corneal clouding

The combination of corneal guttata and anterior polar cataracts has been reported in at least 4 multigenerational families.  Cataracts have their onset in the first decade of life, sometimes as early as 6 months but often are not noted until 3 to 4 years of age.  The polar opacities range in size from that of a small dot to 3 mm in diameter.  These progress slowly and become nearly stationary in early adulthood but can progress sufficiently to interfere with acuity and sometimes require removal by the 3^rd or 4^th decades of life.  The guttata also appear sometime after birth and are more pronounced centrally.  Histologically the stroma is normal but the epithelium shows some edematous changes and the Descemet membrane progressively thickens with age along with the corneal clouding.  Visual impairment early is generally caused by the lens opacity while later in life corneal edema is more likely the cause.

Vision across a variety of ages ranges from 20/20 to 20/40 in patients with more stationary disease.

(OMIM has combined this disorder with PPCD1 (122000) based on genetic and clinical evidence.)

Early onset limbus-to-limbus corneal clouding is the outstanding feature.  Some asymmetry is often present.  Vision is minimally impaired if at all in many children but slow progression occurs and adults often become visually impaired.  Nystagmus does not develop.  Photophobia and tearing are common.  The corneal appearance can lead to the erroneous diagnosis of congenital glaucoma.  However, some infants actually do have congenital glaucoma as well leading some to suggest this may be a disorder of anterior chamber dysgenesis.  The edematous cornea may be of 2-3 times normal thickness.  It may appear generally hazy and sometimes has a diffuse ground glass appearance.  

The posterior surface often appears mottled and has been described as having a peau d'orange appearance.  The endothelium is attenuated or even absent histologically and abnormal, disorganized collagen fibrils have been found in a thickened Descemet layer by electron microscopy.  The remaining endothelial cells are often vacuolated and heaped in double layers, with some containing melanin granules.  Some atrophy and edema of the epithelium with partial loss of Bowman's can be seen histologically.

Schnyder corneal dystrophy has its onset early in life as a haziness of the central cornea with some peripheral extension.  The stroma gradually becomes more hazy and eventually in about 50% of patients yellow-white crystalline deposits can be seen in an annular pattern in the Bowman layer and the adjacent stroma just beneath. The remaining layers of the cornea are not involved.  The needle-shaped crystals are often birefringent and composed of cholesterol and phospholipids. There is considerable variation in the progression of disease and in the symmetry of disease in the two eyes.  Visual acuity may be relatively good in young people but older patients with denser central opacification eventually require corneal transplantation for better vision.

Macular corneal dystrophy is a progressive, bilateral disorder with increasing corneal cloudiness throughout life. The onset of corneal haze is variable.  It can be seen in infancy but usually becomes apparent in the second or later decades of life.  Visual impairment can be severe, especially by mid-life.  The stroma, Descemet membrane, and endothelium are involved as keratocytes and endothelial cells accumulate intracytoplasmic vacuoles of glycosaminoglycans.  Corneal thickness is reduced, presumably due to abnormally dense packing of collagen fibrils in the stroma.  The epithelium does not seem to be involved.

Based on immunohistochemical profiles of inclusions, as well as phenotypic differences, attempts have been made to distinguish at least three types of macular dystrophy, I, IA, and II.  This may not be justified as the same gene is involved, and especially since several types have been described within the same inbred family.  Most likely these are variations in the phenotypic expression of the same gene, a  feature of many genetic disorders.

This disorder of lipoprotein metabolism is associated in many cases with corneal infiltrates, cicatricial ectropion, poor lid closure, and exposure keratopathy.  The corneal clouding alone generally cause little reduction of acuity but those with poor lid function and exposure keratopathy may have severe vision loss.  There may be weakness in the periorbital and lid muscles.  The corneal infiltration occurs late in life but is progressive with older individuals having the greatest visual impairment.  The corneal infiltrates are described as a “dot-like haze”, more prominent centrally and located in the stroma.  On electron microscopy, deposits in the conjunctiva are described as birefringent lipid particles located in pericytes and fibrocytes.  Lipid deposition occurs throughout the body including the conjunctiva.  Corneal hypesthesia has been reported.

In a series of 13 patients, ectropion and corneal scarring were reported in 3 and corneal infiltrates in 9.  Four had orbicular muscle weakness.  The latter together with corneal hypesthesia may be the earliest ocular signs of Tangier disease and should suggest the diagnosis even before the corneal clouding occurs.