Retinal oximetry: Metabolic imaging for diseases of the retina and brain.

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of hemoglobin. 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 and brain disease. 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 edema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia. Glaucomatous retinal atrophy is associated with reduced oxygen consumption resulting in reduced arteriovenous difference and higher retinal venous saturation. The oximetry findings correlate with worse visual field, thinner nerve fiber layer and smaller optic disc rim. This provides an objective biomarker for glaucomatous damage. In retinitis pigmentosa, an association exists between advanced atrophy, worse visual field and higher retinal venous oxygen saturation, lower arteriovenous difference. This biomarker may allow measurement of severity and progression of retinitis pigmentosa and other atrophic retinal diseases. Retinal oximetry offers visible light imaging of systemic and central nervous system vessels. It senses hypoxia in cardiac and pulmonary diseases. Oximetry biomarkers have been discovered in Alzheimer's disease and multiple sclerosis and oxygen levels in the retina correspond well with brain.

Retinal oxygen metabolism in patients with mild cognitive impairment.

INTRODUCTION: We have previously reported that retinal vessel oxygen saturation is increased in mild-to-moderate dementia of Alzheimer's type when compared with healthy individuals. Mild cognitive impairment (MCI) is the predementia stage of the disease. The main purpose was to investigate if these changes are seen in MCI. METHODS: Retinal vessel oxygen saturation was measured in 42 patients with MCI and 42 healthy individuals with a noninvasive retinal oximeter, Oxymap T1. The groups were paired according to age. RESULTS: Arteriolar and venular oxygen saturation was increased in MCI patients compared to healthy individuals (arterioles: 93.1 ± 3.7% vs. 91.1 ± 3.4%, P = .01; venules: 59.6 ± 6.1% vs. 54.9 ± 6.4%, P = .001). Arteriovenous difference was decreased in MCI compared to healthy individuals (33.5 ± 4.5% vs. 36.2 ± 5.2%, P = .01). DISCUSSION: Increased retinal vessel oxygen saturation and decreased arteriovenous difference in MCI could reflect less oxygen extraction by retinal tissue. This indicates that retinal oxygen metabolism may be affected in patients with MCI.

Retinal oximetry is affected in multiple sclerosis.

PURPOSE: Structural and physiological abnormalities have been reported in the retina in patients with multiple sclerosis (MS). Retinal oximetry has recently detected changes in retinal oxygen metabolism in Alzheimer's disease and mild cognitive impairment. Our goal was to determine whether oxygen saturation in retinal blood vessels of patients with patients is different from that of a healthy population. METHODS: Oxygen saturation of haemoglobin was measured in retinal blood vessels, using imaging with spectrophotometric noninvasive retinal oximeter. Eight MS patients with history of optic neuritis were measured and compared to 22 healthy individuals matched in age and gender. RESULTS: Venular oxygen saturation was increased in patients with MS compared to healthy individuals (70.7 ± 3.4% versus 66.2 ± 4.7; p = 0.021, mean ± SD). The arteriovenous (AV) difference was lower in patients with MS compared to healthy (26.6 ± 3.6% versus 30.5 ± 4.8%; p = 0.049). There was no difference measured in arterioles when patients with MS (97.3 ± 1.7%) and healthy individuals (96.7 ± 2.8%) were compared. CONCLUSION: Increased venular oxygen saturation and lower AV difference in patients with MS may indicate reduced oxygen uptake. This may be due to less oxygen demand following atrophy and may be a useful objective biomarker for MS. Further studies are needed to confirm and expand these findings.

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 Alzheimer's 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 Alzheimer's 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 oximetry imaging in Alzheimer's disease.

BACKGROUND: 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. OBJECTIVE: To compare oxygen saturation in retinal blood vessels in patients with AD and a healthy cohort. METHODS: 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. RESULTS: 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). CONCLUSION: 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.