Schnyder crystalline dystrophy

History: first described by Van Went and Wibaut in 1924, but it takes its name from Schnyder, who better elaborated the clinical presentation of the dystrophy. It is often misdiagnosed, since half of cases show no crystal deposits.

Initially described as a non-progressive dystrophy, but progression was later described.

Genetics

AD

Mutation

Chromosome 1p36, through mutations in the UbiA prenyltransferase domain. Often causing a localized abnormality in cholesterol metabolism and transport that can be exacerbated by hyperlipidemia.

Laterality

Bilateral

Symmetry

Often

Systemic factors

Hypercholesterolemia, hypertriglyceridemia (inconstant), genu valgum (inconstant)

Age of onset

Often from an early age, with worsening during the 2nd and 3rd decades. Often children who complain of decreased visual acuity with a family history of familial hypercholesterolemia, which is present in more than half of cases.

Location

Stromal only; Descemet membrane, epithelium, and endothelium are spared.

Appearance:

Direct illumination

begins with an axial, annular, or discoid anterior stromal opacification. The subepithelial crystal deposits, though inconstant (50% of patients), take on a distribution identical to that of the opacification. The stroma is initially clear or contains punctate deposits. During the 3rd decade a lipoid arc appears in almost all patients, followed by progressive opacification extending from the center of the cornea toward the arcus senilis.

Progresses in four phases

central opacity +/- crystals, then lipoid arc, then stromal haze between the two, and finally a decrease in corneal sensitivity.

Retroillumination:

Pain or recurrent erosion

rare

Visual acuity

progressive decrease in visual acuity, with impairment of photopic vision.

Diagnosis:

• Histology: cholesterol deposits (birefringent crystals, non-crystalline cholesterol, and cholesterol ester) and phospholipids within the corneal stroma. Triglyceride and free fatty acid are often absent. The excised tissue must not be fixed in alcohol, which would dissolve the cholesterol. The tissue should usually be submitted fresh or it will have been stained with Sudan black or oil red O.
• Electron microscopy: the epithelial cells are rich in glycogen, along with subepithelial glycogen deposits. Focal round spaces empty of neutral fat that correlate with the punctate stromal deposits. Around these spots, dense granular or fibrillar material corresponding to the stromal haze may be found.
• Confocal microscopy: hyperreflective lesions (thread-like appearance, and organization in a crystalline network or in parallel lines) of cholesterol crystals, mainly in the anterior stroma. Loss of the overlying corneal nerves. The endothelial cells are not visible.
• OCT: hyperreflective anterior stromal opacity.
• Corneal hypoesthesia may develop.

Recurrence ++ Recurrence on the graft: possible