PARAPROTEINEMIC CRYSTALLOIDAL KERATOPATHY - AN ULTRASTRUCTURAL-STUDY OF 2 CASES, INCLUDING IMMUNOELECTRON MICROSCOPY

The ultrastructural appearances of corneal crystalloidal deposits are described in two patients with an IgG-kappa paraproteinemia of uncerta in pathogenesis. The crystalloids in one patient were overwhelmingly i ntracellular and were found mainly in stromal keratocytes, but also in basal corneal epithelial cells and the limbal vascular endothelium. F our types of crystalloid or immunoprotein-containing granules were rec ognizable in this case: 1) fibrillary crystalloids with a curvilinear filamentous substructure; 2) angulated geometric crystalloids that oft en had a linear filamentous substructure and transverse or oblique per iodicity; 3) cordlike crystalloids; and 4) lysosomelike granules with amorphous contents. Immunoelectron microscopy demonstrated that all of these structures labeled for kappa-light chains, and rectangular type 2 crystalloids showed approximately a twofold greater concentration o f the colloidal gold probe than the type 1 fibrillary crystalloids. Th e evidence suggested development of the crystalloids within lysosomes, with a progression from the granules containing amorphous material, t hrough fibrillary crystalloids, to the geometric structures. The circu mferential distribution of the corneal deposits, as well as the presen ce of vascular endothelial crystalloids and reduplication of external laminae around limbal blood vessels, suggests that the crystalloids or iginated predominantly or entirely from the blood, with transport of i mmunoprotein across damaged limbal microvasculature. The abnormal vasc ulature may also have contributed to corneal edema, which in turn may have exacerbated corneal opacification. The crystalloidal deposits in the other case were exclusively extracellular; they were located benea th and between corneal basal epithelial cells, and predominantly as a mantle around individual keratocytes. The crystalloids in this case co nsisted overwhelmingly of thick-walled tubules about 40 nm in diameter that labeled for both kappa-light chains and gamma chains with the co lloidal gold immunoprobe. In addition, lucent vesicles within keratocy tes were found only in sections labeled for kapppa-light chains and we re positive. The factors that might contribute to the formation of cor neal crystalloidal-deposits in immunoproliferative disorders are discu ssed, and include: 1) an inherent propensity for crystallization of so me immunoglobulins or kappa-light chains, perhaps because of abnormal molecular structure; and 2) local factors in the cornea that might pro mote deposition and crystallization of immunoprotein, such as temperat ure, pH, the water content, and extracellular matrix components.