Retinal Oxygen 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.

P215 EFFECT OF OXYGEN LOADING MODEL ON RETINOPATHY OF PREMATURITY IN INTRAUTERINE GROWTH RETARDED MICE

Background and Objective: Fetal growth retardation (IUGR) not only induces various complications in newborns, but is also known to be associated with the future development of lifestyle-related diseases and conditions. Therefore, the neonatal treatment often struggles between life-sustaining and oxygen administration. We have previously reported that IUGR mice born from mothers raised on a low-protein diet show enhanced vascular remodeling. The mechanism is influenced by an increased inflammatory response associated with a decreased angiogenic response due to hypoxic loading in a femoral artery cuff implantation model. Based on this, we hypothesized that in IUGR mice, the reduced angiogenic response in retinopathy of prematurity may work to suppress the onset of the disease. To test this hypothesis, we examined the effects of oxygen loading on the retinal neovasculature using the mouse oxygen-induced retinopathy of prematurity (OIR) model. Methods The OIR model was created in newborns born from mothers raised on a normal protein diet (20%) and in IUGR newborns born from mothers raised on a low protein diet (8%). Specifically, the newborns were exposed to 75% hyperoxia for 5 days starting at 7 days of age, and retinal neovascularization was histologically evaluated 5 days later at 17 days of age for comprehensive transcriptome analysis. Results: Compared to normal birth weight OIR mice, retinal neovascularization was significantly suppressed in OIR mice with FGR. Retinal RNA sequencing revealed decreased expression of angiogenic factors that trigger pathological retinal neovascularization, such as the mitogen-activated protein kinase pathway (MAPK) pathway and corresponding upstream signaling pathways. Conclusions Our findings suggest that IUGR neonates have a weaker response to retinal oxygen stress and consequently are likely to have reduced retinopathy of prematurity. These results indicate that the risk of developing retinopathy of prematurity is attenuated in IUGR neonates compared to mature neonates with normal birth weight.

Relationship Between Retinal Oxygen Saturation and the Severity of Visual Field Damage in Glaucoma.

Increased oxygen saturation (StO 2 ) was significantly associated with the severity of visual field (VF) damage in patients with glaucoma. To investigate the association between retinal StO 2 percentage and the severity of VF loss in glaucoma. A total of 198 eyes from 131 patients with glaucoma were included in this cross-sectional study. Participants underwent imaging using ocular oximetry (Zilia) and 24-2 Swedish Interactive Threshold Algorithm standard VF (Carl Zeiss-Meditec). StO 2 (%) was measured at 2 locations of the peripapillary optic nerve head (superotemporal, and inferotemporal). Measurements were reported as the mean of at least 5 measurements in each location. Associations between the severity of VF loss, reported as mean deviation, and StO 2 (%) were calculated. A total of 198 eyes of 131 patients (mean (95% CI) age, 71.1 (68.9,73.3) years, 68 females (51.9%), and 63 males (48.1%) were analyzed. In univariable analysis, higher StO 2 -0.06 (-0.12, 0.00) was associated with severity in all hemifields ( P = 0.047). Multivariate regression analysis showed that each 1% increase in StO 2 was associated with -0.06 (-0.12, -0.00) dB loss in mean deviation in all hemifields ( P = 0.043). In multivariate regression analysis in the superior hemifields, higher StO 2 -0.07 (-0.16, 0.01) tended to be associated with superior hemifield severity ( P = 0.09). Retinal oximetry enabled the continuous quantitative measurement of retinal StO 2. Increased StO 2 was significantly associated with the severity of VF damage in patients with glaucoma.

Spectral reconstruction of fundus images using retinex-based semantic spectral separation transformer, applied for retinal oximetry

Multispectral imaging, a non-invasive technique to measure retinal oxygen saturation levels, is limited due to its time-consuming and expensive nature. In this paper, we present R3ST (Retinex-based Semantic Spectral Separation Transformer), an innovative end-to-end method for RGB fundus image spectral reconstruction. Our proposed model leverages RGB images to reconstruct multispectral images, making retinal oximetry more accessible for diagnostics.Existing spectral reconstruction methods face challenges in achieving high accuracy and generalizing across camera sources, affecting diagnostic results. R3ST addresses these issues through an unsupervised semantic spectral separation module that strives to encourage the separate reconstruction of pixels with different semantics as much as possible. Additionally, we introduce an oxygen saturation loss to improve reconstruction accuracy within the relevant regions. To overcome the limitations of generalization properties, our model incorporates a self-supervised Retinex reflectance extraction module. This simulates various imaging systems and extracts reflectance information from fundus images for reconstruction.Extensive experiments demonstrate R3ST’s superior performance in spectral reconstruction accuracy, making retinal oximetry a more viable, cost-effective diagnostic option that provides essential eye health and systemic health information. The code of R3ST is available at https://github.com/telesc0pe/R3ST.

Impaired retinal oxygen metabolism and perfusion are accompanied by plasma protein and lipid alterations in recovered COVID-19 patients

The aim of the present study was to investigate retinal microcirculatory and functional metabolic changes in patients after they had recovered from a moderate to severe acute COVID-19 infection. Retinal perfusion was quantified using laser speckle flowgraphy. Oxygen saturation and retinal calibers were assessed with a dynamic vessel analyzer. Arterio-venous ratio (AVR) was calculated based on retinal vessel diameter data. Blood plasma samples underwent mass spectrometry-based multi-omics profiling, including proteomics, metabolomics and eicosadomics. A total of 40 subjects were included in the present study, of which 29 had recovered from moderate to severe COVID-19 within 2 to 23 weeks before inclusion and 11 had never had COVID-19, as confirmed by antibody testing. Perfusion in retinal vessels was significantly lower in patients (60.6 ± 16.0 a.u.) than in control subjects (76.2 ± 12.1 a.u., p = 0.006). Arterio-venous (AV) difference in oxygen saturation and AVR was significantly lower in patients compared to healthy controls (p = 0.021 for AVR and p = 0.023 for AV difference in oxygen saturation). Molecular profiles demonstrated down-regulation of cell adhesion molecules, NOTCH3 and fatty acids, and suggested a bisphasic dysregulation of nitric oxide synthesis after COVID-19 infection. The results of this study imply that retinal perfusion and oxygen metabolism is still significantly altered in patients well beyond the acute phase of COVID-19. This is also reflected in the molecular profiling analysis of blood plasma, indicating a down-regulation of nitric oxide-related endothelial and immunological cell functions.Trial Registration: ClinicalTrials.gov (https://clinicaltrials.gov) NCT05650905.

Electrodiagnostic Biomarkers in Paraneoplastic Retinopathy.

Paraneoplastic retinopathy (PNR) is a rapid-onset photoreceptor and post-photoreceptor dysfunction triggered by a cross-reaction between antigens expressed by the underlying tumour and retinal proteins. The present study aims to determine the electrodiagnostic biomarkers that support the diagnosis of PNR and evaluate the effect of treatment. A retrospective observational case-controlled study including 25 patients with suspected PNR, of which 11 patients were diagnosed with PNR. The presence of PNR was confirmed based on clinical examination, supported by colour fundus photography, fundus autofluorescence imaging, optical coherence tomography, fluorescein angiography, retinal vessel oximetry, colour test, full-field electroretinogram (ffERG), on-/off ERG, S-cone ERG, and multifocal ERG (mfERG). The relationships between the clinical symptomatology and the effect of therapy were evaluated. All PNR patients (Nr: 11) presented with subjective symptoms of newly reported central vision or visual field deterioration. Posterior segment findings showed a severe patchy-like retinal atrophy, attenuation of the retinal vessels, and a waxy optic disc. Optical coherence tomography revealed a discontinued ISe line, and multiple hyperreflective foci. Retinal vessel oxygen saturation was increased. Multifocal ERG revealed reduced central and paracentral responses and ffERG severely attenuated scotopic-, photopic-, on-/off- and S-cone responses. The colour vision test revealed a tritan-tetartan-weakness. Two of the PNR patients underwent rituximab therapy with no further progression and even recovery of electrodiagnostic responses.In 1 nPNR (non-paraneoplastic retinopathy) patient (total Nr: 14) pseudoxanthoma elasticum-related retinopathy was the reason for impaired vision. In 3 of 13 patients with bronchopulmonary cancer a MEK- and FGFR-inhibitor- drug toxicity was the reason for the visual deterioration. Careful investigation for signs of central and/or peripheral visual field deterioration must be performed in the presence of history of a co-existing malignancy. The possibility of PNR should be taken into account. The electrodiagnostic biomarkers, suggested in this study, may help to promptly recognise PNR and also to evaluate the effect of implemented therapy.

The retinal oxygen metabolism and hemodynamics as a substitute for biochemical tests to predict nonproliferative diabetic retinopathy.

Predicting the occurrence of nonproliferative diabetic retinopathy (NPDR) using biochemical parameters is invasive, which limits large-scale clinical application. Noninvasive retinal oxygen metabolism and hemodynamics of 215 eyes from 73 age-matched healthy subjects, 90 diabetic patients without DR, 40 NPDR, and 12 DR with postpanretinal photocoagulation were measured with a custom-built multimodal retinal imaging device. Diabetic patients underwent biochemical examinations. Two logistic regression models were developed to predict NPDR using retinal and biochemical metrics, respectively. The predictive model 1 using retinal metrics incorporated male gender, insulin treatment condition, diastolic duration, resistance index, and oxygen extraction fraction presented a similar predictive power with model 2 using biochemical metrics incorporated diabetic duration, diastolic blood pressure, and glycated hemoglobin A1c (area under curve: 0.73 vs. 0.70; sensitivity: 76% vs. 68%; specificity: 64% vs. 62%). These results suggest that retinal oxygen metabolic and hemodynamic biomarkers may replace biochemical parameters to predict the occurrence of NPDR .

Pretreatment ocular blood flow and retinal oxygen metabolism inthe acute uveitic phase is associated with final outcome in Vogt-Koyanagi-Harada disease.

To investigate the association between pretreatment blood flow velocity in the choroid and optic nerve head (ONH) and retinal oxygen metabolism in the acute uveitic phase and the development of 'sunset glow fundus' in Vogt-Koyanagi-Harada (VKH) disease. Retrospective analysis of 41 patients (82 eyes). Laser speckle flowgraphy and retinal oximetry measurements were performed at the presentation. The main outcome measure was the development of 'sunset glow fundus'. Twenty patients (40 eyes) presented in the phase preceding anterior segment inflammation (early presentation), and 21 patients (42 eyes) presented with anterior segment inflammation (late presentation). In ONH, mean blur rate (MBR)-vessel, representing blood flow velocity in retinal vessels, was significantly lower in the late presentation group, while choroidal MBR was not significantly different. The late presentation group had significantly lower oxygen saturation in retinal venules, a higher arteriovenous oxygen saturation difference and a smaller calibre of retinal arterioles compared with the early presentation group. Eyes that subsequently developed 'sunset glow fundus' had significantly lower ONH MBR-vessels, lower oxygen saturation in retinal venules, a higher arteriovenous oxygen saturation difference and a smaller calibre of retinal arterioles compared with eyes without 'sunset glow fundus'. ONH MBR-vessel had a significant negative correlation with arteriovenous oxygen saturation difference and a significant positive correlation with calibre of retinal arterioles. In the acute uveitic phase of VKH disease, the development of 'sunset glow fundus' is associated with pretreatment reduced retinal blood flow velocity, calibre of retinal arterioles and oxygen saturation in retinal venules, as well as an increased arteriovenous oxygen saturation difference.

WNT-inhibitory factor 1-mediated glycolysis protects photoreceptor cells in diabetic retinopathy

BackgroundIn diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR.MethodTwelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting.ResultTypical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability.ConclusionsWIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders.Graphical

Inner retinal oxygen delivery and metabolism in progressive stages of diabetic retinopathy

Previous studies have reported increased retinal venous oxygen saturation and decreased retinal blood flow and oxygen metabolism in non-proliferative diabetic retinopathy (NPDR). The current study aimed to determine alterations in both inner retinal oxygen delivery (DO2) and metabolism (MO2) in proliferative DR (PDR) as well as at stages of NPDR. A total of 123 subjects participated in the study and were categorized into five groups: non-diabetic control (N = 32), diabetic with no diabetic retinopathy (NDR, N = 34), mild NPDR (N = 31), moderate to severe NPDR (N = 17), or PDR (N = 9). Multi-modal imaging was performed to measure oxygen saturation and blood flow, which were used for derivation of DO2 and MO2. There were significant associations of groups with DO2 and MO2. DO2 was lower in PDR and not significantly different in NDR and NPDR stages as compared to the non-diabetic control group. MO2 was decreased in PDR and moderate to severe NPDR as compared to the control group, and not significantly reduced in NDR and mild NPDR. The findings demonstrate reductions in both DO2 and MO2 in PDR and MO2 in moderate to severe NPDR, suggesting their potential as biomarkers for monitoring progression and treatment of DR.

Amelioration of oxygen-induced retinopathy in neonatal mice with fetal growth restriction.

Introduction: With the aim of optimizing the balance of maintaining a safe oxygen saturation and reducing the risk of retinopathy of prematurity in human neonates with fetal growth restriction (FGR), the present study investigated the distinct effects of oxygen supplementation on the retinal neovasculature using a murine premature neonatal oxygen-induced retinopathy (OIR) model with or without fetal growth restriction. Methods: For comparison with normal birth-weight neonates, maternal low-protein diet-induced FGR neonates were subjected to fluctuating oxygen levels to generate oxygen-induced retinopathy. The retinal neovasculature was histologically evaluated, and comprehensive transcriptome analysis was conducted. Results: Compared to OIR neonates with normal birth weight, significant amelioration of the neovasculature, as indicated by decreases in the number of branch junctions, vascular distribution, maximal vascular radius and microaneurysm-like tufts, was observed in OIR mice with FGR. The results of retinal RNA-sequencing revealed downregulation of angiogenic factors that trigger pathological retinal neovascularization, such as the mitogen-activated protein kinase pathway and corresponding upstream signaling pathways in OIR mice with FGR. Conclusion: Our findings demonstrated that FGR neonates have a higher capacity for retinal oxygen stress, and the risk of OIR development is attenuated compared to that in mature neonates with normal birth weight.

Chronic Sleep Deprivation Impairs Visual Functions via Oxidative Damage in Mice

Sleep deprivation (SD) is a global public health burden, and has a detrimental role in the nervous system. Retina is an important part of the central nervous system; however, whether SD affects retinal structures and functions remains largely unknown. Herein, chronic SD mouse model indicated that loss of sleep for 4 months could result in reductions in the visual functions, but without obvious morphologic changes of the retina. Ultrastructural analysis by transmission electron microscope revealed the deterioration of mitochondria, which was accompanied with the decrease of multiple mitochondrial proteins in the retina. Mechanistically, oxidative stress was provoked by chronic SD, which could be ameliorated after rest, and thus restore retinal homeostasis. Moreover, the supplementation of two antioxidants, α-lipoic acid and N-acetyl-l-cysteine, could reduce retinal reactive oxygen species, repair damaged mitochondria, and, as a result, improve the retinal functions. Overall, this work demonstrated the essential roles of sleep in maintaining the integrity and health of the retina. More importantly, it points towards supplementation of antioxidants as an effective intervention strategy for people experiencing sleep shortages.

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.

A novel approach for measurement of retinal oxygen extraction based on laser speckle flowgraphy and retinal oximetry

Aims/Purpose: Several ocular diseases lead to a reduction in retinal oxygen metabolism. However, measurement of retinal oxygen extraction is mostly based on time‐consuming and custom‐built devices. Hence, the aim of this study is to assess retinal oxygen extraction based on measurement of retinal blood flow with the commercially available laser‐speckle flowgraphy (LSFG) and measurement of retinal oxygen saturation with the commercially available retinal oximetry.Methods: Ten young healthy subjects participated in the present study. Retinal blood flow and retinal oxygen saturation were measured in each vessel around the optic disc at the same position. The corrected arterial (co2, CRA) and venous (co2, CRV) oxygen content was estimated from the parameters evaluated and the difference between these two determined parameters (co2, DIFF) was assessed. Retinal oxygen extraction was calculated using mean vessel flow rate (MV) and cO2, DIFF. To validate the novel approach, baseline measurement and measurement during inhalation of 100% oxygen were performed, as retinal oxygen extraction is known to decrease during hyperoxia.Results: MV significantly decreased during 100% oxygen breathing (−23 ± 10%, p &lt; 0.001). While cO2, CRA only slightly increased by 1 ± 2% (p = 0.093), cO2, CRV increased by 9 ± 14% (p = 0.050). Consequently, cO2, DIFF decreased by 10 ± 20% (p = 0.087). This led to a pronounced decrease in retinal oxygen extraction by −31 ± 18% during hyperoxia (p &lt; 0.001).Conclusions: During breathing of 100% oxygen a significant decrease in TRBF and retinal oxygen extraction was assessed. The decrease in retinal oxygen extraction during hyperoxia is consistent with findings in literature and is physiologically expected. Therefore, the novel approach for measurement of retinal oxygen extraction appears to be feasible. Larger studies in patient cohorts using this method should be conducted in the future.

Retinal Oxygenation With Conventional 100-ms Versus Short-Pulse Pan-Retinal Laser Photocoagulation.

Conventional (100 ms) pan-retinal photocoagulation (PRP) laser burns are larger than short-pulse (10 ms to 20 ms) PRP burns. This study investigates the effect of PRP burns of different sizes on retinal oxygenation. A mathematical model using COMSOL Multiphysics 6 was used to create a three-dimensional abstraction of the coupled biology of the choroid, photoreceptor, and retinal tissues. Laser burn sizes were varied in the model, specifically considering burn diameters of 500 μm, 250 μm, and 125 μm, while keeping the total burn area constant. Total increase in retinal oxygenation was the same for different burn sizes, but the oxygen distribution differed. Smaller burns resulted in a more even lateral oxygen distribution but with reduced penetration into the inner retina. Conventional and short-pulse PRP may affect retinal oxygenation differently, even when total burn area is the same. Further investigation into optimum burn size and pattern is required. [Ophthalmic Surg Lasers Imaging Retina 2024;55:40-45.].

Retinal oximetry in vascular diseases

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of haemoglobin. The imaging technology is non‐invasive and reproducible with remarkably low variability on test–retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic disease. The aim of this presentation is review of state of the art knowledge of us of retinal oximetry in vascular diseases and its possible clinical application.In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment.Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular oedema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia.Retinal oxygen metabolism is altered in uveitis associated with VKH disease. Oxygen saturation profile is abnormal in acute uveitic phase of the disease and returns to normal in those who recover with normal fundus appearance, but not in eyes that suffer permanent anatomical damage with “sunset glow fundus” and chorioretinal atrophy. Retinal oximetry may be of value in evaluating vascular and metabolic aspects of posterior uveitis.

Maximum-A-Posteriori Estimation of Retinal Oxygen Tension Based on Photon Counting Statistics.

The regularization of retinal oxygen tension estimation was previously proposed with an assumption that phosphorescence intensity images are corrupted by additive Gaussian noise. Based on this assumption, a regularized least-squares estimate has been shown to be better than a conventional least-squares estimation. However, this assumption is inconsistent with the acquisition process of phosphorescence intensity images acquired using an intensified charge-coupled device camera. Almost the entire acquisition process is governed by the natural aspects of photons. Therefore, a method based on photon counting statistics is more appropriate. In this study, we propose a regularized oxygen tension estimation method based on photon counting statistics and a phosphorescence lifetime imaging model.

Variations in Retinal Oxygen Saturation in a Diverse Healthy Population.

Local retinal oxygen saturation is a research technique, which has the potential as a biomarker for diabetes. However, normative data has not been established. This study examined differences in oxygen saturation around the macula and characterizes the relationship between age, race, refractive error (RE), sex, blood pressure (BP), prediabetic status and oxygen saturation. Fifty-nine subjects aged 22-69 (38.8 ± 14.7 years) were included who were racially diverse and with equal gender distribution. None had eye disease. Oxygen saturation was taken with the Zilia Ocular in 4 locations around the macula 3.1 degrees from the fovea and they were also averaged. BP, RE, and HbA1c were noted. Regression analyses for oximetry and other factors were completed as were t-tests with multiple comparison corrections. There were significant variations in oximetry measures by race, with higher pigmentation levels associated with lower oximetry values (p < 0.01). There was no relationship between oximetry and sex (p = 0.34), RE (p = 0.67), BP (systolic p = 0.61, diastolic p = 0.71) nor prediabetic status (p = 0.87). Oximetry was associated with age when controlling for race (P < 0.002). Nasal-temporal variations showed nasal oximetry to higher than temporal measures (P < 0.01). This study revealed race/pigmentation is an important influence on oximetry measures. Retinal location also caused variations, likely due to proximity to larger vessels nasally. No differences in sex, RE nor BP were observed to alter local oxygen saturation. However, age was correlated when considered with race. This study will inform our future work in different disease states and is an important first step in evaluating this technology.

Artificial intelligence and hemodynamic studies in optical coherence tomography angiography for diabetic retinopathy evaluation: A review.

Diabetic retinopathy (DR) is a rapidly emerging retinal abnormality worldwide, which can cause significant vision loss by disrupting the vascular structure in the retina. Recently, optical coherence tomography angiography (OCTA) has emerged as an effective imaging tool for diagnosing and monitoring DR. OCTA produces high-quality 3-dimensional images and provides deeper visualization of retinal vessel capillaries and plexuses. The clinical relevance of OCTA in detecting, classifying, and planning therapeutic procedures for DR patients has been highlighted in various studies. Quantitative indicators obtained from OCTA, such as blood vessel segmentation of the retina, foveal avascular zone (FAZ) extraction, retinal blood vessel density, blood velocity, flow rate, capillary vessel pressure, and retinal oxygen extraction, have been identified as crucial hemodynamic features for screening DR using computer-aided systems in artificial intelligence (AI). AI has the potential to assist physicians and ophthalmologists in developing new treatment options. In this review, we explore how OCTA has impacted the future of DR screening and early diagnosis. It also focuses on how analysis methods have evolved over time in clinical trials. The future of OCTA imaging and its continued use in AI-assisted analysis is promising and will undoubtedly enhance the clinical management of DR.

Effects of high-intensity interval training on retinal vessel diameters and oxygen saturation in patients with hypertension: A cross-sectional and randomized controlled trial

IntroductionArterial hypertension is a global healthcare burden that affects macrovascular and microvascular structure and function and can promote vascular end-organ damage. This study aimed 1) to evaluate differences in microvascular health between normotensive individuals and patients with arterial hypertension and 2) to assess the effects of short-term high-intensity interval training (HIIT) on microvascular health in the subgroup with arterial hypertension as add-on treatment to antihypertensive medication. MethodsIn the cross-sectional part, central retinal arteriolar (CRAE) and venular diameter equivalent (CRVE), arteriolar-to-venular diameter ratio (AVR), and retinal oxygen saturation (O2-saturation) were investigated in 19 normotensive healthy controls (mean age 56 ± 7 years) and 41 patients with arterial hypertension (mean age 59 ± 7 years). In the subsequent randomized controlled trial (RCT), patients with arterial hypertension were randomized to an intervention group (HIIT 3×/week) or a control group that received standard physical activity recommendations after baseline assessment. Assessments of retinal vessel biomarkers and patients` characteristics were repeated after the intervention period of 8 weeks. ResultsIn the cross-sectional part, individuals with normal blood pressure (BP) showed lower body mass index (BMI), body fat, 24 h systolic and diastolic BP, higher peak oxygen uptake, wider CRAE (174 ± 17 μm vs. 161 ± 17 μm, p = 0.009), and higher AVR (0.84 ± 0.05 vs. 0.79 ± 0.05, p = 0.003) compared to patients with hypertension. In the RCT, patients with arterial hypertension showed reduced BMI and fasting glucose levels after HIIT and control condition. In addition, the intervention group reduced body fat percentage (27.0 ± 5.5 vs. 25.8 ± 6.1, p = 0.023) and increased peak oxygen uptake (33.3 ± 5.7 vs. 36.7 ± 5.1, p < 0.001). No changes in BP were found in either group. The intervention group showed narrower CRVE (β −4.8 [95 % CI, −8.85, −0.81] p = 0.020) and higher AVR (0.03 [0.01, 0.04] p < 0.001) after eight weeks of HIIT compared to the control group. No statistically significant changes in retinal O2-saturation were found in either group. ConclusionShort-term HIIT proved to be an effective treatment to ameliorate hypertension-induced retinal microvascular abnormalities in patients with hypertension. Retinal vessel diameters may prove to be a sensitive biomarker to quantify treatment efficacy at the microvascular level, at the earliest possible stage in patients with hypertension.