Retinal oxygen saturation changes progressively over time in diabetic retinopathy

Sveinn Hakon Hardarson, Einar Stefánsson, Toke Bek, Sveinn Hakon Hardarson, Einar Stefánsson, Toke Bek

Abstract

Purpose: According to cross-sectional studies, oxygen saturation is elevated in retinal vessels in diabetic patients. We evaluated how retinal oxygenation (metabolic marker), vessel diameters and retinopathy grade (structural markers) change over time in diabetic patients.

Design: Prospective cohort study following screening in a hospital setting.

Methods: Retinal oximetry images were acquired in 214 patients with the Oxymap T1 oximeter. Imaging was repeated after a median of 3.0 years (range 0.76-6.8 years). Oxygen saturation and vessel diameters were measured in the right eye. Semiquantitative grading of retinopathy according to international guidelines and red lesion count were performed on fundus photographs.

Results: Retinopathy grade according to the international semiquantitative grading system was unchanged. Arteriolar saturation increased by 0.75±0.15 percentage points per year of follow-up (p<0.0001). Venular saturation increased by 1.74±0.26 percentage points per year (p<0.0001) and arteriovenous difference decreased by 0.99±0.20 percentage points per year (p<0.0001). Arteriolar diameters decreased by 2.7±8.5μm (p<0.0001) between visits and venular diameters decreased by 2.4±9.1μm (p = 0.0002). Median increase in red lesion count between visits was 2 lesions (range -128 to 212 lesions, p<0.0001). The change in red lesion count and change in diameters did not correlate with the length of follow-up (p>0.44).

Conclusions: Oxygen saturation in larger retinal vessels can increase and arteriovenous difference can decrease over time in diabetic patients without any observable changes in retinopathy grade. The results suggest that changes in retinal oxygen saturation may precede progression of diabetic retinopathy or that oxygen saturation is more sensitive to disease progression than retinopathy grade.

Conflict of interest statement

Sveinn Hakon Hardarson and Einar Stefánsson have commercial interest in the company Oxymap ehf. They have stock in the company, are on its board and are listed on two patents related to retinal oximetry (Automatic registration of images US 7774036 B2, Temporal oximeter WO 2010143208 A3). This does not alter our adherence to PLOS ONE policies on sharing data and materials

Figures

Fig 1. An oximetry image.
Fig 1. An oximetry image.
The two blue circles demarcate the measurement area. The inner circle has a diameter of 1.5 disc diameter. The outer circle has a diameter of 3.0 disc diameters. The main retinal vessel segments in this area are chosen according to a set of detailed rules (Oxymap protocol from November 21st 2013, simple means used).
Fig 2. The change in oxygen saturation.
Fig 2. The change in oxygen saturation.
Change from baseline to follow-up visit, plotted against the time of follow-up. Each point denotes one patient (n = 214). A. Saturation in retinal arterioles increased by 0.75 percent per year of follow-up (p<0.0001). B. Saturation in retinal venules increased by 1.74 percent per year of follow-up (p<0.0001). C. The arteriovenous difference in saturation decreased by 0.99 percent per year of follow-up (p<0.0001).
Fig 3. The change in red lesion…
Fig 3. The change in red lesion count.
Plotted as a function of follow-up time. There was no significant change in red lesions with time.

References

    1. Wilkinson CP, Ferris FL 3rd, Klein RE, Lee PP, Agardh CD, Davis M, et al.. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110(9):1677–82. 10.1016/S0161-6420(03)00475-5 .
    1. Solomon SD, Goldberg MF. ETDRS Grading of Diabetic Retinopathy: Still the Gold Standard? Ophthalmic Res. 2019;62(4):190–5. 10.1159/000501372 .
    1. Bek T. Inner retinal ischaemia: current understanding and needs for further investigations. Acta Ophthalmol. 2009;87(4):362–7. 10.1111/j.1755-3768.2008.01429.x .
    1. Pournaras CJ, Rungger-Brandle E, Riva CE, Hardarson SH, Stefansson E. Regulation of retinal blood flow in health and disease. Prog Retin Eye Res. 2008;27(3):284–330. 10.1016/j.preteyeres.2008.02.002 .
    1. Cogan DG, Kuwabara T. Capillary Shunts in the Pathogenesis of Diabetic Retinopathy. Diabetes. 1963;12:293–300. Epub 1963/07/01. 10.2337/diab.12.4.293 .
    1. Petersen L, Bek T. The Oxygen Saturation in Vascular Abnormalities Depends on the Extent of Arteriovenous Shunting in Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2019;60(12):3762–7. 10.1167/iovs.19-27472 .
    1. Stefansson E, Olafsdottir OB, Eliasdottir TS, Vehmeijer W, Einarsdottir AB, Bek T, et al.. Retinal oximetry: Metabolic imaging for diseases of the retina and brain. Prog Retin Eye Res. 2019;70:1–22. 10.1016/j.preteyeres.2019.04.001 .
    1. Beach J. Pathway to Retinal Oximetry. Translational vision science & technology. 2014;3(5):2. 10.1167/tvst.3.5.2
    1. Bek T. Arterial Oxygen Saturation in Neovascularizations in Proliferative Diabetic Retinopathy. Retina. 2018;38(12):2301–8. 10.1097/IAE.0000000000001870 .
    1. Hammer M, Vilser W, Riemer T, Mandecka A, Schweitzer D, Kuhn U, et al.. Diabetic patients with retinopathy show increased retinal venous oxygen saturation. Graefes Arch Clin Exp Ophthalmol. 2009;247(8):1025–30. Epub 2009/05/01. 10.1007/s00417-009-1078-6 .
    1. Hardarson SH, Stefansson E. Retinal oxygen saturation is altered in diabetic retinopathy. Br J Ophthalmol. 2012;96(4):560–3. 10.1136/bjophthalmol-2011-300640 .
    1. Jorgensen CM, Hardarson SH, Bek T. The oxygen saturation in retinal vessels from diabetic patients depends on the severity and type of vision-threatening retinopathy. Acta Ophthalmol. 2014;92(1):34–9. 10.1111/aos.12283 .
    1. Jorgensen C, Bek T. Increasing oxygen saturation in larger retinal vessels after photocoagulation for diabetic retinopathy. Invest Ophthalmol Vis Sci. 2014;55(8):5365–9. 10.1167/iovs.14-14811 .
    1. Bek T, Stefansson E, Hardarson SH. Retinal oxygen saturation is an independent risk factor for the severity of diabetic retinopathy. Br J Ophthalmol. 2019;103(8):1167–72. 10.1136/bjophthalmol-2018-312764 .
    1. Tayyari F, Khuu LA, Sivak JM, Flanagan JG, Singer S, Brent MH, et al.. Retinal blood oxygen saturation and aqueous humour biomarkers in early diabetic retinopathy. Acta Ophthalmol. 2019;97(5):e673–e9. 10.1111/aos.14016 .
    1. Tayyari F, Khuu LA, Flanagan JG, Singer S, Brent MH, Hudson C. Retinal Blood Flow and Retinal Blood Oxygen Saturation in Mild to Moderate Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2015;56(11):6796–800. 10.1167/iovs.15-17481 .
    1. Kashani AH, Jaime GRL, Saati S, Martin G, Varma R, Humayun MS. Noninvasive Assessment of Retinal Vascular Oxygen Content among Normal and Diabetic Human Subjects a Study Using Hyperspectral Computed Tomographic Imaging Spectroscopy. Retina-J Ret Vit Dis. 2014;34(9):1854–60. WOS:000341630400023. 10.1097/IAE.0000000000000146
    1. 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(10):7103–6. 10.1167/iovs.13-12723 .
    1. Guduru A, Martz TG, Waters A, Kshirsagar AV, Garg S. Oxygen Saturation of Retinal Vessels in All Stages of Diabetic Retinopathy and Correlation to Ultra-Wide Field Fluorescein Angiography. Invest Ophthalmol Vis Sci. 2016;57(13):5278–84. 10.1167/iovs.16-20190 .
    1. Felder AE, Wanek J, Blair NP, Joslin CE, Brewer KC, Chau FY, et al.. The Effects of Diabetic Retinopathy Stage and Light Flicker on Inner Retinal Oxygen Extraction Fraction. Invest Ophthalmol Vis Sci. 2016;57(13):5586–92. 10.1167/iovs.16-20048 .
    1. Blair NP, Wanek J, Felder AE, Joslin CE, Kresovich JK, Lim JI, et al.. Retinal Oximetry and Vessel Diameter Measurements With a Commercially Available Scanning Laser Ophthalmoscope in Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2017;58(12):5556–63. 10.1167/iovs.17-21934
    1. Ibrahim MA, Annam RE, Sepah YJ, Luu L, Bittencourt MG, Jang HS, et al.. Assessment of oxygen saturation in retinal vessels of normal subjects and diabetic patients with and without retinopathy using Flow Oximetry System. Quantitative imaging in medicine and surgery. 2015;5(1):86–96. 10.3978/j.issn.2223-4292.2014.11.26
    1. Geirsdottir A, Palsson O, Hardarson SH, Olafsdottir OB, Kristjansdottir JV, Stefansson E. Retinal vessel oxygen saturation in healthy individuals. Invest Ophthalmol Vis Sci. 2012;53(9):5433–42. 10.1167/iovs.12-9912 .
    1. Grauslund J, Andersen N, Andresen J, Flesner P, Haamann P, Heegaard S, et al.. Evidence-based Danish guidelines for screening of diabetic retinopathy. Acta Ophthalmol. 2018;96(8):763–9. 10.1111/aos.13936 .
    1. Blondal R, Sturludottir MK, Hardarson SH, Halldorsson GH, Stefansson E. Reliability of vessel diameter measurements with a retinal oximeter. Graefes Arch Clin Exp Ophthalmol. 2011;249(9):1311–7. 10.1007/s00417-011-1680-2 .
    1. Teng PY, Wanek J, Blair NP, Shahidi M. Inner retinal oxygen extraction fraction in rat. Invest Ophthalmol Vis Sci. 2013;54(1):647–51. Epub 2013/01/10. 10.1167/iovs.12-11305
    1. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Arch Ophthalmol. 1994;112(9):1217–28. 10.1001/archopht.1994.01090210105023 .
    1. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. IX. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1989;107(2):237–43. 10.1001/archopht.1989.01070010243030 .
    1. Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. X. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more. Arch Ophthalmol. 1989;107(2):244–9. 10.1001/archopht.1989.01070010250031 .
    1. Mehlsen J, Erlandsen M, Poulsen PL, Bek T. Individualized optimization of the screening interval for diabetic retinopathy: a new model. Acta Ophthalmol. 2012;90(2):109–14. 10.1111/j.1755-3768.2010.01882.x .
    1. Mehlsen J, Erlandsen M, Poulsen PL, Bek T. Identification of independent risk factors for the development of diabetic retinopathy requiring treatment. Acta Ophthalmol. 2011;89(6):515–21. Epub 2009/11/17. 10.1111/j.1755-3768.2009.01742.x .
    1. Bek T. Lack of correlation between short-term dynamics of diabetic retinopathy lesions and the arterial blood pressure. Graefes Arch Clin Exp Ophthalmol. 2011;249(2):267–71. 10.1007/s00417-010-1525-4 .
    1. Hardarson SH. Retinal oximetry. Acta Ophthalmol. 2013;91 Thesis 2:1–47. 10.1111/aos.12086 .
    1. Jeppesen SK, Bek T. The Retinal Oxygen Saturation Measured by Dual Wavelength Oximetry in Larger Retinal Vessels is Influenced by the Linear Velocity of the Blood. Curr Eye Res. 2019;44(1):46–52. 10.1080/02713683.2018.1524015 .
    1. Bek T. Glial cell involvement in vascular occlusion of diabetic retinopathy. Acta Ophthalmol Scand. 1997;75(3):239–43. 10.1111/j.1600-0420.1997.tb00764.x .
    1. Torp TL, Kawasaki R, Wong TY, Peto T, Grauslund J. Temporal changes in retinal vascular parameters associated with successful panretinal photocoagulation in proliferative diabetic retinopathy: A prospective clinical interventional study. Acta Ophthalmol. 2018;96(4):405–10. 10.1111/aos.13617
    1. Sin M, Chrapek O, Karhanova M, Sinova I, Spackova K, Langova K, et al.. The effect of pars plana vitrectomy and nuclear cataract on oxygen saturation in retinal vessels, diabetic and non-diabetic patients compared. Acta Ophthalmol. 2016;94(1):41–7. Epub 2015/08/28. 10.1111/aos.12828 .
    1. Vergmann AS, Torp TL, Kawasaki R, Hestoy DH, Wong TY, Peto T, et al.. Retinal vascular oxygen saturation in response to a less extensive laser treatment in proliferative diabetic retinopathy. Acta Ophthalmol. 2020. Epub 2020/12/24. 10.1111/aos.14727 .

Source: PubMed

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