the eyelashes

under slit-lamp magnification.

Microscopy

Microscopic examination can confirm the organism when diagnosis is uncertain.

Characteristic findings include:

• Broad crab-like body
• Large claws on posterior legs

Differential Diagnosis

Important differentials include:

• Seborrheic blepharitis
• Staphylococcal blepharitis
• Demodex blepharitis
• Allergic blepharitis
• Atopic dermatitis
• Eyelid eczema
• Rosacea
• Viral blepharoconjunctivitis
• Herpes simplex blepharitis
• Eyelid malignancy in persistent unilateral disease

Pediculosis vs Demodex

Phthirus pubis

• Visible lice
• Firmly attached nits
• Intense pruritus
• Blood/debris at lash bases

Demodex

Classically produces:

• Cylindrical dandruff / collarettes at lash bases
• Chronic blepharitis
• No visible crab-like lice or nits

Treatment Principles

Treatment has several goals:

1. Eradicate adult lice.
2. Remove nits.
3. Treat infestation elsewhere on the body.
4. Treat close or sexual contacts when appropriate.
5. Prevent reinfestation.

Mechanical Removal

For eyelash infestation:

Mechanical removal of lice and nits is a key treatment.

Under magnification, lice and nits may be removed with:

• Fine forceps

This can substantially reduce parasite burden immediately.

Ophthalmic Ointment / Petrolatum

A bland occlusive ophthalmic ointment or petrolatum may be applied to:

• Eyelid margins
• Eyelashes

several times daily for approximately:

7–10 days

The purpose is to:

• Immobilize
• Suffocate

lice.

Examples may include:

• Plain petrolatum
• Bland ophthalmic ointment

Antibiotic ointment such as erythromycin may be used if there is significant secondary blepharitis, although the antibiotic itself is not the primary pediculicidal mechanism.

Important Medication Safety

Standard pediculicide shampoos or lotions should not be applied directly to the eye or eyelid margin unless specifically formulated and supervised for ophthalmic use.

Avoid ocular exposure to:

• Permethrin creams/rinses
• Pyrethrin products
• Malathion
• Other insecticidal lotions

because they can cause significant ocular irritation or toxicity.

Treatment of Pubic or Body Infestation

If lice are present at genital or other body sites, treatment may include:

• Permethrin 1%
• Pyrethrins with piperonyl butoxide

according to current pediculosis protocols.

These are applied to:

Nonocular affected hair-bearing areas

and should be kept away from the eyes.

Oral Ivermectin

Oral ivermectin may be considered for:

• Extensive infestation
• Refractory disease
• Treatment failure

A common regimen is approximately:

200–250 µg/kg orally, repeated after 7–14 days

depending on local protocol.

Ivermectin does not reliably kill eggs, which is why repeat dosing is often used.

Pregnancy and Breastfeeding

Medication selection requires additional caution.

In general:

• Mechanical removal
• Local bland ophthalmic ointment

are attractive options for eyelash disease.

Systemic ivermectin is generally avoided during pregnancy unless specifically justified.

Lindane

Lindane is no longer favored and is generally avoided because of:

• Neurotoxicity
• Resistance
• Safer alternatives

It should not be considered routine therapy.

Malathion

Malathion may be effective for pubic lice but:

• Is irritating
• Is flammable
• Must not contact the eyes

It is not a standard eyelash treatment.

Treatment of Contacts

Recent sexual partners should be:

• Informed
• Examined when appropriate
• Treated if infested or according to applicable public-health recommendations

Close household contacts should also be considered if exposure is suspected.

Sexual Activity

Patients should avoid:

• Sexual contact
• Close intimate contact

until:

• They have been treated
• Their relevant partners have been treated

Condoms do not reliably prevent pubic lice transmission because lice infest hair-bearing skin outside the area covered by a condom.

Clothing and Bedding

Clothing, towels, and bedding recently used by the affected person should be:

• Machine washed in hot water
• Dried on a hot cycle

Items that cannot be washed may be:

• Dry-cleaned
• Sealed away from body contact for an appropriate interval

Environmental fumigation is unnecessary.

STI Evaluation

Because pubic lice can be sexually transmitted, adolescents and adults with genital infestation should be assessed for risk of other sexually transmitted infections.

Testing may include, according to individual risk:

• HIV
• Syphilis
• Gonorrhea
• Chlamydia

This should be based on sexual history and local recommendations rather than performed identically in every patient.

Pediatric Safeguarding

In a child with phthiriasis palpebrarum:

• Examine for lice elsewhere
• Assess other household members
• Determine whether plausible nonsexual transmission exists
• Consider sexual abuse and other safeguarding concerns

When concern exists, involve:

• Pediatrician
• Child-protection team
• Appropriate safeguarding authorities

according to local legal requirements.

Follow-Up

Re-examination is generally appropriate after approximately:

1 week

Assess for:

• Persistent live lice
• Newly hatched nymphs
• Remaining nits
• Secondary infection

Repeat treatment may be required.

Treatment Failure

Persistent infestation may result from:

• Inadequate mechanical removal
• Failure to repeat treatment
• Untreated contacts
• Re-exposure
• Incorrect diagnosis
• Resistance to topical pediculicides

Prognosis

Prognosis is:

Excellent

when lice are eradicated and reinfestation is prevented.

Symptoms usually resolve promptly after successful treatment.

Complications

Possible complications include:

• Chronic blepharoconjunctivitis
• Excoriation
• Secondary bacterial infection
• Eyelid edema
• Recurrent infestation

Permanent visual loss is extremely unusual.

Ophthalmology Pearls

• Pediculosis ciliaris = infestation of the eyelashes by Phthirus pubis.
• Think of it in persistent, intensely pruritic blepharitis that does not respond to routine treatment.
• Slit-lamp examination may reveal mobile crab-like lice and firmly attached nits on the lashes.
• Nits are attached to the lash shaft and do not brush away like ordinary debris.
• Mechanical removal with fine forceps plus bland occlusive ophthalmic ointment/petrolatum is a mainstay of eyelash treatment.
• Do not apply standard pediculicide shampoos or lotions directly to the ocular surface.
• Treat any simultaneous pubic or body infestation and address exposed contacts to prevent reinfestation.
• Lindane is no longer routine therapy because safer alternatives exist.
• Consider screening for other STIs when sexual transmission is plausible.
• In children, phthiriasis palpebrarum should prompt careful safeguarding assessment for possible sexual abuse, while recognizing that nonsexual transmission can occur.

Synonyms Terms include:  Pediculosis ciliaris Phthiriasis palpebrarum Phthirus pubis infestation Pubic lice Crab lice

Transmission P. pubis is most commonly transmitted through:  Close physical or sexual contact  Eyelash infestation may occur through:  Hand transfer from another body site Close face-to-face contact Contaminated bedding or clothing, less commonly  Fomite transmission is possible but generally less important than direct close contact.

Pediatric Considerations Identification of pubic lice on a child’s eyelashes requires: Careful safeguarding assessment because sexual transmission or abuse must be considered. However, ocular infestation does not by itself prove sexual abuse, since nonsexual transmission can occur. Evaluation should include:  Detailed history Examination for infestation elsewhere Assessment for other injuries or concerning findings Consideration of STI testing when appropriate Involvement of pediatric safeguarding/child-protection professionals according to local law and clinical circumstances

Epidemiology Pubic lice occur worldwide. They can affect:  Adolescents Adults Children  There is no important sex predilection. Ocular infestation is much less common than genital infestation.

Risk Factors Risk factors include:  Close contact with an infested individual Multiple sexual partners Shared bedding or clothing Household exposure Crowded living conditions  Poor hygiene is not required for infestation and should not be assumed.

Organism Phthirus pubis is:  Short Broad Crab-like Approximately 1–2 mm in size  It possesses prominent claws adapted for gripping coarse hair.

Life Cycle The life cycle includes:  Egg / nit Nymph Adult louse  Nits are firmly cemented to hair shafts. Adult lice feed repeatedly on: Human blood and cannot survive for long away from the host.

Pathophysiology The louse attaches to hair and feeds by piercing the skin. Symptoms result from:  Mechanical irritation Local inflammatory response Hypersensitivity to louse saliva Excoriation from scratching

Associated Ocular Disease Ocular infestation may cause:  Blepharitis Blepharoconjunctivitis Follicular conjunctivitis Eyelid edema Excoriation Secondary bacterial infection

History Typical complaints include:  Intense eyelid itching Burning Foreign-body sensation Red eye Chronic “blepharitis” not responding to routine therapy  Symptoms may be worse:  At night  Ask about:  Pruritus elsewhere on the body Genital itching Household contacts Sexual contacts when age-appropriate Previous unsuccessful blepharitis treatment

Physical Examination Slit-lamp examination may directly demonstrate:  Adult lice Nymphs Nits  Look carefully at:  Lash bases Lash shafts Eyelid skin Eyebrows

Appearance of Lice Adult lice may appear as:  Brown-gray Translucent Small mobile bodies  They may be difficult to see because they remain close to the lid margin. Movement under magnification can confirm the diagnosis.

Appearance of Nits Nits appear as:  Small Oval White-gray or translucent structures  firmly attached to: Eyelash shafts Unlike ordinary debris, they cannot be easily brushed away.

Eyelid Findings Other findings may include:  Crusting Excoriation Blood-tinged debris Eyelid erythema Eyelid edema  Severe infestations may produce significant inflammatory swelling.

Conjunctival Findings Possible findings include:  Conjunctival injection Follicular conjunctivitis Irritation Tearing

Maculae Ceruleae Occasionally, painless: Blue-gray macules may occur around affected skin. These are called: Maculae ceruleae and are thought to result from altered blood pigments at louse feeding sites.

Papular Reaction Small erythematous papules may occur at feeding sites because of:  Local hypersensitivity Inflammation

Lymphadenopathy Reactive:  Preauricular Submandibular  lymphadenopathy may occasionally occur.

Diagnosis Diagnosis is usually clinical and made by: Direct visualization of lice or nits on the eyelashes under slit-lamp magnification.

Microscopy Microscopic examination can confirm the organism when diagnosis is uncertain. Characteristic findings include:  Broad crab-like body Large claws on posterior legs

Differential Diagnosis Important differentials include:  Seborrheic blepharitis Staphylococcal blepharitis Demodex blepharitis Allergic blepharitis Atopic dermatitis Eyelid eczema Rosacea Viral blepharoconjunctivitis Herpes simplex blepharitis Eyelid malignancy in persistent unilateral disease

Pediculosis vs Demodex Phthirus pubis  Visible lice Firmly attached nits Intense pruritus Blood/debris at lash bases  Demodex Classically produces:  Cylindrical dandruff / collarettes at lash bases Chronic blepharitis No visible crab-like lice or nits

Treatment Principles Treatment has several goals:  Eradicate adult lice. Remove nits. Treat infestation elsewhere on the body. Treat close or sexual contacts when appropriate. Prevent reinfestation.

Mechanical Removal For eyelash infestation: Mechanical removal of lice and nits is a key treatment. Under magnification, lice and nits may be removed with:  Fine forceps  This can substantially reduce parasite burden immediately.

Ophthalmic Ointment / Petrolatum A bland occlusive ophthalmic ointment or petrolatum may be applied to:  Eyelid margins Eyelashes  several times daily for approximately: 7–10 days The purpose is to:  Immobilize Suffocate  lice. Examples may include:  Plain petrolatum Bland ophthalmic ointment  Antibiotic ointment such as erythromycin may be used if there is significant secondary blepharitis, although the antibiotic itself is not the primary pediculicidal mechanism.

Important Medication Safety Standard pediculicide shampoos or lotions should not be applied directly to the eye or eyelid margin unless specifically formulated and supervised for ophthalmic use. Avoid ocular exposure to:  Permethrin creams/rinses Pyrethrin products Malathion Other insecticidal lotions  because they can cause significant ocular irritation or toxicity.

Treatment of Pubic or Body Infestation If lice are present at genital or other body sites, treatment may include:  Permethrin 1% Pyrethrins with piperonyl butoxide  according to current pediculosis protocols. These are applied to: Nonocular affected hair-bearing areas and should be kept away from the eyes.

Oral Ivermectin Oral ivermectin may be considered for:  Extensive infestation Refractory disease Treatment failure  A common regimen is approximately: 200–250 µg/kg orally, repeated after 7–14 days depending on local protocol. Ivermectin does not reliably kill eggs, which is why repeat dosing is often used.

Pregnancy and Breastfeeding Medication selection requires additional caution. In general:  Mechanical removal Local bland ophthalmic ointment  are attractive options for eyelash disease. Systemic ivermectin is generally avoided during pregnancy unless specifically justified.

Lindane Lindane is no longer favored and is generally avoided because of:  Neurotoxicity Resistance Safer alternatives  It should not be considered routine therapy.

Malathion Malathion may be effective for pubic lice but:  Is irritating Is flammable Must not contact the eyes  It is not a standard eyelash treatment.

Treatment of Contacts Recent sexual partners should be:  Informed Examined when appropriate Treated if infested or according to applicable public-health recommendations  Close household contacts should also be considered if exposure is suspected.

Sexual Activity Patients should avoid:  Sexual contact Close intimate contact  until:  They have been treated Their relevant partners have been treated  Condoms do not reliably prevent pubic lice transmission because lice infest hair-bearing skin outside the area covered by a condom.

Clothing and Bedding Clothing, towels, and bedding recently used by the affected person should be:  Machine washed in hot water Dried on a hot cycle  Items that cannot be washed may be:  Dry-cleaned Sealed away from body contact for an appropriate interval  Environmental fumigation is unnecessary.

STI Evaluation Because pubic lice can be sexually transmitted, adolescents and adults with genital infestation should be assessed for risk of other sexually transmitted infections. Testing may include, according to individual risk:  HIV Syphilis Gonorrhea Chlamydia  This should be based on sexual history and local recommendations rather than performed identically in every patient.

Pediatric Safeguarding In a child with phthiriasis palpebrarum:  Examine for lice elsewhere Assess other household members Determine whether plausible nonsexual transmission exists Consider sexual abuse and other safeguarding concerns  When concern exists, involve:  Pediatrician Child-protection team Appropriate safeguarding authorities  according to local legal requirements.

Follow-Up Re-examination is generally appropriate after approximately: 1 week Assess for:  Persistent live lice Newly hatched nymphs Remaining nits Secondary infection  Repeat treatment may be required.

Treatment Failure Persistent infestation may result from:  Inadequate mechanical removal Failure to repeat treatment Untreated contacts Re-exposure Incorrect diagnosis Resistance to topical pediculicides

Prognosis Prognosis is: Excellent when lice are eradicated and reinfestation is prevented. Symptoms usually resolve promptly after successful treatment.

Complications Possible complications include:  Chronic blepharoconjunctivitis Excoriation Secondary bacterial infection Eyelid edema Recurrent infestation  Permanent visual loss is extremely unusual.

Ophthalmology Pearls  Pediculosis ciliaris = infestation of the eyelashes by Phthirus pubis. Think of it in persistent, intensely pruritic blepharitis that does not respond to routine treatment. Slit-lamp examination may reveal mobile crab-like lice and firmly attached nits on the lashes. Nits are attached to the lash shaft and do not brush away like ordinary debris. Mechanical removal with fine forceps plus bland occlusive ophthalmic ointment/petrolatum is a mainstay of eyelash treatment. Do not apply standard pediculicide shampoos or lotions directly to the ocular surface. Treat any simultaneous pubic or body infestation and address exposed contacts to prevent reinfestation. Lindane is no longer routine therapy because safer alternatives exist. Consider screening for other STIs when sexual transmission is plausible. In children, phthiriasis palpebrarum should prompt careful safeguarding assessment for possible sexual abuse, while recognizing that nonsexual transmission can occur.

Ophthalmology – Pediatric Optic Nerve Hypoplasia

Basics

Description

Optic nerve hypoplasia (ONH) is a congenital, nonprogressive optic nerve disorder characterized by an abnormally small optic nerve with a reduced number of retinal ganglion cell axons.

It may be:

• Unilateral
• Bilateral
• Symmetric
• Asymmetric

Visual function ranges from:

• Normal or near-normal
• Mild impairment
• Profound visual loss

ONH may occur as an isolated ocular finding or with:

• Midline brain abnormalities
• Pituitary dysfunction
• Developmental abnormalities

Septo-Optic Dysplasia

Septo-optic dysplasia (SOD) traditionally refers to the presence of at least two of the following:

• Optic nerve hypoplasia
• Pituitary hormone dysfunction
• Midline brain abnormality

Midline abnormalities may include:

• Absent septum pellucidum
• Corpus callosum hypoplasia or agenesis

The term de Morsier syndrome is historical.

Importantly:

Absence of the septum pellucidum alone does not predict endocrine dysfunction, and significant endocrinopathy can occur even with otherwise normal MRI findings.

Epidemiology

ONH is among the most common congenital optic nerve abnormalities in children.

Most cases are:

Sporadic

Bilateral involvement is common, but unilateral disease is frequently encountered.

Risk Factors

Most children have no clearly identifiable prenatal cause.

Reported associations include:

• Maternal alcohol exposure
• Young maternal age
• Prematurity
• Abnormal fetal growth
• Maternal diabetes
• Certain prenatal medication or drug exposures

Older literature has reported associations with:

• Some anticonvulsants
• Quinine
• PCP
• LSD

but these associations are not consistently established.

Maternal Diabetes

Maternal diabetes is particularly associated with:

Superior segmental optic nerve hypoplasia

also called:

Topless disc syndrome

This causes:

• Superior disc hypoplasia
• Superior RNFL loss
• Corresponding inferior visual field defect

Genetics

Most ONH is sporadic.

Rare genetic associations include abnormalities involving:

• HESX1
• SOX2
• SOX3
• OTX2
• PAX6
• Other genes involved in forebrain and pituitary development

Genetic evaluation is especially appropriate when there is:

• Bilateral severe ONH
• Syndromic appearance
• Multiple congenital anomalies
• Strong family history
• Pituitary abnormalities

Associated Genetic and Developmental Disorders

ONH may occur with:

• Aniridia
• Albinism
• Midline developmental syndromes
• Pituitary developmental abnormalities
• Cortical migration disorders

Congenital infection and prenatal cerebral injury may also coexist with optic nerve hypoplasia-like appearances.

Pathophysiology

The primary abnormality is:

Reduced number of optic nerve axons

Possible mechanisms include:

• Abnormal retinal ganglion cell differentiation
• Excessive developmental apoptosis
• Abnormal axonal guidance
• Prenatal injury to the developing visual system

The outer retinal layers are generally preserved unless another retinal disorder is present.

Pathology

Histologically there is:

• Reduced retinal ganglion cell population
• Reduced RNFL
• Reduced optic nerve axons
• Small optic nerve caliber

Clinical Presentation

Bilateral ONH

Usually presents early with:

• Poor visual behavior
• Poor fixation
• Nystagmus
• Developmental concerns

Nystagmus often appears during the first few months of life.

Unilateral ONH

May present later with:

• Strabismus
• Amblyopia
• Failed vision screening
• Incidental optic disc abnormality

A child with unilateral ONH may otherwise be systemically normal.

Visual Acuity

Visual function is highly variable.

It may range from:

20/20 to profound visual impairment

A key principle:

Disc appearance correlates poorly with visual function.

A very small optic nerve may retain useful vision, while a mildly hypoplastic nerve may function poorly.

History

Ask about:

• Poor fixation
• Nystagmus
• Strabismus
• Developmental delay
• Seizures
• Abnormal growth
• Hypoglycemia
• Prolonged neonatal jaundice
• Excessive thirst or urination
• Prenatal alcohol or medication exposure
• Maternal diabetes
• Family history of developmental or endocrine disease

Endocrine Warning Signs

Important clues to pituitary dysfunction include:

• Neonatal hypoglycemia
• Prolonged jaundice
• Poor growth
• Failure to thrive
• Micropenis
• Cryptorchidism
• Recurrent seizures
• Polyuria/polydipsia
• Abnormal puberty

These findings warrant urgent endocrine assessment.

Physical Examination

Perform a complete pediatric ophthalmic examination including:

• Age-appropriate visual acuity
• Pupils
• Ocular alignment
• Motility
• Cycloplegic refraction
• Slit-lamp examination
• Dilated fundus examination

Optic Disc Appearance

Classic findings include:

• Small optic disc
• Pale or gray disc
• Reduced neuroretinal tissue
• Double-ring sign

Double-Ring Sign

The double-ring sign consists of:

• Small true optic nerve
• Surrounding larger ring corresponding to the normal-sized scleral canal and adjacent tissue

It is one of the classic signs of ONH.

Disc–Macula Relationship

Because the optic disc is abnormally small, the distance from:

• Disc center
• Fovea

appears disproportionately large compared with disc diameter.

A reduced disc diameter-to-disc–macula distance ratio supports the diagnosis.

Retinal Vessels

Associated features may include:

• Relative vessel crowding
• Tortuosity
• Immature vascular pattern

These findings are supportive but not diagnostic.

Foveal Hypoplasia

Some children with ONH may have associated:

Foveal hypoplasia

particularly when there is an underlying developmental or syndromic disorder.

OCT can help identify this.

Associated Microphthalmia

ONH may occasionally coexist with:

• Microphthalmia
• Other congenital ocular abnormalities

Nystagmus

Nystagmus is common in:

• Bilateral ONH
• Severe visual impairment

It usually reflects impaired early visual input.

Strabismus

Strabismus is common, especially in:

• Unilateral ONH
• Asymmetric bilateral disease

It may contribute additional amblyopic visual loss.

Pupils

A RAPD may be present with:

• Unilateral ONH
• Markedly asymmetric bilateral ONH

Visual Fields

When reliable testing becomes possible, defects may include:

• Generalized constriction
• Sectoral defects
• Altitudinal defects
• Central defects

Superior segmental ONH classically produces:

Inferior visual field loss

OCT

OCT may demonstrate:

• Reduced RNFL
• Reduced ganglion cell layer
• Small optic nerve head

It is useful for:

• Structural documentation
• Demonstrating asymmetry
• Distinguishing ONH from acquired optic atrophy

Interpretation can be limited by pediatric normative databases.

MRI

MRI of the brain and orbits is generally appropriate in children with ONH to assess for:

• Pituitary abnormalities
• Hypothalamic abnormalities
• Midline brain defects
• Corpus callosum abnormalities
• Cortical migration disorders

MRI Pituitary Findings

Potential findings include:

• Pituitary hypoplasia
• Absent or abnormal pituitary stalk
• Ectopic posterior pituitary bright spot

These increase concern for pituitary hormone deficiency.

However:

A normal MRI does not exclude endocrinopathy.

Important Imaging Principle

MRI can demonstrate associated structural abnormalities, but:

Optic nerve size on neuroimaging correlates imperfectly with visual function.

Clinical examination remains essential.

Endocrine Dysfunction

Pituitary abnormalities are among the most important systemic associations.

Potential deficiencies include:

• Growth hormone
• ACTH/cortisol
• TSH
• Gonadotropins
• Antidiuretic hormone

Growth Hormone Deficiency

Growth hormone deficiency may present with:

• Poor linear growth
• Falling height percentiles
• Delayed growth velocity

Growth charts should be reviewed longitudinally.

Central Hypothyroidism

Central hypothyroidism may be present despite:

• Normal or low-normal TSH

Therefore:

Free T4 is essential

and TSH alone is insufficient to screen for central hypothyroidism.

ACTH Deficiency

ACTH deficiency may cause:

• Hypoglycemia
• Hypotension
• Lethargy
• Adrenal crisis

This is potentially:

Life-threatening

and must not be missed.

Diabetes Insipidus

Central diabetes insipidus may produce:

• Polyuria
• Polydipsia
• Hypernatremia

Further testing may include:

• Serum sodium
• Serum osmolality
• Urine osmolality

Endocrine Evaluation

A low threshold for pediatric endocrinology referral is appropriate.

Initial assessment may include:

• Free T4
• TSH
• Morning cortisol
• Glucose
• IGF-1
• IGFBP-3
• Electrolytes

Additional testing depends on:

• Age
• Growth pattern
• Pubertal status
• Clinical symptoms

Long-Term Endocrine Surveillance

A normal endocrine evaluation in infancy does not guarantee normal future pituitary function.

Hormonal abnormalities may emerge later.

Therefore monitor:

• Height
• Weight
• Growth velocity
• Puberty
• Symptoms of adrenal or thyroid dysfunction

Neurologic Associations

Possible abnormalities include:

• Corpus callosum hypoplasia
• Agenesis of the corpus callosum
• Cortical ectopia
• Pachygyria
• Schizencephaly
• Other migration abnormalities
• Seizure disorders

Developmental Delay

Developmental problems are more common with:

• Bilateral disease
• Severe visual impairment
• Cerebral abnormalities
• Pituitary dysfunction

Assessment may include:

• Developmental pediatrics
• Neurology
• Early-intervention services

Differential Diagnosis

Important differentials include:

• Optic atrophy
• High hyperopia with small crowded discs
• Tilted optic disc
• Optic nerve coloboma
• Peripapillary staphyloma
• Peripapillary atrophy
• Morning glory disc anomaly

ONH vs Optic Atrophy

Optic Nerve Hypoplasia

• Congenitally small disc
• Double-ring sign
• Nonprogressive
• Reduced axon number from development

Optic Atrophy

• Acquired axonal loss
• Usually normal-sized disc initially
• Pallor predominates
• History may reveal previous neurologic or ocular injury

Treatment

There is:

No treatment that can regenerate the hypoplastic optic nerve

Management focuses on maximizing existing visual function and treating associated systemic disease.

Refractive Correction

Perform cycloplegic refraction and correct:

• Hyperopia
• Myopia
• Astigmatism
• Anisometropia

Optimal refractive correction is important during visual development.

Amblyopia Treatment

Amblyopia may coexist with structural optic nerve disease.

Treat when appropriate with:

• Optical correction
• Patching
• Atropine penalization in selected cases

Therapy should be individualized according to visual potential.

Strabismus

Management may include:

• Refractive correction
• Amblyopia treatment
• Strabismus surgery

Surgery may improve:

• Alignment
• Cosmesis
• Binocular function when sufficient vision exists

Nystagmus

Nystagmus surgery may be considered selectively for:

• Significant abnormal head posture
• Null point
• Associated strabismus

It does not treat the underlying optic nerve abnormality.

Protective Eyewear

When visual function is markedly asymmetric:

Protective spectacles should be recommended for the better-seeing eye.

Low-Vision Support

Children with significant bilateral visual impairment should be referred early for:

• Low-vision assessment
• Early-intervention programs
• Educational support
• Orientation and mobility training
• Adaptive technology

Endocrine Treatment

Hormone replacement is directed by pediatric endocrinology.

Examples include:

• Hydrocortisone for adrenal insufficiency
• Levothyroxine for central hypothyroidism
• Growth hormone when appropriate
• Desmopressin for diabetes insipidus

Genetic Counseling

Genetic consultation may be useful in:

• Bilateral severe disease
• Syndromic cases
• Multiple congenital anomalies
• Family history
• Suspected HESX1/SOX-related disease

Stem Cell Therapy

There is currently:

No convincing scientific evidence that stem cell treatment restores visual function in ONH.

It is not an established therapy.

Follow-Up

Ongoing ophthalmic follow-up should assess:

• Visual acuity
• Refraction
• Amblyopia
• Strabismus
• Nystagmus
• Functional visual development

Children often require more frequent review during:

• Amblyopia treatment
• Early visual development

Growth and Development Monitoring

Longitudinal monitoring should include:

• Height
• Weight
• Growth velocity
• Puberty
• Developmental milestones
• Neurologic symptoms

Prognosis

Visual prognosis is:

Highly variable

and depends primarily on residual optic nerve function.

Disc appearance and MRI findings correlate only poorly with visual outcome.

Stability

ONH itself is generally:

Nonprogressive

Apparent visual improvement with age may occur because of:

• Visual maturation
• Improved fixation
• Amblyopia treatment
• Better testing cooperation

This does not represent optic nerve regeneration.

Complications

Potential complications include:

• Severe visual impairment
• Amblyopia
• Strabismus
• Nystagmus
• Developmental delay
• Seizures
• Growth hormone deficiency
• Central hypothyroidism
• ACTH deficiency
• Diabetes insipidus
• Pubertal abnormalities

Ophthalmology Pearls

• Pediatric optic nerve hypoplasia is a congenital, nonprogressive reduction in optic nerve axons.
• The classic fundus finding is a small optic disc with a double-ring sign.
• Bilateral ONH often presents with poor visual behavior and nystagmus; unilateral disease often presents with strabismus or failed screening.
• Visual function correlates poorly with optic disc size or MRI appearance.
• The most important systemic association is hypothalamic-pituitary dysfunction.
• Free T4 is essential because central hypothyroidism may occur with a normal or low-normal TSH.
• ACTH/cortisol deficiency can be life-threatening and should not be missed.
• A normal MRI does not exclude pituitary dysfunction.
• Endocrine abnormalities may appear later, so longitudinal growth and hormonal surveillance is important.
• SOD does not require all three classic findings; ONH, pituitary dysfunction, and midline brain abnormalities may occur in different combinations.
• Maternal diabetes is associated with superior segmental ONH (“topless disc”), which typically causes an inferior visual field defect.
• Treatment focuses on refractive correction, amblyopia therapy, strabismus care, endocrine treatment, developmental support, and low-vision rehabilitation.
• There is currently no proven regenerative or stem-cell treatment for ONH.

Septo-Optic Dysplasia Septo-optic dysplasia (SOD) traditionally refers to the presence of at least two of the following:  Optic nerve hypoplasia Pituitary hormone dysfunction Midline brain abnormality  Midline abnormalities may include:  Absent septum pellucidum Corpus callosum hypoplasia or agenesis  The term de Morsier syndrome is historical. Importantly: Absence of the septum pellucidum alone does not predict endocrine dysfunction, and significant endocrinopathy can occur even with otherwise normal MRI findings.

Epidemiology ONH is among the most common congenital optic nerve abnormalities in children. Most cases are: Sporadic Bilateral involvement is common, but unilateral disease is frequently encountered.

Risk Factors Most children have no clearly identifiable prenatal cause. Reported associations include:  Maternal alcohol exposure Young maternal age Prematurity Abnormal fetal growth Maternal diabetes Certain prenatal medication or drug exposures  Older literature has reported associations with:  Some anticonvulsants Quinine PCP LSD  but these associations are not consistently established.

Maternal Diabetes Maternal diabetes is particularly associated with: Superior segmental optic nerve hypoplasia also called: Topless disc syndrome This causes:  Superior disc hypoplasia Superior RNFL loss Corresponding inferior visual field defect

Genetics Most ONH is sporadic. Rare genetic associations include abnormalities involving:  HESX1 SOX2 SOX3 OTX2 PAX6 Other genes involved in forebrain and pituitary development  Genetic evaluation is especially appropriate when there is:  Bilateral severe ONH Syndromic appearance Multiple congenital anomalies Strong family history Pituitary abnormalities

Associated Genetic and Developmental Disorders ONH may occur with:  Aniridia Albinism Midline developmental syndromes Pituitary developmental abnormalities Cortical migration disorders  Congenital infection and prenatal cerebral injury may also coexist with optic nerve hypoplasia-like appearances.

Pathophysiology The primary abnormality is: Reduced number of optic nerve axons Possible mechanisms include:  Abnormal retinal ganglion cell differentiation Excessive developmental apoptosis Abnormal axonal guidance Prenatal injury to the developing visual system  The outer retinal layers are generally preserved unless another retinal disorder is present.

Pathology Histologically there is:  Reduced retinal ganglion cell population Reduced RNFL Reduced optic nerve axons Small optic nerve caliber

Clinical Presentation Bilateral ONH Usually presents early with:  Poor visual behavior Poor fixation Nystagmus Developmental concerns  Nystagmus often appears during the first few months of life.

Unilateral ONH May present later with:  Strabismus Amblyopia Failed vision screening Incidental optic disc abnormality  A child with unilateral ONH may otherwise be systemically normal.

Visual Acuity Visual function is highly variable. It may range from: 20/20 to profound visual impairment A key principle: Disc appearance correlates poorly with visual function. A very small optic nerve may retain useful vision, while a mildly hypoplastic nerve may function poorly.

History Ask about:  Poor fixation Nystagmus Strabismus Developmental delay Seizures Abnormal growth Hypoglycemia Prolonged neonatal jaundice Excessive thirst or urination Prenatal alcohol or medication exposure Maternal diabetes Family history of developmental or endocrine disease

Endocrine Warning Signs Important clues to pituitary dysfunction include:  Neonatal hypoglycemia Prolonged jaundice Poor growth Failure to thrive Micropenis Cryptorchidism Recurrent seizures Polyuria/polydipsia Abnormal puberty  These findings warrant urgent endocrine assessment.

Physical Examination Perform a complete pediatric ophthalmic examination including:  Age-appropriate visual acuity Pupils Ocular alignment Motility Cycloplegic refraction Slit-lamp examination Dilated fundus examination

Optic Disc Appearance Classic findings include:  Small optic disc Pale or gray disc Reduced neuroretinal tissue Double-ring sign

Double-Ring Sign The double-ring sign consists of:  Small true optic nerve Surrounding larger ring corresponding to the normal-sized scleral canal and adjacent tissue  It is one of the classic signs of ONH.

Disc–Macula Relationship Because the optic disc is abnormally small, the distance from:  Disc center Fovea  appears disproportionately large compared with disc diameter. A reduced disc diameter-to-disc–macula distance ratio supports the diagnosis.

Retinal Vessels Associated features may include:  Relative vessel crowding Tortuosity Immature vascular pattern  These findings are supportive but not diagnostic.

Foveal Hypoplasia Some children with ONH may have associated: Foveal hypoplasia particularly when there is an underlying developmental or syndromic disorder. OCT can help identify this.

Associated Microphthalmia ONH may occasionally coexist with:  Microphthalmia Other congenital ocular abnormalities

Nystagmus Nystagmus is common in:  Bilateral ONH Severe visual impairment  It usually reflects impaired early visual input.

Strabismus Strabismus is common, especially in:  Unilateral ONH Asymmetric bilateral disease  It may contribute additional amblyopic visual loss.

Pupils A RAPD may be present with:  Unilateral ONH Markedly asymmetric bilateral ONH

Visual Fields When reliable testing becomes possible, defects may include:  Generalized constriction Sectoral defects Altitudinal defects Central defects  Superior segmental ONH classically produces: Inferior visual field loss

OCT OCT may demonstrate:  Reduced RNFL Reduced ganglion cell layer Small optic nerve head  It is useful for:  Structural documentation Demonstrating asymmetry Distinguishing ONH from acquired optic atrophy  Interpretation can be limited by pediatric normative databases.

MRI MRI of the brain and orbits is generally appropriate in children with ONH to assess for:  Pituitary abnormalities Hypothalamic abnormalities Midline brain defects Corpus callosum abnormalities Cortical migration disorders

MRI Pituitary Findings Potential findings include:  Pituitary hypoplasia Absent or abnormal pituitary stalk Ectopic posterior pituitary bright spot  These increase concern for pituitary hormone deficiency. However: A normal MRI does not exclude endocrinopathy.

Important Imaging Principle MRI can demonstrate associated structural abnormalities, but: Optic nerve size on neuroimaging correlates imperfectly with visual function. Clinical examination remains essential.

Endocrine Dysfunction Pituitary abnormalities are among the most important systemic associations. Potential deficiencies include:  Growth hormone ACTH/cortisol TSH Gonadotropins Antidiuretic hormone

Growth Hormone Deficiency Growth hormone deficiency may present with:  Poor linear growth Falling height percentiles Delayed growth velocity  Growth charts should be reviewed longitudinally.

Central Hypothyroidism Central hypothyroidism may be present despite:  Normal or low-normal TSH  Therefore: Free T4 is essential and TSH alone is insufficient to screen for central hypothyroidism.

ACTH Deficiency ACTH deficiency may cause:  Hypoglycemia Hypotension Lethargy Adrenal crisis  This is potentially: Life-threatening and must not be missed.

Diabetes Insipidus Central diabetes insipidus may produce:  Polyuria Polydipsia Hypernatremia  Further testing may include:  Serum sodium Serum osmolality Urine osmolality

Endocrine Evaluation A low threshold for pediatric endocrinology referral is appropriate. Initial assessment may include:  Free T4 TSH Morning cortisol Glucose IGF-1 IGFBP-3 Electrolytes  Additional testing depends on:  Age Growth pattern Pubertal status Clinical symptoms

Long-Term Endocrine Surveillance A normal endocrine evaluation in infancy does not guarantee normal future pituitary function. Hormonal abnormalities may emerge later. Therefore monitor:  Height Weight Growth velocity Puberty Symptoms of adrenal or thyroid dysfunction

Neurologic Associations Possible abnormalities include:  Corpus callosum hypoplasia Agenesis of the corpus callosum Cortical ectopia Pachygyria Schizencephaly Other migration abnormalities Seizure disorders

Developmental Delay Developmental problems are more common with:  Bilateral disease Severe visual impairment Cerebral abnormalities Pituitary dysfunction  Assessment may include:  Developmental pediatrics Neurology Early-intervention services

Differential Diagnosis Important differentials include:  Optic atrophy High hyperopia with small crowded discs Tilted optic disc Optic nerve coloboma Peripapillary staphyloma Peripapillary atrophy Morning glory disc anomaly

ONH vs Optic Atrophy Optic Nerve Hypoplasia  Congenitally small disc Double-ring sign Nonprogressive Reduced axon number from development  Optic Atrophy  Acquired axonal loss Usually normal-sized disc initially Pallor predominates History may reveal previous neurologic or ocular injury

Treatment There is: No treatment that can regenerate the hypoplastic optic nerve Management focuses on maximizing existing visual function and treating associated systemic disease.

Refractive Correction Perform cycloplegic refraction and correct:  Hyperopia Myopia Astigmatism Anisometropia  Optimal refractive correction is important during visual development.

Amblyopia Treatment Amblyopia may coexist with structural optic nerve disease. Treat when appropriate with:  Optical correction Patching Atropine penalization in selected cases  Therapy should be individualized according to visual potential.

Strabismus Management may include:  Refractive correction Amblyopia treatment Strabismus surgery  Surgery may improve:  Alignment Cosmesis Binocular function when sufficient vision exists

Nystagmus Nystagmus surgery may be considered selectively for:  Significant abnormal head posture Null point Associated strabismus  It does not treat the underlying optic nerve abnormality.

Protective Eyewear When visual function is markedly asymmetric: Protective spectacles should be recommended for the better-seeing eye.

Low-Vision Support Children with significant bilateral visual impairment should be referred early for:  Low-vision assessment Early-intervention programs Educational support Orientation and mobility training Adaptive technology

Endocrine Treatment Hormone replacement is directed by pediatric endocrinology. Examples include:  Hydrocortisone for adrenal insufficiency Levothyroxine for central hypothyroidism Growth hormone when appropriate Desmopressin for diabetes insipidus

Genetic Counseling Genetic consultation may be useful in:  Bilateral severe disease Syndromic cases Multiple congenital anomalies Family history Suspected HESX1/SOX-related disease

Stem Cell Therapy There is currently: No convincing scientific evidence that stem cell treatment restores visual function in ONH. It is not an established therapy.

Follow-Up Ongoing ophthalmic follow-up should assess:  Visual acuity Refraction Amblyopia Strabismus Nystagmus Functional visual development  Children often require more frequent review during:  Amblyopia treatment Early visual development

Growth and Development Monitoring Longitudinal monitoring should include:  Height Weight Growth velocity Puberty Developmental milestones Neurologic symptoms

Prognosis Visual prognosis is: Highly variable and depends primarily on residual optic nerve function. Disc appearance and MRI findings correlate only poorly with visual outcome.

Stability ONH itself is generally: Nonprogressive Apparent visual improvement with age may occur because of:  Visual maturation Improved fixation Amblyopia treatment Better testing cooperation  This does not represent optic nerve regeneration.

Complications Potential complications include:  Severe visual impairment Amblyopia Strabismus Nystagmus Developmental delay Seizures Growth hormone deficiency Central hypothyroidism ACTH deficiency Diabetes insipidus Pubertal abnormalities

Ophthalmology Pearls  Pediatric optic nerve hypoplasia is a congenital, nonprogressive reduction in optic nerve axons. The classic fundus finding is a small optic disc with a double-ring sign. Bilateral ONH often presents with poor visual behavior and nystagmus; unilateral disease often presents with strabismus or failed screening. Visual function correlates poorly with optic disc size or MRI appearance. The most important systemic association is hypothalamic-pituitary dysfunction. Free T4 is essential because central hypothyroidism may occur with a normal or low-normal TSH. ACTH/cortisol deficiency can be life-threatening and should not be missed. A normal MRI does not exclude pituitary dysfunction. Endocrine abnormalities may appear later, so longitudinal growth and hormonal surveillance is important. SOD does not require all three classic findings; ONH, pituitary dysfunction, and midline brain abnormalities may occur in different combinations. Maternal diabetes is associated with superior segmental ONH (“topless disc”), which typically causes an inferior visual field defect. Treatment focuses on refractive correction, amblyopia therapy, strabismus care, endocrine treatment, developmental support, and low-vision rehabilitation. There is currently no proven regenerative or stem-cell treatment for ONH.

Ophthalmology – Pattern Dystrophy

Basics

Description

Pattern dystrophies of the retinal pigment epithelium (RPE) are a heterogeneous group of inherited macular disorders characterized by abnormal deposition of lipofuscin and pigment at the level of the:

• RPE
• Photoreceptor–RPE interface

They are usually:

• Bilateral
• Slowly progressive
• Relatively symmetric

but the appearance can differ between the two eyes.

Many patients are discovered incidentally and retain useful central vision for decades.

Major Clinical Patterns

Classically described phenotypes include:

• Butterfly-shaped pattern dystrophy
• Reticular pattern dystrophy
• Adult-onset foveomacular vitelliform lesion/dystrophy
• Fundus pulverulentus
• Multifocal pattern dystrophy simulating fundus flavimaculatus

These categories overlap considerably.

A single patient may:

• Change phenotype over time
• Show different patterns between eyes
• Develop increasing RPE atrophy with age

Epidemiology

The true incidence and prevalence are uncertain because of:

• Mild symptoms
• Variable phenotype
• Overlap with age-related macular disease
• Variable penetrance

Men and women are affected approximately equally.

Presentation is often in:

• Young or middle adulthood

although clinically significant symptoms may not appear until later life.

Genetics

Most classic pattern dystrophies are inherited in an:

Autosomal dominant

fashion.

The most important gene is:

PRPH2

formerly called:

RDS/peripherin

PRPH2 is located on chromosome 6 and encodes a photoreceptor outer-segment membrane protein important for:

• Disc structure
• Photoreceptor maintenance

PRPH2 Phenotypic Variability

PRPH2 variants can produce a wide spectrum of retinal disease, including:

• Pattern dystrophy
• Adult-onset vitelliform lesions
• Central areolar choroidal dystrophy
• Cone–rod dystrophy
• Retinitis pigmentosa-like phenotypes

Therefore:

The same gene can produce markedly different retinal appearances even within the same family.

Other Genetic Associations

Not all pattern dystrophy phenotypes are caused by PRPH2.

Other implicated genes include:

• BEST1
• IMPG1
• IMPG2

depending on phenotype.

Genetic testing is most useful when:

• Diagnosis is uncertain
• Family counseling is needed
• Presentation is atypical
• There is overlap with another inherited retinal disease

Mitochondrial Association

A distinctive macular pattern dystrophy is strongly associated with:

Maternally inherited diabetes and deafness (MIDD)

usually caused by the mitochondrial DNA variant:

m.3243A>G in MT-TL1

The macular phenotype may show:

• Circumferential RPE atrophy
• Pigmentary changes surrounding the fovea
• Relative foveal sparing early

MIDD Clinical Clues

Consider MIDD when pattern dystrophy occurs with:

• Diabetes mellitus
• Sensorineural hearing loss
• Maternal inheritance pattern
• Short stature
• Other mitochondrial features

Because mitochondrial DNA is maternally inherited:

Affected fathers do not transmit the disorder, whereas affected mothers may transmit it to offspring.

Pathophysiology

Pattern dystrophies involve abnormal function of:

• Photoreceptor outer segments
• RPE

with accumulation of:

Lipofuscin and other pigmentary material

Over time this may lead to:

• RPE degeneration
• Photoreceptor loss
• Outer retinal atrophy

Complications of Progressive Disease

With age, patients may develop:

• Geographic-like RPE atrophy
• Photoreceptor loss
• Central visual decline
• Macular neovascularization (MNV/CNV)

Clinical Presentation

Many patients are initially:

Asymptomatic

When symptoms occur they may include:

• Mild reduction in central vision
• Metamorphopsia
• Difficulty reading
• Central scotoma
• Reduced contrast sensitivity

Symptoms usually progress slowly.

Fundus Appearance

Typical fundus findings include:

• Yellow
• Gray
• Orange
• Brown

pigmentary deposits at the macula.

The distribution varies according to phenotype.

Butterfly Pattern Dystrophy

Characteristic finding:

Butterfly- or spoke-shaped pigmentary material centered on the fovea

The lesion consists of:

• Yellow-gray material
• Pigment clumping
• RPE alteration

Reticular Pattern Dystrophy

Shows:

• Reticular
• Net-like
• Branching pigment pattern

typically around the posterior pole.

Adult-Onset Foveomacular Vitelliform Phenotype

Usually demonstrates a:

Round or oval yellow subfoveal vitelliform lesion

It may resemble:

• Best disease
• Acquired vitelliform lesion
• Early AMD

Patients often present in:

• Middle or later adulthood

Fundus Pulverulentus

Characterized by:

• Numerous fine
• Dust-like
• Gray-white or pigmentary macular spots

The changes are usually subtle.

Multifocal Pattern Dystrophy

May produce multiple:

• Yellow-white flecks
• Pigmentary lesions

and can resemble:

Stargardt disease / fundus flavimaculatus

Visual Acuity

Visual acuity is often:

• Normal
• Mildly reduced

for many years.

Substantial loss usually occurs because of:

• Central RPE atrophy
• Photoreceptor loss
• MNV/CNV

Color Vision

Color vision is usually:

Normal early

Abnormality may occur with advanced macular or cone dysfunction.

Visual Fields

Visual fields are often normal early.

Advanced disease may produce:

• Central scotoma
• Paracentral scotoma

Dark Adaptation

Dark adaptation is usually:

Normal or minimally affected

which helps distinguish many pattern dystrophies from more diffuse retinal dystrophies.

OCT

Optical coherence tomography is one of the most useful investigations.

Findings may include:

• Hyperreflective material between RPE and photoreceptors
• Subretinal vitelliform material
• RPE irregularity
• Ellipsoid-zone disruption
• Outer retinal thinning
• RPE atrophy

OCT in Vitelliform Lesions

The yellow lesion usually corresponds to:

Hyperreflective subretinal material above the RPE

Later stages may show:

• Collapse of material
• Outer retinal disruption
• RPE atrophy

Fundus Autofluorescence

FAF is particularly useful because lipofuscin is autofluorescent.

Early lesions often demonstrate:

Increased autofluorescence

because of accumulated lipofuscin.

Areas of advanced RPE loss demonstrate:

Reduced or absent autofluorescence

Fluorescein Angiography

FA findings vary with the pattern.

Pigmented areas may cause:

• Blocked fluorescence

Areas of RPE atrophy may produce:

• Window defects
• Hyperfluorescence without leakage

FA is particularly useful when:

MNV/CNV is suspected

OCT Angiography

OCTA may detect:

• Neovascular networks
• Subclinical MNV

without dye injection.

It is particularly helpful when:

• Fluid or hemorrhage is suspicious for neovascularization
• Structural OCT findings are equivocal

Electroretinography

Full-field ERG is usually:

Normal

because the disease is predominantly macular.

An abnormal full-field ERG should raise suspicion for:

• Cone dystrophy
• Cone–rod dystrophy
• More generalized inherited retinal disease

Electrooculography

EOG may be:

• Normal
• Mildly reduced

It is not routinely needed for diagnosis.

Diagnosis

Diagnosis is based on:

• Characteristic fundus appearance
• OCT
• Fundus autofluorescence
• Family history

Additional testing is directed by phenotype.

When Genetic Testing Is Helpful

Consider testing when:

• PRPH2-associated disease is suspected
• There is a strong family history
• MIDD is suspected
• Diagnosis overlaps with Best disease or Stargardt disease
• Counseling is needed

Differential Diagnosis

Important differentials include:

• Age-related macular degeneration
• Stargardt disease
• Best vitelliform macular dystrophy
• Acquired vitelliform lesion
• Dominant drusen
• Central areolar choroidal dystrophy
• Cone dystrophy
• Benign concentric annular macular dystrophy
• Drug toxicity
• Chronic central serous chorioretinopathy

Pattern Dystrophy vs AMD

This distinction becomes particularly important in older patients.

Pattern dystrophy tends to show:

• Characteristic geometric or patterned pigment
• Family history
• Relatively preserved vision for age
• Bilateral similar lesions
• Hyperautofluorescent lipofuscin

AMD more typically shows:

• Drusen
• Pigmentary changes without a characteristic pattern
• Geographic atrophy
• Age-related macular neovascularization

The two may coexist.

Pattern Dystrophy vs Stargardt Disease

Stargardt disease typically has:

• Younger onset
• More progressive central visual loss
• Flecks extending beyond the macula
• Characteristic FAF changes
• ABCA4-associated inheritance

Pattern dystrophy is more often:

• Autosomal dominant
• Later onset
• Milder

Adult-Onset Vitelliform Lesion vs Best Disease

Best disease usually:

• Begins earlier
• Has BEST1-associated inheritance
• Shows abnormal EOG in classic disease

Adult-onset vitelliform lesions:

• Present later
• Are generally smaller
• Have more limited visual effect early
• May be associated with PRPH2, BEST1, IMPG1, or IMPG2

Treatment

There is currently:

No treatment that reverses the underlying inherited RPE dystrophy

Management focuses on:

• Monitoring
• Treating complications
• Genetic counseling
• Low-vision support when necessary

Macular Neovascularization

The most important treatable complication is:

MNV/CNV

Suspect it when there is:

• Sudden visual decline
• New metamorphopsia
• New hemorrhage
• Intraretinal or subretinal fluid on OCT

Anti-VEGF Therapy

The modern first-line treatment for active MNV/CNV is:

Intravitreal anti-VEGF therapy

Agents include:

• Bevacizumab
• Ranibizumab
• Aflibercept
• Faricimab in selected settings

Treatment generally follows OCT-guided disease activity.

Photodynamic Therapy

PDT was historically used for CNV associated with pattern dystrophy.

Today it has largely been replaced by:

Anti-VEGF therapy

because anti-VEGF generally provides better anatomic and visual outcomes.

Monitoring

Patients without complications may be reviewed:

Approximately annually

depending on:

• Age
• Phenotype
• Visual symptoms
• Degree of atrophy

Home Monitoring

Patients should be advised to report:

• New distortion
• New central blur
• New scotoma

An:

Amsler grid

may be useful for home monitoring.

Low-Vision Rehabilitation

Referral is appropriate when central atrophy causes:

• Reading difficulty
• Reduced contrast sensitivity
• Loss of useful central vision

Genetic Counseling

Counseling should address:

• Autosomal dominant inheritance in many PRPH2 cases
• Variable expression
• Incomplete penetrance in some families
• Mitochondrial inheritance when MIDD is present

Prognosis

Overall visual prognosis is generally:

Good

Most patients retain useful central vision for many years.

Many maintain:

• Reading vision
• Functional independence

into late adulthood.

Poorer Prognostic Factors

More significant visual loss occurs with:

• Extensive RPE atrophy
• Foveal photoreceptor loss
• MNV/CNV
• Recurrent macular hemorrhage

Complications

Important complications include:

• Progressive central visual loss
• RPE atrophy
• Photoreceptor loss
• Central scotoma
• Macular neovascularization
• Subretinal hemorrhage

Ophthalmology Pearls

• Pattern dystrophy is a group of inherited macular RPE disorders characterized by patterned lipofuscin and pigment deposition.
• Most classic cases are autosomal dominant and associated with PRPH2, formerly called RDS/peripherin.
• The phenotype can change with age and may differ between the two eyes or among members of the same family.
• Important patterns include butterfly, reticular, adult-onset vitelliform, fundus pulverulentus, and multifocal pattern dystrophy.
• OCT commonly shows subretinal or RPE-level hyperreflective material with outer retinal disruption.
• FAF is often hyperautofluorescent early from lipofuscin accumulation and becomes hypoautofluorescent where RPE atrophy develops.
• Full-field ERG is usually normal, reflecting the predominantly macular nature of the disease.
• MIDD should be considered when pattern dystrophy accompanies diabetes and sensorineural deafness, particularly with maternal inheritance.
• Pattern dystrophy can mimic AMD, Stargardt disease, and Best disease.
• Most patients retain useful vision for decades.
• The major treatable complication is macular neovascularization, for which intravitreal anti-VEGF is first-line therapy.
• New metamorphopsia, hemorrhage, or sudden visual loss should prompt urgent OCT assessment for MNV/CNV.

Major Clinical Patterns Classically described phenotypes include:  Butterfly-shaped pattern dystrophy Reticular pattern dystrophy Adult-onset foveomacular vitelliform lesion/dystrophy Fundus pulverulentus Multifocal pattern dystrophy simulating fundus flavimaculatus  These categories overlap considerably. A single patient may:  Change phenotype over time Show different patterns between eyes Develop increasing RPE atrophy with age

Epidemiology The true incidence and prevalence are uncertain because of:  Mild symptoms Variable phenotype Overlap with age-related macular disease Variable penetrance  Men and women are affected approximately equally. Presentation is often in:  Young or middle adulthood  although clinically significant symptoms may not appear until later life.

Genetics Most classic pattern dystrophies are inherited in an: Autosomal dominant fashion. The most important gene is: PRPH2 formerly called: RDS/peripherin PRPH2 is located on chromosome 6 and encodes a photoreceptor outer-segment membrane protein important for:  Disc structure Photoreceptor maintenance

PRPH2 Phenotypic Variability PRPH2 variants can produce a wide spectrum of retinal disease, including:  Pattern dystrophy Adult-onset vitelliform lesions Central areolar choroidal dystrophy Cone–rod dystrophy Retinitis pigmentosa-like phenotypes  Therefore: The same gene can produce markedly different retinal appearances even within the same family.

Other Genetic Associations Not all pattern dystrophy phenotypes are caused by PRPH2. Other implicated genes include:  BEST1 IMPG1 IMPG2  depending on phenotype. Genetic testing is most useful when:  Diagnosis is uncertain Family counseling is needed Presentation is atypical There is overlap with another inherited retinal disease

Mitochondrial Association A distinctive macular pattern dystrophy is strongly associated with: Maternally inherited diabetes and deafness (MIDD) usually caused by the mitochondrial DNA variant: m.3243A>G in MT-TL1 The macular phenotype may show:  Circumferential RPE atrophy Pigmentary changes surrounding the fovea Relative foveal sparing early

MIDD Clinical Clues Consider MIDD when pattern dystrophy occurs with:  Diabetes mellitus Sensorineural hearing loss Maternal inheritance pattern Short stature Other mitochondrial features  Because mitochondrial DNA is maternally inherited: Affected fathers do not transmit the disorder, whereas affected mothers may transmit it to offspring.

Pathophysiology Pattern dystrophies involve abnormal function of:  Photoreceptor outer segments RPE  with accumulation of: Lipofuscin and other pigmentary material Over time this may lead to:  RPE degeneration Photoreceptor loss Outer retinal atrophy

Complications of Progressive Disease With age, patients may develop:  Geographic-like RPE atrophy Photoreceptor loss Central visual decline Macular neovascularization (MNV/CNV)

Clinical Presentation Many patients are initially: Asymptomatic When symptoms occur they may include:  Mild reduction in central vision Metamorphopsia Difficulty reading Central scotoma Reduced contrast sensitivity  Symptoms usually progress slowly.

Fundus Appearance Typical fundus findings include:  Yellow Gray Orange Brown  pigmentary deposits at the macula. The distribution varies according to phenotype.

Butterfly Pattern Dystrophy Characteristic finding: Butterfly- or spoke-shaped pigmentary material centered on the fovea The lesion consists of:  Yellow-gray material Pigment clumping RPE alteration

Reticular Pattern Dystrophy Shows:  Reticular Net-like Branching pigment pattern  typically around the posterior pole.

Adult-Onset Foveomacular Vitelliform Phenotype Usually demonstrates a: Round or oval yellow subfoveal vitelliform lesion It may resemble:  Best disease Acquired vitelliform lesion Early AMD  Patients often present in:  Middle or later adulthood

Fundus Pulverulentus Characterized by:  Numerous fine Dust-like Gray-white or pigmentary macular spots  The changes are usually subtle.

Multifocal Pattern Dystrophy May produce multiple:  Yellow-white flecks Pigmentary lesions  and can resemble: Stargardt disease / fundus flavimaculatus

Visual Acuity Visual acuity is often:  Normal Mildly reduced  for many years. Substantial loss usually occurs because of:  Central RPE atrophy Photoreceptor loss MNV/CNV

Color Vision Color vision is usually: Normal early Abnormality may occur with advanced macular or cone dysfunction.

Visual Fields Visual fields are often normal early. Advanced disease may produce:  Central scotoma Paracentral scotoma

Dark Adaptation Dark adaptation is usually: Normal or minimally affected which helps distinguish many pattern dystrophies from more diffuse retinal dystrophies.

OCT Optical coherence tomography is one of the most useful investigations. Findings may include:  Hyperreflective material between RPE and photoreceptors Subretinal vitelliform material RPE irregularity Ellipsoid-zone disruption Outer retinal thinning RPE atrophy

OCT in Vitelliform Lesions The yellow lesion usually corresponds to: Hyperreflective subretinal material above the RPE Later stages may show:  Collapse of material Outer retinal disruption RPE atrophy

Fundus Autofluorescence FAF is particularly useful because lipofuscin is autofluorescent. Early lesions often demonstrate: Increased autofluorescence because of accumulated lipofuscin. Areas of advanced RPE loss demonstrate: Reduced or absent autofluorescence

Fluorescein Angiography FA findings vary with the pattern. Pigmented areas may cause:  Blocked fluorescence  Areas of RPE atrophy may produce:  Window defects Hyperfluorescence without leakage  FA is particularly useful when: MNV/CNV is suspected

OCT Angiography OCTA may detect:  Neovascular networks Subclinical MNV  without dye injection. It is particularly helpful when:  Fluid or hemorrhage is suspicious for neovascularization Structural OCT findings are equivocal

Electroretinography Full-field ERG is usually: Normal because the disease is predominantly macular. An abnormal full-field ERG should raise suspicion for:  Cone dystrophy Cone–rod dystrophy More generalized inherited retinal disease

Electrooculography EOG may be:  Normal Mildly reduced  It is not routinely needed for diagnosis.

Diagnosis Diagnosis is based on:  Characteristic fundus appearance OCT Fundus autofluorescence Family history  Additional testing is directed by phenotype.

When Genetic Testing Is Helpful Consider testing when:  PRPH2-associated disease is suspected There is a strong family history MIDD is suspected Diagnosis overlaps with Best disease or Stargardt disease Counseling is needed

Differential Diagnosis Important differentials include:  Age-related macular degeneration Stargardt disease Best vitelliform macular dystrophy Acquired vitelliform lesion Dominant drusen Central areolar choroidal dystrophy Cone dystrophy Benign concentric annular macular dystrophy Drug toxicity Chronic central serous chorioretinopathy

Pattern Dystrophy vs AMD This distinction becomes particularly important in older patients. Pattern dystrophy tends to show:  Characteristic geometric or patterned pigment Family history Relatively preserved vision for age Bilateral similar lesions Hyperautofluorescent lipofuscin  AMD more typically shows:  Drusen Pigmentary changes without a characteristic pattern Geographic atrophy Age-related macular neovascularization  The two may coexist.

Pattern Dystrophy vs Stargardt Disease Stargardt disease typically has:  Younger onset More progressive central visual loss Flecks extending beyond the macula Characteristic FAF changes ABCA4-associated inheritance  Pattern dystrophy is more often:  Autosomal dominant Later onset Milder

Adult-Onset Vitelliform Lesion vs Best Disease Best disease usually:  Begins earlier Has BEST1-associated inheritance Shows abnormal EOG in classic disease  Adult-onset vitelliform lesions:  Present later Are generally smaller Have more limited visual effect early May be associated with PRPH2, BEST1, IMPG1, or IMPG2

Treatment There is currently: No treatment that reverses the underlying inherited RPE dystrophy Management focuses on:  Monitoring Treating complications Genetic counseling Low-vision support when necessary

Macular Neovascularization The most important treatable complication is: MNV/CNV Suspect it when there is:  Sudden visual decline New metamorphopsia New hemorrhage Intraretinal or subretinal fluid on OCT

Anti-VEGF Therapy The modern first-line treatment for active MNV/CNV is: Intravitreal anti-VEGF therapy Agents include:  Bevacizumab Ranibizumab Aflibercept Faricimab in selected settings  Treatment generally follows OCT-guided disease activity.

Photodynamic Therapy PDT was historically used for CNV associated with pattern dystrophy. Today it has largely been replaced by: Anti-VEGF therapy because anti-VEGF generally provides better anatomic and visual outcomes.

Monitoring Patients without complications may be reviewed: Approximately annually depending on:  Age Phenotype Visual symptoms Degree of atrophy

Home Monitoring Patients should be advised to report:  New distortion New central blur New scotoma  An: Amsler grid may be useful for home monitoring.

Low-Vision Rehabilitation Referral is appropriate when central atrophy causes:  Reading difficulty Reduced contrast sensitivity Loss of useful central vision

Genetic Counseling Counseling should address:  Autosomal dominant inheritance in many PRPH2 cases Variable expression Incomplete penetrance in some families Mitochondrial inheritance when MIDD is present

Prognosis Overall visual prognosis is generally: Good Most patients retain useful central vision for many years. Many maintain:  Reading vision Functional independence  into late adulthood.

Poorer Prognostic Factors More significant visual loss occurs with:  Extensive RPE atrophy Foveal photoreceptor loss MNV/CNV Recurrent macular hemorrhage

Complications Important complications include:  Progressive central visual loss RPE atrophy Photoreceptor loss Central scotoma Macular neovascularization Subretinal hemorrhage

Ophthalmology Pearls  Pattern dystrophy is a group of inherited macular RPE disorders characterized by patterned lipofuscin and pigment deposition. Most classic cases are autosomal dominant and associated with PRPH2, formerly called RDS/peripherin. The phenotype can change with age and may differ between the two eyes or among members of the same family. Important patterns include butterfly, reticular, adult-onset vitelliform, fundus pulverulentus, and multifocal pattern dystrophy. OCT commonly shows subretinal or RPE-level hyperreflective material with outer retinal disruption. FAF is often hyperautofluorescent early from lipofuscin accumulation and becomes hypoautofluorescent where RPE atrophy develops. Full-field ERG is usually normal, reflecting the predominantly macular nature of the disease. MIDD should be considered when pattern dystrophy accompanies diabetes and sensorineural deafness, particularly with maternal inheritance. Pattern dystrophy can mimic AMD, Stargardt disease, and Best disease. Most patients retain useful vision for decades. The major treatable complication is macular neovascularization, for which intravitreal anti-VEGF is first-line therapy. New metamorphopsia, hemorrhage, or sudden visual loss should prompt urgent OCT assessment for MNV/CNV.

Ophthalmology – Papilledema in Children

Basics

Description

Papilledema in children is optic disc swelling caused specifically by elevated intracranial pressure (ICP).

It is usually:

• Bilateral
• Relatively symmetric

but may be:

• Markedly asymmetric
• Rarely apparently unilateral

Papilledema is a sign of raised ICP, not a diagnosis itself.

In children, important causes include:

• Hydrocephalus
• Brain tumor
• Cerebral venous sinus thrombosis
• Meningitis
• Craniosynostosis
• Shunt malfunction
• Idiopathic intracranial hypertension (IIH)

Important Pediatric Principle

In young infants:

Markedly elevated ICP may occur without papilledema

because:

• Cranial sutures remain open
• Fontanelles can expand
• Head circumference may increase rather than pressure being transmitted fully to the optic nerve

Therefore:

Absence of papilledema does not exclude raised ICP in infants or young children.

Epidemiology

The incidence of pediatric papilledema depends on the underlying cause.

Common settings include:

• Hydrocephalus
• Brain tumors
• Craniosynostosis
• Cerebral venous sinus thrombosis
• IIH

Pediatric IIH differs from adult disease.

Pediatric IIH Demographics

Prepubertal Children

There is:

• Less female predominance
• Weaker association with obesity

Postpubertal Adolescents

The pattern becomes more similar to adults:

• Female predominance
• Stronger association with obesity and weight gain

Risk Factors

Risk factors for raised ICP in children include:

• Hydrocephalus
• Ventricular shunts
• Brain tumors
• Head trauma
• Craniosynostosis
• Severe intracranial hemorrhage
• Cerebral venous sinus thrombosis

Risk Factors for Pediatric IIH

Associations include:

• Obesity, especially after puberty
• Recent weight gain
• Obstructive sleep apnea
• Certain medications

Medications associated with intracranial hypertension include:

• Tetracyclines
• Vitamin A derivatives / systemic retinoids
• Growth hormone
• Steroid withdrawal
• Lithium in selected cases

The offending medication should be discontinued when clinically appropriate.

Pathophysiology

Elevated ICP is transmitted through the optic nerve subarachnoid space.

This causes:

Increased retrolaminar pressure → impaired axoplasmic transport → optic disc edema

As swelling progresses:

• Venous congestion develops
• Axons become compressed
• Retinal hemorrhages may occur

With prolonged disease:

• Retinal ganglion cell axons are lost
• Optic atrophy develops
• Permanent visual loss may result

Etiology

Important causes include:

• Hydrocephalus
• Brain tumor
• Cerebral venous sinus thrombosis
• Meningitis
• Encephalitis
• Intracranial hemorrhage
• Cerebral edema
• Craniosynostosis
• Shunt malfunction
• IIH

Rare causes include:

• Spinal tumors
• Craniocervical junction lesions
• Severe venous outflow obstruction

Hydrocephalus

Hydrocephalus is an important pediatric cause of papilledema.

It may result from:

• Obstruction of CSF flow
• Impaired CSF absorption
• Congenital abnormalities
• Tumors
• Hemorrhage
• Infection

Children with a ventricular shunt remain at risk for:

Shunt malfunction and recurrent elevated ICP

Brain Tumors

Infratentorial tumors are particularly likely to cause raised ICP because they may obstruct:

• Fourth ventricle
• Cerebral aqueduct
• CSF pathways

Symptoms may include:

• Morning headache
• Vomiting
• Ataxia
• Cranial nerve palsies

Craniosynostosis

Premature fusion of cranial sutures may restrict skull growth and produce:

• Elevated ICP
• Papilledema
• Optic atrophy
• Permanent visual loss

Children with syndromic craniosynostosis require long-term ophthalmic monitoring.

Idiopathic Intracranial Hypertension

Pediatric IIH is raised ICP without:

• Intracranial mass
• Hydrocephalus
• Cerebral venous thrombosis
• Abnormal CSF composition
• Another identifiable secondary cause

It was historically termed:

Pseudotumor cerebri

History

Ask about:

• Headache
• Vomiting
• Transient visual obscurations
• Diplopia
• Pulsatile tinnitus
• Visual loss
• Medication exposure
• Recent weight gain
• Shunt history
• Head trauma
• Fever
• Neurologic symptoms

Headache

Concerning headache features include:

• Awakening from sleep
• Present on awakening
• Progressive severity
• Worsened by coughing or Valsalva
• Associated vomiting
• Associated diplopia

In a child with known hydrocephalus or a ventricular shunt, a new headache should raise concern for:

Shunt dysfunction or recurrent elevated ICP

Infants and Preverbal Children

They may not report headache.

Possible manifestations include:

• Irritability
• Lethargy
• Somnolence
• Poor feeding
• Vomiting
• Developmental regression
• Increasing head circumference
• Bulging fontanelle
• Abnormal eye movements

Transient Visual Obscurations

Children may report:

• Brief blackouts
• Graying of vision
• Momentary blur

usually lasting:

Seconds

These may occur repeatedly and are often provoked by:

• Standing
• Bending
• Position changes

Diplopia

Diplopia most commonly results from:

Sixth nerve palsy

which may be:

• Unilateral
• Bilateral

In younger children, CN VI palsy may present as:

• New esotropia
• Head turn
• Failure to abduct one or both eyes

Visual Acuity

In early papilledema:

Central visual acuity may remain normal

This is an important distinction from many other optic neuropathies.

Once significant visual acuity loss develops, axonal injury may already be substantial.

Color Vision

Color vision is often preserved early.

Loss of color vision suggests:

• Progressive optic nerve dysfunction
• Axonal injury
• More advanced disease

Pupils

Pupils are often normal early.

A RAPD may occur when optic nerve damage is:

• Asymmetric
• Advanced

Fundus Findings

Typical findings include:

• Swollen optic discs
• Blurred disc margins
• RNFL edema
• Loss of physiologic cup
• Obscuration of vessels crossing the disc margin
• Venous engorgement

Disc Hemorrhages

More severe papilledema may cause:

• Peripapillary flame hemorrhages
• Disc hemorrhages
• Cotton-wool spots

Spontaneous Venous Pulsation

Visible spontaneous venous pulsation makes markedly raised ICP less likely.

However:

Absence of venous pulsation is not diagnostic, because it is absent in some normal individuals.

This sign should not be used alone to exclude or confirm intracranial hypertension.

Paton Lines

Paton lines are concentric peripapillary retinal folds caused by optic disc swelling.

They support the presence of significant true disc edema.

Visual Fields

When children are old enough to perform reliable testing, common abnormalities include:

• Enlarged blind spot
• Nasal defects
• Arcuate defects
• Peripheral constriction

Advanced disease can produce:

• Severe generalized field loss
• Central visual loss

Automated Perimetry in Children

Standard automated visual fields may be difficult in young children.

Reliability improves with:

• Age
• Practice
• Shorter strategies
• Experienced pediatric technicians

Children younger than approximately school age may require alternative functional assessment.

Chronic Papilledema

Long-standing papilledema can produce:

• Disc pallor
• RNFL thinning
• Gliosis
• Optic atrophy
• Permanent visual field loss

An atrophic optic nerve may no longer swell significantly even if ICP rises again.

Therefore:

Absence of recurrent papilledema does not reliably exclude shunt malfunction in an optic nerve that is already atrophic.

Diagnostic Approach

The evaluation should answer:

1. Is the disc truly swollen?
2. Is the swelling due to raised ICP?
3. What is causing the raised ICP?

Neuroimaging

Urgent neuroimaging is required for suspected papilledema.

Preferred imaging is:

MRI brain with and without contrast

plus:

MR venography

when feasible.

Why MRV Matters

MRV helps exclude:

Cerebral venous sinus thrombosis

which can occur in children and may mimic IIH.

Risk factors include:

• Dehydration
• Infection
• Inflammatory disease
• Hypercoagulable states
• Malignancy

CT

CT may be appropriate when:

• MRI is unavailable
• Emergency imaging is needed
• Hydrocephalus or mass effect must be assessed rapidly

However, MRI gives superior evaluation of:

• Posterior fossa
• Venous sinuses
• Infiltrative lesions
• Craniovertebral junction

MRI Findings of Raised ICP

Supportive but nonspecific signs include:

• Empty or partially empty sella
• Enlarged perioptic CSF spaces
• Optic nerve tortuosity
• Posterior globe flattening
• Optic disc protrusion
• Venous sinus stenosis

These findings support but do not independently establish IIH.

Lumbar Puncture

After neuroimaging excludes a dangerous mass lesion or obstructive process, LP may be performed.

Evaluate:

• Opening pressure
• CSF cell count
• Protein
• Glucose
• Additional studies as indicated

Pediatric Opening Pressure

In children, an opening pressure of approximately:

≥28 cm H₂O

is generally considered elevated when measured correctly.

A lower threshold around:

≥25 cm H₂O

may be appropriate in a child who is:

• Not obese
• Not sedated

Clinical interpretation is essential.

Proper LP Technique

Opening pressure should ideally be measured:

• In lateral decubitus position
• With the child relaxed
• Without excessive Valsalva
• Without excessive hip flexion

Sedation can influence measurements.

A single borderline number should not override the overall clinical picture.

OCT

OCT is increasingly valuable in pediatric papilledema.

Assess:

• Peripapillary RNFL
• Optic nerve head volume
• Macular ganglion cell layer

OCT Interpretation

Active papilledema causes:

RNFL thickening

As edema improves:

• RNFL thickness falls

However, a fall in RNFL can represent either:

• Resolution of edema
• Axonal loss

Therefore correlate with:

• Ganglion cell layer
• Visual acuity
• Visual fields

Optic Disc Drusen

The most important cause of pediatric pseudopapilledema is:

Optic disc drusen

Children often have:

• Buried drusen
• Elevated disc appearance
• Indistinct margins

without true increased ICP.

Enhanced-Depth OCT

EDI-OCT can help identify:

• Buried optic disc drusen
• Hyperreflective calcified deposits

It is increasingly preferred over older ultrasound-only approaches.

B-Scan Ultrasonography

B-scan may demonstrate:

• Highly reflective calcified optic disc drusen
• Optic nerve sheath enlargement

It remains useful when the diagnosis is uncertain.

Fundus Autofluorescence

Superficial optic disc drusen may show:

Autofluorescence

Buried pediatric drusen may be less detectable.

Differential Diagnosis

Important mimics include:

• Optic disc drusen
• Crowded hyperopic discs
• Tilted optic discs
• Myelinated RNFL
• Optic neuritis
• Neuroretinitis
• NAION, rare in children
• Infiltrative optic neuropathy
• Hypertensive optic disc edema

Papilledema vs Pediatric Optic Neuritis

Papilledema

Usually:

• Bilateral
• Central acuity preserved early
• Symptoms of raised ICP
• Enlarged blind spot

Optic Neuritis

More likely:

• Significant acuity loss
• Dyschromatopsia
• RAPD if asymmetric
• Pain with eye movement
• Asymmetric or unilateral disease

Children with MOG-associated optic neuritis may have dramatic bilateral disc swelling, so clinical distinction can occasionally be difficult.

Neuroretinitis

Neuroretinitis typically produces:

• Optic disc edema
• Macular star

with visual loss.

Bartonella is a classic cause.

This differs from papilledema, although severe papilledema can occasionally also produce macular exudates.

Treatment Principles

There is no treatment directed specifically at the swollen optic disc.

Treatment must address:

The underlying cause of raised ICP

while protecting vision.

Hydrocephalus

Treatment may require:

• Ventriculoperitoneal shunt
• Endoscopic third ventriculostomy in selected cases
• Revision of a malfunctioning shunt

Shunt Malfunction

Children with ventricular shunts may develop:

• Headache
• Vomiting
• Lethargy
• Diplopia
• Visual changes

Papilledema may recur, but:

A normal optic disc does not exclude shunt malfunction, especially in infants or children with prior optic atrophy.

Pediatric IIH – Weight Management

In children with obesity, particularly adolescents:

Gradual weight reduction is disease-modifying therapy.

Management should be developmentally appropriate and often involves:

• Pediatrician
• Dietitian
• Endocrinology or obesity specialist

Aggressive calorie restriction is inappropriate in growing children.

Acetazolamide

Acetazolamide is the principal medication used to lower ICP in pediatric IIH.

It works by decreasing:

CSF production

Dosing is weight-based and individualized.

A commonly used starting range is approximately:

15–25 mg/kg/day divided into several doses

with titration according to:

• Response
• Tolerance
• Severity

Higher doses may be used under specialist supervision.

Acetazolamide Adverse Effects

Potential adverse effects include:

• Paresthesias
• Fatigue
• GI symptoms
• Dysgeusia
• Metabolic acidosis
• Electrolyte abnormalities
• Kidney stones

Monitor:

• Electrolytes
• Renal function

when treatment is prolonged or high-dose.

Topiramate

Topiramate may be useful when:

• Headache is prominent
• Weight management is relevant
• Acetazolamide is poorly tolerated

Potential adverse effects include:

• Cognitive slowing
• Paresthesias
• Appetite suppression
• Nephrolithiasis

Rarely it can cause:

Acute bilateral angle closure with myopic shift

Furosemide

Furosemide may be used as:

• Adjunctive therapy
• Alternative when acetazolamide cannot be used

Evidence is weaker than for acetazolamide.

Corticosteroids

Systemic corticosteroids are not routine treatment for pediatric IIH.

They can cause:

• Weight gain
• Systemic toxicity
• Rebound intracranial hypertension during withdrawal

Steroids are reserved for specific underlying inflammatory or mass-related conditions.

Repeated Lumbar Punctures

Older teaching suggested serial LPs as treatment.

Modern practice:

Repeated lumbar punctures are not routine definitive therapy for IIH and are not reliably curative.

CSF is rapidly regenerated.

LP may occasionally be used as a:

• Short-term temporizing measure

while definitive therapy is arranged.

Optic Nerve Sheath Fenestration

ONSF may be considered for:

• Progressive visual field loss
• Severe papilledema
• Failure of medical treatment
• Vision-threatening IIH

It is particularly useful when:

• Vision is the dominant concern

rather than headache.

CSF Diversion

Options include:

• Ventriculoperitoneal shunt
• Lumboperitoneal shunt

VP shunting is often preferred in many centers.

Indications include:

• Progressive visual loss
• Medically refractory ICP elevation
• Fulminant disease

Fulminant Pediatric IIH

Rapidly progressive papilledema with visual loss is an emergency.

Urgent treatment may require:

• ONSF
• CSF diversion

rather than prolonged trials of medication.

Brain Tumor

Management may require:

• Neurosurgical resection
• Oncology treatment
• CSF diversion
• Corticosteroids for tumor-associated vasogenic edema when appropriate

Cerebral Venous Sinus Thrombosis

CVST generally requires:

Anticoagulation

under pediatric neurology/hematology supervision, unless there is a specific contraindication.

Medication-Induced Intracranial Hypertension

Potential offending drugs should be discontinued when possible.

Important examples:

• Tetracyclines
• Isotretinoin/other systemic retinoids
• Growth hormone in selected cases

Do not combine tetracycline-class antibiotics with systemic retinoids because both are associated with intracranial hypertension.

Craniosynostosis

Treatment may require:

• Craniofacial surgery
• Neurosurgical decompression

Ophthalmic follow-up remains important before and after surgery.

Referral

Children with suspected papilledema generally require urgent coordination between:

• Pediatric ophthalmology / neuro-ophthalmology
• Pediatric neurology
• Neurosurgery

Depending on cause:

• Neuro-oncology
• Hematology
• Endocrinology
• Craniofacial surgery

may be required.

Follow-Up

Follow-up frequency depends on:

• Severity of papilledema
• Visual field status
• Underlying diagnosis
• Rate of progression

Vision-threatening disease may require reassessment within:

Days to weeks

Monitoring

Serial ophthalmic examinations should include:

• Visual acuity
• Pupils
• Color vision
• Optic disc examination
• Fundus photography
• OCT
• Visual fields when reliable

Children With Shunts

Periodic ophthalmic surveillance can help detect recurrent elevated ICP.

However:

The eye examination should never be used as the sole test of shunt function.

Papilledema may be absent despite shunt failure.

Resolution of Papilledema

Disc edema may take:

Several weeks

to resolve after ICP has normalized.

Therefore, persistent swelling immediately after successful treatment does not necessarily indicate treatment failure.

Prognosis

When elevated ICP is identified and treated promptly:

Visual prognosis is generally good

Poorer outcomes occur with:

• Severe papilledema
• Delayed diagnosis
• Recurrent raised ICP
• Shunt malfunction
• Fulminant IIH
• Established optic atrophy

Optic Atrophy

Long-standing pressure may cause irreversible:

• RNFL loss
• Optic pallor
• Visual field loss
• Central visual loss

Once optic atrophy occurs:

Normalization of ICP cannot restore lost axons.

Patient and Family Education

Families should understand warning symptoms of recurrent raised ICP:

• New or worsening headache
• Vomiting
• Lethargy
• New strabismus or diplopia
• Transient visual obscurations
• New visual loss
• Seizure
• Behavioral change

Children with shunts require particular vigilance for:

Shunt malfunction

Complications

Potential complications include:

• Permanent visual field loss
• Optic atrophy
• Reduced visual acuity
• CN VI palsy
• Chronic headache

Underlying disease may also produce:

• Neurologic injury
• Seizures
• Hydrocephalus
• Stroke
• Death

Treatment complications include:

• Medication toxicity
• Post-LP headache
• Shunt infection
• Shunt obstruction
• Shunt revision
• ONSF-related diplopia or optic nerve injury

Ophthalmology Pearls

• Papilledema in children = optic disc swelling from elevated intracranial pressure.
• Infants with open sutures or fontanelles may have markedly elevated ICP without papilledema.
• The same is true after severe optic atrophy: a damaged optic nerve may be unable to swell.
• In young children, raised ICP may present with irritability, lethargy, vomiting, increasing head circumference, or new strabismus rather than a verbalized headache.
• Sixth nerve palsy is the classic ocular motor manifestation of raised ICP.
• Early papilledema may have normal visual acuity, whereas pediatric optic neuritis usually causes more prominent acuity and color loss.
• The most important pseudopapilledema mimic is buried optic disc drusen.
• MRI brain plus MRV is preferred when papilledema is suspected and the child is stable enough for MRI.
• Pediatric LP opening pressure around ≥28 cm H₂O is generally considered elevated; interpretation depends on obesity, sedation, and technique.
• In adolescents with obesity and IIH, weight management plus acetazolamide are standard initial treatments.
• Systemic corticosteroids and serial lumbar punctures are not routine long-term therapy for IIH.
• Rapidly progressive visual loss from fulminant IIH requires urgent surgical consideration.
• Papilledema can take weeks to resolve after ICP normalizes.
• In a child with a ventricular shunt, absence of papilledema does not exclude shunt malfunction.

Ophthalmology – Papilledema

Basics

Description

Papilledema is optic disc swelling caused specifically by elevated intracranial pressure (ICP).

It is usually:

• Bilateral
• Relatively symmetric

but may be:

• Markedly asymmetric
• Rarely apparently unilateral

Papilledema is a sign rather than a diagnosis. The underlying cause of raised ICP must be identified.

Clinical Importance

Papilledema may signal a potentially life-threatening disorder, including:

• Intracranial mass lesion
• Cerebral venous sinus thrombosis (CVST)
• Hydrocephalus
• Meningitis or encephalitis
• Intracranial hemorrhage
• Severe cerebral edema

Therefore:

New true papilledema requires urgent neurologic evaluation and neuroimaging.

Papilledema vs Optic Disc Edema

These terms should not be used interchangeably.

Papilledema

Optic disc edema specifically due to:

Raised ICP

Other Causes of Optic Disc Edema

Include:

• Optic neuritis
• NAION
• AAION
• Neuroretinitis
• Infiltrative optic neuropathy
• Compressive optic neuropathy
• Malignant hypertension

Epidemiology

The epidemiology depends on the underlying cause.

A common cause encountered in neuro-ophthalmology is:

Idiopathic intracranial hypertension (IIH)

IIH most commonly affects:

• Women of reproductive age
• Patients with obesity
• Patients with recent weight gain

However, IIH can occur outside this classic demographic.

Pediatric Considerations

Before puberty:

• IIH has less female predominance
• Obesity is a less consistent association

After puberty, the demographic pattern becomes more similar to adults.

Risk Factors for IIH

Important associations include:

• Obesity
• Recent weight gain
• Female sex after puberty
• Obstructive sleep apnea

Drugs associated with intracranial hypertension include:

• Tetracyclines
• Vitamin A derivatives / retinoids
• Growth hormone
• Lithium in selected cases

Medication history should be reviewed carefully.

Risk Factors for CVST

Important risk factors include:

• Pregnancy and postpartum state
• Estrogen-containing contraception
• Hypercoagulable disorders
• Malignancy
• Systemic infection
• Severe dehydration
• Inflammatory disease

CVST may cause:

• Papilledema
• Stroke
• Seizure
• Intracranial hemorrhage

Pathophysiology

Raised CSF pressure is transmitted through the subarachnoid space surrounding the optic nerve.

This causes:

Elevated retrolaminar pressure → impaired axoplasmic transport → axonal swelling

Secondary effects include:

• Venous congestion
• Capillary leakage
• Hemorrhage
• Peripapillary folds

With prolonged disease:

• Axons are lost
• Optic atrophy develops
• Permanent visual loss may occur

Monro-Kellie Principle

Intracranial volume is composed mainly of:

• Brain tissue
• Blood
• CSF

Because the cranial vault is relatively fixed, expansion of one component without adequate compensation can elevate ICP.

Etiology

Important causes include:

• Idiopathic intracranial hypertension
• Cerebral venous sinus thrombosis
• Intracranial mass
• Hydrocephalus
• Meningitis
• Encephalitis
• Intracranial hemorrhage
• Cerebral edema
• Craniosynostosis
• Venous outflow obstruction
• Rare spinal cord or spinal subarachnoid lesions

Idiopathic Intracranial Hypertension

IIH is raised ICP without an identifiable structural, vascular, or CSF cause.

Historically called:

Pseudotumor cerebri

Diagnostic Features of IIH

Typical criteria include:

• Papilledema
• Otherwise normal neurologic examination except possible cranial nerve abnormalities, especially CN VI palsy
• Neuroimaging showing no mass or hydrocephalus
• Normal CSF composition
• Elevated lumbar puncture opening pressure

In adults, an opening pressure around:

≥25 cm H₂O

supports the diagnosis when measured correctly and interpreted in context.

History

Ask about symptoms of:

• Raised ICP
• Underlying neurologic disease
• Venous thrombosis
• Infection

Important symptoms include:

• Headache
• Nausea
• Vomiting
• Pulsatile tinnitus
• Transient visual obscurations
• Diplopia
• Progressive visual loss

Headache

Headache is common but nonspecific.

It may be:

• Daily or near-daily
• Worse on awakening
• Worse when lying flat
• Worse with coughing or Valsalva
• Migraine-like

Importantly:

Headache severity does not reliably predict the severity of papilledema or visual loss.

Pulsatile Tinnitus

A classic symptom is:

Pulse-synchronous whooshing tinnitus

It is thought to relate to turbulent venous flow.

Transient Visual Obscurations

Patients may experience brief episodes of:

• Graying
• Dimming
• Blackout of vision

usually lasting:

Seconds

Often triggered by:

• Standing
• Bending
• Position change

These are strongly associated with optic disc swelling but do not themselves indicate permanent visual loss.

Diplopia

Diplopia most commonly results from:

Sixth nerve palsy

which may be:

• Unilateral
• Bilateral

CN VI palsy is a classic false-localizing sign of raised ICP.

Visual Acuity

In early papilledema:

Central visual acuity is often normal

Reduced acuity may indicate:

• Advanced papilledema
• Macular edema
• Choroidal folds
• Another optic neuropathy

Color Vision

Usually preserved early.

Progressive dyschromatopsia suggests:

• Optic nerve dysfunction
• Axonal injury
• Advanced disease

Pupils

Pupillary responses are generally normal early.

A RAPD may occur when papilledema or optic nerve injury is:

• Markedly asymmetric

Visual Fields

Early abnormalities commonly include:

• Enlarged blind spot
• Nasal defects
• Arcuate defects

Progressive disease may produce:

• Nasal step
• Peripheral constriction
• Generalized depression
• Central loss in advanced cases

Serial automated perimetry is crucial for monitoring.

Fundus Findings

Early papilledema may show:

• Blurring of disc margins
• RNFL opacification
• Loss of physiologic cup
• Vessel obscuration at the disc edge
• Disc elevation

Spontaneous Venous Pulsation

Loss of spontaneous venous pulsation may occur with elevated ICP.

However:

Absence of spontaneous venous pulsation is not diagnostic, because it may also be absent in normal individuals.

Visible spontaneous venous pulsation makes markedly elevated ICP less likely but does not absolutely exclude it.

Moderate Papilledema

More advanced findings include:

• Disc hyperemia
• Increased elevation
• Venous engorgement
• Peripapillary hemorrhages
• Cotton-wool spots
• Hard exudates
• Retinal folds

Paton Lines

Paton lines are concentric folds around the optic nerve caused by mechanical distortion of the peripapillary retina.

They are characteristic of significant optic disc swelling.

Choroidal Folds

Papilledema may produce:

• Horizontal choroidal folds
• Macular folds

These may cause:

• Metamorphopsia
• Reduced visual acuity

Macular Star

Hard exudates may occasionally form a:

Macular star

This may mimic neuroretinitis.

The overall clinical context is important.

Severe Papilledema

Severe disease may produce:

• Extensive hemorrhages
• Subhyaloid hemorrhage
• Vitreous hemorrhage
• Retinal vascular occlusion
• Macular edema

Chronic Papilledema

Long-standing papilledema may eventually lead to:

• Optic disc pallor
• Gliosis
• RNFL thinning
• Permanent visual field loss
• Optic atrophy

An important point:

An atrophic optic nerve may stop swelling even when ICP remains elevated.

Thus, disappearance of disc edema does not always mean successful treatment.

Frisén Grading

Papilledema can be graded using the:

Frisén scale

ranging from:

Grade 0 to Grade 5

It provides a semiquantitative description of disc swelling.

Visual function must still be assessed independently with:

• Acuity
• Visual fields
• OCT

Diagnostic Approach

The evaluation should answer:

1. Is there true optic disc edema?
2. Is it due to raised intracranial pressure?
3. What is causing the raised ICP?

Neuroimaging

Urgent imaging is required before lumbar puncture in most patients with suspected papilledema.

Preferred study:

MRI brain with and without contrast

plus:

MR venography

to evaluate the cerebral venous sinuses.

Why MRV/CTV Is Important

Venous imaging helps exclude:

Cerebral venous sinus thrombosis

which may closely mimic IIH.

MRV or CTV is especially important when:

• The patient does not fit the classic IIH demographic
• Thrombotic risk factors are present
• Symptoms are acute or atypical

In modern practice, venous imaging is commonly incorporated into the workup of confirmed papilledema.

CT

CT may be used when:

• MRI is unavailable
• Emergency imaging is needed immediately

However, MRI is more sensitive for many structural causes.

MRI Findings Associated With Raised ICP

Supportive but nonspecific findings include:

• Empty or partially empty sella
• Enlarged perioptic CSF spaces
• Optic nerve tortuosity
• Posterior globe flattening
• Optic disc protrusion
• Transverse venous sinus stenosis

These findings support but do not independently establish IIH.

Venous Sinus Stenosis

Transverse sinus stenosis is common in IIH.

It may be:

• A contributor to raised ICP
• A consequence of raised ICP
• Both

Its presence alone is not diagnostic.

Lumbar Puncture

After appropriate imaging has excluded a dangerous mass or obstructive process, LP is performed to assess:

• Opening pressure
• CSF cell count
• Protein
• Glucose
• Additional infectious/inflammatory studies when indicated

Opening Pressure Technique

Opening pressure should ideally be measured:

• In lateral decubitus position
• With the patient relaxed
• Without excessive hip flexion or Valsalva
• Before significant CSF removal

A single pressure reading should always be interpreted in clinical context.

OCT

OCT is extremely useful for monitoring papilledema.

Assess:

• Peripapillary RNFL
• Optic nerve head volume
• Macular ganglion cell layer

Important OCT Principle

In active papilledema:

• RNFL becomes thick

As the edema improves:

• RNFL thickness falls

However, decreasing RNFL may mean either:

• Resolution of edema
• Development of optic atrophy

Therefore, correlate with:

• Ganglion cell analysis
• Visual fields
• Visual acuity

Fundus Photography

Serial disc photographs help document:

• Disc elevation
• Hemorrhages
• Vascular changes
• Treatment response

Optic Disc Ultrasound

B-scan ultrasonography may help distinguish papilledema from:

Optic disc drusen

Other useful modalities include:

• Enhanced-depth imaging OCT
• Fundus autofluorescence

Differential Diagnosis

Important mimics include:

• Optic disc drusen
• Crowded hyperopic discs
• Tilted discs
• Myelinated nerve fibers
• Congenital disc anomalies
• Optic neuritis
• NAION
• AAION
• Neuroretinitis
• Infiltrative optic neuropathy
• Compressive optic neuropathy
• Malignant hypertension

Papilledema vs Optic Disc Drusen

Papilledema favors:

• True edema
• Vessel obscuration
• Hyperemia
• Hemorrhage
• Symptoms of raised ICP

Optic disc drusen favors:

• Lumpy disc surface
• Little hyperemia
• Minimal hemorrhage
• Hyperreflective deposits on OCT
• Autofluorescence if superficial

Buried drusen in children can be particularly difficult to distinguish.

Treatment Principles

Treatment is directed toward:

The cause of intracranial hypertension

while preserving:

• Vision
• Neurologic function
• Life

IIH Treatment Goals

The main goals are:

1. Preserve vision
2. Reduce ICP
3. Treat headache
4. Modify disease risk factors

Weight Loss

For patients with overweight or obesity:

Weight loss is the major disease-modifying treatment for IIH.

Sustained weight reduction may:

• Lower ICP
• Improve papilledema
• Produce remission

Even modest weight loss may help, while greater sustained loss is often needed for durable control.

Bariatric Surgery

For selected patients with:

• Severe obesity
• Persistent IIH
• Inadequate response to conventional weight management

bariatric surgery can produce substantial long-term improvement.

Acetazolamide

Acetazolamide is the principal medication for IIH when papilledema or visual dysfunction is present.

Mechanism:

Decreases CSF production via carbonic anhydrase inhibition

Acetazolamide Dosing

Dose is individualized according to:

• Disease severity
• Visual field loss
• Tolerance

Treatment often begins with a modest dose and is increased as needed.

Acetazolamide Adverse Effects

Common adverse effects include:

• Paresthesias
• Fatigue
• Dysgeusia
• GI upset
• Kidney stones
• Metabolic acidosis
• Electrolyte abnormalities

Monitor:

• Renal function
• Electrolytes

when clinically appropriate.

Topiramate

Topiramate may help because it can:

• Treat migraine-type headache
• Promote weight loss
• Produce mild carbonic anhydrase inhibition

Potential adverse effects include:

• Cognitive slowing
• Paresthesias
• Mood change
• Nephrolithiasis

It can rarely cause:

Acute bilateral angle closure with myopic shift

Furosemide

May occasionally be used as an adjunct when:

• Acetazolamide is not tolerated
• Additional ICP reduction is required

Evidence is less robust.

Corticosteroids

Corticosteroids are not routine long-term treatment for IIH.

They may:

• Cause weight gain
• Produce systemic toxicity
• Cause rebound raised ICP during withdrawal

They remain useful for selected underlying causes such as:

• Vasogenic edema from certain brain tumors
• Inflammatory CNS disease

Serial Lumbar Punctures

Repeated LPs are not recommended for routine long-term treatment because CSF is rapidly replaced.

They may occasionally be used as a temporary bridge while:

• Definitive treatment is arranged
• Pregnancy limits other options

Fulminant IIH

Fulminant IIH involves:

• Rapidly developing severe papilledema
• Rapid visual deterioration

This is a neuro-ophthalmic emergency.

Urgent treatment may require:

• Optic nerve sheath fenestration
• CSF diversion
• Other rapid ICP-lowering intervention

Optic Nerve Sheath Fenestration

ONSF reduces pressure around the optic nerve by creating an opening in the optic nerve sheath.

It is especially considered when:

• Vision is progressively worsening
• Papilledema is severe
• Medical treatment is insufficient
• Headache is not the dominant problem

ONSF Complications

Potential complications include:

• Diplopia
• Optic nerve injury
• Vascular injury
• Visual loss
• Recurrence of papilledema

CSF Diversion

Options include:

• Ventriculoperitoneal shunt
• Lumboperitoneal shunt

VP shunts are commonly favored in many centers.

Indications include:

• Progressive visual loss
• Medically refractory disease
• Fulminant IIH

Shunt Complications

Include:

• Obstruction
• Infection
• Migration
• Overdrainage
• Low-pressure headache
• Need for revision

Venous Sinus Stenting

Venous sinus stenting may be considered for selected patients with:

• Medically refractory IIH
• Significant venous sinus stenosis
• Demonstrable trans-stenotic pressure gradient
• Appropriate neurointerventional evaluation

It should not be performed simply because MRV shows sinus narrowing.

CVST Treatment

Cerebral venous sinus thrombosis generally requires:

Systemic anticoagulation

with management by:

• Neurology/stroke team
• Hematology when appropriate

Intracranial Mass

Treatment may include:

• Neurosurgery
• Oncology therapy
• Corticosteroids for vasogenic edema when appropriate
• CSF diversion

depending on etiology.

Meningitis

Requires urgent cause-specific antimicrobial treatment.

Papilledema in suspected meningitis increases concern about raised ICP and the safety of immediate lumbar puncture.

Pregnancy

IIH may occur or recur during pregnancy.

Management balances:

• Maternal vision
• Maternal health
• Fetal safety

Acetazolamide During Pregnancy

Older teaching recommended complete avoidance.

Modern practice is more individualized.

Acetazolamide is often:

• Avoided when possible during the first trimester
• Considered later, or earlier in vision-threatening disease, when benefits outweigh potential fetal risks

Care should be coordinated with:

• Obstetrics
• Neurology
• Neuro-ophthalmology

Surgical Treatment in Pregnancy

When vision is threatened, options may include:

• Optic nerve sheath fenestration
• CSF diversion
• Temporary lumbar puncture

depending on severity and gestational considerations.

Follow-Up

Follow-up frequency depends on:

• Frisén grade
• Visual field status
• Acuity
• Rate of change
• Treatment response

Severe or rapidly progressive disease may require review within:

Days to weeks

Monitoring

At follow-up, assess:

• Visual acuity
• Pupils
• Color vision
• Optic disc appearance
• OCT
• Automated visual fields
• Symptoms

Headache vs Papilledema

Headache and papilledema should be monitored separately.

A patient may have:

• Resolved papilledema
• Persistent migraine-like headache

Persistent headache alone does not necessarily indicate persistent raised ICP.

Patient Education

Patients should seek urgent reassessment for:

• New visual loss
• Increasing transient visual obscurations
• New diplopia
• Severe worsening headache
• Repeated vomiting
• Seizure
• Focal neurologic symptoms

Prognosis

Visual prognosis is generally excellent when:

• Papilledema is mild
• Visual fields are preserved
• The cause is treated promptly

Poor prognostic factors include:

• Severe papilledema
• Delayed treatment
• Rapid progression
• Significant field loss at presentation
• Optic atrophy

Complications

Potential complications include:

• Permanent visual field loss
• Reduced central acuity
• Optic atrophy
• Chronic headache
• Diplopia from CN VI palsy

Treatment-related complications include:

• Acetazolamide toxicity
• Post-LP headache
• CSF leak
• Shunt infection/failure
• ONSF complications
• Venous stent complications

Ophthalmology Pearls

• Papilledema = optic disc edema specifically due to raised intracranial pressure.
• It is usually bilateral but may be markedly asymmetric.
• True papilledema can indicate brain mass, CVST, hydrocephalus, meningitis, or other life-threatening disease.
• Early central acuity may remain normal; visual field testing is often more sensitive to early functional loss.
• The classic early field defect is enlargement of the blind spot.
• Transient visual obscurations, pulsatile tinnitus, and CN VI palsy are classic symptoms/signs of raised ICP.
• Loss of spontaneous venous pulsation is supportive but not diagnostic.
• MRI brain plus MRV/CTV should exclude mass lesion and venous sinus thrombosis before labeling a patient as IIH.
• After appropriate imaging, lumbar puncture confirms opening pressure and normal CSF composition.
• In adults, ≥25 cm H₂O supports elevated opening pressure when measured correctly.
• OCT is useful, but a falling RNFL thickness can reflect either resolution of edema or optic atrophy.
• In IIH, weight loss is the key disease-modifying treatment.
• Acetazolamide is the main medication used to protect vision in IIH.
• Routine long-term corticosteroids and serial lumbar punctures are generally not recommended for IIH.
• Fulminant IIH with rapidly declining vision requires urgent surgical consideration.
• An optic nerve that has become atrophic may stop swelling despite persistent high ICP, so “less swelling” does not always mean recovery.

Ophthalmology – Paget Disease of Bone

Basics

Description

Paget disease of bone is a chronic disorder of focal bone remodeling characterized by:

• Excessive osteoclastic bone resorption
• Compensatory but disorganized osteoblastic bone formation
• Structurally enlarged but mechanically abnormal bone

Affected bone may become:

• Thickened
• Deformed
• Hypervascular
• Fragile

Many patients are asymptomatic.

Potential complications include:

• Bone pain
• Pathologic fracture
• Skeletal deformity
• Osteoarthritis
• Hearing loss
• Cranial nerve compression
• Rare malignant transformation

Important ophthalmic manifestations include:

• Angioid streaks
• Secondary choroidal neovascularization (CNV)
• Compressive optic neuropathy from skull involvement
• Rare orbital involvement by sarcomatous transformation

Epidemiology

Paget disease primarily affects:

• Older adults
• Usually patients >50 years

Prevalence rises with age.

It is more common in:

• People of European ancestry
• Historically, populations from the United Kingdom and other regions with British ancestry

Its prevalence has declined in many countries over recent decades.

Risk Factors

The cause is incompletely understood.

Risk factors include:

• Increasing age
• Family history
• Genetic susceptibility
• Geographic and ethnic background

Older hypotheses proposed chronic viral infection as a trigger, but a specific viral cause has not been established.

Genetics

Familial disease occurs in a minority of patients.

The best-known gene association is:

SQSTM1

which may produce autosomal dominant familial Paget disease with variable penetrance.

Other genes affecting osteoclast biology have also been identified.

Pathophysiology

Paget disease usually progresses through phases:

Osteolytic Phase

Excessive osteoclastic bone resorption.

Mixed Phase

Simultaneous increased:

• Osteoclastic resorption
• Osteoblastic bone formation

Sclerotic / Burned-Out Phase

Predominantly disorganized bone formation.

The resulting bone has:

• Abnormal architecture
• Increased vascularity
• Reduced mechanical strength

Histopathology

The classic pathologic finding is:

Mosaic pattern of lamellar bone

with irregular cement lines.

There may also be:

• Marrow fibrosis
• Increased local blood flow
• Increased osteoblastic and osteoclastic activity

Commonly Affected Bones

Paget disease commonly affects:

• Pelvis
• Spine
• Femur
• Skull
• Tibia

Less commonly:

• Humerus
• Clavicle

Disease may be:

• Monostotic
• Polyostotic

Skull Involvement

Pagetic skull disease may cause:

• Enlarged head
• Frontal bossing
• Headache
• Hearing loss
• Cranial neuropathies
• Rare optic nerve compression

Skull involvement is particularly relevant to ophthalmology.

Hearing Loss

Hearing impairment is one of the classic complications of skull Paget disease.

Mechanisms may include:

• Abnormal temporal bone remodeling
• Ossicular dysfunction
• Cochlear or neural involvement

Ocular Manifestations

The major ocular associations include:

• Angioid streaks
• CNV
• Subretinal hemorrhage
• Optic neuropathy
• Rare orbital sarcoma

Angioid Streaks

Angioid streaks are:

Crack-like breaks in an abnormal, calcified, or brittle Bruch membrane

They appear as:

• Irregular
• Reddish-brown to gray
• Radiating lines extending from the optic disc

They are usually:

• Bilateral
• Asymmetric

Pathophysiology of Angioid Streaks

In Paget disease, systemic abnormalities in connective tissue and mineralization can produce:

Thickening and fragility of Bruch membrane

Breaks then develop in Bruch membrane and may extend outward from the optic nerve.

Other Associations of Angioid Streaks

Important associations include:

• Pseudoxanthoma elasticum
• Paget disease
• Sickle cell disease and other hemoglobinopathies
• Occasionally other connective tissue disorders
• Idiopathic cases

The classic mnemonic PEPSI is historically used, but pseudoxanthoma elasticum is the strongest systemic association.

Fundus Appearance

Angioid streaks may appear:

• Dark red
• Brown
• Gray

and radiate outward from the optic nerve.

Associated findings may include:

• RPE mottling
• RPE atrophy
• Focal pigment clumping

Peau d’Orange

Peau d’orange refers to a mottled orange-peel appearance of the temporal or midperipheral fundus.

It is more classically associated with:

Pseudoxanthoma elasticum

and may coexist with angioid streaks.

It is not specific for Paget disease.

Choroidal Neovascularization

The most important vision-threatening complication of angioid streaks is:

Choroidal neovascularization

CNV can develop through breaks in Bruch membrane.

Symptoms include:

• Metamorphopsia
• Central blur
• Central scotoma
• Sudden visual loss

Subretinal Hemorrhage

Because Bruch membrane is fragile, even relatively minor ocular trauma may cause:

• Choroidal rupture
• Subretinal hemorrhage

Patients with angioid streaks should therefore avoid significant ocular trauma.

Compressive Optic Neuropathy

Severe skull involvement may rarely cause:

• Optic canal narrowing
• Optic nerve compression

Clinical findings may include:

• Decreased visual acuity
• Dyschromatopsia
• RAPD
• Visual field loss
• Optic atrophy

This is an uncommon but important neuro-ophthalmic complication.

Orbital Sarcoma

Pagetic bone has an increased risk of malignant transformation.

Rare orbital or craniofacial tumors may include:

• Osteosarcoma
• Other sarcomas

Warning features include:

• New severe bone pain
• Rapidly enlarging mass
• New proptosis
• Cranial neuropathy
• Sudden worsening of previously stable symptoms

Associated Systemic Conditions

Complications of extensive disease may include:

• Secondary osteoarthritis
• Pathologic fractures
• Spinal stenosis
• Nerve compression
• Hearing loss
• High-output cardiac failure in very extensive active disease
• Rare osteosarcoma

History

Many patients are asymptomatic and are diagnosed after:

• Elevated alkaline phosphatase
• Incidental abnormal radiograph

When symptomatic, ask about:

• Bone pain
• Fractures
• Hearing loss
• Headache
• Increased hat size
• Bowing of long bones
• Back pain
• Weakness or numbness

Ophthalmic History

Ask about:

• Decreased central vision
• Metamorphopsia
• Scotoma
• Sudden visual decline
• Previous subretinal hemorrhage
• Ocular trauma

These symptoms raise concern for:

CNV or choroidal rupture

Physical Examination

Systemic findings may include:

• Enlarged skull
• Frontal bossing
• Tibial bowing
• Skeletal deformity
• Warmth over active pagetic bone

Neurologic examination should assess for:

• Hearing impairment
• Cranial neuropathies
• Spinal cord or nerve-root compromise

Ophthalmic Examination

Evaluate:

• Visual acuity
• Pupils
• Color vision
• Amsler grid
• Dilated fundus
• Macula
• Optic nerve

Look for:

• Angioid streaks
• RPE changes
• Subretinal hemorrhage
• CNV
• Optic atrophy

Laboratory Testing

The most useful laboratory marker is:

Serum total alkaline phosphatase (ALP)

It is usually elevated when disease is metabolically active and sufficiently extensive.

Alkaline Phosphatase

ALP is useful for:

• Diagnosis
• Assessing disease activity
• Monitoring response to treatment

However, ALP may be normal in:

• Limited monostotic disease
• Inactive disease

If liver disease may confound interpretation, bone-specific ALP can be helpful.

Calcium and Phosphate

Serum:

• Calcium
• Phosphate

are usually normal.

Hypercalcemia should prompt consideration of:

• Prolonged immobilization
• Hyperparathyroidism
• Another metabolic disorder

rather than being attributed automatically to Paget disease.

Vitamin D

Before bisphosphonate therapy, assess and correct:

• Vitamin D deficiency
• Hypocalcemia

because antiresorptive therapy may precipitate or worsen hypocalcemia.

Renal Function

Check renal function before IV bisphosphonate therapy.

Significant renal impairment may limit use of:

Zoledronic acid

Imaging

Plain Radiography

Typical radiographic findings include:

• Cortical thickening
• Bone enlargement
• Coarse trabeculation
• Mixed lytic and sclerotic change

In the skull, a classic late appearance is:

“Cotton wool” skull

Bone Scan

Radionuclide bone scintigraphy is highly sensitive for determining:

• Extent of skeletal involvement
• Distribution of active disease

Pagetic lesions show:

Increased tracer uptake

CT and MRI

CT or MRI is useful when evaluating:

• Neurologic compression
• Optic canal involvement
• Suspected sarcoma
• Spinal stenosis
• Skull-base disease

They are not routinely needed for uncomplicated disease.

Ophthalmic Imaging

Optical Coherence Tomography

OCT is essential when CNV is suspected.

It can demonstrate:

• Subretinal fluid
• Intraretinal fluid
• Pigment epithelial detachment
• Subretinal hyperreflective material

Fluorescein Angiography

FA may help demonstrate:

• CNV leakage
• Lesion extent

It is less routinely required when OCT clearly establishes active CNV.

OCT Angiography

OCTA may demonstrate:

• Neovascular vascular networks

without dye injection.

It may assist with:

• Diagnosis
• Follow-up

but structural OCT remains essential for activity assessment.

Differential Diagnosis

Important systemic differentials include:

• Osteomalacia
• Hyperparathyroidism
• Vitamin D deficiency
• Bone metastasis
• Multiple myeloma
• Fibrous dysplasia
• Osteosarcoma

Differential Diagnosis of Angioid Streaks

Consider:

• Pseudoxanthoma elasticum
• Sickle cell disease
• Other hemoglobinopathies
• Idiopathic angioid streaks
• Choroidal rupture

Treatment Principles

Treatment of Paget disease is aimed at:

• Suppressing excessive bone turnover
• Relieving bone pain
• Preventing or treating complications

Not every asymptomatic patient requires treatment.

Bisphosphonates

Bisphosphonates are the main treatment.

They inhibit:

Osteoclast-mediated bone resorption

Zoledronic Acid

For most patients requiring treatment, the preferred regimen is:

Zoledronic acid 5 mg IV as a single infusion

It usually produces:

• Rapid biochemical remission
• Prolonged suppression of disease activity
• Durable symptom control

It is generally more effective than older oral regimens.

Indications for Treatment

Treatment is generally considered for:

• Symptomatic active disease
• Significant bone pain attributable to Paget disease
• Neurologic complications
• Active disease at sites where progression could cause complications
• Hypercalcemia related to immobilization in active disease
• Before selected orthopedic procedures involving highly active pagetic bone

Treatment decisions should be individualized.

Oral Bisphosphonates

Alternatives when IV zoledronic acid is unsuitable include:

• Risedronate
• Alendronate

They are effective but generally produce less durable remission than zoledronic acid.

Calcitonin

Calcitonin is now:

Rarely used

It may be considered when bisphosphonates are contraindicated or not tolerated.

Bisphosphonate Adverse Effects

Potential adverse effects include:

• Acute flu-like reaction after IV infusion
• Hypocalcemia
• Renal toxicity
• Musculoskeletal pain
• Esophagitis with oral agents
• Rare osteonecrosis of the jaw
• Rare atypical femoral fracture with prolonged exposure

Ocular inflammatory reactions such as:

• Uveitis
• Episcleritis
• Scleritis

are uncommon but recognized.

Oral Bisphosphonate Administration

Oral agents should usually be taken:

• First thing in the morning
• With plain water
• On an empty stomach

Patients should remain upright and avoid food or other medication for the recommended interval.

This reduces:

• Esophageal irritation
• Impaired absorption

Calcium and Vitamin D

Adequate:

• Calcium
• Vitamin D

should be ensured before and after bisphosphonate therapy unless contraindicated.

Treatment of Angioid Streaks

There is:

No treatment for angioid streaks themselves

Management focuses on preventing and treating complications.

Treatment of CNV

The modern first-line treatment for CNV associated with angioid streaks is:

Intravitreal anti-VEGF therapy

Examples include:

• Bevacizumab
• Ranibizumab
• Aflibercept
• Faricimab in selected settings

Treatment is guided by:

• OCT activity
• Visual response
• Recurrent fluid or hemorrhage

Historical CNV Treatments

Older therapies such as:

• Thermal laser photocoagulation
• Photodynamic therapy

have largely been replaced by anti-VEGF because they generally provide inferior visual outcomes or have more limited indications.

Amsler Grid Monitoring

Patients with angioid streaks can use an:

Amsler grid

to detect:

• New metamorphopsia
• New central scotoma

Any new distortion should prompt urgent retinal evaluation.

Protective Eyewear

Because Bruch membrane is fragile, recommend:

Protective eyewear for activities with risk of ocular trauma

This may reduce the risk of traumatic:

• Choroidal rupture
• Subretinal hemorrhage

Optic Neuropathy Management

If visual loss is suspected to result from optic canal compression:

• Obtain orbital/skull imaging
• Coordinate with neurology/neurosurgery/endocrinology or metabolic bone specialists as appropriate
• Treat active Paget disease

Decompressive surgery is reserved for carefully selected cases.

Orthopedic Surgery

Surgery may be required for:

• Severe osteoarthritis
• Fracture
• Major deformity
• Spinal stenosis

Historically, pretreatment of active Paget disease with bisphosphonate was used to reduce surgical blood loss, but evidence for routine preoperative treatment solely for this purpose is limited.

Referral

Consider referral to:

• Endocrinology or metabolic bone specialist
• Ophthalmology/retina
• Neuro-ophthalmology
• Orthopedics
• Neurosurgery

depending on complications.

Follow-Up

Monitor according to:

• Symptoms
• Disease activity
• Treatment response

Serum ALP is commonly rechecked after therapy to document biochemical response.

Once remission is achieved, monitoring intervals can be lengthened.

Ophthalmic Follow-Up

Patients with angioid streaks should undergo periodic:

• Dilated retinal examination
• OCT when symptoms or macular changes arise

Closer follow-up is required after:

• CNV
• Subretinal hemorrhage
• Anti-VEGF therapy

Prognosis

Most patients with Paget disease have:

Good overall prognosis

when complications are recognized and treated.

Visual prognosis depends primarily on:

• Development of CNV
• Macular scarring
• Subretinal hemorrhage
• Optic nerve compression

Malignant Transformation

Malignant transformation is:

Rare

but most commonly results in:

• Osteosarcoma

It should be suspected with:

• New severe pain
• Rapidly enlarging mass
• Cortical destruction
• Soft tissue extension

Complications

Systemic complications include:

• Bone pain
• Skeletal deformity
• Fracture
• Secondary osteoarthritis
• Hearing loss
• Spinal stenosis
• Nerve compression
• Rare hypercalcemia
• Rare high-output heart failure
• Rare osteosarcoma

Ocular complications include:

• CNV
• Subretinal hemorrhage
• Macular scar
• Optic neuropathy
• Permanent visual loss

Ophthalmology Pearls

• Paget disease is a disorder of excessive, disorganized bone remodeling in older adults.
• The characteristic laboratory abnormality is elevated serum alkaline phosphatase with usually normal calcium and phosphate.
• The classic histologic appearance is mosaic lamellar bone.
• Skull involvement can cause hearing loss and, rarely, compressive optic neuropathy.
• The most important ocular association is angioid streaks, representing breaks in abnormal Bruch membrane.
• Angioid streaks are usually bilateral, irregular, reddish-brown lines radiating from the optic disc.
• The major vision-threatening complication is choroidal neovascularization.
• New metamorphopsia or central blur in a patient with angioid streaks should prompt urgent OCT for CNV.
• Intravitreal anti-VEGF is the modern first-line treatment for CNV associated with angioid streaks.
• Laser and photodynamic therapy are largely historical or highly selective treatments for angioid-streak CNV.
• Patients with angioid streaks should use protective eyewear because relatively minor trauma may cause choroidal rupture and hemorrhage.
• Zoledronic acid 5 mg IV once is generally the preferred systemic treatment when active Paget disease requires therapy.
• Osteosarcoma transformation is rare but should be suspected with new severe bone pain or a rapidly enlarging mass.

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.

Orthopaedic Surgery - Schmorl Nodes

Basics

Schmorl nodes are:

Intraosseous herniations of intervertebral disc material

through a vertebral endplate and into the adjacent:

Vertebral body.

They are common incidental findings on:

Plain radiographs

CT

and

MRI of the spine.

Synonyms

Schmorl nodes may also be described as:

Intraosseous disc herniations

or

Vertebral endplate defects or irregularities.

Pathoanatomy

The lesion develops when:

Nucleus pulposus or other disc material penetrates through the superior or inferior vertebral endplate.

This produces an indentation or defect within the:

Adjacent vertebral body.

Endplate Vulnerability

In younger patients, some endplate weak points may be related to the normal regression of:

Vascular channels

near the end of vertebral growth.

In other patients, Schmorl nodes develop through:

Degenerated or weakened endplates

or weakened:

Subchondral vertebral bone.

Typical Location

Schmorl nodes most commonly occur in the:

Thoracic spine

and

Lumbar spine.

They have also been described in the:

Cervical spine, although this is much less common.

Historical Background

The lesions were described by:

Christian Georg Schmorl.

They were historically associated with:

Scheuermann kyphosis.

Relationship to Scheuermann Kyphosis

Scheuermann kyphosis is characterized by anterior vertebral wedging involving multiple adjacent vertebral bodies.

Although Schmorl nodes are frequently seen in this disorder, they are:

Not consistently present

and are therefore unlikely to be the sole cause of:

Scheuermann kyphosis.

Epidemiology

Schmorl nodes are:

Common.

Historical studies have reported them in approximately:

10% of the general population

although prevalence varies considerably depending on:

Age

Imaging technique

and

Definition used.

Age

They may occur from:

Childhood through old age.

The age at presentation depends partly on the underlying cause, such as:

Developmental endplate weakness

Trauma

Degeneration

or

Metabolic bone disease.

Sex

There is no strong consistent:

Sex predilection.

Genetics

No specific single-gene association has been established.

However, some inherited:

Metabolic bone disorders

may indirectly increase susceptibility by reducing:

Bone density

or altering the:

Vertebral bony matrix.

Risk Factors

Potential predisposing factors include:

Endplate weakness

Osteoporosis

Degenerative disc disease

High axial loading

Spinal trauma

Metabolic bone disease

Neoplastic weakening of bone

Etiology

Schmorl nodes form when sufficient force or structural weakness allows disc material to breach the:

Vertebral endplate.

Acute Mechanism

In otherwise normal bone, an acute lesion may occur after:

Trauma

or substantial:

Axial compressive loading.

The force causes rupture or deformation of the endplate with penetration of disc material into the vertebral body.

Degenerative Mechanism

In degenerative conditions, penetration may occur:

Gradually over time

because of progressive weakening of the:

Endplate