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.