CLASSIFICATION AND CLINICAL PRESENTATION
Ocular amyloidosis is classified as either primary (idiopathic) or secondary (to a chronic disease) and as either localized or systemic. A useful classification of amyloidosis considers these 4 types. Each type is summarized in Table 8-4.
Primary localized amyloidosis is the most common form of ocular amyloidosis. Conjunctival amyloid plaques occur in the absence of systemic involvement (Fig 8-7). Gelatinous droplike corneal dystrophy (formerly primary familial amyloidosis), classic lattice corneal dystrophy (LCD1), and lattice variants are special forms of primary localized amyloidosis and are discussed in Chapter 7. Polymorphic amyloid degeneration is discussed in Chapter 6.
Table 8-4 Amyloid in the Eye
Figure 8-7 Clinical photograph of the inferior palpebral conjunctiva, showing moderate thickening with yellowish amyloid deposition.
(Courtesy of Stephen E. Orlin, MD.)
Primary systemic amyloidosis is a heterogeneous group of diseases in which waxy, ecchymotic eyelid papules occur in association with vitreous veils and opacities as well as with pupillary anomalies such as light–near dissociation. Orbital involvement, extraocular muscle involvement with ophthalmoplegia, and scleral infiltration with uveal effusion have been reported. The most common form of primary systemic amyloidosis is an autosomal dominant group of diseases linked to mutations in the transthyretin gene (TTR, prealbumin) on chromosome 18 (18q11.2–q12.1); more than 40 mutations in this gene have been described.
Familial amyloidosis, Finnish type, or gelsolin type (Meretoja syndrome) is an example of primary systemic amyloidosis. This condition was initially described in persons of Finnish descent but was later reported in individuals of other ethnicities. Previously called lattice corneal dystrophy type 2, it has been excluded as a corneal dystrophy by the International Committee for the Classification of Corneal Dystrophies (IC3D) because of its systemic associations.
Familial amyloidosis presents in the third to fourth decade of life. Because the ocular symptoms are the first to arise, the ophthalmologist is often the first physician to see patients with this condition, who typically present with corneal findings. Affected patients have a characteristic facial mask; dermatochalasis; lagophthalmos; pendulous ears; cranial and peripheral nerve palsies; and dry, lax skin with amyloid deposition (Fig 8-8). The classic corneal lattice lines are less numerous and more peripheral, and they spread centripetally from the limbus. The central cornea is relatively spared; corneal sensation is reduced. The risk of open-angle glaucoma may be increased, and dry eye and recurrent erosions may occur late in life.
PATHOLOGY OF FAMILIAL AMYLOIDOSIS
Light microscopy shows amyloid in the lattice lines as a discontinuous band under the Bowman layer and within the sclera. The amyloid in this condition is related to gelsolin and does not stain for type AA or AP. The mutated gelsolin is observed to be deposited in the conjunctiva, sclera, and ciliary body; along the choriocapillaris; in the ciliary nerves and vessels; and in the optic nerve. Extraocularly, amyloid is detected in arterial walls, peripheral nerves, and glomeruli. On confocal microscopy, deposits are observed along the basal epithelial cells and stromal nerves.
A, Diffuse lattice lines in Meretoja syndrome. B, Typical facies.
(Reproduced with permission from Weiss JS, Møller H, Lisch W, et al. The ICD3 classification of the corneal dystrophies. Cornea. 2008; 27(10 Suppl 2):S16.)
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