Ophthalmology – Phlyctenular Keratoconjunctivitis

Basics

Description

Phlyctenular keratoconjunctivitis (PKC) is an inflammatory disorder of the conjunctiva and/or cornea caused by a delayed type IV hypersensitivity reaction to microbial antigens.

It typically presents as a small:

• White
• Yellow-white
• Pink-white

elevated inflammatory nodule near the limbus.

It is seen most commonly in:

• Children
• Adolescents
• Young adults

The disorder may involve:

• Conjunctiva alone
• Cornea
• Both conjunctiva and cornea

Corneal involvement is usually more symptomatic and carries the greatest risk of visual sequelae.

Pathophysiology

PKC is not usually an active infection of the cornea.

Instead:

Microbial antigen exposure → delayed hypersensitivity reaction → localized lymphocytic inflammation at the limbus/cornea

The inflammatory lesion is called a:

Phlyctenule

Etiology

The most common antigenic stimulus in many modern clinical settings is:

Staphylococcal blepharitis

Other recognized triggers include:

• Mycobacterium tuberculosis
• Chlamydial infection
• Rosacea-associated lid disease
• Less commonly other bacterial, fungal, or parasitic antigens

The relative importance of tuberculosis depends strongly on:

• Geographic region
• Local prevalence
• Individual exposure risk

Associated Conditions

The strongest common association is:

Chronic blepharitis / meibomian gland dysfunction

Other associations include:

• Ocular rosacea
• Recurrent styes or chalazia
• Tuberculosis in endemic or high-risk settings
• Chronic lid colonization with Staphylococcus

Epidemiology

PKC occurs most often in younger patients.

It may be:

• Unilateral
• Bilateral
• Recurrent

Historically a female predominance has been reported, but this is not essential for diagnosis.

Risk Factors

Important risk factors include:

• Chronic blepharitis
• Meibomian gland dysfunction
• Poor lid hygiene
• Ocular rosacea
• Tuberculosis exposure
• Recurrent bacterial lid disease

History

Symptoms depend on whether the lesion is primarily conjunctival or corneal.

Conjunctival Phlyctenule

May cause:

• Mild redness
• Foreign-body sensation
• Tearing
• Irritation

Symptoms may be relatively mild.

Corneal Phlyctenule

Usually causes more prominent:

• Photophobia
• Pain
• Tearing
• Blepharospasm
• Foreign-body sensation
• Redness
• Reduced vision if central involvement occurs

Physical Examination

Conjunctival Phlyctenule

Typical appearance:

• Small
• Round
• Elevated
• Yellow-white or pink-white

nodule close to the:

Limbus

It may be surrounded by:

• Conjunctival injection
• Local vascular congestion

Corneal Phlyctenule

A corneal lesion often begins near the:

Limbus

and may migrate centrally.

Findings may include:

• Elevated peripheral corneal infiltrate
• Overlying epithelial defect
• Focal stromal inflammation
• Associated superficial vascularization

Leash of Vessels

A classic finding is:

A superficial vascular leash extending from the limbus toward the phlyctenule

This may become particularly evident in recurrent or migrating corneal disease.

Migrating Phlyctenule

A corneal phlyctenule may:

• Begin at the limbus
• Progress centrally
• Leave superficial neovascularization behind

Repeated episodes can produce:

• Corneal scar
• Lipid deposition
• Irregular astigmatism

Corneal Ulceration

The overlying epithelium may break down, producing:

• Small epithelial defect
• Shallow peripheral ulcer

Severe disease can rarely progress to:

• Stromal thinning
• Significant scarring

Blepharitis Findings

Look carefully for:

• Lid-margin erythema
• Collarettes
• Crusting
• Meibomian gland plugging
• Telangiectasia
• Recurrent chalazia

because treatment of the lid disease is critical for preventing recurrence.

Visual Acuity

Vision is usually preserved when lesions remain peripheral.

Reduced vision may result from:

• Central corneal involvement
• Scarring
• Irregular astigmatism
• Significant photophobia

Diagnosis

Diagnosis is primarily:

Clinical

based on:

• Characteristic limbal/corneal nodule
• Associated blepharitis
• Typical symptoms

Routine laboratory testing is unnecessary in straightforward staphylococcal-associated disease.

Tuberculosis Evaluation

Investigate for TB when there are:

• Epidemiologic risk factors
• Known exposure
• Travel or residence in endemic areas
• Recurrent or severe PKC without obvious lid disease
• Systemic symptoms

Testing may include:

• IGRA
• Tuberculin skin test
• Chest imaging when indicated

IGRA is often preferred in BCG-vaccinated patients.

Important Modern Point

TB testing should be:

Risk-based rather than routine in every patient

unless local prevalence or clinical circumstances justify universal screening.

Corneal Cultures

Culture or scraping is appropriate if the lesion appears more consistent with:

Infectious keratitis

especially when there is:

• Large epithelial defect
• Dense stromal infiltrate
• Purulent discharge
• Hypopyon
• Rapid progression

Histopathology

Phlyctenules contain predominantly:

• Lymphocytes
• Histiocytes
• Plasma cells

reflecting a delayed hypersensitivity inflammatory response.

Differential Diagnosis

Important differentials include:

• Staphylococcal marginal keratitis
• Microbial keratitis
• Herpes simplex keratitis
• Nodular episcleritis
• Ocular rosacea
• Inflamed pinguecula
• Peripheral ulcerative keratitis
• Contact-lens-related infiltrates

PKC vs Staphylococcal Marginal Keratitis

Both may be associated with blepharitis.

PKC

• Focal limbal nodule
• May migrate centrally
• May develop vascular leash
• Common in younger patients

Marginal Keratitis

• Peripheral stromal infiltrates
• Often multiple
• Typically separated from limbus by a clear zone
• Strong association with staphylococcal lid disease

PKC vs Microbial Keratitis

Features favoring microbial keratitis include:

• Larger epithelial defect
• Dense focal stromal infiltrate
• Purulent discharge
• Significant anterior chamber reaction
• Hypopyon
• Rapid progression

If infection is possible:

Do not treat with corticosteroid alone.

PKC vs HSV Keratitis

HSV may show:

• Dendritic epithelial ulcer
• Reduced corneal sensation
• Recurrent unilateral disease

Corneal HSV should be excluded before using topical steroid if the diagnosis is uncertain.

Treatment Principles

Treatment has two major goals:

1. Suppress the hypersensitivity inflammation
2. Treat the underlying antigenic source, especially blepharitis

Lid Hygiene

Management of blepharitis is essential.

Measures include:

• Warm compresses
• Lid hygiene
• Gentle lid-margin cleaning
• Artificial tears as needed

This reduces:

• Bacterial antigen load
• Recurrence risk

Topical Antibiotic

If significant bacterial lid disease is present, options may include:

• Erythromycin ophthalmic ointment
• Bacitracin ophthalmic ointment

applied to the lid margins.

These treat the associated blepharitis rather than the immune lesion itself.

Topical Corticosteroids

For symptomatic conjunctival or corneal PKC:

Topical corticosteroid is the main anti-inflammatory treatment

provided infectious keratitis has been excluded.

Options may include:

• Prednisolone acetate
• Loteprednol
• Fluorometholone

depending on severity.

Steroid Response

Phlyctenular inflammation often improves rapidly with corticosteroid therapy.

Treatment is usually:

• Short term
• Tapered according to clinical response

Avoid abrupt withdrawal in recurrent or severe disease.

Steroid Monitoring

With repeated or prolonged topical steroid use, monitor for:

• Ocular hypertension
• Glaucoma
• Cataract
• Secondary infection

Antibiotic–Steroid Combination

A combination preparation may be reasonable when there is:

• Significant concurrent blepharitis
• Epithelial breakdown
• Concern for secondary bacterial colonization

However, combination therapy is not mandatory in every case.

Oral Tetracycline-Class Therapy

For recurrent PKC associated with:

• Ocular rosacea
• Severe meibomian gland dysfunction
• Chronic blepharitis

an oral tetracycline-class drug may be useful because of:

• Anti-inflammatory effects
• Reduction in bacterial lipase activity

Doxycycline

In adults and appropriate older adolescents, doxycycline is generally preferred over older high-dose tetracycline regimens.

It can help control:

• Ocular rosacea
• MGD
• Recurrent phlyctenulosis

Pediatric Considerations

Avoid tetracycline-class drugs in young children when age-related safety concerns apply.

Alternatives for associated lid disease may include:

• Oral azithromycin
• Erythromycin

when systemic therapy is necessary.

Exact therapy should be individualized by age and clinical context.

Pregnancy Considerations

Tetracyclines are generally avoided during:

• Pregnancy

Alternative antibiotics should be selected when needed.

Tuberculosis-Associated PKC

If TB is identified:

Treat the tuberculosis itself

with appropriate multidrug therapy coordinated with:

• Infectious disease
• Pulmonology
• Public-health services

Topical steroids may still be used for ocular inflammation when appropriate, but they do not replace systemic TB therapy.

Ocular Rosacea

In patients with rosacea-associated disease, management may include:

• Lid hygiene
• Warm compresses
• Artificial tears
• Topical anti-inflammatory therapy
• Oral doxycycline or macrolide in selected patients

Recurrent Disease

Frequent recurrences should prompt reassessment for:

• Poorly controlled blepharitis
• Ocular rosacea
• Tuberculosis exposure
• Incorrect diagnosis
• Steroid dependence

Follow-Up

Follow-up depends on severity.

Mild conjunctival disease may be reviewed within:

• 1–2 weeks

Corneal disease may require earlier review, particularly if there is:

• Epithelial defect
• Stromal thinning
• Central progression

Monitoring

Monitor for:

• Resolution of infiltrate
• Epithelial healing
• Corneal vascularization
• Stromal thinning
• Scar formation
• IOP during steroid treatment

Prognosis

Overall prognosis is:

Good

Most lesions resolve with appropriate treatment.

Visual prognosis is excellent when:

• Disease remains peripheral
• Recurrences are controlled
• Corneal scarring is avoided

Poorer Visual Outcome

Vision may be reduced by:

• Central corneal scar
• Irregular astigmatism
• Corneal neovascularization
• Recurrent central lesions

Complications

Possible complications include:

• Corneal scarring
• Corneal neovascularization
• Irregular astigmatism
• Reduced visual acuity
• Recurrent keratitis
• Rare stromal thinning

Steroid-related complications include:

• Ocular hypertension
• Glaucoma
• Cataract
• Secondary infection

Ophthalmology Pearls

• Phlyctenular keratoconjunctivitis is a type IV delayed hypersensitivity reaction to microbial antigens.
• In many modern settings, the most common trigger is staphylococcal blepharitis, not active corneal infection.
• A phlyctenule is a small yellow-white inflammatory nodule near the limbus.
• Corneal involvement causes much more pain and photophobia than isolated conjunctival disease.
• A corneal phlyctenule may migrate centrally with a characteristic leash of superficial vessels.
• Always look for and treat blepharitis or meibomian gland dysfunction, because lid disease drives recurrence.
• Topical corticosteroids are the main treatment for significant inflammation once infectious keratitis has been excluded.
• Antibiotic ointment is directed mainly at associated lid-margin bacterial disease.
• Recurrent disease should prompt consideration of ocular rosacea and tuberculosis risk.
• TB evaluation should be risk-based, using IGRA/skin testing and chest imaging when indicated.
• Doxycycline can be useful in older patients with recurrent blepharitis/rosacea-associated disease; use age-appropriate alternatives in children.
• Severe or recurrent corneal disease can leave permanent scar, neovascularization, irregular astigmatism, and reduced vision.

Ophthalmology – Phacomorphic Glaucoma

Basics

Description

Phacomorphic glaucoma is a secondary angle-closure glaucoma caused by an enlarged or intumescent cataractous lens that pushes the iris–lens diaphragm forward and produces:

• Shallow anterior chamber
• Increased iridolenticular contact
• Relative pupillary block
• Peripheral angle closure
• Markedly elevated intraocular pressure

It is classically seen in an older patient with a:

Mature or intumescent cataract

and presents as an acute painful red eye.

Key Clinical Concept

The typical sequence is:

Swollen cataractous lens → shallowing of anterior chamber → pupillary block → iris bombe → angle closure → acute IOP elevation

The definitive treatment is:

Cataract extraction

after the acute attack has been medically stabilized.

Epidemiology

Phacomorphic glaucoma is more common where patients present late with advanced cataracts.

Typical patients are:

• Older adults
• Often hyperopic
• Frequently have a short axial length
• Have a thick or swollen lens

Risk Factors

Risk factors include:

• Mature/intumescent cataract
• Hyperopia
• Short axial length
• Shallow anterior chamber
• Thick crystalline lens
• Crowded anterior segment anatomy

Pathophysiology

As the cataractous lens becomes intumescent:

• Lens thickness increases
• Anterior lens curvature increases
• Iris–lens contact increases

This creates:

Relative pupillary block

Aqueous cannot move freely from the posterior to the anterior chamber.

Posterior chamber pressure rises, causing:

• Forward bowing of the peripheral iris
• Further narrowing of the angle
• Trabecular meshwork obstruction

Eventually:

Acute angle closure occurs

Lens-Induced Angle Crowding

The mechanism may include more than simple pupillary block.

The swollen lens also directly contributes to:

• Forward displacement of the iris–lens diaphragm
• Reduced anterior chamber depth
• Crowding of the iridocorneal angle

Therefore some eyes may remain angle-closed even after an iridotomy.

Etiology

The usual cause is:

• Intumescent mature cataract

Less commonly:

• Traumatic cataract
• Marked lens swelling from other lens pathology

The key factor is:

Increase in lens volume and thickness

Miotics

Miotics such as pilocarpine may worsen lens-related angle crowding by:

• Increasing zonular relaxation
• Allowing the lens to move slightly forward
• Promoting further shallowing of the anterior chamber

Therefore pilocarpine is generally not preferred in acute phacomorphic glaucoma, especially when IOP is very high and the iris sphincter is ischemic.

Clinical Presentation

Typical presentation:

Long-standing progressive cataractous visual loss followed by sudden painful red eye with very high IOP

Symptoms may include:

• Severe ocular pain
• Headache
• Blurred vision
• Halos around lights
• Nausea
• Vomiting

History

Ask about:

• Months or years of progressive visual decline
• Prior cataract diagnosis
• Previous intermittent episodes of pain or halos
• Hyperopic refractive history
• Previous angle-closure symptoms

Intermittent symptoms may occur before full acute closure.

Physical Examination

Typical findings include:

• Conjunctival and ciliary injection
• Diffuse corneal edema
• Shallow anterior chamber
• Mature or intumescent cataract
• Mid-dilated or sluggish pupil
• Elevated IOP
• Closed or nearly closed angle
• Mild anterior chamber cell and flare

Corneal Edema

Marked IOP elevation can cause:

• Microcystic epithelial edema
• Stromal edema

which may make:

• Gonioscopy
• Lens assessment

difficult initially.

Pupil

The pupil may be:

• Mid-dilated
• Sluggish
• Poorly reactive

because of:

• Iris ischemia
• Sphincter dysfunction

Anterior Chamber

The chamber is typically:

Shallow centrally and peripherally

This is a key distinction from phacolytic glaucoma, where the angle is usually open.

Gonioscopy

When possible, gonioscopy demonstrates:

• Narrow or closed angle
• Possible peripheral anterior synechiae

Gonioscopy should be performed after sufficient corneal clearing if the initial view is poor.

Fellow Eye

The fellow eye may also have:

• Narrow angle
• Hyperopic anatomy
• Advanced cataract

but may have a deeper chamber than the affected eye if the lens is less intumescent.

The fellow eye should be assessed carefully because it may also be at risk for angle closure.

Diagnosis

Diagnosis is based on:

• Intumescent or mature cataract
• Shallow anterior chamber
• Angle closure
• Elevated IOP
• Acute pain/redness

Anterior Segment OCT / UBM

Anterior segment imaging may be useful when anatomy is unclear.

It may demonstrate:

• Increased lens vault
• Shallow anterior chamber
• Iridotrabecular contact
• Forward iris–lens configuration

UBM can be especially useful if the cornea is too edematous for gonioscopy.

B-Scan Ultrasonography

B-scan may be helpful when the posterior segment cannot be visualized because of:

• Dense cataract
• Corneal edema

It can exclude:

• Retinal detachment
• Intraocular mass
• Other major posterior segment pathology

Differential Diagnosis

Important differentials include:

• Acute primary angle closure
• Phacolytic glaucoma
• Lens-particle glaucoma
• Uveitic glaucoma
• Neovascular glaucoma
• Angle closure from intraocular mass
• Lens subluxation/dislocation

Phacomorphic vs Phacolytic Glaucoma

Phacomorphic Glaucoma

• Intumescent swollen lens
• Shallow anterior chamber
• Closed angle
• Pupillary-block/lens-crowding mechanism
• Usually no major proteinaceous material in aqueous

Phacolytic Glaucoma

• Mature/hypermature cataract
• Lens protein leakage
• Open angle
• Relatively deeper chamber
• White proteinaceous particles and macrophages

This distinction is highly exam-relevant.

Phacomorphic vs Acute Primary Angle Closure

Both may present with:

• Pain
• Halos
• Nausea
• Corneal edema
• Very high IOP
• Shallow chamber

Phacomorphic glaucoma is suggested by:

• Intumescent cataract
• Marked lens thickness
• Greater asymmetry in chamber depth
• Lens-induced anterior segment crowding

Phacomorphic vs Lens Subluxation

Lens subluxation may cause secondary angle closure through:

• Forward displacement
• Pupillary block

Look for:

• Phacodonesis
• Iridodonesis
• Asymmetric chamber depth
• Visible zonular weakness

Treatment Principles

Management has two phases:

1. Rapid medical control of IOP and inflammation
2. Definitive cataract extraction

Initial IOP-Lowering Therapy

Aqueous suppressants are preferred.

Options include:

• Topical beta-blocker
• Topical carbonic anhydrase inhibitor
• Alpha-2 agonist
• Oral acetazolamide when needed

Systemic Acetazolamide

Acetazolamide is useful when:

• IOP is markedly elevated
• Topical therapy alone is inadequate

It helps rapidly suppress aqueous production.

Hyperosmotic Agents

If IOP remains very high, consider:

• IV mannitol
• Oral hyperosmotic agents in selected patients

These reduce vitreous volume and may:

• Deepen the anterior chamber slightly
• Facilitate surgery

Topical Corticosteroids

Topical steroids help reduce:

• Secondary anterior chamber inflammation
• Iris edema

They are supportive rather than definitive.

Cycloplegics

Cycloplegics are not routinely central to management and may worsen pupillary dilation in a crowded angle.

Use should be individualized.

Pilocarpine

Pilocarpine is generally avoided in phacomorphic glaucoma.

Reasons include:

• Iris sphincter may be ischemic and unresponsive at very high IOP
• Miotics can relax zonules
• Lens may move anteriorly
• Angle crowding may worsen

Laser Peripheral Iridotomy

LPI can relieve the:

Pupillary-block component

and may be useful as a temporary measure.

However:

LPI is not definitive treatment

because the enlarged cataractous lens continues to crowd the angle.

Limitations of LPI

LPI may be difficult or ineffective when:

• Corneal edema obscures the iris
• Chamber is extremely shallow
• The lens is markedly intumescent
• Non-pupillary-block lens crowding persists

Therefore:

Cataract extraction remains the definitive treatment.

Surgical Peripheral Iridectomy

Surgical iridectomy may occasionally be considered when:

• Laser cannot be performed
• Pupillary block persists
• Cataract surgery must be delayed

It is far less commonly used than definitive lens extraction.

Definitive Treatment – Cataract Extraction

The definitive treatment is:

Removal of the swollen cataractous lens

This:

• Deepens the anterior chamber
• Relieves pupillary block
• Opens the angle
• Removes the source of lens-induced crowding

Timing of Cataract Surgery

Surgery is typically performed after:

• IOP has been lowered
• Corneal edema has improved
• Inflammation is better controlled

However, definitive surgery should not be unnecessarily delayed.

Surgical Challenges

Phacomorphic eyes may be technically difficult because of:

• Very shallow anterior chamber
• Corneal edema
• High posterior pressure
• Weak zonules
• Intumescent lens
• Poor red reflex

Capsulorhexis Risk

Intumescent cataracts have increased risk of:

Argentinian flag sign

where liquefied cortex and high intralenticular pressure cause a capsular tear to extend radially.

Strategies may include:

• Controlled chamber pressurization
• Small initial capsulotomy
• Decompression of liquefied cortex
• Careful enlargement of capsulorhexis

Cataract Surgical Options

Depending on the lens and surgeon:

• Phacoemulsification
• Manual small-incision cataract surgery
• Extracapsular extraction

may be used.

The choice depends on:

• Lens density
• Corneal clarity
• Zonular status
• Available expertise

Postoperative IOP

After lens removal:

• IOP usually falls
• Angle depth improves significantly

However, glaucoma may persist if there is:

• Peripheral anterior synechiae
• Chronic trabecular damage
• Preexisting glaucoma

Peripheral Anterior Synechiae

If angle closure has been prolonged:

• PAS may become permanent
• Angle may not fully reopen after cataract extraction

This can result in:

Chronic angle-closure glaucoma

Persistent Glaucoma

If IOP remains uncontrolled after cataract removal, treatment may include:

• Topical medications
• Goniosynechialysis in selected recent PAS
• Trabeculectomy
• Glaucoma drainage device

Choice depends on:

• Extent of PAS
• Optic nerve damage
• Residual angle anatomy

Goniosynechialysis

In selected cases with relatively recent PAS, goniosynechialysis performed with cataract surgery may:

• Reopen portions of the angle
• Improve trabecular access

Benefit is less likely when synechiae are long-standing.

Fellow-Eye Management

The fellow eye should undergo:

• Gonioscopy
• Anterior chamber assessment
• Cataract evaluation

If anatomically narrow, treatment may include:

• Cataract extraction
• LPI in selected cases

based on the mechanism and degree of angle crowding.

Important Prevention Update

Routine prophylactic laser iridotomy is not a general preventive treatment for phacomorphic glaucoma in every patient with cataract.

The most effective prevention is:

Timely cataract extraction before severe intumescence and angle closure develop.

LPI is appropriate only when the fellow eye or patient has a genuine pupillary-block/narrow-angle indication.

Follow-Up

During the acute episode, monitoring should be frequent.

Assess:

• IOP
• Corneal edema
• Anterior chamber depth
• Inflammation
• Optic nerve when visible

After surgery monitor:

• IOP
• Angle status
• PAS
• Optic nerve damage
• Visual recovery

Optic Nerve Assessment

Once the media clear, evaluate:

• Optic disc
• RNFL OCT
• Visual field when possible

because acute or prolonged severe IOP elevation may produce:

Permanent glaucomatous optic neuropathy

Prognosis

Visual prognosis can be good when:

• Attack is recognized promptly
• IOP is rapidly controlled
• Cataract extraction is successful
• Optic nerve damage has not occurred

Even very poor presenting vision may improve markedly if visual loss is primarily due to:

• Cataract
• Corneal edema
• Acute angle closure

Poor Prognostic Factors

Include:

• Delayed presentation
• Prolonged high IOP
• Advanced optic nerve damage
• Extensive PAS
• Corneal endothelial damage
• Complicated cataract surgery
• Coexisting retinal disease

Complications

Potential complications include:

• Permanent glaucomatous optic neuropathy
• Chronic angle-closure glaucoma
• Peripheral anterior synechiae
• Corneal endothelial decompensation
• Iris atrophy
• Fixed dilated pupil
• Cataract surgical complications
• Zonular dialysis
• Vitreous loss
• Persistent postoperative glaucoma

Ophthalmology Pearls

• Phacomorphic glaucoma is secondary angle closure caused by an intumescent cataractous lens.
• The classic mechanism is lens enlargement → pupillary block + anterior segment crowding → acute angle closure.
• Typical findings are painful red eye, corneal edema, shallow anterior chamber, mature/intumescent cataract, and very high IOP.
• Hyperopia, short axial length, and a shallow anterior chamber increase risk.
• The key distinction from phacolytic glaucoma is that phacomorphic glaucoma has a shallow chamber and closed angle, whereas phacolytic glaucoma is an open-angle lens-protein leakage syndrome.
• Initial treatment uses aqueous suppressants, systemic acetazolamide, hyperosmotics when necessary, and topical corticosteroids.
• Pilocarpine is generally avoided because it may worsen lens-induced crowding and is often ineffective at very high IOP.
• LPI can relieve a pupillary-block component but does not remove the enlarged lens and is therefore not definitive.
• Cataract extraction is the definitive treatment.
• Intumescent cataracts carry increased risk of Argentinian flag capsular tear during capsulorhexis.
• Persistent glaucoma after surgery usually reflects PAS, chronic trabecular damage, or preexisting glaucoma.
• The most effective prevention is timely cataract surgery before the lens becomes markedly intumescent and angle closure develops.

Ophthalmology – Phacolytic Glaucoma

Basics

Description

Phacolytic glaucoma is an acute secondary open-angle glaucoma caused by leakage of soluble lens proteins from a mature or hypermature cataract through a lens capsule that is usually clinically intact.

It classically presents with:

• Long-standing severe cataract
• Sudden painful red eye
• Markedly elevated intraocular pressure
• Anterior chamber inflammation
• Open anterior chamber angle

The definitive treatment is:

Removal of the cataractous lens.

Key Clinical Concept

The typical sequence is:

Mature/hypermature cataract → leakage of lens proteins → trabecular obstruction → acute IOP elevation

Inflammatory cells and macrophages contribute to the anterior chamber reaction but are not considered the sole cause of the glaucoma.

Epidemiology

Phacolytic glaucoma is now relatively uncommon where:

• Cataracts are treated early
• Cataract surgery is readily accessible

It remains more common where patients present with:

• Long-standing mature cataracts
• Hypermature cataracts

Most patients are:

• Older adults
• Unilaterally affected

Cataract Association

The classic lens is:

• Mature white cataract
• Hypermature cataract
• Morgagnian cataract

A Morgagnian cataract has:

• Liquefied cortex
• Dense nucleus sinking within the capsular bag

Risk Factors

The principal risk factor is:

Long-standing untreated advanced cataract

Other relevant factors include:

• Limited access to cataract surgery
• Delayed presentation
• Very mature lens changes

Pathophysiology

As a cataract becomes mature or hypermature:

• Lens proteins undergo degeneration
• High-molecular-weight proteins leak through the capsule
• These proteins enter the anterior chamber

Although the capsule appears intact clinically, it becomes sufficiently permeable for protein leakage.

Trabecular Obstruction

Elevated IOP results from impaired aqueous outflow due to:

• High-molecular-weight lens proteins
• Proteinaceous debris
• Macrophages containing lens material
• Inflammatory cells

The angle itself generally remains:

Open

Role of Macrophages

Macrophages are commonly found in:

• Anterior chamber
• Trabecular meshwork

They may contain:

• Phagocytosed lens protein

Older theories considered macrophages the primary cause of obstruction.

Modern understanding favors:

Direct obstruction by leaked high-molecular-weight lens proteins, with macrophages contributing to the inflammatory response.

Associated Uveitis

Lens protein leakage also produces:

• Anterior chamber cells
• Flare
• Proteinaceous material

Therefore phacolytic glaucoma is a form of:

Lens-induced inflammatory glaucoma

History

Typical history:

• Gradual painless visual decline over months or years from cataract
• Followed by sudden:
• Ocular pain
• Redness
• Headache
• Further visual deterioration

There is often no history of:

• Cataract surgery
• Trauma

which helps distinguish it from some other lens-induced glaucomas.

Clinical Presentation

The classic presentation is:

Elderly patient + mature white cataract + acutely painful red eye + very high IOP + open angle

Symptoms

Common symptoms include:

• Ocular pain
• Red eye
• Blurred vision
• Headache
• Halos
• Nausea or vomiting if IOP is very high

Vision may already have been poor because of the cataract.

External Examination

Findings may include:

• Conjunctival injection
• Ciliary flush
• Corneal edema

Severe corneal edema may initially obscure anterior segment details.

Intraocular Pressure

IOP is usually:

Markedly elevated

It can reach levels high enough to cause:

• Corneal edema
• Severe pain
• Optic nerve damage

Anterior Chamber

Typical findings include:

• Cells
• Flare
• Proteinaceous debris
• Floating white particles
• Macrophages containing lens proteins

The reaction may appear intense despite the absence of infection.

White Material in the Anterior Chamber

Characteristic findings may include:

• White clumps
• Flocculent material
• Hyperrefractile particles

in front of a:

Mature or hypermature cataract

Keratic Precipitates

Classic descriptions often emphasize that prominent granulomatous KPs are not typical.

Marked:

• Mutton-fat KPs
• Granulomatous inflammation

should raise consideration of:

• Phacoantigenic uveitis
• Another uveitic process

Lens Examination

The lens usually shows:

• Mature white cataract
• Hypermature cataract
• Liquefied cortex

A Morgagnian lens may show:

• Free or sunken dense nucleus
• Liquefied cortical material

Anterior Chamber Depth

Unlike phacomorphic glaucoma, the anterior chamber is often:

Relatively deep

and the angle is open.

This is a crucial distinction.

Gonioscopy

When corneal clarity allows, gonioscopy typically demonstrates:

An open angle

Possible findings include:

• Proteinaceous material
• Inflammatory debris
• Trabecular pigmentation

Fellow Eye

The fellow eye may also have:

• Advanced cataract

but typically does not have:

• Acute IOP elevation
• Inflammation

unless bilateral advanced cataracts are present.

Diagnosis

Diagnosis is usually clinical.

The key combination is:

• Mature/hypermature cataract
• Open angle
• Elevated IOP
• Anterior chamber inflammation
• Lens protein/debris in aqueous

Laboratory Testing

Routine laboratory testing is:

Not required

unless another cause of uveitis or infection is suspected.

Anterior Chamber Aspiration

Aqueous aspiration was historically used to identify:

• Macrophages
• Eosinophilic lens protein

It is rarely necessary in a classic case.

The diagnosis is generally made clinically.

B-Scan Ultrasonography

B-scan may be useful when the fundus cannot be seen because of:

• Dense cataract
• Corneal edema

It can exclude major posterior segment pathology such as:

• Retinal detachment
• Vitreous hemorrhage
• Intraocular mass

before cataract surgery.

Differential Diagnosis

Important differentials include:

• Phacomorphic glaucoma
• Lens-particle glaucoma
• Phacoantigenic uveitis with glaucoma
• Acute primary angle closure
• Uveitic glaucoma
• Endophthalmitis
• Neovascular glaucoma

Phacolytic vs Phacomorphic Glaucoma

Phacolytic Glaucoma

• Mature/hypermature cataract
• Leakage of lens proteins
• Open angle
• Usually relatively deep anterior chamber
• Inflammatory cells and proteinaceous material

Phacomorphic Glaucoma

• Intumescent swollen lens
• Pupillary block / angle crowding
• Closed or occludable angle
• Shallow anterior chamber
• Lens-induced secondary angle closure

This is one of the most important exam distinctions.

Phacolytic vs Lens-Particle Glaucoma

Phacolytic

• Lens capsule clinically intact
• Mature/hypermature cataract
• Protein leakage
• No preceding surgery or trauma required

Lens-Particle Glaucoma

Occurs after:

• Cataract surgery
• Trauma
• Capsular rupture

and results from direct obstruction by:

Gross lens particles

Phacolytic vs Phacoantigenic Uveitis

Phacolytic

• Mature/hypermature cataract
• Capsule usually clinically intact
• Protein leakage
• Macrophage-rich inflammation
• Open-angle glaucoma

Phacoantigenic Uveitis

• Requires capsular disruption
• Usually follows surgery or trauma
• Granulomatous immune-mediated reaction
• May produce secondary glaucoma

Phacolytic vs Acute Primary Angle Closure

Acute primary angle closure usually shows:

• Shallow anterior chamber
• Mid-dilated pupil
• Closed angle
• No mature cataract requirement

Phacolytic glaucoma generally shows:

• Mature cataract
• Open angle
• Significant inflammatory material

Phacolytic Glaucoma vs Endophthalmitis

Features concerning for infection include:

• Recent intraocular surgery
• Severe pain
• Hypopyon
• Dense vitritis
• Poor red reflex beyond that explained by cataract
• Rapidly progressive inflammation

When infection is plausible:

Endophthalmitis must be excluded urgently.

Treatment Principles

Management has two stages:

1. Rapidly control IOP and inflammation
2. Remove the cataract

Cataract extraction is definitive because the lens is the source of leaking proteins.

Initial IOP Control

Aqueous suppressants are preferred.

Common options include:

• Topical beta-blocker
• Topical carbonic anhydrase inhibitor
• Alpha-2 agonist
• Oral acetazolamide when needed

Systemic Acetazolamide

Oral or IV acetazolamide may be used when:

• IOP is markedly elevated
• Topical therapy is insufficient

Avoid or modify use appropriately in patients with:

• Severe renal disease
• Significant electrolyte disturbance
• Relevant sulfonamide-related concerns

Hyperosmotic Therapy

For severe acute IOP elevation:

• IV mannitol

may be used temporarily.

This is a:

Short-term bridge to definitive lens extraction

rather than definitive treatment.

Topical Corticosteroids

Topical corticosteroids are used to control:

• Anterior chamber inflammation
• Lens-protein-induced uveitis

Examples include:

• Prednisolone acetate

Treatment is subsequently tapered according to clinical response.

Cycloplegia

Cycloplegic drops may be useful when there is:

• Significant anterior uveitis
• Ciliary spasm
• Pain
• Risk of posterior synechiae

Miotics

Pilocarpine is generally avoided.

It may:

• Worsen inflammation
• Promote posterior synechiae
• Increase ciliary spasm

and does not address the principal mechanism.

Prostaglandin Analogs

Prostaglandin analogs are not usually the first choice during intense acute intraocular inflammation.

They may be considered later if persistent glaucoma remains after the inflammatory episode resolves.

Definitive Treatment

The definitive treatment is:

Cataract extraction with removal of the source of lens proteins

and irrigation of proteinaceous material from the anterior chamber as required.

Timing of Cataract Surgery

Initial medical therapy is used to:

• Reduce IOP
• Improve corneal clarity
• Suppress inflammation
• Optimize surgical conditions

However, surgery should not be unnecessarily delayed because:

The cataract remains the source of ongoing protein leakage.

Cataract Surgery

The operative approach depends on:

• Lens density
• Capsular integrity
• Zonular stability
• Corneal clarity
• Surgeon experience

Modern surgery is generally performed using:

• Phacoemulsification when technically feasible
• Manual small-incision or extracapsular techniques in selected very dense cataracts

Surgical Challenges

Hypermature lenses may have:

• Weak zonules
• Fibrotic or fragile capsule
• Liquefied cortex
• Dense nucleus

Increasing the risk of:

• Posterior capsule rupture
• Zonular dialysis
• Dropped lens fragments
• Vitreous loss

After Cataract Extraction

Following removal of the lens:

• Inflammation usually falls rapidly
• Protein leakage stops
• IOP often normalizes

Topical steroids can then be tapered according to:

• Anterior chamber reaction
• IOP
• Corneal status

Persistent Elevated IOP

Some eyes continue to have glaucoma because of:

• Chronic trabecular damage
• Preexisting glaucoma
• Peripheral anterior synechiae
• Steroid response

These eyes may require:

• Long-term topical therapy
• Laser or glaucoma surgery in selected cases

Glaucoma Surgery

Glaucoma surgery is rarely required when the disease is treated promptly.

If IOP remains uncontrolled after cataract extraction and inflammation has settled, options may include:

• Trabeculectomy
• Glaucoma drainage device
• Other glaucoma procedures according to angle and optic nerve status

Cystoid Macular Edema

CME may develop because of:

• Severe anterior segment inflammation
• Cataract surgery

It can be assessed with:

Macular OCT

after the media are clear.

Treatment may include:

• Topical corticosteroid
• Topical NSAID

with escalation in selected cases.

Follow-Up

Initially, follow-up should be:

Very close

to monitor:

• IOP
• Corneal edema
• Anterior chamber inflammation
• Optic nerve status
• Response to medication

After cataract surgery, monitor for:

• Persistent glaucoma
• CME
• Corneal edema
• Posterior segment abnormalities

Optic Nerve Assessment

Once the cornea and media clear, evaluate:

• Optic disc
• RNFL/OCT if possible
• Visual field when appropriate

because prolonged high IOP can cause:

Permanent glaucomatous optic neuropathy

Prognosis

Visual prognosis can be surprisingly good even when presenting vision is extremely poor because much of the visual loss may be due to:

• Dense cataract
• Corneal edema
• Acute IOP elevation

rather than irreversible retinal or optic nerve damage.

Poor Prognostic Factors

Include:

• Prolonged severe IOP elevation
• Advanced glaucomatous optic neuropathy
• Corneal decompensation
• Macular disease
• Retinal disease
• Delayed cataract extraction

Complications

Potential complications include:

• Permanent glaucomatous optic neuropathy
• Chronic ocular inflammation
• Corneal edema
• Posterior synechiae
• Cystoid macular edema
• Persistent secondary glaucoma
• Complications of complex cataract surgery

Ophthalmology Pearls

• Phacolytic glaucoma is an acute secondary open-angle glaucoma caused by leakage of lens proteins from a mature or hypermature cataract.
• The classic patient has long-standing poor vision from a white cataract followed by sudden pain, redness, and markedly elevated IOP.
• The lens capsule is usually clinically intact, despite leakage of soluble proteins.
• High-molecular-weight lens proteins are believed to be the principal cause of trabecular obstruction; macrophages are an important associated finding.
• The anterior chamber often contains cells, flare, and white proteinaceous particles.
• The angle is open, which distinguishes phacolytic glaucoma from phacomorphic glaucoma, where an intumescent lens causes secondary angle closure.
• Lens-particle glaucoma usually follows surgery or trauma with capsular disruption, whereas phacolytic glaucoma does not.
• Initial treatment uses aqueous suppressants, systemic acetazolamide or hyperosmotics when necessary, and topical corticosteroids.
• Cataract extraction is the definitive treatment because it removes the source of leaking lens protein.
• Medical IOP control should optimize the eye for surgery but should not lead to unnecessary delay of cataract extraction.
• IOP usually falls after lens removal, but persistent glaucoma may remain if trabecular or optic nerve damage has already occurred.
• Even an eye presenting with extremely poor vision may recover useful vision if treatment occurs before irreversible glaucomatous or posterior segment damage develops.

Ophthalmology – Phacoanaphylactic Glaucoma

Basics

Description

Phacoanaphylactic glaucoma is an older term for secondary glaucoma occurring with phacoantigenic uveitis, an immune-mediated granulomatous inflammation directed against exposed lens proteins after disruption of the lens capsule.

Preferred modern terminology includes:

• Phacoantigenic uveitis
• Lens-induced uveitis with secondary glaucoma

The historical term phacoanaphylactic endophthalmitis is misleading because the reaction is not a true IgE-mediated anaphylactic process.

The disorder typically follows:

• Cataract surgery with retained lens material
• Penetrating or blunt trauma causing lens capsule rupture
• Rare spontaneous lens capsule disruption

Clinical Importance

The characteristic clinical combination is:

Persistent granulomatous anterior uveitis + elevated IOP after disruption of the lens capsule

The principal management goals are to:

1. Suppress inflammation.
2. Control IOP.
3. Identify and remove residual lens material when present.
4. Exclude infectious postoperative endophthalmitis.

Epidemiology

The condition is uncommon in modern cataract surgery because of:

• Improved phacoemulsification
• Better removal of cortical material
• Smaller incisions
• Improved vitreoretinal management of dropped lens fragments

It is more likely after:

• Complicated cataract surgery
• Posterior capsule rupture
• Retained lens fragments
• Lens trauma

Terminology

Several lens-induced inflammatory glaucomas must be distinguished.

Phacoantigenic Uveitis

• Immune-mediated granulomatous inflammation
• Requires lens capsule disruption
• Usually follows surgery or trauma
• Secondary glaucoma may occur

Lens-Particle Glaucoma

• Trabecular obstruction by lens particles and inflammatory cells
• Usually after surgery or trauma
• Less dependent on a specific immune sensitization mechanism

Phacolytic Glaucoma

• Occurs with a hypermature cataract
• Capsule is usually grossly intact
• Leakage of high-molecular-weight lens proteins produces macrophage-mediated trabecular obstruction

These entities may overlap clinically.

Pathophysiology

Normally, lens proteins are relatively sequestered from the immune system.

When the capsule is disrupted:

Lens proteins become exposed to the immune system

This can trigger a:

• Delayed immune response
• Granulomatous inflammatory reaction

Histologically, inflammation develops around lens material.

Mechanism of Glaucoma

IOP may rise because of:

• Inflammatory cells obstructing the trabecular meshwork
• Macrophages containing lens material
• Free lens particles
• Lens proteins
• Trabeculitis
• Peripheral anterior synechiae
• Posterior synechiae with secondary pupillary block in selected cases
• Steroid response during treatment

Therefore the glaucoma may be:

• Open-angle
• Secondary angle-closure
• Mixed mechanism

Etiology

Typical precipitating events include:

• Cataract surgery
• Posterior capsule rupture
• Dropped nuclear fragments
• Retained cortical material
• Penetrating ocular trauma
• Traumatic lens rupture

Rarely, spontaneous capsular rupture may occur.

History

Ask specifically about:

• Recent cataract surgery
• Complicated phacoemulsification
• Posterior capsule rupture
• Retained lens fragments
• Pars plana vitrectomy
• Ocular trauma
• Previous episodes of uveitis

Symptoms may include:

• Ocular pain
• Photophobia
• Redness
• Blurred vision
• Halos
• Headache if IOP is markedly elevated

Timing

Presentation may occur:

• Days
• Weeks
• Occasionally longer

after lens capsule disruption.

Persistent or recurrent postoperative inflammation should raise suspicion for:

• Retained lens material
• Phacoantigenic uveitis
• Chronic postoperative endophthalmitis
• TASS

Physical Examination

Typical findings include:

• Ciliary injection
• Anterior chamber cells and flare
• Granulomatous inflammation
• Mutton-fat keratic precipitates
• Posterior synechiae
• Elevated IOP
• Visible lens fragments in some cases

Granulomatous Uveitis

Inflammation may be characterized by:

• Large keratic precipitates
• Iris nodules occasionally
• Posterior synechiae
• Significant anterior chamber cellular reaction

The inflammation may persist until the inciting lens material is removed.

Lens Material

Residual lens material may be found:

• In the anterior chamber
• In the capsular bag
• Behind the iris
• In the vitreous cavity

Posteriorly retained lens fragments can be difficult to visualize directly.

Posterior Segment Findings

If lens material has dropped posteriorly, there may be:

• Vitritis
• Retained nuclear fragment
• Cystoid macular edema
• Retinal edema
• Reduced fundus view

Intraocular Pressure

IOP may range from mildly elevated to:

Severely elevated

Mechanisms include:

• Trabecular inflammatory obstruction
• Lens-particle obstruction
• Peripheral anterior synechiae
• Steroid response

Diagnostic Approach

The key questions are:

1. Is retained lens material present?
2. Is this sterile inflammation or infection?
3. What mechanism is causing the elevated IOP?
4. Is there posterior segment involvement?

Slit-Lamp Examination

Evaluate for:

• Corneal edema
• Keratic precipitates
• Anterior chamber cell/flare
• Hypopyon
• Lens fragments
• Posterior synechiae
• Surgical wound integrity

Gonioscopy

When feasible, gonioscopy may demonstrate:

• Lens material in the angle
• Trabecular inflammatory debris
• Peripheral anterior synechiae
• Secondary angle closure

Dilated Fundus Examination

Assess for:

• Dropped lens fragments
• Vitritis
• Retinal inflammation
• Cystoid macular edema
• Retinal tears or detachment after complicated surgery

B-Scan Ultrasonography

B-scan is useful when the posterior segment cannot be visualized because of:

• Corneal edema
• Severe inflammation
• Media opacity

It may help identify:

• Retained lens fragments
• Vitreous opacities
• Retinal detachment

Anterior Segment Imaging

UBM or AS-OCT may occasionally help detect:

• Retained anterior lens material
• Angle abnormalities
• Capsular remnants

particularly when fragments are hidden behind the iris.

Aqueous or Vitreous Sampling

Sampling is not routinely required for classic sterile phacoantigenic inflammation.

It becomes important when:

Infectious endophthalmitis cannot be excluded.

Possible tests include:

• Gram stain
• Culture
• PCR in selected cases

Histopathology

Classic histology demonstrates:

• Polymorphonuclear leukocytes
• Epithelioid histiocytes
• Multinucleated giant cells

arranged around:

Lens material

This produces a zonal granulomatous inflammatory pattern.

Differential Diagnosis

Important differentials include:

• Lens-particle glaucoma
• Phacolytic glaucoma
• Chronic postoperative endophthalmitis
• Toxic anterior segment syndrome
• Exacerbation of preexisting uveitis
• Retained lens fragments without immune granulomatous reaction
• Sympathetic ophthalmia
• Uveitic glaucoma from another cause

Chronic Postoperative Endophthalmitis

One of the most important mimics is indolent infection, particularly from:

Cutibacterium acnes

formerly Propionibacterium acnes.

Clues include:

• Recurrent inflammation after steroid taper
• White plaque within the capsular bag
• Vitritis
• Chronic postoperative course

Infection must be excluded before assuming the process is purely immune-mediated.

Toxic Anterior Segment Syndrome

TASS usually presents:

• Within approximately 12–48 hours after surgery
• With diffuse limbus-to-limbus corneal edema
• Marked anterior chamber inflammation
• Minimal pain
• No significant vitritis

It results from:

Sterile toxic injury, not lens-protein sensitization.

Phacolytic Glaucoma

Phacolytic glaucoma generally occurs in an eye with:

• Mature or hypermature cataract
• Intact-appearing capsule
• High IOP
• Anterior chamber inflammation

Macrophages and lens proteins obstruct the trabecular meshwork.

Definitive treatment is:

Cataract extraction

after initial IOP control.

Lens-Particle Glaucoma

Lens-particle glaucoma occurs when:

• Lens fragments physically enter the anterior chamber

usually after:

• Trauma
• Cataract surgery

It may resemble phacoantigenic uveitis but is primarily a:

Mechanical-inflammatory trabecular obstruction

rather than a classic granulomatous immune response.

Treatment Principles

Management consists of:

1. Control inflammation.
2. Lower IOP.
3. Remove retained lens material.
4. Treat complications.

Definitive control often requires:

Removal of the inciting lens material.

Topical Corticosteroids

Topical corticosteroids are first-line for ocular inflammation.

Examples include:

• Prednisolone acetate
• Difluprednate in selected severe cases

Dosing depends on severity and may initially be frequent.

Steroids should subsequently be:

Tapered according to clinical response

after definitive treatment.

Cycloplegic Therapy

Cycloplegics may be useful when there is:

• Significant ciliary spasm
• Pain
• Posterior synechiae

Examples include:

• Cyclopentolate
• Atropine in more severe disease

IOP-Lowering Therapy

Aqueous suppressants are generally preferred.

Options include:

• Topical beta-blockers
• Topical carbonic anhydrase inhibitors
• Alpha-2 agonists
• Oral acetazolamide when needed

Hyperosmotic Therapy

For severe acute IOP elevation, temporary treatment may include:

• IV mannitol
• Oral hyperosmotic agents in selected patients

This is generally a bridge to definitive treatment rather than long-term therapy.

Prostaglandin Analogs

Prostaglandin analogs may lower IOP but are often used cautiously during:

• Active severe uveitis
• Significant cystoid macular edema

They are not absolutely contraindicated in every inflammatory glaucoma but are often not the first choice during active postoperative inflammation.

Miotics

Miotics are generally avoided because they may:

• Worsen inflammation
• Promote posterior synechiae
• Increase ciliary spasm

Surgical Removal of Lens Material

The definitive treatment is:

Removal of retained lens material when clinically significant.

The surgical approach depends on location.

Anterior Segment Lens Fragments

Fragments in the:

• Anterior chamber
• Capsular bag
• Anterior vitreous

may be removed by an:

Anterior segment surgeon

using irrigation/aspiration or other appropriate techniques.

Posteriorly Retained Lens Fragments

Posteriorly displaced nuclear fragments usually require:

Pars plana vitrectomy

by a vitreoretinal surgeon.

Surgery may include:

• Vitrectomy
• Removal of lens fragments
• Fragmatome-assisted removal for dense nuclear material

Timing of Vitrectomy

Timing depends on:

• Fragment size
• Degree of inflammation
• IOP
• Corneal edema
• Macular status

Significant retained nuclear material with:

• Severe inflammation
• Uncontrolled IOP
• Persistent corneal edema

generally favors timely vitreoretinal intervention.

Cystoid Macular Edema

CME may accompany chronic postoperative inflammation.

Treatment may include:

• Topical corticosteroids
• Topical NSAIDs
• Periocular or intraocular corticosteroids in selected cases

after infection has been excluded.

Persistent Glaucoma

IOP may remain elevated after lens removal because of:

• Trabecular damage
• Peripheral anterior synechiae
• Steroid response
• Chronic uveitic glaucoma

Long-term glaucoma therapy may therefore be necessary.

Glaucoma Surgery

If IOP remains uncontrolled despite:

• Lens removal
• Control of inflammation
• Maximal tolerated medical treatment

surgery may be required.

Options include:

• Glaucoma drainage device
• Trabeculectomy in selected eyes
• Cyclophotocoagulation in refractory disease

In uveitic eyes, drainage devices are frequently important because filtration surgery may fail from inflammation and scarring.

Follow-Up

During active disease, follow-up should be:

Frequent

depending on:

• IOP
• Degree of inflammation
• Corneal edema
• Retained lens material
• Response to therapy

Some patients require review every:

• Day
• Few days

until stable.

Long-Term Monitoring

After inflammation resolves, monitor for:

• Persistent glaucoma
• Peripheral anterior synechiae
• Steroid-induced ocular hypertension
• Cystoid macular edema
• Optic nerve damage

Prognosis

Prognosis depends on:

• Duration of inflammation
• Magnitude of IOP elevation
• Amount and location of retained lens material
• Corneal damage
• Macular involvement
• Timing of definitive treatment

Prompt recognition and removal of significant retained material generally improves outcome.

Complications

Potential complications include:

• Secondary glaucoma
• Permanent optic nerve damage
• Peripheral anterior synechiae
• Posterior synechiae
• Cystoid macular edema
• Corneal edema
• Chronic uveitis
• Vitreous inflammation
• Surgical complications from vitrectomy or glaucoma surgery

Ophthalmology Pearls

• “Phacoanaphylactic glaucoma” is an older term; the preferred modern concept is phacoantigenic uveitis with secondary glaucoma.
• It occurs after lens capsule disruption, most commonly from cataract surgery or trauma.
• The inflammatory reaction is granulomatous and directed against exposed lens proteins, not a true anaphylactic reaction.
• Think of it in a patient with persistent granulomatous uveitis and elevated IOP after complicated cataract surgery or lens trauma.
• Retained lens fragments may be located in the anterior chamber or vitreous cavity.
• Removal of clinically significant retained lens material is the definitive treatment.
• Posteriorly dropped nuclear fragments usually require pars plana vitrectomy.
• Use topical corticosteroids plus aqueous-suppressant glaucoma therapy while arranging definitive management.
• Avoid routine miotics during active inflammation.
• Always distinguish this disorder from chronic postoperative endophthalmitis, especially Cutibacterium acnes infection.
• Also distinguish it from phacolytic glaucoma, in which the capsule is generally intact and hypermature lens proteins leak into the anterior chamber.
• Persistent IOP elevation after inflammation resolves may reflect permanent trabecular damage or synechial angle closure and can require long-term glaucoma treatment or surgery.

Ophthalmology – Peters Anomaly

Basics

Description

Peters anomaly is a congenital anterior segment dysgenesis characterized by a central or paracentral corneal opacity associated with focal absence or maldevelopment of:

• Descemet membrane
• Corneal endothelium

The posterior corneal defect may be associated with abnormal adherence of:

• Iris to posterior cornea
• Lens to posterior cornea

Disease may be:

• Unilateral or bilateral
• Isolated
• Associated with other ocular abnormalities
• Part of a multisystem genetic syndrome

The major threats to vision are:

• Deprivation amblyopia
• Glaucoma
• Cataract
• Associated posterior segment abnormalities

Pathophysiology

Peters anomaly results from abnormal development of the anterior segment during embryogenesis.

Proposed mechanisms include:

• Abnormal neural crest migration or differentiation
• Failure of normal lens–cornea separation
• Abnormal development of posterior corneal structures

This results in:

• Focal absence of endothelium
• Focal absence of Descemet membrane
• Corneal stromal opacity
• Variable iridocorneal or lenticulocorneal adhesions

Epidemiology

Peters anomaly is:

• Rare
• Usually diagnosed at birth or early infancy
• Variable in severity

Bilateral involvement is particularly important because it carries a greater risk of:

• Severe visual deprivation
• Genetic disease
• Associated systemic abnormalities

Genetics

Most cases are sporadic, but both:

• Autosomal dominant
• Autosomal recessive

inheritance have been reported.

Associated genes include:

• PAX6
• FOXC1
• PITX2
• CYP1B1
• FOXE3
• PITX3
• Other anterior segment developmental genes

Because these genes can produce overlapping phenotypes, Peters anomaly is best considered part of a broad:

Anterior segment dysgenesis spectrum

Peters Plus Syndrome

Peters plus syndrome is a syndromic disorder combining Peters anomaly with systemic developmental abnormalities.

Typical features include:

• Short stature
• Rhizomelic limb shortening
• Brachydactyly
• Characteristic craniofacial appearance
• Developmental delay
• Cleft lip and/or palate in some patients

It is caused by biallelic pathogenic variants in:

B3GLCT

formerly called B3GALTL.

Inheritance is:

Autosomal recessive

Other Systemic Associations

Peters anomaly may occur with:

• CNS malformations
• Developmental delay
• Microcephaly
• Seizures
• Congenital heart disease
• Renal/genitourinary abnormalities
• Craniofacial anomalies
• Skeletal abnormalities
• Ear abnormalities

Systemic abnormalities are particularly important in:

• Bilateral disease
• Syndromic appearance
• Multiple congenital anomalies

Ocular Associations

Associated ocular abnormalities include:

• Glaucoma
• Cataract
• Microphthalmia
• Microcornea
• Iris hypoplasia
• Corectopia
• Polycoria
• Iris coloboma
• Aniridia-like abnormalities
• Lens abnormalities
• Ptosis

Posterior segment abnormalities may also occur.

Posterior Segment Associations

Possible findings include:

• Optic nerve hypoplasia
• Foveal hypoplasia
• Retinal dysplasia
• Chorioretinal coloboma
• Persistent fetal vasculature
• Posterior staphyloma
• Macular developmental abnormalities

These can limit visual recovery even when the cornea is successfully cleared.

Glaucoma

Glaucoma is one of the most important complications.

Reported frequency is approximately:

30–70%

depending on case severity and series.

Mechanisms include:

• Abnormal anterior chamber angle development
• Trabecular dysgenesis
• Secondary structural changes

Glaucoma may present:

• At birth
• During infancy
• Later in childhood

Therefore:

Long-term glaucoma surveillance is mandatory.

Clinical Presentation

Typical presentation includes:

• Congenital corneal opacity
• Abnormal red reflex
• Poor fixation
• Nystagmus in bilateral severe cases
• Strabismus
• Leukocoria-like appearance

Corneal Appearance

The hallmark is:

Central or paracentral congenital corneal opacity

The opacity may be:

• Small
• Eccentric
• Dense
• Diffuse centrally
• Unilateral or bilateral

Peripheral cornea may remain relatively clear.

Iris Adhesions

Iris strands may extend from the:

• Iris collarette
• Midperipheral iris

to the posterior surface of the opaque cornea.

These:

Iridocorneal adhesions

are a classic feature.

Lens Involvement

More severe disease may show:

• Lens adherence to posterior cornea
• Cataract
• Lens malposition

Lens involvement generally indicates a more complex developmental abnormality.

Historical Classification

Type I Peters Anomaly

Traditionally characterized by:

• Central/paracentral corneal opacity
• Iridocorneal adhesions
• No major lens adherence

Type II Peters Anomaly

Traditionally includes:

• Lenticulocorneal adhesion
• Often cataract
• More extensive anterior segment dysgenesis

The Type I/II distinction remains useful descriptively but is now considered an oversimplification of a continuous developmental spectrum.

History

Important history includes:

• Pregnancy and birth history
• Family history
• Consanguinity
• Developmental milestones
• Growth abnormalities
• Other congenital malformations

Ask specifically about:

• Poor visual behavior
• Photophobia
• Tearing
• Eye enlargement
• Corneal enlargement
• Nystagmus
• Strabismus

which may suggest associated glaucoma or severe visual deprivation.

Examination

Perform a complete pediatric ophthalmic examination including:

• Age-appropriate visual assessment
• Pupils
• Ocular alignment
• Motility
• Corneal diameter
• Corneal opacity location and density
• Anterior chamber depth
• Iris anatomy
• Lens status
• IOP
• Cycloplegic refraction when possible
• Posterior segment examination when visible

Examination Under Anesthesia

Examination under anesthesia may be required in infants to assess:

• IOP
• Corneal diameter
• Angle anatomy
• Lens
• Axial length
• Optic nerve
• Posterior segment

It is often necessary for treatment planning.

Anterior Segment OCT

AS-OCT can demonstrate:

• Posterior corneal defect
• Iridocorneal adhesion
• Lenticulocorneal adhesion
• Anterior chamber configuration

It is useful when sufficient corneal transparency exists.

Ultrasound Biomicroscopy

UBM is particularly valuable for evaluating:

• Iris
• Ciliary body
• Angle
• Lens position
• Posterior corneal adhesions

especially when direct visualization is limited.

B-Scan Ultrasonography

When the posterior segment cannot be visualized, B-scan may assess:

• Retina
• Vitreous
• Optic nerve region
• Retinal detachment
• Major posterior structural abnormalities

Systemic Evaluation

Further testing should be guided by clinical findings.

Depending on phenotype, consider:

• Clinical genetics
• Developmental assessment
• Echocardiography
• Renal ultrasound
• Neuroimaging
• Skeletal evaluation

Genetic Testing

Genetic testing is particularly appropriate for:

• Bilateral Peters anomaly
• Family history
• Peters plus phenotype
• Developmental delay
• Multiple congenital abnormalities

Testing may include:

• Targeted anterior segment dysgenesis panel
• Chromosomal microarray
• Exome/genome sequencing in selected patients

Differential Diagnosis

Important causes of congenital corneal opacity include:

• Congenital glaucoma
• Sclerocornea
• Congenital hereditary endothelial dystrophy
• Corneal dermoid
• Birth trauma / forceps injury
• Intrauterine keratitis
• Metabolic storage disorders
• Congenital infection
• Ocular trauma

Peters Anomaly vs Congenital Glaucoma

Peters Anomaly

Usually shows:

• Focal central opacity
• Posterior corneal defect
• Iris/lens adhesions
• Anterior segment dysgenesis

Congenital Glaucoma

More often shows:

• Enlarged corneal diameter
• Buphthalmos
• Diffuse corneal edema
• Haab striae
• Elevated IOP

The two disorders can coexist.

Peters Anomaly vs Sclerocornea

Peters Anomaly

• Central or paracentral opacity
• Posterior corneal defect
• Iridocorneal or lenticulocorneal adhesions

Sclerocornea

• Peripheral or diffuse scleralization of cornea
• Poorly defined limbus
• Often bilateral
• No characteristic focal posterior corneal defect

Peters Anomaly vs Birth Trauma

Forceps injury may cause:

• Corneal edema
• Linear Descemet tears
• Characteristic vertical or oblique breaks

A clear history of birth trauma and absence of congenital anterior segment dysgenesis favor traumatic injury.

Treatment Goals

Management aims to:

1. Establish a useful visual axis.
2. Prevent severe amblyopia.
3. Treat glaucoma.
4. Correct refractive error.
5. Manage cataract or other structural abnormalities.

Treatment must be individualized.

Observation

Observation may be appropriate when:

• Corneal opacity is small
• Opacity is eccentric
• Visual axis remains sufficiently clear
• Fixation is good
• There is no significant glaucoma

Some small opacities become functionally less significant as the eye grows.

Optical Iridectomy

Optical iridectomy can be useful when:

• Central cornea is opaque
• Peripheral cornea is clear
• Lens is sufficiently transparent

A sector iridectomy creates an alternative visual axis through clear peripheral cornea.

Advantages include avoiding:

• Corneal graft rejection
• Graft failure
• Intensive graft surveillance

Penetrating Keratoplasty

Penetrating keratoplasty may be considered for:

• Dense bilateral central opacity
• Severe visual-axis obstruction
• Significant deprivation amblyopia risk

The decision is complex because infant corneal grafting has:

• High rejection risk
• High graft failure rate
• Frequent glaucoma
• Suture-related complications
• Need for repeated examinations under anesthesia

Timing of Keratoplasty

Early surgery may improve amblyopia potential but increases technical and postoperative difficulty.

Delayed surgery may:

• Improve surgical ease
• Reduce some graft-related risks

but may allow irreversible:

Deprivation amblyopia

Therefore timing is individualized according to:

• Laterality
• Opacity density
• Visual behavior
• Associated abnormalities

Pediatric Graft Prognosis

Long-term graft survival is substantially poorer than routine adult keratoplasty.

Even with a clear graft, visual outcome may remain limited by:

• Amblyopia
• Glaucoma
• Cataract
• Optic nerve hypoplasia
• Retinal abnormalities

Endothelial Keratoplasty

Procedures such as DMEK or DSAEK are generally not standard primary treatment for classic Peters anomaly because the disorder involves structural developmental defects beyond isolated endothelial dysfunction.

Glaucoma Treatment

Medical therapy may include:

• Topical beta blockers
• Carbonic anhydrase inhibitors
• Other age-appropriate agents

Medical therapy alone is frequently insufficient.

Glaucoma Surgery

Surgical options include:

• Trabeculotomy
• Goniotomy in selected eyes
• Trabeculectomy
• Glaucoma drainage devices

Angle surgery may be difficult because of:

• Severe developmental angle abnormalities
• Poor visualization
• Abnormal anatomy

Glaucoma drainage devices are often important in refractory disease.

Cyclodestructive Procedures

Cyclophotocoagulation is generally reserved for:

• Refractory glaucoma
• Poor visual potential
• Eyes in which other surgery has failed

Cataract Surgery

Lensectomy may be required for:

• Significant cataract
• Lenticulocorneal adhesion
• Lens displacement
• Visual-axis obstruction

Vitrectomy may also be required depending on associated anatomy.

Amblyopia Therapy

Amblyopia treatment is essential.

Management may include:

• Refractive correction
• Contact lens
• Spectacles
• Patching
• Atropine penalization in selected cases

A technically successful corneal procedure may still produce poor vision if amblyopia is not treated aggressively.

Refractive Error

Children may develop substantial:

• Astigmatism
• Anisometropia
• High refractive error

especially after:

• Keratoplasty
• Cataract surgery

Repeat cycloplegic refraction is therefore essential.

Low-Vision Rehabilitation

Children with severe bilateral visual impairment should receive early:

• Low-vision services
• Developmental intervention
• Educational support
• Orientation and mobility services when needed

Follow-Up

Long-term surveillance should include:

• Visual acuity
• Fixation behavior
• Amblyopia
• Refraction
• Corneal clarity
• Graft status
• IOP
• Optic nerve
• Lens
• Posterior segment

Glaucoma Monitoring

Because glaucoma may develop later:

Surveillance should continue throughout childhood and beyond.

Young children may require repeated EUA when reliable office IOP assessment is impossible.

Prognosis

Visual prognosis is highly variable.

More favorable features include:

• Small or eccentric opacity
• Unilateral mild disease
• Clear peripheral cornea
• Normal lens
• No glaucoma
• Normal posterior segment

Poor Prognostic Features

Include:

• Dense bilateral central opacity
• Severe glaucoma
• Lens involvement
• Microphthalmia
• Optic nerve hypoplasia
• Retinal dysplasia
• Delayed visual rehabilitation

Systemic Prognosis

Systemic prognosis depends on associated abnormalities.

Children with isolated unilateral disease may otherwise be entirely healthy.

Patients with:

• Peters plus syndrome
• CNS abnormalities
• Multisystem congenital disease

require multidisciplinary follow-up.

Complications

Major complications include:

• Amblyopia
• Glaucoma
• Cataract
• Corneal graft rejection
• Graft failure
• Irregular astigmatism
• Anisometropia
• Strabismus
• Permanent visual impairment

Ophthalmology Pearls

• Peters anomaly is a congenital central or paracentral corneal opacity caused by posterior corneal dysgenesis involving Descemet membrane and endothelium.
• Classic associated findings are iridocorneal adhesions and, in more severe cases, lenticulocorneal adhesion with cataract.
• It belongs to the broader spectrum of anterior segment dysgenesis.
• Glaucoma is common, potentially severe, and may develop later, so lifelong surveillance is essential.
• The historical Type I/Type II classification is useful descriptively but does not capture the full phenotypic spectrum.
• Bilateral Peters anomaly should prompt consideration of genetic and systemic evaluation.
• Peters plus syndrome is caused by biallelic B3GLCT variants and is associated with short stature, skeletal abnormalities, craniofacial features, and developmental delay.
• AS-OCT and UBM help define the relationship among the cornea, iris, angle, and lens.
• Optical iridectomy can sometimes avoid penetrating keratoplasty when a clear peripheral corneal window is available.
• Pediatric keratoplasty is challenging because of graft rejection, glaucoma, suture complications, and amblyopia.
• A clear corneal graft does not guarantee good vision; final outcome is often determined by amblyopia, glaucoma, lens status, optic nerve development, and retinal anatomy.

Ophthalmology – Persistent Hyperplastic Primary Vitreous / Persistent Fetal Vasculature

Basics

Description

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

• Hyaloid vascular system
• Primary vitreous
• Tunica vasculosa lentis

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

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

PFV is usually:

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

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

Classification

PFV is classified as:

• Anterior PFV
• Posterior PFV
• Combined PFV

Combined anterior-posterior disease is common.

Anterior PFV

Anterior abnormalities may include:

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

Posterior PFV

Posterior disease may demonstrate:

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

Embryology

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

It normally undergoes regression before birth.

Normal remnants may include:

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

PFV represents more extensive persistence with secondary fibrovascular contraction.

Pathophysiology

Failure of fetal vascular regression leaves:

• Persistent vessels
• Fibrous tissue
• Primary vitreous

Contraction of this tissue may pull on the:

• Lens
• Ciliary body
• Retina
• Optic disc

producing progressive structural distortion.

Epidemiology

PFV is uncommon.

The majority of cases are:

Unilateral and sporadic

Bilateral disease is unusual and should prompt consideration of an:

• Inherited retinal disorder
• Syndromic developmental disorder

Genetics

Most isolated PFV has no identifiable inherited cause.

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

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

Genetic evaluation becomes particularly important in:

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

Bilateral PFV – Important Principle

True bilateral isolated PFV is uncommon.

When both eyes show severe fibrovascular retinal abnormalities, consider:

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

NDP-Related Retinopathy

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

The most severe form is:

Norrie disease

Typical features include:

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

Associated systemic manifestations may include:

• Progressive sensorineural hearing loss
• Developmental or behavioral abnormalities

Familial Exudative Vitreoretinopathy

FEVR may produce:

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

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

Clinical Presentation

The classic presentation is:

Leukocoria in an infant with a microphthalmic eye

Other presentations include:

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

Microphthalmia

The affected eye is frequently:

Smaller than the fellow eye

This is an important diagnostic clue.

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

• Microphthalmia
• Microcornea

Anterior Segment Findings

Possible findings include:

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

Iridohyaloid Vessels

Persistent fetal vessels may connect the:

• Iris
• Ciliary body
• Retrolental fibrovascular tissue

Contraction can cause:

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

Mittendorf Dot

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

Posterior lens capsule

An isolated Mittendorf dot does not constitute severe PFV.

Posterior Segment Findings

Potential findings include:

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

Bergmeister Papilla

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

It may be:

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

Macular Abnormalities

Posterior PFV may produce:

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

These substantially limit visual potential.

Optic Nerve Abnormalities

Associated findings may include:

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

These are important prognostic factors.

Diagnosis

Diagnosis is based on the combination of:

• Clinical examination
• Ocular imaging
• Characteristic anatomy

The most important diagnostic objective is:

Exclusion of retinoblastoma

Examination Under Anesthesia

Infants may require examination under anesthesia to evaluate:

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

B-Scan Ultrasonography

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

It may show:

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

A classic finding is:

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

Doppler Ultrasound

Color Doppler may occasionally demonstrate persistent blood flow within:

• Hyaloid vessels
• Fibrovascular stalk

particularly in younger infants.

MRI

MRI is preferred when cross-sectional imaging is needed.

It can demonstrate:

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

MRI is also useful when evaluating:

• CNS abnormalities
• Syndromic disease
• Possible noncalcified retinoblastoma

CT

CT historically played an important role because it detects:

Calcification

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

• Ionizing radiation

Calcification – Critical Pearl

PFV

Typically:

No intraocular calcification

Retinoblastoma

Commonly:

Calcified retinal mass

However:

Absence of calcification does not completely exclude retinoblastoma.

Fluorescein Angiography

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

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

It is not routinely required in classic unilateral PFV.

OCT

Handheld or conventional OCT may show:

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

It can help estimate visual potential and assist surgical planning.

Visual Evoked Potentials

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

Its predictive value is limited.

Modern prognosis is more strongly based on:

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

Differential Diagnosis

Important differential diagnoses include:

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

PFV vs Retinoblastoma

PFV

Usually:

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

Retinoblastoma

Usually shows:

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

PFV vs Retinopathy of Prematurity

Severe ROP usually occurs in:

• Premature infants
• Often bilaterally

End-stage disease may cause:

• Retrolental fibrosis
• Funnel retinal detachment
• Leukocoria

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

PFV vs FEVR

FEVR favors:

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

PFV favors:

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

Treatment Principles

Treatment depends on:

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

Management ranges from:

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

Observation

Observation is reasonable for:

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

It may also be appropriate for very severe disease with:

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

Surgical Indications

Surgery may be considered for:

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

Goals of Surgery

The aims are to:

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

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

Anterior PFV Surgery

Potential procedures include:

• Lensectomy
• Membranectomy
• Anterior vitrectomy

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

Significant intraoperative hemorrhage

Posterior and Combined PFV Surgery

More severe cases may require:

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

These operations can be technically difficult because of:

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

Lens-Sparing Vitrectomy

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

Lens-sparing vitrectomy

may be considered.

Preserving the lens can reduce:

• Aphakic anisometropia
• Optical rehabilitation burden
• Amblyopia

Aphakia Management

After infantile lensectomy, visual rehabilitation may require:

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

Primary IOL implantation is individualized according to:

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

Amblyopia

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

Management may include:

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

Strabismus

Strabismus is common because of:

• Structural visual impairment
• Anisometropia
• Amblyopia

Surgery may later be performed for:

• Alignment
• Cosmesis
• Functional binocular goals when possible

Glaucoma

Secondary glaucoma can result from:

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

Regular IOP surveillance is important.

Vitreous Hemorrhage

Persistent vascular tissue may bleed, causing:

• Recurrent vitreous hemorrhage
• Further visual deprivation

Persistent or severe hemorrhage may become an indication for vitrectomy.

Retinal Detachment

Tractional retinal detachment may:

• Remain stable
• Progress over time

Surgery is considered according to:

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

Severe End-Stage Disease

Some eyes have such profound:

• Retinal dysplasia
• Optic nerve abnormalities
• Total detachment

that meaningful visual improvement is unlikely.

Management may then focus on:

• Comfort
• Globe preservation
• Cosmetic outcome

Enucleation is now uncommon unless:

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

Protective Eyewear

Children with profound unilateral visual impairment should use:

Impact-resistant protective spectacles

to protect the better-seeing eye.

Genetic Counseling

Genetic counseling is appropriate when there is:

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

Follow-Up

All patients require ongoing ophthalmic follow-up.

Monitor:

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

Prognosis

Visual prognosis is highly variable and depends more on:

Posterior segment anatomy

than on the anterior appearance alone.

Favorable Prognostic Features

Include:

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

Poor Prognostic Features

Include:

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

Anterior PFV Prognosis

Anterior PFV generally has the:

Best visual potential

particularly when the retina and optic nerve are relatively normal.

Posterior / Combined PFV Prognosis

These forms generally have worse visual outcomes because of:

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

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

Complications

Potential complications include:

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

Ophthalmology Pearls

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

Ophthalmology – Persistent Fetal Vasculature (PFV)

Basics

Description

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

• Primary vitreous
• Hyaloid vascular system
• Tunica vasculosa lentis

The older term:

Persistent hyperplastic primary vitreous (PHPV)

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

PFV is usually:

• Unilateral
• Sporadic
• Associated with a smaller affected eye

It may cause:

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

Clinical Importance

The most important diagnostic issue is:

PFV must be distinguished from retinoblastoma.

Both may present in infancy with:

• Leukocoria
• Retrolental opacity
• Poor vision

Misdiagnosis can have major consequences.

Classification

PFV is divided into:

• Anterior PFV
• Posterior PFV
• Combined PFV

Combined disease is common.

Anterior PFV

Anterior findings may include:

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

The retrolental membrane may exert traction on the:

• Ciliary processes
• Lens
• Iris

Posterior PFV

Posterior findings may include:

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

Combined PFV

Combined PFV contains both:

• Anterior segment changes
• Posterior segment tractional abnormalities

Visual prognosis is generally worse than in isolated anterior PFV.

Epidemiology

PFV is rare.

Most cases are:

• Unilateral
• Sporadic

Bilateral disease is uncommon and should raise suspicion for:

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

Embryology

The fetal hyaloid vascular system supplies the developing:

• Lens
• Primary vitreous

during early gestation.

It normally regresses before birth.

Remnants of this system can persist physiologically as:

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

PFV represents a much more extensive failure of involution.

Pathophysiology

Failure of normal fetal vascular regression produces persistent:

• Fibrovascular tissue
• Hyaloid vessels
• Primary vitreous

Subsequent contraction may cause:

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

Genetics

Most PFV is:

Sporadic

Rare familial and syndromic forms have been described.

Genes associated with PFV or PFV-like phenotypes include:

• ATOH7
• NDP
• FZD4
• LRP5
• PAX6

depending on phenotype.

Genetic evaluation is particularly appropriate when PFV is:

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

Bilateral PFV

True bilateral PFV is unusual.

The differential should include:

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

Clinical Presentation

The classic presentation is:

Unilateral leukocoria in an infant with microphthalmia

Other presentations include:

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

History

Ask about:

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

Microphthalmia

The affected eye is often:

Smaller than the fellow eye

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

• Normal-sized
• Sometimes enlarged

eye rather than a microphthalmic eye.

Anterior Segment Findings

Possible findings include:

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

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

Posterior Lens Appearance

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

• Fibrovascular plaque
• Membrane
• Cataract

A vascular stalk may attach to this posterior region.

Retrolental Fibrovascular Membrane

This may appear as:

• White
• Gray-white
• Vascularized

tissue behind the lens.

It contributes to the leukocoria.

Persistent Hyaloid Stalk

A classic posterior finding is:

Fibrovascular stalk extending from the optic disc toward the posterior lens

This corresponds to persistent fetal hyaloid tissue.

Posterior Segment Findings

May include:

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

Retinal Fold

A retinal fold may extend:

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

and may substantially limit visual potential.

Retinal Dysplasia

Retinal dysplasia is an important determinant of visual prognosis.

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

Diagnosis

Diagnosis is based on:

• Clinical examination
• Ocular ultrasound
• MRI when needed

The major diagnostic goal is to exclude:

Retinoblastoma

before proceeding with surgery.

Examination Under Anesthesia

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

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

B-Scan Ultrasonography

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

It may demonstrate:

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

A classic appearance is:

A stalk extending from posterior lens to optic disc

Calcification

A critical imaging distinction:

Retinoblastoma

Often demonstrates:

Intraocular calcification

PFV

Typically:

Does not contain calcification

However:

Absence of calcification does not completely exclude retinoblastoma.

Therefore imaging must be interpreted with the entire clinical picture.

MRI

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

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

MRI Findings

Possible findings include:

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

CT

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

However:

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

OCT

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

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

This may help estimate visual potential.

Fluorescein Angiography

Wide-field fluorescein angiography may occasionally help evaluate:

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

It is not required in every classic unilateral case.

Visual Evoked Potentials

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

Its ability to predict postoperative visual outcome is limited.

Modern surgical decisions rely more heavily on:

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

Differential Diagnosis

The most important differential is:

• Retinoblastoma

Other differentials include:

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

PFV vs Retinoblastoma

PFV

Usually:

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

Retinoblastoma

Typically:

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

PFV vs Congenital Cataract

Congenital cataract may cause:

• Leukocoria
• Poor red reflex

but lacks:

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

unless associated with PFV.

PFV vs Norrie Disease

Norrie disease usually causes:

• Bilateral severe retinal dysplasia
• Pseudoglioma
• Retinal detachment

and may later cause:

• Sensorineural hearing loss
• Neurodevelopmental problems

Bilateral PFV-like disease should therefore prompt consideration of:

NDP-related disease

PFV vs FEVR

FEVR may produce:

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

Unlike classic unilateral PFV, FEVR is often:

• Bilateral
• Familial

although asymmetry can be marked.

Treatment Principles

Treatment depends on:

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

Options include:

• Observation
• Surgery
• Amblyopia therapy

Observation

Observation may be appropriate for:

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

Indications for Surgery

Consider surgery when there is:

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

Surgical Goals

The major goals are:

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

Anterior PFV Surgery

Typical procedures may include:

• Lensectomy
• Membranectomy
• Anterior vitrectomy

Care must be taken because the retrolental tissue can be:

Highly vascular

and intraoperative bleeding may occur.

Posterior / Combined PFV Surgery

May require:

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

These cases are technically challenging because:

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

Lens-Sparing Surgery

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

Lens-sparing vitrectomy

to reduce:

• Aphakia
• Anisometropia
• Amblyopia

However, this is feasible only in selected cases.

Intraocular Lens

Primary IOL implantation in PFV is individualized.

Factors include:

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

Many infants are initially managed with:

• Contact lens
• Aphakic spectacles

after lensectomy.

Amblyopia Treatment

Amblyopia is often a major limitation to visual recovery.

Treatment may include:

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

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

Strabismus

Strabismus is common because of:

• Poor unilateral vision
• Anisometropia
• Structural retinal abnormalities

Surgery may later be considered for:

• Alignment
• Cosmesis
• Binocular function when possible

Glaucoma

Secondary glaucoma may develop from:

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

Monitor:

• IOP
• Corneal diameter
• Optic nerve
• Axial growth

Severe End-Stage Disease

Historically, some severely malformed eyes underwent enucleation.

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

• Comfortable
• Not suspicious for malignancy

Enucleation is uncommon and usually reserved for:

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

Follow-Up

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

Monitor:

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

Prognosis

Visual prognosis depends strongly on the subtype.

Anterior PFV Prognosis

Isolated anterior PFV generally has the:

Best visual prognosis

particularly when:

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

Useful visual acuity is possible.

Posterior PFV Prognosis

Posterior disease has a less favorable prognosis because of:

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

Combined PFV Prognosis

Combined disease generally has the poorest visual potential.

Nevertheless, modern surgery may sometimes achieve:

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

in selected patients.

Prognostic Factors

Poor visual prognosis is associated with:

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

Complications

Potential complications include:

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

Ophthalmology Pearls

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

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.