Q: I saw a patient who was diagnosed with multiple myeloma (MM) six months prior to her annual exam. Upon examination, I observed significant superficial corneal crystals in both eyes. Do these crystals signal MM in a previously undiagnosed patient?

A: To begin with, MM is a cancer of the plasma cell. The plasma cell produces immunoglobulins that help fight infection and disease.¹

So, do these crystals signal MM in a previously undiagnosed patient? No, says Evan C. Canellos, O.D., of Brooklyn, N.Y. There are many other systemic diseases that can cause corneal crystals; MM should definitely be considered in the differential diagnosis, but so should these other conditions, he says. The medical literature lists six categoriesfive of are types of systemic disease, and one is medicationknown to cause corneal cry- stals, says Robert Latkany, M.D., of New York. The following are examples from each category:

Waldenstrms macroglobulinemia. Like MM, this is an example of an acquired systemic disease. It is a rare chronic cancer that affects the plasma cells. These plasma cells develop from white blood cells (B-lymphocytes).² 

Cystinosis. This systemic disease results from errors in protein metabolism. The amino acid cystine accumulates in various organs, such as the kidney, eye, muscle, pancreas and brain.³ There are three different forms of this disease: infantile (progressive nephro- pathy), adolescent (intermediate nephropathy) and adult (non-nephrotic) cystinosis, says Dr. Canellos.

Tangier disease. This is an example of a lipid keratopathy systemic disease. Tangier disease decreases concentrations of fat compounds (high-density lipoproteins) in the blood. Large numbers of these compounds may accumulate in certain organs of the body, causing tissue discoloration. In later stages, enlargement and/or blood circulation issues may occur due to these accumulations.⁴


Infectious crystalline keratopathy (ICK). This is an example of an infectious systemic disease. ICK causes a chronic and insidious non-inflammatory bacterial infiltration of the cornea.⁵

Bietti crystalline dystrophy (BCD). This systemic disease is part of the miscellaneous systemic disease category. BCD appears to be more prevalent in people of Asian descent and includes crystals in the cornea, yellow shiny deposits on the retina and progressive atrophy of the retina, the choriocapillaries and the choroid. BCD tends to lead to progressive night blindness and visual field constriction.⁶

Aralen (chloroquine phosphate, Sanofi-Synthelabo) and Largactil (chlorpromazine, Hawgreen). These two drugs have been shown to cause corneal crystals, says Dr. Latkany. Chloroquine is an anti-inflammatory used to treat malaria and lupus. Chlorpromazine is an anti-psychotic used to treat manic depression, among other psychotic
disorders.

The corneal crystals seen in each separate systemic disease category are composed of different substan-ces, explains Dr. Canellos. In MM, for instance, the crystals are composed of Immunoglobulin G. These substances cannot be seen within the corneal crystals, he says. A differential diagnosis can only be achieved via a hematology consult, so send this patient to his primary-care doctor with a note that details your suspicions, and suggest hematological testing. 

1. Multiple Myeloma Research Foundation. About Mye-loma.www.multiplemyeloma.org/about_myeloma/index.html (25 April 2005).
2. International Waldenstroms Macroglobulinemia Foun-dation. What is Waldenstroms Macroglobulinemia? www.iwmf.com/WhatIsWM.htm. (25 April 2005).
3. Cystinosis Foundation. Facts about Cystinosis (From the Brochure). www.cystinosisfoundation.org/brochure2.html. (25 April 2005).
4. Web MD Health Guide A-Z. Tangier Disease. http://my.webmd.com/hw/health_guide_atoz/nord385.asp (25 April 2005).
5. Morrison DA, Fahy GT, Brown LJ. Unsuspected infections crystalline keratopathy masquerading as corneal graft rejection. Br J Ophthalmol 1997 Jul;81(7):608.
6. National Eye Institute. Resource Guide. Bietti"s Crystalline Dystrophy. www.nei.nih.gov/health/biettis/index.asp#2 (25 April 2005).

Vol. No: 142:5Issue: 5/15/05