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Ocular Blood Flow Measurement BritishJournal ofOphthalmology 1994; 78: 939-945 939 PERSPECTIVE Br J Ophthalmol: first published as 10.1136/bjo.78.12.939 on 1 December 1994. Downloaded from Ocular blood flow measurement Tom H Williamson, Alon Harris Many techniques have been devised to measure the haemo- is sacrificed, histological or radiographic measurement ofthe dynamics of the human and animal eye. In this perspective density of the microspheres is performed to allow an estima- these are outlined and their use in ophthalmic investigation tion ofblood flow. Dye enclosed within heat labile liposomes summarised. Some have exploited the ability of an observer has also been used to examine flow in localised areas of the to directly visualise the retinal vasculature by optical means, retina7"9 and involves an intravenous injection and release of others have been designed to study the haemodynamics ofthe the dye from the liposomes usinglaserlight ofthe appropriate invisible parts of the eye such as the choroid, optic nerve wavelength. The velocity of the dye as it passes through the head, and ciliary body. Although useful in ophthalmic vessel is recorded allowing a calculation offlow ifthe diameter investigation, none have satisfied all of the requirements of of the vessel is measured. Radioactive tracers and radio- the researchers in this field and most have not achieved graphy have also been employed - for example, '4C iodo- regular use in clinical practice. antipyrine has been used to estimate optic nerve blood flow in In any examination of blood flow a multitude of variables cats.' By cutting a hole in the sclera blood velocity measure- must be studied (Table 1). The interrelation ofthese variables ments have been taken from the retinal circulation.'0 The must be determined while considering physical or physio- Fick principle using nitrous oxide concentrations in uveal logical principles (Table 2) which are often not strictly blood samples has also been employed." applicable to the vasculature - for example, the Hagen These methods are invasive and not applicable to the Poiseuille law was described for a rigid tube and not for elastic investigation of the human for obvious reasons. The mini- walled tubes such as blood vessels. In the human, study ofthe mally invasive procedure offluorescein angiography remains circulation is further hindered by the requirement for a non- invasive and safe method for obtaining measurements. Table 2 Physical andphysiological principles in bloodflow Study of the haemodynamics must be performed if we are to understand the mechanisms leading to the large variety of Flow (Q)=velocityxcross sectional area vascular diseases which affect the eye. The blood flow to the Ohm's law eye is ofparticular interest because: (1) Many localised and systemic disorders affect the Q pressure difference vasculature of the eye. resistance http://bjo.bmj.com/ (2) The eye has unusual haemodynamic properties because Reynold's number (R) (turbulence) the tissues are subjected to a high intraocular pressure. R p2rV (3) Ocular blood flow is autoregulated - for example, n during changes in retinal illumination, blood pressure, or posture. Hagen Poiseuille law (4) Pharmacological agents which are routinely used in (Pa-?b) 8nr systemic and ocular diseases may affect the blood supply of on September 30, 2021 by guest. Protected copyright. the eye. L8n resistance =L8n tr4 Techniques for the measurement ofocular blood flow Many ingenious and varied techniques exist for the measure- Laplace's law wall tension ment ofocular blood flow. Some are restricted to experimen- transmural pressure = tal studies on animal models because of their destructive or r where invasive nature. For example, unlabelled or radioactively p=density ofthe fluid labelled microspheres in cats,'2 dogs,3 and monkeys' may be r=radius of the tube V=velocity of the fluid injected into the left ventricle ofthe heart and after the animal n=viscosity ofthe fluid Pa-Pb=pressure difference L=length ofthe tube Table I Some ofthe measurements which might be required to allow an Bemoulli's principk: assessment ofthe haemodynamics ofthe ocular circulation a constriction of a vessel causes a conversion of pressure into kinetic energy thereby increasing the velocity and decreasing the pressure ofthe fluid in the vessel. Haemodynamic measurements Vessel length Doppler equation Vessel cross sectional area Blood pressure Blood flow V Dfc Pulsatile flow 2 Fo cos A Intraocular pressure where Vessel wall tension V=velocity Resistance to flow Df=Doppler frequency shift Blood viscosity c=propagation frequency Turbulence Fo=transmit frequency Critical closing pressure A=angle ofincidence of Doppler beam to direction offlow 940 Williamson, Hams graphs thereafter allows estimation ofthe blood flow from the formula: Br J Ophthalmol: first published as 10.1136/bjo.78.12.939 on 1 December 1994. Downloaded from blood flow = x diameter xmean velocity 4 Estimation of total retinal volumetric flow in this way 40 requires measurements of each major branch of the central one branch 70 0 1 retinal artery and vein. Although estimation from alone may correlate well with total retinal blood flow in healthy subjects this is unlikely to be the case in disease where areas of the retina are often disparately affected. Repro- ducibility from the retinal arterioles is poorer than from the Elapsed time (seconds) venules, probably because the short examination interval ofa Figure The dye bolus intensity curves from afluorescein angiogram of an few seconds results in error from the pulsatility of the adjacent retinal arteriole (E) and venule (F) are shownfrom a patient with be to central retinal vein occlusion. The delay between the two curves provides a arteriolar blood flow. The technique may difficult measure ofthe rapidity oftheflow through the retinal circulation. perform because ofa susceptibility to error from saccadic eye movements and requires specialised equipment which has confined its use so far to the research laboratory. Recently, laser Doppler velocimetry has also been applied to the the mainstay of clinical vascular investigation and has measurement ofchoroidal2' and optic nerve head blood flow22 resulted in a number of techniques for the estimation of in animals. retinal blood flow. In particular, the time required for the dye Another method employing laser light to estimate retinal to pass through the circulation has been estimated. Dye blood flow is the laser speckle phenomenon.2324 The scatter of dilution curves produced from the intensity of the fluores- laser light caused by movement ofan object is proportional to cence in the retinal vessels have been calculated,'2 more the velocity of the object. Measurement of the scatter from a recently employing videoangiography and computerised retinal vessel allows an estimation ofthe velocity of the blood image analysis. 3 14 Two curves ofthe intensity offluorescence cells in the vessel. This technique may be useful for the are plotted against time, for example from a retinal arteriole estimation ofcapillary flow but as yet has not been extensively and an adjacent venule (Fig 1) and the time delay between investigated. these two curves measured at various intensity levels of the Any determination of blood flow by visualisation of the - dye - for example, at 0%, 25%, 50%, 75%, and 100% of the retina for example, by fluorescein angiography, BLDV, or peak fluorescence.'5 The time delay between the passage of laser speckle phenomenon requires the use of mydriatics in dye is presumably inversely proportional to the blood flow most circumstances. These agents by their sympathomimetic rate through the retinal vessels therefore providing a measure or anticholinergic actions may affect blood flow. In addition, ofthe retinal haemodynamics. any system which requires the measurement of the diameter The temporal resolution of the scanning laser ophthalmo- ofretinal blood vessels requires adjustment ofthose measure- scope has been exploited to allow measurement of macular ments for the refractive error, axial length, or keratometry of blood velocities from fluorescein angiography.''"" This has the eye. Correction factors have been devised by Littman2" 26 been performed by injecting a bolus ofdye and measuring the and Bengetson2" but their accuracy has recently been ques- velocity offluorescent white blood cells or gaps in columns of tioned.28 If serial measurements are being used and absolute http://bjo.bmj.com/ red blood cells as they pass through the perifoveal capillaries. blood flow values are not required then a measurement of the These may be travelling at different speeds dependent on the distance between the disc and the fovea may be used to orientation of the vessel; therefore, multiple gaps or cells standardise the magnification of photographs of the same must be measured to provide an assessment of mean velocity individual.29 The use of light to examine the retina can also in the capillaries. The capillary diameters are too small to be affect the blood flow which may vary after short durations of measured and so the flow in the vessels cannot be estimated retinal illumination and dark adaptation.' from these velocities. It is also uncertain whether the rate of Blood velocities in the macular capillaries have been on September 30, 2021 by guest. Protected copyright. flow of the leucocytes which may stick to the endothelium of assessed by non-optical means using the blue field entoptic the capillaries, particularly in disease processes, is the same as phenomenon, appreciable
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