Peters Anomaly

Peters anomaly is a rare congenital form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. It is characterized by a central corneal opacity (leukoma) due to defects in the posterior stroma, Descemet membrane, and endothelium.[1, 2, 3, 4, 5]

Peters anomaly is differentiated into 2 types: the milder type 1 Peters anomaly, which typically does not include the lens, and the more severe type 2 Peters anomaly, in which the lens adheres to the cornea (keratolenticular adhesions).[1] Peters anomaly may also be associated with systematic abnormalities.[6, 7]

Genetic mutations within FOXC1, PAX6, PITX2, and CYP1B1 can all result in abnormal neural crest cell migration to the posterior cornea, which can lead to Peters anomaly.[2, 7, 8, 9]

Peters anomaly type 1 presents with central or paracentral corneal opacity and iridocorneal adhesions. Keratolenticular adhesions are absent in this type, although the lens may be cataractous.

Peters anomaly type 2 is commonly associated with a denser corneal opacification. It presents with keratolenticular adhesions.

Peters anomaly is bilateral in 60%-80% of cases.[10] It may be associated with other abnormalities of the eye, including congenital glaucoma, myopia, aniridia, iris coloboma, microphthalmos, persistent hyperplasia of primary vitreous (PHPV), and optic disc hypoplasia.[11, 12]

Systemic associations with Peters anomaly include trisomy 13-15, partial deletion of chromosome arm 11q, and Norrie disease. Peters plus syndrome is characterized by cleft lip or palate, short stature, facial dysmorphism, genitourinary abnormalities, syndactyly, brachycephaly, and cardiac, neural, and hearing abnormalities.[6, 13]

Freqency 

United States

The incidence of Peters anomaly in the United States is estimated to be 44-60 cases annually.[14]

International

The incidence of Peters anomaly outside the United States is unknown.

Mortality/Morbidity

In addition to corneal opacity and cataract, glaucoma and deprivation amblyopia may increase morbidity.[13]

The risk of mortality may be increased because of other systemic involvement, especially cardiac and neural abnormalities.[6, 13]

Race

Peters anomaly has no known racial predilection.

Sex

Peters anomaly has no known sexual predilection.

Age

Peters anomaly manifests in utero during the first trimester of pregnancy (10-16 weeks' gestation) and is therefore noted at birth. The anterior segment is formed completely by the 10th week of gestation, and, by the 16th week, most of the Descemet membrane is formed.

The visual prognosis in individuals with Peters anomaly is guarded. The earlier the keratoplasty is performed, the better the chance of preventing deprivation amblyopia. However, keratoplasty is often challenging to perform in infants and young children. The visual acuity in patients after keratoplasty was 20/80 or worse in most series. The likelihood that patients maintain a clear graft was also quite low at 10 years. Patients with glaucoma and cataract had a worse visual prognosis.

Penetrating keratoplasty has a success rate of 22%-83% in patients with Peters anomaly.[2]

Prognosis depends on the severity of the disease.[5]

Peters anomaly type 1 has a significantly higher rate of a clear graft than does type 2.

Patients with glaucoma and cataract have a worse prognosis.

Penetrating keratoplasty should be performed before age 12 months.

Morbidity and mortality depends on concomitant systemic anomalies.

Children with Peters anomaly require special educational needs depending on the visual acuity. A low-vision specialist should evaluate these children. Patients may need special equipment (loupes, binoculars, other low vision aids) depending on the visual potential.

Because the ocular abnormalities of Peters anomaly are noted at birth, the obstetrician or the pediatrician is often the first to observe them. The child may be completely asymptomatic or may have other ocular or systemic anomalies.

Central, paracentral, or complete corneal opacity (leukoma) is always present in patients with Peters anomaly. The size and density of the leukoma vary. Usually, no vascularization of this opacity occurs, which helps in distinguishing it from other causes of congenital corneal opacity.[15, 16, 17] The corneal periphery is usually more lucent.

Eighty percent of type 1 Peters anomaly cases are bilateral. Central or paracentral corneal opacity is present. The surrounding peripheral cornea may be clear or edematous because of glaucoma. The cornea is avascular. Iris strands often extend across the anterior chamber to the posterior surface of the cornea. These may be filamentous or thick strands or sheets. The opacity is caused by a defect in the underlying corneal endothelium and the Descemet membrane. The lens may be clear or cataractous.[6]

Type 2 Peters anomaly is characterized by adhesions between the lens and the cornea. Cases are usually bilateral. The corneal opacity is denser and may be central or eccentric. The lens is usually cataractous and typically is juxtaposed to the cornea. The posterior stroma, the Descemet membrane, and the endothelium are defective. Iris strands may or may not be present. Other ocular and systemic abnormalities are more common in type 2 than in type 1.

Bilateral Peters anomaly has a stronger association with systemic malformations than does unilateral Peters anomaly.[2]

Other ocular abnormalities

Peters anomaly may be associated with microcornea, cornea plana, sclerocornea aniridia, and glaucoma due to dysgenesis of the angle[18] . Glaucoma occurs in up to 90% of cases. Colobomas of the iris and the choroid, as well as PHPV, have been reported. Optic nerve hypoplasia or atrophy also can occur. One case of Goldenhar syndrome with Peters anomaly has been reported.[19]

Systemic abnormalities

Peters anomaly is seen in trisomy 13-15, ring chromosome 21,[20] Norrie disease, partial deletion of chromosome arm 11q, mosaic trisomy 9, and 49XXXXY syndrome.

Systemic associations in Peters anomaly include developmental delay, congenital heart disease, structural defects of the neurologic system, spinal defects, genitourinary abnormalities, external ear abnormalities, hearing loss, cleft lip and palate, and short stature.

Krause-Kivlin syndrome

Krause-Kivlin syndrome is an autosomal-recessive condition characterized by Peters anomaly, short stature, facial dysmorphism, developmental delay, and delayed skeletal maturation.[21]

Other associated abnormalities

Peters anomaly may also be associated with brachycephaly, brain malformation, cardiac anomalies, genitourinary anomalies, syndactyly, cleft lip and palate, and hearing abnormalities.[22, 23, 24, 25]

The cause of Peters anomaly is unknown; it may be caused by genetic factors, environmental factors, or both. The critical event must occur in the first trimester of pregnancy during the formation of the anterior chamber.

Most cases of Peters anomaly are sporadic; however, the literature has described autosomal-recessive pedigrees and rare autosomal-dominant pedigrees.

Mutations in FOXC1, PAX6, or PITX2 can cause Peters anomaly. The FOXC1, PAX6, and PITX2 genes are all homeobox genes that are involved in the development of the anterior segment of the eyes.[26]

Mutations in the CYP1B1 gene can also cause Peters anomaly. The CYP1B1 gene provides instructions for making an enzyme active in the eye. The role of the enzyme is unclear; however, it is likely involved in the development of the anterior segment.[27]

The RIEG1 gene is associated with Reiger syndrome. This gene is located on band 4q25. A case of Peters anomaly has been reported with this gene mutation.[9]

Another case of Peters anomaly was associated with abnormal centromere-chromatid apposition.[26]

Complications include amblyopia and decreased vision or blindness from glaucoma.

Peters anomaly is a clinical diagnosis. Depending on the physical examination, laboratory studies may be warranted.

The following imaging studies may be performed based on the clinical findings from the physical examination:

Ocular ultrasonography

Ocular ultrasonography is a useful tool to help diagnose Peters anomaly and to differentiate it from other causes of corneal opacity.

Ocular ultrasonography is also helpful in assessing associated anterior segment abnormalities.[29]

Ocular ultrasonography shows hypoechogenicity of the anterior stroma that histopathologically correlates with the absence of the Bowman layer and the presence of stromal edema.[29]

Ultrasound biomicroscopy

Ultrasound biomicroscopy (UBM) is a type of ultrasonography that provides detailed information about the anterior segment of the eye and can visualize iridocorneal and lenticular-corneal adhesions that may be seen in Peters anomaly.

Topical endoscopic imaging

Topical endoscopic imaging (TEI) is a method used to examine the anterior segment using an otoscope through a small clear area of cornea.[30]

Infrared anterior segment camera

An infrared anterior segment camera is a tool used to observe the iris and its relation to the cornea. The mobility of the camera is useful in infants, although the resolution of the imaging may be too low in some cases.[31]

Additional testing should be performed if Peters plus syndrome is suspected or if there is concern for systemic associations.

Hearing tests

Hearing tests may be performed to rule out hearing abnormalities.

MRI

MRI of the brain and the spinal cord are indicated to rule out neurologic defects.

MRI of the abdomen is indicated to rule out genitourinary abnormalities.

Echocardiography

Echocardiography (ECHO) is indicated to rule out cardiac defects.

A thorough ocular examination may be performed under anesthesia. Any clinical manifestations and systemic abnormalities must be determined before any procedure is performed under anesthesia.[13]  Associated abnormalities, including a difficult airway or congenital heart disease, will affect anesthesia management.

External photography, ocular ultrasonography (see Imaging Studies), intraocular pressure assessment, and retinoscopy may also be performed.

Histopathology is often diagnostic. Histologic findings show either thinning or absence of the Descemet membrane or the endothelium. The lens may be normal, or it may be cataractous and adhere to the cornea. The stromal lamellae are irregular and more closely packed. Undifferentiated iris strands attach to the posterior surface of the cornea.[32]

Histochemical studies have shown absence of keratan sulfate in both the cornea and the sclera.[33]

Immunohistochemical studies have shown increased amounts of fibronectin and type VI collagen in the corneas of patients with Peters anomaly.[33, 34]

General

In a child suspected of having Peters anomaly, a thorough physical examination by a pediatrician is warranted.

Genetic counseling must be offered as needed.

Ocular

Glaucoma is very common in patients with Peters anomaly, occurring in up to 90% of cases.

Topical medications or surgery may be necessary to control elevated intraocular pressure (IOP).

Peripheral optical iridectomy

Peripheral optical iridectomy may be performed in patients with a clear peripheral cornea..

Penetrating keratoplasty

Penetrating keratoplasty is recommended in patients with bilateral visually disabling corneal opacity. To prevent amblyopia, the surgery should be performed at age 2-12 months.

Peters anomaly type 1 has a significantly higher rate of graft clarity (80%) than type 2 (20%).[2]

Intense postoperative care, consisting of frequent follow-up visits, high-dose topical corticosteroids, and early suture removal, is necessary.[1]

In patients with unilateral Peters anomaly, the decision whether to perform a penetrating keratoplasty or observe is challenging and must be made after a comprehensive discussion between the family and ophthalmologists, weighing the risks of transplantation (rejection, infection, permanent vision loss) versus the risks of Peters anomaly (usually, dense amblyopia).

Lensectomy/vitrectomy

Lensectomy/vitrectomy is indicated in patients with cataract. If left aphakic, these patients will require aphakic contact lenses or aphakic spectacles.

Filtration surgery, cryoablation, or tube shunt

Filtration surgery, cryoablation, or a tube shunt may be required in patients with glaucoma whose increased intraocular pressure cannot be managed with medications.[35]

Pupil dilatation or iridectomy

Pupil dilatation or iridectomy can be performed to optimize visual function in patients with small corneal opacity.[2]

See the list below:

• Pediatrician - Thorough examination to rule out other systemic abnormalities
• Neonatologist
• Geneticist - Genetic counseling
• Glaucoma specialist- Management of glaucoma (Most patients with Peters anomaly have glaucoma. No FDA-approved glaucoma medications are available for children.)
• Vitreoretinal surgeon – if lensectomy/vitrectomy is necessary
• Cornea specialist - Keratoplasty
• Low-vision specialist - Management of poor vision, provision of optical aids

Complications of corneal transplantation and cataract surgery are numerous, especially in children.

An ophthalmologist should provide regular follow-up care to monitor the status of the cornea and glaucoma.

A pediatrician should monitor patients with Peters anomaly for other congenital anomalies.

Patients should receive visual rehabilitation as needed.

A pediatric contact lens specialist should fit patients with aphakic contact lenses if the natural lens is removed.

Aggressive amblyopia therapy should be performed to aid with good visual acuity. 

Medications may be indicated for glaucoma and postgraft treatment.