Monoclonal proliferation of plasma cells (B lymphocytes) leads to over-production of both light (κ or λ) chains and heavy (α, γ, ε, δ, or μ) chains (collectively termed 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 that may be related to corneal temperature or local tissue factors.
Ophthalmic findings may 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 immunoglobulin G κ-chain deposition and may be related to the size of the paraprotein and the chronicity of the disease.
Waldenström macroglobulinemia is characterized by malignant proliferation of plasma cells generating immunoglobulin M, causing hyperviscosity syndrome, principally in older men. It has been associated with needlelike crystals and amorphous deposits subepithelially and in deep stroma (Fig 8-15).
Benign monoclonal gammopathy is a frequent (up to 6%) finding in individuals older than 60 years. Results of the systemic evaluation in these cases are negative, but a mild increase in paraprotein (<3 g/dL) is detected. Slit-lamp findings of iridescent crystals resemble those of myeloma and are very infrequent (approximately 1%–2% of affected patients).
Cryoglobulins, proteins that precipitate upon exposure to cold, occur nonspecifically in autoimmune disorders, immunoproliferative disorders, and hepatitis B infection. Ophthalmic findings include signs of retinal hyperviscosity, occasional crystalline corneal deposits, amorphous limbal masses, and signs of autoimmune disease.
Figure 8-15 Clinical photograph from a patient with Waldenström macroglobulinemia, showing amorphous deposits in the stroma.
(Courtesy of Robert W. Weisenthal, MD.)
There are many causes of corneal crystalline deposits. The appearance and location of the deposits can help distinguish the underlying etiology.
Serum protein electrophoresis, complete blood count (CBC), and general screening for albumin/globulin and calcium levels are performed when clinical suspicion of immunoglobulin excess arises. Further testing for systemic evaluation depends on clinical suspicion and the initial findings.
No ophthalmic treatment is necessary unless the amorphous deposits interfere with vision and need to be removed with LK. Crystals resolve slowly after successful treatment of an underlying malignancy. See Table 8-2 for a list of other causes of corneal crystals.
Choulakian MY. Hematologic diseases and malignancies. In: Mannis MJ, Holland EJ, eds. Cornea. Vol 1. 4th ed. Philadelphia: Elsevier; 2017:688–695.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.