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Intrinsic optical signals constitute a noninvasive biomarker promising the objective assessment of retinal photoreceptor function. We employed a commercial optical coherence tomography (OCT) system and an OCT signal model for evaluation of optical path length (OPL) changes in the temporal outer retina of five healthy subjects during light adaptation. Data were acquired at 30 time points, in ambient light and during long duration stimulation with white light, and analyzed, employing a signal model based on the sum of seven Gaussian curves corresponding to all relevant anatomical structures of the outer retina. During light stimulation, mean OPL between rod outer segment tips (ROST) and the retinal pigment epithelium (RPE) decreased by 21.4 ± 3.5%. Further, OPL between the external-limiting membrane (ELM) and the RPE decreased by 5.2 ± 0.9% versus baseline, while OPL between ELM and ROST showed an initial decrease by 2.1 ± 1.6% versus baseline and, thereafter, increased by 2.8 ± 2.1% versus baseline. Thus, the presented approach allowed for assess to dynamic changes in the outer retina in response to light. The change in the subretinal space occurring in the context of light adaptation could be measured using a standard OCT platform and a dedicated signal model. Published version The research has been funded by the Vienna Science and Technology Fund (WWTF) through project LS14-067.

Purpose: To determine the association between tear film thickness (TFT) as measured with ultra-high resolution optical coherence tomography (UHR-OCT) and signs and symptoms of dry eye disease (DED). Methods: A total of 450 eyes from 225 patients with DED from six different randomized clinical trials were included in this pooled analysis. In all subjects, TFT was measured with a custom-built UHR-OCT system. Symptoms of DED were quantified using a standardized Ocular Surface Disease Index (OSD)I questionnaire and clinical signs including tear film break up time (TFBUT) and Schirmer I test were assessed. Associations of the average TFT with OSDI, TFBUT, and Schirmer I test were calculated using a linear regression analysis. Results: The average TFT of the included sample (mean age, 45.0 &plusmn, 13.3 years, 65% female) was 4.2 &plusmn, 0.5 &micro, m and the OSDI 36.2 &plusmn, 10.4. A significant negative correlation was found between TFT and OSDI (r = &minus, 0.36 to &minus, 0.31, p &lt, 0.001). Tear break up time and Schirmer I test were not correlated with OSDI. Significant albeit weak correlations were found between TFT and TFBUT (r = 0.17 to 0.25, 0.01) as well as Schirmer I (r = 0.36 to 0.37, 0.001). Subgroup analysis revealed that the correlation was stronger in the subjects with abnormal Schirmer I (&lt, 15 mm, r = 0.50 to 0.54, 0.001). Conclusions: The present study demonstrates an objective measurement of TFT using a novel OCT approach for DED that correlates with symptoms and signs of DED. Our data are consistent with the idea that TFT represents the aqueous-deficient component of DED.

ZusammenfassungDie optische Kohärenztomografie (OCT) hat seit ihrer Einführung für die retinale Bildgebung in den 90er-Jahren eine rasante Entwicklung genommen und die Ophthalmologie revolutioniert. Während sie zu Beginn nur zur Untersuchung der Retina zum Einsatz kam, wurden in der Zwischenzeit auch zahlreiche Systeme zur Beurteilung des vorderen Augenabschnitts entwickelt. Basierend auf der Detektion und Verarbeitung des vom Gewebe zurückreflektierten und gestreuten Lichts, eröffnete sie dem Ophthalmologen völlig neue Möglichkeiten zur Untersuchung der Strukturen des vorderen Augenabschnitts. Je nach technischer Umsetzung erlauben OCT-Systeme für den vorderen Augenabschnitt die präzise Vermessung einzelner Schichten der Kornea und des Kammerwinkels oder – in Form von ultrahoch auflösender OCT – die detailreiche Darstellung der Hornhautmorphologie mit nahezu histologischer Auflösung. Letztere könnte durch weitere technische Entwicklungen vor allem hinsichtlich der Erhöhung der Aufnahmegeschwindigkeit zu einem wesentlichen Werkzeug in der Differenzialdiagnose und Verlaufsbeobachtung verschiedenster Erkrankungen der Hornhaut werden, das auch neue Einsichten in die Pathophysiologie dieser Erkrankungen liefert.

Purpose: The aim of this mechanistic clinical study was to explore the effect of water-free perfluorohexyloctane eye drops on tear film thickness (TFT) in patients with dry eye disease (DED). Metho...

The tear meniscus contains most of the tear fluid and therefore is a good indicator for the state of the tear film. Previously, we used a custom-built optical coherence tomography (OCT) system to study the lower tear meniscus by automatically segmenting the image data with a thresholding-based segmentation algorithm (TBSA). In this report, we investigate whether the results of this image segmentation algorithm are suitable to train a neural network in order to obtain similar or better segmentation results with shorter processing times. Considering the class imbalance problem, we compare two approaches, one directly segmenting the tear meniscus (DSA), the other first localizing the region of interest and then segmenting within the higher resolution image section (LSA). A total of 6658 images labeled by the TBSA were used to train deep convolutional neural networks with supervised learning. Five-fold cross-validation reveals a sensitivity of 96.36% and 96.43%, a specificity of 99.98% and 99.86% and a Jaccard index of 93.24% and 93.16% for the DSA and LSA, respectively. Average segmentation times are up to 228 times faster than the TBSA. Additionally, we report the behavior of the DSA and LSA in cases challenging for the TBSA and further test the applicability to measurements acquired with a commercially available OCT system. The application of deep learning for the segmentation of the tear meniscus provides a powerful tool for the assessment of the tear film, supporting studies for the investigation of the pathophysiology of dry eye-related diseases.

Purpose To compare the effect of a single drop of different lubricant eye gels on tear film thickness (TFT) as measured with ultrahigh-resolution optical coherence tomography (UHR-OCT) in patients with mild-to-moderate dry eye disease (DED). Methods The study followed a randomized, single-masked, observer-blinded parallel group design. Patients received a single dose of either unpreserved trehalose 3% + hyaluronic acid 0.15% (TH), hyaluronic acid 0.2% (HA) or polyethylene glycol 0.4% + propylene glycol 0.3% (PP) eye drops. In total, 60 patients were included and TFT was measured using a custom-built UHR-OCT system. Results The mean TFT at baseline was 3.5 ± 0.7 μm. There was a significant difference in the time–course of TFT between the three groups (p = 0.001 between groups). Ten minutes after instillation, TFT increased by 155.8 ± 86.6%, 65.7 ± 71.5% and 33.4 ± 19.6% in the PP, TH and HA group, respectively (p

Photoreceptor function is impaired in many retinal diseases like age-related macular degeneration. Currently, assessment of the photoreceptor function for the early diagnosis and monitoring of these diseases is either subjective, as in visual field testing, requires contact with the eye, like in electroretinography, or relies on research prototypes with acquisition speeds unattained by conventional imaging systems. We developed an objective, noncontact method to monitor photoreceptor function using a standard optical coherence tomography system. This method can be used with various white light sources for stimulation. The technique was applied in five volunteers and detected a decrease of volume of the subretinal space associated with light adaptation processes of the retina.

We present a system for automatic determination of the intradermal volume of hydrogels based on optical coherence tomography (OCT) and deep learning. Volumetric image data was acquired using a custom-built OCT prototype that employs an akinetic swept laser at ~1310 nm with a bandwidth of 87 nm, providing an axial resolution of ~6.5 μm in tissue. Three-dimensional data sets of a 10×10 mm skin patch comprising the intradermal filler and the surrounding tissue were acquired. A convolutional neural network using a u-net-like architecture was trained from slices of 100 OCT volume data sets where the dermal filler volume was manually annotated. Using six-fold cross-validation, a mean accuracy of 0.9938 and a Jaccard similarity coefficient of 0.879 were achieved. Published version

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 version The 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’.

Since its introduction for retinal imaging in the early 1990s, optical coherence tomography (OCT) has undergone rapid development and has revolutionised ophthalmology. Although OCT was initially used mainly for the examination of the retina, numerous systems for the assessment of the anterior segment of the eye have now been developed. OCT is based on the detection and processing of the light back-scattered and back-reflected by the tissue, and provides completely new possibilities for the ophthalmologist to examine the structures of the anterior eye segment. Depending on the technical implementation, OCT systems for the anterior eye allow precise measurement of individual layers of the cornea and the chamber angle or - in the form of ultrahigh resolution OCT - the detailed visualisation of corneal morphology with near histological resolution. Through further technical developments, especially with respect to an increase in acquisition speeds, OCT has become an essential tool in the differential diagnosis and follow-up of various diseases of the cornea and might also provide new insights into their pathophysiology.Die optische Kohärenztomografie (OCT) hat seit ihrer Einführung für die retinale Bildgebung in den 90er-Jahren eine rasante Entwicklung genommen und die Ophthalmologie revolutioniert. Während sie zu Beginn nur zur Untersuchung der Retina zum Einsatz kam, wurden in der Zwischenzeit auch zahlreiche Systeme zur Beurteilung des vorderen Augenabschnitts entwickelt. Basierend auf der Detektion und Verarbeitung des vom Gewebe zurückreflektierten und gestreuten Lichts, eröffnete sie dem Ophthalmologen völlig neue Möglichkeiten zur Untersuchung der Strukturen des vorderen Augenabschnitts. Je nach technischer Umsetzung erlauben OCT-Systeme für den vorderen Augenabschnitt die präzise Vermessung einzelner Schichten der Kornea und des Kammerwinkels oder – in Form von ultrahoch auflösender OCT – die detailreiche Darstellung der Hornhautmorphologie mit nahezu histologischer Auflösung. Letztere könnte durch weitere technische Entwicklungen vor allem hinsichtlich der Erhöhung der Aufnahmegeschwindigkeit zu einem wesentlichen Werkzeug in der Differenzialdiagnose und Verlaufsbeobachtung verschiedenster Erkrankungen der Hornhaut werden, das auch neue Einsichten in die Pathophysiologie dieser Erkrankungen liefert.

Purpose: This study investigated the effect of single administration of 2 different hyaluronic acid-based topical lubricants on tear film thickness (TFT) in patients with moderate-to-severe dry eye disease (DED). Methods: Sixty patients were randomized to receive eye drops containing unpreserved sodium hyaluronate, triglycerides, and phospholipids (HTP), unpreserved sodium hyaluronate (HA), or unpreserved sodium chloride (NaCl). TFT and lipid layer thickness (LLT) were assessed before and at defined time points after single instillation with a custom-built ultrahigh-resolution optical coherence tomography system and a white light interferometer. Standard tests for DED such as a visual analogue scale (VAS), corneal fluorescein staining (CFS), Schirmer I test, and tear break-up time (BUT) were performed. Results: The time course in TFT was significantly different between the 3 administered agents (P

PURPOSE This study was designed to investigate the effect of a single-drop instillation of different lacrimal substitutes on tear film thickness (TFT) assessed with optical coherence tomography in patients with mild to moderate dry eye disease. METHODS The study was performed in a randomized, double-masked, controlled parallel group design. Patients received a single dose of either unpreserved trehalose 30 mg/mL and sodium hyaluronate 1.5 mg/mL (TH-SH, Thealoz Duo), unpreserved sodium hyaluronate, 0.15% (HA, Hyabak) or sodium chloride, 0.9% (NaCl, Hydrabak) eye drops. Sixty patients finished the study according to the protocol. TFT was measured with a custom-built ultrahigh-resolution Fourier domain optical coherence tomography system providing a resolution of 1.2 μm. RESULTS The mean TFT before treatment was 2.5 ± 0.4 μm. Ten minutes after instillation, TFT significantly increased in the TH-SH group from 2.4 ± 0.4 to 3.1 ± 0.9 μm (P < 0.01) and in the HA group from 2.4 ± 0.3 to 2.9 ± 0.5 μm (P < 0.01), whereas no significant change was observed in the NaCl group (from 2.6 ± 0.4 to 2.7 ± 0.4 μm, P = 0.76). The increase in TFT remained statistically significant up to 240 minutes after administration of TH-SH. In contrast, the increase in TFT after administration of HA was only statistically significant at 10, 20, and 40 minutes after drop instillation. CONCLUSIONS The findings of this study indicate that single instillation of TH-SH and HA eye drops increases TFT in patients with dry eye disease. The data also indicate longer corneal residence of the TH-containing eye drops. The effect of multiple instillation and long-term use of artificial tears on TFT warrants further investigation.

Purpose The aim of this study was to assess the effect of a single drop of hyaluronic acid on tear film thickness (TFT) in healthy subjects. Methods Sixteen healthy subjects (eight male/eight female) aged between 20 and 36 years were included in this randomized, double-masked placebo-controlled study. One eye received a single dose of hyaluronic acid (Olixia pure®; Croma Pharma, Korneuburg, Austria) eye drops, and the fellow eye received physiologic saline solution as placebo control. The study eye was chosen randomly. TFT as measured with a custom-built Fourier-domain optical coherence tomography (FD-OCT) system was the main outcome variable and measured before and every 10 min until 1 hr after topical administration. Results Baseline TFT was 4.8 ± 0.5 μm in the study eye and 5.0 ± 0.4 μm in the control eyes. Hyaluronic acid significantly increased TFT (p = 0.008 versus placebo) with a maximum effect 10 min after instillation (13.9 ± 11.9%). Post hoc analysis revealed that an increase in TFT was seen until 30 min after administration compared to placebo. Data in the placebo group show high reproducibility with an intraclass correlation coefficient of 0.93 and a coefficient of variation of 5.4 ± 3.3%. Conclusion The data of this study indicate that hyaluronic acid increases TFT for as long as 30 min in healthy subjects. In addition, our data provide evidence that our custom-built OCT system is capable of measuring residence time of lubricants on the ocular surface.

Optical coherence tomography (OCT) provides non-contact, rapid in vivo imaging of ocular structures, and has become a key part of evaluating the anterior segment of the eye. Over the years, improvements to technology have increased the speed of capture and resolution of images, leading to the increasing impact of anterior segment OCT imaging on clinical practice. In this review, we summarize the historical development of anterior segment OCT, and provide an update on the research and clinical applications of imaging the ocular surface, cornea, anterior chamber structures, aqueous outflow system, and most recently anterior segment vessels. We also describe advancements in anterior segment OCT technology that have improved understanding with greater detail, such as tear film in dry eye disease evaluation, intra-operative real-time imaging for anterior segment surgery, and aqueous outflow with angle assessment for glaucoma. Improvements to image processing and software have also improved the ease and utility of interpreting anterior segment OCT images in everyday clinical practice. Future developments include refinement of assessing vascular networks for the anterior segment, in vivo ultra-high resolution anterior segment optical coherence tomography with histology-like detail, en-face image with 3-dimensional reconstruction as well as functional extensions of the technique.

OCT imaging in the super-resolution regime was investigated using simulations and experiments. Samples of known thickness in the range 46-163 nm were fabricated and imaged. Measurements of the tear film lipid layer were performed.

A custom-built ultrahigh-resolution optical coherence tomography (UHR-OCT) system and fluorescein staining were employed for investigation of a scopolamine induced dry eye mouse model. Acquired data was used to evaluate common and complementary findings of the two modalities. Central corneal thickness as measured by UHR-OCT increased significantly over the study period of 24 hours, from 89.0 ± 3.57 µm to 92.2 ± 4.07 µm. Both techniques were able to show corneal lesions with a large range of severity. Localized fluorescein staining was detected in 5% and diffuse staining in 45% of cases where no epithelial damage was visible with OCT. However, OCT revealed stromal defects in 6% and endothelial defects in 18% of the cases, which could not be visualized via fluorescein staining. Thus, while fluorescein staining widely detected defects of the corneal surface in a mouse model of dry eye disease, OCT non-invasively revealed additional information about defect depth and involvement of particular layers.

Purpose To estimate the relationship between the characteristics of the corneal pulse (CP) signal and those of the fundus pulse (FP) signal measured with a combined noncontact ultrasonic and laser interferometry technique in healthy subjects. Methods Twenty-two healthy subjects participated in experiments that included measurements of intraocular pressure, ocular pulse amplitude, ocular biometry, blood pressure, and heart rate. Additionally, simultaneous recordings of CP and FP signals were acquired with a noncontact ultrasonic device combined with laser interferometry. Subsequently, ocular perfusion pressure (OPP) and the time and spectral parameters of CP and FP signals were computed. A system model was proposed to relate the FP signal to the CP signal. Results The system model revealed that the eye globe transfers information between signals of the posterior and anterior eye, relatively amplifying higher spectral harmonics. The amplitude of the second CP harmonic is predicted by FPRMS and OPP (R2 = 0.468, P = 0.002). Partial correlation analysis showed that the CP signal parameters are statistically significantly correlated with those of the FP signal and OPP, after correcting for age and sex. Conclusions The eye globe can be viewed as a high pass filter, in which the CP characteristic changes in relation to the fundus pulsation. The FP signal and OPP have an impact on the variations of the CP signal morphology. Translational Relevance Investigation of differences between the characteristics of the anterior and posterior tissue movements is a promising method for evaluating the role of circulatory and biomechanical components in the pathophysiology of ocular diseases.

Many different parameters exist for the investigation of tear film dynamics. We present a new tear meniscus segmentation algorithm which automatically extracts tear meniscus area (TMA), height (TMH), depth (TMD) and radius (TMR) from UHR-OCT measurements and apply it to a data set including repeated measurements from ten healthy subjects. Mean values and standard deviations are 0.0174 ± 0.007 mm2, 0.272 ± 0.069 mm, 0.191 ± 0.049 mm and 0.309 ± 0.123 mm for TMA, TMH, TMD and TMR, respectively. A significant correlation was found between all respective tear meniscus parameter pairs (all p < 0.001, all Pearson’s r ≥ 0.657). Challenges, limitations and potential improvements related to the data acquisition and the algorithm itself are discussed. The automatic segmentation of tear meniscus measurements acquired with UHR-OCT might help in a clinical setting to further understand the tear film and related medical conditions like dry eye disease. Published version

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 version

Deep learning has dramatically improved object recognition, speech recognition, medical image analysis and many other fields. Optical coherence tomography (OCT) has become a standard of care imaging modality for ophthalmology. We asked whether deep learning could be used to segment cornea OCT images. Using a custom-built ultrahigh-resolution OCT system, we scanned 72 healthy eyes and 70 keratoconic eyes. In total, 20,160 images were labeled and used for the training in a supervised learning approach. A custom neural network architecture called CorneaNet was designed and trained. Our results show that CorneaNet is able to segment both healthy and keratoconus images with high accuracy (validation accuracy: 99.56%). Thickness maps of the three main corneal layers (epithelium, Bowman’s layer and stroma) were generated both in healthy subjects and subjects suffering from keratoconus. CorneaNet is more than 50 times faster than our previous algorithm. Our results show that deep learning algorithm scan be used for OCT image segmentation and could be applied in various clinical settings. In particular, CorneaNet could be used for early detection of keratoconus and more generally to study other diseases altering corneal morphology. Published version

Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new noninvasive approach to measure tear film thickness using an efficient delay estimator and ultrahigh resolution spectral domain OCT. Silicon wafer phantoms with layers of known thickness and group index were used to validate the estimator-based thickness measurement. A theoretical analysis of the fundamental limit of the precision of the estimator is presented and the analytical expression of the Cramer-Rao lower bound (CRLB), which is the minimum variance that may be achieved by any unbiased estimator, is derived. The performance of the estimator against noise was investigated using simulations. We found that the proposed estimator reaches the CRLB associated with the OCT amplitude signal. The technique was applied in vivo in healthy subjects and dry eye patients. Series of tear film thickness maps were generated, allowing for the visualization of tear film dynamics. Our results show that the central tear film thickness precisely measured in vivo with a coefficient of variation of about 0.65% and that repeatable tear film dynamics can be observed. The presented method has the potential of being an alternative to breakup time measurements (BUT) and could be used in clinical setting to study patients with dry eye disease and monitor their treatments.

Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new non-invasive fully automated approach to measure tear film thickness based on spectral domain optical coherence tomography and on an efficient delay estimator. Silicon wafer phantom were used to validate the thickness measurement. The technique was applied in vivo in healthy subjects. Series of tear film thickness maps were generated, allowing for the visualization of tear film dynamics. Our results show that the in vivo central tear film thickness measurements are precise and repeatable with a coefficient of variation of about 0.65% and that repeatable tear film dynamics can be observed. The presented approach could be used in clinical setting to study patients with dry eye disease and monitor their treatments.

Purpose We assess the increase in total retinal blood flow (TRBF) induced by flicker stimulation of the human retina in vivo and investigate the flicker induced hyperemia by means of a vascular flow model of the retinal circulation to study neurovascular coupling (NC). Methods In six healthy subjects, TRBF was measured before and during stimulation with diffuse luminance flicker. Blood flow velocities in retinal vessels were measured via dual-beam bidirectional Doppler Fourier-domain optical coherence tomography (FD-OCT), retinal vessel diameters were assessed based on FD-OCT phase data. This allowed for the calculation of TRBF before and during visual stimulation. Additionally, a mathematical flow model for the retinal vasculature was adapted to study the implications of diameter variations on retinal perfusion. Measured and simulated perfusion was compared to draw conclusions on the diameter variations in different layers of the vascular tree. Results The measured mean baseline flow was 36.4 ± 6.5 μl/min while the mean flow during flicker stimulation was 53.4% ± 8.3 μl/min. The individual increase in TRBF during flicker stimulation ranged between 34% and 66%. The average increase in TRBF over all measured subjects was 47.6% ± 12.6%. Conclusions Dual-beam bidirectional Doppler FD-OCT allowed quantifying NC in the human retina in vivo and may be a promising method for monitoring alterations in NC caused by various pathologies. The comparison of the measured data with the results obtained in the simulated vasculature indicates that the vasodilation induced by NC is more pronounced in smaller vessels.

Importance Corneal abrasions are frequent after standard (epithelium-off [epi-off]) corneal collagen cross-linking (CXL) in patients with progressive keratoconus. A new matrix therapy agent (ReGeneraTing Agent [RGTA]) has been developed to promote corneal wound healing. Objective To assess the effect of the new type of matrix therapy agent on corneal wound healing after epi-off CXL in patients with keratoconus. Design, Setting, and Participants This double-masked randomized clinical trial enrolled 40 patients with keratoconus undergoing epi-off CXL from July 18, 2014, to October 21, 2015, when the last follow-up was completed. The analysis of the intention-to-treat population was performed at the Department of Clinical Pharmacology in cooperation with the Center for Medical Physics and Biomedical Engineering and the Department of Ophthalmology and Optometry of the Medical University of Vienna. Interventions Patients were randomized to receive the matrix therapy agent or hyaluronic acid–containing eyedrops, 0.1%, every other day starting immediately after surgery. The size of the corneal defect was measured using ultrahigh-resolution optical coherence tomography (OCT) and slitlamp photography (SLP) with fluorescein staining. Main Outcomes and Measures Corneal wound healing rate, defined as the size of the defect over time. Results Among the 40 patients undergoing epi-off CXL (31 men; 9 women; mean [SD] age, 31 [10] years), wound healing was significantly faster in the matrix therapy agent group compared with the hyaluronic acid group (4.4 vs 6.1 days; mean difference, 1.7 days; 95% CI, 0.25-3.15 days; P = .008). The defect size was smaller in the matrix therapy agent group than in the hyaluronic acid group as measured with OCT (12.4 vs 23.9 mm 2 ; mean difference, 11.6 mm 2 ; 95% CI, 0.8-23.5 mm 2 ; P = .045) and SLP (11.9 vs 23.5 mm 2 ; mean difference, 11. 6 mm 2 ; 95% CI, 1.3-22.9 mm 2 ; P = .03). A correlation between the defect size measured with OCT and SLP was found ( r = 0.89; P Conclusions and Relevance Use of a new matrix therapy agent appears to improve corneal wound healing after CXL in patients with keratoconus. Monitoring of corneal wound healing using ultrahigh-resolution OCT might be an attractive alternative to SLP because OCT provides an objective and 3-dimensional evaluation of the corneal defect. Trial Registration clinicaltrials.gov Identifier:NCT02119039