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.

Ophthalmology – Phacoanaphylactic Glaucoma

Basics

Description

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

Preferred modern terminology includes:

• Phacoantigenic uveitis
• Lens-induced uveitis with secondary glaucoma

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

The disorder typically follows:

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

Clinical Importance

The characteristic clinical combination is:

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

The principal management goals are to:

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

Epidemiology

The condition is uncommon in modern cataract surgery because of:

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

It is more likely after:

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

Terminology

Several lens-induced inflammatory glaucomas must be distinguished.

Phacoantigenic Uveitis

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

Lens-Particle Glaucoma

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

Phacolytic Glaucoma

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

These entities may overlap clinically.

Pathophysiology

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

When the capsule is disrupted:

Lens proteins become exposed to the immune system

This can trigger a:

• Delayed immune response
• Granulomatous inflammatory reaction

Histologically, inflammation develops around lens material.

Mechanism of Glaucoma

IOP may rise because of:

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

Therefore the glaucoma may be:

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

Etiology

Typical precipitating events include:

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

Rarely, spontaneous capsular rupture may occur.

History

Ask specifically about:

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

Symptoms may include:

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

Timing

Presentation may occur:

• Days
• Weeks
• Occasionally longer

after lens capsule disruption.

Persistent or recurrent postoperative inflammation should raise suspicion for:

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

Physical Examination

Typical findings include:

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

Granulomatous Uveitis

Inflammation may be characterized by:

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

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

Lens Material

Residual lens material may be found:

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

Posteriorly retained lens fragments can be difficult to visualize directly.

Posterior Segment Findings

If lens material has dropped posteriorly, there may be:

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

Intraocular Pressure

IOP may range from mildly elevated to:

Severely elevated

Mechanisms include:

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

Diagnostic Approach

The key questions are:

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

Slit-Lamp Examination

Evaluate for:

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

Gonioscopy

When feasible, gonioscopy may demonstrate:

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

Dilated Fundus Examination

Assess for:

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

B-Scan Ultrasonography

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

• Corneal edema
• Severe inflammation
• Media opacity

It may help identify:

• Retained lens fragments
• Vitreous opacities
• Retinal detachment

Anterior Segment Imaging

UBM or AS-OCT may occasionally help detect:

• Retained anterior lens material
• Angle abnormalities
• Capsular remnants

particularly when fragments are hidden behind the iris.

Aqueous or Vitreous Sampling

Sampling is not routinely required for classic sterile phacoantigenic inflammation.

It becomes important when:

Infectious endophthalmitis cannot be excluded.

Possible tests include:

• Gram stain
• Culture
• PCR in selected cases

Histopathology

Classic histology demonstrates:

• Polymorphonuclear leukocytes
• Epithelioid histiocytes
• Multinucleated giant cells

arranged around:

Lens material

This produces a zonal granulomatous inflammatory pattern.

Differential Diagnosis

Important differentials include:

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

Chronic Postoperative Endophthalmitis

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

Cutibacterium acnes

formerly Propionibacterium acnes.

Clues include:

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

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

Toxic Anterior Segment Syndrome

TASS usually presents:

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

It results from:

Sterile toxic injury, not lens-protein sensitization.

Phacolytic Glaucoma

Phacolytic glaucoma generally occurs in an eye with:

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

Macrophages and lens proteins obstruct the trabecular meshwork.

Definitive treatment is:

Cataract extraction

after initial IOP control.

Lens-Particle Glaucoma

Lens-particle glaucoma occurs when:

• Lens fragments physically enter the anterior chamber

usually after:

• Trauma
• Cataract surgery

It may resemble phacoantigenic uveitis but is primarily a:

Mechanical-inflammatory trabecular obstruction

rather than a classic granulomatous immune response.

Treatment Principles

Management consists of:

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

Definitive control often requires:

Removal of the inciting lens material.

Topical Corticosteroids

Topical corticosteroids are first-line for ocular inflammation.

Examples include:

• Prednisolone acetate
• Difluprednate in selected severe cases

Dosing depends on severity and may initially be frequent.

Steroids should subsequently be:

Tapered according to clinical response

after definitive treatment.

Cycloplegic Therapy

Cycloplegics may be useful when there is:

• Significant ciliary spasm
• Pain
• Posterior synechiae

Examples include:

• Cyclopentolate
• Atropine in more severe disease

IOP-Lowering Therapy

Aqueous suppressants are generally preferred.

Options include:

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

Hyperosmotic Therapy

For severe acute IOP elevation, temporary treatment may include:

• IV mannitol
• Oral hyperosmotic agents in selected patients

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

Prostaglandin Analogs

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

• Active severe uveitis
• Significant cystoid macular edema

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

Miotics

Miotics are generally avoided because they may:

• Worsen inflammation
• Promote posterior synechiae
• Increase ciliary spasm

Surgical Removal of Lens Material

The definitive treatment is:

Removal of retained lens material when clinically significant.

The surgical approach depends on location.

Anterior Segment Lens Fragments

Fragments in the:

• Anterior chamber
• Capsular bag
• Anterior vitreous

may be removed by an:

Anterior segment surgeon

using irrigation/aspiration or other appropriate techniques.

Posteriorly Retained Lens Fragments

Posteriorly displaced nuclear fragments usually require:

Pars plana vitrectomy

by a vitreoretinal surgeon.

Surgery may include:

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

Timing of Vitrectomy

Timing depends on:

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

Significant retained nuclear material with:

• Severe inflammation
• Uncontrolled IOP
• Persistent corneal edema

generally favors timely vitreoretinal intervention.

Cystoid Macular Edema

CME may accompany chronic postoperative inflammation.

Treatment may include:

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

after infection has been excluded.

Persistent Glaucoma

IOP may remain elevated after lens removal because of:

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

Long-term glaucoma therapy may therefore be necessary.

Glaucoma Surgery

If IOP remains uncontrolled despite:

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

surgery may be required.

Options include:

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

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

Follow-Up

During active disease, follow-up should be:

Frequent

depending on:

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

Some patients require review every:

• Day
• Few days

until stable.

Long-Term Monitoring

After inflammation resolves, monitor for:

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

Prognosis

Prognosis depends on:

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

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

Complications

Potential complications include:

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

Ophthalmology Pearls

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

Ophthalmology – Peters Anomaly

Basics

Description

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

• Descemet membrane
• Corneal endothelium

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

• Iris to posterior cornea
• Lens to posterior cornea

Disease may be:

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

The major threats to vision are:

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

Pathophysiology

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

Proposed mechanisms include:

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

This results in:

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

Epidemiology

Peters anomaly is:

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

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

• Severe visual deprivation
• Genetic disease
• Associated systemic abnormalities

Genetics

Most cases are sporadic, but both:

• Autosomal dominant
• Autosomal recessive

inheritance have been reported.

Associated genes include:

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

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

Anterior segment dysgenesis spectrum

Peters Plus Syndrome

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

Typical features include:

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

It is caused by biallelic pathogenic variants in:

B3GLCT

formerly called B3GALTL.

Inheritance is:

Autosomal recessive

Other Systemic Associations

Peters anomaly may occur with:

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

Systemic abnormalities are particularly important in:

• Bilateral disease
• Syndromic appearance
• Multiple congenital anomalies

Ocular Associations

Associated ocular abnormalities include:

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

Posterior segment abnormalities may also occur.

Posterior Segment Associations

Possible findings include:

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

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

Glaucoma

Glaucoma is one of the most important complications.

Reported frequency is approximately:

30–70%

depending on case severity and series.

Mechanisms include:

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

Glaucoma may present:

• At birth
• During infancy
• Later in childhood

Therefore:

Long-term glaucoma surveillance is mandatory.

Clinical Presentation

Typical presentation includes:

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

Corneal Appearance

The hallmark is:

Central or paracentral congenital corneal opacity

The opacity may be:

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

Peripheral cornea may remain relatively clear.

Iris Adhesions

Iris strands may extend from the:

• Iris collarette
• Midperipheral iris

to the posterior surface of the opaque cornea.

These:

Iridocorneal adhesions

are a classic feature.

Lens Involvement

More severe disease may show:

• Lens adherence to posterior cornea
• Cataract
• Lens malposition

Lens involvement generally indicates a more complex developmental abnormality.

Historical Classification

Type I Peters Anomaly

Traditionally characterized by:

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

Type II Peters Anomaly

Traditionally includes:

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

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

History

Important history includes:

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

Ask specifically about:

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

which may suggest associated glaucoma or severe visual deprivation.

Examination

Perform a complete pediatric ophthalmic examination including:

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

Examination Under Anesthesia

Examination under anesthesia may be required in infants to assess:

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

It is often necessary for treatment planning.

Anterior Segment OCT

AS-OCT can demonstrate:

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

It is useful when sufficient corneal transparency exists.

Ultrasound Biomicroscopy

UBM is particularly valuable for evaluating:

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

especially when direct visualization is limited.

B-Scan Ultrasonography

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

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

Systemic Evaluation

Further testing should be guided by clinical findings.

Depending on phenotype, consider:

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

Genetic Testing

Genetic testing is particularly appropriate for:

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

Testing may include:

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

Differential Diagnosis

Important causes of congenital corneal opacity include:

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

Peters Anomaly vs Congenital Glaucoma

Peters Anomaly

Usually shows:

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

Congenital Glaucoma

More often shows:

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

The two disorders can coexist.

Peters Anomaly vs Sclerocornea

Peters Anomaly

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

Sclerocornea

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

Peters Anomaly vs Birth Trauma

Forceps injury may cause:

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

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

Treatment Goals

Management aims to:

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

Treatment must be individualized.

Observation

Observation may be appropriate when:

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

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

Optical Iridectomy

Optical iridectomy can be useful when:

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

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

Advantages include avoiding:

• Corneal graft rejection
• Graft failure
• Intensive graft surveillance

Penetrating Keratoplasty

Penetrating keratoplasty may be considered for:

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

The decision is complex because infant corneal grafting has:

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

Timing of Keratoplasty

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

Delayed surgery may:

• Improve surgical ease
• Reduce some graft-related risks

but may allow irreversible:

Deprivation amblyopia

Therefore timing is individualized according to:

• Laterality
• Opacity density
• Visual behavior
• Associated abnormalities

Pediatric Graft Prognosis

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

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

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

Endothelial Keratoplasty

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

Glaucoma Treatment

Medical therapy may include:

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

Medical therapy alone is frequently insufficient.

Glaucoma Surgery

Surgical options include:

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

Angle surgery may be difficult because of:

• Severe developmental angle abnormalities
• Poor visualization
• Abnormal anatomy

Glaucoma drainage devices are often important in refractory disease.

Cyclodestructive Procedures

Cyclophotocoagulation is generally reserved for:

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

Cataract Surgery

Lensectomy may be required for:

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

Vitrectomy may also be required depending on associated anatomy.

Amblyopia Therapy

Amblyopia treatment is essential.

Management may include:

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

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

Refractive Error

Children may develop substantial:

• Astigmatism
• Anisometropia
• High refractive error

especially after:

• Keratoplasty
• Cataract surgery

Repeat cycloplegic refraction is therefore essential.

Low-Vision Rehabilitation

Children with severe bilateral visual impairment should receive early:

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

Follow-Up

Long-term surveillance should include:

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

Glaucoma Monitoring

Because glaucoma may develop later:

Surveillance should continue throughout childhood and beyond.

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

Prognosis

Visual prognosis is highly variable.

More favorable features include:

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

Poor Prognostic Features

Include:

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

Systemic Prognosis

Systemic prognosis depends on associated abnormalities.

Children with isolated unilateral disease may otherwise be entirely healthy.

Patients with:

• Peters plus syndrome
• CNS abnormalities
• Multisystem congenital disease

require multidisciplinary follow-up.

Complications

Major complications include:

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

Ophthalmology Pearls

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

Ophthalmology – Persistent Hyperplastic Primary Vitreous / Persistent Fetal Vasculature

Basics

Description

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

• Hyaloid vascular system
• Primary vitreous
• Tunica vasculosa lentis

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

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

PFV is usually:

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

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

Classification

PFV is classified as:

• Anterior PFV
• Posterior PFV
• Combined PFV

Combined anterior-posterior disease is common.

Anterior PFV

Anterior abnormalities may include:

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

Posterior PFV

Posterior disease may demonstrate:

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

Embryology

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

It normally undergoes regression before birth.

Normal remnants may include:

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

PFV represents more extensive persistence with secondary fibrovascular contraction.

Pathophysiology

Failure of fetal vascular regression leaves:

• Persistent vessels
• Fibrous tissue
• Primary vitreous

Contraction of this tissue may pull on the:

• Lens
• Ciliary body
• Retina
• Optic disc

producing progressive structural distortion.

Epidemiology

PFV is uncommon.

The majority of cases are:

Unilateral and sporadic

Bilateral disease is unusual and should prompt consideration of an:

• Inherited retinal disorder
• Syndromic developmental disorder

Genetics

Most isolated PFV has no identifiable inherited cause.

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

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

Genetic evaluation becomes particularly important in:

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

Bilateral PFV – Important Principle

True bilateral isolated PFV is uncommon.

When both eyes show severe fibrovascular retinal abnormalities, consider:

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

NDP-Related Retinopathy

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

The most severe form is:

Norrie disease

Typical features include:

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

Associated systemic manifestations may include:

• Progressive sensorineural hearing loss
• Developmental or behavioral abnormalities

Familial Exudative Vitreoretinopathy

FEVR may produce:

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

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

Clinical Presentation

The classic presentation is:

Leukocoria in an infant with a microphthalmic eye

Other presentations include:

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

Microphthalmia

The affected eye is frequently:

Smaller than the fellow eye

This is an important diagnostic clue.

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

• Microphthalmia
• Microcornea

Anterior Segment Findings

Possible findings include:

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

Iridohyaloid Vessels

Persistent fetal vessels may connect the:

• Iris
• Ciliary body
• Retrolental fibrovascular tissue

Contraction can cause:

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

Mittendorf Dot

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

Posterior lens capsule

An isolated Mittendorf dot does not constitute severe PFV.

Posterior Segment Findings

Potential findings include:

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

Bergmeister Papilla

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

It may be:

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

Macular Abnormalities

Posterior PFV may produce:

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

These substantially limit visual potential.

Optic Nerve Abnormalities

Associated findings may include:

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

These are important prognostic factors.

Diagnosis

Diagnosis is based on the combination of:

• Clinical examination
• Ocular imaging
• Characteristic anatomy

The most important diagnostic objective is:

Exclusion of retinoblastoma

Examination Under Anesthesia

Infants may require examination under anesthesia to evaluate:

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

B-Scan Ultrasonography

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

It may show:

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

A classic finding is:

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

Doppler Ultrasound

Color Doppler may occasionally demonstrate persistent blood flow within:

• Hyaloid vessels
• Fibrovascular stalk

particularly in younger infants.

MRI

MRI is preferred when cross-sectional imaging is needed.

It can demonstrate:

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

MRI is also useful when evaluating:

• CNS abnormalities
• Syndromic disease
• Possible noncalcified retinoblastoma

CT

CT historically played an important role because it detects:

Calcification

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

• Ionizing radiation

Calcification – Critical Pearl

PFV

Typically:

No intraocular calcification

Retinoblastoma

Commonly:

Calcified retinal mass

However:

Absence of calcification does not completely exclude retinoblastoma.

Fluorescein Angiography

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

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

It is not routinely required in classic unilateral PFV.

OCT

Handheld or conventional OCT may show:

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

It can help estimate visual potential and assist surgical planning.

Visual Evoked Potentials

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

Its predictive value is limited.

Modern prognosis is more strongly based on:

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

Differential Diagnosis

Important differential diagnoses include:

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

PFV vs Retinoblastoma

PFV

Usually:

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

Retinoblastoma

Usually shows:

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

PFV vs Retinopathy of Prematurity

Severe ROP usually occurs in:

• Premature infants
• Often bilaterally

End-stage disease may cause:

• Retrolental fibrosis
• Funnel retinal detachment
• Leukocoria

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

PFV vs FEVR

FEVR favors:

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

PFV favors:

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

Treatment Principles

Treatment depends on:

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

Management ranges from:

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

Observation

Observation is reasonable for:

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

It may also be appropriate for very severe disease with:

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

Surgical Indications

Surgery may be considered for:

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

Goals of Surgery

The aims are to:

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

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

Anterior PFV Surgery

Potential procedures include:

• Lensectomy
• Membranectomy
• Anterior vitrectomy

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

Significant intraoperative hemorrhage

Posterior and Combined PFV Surgery

More severe cases may require:

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

These operations can be technically difficult because of:

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

Lens-Sparing Vitrectomy

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

Lens-sparing vitrectomy

may be considered.

Preserving the lens can reduce:

• Aphakic anisometropia
• Optical rehabilitation burden
• Amblyopia

Aphakia Management

After infantile lensectomy, visual rehabilitation may require:

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

Primary IOL implantation is individualized according to:

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

Amblyopia

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

Management may include:

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

Strabismus

Strabismus is common because of:

• Structural visual impairment
• Anisometropia
• Amblyopia

Surgery may later be performed for:

• Alignment
• Cosmesis
• Functional binocular goals when possible

Glaucoma

Secondary glaucoma can result from:

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

Regular IOP surveillance is important.

Vitreous Hemorrhage

Persistent vascular tissue may bleed, causing:

• Recurrent vitreous hemorrhage
• Further visual deprivation

Persistent or severe hemorrhage may become an indication for vitrectomy.

Retinal Detachment

Tractional retinal detachment may:

• Remain stable
• Progress over time

Surgery is considered according to:

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

Severe End-Stage Disease

Some eyes have such profound:

• Retinal dysplasia
• Optic nerve abnormalities
• Total detachment

that meaningful visual improvement is unlikely.

Management may then focus on:

• Comfort
• Globe preservation
• Cosmetic outcome

Enucleation is now uncommon unless:

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

Protective Eyewear

Children with profound unilateral visual impairment should use:

Impact-resistant protective spectacles

to protect the better-seeing eye.

Genetic Counseling

Genetic counseling is appropriate when there is:

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

Follow-Up

All patients require ongoing ophthalmic follow-up.

Monitor:

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

Prognosis

Visual prognosis is highly variable and depends more on:

Posterior segment anatomy

than on the anterior appearance alone.

Favorable Prognostic Features

Include:

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

Poor Prognostic Features

Include:

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

Anterior PFV Prognosis

Anterior PFV generally has the:

Best visual potential

particularly when the retina and optic nerve are relatively normal.

Posterior / Combined PFV Prognosis

These forms generally have worse visual outcomes because of:

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

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

Complications

Potential complications include:

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

Ophthalmology Pearls

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

Ophthalmology – Persistent Fetal Vasculature (PFV)

Basics

Description

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

• Primary vitreous
• Hyaloid vascular system
• Tunica vasculosa lentis

The older term:

Persistent hyperplastic primary vitreous (PHPV)

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

PFV is usually:

• Unilateral
• Sporadic
• Associated with a smaller affected eye

It may cause:

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

Clinical Importance

The most important diagnostic issue is:

PFV must be distinguished from retinoblastoma.

Both may present in infancy with:

• Leukocoria
• Retrolental opacity
• Poor vision

Misdiagnosis can have major consequences.

Classification

PFV is divided into:

• Anterior PFV
• Posterior PFV
• Combined PFV

Combined disease is common.

Anterior PFV

Anterior findings may include:

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

The retrolental membrane may exert traction on the:

• Ciliary processes
• Lens
• Iris

Posterior PFV

Posterior findings may include:

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

Combined PFV

Combined PFV contains both:

• Anterior segment changes
• Posterior segment tractional abnormalities

Visual prognosis is generally worse than in isolated anterior PFV.

Epidemiology

PFV is rare.

Most cases are:

• Unilateral
• Sporadic

Bilateral disease is uncommon and should raise suspicion for:

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

Embryology

The fetal hyaloid vascular system supplies the developing:

• Lens
• Primary vitreous

during early gestation.

It normally regresses before birth.

Remnants of this system can persist physiologically as:

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

PFV represents a much more extensive failure of involution.

Pathophysiology

Failure of normal fetal vascular regression produces persistent:

• Fibrovascular tissue
• Hyaloid vessels
• Primary vitreous

Subsequent contraction may cause:

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

Genetics

Most PFV is:

Sporadic

Rare familial and syndromic forms have been described.

Genes associated with PFV or PFV-like phenotypes include:

• ATOH7
• NDP
• FZD4
• LRP5
• PAX6

depending on phenotype.

Genetic evaluation is particularly appropriate when PFV is:

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

Bilateral PFV

True bilateral PFV is unusual.

The differential should include:

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

Clinical Presentation

The classic presentation is:

Unilateral leukocoria in an infant with microphthalmia

Other presentations include:

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

History

Ask about:

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

Microphthalmia

The affected eye is often:

Smaller than the fellow eye

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

• Normal-sized
• Sometimes enlarged

eye rather than a microphthalmic eye.

Anterior Segment Findings

Possible findings include:

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

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

Posterior Lens Appearance

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

• Fibrovascular plaque
• Membrane
• Cataract

A vascular stalk may attach to this posterior region.

Retrolental Fibrovascular Membrane

This may appear as:

• White
• Gray-white
• Vascularized

tissue behind the lens.

It contributes to the leukocoria.

Persistent Hyaloid Stalk

A classic posterior finding is:

Fibrovascular stalk extending from the optic disc toward the posterior lens

This corresponds to persistent fetal hyaloid tissue.

Posterior Segment Findings

May include:

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

Retinal Fold

A retinal fold may extend:

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

and may substantially limit visual potential.

Retinal Dysplasia

Retinal dysplasia is an important determinant of visual prognosis.

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

Diagnosis

Diagnosis is based on:

• Clinical examination
• Ocular ultrasound
• MRI when needed

The major diagnostic goal is to exclude:

Retinoblastoma

before proceeding with surgery.

Examination Under Anesthesia

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

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

B-Scan Ultrasonography

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

It may demonstrate:

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

A classic appearance is:

A stalk extending from posterior lens to optic disc

Calcification

A critical imaging distinction:

Retinoblastoma

Often demonstrates:

Intraocular calcification

PFV

Typically:

Does not contain calcification

However:

Absence of calcification does not completely exclude retinoblastoma.

Therefore imaging must be interpreted with the entire clinical picture.

MRI

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

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

MRI Findings

Possible findings include:

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

CT

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

However:

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

OCT

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

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

This may help estimate visual potential.

Fluorescein Angiography

Wide-field fluorescein angiography may occasionally help evaluate:

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

It is not required in every classic unilateral case.

Visual Evoked Potentials

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

Its ability to predict postoperative visual outcome is limited.

Modern surgical decisions rely more heavily on:

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

Differential Diagnosis

The most important differential is:

• Retinoblastoma

Other differentials include:

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

PFV vs Retinoblastoma

PFV

Usually:

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

Retinoblastoma

Typically:

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

PFV vs Congenital Cataract

Congenital cataract may cause:

• Leukocoria
• Poor red reflex

but lacks:

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

unless associated with PFV.

PFV vs Norrie Disease

Norrie disease usually causes:

• Bilateral severe retinal dysplasia
• Pseudoglioma
• Retinal detachment

and may later cause:

• Sensorineural hearing loss
• Neurodevelopmental problems

Bilateral PFV-like disease should therefore prompt consideration of:

NDP-related disease

PFV vs FEVR

FEVR may produce:

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

Unlike classic unilateral PFV, FEVR is often:

• Bilateral
• Familial

although asymmetry can be marked.

Treatment Principles

Treatment depends on:

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

Options include:

• Observation
• Surgery
• Amblyopia therapy

Observation

Observation may be appropriate for:

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

Indications for Surgery

Consider surgery when there is:

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

Surgical Goals

The major goals are:

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

Anterior PFV Surgery

Typical procedures may include:

• Lensectomy
• Membranectomy
• Anterior vitrectomy

Care must be taken because the retrolental tissue can be:

Highly vascular

and intraoperative bleeding may occur.

Posterior / Combined PFV Surgery

May require:

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

These cases are technically challenging because:

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

Lens-Sparing Surgery

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

Lens-sparing vitrectomy

to reduce:

• Aphakia
• Anisometropia
• Amblyopia

However, this is feasible only in selected cases.

Intraocular Lens

Primary IOL implantation in PFV is individualized.

Factors include:

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

Many infants are initially managed with:

• Contact lens
• Aphakic spectacles

after lensectomy.

Amblyopia Treatment

Amblyopia is often a major limitation to visual recovery.

Treatment may include:

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

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

Strabismus

Strabismus is common because of:

• Poor unilateral vision
• Anisometropia
• Structural retinal abnormalities

Surgery may later be considered for:

• Alignment
• Cosmesis
• Binocular function when possible

Glaucoma

Secondary glaucoma may develop from:

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

Monitor:

• IOP
• Corneal diameter
• Optic nerve
• Axial growth

Severe End-Stage Disease

Historically, some severely malformed eyes underwent enucleation.

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

• Comfortable
• Not suspicious for malignancy

Enucleation is uncommon and usually reserved for:

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

Follow-Up

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

Monitor:

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

Prognosis

Visual prognosis depends strongly on the subtype.

Anterior PFV Prognosis

Isolated anterior PFV generally has the:

Best visual prognosis

particularly when:

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

Useful visual acuity is possible.

Posterior PFV Prognosis

Posterior disease has a less favorable prognosis because of:

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

Combined PFV Prognosis

Combined disease generally has the poorest visual potential.

Nevertheless, modern surgery may sometimes achieve:

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

in selected patients.

Prognostic Factors

Poor visual prognosis is associated with:

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

Complications

Potential complications include:

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

Ophthalmology Pearls

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