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Congenital Clouding of the Cornea Clinical Presentation

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Hampton Roy, Sr, MD  more...
Updated: Jan 21, 2016


A variety of historical scenarios are described for congenital clouding of the cornea. For example, a milky quality of the cornea may be noted at birth, with a decreased responsiveness to light. The obstetrician or the pediatrician may be the first to observe these ocular properties. The neonate may be completely asymptomatic, or he or she may have other ocular or systemic anomalies. The mother might give a history of prenatal exposure to a pathogen. Childhood unilateral congenital glaucoma involving optic nerve aplasia has been noted.[21]

Trisomy 8

A finding described in several patients with trisomy 8 is a central corneal opacity, but data regarding the natural history of this finding are lacking. In 1 patient, the corneal opacity spontaneously improved.

New syndrome

A new syndrome of hereditary congenital corneal opacities, cornea guttata, and corectopia was reported.[22]

Peters anomaly

A child might have a history of Peters anomaly. A boy, born at the gestational age of 39 weeks, had Peters anomaly in association with a ring 21 chromosomal abnormality. Dysmorphic features included low-set ears, hypoplastic mandible, delicate and dry skin, narrow and arched palate, wide-spaced nipples, and hypotonia. He also had a cloudy right cornea. Chromosomal analysis disclosed a ring 21 defect. The cornea had a paracentral, white opacity with a loss of posterior stroma and no adherence of the iris to the leukoma. IOP, the lens, and the posterior pole were normal.[23]

Maternal alcohol abuse

Three of 4 siblings born to parents with a history of heavy alcohol abuse had bilateral diffusely cloudy corneas at birth. The three siblings, who had mild systemic features of fetal alcohol syndrome, underwent corneal transplantations, and their specimens were examined under light and electron microscopy. On histology, alterations in the Bowman layer ranged from thickening to total loss. Various degrees of corneal stromal edema were observed. The unique pathologic feature in the corneas was the anomaly of the anterior banded zone of the Descemet membrane, which was absent, poorly formed, or thinned in the central and peripheral cornea. The corneal endothelium was attenuated or multilayered. The diffuse clouding and the range of histologic abnormalities in the corneas might have been related to the maternal alcohol abuse.[24]

De Barsy syndrome

A male newborn had bilateral congenital corneal opacification. Examination revealed a variety of dysmorphic features, including cutis laxa, progeroid aspect, short stature, multiple hyperextensible subluxated joints, muscular hypotonia, and hyperreflexia. Bilateral penetrating keratoplasties were performed. Histopathologic examination revealed diffuse epithelial thickening, loss of the Bowman layer, and stromal attenuation with anterior stromal scarring. Special stains showed no deposition of abnormal material in the corneas. Electron microscopy demonstrated absence of the Bowman layer differentiation with a paucity of collagen fibers and extensive small, elastic fibers in the anterior stroma. The diagnosis was De Barsy syndrome, a rare, progeroid syndrome associated with characteristic ocular, facial, skeletal, dermatologic, and neurologic abnormalities.

De Barsy syndrome should be included in the differential diagnosis of congenital corneal opacification; its distinctive clinical features enable the clinician to easily differentiate it from other causes of congenital cloudy corneas.[25]

Congenital rubella

A cloudy cornea was observed in microphthalmic eyes in patients with congenital rubella.[26]

Clinical variant of Sanfilippo syndrome

A 4-month-old male infant had severe corneal opacity since birth.[27] Examination revealed buphthalmos, increased IOP, and corneal opacity with neovascularization but not a dysmorphic face or hirsutism. The liver and spleen were impalpable. Hypotonia, poor head control, and absence of Moro and grasping reflexes were noted. He had no evidence of congenital infection (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex [TORCH] study). Urine and plasma amino acid levels were normal. However, thin-layer chromatography showed excessive urinary excretion of heparan sulfate. Corneal transplantation was performed at 6 months of age. Histopathology of the corneal button showed homogeneous thickening of the Bowman layer and pinkish intracytoplasmic substances in the corneal stroma. The Alcian blue stain was positive, consistent with MPS of the cornea.

The manifestation in this case may be a clinical variant of Sanfilippo syndrome (MPS III).


Mucopolysaccharidoses can result in corneal clouding but do not necessarily manifest in the natal period.



Central, paracentral, or complete corneal opacity is always present in infants with congenital corneal clouding. Systemic and ocular symptoms that accompany the clouding allow for the syndromic classification of the infant's condition.

Peters anomaly is an uncommon syndrome that manifests with corneal clouding. (See also Peters Anomaly.)

In type 1 Peters anomaly, 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 strands may be filamentous or thick strands or sheets. A defect in the underlying corneal endothelium and the Descemet membrane causes the opacity. The lens may be clear or cataractous.

In type 2 Peters anomaly, cases are usually bilateral. The corneal opacity is dense and may be central or eccentric. The lens is usually cataractous and typically 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.

Corneal clouding, as observed by using a slit lamp, may be used in the differential diagnosis of mucopolysaccharidoses. Corneal clouding is present in MPS I, VI, and VII but absent in MPS II.



Causes of congenital corneal clouding are genetic, metabolic, developmental, infectious, and idiopathic.

Contributor Information and Disclosures

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.


Benjamin D Freilich, MD, FACS Assistant Clinical Professor, Department of Ophthalmology, Icahn School of Medicine at Mount Sinai; Director of Retina Service, Bronx Veterans Administration Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christopher J Rapuano, MD Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Ophthalmological Society, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, International Society of Refractive Surgery, Cornea Society, Eye Bank Association of America

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, Allergan, Bausch & Lomb, Bio-Tissue, Shire, TearScience, TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Allergan, Bausch & Lomb, Bio-Tissue, TearScience.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Richard W Allinson, MD Associate Professor, Department of Ophthalmology, Texas A&M University Health Science Center; Senior Staff Ophthalmologist, Scott and White Clinic

Richard W Allinson, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.


Jonathan Freilich, MD, FACS Clinical Instructor, Department of Ophthalmology, Mount Sinai School of Medicine; Consulting Staff, Department of Ophthalmology, Mount Sinai Hospital, St Luke's Roosevelt Hospital Center

Disclosure: Nothing to disclose.

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Congenital stromal dystrophy. The cornea is particularly opaque in the anterior stroma by slit-lamp biomicroscopy. Courtesy of Wikipedia (© 2009 Klintworth; licensee BioMed Central Ltd).
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