Originalbeiträge (Originals). Altered microvascular density in patients with anorexia nervosa ­ an optical coherence tomography angiography (OCTA) pilot study.

OBJECTIVES: To investigate macular and peripapillary vascular density (VD) in patients with anorexia nervosa (AN) compared to healthy controls. Methods:Whole face scans of the superficial and deep macular layers and whole face and peripapillary scans of the radial peripapillary capillaries (RPC) were obtained using optical coherence tomography angiography (OCTA, AngioVueR, Optovue) in ten patients with AN and ten age-matched controls.The primary objective was to determine whether there was a difference between the vessel density (VD) in the above areas in AN and controls. P-values ≤ 0.0125 were considered statistically significant. Results: VD in the superficialmacular en-face OCTA image was significantly lower in the study group compared to the control group. Neither the deepmacula nor the radial peripapillary capillary (RPC) in the whole-face image nor the RPC-peripapillary imaging appeared to be significantly different. Conclusion: Patients with AN showed reduced VD in the superficialmacular layers compared to healthy controls, which can be discussed as a consequence of the malnutrition. OCTA could be a useful non- invasive tool to detect reduced peripheral blood supply to show vascular changes that occur before ocular symptoms.

Light conditions influence optic nerve OCT angiography parameter in healthy subjects with neutral pupils.

Optical coherence tomography angiography measurements are influenced by a range of environmental factors as blood pressure and physical fitness. The present study aimed to evaluate the effects of light and dark exposure in eyes with neutral and mydriatic pupils on vessel density in the macular and optic nerve head regions, as measured using optical coherence tomography angiography (OCTA). 55 eyes of 55 healthy volunteers (28 patients with neutral pupils; 27.18 ± 4.33 years) were examined using a high-speed and high-resolution spectral-domain OCT XR Avanti system with a split-spectrum amplitude de-correlation angiography algorithm. OCTA imaging was performed after dark adaptation and after exposure to light. The vessel density data of the superficial and deep retinal macular and optic nerve head region OCT-angiogram were analyzed for these two light conditions. Through Bonferroni correction for multiple testing, the p- value was adapted from 0.05 to 0.017. In eyes with neutral pupils, a significant increase was found in the capillary region of the optic nerve head region (p = 0.002), comparing dark- and light-adaptation. In the macular region of eyes with neutral (p = 0.718) and mydriatic pupils (p = 0.043), no significant differences were observed, as were any in the optic nerve head region of the mydriatic eyes (p = 0.797). This observation suggests that light conditions could be a possible factor influencing OCTA measurements. After dark exposure, vessel density data were significantly different between eyes with neutral and mydriatic pupils (nerve head region: p < 0.0001, superficial macula: p < 0.0001, deep macula: p = 0.0025). These data warn for the effect of mydriatic drops on vessel density measurements.

Assessment of Retinal Pigment Epithelium Alterations and Chorioretinal Vascular Network Analyses in Patients under Treatment with BRAF/MEK Inhibitor for Different Malignancies: A Pilot Study.

In the last two decades, an increasing number of so-called molecular-targeted therapies have become available for the treatment of patients with advanced malignancies. These drugs have included inhibitors of proteins in the MAPK pathway, such as BRAF and MEK inhibitors, which are characterized by a distinct toxicity profile. The eye is particularly susceptible to adverse effects due to MEK inhibitors, and the term MEKAR (MEK-inhibitor-associated retinopathy) indicates the presence of subretinal fluid, mimicking central serous chorioretinopathy (CSC). The pathogenesis of the retinal alterations related to MAPK pathway inhibitors is still unclear, and questions are still open. The present study aims to assess the presence of retinal pigment epithelium alterations as predictive parameters for retinal toxicity, analyzing, at the same time, the chorioretinal vascular network in patients undergoing BRAF/MEK inhibitor treatment for different malignancies.

Choroidal and Choriocapillaris Morphology in Pan-FGFR Inhibitor-Associated Retinopathy: A Case Report.

Emerging anticancer agents such as the pan-FGFR Inhibitor have achieved remarkable improvements in the survival of patients with metastatic malignancies. Nevertheless they are still associated with specific ophthalmic toxicities. Understanding their pathophysiology can lead us to better clinical practice of life-threatening and vision-threatening circumstances. To investigate choroidal alterations as a potential pathophysiological mechanism of a serous detachment in bilateral pan-FGFR Inhibitor-Associated Retinopathy (FGFRAR), the morphology of the choroid and choriocapillaris were assessed. The choroidal thickness (ChT) and choriocapillaris flow void were measured by macular optical coherence tomography (OCT) and angiography (OCT-A), respectively. Data were collected at the baseline, then at one-month and two-months follow-ups after starting erdafitinib, in a single case of pulmonary angiosarcoma. Choroidal and choriocapillaris morphology showed stable ChT and choriocapillaris flow void at FGFRAR onset and relapse. To the best of our knowledge, this is the first analyzed case reported with flow-void OCT-angiography. Considering these results, FGFRAR in this patient does not seem to match the pachychoroid spectrum disorder definition; rather, an intracellular mechanism based on intracellular transduction pathways may be at work.

Choriocapillaris Assessment In Patients Under Mek-Inhibitor Therapy For Cutaneous Melanoma: An Optical Coherence Tomography Angiography Study.

PURPOSE: The present study investigates by optical coherence tomography angiography (OCTA) the retinal capillary plexus and choriocapillaris flow voids and their possible correlation with MEKAR. METHODS: 34 eyes of 17 patients (61.5 years [30.4-77.4]) with stage IV cutaneous melanoma were included prospectively. All patients showed disease progression under treatment with Nivolumab/Ipilimumab and were subsequently treated with the MEK-inhibitor Trametinib 2 mg once daily. At the start and every 6 weeks during follow-up of 4 months, patients underwent a complete ophthalmologic exam, OCTA and when needed fluorescein angiography. RESULTS: Statistical analysis was performed on 17 eyes of 9 patients. Eight patients were excluded due to missing OCTA images or due to drop-out because of decease or change of treatment. Comparing vessel area density (P = .625 and 0.681, respectively), vessel skeleton density (P = .996 and 0.766, respectively) of the superficial and deep capillary plexus, flow void number and total flow void area (mm2 and %) (P = .495; 0.197 and 0.298, respectively) of choriocapillaris slab, before and after treatment, revealed no significant difference. The evolution of choriocapillaris flow void parameter did not significantly differ in patients, who developed MEKAR compared to patients who did not. CONCLUSION: In patients receiving MEK-inhibitor with and without MEKAR, no significant different characteristics of the retinal capillary plexus and choriocapillaris were found. These data suggest that the development of MEKAR, has no correlation with vascular alteration.

Effect of high-intensity interval training in patients with type 1 diabetes on physical fitness and retinal microvascular perfusion determined by optical coherence tomography angiography.

OBJECTIVE: Physical activity may protect from ocular complications of diabetic retinopathy (DR). We investigated exercise training effects on the retinal microvasculature using optical coherence tomography angiography (OCTA) in type 1 diabetes (T1D). METHODS: Twenty T1D patients without clinical signs of DR performed four weeks of high-intensity interval training (HIIT). Cycle ergometry was used for determination of physical fitness. OCTA of the macula and optic nerve head was applied to analyze effects on the foveal avascular zone area, vessel density, vessel diameter index and fractal dimension of the superficial plexus, deep plexus and radial peripapillary capillaries. RESULTS: Large effects for improvement of physical fitness in terms of power output at the individual lactate threshold (+10.7 ± 11.3%, p < .001, ES = 0.95) and maximal power output (+8.2 ± 6.4%, p < .001, ES = 1.4) were detected. Participants presented a reduced increase in heart rate (HR) and lactate (LA) at given exercise intensities at follow-up (p ≤ .0176). Baseline OCTA revealed that HbA1c levels were associated with vessel density in the radial peripapillary capillary and the parafoveal superficial region (p ≤ .014). None of the analyzed microvascular parameters changed in response to the intervention. CONCLUSION: Despite favorable effects of HIIT on physical fitness of T1D patients, disease-specific training protocols may be needed to overcome potentially impaired retinal microvascular adaptations.

Author Correction: Optical coherence tomography angiography as a novel approach to contactless evaluation of sublingual microcirculation: A proof of principle study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Optical coherence tomography angiography as a novel approach to contactless evaluation of sublingual microcirculation: A proof of principle study.

Microcirculatory disorders are crucial in pathophysiology of organ dysfunction in critical illness. Evaluation of sublingual microcirculation is not routinely conducted in daily practice due to time-consuming analysis and susceptibility to artifacts. We investigated the suitability of optical coherence tomography angiography (OCTA) for contactless evaluation of sublingual microcirculation. Sublingual microcirculation was imaged in 10 healthy volunteers, using an OCTA device and an incident dark field (IDF) illumination microscopy (current gold standard). OCTA images were analyzed with regard to flow density and perfused vessel density (PVDbyOCTA). IDF videos were analyzed following current recommendations. Flow density was automatically extracted from OCTA images (whole en face 48.9% [43.2; 54.5]; central ring 52.6% [43.6; 60.6]). PVDbyOCTA did not differ from the PVD calculated from IDF videos (PVDbyOCTA 18.6 mm/mm² [18.0; 21.7]) vs. PVDbyIDF 21.0 mm/mm² [17.5; 22.9]; p = 0.430). Analysis according to Bland-Altman revealed a mean bias of 0.95 mm/mm² (95% Confidence interval -1.34 to 3.25) between PVDbyOCTA and PVDbyIDF with limits of agreement of -5.34 to 7.24 mm/mm². This study is the first to demonstrate the suitability of OCTA for evaluating sublingual microcirculation. Comparison of the perfused vessel density between methods showed a plausible level of agreement.

Correlation analysis of physical fitness and retinal microvasculature by OCT angiography in healthy adults.

Optical coherence tomography angiography (OCT-A) represents the most recent modality in retinal imaging for non-invasive and depth-selective visualization of blood flow in retinal vessels. With regard to quantitative OCTA measurements for early detection of subclinical alterations, it is of great interest, which intra- and extra-ocular factors affect the results of OCTA measurements. Here, we performed OCTA imaging of the central retina in 65 eyes of 65 young healthy female and male participants and evaluated individual physical fitness levels by standard lactate diagnostic using an incremental maximal performance running test. The main finding was that OCTA measurements of the foveal avascular zone (FAZ) area were associated with physical fitness. Using multivariate regression analysis, we found that running speed at the individual lactate threshold, a marker strongly associated with aerobic performance capacity, significantly contributed to differences in FAZ area (ß = 0.111, p = 0.032). The data indicates that smaller FAZ areas are likely observed in individuals with higher aerobic exercise capacity. Our findings are also of interest with respect to the potential use of retinal OCTA imaging to detect exercise-induced microvascular adaptations in future studies.

Influence of mydriasis on optical coherence tomography angiography imaging in patients with age-related macular degeneration.

PURPOSE: To evaluate the effect of topical mydriatic eye drops on optical coherence tomography angiography (OCTA) parameters in patients with age-related macular degeneration (AMD). METHODS: 27 eyes of 27 patients suffering from AMD were included in this cross-sectional study. Patients with ≥-4.5 diopters spherical equivalent, corneal opacities or dense cataract preventing high-quality imaging were excluded. Whole-en-face scans of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the central 3x3mm foveal region as well as whole-en-face and peripapillary scans of the radial peripapillary capillaries (RPC) were generated using OCTA (AngioVue®, Optovue). Imaging was first conducted with patients' eyes in miosis, then in mydriasis after instillation of a dilating eye drop (0.5% tropicamide, 2.5% phenylephrine-HCl). Main outcome measures were flow density (FD), foveal avascular zone (FAZ), signal strength index (SSI) and motion artifact score (MAS). RESULTS: Our results reveal that in AMD patients there is no significant difference between FD measurements taken in miosis and those taken in mydriasis around the SCP (p = 0.198), DCP (p = 0.458), RPC whole-en-face (p = 0.275) and RPC peripapillary (p = 0.503). Measurements taken in these two states appear to be equivalent for assessment of FD (90%CI within ± 0.05). No significant difference was found either in the area of the FAZ (p = 0.338) or in the SSI (p = 0.371) before and after the instillation of tropicamide/phenylephrine. MAS was significantly lower after the application of mydriatic eye drops (p = 0.003). CONCLUSIONS: Our findings reveal that neither measurements of FD nor measurements of the FAZ area changed significantly in AMD patients after the application of tropicamide/phenylephrine. Since MAS improved significantly in dilation, mydriatic examination is recommended. Nevertheless, a comparison of OCTA metrics from images taken with different pupil states (miosis versus mydriasis) is valid for clinical trials.

[Optical coherence tomography angiography as a future diagnostic tool in sports medicine?] / Optische Kohärenztomographie-Angiographie als zukünftiges Diagnostikum in der Sportmedizin?

BACKGROUND: High-intensity interval training (HIIT) proved to be efficient for increasing health-related fitness in general and in patients with life style-induced chronic diseases. This study aimed to evaluate if (I) individual physical fitness and (II) a HIIT intervention affects optical coherence tomography angiography (OCTA) measurements at the ocular fundus of healthy young adults. METHODS: A total of 65 healthy participants performed a standardized incremental running test to determine their physical fitness. This was defined as speed at the individual anaerobic threshold and maximum running speed followed by a 4-week HIIT with two exercise sessions/week. The OCTA measurements of the foveal avascular zone (FAZ) and flow densities in various segments of the macula and optic nerve head were performed at rest before and after HIIT. RESULTS: An inverse correlation between individual fitness and FAZ area was detected. No further correlations between individual physical fitness and other OCTA parameters were found. In response to HIIT the mean FAZ area in the deep retinal plexus and macular flow density of the superficial layer decreased by 14.00 ± 13.02% and 1.26 ± 3.20%, respectively. The flow density of the nerve head layer in the peripapillary area showed an increase of 1.94 ± 2.39%. All other parameters showed no differences between measurements before and after HIIT. CONCLUSION: Differences were found in the OCTA measurements of the FAZ depending on the individual physical fitness. Performing HIIT can induce significant changes in certain OCTA parameters. Therefore, OCTA imaging appears to be a promising imaging modality in the field of sports medicine.

Diurnal variations in flow density measured using optical coherence tomography angiography and the impact of heart rate, mean arterial pressure and intraocular pressure on flow density in primary open-angle glaucoma patients.

PURPOSE: To determine the diurnal variations in peripapillary and macular flow density (FD), as measured using optical coherence tomography angiography (OCTA) and to elaborate on the relationship between diurnal FD, circulatory parameters and intraocular pressure (IOP) variations in primary open-angle glaucoma (POAG). METHODS: Forty eyes of 40 POAG patients were drawn into this cross-sectional study. The retinal microvasculature of the macula (superficial and deep layers) and optic nerve [radial peripapillary capillary (RPC)] was examined by OCTA (AngioVue® , Optovue). Optical coherence tomography angiography (OCTA) measurements were conducted at 08:00, 11:00, 15:00 and 20:00 over the course of two consecutive days. Intraocular pressure (IOP) and circulatory parameters were assessed accordingly. Diurnal variations in FD were analysed using linear mixed models. RESULTS: While superficial macular FD and RPC FD revealed not to be affected by diurnal variations (p = 0.492, p = 0.319), FD in the deep layer of the macula increased throughout the day (p < 0.001). Superficial macular FD was influenced significantly by mean arterial pressure (MAP) (p = 0.006) and heart rate (HR) (p = 0.033), whereas FD in the RPC layer was significantly affected by HR (p = 0.010). No statistically significant effect of IOP fluctuations on FD was observed. CONCLUSION: This study shows diurnal fluctuations of deep macular FD measured by OCTA and outlines the relationship between FD and hemodynamic parameters (MAP/HR) in POAG patients.

Changes in retinal flow density measured by optical coherence tomography angiography in patients with carotid artery stenosis after carotid endarterectomy.

The aim of the study presented here was to evaluate retinal and optic nerve head (ONH) perfusion in patients with severe asymptomatic carotid artery stenosis (CAS) compared with healthy controls and to analyze the impact of carotid endarterectomy using optical coherence tomography angiography (OCT-A). 25 eyes of 25 patients with CAS (study group) and 25 eyes of 25 healthy controls (control group) were prospectively included in this study. OCT-A was performed using RTVue XR Avanti (Optovue, Inc, Fremont, California, USA). The flow density data in the superficial and deep retinal OCT-angiogram of the macula and in the radial peripapillary capillary network (RPC) of the ONH were extracted and analyzed. The flow density in the superficial retinal OCT angiogram of the macula and in the ONH were significantly lower in the study group compared with the control group (macula: p = 0.003) (ONH: p = 0.013). The flow density in the ONH improved significantly after carotid endarterectomy (p = 0.004). A reduced flow density was observed in patients with CAS when compared with healthy controls. The flow density also improved after carotid endarterectomy. Quantitative changes in the microvascular density, as measured using OCT-A, could well be useful in the diagnosis of CAS and the evaluation of therapy success.

Effects of high-intensity interval training on optic nerve head and macular perfusion using optical coherence tomography angiography in healthy adults.

BACKGROUND AND AIMS: High-intensity interval training (HIIT) has been identified to be efficient for increasing health-related fitness in general and in lifestyle-induced chronic diseases such as hypertension, obesity and metabolic syndrome. This study aimed to evaluate HIIT effects on optic nerve head (ONH) and macular perfusion in healthy adults using optical coherence tomography angiography (OCTA). METHODS: Fifty-eight healthy participants (22.0 ±â€¯2.02 years, 40 females (69.0%)) performed a 4-week HIIT with two exercise sessions/week: Group 1, 4 × 30 HIIT, running at maximal speed (all-out) for 4 × 30 s with 30 s active recovery, Group 2, 8 × 15 HIIT, running at maximal speed (all-out) for 8 × 15 s with 15 s active recovery. OCTA of the ONH and the macula was performed at baseline and follow-up to detect changes of the foveal avascular zone (FAZ). Flow density was evaluated in the superficial and deep plexus of the central macula, in the radial peripapillary capillary layer, the nerve head layer of the disc region and of the peripapillary region. RESULTS: The mean deep FAZ area and flow density of the superficial layer decreased by 14.00 ±â€¯13.02% and 1.26 ±â€¯3.20%, respectively, in response to overall HIIT (pre vs. post p <0.0001; p = 0.0041). The flow density of the nerve head layer in the peripapillary area showed an overall increase by 1.94 ±â€¯2.39% (pre vs post p < 0.0001). All other parameters showed no difference. CONCLUSIONS: HIIT may be performed to induce changes in ophthalmic measures such as FAZ and nerve head perfusion. OCTA imaging of the central retina and the ONH could represent a sensitive tool for the early detection of systemic vascular changes.

OCT-Angiography reveals reduced vessel density in the deep retinal plexus of CADASIL patients.

Optical coherence tomography angiography (OCT-A) represents the most recent tool in ophthalmic imaging. It allows for a non-invasive, depth-selective and quantitative visualization of blood flow in central retinal vessels and it has an enormous diagnostic potential not only in ophthalmology but also with regards to neurologic and systemic diseases. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary vascular small-vessel disease caused by Notch3 mutations and represents the most common form of hereditary stroke disorder. In this study, CADASIL patients prospectively underwent OCT-A imaging to evaluate retinal and choriocapillaris blood flow as well as blood flow at the optic nerve head. The vessel density of the macular region and the size of the foveal avascular zone in the superficial and deep retinal plexus were determined as well as the vessel density at the optic nerve head and in the choriocapillaris. Additionally, cerebral magnetic resonance images were evaluated. The main finding was that vessel density of the deep retinal plexus was significantly decreased in CADASIL patients compared to healthy controls which may reflect pericyte dysfunction in retinal capillaries.

Comparison of Choriocapillaris Flow Measurements between Two Optical Coherence Tomography Angiography Devices.

PURPOSE: To evaluate choriocapillaris (CC) perfusion in healthy subjects using 2 different optical coherence tomography angiography (OCT-A) devices. PROCEDURES: Macular OCT-A imaging (36 eyes of 36 subjects) was performed using Optovue AngioVue and Zeiss AngioPlex devices. CC decorrelation signal index was assessed, and CC data were analyzed regarding intra-device variability, inter-device correlation, age, signal strength, and fields of view. RESULTS: The intra-device variability of CC measurements in the 3 × 3 mm2 field was 5.3 and 2.6% (Angiovue and Angioplex, coefficients of variation; 6 × 6 mm2: 8.0 and 2.8%, respectively). Mean CC decorrelation signal index in 3 × 3 mm2 was 104.3 ± 6.7 (Angiovue) and 81.3 ± 9.2 (Angioplex) (6 × 6 mm2: 95.6 ± 8.1, 81.1 ± 6.5) with high correlation between both devices (3 × 3 mm2: p = 0.0053; 6 × 6 mm2: p = 0.0139). CC decorrelation signal index in 3 × 3 mm2 was significantly higher in subjects aged ≤58 years compared to subjects aged ≥59 years (Angiovue: 107.3 ± 3.6, 101.3 ± 7.7, p = 0.0156; Angioplex: 84.6 ± 7.6, 78.0 ± 9.5, p = 0.0371). Signal strength was 64.6 ± 8.9 (Angiovue) and 9.5 ± 0.8 (Angioplex). CONCLUSION: Both devices showed low intra-device variability and a high inter-device correlation. CC decorrelation signal index was negatively correlated with advancing age.

Optical coherence tomography (OCT) angiography findings in retinal arterial macroaneurysms.

BACKGROUND: Optical coherence tomography angiography is a novel imaging technique that allows dyeless in vivo visualization of the retinal and choroidal vasculature. The purpose of this study was to describe optical coherence tomography (OCT) angiography findings in patients with retinal arterial macroaneurysms (RAMs). METHODS: Three eyes of three patients with RAMs were retrospectively included. Fundus photography, OCT, fluorescein angiography (FA), and OCT angiography were performed. The entire imaging data was analyzed in detail. RESULTS: OCT angiography could detect the RAMs noninvasively without dye injection. By simultaneously observing the OCT scans, it was possible to determine the depth of the RAMs in the retina, to detect the exact localization in relation to the main vessel, and to determine the level of blood flow in the RAMs. CONCLUSIONS: OCT angiography can clearly visualize RAMs without use of a dye. It also allows layer-specific observation of blood flow in each layer of the RAM. OCT angiography provides additional dynamic information on RAMs, which is not obtained with FA and facilitates a better understanding of its morphology and activity. This information in combination with ICG and fluorescein angiography can help to optimize direct laser treatment.