Validation of retinal oximetry vessel selection using fluorescein angiography in patients with optic disc drusen.

Retinal oximetry could provide insights into the pathophysiology of optic nerve disease, including optic disc drusen (ODD). Vessel selection for oximetry analysis is based on morphological characteristics of arterioles and venules and supported by an overlay of estimated blood oxygen saturations. The purpose of this cross-sectional study was to determine the validity of this vessel selection procedure by comparing it with vessel selection supported by video fluorescein angiography (FA). The study included 36 eyes of 36 patients with ODD who underwent retinal oximetry (Oxymap retinal oximeter T1) followed by FA (Heidelberg Spectralis). Two trained graders selected vessel segments in a pre-defined measurement area around the optic disc. One of these graders additionally performed the vessel segment selection with the support of FA images. When performed by the same grader, FA-supported and non-FA-supported vessel selection did not lead to significant differences in total vessel segment length, estimated oxygen saturations or vessel diameters (all p > 0.05). Inter-grader differences were found for arterial and venous segment lengths and arterial saturation (p < 0.05). A similar tendency was found for the arteriovenous saturation difference (p = 0.10). In conclusion, identifying vessel segments for retinal oximetry analysis based on vessel morphology and supported by a color-coded saturation overlay appears to be a valid method without the need for invasive angiography. A numerically small inter-grader variation may influence oximetry results. Further studies of retinal oximetry in ODD are warranted.

Retinal oxygen metabolic function in choroideremia and retinitis pigmentosa.

PURPOSE: 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. METHODS: Prospective observational study including 18 eyes of 9 molecularly confirmed CHM patients (9♂; 40.2 ± 21.2 years (mean ± SD), 77 eyes from 39 patients with RP (15♀ 24♂; 45.6 ± 14.7 years) and 100 eyes from 53 controls (31♀ 22♂; 40.2 ± 13.4 years). 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. RESULTS: 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. CONCLUSION: 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. KEY MESSAGES: What was known before? Retinal oxygen metabolic function measured with retinal oximetry (RO) shows significant alterations in patients with retinitis pigmentosa. WHAT THIS STUDY ADDS: 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.

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

PURPOSE: 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 2020-00,122), 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 > 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. CONCLUSION: 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.

Alterations in ocular microcirculation and oxygen metabolism in patients with lipemia retinalis.

PURPOSE: The study aims to assess the alterations in retinal oxygen saturation and retinal and choroidal blood flow in lipemia retinalis. METHODS: This was a cross-sectional study on 10 eyes (5 patients) with history of lipemia retinalis. The study comprised 10 eyes with documented history of lipemia retinalis and 10 participants as healthy controls. Patients with a confirmed history of lipemia retinalis were grouped into two cohorts based on their most recent fundus examination: untreated lipemia retinalis (abnormal fundus) and resolved lipemia retinalis (normal fundus). Both retinal arteriolar and venular oxygen saturation were measured using the non-invasive spectrophotometric retinal oximeter (Oxymap T1). The mean blur rate (MBR) of the optic nerve and choroidal blood flow were analyzed using a laser speckle flowgraph (LSFG). RESULTS: Patients with untreated lipemia retinalis had a significantly higher retinal arteriolar and venular oxygen saturation than that of the other two groups (p < 0.001). Moreover, patients with untreated lipemia retinalis had significantly smaller retinal arteriolar and venular diameters (p < 0.001). On LSFG, there was a significant difference in the overall MBR (p = 0.007) and vessel MBR of the optic nerve between the groups (p = 0.011). The patients with history of lipemia retinalis (untreated and resolved) exhibited a high overall MBR and vessel MBR of the optic nerve than that of the control group. There was a significant elevation of the optic nerve (p = 0.002) and choroidal blowout score (p < 0.001), while the resistivity index of the optic nerve (p = 0.001) and choroids (p = 0.002) was significantly lower in patients with resolved and untreated lipemia retinalis. CONCLUSIONS: There was a significant alteration in retinal oximetry, in untreated lipemia retinalis, and in retinal blood flow, in both the resolved and untreated groups. The increase in retinal blood flow and oxygen saturation may elucidate the preservation of visual acuity and function despite the fundus changes observed in lipemia retinalis.

Altered retinal oxygen metabolism in patients with combined ocular and central nervous system sarcoidosis.

OBJECTIVE: To evaluate retinal oxygen metabolism by retinal oximetry for ocular and CNS diseases in a cross-sectional study of sarcoidosis. METHODS: Overall 201 eyes from 103 biopsy-verified sarcoidosis patients were included and divided into four groups depending on the organ affection: (i) sarcoidosis without ocular or CNS affection, (ii) ocular sarcoidosis, (iii) CNS sarcoidosis, and (iv) combined ocular and CNS sarcoidosis. Retinal oximetry was obtained and analysed, with the mean retinal arteriolar and venular saturation as well as arteriovenous difference as principal outcomes. Comparison between groups was done in a multi linear regression model adjusted for age, sex, duration of sarcoidosis, best corrected visual acuity and retinal oximetry quality. RESULTS: Mean (s.d.) age was 50.5 (13.4) (95% CI: 47.9, 53.1) years and 52.2% were males. Eyes of the combined Ocular/CNS group had a higher retinal arteriovenous difference than eyes of the Non-ocular/no-CNS group (42.1% vs 37.7%, P = 0.012) but did not differ between other groups. Eyes in the four groups (Non-ocular/no-CNS, Ocular, CNS and Ocular/CNS) did not differ according to retinal arterial (94.5%, 93.5%, 93.5% and 94.5%, respectively) or venular (57.5%, 56.4%, 55.0% and 52.5%, respectively) oxygen saturation. CONCLUSIONS: The results of this study suggest that eyes of sarcoidosis patients with combined ocular and CNS affection have an altered oxygen metabolism indicating a subclinical eye affection that is not recognized by conventional screening methods.

The impact of macular edema on microvascular and metabolic alterations in retinitis pigmentosa.

PURPOSE: The primary aim of our study was to evaluate retinal microvascular anomalies recorded with optical coherence tomography angiography (OCTA) and the retinal metabolic function measured with retinal oximetry (RO) in patients with retinitis pigmentosa (RP). The secondary aim of the study was to link the presence of macular edema to microvascular and metabolic parameters in RP. METHODS: OCTA and RO were performed on 94 eyes: 64 eyes diagnosed with RP with (ME-RP) and without (no-ME-RP) macular edema were compared with 30 control eyes. Study end points were as follows: mean superficial (FAZ-S) and deep foveal avascular zone (FAZ-D) determined by OCTA. In addition, we evaluated the mean arterial (A-SO2; %), venular (V-SO2; %) oxygen saturation, their difference (A-V SO2; %), as well as the corresponding mean diameter of the retinal arterioles (D-A; µm) and venules (D-V; µm). RESULTS: RP patients differed from controls by enlarged FAZ-S and FAZ-D (p ≤ 0.001), attenuated retinal vessels (p ≤ 0.001), and increased retinal vessel oxygen saturation (p ≤ 0.010). Subgroup analyses within RP patients revealed more pronounced alterations of microvascular parameters and metabolic function in the presence of macular edema. In the no-ME-RP subgroup, significant interactions were present between FAZ-S, A-SO2, and V-SO2, whereas in the ME-RP subgroup, we found significant correlations between FAZ-D and D-A. CONCLUSION: A combined microvascular structure-metabolic function approach enhances our understanding of inherited retinal diseases. The presence of macular edema in RP seems to be a result of more altered microvascular-metabolic function. Macular edema should thus be taken into consideration when evaluating microvascular and/or metabolic changes in RP.

Correlation between Diabetic Retinopathy Severity and Oxygen Metabolism in Patients with Diabetic Macular Edema during Treatment with Intravitreal Aflibercept.

PURPOSE: To attribute data on changes in diabetic retinopathy (DR) severity during treatment of diabetic macular edema (DME) with vascular endothelial growth factor inhibitors (anti-VEGF), this study aimed to (1) examine the correlation between oxygen saturations in retinal vessels and the number of DR lesions on ultra-wide field color fundus photographs prior to anti-VEGF treatment and (2) compare changes in oxygen saturations in retinal vessels with changes in the number of DR lesions after a loading dose of three monthly intravitreal injections of 2.0 mg of aflibercept. METHODS: This 3-month prospective study included 37 eyes of patients with DME and varying severity of peripheral DR lesions. DR lesions were graded on wide field images and retinal oxygen saturations were evaluated by retinal oximetry. Patients were then treated with three monthly intravitreal injections of 2 mg aflibercept and wide field imaging and retinal oximetry were repeated 4 weeks after the last injection. Patients with proliferative DR or previous panretinal photocoagulation were excluded. RESULTS: Baseline retinal arteriolar oxygen saturation increased with increasing DR severity and numbers of microaneurysms, hemorrhages, and cotton wool spots (p = 0.03, 0.01, 0.03, and <0.001), while no correlation between the severity of DR lesions and retinal venular oxygen saturation was found. After treatment with intravitreal aflibercept, the severity of DR lesions significantly reduced, while retinal arteriolar and venular oxygen saturation as well as the arteriolar-venular difference remained unchanged (95.5 vs. 95.8%, p = 0.44; 62.9 vs. 64.5%, p = 0.08; 32.5 vs. 31.4%, p = 0.33). CONCLUSION: This study demonstrated that structural DR lesions correlate with retinal arteriolar oxygen saturation in patients with DME prior to anti-VEGF treatment and that improvement in the severity of DR lesions can occur without corresponding changes in retinal oxygen metabolism during intravitreal therapy. Our results suggest that DR severity on color fundus photographs should be interpreted with caution once intravitreal therapy is initiated.

Preliminary investigation of multispectral retinal tissue oximetry mapping using a hyperspectral retinal camera.

Oximetry measurement of principal retinal vessels represents a first step towards understanding retinal metabolism, but the technique could be significantly enhanced by spectral imaging of the fundus outside of main vessels. In this study, a recently developed Hyperspectral Retinal Camera was used to measure relative oximetric (SatO2) and total hemoglobin (HbT) maps of the retina, outside of large vessels, in healthy volunteers at baseline (N = 7) and during systemic hypoxia (N = 11), as well as in patients with glaucoma (N = 2). Images of the retina, on a field of view of ∼30°, were acquired between 500 and 600 nm with 2 and 5 nm steps, in under 3 s. The reflectance spectrum from each pixel was fitted to a model having oxy- and deoxyhemoglobin as the main absorbers and scattering modeled by a power law, yielding estimates of relative SatO2 and HbT over the fundus. Average optic nerve head (ONH) saturation over 8 eyes was 68 ± 5%. During systemic hypoxia, mean ONH saturation decreased by 12.5% on average. Upon further development and validation, the relative SatO2 and HbT maps of microvasculature obtained with this imaging system could ultimately contribute to the diagnostic and management of diseases affecting the ONH and retina.

Associations of retinal oximetry in persons with diabetes.

BACKGROUND: There are limited data available on the variables that might affect retinal vessel oxygen saturation (SO2) in diabetes. Therefore, the aim of this study is to assess factors associated with retinal oximetry values in persons with diabetes. DESIGN: Clinic-based cross-sectional study. PARTICIPANTS: Fifty-eight persons with diabetes aged 18+ years, recruited from the University of Melbourne, the Royal Victorian Eye and Ear Hospital, and St. Vincent's Hospital (Melbourne), Australia. METHODS: Retinal oximetry was performed using the oximetry module of the Vesselmap system (Imedos UG, Jena, Germany) in 92 diabetic eyes. Generalized estimating equation models were used to estimate the associations between candidate variables (age; gender; retinal capillary flow; duration of diabetes; hypertension; smoking status; presence of diabetic retinopathy [DR]; glycated haemoglobin; triglyceride; total cholesterol; finger SO2 and ocular perfusion pressure) with retinal oximetry measures. MAIN OUTCOME MEASURE: Arteriolar SO2, venular SO2 and the arterio-venous (A-V) difference. RESULTS: Of the candidate factors assessed, only the presence of DR was significantly associated with increased venular SO2 and decreased A-V difference in unadjusted analyses. In models adjusting for age and gender and significant variables from unadjusted analyses, compared with no DR, the presence of DR was significantly associated with greater retinal venular SO2 values (ß = 3.65%, 95% confidence interval: 0.67-6.63%) and decreased A-V difference (ß = -2.00%, 95% confidence interval: -3.46 to -0.53%). CONCLUSION: In patients with diabetes, eyes with DR were associated with increased venular SO2 and decreased A-V difference compared with eyes without DR, suggesting an altered metabolic state in DR.

Evaluation of a retinal oximetry image quality indicator in patients with cataract.

PURPOSE: To evaluate a new automated retinal oximetry image quality indicator with cataract as a clinical model. METHODS: Sixty-one eyes in 61 patients were imaged by the Oxymap T1 Retinal Oximeter at baseline and 25 eyes were also examined 3 weeks after cataract surgery. Image quality (0-10 on a continuous scale) was compared with standardized AREDS cataract grading and Pentacam lens densitometry. Associations with retinal oximetry measurements and visual acuity were examined. RESULTS: Image quality correlated with total, nuclear and posterior subcapsular cataract grades (ANOVA, p < 0.05), tended to be associated with lens densitometry and it improved from 4.3 ± 1.4 to 5.7 ± 1.0 (p < 0.05) after cataract surgery. Very low image quality, below 3, led to vessel detection failure in retinal oximetry images. Higher image qualities were linearly associated with higher measured retinal oxygen saturations (r = 0.52 in arteries and r = 0.46 in veins; p < 0.001). CONCLUSION: Retinal oximetry image quality deteriorated with increasing cataract density and improved after cataract surgery, supporting its use as a measure of optical clarity. The numerical quality indicator demonstrated a threshold below which images of poor optical quality should be discarded. Image quality affects the estimates of retinal oximetry parameters and should therefore be included in future analyses.

Potential measurement error from vessel reflex and multiple light paths in dual-wavelength retinal oximetry.

PURPOSE: This study aims to characterize the dependence of measured retinal arterial and venous saturation on vessel diameter and central reflex in retinal oximetry, with an ultimate goal of identifying potential causes and suggesting approaches to improve measurement accuracy. METHODS: In 10 subjects, oxygen saturation, vessel diameter and optical density are obtained using Oxymap Analyzer software without diameter correction. Diameter dependence of saturation is characterized using linear regression between measured values of saturation and diameter. Occurrences of negative values of vessel optical densities (ODs) associated with central vessel reflex are acquired from Oxymap Analyzer. A conceptual model is used to calculate the ratio of optical densities (ODRs) according to retinal reflectance properties and single and double-pass light transmission across fixed path lengths. Model-predicted values are compared with measured oximetry values at different vessel diameters. RESULTS: Venous saturation shows an inverse relationship with vessel diameter (D) across subjects, with a mean slope of -0.180 (SE = 0.022) %/µm (20 < D < 180 µm) and a more rapid saturation increase at small vessel diameters reaching to over 80%. Arterial saturation yields smaller positive and negative slopes in individual subjects, with an average of -0.007 (SE = 0.021) %/µm (20 < D < 200 µm) across all subjects. Measurements where vessel brightness exceeds that of the retinal background result in negative values of optical density, causing an artifactual increase in saturation. Optimization of model reflectance values produces a good fit of the conceptual model to measured ODRs. CONCLUSION: Measurement artefacts in retinal oximetry are caused by strong central vessel reflections, and apparent diameter sensitivity may result from single and double-pass transmission in vessels. Improvement in correction for vessel diameter is indicated for arteries however further study is necessary for venous corrections.

Retinal oximetry and microvascular assessment after hypertensive pregnancy complications.

PURPOSE: Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non-invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group. METHODS: We examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non-parametric tests and multiple regression analyses, adjusted for age and body mass index. RESULTS: Median arteriolar oxygen saturation (SaO2; 94.2% vs. 93.0%), venular oxygen saturation (SvO2; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV-difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm2) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV-difference (R2 = 0.209) and negatively correlated with arteriolar diameter (CRAE; r2 = 0.382). CONCLUSIONS: Structural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV-difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women.

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

PURPOSE: 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. METHODS: 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'. RESULTS: 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. CONCLUSIONS: 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.

Association Between Corneal Changes and Retinal Oximetry in Diabetes Mellitus.

Purpose: 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. Methods: 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. Results: 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). Conclusion: 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 changes are particularly important for ophthalmologists in the management of diabetes mellitus. These are primarily consequences of diabetic vascular changes that can lead to a lack of oxygen. However, there is also evidence of significant changes in the cornea of patients with diabetes. In the present study, the associations between changes in corneal thickness profile, optical density of the cornea, and oxygen saturation of retinal vessels in diabetes mellitus were demonstrated for the first time. Therefore, this study could contribute to clarifying the possible causes of corneal changes in patients with diabetes.

Study protocol - Prospective case-control trial - Impact of significant carotid stenosis on retinal perfusion measured with automated retinal oximetry.

BACKGROUND: Large vessel carotid stenosis is a significant cause of ischaemic stroke. Indications for surgical revascularisation depend on the severity of the stenosis and clinical symptoms. However, mild symptoms such as TIA (Transient ischaemic attack), amaurosis fugax or minor stroke precede large strokes in only 15% of cases. AIM: The aim of this prospective study is to evaluate whether retinal perfusion is impacted in significant carotid stenosis. Automated retinal oximetry will be used to better assess perfusion in the post-stenotic basin. We presume the more stenotic the blood vessel, the more reduced the retinal perfusion is, resulting in adaptive changes such as greater arteriovenous saturation difference due to greater oxygen extraction. This could broaden the indication spectrum for revascularisation for carotid stenosis. METHODS: We plan to enroll yearly 50 patients with significant carotid stenosis and cross-examine them with retinal oximetry. The study group will provide stenotic vessels and, non-stenotic vessels will form the control group. Patients with significant carotid stenosis will undergo an MRI (Magnetic Resonnance imaging) examination to determine the presence of asymptomatic recent ischaemic lesions in the stenotic basin, and the correlation to oximetry parameters. STATISTICS: The stenosis severity and retinal oximetry parameters will be compared for study and control groups with a threshold of 70%, respectively 80% and 90% stenosis. Results will be then reevaluated with emphasis on MRI findings in the carotid basin. CONCLUSION: This prospective case control study protocol will be used to launch a multicentre trial assessing the relationship between significant carotid stenosis and retinal perfusion measured with automated retinal oximetry. Despite these differences, the findings indicate the potential of retinal oximetry for noninvasive real-time measurements of oxyhaemoglobin saturation in central nervous system vessels. Following calibration upgrade and technological improvement, verification retinal oximetry may potentially be applied to critically ill and anaesthesia care patients. The study on combined scanning laser ophthalmoscope and retinal oximetry supports the feasibility of the technique for oximetry analysis in newly born babies. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT06085612.

The effect of simulated cataract light scatter on retinal vessel oximetry.

To assess the impact of light scatter, similar to that introduced by cataract on retinal vessel blood oxygen saturation measurements using poly-bead solutions of varying concentrations. Eight healthy, young, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intraocular pressure, pupil dilation and retinal vessel oximetry using dual wavelength photography (Oximetry Module, Imedos Systems, Germany). To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations (0.001, 0.002 and 0.004%) of polystyrene microspheres (Polysciences Inc., USA). The adopted light scatter model showed an artifactual increase in venous optical density ratio (p = 0.036), with the 0.004% condition producing significantly higher venous optical density ratio values when compared to images without a cell in place. Spectrophotometric analysis, and thus retinal vessel oximetry of the retinal vessels, is altered by artificial light scatter.

Regional variation in human retinal vessel oxygen saturation.

The purpose of this study was to investigate regional differences in oxygen saturation of blood in first degree retinal vessels using a novel non-flash hyperspectral retinal camera (Photon etc Inc). Nine healthy individuals (mean age 24.4 ± 3.6 yrs, 5 males) were imaged at 548, 569, 586, 600, 605 and 610 nm wavelengths. Optical density values were extracted with the aid of Image-J software for blood oxygen saturation (SO2) determination. Arteriolar and venular SO2 were measured at three locations (ranging 1-3 optic nerve head radii) from the disc margin along the vessels in the superior and inferior temporal quadrants. Retinal SO2 was significantly higher in the superior temporal arteriole and venule as compared to the inferior temporal vessels (p = 0.033 and p = 0.032 for arterioles and venules, respectively). SO2 was not significantly different between the three measurement sites for any of the given vessels imaged (p > 0.05). In conclusion, greater SO2 values were found in the superior temporal first degree retinal arterioles and venules in young healthy individuals than in the equivalent inferior vessels. However, there were no detectable differences in retinal SO2 along each of the major vessels, a finding that is consistent with the concept of these vessels not contributing primarily to gas exchange. Moreover, the SO2 was consistently higher in the arterioles than in the equivalent venules (p < 0.0001).

Predictive value of retinal oximetry, optical coherence tomography angiography and microperimetry in patients with treatment-naïve branch retinal vein occlusion.

Vascular endothelial growth factor inhibitors have substantially improved the visual outcomes in patients with macular edema (ME) caused by branch retinal vein occlusion (BRVO), but treatment outcomes are highly variable and early prediction of expected clinical outcome would be important for individualized treatment.As non-invasive metabolic, structural and functional retinal markers might act as early predictors of clinical outcomes, we performed a 12-month, prospective study aimed to evaluate if baseline retinal oximetry, optical coherence tomography angiography (OCT-A) or microperimetry were able to predict need of treatment, structural or functional outcome in patients with ME caused by treatment-näive BRVO.We evaluated 41 eyes of 41 patients with a mean age of 69.6 years and 56% females. We found a strong tendency towards a higher retinal arteriolar oxygen saturation in patients without a need of additional aflibercept treatment after the loading phase (99.8% vs. 92.3%, adjusted odds ratio 0.80 (95% confidence interval 0.64-1.00), adjusted p = 0.058), but otherwise, retinal oximetry, OCT-A or microperimetry were not able to predict need of treatment, structural nor functional outcomes. (Trial registration: clinicaltrials.gov, S-20,170,084. Registered 24 August 2014, https://clinicaltrials.gov/ct2/show/NCT03651011 ).

Retinal oxygen saturation in monoclonal gammopathies patients: A pilot study.

PURPOSE: The aim of this pilot study was to assess oxygen saturation in retinal blood vessels in patients with monoclonal gammopathies (MGs). METHODS: Thirty-one patients with MGs (11 women and 20 men, mean age 65.9 ± 8.9 years) were enrolled during 2016-2020. The patients were diagnosed at the Haemato-Oncology Department and subsequently examined at the Ophthalmology Department before initiating systemic therapy. All patients were subjected to automatic retinal oximetry (Oxymap ehf.) and had their fundus photographed (Topcon TRC-50DX retinal camera). We assessed the association between retinal oxygen saturation (SatO2 ) - arterial SatO2 , venous SatO2 and arterio-venous (AV) difference-and MGs parameters: serum monoclonal immunoglobulin (M-protein) level and serum immunoglobulin-free light chains (FLC kappa and lambda), total protein, serum viscosity, haemoglobin, albumin, lactate dehydrogenase, C-reactive protein, creatinine and serum calcium level. Hyperviscosity-related retinopathy was also evaluated. RESULTS: Statistical analysis showed a significant positive correlation (r = 0.462; p = 0.009) between the AV difference and the haemoglobin level. A significant, medium strong negative correlation was found between the AV difference and the serum levels of the monoclonal light lambda chains (r = -0.450; p = 0.011). Contrary to expectations, no statistically significant correlation was found between retinal oxygen saturation and the total protein or viscosity. CONCLUSION: This study found correlation between retinal oxygen saturation and certain parameters in the blood of patients with MGs. Increasing levels of monoclonal immunoglobulin seem to reduce oxygen absorption in retinal arterioles, resulting in a lower AV difference, particularly in patients with a high free light chain level.

Exploring Retinal Blood Vessel Diameters as Biomarkers in Multiple Sclerosis.

We aimed to determine whether retinal vessel diameters and retinal oxygen saturation in newly diagnosed patients with multiple sclerosis (pwMS) are different from those of a healthy population. Retinal blood vessel diameters were measured using imaging with a spectrophotometric non-invasive retinal oximeter. Twenty-three newly diagnosed untreated relapsing-remitting MS (RRMS) patients (mean age: 32.2 ± 7.5 years, age range = 18-50 years, 56.5% female) were measured and compared to 23 age- and sex-matched healthy controls (HCs) (mean age: 34.8 ± 8.1 years). Patients with Optic Neuritis were excluded. Retinal venular diameter (143.8 µm versus 157.8 µm: mean; p = 0.0013) and retinal arteriolar diameter (112.6 µm versus 120.6 µm: mean; p = 0.0089) were smaller in pwMS when compared with HCs, respectively. There was no significant difference in the oxygen saturation in retinal venules and arterioles in pwMS (mean: 60.0% and 93.7%; p = 0.5980) compared to HCs (mean: 59.3% and 91.5%; p = 0.8934), respectively. There was a significant difference in the median low contrast visual acuity (2.5% contrast) between the pwMS and the HC groups (p = 0.0143) Retinal arteriolar and venular diameter may have potential as objective biomarkers for MS.