Structural And Cellular Characterization Of Post-Cxl Extreme-Flattened Corneas: Evidence Of Keratocyte Depletion
Published 2026 - 44th Congress of the ESCRS
Reference: FP02.11 | Type: Free paper | DOI: 10.82333/p2yz-jm48
Authors: Dr Erika Bonacci* 1 , A/Prof. Riccardo Vinciguerra 2 , Dr Arianna Serraiotto 3 , A/Prof. Paolo Vinciguerra 4 , A/Prof. Emilio Pedrotti 3
1Department of Engineering for Innovation Medicine,University of Verona,Verona,Italy, 2Department of Biomedical Sciences,Humanitas University, 20090 Milan, Italy.,Italy;Humanitas San Pio X Hospital,Milan, Italy ,Italy, 3Department of Surgery, Dentistry, Maternity and Infant,University of Verona,Verona,Italy, 4Department of Biomedical Sciences,Humanitas University,Milan, Italy ,Italy;Department of Ophthalmology,IRCCS Humanitas Research Hospital,Milan, Italy ,Italy
Purpose
To characterize structural, cellular, and biomechanical features of corneas exhibiting progressive extreme flattening after corneal collagen cross-linking (CXL) and to compare them with CXL-treated corneas without progressive flattening.
Setting
Multicenter matched case–control study.
University of Verona, Verona, Italy
Humanitas University, Milan, Italy
Methods
We enrolled patients who developed progressive extreme corneal flattening between 2023 and 2025 after CXL. Patients were divided into two groups: 1) the first group included patients with documented super post-operative corneal flattening (≥5.00 D reduction in K values based on corneal tomography); 2) the second group involved patients with <5.00 D flattening. All patients underwent IVCM (HRT-II Rostock Corneal Module) of the entire cornea, from epithelium to endothelium. Epithelium, sub basal nerve plexus, and endothelium were qualitatively evaluated. Keratocyte density was quantified by two masked observers using semi-automated cell-counting software. Corneal biomechanics parameters were evaluated.
Results
Hyperflattened corneas showed significantly reduced anterior (107.1 ± 141.4 vs 260.7 ± 133.2 cells/mm²; p = 0.02) and mid-stromal KD (189.1 ± 86.6 vs 278.4 ± 89.2 cells/mm²; p = 0.04), with no difference posteriorly. Thinnest corneal thickness was lower in hyperflattened eyes (430.3 ± 70.7 vs 478.3 ± 30.8 µm; p = 0.040). Within the hyperflattened group, flattening magnitude correlated inversely with anterior KD (ρ = −0.73, p = 0.001), thinnest corneal thickness (ρ = −0.65, p = 0.012), and stress–strain index (ρ = −0.62, p = 0.024). Anterior KD strongly correlated with corneal thickness (ρ = 0.82, p = 0.0003). Preoperative thickness was not associated with flattening magnitude or long-term KD.
Conclusions
Progressive extreme flattening after CXL is associated with anterior stromal keratocyte depletion, stromal thinning, and altered biomechanical behavior. These findings suggest that hyperflattening represents a distinct maladaptive remodeling phenotype rather than enhanced cross-linking efficacy, underscoring the potential role of cellular biomarkers in post-CXL risk stratification.