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nonischemic CRVO, Þxation was stable in only 1 of 12 patients (8%), and Þxation was predominantly central in only 2 of 12 patients (17%). With improvement of macular edema after intravitreal triamcinolone injection, both Þxation location and stability improved.86 Scanning laser perimetry and microperimetry are research techniques not used in clinical care of RVO.86
8.5 Electroretinography
Electroretinography (ERG) measures the electrical responses of different cell types within the retina to standardized light stimuli. In RVOs,
ERG provides functional information that complements the morphologic information contained in OCT images and ßuorescein angiography. Techniques used include standard full-Þeld ERG and multifocal ERG (mfERG).18,19,25,44,88,98 One advantage of the ERG over a different functional test, the relative afferent pupillary defect, is that it does not depend on having a normal fellow eye.39 ERG and mfERG are not widely available, are not part of the clinicianÕs regular workup of patients with RVO, and, if available, are timeconsuming, especially if dark adaptation for scotopic testing is done.62 The results of ERG testing vary from one center to another despite attempts at international standards, and published results may not be generalizable.10
Electroretinography Essentials for Retinal Vein Occlusions
In standard ERG, the retina is stimulated by light from a Ganzfeld bowl while recordings are made from one electrode embedded in a contact lens placed on the cornea and another stuck to the skin near the eye. Recordings are made under conditions of dark adaptation and light adaptation. Single-ßash recordings are made as well as responses to a 30-Hz ßicker stimulus. Implicit times are measured from the ßash to the part of the waveform being measured.102
The a-wave is mediated by the photoreceptors with some postreceptor modulation (Fig. 8.7).47 The b-wave is generated from bipolar cells of the inner nuclear layer and is expected to be diminished more in ischemic CRVOs (Fig. 8.7).19,47 The oscillatory potentials reßect activity of the inner retina, which would be expected to be affected by decreased perfusion of the retinal veins in RVO.44 The photopic negative response (PhNR) follows the b-wave and originates from the inner retina as do the oscillatory potentials and ßicker fusion signals.19 This response is best elicited by red ßashes against a blue background but can be elicited less prominently with white ßashes as well.19 In the mfERG, the P1 response reßects the activity of bipolar and Muller cells of the middle retina.57
To determine retinal sensitivity, the dark-adapted single-ßash ERG is recorded in response to different stimulus light intensities. The number of light stimuli used can affect the results obtained. Nine stimuli are thought to be enough to allow accurate curve Þtting of the NakaÐ Rushton function (Fig. 8.8).102 The ERG amplitude from the a-wave trough to b-wave peak (R) is plotted against stimulus intensity I and the data Þt by the NakaÐRushton function.
R = Rmax á In/(In + Kn). Rmax is a measure of the loss of cells in the retina.102 K is a Þtting parameter that equals the intensity required to produce half the maximal response. It is there-
fore a measure of retinal sensitivity.102 n is the slope of the Þtting function and is a measure of the homogeneity of retinal sensitivity.102
There are considerable variations in ERG testing conditions such as stimulus luminances used across laboratories, although international standards have been set to reduce this problem. The variability across laboratories makes generalization of published data of questionable reliability.53 In mfERG, the stimulus is a hexagonal pattern of light and dark areas that stimulates small separate regions of the macula. The readings are tied to the regions that generate them and
presented as a map of voltage amplitudes that overlays the macula.
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8 Ancillary Testing in the Management of Retinal Vein Occlusions |
Fig. 8.7 Typical scotopic white-ßash global electroretinogram waveform. The red arrow indicates the a-wave trough. The green arrow indicates the b-wave peak. In central retinal vein occlusion, the b-wave peak diminishes more as the degree of ischemia increases
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Fig. 8.8 Plot of response amplitude (amplitude of the b-wave) versus logarithm of the stimulus intensity for the scotopic, white-ßash electroretinogram. Each data point represents a measurement in which stimulus intensity is changed and the b-wave amplitude response is measured. Rmax is the maximal response
amplitude in microvolts. Log K is the logarithm of the stimulus intensity at which half the maximal response amplitude is reached. I is the stimulus intensity in candela seconds per square meter. n is an exponent that is chosen to provide the best Þt of the regression curve to the data points
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There are many outcome measures that can be chosen with standard mfERG. Mean P1 amplitude of the central seven hexagons has been used to compare the effect of arteriovenous sheathotomy on the central macular function of patients with BRVO and macular edema.21 Multifocal oscillatory potentials were lost in areas of nonperfused retina in a study of three patients with central or branch vein occusion.88 Loss of mfERG response amplitude correlated with sensitivity loss on perimetry in patients with BRVO.98
8.5.1 Branch Retinal Vein Occlusion
The full-Þeld electroretinogram usually remains normal after BRVO.34 The oscillatory potential that can be extracted from ERG recordings, however, is affected. The summed difference of components of the oscillatory potential (termed O1, O2, O3, and O4) was different in eyes with BRVO compared to the normal fellow eyes.34 The photopic negative response (phNR) has been reported to be reduced in BRVO.19 In the mfERG, reduced amplitudes and increased latencies have been reported in the affected retinal quadrants.44
8.5.2 Central Retinal Vein Occlusion
Decreased amplitudes of the ERG have been equated with cell death in the inner retina.63 Changes in the b-wave are seen in CRVO, as predicted from the physiology. For both photopic and scotopic ERG, b-wave amplitude of 60% of normal or less or reduced by one or more standard deviations from normal had an 80Ð90% sensitivity and 71Ð80% speciÞcity to detect ischemic CRVO in one study.39 Paradoxically, however, changes in the a-wave are sometimes seen as well. How CRVO might affect ERG variables related to outer retinal cells is speculative because the outer retina receives oxygen from the choroid, which should not differ in CRVO from normal. Johnson and colleagues suggested that inner
retinal hypoxia leads to greater diffusion of oxygen from outer to inner retina with adverse effects on the sodiumÐpotassium pump of the rods.48
The ERG has been studied most in CRVO in relation to predicting subsequent neovascularization of the iris (NVI). The ERG in ischemic CRVO changes over time.63 The optimal time to perform an ERG with the goal of predicting later NVI has been suggested to be 3 weeks.63 There is controversy regarding which ERG variable is most useful in this regard.19,102 Scotopic and photopic b-/a-wave amplitude ratios have inconsistently been reported to be useful prognostic indicators. One study reported that Þve of eight patients with CRVO who developed NVI had scotopic b-/a-amplitude ratios less than one, but another found this ratio insensitive, as only one of nine patients who had or later developed NVI had this characteristic.48,82 Kaye and Harding reported that scotopic b-/a-wave amplitude ratio was useful as a predictor of later NVI. Eyes that later developed rubeosis had a mean ratio of 1.28±SD0.22 compared to 1.80±SD0.24 for the unaffected fellow eyes (P<0.001).53,82
Other aspects of the ERG have been found useful for later prediction of NVI. In one study, the b-wave amplitude was smaller in eyes that later developed NVI.53 The mean intereye difference in b-wave amplitude was 102±SD47 mV. Of greater predictive power was the b-wave implicit time, which was prolonged in the eyes that later developed NVI. The mean intereye difference in b-wave implicit time was 9.6 ms (95% CI 7.4Ð11.8 ms).53 By testing over a range of luminances, the authors concluded that a b-wave implicit time of greater than 47.2 ms or an intereye difference of greater than 7.4 ms was strongly associated with later NVI.53 The PhNR response was found to be the most sensitive predictor of NVI in another study.19
In yet another study, a mean cone implicit time of 35.0 ms or more was 88% sensitive and 100% speciÞc for detecting eventual NVI and was suggested as the most useful ERG variable for predicting later NVI.56 In a study of 15 patients with CRVO, 9 of whom had or later developed NVI and 6 of whom did not, log K was the most sensitive for discriminating the eyes developing NVI from those not developing NVI. Using a forced