Supplementary Files
How to Cite
Copyright notice
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication, with the work twelve (12) months after publication simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work’s authorship and initial publication in this journal.
- After 12 months from the date of publication, authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Keywords
Abstract
Purpose: Vascular changes have been observed among glaucoma patients, but it is not yet known whether these vascular changes occur primary or secondary to glaucomatous damage. In this study, a theoretical mathematical model of the retinal vasculature is applied to a set of oximetry data obtained from healthy individuals and glaucoma patients and is used to propose possible explanations for the clinically observed increases in venous blood oxygen saturation in advanced glaucoma patients.
Methods: Given clinical measurements of intraocular pressure (IOP), mean arterial pressure and arterial blood oxygen saturation from healthy persons and advanced (visual field mean defect (MD) ≥ 10 dB) primary open angle glaucoma (POAG, IOP > 21 mmHg) patients and advanced normal tension glaucoma (NTG, IOP ≤ 21 mmHg)patients, the model is used to predict the oxygen demand or Krogh cylinder tissue width that would yield the clinically-measured venous oxygen saturation in each population.
Results: A decrease in retinal tissue oxygen demand (M0), an impairment in blood flow autoregulation, or a decrease in Krogh cylinder tissue width (d) can independently lead to increased venous saturation. The model predicts that a decrease in M0 or a decrease in d is more likely to yield the increased venous saturation levels observed in POAG patients, while impairing blood flow autoregulation with no change in M0 or d is more likely to yield the increased venous saturation levels observed in NTG patients.
Conclusions: The combined theoretical and clinical model predictions suggest that the mechanisms leading to increased venous saturation might differ between POAG and NTG patients. The model predictions are used to hypothesize that a decrease in oxygen demand might be more relevant to the increase in venous saturation observed in advanced POAG, while impairment in autoregulation mechanisms might be more relevant to the increase in venous saturation observed in advanced NTG.
References
Moore D, Harris A, Wudunn D, Kheradiya N, Siesky B. Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma? Clin Ophthalmol. 2008;2(4):849-61.
Harris A, Kagemann L, Ehrlich R, Rospigliosi C, Moore D, Siesky B. Measuring and interpreting ocular blood flow and metabolism in glaucoma. Canadian journal of ophthalmology Journal canadien d'ophtalmologie. 2008;43(3):328-36.
Olafsdottir OB, Hardarson SH, Gottfredsdottir MS, Harris A, Stefansson E. Retinal oximetry in primary open-angle glaucoma. Investigative ophthalmology & visual science. 2011;52(9):6409-13.
Olafsdottir OB, Vandewalle E, Abegao Pinto L, Geirsdottir A, Clerck, De E, Stalmans P, et al. Retinal oxygen metabolism in healthy subjects and glaucoma patients. The British journal of ophthalmology. 2014;98(3):329-33.
Geirsdottir A, Hardarson SH, Olafsdottir OB, Stefansson E. Retinal oxygen metabolism in exudative age-related macular degeneration. Acta ophthalmologica. 2014;92(1):27-33.
Michelson G, Scibor M. Intravascular oxygen saturation in retinal vessels in normal subjects and open-angle glaucoma subjects. Acta Ophthalmologica Scandinavica. 2006;84(3):289-95.
Abegao Pinto L, Vandewalle E, De Clerck E, Marques-Neves C, Stalmans I. Ophthalmic artery Doppler waveform changes associated with increased damage in glaucoma patients. Investigative ophthalmology & visual science. 2012;53(4):2448-53.
Akarsu C, Bilgili MY. Color Doppler imaging in ocular hypertension and open-angle glaucoma. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2004;242(2):125-9.
Butt Z, O'Brien C, McKillop G, Aspinall P, Allan P. Color Doppler imaging in untreated high- and normal-pressure open-angle glaucoma. Investigative ophthalmology & visual science. 1997;38(3):690-6.
Rojanapongpun P, Drance SM, Morrison BJ. Ophthalmic artery flow velocity in glaucomatous and normal subjects. The British journal of ophthalmology. 1993;77(1):25-9.
Tobe LA, Harris A, Hussain RM, Eckert G, Huck A, Park J, et al. The role of retrobulbar and retinal circulation on optic nerve head and retinal nerve fibre layer structure in patients with open-angle glaucoma over an 18-month period. The British journal of ophthalmology. 2015;99(5):609-12.
Grieshaber MC, Flammer J. Blood flow in glaucoma. Current opinion in ophthalmology. 2005;16(2):79-83.
Flammer J. The vascular concept of glaucoma. Survey of ophthalmology. 1994;38 Suppl:S3-6.
Jia Y, Morrison JC, Tokayer J, Tan O, Lombardi L, Baumann B, et al. Quantitative OCT angiography of optic nerve head blood flow. Biomedical optics express. 2012;3(12):3127-37.
Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Optics express. 2012;20(4):4710-25.
Jia Y, Wei E, Wang X, Zhang X, Morrison JC, Parikh M, et al. Optical coherence tomography angiography of optic disc perfusion in glaucoma. Ophthalmology. 2014;121(7):1322-32.
Harris A, Jonescu-Cuypers C, Kagemann L, Ciulla T, Krieglstein G. Atlas of ocular blood flow: Butterworth-Heinemann; 2003.
Weinreb R, Harris A. Ocular blood flow in glaucoma: the 6th consensus report of the world glaucoma association. Amsterdam, The Netherlands: Kugler Publications; 2009.
Ito M, Murayama K, Deguchi T, Takasu M, Gil T, Araie M, et al. Oxygen saturation levels in the juxta-papillary retina in eyes with glaucoma. Experimental eye research. 2008;86(3):512-8.
Vandewalle E, Abegao Pinto L, Olafsdottir OB, De Clerck E, Stalmans P, Van Calster J, et al. Oximetry in glaucoma: correlation of metabolic change with structural and functional damage. Acta ophthalmologica. 2014;92(2):105-10.
Mordant DJ, Al-Abboud I, Muyo G, Gorman A, Harvey AR, McNaught AI. Oxygen saturation measurements of the retinal vasculature in treated asymmetrical primary open-angle glaucoma using hyperspectral imaging. Eye. 2014;28(10):1190-200.
Ramm L, Jentsch S, Peters S, Augsten R, Hammer M. Investigation of blood flow regulation and oxygen saturation of the retinal vessels in primary open-angle glaucoma. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2014;252(11):1803-10.
Arciero J, Harris A, Siesky B, Amireskandari A, Gershuny V, Pickrell A, et al. Theoretical analysis of vascular regulatory mechanisms contributing to retinal blood flow autoregulation. Investigative ophthalmology & visual science. 2013;54(8):5584-93.
Pries AR, Secomb TW, Gessner T, Sperandio MB, Gross JF, Gaehtgens P. Resistance to Blood-Flow in Microvessels in-Vivo. Circ Res. 1994;75(5):904-15.
Ye GF, Moore TW, Buerk DG, Jaron D. A compartmental model for oxygen-carbon dioxide coupled transport in the microcirculation. Annals of biomedical engineering. 1994;22(5):464-79.
Orgul S, Cioffi GA, Wilson DJ, Bacon DR, Van Buskirk EM. An endothelin-1 induced model of optic nerve ischemia in the rabbit. Investigative ophthalmology & visual science. 1996;37(9):1860-9.
Orgul S, Gugleta K, Flammer J. Physiology of perfusion as it relates to the optic nerve head. Survey of ophthalmology. 1999;43 Suppl 1:S17-26.
Causin P, Guidoboni G, Malgaroli F, Sacco R, Harris A. Blood flow mechanics and oxygen transport and delivery in the retinal microcirculation: multiscale mathematical modeling and numerical simulation. Biomechanics and modeling in mechanobiology. 2015.
Palsson O, Geirsdottir A, Hardarson SH, Olafsdottir OB, Kristjansdottir JV, Stefansson E. Retinal oximetry images must be standardized: a methodological analysis. Investigative ophthalmology & visual science. 2012;53(4):1729-33.
Michelson G, Welzenbach J, Pal I, Harazny J. Functional imaging of the retinal microvasculature by scanning laser Doppler flowmetry. International ophthalmology. 2001;23(4-6):327-35.
Hardarson SH, Basit S, Jonsdottir TE, Eysteinsson T, Halldorsson GH, Karlsson RA, et al. Oxygen saturation in human retinal vessels is higher in dark than in light. Investigative ophthalmology & visual science. 2009;50(5):2308-11.
Quigley HA. Neuronal death in glaucoma. Progress in retinal and eye research. 1999;18(1):39-57.
Medrano CJ, Fox DA. Oxygen consumption in the rat outer and inner retina: light- and pharmacologically-induced inhibition. Experimental eye research. 1995;61(3):273-84.
Braun RD, Linsenmeier RA, Goldstick TK. Oxygen consumption in the inner and outer retina of the cat. Investigative ophthalmology & visual science. 1995;36(3):542-54.
Wangsa-Wirawan ND, Linsenmeier RA. Retinal oxygen: fundamental and clinical aspects. Archives of ophthalmology. 2003;121(4):547-57.
Kur J, Newman EA, Chan-Ling T. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Progress in retinal and eye research. 2012;31(5):377-406.
Cringle SJ, Yu DY. A multi-layer model of retinal oxygen supply and consumption helps explain the muted rise in inner retinal PO(2) during systemic hyperoxia. Comparative biochemistry and physiology Part A, Molecular & integrative physiology. 2002;132(1):61-6.
Haugh LM, Linsenmeier RA, Goldstick TK. Mathematical models of the spatial distribution of retinal oxygen tension and consumption, including changes upon illumination. Annals of biomedical engineering. 1990;18(1):19-36.
Lau JC, Linsenmeier RA. Oxygen consumption and distribution in the Long-Evans rat retina. Experimental eye research. 2012;102:50-8.
Roos MW. Theoretical estimation of retinal oxygenation during retinal artery occlusion. Physiological measurement. 2004;25(6):1523-32.
Riva CE, Pournaras CJ, Tsacopoulos M. Regulation of local oxygen tension and blood flow in the inner retina during hyperoxia. Journal of applied physiology. 1986;61(2):592-8.
Bek T. Regional morphology and pathophysiology of retinal vascular disease. Progress in retinal and eye research. 2013;36:247-59.
Abegao Pinto L, Vandewalle E, De Clerck E, Marques-Neves C, Stalmans I. Lack of spontaneous venous pulsation: possible risk indicator in normal tension glaucoma? Acta ophthalmologica. 2013;91(6):514-20.
Oettli A, Gugleta K, Kochkorov A, Katamay R, Flammer J, Orgul S. Rigidity of retinal vessel in untreated eyes of normal tension primary open-angle glaucoma patients. Journal of glaucoma. 2011;20(5):303-6.
Hardarson SH, Basit S, Jonsdottir TE, Eysteinsson T, Halldorsson GH, Karlsson RA, et al. Oxygen saturation in human retinal vessels is higher in dark than in light. Investigative ophthalmology & visual science. 2009;50(5):2308-11.