Is Keratoconus an Inflammatory Disease? The Implication of Inflammatory Pathways.

PURPOSE: Keratoconus is considered a non-inflammatory condition. Recently however, increased proinflammatory cytokines have been detected in the tears of keratoconic patients and clinical and immunohistochemical observations reported infiltration of matured dendritic cells and leukocytes. Our laboratory utilized cytokine antibody arrays to elucidate the inflammatory aspects of keratoconus. METHODS: Protein was extracted from 42 corneal buttons (14 keratoconic and 28 non-keratoconic) and incubated with cytokine antibody arrays scanning 120 cytokines. Mann Whitney U test with a p-value of <0.05 was considered significant. RESULTS: Pathways for wound healing, neuroprotection, angiogenesis, and inflammation were activated in keratoconic samples with 23 cytokines showing significant elevation. Fifteen were expressed only in keratoconus with 8 cytokines elevated 1.7-42-fold. CONCLUSION: This study identified elevated inflammatory pathways covering immune responses in keratoconus. Our results support the evidence for inflammatory pathway activation in keratoconus and a possible redefinition of keratoconus as a chronic inflammatory corneal disease.

Extreme Descemet's membrane rupture with hydrops in keratoconus: Clinical and histological manifestations.

PURPOSE: To study the clinical and histological manifestations of an extreme Descemet's membrane rupture as a result of keratoconus. OBSERVATIONS: Using Periodic acid-Schiff assay to study a keratoconic cornea with an extreme rupture showed that the ruptured Descemet's membrane had retracted and folded into scrolls and ridges. The dimensions of the rupture were estimated to be 3.7mm2, and the central cornea was extremely thinned with a thickness of only 260µm. Stromal scarring and loosely packed lamellae were present anterior to the scrolls and ridges. Antibodies targetting the major components of Descemet's membrane, Laminin and type IV collagen, displayed intense labelling adjacent to the scrolls where the stroma was denuded and differential expression patterns lined the ridges. Environmental scanning electron microscopy showed possible collagen deposition at the site of rupture. CONCLUSIONS AND IMPORTANCE: The specific staining patterns of laminin and type IV collagen suggest these components have an important role in re-endothelisation of the cornea. This is the first known report of spatial resolution of the topography of the Descemet's membrane rupture established by environmental scanning electron microscopic image montage.

An Immunohistochemical Study of Inflammatory Cell Changes and Matrix Remodeling With and Without Acute Hydrops in Keratoconus.

PURPOSE: To determine the inflammatory cell and matrix changes in advanced keratoconus, including acute hydrops, using immunohistochemical analysis. METHODS: The corneal tissue from eight subjects with keratoconus undergoing corneal transplantation (three keratoconic buttons, five buttons post acute hydrops­one of them with extensive neovascularization following hydrops) was compared with tissue from two normal corneoscleral rims (n = 10). The corneas were sectioned and analyzed with specific markers for macrophages, lymphocytes, dendritic cells, and scar associated matrix molecules laminin, fibronectin, tenascin-C, and type III collagen. RESULTS: Populations of cells using markers for macrophages, leucocytes and antigen presenting cells were found to be associated with the epithelium and stroma of keratoconic tissue. Populations of these cells appeared decreased in hydrops-associated keratoconus except for a large increase in leucocytes in the stroma and endothelium associated with neovascularization. Extracellular matrix deposition was found to be uniquely demonstrated in localized areas of the stroma, corresponding to the site of hydrops involvement. CONCLUSIONS: Immunohistochemical analysis revealed a chronic, inflammatory process with recruitment of immunoinflammatory cells and deposition of scar tissue in keratoconus. The inflammatory markers were somewhat attenuated in hydrops-associated keratoconus corneas and thus inflammation was not considered to be a major factor in the development of acute corneal hydrops.

A Study Investigating a Possible Link Between Lens Protein in the Vitreous Fluid of Eyes After Uncomplicated Cataract Surgery and Chronic Cystoid Macular Edema.

PURPOSE: This study aimed to determine if the lens protein aquaporin 0 (AQP0) is present in the vitreous of pseudophakic eyes of patients presenting with chronic cystoid macular edema (CME). DESIGN: A case-control study was conducted. METHODS: Ten patients undergoing therapeutic vitrectomy for chronic CME after uncomplicated cataract surgery were enrolled in this study. Fourteen patients with pseudophakia undergoing vitrectomy surgery for indications other than CME acted as the comparison group.The vitreous fluid from the 2 groups was analyzed for the presence of the lens protein AQP0 and type II collagen (used as a positive control). RESULTS: Type II collagen was detected in all the vitreous samples, whereas AQP0 was documented in 50% of eyes with chronic CME but was not found in the vitreous of any eyes without a documented history of CME. CONCLUSIONS: Aquaporin 0 is found in some eyes with chronic CME after uncomplicated cataract surgery, suggesting contamination of the vitreous by lens protein may have a role in the pathogenesis of this disorder.