choice experimental design, ERG analysis based on log K comparison was more than twice as sensitive for detecting eyes having or destined to develop NVI than analysis of FA.48 Implicit times for the a-wave, b-wave, and ßicker fusion were signiÞcantly delayed in eyes with or destined to develop NVI.48 Larsson and Andreasson found the average implicit time of the photopic 30-Hz ßicker ERG to be the most predictive test for subsequent NVI. The average time in those going on to develop NVI was 38.3 ms compared to 31.3 ms in those who did not develop NVI (P < 0.001).62 Moreover, this test required no dark adaptation and could be performed in 10 min once the pupil was dilated.62 Lastly, one study reported that the photopic single-ßash b-/a-ratio was the best predictor of later NVI and was practical because no dark adaptation was required.102

Whereas many ERG variables have purported value in predicting later NVI, some have been reported to be of little use. The scotopic a-wave amplitude and implicit time were not predictive for later development of neovascularization of the iris (NVI) in one study.53 Flicker ERG variables were not usefully predictive of later NVI in another study.102

The inconsistency of recommendations and results may stem from differences in methods of performing the ERG despite attempts to standardize ERG methodology.67 In clinical practice, ERG is rarely used in the evaluation of patients with CRVO. Instead, close follow-up of all patients has been the more practical approach to the issue of detecting later anterior segment neovascularization.

8.5.3Hemicentral Retinal Vein Occlusion

Wide-Þeld multifocal ERG has been used to study HCRVO. WF-mfERG N1 and P1 implicit times are greater for the affected hemiretina compared to the unaffected hemiretina.25 ERG maximal b-wave, cone b-wave, and ßicker fusion implicit times are delayed compared to the fellow eye. Unlike CRVO, scotopic and photopic b-/a-

amplitude ratios were no different between affected and fellow eyes.25

8.6Indocyanine Green Angiography

Indocyanine green (ICG) is a larger molecule than ßuorescein and is more highly protein-bound. Therefore, it leaks less from the fenestrated choroidal vessels and is better adapted than ßuorescein for imaging the choroidal vasculature. It is also useful for imaging in cases with prominent intraretinal hemorrhage because the exciting light from the infrared spectrum penetrates hemorrhage better than does white light. It has been used to detect focal hyperßuorescence at arteriovenous crossing causing a BRVO. It may have a slight advantage because the leakage at the site is less massive with ICG, but sensitivity was comparable to that with ßuorescein angiography.36 ICG angiography is unable to resolve retinal capillary detail and judge retinal ischemia.36 When used in the study of BRVO, the area of leakage is smaller than the area of leakage with ßuorescein in ßuorescein angiography.85 Together with simultaneous ßuorescein angiography, ICG angiography is part of a technique called topographical angiography that attempts to study the dynamics of retinal vascular leakage after RVO.85

ICG angiography has been used to explore pulsatile blood ßow in Þrst-order veins during acutephase CRVO. In this technique, a painstaking frame by frame analysis of images is done and has shown that pulsatile blood ßow in Þrst-order venules may be related to cardiac cyclical compression of the central retinal vein by the adjacent central retinal artery within the optic nerve or to the effects of the cyclical IOP related to the cardiac cycle.78 Pulsatile venular outßow is common in the acute phase of CRVO but less commonly observed after several months have passed.79

Similarly, pulsatility of blood ßow in retinal arterioles has been shown with ICG angiography.79 Arterial pulsatility is more commonly seen soon after CRVO and vanishes as time goes on.79 Concomitant with loss of arterial and venular

pulsatility, arteriovenous Þlling time decreases with increasing time after onset of CRVO.79

Although some abnormalities of choroidal perfusion have been described occasionally in BRVO and CRVO, a biological rationale for the observations has not been advanced, and they have not been systematically investigated.95 When laser chorioretinal venous anastomosis was a serious treatment alternative for CRVO, ICG angiography was useful to demonstrate that an anastomosis had been achieved.12 With the abandonment of that treatment, this use for ICG angiography has vanished.

ICG angiography is rarely used in the clinical care of patients with RVO.

8.7Color Doppler Ultrasonographic Imaging

Color Doppler ultrasonic imaging (CDUI) was developed to measure blood ßow in ocular arteries and veins at their point of entrance in the posterior globe and in more posterior orbital vessels. It allows measurement of pulsatile blood ßow velocity in the ophthalmic artery, central retinal artery, and posterior ciliary arteries.84 Peak systolic blood velocity can be measured in the central retinal vein84 A calculated resistive index of the central retinal artery can be assessed. It cannot measure vessel diameter and therefore cannot measure volumetric blood ßow.55,84,100 The technique involves placing the patient in a supine position and applying a 7.5-MHz probe to the eye. The angle between the incident beam and the blood vessel is small, allowing the frequency shift in the signal to be used as a velocity measurement of the blood ßowing in the vessel.1 A video-imaging unit displays colored pixels representing Doppler frequency shifts, and these indicate the presence of blood vessels that are identiÞed by knowledge of the orbital anatomy. Once the vessel of interest is located, pulsed Doppler is used to obtain a spectral waveform of the blood velocity.103 The peak systolic ßow velocity (PSV) and end

diastolic ßow velocity (EDV) are measured in this way, and a quantity called resistive index (RI) is deÞned by RI = (PSV − EDV)/PSV. RI is thought to reßect distal vascular resistance in vascular beds with constant oxygen demand.84 A quantity called pulsatile velocity amplitude is (PVA) deÞned by PVA = PSV − EDV. The venous pulsatility index (VPI) is deÞned as

VPI = (Vmax − Vmin)/Vmax, where Vmax = maximum peak velocity and Vmin = minimum peak velocity

of the central retinal vein.103 This index is speciÞc to the central retinal vein which, unlike other veins in the body, shows blood velocity variations in synchrony with the cardiac cycle rather than with changes in intrathoracic pressure related to respiration. Expansion of the central retinal artery with the systemic pulse causes constriction of the central retinal vein, thereby increasing blood velocity.103 This unusual behavior is caused by the CRA and CRV sharing an adventitial sheath so that an expansion of the CRA causes a compression of the CRV.103

The ophthalmic artery, central retinal artery, and central retinal vein can be speciÞcally located, but it is not possible to determine if the signal recognized as arising from the PCAs is arising from a single one or a cluster of these. This is due to their small size and the fact that, in general, measurements from PCAs are difÞcult to obtain.84 Reproducibility of Doppler ultrasonographic imaging measurements improves as vessel diameter increases.84 Reproducibilities are especially poor for the PCAs (Table 8.3).37,100 The location of the volume measured is critical in interpreting measurements. Thus, the blood velocities of the central retinal artery within the optic nerve and in the region of the lamina cribrosa, two locations close together, vary by a third. The higher velocity at the lamina cribrosa indicates that the central retinal artery narrows there.99 The effect is even greater for the central retinal vein, in which blood velocity at the level of the lamina cribrosa is 3.6 times as great as at the level of the optic nerve.99 Low blood velocities degrade reproducibility of measurements, so in venous measurements, end diastolic velocity is not usually measured. Measurements depend on operator experience and

are sensitive to the angle of incidence of the ultrasound (determined by how the probe is held) relative to the course of the vessel.37,99,100 Even using peak systolic velocities, reproducibility is rather low with a coefÞcient of variation for central retinal vein peak systolic velocity of 15.2%.99 There are many confounding variables as well, such as patient age, blood viscosity, and history of smoking.103 This test is used only in research studies.

Results of CDUI are inconsistent in CRVO. In one study, the PSV of blood in the CRA was lower in eyes with CRVO than in fellow eyes or control eyes of patients without CRVO.99 However, in another study, the results were dependent on perfusion status. For nonischemic CRVO, there were no signiÞcant differences of ßow velocity in the ophthalmic or central retinal arteries of patients with nonischemic CRVO.3

However, in ischemic CRVO, the ßow velocities were signiÞcantly lower in the affected compared to the fellow eyes, presumably due to transmitted backpressure through the capillaries to the arterial side of the vascular tree.3 Laser PRP further reduced ßow velocities in the OA and CRA.3

The PSV of blood in the CRV was not statistically different in eyes with CRVO than in fellow eyes or eyes with controls without CRVO.99

8.8 Laser Doppler Flowmetry

Retinal major arterial and venous branch blood ßow can be measured with the laser Doppler blood-ßow meter (LDBFM).28,69 The LDBFM

uses two lasers, one of which measures vessel diameter, and the other of which measures blood velocity using the Doppler principle.28 This instrument is unable to measure blood ßow in second-order and smaller retinal arteries and veins.69 An automatic vessel-tracking system allows maintenance of centration of the device on a target vessel. A 675-nm diode laser is used to measure centerline blood velocity using Doppler velocimetry.108 Vessel diameter is measured automatically by the instrument, and blood ßow in microliter per minute is computed, unlike measurements yielding less useful units (e.g., pixels/s) made with other techniques such as FA.43 The LDBFM has the weakness that it assumes a relationship between maximum Doppler shift and true average blood velocity that may not be true.28 Its strength is that it gives retinal blood ßow in real rather than arbitrary units.28

Reproducibility is the main concern with this technology, with reported coefÞcients of variation of 12Ð20%.37 Reduced blood ßow to the affected quadrant in a patient with BRVO and improved blood ßow in a patient with CRVO after spontaneous improvement have been demonstrated.108 This is a research technique not used in clinical care.

8.9 Ophthalmodynamometry

Ophthalmodynamometry is a technique in which external pressure is applied to the globe while viewing the central retinal artery and vein at the optic disk.33 Measurements can be made in arbitrary units to record the pressure that leads to collapse of the vessels during diastole and systole.

The technique is beset by problems of low reproducibility possessing a coefÞcient of variation of 9.1%, thus requiring one to obtain many measurements (e.g., nine) to allow averaging in reaching a value for an eye.49 Ophthalmodynamometric pressure (ODP) cannot be measured in absolute units because it is a composite of IOP and the externally applied pressure. The measurement itself changes IOP, thus there

is inherent unreliability as used in the clinic. Intraoperatively, ODP can be measured accurately using the vented-gas forced-infusion system available with many vitrectomy machines.89 In this setting, ODP is signiÞcantly correlated with diastolic and mean arterial, but not systolic blood pressure. In a study of 75 patients undergoing vitrectomy for complications of diabetic retinopathy, ODP on average was 12.2 mmHg less than diastolic blood pressure and 62 mmHg less than mean arterial pressure.89

In one study, the central retinal vein collapse pressure was, on average, 1.8 times higher in eyes with more severe central retinal vein occlusion than eyes with less severe CRVO. Both groups were higher than the central retinal vein collapse pressure in normal eyes or eyes with BRVO.49

The technique is not used in routine clinical practice.

8.10Scanning Laser Doppler Flowmetry

In this technique, blood ßow within capillaries in regions of the retina is determined through a combination of laser Doppler ßowmetry and scanning laser technology.2 Microvascular ßow values (volume, ßow, and velocity) are measured in arbitrary units. A region of the retina is illuminated with the scanning laser. The Doppler shift of the light due to moving blood cells produces an intensity oscillation in the unshifted reßected light that is proportional to the blood cell velocity. The laser scanning tomography allows sampling of a retinal region, and retinal blood volume and ßow are directly measured. However, they are measured in standardized units that are not intuitively related to physiologic units such as milliliters or millimeter per second.2 The method is therefore useful for paired comparisons, such as region to region within the same eye or region to region in two fellow eyes or region to region in normal and diseased eyes.2 This is a research method only.