Introduction of quantitative and qualitative cornea optical coherence tomography findings induced by collagen cross-linking for keratoconus: a novel effect measurement benchmark

A John Kanellopoulos1,2 George Asimellis11Laservision.gr Institute, Athens, Greece; 2New York University Medical School, New York, NY, USAPurpose: To introduce a novel, noninvasive technique to determine the depth and extent of anterior corneal stroma changes induced by collagen cross-linking (CXL) using quantitative analysis of high-resolution anterior-segment optical coherence tomography (OCT) post-operative images.Setting: Private clinical ophthalmology practice.Patients and methods: Two groups of corneal cross-sectional images obtained with the OptoVue RTVue anterior-segment OCT system were studied: group A (control) consisted of unoperated, healthy corneas, with the exception of possible refractive errors. The second group consisted of keratoconic corneas with CXL that were previously operated on. The two groups were investigated for possible quantitative evidence of changes induced by the CXL, and specifically, the depth, horizontal extent, as well as the cross-sectional area of intrastromal hyper-reflective areas (defined in our study as the area consisting of pixels with luminosity greater than the mean +2 × standard deviation of the entire stromal cross section) within the corneal stroma.Results: In all images of the second group (keratoconus patients treated with CXL) there was evidence of intrastromal hyper-reflective areas. The hyper-reflective areas ranged from 0.2% to 8.8% of the cross-sectional area (mean ± standard deviation; 3.46% ± 1.92%). The extent of the horizontal hyper-reflective area ranged from 4.42% to 99.2% (56.2% ± 23.35%) of the cornea image, while the axial extent (the vertical extent in the image) ranged from 40.00% to 86.67% (70.98% ± 7.85%). There was significant statistical difference (P < 0.02) in these values compared to the control group, in which, by application of the same criteria, the same hyper-reflective area (owing to signal noise) ranged from 0.00% to 2.51% (0.74% ± 0.63%).Conclusion: Herein, we introduce a novel, noninvasive, quantitative technique utilizing anterior segment OCT images to quantitatively assess the depth and cross-sectional area of CXL in the corneal stroma based on digital image analysis. Mean cross-sectional area showing evidence of CXL was 3.46% ± 1.92% of a 6 mm long segment.Keywords: Collagen cross-linking, keratoconus, optical coherence tomography, higher fluence cross-linking, cornea ectasia, Athens Protoco