Thorunn Scheving Eliasdottir

Venous oxygen saturation is reduced and variable in central retinal vein occlusion

Purpose To estimate the presence and variability of retinal hypoxia in patients with central retinal vein occlusion (CRVO).

Retinal Oximetry With a Scanning Laser Ophthalmoscope

PURPOSE The purpose of the study was to assess if a scanning laser ophthalmoscope (SLO), Optomap 200Tx, could be used for measurements of hemoglobin oxygen saturation in retinal blood vessels. METHODS Optomap 200Tx uses two lasers for image acquisition, 532 and 633 nm. Retinal images of healthy individuals and patients with retinal vein occlusion were analyzed with modified Oxymap Analyzer software, which tracks retinal vessels and calculates relative hemoglobin oxygen saturation. RESULTS Oxygen saturation in healthy individuals was measured as 92% ± 13% for arterioles and 57% ± 12% for venules (mean ± SD, n = 11, P = 0.0001). Standard deviation for repeated measurements of the same eye was 3.5% for arterioles and 4.4% for venules. In patients with confirmed venular hypoxia, central retinal vein occlusion (CRVO) or hemivein occlusion, the average venular oxygen saturation was measured as 23% ± 3% in the affected eyes and 59% ± 3% in the fellow eyes (n = 4, P = 0.0009). CONCLUSIONS Technically, it is possible to derive information on retinal oxygen saturation from an SLO with a 2-wavelength oximetry algorithm. The system produced both sensitive and repeatable results. The remaining challenges include decreasing variability between vessels of the same eye and variability between individuals. Given the advantages that SLO imaging has over conventional fundus camera optics in retinal oximetry, further development of SLO oximetry may provide the optimal approach to retinal oximetry.

Retinal Oximetry Discovers Novel Biomarkers in Retinal and Brain Diseases

Purpose Biomarkers for several eye and brain diseases are reviewed, where retinal oximetry may help confirm diagnosis or measure severity of disease. These include diabetic retinopathy, central retinal vein occlusion (CRVO), retinitis pigmentosa, glaucoma, and Alzheimers disease. Methods Retinal oximetry is based on spectrophotometric fundus imaging and measures oxygen saturation in retinal arterioles and venules in a noninvasive, quick, safe manner. Retinal oximetry detects changes in oxygen metabolism, including those that result from ischemia or atrophy. Results In diabetic retinopathy, venous oxygen saturation increases and arteriovenous difference decreases. Both correlate with diabetic retinopathy severity as conventionally classified on fundus photographs. In CRVO, vein occlusion causes hypoxia, which is measured directly by retinal oximetry to confirm the diagnosis and measure severity. In both diseases, the change in oxygen levels is a consequence of disturbed blood flow with resulting tissue hypoxia and vascular endothelial growth factor (VEGF) production. In atrophic diseases, such as retinitis pigmentosa and glaucoma, retinal oxygen consumption is reduced and this is detected by retinal oximetry. Retinal oximetry correlates with visual field damage and retinal atrophy. It is an objective metabolic measure of the degree of retinal atrophy. Finally, the retina is part of the central nervous system tissue and reflects central nervous system diseases. In Alzheimers disease, a change in retinal oxygen metabolism has been discovered. Conclusions Retinal oximetry is a novel, noninvasive technology that opens the field of metabolic imaging of the retina. Biomarkers in metabolic, ischemic, and atrophic diseases of the retina and central nervous system have been discovered.

Retinal Vessel Oxygen Saturation during 100% Oxygen Breathing in Healthy Individuals

Purpose To detect how systemic hyperoxia affects oxygen saturation in retinal arterioles and venules in healthy individuals. Methods Retinal vessel oxygen saturation was measured in 30 healthy individuals with a spectrophotometric retinal oximeter (Oxymap T1). Oximetry was performed during breathing of room air, 100% oxygen (10 minutes, 6L/min) and then again room air (10 minutes recovery). Results Mean oxygen saturation rises modestly in retinal arterioles during 100% oxygen breathing (94.5%±3.8 vs. 92.0%±3.7% at baseline, p<0.0001) and dramatically in retinal venules (76.2%±8.0% vs. 51.3%±5.6%, p<0.0001). The arteriovenous difference decreased during 100% oxygen breathing (18.3%±9.0% vs. 40.7%±5.7%, p<0.0001). The mean diameter of arterioles decreased during 100% oxygen breathing compared to baseline (9.7±1.4 pixels vs. 10.3±1.3 pixels, p<0.0001) and the same applies to the mean venular diameter (11.4±1.2 pixels vs. 13.3±1.5 pixels, p<0.0001). Conclusions Breathing 100% oxygen increases oxygen saturation in retinal arterioles and more so in venules and constricts them compared to baseline levels. The dramatic increase in oxygen saturation in venules reflects oxygen flow from the choroid and the unusual vascular anatomy and oxygen physiology of the eye.

Choroidal Oximetry With a Noninvasive Spectrophotometric Oximeter

PURPOSE The purpose of the study was to establish a new technology to measure hemoglobin oxygen saturation in human choroidal vasculature with a noninvasive spectrophotometric oximeter. METHODS The fundus camera-based oximeter captures dual-wavelength oximetry images of the fundus and calculates optical density ratio (ODR), which is inversely related to hemoglobin oxygen saturation. Sixteen healthy and lightly pigmented individuals were imaged during normoxia and six during both normoxia and pure oxygen breathing (hyperoxia). ODR was measured for choroidal vessels, vortex veins, and retinal arterioles and venules. RESULTS ODR was 0.10 ± 0.10 (mean ± SD) for choroidal vessels, 0.13 ± 0.12 for vortex veins, 0.22 ± 0.04 for retinal arterioles, and 0.50 ± 0.09 for retinal venules. Inhalation of pure oxygen lowered ODR levels in all vessel types; the decrease was 0.035 ± 0.028 in choroidal vessels (P = 0.029, paired t-test), 0.022 ± 0.017 in the retinal arterioles (P = 0.022, paired t-test), and 0.246 ± 0.067 in retinal venules (P = 0.0003, paired t-test). CONCLUSIONS The ODR can be measured noninvasively in the choroidal vessels of lightly pigmented individuals and is significantly lower in choroidal vessels than in retinal arterioles. This may suggest higher oxygen saturation but is also compatible with the reduced contrast of choroidal vessels at both wavelengths that is expected from scattering of light within the choroid. The decrease of ODR during hyperoxia was significant for all vessel types, which confirms that the oximeter is sensitive to changes in oxygen saturation in both choroidal and retinal vessels.

Retinal Oximetry with Scanning Laser Ophthalmoscope in Infants

Purpose Dual wavelength retinal oximetry has been developed for adults, but is not available for infants. Retinal oximetry may provide insight into the pathophysiology of oxygen-mediated diseases like retinopathy of prematurity. More insight in the oxygen metabolism of the retina in infants may provide valuable clues for better understanding and subsequent prevention or treatment of the disease. The measurements of oxygen saturation are obtained with two fundus images simultaneously captured in two different wavelengths of light. The comparison in light absorption of oxygenated and deoxygenated hemoglobin can be used to estimate the oxygen saturation within the retinal vessels by means of a software algorithm. This study aims to make retinal oximetry available for neonates. The first step towards estimating retinal oxygen saturation is determining the optical density ratio. Therefore, the purpose of this study is to image healthy newborn infants with a scanning laser ophthalmoscope and determine the optical density ratio for retinal oximetry analysis. Methods Images of the retina of full-term healthy infants were obtained with an SLO, Optomap 200Tx (Optos), with two laser wavelengths (532nm and 633nm). The infant lay face down on the lower arm of the parent, while the parent supported the chest and chin with one hand, and stabilized the back with the other hand. No mydriatics or eyelid specula were used during this study. The images were analyzed with modified Oxymap Analyzer software for calculation of the Optical Density Ratio (ODR) and vessel width. The ODR is inversely and approximately linearly related to the oxygen saturation. Measurements were included from the superotemporal vessel pair. A paired t-test was used for statistical analysis. Results Fifty-nine infants, (58% female), were included with mean gestational age of 40 ± 1.3 weeks (mean ± SD) and mean post-natal age of 16 ± 4.8 days. A total of 28 images were selected for retinal oximetry analysis. The ODR was 0.256 ± 0.041 for the arterioles and 0.421 ± 0.089 for the venules (n = 28, p < 0.001). The measured vessel-width for the arterioles was 14.1 ± 2.7 pixels and for the venules 19.7 ± 3.7 pixels (n = 28, p < 0.001). Conclusions Retinal oximetry can be performed in newborn infants by combining an SLO and a dual-wavelength algorithm software. Sensitivity of the approach is indicated by the fact that the ODR measurements are significantly different between the arterioles and the venules. However, more variability in ODR is seen with the SLO approach in babies than is seen with conventional oximetry in adults. This approach is completely non-invasive, non-contact and even avoids the use of mydriatics or eyelid specula.

Retinal oximetry measures systemic hypoxia in central nervous system vessels in chronic obstructive pulmonary disease

Background Determination of the blood oxyhemoglobin saturation in the retinal vessels of the eye can be achieved through spectrophotometric retinal oximetry which provides access to the state of oxyhemoglobin saturation in the central nervous system circulation. The purpose of this study was to test the capability of the Oxymap T1 oximeter to detect systemic hypoxemia and the effect of supplemental oxygen on retinal vessel oxyhemoglobin saturation. Methods Oxygen saturation of hemoglobin in retinal arterioles and venules was measured in 11 subjects with severe chronic obstructive pulmonary disease (COPD) on long term oxygen therapy. Measurements were made with and without their daily supplemental oxygen. Eleven healthy age and gender matched subjects were measured during ambient air breathing for comparison of oxyhemoglobin saturation in retinal arterioles and venules. Retinal arteriolar oxyhemoglobin saturation in COPD subjects inspiring ambient air was compared with finger pulse oximetry and blood samples from radial artery. Results COPD subjects had significantly lower oxyhemoglobin saturation during ambient air breathing than healthy controls in both retinal arterioles (87.2%±4.9% vs. 93.4%±4.3%, p = 0.02; n = 11) and venules (45.0%±10.3% vs. 55.2%±5.5%, p = 0.01). Administration of their prescribed supplemental oxygen increased oxyhemoglobin saturation in retinal arterioles (87.2%±4.9% to 89.5%±6.0%, p = 0.02) but not in venules (45.0%±10.3% to 46.7%±12.8%, p = 0.3). Retinal oximetry values were slightly lower than radial artery blood values (mean percentage points difference = -5.0±5.4, 95% CI: -15.68 to 5.67) and finger pulse oximetry values (-3.1±5.5, 95% CI: -14.05 to 7.84). Conclusions The noninvasive Oxymap T1 retinal oximetry detects hypoxemia in central nervous system vessels in patients with severe COPD compared with healthy controls. The instrument is sensitive to changes in oxygen breathing but displays slightly lower measures than finger pulse oximetry or radial artery measures. With further technological improvement, retinal oximetry may offer noninvasive “on-line” measurement of oxygen levels in central circulation in general anesthesia and critically ill patients.

Fundus imaging in newborn children with wide-field scanning laser ophthalmoscope

Current fundus imaging in newborn babies requires mydriatics, eye specula and corneal contact. We propose that a scanning laser ophthalmoscope (SLO) allows ultra wide‐field imaging with reduced stress for the child.

Response to the letter to the editor: Venous oxygen saturation is reduced and variable in central retinal vein occlusion

Dear editor; We want to thank Yolcu et al. for their insightful letter about our study. We fully agree with their opinion on pertinence for oximetric results of central retinal vein occlusion (CRVO) eyes with and without macular edema or retinal ischemia to be compared with each other. We also agree that its results can be compared with fluorescein angiography and optical coherence tomography findings in different sectors of the retinal fundus. This is important in order to explore the clinical utility of the oximeter. Our study [1] demonstrates variable retinal hypoxia in CRVO eyes that in general seems to get better with time, treatment and improving clinical symptoms. Our preliminary findings suggest a correlation between retinal oximeter measurements and clinical signs and symptoms. Hypoxia measurements in retinal venules were consistent with capillary nonperfusion on fluorescein angiography [1]. We agree that assessing patients by optical coherence tomography and fluorescein angiography and comparing with retinal oximeter measurements will provide valuable information for the pathogenesis and management of CRVO. We have started a multicenter study in order to answer the aforementioned questions and pursue the clinical utility of retinal oximetry in CRVO.