Peripheral hypertrophic subepithelial corneal degeneration - clinical and histopathological features

To refine the diagnostic criteria for peripheral hypertrophic subepithelial corneal degeneration (PHSD) and characterize its clinical phenotype, histopathology and immunohistochemical features.

Diagnostic criteria were refined on the basis of literature data. Fourteen patients (13 women and one man; median age 52 years, range 33-66) were identified based on these criteria. Keratectomy specimens were evaluated via routine and immunohistochemical stainings. The main outcome measures were symptoms, clinical phenotype, immunological status and histopathologic results.

We defined the diagnostic criteria of typical PHSD as elevated circumferential and perilimbal subepithelial fibrosis with focal superficial corneal neovascularization, which were supported by female sex (93%), bilaterality (86%), the centre being in the upper quadrants (81%) and irregular astigmatism of two dioptres or more. The typical symptoms were reduced vision (86%) and the symptoms of ocular surface disease (64%). Light microscopy showed fibrosis with abundant collagen deposition but no inflammation in all patients. An immunohistochemical analysis of nine patients showed uniform staining for vimentin in three distinct types of fibroblasts in variable proportions: keratocyte-like cells that were positive for CD34, myofibroblasts that were positive for smooth muscle actin (SMA) and fibroblasts that were negative for CD34 and SMA. Small numbers of CD68-positive macrophages were also found.

Peripheral hypertrophic subepithelial degeneration is characteristic of middle-aged women, in whom it is typically a bilateral idiopathic degeneration of the cornea associated with ocular surface disease and reduced vision. The fibrotic lesions probably undergo remodelling, inducing changes in corneal contour. A smouldering low-grade inflammation favouring low TGF-β1 concentrations is postulated as the primary pathological process leading to PHSD.