Valentin Aranha dos Santos

Effect of hyaluronic acid on tear film thickness as assessed with ultra‐high resolution optical coherence tomography

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.

In vivo tear film thickness measurement and tear film dynamics visualization using spectral domain optical coherence tomography.

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.

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 Fuchss 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 Descemets 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.

Effect of a Matrix Therapy Agent on Corneal Epithelial Healing After Standard Collagen Cross-linking in Patients With Keratoconus: A Randomized Clinical Trial

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 mm2; mean difference, 11.6 mm2; 95% CI, 0.8-23.5 mm2; P = .045) and SLP (11.9 vs 23.5 mm2; mean difference, 11. 6 mm2; 95% CI, 1.3-22.9 mm2; P = .03). A correlation between the defect size measured with OCT and SLP was found (r = 0.89; P < .001). No ocular or serious adverse events occurred. 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.

Effect of different lubricant eye gels on tear film thickness as measured with ultrahigh-resolution optical coherence tomography

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).

Anterior segment optical coherence tomography

ABSTRACT 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. HighlightsOptical coherence tomography (OCT) technology has increased clinical applications in cornea and anterior segment imaging.Ultra‐high resolution anterior segment OCT may provide in vivo ‘histology’ images of the cornea with greater detail.OCT enables better understanding of glaucoma mechanisms via imaging of the aqueous outflow system and angles.OCT of the tear film and corneal layers has improved understanding and treatment of dry eye disease.Non‐invasive angiography of the anterior segment is now possible with novel OCT algorithms.

Effect of Diffuse Luminance Flicker Light Stimulation on Total Retinal Blood Flow Assessed With Dual-Beam Bidirectional Doppler OCT

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.

Super-resolved thickness maps of thin film phantoms and in vivo visualization of tear film lipid layer using OCT

In optical coherence tomography (OCT), the axial resolution is directly linked to the coherence length of the employed light source. It is currently unclear if OCT allows measuring thicknesses below its axial resolution value. To investigate spectral-domain OCT imaging in the super-resolution regime, we derived a signal model and compared it with the experiment. Several island thin film samples of known refractive indices and thicknesses in the range 46 - 163 nm were fabricated and imaged. Reference thickness measurements were performed using a commercial atomic force microscope. In vivo measurements of the tear film were performed in 4 healthy subjects. Our results show that quantitative super-resolved thickness measurement can be performed using OCT. In addition, we report repeatable tear film lipid layer visualization. Our results provide a novel interpretation of the OCT axial resolution limit and open a perspective to deeper extraction of the information hidden in the coherence volume.

Effect of Single Instillation of Two Hyaluronic Acid-Based Topical Lubricants on Tear Film Thickness in Patients with Dry Eye Syndrome

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 < 0.001). Single administration of HTP significantly increased TFT over a period of 40 min, an increase in TFT over 20 min was observed after instillation of HA, whereas NaCl had no effect. No significant difference in the change in BUT, CFS, or LLT was observed between the 3 groups (P = 0.57, 0.97, and 0.86, respectively). A significant improvement in subjective symptoms (VAS) was found after single instillation of HTP (P = 0.03 vs. baseline) and HA, but not after administration of NaCl (P = 0.03, P < 0.01, and P = 0.08 vs. baseline, respectively, P = 0.57 between groups). CONCLUSIONS Single administration of HTP and HA significantly increased TFT showing a longer residence time and improved subjective symptoms, whereas instillation of NaCl had no effect. Long-term studies with multiple instillations will be necessary to further investigate the effect of the tested products on the clinical outcome. ClinicalTrials.gov ID: NCT03161080.

Super-resolved thickness maps using ultrahigh resolution OCT

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.