Paraproteinemic Keratopathy

Excerpt

Ocular monoclonal gammopathy, also known as paraproteinemia, is a family of specific processes that result in ocular damage from the deposition of monoclonal immunoglobulins in various parts of the eye. This deposition comes from high levels of circulating immunoglobulin in the blood, as seen most often in multiple myeloma, Waldenström macroglobulinemia, and monoclonal gammopathy of unknown significance (MGUS). Other disease processes also cause gammopathy, including B-cell lymphoma, primary amyloidosis, smoldering multiple myeloma, plasmacytoma, chronic lymphocytic leukemia, and polyclonal hypergammaglobulinemia. While ocular symptoms due to gammopathy are rare, they have been among the first symptoms leading to the diagnosis of systemic disease in several patients.

Ocular diseases resulting from systemic gammopathy include paraproteinemic keratopathy, retinal vein occlusion, paraproteinemic maculopathy, crystal storing histiocytosis, corneal copper aggregation, and others. While the above presentations of ocular gammopathy will be briefly reviewed, this article primarily covers paraproteinemic keratopathy. Other presentations may be discussed in greater detail elsewhere.

Paraproteinemic keratopathy (PPK) is among the best-studied ocular disease processes occurring with monoclonal gammopathy. It is also called corneal crystalline deposition, MGUS keratopathy, or MGUS associated corneal opacification. In this disease, deposits of monoclonal immunoglobulin accumulate and crystalize in the cornea resulting in the loss of visual acuity. The disease is most commonly associated with MGUS and multiple myeloma, although it has been reported with cryoglobulinemia, lymphoma, or autoimmune diseases. The exact clinical presentation and examination findings in patients with PPK vary widely.

Retinal vein occlusion can also result from systemic gammopathy. It occurs most commonly in Waldenström macroglobulinemia as a result of high concentrations of IgM that result in hyperviscosity and increased risk of venous occlusion. IgM is a pentamer and the largest immunoglobulin. High levels, therefore, cause a significant increase in blood viscosity and increase the risk of coagulation.

Paraproteinemic maculopathy is another disease of the eye that results from systemic gammopathy. It results from fluid accumulation behind the retina and resultant retinal detachment leading to the loss of vision. Paraproteinemic maculopathy is most common in Waldenström macroglobulinemia and has also been associated with multiple myeloma and MGUS.

Ocular crystal storing histiocytosis (CSH) is extremely rare, with fewer than ten known cases, according to one source. This disease results from crystalized immunoglobulin deposits, which accumulate in multiple tissues. CSH more commonly affects the bone marrow, spleen, lymphatics, and kidneys; however, CSH deposits have been seen in the conjunctiva, periorbital fat, and extraocular muscles. These occasionally cause masses that can displace or damage adjacent tissue. They are most associated with multiple myeloma, plasmacytoma, and lymphoplasmacytic lymphoma.

Corneal copper aggregation secondary to monoclonal gammopathy is extremely rare and results from monoclonal gammopathy of IgG with a high affinity for copper. These immunoglobulins accumulate along the Descemet membrane and the anterior lens capsule. It has been associated with multiple myeloma, MGUS, chronic lymphocytic leukemia, pulmonary carcinoma, and benign monoclonal gammopathy.

Occasional cases of open-angle glaucoma and anterior uveitis have also been reported in connection with monoclonal gammopathies. As previously mentioned, this article is primarily concerned with paraproteinemic keratopathy.