Chang RI, Ching SST. Corneal and conjunctival degenerations. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. 3rd ed. Vol 1. Philadelphia: Elsevier/Mosby; 2011:901–917.

Demirci H, Shields CL, Eagle RC Jr, Shields JA. Conjunctival amyloidosis: report of six cases and review of the literature. Surv Ophthalmol. 2006;51(4):419–433.

Disorders of Immunoglobulin Synthesis

The excess synthesis of immunoglobulins by plasma cells in multiple myeloma, Waldenström macroglobulinemia, and benign monoclonal gammopathy may be associated with crystalline corneal deposits.

PATHOGENESIS Monoclonal proliferation of plasma cells (B lymphocytes) leads to overproduction of both light (K or λ) chains and heavy (α, γ, ε, δ, or μ) chains (together, M proteins), overproduction of light chains with or without production of heavy chains (Bence Jones protein), or overproduction of heavy chains without light chains (heavy chain disease). Pathogenesis is related either to direct tissue invasion, particularly of the bone marrow, or to hyperviscosity syndrome. Secondary hypercalcemia may occur. Deposition of paraproteins in the cornea is very rare and is related to diffusion of the proteins, probably from the limbal vessels or, alternatively, from the tears or aqueous humor, followed by precipitation perhaps related to corneal temperature or local tissue factors.

CLINICAL FINDINGS Ophthalmic findings include the following:

crystalline deposition in all layers of the cornea or in the conjunctiva copper deposition in the cornea

sludging of blood flow in the conjunctiva and retina pars plana proteinaceous cysts

infiltration of the sclera

orbital bony invasion with proptosis

Corneal deposits are numerous, scintillating, and polychromatic. They are typical of IgG K chain deposition and possibly related to the size of the paraprotein and the chronicity of the disease.

Waldenström macroglobulinemia is characterized by malignant proliferation of plasma cells generating IgM, causing hyperviscosity syndrome, principally in older men. It has been associated with needlelike crystals and amorphous deposits subepithelially and in deep stroma.

Benign monoclonal gammopathy is a frequent finding in individuals older than 60 years (up to 6%). The systemic evaluation in these cases is negative, but a mild increase in paraprotein is detected (<3 g/dL). Slit-lamp findings of iridescent crystals resemble those of myeloma and are also very infrequent (about 1%–2% of affected patients).

Cryoglobulins are proteins that precipitate on exposure to cold. They occur nonspecifically in autoimmune disorders, immunoproliferative disorders, or hepatitis B infection. Ophthalmic findings include retinal hyperviscosity signs, occasional crystalline corneal deposits, amorphous limbal masses, and signs of autoimmune disease.

LABORATORY EVALUATION There are many causes of corneal crystalline deposits. The appearance and location of the deposits can help distinguish the underlying etiology. Table 11-4 summarizes the differential diagnosis of corneal deposits based on the depth of corneal involvement, color and refractile character of the deposit, and involvement of the conjunctiva.

Table 11-4