Investigative Ophthalmology and Visual Science / Mapping of Corneal Layer Thicknesses With Polarization-Sensitive Optical Coherence Tomography Using a Conical Scan Pattern

Purpose: We demonstrate segmentation and mapping of corneal layers (epithelium, Bowman's layer, and stroma) across the entire cornea (limbus to limbus), using additional contrast provided by polarization-sensitive optical coherence tomography (PS-OCT) and analyze the reproducibility of the procedure. Methods: A custom built PS-OCT system operating at 1045 nm central wavelength with conical scanning was used for image acquisition. Conical scanning allows for almost perpendicular beam incidence on the corneal surface and provides good signal quality over the entire field of view. Epithelium, Bowman's layer, and stroma were segmented using the additional contrast provided by PS-OCT. Thickness maps were computed and analyzed in sectors. Both eyes of 20 healthy volunteers were imaged at least three times to test this method and to quantify reproducibility. Results: Thickness maps of the epithelium show significant (P < 0.001) superior thinning and an inferior thickening. Bowman's layer appears homogeneous within the central 7 to 8 mm diameter of the cornea and gets thinner toward the periphery until this layer disappears between 4 and 5.5 mm eccentricity from the center. Intersubject variations of the measured thicknesses of epithelium (coefficient of variation [CV] 8%), Bowman's layer (CV25%), and stroma (CV10%) were observed. Very good reproducibility of thickness measurements of epithelium (CV < 3%), Bowman's layer (CV < 5%), and stroma (CV < 2%) was found. Furthermore, a significant correlation (P < 0.001) between layer thicknesses of the right and left eyes of the same subject was found. Conclusions: PS-OCT with conical scanning is a feasible approach for determining thickness maps of corneal layers on a large field of view with high reproducibility.(VLID)467270

Graefe's Archive for Clinical and Experimental Ophthalmology / Correlation between central stromal demarcation line depth and changes in K values after corneal cross-linking (CXL)

Purpose A stromal demarcation line (DL) after corneal cross-linking (CXL) has lately been suggested as a surrogate parameter for the success of CXL. The aim of this study was to investigate the correlation between depth of the central DL 1 month and the change in K values 12 months after CXL. Methods Treatment-naive subjects with keratoconus were treated using an accelerated CXL protocol [A-CXL(9*10)]. Depth of the DL/relative depth of the DL (DL%) was measured using Visante OCT imaging 1 month postoperatively (OP). Kmax/K2.5 (preOP) and change in Kmax/K2.5 (preOP12 months postOP) were assessed using corneal tomography (Pentacam HR, Oculus GmBH). Results Forty eyes were treated following the A-CXL(9*10). The mean DL depth was 20099 m (range 71 to 479)/mean DL%=42.7020.00% (range 1790). There was no statistically significant correlation between stromal depth of the DL and change in Kmax or K2.5, respectively (Spearman rho DL/Kmax 0.14 and DL/K2.5 0.14). Between DL% and the changes in maximum K values or K2.5, no statistically significant correlation was found as well (Spearman rho DL%/Kmax 0.10 and DL%/K2.5 0.19). Mean change in Kmax after 12 months was 0.682.26 diopters (D) (median 0.35 D) and 0.821.6 D (median 0.65 D) for K2.5 (p=0.07; p=0.02). Conclusions No statistically significant correlation was found between the stromal central depth of the DL and any outcome parameter for CXL after 12 months. Therefore, the interpretation of the DL as a predictive parameter for the effect of the procedure may not apply.(VLID)357508

Ultrahigh‐resolution anterior segment optical coherence tomography for analysis of corneal microarchitecture during wound healing

Purpose: To employ ultrahigh‐resolution (UHR) optical coherence tomography (OCT) for investigation of the early wound healing process in corneal epithelium. Methods: A custom‐built UHR‐OCT system assessed epithelial healing in human keratoconic cornea after epi‐off crosslinking (CXL) procedure and a wound healing model in rabbits with iatrogenic corneal injury. 3D OCT data sets enhanced obtaining epithelial thickness maps and evaluation of reepithelization stage. Accompanying changes in deeper corneal microarchitecture were analysed. Results: The mean central corneal thickness in 40 eyes with keratoconus at baseline was 482.7 ± 38.2 μm, while mean central epithelial thickness (CET) was 43.8 ± 6.4 μm. At the final visit 20 ± 5 days post‐CXL procedure, CET was 35.0 ± 5.8 μm, significantly thinner after reepithelization (p < 0.001). Surgical success was assessed at the final visit through the demarcation line (DL), identified at 43.7 ± 13.5% stromal depth. In rabbits, the mean CET in 20 eyes at baseline was 35.9 ± 2.6 μm. In rabbits that revealed complete wound closure (10/20 eyes) at the last study day at 72 hr, CET was significantly thinner compared to baseline (30.4 ± 2.8 μm versus 35.4 ± 2.9 μm, p = 0.005). An intra‐stromal landmark indicating early keratocyte apoptosis was measured at 30.0 ± 5.1% stromal depth. Epithelial thickness maps showed the time–course of corneal healing. Conclusion: Ultrahigh‐resolution (UHR)‐OCT provided precise assessment of epithelial wound and its healing by 3D‐mapping. In addition, microarchitectural changes in the cornea in early phases of epithelial healing were revealed.Published versionThe financial support by the Christian DopplerResearch Association, the Austrian Federal Ministry of Digital and Economic Affairs and the National Foundation of Research, Technology and Development as well as the Hochschuljubil€aumss-tiftung der Stadt Wien (project H-289408/2013) is gratefully acknowledged. Thea Pharma provided the study drugs for the clinical trial in humans. Croma-Pharma provided test substances evaluated within the rabbit cornea wound healing model. This project was funded by the Christian Doppler laboratory for ‘Ocular and dermal effects of Thiomers’

Ultrahigh-resolution OCT imaging of the human cornea

We present imaging of corneal pathologies using optical coherence tomography (OCT) with high resolution. To this end, an ultrahigh-resolution spectral domain OCT (UHR-OCT) system based on a broad bandwidth Ti:sapphire laser is employed. With a central wavelength of 800 nm, the imaging device allows to acquire OCT data at the central, paracentral and peripheral cornea as well as the limbal region with 1.2 µm x 20 µm (axial x lateral) resolution at a rate of 140 000 A-scans/s. Structures of the anterior segment of the eye, not accessible with commercial OCT systems, are visualized. These include corneal nerves, limbal palisades of Vogt as well as several corneal pathologies. Cases such as keratoconus and Fuchs’s endothelial dystrophy as well as infectious changes caused by diseases like Acanthamoeba keratitis and scarring after herpetic keratitis are presented. We also demonstrate the applicability of our system to visualize epithelial erosion and intracorneal foreign body after corneal trauma as well as chemical burns. Finally, results after Descemet’s membrane endothelial keratoplasty (DMEK) are imaged. These clinical cases show the potential of UHR-OCT to help in clinical decision-making and follow-up. Our results and experience indicate that UHR-OCT of the cornea is a promising technique for the use in clinical practice, but can also help to gain novel insight in the physiology and pathophysiology of the human cornea.Published versio

Eosinophil-platelet interactions promote atherosclerosis and stabilize thrombosis with eosinophil extracellular traps

Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cells and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo, which identifies this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi, we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil-inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.status: publishe