20.6  How Can the Data from Ocular Hemodynamic Studies Be Used in Clinical Practice?

It is clear that controlling IOP alone is not enough to prevent disease progression in some glaucoma patients. Growing evidence demonstrates that vascular risk factors possibly contribute to disease prevalence, incidence,­

and progression [3–6]. Several large population-based studies have shown that low ocular and particularly low diastolic perfusion pressure is an important consideration in glaucoma management [3–6]. Recently, the EMGT report found lower systolic perfusion pressure to be a predictor and an important risk factor for glaucoma progression [7]. Clinical practitioners can calculate ocular perfusion pressure by using systemic blood pressure and IOP measurements. Perfusion pressure is the difference between arterial and venous pressure. Since in the eye venous pressure is approximately equal to IOP, ocular perfusion pressure is calculated as 2/3 of the mean arterial blood pressure minus IOP. This can further be broken down into systolic and diastolic components by taking the systolic or diastolic blood pressure, respectively, minus the IOP [40]. In this capacity, it is strongly suggested that blood pressure measurements be taken during ophthalmic examinations and be evaluated in relation to IOP.

Nevertheless, there remains lack of a clear association between blood flow deficiencies and structural optic nerve head changes or visual field progression in some glaucoma patients. Structural changes in the optic nerve were reported to be related to abnormal ocular blood flow [41]. Reduced blood flow has been reported to correspond with areas of glaucomatous visual field loss [42]. Furthermore, normal tension glaucoma patients with progressive visual field loss were found to have impaired blood flow parameters compared with patients with stable visual fields [43]. Although the preliminary studies presented in this chapter highlight the initial evidence for associations between ocular blood flow and structural and functional alterations, large, long-term, population-based studies and standardized technologies for clinical use are necessary to strengthen the correlation. Ocular blood flow data is currently only a research tool and cannot guide patient treatment. Additional studies can determine whether interventions in blood pressure, perfusion pressure, or ocular blood flow may influence glaucoma progression.

Summary for the Clinician

››Low ocular perfusion pressure may be used to explain glaucoma progression even after reaching an optimal IOP.

››In progressive OAG, evaluation of a patient’s blood pressure, perfusion pressure, and blood flow may be suggested.

››At present, ocular hemodynamic data cannot guide the way a patient with OAG is treated.

››Future long-term studies are needed to address the question of how changes in blood pressure, perfusion pressure, and ocular blood flow may alter glaucoma patients’ outcome and whether ocular circulation interventions improve disease prognosis.

References

 1. Leske MC, Wu SY, Hennis A, et al.; BESs Study Group (2008). Risk factors for incident open-angle glaucoma: the Barbados Eye Studies. Ophthalmology 115:85–93

 2. Leske MC, Wu SY, Honkanen R, et al.; Barbados Eye Studies Group (2007). Nine-year incidence of open-angle glaucoma in the Barbados Eye Studies. Ophthalmology 114:1058–64

 3. Tielsh JM, Katz J, Sommer A, et al. (1995). Hypertension, perfusion pressure, and primary open-angle glaucoma. Arch Ophthalmol 113:216–21

 4. Leske MC, Wu SY, Nemesure B, et al. (2002). Incident open-angle glaucoma and blood pressure. Arch Ophthalmol 120:954–9

 5. Bonomi L, Marchini G, Marraffa M, et al. (2000). Vascular risk factors for primary open angle glaucoma: the EgnaNeumarkt Study. Ophthalmology 107:1287–93

 6. Quigley HA, West SK, Rodriguez J, et al. (2001). The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch Ophthalmol 119:1819–26

 7. Leske MC, Heijl A, Hyman L, et al.; EMGT Group (2007). Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology 114(11):1965–72

 8. Harris A, Rechtman E, Siesky B, et al. (2005). The role of optic nerve blood flow in the pathogenesis of glaucoma. Ophthalmol Clin North Am 18(3):345–53

 9. Orge F, Harris A, Kagemann L, et al. (2002). The first technique for non-invasive measurements of volumetric ophthalmic

artery blood flow in humans. Br J Ophthalmol 86(11):1216–9

10.Jonescu-Cuypers CP, Harris A, Wilson R, et al. (2004). Reproducibility of the Heidelberg retinal flowmeter in determining low perfusion areas in peripapillary retina. Br J Ophthalmol 88(10):1266–9

11.Feke GT (2006). Laser Doppler instrumentation for the measurement of retinal blood flow: theory and practice. Bull Soc Belge Ophtalmol 302:171–84

12.Yoshida A, Feke GT, Mori F, et al. (2003). Reproducibility and clinical application of a newly developed stabilized retinal­ laser Doppler instrument. Am J Ophthalmol 135: 356–61

13.Riva CE, Cranstoun SD, Grunwald JE, et al. (1994). Choroidal blood flow in the foveal region of the human ocular fundus. Invest Ophthalmol Vis Sci 35:4273–81

14.Riva CE, Harino S, Petrig BL, et al. (1992). Laser Doppler flowmetry in the optic nerve. Exp Eye Res 55:499–506

15.Blum M, Bachmann K, Wintzer D, et al. (1999). Noninvasive measurement of the Bayliss effect in retinal autoregulation. Graefes Arch Clin Exp Ophthalmol 237:296–300

16.Rechtman E, Harris A, Kumar R, et al. (2003). An update on retinal circulation assessment technologies. Curr Eye Res 27(6):329–43

17.Flower RW (1993). Extraction of choriocapillaris hemodynamic data from ICG fluorescence angiogram. Invest Ophthalmol Vis Sci 34:2720–9.

18.Weizer JS, Asrani S, Stinnett SS, et al. (2007). The clinical utility of dynamic contour tonometry and ocular pulse amplitude. J Glaucoma 16(8):700–3

19.Kerr J, Nelson P, O’Brien C (2003). Pulsatile ocular blood flow in primary open-angle glaucoma and ocular hypertension. Am J Ophthalmol 136(6):1106–13

20.Rankin SJA, Walman BE, Buckley AR, et al. (1995). Color Doppler imaging and spectral analysis of the optic nerve vasculature in glaucoma. Am J Ophthalmol 119:685–93

21.Galassi F, Sodi A, Ucci F, et al. (2003). Ocular hemodynamics and glaucoma prognosis: a color Doppler imaging study. Arch Ophthalmol 121:1711–5.

22.Michaelson G, Longhans MJ, Groh MJM (1996). Perfusion of the juxta-papillary retina and neuroretinal rim in primary open angle glaucoma. J Glaucoma 5:91–8

23.Sato EA, Ohtake Y, Shinoda K, et al. (2006). Decreased blood flow at neuroretinal rim of optic nerve head corresponds with visual field deficit in eyes with normal tension glaucoma. Graefes Arch Clin Exp Ophthalmol 244:795–801

24.Feke GT, Pasquale LR (2007). Retinal blood flow response to posture change in glaucoma patients compared with healthy subjects. Ophthalmology 115(2):246–52

25.Boehm AG, Pillunat LE, Koeller U, et al. (1999). Regional distribution of optic nerve head blood flow. Graefes Arch Clin Exp Ophthalmol 237:484–8

26.Nagel E, Vilser W, Lanzl IM (2001). Retinal vessel reaction to short-term IOP elevation in ocular hypertensive and glaucoma patients. Eur J Ophthalmol 11:338–44

27.Garhofer G, Zawinka C, Resch H, et al. (2004). Response of retinal vessel diameters to flicker stimulation in patients with early open angle glaucoma. J Glaucoma 13:340–4

28.Harris A, Jonescu-Cuypers CP, Kagemann L, et al. (2001). Effect of dorzolamide timolol combination versus timolol

0.5% on ocular blood flow in patients with primary openangle glaucoma. Am J Ophthalmol 132(4):490–5

29.Harris A, Chung HS, Ciulla TA, et al. (1999). Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration: review. Prog Retin Eye Res 18(5):669–87

30.Arend O, Remky A, Plange N, et al. (2002). A capillary density and retinal diameter measurements and their impact on altered retinal circulation in glaucoma: a digital fluorescein angiographic study. Br J Ophthalmol 86(4):429–33.

31.Marengo J, Ucha RA, Martinez-Cartier M, et al. (2001). Glaucomatous optic nerve head changes with scanning laser ophthalmoscopy. Int Ophthalmol 23:413–23

32.O’Brart DP, de Souza Lima M, Bartsch DU, et al. (1997). Indocyanine green angiography of the peripapillary region in glaucomatous eyes by confocal scanning laser ophthalmoscopy. Am J Ophthalmol 123:657–66

33.James CB, Smith SE (1991). Pulsatile ocular blood flow in patients with low tension glaucoma. Br J Ophthalmol 75:466–70

34.von Schulthess SR, Kaufmann C, Bachmann LM, et al. (2006). Ocular pulse amplitude after trabeculectomy. Graefes Arch Clin Exp Ophthalmol 244:46–51

35.Spencer JA, Giussani DA, Moore PJ, et al. (1991). In vitro validation of Doppler indices using blood and water. J Ultrasound Med 10(6):305–8

36.Harris A, Serra LM, Rechtman E, et al. (2005). Vascular Abnormalities in Glaucoma: from Epidemiology to the Clinic. Impresse 4: Amadora, Portugal

37.MavroudisL,HarrisA,TopouzisF,etal.(2008).Reproducibility of pixel-by-pixel analysis of Heidelberg retinal flowmetry images: the Thessaloniki Eye Study. Acta Ophthalmol Scand 86(1):81–6

38.Polska E, Polak K, Luksch A, et al. (2004). Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects. Br J Ophthalmol 88:533–7

39.Zion IB, Harris A, Siesky B, et al. (2007). Pulsatile ocular blood flow: relationship with flow velocities in vessels supplying the retina and choroid. Br J Ophthalmol 91(7):882–4

40.Sehi M, Flanagan JG, Zeng L, et al. (2005). Relative change in diurnal mean ocular perfusion pressure: a risk factor for the diagnosis of primary open-angle glaucoma. Invest Ophthalmol 46:561–7

41.Logan JF, Rankin SJ, Jackson AJ (2004). Retinal blood flow measurements and neuroretinal rim damage in glaucoma. Br J Ophthalmol 88(8):1049–54

42.Satilmis M, Orgül S, Doubler B, et al. (2003). Rate of progression of glaucoma correlates with retrobulbar circulation and intraocular pressure. Am J Ophthalmol 135(5):664–9

43.Yamazaki Y, Drance SM (1997). The relationship between progression of visual field defects and retrobulbar circulation in patients with glaucoma. Am J Ophthalmol 124(3):287–95

Core Messages

››The multifocal visually evoked potential (mfVEP) provides an objective, topographical measure of local glaucomatous damage.

››The mfVEP can help in deciding upon treatment in patients with inconclusive visual field and disc examinations.

››The mfVEP is useful for confirming suspected scotomas detected on perimetric examination.

››The mfVEP permits objective testing of patients unable or unwilling to produce reliable fields.

››Prolonged latency of the mfVEP can signal a contribution from retinal disease, compressive tumors, or optic tract demyelineating disease.

››The mfVEP is not recommended as a replacement for standard automated perimetry.

››The test is best performed at centers capable of recording and interpreting mfVEPs.

21.1  What Is a Multifocal Visual Evoked

Potential (mfVEP)?

21.1.1  The Visual Evoked Potential (VEP)

Numerous electrophysiological tests have been proposed for detecting glaucomatous damage. Some involve electrical recordings from the eye, while others involve

D. C. Hood ( )

Department of Psychology, Columbia University, 1190 Amsterdam Avenue. MC5501, New York, NY 10027, USA e-mail: dch3@columbia.edu

recordings from the cortex [1]. The focus of this chapter is on the latter, particularly the VEP, an electrical potential recorded with one or more electrodes placed over the occipital region of the skull. A variety of visual displays have been used to record VEPs and standards are available that describe clinical recording and analysis of the “conventional” VEP [2]. While the VEP is useful in the diagnosis of a variety of conditions [3], to date there is no convincing evidence that any of the standard VEP procedures perform better than standard automated perimetry (SAP) for detecting glaucomatous damage. However, a relatively new technique, the multifocal VEP (mfVEP), can be clinically useful.

21.1.2  The Multifocal Visual Evoked

Potential

The mfVEP is a potential recorded from the same occipital region with the same electrodes as the conventional VEP [4, 5]. However, while the standard VEP produces a response to a single visual stimulus, the mfVEP allows the simultaneous measurement of many small VEP responses from a central field of vision. Figure 21.1a–c show two displays to stimulate the eyes that have been used: the one we use (panel A) produced by VERIS (EDI, San Mateo, CA) [5, 6] and the one used by Grahamet et al. produced by Accumap (ObjectiVision, Sidney, Australia) [7–9]. The display in Fig. 21.1a has 60 sectors, each a black and white checkerboard with 16 elements. As illustrated in the insets, the sectors increase in area with retinal eccentricity. This results in the different sectors stimulating roughly the same area of the occipital cortex and producing mfVEP responses of roughly the same size, as

shown in Fig. 21.1b. The display in Fig. 21.1c is similar in size and composition. Both displays cover about the same extent of the visual field, roughly 50° in diameter, as does the 24-2 SAP test of the Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA). The display in Fig. 21.1c, configured for stimulation of the right eye, has two sectors that extend into the region of the nasal step.

With the mfVEP technique, multiple VEP responses can be measured simultaneously. Although these waveforms are technically mathematical abstractions rather than little VEP responses [5, 10], we refer them here as “responses.” Figure 21.1b–d shows the local responses for the displays in Fig. 21.1a–c. Each of the

small waveforms is a response elicited by the corresponding checkerboard sector. In Fig. 21.1b, the black and gray responses are from the right and left eyes, respectively. The responses from the two eyes of an individual with normal vision are essentially identical [5, 6, 8].

The mfVEP provides topographical information. Each response in Fig. 21.1b–d is due to stimulation of a local region of the retina covered by the corresponding sector. The topographical nature of the response makes it possible to relate changes in mfVEP responses to local changes seen with SAP. As given below, local glaucomatous damage produces local changes in amplitude [5, 6, 9]. For reviews see [5, 9, 11–13].

Fig. 21.1  (a) The display we employ for mfVEP recording [5, 6]. The insets illustrate the relative sizes of the individual sectors. (b) Responses obtained with display in (a). (c) The display

employed in mfVEP recording by Graham et al. [7–9]. (d) Responses obtained with display in panel B. Panels C and D are modified from [7] and reproduced with permission