Morphological characteristics of acquired corneal sub-epithelium hypertrophy: a case series

Acquired Corneal Subepithelial Hypertrophy (ACSH) is a rare corneal opacity secondary to ocular surgery or trauma. It is characterized by subepithelial fibrosis, a marked male predominance, and a high risk of misdiagnosis due to non-specific slit-lamp findings. This study aimed to characterize the in vivo morphological features of ACSH using anterior segment optical coherence tomography (AS-OCT) and clarify its histopathological composition.

This retrospective single-center case series enrolled 11 patients (12 eyes) with ACSH who underwent surgical intervention at our institution between 2018 and 2022. AS-OCT imaging was performed to evaluate subepithelial fibrosis features. All specimens underwent histopathological evaluation with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson trichrome staining. Immunofluorescence analysis was conducted on five specimens to assess cytokeratins (CK3, CK14), nucleoprotein (P40-ΔNp63), cytoskeletal proteins (alpha-smooth muscle actin, vimentin), and extracellular matrix components (Collagen I, Collagen IV). Primary outcomes included AS-OCT morphological characteristics from baseline to final follow-up and corresponding histopathological findings.

Most patients were male, and the primary presenting symptom was blurred vision. Superficial keratectomy restored corneal clarity without recurrence during follow-up. ACSH was categorized into three subtypes: paracentral patchy opacification (PPO, 41.7%), peripheral sectorial nodules (PSN, 41.7%), and central diffuse mass (CDM, 16.7%). AS-OCT revealed hyperreflective lamellar deposits between the epithelium and stroma. The maximum thickness of fibrosis was strongly correlated with corneal surface thickness (r = 0.96; p < 0.0001). Histopathological findings suggested that corneal injury from surgery or trauma may drive subepithelial fibrosis via abnormal tissue repair and disorganized extracellular matrix deposition.

AS-OCT enables reliable identification of ACSH and differentiation from corneal leucoma and haze. Histopathological observations provide insights into potential pathogenic mechanisms. These findings may inform clinical strategies to prevent ACSH, such as using topical medications or contact lenses to enhance epithelial healing after anterior segment surgery or injury.