Retinal Oximetry

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Definition

Retinal oximetry is a non-invasive imaging technique that allows reproducible calculation of retinal blood vessel oxygen saturation.

History

The first use of oximetry in a clinical setting was in 1935, when a German doctor produced an ear oximeter. Early versions of retinal oximetry arose in the 1950s, but advances in digital technology within the past decade have allowed for emergent clinical and research applications. There are currently two main systems: the Oxymap Retinal Oximeter (Fig. 1-2) and the Vesselmap system (Fig. 3). [1] [2] [3]

Fig 1 oximetry.jpg

Figure 1. Image from the Oxymap system showing the oxygen saturation in the retinal vessels; Retrieved from http://www.oxymap.com/ on 12/18/14.

Fig 2 oximetry.jpg

Figure 2. Picture of the Oxymap device installed and mounted on top of the Topcon TRC-50DX/IX fundus cameras; Retrieved from http://www.oxymap.com/?page_id=1196 on 12/18/14.

Fig 3 oximetry.jpg

Figure 3. Image from the Vesselmap system showing the oxygen saturation in the retinal vessels; Retrieved from http://www.imedos.de/Oxygen-Module.147.0.html?&L=1 on 12/18/14.

Technique

Although retinal oximetry systems can differ slightly, the foundation consists of a fundus camera with an attached image splitter. The image splitter contains mirrors that split the beam from the camera into smaller beams based on wavelengths of light. Some systems will employ filters that further filter the beam. The apparatus also includes a digital camera to record the fundus images. Analysis of the images has been shown to be most effective with comparison of the images at two distinct wavelengths, at about 600 nm (sensitive to oxyhemoglobin) and about 570 nm (not sensitive to oxyhemoglobin). Computer software uses light absorption and optical density to calculate relative vessel oxygenation. Multivariate regression analyses of studies on normative values in healthy subjects has shown no significant associations between retinal oxygen saturation (SO2) and iris pigmentation, ethnicity, gender, and smoking status. Aging, however, is a factor that has been shown in some studies to decrease retinal venous (SvO2) and arterial oxygen saturation (SaO2) and therefore must be accounted for in interpreting and comparing measurements.[1][2][3][4]

Retinal Oximetry in Ocular Diseases

Retinal Vessel Occlusions

Retinal vessel occlusions[5] [6] are blockages of the blood vessels in the retina, often due to atherosclerosis and blood clot formation. There are both central vessel occlusions, near the optic nerve, and branch vessel occlusions, at branches in arterioles or venules. The subsequent blockage of blood flow can lead to blood supply deprivation (ischemia) in areas of the retina.

Retinal oximetry studies have suggested that retinal oxygenation saturation can be a useful biomarker in these disease entities[7]. In central retinal vein occlusions, oxygen saturation has been found to be lower in venules which corresponds to the venous hypoxia expected in this condition. Hypoxia is a primary driver of VEGF-mediated macular edema, neovascularization and other sequelae that occurs after CRVO. Studies show that retinal venous oxygen saturation correlates with the level of ischemia and can also predict disease sequelae[8]. In contrast, central retinal arterial occlusions show decrease oxygen saturation in the retinal arterioles. This feature might be useful diagnostically, especially in cases that affect both venous and arteriolar vascular supplies.

Oxygenation data on branch vessel occlusions is variable and necessitates further study for conclusive results.

Diabetic Retinopathy

Diabetic retinopathy[6][9] [10] is a disease caused by damage to the retinal capillaries as a result of chronic hyperglycemia. Similar to retinal vascular occlusions, hypoxia is a central feature of the disease process and pathophysiology. Retinal oximetry analysis indicates that patients with retinopathy in general have higher venous oxygen saturation levels than healthy subjects. This seemingly paradoxical oximetry finding is likely due to poor oxygen distribution, increased total blood flow, and/or decreased oxygen consumption[7]. The relative increase in venous oxygenation has been shown to correlate with diabetic retinopathy severity[11][12]. In addition, following laser photocoagulation treatment, the arteriovenous saturations indicate improved distribution of oxygen delivery[13]. As such, retinal oximetry has promising clinical applications for the diagnosis and management of the disease. (Fig 4A & B)

Fig 4A oximetry.jpg

Fig 4B oximetry.jpg

Figures 4A & B. Comparison of oximetry for a healthy patient in top image (A) and a patient with moderate NPDR in image directly below (B); Retrieved from the UNC Kittner Eye Center.

Glaucoma

Glaucoma[6][14] [15] is a chronic optic neuropathy with progressive injury to optic nerve axons and subsequent atrophy of retinal nerve fiber layer and ganglion cells. This atrophy is expected to reduce oxygen consumption in the inner retina. Consequently, venous oxygen saturation and arteriovenous saturation differences can offer insight into glaucomatous disease progression and provide new modalities of monitoring patients. Research also suggests that retinal vascular dysregulation might be part of the primary pathophysiology in certain types of glaucoma[7]. In addition to aiding in diagnosis and monitoring glaucoma, retinal oximetry might therefor offer new insight into a incompletely understood disease entity. Additional oximetry studies have shown a mild difference in oxygenation pre- and post-glaucoma treatment which correlates with intraocular pressure changes[16].

Emerging Applications

In addition to characterizing other ischemic retinal diseases such as age-related macular degeneration and retinitis pigmentosa, retinal oximetry can exist as a potential biomarker for systemic diseases. Investigation into its utility for cardiopulmonary disease states and as a surrogate for systemic oxygenation show early promise, as do studies hypothesizing retinal vascular changes might relate to Alzheimer's disease in the central nervous system.

Additional Resources

References

  1. 1.0 1.1 Beach JM, Schwenzer KJ, Srinivas S, Kim D, Tiedeman JS. Oximetry of retinal vessels by dual-wavelength imaging: calibration and influence of pigmentation. J Appl Physiol. 1999;86:748–758.
  2. 2.0 2.1 Hardarson SH. Retinal oximetry. Acta Ophthalmologica. 2012;91: 489–490.
  3. 3.0 3.1 Hardarson SH, Harris A, Karlsson RA, et al. Automatic retinal oximetry. Invest Ophthalmol Vis Sci. 2006; 47(11):5011-5016.
  4. Jani PD, Mwanza JC, Billow KB, et al. Normative values and predictors of retinal oxygen saturation. Retina. 34(2):394-401, 2014
  5. Hardarson SH, and E Stefánsson. "Oxygen saturation in central retinal vein occlusion." American journal of ophthalmology 150.6 (2010): 871-875.
  6. 6.0 6.1 6.2 Boeckaert J., E. Vandewalle, and Ingeborg Stalmans. "Oximetry: recent insights into retinal vasopathies and glaucoma." Bull Soc Belge Ophtalmol 319 (2012): 75-83.
  7. 7.0 7.1 7.2 Stefansson E et al. Retinal oximetry: Metabolic imaging for diseases of the retina and brain, Progress in Retinal and Eye Research, Volume 70, 2019, Pages 1-22,
  8. I. Sinova, J. Rehak, J. Nekolova, N. Jiraskova, P. Haluzova, T. Rehakova, B. Babkova, L. Hejsek, M. Sin. Correlation between ischemic index of retinal vein occlusion and oxygen saturation in retinal vessels. Am. J. Ophthalmol., 188 (2018), pp. 74-80
  9. Hammer M, Vilser W, Riemer T, et al. Diabetic patients with retinopathy show increased retinal venous oxygen saturation. Graefes Arch Clin Exp Ophthalmol. 2009;247:1025-1030.
  10. Khoobehi B, Firn K, Thompson H, Reinoso M, Beach J. Retinal arterial and venous oxygen saturation is altered in diabetic patients. Invest Ophthalmol Vis Sci. 2013;54:7103–7106.
  11. C.M. Jorgensen, S.H. Hardarson, T. Bek. The oxygen saturation in retinal vessels from diabetic patients depends on the severity and type of vision-threatening retinopathy. Acta Ophthalmol., 92 (2014), pp. 34-39
  12. B. Khoobehi, K. Firn, H. Thompson, M. Reinoso, J. Beach. Retinal arterial and venous oxygen saturation is altered in diabetic patient. Invest Ophthalmol Vis Sci, 54 (2013), pp. 7103-7106
  13. C. Jorgensen, T. Bek. Increasing oxygen saturation in larger retinal vessels after photocoagulation for diabetic retinopathy. Invest Ophthalmol Vis Sci, 55 (2014), pp. 5365-5369
  14. Olafsdottir Olof Birna, et al. "Retinal oximetry in primary open-angle glaucoma."Investigative ophthalmology & visual science 52.9 (2011): 6409-6413.
  15. Osborne N. N., et al. "Neuroprotection in relation to retinal ischemia and relevance to glaucoma." Survey of ophthalmology 43 (1999): S102-S128.
  16. S. Du, X. Gao, X. Zhang, J. Wang, W. Huang, M. Zhou, W. Wang, X. Li, Y. Zhang, D.S. LamChanges in retinal oxygen saturation, choroidal thickness. , and retinal nerve fibre layer. Can. J. Ophthalmol., 50 (2015), pp. 159-165