AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Background

Peters anomaly is a rare form of anterior segment dysgenesis in which abnormal cleavage of the anterior chamber occurs. Involving the central or entire cornea, Peters anomaly is divided into 2 types depending on whether or not the lens is abnormal. Peters anomaly may have an inherited pattern. Mutations involve the PAX6 gene. Peters anomaly may also be associated with other ocular or systemic abnormalities.

Pathophysiology

In Peters anomaly, central or paracentral corneal opacity is present. In some cases, this opacity may involve the entire cornea. In type 1, the lens may or may not be cataractous; however, the lens does not adhere to the cornea. In type 2, the lens is cataractous and adheres to the cornea.

Peters anomaly may be associated with other abnormalities of the eye, including myopia, aniridia, coloboma of the iris, choroid, microphthalmos, persistent hyperplasia of primary vitreous (PHPV), and optic disk hypoplasia.

Systemic associations with Peters anomaly include trisomy 13-15, partial deletion of chromosome arm 11q, and Norrie disease. In Krause-Kivlin syndrome, the patient is of short stature with developmental delay and facial dysmorphism. Peters plus syndrome is characterized by genitourinary abnormalities; syndactyly; brachycephaly; and cardiac, neural, and hearing abnormalities. Bilateral Peters anomaly was reported in an infant with 49XXXXY syndrome.

Frequency

United States

Incidence rates in the United States and throughout the world are unknown (very rare).

Mortality/Morbidity

In addition to corneal opacity and cataract, glaucoma may increase morbidity. Mortality may be increased because of other systemic involvement, especially cardiac anomalies.

Race

Peters anomaly occurs in all races. No known racial predilection exists.

Sex

No known sexual predilection exists.

Age

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

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

History

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

Physical

Central, paracentral, or complete corneal opacity is always present in patients with Peters anomaly. Usually, no vascularization of this opacity occurs, which helps in distinguishing it from other causes of congenital corneal opacity.

• In type 1, 80% of cases are bilateral. Central or paracentral annular corneal opacity is present. The surrounding peripheral cornea may be clear or edematous because of glaucoma. The cornea is avascular. Iris strands often extend from the collarette, 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.
• In type 2, 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.
• Other ocular abnormalities: Peters anomaly may be associated with microcornea, cornea plana, sclerocornea aniridia, and glaucoma due to dysgenesis of the angle. Glaucoma occurs in up to 90% of cases. Colobomas of the iris and 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.
• Systemic abnormalities
• • Peters anomaly is seen in trisomy 13-15, ring chromosome 21, 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 is an autosomal recessive condition with short stature, facial dysmorphism, developmental delay, and delayed skeletal maturation.
• Peters plus syndrome also is an autosomal recessive condition. Clinical manifestations include brachycephaly, brain malformation, cardiac anomalies, genitourinary anomalies, syndactyly, cleft lip and palate, and hearing abnormalities.

Causes

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 or autosomal recessive. They are rarely autosomal dominant.

• The PAX6 gene is involved in ocular embryogenesis. This gene seems to regulate other genes that also are involved in ocular development by impairing paired box sequence within a gene. Mutations in the PAX6 gene have been detected in various ocular anomalies, including Peters anomaly, aniridia, Axenfeld anomaly, and autosomal dominant keratitis characterized by corneal opacification and vascularization. Because some studies have found no mutation of the PAX6 gene in a large cohort of patients with Peters anomaly, other unidentified mutations also may cause Peters anomaly.
• The RIEG1 gene is associated with Reiger syndrome. This gene is located on band 4q25. A case of Peters anomaly has been reported with mutation of this gene.
• Another case of Peters anomaly was associated with abnormal centromere-chromatid apposition.

DIFFERENTIALS

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Posterior keratoconus: Clinically, both conditions are similar, although minimal opacity is present in posterior keratoconus. Histopathologically, in Peters anomaly, the corneal endothelium and the Descemet membrane are thin or absent. In posterior keratoconus, the Descemet membrane and the endothelium are present. The Descemet membrane is disorganized. Electron microscopy (EM) shows abnormalities of the anterior banded zone. The endothelial cells are attenuated in the area of guttae. No iris adhesions are seen in posterior keratoconus.

Sclerocornea: The entire cornea is opacified and flattened. Inheritance may be autosomal dominant or autosomal recessive. The normal lamellar orientation of the stroma is lost.

Trauma: This includes birth trauma from forceps delivery.

Other differential diagnoses to be considered are as follows:

Intrauterine keratitis
Mucopolysaccharidoses
Congenital hereditary endothelial dystrophy
Corneal dermoids
Congenital hereditary endothelial dystrophy
Posterior polymorphous dystrophy

WORKUP

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Lab Studies

• Peters anomaly is a clinical diagnosis. Depending on the physical examination, other laboratory studies may be warranted. The only specific test for Peters anomaly is histopathology of the cornea. (See Histologic Findings.)

Imaging Studies

• The following imaging studies may be performed based on the clinical findings from the physical examination:
• • MRI of the brain and spinal cord are indicated to rule out neurologic defects, and MRI of the abdomen is indicated to rule out genitourinary abnormalities.
  • Echocardiogram (ECHO) is indicated to rule out cardiac defects.
  • Ocular ultrasonogram is a very useful tool to help diagnose Peters anomaly and to differentiate it from other causes of corneal opacity. Ocular ultrasonogram is also helpful in assessing associated anterior segment abnormalities.

Other Tests

• To rule out hearing abnormalities, hearing tests may be performed.

Procedures

• A thorough ocular examination is done under anesthesia. External photographs, ocular ultrasonogram, intraocular pressure, and retinoscopy may also be performed.

Histologic Findings

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.

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

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

TREATMENT

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical Care

• 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 them. No Food and Drug Administration (FDA)-approved medications are available for the treatment of glaucoma in children.
  • A pediatric glaucomatologist best manages these patients.

Surgical Care

• For patients with a clear peripheral cornea, peripheral optical iridectomy may be performed.
• For patients with bilateral visually disabling corneal opacity, penetrating keratoplasty is recommended. To prevent amblyopia, the earlier the surgery is performed (eg, before 3-6 mo), the better the results.
• For patients with cataract, lensectomy/vitrectomy is indicated. If left aphakic, these patients will require aphakic contact lenses or aphakic spectacles.
• Filtration surgery, cryoablation, or a tube shunt may be required for those patients with glaucoma whose increased intraocular pressure (IOP) cannot be managed by medications.

Consultations

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

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• An ophthalmologist should provide regular follow-up care for patients with graft rejection and glaucoma. In addition, a pediatrician should monitor patients for other congenital anomalies.
• Patients should receive visual rehabilitation as needed.
• A pediatric contact lens specialist should fit patients with aphakic contact lenses.

In/Out Patient Meds

• Medications may be indicated for glaucoma and postgraft treatment.

Complications

• Complications include amblyopia and decreased vision or blindness from glaucoma. Complications of corneal transplantation and cataract surgery are numerous.

Prognosis

• The visual prognosis is guarded. The earlier the keratoplasty is performed, the better the chances of preventing deprivation amblyopia. The visual acuity in patients after keratoplasty was 20/80 or worse in most series; some series reported a visual acuity of 20/40 in patients. Also, in most series, the chances that patients maintain a clear graft were 30-50% at 10 years. Patients with glaucoma and cataract had a worse prognosis.
• The prognosis for life depends on other systemic anomalies.

Patient Education

• Children with Peters anomaly require special educational needs depending on the visual outcome. A low-vision specialist should evaluate these children. Patients may need loupes and binoculars depending on the visual potential.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize Peters anomaly from other conditions that mimic it
• Failure to refer to other specialists to rule out systemic anomalies
• Failure to provide regular follow-up care for those children with graft rejection or glaucoma
• Failure to offer visual rehabilitation

Special Concerns

• Cases of Peters anomaly have been reported to occur with fetal alcohol syndrome. Drinking during pregnancy should be discouraged.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• Miscellaneous
• References

• Azuma N, Yamaguchi Y, Handa H, et al. Missense mutation in the alternative splice region of the PAX6 gene in eye anomalies. Am J Hum Genet. Sep 1999;65(3):656-63. [Medline].
• Cameron JA. Good visual result following early penetrating keratoplasty for Peters'' anomaly. J Pediatr Ophthalmol Strabismus. Mar-Apr 1993;30(2):109-12. [Medline].
• Churchill AJ, Booth AP, Anwar R, Markham AF. PAX 6 is normal in most cases of Peters'' anomaly. Eye. 1998;12 (Pt 2):299-303. [Medline].
• Cibis GW, Waeltermann J, Harris DJ. Peters'' anomaly in association with ring 21 chromosomal abnormality. Am J Ophthalmol. Nov 15 1985;100(5):733-4. [Medline].
• Dana MR, Schaumberg DA, Moyes AL, Gomes JA. Corneal transplantation in children with Peters anomaly and mesenchymal dysgenesis. Multicenter Pediatric Keratoplasty Study. Ophthalmology. Oct 1997;104(10):1580-6. [Medline].
• Doward W, Perveen R, Lloyd IC, et al. A mutation in the RIEG1 gene associated with Peters'' anomaly. J Med Genet. Feb 1999;36(2):152-5. [Medline].
• Frydman M, Weinstock AL, Cohen HA, et al. Autosomal recessive Peters anomaly, typical facial appearance, failure to thrive, hydrocephalus, and other anomalies: further delineation of the Krause-Kivlin syndrome. Am J Med Genet. Jul 1 1991;40(1):34-40. [Medline].
• Ghose S, Kishore K, Patil ND. Oculoauricular dysplasia syndrome of Goldenhar and Peters'' anomaly: a new association. J Pediatr Ophthalmol Strabismus. Nov-Dec 1992;29(6):384-6. [Medline].
• Gollamudi SR, Traboulsi EI, Chamon W. Visual outcome after surgery for Peters'' anomaly. Ophthalmic Genet. Mar 1994;15(1):31-5. [Medline].
• Hennekam RC, Van Schooneveld MJ, Ardinger HH, et al. The Peters''-Plus syndrome: description of 16 patients and review of the literature. Clin Dysmorphol. Oct 1993;2(4):283-300. [Medline].
• Lee CF, Yue BY, Robin J, et al. Immunohistochemical studies of Peters'' anomaly. Ophthalmology. Jul 1989;96(7):958-64. [Medline].
• Mayer UM. Peters'' anomaly and combination with other malformations (series of 16 patients). Ophthalmic Paediatr Genet. Jun 1992;13(2):131-5. [Medline].
• Mirzayans F, Pearce WG, MacDonald IM, Walter MA. Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Am J Hum Genet. Sep 1995;57(3):539-48. [Medline].
• Nischal KK, Naor J, Jay V. Clinicopathological correlation of congenital corneal opacification using ultrasound biomicroscopy. Br J Ophthalmol. Jan 2002;86(1):62-9. [Medline].
• Ozeki H, Shirai S, Ikeda K, et al. [Histochemical studies on two cases of Peters'' anomaly]. Nippon Ganka Gakkai Zasshi. Jun 1996;100(6):471-7. [Medline].
• Ozeki H, Shirai S, Nozaki M. Ocular and systemic features of Peters'' anomaly. Graefes Arch Clin Exp Ophthalmol. Oct 2000;238(10):833-9. [Medline].
• Parmley VC, Stonecipher KG, Rowsey JJ. Peters'' anomaly: a review of 26 penetrating keratoplasties in infants. Ophthalmic Surg. Jan 1993;24(1):31-5. [Medline].
• Thompson EM, Winter RM, Baraitser M. Kivlin syndrome and Peters''-Plus syndrome: are they the same disorder?. Clin Dysmorphol. Oct 1993;2(4):301-16. [Medline].
• Traboulsi EI, Maumenee IH. Peters'' anomaly and associated congenital malformations. Arch Ophthalmol. Dec 1992;110(12):1739-42. [Medline].
• Wertelecki W, Dev VG, Superneau DW. Abnormal centromere-chromatid apposition (ACCA) and Peters'' anomaly. Ophthalmic Paediatr Genet. Aug 1985;6(1-2):247-55. [Medline].
• Yang LL, Lambert SR, Lynn MJ, Stulting RD. Long-term results of corneal graft survival in infants and children with peters anomaly. Ophthalmology. Apr 1999;106(4):833-48. [Medline].

Article Last Updated: Jun 22, 2006