Ophthalmology – Peripapillary Staphyloma

Basics

Description

Peripapillary staphyloma is a rare congenital optic nerve anomaly characterized by a deep excavation of the posterior fundus surrounding an otherwise relatively normal optic disc.

The optic disc lies at the bottom of the excavation and may appear:

• Normal
• Mildly pale
• Occasionally tilted or distorted by the surrounding ectasia

The surrounding:

• Retina
• Retinal pigment epithelium
• Choroid

often show atrophic or pigmentary changes.

This congenital lesion should be distinguished from the much more common acquired posterior staphyloma of pathologic myopia.

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Important Terminology

The older term posterior staphyloma can be confusing.

In this congenital optic-disc context, the preferred descriptive term is:

Peripapillary staphyloma

This is a developmental optic nerve anomaly.

By contrast, myopic posterior staphyloma is an acquired outward bulging of the posterior eyewall in pathologic myopia.

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Epidemiology

Peripapillary staphyloma is:

• Very rare
• Usually unilateral
• Congenital

It may occasionally be:

• Bilateral
• Associated with another congenital ocular anomaly in the fellow eye

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Genetics

Most cases are:

Sporadic

A consistent Mendelian inheritance pattern has not been established.

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Embryology and Pathogenesis

The exact mechanism is uncertain.

A developmental defect of the posterior globe is thought to occur after formation of the optic disc.

The result is:

Localized ectasia of the scleral and choroidal tissues surrounding the optic nerve

while the optic disc itself remains relatively normally formed.

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Key Anatomical Feature

The defining feature is:

A normal or near-normal optic disc situated at the base of a broad, deep peripapillary excavation.

This distinguishes peripapillary staphyloma from:

• Morning glory disc anomaly
• Optic disc coloboma

where the disc itself is directly malformed.

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Clinical Presentation

Patients may present with:

• Reduced unilateral visual acuity
• Strabismus
• Nystagmus if bilateral/severe
• Abnormal head posture
• Failed childhood vision screening

Some patients have surprisingly good vision despite striking anatomy.

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Visual Acuity

Visual acuity is highly variable.

It may range from:

• Near-normal vision
• Moderate visual impairment
• Severe visual loss

Reduced vision may result from:

• Congenital retinal/optic nerve dysfunction
• Macular involvement
• Refractive error
• Amblyopia
• Retinal detachment

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Refractive Error

Unlike myopic posterior staphyloma, the affected eye may be:

• Emmetropic
• Mildly myopic
• Occasionally hyperopic

Therefore:

High myopia is not required.

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Visual Field

A visual field defect may include:

• Central scotoma
• Cecocentral scotoma
• Other defects corresponding to abnormal posterior pole anatomy

Formal field testing is useful when age and visual function permit.

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Fundus Examination

Typical findings include:

• Deep bowl-shaped excavation surrounding optic nerve
• Optic disc at the bottom of the excavation
• Peripapillary chorioretinal atrophy
• Pigmentary changes at the margin
• Relatively normal retinal vessels emerging from the disc

Unlike morning glory anomaly, there is generally no:

• Central glial tuft
• Markedly abnormal radial vascular pattern

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Optic Disc

The optic disc itself may be:

• Normal in appearance
• Mildly pale
• Occasionally temporally pale

A normal-appearing disc within the excavation is diagnostically helpful.

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Contractile Movement

Rare cases have demonstrated:

Spontaneous contractile movement of the staphylomatous excavation

The mechanism is uncertain but may involve:

• Smooth-muscle-like or contractile tissue
• Changes in intraocular pressure or choroidal circulation

This phenomenon is unusual and not required for diagnosis.

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Associated Ocular Findings

Possible associations include:

• Strabismus
• Nystagmus
• Amblyopia
• Abnormal head posture
• Fellow-eye congenital anomalies

The contralateral eye should always be examined carefully.

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Retinal Detachment

The most important acquired complication is:

Retinal detachment

Detachment may be:

• Rhegmatogenous
• Tractional
• Serous in selected congenital excavation anomalies

Risk is related to abnormal posterior pole anatomy.

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Macular Involvement

Visual potential depends heavily on:

• Foveal development
• Macular position relative to the excavation
• Secondary retinal abnormalities

OCT is useful when the macula can be imaged.

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Diagnosis

Diagnosis is usually clinical based on:

• Characteristic fundus appearance
• Optic disc located at the base of a broad surrounding excavation
• Absence of classic features of morning glory disc anomaly or optic disc coloboma

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Optical Coherence Tomography

OCT can document:

• Depth and contour of the excavation
• Retinal layer architecture
• Macular involvement
• Peripapillary atrophy
• Associated schisis or detachment

Enhanced-depth imaging or swept-source OCT may further demonstrate:

• Choroid
• Scleral contour

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B-Scan Ultrasonography

B-scan may be useful to assess:

• Posterior globe contour
• Depth of excavation
• Associated retinal detachment

It can help distinguish a true posterior wall ectasia from optic-disc-only excavation.

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Fundus Photography

Wide-field or standard fundus photography is helpful for:

• Baseline documentation
• Monitoring structural change
• Demonstrating the relationship between optic disc and excavation

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OCT-A / Angiography

Not routinely required.

May be useful if there is concern for:

• Secondary choroidal neovascularization
• Vascular abnormality
• Associated retinal complication

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Differential Diagnosis

The major differentials are:

• Morning glory disc anomaly
• Optic disc coloboma
• Myopic posterior staphyloma
• Optic disc pit
• Tilted disc syndrome

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Peripapillary Staphyloma vs Morning Glory Disc Anomaly

Peripapillary Staphyloma

• Deep excavation surrounding the optic disc
• Disc itself relatively normal
• No central glial tuft
• Retinal vessels not classically arranged radially
• Usually no pigment ring encircling a malformed disc

Morning Glory Disc Anomaly

• Funnel-shaped excavation incorporating the disc
• Enlarged anomalous disc
• Central white glial tuft
• Radial spoke-like vessels
• Peripapillary pigment ring
• Associated with CNS and vascular anomalies, including moyamoya and basal encephalocele

This distinction is important because morning glory anomaly has much stronger systemic associations.

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Peripapillary Staphyloma vs Optic Disc Coloboma

Peripapillary Staphyloma

• Excavation surrounds the disc
• Disc relatively preserved
• No typical inferonasal embryonic fissure defect

Optic Disc Coloboma

• Excavation involves the optic disc itself
• Usually inferior or inferonasal
• May extend into adjacent choroid/retina
• Often associated with other colobomatous defects

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Peripapillary Staphyloma vs Myopic Posterior Staphyloma

Congenital Peripapillary Staphyloma

• Usually unilateral
• Congenital
• May occur without high myopia
• Optic-disc-centered excavation

Myopic Posterior Staphyloma

• Associated with pathologic axial myopia
• Acquired/progressive
• Outpouching of posterior eyewall
• May involve macula or other posterior pole regions
• Associated with myopic maculopathy, traction maculopathy, and CNV

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Treatment

There is:

No treatment that corrects the congenital staphylomatous excavation itself.

Management focuses on:

• Maximizing vision
• Treating amblyopia
• Correcting refractive error
• Managing strabismus
• Monitoring for retinal detachment

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Refractive Correction

Perform:

Cycloplegic refraction

particularly in children.

Correct:

• Myopia
• Hyperopia
• Astigmatism
• Anisometropia

to optimize visual potential.

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Amblyopia Therapy

If unilateral reduced vision is partly amblyopic, treatment may include:

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

The response may be limited by underlying congenital retinal or optic nerve abnormalities.

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Strabismus

Strabismus may develop because of reduced vision.

Management may include:

• Amblyopia treatment first
• Prism in selected cases
• Strabismus surgery when appropriate

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Retinal Detachment

Retinal detachment requires:

Prompt vitreoretinal evaluation

Treatment depends on the mechanism and may include:

• Vitrectomy
• Laser photocoagulation
• Tamponade
• Other retinal surgical techniques

Surgery can be challenging because of abnormal posterior anatomy.

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Protective Eyewear

If one eye has substantially reduced vision:

Impact-resistant protective eyewear is recommended

to protect the better-seeing eye.

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Low-Vision Rehabilitation

For significant bilateral impairment, consider:

• Low-vision evaluation
• Magnification
• Educational accommodations
• Orientation and mobility support when necessary

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Follow-Up

Follow-up should include:

• Visual acuity
• Refraction
• Amblyopia assessment
• Alignment
• Dilated retinal examination
• OCT when useful

Frequency depends on:

• Age
• Visual function
• Retinal status
• Presence of complications

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Retinal Surveillance

Patients should be monitored for:

• New retinal breaks
• Retinal detachment
• Macular changes

Urgent assessment is warranted for:

• New flashes
• Floaters
• Curtain or shadow
• Sudden visual decline

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Pediatric Considerations

In children, the priority is to maximize visual development.

Evaluate promptly for:

• Refractive error
• Anisometropia
• Strabismus
• Amblyopia

Failure to treat a superimposed amblyopic component may unnecessarily reduce final visual acuity.

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Prognosis

Visual prognosis is highly variable.

Some patients retain:

• Good central vision

while others have substantial congenital visual impairment.

Outcome depends on:

• Macular anatomy
• Optic nerve function
• Degree of amblyopia
• Refractive error
• Development of retinal detachment

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Complications

The major complications are:

• Amblyopia
• Strabismus
• Retinal detachment
• Permanent visual loss

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Ophthalmology Pearls

• Peripapillary staphyloma is a congenital deep excavation surrounding a relatively normal optic disc.
• The optic disc lies at the bottom of the excavation, rather than being the malformed excavated structure itself.
• The lesion is usually unilateral and sporadic.
• High myopia is not required, distinguishing it from acquired myopic posterior staphyloma.
• The most important differentials are morning glory disc anomaly and optic disc coloboma.
• Morning glory anomaly has a central glial tuft, radial vessels, and funnel-shaped anomalous disc, while peripapillary staphyloma usually does not.
• Optic disc coloboma typically involves the disc itself, often inferiorly.
• OCT and B-scan can help define the posterior globe excavation and detect associated retinal pathology.
• There is no treatment for the congenital excavation itself.
• Management should maximize visual potential with refractive correction and amblyopia therapy.
• Patients require surveillance for retinal detachment, the major sight-threatening acquired complication.
• In unilateral disease with poor vision, recommend protective eyewear for the better eye.

Ophthalmology – Posterior Polymorphous Corneal Dystrophy

Basics

Description

Posterior polymorphous corneal dystrophy (PPCD/PPMD) is an inherited disorder of the corneal endothelium and Descemet membrane, usually bilateral but often markedly asymmetric.

The hallmark abnormality is transformation of corneal endothelial cells toward an:

Epithelial-like phenotype

This may produce:

• Vesicular posterior corneal lesions
• Band-like or geographic opacities
• Thickened/abnormal Descemet membrane
• Peripheral anterior synechiae
• Secondary glaucoma
• Corneal edema in more severe disease

Most affected patients remain:

Asymptomatic throughout life.

Clinical Importance

Although PPCD is usually mild, severe disease may cause:

• Progressive endothelial failure
• Stromal and epithelial edema
• Reduced visual acuity
• Secondary glaucoma
• Iridocorneal adhesions

In children, dense corneal edema or opacity can additionally cause:

Deprivation amblyopia

Epidemiology

PPCD is rare.

The exact:

• Incidence
• Prevalence

are unknown because many patients are asymptomatic and never diagnosed.

Inheritance

PPCD is most commonly inherited in an:

Autosomal dominant

pattern with variable expressivity.

Disease severity may differ substantially:

• Between family members
• Between the two eyes of the same patient

Genetics

Important modern genetic associations include:

• ZEB1
• OVOL2 regulatory variants
• GRHL2 regulatory variants

Older classifications described a COL8A2-associated “PPCD2” phenotype, but current molecular classification has evolved, and COL8A2 is more strongly associated with certain endothelial dystrophy phenotypes such as early-onset Fuchs disease rather than being a major cause of typical PPCD.

Genetic testing is most useful when:

• Disease is familial
• Presentation is early or severe
• Diagnosis is uncertain
• Counseling is desired

ZEB1-Associated PPCD

ZEB1 is an important cause of PPCD.

ZEB1 normally helps maintain:

Corneal endothelial identity

Loss of normal ZEB1 activity promotes:

• Endothelial-to-epithelial transformation
• Abnormal multilayering
• Epithelial marker expression

This explains much of the characteristic histology of PPCD.

Pathophysiology

Normal corneal endothelium consists of a:

• Single layer
• Nonregenerating
• Hexagonal endothelial cells

In PPCD, endothelial cells may acquire epithelial-like characteristics, including:

• Cellular proliferation
• Multilayering
• Desmosomes
• Cytokeratin expression
• Microvilli

These abnormal cells may migrate onto:

• Trabecular meshwork
• Peripheral iris

leading to:

• Peripheral anterior synechiae
• Angle obstruction
• Secondary glaucoma

Descemet Membrane Abnormalities

Descemet membrane may show:

• Irregular thickening
• Abnormal posterior collagenous material
• Focal excrescences
• Vesicular or band-like changes

These correspond clinically to the classic posterior corneal lesions.

Clinical Presentation

Most patients are:

Asymptomatic

and diagnosed incidentally.

Symptomatic patients may report:

• Blurred vision
• Glare
• Foreign-body sensation
• Photophobia
• Fluctuating vision

Symptoms usually result from:

• Corneal edema
• Irregular astigmatism
• Secondary glaucoma

Laterality

PPCD is generally:

Bilateral

but can be strikingly asymmetric.

Occasionally one eye appears clinically normal.

Slit-Lamp Findings

Classic posterior corneal findings include:

• Vesicles
• Band-like lesions
• Geographic opacities
• “Railroad-track” lesions
• Abnormal thickening of Descemet membrane

Vesicular Lesions

The classic lesion is a:

Small posterior corneal vesicle

which may be:

• Solitary
• Grouped
• Surrounded by a gray halo

They arise at the level of:

• Endothelium
• Descemet membrane

Band Lesions

Linear or curvilinear lesions may appear as:

Parallel tracks

sometimes described as:

• Railroad tracks
• Snail-track-like posterior opacities

These reflect broader areas of abnormal endothelium and Descemet membrane.

Geographic Lesions

Some patients develop:

• Irregular
• Geographic
• Sheet-like posterior corneal opacities

These may be associated with more extensive endothelial dysfunction.

Corneal Edema

Most patients do not develop significant edema.

In advanced disease:

• Endothelial pump failure

can produce:

• Stromal edema
• Epithelial edema
• Bullous keratopathy
• Subepithelial fibrosis

Pediatric Disease

Rare severe cases may present in infancy or childhood with:

• Corneal edema
• Corneal haze
• Reduced vision

This may cause:

Form-deprivation amblyopia

and requires early visual rehabilitation.

Iris and Angle Findings

Abnormal endothelial-like cells may extend across the angle.

Findings may include:

• Peripheral anterior synechiae
• Iridocorneal adhesions
• Distorted pupil in severe cases
• Abnormal angle membranes

These features increase the risk of:

Secondary glaucoma

Glaucoma

Glaucoma is the most important noncorneal complication.

Possible mechanisms include:

• Endothelial-like membrane extending over trabecular meshwork
• PAS formation
• Developmental angle abnormalities
• Open-angle outflow obstruction

Glaucoma can therefore occur with:

• Open angles
• Synechially closed angles
• Mixed mechanisms

Intraocular Pressure

IOP should be measured in all patients because glaucoma may be:

• Asymptomatic
• Progressive
• Disproportionate to the degree of corneal disease

Optic Nerve Assessment

Evaluate:

• Cup-to-disc ratio
• Neuroretinal rim
• RNFL OCT
• Macular GCIPL/GCC
• Visual fields

when age and visual function permit.

Gonioscopy

Gonioscopy is important to assess for:

• PAS
• Abnormal endothelial membrane
• Angle closure
• Developmental angle abnormalities

This helps determine the glaucoma mechanism.

Pachymetry

Central corneal thickness may increase with:

• Endothelial dysfunction
• Corneal edema

Serial pachymetry can help monitor:

• Progression
• Response to treatment

but is not specific for PPCD.

Specular Microscopy

Specular microscopy may show:

• Abnormal endothelial morphology
• Multilayered or vesicular lesions
• Reduced normal hexagonal pattern
• Highly irregular endothelial mosaic

It can help distinguish PPCD from other endothelial dystrophies.

Confocal Microscopy

In vivo confocal microscopy may demonstrate:

• Abnormal endothelial morphology
• Epithelial-like cells
• Vesicular lesions
• Multilayered cell patterns

It can be useful when:

• Slit-lamp visualization is poor
• Corneal edema obscures the posterior cornea

Anterior Segment OCT

AS-OCT may help document:

• Descemet abnormalities
• Posterior corneal lesions
• Corneal thickness
• Peripheral adhesions

but diagnosis is usually clinical.

Corneal Tomography

Corneal topography/tomography may be useful if there is:

• Significant astigmatism
• Suspected keratoconus
• Irregular corneal shape

Associated Corneal Disorders

PPCD has occasionally been reported with:

• Keratoconus
• Keratoglobus
• Other ectatic corneal disorders

Some ZEB1-associated phenotypes may have:

• Steeper corneas
• Abnormal corneal biomechanics

but these associations are variable.

Diagnosis

Diagnosis is usually based on:

• Characteristic slit-lamp appearance
• Bilaterality/asymmetry
• Family history
• Gonioscopy
• Specular or confocal microscopy when needed

Genetic Testing

Genetic testing may support the diagnosis in selected patients.

Consider especially when there is:

• Strong autosomal dominant family history
• Severe childhood disease
• Atypical presentation
• Need for family counseling

Differential Diagnosis

Important differentials include:

• Iridocorneal endothelial syndrome
• Fuchs endothelial corneal dystrophy
• Congenital hereditary endothelial dystrophy
• Descemet membrane tears
• Birth trauma
• Corneal edema from glaucoma
• Other posterior corneal dystrophies

PPCD vs ICE Syndrome

This is one of the most important distinctions.

PPCD

Usually:

• Bilateral
• Familial
• Younger onset
• Often relatively stable
• Endothelial cells have epithelial-like characteristics

ICE Syndrome

Typically:

• Unilateral
• Sporadic
• Adult onset
• Progressive
• More common in women
• Associated with:
• Corectopia
• Iris atrophy
• PAS
• Secondary glaucoma

PPCD vs Fuchs Endothelial Corneal Dystrophy

PPCD

• Vesicles/bands
• Often younger onset
• Epithelialized endothelial cells
• PAS may occur
• Autosomal dominant families possible

Fuchs

• Central guttae
• Progressive endothelial loss
• Central-to-peripheral edema
• Usually later onset
• No characteristic epithelial transformation of endothelium

PPCD vs Congenital Hereditary Endothelial Dystrophy

CHED typically presents with:

• Bilateral diffuse corneal edema
• Corneal clouding from infancy or childhood
• No classic posterior vesicles or railroad-track lesions

Modern CHED is primarily associated with:

SLC4A11

and usually follows an:

Autosomal recessive

inheritance pattern.

PPCD vs Descemet Tears

Descemet tears may occur after:

• Birth trauma
• Congenital glaucoma
• Surgery

They usually appear:

• Linear
• Localized

and lack the typical familial bilateral pattern of PPCD.

Treatment Principles

Most patients require:

Observation only

Treatment is directed toward complications rather than the dystrophy itself.

Mild Disease

If the patient is asymptomatic with:

• Clear cornea
• Normal IOP
• No progressive glaucoma

management consists of:

• Observation
• Periodic corneal examination
• Glaucoma surveillance

Hypertonic Saline

Hypertonic sodium chloride may reduce symptoms from:

• Epithelial edema
• Morning blur

It can be used as:

• Drops
• Ointment

However:

It does not reverse endothelial dysfunction or prevent progression.

Lubrication

Artificial tears may help if there is:

• Surface irritation
• Recurrent epithelial symptoms

Glaucoma Treatment

IOP-lowering therapy may include:

• Prostaglandin analogs
• Beta-blockers
• Carbonic anhydrase inhibitors
• Alpha-2 agonists

Treatment depends on:

• Angle status
• Severity
• Optic nerve damage

Glaucoma Surgery

Surgery may be required when:

• IOP remains uncontrolled
• PAS are extensive
• Glaucomatous progression occurs

Options include:

• Trabeculectomy
• Glaucoma drainage device
• Other glaucoma procedures based on angle anatomy

Angle surgery may have limited success in eyes with significant:

• PAS
• Endothelial membrane overgrowth

Endothelial Keratoplasty

For visually significant endothelial failure:

Endothelial keratoplasty is generally preferred over penetrating keratoplasty when anatomy permits.

Options include:

• DMEK
• DSAEK/DSEK

DMEK

DMEK offers:

• Rapid visual rehabilitation
• Minimal induced astigmatism
• Low rejection risk

However, PPCD can be technically challenging because of:

• Abnormal Descemet membrane
• PAS
• Irregular posterior corneal anatomy

Case selection is important.

DSAEK / DSEK

DSAEK may be preferred in some complex eyes because:

• Tissue is easier to manipulate
• Surgery may be more forgiving when the anterior segment is abnormal

Visual recovery may be slightly less optimal than with DMEK.

Penetrating Keratoplasty

PK is now generally reserved for cases with:

• Significant stromal scarring
• Extensive structural abnormalities
• Failed endothelial keratoplasty
• Anatomy unsuitable for endothelial keratoplasty

Pediatric Surgery

In children with severe corneal edema, early intervention may be needed to prevent:

Irreversible amblyopia

Management should include:

• Corneal surgery when indicated
• Optical correction
• Amblyopia therapy

Amblyopia

Children with asymmetric or bilateral corneal opacity require:

• Cycloplegic refraction
• Spectacle/contact lens correction
• Patching when appropriate
• Close pediatric ophthalmic follow-up

A clear graft alone does not guarantee good visual development.

Follow-Up

Follow-up should assess:

• Visual acuity
• Corneal clarity
• Corneal thickness
• IOP
• Gonioscopy
• Optic nerve
• OCT
• Visual fields when appropriate

Family Screening

Because many cases are autosomal dominant:

First-degree relatives may benefit from slit-lamp examination and IOP screening.

Family screening may reveal:

• Mild vesicular disease
• Previously unrecognized glaucoma

Prognosis

Overall prognosis is:

Excellent in most patients

because disease is often mild or slowly progressive.

Only a minority develop:

• Significant endothelial failure
• Severe glaucoma
• Need for corneal transplantation

Poor Prognostic Features

More severe disease is associated with:

• Early corneal edema
• Extensive PAS
• Secondary glaucoma
• Significant endothelial failure
• Dense stromal scarring

Complications

Potential complications include:

• Secondary glaucoma
• Peripheral anterior synechiae
• Corneal edema
• Bullous keratopathy
• Stromal scarring
• Reduced vision
• Amblyopia in children

Ophthalmology Pearls

• Posterior polymorphous corneal dystrophy is an inherited disorder of Descemet membrane and corneal endothelium, usually bilateral but often asymmetric.
• The classic lesions are posterior corneal vesicles, band-like “railroad-track” lesions, and geographic opacities.
• The fundamental cellular abnormality is epithelial-like transformation of corneal endothelial cells.
• Important modern genetic associations include ZEB1, OVOL2, and GRHL2.
• Most patients are asymptomatic and need only observation.
• Always screen for glaucoma, because abnormal endothelial cells can extend across the angle and produce PAS or trabecular obstruction.
• Gonioscopy is important to identify peripheral anterior synechiae and angle involvement.
• PPCD differs from ICE syndrome because PPCD is usually bilateral and familial, whereas ICE is typically unilateral, sporadic, and progressive.
• PPCD differs from Fuchs dystrophy by its vesicular/band lesions and epithelialized endothelium rather than central guttae.
• Hypertonic saline may improve symptoms from edema but does not correct endothelial failure.
• When corneal decompensation becomes visually significant, DMEK or DSAEK/DSEK is generally preferred over PK when anatomy is suitable.
• In children, severe corneal edema requires early treatment because of the risk of deprivation amblyopia.
• Family members may benefit from screening because PPCD is commonly autosomal dominant with variable expressivity.

Ophthalmology – Posterior Embryotoxon

Basics

Description

Posterior embryotoxon (PE) is a congenital anterior segment anomaly in which Schwalbe line is abnormally thickened and displaced anteriorly, making it visible on slit-lamp examination or gonioscopy.

Schwalbe line represents the peripheral termination of:

• Descemet membrane
• Corneal endothelium

at the junction with the:

• Trabecular meshwork

Posterior embryotoxon may be:

• Continuous or discontinuous
• Unilateral or bilateral
• Isolated
• Associated with anterior segment dysgenesis or systemic syndromes

Isolated PE is usually:

Benign and visually insignificant.

Clinical Importance

The main clinical importance of posterior embryotoxon is not the lesion itself, but its association with:

• Axenfeld–Rieger spectrum
• Alagille syndrome
• Other anterior segment developmental disorders
• Glaucoma in selected patients

Therefore the examiner should determine whether PE is:

An isolated incidental finding or part of a broader developmental disorder.

Embryology

The structures of the anterior chamber angle are derived largely from:

Neural crest cells

including elements contributing to:

• Corneal endothelium
• Descemet membrane
• Trabecular meshwork
• Iris stroma

Abnormal development or migration of these tissues can produce:

• Anterior displacement of Schwalbe line
• Iridocorneal strands
• Angle dysgenesis

Epidemiology

Posterior embryotoxon is relatively common in otherwise normal individuals.

Reported prevalence in the general population is approximately:

8–15%

Therefore:

The presence of PE alone does not imply a systemic syndrome.

Associated Disorders

Important associations include:

• Axenfeld–Rieger spectrum
• Alagille syndrome
• 22q11.2 deletion syndrome in selected cases
• Other developmental syndromes

Genetics

Isolated posterior embryotoxon is usually:

• Sporadic

Familial cases have been described.

When PE occurs as part of a syndrome, inheritance follows the underlying disorder.

Axenfeld–Rieger Spectrum

Axenfeld–Rieger spectrum is usually associated with pathogenic variants involving:

• FOXC1
• PITX2

and generally follows:

Autosomal dominant inheritance

with variable expressivity.

Alagille Syndrome

Alagille syndrome is most commonly caused by pathogenic variants in:

• JAG1
• Less commonly NOTCH2

Important correction:

JAG1 encodes the JAGGED1 ligand in the Notch signaling pathway; it does not encode NOTCH1.

Inheritance is usually:

Autosomal dominant

although many cases result from a de novo variant.

Posterior Embryotoxon in Alagille Syndrome

PE is one of the most common ocular findings in Alagille syndrome.

It occurs in a large proportion of affected patients and can provide an important diagnostic clue.

Other ophthalmic findings may include:

• Iris abnormalities
• Optic disc abnormalities
• Optic disc drusen
• Retinal pigmentary changes
• Diffuse fundus hypopigmentation

Visual acuity is often relatively preserved unless another ocular abnormality is present.

Alagille Syndrome – Systemic Features

Important systemic manifestations include:

• Cholestatic liver disease
• Congenital heart disease
• Pulmonary artery stenosis
• Characteristic facial features
• Vertebral abnormalities
• Renal disease
• Vascular abnormalities

Hepatic Findings in Alagille Syndrome

Children may present with:

• Neonatal or infantile jaundice
• Cholestasis
• Pruritus
• Hyperbilirubinemia
• Progressive liver disease

The characteristic liver abnormality is:

Paucity of intrahepatic bile ducts

Cardiac Findings in Alagille Syndrome

Congenital heart disease is common.

The classic cardiovascular abnormality is:

Peripheral pulmonary artery stenosis

Other cardiac abnormalities may also occur.

Skeletal Findings

A classic radiographic feature is:

Butterfly vertebrae

most commonly involving the thoracic spine.

Facial Features

Characteristic facial features may include:

• Broad or prominent forehead
• Deep-set eyes
• Straight or saddle nose
• Bulbous nasal tip
• Pointed chin

The overall appearance may become more recognizable with age.

Axenfeld–Rieger Spectrum

Posterior embryotoxon is a common component of:

Axenfeld–Rieger anterior segment dysgenesis

Associated findings may include:

• Iridocorneal adhesions
• Iris hypoplasia
• Corectopia
• Polycoria
• Abnormal angle development

Axenfeld Anomaly

The historical term Axenfeld anomaly generally describes:

• Posterior embryotoxon
• Iris strands extending to the prominent Schwalbe line

without the more extensive iris abnormalities of Rieger anomaly.

Modern usage increasingly considers these conditions part of a continuous:

Axenfeld–Rieger spectrum

Glaucoma Risk

The major ocular complication of Axenfeld–Rieger spectrum is:

Developmental glaucoma

which may occur in childhood or later.

The risk results from:

• Abnormal angle development
• Trabecular dysgenesis

rather than the posterior embryotoxon itself.

Important Principle

Isolated posterior embryotoxon is not synonymous with glaucoma.

Glaucoma risk becomes much more relevant when there are associated:

• Iridocorneal adhesions
• Angle abnormalities
• Iris dysgenesis
• Axenfeld–Rieger features

Clinical Presentation

Most patients with isolated PE are:

Asymptomatic

The finding is often discovered incidentally during:

• Routine slit-lamp examination
• Gonioscopy

Slit-Lamp Appearance

PE appears as a:

• Gray-white
• Hyaline
• Glassy
• Sharply defined

line near the peripheral posterior cornea.

It lies anterior to the normal expected position of:

Schwalbe line

Location

The visible line is typically:

• Concentric with the limbus
• Approximately 0.5–2 mm inside the limbus

It may be:

• Segmental
• Discontinuous
• More prominent in some quadrants than others

Gonioscopy

Gonioscopy is important when PE is suspected.

It can demonstrate:

• Anteriorly displaced Schwalbe line
• Associated iris processes
• Iridocorneal strands
• Abnormal angle anatomy

Iris Strands

Fine iris strands may extend across the angle and insert onto:

Posterior embryotoxon

These are particularly suggestive of:

• Axenfeld anomaly
• Broader anterior segment dysgenesis

Peripheral Anterior Synechiae vs Developmental Strands

Developmental iris strands should be distinguished from:

Peripheral anterior synechiae (PAS)

PAS usually result from:

• Inflammation
• Angle closure
• Trauma
• Surgery

and have a different clinical context.

Intraocular Pressure

IOP is usually normal in isolated PE.

Elevated IOP should prompt evaluation for:

• Developmental glaucoma
• Axenfeld–Rieger spectrum
• Another glaucoma mechanism

Optic Nerve Examination

Assess:

• Cup-to-disc ratio
• Rim integrity
• Asymmetry
• RNFL

particularly when:

• Angle abnormalities are present
• Family history of glaucoma exists
• IOP is elevated

Anterior Segment OCT

AS-OCT may demonstrate:

• Prominent Schwalbe line
• Abnormal angle anatomy

It can be useful for structural documentation but is usually not required in straightforward cases.

Ultrasound Biomicroscopy

UBM may be helpful when there is:

• Complex anterior segment dysgenesis
• Poor visualization
• Suspicion of associated ciliary body abnormalities

Routine isolated PE generally does not require UBM.

Laboratory Evaluation

No laboratory testing is required for:

Isolated posterior embryotoxon

Systemic investigations are guided by associated findings.

Evaluation for Alagille Syndrome

If PE occurs with suggestive systemic features, consider evaluation for:

• Liver disease
• Cardiac disease
• Renal abnormalities
• Vertebral anomalies

This may include:

• Liver function testing
• Bilirubin
• Cardiac evaluation
• Renal evaluation
• Genetic testing

according to the clinical situation.

Genetic Testing

Genetic referral may be appropriate when there are features of:

Axenfeld–Rieger Spectrum

Consider:

• FOXC1
• PITX2

Alagille Syndrome

Consider:

• JAG1
• NOTCH2

Broader testing may be appropriate in complex congenital presentations.

Family Examination

When a heritable anterior segment dysgenesis syndrome is suspected, examination of:

• Parents
• Siblings
• Children

may reveal subtle:

• Posterior embryotoxon
• Iris abnormalities
• Glaucoma

because expressivity can vary considerably within a family.

Differential Diagnosis

Important differentials include:

• Peripheral anterior synechiae
• Peripheral corneal scar
• Peripheral endothelial opacity
• Peripheral stromal opacity
• Surgical wound scar
• Previous trauma
• Corneal endothelial deposits

Posterior Embryotoxon vs Arcus

Corneal arcus is located within:

• Peripheral corneal stroma

and usually appears:

• White-gray
• Circumferential
• Separated from limbus by a clear interval

Posterior embryotoxon is located at:

The posterior corneal/angle level

and corresponds to anteriorly displaced Schwalbe line.

Posterior Embryotoxon vs Peripheral Anterior Synechiae

Posterior Embryotoxon

• Congenital
• Smooth prominent Schwalbe line
• Usually circumferential or segmental

PAS

• Iris adherent directly to angle structures
• Often acquired
• Associated with inflammation, angle closure, trauma, or surgery

Treatment

There is:

No treatment required for isolated posterior embryotoxon.

The finding itself does not need to be:

• Excised
• Lasered
• Surgically corrected

Glaucoma Treatment

If glaucoma develops, treatment follows the underlying glaucoma mechanism.

Options may include:

• Topical IOP-lowering medication
• Angle surgery
• Trabeculectomy
• Glaucoma drainage device

depending on:

• Age
• Angle anatomy
• Disease severity

Iridocorneal Strands

Developmental iris strands generally do:

Not require surgical lysis

unless an unusual specific indication exists.

Management is directed toward:

• IOP
• Glaucoma
• Associated structural abnormalities

rather than the strands themselves.

Follow-Up

Isolated PE with:

• Normal IOP
• Normal angle
• Normal optic nerve

generally requires only routine ophthalmic surveillance.

Closer follow-up is appropriate when there is:

• Iridocorneal adhesion
• Elevated IOP
• Abnormal optic nerve
• Axenfeld–Rieger syndrome
• Family history of glaucoma

Monitoring

Follow-up may include:

• IOP measurement
• Gonioscopy
• Optic disc examination
• RNFL OCT when appropriate
• Visual field testing in older cooperative patients

Prognosis

For isolated posterior embryotoxon:

Visual prognosis is excellent.

The prognosis is determined primarily by associated disease rather than PE itself.

Prognosis in Axenfeld–Rieger Spectrum

Visual outcome depends heavily on:

• Development of glaucoma
• Severity of anterior segment dysgenesis
• Age at glaucoma onset
• Degree of optic nerve damage

Prognosis in Alagille Syndrome

Posterior embryotoxon itself generally causes:

Little or no visual impairment

and, unlike Axenfeld–Rieger spectrum, is not usually associated with a major intrinsic glaucoma risk.

Overall prognosis is driven primarily by:

• Hepatic disease
• Cardiovascular abnormalities
• Other systemic manifestations

Complications

Posterior embryotoxon itself usually causes no complications.

When associated with anterior segment dysgenesis, complications may include:

• Glaucoma
• Progressive optic neuropathy
• Visual field loss

Systemic complications depend on the underlying syndrome.

Ophthalmology Pearls

• Posterior embryotoxon is a thickened, anteriorly displaced Schwalbe line.
• It is relatively common in the normal population, so isolated PE is usually a benign incidental finding.
• Gonioscopy is useful to confirm PE and detect associated iridocorneal strands or angle dysgenesis.
• PE plus iris strands inserting onto Schwalbe line is characteristic of the Axenfeld component of Axenfeld–Rieger spectrum.
• Axenfeld–Rieger spectrum is most strongly associated with FOXC1 and PITX2 and carries a significant risk of glaucoma.
• Posterior embryotoxon is also a classic ocular finding of Alagille syndrome.
• Alagille syndrome is usually caused by JAG1, less commonly NOTCH2; JAG1 encodes the JAGGED1 ligand of the Notch pathway.
• Classic systemic clues to Alagille include cholestatic liver disease, peripheral pulmonary artery stenosis, butterfly vertebrae, and characteristic facies.
• Isolated PE itself does not require treatment.
• The glaucoma risk arises mainly from associated angle dysgenesis, not simply from the visible Schwalbe line.
• Developmental iridocorneal strands generally do not require surgical lysis.
• In Alagille syndrome, PE is common but usually does not itself confer the same glaucoma risk seen in Axenfeld–Rieger spectrum.

Ophthalmology – Polymyalgia Rheumatica

Basics

Description

Polymyalgia rheumatica (PMR) is an inflammatory disorder of adults aged ≥50 years characterized by:

• Bilateral shoulder pain
• Marked morning stiffness
• Hip-girdle pain or stiffness
• Elevated inflammatory markers in most patients
• Rapid symptomatic response to glucocorticoids

Despite the name, PMR is primarily a disorder of:

• Bursae
• Synovial structures
• Periarticular tissues

rather than a primary inflammatory myopathy.

The most important ophthalmic association is:

Giant cell arteritis (GCA)

because GCA can cause sudden, irreversible blindness.

PMR and Giant Cell Arteritis

PMR and GCA are closely related inflammatory diseases occurring in the same age group.

Approximately:

• 10–20% of patients with PMR develop clinically apparent GCA
• Roughly 40–60% of patients with GCA have PMR-type symptoms

Therefore every patient with PMR should be questioned about symptoms of GCA.

Ophthalmic Importance

The key clinical priority is identifying GCA before permanent visual loss occurs.

Ask specifically about:

• New headache
• Scalp tenderness
• Jaw claudication
• Transient monocular visual loss
• Diplopia
• Sudden visual loss
• Constitutional symptoms

Any of these should prompt:

Urgent evaluation for GCA

Epidemiology

PMR occurs almost exclusively in people:

Older than 50 years

Incidence rises substantially with age.

It is more common in:

• Women
• People of Northern European ancestry

but can occur in all ethnic groups.

Risk Factors

Established associations include:

• Age >50 years
• Female sex
• Northern European ancestry

Genetic susceptibility has been associated with:

• HLA-DRB1
• Other immune-regulatory loci

There is no simple Mendelian inheritance pattern.

Pathophysiology

PMR is characterized by systemic inflammation involving:

• Subacromial-subdeltoid bursae
• Trochanteric bursae
• Glenohumeral synovium
• Hip synovium
• Periarticular structures

A major inflammatory mediator is:

Interleukin-6 (IL-6)

which helps explain the effectiveness of IL-6 pathway inhibition in selected patients.

Etiology

The precise cause is unknown.

Likely contributors include:

• Genetic susceptibility
• Immune dysregulation
• Environmental triggers

No single infectious agent has been established as the cause.

Clinical Presentation

The classic patient is:

An adult over 50 with new bilateral shoulder aching and prolonged morning stiffness

Symptoms often develop:

• Over days to weeks
• Occasionally quite abruptly

Pain Distribution

Typical areas include:

• Shoulders
• Neck
• Upper arms
• Hips
• Buttocks
• Thighs

Pain is usually:

• Bilateral
• Symmetric
• Worse after inactivity

Morning Stiffness

A characteristic feature is:

Morning stiffness lasting >45 minutes

Patients may report difficulty:

• Getting out of bed
• Dressing
• Raising the arms
• Combing hair
• Rising from a chair

Muscle Strength

Despite severe subjective weakness:

True muscle strength is usually normal

when pain is overcome.

True objective weakness should prompt consideration of:

• Inflammatory myopathy
• Neuromuscular disease
• Neurologic disorders

Constitutional Symptoms

Patients may also have:

• Fatigue
• Malaise
• Low-grade fever
• Anorexia
• Weight loss
• Depression

Prominent constitutional symptoms should also raise consideration of:

• GCA
• Infection
• Malignancy

Peripheral Manifestations

Some patients develop:

• Wrist or knee synovitis
• Distal extremity edema
• Carpal tunnel syndrome

A syndrome of remitting seronegative symmetrical synovitis with pitting edema may overlap clinically.

Diagnosis

PMR remains a:

Clinical diagnosis supported by inflammatory markers and exclusion of mimics

There is no single confirmatory test.

Typical Diagnostic Features

Features supporting PMR include:

• Age ≥50 years
• Bilateral shoulder pain
• Morning stiffness >45 minutes
• Hip pain or restricted movement
• Elevated ESR and/or CRP
• Negative RF and anti-CCP
• Rapid improvement with low-to-moderate-dose glucocorticoid

Inflammatory Markers

Typical laboratory abnormalities include:

• Elevated CRP
• Elevated ESR
• Thrombocytosis
• Mild normocytic anemia

ESR may exceed:

• 40 mm/h
• Occasionally >100 mm/h

However:

A normal ESR does not exclude PMR

and a small minority can have relatively normal inflammatory markers.

CRP

CRP is often especially useful because it:

• Responds rapidly to inflammatory activity
• Is less affected by age or anemia than ESR

Both ESR and CRP should be interpreted with the clinical picture.

Creatine Kinase

CK is generally:

Normal

This helps distinguish PMR from:

• Polymyositis
• Dermatomyositis
• Some drug-induced myopathies

Rheumatoid Factor and Anti-CCP

RF and anti-CCP are usually:

Negative

Positive anti-CCP, especially with peripheral synovitis, raises concern for:

Elderly-onset rheumatoid arthritis

rather than pure PMR.

Ultrasound

Musculoskeletal ultrasound may support the diagnosis.

Typical findings include:

• Subacromial-subdeltoid bursitis
• Biceps tenosynovitis
• Glenohumeral synovitis
• Trochanteric bursitis
• Hip synovitis

Ultrasound is particularly helpful when:

• Diagnosis is uncertain
• Inflammatory markers are equivocal
• RA is in the differential

PET/CT

FDG-PET/CT is not routinely required for uncomplicated PMR.

It may be useful when evaluating:

• Large-vessel GCA
• Atypical systemic inflammation
• Persistent unexplained inflammatory markers

Giant Cell Arteritis – Symptoms

Ask every PMR patient about:

• New headache
• Temporal or occipital scalp tenderness
• Jaw claudication
• Tongue pain or claudication
• Transient visual obscurations
• Amaurosis fugax
• Diplopia
• Sudden vision loss

Jaw claudication is particularly suggestive of GCA.

Giant Cell Arteritis – Ocular Manifestations

Ocular ischemia may produce:

• Arteritic anterior ischemic optic neuropathy (AAION)
• Central retinal artery occlusion
• Cilioretinal artery occlusion
• Ocular ischemic syndrome
• Diplopia from ischemic cranial neuropathy
• Rare posterior ischemic optic neuropathy
• Choroidal ischemia

The most common cause of permanent visual loss is:

AAION

AAION Appearance

Typical optic disc findings include:

• Profound visual loss
• RAPD if unilateral/asymmetric
• Chalky-white or pale disc edema
• Occasionally peripapillary hemorrhages

This contrasts with the more hyperemic disc often seen in NAION.

Visual Symptoms Are an Emergency

In a patient over 50 with suspected GCA:

Transient or permanent visual symptoms require immediate treatment.

Do not wait for:

• Temporal artery biopsy
• Ultrasound
• Imaging results

before starting glucocorticoids when clinical suspicion is high.

GCA Laboratory Testing

Order urgently:

• ESR
• CRP
• CBC with platelet count

Possible findings include:

• High ESR
• High CRP
• Thrombocytosis
• Normocytic anemia

Normal inflammatory markers reduce the likelihood but do not absolutely exclude GCA.

Temporal Artery Examination

Look for:

• Tenderness
• Nodularity
• Reduced pulsation
• Thickened artery

However:

A normal temporal artery examination does not exclude GCA.

Temporal Artery Ultrasound

High-resolution vascular ultrasound is increasingly important.

The classic finding is:

Halo sign

representing circumferential arterial wall edema.

Ultrasound can assess:

• Temporal arteries
• Axillary arteries in selected protocols

In experienced centers it may be the preferred initial diagnostic test.

Temporal Artery Biopsy

Temporal artery biopsy remains useful when:

• Diagnosis remains uncertain
• Imaging is unavailable or equivocal
• Histologic confirmation is desired

Classic histology may show:

• Granulomatous arteritis
• Multinucleated giant cells
• Fragmentation of internal elastic lamina

Giant cells are not required for a positive diagnosis.

Biopsy Timing

Treatment should never be delayed for biopsy.

Biopsy is ideally performed promptly, but diagnostic histologic abnormalities may persist for:

At least 1–2 weeks and often longer after starting glucocorticoids.

Large-Vessel GCA

GCA may involve:

• Aorta
• Subclavian arteries
• Axillary arteries
• Other large vessels

Large-vessel disease may occur without classic temporal artery symptoms.

Imaging options include:

• Ultrasound
• CTA
• MRA
• FDG-PET/CT

depending on presentation.

Differential Diagnosis of PMR

Important mimics include:

• Elderly-onset rheumatoid arthritis
• Fibromyalgia
• Polymyositis
• Dermatomyositis
• Hypothyroidism
• Rotator cuff disease
• Osteoarthritis
• Cervical spondylosis
• Statin-associated myopathy
• Infection
• Endocarditis
• Malignancy
• Multiple myeloma

PMR vs Polymyositis

PMR

• Pain and stiffness
• True strength usually preserved
• CK normal

Polymyositis

• True proximal muscle weakness
• CK elevated
• Less prominent shoulder-girdle stiffness

PMR vs Rheumatoid Arthritis

RA is more likely with:

• Persistent peripheral joint synovitis
• MCP/PIP involvement
• Positive anti-CCP
• Erosive changes

PMR more strongly favors:

• Shoulder/hip girdle stiffness
• Bursitis
• Dramatic response to low-dose prednisone

Treatment

First-Line – Glucocorticoids

Initial treatment for uncomplicated PMR is typically:

Prednisone approximately 12.5–25 mg/day

The exact dose depends on:

• Body size
• Symptom severity
• Relapse risk
• Comorbidities

Most patients improve dramatically within:

Several days

Response to Prednisone

A strong clinical response supports the diagnosis.

However:

Steroid response is not specific for PMR

and should not be used as the sole diagnostic test.

Failure to improve substantially should prompt reconsideration of the diagnosis.

Steroid Taper

Once symptoms and inflammatory markers improve:

• Gradually reduce prednisone
• Avoid rapid tapering

A common approach is to taper toward:

10 mg/day over several weeks

then reduce more slowly, often by approximately:

1 mg every 1–2 months

depending on relapse and tolerance.

There is no single taper suitable for every patient.

Duration of Treatment

Older teaching suggested a short self-limited course.

In practice:

Many patients require glucocorticoids for 1–2 years or longer.

Relapses are common.

Relapse

Relapse usually presents with recurrence of:

• Shoulder/hip stiffness
• Pain
• Constitutional symptoms

often accompanied by increased:

• CRP
• ESR

Treatment generally involves:

• Returning temporarily to the previous effective steroid dose
• Then tapering more slowly

Methotrexate

Methotrexate may be added when there is:

• Recurrent relapse
• High glucocorticoid requirement
• High risk of steroid toxicity

Typical weekly doses are approximately:

10–15 mg or more depending on regimen

with:

Folic acid supplementation

IL-6 Inhibition

IL-6 blockade is an increasingly important steroid-sparing strategy.

Sarilumab is approved for adults with PMR who:

• Have inadequate response to corticosteroids
• Cannot adequately tolerate a corticosteroid taper

It can reduce glucocorticoid exposure in selected patients.

Tocilizumab

Tocilizumab has strong evidence and regulatory approval for:

Giant cell arteritis

and may also have efficacy in PMR, although its routine role in isolated PMR depends on local practice and regulatory approval.

Giant Cell Arteritis Treatment

Suspected GCA requires:

Immediate high-dose systemic glucocorticoids

Treatment should begin before diagnostic confirmation if clinical suspicion is substantial.

GCA Without Visual Loss

A typical regimen is approximately:

Prednisone 40–60 mg/day

or about:

1 mg/kg/day up to approximately 60 mg

followed by a prolonged taper.

GCA With Visual Loss or Amaurosis Fugax

When there is:

• Acute visual loss
• Amaurosis fugax
• Strongly threatened vision

many specialists use:

IV methylprednisolone 500–1000 mg/day for 3 days

followed by high-dose oral glucocorticoids.

The goal is primarily to:

Protect the fellow eye

because established ischemic visual loss is often irreversible.

Tocilizumab in GCA

Tocilizumab is an important steroid-sparing treatment for GCA.

It can:

• Reduce relapse
• Reduce cumulative glucocorticoid exposure

Management is coordinated with rheumatology.

Glucocorticoid Toxicity Prevention

Long-term steroid therapy requires monitoring for:

• Hypertension
• Diabetes
• Osteoporosis
• Infection
• Cataract
• Glaucoma
• Weight gain
• Adrenal suppression

Bone Protection

Assess:

• Calcium intake
• Vitamin D
• Fracture risk
• Bone density

Bisphosphonate therapy may be indicated depending on:

• Steroid dose
• Duration
• Baseline fracture risk

Ophthalmic Steroid Monitoring

Patients on prolonged systemic corticosteroids may develop:

• Steroid-induced ocular hypertension/glaucoma
• Posterior subcapsular cataract

Periodic ophthalmic evaluation is appropriate, especially with prolonged treatment.

Follow-Up

Monitor:

• Clinical symptoms
• ESR/CRP when clinically useful
• Glucocorticoid adverse effects
• Signs of relapse
• New symptoms of GCA

Inflammatory markers should support, not replace:

Clinical assessment

Important Monitoring Point With IL-6 Inhibitors

IL-6 inhibitors can markedly suppress:

• CRP
• ESR

Therefore these laboratory markers become less reliable indicators of active disease during therapy.

Clinical evaluation becomes especially important.

Prognosis

PMR generally has a:

Good overall prognosis

but the course is often longer than older descriptions suggested.

Many patients experience:

• Relapses
• Prolonged steroid requirements

The major serious concern is:

Development of GCA

Visual Prognosis in GCA

Once profound visual loss from arteritic ischemic optic neuropathy occurs:

Recovery is usually limited

Therefore treatment is aimed at:

• Preventing additional visual loss
• Protecting the fellow eye
• Preventing systemic vascular complications

Complications

Complications of PMR itself include:

• Recurrent symptoms
• Functional disability
• Development of GCA

Complications of treatment include:

• Osteoporosis
• Diabetes
• Hypertension
• Infection
• Cataract
• Glaucoma
• Adrenal suppression

GCA complications include:

• Permanent blindness
• Stroke
• Aortic aneurysm
• Aortic dissection

Ophthalmology Pearls

• PMR causes bilateral shoulder/hip girdle pain and prolonged morning stiffness in patients aged ≥50 years; true muscle weakness is usually absent.
• ESR and CRP are usually elevated, but normal inflammatory markers do not completely exclude PMR or GCA.
• CK is generally normal, helping distinguish PMR from inflammatory myopathy.
• The most important ophthalmic association is giant cell arteritis.
• Every PMR patient should be asked about new headache, scalp tenderness, jaw claudication, diplopia, amaurosis fugax, and visual loss.
• Jaw claudication and transient visual loss are major red flags for GCA.
• The classic ocular emergency is arteritic anterior ischemic optic neuropathy with profound vision loss and chalky-pale disc edema.
• If GCA is strongly suspected, start glucocorticoids immediately—do not wait for temporal artery biopsy or imaging.
• Temporal artery ultrasound showing a halo sign is increasingly important; biopsy remains useful when diagnosis is uncertain.
• Uncomplicated PMR usually responds to prednisone about 12.5–25 mg/day, whereas GCA requires much higher doses.
• Visual symptoms from GCA often prompt IV methylprednisolone followed by high-dose oral therapy.
• Tocilizumab is an established steroid-sparing treatment for GCA; sarilumab is an option for relapsing or glucocorticoid-refractory PMR.
• PMR commonly requires treatment for 1–2 years or longer, and relapse is frequent.
• The ophthalmologist’s critical role is recognizing GCA early enough to prevent irreversible bilateral visual loss.

Ophthalmology – Plateau Iris Glaucoma

Basics

Description

Plateau iris is an anatomic configuration that predisposes to angle closure despite a relatively normal central anterior chamber depth.

The mechanism is primarily:

Anteriorly positioned and/or enlarged ciliary processes → peripheral iris pushed forward → crowding of the iridocorneal angle

Unlike conventional pupillary-block angle closure, the central iris may appear relatively flat.

A key feature is that the angle may remain:

Narrow or occludable despite a patent laser peripheral iridotomy (LPI).

Important Terminology

Two related terms should be distinguished:

Plateau Iris Configuration

An anatomic appearance characterized by:

• Relatively deep or normal central anterior chamber
• Flat central iris plane
• Abrupt peripheral iris angulation
• Narrow/occludable angle

It may exist before or after LPI.

Plateau Iris Syndrome

Refers to clinically significant angle closure that:

• Persists or recurs after a patent LPI
• Cannot be explained by residual pupillary block alone

It may cause:

• IOP elevation
• Peripheral anterior synechiae
• Acute angle closure
• Chronic angle-closure glaucoma

Key Clinical Concept

Think of plateau iris when:

The central anterior chamber looks reasonably deep, but gonioscopy shows a very narrow or closed peripheral angle.

This is why slit-lamp estimation alone can miss the diagnosis.

Epidemiology

Plateau iris anatomy is not rare among patients with:

• Primary angle-closure suspect
• Primary angle closure
• Angle-closure glaucoma

It is often detected in:

• Younger patients than typical pupillary-block angle closure
• Women
• Patients in their 30s–50s

It can occur across different refractive groups.

Risk Factors

Associations include:

• Female sex
• Younger age relative to conventional angle-closure patients
• Family history of angle closure
• Anteriorly positioned ciliary processes

Unlike classic pupillary-block angle closure:

Marked hyperopia is not required.

Plateau iris can occur in:

• Emmetropic
• Mildly hyperopic
• Occasionally myopic eyes

Pathophysiology

The ciliary processes are positioned:

• Anteriorly
• Close to the posterior iris

This supports the peripheral iris from behind and pushes it toward the trabecular meshwork.

The resulting configuration produces:

• Peripheral angle crowding
• Iridotrabecular contact
• Potential synechial closure

Role of Pupillary Block

A patient with plateau iris may also have:

A component of pupillary block

Therefore, LPI is generally performed first in an occludable angle.

After LPI:

• Pupillary block is relieved
• Any residual angle closure reflects non-pupillary-block anatomy, such as plateau iris

Persistent Angle Narrowing After LPI

This is the classic clue:

Patent LPI + persistent narrow/closed angle = consider plateau iris

Other causes of persistent angle closure must also be excluded.

Pseudoplateau Iris

A plateau-like configuration may be caused by:

• Multiple ciliary body cysts
• Iris cysts
• Ciliary body tumor or mass

This is termed:

Pseudoplateau iris

UBM is especially useful for distinguishing true plateau iris from these conditions.

Clinical Presentation

Many patients are:

Asymptomatic

and are discovered during routine gonioscopy.

Others may experience:

• Intermittent blurred vision
• Halos
• Ocular pain
• Headache

particularly after:

• Pharmacologic dilation
• Dark adaptation
• Other circumstances causing pupillary enlargement

Acute Angle Closure

Plateau iris can produce an acute attack with:

• Severe ocular pain
• Red eye
• Blurred vision
• Halos
• Headache
• Nausea
• Vomiting

Examination may show:

• Corneal edema
• Elevated IOP
• Mid-dilated pupil
• Closed angle

Chronic Disease

Repeated or prolonged iridotrabecular contact can produce:

• Peripheral anterior synechiae (PAS)
• Chronic angle closure
• Persistent elevation of IOP
• Glaucomatous optic neuropathy

Slit-Lamp Examination

The central anterior chamber often appears:

• Normal or only mildly shallow

The iris may look:

• Relatively flat centrally

This contrasts with the more uniformly convex iris seen in classic pupillary-block angle closure.

Van Herick Testing

Van Herick estimation can be misleading.

A patient may have:

• Reasonably preserved peripheral chamber depth by slit lamp

yet still have significant angle crowding on gonioscopy.

Therefore:

Van Herick examination cannot exclude plateau iris.

Gonioscopy

Gonioscopy is essential for diagnosis.

Typical findings include:

• Narrow or closed angle
• Steep peripheral iris insertion
• Relatively flat central iris
• Persistent appositional closure after LPI

Indentation gonioscopy is particularly useful.

Double-Hump Sign

The classic gonioscopic sign is the:

Double-hump sign

During indentation:

• First hump = peripheral iris overlying the ciliary body
• Second hump = iris overlying the lens
• A depression lies between them

This strongly supports plateau iris configuration.

Indentation Gonioscopy

Indentation helps distinguish:

Appositional Closure

The angle opens with indentation.

Synechial Closure

The angle remains closed because of:

Peripheral anterior synechiae

This distinction affects prognosis and management.

Peripheral Anterior Synechiae

PAS may develop from repeated or chronic contact between:

• Peripheral iris
• Trabecular meshwork

Extensive PAS can produce:

Chronic angle-closure glaucoma

even after the initial plateau mechanism is treated.

Ultrasound Biomicroscopy

UBM is the best imaging modality for demonstrating the ciliary body anatomy underlying plateau iris.

Typical findings include:

• Anteriorly positioned ciliary processes
• Absent or reduced ciliary sulcus
• Peripheral iris pushed anteriorly
• Iridotrabecular contact
• Relatively flat central iris

Why UBM Is Important

UBM directly images structures posterior to the iris, including:

• Ciliary body
• Ciliary processes

It is particularly useful when:

• Diagnosis is uncertain
• Pseudoplateau iris is suspected
• Angle remains narrow after LPI

Anterior Segment OCT

AS-OCT is useful for demonstrating:

• Narrow angle
• Iridotrabecular contact
• Central anterior chamber depth
• Iris configuration

However:

AS-OCT generally cannot image the ciliary body as well as UBM

and therefore may suggest but not fully establish the mechanism.

Optic Nerve Evaluation

Assess for glaucomatous damage with:

• Optic disc examination
• RNFL OCT
• Macular GCIPL/GCC
• Visual fields

Plateau iris anatomy alone does not equal glaucoma.

Plateau Iris Configuration vs Plateau Iris Glaucoma

Plateau Iris Configuration

• Narrow/occludable angle
• No definite glaucomatous damage required

Plateau Iris Syndrome

• Persistent/recurrent angle closure after patent LPI

Plateau Iris Glaucoma

• Plateau iris mechanism
• Elevated IOP and/or PAS
• Glaucomatous optic neuropathy with corresponding functional damage

Differential Diagnosis

Important differentials include:

• Pupillary-block angle closure
• Phacomorphic glaucoma
• Aqueous misdirection
• Pseudoplateau iris from ciliary body cysts
• Ciliary body tumor
• Lens subluxation
• Choroidal effusion

Plateau Iris vs Pupillary-Block Angle Closure

Plateau Iris

• Relatively deep central chamber
• Flat central iris
• Abrupt peripheral iris rise
• Angle may remain narrow after LPI
• Double-hump sign

Pupillary Block

• More uniformly convex iris
• Shallower central chamber
• Angle usually widens substantially after LPI

Plateau Iris vs Phacomorphic Glaucoma

Phacomorphic glaucoma typically shows:

• Intumescent cataract
• Markedly shallow anterior chamber
• Large lens component
• Acute secondary angle closure

Plateau iris typically has:

• More normal central chamber depth
• Characteristic ciliary body configuration

Plateau Iris vs Aqueous Misdirection

Aqueous misdirection usually shows:

• Diffuse shallowing of both central and peripheral anterior chamber
• Often follows ocular surgery
• Patent iridotomy
• Anterior displacement of lens–iris diaphragm

This differs from the relatively preserved central chamber in plateau iris.

Treatment Principles

Management has several goals:

1. Eliminate any pupillary-block component.
2. Open the peripheral angle.
3. Prevent PAS formation.
4. Control IOP.
5. Prevent glaucomatous optic neuropathy.

Laser Peripheral Iridotomy

For an occludable angle with suspected plateau iris:

LPI is generally performed first

because pupillary block commonly coexists.

LPI:

• Equalizes pressure between posterior and anterior chambers
• Removes the pupillary-block component

Important Principle After LPI

A patent LPI does not cure the underlying ciliary-body anatomy of plateau iris.

If the angle remains occludable after LPI:

Residual plateau iris should be considered.

Argon Laser Peripheral Iridoplasty

Laser peripheral iridoplasty is the classic treatment for residual appositional angle closure from plateau iris after LPI.

It is also called:

Laser iridoplasty

Modern lasers other than argon may be used depending on equipment.

Mechanism of Iridoplasty

Laser burns are placed in the far peripheral iris.

Thermal contraction causes:

• Peripheral iris thinning
• Stromal contraction
• Pulling of the iris away from the trabecular meshwork

This widens the angle.

Indications for Iridoplasty

Consider ALPI when there is:

• Persistent occludable angle after LPI
• Plateau iris syndrome
• Recurrent angle closure after LPI
• Persistent appositional iridotrabecular contact

Limitations of Iridoplasty

Iridoplasty:

• Does not remove the underlying anterior ciliary processes
• May lose effectiveness over time
• Does not reverse established PAS

Some patients require:

• Repeat treatment
• Additional glaucoma therapy

Pilocarpine

Low-dose pilocarpine may:

• Constrict the pupil
• Pull the peripheral iris away from the angle

and can reduce angle closure.

However, chronic pilocarpine is now used less often because of:

• Brow ache
• Accommodative spasm
• Induced myopia
• Reduced night vision
• Retinal traction concerns

It is generally a:

Selective or temporary therapy rather than preferred long-term management.

Acute Angle-Closure Attack

If plateau iris presents with acute angle closure, initially treat as an acute angle-closure emergency.

Therapy may include:

• Topical beta-blocker
• Alpha-2 agonist
• Topical carbonic anhydrase inhibitor
• Systemic acetazolamide
• Hyperosmotic agent if required
• Topical corticosteroid

Pilocarpine During Acute Attack

Pilocarpine may be used after IOP has begun to fall and iris perfusion improves.

At extremely high IOP:

• Iris sphincter ischemia may make pilocarpine ineffective

LPI After Acute Attack

Once corneal edema and IOP permit:

LPI should be performed to remove any pupillary-block component.

The angle must then be reassessed.

If it remains narrow:

• Plateau iris syndrome is likely
• Iridoplasty may be required

Dilation After LPI

Pharmacologic dilation may precipitate angle closure in plateau iris.

Historically, a formal dilation challenge was sometimes used.

Modern practice generally favors:

• Repeat gonioscopy
• IOP assessment
• Anterior segment imaging

rather than deliberately provoking angle closure solely for diagnosis.

Lens Extraction

Lens extraction deepens the anterior chamber and can reduce angle crowding.

It is particularly useful when there is:

• Cataract
• Significant lens component
• Coexisting pupillary-block anatomy

Important Lens Extraction Principle

Unlike pure lens-induced angle closure:

Cataract extraction may not completely eliminate plateau iris anatomy

because the primary abnormality is the:

• Ciliary body
• Ciliary process position

Residual angle narrowing can remain after lens extraction.

Clear-Lens Extraction

Clear-lens extraction is not routinely required solely because plateau iris configuration is present.

It may be considered in selected patients with:

• Recurrent angle closure
• Significant lens-related crowding
• Poor control with laser/medical treatment

Treatment should be individualized.

Chronic Angle-Closure Glaucoma

If extensive PAS or permanent trabecular damage develops, management follows principles of chronic angle-closure glaucoma.

Options may include:

• IOP-lowering medications
• Lens extraction when appropriate
• Goniosynechialysis in selected cases
• Glaucoma surgery

Glaucoma Medications

If IOP remains elevated, options include:

• Prostaglandin analogs
• Beta-blockers
• Carbonic anhydrase inhibitors
• Alpha-2 agonists

The treatment target depends on:

• Optic nerve damage
• Visual field loss
• Disease progression

Goniosynechialysis

In selected eyes with relatively recent PAS, goniosynechialysis may be performed, often at the time of:

Lens extraction

to restore trabecular access.

Long-standing PAS is less likely to respond.

Filtering / Glaucoma Surgery

If IOP remains uncontrolled despite:

• LPI
• Iridoplasty
• Lens management
• Medications

surgical options may include:

• Trabeculectomy
• Glaucoma drainage device
• Other glaucoma procedures depending on anatomy

Follow-Up

Patients require ongoing surveillance even after successful:

• LPI
• Iridoplasty
• Cataract surgery

because the angle can narrow again.

Monitoring

Follow-up should include:

• IOP
• Gonioscopy
• LPI patency
• PAS assessment
• Optic nerve examination
• OCT
• Visual fields when glaucoma is present

Gonioscopy

Serial gonioscopy is essential.

Look for:

• Increasing iridotrabecular contact
• New PAS
• Progressive angle narrowing

A patent LPI does not remove the need for gonioscopic surveillance.

Dilation

Before routine dilation in a patient with plateau iris:

• Confirm angle status
• Confirm LPI patency when applicable

After dilation, selected high-risk patients may benefit from:

• IOP reassessment

Prognosis

Most patients do well when:

• Anatomy is recognized early
• Pupillary block is treated
• Persistent peripheral closure is identified
• IOP is controlled

Visual prognosis depends primarily on whether:

Glaucomatous optic nerve damage has already occurred.

Complications

Potential complications include:

• Acute angle-closure attack
• Recurrent angle closure
• Peripheral anterior synechiae
• Chronic angle-closure glaucoma
• Progressive glaucomatous optic neuropathy
• Visual field loss

Ophthalmology Pearls

• Plateau iris is caused by anteriorly positioned ciliary processes that push the peripheral iris forward and crowd the angle.
• The central anterior chamber can look relatively normal, so Van Herick examination alone can miss the diagnosis.
• The key diagnostic test is gonioscopy with indentation.
• The classic gonioscopic finding is the double-hump sign.
• Plateau iris configuration describes the anatomy; plateau iris syndrome describes persistent or recurrent angle closure after a patent LPI.
• Perform LPI first when an occludable angle is present because pupillary block commonly coexists.
• A patent LPI with persistent angle narrowing strongly suggests a non-pupillary-block mechanism such as plateau iris.
• UBM is particularly useful because it directly demonstrates the anteriorly positioned ciliary processes and can identify ciliary body cysts causing pseudoplateau iris.
• AS-OCT can document angle closure but is less effective than UBM for imaging the ciliary body.
• Laser peripheral iridoplasty is the classic treatment for persistent appositional closure after LPI.
• Chronic pilocarpine is now used selectively because of significant adverse effects.
• Lens extraction can deepen the angle, especially when cataract or lens crowding coexists, but it may not completely eliminate true plateau iris anatomy.
• Even after LPI or iridoplasty, long-term gonioscopic surveillance is essential because PAS and chronic angle-closure glaucoma can still develop.

Ophthalmology – Hydroxychloroquine (Plaquenil) Retinal Toxicity

Basics

Description

Hydroxychloroquine (HCQ; Plaquenil) retinopathy is a potentially irreversible toxic retinopathy caused by long-term exposure to hydroxychloroquine.

Chloroquine can cause a similar retinopathy but is:

• More retinotoxic
• Used much less frequently

HCQ is commonly prescribed for:

• Systemic lupus erythematosus
• Rheumatoid arthritis
• Other connective-tissue and inflammatory disorders

The principal ophthalmic objective is:

Detect toxicity before symptomatic or funduscopically obvious retinal damage develops.

Key Modern Principle

The classic bull’s-eye maculopathy is a late finding.

Modern screening aims to identify toxicity much earlier using:

• Spectral-domain OCT
• Automated visual fields
• Fundus autofluorescence

before major visual acuity loss occurs.

Epidemiology

Retinal toxicity is strongly related to:

• Daily dose
• Duration of therapy

At recommended dosing, risk is:

• Very low during the first 5 years
• Still low during the first 10 years
• Progressively higher with prolonged therapy

Long-term exposure, particularly beyond 15–20 years, substantially increases cumulative risk.

Hydroxychloroquine vs Chloroquine

Hydroxychloroquine is preferred because it has:

Lower retinal toxicity

than chloroquine.

Both drugs can cause a similar pattern of:

• Photoreceptor injury
• RPE degeneration
• Progressive maculopathy

Major Risk Factors

The most important risk factors are:

• High daily dose
• Long duration of use
• Renal impairment
• Concomitant tamoxifen therapy
• Older age at initiation or during long-term exposure
• Preexisting macular disease that complicates screening

Daily Dose

For hydroxychloroquine, the recommended maximum dose is approximately:

≤5 mg/kg/day using actual body weight

This replaced older recommendations based on:

• Ideal body weight
• 6.5 mg/kg/day thresholds

Actual body weight is now preferred for routine HCQ dose calculation.

Chloroquine Dose

For chloroquine, an approximate recommended ceiling is:

≤2.3 mg/kg/day using actual body weight

Chloroquine carries a higher toxicity risk than HCQ.

Important Correction – Obesity

Older teaching recommended calculating HCQ dose using:

Ideal body weight

This is no longer the standard approach.

Modern screening recommendations generally use:

Actual body weight

while avoiding unnecessarily high absolute daily doses in very obese patients.

Duration of Therapy

Duration is one of the strongest predictors of toxicity.

Risk rises substantially after:

5 years of continuous treatment

and continues increasing with cumulative exposure.

Renal Disease

Hydroxychloroquine is partly cleared by the kidneys.

Reduced renal function can increase:

• Drug exposure
• Retinal toxicity risk

Therefore patients with chronic kidney disease may require:

• Dose adjustment
• Earlier and/or more frequent ophthalmic screening

Tamoxifen

Concomitant tamoxifen significantly increases the risk of HCQ retinopathy.

These patients should be considered:

Higher risk

and monitored accordingly.

Liver Disease

Severe hepatic dysfunction may alter drug metabolism, but renal function is a better-established major risk factor in contemporary screening recommendations.

Pathophysiology

The exact mechanism is incompletely understood.

HCQ accumulates within:

• Lysosomes
• RPE
• Retinal tissues

It interferes with:

• Lysosomal function
• Autophagy
• Photoreceptor–RPE metabolism

The earliest clinically detectable damage usually involves:

Outer retinal photoreceptors

particularly the:

• Ellipsoid zone
• Outer nuclear layer
• Photoreceptor outer segments

RPE damage becomes more prominent later.

Distribution of Toxicity

Two major patterns occur:

Parafoveal Pattern

Most common in many non-Asian populations.

Damage forms a ring approximately:

2–6° from fixation

Pericentral Pattern

More common in patients of:

Asian ancestry

Damage occurs farther from the fovea, often along the vascular arcades.

This is critically important when selecting:

• Visual field strategy
• OCT scan width
• FAF imaging area

Clinical Presentation

Early toxicity is usually:

Asymptomatic

This is why screening is essential.

When symptoms occur they may include:

• Difficulty reading
• Paracentral missing areas
• Blurred vision
• Metamorphopsia
• Reduced contrast
• Glare
• Central or paracentral scotoma

Visual Acuity

Central acuity may remain:

Normal until relatively late

because the fovea can remain structurally preserved during early parafoveal disease.

Therefore:

Normal 20/20 acuity does not exclude HCQ toxicity.

Fundus Examination

Early toxicity may show:

• No visible abnormalities

Later disease may show:

• Parafoveal pigmentary changes
• RPE mottling
• RPE atrophy

Advanced disease produces the classic:

Bull’s-eye maculopathy

Bull’s-Eye Maculopathy

The classic appearance consists of:

• Central relative foveal preservation
• Surrounding ring of RPE atrophy
• Outer surrounding pigmentary change

This represents:

Established, relatively advanced toxicity

and should not be the stage at which screening first detects disease.

Advanced Toxicity

Severe disease may eventually produce:

• Diffuse RPE atrophy
• Vascular attenuation
• Peripheral retinal degeneration
• Optic disc pallor

At this stage, vision may be severely and permanently affected.

Screening Principles

The goals of screening are to identify:

Definite early toxicity before irreversible central visual loss

while avoiding unnecessary discontinuation of a systemically valuable drug based on an equivocal test.

Abnormal findings should therefore be:

• Reproducible
• Corroborated by complementary structural or functional testing

before recommending drug cessation whenever possible.

Baseline Examination

A baseline ophthalmic examination should be performed soon after starting long-term HCQ therapy.

The baseline helps identify:

• Preexisting macular disease
• Abnormal visual fields
• Structural abnormalities that may later mimic toxicity

Baseline assessment typically includes:

• Dilated fundus examination
• SD-OCT
• Often FAF and/or visual field testing depending on practice and risk

When to Begin Annual Screening

For patients taking an appropriate dose and without major risk factors:

Annual screening generally begins by 5 years of therapy.

Earlier annual screening is appropriate when major risk factors are present, such as:

• High daily dose
• Renal disease
• Tamoxifen therapy
• Significant preexisting retinal disease

Primary Screening Test – OCT

Spectral-domain OCT is one of the most important modern screening tests.

Early findings include:

• Parafoveal outer nuclear layer thinning
• Ellipsoid-zone disruption
• Photoreceptor outer-segment loss
• Relative central foveal preservation

Flying-Saucer Sign

Advanced parafoveal outer retinal loss with relative foveal preservation may produce the classic OCT:

“Flying saucer” sign

However:

This is not an early sign and should not be required to diagnose toxicity.

Modern screening aims to detect disease before this develops.

OCT in Pericentral Disease

Routine narrow macular OCT scans can miss pericentral toxicity.

In patients at risk for a pericentral phenotype, particularly Asian patients, use:

• Wider OCT scans
• Scans extending beyond the central macula
• Correlation with wide-field FAF

Automated Visual Fields

Visual field testing detects functional loss.

Typical early abnormalities include:

• Paracentral scotomas
• Partial ring scotoma

These can become:

• Complete parafoveal ring scotomas
• Central defects in advanced disease

10-2 Visual Field

For typical parafoveal toxicity:

Humphrey 10-2

is commonly used because it densely samples the central macula.

Wider Visual Fields

When pericentral toxicity is possible, consider:

• 24-2
• 30-2
• Other wider-field strategies

because a 10-2 alone may miss disease occurring farther from fixation.

Visual Field Reliability

Visual fields are subjective and may produce:

• Learning effects
• Fixation artifacts
• False positives

A suspicious field abnormality should usually be:

Repeated and correlated with OCT or another objective test.

Fundus Autofluorescence

FAF is useful for mapping the distribution of RPE stress and damage.

Possible findings include:

Earlier Disease

• Parafoveal or pericentral hyperautofluorescence

Later Disease

• Hypoautofluorescence from established RPE loss

Wide-field FAF is particularly useful for:

Pericentral toxicity

Multifocal ERG

mfERG objectively assesses localized retinal function.

It may demonstrate:

• Reduced parafoveal responses
• Ring-like functional depression

It is particularly useful when:

• Visual fields are unreliable
• OCT and field findings disagree
• Confirmation of suspected toxicity is needed

It is generally a:

Confirmatory rather than universal first-line test.

Full-Field ERG

Full-field ERG is usually:

• Normal in early disease

because early HCQ toxicity is localized to the macula or pericentral retina.

It becomes abnormal mainly in:

Advanced widespread retinopathy

and is not a routine screening test.

Electrooculography

EOG has:

No significant routine role in modern HCQ screening.

Amsler Grid

Amsler grid testing is insufficiently sensitive for early toxicity.

It should not replace modern screening with OCT and automated perimetry.

Color Vision

Color vision testing is:

• Nonspecific
• Usually abnormal only later

It is not a primary modern screening test.

Fundus Photography

Photography may document:

• Pigmentary change
• Bull’s-eye maculopathy

but is relatively insensitive for early toxicity.

Fluorescein Angiography

FA is not routinely useful for early screening.

It may demonstrate:

• Window defects
• RPE atrophy

in established disease.

Diagnostic Pattern

A convincing diagnosis often involves concordant abnormalities such as:

Typical OCT outer retinal loss + matching visual field defect

or:

OCT abnormality + corresponding FAF/mfERG abnormality

Differential Diagnosis

HCQ toxicity may mimic:

• Age-related macular degeneration
• Pattern dystrophy
• Stargardt disease
• Cone dystrophy
• Cone–rod dystrophy
• Macular telangiectasia type 2
• Epiretinal membrane-related field/OCT changes
• High myopia
• Other toxic retinopathies

HCQ Toxicity vs AMD

HCQ toxicity favors:

• Bilateral symmetric parafoveal/pericentral outer retinal loss
• Ring-like distribution
• Relative early foveal preservation

AMD more commonly shows:

• Drusen
• Pigment epithelial detachments
• Sub-RPE deposits
• Geographic atrophy in a different distribution

HCQ Toxicity vs Pattern Dystrophy

Pattern dystrophy may produce:

• Lipofuscin abnormalities
• RPE pigment patterns
• Vitelliform material

but usually lacks the classic symmetric parafoveal outer retinal loss pattern seen in HCQ toxicity.

Treatment

There is:

No proven treatment that reverses established HCQ retinal toxicity.

The key intervention is:

Stopping the offending drug before severe damage occurs.

Drug Discontinuation

When toxicity is considered definite or highly likely:

• Communicate promptly with the prescribing physician
• Discuss discontinuation or substitution

HCQ should not usually be stopped casually on a single questionable screening abnormality because it may be medically important for control of:

• Lupus
• Rheumatoid arthritis
• Other systemic disease

Ophthalmologist–Prescriber Collaboration

The ophthalmologist should communicate:

• Whether toxicity is definite, probable, or uncertain
• Severity
• Structural progression
• Functional involvement

The prescribing physician weighs this against:

• Systemic disease control
• Alternative therapies
• Risk of stopping HCQ

Dose Reduction

If toxicity is not present but the daily dose is excessive, consider discussing:

Dose reduction to ≤5 mg/kg/day actual body weight

with the prescribing clinician.

Progression After Drug Cessation

An important feature is:

HCQ retinopathy may continue to progress after the medication is stopped.

This occurs because:

• Drug persists in tissues
• Established retinal injury may continue biologically

Progression is most likely when toxicity is already:

• Severe
• Associated with RPE damage

Early Toxicity After Cessation

When toxicity is detected before significant RPE loss:

• Progression may be limited
• Central vision may remain good

However, true structural damage generally does not simply regenerate.

Thus the goal is:

Preservation rather than reversal.

Important Correction – “Reversible Premaculopathy”

Older literature suggested that early toxicity might reverse completely after drug cessation.

Modern understanding is more cautious:

Established HCQ retinal toxicity is generally considered irreversible.

Early detection prevents progression to disabling disease rather than reliably restoring damaged photoreceptors.

Follow-Up After Toxicity

Patients with confirmed toxicity should continue ophthalmic monitoring even after stopping HCQ.

Follow with:

• OCT
• Visual fields
• FAF

because progression can continue.

Other Ocular Effects

HCQ and especially chloroquine may cause:

• Corneal epithelial deposits / vortex keratopathy

These deposits are usually:

• Reversible
• Not predictive of retinal toxicity
• Rarely visually significant

Corneal Verticillata

Drug-related corneal deposits can appear as:

Whorl-like epithelial lines

They do not require stopping HCQ unless:

• Symptoms are significant
• Other toxicity is present

Accommodation and Lens Effects

Older chloroquine literature described:

• Accommodation abnormalities
• Lens changes

These are much less clinically important than retinal toxicity with modern HCQ use.

Patient Education

Patients should understand:

• Why screening is needed
• That early toxicity may be asymptomatic
• That retinal damage can be irreversible
• The importance of attending scheduled screening

Patients should report:

• New paracentral missing areas
• Reading difficulty
• Metamorphopsia
• Unexplained visual decline

Prognosis

Prognosis depends mainly on:

Stage at which toxicity is detected

Early Detection

If detected before major RPE damage:

• Central acuity may remain excellent
• Progression after cessation is often limited
• Long-term functional vision can remain good

Advanced Disease

If bull’s-eye maculopathy or extensive RPE loss is already present:

• Visual field loss may progress
• Central vision may eventually decline
• Structural progression can continue despite stopping the drug

Complications

The major complication is:

Permanent bilateral visual impairment

Advanced toxicity may cause:

• Central/paracentral scotomas
• Reading difficulty
• Reduced contrast sensitivity
• Extensive macular atrophy

Ophthalmology Pearls

• Hydroxychloroquine retinal toxicity is dose- and duration-dependent and may be irreversible.
• The modern recommended HCQ dose is approximately ≤5 mg/kg/day using actual body weight, not the older 6.5 mg/kg ideal-body-weight rule.
• Major risk factors are high daily dose, long duration, renal disease, and tamoxifen use.
• Early toxicity is usually asymptomatic with normal visual acuity and a normal-looking fundus.
• Bull’s-eye maculopathy is a late sign, not the goal of screening.
• SD-OCT is a cornerstone of modern screening, looking for parafoveal or pericentral outer retinal damage.
• Use 10-2 fields for typical parafoveal disease, but wider fields such as 24-2/30-2 are important when pericentral toxicity is possible.
• Asian patients are more likely to develop pericentral toxicity, so screening must extend beyond the central macula.
• FAF helps map the topographic extent of disease; mfERG is useful for objective confirmation when results are equivocal.
• Amsler grid, color testing, EOG, and fluorescein angiography are not adequate primary screening tests for early toxicity.
• Patients at standard dose without major risk factors generally begin annual screening by 5 years of therapy; high-risk patients require earlier surveillance.
• Do not stop HCQ solely on one questionable test—confirm toxicity whenever possible and coordinate with the prescribing physician.
• Once true retinopathy is established, retinal damage is generally not reversible and may continue to progress even after HCQ is discontinued.

Ophthalmology – Pigmentary Glaucoma

Basics

Description

Pigment dispersion syndrome (PDS) is characterized by liberation of pigment from the posterior iris pigment epithelium with deposition throughout the anterior segment.

Pigmentary glaucoma (PG) is a secondary open-angle glaucoma in which pigment dispersion is associated with:

• Elevated IOP and/or
• Characteristic glaucomatous optic neuropathy
• Corresponding visual field loss

The major pathogenic event is:

Mechanical rubbing of the posterior iris against lens zonules → pigment release → trabecular meshwork dysfunction → elevated IOP

Classic Triad of Pigment Dispersion Syndrome

The classic findings are:

1. Krukenberg spindle
2. Radial midperipheral iris transillumination defects
3. Dense trabecular meshwork pigmentation

Not every patient demonstrates all three findings.

Epidemiology

PDS and PG typically present in:

• Young to middle-aged adults
• Often during the 20s–40s
• Myopic individuals
• More commonly men in clinically significant pigmentary glaucoma

PDS can occasionally be detected:

• In adolescence
• Later in adulthood

Pigment Dispersion vs Pigmentary Glaucoma

Pigment Dispersion Syndrome

• Pigment dispersion present
• Open angle
• May have normal or elevated IOP
• No definite glaucomatous optic neuropathy

Pigmentary Glaucoma

• Pigment dispersion
• Elevated IOP often present
• Glaucomatous optic nerve/RNFL damage
• Corresponding visual field loss

Therefore:

Pigment in the angle alone does not equal glaucoma.

Conversion to Glaucoma

Only a subset of patients with PDS develop pigmentary glaucoma.

Long-term studies suggest conversion is considerably less than the historically quoted “one third” in many populations, with risk increasing in patients with:

• Higher baseline IOP
• Greater trabecular pigmentation
• Male sex
• Younger age at diagnosis
• Significant pigment liberation

Long-term monitoring remains essential.

Risk Factors

Typical associations include:

• Myopia
• Young or middle adulthood
• Male sex
• Deep anterior chamber
• Concave peripheral iris configuration

High myopia may also independently increase glaucoma risk.

Genetics

Most cases appear to be:

Sporadic or multifactorial

Familial clustering has been described, but a simple autosomal dominant inheritance pattern is not established for most patients.

Genetic mechanisms are likely heterogeneous.

Pathophysiology

The central mechanism is:

Iridozonular contact

The peripheral iris bows posteriorly and rubs against the:

• Anterior lens zonules

This mechanically disrupts the posterior iris pigment epithelium.

Pigment is released into the aqueous and deposits on:

• Corneal endothelium
• Trabecular meshwork
• Iris
• Lens
• Zonules

Reverse Pupillary Block

A characteristic mechanism is:

Reverse pupillary block

A pressure gradient develops with relatively higher pressure in the anterior chamber than behind the iris.

This causes:

• Posterior bowing of peripheral iris
• Increased iris–zonule contact
• Greater pigment liberation

Concave Iris Configuration

The peripheral iris often has a:

Posteriorly concave configuration

This can be seen on:

• Slit lamp
• Gonioscopy
• Ultrasound biomicroscopy
• Anterior segment OCT

Triggers of Pigment Release

Pigment liberation may increase with:

• Pupillary dilation
• Exercise in some individuals
• Accommodation
• Mechanical jarring

However, routine activity restriction is generally unnecessary.

Trabecular Meshwork Damage

Pigment accumulates within the trabecular meshwork.

Consequences include:

• Pigment phagocytosis by trabecular endothelial cells
• Cellular dysfunction
• Reduced outflow facility
• Structural trabecular damage

This can produce sustained or episodic:

IOP elevation

Age-Related Changes

Pigment dispersion often becomes less active with age.

Possible reasons include:

• Lens enlargement altering iris–zonule relationships
• Increasing relative pupillary block
• Less posterior iris concavity
• Reduced physical activity/pupil dynamics

This may lead to a:

“Burnout” or pigment reversal phase

but previously established glaucomatous damage does not reverse.

Clinical Presentation

Most patients are:

Asymptomatic

Diagnosis is commonly made during:

• Routine eye examination
• Glaucoma assessment

Symptomatic IOP Spikes

Acute pigment liberation can occasionally produce transient IOP elevation causing:

• Blurred vision
• Halos around lights
• Ocular discomfort
• Headache

These episodes can resemble angle closure, but the angle in PDS is typically:

Wide open

Slit-Lamp Findings

Pigment may be visible on multiple anterior segment structures.

Important findings include:

• Krukenberg spindle
• Pigment in anterior chamber
• Iris transillumination defects
• Pigment on lens and zonules

Krukenberg Spindle

A Krukenberg spindle is a vertical spindle-shaped deposit of pigment on the:

Corneal endothelium

It results from aqueous convection currents.

It is:

• Suggestive of pigment dispersion
• Not pathognomonic

Iris Transillumination Defects

Characteristic defects are:

• Radial
• Spoke-like
• Midperipheral

They correspond to areas of:

Iris–zonule contact

They are best seen using:

• Retroillumination
• Narrow slit beam
• Relatively dark room before dilation

Iris Pigment Changes

Additional findings may include:

• Pigment accumulation in iris furrows
• Asymmetric iris pigmentation
• Mild heterochromia

The more heavily affected eye may appear:

Darker

Anisocoria

The pupil may be slightly larger in the more heavily affected eye due to:

• Iris structural changes
• Pigment epithelial damage

Marked anisocoria should prompt consideration of other diagnoses.

Zentmayer Ring / Scheie Stripe

Pigment may accumulate on the posterior lens capsule along the:

Zonular insertion

This circumferential line is termed:

• Zentmayer ring
• Scheie stripe

It is a classic but not universally present finding.

Gonioscopy

Gonioscopy is essential.

Typical findings include:

• Wide-open angle
• Dense trabecular pigmentation
• Pigmentation often relatively homogeneous
• Pigment may involve 360°

A Sampaolesi line may also be seen.

Sampaolesi Line

A Sampaolesi line is pigment anterior to Schwalbe line.

It may occur in:

• Pigment dispersion
• Pseudoexfoliation
• Other pigmentary disorders

Therefore it is not specific.

Degree of Pigmentation

The trabecular meshwork may appear:

• Dark brown
• Black
• Densely and relatively uniformly pigmented

The amount of angle pigment does not always correlate directly with:

• Current IOP
• Degree of optic nerve damage

Optic Nerve Findings

Once pigmentary glaucoma develops, optic nerve findings resemble other open-angle glaucomas:

• Increased cupping
• Focal rim thinning
• Notching
• RNFL defects
• Disc hemorrhage occasionally

Visual Field Defects

Typical glaucomatous defects include:

• Paracentral scotoma
• Nasal step
• Arcuate scotoma
• Advanced peripheral constriction

OCT

OCT should evaluate:

• Peripapillary RNFL
• Macular ganglion cell complex / GCIPL
• Optic nerve head

Progression analysis is particularly useful in younger patients who may require decades of monitoring.

IOP Characteristics

IOP may demonstrate:

• Significant fluctuation
• Intermittent spikes
• Exercise- or dilation-associated elevations in selected patients

A single normal IOP does not exclude pigmentary glaucoma.

IOP After Dilation

Some patients experience:

• Increased pigment release
• Temporary IOP elevation

after pharmacologic dilation.

Routine post-dilation IOP measurement is not required for every patient but may be useful when there is:

• Prior history of spikes
• Advanced glaucoma
• Marked pigment dispersion

Pachymetry

Central corneal thickness should be measured as part of glaucoma risk assessment.

CCT influences:

• Interpretation of measured IOP
• Overall glaucoma risk assessment

Do not use a simple numerical “IOP correction formula.”

Anterior Segment OCT

AS-OCT may demonstrate:

• Deep anterior chamber
• Posteriorly bowed peripheral iris
• Increased iris concavity

It is helpful when the mechanism is uncertain.

Ultrasound Biomicroscopy

UBM can directly demonstrate:

• Iridozonular contact
• Concave peripheral iris
• Reverse pupillary block
• Posterior iris insertion
• Deep anterior segment anatomy

It is not routinely required when the clinical diagnosis is clear.

Peripheral Retinal Examination

Many patients are myopic and therefore have increased prevalence of:

• Lattice degeneration
• Retinal holes
• Retinal tears

A careful dilated peripheral retinal examination is appropriate, especially in highly myopic patients.

Differential Diagnosis

Important differentials include:

• Pseudoexfoliation glaucoma
• Primary open-angle glaucoma
• Uveitic glaucoma
• UGH syndrome / IOL-related iris chafing
• Iris or ciliary body tumor
• Previous ocular trauma
• Postoperative pigment dispersion
• Bilateral acute iris transillumination syndrome

Pigmentary vs Pseudoexfoliation Glaucoma

Pigmentary Glaucoma

Typically:

• Younger
• Myopic
• Deep anterior chamber
• Midperipheral radial iris transillumination defects
• Dense relatively homogeneous TM pigment
• Krukenberg spindle

Pseudoexfoliation Glaucoma

Typically:

• Older age
• Pseudoexfoliative material on lens and pupillary margin
• Pupillary-margin transillumination
• Often asymmetric
• Patchier angle pigmentation
• Zonular weakness common

Zonules

Unlike pseudoexfoliation syndrome:

Classic PDS does not characteristically produce progressive zonular weakness.

This distinction is useful before cataract surgery.

Pigmentary Glaucoma vs POAG

POAG may have:

• Mild angle pigmentation

but usually lacks the characteristic combination of:

• Krukenberg spindle
• Midperipheral radial transillumination defects
• Dense circumferential trabecular pigmentation

IOL-Related Pigment Dispersion

After cataract surgery, pigment dispersion may result from:

• Malpositioned posterior chamber IOL
• Sulcus IOL chafing
• IOL haptic contact with iris

This may cause:

UGH syndrome

with:

• Uveitis
• Glaucoma
• Hyphema

Treatment Principles

Treatment is directed at:

Lowering IOP sufficiently to prevent progression of glaucomatous optic neuropathy.

Management broadly follows principles used for:

• Primary open-angle glaucoma

Observation of PDS

Patients with PDS but:

• Normal IOP
• Normal optic nerve
• Normal visual field

usually require:

Observation rather than treatment

with periodic glaucoma surveillance.

Medical Therapy

Common first-line medications include:

• Prostaglandin analogs
• Beta-blockers
• Topical carbonic anhydrase inhibitors
• Alpha-2 agonists

Choice depends on:

• Target IOP
• Age
• Side-effect profile
• Comorbidities

Prostaglandin Analogs

Prostaglandin analogs are highly effective for IOP reduction.

They do not appear to meaningfully worsen posterior iris pigment dispersion.

Possible iris darkening results from:

Increased melanin production in iris melanocytes

rather than liberation of iris pigment epithelium.

Pilocarpine

Pilocarpine can:

• Flatten the peripheral iris
• Reduce iridozonular contact
• Increase trabecular outflow

and historically was used to suppress pigment liberation.

However, it is now used infrequently because of:

• Brow ache
• Accommodative spasm
• Induced myopia
• Poor night vision
• Retinal traction concerns in highly myopic patients

It is not routine first-line therapy.

Selective Laser Trabeculoplasty

SLT can be effective in pigmentary glaucoma.

However, the heavily pigmented trabecular meshwork absorbs laser energy strongly.

This increases the risk of:

• Post-laser IOP spike
• Excessive inflammation

SLT Technique

Practical considerations include:

• Lower initial energy
• Careful titration
• Sometimes treating fewer degrees initially
• Close post-laser IOP monitoring

SLT efficacy may diminish over time, as with other glaucomas.

Argon Laser Trabeculoplasty

ALT can lower IOP but is now used less frequently because:

SLT is generally preferred

when laser trabeculoplasty is appropriate.

Laser Peripheral Iridotomy

LPI can eliminate:

Reverse pupillary block

and may flatten a concave iris.

However:

Routine prophylactic LPI is not established as an effective method for preventing pigmentary glaucoma.

Modern Role of LPI

LPI may be considered selectively when there is:

• Marked posterior iris concavity
• Documented reverse pupillary block
• Recurrent pigment liberation or IOP spikes

But evidence that it:

• Prevents glaucoma
• Prevents progression
• Provides durable IOP lowering

is limited.

Therefore it is not routinely performed solely because PDS is present.

Incisional Surgery

Surgery is indicated when:

• Target IOP is not achieved
• Structural or visual field progression continues

despite medical and laser treatment.

Options include:

• Trabeculectomy
• Glaucoma drainage device
• Selected MIGS procedures

Trabeculectomy

Trabeculectomy can achieve a low target IOP.

However, many PG patients are:

• Young
• Myopic

and therefore may be at increased risk of:

Hypotony maculopathy

particularly with aggressive antifibrotic use.

MIGS

MIGS may be considered in:

• Mild to moderate pigmentary glaucoma
• Especially when combined with cataract surgery

However:

• Achievable IOP reduction is generally less than with trabeculectomy
• MIGS may not be sufficient for advanced disease requiring very low target pressures

Cataract Surgery

Cataract extraction may:

• Deepen/change anterior segment anatomy
• Reduce iridozonular contact in some eyes
• Decrease active pigment dispersion

but it is not performed solely as primary treatment for uncomplicated PDS in a clear lens.

Exercise

Routine prohibition of exercise is generally unnecessary.

Patients who repeatedly experience:

• Blurred vision
• Halos
• Documented IOP spikes

after vigorous exercise may warrant individualized assessment.

Follow-Up – Pigment Dispersion Syndrome

Monitor periodically for development of glaucoma with:

• IOP
• Gonioscopy
• Optic nerve examination
• OCT
• Visual field when appropriate

Follow-up interval depends on:

• Baseline IOP
• Age
• Degree of pigmentation
• Optic nerve appearance

Follow-Up – Pigmentary Glaucoma

Monitoring is similar to other open-angle glaucomas.

Assess:

• IOP
• Target IOP
• Optic disc
• RNFL/GCIPL OCT
• Visual fields
• Gonioscopy
• Treatment adherence

Frequency depends on severity and progression.

Burnout Phase

With age, pigment liberation may decrease.

Clinical findings may become less obvious:

• Less iris concavity
• Less visible pigment release
• IOP may fall
• Trabecular pigment may fade

This can make the original diagnosis difficult to recognize in an older patient.

Important Burnout Principle

An older patient may have:

• Normal IOP
• Established optic nerve cupping
• Historical glaucomatous visual field defects

after earlier pigmentary glaucoma.

This should not automatically be labeled:

Normal-tension glaucoma

without considering previous pigmentary disease.

Prognosis

With appropriate IOP control:

Visual prognosis is generally good.

Poor outcomes occur when:

• IOP remains very high
• Diagnosis is delayed
• Follow-up is poor
• Advanced optic nerve damage develops

Complications

Major complications include:

• Progressive glaucomatous optic neuropathy
• Visual field loss
• Permanent visual impairment

Myopic patients may also have increased risk of:

• Lattice degeneration
• Retinal tears
• Rhegmatogenous retinal detachment

This risk is related largely to the underlying myopia rather than pigment dispersion alone.

Ophthalmology Pearls

• Pigment dispersion syndrome = iris pigment liberation without necessarily having glaucoma; pigmentary glaucoma = PDS plus glaucomatous optic neuropathy.
• The classic triad is Krukenberg spindle + radial midperipheral iris transillumination defects + dense trabecular meshwork pigmentation.
• The typical patient is a young or middle-aged myope, often male.
• The key mechanism is posterior iris bowing with iris–zonule rubbing.
• Gonioscopy shows a wide-open, heavily pigmented angle, distinguishing it from angle-closure disease.
• A Krukenberg spindle is suggestive but not pathognomonic.
• PDS often becomes less active with age, but existing glaucomatous damage does not disappear during the “burnout” phase.
• Treatment of pigmentary glaucoma follows standard glaucoma principles: IOP lowering with medications, SLT, and surgery when needed.
• SLT works well but should be performed cautiously at lower energy because heavily pigmented trabecular meshwork increases the risk of IOP spikes.
• Pilocarpine can reduce pigment release but is rarely used routinely because of significant side effects, particularly in young myopic patients.
• Routine prophylactic laser peripheral iridotomy is not recommended for all patients with PDS; although it can flatten the iris, evidence that it prevents glaucoma is limited.
• Always differentiate PG from pseudoexfoliation glaucoma, which occurs at an older age and is associated with pseudoexfoliative material and zonular weakness.
• In an older patient with glaucomatous damage and normal current IOP, consider previous “burned-out” pigmentary glaucoma rather than assuming normal-tension glaucoma.

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.