Mixed cryoglobulins are complexes of immunoglobulins that reversibly precipitate in the cold and lead to a systemic disease in humans. Renal involvement usually manifests as a membranoproliferative glomerulonephritis with marked monocyte infiltration and, at times, intracapillary thrombi. Thymic stromal lymphopoietin (TSLP) is a recently cloned cytokine that supports differentiation and long-term growth of B cells. Here we report that TSLP overexpression in mice results in the development of mixed cryoglobulins, with renal involvement closely resembling cryoglobulinemic glomerulonephritis as it occurs in humans. One hundred twenty-three mice were sacrificed at monthly intervals, with at least five TSLP transgenic mice and five controls in each group. Blood, kidneys, spleen, liver, lung, and ear were collected and studied by routine microscopy, immunofluorescence, immunohistochemistry, and electron microscopy. TSLP transgenic animals developed polyclonal mixed cryoglobulinemia (type III) and a systemic inflammatory disease involving the kidney, spleen, liver, lung, and ears. Renal involvement was of a membranoproliferative type demonstrating thickened capillary walls with cellular interposition and double contours of the basement membrane, expansion of the mesangium because of increased matrix and accumulation of immune-deposits, subendothelial immune-deposits, focal occlusion of capillary loops, and monocyte/macrophage influx. In contrast to the severe glomerular lesions, the tubulointerstitium was not involved in the disease process. The renal lesions and the disease course were more severe in females when compared to males. We describe a mouse strain in which a B-cell-promoting cytokine leads to formation of large amounts of mixed cryoglobulins and a systemic inflammatory injury that resembles important aspects of human cryoglobulinemia. This is the first reproducible mouse model of renal involvement in mixed cryoglobulinemia, which enables detailed studies of a membranoproliferative pattern of glomerular injury.

Abstract. Fabry disease is an X-linked lysosomal storage disorder due to deficiency of ␣-galactosidase A (GLA) activity that results in the widespread accumulation of neutral glycosphingolipids. Renal failure, neuropathy, premature myocar-

PURPOSE To identify possible associations with the development of diffuse lamellar keratitis (DLK) after laser in situ keratomileusis (LASIK) with femtosecond laser flap creation. SETTING University-based academic practice, Ann Arbor, Michigan, USA. DESIGN Case-control study. METHODS Myopic LASIK was performed between October 2006 and December 2010 using an Intralase 60 kHz femtosecond laser for flap creation. Preoperative clinical characteristics, treatment parameters, and intraoperative and postoperative complications were recorded. Statistical comparisons were made using t, chi-square, and Fisher exact tests and repeated-measures logistic regression to adjust for inter-eye dependency. RESULTS The study enrolled 801 eyes (419 patients). Ninety-nine eyes (12.4%) of 70 patients developed DLK; most cases comprised mild flap interface inflammation and were treated with a routine postoperative antiinflammatory regimen. Twenty-two eyes (2.7%) required more than 1 week of antiinflammatory treatment. There was a statistically significant increase in the incidence of DLK with larger flap diameter (P = .0171), higher side-cut energy (P = .0037), and higher raster energy (P = .0033). Patients with DLK were less likely to achieve corrected distance visual acuity of 20/20 or better 1 day postoperatively (P = .0453). The difference in acuity was no longer present at 1 week. There were no significant associations between the incidence of DLK and preoperative refractive error, flap thickness, ablation depth, or other treatment parameters. CONCLUSIONS Diffuse lamellar keratitis after LASIK with femtosecond laser flap creation tended to be mild with little effect on visual acuity. Higher energy level for flap creation and larger flap diameter were associated with an increased risk for DLK.