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To compare the relative 12-month corneal crosslinking (CXL) functional outcomes using standard protocol and accelerated protocols in patients with progressive keratoconus.CXL was performed using 3 epithelium-off protocols: standard [3 mW/cm for 30 minutes, 5.4 J/cm (S3/30-CXL)], accelerated with equivalent total irradiance [9 mW/cm for 10 minutes, 5.4 J/cm (A9/10-CXL)], and accelerated with increased total irradiance [30 mW/cm for 4 minutes, 7.2 J/cm (A30/4-CXL)]. Efficacy measurements were evaluated 12 months after treatment with Scheimpflug imaging (Pentacam HR) and included change in maximum keratometry (K Max), corrected distance visual acuity (CDVA), other keratometric variables, pachymetry, keratoconus indices, astigmatism, asphericity, manifest refraction, and higher order aberrations.Ninety-three eyes (67 patients) were evaluated: 35 eyes (26 patients) with S3/30-CXL, 29 eyes (19 patients) with A9/10-CXL, and 29 eyes (22 patients) with A30/4-CXL. Mean [INCREMENT]K Max was -1.53 ± 2.1 diopter (D) for S3/30-CXL, -0.71 ± 1.3 D for A9/10-CXL, and -0.70 ± 2.3 D for A30/4-CXL (P = 0.37). Mean [INCREMENT]CDVA(logMAR) was -0.18 ± 0.2 for S3/30-CXL, -0.13 ± 0.2 for A9/10-CXL, and -0.18 ± 0.2 for A30/4-CXL (P = 0.79). [INCREMENT]K Mean (r = -0.29 to -0.46), anterior asphericity (r = -0.34 to -0.40), and central keratoconus index (r = -0.18 to -0.38) best correlated with [INCREMENT]CDVA. S3/30-CXL had greater changes in index of surface variance, index of vertical asymmetry, keratoconus index, and regularization index compared to A9/10-CXL and A30/4-CXL. There were no other differences between protocols.All 3 protocols showed improvements in K Max, CDVA, and other variables, with similar functional outcomes for each despite greater change in keratoconus indices after S3/30-CXL. Correlations between change in measured variables and CDVA were poor overall; however, K Mean, central keratoconus index, and anterior asphericity were better correlated with CDVA than K Max.

Brillouin microscopy has been applied successfully to in-vivo corneal imaging to understand stiffness variation along different phases of keratoconus. However, the in-vivo spatial resolution is restricted due to a conflict between a slow Brillouin acquisition rate of hundreds of milliseconds and human movement during acquisition. In this research, frequency domain optical coherence tomography and image tracking are proved to be effective methods to locate points measured by Brillouin microscopy in axial and radial directions, respectively. Results show that OCT has an accuracy of better than 2 μm while image tracking has an accuracy better than 3 μm.

Purpose The purpose of this study was to detect the mechanical anisotropy of the cornea using Brillouin microscopy along different perturbation directions. Methods Brillouin frequency shift of both whole globes (n = 10) and cornea punches (n = 10) were measured at different angles to the incident laser, thereby probing corneal longitudinal modulus of elasticity along different directions. Frequency shift of virgin (n = 26) versus cross-linked corneas (n = 15) over a large range of hydration conditions were compared in order to differentiate the contributions to Brillouin shift due to hydration from those due to stromal tissue. Results We detected mechanical anisotropy of corneas, with an average frequency shift increase of 53 MHz and 96 MHz when the instrument probed from 0° to 15° and 30° along the direction of the stromal fibers. Brillouin microscopy did not lose sensitivity to mechanical anisotropy up to 96% water content. We experimentally measured and theoretically modeled how mechanical changes independent of hydration affect frequency shift as a result of corneal cross-linking by isolating an approximately 100 MHz increase in frequency shift following a cross-linking procedure purely due to changes of stromal tissue mechanics. Conclusions Brillouin microscopy is sensitive to mechanical anisotropy of the stroma even in highly hydrated corneas. The agreement between model and experimental data suggested a quantitative relationship between Brillouin frequency shift, hydration state of the cornea, and stromal tissue stiffness. Translational relevance The protocol and model validated throughout this study offer a path for comprehensive measurements of corneal mechanics within the clinic; allowing for improved evaluation of the long-term mechanical efficacy of cross-linking procedures.