Associations of retinal neurovascular dysfunction with inner retinal layer thickness in non-proliferative diabetic retinopathy.

PURPOSE: Neurovascular coupling impairment and inner retinal layer thinning are early detectable retinal changes in diabetes, and both worsen during progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyze associations between the retinal functional hyperemic response to light stimulation and the thickness of individual neuroretinal layers in eyes with early non-proliferative DR. METHODS: Thirty patients with type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non-proliferative DR and 14 healthy subjects were included in this cross-sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyzer. Individual layer thickness in the macula was analyzed from spectral domain optical coherence tomography. RESULTS: Flicker light-induced vessel dilation was significantly reduced in patients compared to healthy controls (veins: 3.0% vs. 6.1%, p < 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010), and negatively with hemoglobin A1c (HbA1c) levels (r=-0.41, p = 0.023) and age (r=-0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only GCL thickness (p = 0.017, ß = 0.42) and HbA1c (p = 0.045, ß=-0.35) remained significantly associated with the vascular flicker light response. CONCLUSION: The results indicate that thinner GCL and worse glycemic control both contribute to reduced retinal neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.

The Optical Coherence Tomography and Microperimetry Biomarker Evaluation in Patients with Geographic Atrophy (OMEGA) Study: Design and Baseline Characteristics - OMEGA Report 1.

INTRODUCTION: The aim of this study was to describe the design and the participants' baseline characteristics of a prospective natural history study of geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: The optical coherence tomography (OCT) and microperimetry biomarker evaluation in patients with GA (OMEGA) study was conducted at a tertiary referral center (ClinicalTrials.gov identifier: NCT05963646). Participants were followed for 12 months during 4 visits (baseline and follow-up exams at weeks 12, 24, and 48) with best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity, low-luminance visual acuity (LLVA), and quick contrast sensitivity function testing. Further, participants underwent spectral-domain OCT, OCT angiography, fundus autofluorescence imaging, and mesopic microperimetry testing. RESULTS: Thirty participants (median [IQR] age of 79 [77, 84] years) and 37 study eyes were included with a (median [IQR]) GA area of 1.40 mm2 (0.49, 5.24) at baseline. Out of 37 study eyes, six developed macular neovascularizations (16%). The study-eye best-corrected visual acuity was (median [IQR]) 0.18 logarithm of the minimum angle of resolution (logMAR) (0.06, 0.26), LLVA 0.66 logMAR (0.36, 0.88), and the microperimetry mean sensitivity 18.4 dB (9.21, 20.9). The highest correlation between square root GA area and a visual function test was evident for LLVA (R2 of 0.578), followed by area under the log contrast sensitivity function curve (0.519) and microperimetral retinal sensitivity (0.487). CONCLUSION: This report lays out the design and baseline characteristics of the OMEGA study, which aims to contribute to the understanding of the natural history of GA. The OMEGA study will provide estimates of the ability to detect change and retest reliability for a panel of structure and functional assessments.

MACULAR SENSITIVITY AND CAPILLARY PERFUSION IN HIGHLY MYOPIC EYES WITH MYOPIC MACULAR DEGENERATION.

PURPOSE: To evaluate the interrelationship between macular sensitivity and retinal perfusion density (PD) in eyes with myopic macular degeneration (MMD). METHODS: One hundred and thirty-eight highly myopic eyes from 82 adult participants were recruited. Macular sensitivity was evaluated using the Microperimeter MP-3. Retinal PD was measured using the PLEX Elite 9000 swept source optical coherence tomography angiography. Macular sensitivity values between different categories of MMD and its relationship with optical coherence tomography angiography measurements were evaluated using multivariable linear mixed models, adjusting for age and axial length. RESULTS: Macular sensitivity reduced with increasing severity of MMD (ß ≤ -0.95, P < 0.001), whereas the best-corrected visual acuity was not associated with MMD severity (P > 0.04). Persons who were older (ß = -0.08, P < 0.001), with longer axial length (ß = -0.32, P = 0.005), presence of macular diffuse choroidal atrophy (ß = -2.16, P < 0.001) or worse MMD (ß = -5.70, P < 0.001), and presence of macular posterior staphyloma (ß ≤ -2.98, P < 0.001) or Fuchs spot (ß = -1.58, P = 0.04) were associated with reduced macular sensitivity. Macular sensitivity was significantly associated with deep retinal PD in MMD (ß = 0.15, P = 0.004) but not with superficial retinal PD (P = 0.62). CONCLUSION: There was a strong correlation between reduced macular sensitivity and increasing MMD severity, even in mild MMD independent of the best-corrected visual acuity. Furthermore, macular sensitivity was correlated with deep retinal PD, suggesting a vasculature-function relationship in MMD.

Retinal Oxygen Extraction in Patients with Primary Open-Angle Glaucoma.

Objective: To compare total retinal oxygen extraction between patients with primary open-angle glaucoma (POAG) and healthy control subjects. Design: A prospective, single-center, cross-sectional, case−control study performed at the Medical University of Vienna. Subjects: Forty patients with POAG and 40 age- and sex-matched control subjects. Methods: Total retinal blood flow was measured using Doppler optical coherence tomography (OCT). Retinal arterial and venous oxygen saturation was measured using reflectance spectroscopy. From these parameters, oxygen content in the retinal arterial and venous circulation as well as total retinal oxygen extraction were calculated. Results: Total retinal blood flow was lower in POAG (25.2 ± 6.7 µL/min) as compared to healthy control subjects (35.6 ± 8.3 µL/min, p < 0.001). Retinal arterial oxygen content was not different between the two groups (0.18 ± 0.01 mL(O2)/mL in both groups, p < 0.761), but retinal venous oxygen content was higher in POAG (0.15 ± 0.01 mL(O2)/mL) than in healthy controls (0.14 ± 0.01 mL(O2)/mL p < 0.001). Accordingly, retinal oxygen extraction was reduced in POAG (0.8 ± 0.3 µL(O2)/min as compared to healthy controls: 1.4 ± 0.4 µL(O2)/min, p < 0.001). There was a significant association between total retinal blood flow and total retinal oxygen extraction with measures of structural and functional damage (p < 0.001 each). Conclusions: This study indicates that POAG is associated with a reduction in total retinal oxygen extraction linked to structural and functional damage of the disease. Since the technology is non-invasive, it allows for longitudinal studies investigating to which degree low retinal oxygen extraction is linked to the progression of the disease.

Plexus-specific effect of flicker-light stimulation on the retinal microvasculature assessed with optical coherence tomography angiography.

In neural tissues, the coupling between neural activity and blood flow is a physiological key principle in blood flow regulation. We used optical coherence tomography angiography to investigate stimulus-evoked hemodynamic responses in different microvascular layers of the human retina. Twenty-two healthy subjects were included. Vessel density before and during light stimulation was measured using optical coherence tomography angiography and assessed for the superficial, intermediate, and deep capillary plexus of the retinal circulation. Volumetric blood flow was measured using a custom-built Doppler optical coherence tomography system. Our results show that flicker stimulation induced a significant increase in the vessel density of +9.9 ± 6.7% in the superficial capillary plexus, +6.6 ± 1.7% in the intermediate capillary plexus, and +4.9 ± 2.3% in the deep capillary plexus. The hyperemic response of the superficial capillary plexus was significantly higher compared to the intermediate capillary plexus (P = 0.02) and deep capillary plexus (P = 0.002). Volumetric retinal blood flow increased by +39.9 ± 34.9% in arteries and by +29.8 ± 16.8% in veins. In conclusion, we showed a strong increase in the retinal microvascular density in response to light stimulation, with the most pronounced effect in the superficial capillary plexus. This is compatible with the hypothesis that the microvasculature exerts an important function in mediating functional hyperemia in humans.NEW & NOTEWORTHY We present vessel density alterations in response to flicker stimulation using optical coherence tomography angiography and identified the superficial capillary plexus as the layer with the most pronounced effect. This points out the physiological importance of the microvasculature in mediating functional hyperemia and suggests a fine-tuned plexus-specific mechanism to meet cellular metabolic demands.

Association of Antihypertensive Medication with Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer Thickness.

PURPOSE: To evaluate the association between different classes of antihypertensive medication with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness in a nonglaucomatous multiethnic Asian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 9144 eyes for RNFL analysis (2668 Malays, 3554 Indians, and 2922 Chinese) and 8549 eyes for GC-IPL analysis (2460 Malays, 3230 Indians, and 2859 Chinese) aged 44 to 86 years. METHODS: Participants underwent standardized systemic and ocular examinations and interviewer-administered questionnaires for collection of data on medication and other variables. Intraocular pressure (IOP) readings were obtained by Goldmann applanation tonometry before pupil dilation for fundoscopy and OCT imaging. Blood pressure (BP) was measured with an automatic BP monitor. Mean arterial pressure (MAP) was defined as diastolic BP plus 1/3 (systolic BP - diastolic BP). Regression models were used to investigate the association of antihypertensive medication with OCT measurements of RNFL and GC-IPL. MAIN OUTCOME MEASURES: Average and sectoral RNFL and GC-IPL thickness. RESULTS: After adjusting for age, gender, ethnicity, MAP, IOP, body mass index (BMI), and presence of diabetes, we found that participants taking any type of antihypertensive medication (ß = -0.83; 95% confidence interval [CI], -1.46 to -0.02; P = 0.01), specifically angiotensin-converting enzyme inhibitors (ACEIs) (ß = -1.66; 95% CI, -2.57 to -0.75; P < 0.001) or diuretics (ß = -1.38; 95% CI, -2.59 to -0.17; P < 0.05), had thinner average RNFL in comparison with participants who were not receiving antihypertensive treatment. Use of a greater number of antihypertensive medications was significantly associated with thinner average RNFL (P for trend = 0.001). This association was most evident in the inferior RNFL quadrant in participants using ACEIs (ß = -2.44; 95% CI, -3.99 to -0.89; P = 0.002) or diuretics (ß = -2.76; 95% CI, -4.76 to -0.76; P = 0.007). A similar trend was noted in our analysis of macular GC-IPL thickness. CONCLUSIONS: Use of 2 or more antihypertensive medications, ACEI, and diuretics were associated with a loss of structural markers of retinal ganglion cell health in a multiethnic Asian population.

Using image data to numerically correct the jitter in polarization depth encoding PS-OCT.

In swept source polarization depth encoding polarization sensitive optical coherence tomography (PS-OCT), the laser jitter induces additional noise to the polarization sensitive measurement. In this Letter, we developed a numerical algorithm to correct the jitter phases based on the image data using the Mueller matrix calculus. The algorithm was demonstrated on in vivo retina imaging of a guinea pig with a custom-built PS-OCT system. The performance of the proposed algorithm was almost comparable to the conventional method of using a physical calibration signal. By not requiring a hardware generated calibration signal and k-clock, the proposed algorithm is useful to reduce the complexity and the cost of a polarization depth encoding PS-OCT system.

Updates in deep learning research in ophthalmology.

Ophthalmology has been one of the early adopters of artificial intelligence (AI) within the medical field. Deep learning (DL), in particular, has garnered significant attention due to the availability of large amounts of data and digitized ocular images. Currently, AI in Ophthalmology is mainly focused on improving disease classification and supporting decision-making when treating ophthalmic diseases such as diabetic retinopathy, age-related macular degeneration (AMD), glaucoma and retinopathy of prematurity (ROP). However, most of the DL systems (DLSs) developed thus far remain in the research stage and only a handful are able to achieve clinical translation. This phenomenon is due to a combination of factors including concerns over security and privacy, poor generalizability, trust and explainability issues, unfavorable end-user perceptions and uncertain economic value. Overcoming this challenge would require a combination approach. Firstly, emerging techniques such as federated learning (FL), generative adversarial networks (GANs), autonomous AI and blockchain will be playing an increasingly critical role to enhance privacy, collaboration and DLS performance. Next, compliance to reporting and regulatory guidelines, such as CONSORT-AI and STARD-AI, will be required to in order to improve transparency, minimize abuse and ensure reproducibility. Thirdly, frameworks will be required to obtain patient consent, perform ethical assessment and evaluate end-user perception. Lastly, proper health economic assessment (HEA) must be performed to provide financial visibility during the early phases of DLS development. This is necessary to manage resources prudently and guide the development of DLS.

Generative adversarial networks in ophthalmology: what are these and how can they be used?

PURPOSE OF REVIEW: The development of deep learning (DL) systems requires a large amount of data, which may be limited by costs, protection of patient information and low prevalence of some conditions. Recent developments in artificial intelligence techniques have provided an innovative alternative to this challenge via the synthesis of biomedical images within a DL framework known as generative adversarial networks (GANs). This paper aims to introduce how GANs can be deployed for image synthesis in ophthalmology and to discuss the potential applications of GANs-produced images. RECENT FINDINGS: Image synthesis is the most relevant function of GANs to the medical field, and it has been widely used for generating 'new' medical images of various modalities. In ophthalmology, GANs have mainly been utilized for augmenting classification and predictive tasks, by synthesizing fundus images and optical coherence tomography images with and without pathologies such as age-related macular degeneration and diabetic retinopathy. Despite their ability to generate high-resolution images, the development of GANs remains data intensive, and there is a lack of consensus on how best to evaluate the outputs produced by GANs. SUMMARY: Although the problem of artificial biomedical data generation is of great interest, image synthesis by GANs represents an innovation with yet unclear relevance for ophthalmology.

New Technologies in Clinical Trials in Corneal Diseases and Limbal Stem Cell Deficiency: Review from the European Vision Institute Special Interest Focus Group Meeting.

To discuss and evaluate new technologies for a better diagnosis of corneal diseases and limbal stem cell deficiency, the outcomes of a consensus process within the European Vision Institute (and of a workshop at the University of Cologne) are outlined. Various technologies are presented and analyzed for their potential clinical use also in defining new end points in clinical trials. The disease areas which are discussed comprise dry eye and ocular surface inflammation, imaging, and corneal neovascularization and corneal grafting/stem cell and cell transplantation. The unmet needs in the abovementioned disease areas are discussed, and realistically achievable new technologies for better diagnosis and use in clinical trials are outlined. To sum up, it can be said that there are several new technologies that can improve current diagnostics in the field of ophthalmology in the near future and will have impact on clinical trial end point design.

A pilot study to assess the effect of a three-month vitamin supplementation containing L-methylfolate on systemic homocysteine plasma concentrations and retinal blood flow in patients with diabetes.

Purpose: The aim of the present study was to investigate the effect of a three-month dietary supplementation with a methylfolate formulation on homocysteine plasma concentrations and ocular blood flow parameters in patients with diabetes. Methods: Twenty-four patients with diabetes received a dietary supplement (Oculofolin, Aprofol AG, Switzerland) containing 900 µg L­methylfolate (levomefolate calcium or [6S]-5-methyltetrahydrofolic acid, calcium salt), methylcobalamin, and other ingredients for three consecutive months. The patients' plasma homocysteine concentration and retinal blood flow were assessed at baseline and after three months of folate intake. Retinal blood flow was measured using a custom-built dual-beam Doppler optical coherence tomography (OCT) system. In addition, flicker-induced retinal vasodilatation was assessed by means of a commercially available dynamic vessel analyzer (IMEDOS, Jena, Germany). Results: Supplementation was well tolerated by all patients. After three months, plasma homocysteine concentration significantly decreased from 14.2 ± 9.3 to 9.6 ± 6.6 µmol/L (p < 0.001). In addition, a tendency toward an increased total retinal blood flow from 36.8 ± 12.9 to 39.2 ± 10.8 µl/min was observed, but this effect did not reach the level of significance (p = 0.11). Supplementation had no effect on retinal vessel diameter or flicker-induced vasodilatation. Conclusions: The present data show that a three-month intake of a dietary supplement containing methylfolate can significantly reduce blood homocysteine levels in patients with diabetes. This is of importance because higher homocysteine plasma levels have been found to be associated with an increased risk of vascular associated systemic diseases and eye diseases. Whether systemic methylfolate supplementation affects retinal perfusion must be studied in a larger population.

Stable complex conjugate artifact removal in OCT using circularly polarized light as reference.

In Fourier domain optical coherence tomography (FDOCT), the depth profile is mirrored about the zero delay between the sample and reference optical paths, limiting the imaging depth to half of the entire ranging space and undermining the optimal sensitivity window. We present a new method, to the best of our knowledge, to remove the complex conjugate artifact by using circularly polarized light as reference. Quadrature detection of the complex fringe is achieved by utilizing the intrinsic λ/4 delay between two polarization channels. We use passive broadband polarization optics to control the polarization state of the light in the reference and sample arms and a balanced polarization diversity detection unit to simultaneously detect phase-shifted fringes. We demonstrate a 40 dB artifact suppression ratio with a swept-source optical coherence tomography system. Our proposed method is immune to sample motion and laser phase noise, and imposes no restrictions to the source bandwidth, imaging speed, or computational power. In vivo images of the human finger, as well as the cornea and retina of a non-human primate, were demonstrated.

Effect of spectral leakage on the image formation of Fourier-domain optical coherence tomography.

We report on the investigation of spectral leakage's impact on the reconstruction of Fourier-domain optical coherence tomography (FD-OCT). We discuss the shift-variant nature introduced by the spectral leakage and develop a novel spatial-domain FD-OCT image formation model. A proof-of-concept phantom experiment is conducted to validate our model. Compared with previous models, the proposed framework could better describe the image formation process, especially when the fineness of the axial structure approaches the theoretical resolution limit.

Techniques and Applications in Skin OCT Analysis.

The skin is the largest organ of our body. Skin disease abnormalities which occur within the skin layers are difficult to examine visually and often require biopsies to make a confirmation on a suspected condition. Such invasive methods are not well-accepted by children and women due to the possibility of scarring. Optical coherence tomography (OCT) is a non-invasive technique enabling in vivo examination of sub-surface skin tissue without the need for excision of tissue. However, one of the challenges in OCT imaging is the interpretation and analysis of OCT images. In this review, we discuss the various methodologies in skin layer segmentation and how it could potentially improve the management of skin diseases. We also present a review of works which use advanced machine learning techniques to achieve layers segmentation and detection of skin diseases. Lastly, current challenges in analysis and applications are also discussed.

Long-Term Shape, Curvature, and Depth Changes of the Lamina Cribrosa after Trabeculectomy.

PURPOSE: To evaluate changes in lamina cribrosa (LC) shape, curvature, and depth after trabeculectomy. DESIGN: Prospective, observational case series. PARTICIPANTS: A total of 112 patients (118 eyes) with open- or closed-angle glaucoma undergoing trabeculectomy. METHODS: The optic nerve head was imaged using enhanced depth imaging spectral-domain OCT before trabeculectomy and at 6 follow-up visits throughout the first postoperative year. The anterior LC surface and Bruch's membrane opening were marked in the serial horizontal B scans for the analysis of LC parameters using Morphology 1.0 software. Postoperative morphologic LC changes were assessed. MAIN OUTCOME MEASURES: The postoperative LC global shape index (GSI), nasal-temporal (N-T) and superior-inferior (S-I) curvatures, and mean and sectoral LC depth (LCD). RESULTS: The mean LC GSI increased only during the early postoperative period (P = 0.02), resulting in a change toward the saddle-rut shape. There was a flattening of the LC curvature in N-T (P < 0.001) and S-I (P = 0.003) meridians 12 months after trabeculectomy. A shallowing of the mean and sectoral LCD from baseline was significant throughout the entire follow-up period (P < 0.001) and progressed up to postoperative month 6. Twenty-eight patients showed a deepening of the LC from baseline in at least 1 visit. Eyes with shallower LCD compared with baseline responded to intraocular pressure (IOP) reduction with greater movement anteriorly than eyes with deeper LCD (P = 0.002). Greater IOP reduction (P = 0.007), less retinal nerve fiber layer thinning over the year (P = 0.003), and more superiorly-inferiorly curved baseline LC (P = 0.001) were associated with an increase in GSI. Younger age and IOP reduction were related to LC shallowing (P < 0.001, P = 0.002) and N-T flattening (P < 0.001). CONCLUSIONS: In most eyes, trabeculectomy resulted in long-term flattening and shallowing of the LC. However, in some eyes, LC deepened from baseline. Change in LC global shape appeared to be temporal. Reduction in IOP plays an important role in the early phase of LC change; however, in the later phase, LC remodeling may play a crucial role in view of stable IOP.

Optical coherence tomography angiography: a review of current and future clinical applications.

Optical coherence tomography angiography is a non-invasive imaging technique that now allows for simultaneous in vivo imaging of the morphology as well as the vasculature in the eye. In this review, we provide an update on the existing clinical applications of optical coherence tomography angiography technology from the anterior to posterior segment of the eye. We also discuss the limitations of optical coherence tomography angiography technology, as well as the caveats to the interpretation of images. As current optical coherence tomography angiography systems are optimized for the retina, most studies have focused on interpreting images from conditions such as age related macular degeneration and retinal vascular diseases. However, the interpretation of these optical coherence tomography angiography images should be taken in consideration with other multi-modal imaging to overcome the limitations of each technique. In addition, there are a growing variety of clinical applications for optical coherence tomography angiography imaging in optic nerve head evaluation for glaucoma and optic neuropathies. Further developments in anterior optical coherence tomography angiography have now allowed for evaluation of anterior segment pathology such as glaucoma, ocular surface diseases, corneal vascularisation, and abnormal iris vasculature. Future developments in software could allow for improved segmentation and image resolution with automated measurements and analysis.

Photoacoustic imaging of lamina cribrosa microcapillaries in porcine eyes.

Due to the embedded nature of the lamina cribrosa (LC) microcapillary network, conventional imaging techniques have failed to obtain the high-resolution images needed to assess the perfusion state of the LC. In this study, both optical resolution (OR) and acoustic resolution (AR) photoacoustic microscopy (PAM) techniques were used to obtain static and dynamic information about LC perfusion in ex vivo porcine eyes. The OR-PAM system could resolve a perfused LC microcapillary network with a lateral resolution of 4.2 µm and also provided good depth information (33 µm axial resolution) to visualize through-thickness vascular variations. The AR-PAM system was capable of detecting time-dependent perfusion variations. This study represents the first step towards using an emerging imaging modality (PAM) to study the LC's perfusion, which could be a basis for further investigation of the hemodynamic aspects of glaucomatous optic neuropathy.

[Cornea Imaging by Optical Coherence Tomography - Historical Aspects and Most Recent Technical Developments]. / Bildgebung in der Kornea mittels optischer Kohärenztomografie ­ historische Entwicklung und neueste technische Fortschritte.

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.

Retinal oxygen extraction in individuals with type 1 diabetes with no or mild diabetic retinopathy.

AIMS/HYPOTHESIS: The aim of this study was to compare retinal oxygen extraction in individuals with diabetes with no or mild non-proliferative diabetic retinopathy and healthy age- and sex-matched volunteers. METHODS: A total of 24 participants with type 1 diabetes and 24 healthy age- and sex-matched volunteers were included in this cross-sectional study. Retinal oxygen extraction was measured by combining total retinal blood flow measurements using a custom-built bi-directional Doppler optical coherence tomography system with measurements of oxygen saturation using spectroscopic reflectometry. Based on previously published mathematical modelling, the oxygen content in retinal vessels and total retinal oxygen extraction were calculated. RESULTS: Total retinal blood flow was higher in diabetic participants (46.4 ± 7.4 µl/min) than in healthy volunteers (40.4 ± 5.3 µl/min, p = 0.002 between groups). Oxygen content in retinal arteries was comparable between the two groups, but oxygen content in retinal veins was higher in participants with diabetes (0.15 ± 0.02 ml O2/ml) compared with healthy control participants (0.13 ± 0.02 ml O2/ml, p < 0.001). As such, the arteriovenous oxygen difference and total retinal oxygen extraction were reduced in participants with diabetes compared with healthy volunteers (total retinal oxygen extraction 1.40 ± 0.44 vs 1.70 ± 0.47 µl O2/min, respectively, p = 0.03). CONCLUSIONS/INTERPRETATION: Our data indicate early retinal hypoxia in individuals with type 1 diabetes with no or mild diabetic retinopathy as compared with healthy control individuals. Further studies are required to fully understand the potential of the technique in risk stratification and treatment monitoring. TRIAL REGISTRATION: ClinicalTrials.gov NCT01843114.

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.