No abstract

Imaging has become indispensable in the diagnosis and management of diseases in the posterior part of the eye. In recent years, imaging techniques for the anterior segment are also gaining importance and are nowadays routinely used in clinical practice. Ocular surface disease is often synonymous with dry eye disease, but also refers to other conditions of the ocular surface, such as Meibomian gland dysfunction or keratitis and conjunctivitis with different underlying causes, i.e., allergies or infections. Therefore, correct differential diagnosis and treatment of ocular surface diseases is crucial, for which imaging can be a helpful tool. A variety of imaging techniques have been introduced to study the ocular surface, such as anterior segment optical coherence tomography, in vivo confocal microscopy, or non-contact meibography. The present review provides an overview on how these techniques can be used in the diagnosis and management of ocular surface disease and compares them to clinical standard methods such as slit lamp examination or staining of the cornea or conjunctiva. Although being more cost-intensive in the short term, in the long term, the use of ocular imaging can lead to more individualized diagnoses and treatment decisions, which in turn are beneficial for affected patients as well as for the healthcare system. In addition, imaging is more objective and provides good documentation, leading to an improvement in patient follow-up and education.

To investigate the response of the superficial and deep capillary plexuses to hyperoxia and hypoxia using optical coherence tomography angiography (OCT-A) and retinal vessel analyzer.Methods: Twenty-four healthy volunteers participated in this randomized, double-masked, crossover study. For each subject, two study days were scheduled: on one study day, hyperoxia was induced by breathing 100% oxygen whereas on the other study day, hypoxia was induced by breathing a mixture of 88% nitrogen and 12% oxygen. Perfusiondensity wascalculated in the superficial vascular plexus (SVP) and the deep capillary plexus (DCP), using OCT-A before (normal breathing) and during breathing of the gas mixtures. Retinal vessel calibres in major retinal vessels were measured using a dynamic vessel analyzer.Results: During 100% oxygen breathing, a significant decrease in DCP perfusion density from 41.7 AE 2.4 a.u to 35.6 AE 3.1 a.u. (p < 0.001) was observed, which was accompanied by a significant decrease in vessel diameters in majorretinal arteries and veins(p < 0.001 each). No significant change in perfusion density in the SVP occurred (p = 0.33). In contrast, during hypoxia, perfusion density in the SVP significantly increased from 34.4 AE 3.0a.u.to 37.1 AE 2.2 a.u. (p < 0.001), while it remained stable in the DCP (p = 0.25). A significant increase in retinal vessel diameters was found (p < 0.01). Systemic oxygen saturation correlated negatively with perfusion density in the SVP and the DCP and retinal vessel diameters (p < 0.005 each). Conclusion:Our results show that systemic hyperoxia induces a significant decrease in vessel density in the DCP, while hypoxia leads to increased vessel density limited to the SVP. These results indicate that the retinal circulation shows the ability to adapt its blood flow to metabolic changes with high local resolution dependent on the capillary plexus.

Background/aims Concerning healthcare approaches, a paradigm change from reactive medicine to predictive approaches, targeted prevention, and personalisation of medical services is highly desirable. This raises demand for biomarker signatures that support the prediction and diagnosis of diseases, as well as monitoring strategies regarding therapeutic efficacy and supporting individualised treatments. New methodological developments should preferably rely on non-invasively sampled biofluids like sweat and tears in order to provide optimal compliance, reduce costs, and ensure availability of the biomaterial. Here, we have thus investigated the metabolic composition of human tears in comparison to finger sweat in order to find biofluid-specific marker molecules derived from distinct secretory glands. The comprehensive investigation of numerous biofluids may lead to the identification of novel biomarker signatures. Moreover, tear fluid analysis may not only provide insight into eye pathologies but may also be relevant for the prediction and monitoring of disease progression and/ or treatment of systemic disorders such as type 2 diabetes mellitus. Methods Sweat and tear fluid were sampled from 20 healthy volunteers using filter paper and commercially available Schirmer strips, respectively. Finger sweat analysis has already been successfully established in our laboratory. In this study, we set up and evaluated methods for tear fluid extraction and analysis using high-resolution mass spectrometry hyphenated with liquid chromatography, using optimised gradients each for metabolites and eicosanoids. Sweat and tears were systematically compared using statistical analysis. As second approach, we performed a clinical pilot study with 8 diabetic patients and compared them to 19 healthy subjects. Results Tear fluid was found to be a rich source for metabolic phenotyping. Remarkably, several molecules previously identified by us in sweat were found significantly enriched in tear fluid, including creatine or taurine. Furthermore, other metabolites such as kahweol and various eicosanoids were exclusively detectable in tears, demonstrating the orthogonal power for biofluid analysis in order to gain information on individual health states. The clinical pilot study revealed that many endogenous metabolites that have previously been linked to type 2 diabetes such as carnitine, tyrosine, uric acid, and valine were indeed found significantly up-regulated in tears of diabetic patients. Nicotinic acid and taurine were elevated in the diabetic cohort as well and may represent new biomarkers for diabetes specifically identified in tear fluid. Additionally, systemic medications, like metformin, bisoprolol, and gabapentin, were readily detectable in tears of patients. Conclusions The high number of identified marker molecules found in tear fluid apparently supports disease development prediction, developing preventive approaches as well as tailoring individual patients’ treatments and monitoring treatment efficacy. Tear fluid analysis may also support pharmacokinetic studies and patient compliance control.

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.

Vascular changes and alterations of oxygen metabolism are suggested to be implicated in multiple sclerosis (MS) pathogenesis and progression. Recently developed in vivo retinal fundus imaging technologies provide now an opportunity to non-invasively assess metabolic changes in the neural retina. This study was performed to assess retinal oxygen metabolism, peripapillary capillary density (CD), large vessel density (LVD), retinal nerve fiber layer thickness (RNFLT) and ganglion cell inner plexiform layer thickness (GCIPLT) in patients with diagnosed relapsing multiple sclerosis (RMS) and history of unilateral optic neuritis (ON). 16 RMS patients and 18 healthy controls (HC) were included in this study. Retinal oxygen extraction was modeled using O2 saturations and Doppler optical coherence tomography (DOCT) derived retinal blood flow (RBF) data. CD and LVD were assessed using optical coherence tomography (OCT) angiography. RNFLT and GCIPLT were measured using structural OCT. Measurements were performed in eyes with (MS+ON) and without (MS-ON) history for ON in RMS patients and in one eye in HC. Total oxygen extraction was lowest in MS+ON (1.8 ± 0.2 μl O2/min), higher in MS-ON (2.1 ± 0.5 μl O2/min, p = 0.019 vs. MS+ON) and highest in HC eyes (2.3 ± 0.6 μl O2/min, p = 0.002 vs. MS, ANOVA p = 0.031). RBF was lower in MS+ON (33.2 ± 6.0 μl/min) compared to MS-ON (38.3 ± 4.6 μl/min, p = 0.005 vs. MS+ON) and HC eyes (37.2 ± 4.7 μl/min, p = 0.014 vs. MS+ON, ANOVA p = 0.010). CD, LVD, RNFLT and GCIPL were significantly lower in MS+ON eyes. The present data suggest that structural alterations in the retina of RMS patients are accompanied by changes in oxygen metabolism, which are more pronounced in MS+ON than in MS-ON eyes. Whether these alterations promote MS onset and progression or occur as consequence of disease warrants further investigation.Clinical Trial Registration:ClinicalTrials.gov registry, NCT03401879.

We compare the focal structure–function correlation of structural measurements of peripapillary retinal nerve fiber layer thickness (RNFL‐T) using optical coherence tomography (OCT), capillary density (CD) measurements using OCT‐angiography (OCT‐A), or a combination of both, with visual field deviation (VFD) in early to advanced glaucoma. Primary open angle glaucoma patients (n = 46, mean ± SD age: 67 ± 10 years; VF mean deviation: −10.41 ± 6.76 dB) were included in this cross‐sectional study. We performed 30–2 standard automated perimetry OCT (3.5‐mm diameter ring scan) and 15°×15° OCT‐A (superficial vascular complex slab). Based on a nerve fiber trajectory model, each VF test spot was assigned to an OCT‐A wedge and an OCT ring‐sector. Two univariate linear models (Mv and Mt) using either CD‐based vascular (Mv) or RNFL‐T–based thickness information (Mt) and one multivariate model using both (Mv:t) were compared in their associations with measured focal VFD, which were higher for the multivariate model Mv:t (mean ± SD correlation coefficient: 0.710 ± 0.086) than for either nested model (0.627 ± 0.078 for Mv and 0.578 ± 0.095 for Mt). Using a focal visual field approach, the combination of RNFL‐T and CD showed better structure–function correlations than thickness or vascular information only.

The aim of the present study was to assess retinal oxygen metabolism in patients with type II diabetes and different stages of non-proliferative diabetic retinopathy (DR) and compare these findings to healthy controls. For this purpose, 67 patients with type II diabetes and 20 healthy controls were included in this cross-sectional study. 34 patients had no, 15 had mild and 18 had moderate to severe DR. Retinal oxygen saturation in arteries and veins was measured using the oxygen module of the Retinal Vessel Analyzer (RVA). Total retinal blood flow (TFBF) was measured using a custombuilt Doppler optical coherence tomography system. Retinal oxygen extraction was calculated out of retinal oxygen saturation and TRBF. Arteriovenous difference in oxygen saturation was highest in healthy subjects (34.9±7.5%), followed by patients with no DR (32.5±6.3%) and moderate to severe DR (30.3±6.5%). The lowest values were found in patients with mild DR (27.3±8.0%, p=0.010 vs. healthy subjects). TRBF tended to be higher in patients with no DR (40.1±9.2µl/min) and mild DR (41.8±15.0µl/min) compared to healthy subjects (37.2±5.7µl/min) and patients with moderate to severe DR (34.6±10.4µl/min). Retinal oxygen extraction was the highest in healthy subjects (2.24±0.57µl O2/min), followed by patients with no DR (2.14±0.6µl O2/min), patients with mild DR (1.90±0.77µl O2/min) and patients with moderate to severe DR (1.78±0.57µl O2/min, p=0.040 vs. healthy subjects). These results indicate that retinal oxygen metabolism is altered in patients with type II diabetes. Further, retinal oxygen extraction decreases with increasing severity of DR.