Granular dystrophy

Granular dystrophy type I, or Groenouw type I

History

It takes its name from the German ophthalmologist who first described it at the end of the 19th century, Arthur Groenouw. He described two dystrophies, the granular and the macular, which to him were a variant of the same disorder.

Genetics

AD Autosomal dominant (AD); the dystrophy is more severe in homozygotes and appears earlier.

Mutation

TGFBI, R555W (arginine to tryptophan)

Laterality

Bilateral

Symmetry

Yes

Systemic factors

no

Age of onset

From childhood.

Location

Mainly the anterior stroma

Appearance:

Direct illumination

gray-white deposits, initially small (<300 microns in diameter) and well demarcated within the anterior stroma. They generally take three different forms: drops, crumbs, and rings. The stroma between the deposits is transparent early in the disease and remains distant from the limbus. As the disease progresses, the deposits become confluent, extend into deeper layers, and approach the limbus (the 2-3 mm nearest the limbus remain spared), while the stroma between the deposits loses its transparency.

Retroillumination

the lesions are more or less translucent (dots and radial ridges) with a breadcrumb appearance; the stroma shows a granular pattern.

Pain or recurrent erosion

rare

Visual acuity

preserved for a long time; patients often complain of photophobia early on, and it is only as the disease progresses that acuity declines, often around the 5th decade.

Additional investigations:

• Histology: hyaline deposits, rod-shaped or trapezoidal and clustered, in the subepithelial region and the anterior stroma. Stains red with Masson trichrome, and is PAS negative. Immunohistochemistry positive for keratoepithelin, the TGFBI protein (TGFBIp).
• Electron microscopy: well-defined extracellular material, rod-shaped or trapezoidal, with a width ranging from 100 to 500 microns, surrounded by an amorphous matrix.
• Confocal microscopy: hyperreflective extracellular subepithelial and stromal deposits with a crumb-like appearance. Hyperreflective appearance of Bowman layer. Helpful in diagnosing recurrence on the graft.
• OCT: hyperreflective deposits, well defined, polygonal, trapezoidal, or rod-shaped. The stromal surface is irregular and wavy, whereas the epithelial surface is smooth.

Recurrence +++ Recurrence on the graft: Frequent, the earliest of the dystrophies. The recurrence differs from the original disease. It often appears as diffuse subepithelial lesions beginning at the periphery, but may sometimes begin centrally with an appearance resembling cornea verticillata. This dystrophy appears to be of epithelial origin based on the pattern of recurrence on the graft.

Granular dystrophy type II, or combined granular-lattice dystrophy, or Avellino dystrophy.

Genetics

AD Autosomal dominant (AD)

History

It takes its name from the Avellino region of Italy, where the first described cases originated.

Genetics

AR Autosomal recessive (AD); the dystrophy is more severe in homozygotes and appears earlier. Always examine the family.

Mutation

TGFBI, R124H (arginine to histidine)

Laterality

Bilateral

Symmetry

Yes

Systemic factors:

Age of onset

From childhood.

Location

Mainly the anterior stroma

Appearance:

Direct illumination: gray-white deposits in the anterior and mid stroma. They take on various appearances: snowflake, star, dendritic, or fireworks. In addition, lattice deposits also appear, deeper than the granular deposits and often difficult to visualize clinically in the absence of retroillumination. The stroma between the deposits is transparent early in the disease and then becomes opaque with age (haze). These signs constitute a triad:

• Discrete gray-white granular deposits in the anterior stroma, the earliest sign.
• Lattice lesions in the mid and deep stroma, never found without the granular deposits.
• Anterior stromal haze. The last sign to appear.

Retroillumination

the lesions are more opaque than in type I; the stroma shows a granular pattern with amyloid lesions.

Pain or recurrent erosion

More frequent than in type I.

Visual acuity

initially preserved; patients often complain of photophobia and a foreign body sensation early on, and it is only as the disease progresses that acuity declines, often around the 2nd decade.

Diagnosis:

• Histology: both hyaline and amyloid deposits, extending from the basement membrane to the deep stroma. Stains red with Masson trichrome or red with Congo red.
• Electron microscopy: similar to lattice and granular dystrophy; the deposits extend from the subepithelial region to the deep stroma.
• Confocal microscopy: a combination of the two dystrophies; hyperreflective trapezoidal or rod-shaped deposits (granular) and hyperreflective branching linear deposits (lattice).
• OCT: a combination of the two dystrophies.

Recurrence +++ Recurrence on the graft: Frequent.