Retinal Vessel Analyzer Research Articles

Retinal oxygen metabolic function in choroideremia and retinitis pigmentosa.

To measure the retinal oxygen metabolic function with retinal oximetry (RO) in patients with choroideremia (CHM) and compare these findings with retinitis pigmentosa (RP) patients and controls. Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.2years (mean ± SD), 77 eyes from 39 patients with RP (15♀ 24♂; 45.6 ± 14.7years) and 100 eyes from 53 controls (31♀ 22♂; 40.2 ± 13.4years). Main outcome parameters were the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, and their difference (A-V SO2; %) recorded with the oxygen saturation tool of the Retinal Vessel Analyzer (IMEDOS Systems UG, Germany). Statistical analyses were performed with linear mixed-effects models. Eyes suffering from CHM differed significantly from both RP and control eyes, when the retinal oxygen metabolic parameters were taken into account. While RP showed significantly higher A-SO2 and V-SO2 values when compared to controls, CHM showed opposite findings with significantly lower values when compared to both RP and controls (P < 0.001). The A-V SO2, which represents the retinal oxygen metabolic consumption, showed significantly lower values in CHM compared to controls. The retina in CHM is a relatively hypoxic environment. The decrease in oxygen levels may be due to the profound choroidal degeneration, leading to decreased oxygen flux to the retina. RO measurements may help understand the pathogenesis of CHM and RP. These findings may provide useful details to inform the planning of clinical trials of emerging therapies for CHM. What was known before? Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa. RO function in choroideremia is significantly altered when compared to controls. Furthermore, RO in choroideremia shows opposing findings within different oxygen metabolic parameters to those that were so far known for retinitis pigmentosa. By providing insights into the retinal oxygen metabolic mechanisms, RO can help understand the underlying pathophysiology in choroideremia.

OCTA-ReVA: an open-source toolbox for comprehensive retinal vessel feature analysis in optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) has significantly advanced the study and diagnosis of eye diseases. However, current clinical OCTA systems and software tools lack comprehensive quantitative analysis capabilities, limiting their full clinical utility. This paper introduces the OCTA Retinal Vessel Analyzer (OCTA-ReVA), a versatile open-source platform featuring a user-friendly graphical interface designed for the automated extraction and quantitative analysis of OCTA features. OCTA-ReVA includes traditional established OCTA features based on binary vascular image processing, such as blood vessel density (BVD), foveal avascular zone area (FAZ-A), blood vessel tortuosity (BVT), and blood vessel caliber (BVC). Additionally, it introduces new features based on blood perfusion intensity processing, such as perfusion intensity density (PID), vessel area flux (VAF), and normalized blood flow index (NBFI), which provide deeper insights into retinal perfusion conditions. These additional capabilities are crucial for the early detection and monitoring of retinal diseases. OCTA-ReVA demystifies the intricate task of retinal vasculature quantification, offering a robust tool for researchers and clinicians to objectively evaluate eye diseases and enhance the precision of retinal health assessments.

Association Between Corneal Changes and Retinal Oximetry in Diabetes Mellitus.

Diabetes mellitus (DM) causes different corneal changes that are associated with the severity of diabetic retinopathy. To identify the pathophysiological reasons for this, corneal tomography and optical densitometry (COD) were combined with retinal oximetry. Patients with DM and healthy subjects were included in this pilot study. Spatially resolved corneal thickness and COD were assessed using the Pentacam HR (Oculus). The pachymetry difference (PACDiff) was calculated as an indicator of an increase in the peripheral corneal thickness. Oxygen saturation (SO2) of the retinal vessels was measured using the Retinal Vessel Analyzer (Imedos Systems UG). Subsequently, the associations between corneal and retinal parameters were analyzed. Data from 30 patients with DM were compared with those from 30 age-matched healthy subjects. In DM, arterial (P = 0.048) and venous (P < 0.001) SO2 levels were increased, and arteriovenous SO2 difference was decreased (P < 0.001). In patients, PACDiff was higher than that in healthy subjects (P < 0.05), indicating a stronger increase in peripheral corneal thickness. The COD was reduced in DM (P = 0.004). The PACDiff of concentric rings with a diameter of 4 mm (r = -0.404; P = 0.033) to 8 mm (r = -0.522; P = 0.004) was inversely correlated with the arteriovenous SO2 difference. Furthermore, PACDiff 4 mm was negatively associated with arterial SO2 (r = -0.389; P = 0.041), and the COD of the peripheral corneal areas correlated positive with arterial SO2 (COD total 10-12 mm: r = 0.408; P = 0.025). These associations might indicate a common pathogenesis of corneal and retinal changes in DM, which could be caused by reduced oxygen supply, mitochondrial dysfunction, oxidative stress, and cytokine effects.

Retinal microcirculation alterations in rheumatoid arthritis patients compared to healty volunteers and their correlation to the disease activity and duration of disease

Aims/Purpose: Patients with rheumatoid arthritis (RA) have a high risk of developing cardiovascular diseases due to endothelial dysfunction, which is a risk factor for cardiovascular events. The retinal Vessel Analyzer (RVA, IMEDOS Systems) can capture retinal vessels non‐invasively in real‐time and analyse their dynamic responses to stimuli.Methods: In order to assess the structural and functional changes in the retinal microvasculature, a non‐invasive Retinal Vessels Analyzer (RVA) was used to study 44 patients with RA (mean age 57.4 ± 13.2 years) and compare them to a control group of 44 age‐matched healthy individuals. The RVA was used to measure various parameters, including the Central Retinal Artery Equivalent (CRAE), Central Retinal Vein Equivalent (CRVE), and Arterio‐Venous Ratio (AVR), as well as the response of the retinal vessels to flickering light. After a 50 s baseline, rectangular shape, monochromatic flickering light (530–600 nm) of 12.5 Hz for 20 s was applied three times. The dilation of retinal vessels after flicker light stimulation was analysed.Results: The results of the study showed that patients with RA had significantly higher CRVE and lower AVR compared to the control group (p = 0.04 and p = 0.01, respectively), indicating structural changes in the retinal microvasculature. The patients with RA also had a significantly stronger arterial dilation response to flickering light compared to the control group (n = 43), indicating functional changes in the retinal microvasculature. In patients with moderate to high disease activity according to the Disease Activity Score (DAS‐28 &gt; 3.2) (n = 9), there was a negative significant correlation between the maximum arterial diameter (aMAX) and interleukin‐6 (IL‐6).Conclusions: These findings suggest that RVA can be a useful tool for detecting structural and functional changes in the retinal microvasculature of patients with RA and that the disease activity and inflammation in RA may be related to these changes. However, the study notes that a larger cohort with a wider range of disease activity is needed to fully understand the effect of chronic inflammatory diseases on endothelial function.

Retinal oxygen extraction and hyperemic response in patients with Type II diabetes at different stages of non‐proliferative diabetic retinopathy

Purpose: Diabetic retinopathy (DR) is a worldwide cause of irreversible vision loss. Vascular factors such as reduced oxygen supply and impaired neurovascular coupling play a major role in the development of DR. We therefore investigated retinal oxygen metabolism and functional hyperemia in patients with Type II diabetes at different stages of non‐proliferative DR and healthy controls.Methods: To study retinal oxygen metabolism, a total of 67 patients with Type II diabetes (34 patients with no, 15 with mild and 18 with moderate‐to‐severe DR) and 20 healthy controls were recruited. We used the oxygen module of a Retinal Vessel Analyzer to measure retinal oxygen saturation in arteries and veins, and a custom‐built Doppler optical coherence tomography (DOCT) system to assess total retinal blood flow (TRBF). Values of retinal oxygen saturation and TRBF were then used to calculate retinal oxygen extraction. To measure the hyperaemic response, 29 patients with no, 12 with mild, 15 with moderate‐to‐severe DR and 20 healthy controls were included. Retinal blood flow was assessed before and during visual stimulation by combined measurement of retinal vessel calibres and blood velocity using the Dynamic Vessel Analyzer (Imedos, Germany) and DOCT.Results: Retinal oxygen extraction was lowest in patients with moderate‐to‐severe DR (1.78 ± 0.57 μL O2/min, p = 0.040 vs. healthy controls), followed by mild DR (1.90 ± 0.77 μL O2/min), no DR (2.14 ± 0.6 μL O2/min) and healthy controls (2.24 ± 0.57 μL O2/min). Compared to healthy controls (40.4 ± 27.2%), flicker responses were significantly decreased in patients with DR depending on the stage of DR (no DR 37.7 ± 26.0%, mild DR 26.2 ± 28.2%, moderate‐to‐severe DR 22.3 ± 13.9%; p = 0.035, ANOVA).Conclusions: Our results indicate that retinal oxygen extraction as well as hyperaemic response decreases with increasing severity of DR. Further studies are needed to assess whether these retinal functional changes can be used to identify high‐risk patients.

Automated Retinal Vessel Analysis Based on Fundus Photographs as a Predictor for Non-Ophthalmic Diseases-Evolution and Perspectives.

The study of retinal vessels in relation to cardiovascular risk has a long history. The advent of a dedicated tool based on digital imaging, i.e., the retinal vessel analyzer, and also other software such as Integrative Vessel Analysis (IVAN), Singapore I Vessel Assessment (SIVA), and Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE), has led to the accumulation of a formidable body of evidence regarding the prognostic value of retinal vessel analysis (RVA) for cardiovascular and cerebrovascular disease (including arterial hypertension in children). There is also the potential to monitor the response of retinal vessels to therapies such as physical activity or bariatric surgery. The dynamic vessel analyzer (DVA) remains a unique way of studying neurovascular coupling, helping to understand the pathogenesis of cerebrovascular and neurodegenerative conditions and also being complementary to techniques that measure macrovascular dysfunction. Beyond cardiovascular disease, retinal vessel analysis has shown associations with and prognostic value for neurological conditions, inflammation, kidney function, and respiratory disease. Artificial intelligence (AI) (represented by algorithms such as QUantitative Analysis of Retinal vessel Topology and siZe (QUARTZ), SIVA-DLS (SIVA-deep learning system), and many others) seems efficient in extracting information from fundus photographs, providing prognoses of various general conditions with unprecedented predictive value. The future challenges will be integrating RVA and other qualitative and quantitative risk factors in a unique, comprehensive prediction tool, certainly powered by AI, while building the much-needed acceptance for such an approach inside the medical community and reducing the "black box" effect, possibly by means of saliency maps.

Opening a window to the acutely injured brain: Simultaneous retinal and cerebral vascular monitoring in rats.

Many recent research projects have described typical chronic changes in the retinal vasculature for diverse neurovascular and neurodegenerative disorders such as stroke or Alzheimer's disease. Unlike cerebral vasculature, retinal blood vessels can be assessed non-invasively by retinal vessel analysis. To date, there is only a little information about potential simultaneous reactions of retinal and cerebral vessels in acute neurovascular diseases. The field of applications of retinal assessment could significantly be widened if more information about potential correlations between those two vascular beds and the feasibility of non-invasive retinal vessel analysis in acute neurovascular disease were available. Here, we present our protocol for the simultaneous assessment of retinal and cerebral vessels in an acute setting in anesthetized rats using a non-invasive retinal vessel analyzer and a superficial tissue imaging system for laser speckle contrast analysis via a closed bone window. We describe the experimental set-up in detail, outline the pitfalls of repeated retinal vessel analyses in an experimental set-up of several hours, and address issues that arise from the simultaneous use of two different assessment tools. Finally, we demonstrate the robustness and variability of the reactivity of retinal vessels to hypercapnia at baseline as well as their reproducibility over time using two anesthetic protocols common for neurovascular research. In summary, the procedures described in this protocol allow us to directly compare retinal and cerebral vascular beds and help to substantiate the role of the retina as a "window to the brain."

Functionality of retinal vessels in central serous retinopathy: A comparison between eplerenone and photodynamic therapy.

To investigate retinal vessels functionality in patients with acute central serous chorioretinopathy (CSC) undergoing oral eplerenone or photodynamic therapy (PDT) using Retinal Vessel Analyzer (RVA) and Dynamic Vessel Analyzer (DVA), respectively. Treatment naïve acute CSC patients presenting between May 2017 and June 2017 were recruited. A complete ophthalmological examination was performed in all participants before and after oral eplerenone (eplerenone group) or half-dose PDT (PDT group). Eighteen eyes of 18 patients affected by acute CSC underwent either oral eplerenone (10 eyes of 10 patients, 47.6 ± 8.9 years old) or half-dose PDT (8 eyes of 8 patients, 57.4 ± 6.2 years old), respectively. After 2 months of treatment, non-significant variations of static retinal vessels analysis, dynamic arterial and venous dilatation were reported in eplerenone group. Similarly, in PDT group non-significant variations of static retinal vessels analysis, dynamic arterial and venous dilatation were found after 2 months of treatment. Static and dynamic retinal functionalities in acute CSC may not be significantly improved by oral eplerenone and half-dose PDT. Although their choroidal effects, these treatments could not exert a significant effect on retinal vessels motility. Thus, both local and systemic therapies might not help avoiding the onset of vascular and other retinal known alterations of CSC.

Oxygen metabolic retinal function in retinitis pigmentosa correlates with disease severity

AbstractPurpose: The aim of our study was to evaluate retinal function with white light dark‐adapted full‐field sensitivity threshold (FST) and find possible correlations with metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP).Methods: In this prospective observational study (BASEC 2020–00122), FST and RO measurements were performed on 66 RP eyes (33 subjects, 12♀ 21♂) aged between 18 and 80 years (mean 43.2 years); all eyes were graded for disease severity. Main outcome parameters were white FST thresholds using the Diagnosys Espion system with the ColorDomeTM LED full‐field stimulator (Diagnosys LLC, Lowell, MA) as well as the main RO parameters: the mean arterial (A‐SO2; %), venular (V‐SO2; %) oxygen saturation, their difference (A‐V SO2; %), and the corresponding mean diameters of the peripapillary retinal arterioles (D‐A; μm) and venules (D‐V; μm) recorded with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). In addition, semi‐automated kinetic perimetry (V4e, III4e, I4e, III3e isopters, Octopus 900®, Haag‐Streit AG Bern, Switzerland) was performed and included in the linear mixed‐effects models analysis calculated with SPSS®.Results: Neither the oxygen saturation parameters (p &gt; 0.21) nor the D‐A and D‐V (p &gt; 0.13) showed significant correlations with the FST. However, when compared systematically with the visual field (VF) areas of the different isopters, RO parameters V‐SO2 (p = 0.024) and A‐V SO2 (p &lt; 0.02) showed significant correlations. Furthermore, both V‐SO2 and A‐V SO2 showed gradual changes with more pronounced impairment in oxygen metabolic function in advanced stages of RP when analysed in subgroups of disease severity grades.Conclusions: In advanced stages of RP, RO showed a significant association with standardized VF testing parameters and presented with gradual changes of more pronounced impairment in retinal oxygen metabolic function. Unlike standardized VF parameters, white dark‐adapted FST does not appear to correlate with retinal oxygen metabolic function in RP patients, implying that the two examinations may capture unrelated aspects of the retinal pathological process.

Metabolic long‐term monitoring of transcorneal electrical stimulation in retinitis pigmentosa

AbstractPurpose: Transcorneal electrical stimulation (TES) is a new therapeutical approach for retinitis pigmentosa (RP). With progression of RP, degeneration of photoreceptors results in lower oxygen consumption of the retina. Retinal oximetry (RO) is a noninvasive method to analyse oxygen saturation in retinal vessels and has shown promising short‐term results as a therapy monitoring tool for TES. The aim of our study was to measure the long‐term effects of TES on RO parameters over a period of 3 years (3Y).Methods: A total of 18 eyes of 9 subjects (5♀ 4♂) suffering from RP were examined at baseline (BL), 6 months, and 3Y of TES (OkuStim®) treatment. TES was performed for 30 min once a week at 200% of the individual phosphene threshold simultaneously on both eyes. The oxygen saturation was examined at BL and following TES therapy with the oxygen saturation tool of the Retinal Vessel Analyser (IMEDOS Systems UG, Jena, Germany). The global oxygen saturation parameters (in %), within 1.0–1.5 optic‐disc diameters from the disc margin, in retinal arterioles (A‐SO2) and venules (V‐SO2) were measured and their difference (A‐V SO2) was calculated. In addition, we recorded the diameters in the main arterioles (D‐A) and venules (D‐V). ANOVA‐based linear mixed‐effects models were employed for statistical analysis using SPSS®.Results: After 3Y of TES treatment both the mean A‐SO2 (from 96.35 ± 12.76% to 100.89 ± 5.87%, p = 0.22) and V‐SO2 (from 62.20 ± 11.55% to 64.55 ± 8.24%, p = 0.77) increased slightly. The A‐V SO2, which corresponds to the oxygen consumption of the retina, presented also with a slight increment from 34.15 ± 9.68% at BL to 36.23 ± 7.71% without reaching statistical significance (p = 0.27). TES also did not appear to alter the vascular diameter parameters, D‐A and D‐V (p &gt; 0.05).Conclusions: Our long‐term observations indicate that TES therapy in RP might lead to a slight increment in oxygen consumption of the retina. However, a larger cohort and longer duration may be needed to adequately power a follow‐up study and to confirm this trend reflecting a possible benefit of TES for RP.

Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk.

Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30−55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1: <5%—n = 53) or a normal FMD response (group 2: 7−10%—n = 47). Results: Individuals exhibiting reduced FMD responses showed a reduced baseline-corrected microvascular arterial dilation response to flickering light (p = 0.039). In addition, they also exhibited a reduced arteriolar maximum dilation (p = 0.034), as well as a longer dilation reaction time (p = 0.048) and a lower dilation amplitude (p = 0.042) when compared to those with normal FMD values. Conclusion: In otherwise healthy middle-aged individuals, early signs of vascular dysfunction are reflected simultaneously at both macro- and microvascular levels.

Retinal Microvascular Abnormalities and Systemic Arterial Stiffness Are the First Manifestation of Cardiovascular Abnormalities in Patients with Untreated Moderate to Severe Obstructive Sleep Apnoea and with Low to Intermediate Cardiovascular Risk-A Pilot Study.

This study aimed to investigate macro- and microvascular function parameters and their relationship with known markers of cardiovascular risk in patients with untreated moderate to severe obstructive sleep apnoea (OSA). Fourteen patients with moderate to severe OSA and fourteen controls were included in the present study. General assessments included BMI, systemic blood pressure (BP) and circulating markers for oxidative stress and endothelial function. Additional assessments included 24 h BP and heart rate monitoring, as well as the assessment of heart rate variability. Macro- and microvascular assessments included augmentation index, carotid intima-media thickness, brachial artery flow-mediated dilation, as well as various retinal microvascular function assessments, using the Dynamic Retinal Vessel Analyzer. All participants completed the Short Form Health Survey, Functional Outcomes of Sleep Questionnaire, and Epworth Sleepiness Scale. The results show that, in comparison to controls, BMI (p = 0.003) and AIx (p = 0.025) were significantly higher in the OSA group. There was, however, no significant difference between groups with regard to other measured systemic general, vascular and circulatory parameters (all p > 0.05). Nevertheless, the retinal microvascular function showed various alterations in the OSA patients, including a delayed reaction time in response to flicker (p = 0.047), as well as a decreased dilation amplitude (p = 0.004), dilation slope (p = 0.004), and post-flicker constriction (p = 0.015). In addition, the observed SlopeAD alterations correlated negatively with BMI values only in the OSA group (r = −0.46, p = 0.045). In conclusion, individuals with untreated moderate to severe OSA but without overt CVD, exhibit signs of increased arterial stiffness and retinal microvascular dysfunction, which can be early indicators for future vascular complications.

Retinal Oxygen Metabolism in Patients With Type 2 Diabetes and Different Stages of Diabetic Retinopathy.

The aim of this cross-sectional study was to assess retinal oxygen metabolism in patients with type 2 diabetes and different stages of nonproliferative diabetic retinopathy (DR) (n = 67) compared with healthy control subjects (n = 20). Thirty-four patients had no DR, 15 had mild DR, and 18 had moderate to severe DR. Retinal oxygen saturation in arteries and veins was measured using the oxygen module of a retinal vessel analyzer. Total retinal blood flow (TRBF) was measured using a custom-built Doppler optical coherence tomography system. Retinal oxygen extraction was calculated from 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 ± 9.2 μL/min) and mild DR (41.8 ± 15.0 μL/min) than in healthy subjects (37.2 ± 5.7 μL/min) and patients with moderate to severe DR (34.6 ± 10.4 μL/min). Retinal oxygen extraction was the highest in healthy subjects (2.24 ± 0.57 μL O2/min), followed by patients with no DR (2.14 ± 0.6 μL O2/min), mild DR (1.90 ± 0.77 μL O2/min), and moderate to severe DR (1.78 ± 0.57 μL O2/min, P = 0.040 vs. healthy subjects). These results indicate that retinal oxygen metabolism is altered in patients with type 2 diabetes. Furthermore, retinal oxygen extraction decreases with increasing severity of DR.

Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance

Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.

This issue of ACTA

This issue of ACTA

Peripapillary Oxygenation and Retinal Vascular Responsiveness to Flicker Light in Primary Open Angle Glaucoma.

The aim of our study was to evaluate peripapillary oxygenation and its relationship to retinal vascular responsiveness to flicker light in patients with primary open angle glaucoma (POAG). Retinal vessel oxygen saturation was measured in 46 eyes of 34 Caucasian patients with POAG and in 21 eyes of 17 age-matched controls using the oximetry tool of Retinal Vessel Analyser (RVA: IMEDOS Systems UG, Jena, Germany). The mean oxygen saturation of the major arterioles (A-SO2; %) and venules (V-SO2; %), as well as the corresponding arterio–venular difference (A-V SO2; %), were calculated. We also measured retinal vascular responsiveness (RVR) to flicker light by means of RVA. Glaucoma patients were divided in two subgroups according to their median arteriolar and venular vascular responsiveness to flicker light (AFR and VFR). Glaucomatous damage was assessed by optical coherence tomography (Carl Zeiss Meditec, Dublin, CA, USA) and static automated perimetry (Octopus, program G2/standard strategy: Haag-Streit International, Köniz, Switzerland). In addition, we calculated the mean peripapillary oxygen exposure [ppO2E; %/µm] by dividing the mean A-V SO2 with the mean retinal nerve fibre layer (RNFL) thickness. In glaucoma patients, A-SO2 and V-SO2 values were significantly increased, and their difference decreased when compared to controls (p < 0.017; linear mixed-effects model). Grouped with respect to retinal vascular responsiveness to flicker light, subjects with reduced VFR (≤2.9%) had significantly higher ppO2E (0.49 ± 0.08%/µm, respectively, 0.43 ± 0.06%/µm; p = 0.027). Additionally, higher ppO2E in glaucoma patients correlated negatively with the neuroretinal rim area (p < 0.001) and the RNFL thickness (p = 0.017), and positively with the mean defect of the visual field (p = 0.012). Reduced venular vascular responsiveness in our glaucoma patients was associated with increased peripapillary oxygenation exposure. Thus, ganglion cells and their axons in glaucomatous eyes with reduced retinal vascular responsiveness are prone to be more exposed to higher oxidative stress, probably contributing to the further progression of glaucomatous damage.

Obesity, blood pressure and retinal microvascular phenotype in a bi-ethnic cohort of young children

Background and aimsChildhood obesity and high blood pressure (BP) are main determinants for cardiovascular disease development with regional and ethnic differences. Narrower arteriolar (CRAE) and wider venular (CRVE) retinal vessel diameters are sensitive markers of early vascular compromise in children. We aimed to compare retinal vessel diameters and investigate associations and odds ratios with body mass index (BMI) and BP in a multi-national/ethnic childhood study. MethodsBMI, systolic (SBP) and diastolic BP (DBP) were screened in 929 black and white South African (SA) and 1171 Swiss children (aged 5–9 years). Retinal assessments were performed using a retinal vessel analyzer to determine CRAE and CRVE. ResultsBlack SA children had wider CRVE compared to white SA and Swiss children (all p < 0.001). However, BMI or BP was not associated with CRVE in black SA children. Higher BMI and BP associated with narrower CRAE in all children, except for BMI in black SA children, in whom narrower CRAE was found for every unit increase in SBP (β = −0.199 μm, p = 0.001) and DBP (β = −0.312 μm, p < 0.001). Obesity (OR:1.38[1.01; 1.89]), hypertension (OR:1.90[1.53; 2.36]) and black ethnicity (OR:1.50[1.18; 1.92]) increased the likelihood for arteriolar narrowing. ConclusionsBlack SA children presented with wider retinal venules compared to their white SA and Swiss peers, which was unexplained by conventional risk factors. The overall risk of arteriolar narrowing was driven by obesity, hypertension and ethnicity. Our findings indicate the importance to differentiate cardiovascular risk by microvascular phenotype in different populations and ethnicity early in life.

Full-field sensitivity threshold and the relation to the oxygen metabolic retinal function in retinitis pigmentosa.

The aim of our study was to evaluate retinal function with white light dark-adapted full-field sensitivity threshold (FST) and find possible correlations with metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP). In this prospective observational study (BASEC 2020-00,122), FST and RO measurements were performed on 66 RP eyes (33 subjects, 12♀ 21♂) aged between 18 and 80years (mean 43.2years); all eyes were graded for disease severity. Main outcome parameters were white FST thresholds using the Diagnosys Espion system with the ColorDomeTM LED full-field stimulator (Diagnosys LLC, Lowell, MA) as well as the main RO parameters: the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, their difference (A-V SO2; %), and the corresponding mean diameters of the peripapillary retinal arterioles (D-A; μm) and venules (D-V; μm) recorded with the oxygen saturation tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). In addition, semi-automated kinetic perimetry (V4e, III4e, I4e, III3e isopters, Octopus 900®, Haag-Streit AG Bern, Switzerland) was performed and included in the linear mixed-effects models analysis calculated with SPSS®. Neither the oxygen saturation parameters (p > 0.21) nor the D-A and D-V (p > 0.13) showed significant correlations with the FST. However, when compared systematically with the visual field (VF) areas of the different isopters, RO parameters V-SO2 (p = 0.024) and A-V SO2 (p < 0.02) showed significant correlations. Furthermore, both V-SO2 and A-V SO2 showed gradual changes with more pronounced impairment in oxygen metabolic function in advanced stages of RP when analyzed in subgroups of disease severity grades. In contrast to standardized VF parameters, white dark-adapted FST appears not to correlate with retinal oxygen metabolic function measured with RO in patients with RP, suggesting that the two examinations may capture unrelated aspects of the retinal pathological process. However, RO showed a significant association with standardized VF testing parameters and may, therefore, offer an alternative outcome measure for interventional trials.

Oxygen exposure in inherited diseases of the retina

AbstractPurposePatients with inherited retinal diseases (IRDs) share altered retinal metabolic function. The aim of our study was to investigate the relationship between retinal metabolic alterations (retinal vessel Oximetry, RO) and structural findings (central retinal thickness and retinal nerve fibre layer thickness, RNFL) in IRDs.MethodsA total of 181 eyes of 92 subjects were examined: 121 eyes of 62 patients with IRDs were compared to 60 eyes of 30 healthy age‐matched controls. The retinal vessel oximetry was performed with the oxygen saturation measurement tool of the Retinal Vessel Analyser (RVA; IMEDOS Systems UG, Jena, Germany). The oxygen saturation in all four major peripapillary retinal arterioles (A‐SO2; %) and venules (V‐SO2; %) were measured and their difference (A‐V SO2; %) was calculated. In addition, we calculated the mean central retinal oxygen exposure (cO2‐E; %/µm) and the mean peripapillary oxygen exposure (pO2‐E; %/µm) per micron of central retinal thickness and nerve fibre layer thickness.ResultsRod‐cone dystrophy patients had the highest V‐SO2 and A‐SO2, the lowest A‐V SO2, the narrower D‐A and D‐V and the thickest RNFL, when compared to controls (p≤0.040), but also to patients with other IRDs. Furthermore, in rod‐cone dystrophies, the cO2‐E and the pO2‐E were higher in comparison to controls and to patients with other IRDs (p≤0.005). Cone‐rod dystrophy patients had the lowest cO2‐E compared to controls and patients with other IRDs (p≤0.035). Evaluated in central zones, the cO2‐E was significantly different when comparing CRD‐ against RCD patients in all zones (p&lt;0.001), whereas against controls and patients with inherited macular dystrophy only in zones 1 and 2 (p≤0.018). The oxygen exposure was also the highest in the RCD, for both the nasal and the temporal peripapillary area among evaluated groups (p ≤ 0.025)ConclusionsClearly demonstrated through the O2‐E comparisons, rod‐cone dystrophy eyes seem to be more exposed to oxygen, the later presumably leading to more pronounced oxidative damage‐related remodeling.

Oxygenation in glaucoma patients: Influence of age and oxidative stress

AbstractPurposeTo evaluate retinal oxygenation in glaucoma patients and to compare it with that of healthy controls.MethodsRetinal vessel oxygen saturation was measured in 46 eyes of 34 Caucasian individuals with primary open angle glaucoma (POAG) and in 21 eyes of 17 age‐matched controls using the oximetry tool of Retinal Vessel Analyser (RVA: IMEDOS Systems UG, Jena, Germany). The mean oxygen saturation of the major arterioles (A‐SO2) and venules (V‐SO2), as well as the corresponding arterio‐venular difference (A‐V SO2), were calculated. Glaucomatous damage was assessed by Optical Coherence Tomography (Carl Zeiss Meditec, Dublin, CA, USA) and static automated perimetry (Octopus, program G2/ standard strategy: Haag‐Streit International, Köniz, Switzerland). In addition, we calculated the mean retinal oxygen extraction (O2‐E) per micron of nerve fibre layer thickness, O2‐E [µm/%] by dividing the mean retinal nerve fibre layer (RNFL) thickness with the mean A‐V SO2.ResultsIn glaucoma patients, A‐SO2 and V‐SO2 values were significantly increased and their difference decreased, when compared to controls (p &lt; 0.017; linear mixed‐effects model). Whereas V‐SO2 and A‐V SO2 were not influenced by age, the A‐SO2 was severely reduced and the O2‐E significantly increased in elderly glaucoma patients, than in younger glaucoma patients (p = 0.003, correspondingly p = 0.004). Also, higher O2‐E in glaucoma patients correlated negatively with the neuroretinal rim area (p &lt; 0.019), and positively with the mean defect of the visual field (p = 0.012)ConclusionsThe presented structure‐metabolic approach supposes that ganglion cells axons in glaucomatous eyes are influenced by aging and are probaly more exposed to oxidative stress, which seems to contribute to progression of glaucomatous damage.