Retinal Oxygen Metabolism Research Articles

Increased Retinal Oxygen Metabolism Precedes Microvascular Alterations in Type 1 Diabetic Mice.

PurposeTo investigate inner retinal oxygen metabolic rate (IRMRO2) during early stages of type 1 diabetes in a transgenic mouse model.MethodsIn current study, we involved seven diabetic mice (Akita/+, TSP1−/−) and seven control mice (TSP1−/−), and applied visible-light optical coherence tomography (vis-OCT) to image functional parameters including retinal blood flow rate, oxygen saturation (sO2) and the IRMRO2 value longitudinally from 5 weeks of age to 13 weeks of age. After imaging at 13 weeks of age, we analyzed the imaging results, and examined histology of mouse retina.ResultsBetween diabetic mice and the control group, we observed significant differences in venous sO2 from 9 weeks of age (P = 0.006), and significant increment in IRMRO2 from 11 weeks of age (P = 0.001) in diabetic mice compared with control group. We did not find significant differences in retinal blood flow rate as well as arterial sO2 during imaging between diabetic and control mice. Histologic examination of diabetic and control mice at 13 weeks of age also revealed no anatomical retinal alternations.ConclusionsIn diabetic retinopathy, complications in retinal oxygen metabolism may occur before changes of retinal anatomical structure.

Inner Retinal Oxygen Delivery, Metabolism, and Extraction Fraction in Ins2Akita Diabetic Mice.

PurposeRetinal nonperfusion and hypoxia are important factors in human diabetic retinopathy, and these presumably inhibit energy production and lead to cell death. The purpose of this study was to elucidate the effect of diabetes on inner retinal oxygen delivery and metabolism in a mouse model of diabetes.MethodsPhosphorescence lifetime and blood flow imaging were performed in spontaneously diabetic Ins2Akita (n = 22) and nondiabetic (n = 22) mice at 12 and 24 weeks of age to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). Inner retinal oxygen delivery (DO2) and metabolism (MO2) were calculated as F ∗ O2A and F ∗ (O2A − O2V), respectively. Oxygen extraction fraction (OEF), which equals MO2/DO2, was calculated.ResultsDO2 at 12 weeks were 112 ± 40 and 97 ± 29 nL O2/min in nondiabetic and diabetic mice, respectively (NS), and 148 ± 31 and 85 ± 37 nL O2/min at 24 weeks, respectively (P < 0.001). MO2 were 65 ± 31 and 66 ± 27 nL O2/min in nondiabetic and diabetic mice at 12 weeks, respectively, and 79 ± 14 and 54 ± 28 nL O2/min at 24 weeks, respectively (main effects = NS). At 12 weeks OEF were 0.57 ± 0.17 and 0.67 ± 0.09 in nondiabetic and diabetic mice, respectively, and 0.54 ± 0.07 and 0.63 ± 0.08 at 24 weeks, respectively (main effect of diabetes: P < 0.01).ConclusionsInner retinal MO2 was maintained in diabetic Akita mice indicating that elevation of the OEF adequately compensated for reduced DO2 and prevented oxidative metabolism from being limited by hypoxia.

The synthetic progestin norgestrel modulates Nrf2 signaling and acts as an antioxidant in a model of retinal degeneration

Retinitis pigmentosa (RP) is one of the most common retinal degenerative conditions affecting people worldwide, and is currently incurable. It is characterized by the progressive loss of photoreceptors, in which the death of rod cells leads to the secondary death of cone cells; the cause of eventual blindness. As rod cells die, retinal-oxygen metabolism becomes perturbed, leading to increased levels of reactive oxygen species (ROS) and thus oxidative stress; a key factor in the secondary death of cones. In this study, norgestrel, an FDA-approved synthetic analog of progesterone, was found to be a powerful neuroprotective antioxidant, preventing light-induced ROS in photoreceptor cells, and subsequent cell death. Norgestrel also prevented light-induced photoreceptor morphological changes that were associated with ROS production, and that are characteristic of RP. Further investigation showed that norgestrel acts via post-translational modulation of the major antioxidant transcription factor Nrf2; bringing about its phosphorylation, subsequent nuclear translocation, and increased levels of its effector protein superoxide dismutase 2 (SOD2). In summary, these results demonstrate significant protection of photoreceptor cells from oxidative stress, and underscore the potential of norgestrel as a therapeutic option for RP.

Normative values of retinal vessel oximetry in healthy children against adults

PurposeRetinal oximetry (RO) has been established as a non‐invasive method to analyze oxygen saturation in retinal vessels. The aim of our study was to compare metabolic (oxygen saturation) and anatomical (retinal vessel diameter) RO parameters of healthy children against adults.MethodsA total of 157 eyes of 79 healthy subjects were examined: 20 eyes of children (7–18 year) were compared to adults of different age groups [20–29 year (n = 16); 30–39 year (n = 46); 40–49 year (n = 38); 50–59 year (n = 25), 60–87 year (n = 12)]. RO 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 evaluated the corresponding diameter in retinal arterioles (D‐A) and venules (D‐V). For statistical evaluation non‐parametric tests (Friedman test for multiple comparisons, paired Wilcoxon rank sum test for pairwise comparisons) were performed.ResultsChildren showed statistically significant lower arterial oxygen saturation values (A‐SO2) compared to all adult subgroups (Friedman test, p = 0.0005). Although not statistically significant, the values of V‐SO2 (p = 0.06) and A‐V SO2 (p = 0.30) showed a trend to be lower in children. The D‐A (p = 0.49) and D‐V (p = 0.82) values were not significantly different between groups.ConclusionsThese data indicate that the retinal oxygen metabolism changes throughout lifetime. Therefore, normative data for different age groups are mandatory.

Shifts in retinal vessel diameter and oxygen saturation in Chinese type 2 diabetes mellitus patients.

BackgroundThe aim of this study was to analyze the shifts in retinal vessel diameter and oxygen saturation in diabetic patients with and without diabetic retinopathy (DR), as well as to assess the association between diabetes duration and either vessel diameter or oxygen saturation.MethodsIn total, 99 Type 2 DM patients were recruited for the study and were divided into three groups: DM with non-obvious retinopathy (DM, n = 29), non-proliferative diabetic retinopathy (NPDR, n = 40), and proliferative diabetic retinopathy (PDR, n = 30). In addition, 78 age-matched healthy individuals were chosen as the control. The diameter and oxygen saturation of the retinal vessels were analyzed using a noninvasive retinal oximeter, and then compared between the three groups and the normal control. Association analysis was applied to analyze the possible influencing factors, including the diameter and oxygen saturation of retinal vessels, on best corrected visual acuity BCVA, as well as the relationship between diabetes duration and the oximetry values.ResultsAll of the diabetic patients showed thinner arterioles, wider venules, and a smaller arteriolar-to-venular ratio (AVR) than the healthy individuals. The AVR results from the controls through to the PDR group were 0.81 ± 0.07, 0.78 ± 0.07, 0.76 ± 0.07 and 0.67 ± 0.07, respectively. Both the NPDR and PDR groups showed significantly smaller AVR than the control. All of the diabetic patients exhibited higher retinal vessel oxygen saturation than the healthy individuals. Among all of the oximetry values, AVR exhibited the most significant correlation with best corrected visual acuity (BCVA) (β = 1.533, P < 0.0001). An increased diabetes duration was associated with decreased arteriolar diameter (slope = −0.082 pixels/year, r2 = 0.085, P = 0.004) and AVR (slope = −0.009/year, r2 = 0.349, P < 0.001), and with increased venular diameter (slope = 0.104 pixels/year, r2 = −0.109, P = 0.001).ConclusionsIn this Chinese population with type 2 DM, the thinner arterioles and wider venules point to microvascular dysfunction in DR. The increased oxygen saturation of the retinal vessels suggests that retinal oxygen metabolism is affected in diabetic retinopathy.

Retinal vessel oxygen saturation in a healthy young Chinese population.

To measure retinal vessel oxygen saturation in a healthy young Chinese population and to determine the effects of multiple factors (gender, age, dioptre, vessel diameter and ocular perfusion pressure - OPP) on retinal oxygen saturation. A total of 126 healthy Chinese individuals aged from 19 to 30 were included in this study. A retinal oximeter (Oxymap T1) was used to measure retinal vessel oxygen saturation by retinal imaging at two different wavelengths. The mean retinal vessel oxygen saturation (Sat_O2 ) of arterioles, venules and arteriovenous (AV) difference overall and in four separate quadrants were measured. Intra-ocular pressure, blood pressure, finger pulse oximetry value, vessel diameter and dioptre were also measured. The correlations between OPP and dioptre, OPP and vessel diameter, and dioptre and vessel diameter were analysed. And the effects of multiple factors on the retinal oxygen saturation were analysed. The mean oxygen saturation was 93.2±6.3% in the retinal arterioles, 60.4±5.3% in venules and 32.9±6.4% in AV difference. The temporal quadrants had lower measurements of arteriolar and venular oxygen saturation and AV difference compared with nasal quadrants (p<0.001). The oxygen saturation of the arterioles, venules and AV difference were unaffected by any unique factor. Arteriolar and venular retinal oxygen saturation correlated negatively with the product of dioptre and OPP. Arteriolar retinal oxygen saturation correlated positively with the product of dioptre and vessel diameter. This study provided a normal reference of Sat_O2 in healthy young Chinese individuals. It was a reflection of the normal state of retinal oxygen metabolism affected by several factors.

Inner retinal oxygen metabolism in the 50/10 oxygen-induced retinopathy model.

Retinopathy of prematurity (ROP) represents a major cause of childhood vision loss worldwide. The 50/10 oxygen-induced retinopathy (OIR) model mimics the findings of ROP, including peripheral vascular attenuation and neovascularization. The oxygen metabolism of the inner retina has not been previously explored in this model. Using visible-light optical coherence tomography (vis-OCT), we measured the oxygen saturation of hemoglobin and blood flow within inner retinal vessels, enabling us to compute the inner retinal oxygen delivery (irDO2) and metabolic rate of oxygen (irMRO2). We compared these measurements between age-matched room-air controls and rats with 50/10 OIR on postnatal day 18. To account for a 61% decrease in the irDO2 in the OIR group, we found an overall statistically significant decrease in retinal vascular density affecting the superficial and deep retinal vascular capillary networks in rats with OIR compared to controls. Furthermore, matching the reduced irDO2, we found a 59% decrease in irMRO2, which we correlated with a statistically significant reduction in retinal thickness in the OIR group, suggesting that the decreased irMRO2 was due to decreased neuronal oxygen utilization. By exploring these biological and metabolic changes in great detail, our study provides an improved understanding of the pathophysiology of OIR model.

Retinal oximetry imaging in Alzheimer's disease.

Structural and physiological abnormalities have been reported in the retina in Alzheimer's disease (AD). Retinal oximetry detects changes in retinal oxygen metabolism in many eye diseases, where structural changes are seen. To compare oxygen saturation in retinal blood vessels in patients with AD and a healthy cohort. Oxygen saturation of hemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric noninvasive retinal oximeter. 18 individuals with mild to moderate dementia of the Alzheimer-type (stage 3-5 according to the Global Deterioration Scale) and 18 healthy subjects underwent retinal oximetry in a case control study. Retinal oxygen saturation in arterioles and venules in patients with moderate AD was significantly elevated compared to healthy individuals. Retinal arterioles have 94.2 ± 5.4% oxygen saturation in moderate AD compared with 90.5 ± 3.1% in healthy subjects (mean ± SD, n = 10, p = 0.028). Retinal venules were 51.9 ± 6.0% saturated in moderate AD compared with 49.7 ± 7.0% in healthy subjects (mean ± SD, n = 10, p = 0.02). This is the first study of retinal oxygen metabolism in any central nervous system disease. It discovers abnormalities in retinal oxygen metabolism in AD. The findings are similar to those seen in age-related macular degeneration and diabetic retinopathy. Noninvasive retinal oximetry may offer new insights into pathophysiology of AD. Further studies are needed to confirm and expand these findings.

The effect of intravitreal vascular endothelial growth factor on inner retinal oxygen delivery and metabolism in rats

Vascular endothelial growth factor (VEGF) is stimulated by hypoxia and plays an important role in pathologic vascular leakage and neovascularization. Increased VEGF may affect inner retinal oxygen delivery (DO2) and oxygen metabolism (MO2), however, quantitative information is lacking. We tested the hypotheses that VEGF increases DO2, but does not alter MO2. In 10 rats, VEGF was injected intravitreally into one eye, whereas balanced salt solution (BSS) was injected into the fellow eye, 24 h prior to imaging. Vessel diameters and blood velocities were determined by red-free and fluorescent microsphere imaging, respectively. Vascular PO2 values were derived by phosphorescence lifetime imaging of an intravascular oxyphor. Retinal blood flow, vascular oxygen content, DO2 and MO2 were calculated. Retinal arterial and venous diameters were larger in VEGF-injected eyes compared to control eyes (P < 0.03), however no significant difference was observed in blood velocity (P = 0.21). Thus, retinal blood flow was greater in VEGF-injected eyes (P = 0.007). Retinal vascular PO2 and oxygen content were similar between control and VEGF-injected eyes (P > 0.11), while the arteriovenous oxygen content difference was marginally lower in VEGF-injected eyes (P = 0.05). DO2 was 950 ± 340 and 1380 ± 650 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.005). MO2 was 440 ± 150 and 490 ± 190 nL O2/min in control and VEGF-injected eyes, respectively (P = 0.31). Intravitreally administered VEGF did not alter MO2 but increased DO2, suggesting VEGF may play an offsetting role in conditions characterized by retinal hypoxia.

Inner Retinal Oxygen Extraction Fraction in Response to Light Flicker Stimulation in Humans

Light flicker has been shown to stimulate retinal neural activity, increase blood flow, and alter inner retinal oxygen metabolism (MO2) and delivery (DO2). The purpose of the study was to determine the change in MO2 relative to DO2 due to light flicker stimulation in humans, as assessed by the inner retinal oxygen extraction fraction (OEF). An optical imaging system, based on a modified slit lamp biomicroscope, was developed for simultaneous measurements of retinal vascular diameter (D) and oxygen saturation (SO2). Retinal images were acquired in 20 healthy subjects before and during light flicker stimulation. Arterial and venous D (DA and DV) and SO2 (SO2A and SO2V) were quantified within a circumpapillary region. Oxygen extraction fraction was defined as the ratio of MO2 to DO2 and was calculated as (SO2A - SO2V)/SO2A. Reproducibility of measurements was assessed. Coefficients of variation and intraclass correlation coefficients of repeated measurements were <5% and ≥0.83, respectively. During light flicker stimulation, DA, DV , and SO2V significantly increased (P ≤ 0.004). Oxygen extraction fraction was 0.37 ± 0.08 before light flicker and significantly decreased to 0.31 ± 0.07 during light flicker (P = 0.001). Oxygen extraction fraction before and during light flicker stimulation is reported in human subjects for the first time. Oxygen extraction fraction decreased during light flicker stimulation, indicating the change in DO2 exceeded that of MO2. This technology is potentially useful for the detection of changes in OEF response to light flicker in physiological and pathological retinal conditions.

Regulation of retinal oxygen metabolism in humans during graded hypoxia.

Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O₂ in 88% N₂ as well as breathing 15% O₂ in 85% N₂. Oxygen saturation in a retinal artery (SO₂art) and an adjacent retinal vein (SO₂vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O₂ breathing, respectively. SO₂art as well as SO₂vein decreased during both 12% O₂ breathing (SO₂art: -11.2 ± 4.3%, P < 0.001; SO₂vein: -3.9 ± 8.5%, P = 0.012) and 15% O₂ breathing (SO₂art: -7.9 ± 3.6%, P < 0.001; SO₂vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O₂: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O₂: -2.8 ± 18.9%, P = 0.65; 15% O₂: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia.

Retinal oxygen metabolism during normoxia and hyperoxia in healthy subjects.

To characterize retinal metabolism during normoxia and hyperoxia in healthy subjects. Forty-six healthy subjects were included in the present study, and data of 41 subjects could be evaluated. Retinal vessel diameters, as well as oxygen saturation in arteries and veins, were measured using the Dynamic Vessel Analyzer. In addition, retinal venous blood velocity was measured using bidirectional laser Doppler velocimetry, retinal blood flow was calculated, and oxygen and carbon dioxide partial pressures were measured from arterialized capillary blood from the earlobe. Measurements were done during normoxia and during 100% oxygen breathing. Systemic hyperoxia caused a significant decrease in retinal venous diameter (-13.0% ± 4.5%) and arterial diameter (-12.1% ± 4.0%), in retinal blood velocity (-43.4% ± 7.7%), and in retinal blood flow (-57.0% ± 5.7%) (P < 0.001 for all). Oxygen saturation increased in retinal arteries (+4.4% ± 2.3%) and in retinal veins (+19.6% ± 6.2%), but the arteriovenous oxygen content difference significantly decreased (-29.4% ± 19.5%) (P < 0.001 for all). Blood oxygen tension in arterialized blood showed a pronounced increase from 90.2 ± 7.7 to 371.3 ± 92.7 mm Hg (P < 0.001). Calculated oxygen extraction in the eye decreased by as much as 62.5% ± 9.5% (P < 0.001). Our data are compatible with the hypothesis that during 100% oxygen breathing a large amount of oxygen, consumed by the inner retina, comes from the choroid, which is supported by previous animal data. Interpretation of oxygen saturation data in retinal arteries and veins without quantifying blood flow is difficult. (ClinicalTrials.gov number, NCT01692821.).

Inner Retinal Oxygen Delivery and Metabolism in Streptozotocin Diabetic Rats

The purpose of the study is to report global measurements of inner retinal oxygen delivery (DO2_IR) and oxygen metabolism (MO2_IR) in streptozotocin (STZ) diabetic rats. Phosphorescence lifetime and blood flow imaging were performed in rats 4 (STZ/4 wk; n = 10) and 6 (STZ/6 wk; n = 10) weeks following injection of STZ to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). DO2_IR and MO2_IR were calculated from measurements of F and O2A and of F and the arteriovenous oxygen content difference, respectively. Data in STZ rats were compared to those in healthy control rats (n = 10). Measurements of O2A and O2V were not significantly different among STZ/4 wk, STZ/6 wk, and control rats (P ≥ 0.28). Likewise, F was similar among all groups of rats (P = 0.81). DO2_IR measurements were 941 ± 231, 956 ± 232, and 973 ± 243 nL O2/min in control, STZ/4 wk, and STZ/6 wk rats, respectively (P = 0.95). MO2_IR measurements were 516 ± 175, 444 ± 103, and 496 ± 84 nL O2/min in control, STZ/4 wk, and STZ/6 wk rats, respectively (P = 0.37). Global inner retinal oxygen delivery and metabolism were not significantly impaired in STZ rats in early diabetes.

Retinal oxygen metabolism in healthy subjects and glaucoma patients

BackgroundTo test whether retinal oxygen metabolism is different in glaucoma patients compared with healthy subjects.MethodsThis was a two-centre study where retinal vessel oxygen saturation was measured in glaucoma patients and...

Retinal oxygen metabolism in exudative age‐related macular degeneration

To determine whether retinal vessel oxygen saturation in patients with exudative age-related macular degeneration (AMD) is different from that of a healthy population. Oxygen saturation was measured in retinal arterioles and venules in 46 eyes of 46 treatment-naïve exudative AMD patients and 120 eyes of 120 healthy controls. Simple and multiple linear regression analyses were used to compare the two study groups. Oxygen saturation in retinal venules increases with age in patients with exudative AMD (0.45 ± 0.19% per year; p = 0.026), while it decreases with age in healthy individuals (-0.13 ± 0.03% per year; p = 0.0002). The slopes are statistically different (ANCOVA; p = 0.0003). The reverse is true for the arteriovenous difference in oxygen saturation, which decreases with age in AMD patients (-0.29 ± 0.16% per year; p = 0.065) and increases in healthy individuals (0.12 ± 0.03% per year; p < 0.0001). At age 80 years, AMD patients have 2.7 percentage points higher venous oxygen saturation than healthy persons and 4.2 percentage points less arteriovenous difference. The data suggest that retinal oxygen metabolism may be altered in exudative AMD. The arteriovenous difference is smaller in exudative AMD than in a healthy cohort, consistent with reduced oxygen extraction by retinal vessels in AMD patients. Further studies are needed to fully understand the role of retinal oxygen metabolism in the pathophysiology of exudative AMD.

Retinal Oximetry – Metabolic Imaging of the Retina

AbstractDiagnostic imaging of retinal disease has been limited to structural analysis, angiography and testing of visual function. Until the advent of retinal oximetry, no metabolic retinal imaging has been available in the clinic. Metabolic imaging has obvious relevance to metabolic disease such as diabetic retinopathy and oxygen imaging is particularly appropriate for ischemic disease such as retinal vein and artery occlusion. Fundus camera based spectrophotometric retinal oximeters have allowed clinical studies over the last several years. Remarkably, abnormalities in retinal oxygen metabolism have been discovered in most major retinal diseases, including diabetic retinopathy, retinal vein occlusions, glaucoma and age related macular degeneration. These results open a new window into the pathophysiology of these diseases and may help evaluate severity and progression.

The retina, private practice and being your own boss

Interview by Jitesh PatelAbdhish R Bhavsar, MD, is a retina and vitreous surgeon who was born in Connecticut, USA, grew up in Michigan and has practiced in the Minneapolis/St. Paul (MN, USA) area since August 1997. He graduated from Dartmouth College with an Honors Thesis in Biochemistry and from the Wayne State University School of Medicine with Alpha Omega Alpha honors. He completed his internship in internal medicine at Duke University (NC, USA), his ophthalmology residency at the University of Illinois Eye and Ear Infirmary in Chicago, USA, and his retina surgery fellowship training at the Jules Stein Eye Institute at UCLA (CA, USA). He was also a Heed Ophthalmic Foundation Fellow.Bhavsar has maintained research interests in macular degeneration, diabetic retinopathy, endophthalmitis and retinal oxygen metabolism. He is a principal investigator in multiple clinical trials in macular degeneration, diabetic retinopathy and venous occlusive disease and also maintains a broad range of interests in managing vitreoretinal, medical and surgical diseases, with additional interests in retinopathy of prematurity and intraocular tumors.Bhavsar is an active member of the American Academy of Ophthalmology, the American Society of Retina Specialists and the Association for Research in Vision and Ophthalmology. He is a Clinical Assistant Professor at the University of Minnesota and an Attending Surgeon at the Phillips Eye Institute in Minneapolis. Bhavsar is a past President of the Minnesota Academy of Ophthalmology, past President of the Minneapolis Ophthalmological Society, past Chair of the Phillips Eye Institute Department of Ophthalmology, founding Chair of the Minnesota Academy of Ophthalmology Web Site Committee and the state Chair for Diabetes Eye Exam Initiative. Dr. Bhavsar was the first Chair of the American Academy of Ophthalmology Web Advisory Task Force and graduated from the American Academy of Ophthalmology Leadership Development Program in 2001.

Inner Retinal Oxygen Delivery and Metabolism Under Normoxia and Hypoxia in Rat

Retinal hypoxia is a common pathological condition usually caused by ischemia that may result in alterations in oxidative energy metabolism. We report measurements of oxygen delivery by the retinal circulation (DO2_IR) and inner retinal oxygen metabolism (MO2_IR) under systemic normoxia and hypoxia in rat. Rats were ventilated with fractions of inspired oxygen (FiO2) to induce either normoxia (n = 10), moderate hypoxia (n = 14), or severe hypoxia (n = 10). Oxygen tension was measured in retinal vessels using phosphorescence lifetime imaging and converted to arterial (O2A) and venous (O2V) oxygen contents. Total retinal blood flow (F) was assessed by red-free and fluorescent microsphere imaging. DO2_IR and MO2_IR were calculated as the products of F and O2A, and F and the arteriovenous oxygen content difference (O2A-V), respectively. Measurements of O2A, O2V, and O2A-V were significantly reduced with decreased FiO2 (P < 0.001). In response to reduced oxygen availability, F increased under moderate hypoxia (P < 0.001) but did not increase further under severe hypoxia (P = 0.5). DO2_IR was similar under normoxia and moderate hypoxia (P = 0.7), but significantly lower under severe hypoxia (P < 0.001). Likewise, MO2_IR under normoxia and moderate hypoxia was similar (P = 0.1), but significantly reduced under severe hypoxia (P ≤ 0.02). DO2_IR and MO2_IR were maintained during moderate hypoxia, but reduced under severe hypoxia, indicating blood flow compensation became insufficient for the reduced oxygen availability. Future studies may aid our understanding of retinal metabolic function in ischemic conditions.

Retinal Oxygen Saturation and Metabolism: How does it Pertain to Glaucoma? An Update on the Application of Retinal Oximetry in Glaucoma

To discuss the techniques and mechanisms of retinal oximetry with a focus on utilization of retinal oximetry in the assessment of retinal oxygen saturation in glaucoma. We reviewed recent literature found by searching combinations of the following search terms: glaucoma, retinal oximetry, ocular blood flow, retinal blood flow, oxygen saturation. We also reviewed pertinent references from articles found in this search. Retinal oximetry offers the potential for directly assessing oxygen saturation in retinal tissue. This capability can contribute to the knowledge of ocular blood flow and its role in the pathogenesis of glaucoma. Recent research has shown that retinal oximetry could become an important clinical tool in glaucoma. However, more research is needed to validate the reliability and reproducibility of retinal oximetry, and to fully deduce its clinical role in ocular diseases.

Oxygen metabolism in age related macular degeneration

AbstractPurpose To determine whether oxygen saturation in retinal vessels of patients with age‐related macular degeneration (AMD) is different from that of a healthy population.Methods The non‐invasive retinal oximeter is based on a fundus camera. It simultaneously captures images of the retina at 600 nm and 570 nm and estimates retinal vessel oxygen saturation. Mean oxygen saturation of hemoglobin was measured in retinal arterioles and venules of 28 individuals with AMD, 6 were males. Eight patients had early AMD in at least one eye, 8 patients had untreated exudative AMD in at least one eye, and 12 patients had early AMD in one eye and untreated exudative AMD in the other eye. The age of AMD patients was 78 ± 9 years (mean ± SD) compared to 66 ± 4 years for the healthy controls (n=26).Results Oxygen saturation of hemoglobin in arterioles, after adjusting for vessel width, was 94.3 ± 3.7% in the healthy population compared to 93.5 ± 3.1% in early AMD (n= ;p=0.42) and 93.7 ± 3.8% in exudative AMD (n= ;p=0.55). The corresponding values in venules were 60.9 ± 5.6% in healthy eyes compared to 64.9 ± 7.0% in exudative AMD (p=0.017). In eleven patients with early AMD in one eye and exudative AMD in the other eye, oxygen saturation in arterioles was 93.5 ± 3.0% and 92.4 ± 2.8% (p=0.52) and in venules 66.3 ± 4.9% and 64.4 ± 5.3% (p=0.080).Conclusion Oxygen saturation in venules in exudative AMD is higher than in healthy controls and there is a similar trend in early AMD. Arteriovenous difference is smaller in AMD subjects than normals. The study suggests that retinal oxygen metabolism is affected in AMD. Commercial interest