application of the spatiochromatic visual evoked potential to detection of congenital and acquired...

1818 J. Opt. Soc. Am. A/Vol. 10, No. 8/August 1993

Application of the spatiochromatic visual evokedpotential to detection of

congenital and acquired color-vision deficiencies

Michael A. Crognale

School of Optometry, University of California, Berkeley, Berkeley, California 94720

Eugene Switkes

Departments of Chemistry and Psychobiology, University of California, Santa Cruz, Santa Cruz, California 95064

Jeff Rabin, Marilyn E. Schneck, Gunilla Haegerstr6m-Portnoy, and Anthony J. Adams

School of Optometry, University of California, Berkeley, Berkeley, California 94720

Received July 20, 1992; revised manuscript received December 3, 1992; accepted January 22, 1993

Visual evoked potentials were recorded in response to spatiochromatic stimuli modulated in different directionsin cone-activation color space from subjects with congenital and acquired color defects. This technique waseffective for detection and classification of both mild and severe forms of congenital deficits. Results suggestthat the visual evoked potential is useful for early identification of color abnormalities in acquired deficits suchas diabetes and that it is sensitive enough to detect regional retinal losses of sensitivity (e.g., as in centralserous choroidopathy). The spatiochromatic visual evoked potential provides a systematic and sensitive indica-tion of different color-vision anomalies.

INTRODUCTION

The development of objective techniques to assess chro-matic processing has been the subject of recent research.The interest in this area can be attributed, in part, to theobservation that many ocular diseases, including glau-coma, diabetic retinopathy, retinitis pigmentosa, and cen-tral serous choroidopathy (CSC), result in changes in colorvision and, in particular, in a loss of short-wavelengthsensitivity.'-" These changes can often be revealed be-fore detection of pathology by use of conventional clinicaltests. Thus measures that reveal these early selectivelosses are useful for considering early treatment of suchdiseases. Objective assessment of color-vision losses canalso aid the clinician in discriminating between stablecongenital achromatopsia and progressive degenerativediseases in infants and nonverbal patients. Most previ-ous studies have used threshold psychophysical measures,with few attempting to quantify sensitivity losses objec-tively at suprathreshold levels. Suprathreshold sensitiv-ity loss potentially occurs independently of threshold loss,is more difficult to identify in psychophysical tests, andrelates more directly to functional vision of the patient.

The visual evoked potential (VEP) has been shown tobe a sensitive indicator of central visual function.' 2 '14

VEP responses to luminance-varying stimuli have beeninvestigated extensively and have been correlated withpsychophysical results as well as with single-unit electro-physiology; they are used clinically for both diagnosisof disease and measurements of vision function such asvisual acuity. VEP's that use various isoluminant stimulihave also been reported previously.5 -8 We investigated

VEP responses to spatiochromatic stimuli defined in acolor space based on cone activation.9 2 0 In this paper wereport the application of these VEP methods to the assess-ment of congenital and acquired color-vision anomalies.

METHODS

Color SpaceGratings that vary in different directions in the colorspace that was proposed by MacLeod and Boynton2 andthat was augmented with the luminance dimension byKrauskopf et al.22 were used as stimuli. In this spacechromatic directions are designated by the elevation 0 andazimuth p.22 Except where otherwise noted, the colorswere modulated symmetrically around the achromatic(illuminant C) origin of the color space (CIE; x = 0.310,y = 0.316) keeping the space-averaged chromaticity andluminance (17.1 cd/m2 ) constant. These stimuli avoid thecomplications of chromatic adaptation while permittingselective activation of various visual pathways.

ProceduresThe stimuli were 1-cycle-per-degree sine-wave gratingspresented in an 18-deg circular patch, viewed from 57 cm.The edges of the patterns were Gaussian tapered to re-move high spatial frequencies. The patterns were gener-ated by use of a Sun-TAAC color graphics system and weredisplayed on a Sony monitor at a 66-Hz refresh rate.Monocular VEP's were recorded to pattern onset at 2 Hz.During each cycle the pattern was on for 106 ms and wasoff for 394 ms. The temporal parameters were chosen to

0740-3232/93/081818-09$06.00 ( 1993 Optical Society of America

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Vol. 10, No. 8/August 1993/J. Opt. Soc. Am. A 1819

maximize the chromatic response and are similar to thoseemployed in previous research on chromatic VEP's.'6-2 0

The active electrode was placed 2 cm above the inion;reference and ground electrodes were clipped to the ear-lobes. Waveforms were averaged over 40-80 presentationsof the stimulus. Amplification filtering (low cut, 0.3 Hz;high cut, 30.0 Hz), averaging, and data analysis were per-formed on either a Nicolet or an LKC commercial system.The filtering and averaging parameters were set to beequivalent for the two systems, and simultaneous record-ing of VEP's by use of both systems resulted in nearly in-distinguishable waveforms. Amplitudes of the waveformswere measured from the trough of the first large negativewave to the peak of the following positive wave. Laten-cies were measured from light onset to the trough of thefirst large negative wave.

VEP's were measured for patterns occurring along avariety of directions in the color space, including the lumi-nance axis (LUM axis), wherein all cones are modulatedproportionally, various axes in the isoluminant plane[these correspond to variations of p, with 0 = 0 deg; e.g.,the LM axis, wherein the long-wavelength-sensitive (L)and middle-wavelength-sensitive (M) cones are modulatedequally but 180 deg out of phase without stimulation ofshort-wavelength-sensitive (S) cones, and the S axis,wherein only the S cones are modulated], and two axesthat produce modulation of only L and M cones, respec-tively. The latter two axes vary in both chromaticity andluminance (0 # 0 deg or 90 deg). A large variety of colordirections were employed beyond those implied by specificmodels for the site of color deficits, e.g., cardinality of

22 2cone axes or perceptual opponent mechanisms.2 'In this paper, grating contrast was expressed as per-

centage of the maximum that was available on our displayfor a given axis. The maximum available cone con-trasts2 4 along that major axes were as follows: LM axis(L = 0.094, M = 0.179, S = 0); S axis (L = 0, M = 0,S = 0.795). CIE (1931) (x,y) coordinates for the endpoints of the LM axis were (0.388, 0.280) and (0.210,0.363); those for the S axis were (0.273, 0.230) and (0.389,0.501). The axes of maximum and minimum (D-isolumi-nant2 5 ) rod modulation in the isoluminant plane wereS = 105 deg and so = 15 deg respectively. Small devia-tions from individual isoluminance values produced littleor no change in the spatiochromatic VEP recorded underthese conditions.9 Therefore the Smith-Pokorny2 6 fun-damentals and the CIE (1951) photopic-luminosity func-tion were used to calculate cone activations and luminosityand were applied for all individuals.

SubjectsSubjects were drawn from a clinical population andincluded two diabetics, a subject with a history of CSC,and five subjects with congenital color deficits. Ten sub-jects with normal color vision (aged 21-50 years; mean33.4 years) were also tested.

RESULTS AND DISCUSSION

Normal ObserversIn a related study that used observers with normal colorvision,'9 we investigated spatiochromatic VEP's and theirdependence on contrast, chromaticity, spatial, and tempo-

ral parameters. The relevant findings from this studyare (1) amplitude increases with contrast, saturating at-50% contrast; (2) latency decreases with contrast for allavailable contrasts; (3) at 25-50% contrast the amplitudesfor gratings along the LM and S axes are approximatelyequal; and (4) when amplitudes are equated in this man-ner, the latency of the S-axis VEP is significantly longer(-40 ms) than that of the LM response. With the stimu-lus parameters used in the present investigation, re-sponses to luminance modulations were typically smaller,more complex, and more variable than were responses tochromatic stimuli.'4 Measurements of amplitude werefar less reliable and showed much larger interindividualvariation than did measurements of latency. For this rea-son quantitative comparisons to normal observers are re-stricted to measurements of latency.

Figure 1 (top row) shows waveforms obtained in re-sponse to 40% contrast modulations along five differentaxes (LUM, LM, L, M, and S) from a subject with normalcolor vision. In agreement with previous reports6 20

of research that used similar stimuli (low spatial fre-quency, pattern onset), the chromatic waveforms show alarge negative-going peak and longer latencies for S-axismodulation. Although L- and M-axis modulations con-tain both chromatic and luminance components, the re-sponses are similar to those obtained along the LM axis,which contains only chromatic components. As men-tioned above, this result can be attributed to the choice ofparameters that favor the chromatic response.

Congenital Deficits

DyschromatopsiaThe results obtained from color-defective subjects in re-sponse to stimulus modulations along five different axesare shown in Fig. 1. The responses from a color-normalsubject are shown in the top row for comparison. Thosefrom a congenital tritanope [diagnosed by use of Hardy-Rand-Rittler test plates, neutral-point determination, andnormal matches on the Nagel anomaloscope] and from aprotanopic individual [diagnosed by Nagel anomaloscope,

S LM M L LUM

Normal

Tritanope 9~

Protanope .... ..wd .I

jo,0v L100 ms

Fig. 1. Waveforms obtained from severely color-defective observ-ers (middle row, tritanope; bottom row, protanope) by use ofmodulation along five axes in color space. Waveforms from anormal observer are shown in the top row for comparison. Thevertical lines indicate the latency of the normal waveforms.Waveforms that appear to have much longer latencies and/ormuch smaller amplitudes than those of the normal observer areshaded (the luminance waveforms are typically highly variableand consequently are not shaded).

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Farnsworth Panel D-15 test (D-15), and Hardy-Rand-Rittler test plates] are shown in the middle and bottomrows, respectively. The vertical lines are drawn throughthe normal subject's response troughs to aid in compari-son of latencies. The shaded boxes indicate chromaticwaveforms judged to have much longer latencies and/ormuch smaller amplitudes than those of the normal ob-server's waveforms. As expected, the responses of thetritanope are absent along the S axis and are similar tothose of normal observers on all other axes. Responses ofthe protanope have increased latencies along the LM andM axes and are nearly absent along the L axis.

These results are consistent with the Regan-Spekreijse2 7

report of a deuteranopic subject and the Kinney-McKaystudy,28 which used very different methods and stimuli.For the tritanopic individual, as expected, only the wave-forms from S-axis modulation differ substantially fromthose of normal observers, since tritanopia is believedto result from an abnormality of the S cones.2930 Thetritanope's responses along the S axis also provide an esti-mate of the rod contribution to the chromatic VEP. Thisestimate is possible because the axis of maximum rodmodulation is near the S axis (p 105 deg) and becausethe tritanope would be expected to have normal rod func-tion. The waveform indicates that, for our presentationconditions, rod contribution to the VEP in the isoluminantplane is minimal.

The waveforms for the protanope are normal along theS axis but are nearly absent along the L axis. In addition,the waveforms for modulation along the LM and M axesexhibit near-normal amplitude but have long latencies,similar to those found for modulation along the S axis.This result is consistent with a model in which spatiochro-matic VEP's in normal observers reflect signals that havepassed through chromatic-opponent stages [S - (L + M)and M - L], with the [S - (L + M)] pathway beingslower. For the protanope, who presumably lacks L conesand therefore also has no (M - L) chromatic signal, stim-uli along the S, M, and LM axes would produce modulationin the remaining (S - M) slower chromatic pathway.

It should be noted that modulation along the LM axis inthe protanope and along the L- and M-cone axes in thenormal and tritanope produces luminance modulation aswell as chromatic modulation. However, as mentionedabove, the stimulus parameters that were chosen heregreatly favor responses to chromatic stimuli as opposed tothose obtained with the use of purely achromatic stimuli.Consequently, for each subject the waveforms obtained byuse of modulations along axes that are, for the respectiveindividual cases, mixed chromatic-achromatic axes,largely resemble the isoluminant responses as opposed tothe achromatic responses. Thus the LM and M axes inthe protanope produce VEP's that are similar to thosealong the S axis, and L- or M-cone modulation in normalobservers yields responses that are similar to isoluminantVEP's along the LM axis.

The luminance waveforms in Fig. 1 differ idiosyncrati-cally among the observers (and within the normal ob-server's data'9). The differences between individualluminance waveforms actually may be a reflection of thesensitivity of the VEP to chromatic intrusion. The whitechosen for the the achromatic origin of the color space isintended to minimize activation of chromatic mecha-

nisms. However, since the present technique is sensitiveto chromatic changes, one would expect to see individualdifferences in waveforms for modulations along the lumi-nance axis because it is unlikely that all individuals' whitepoints correspond to that of the origin.

Figure 2 illustrates latency differences between con-genital color-defective observers and normal observers asa function of direction in color space within the isolumi-nant plane. The data points represent the differencebetween the color-defective latencies (average of 2 deter-minations) and the average normal latencies (n = 10;2 determinations each) for each direction; i.e., points nearinnermost rings indicate latencies close to those for nor-mal observers. The gray rings indicate a latency differ-ence of 20 ms.

The polar plot at the top of Fig. 2 shows the responsesobtained from a protanomalous individual and a pro-tanope. The relative reponse latencies for these subjectsare greatest near the LM (horizontal) axis and are nearnormal along the S (vertical) axis. The magnitude of thelatency increase is greater for the protanope than for theprotanomalous subject. The response latency differencesfor a mildly deuteranomalous individual are shown in thecenter plot. As expected, the greatest differences areagain aligned along the LM axis with near-normal S-axislatencies. The polar plot in the bottom of Fig. 2 shows thelatency differences of responses obtained from a tri-tanopic individual. The greatest latency increases occurnear the S axis. The arrows in this plot indicate that theresponses to stimuli near the S-axis produced waveformsthat were indistinguishable from the noise; these re-sponses consequently had indeterminate latencies.

The protanopic and protanomalous latencies in Fig. 2demonstrate that even though the isoluminant plane forthe normal observer is not isoluminant for protan indi-viduals, and thus luminance modulation is necessarilypresent, losses are clearly evident near the LM axis. Theprotanomalous observer also shows increased latencyalong the LM axis (although to a lesser extent than theprotanope), demonstrating that the spatiochromatic VEPis sensitive to mild color losses and that the magnitude ofdyschromatopsia is reflected in the VEP response. TheVEP also detects mild color losses in the deuteranomalousobserver; there is a clear deficit along the LM axis. Theaxis of greatest latency increase aligns better with thenormal LM axis than does the axis of greatest loss inthe protanopic data. This may reflect the fact that thedeutan observers' isoluminant plane is more similar to thenormals' than is that of the protanope.

We note that in the isoluminant plane chromatici-ties corresponding to deuteranopic and protanopic confu-sion lines lie very close to the LM axis ( = 1.5 deg and-3.0 deg, respectively). More importantly, however, col-ors along confusion lines are only confused if they are in-dividually equated in brightness. For protanopes anddeuteranopes these axes are equivalent to the L- and M-cone axes (not in the isoluminant plane) described above.However, within the isoluminant plane our presentationprotocol (which emphasizes chromatic signals) gives maxi-mum latency increases near the LM axis for deuteranopicand protanopic observers.

With more severe color defects latencies become in-creasingly difficult to estimate as one nears the axis of

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S axis90

180

Protanomalousand Protanope

0

0 LM axis

S axis90

270

Deuteranomalous180

S axis90

0 LM axis

270

180 0 LM axis

Tritanope

270Fig. 2. Polar plots of the latency differences obtained by use of modulation within the isoluminant plane in congenital color-defectiveobservers (top, protanomalous and protanope; middle, deuteranomalous; bottom, tritanope). The latencies are plotted relative to normalobservers for each direction in color space (innermost ring, zero difference; gray ring, 20-ms difference).

greatest loss because of the great reduction in signal size.Nonetheless, the tritanope's data show that the expectedloss is aligned fairly well with the S axis. This result isstrengthened by the concurrence of the tritanopic andnormal isoluminant planes. VEP data obtained from nor-mal subjects during exposure to short-wavelength adapt-ing lights show a qualitatively similar increase in S-axislatencies.

In general, assessing the color-selective VEP losseswithin the isoluminant plane is effective in demonstratingdeficits at both receptor and opponent stages. However,mechanistic interpretation of these data is complicated bythe differences between the normal observers' color spaceand that of the color-defective subjects. For conditionsarising directly from cone defects it may be more mean-

ingful to utilize directions in color space that correspondto cone axes rather than cardinal axes.22 When latenciesfor color-defective observers are plotted relative to normallatencies for VEP responses along the three cone axes, aclear pattern distinguishes each of the protan, deutan,and tritanopic defects from one another (Fig. 3). Pro-tanopic and protanomalous response latencies show thegreatest increase along the L axis, as expected; the pro-tanomalous subject's responses are less delayed. Thedeuteranomalous subject shows the largest latency differ-ences along the M-cone axis. The tritanope's responsesare normal along the L- and M-cone axes and are unmea-surable along the S axis. This procedure not only cor-rectly identifies the type of color deficit but also may beuseful for quantifying the magnitude. The clinical ad-

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E 1200zE0J_ 80

0 . 4

a* 400C

-J 0

Protanope

Protanomalous

Deuteranomalous

Tritanope

L M S

Fig. 3. VEP latency differences obtained from congenital color-defective observers in response to modulations along the S-, L-,and M-cone axes at 40% contrast. The shaded rectangles indi-cate the range of four normal observers. Color-defective laten-cies are plotted relative to those of the average normal observer.

vantage to this technique is that it is rapid, requiring mea-surement of VEP's to modulations along only three direc-tions in color space, and thus consumes only a few minutesof time.

Since the latency of the VEP depends on the contrast ofthe stimulus it is important to establish whether detectionof color loss with the VEP depends critically on the stimu-lus contrast chosen. It does not. Figure 4 plots the laten-cies of the VEP for modulations along the S and LM axesfor two mildly deuteranomalous subjects. The shadedregions indicate the average of ten normal observers+1 standard deviation. At each contrast of S-axis modu-lation the deuteranomalous latencies fall well within thenormal range. However, the deuteranomalous latenciesfor LM-axis modulations are consistently greater than arethose for normal observers. These losses occur over alarge range of contrasts, enhancing the clinical utility ofthis measurement.

S axis300

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AchromatopsiaObjective assessment of color blindness (monochroma-tism) would have clinical and scientific value. Figure 5displays the VEP results from two rod monochromats.The stimuli for these VEP responses were sinusoidal red-green gratings in which the luminance of the red compo-nent remained fixed (27.75 cd/M2 ) and that of the greencomponent was varied. The latency of the response isplotted as a function of the log photopic luminance. Thedata for a normal observer are plotted for comparison. Ascan be seen, there is a point at which the latency of the rodmonochromat's responses increases dramatically. It isat this point that the subjects also report that the gratingis least visible. This is near the point at which the sco-topic luminances of the red and green stripes are matched(0.65) and the point at which a scotopic match was psycho-physically determined in a normal observer (arrow).These data suggest that there is no contribution to theVEP from cone mechanisms in these two monochromats.

The results of testing the rod monochromats demon-strate that investigation of color losses with the VEP maybe extended to individuals with severe congenital color vi-sion losses. This technique may permit differential diag-nosis of congenital achromatopsia (which is stable) from adisease such as rod-cone dystrophy (which is progressiveand typically results in more severe vision loss) at an earlyage. Differential diagnosis by means of conventionalclinical procedures at an early age is difficult since thesymptoms are similar, and psychophysical testing is oftendifficult or impossible. Further experiments are beingconducted to test whether this technique might also per-mit differentiation of blue-cone (X-linked) and rod mono-chromats (autosomal recessive) and between complete andincomplete achromatopsia; these distinctions affect clini-cal management and counseling.

Acquired Deficits

DiabetesThe utility of the spatiochromatic VEP for assessment ofmore subtle losses reported previously in diabetics was

LM axis300

250

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150

100

50

.* *

N

N

*U -

1.0 1.2 1.4 1.6 1.8

Log Contrast(percent maximum)

2 1 1.2 1.4 1.6 1.8 2

Log Contrast(percent maximum)

Fig. 4. Latency of VEP response from two deuteranomalous subjects (squares) to stimuli along the S and LM axes plotted as a functionof log contrast. The shaded region indicates the average latency from ten normal observers (±1 standard deviation).

....... .....

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500r

401v

Latency (ins) 20 M.w d2 .-.- u1/-u-.-.U-a-.UA Normal

0.0 0.3 0.6 0.9 1.2 1.5

Log Photopic R/GFig. 5. VEP latencies from two rod monochromats (Ml and M2)plotted as a function of the log photopic luminance ratio of thered and green components of a red-green sine-wave grating.Normal latencies are also plotted for comparison. The calculatedscotopic isoluminant point is 0.65. The arrow indicates thepsychophysical scotopic match for a normal observer.

also assessed. Figure 6 plots VEP latencies for modula-tions along the S and LM axes as a function of log contrast(as in Fig. 4) from two diabetics (GD: aged 47 years;mild background retinopathy; normal on the D-15, theAdams' desaturated D-15, and the Farnsworth-Munsell100-hue test (FM 100-hue); acuity, 20/20; PS: aged62 years; very mild background retinopathy; multiplesingle-place errors on the Adams desaturated D-15; nor-mal on the FM 100-hue; acuity, 20/25). The shaded re-gions in each plot indicate the average of ten normalobservers ±1 SD. The latencies for the S-axis modulationin the two observers are consistently greater than those ofnormal observers for this range of contrasts; the latenciesobserved for modulations along the LM axis fall close tothose of the normal observers.

Psychophysical investigations in diabetics show earlyS-cone pathway deficits that precede detectable retinalpathology.7', Our results demonstrate that the spatio-chromatic VEP may also be useful in this context. In thepresence of significant retinopathy poor VEP responses

S axis

are generated by any of the stimuli used here. However,both of the observers described in Fig. 6 had only mildbackground retinopathy. This suggests that the tech-nique is quite sensitive and may show greatest value as anearly expression of progressive retinopathy. Identifyingthe earliest stage at which significant functional loss oc-curs is important. Once retinopathy occurs, it is generallythought to be irreversible; treatment is currently limitedto laser photocoagulation, which can only halt or retarddegeneration. The current Diabetes Control and Compli-cations Trial3 l is designed to determine whether interven-tion and institution of tight metabolic controls earlier inthe disease, when function is first changed but structureis not, offers the possibility of treatment.

Central Serous ChoroidopathyCSC is a condition in which there is leakage and accumu-lation of serous fluid from the choroid that elevates thesensory retina.32 This condition results in some selec-tive loss in S-cone system sensitivity.5 CSC is interestingfor a number of reasons: (1) it frequently occurs in other-wise healthy eyes; (2) it is often a unilateral condition;(3) it is typically confined to patches of the retina; and(4) it usually resolves itself after a period of weeks ormonths with no overt residual visual losses or retinal ab-normalities. We used the spatiochromatic VEP to exam-ine the losses in a patient with a history of CSC.0 Thissubject had suffered an active episode 10 years beforethe VEP testing reported here. His present visual acuityis 20/15, and he tests as normal on standard clinical testsof color vision (e.g., FM 100-hue, D-15).

A demonstration of sensitivity loss was obtained bycomparing the responses of the affected and unaffectedeyes.2 0 Interocular comparison is particularly powerfulbecause individual differences in isoluminance or prereti-nal filtering between eyes are unlikely to be significant.The responses from the two eyes were shown to be similaralong each of the axes exept for S-axis modulation. ForS-cone stimulation, the amplitude of the response fromthe affected eye was greatly reduced and the latency wasgreatly increased compared with that of the unaffected eye.

LM axis300

U E

.. ,,,,,X j' WW a- U U U~

U

U E

250

200

150

100

50

1 1.2 1.4 1.6 1.8 2

EN.0'"'. :

W ~ .. . M.?..... |. E. E.. . ..... ... . ..

1 1.2 1.4 1.6 1.8 2

Log Contrast Log Contrast(percent maximum) (percent maximum)

Fig. 6. Latencies of the VEP obtained from two diabetic subjects (squares) for modulations along the S and LM axes.the same as in Fig. 4.

Other details are

300 r

250 .

200 .Latency

(ms) 150 .

100 .

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S axis400

300

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S

a.

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. Latency(Ms)

200S 0

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"A�1-.

a . I . I - . - .

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Log Contrast

(Percent Maximum)

* | . | * I * I * --

1.0 1.2 1.4 1.6 1.8 2.0

Log Contrast

(Percent Maximum)Fig. 7. Latencies of the VEP obtained from a subject with CSC (affected eye, circles; unaffected eye, squares) for modulations along theS and LM axes. Other details are the same as in Fig. 4.

The selective sensitivity loss does not depend on con-trast (Fig. 7). This figure plots VEP latency as a func-tion of contrast for both eyes of the CSC subject. Formodulations along the LM axis the latency of the responseof the affected eye is close to that of the normal observersat all contrasts, but for modulations along the S axisthe response latency is much longer. The unaffectedeye shows near-normal latencies at all contrasts alongboth axes.

The unilateral, selective losses are further demon-strated by plotting amplitude ratios and latency differ-ences between eyes as a function of direction within theisoluminant plane (Fig. 8). The amplitude of the re-sponse is most attenuated near the S axis, although theresponse amplitudes are slightly reduced for most chro-matic directions. These data also reveal a selective in-crease in latency near the S axis. The exact orientationof the axis of maximum latency may not accurately reflectthe axis of greatest loss because, as the stimuli departfrom the LM axis, the amplitudes of the waveforms dimin-ish to near-noise levels in the affected eye, making it diffi-cult to determine response latency. Within a subject,amplitude data may be more useful to determine the axisof loss.

It is well documented that CSC is localized to retinalareas. Fluorescein and fundus photographs were used todetermine the locations and extent of the involved retinalregions for this patient. Fundus examination of the af-fected eye during the active phase of the initial episode inMay 1981 revealed an -12-deg area of subretinal leakagesuperior to the fovea. Fundus examination 1 year later,and again after completion of the present experiments(June 1991), revealed that the condition had been re-solved. Comparison of VEP's recorded for gratingpatches that were presented to affected and unaffectedregions of the retina revealed a residual regional loss ofS-cone mechanism sensitivity in CSC.20 Comparison ofwaveforms from the same regions of the unaffected eye

yielded no significant difference between the two regions.Thus it is unlikely that the latency differences are due toretinal inhomogeneity. Media effects are obviously an un-likely cause of latency differences within the affected eye.One intriguing aspect of these results is that, although thecondition appeared to have completely resolved itself

S axis

S axis

Amplitude) LM axis

Latency

LM axis

Fig. 8. Polar plots of the VEP responses from a subject withCSC. Top, the ratio of the amplitudes (affected eye/unaffectedeye) as a function of direction within the isoluminant plane. Thegray ring indicates a ratio of 1, i.e., equivalent amplitudes ineach eye. Bottom, the difference in latency between the affectedand unaffected eyes (innermost ring, zero difference; gray ring,20-ms difference).

L

1.1,b * X * |

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shortly after the episode, examination by use of the cur-rent technique 10 years later reveals a regional and se-lective loss in S-cone mechanism sensitivity. Retinallocalization of color loss also explains why the subject couldperform normally on clinical tests of color vision. At thefovea, where clinical tests of color vision are most appli-cable, the subject's retina was relatively unaffected. Theability to detect color -defects outside the fovea seems tooffer significant advantage. It is worth remembering thatthe selective loss of S-cone mechanism sensitivity was alsorevealed without localization of the stimulus by use of alower contrast and a large-field presentation. Thisgreatly increases the clinical utility of the VEP technique.

Our results from a patient with resolved CSC indicate aselective loss of S-cone-pathway sensitivity and alsodemonstrate the utility of the VEP technique for assess-ing acquired color-vision losses. The unilateral natureof this condition permitted us to make an interocularcomparison of waveforms. The results from localizedstimulation demonstrated that regional losses in S-conesensitivity can be revealed by use of the spatiochroma-tic VEP.

Utilization of the spatiochromatic VEP in conjunctionwith the framework provided by a cone-activation colorspace provides a means for investigating a large variety ofcongenital and acquired color-vision deficits. This tech-nique permits a rapid and sensitive addition to clinicalprotocols and is particularly applicable to instances inwhich early detection is important.

ACKNOWLEDGMENT

This research was supported by National Institutes ofHealth grants EY02271, EY07043, EY07345, and EY00014.

REFERENCES

1. W Jeager and A. Nover, "Storungen des Lichtsinns undFarbensinns bei Chorioretinitis centralis serosa," Graefe'sArch. Clin. Exp. Ophthalmol. 152, 111-120 (1951).

2. G. Verriest, "Further studies on acquired deficiency of colordiscrimination," J. Opt. Soc. Am. 53, 185-195 (1963).

3. E. Marre and M. Marre, "The influence of three color visionmechanisms on the spectral sensitivity of the fovea," Mod.Probl. Ophthalmol. 11, 219-223 (1972).

4. M. A. Sandberg and E. L. Berson, "Blue and green conemechanisms in retinitis pigmentosa," Invest. Ophthalmol.Vis. Sci. 16, 149-157 (1977).

5. A. J. Adams, "Selective loss of blue cone mechanism in cen-tral serous choroidopathy," Invest. Ophthalmol. Vis. Sci.Suppl. 22, 62 (1982).

6. A. J. Adams, R. Rodic, R. Husted, and R. Stamper, "Spectralsensitivity and color discrimination changes in glaucoma andglaucoma-suspect patients," Invest. Ophthalmol. Vis. Sci. 23,516-524 (1982).

7. A. J. Adams, Zisman, and G. Bresnick, "Macular edemareduces B cone sensitivity in diabetics," Appl. Opt. 26, 1455-1457 (1987).

8. V C. Greenstein, D. C. Hood, R. Ritch, D. Steinberger, andR. E. Carr, "S (blue) cone pathway vulnerability in retinitispigmentosa diabetes and glaucoma," Invest. Ophthalmol. Vis.Sci. 30, 1732-1737 (1989).

9. A. Serra, M. Fossarello, G. De Martini, M. D'Atri, I. Zucca,and M. G. Mulas, "Color discrimination in long-term idio-pathic central serous choroidopathy," in Color Vision Defi-ciencies IX, Documenta Ophthalmologica Proceedings Series,B. Drum and G. Verriest, eds. (Kluwer, Dordrecht, TheNetherlands, 1989), Vol. 52, pp. 229-232.

10. J. Pokorny, V C. Smith, G. Verriest, and A. J. L. G. Pinckers,Congenital and Acquired Color Vision Defects (Grune &Stratton, New York, 1979).

11. V C. Smith, J. Pokorny, and K. R. Diddie, "Color matchingand Stiles-Crawford effect in central serous choroidopathy,"Mod. Probl. Ophthalmol. 19, 284-295 (1978).

12. F. W. Campbell and L. Maffei, "Electrophysiological evidencefor the existence of orientation and size detectors in the hu-man visual system," J. Physiol. (London) 207, 635-652 (1970).

13. F. W Campbell and J. J. Kulikowski, "The visual evoked po-tential as a function of the contrast of a grating pattern,"J. Physiol. (London) 222, 345-356 (1972).

14. D.'Regan, Human Brain Electrophysiology (Elsevier, NewYork, 1989).

15. D. Regan and H. Sperling, 'A method of evoking contour-specific scalp potentials by chromatic checkerboard patterns,"Vision Res. 11, 173-176 (1971).

16. I. J. Murray, N. R. A. Parry, D. Carden, and J. J. Kulikowski,"Human visual evoked potentials to chromatic and achro-matic gratings," Clin. Vision Sci. 1, 231-244 (1987).

17. J. J. Kulikowski, I. J. Murray, and N. R. A. Parry, "Electro-physiological correlates of chromatic-opponent and achro-matic stimulation in man," in Color Vision Deficiencies IX,Documenta Ophthalmologica Proceedings Series, B. Drumand G. Verriest, eds. (Kluwer, Dordrecht, The Netherlands,1989), Vol. 52, pp. 145-153.

18. T. A. Berninger, G. B. Arden, C. R. Hogg, and T. Frumkes,"Separable evoked retinal and cortical potentials from eachmajor visual pathway: preliminary results," Br. J. Ophthal-mol. 73, 502-511 (1989).

19. M. A. Crognale, J. R. Rabin, A. J. Adams, and E. Switkes,"VEP correlates of spatio-chromatic processing," Invest.Ophthalmol. Vis. Sci. Suppl. 33, 701 (1992).

20. M. A. Crognale, J. Rabin, E. Switkes, and A. J. Adams,"Selective loss of S-pathway sensitivity in central serouschoroidopathy revealed by spatio-chromatic visual evokedcortical potential (VECP)," in Color Vision Deficiencies XI,B. Drum, ed., Vol. 56 of Documenta Ophthalmologica Pro-ceedings Series (Kluwer, Dordrecht, The Netherlands, 1993),pp. 229-239.

21. D. I. A. Macleod and R. M. Boynton, "Chromaticity diagramshowing cone excitation by stimuli of equal luminance,"J. Opt. Soc. Am. 69, 1183-1186 (1978).

22. J. Krauskopf, D. R. Williams, and D. W Heeley, "Cardinaldirections of color space," Vision Res. 22, 1123-1131 (1982).

23. D. Jameson and L. M. Hurvich, "Some quantitative aspects ofan opponent-colors theory. I. Chromatic responses andspectral saturation," J. Opt. Soc. Am. 46, 546-552 (1955).

24. G. R. Cole, D. F. Stromeyer III, and R. E. Kronauer, "Visualinteractions with luminance and chromatic stimuli," J. Opt.Soc. Am. A 7, 128-140 (1990).

25. R. S. L. Young and D. Y. Teller, "Determination of lights thatare isoluminant for both scotopic and photopic vision," J. Opt.Soc. Am. A 8, 2048-2052 (1991).

26. V C. Smith and J. Pokorny, "Spectral sensitivity of the fovealcone photopigments between 400-500 nm," Vision Res. 15,161-171 (1975).

27. D. Regan and H. Spekreijse, "Evoked potential indications ofcolour blindness," Vision Res. 14, 89-95 (1974).

28. J. S. Kinney and C. L. McKay, "Tests of color-defective visionusing the visual evoked response," J. Opt. Soc. Am. 64, 1244-1250 (1974).

29. C. J. Weitz, Y Miyake, K. Shinzato, E. Montag, E. Zrenner,L. N. Went, and J. Nathans, "Human tritanopia associatedwith two amino acid substitutions in the blue sensitive opsin,"Am. J. Hum. Genet. 50, 498-507 (1992).

30. C. J. Weitz, L. N. Went, and J. Nathans, "Human tritanopiaassociated with a third amino acid substitution in the bluesensitive visual pigment," Am. J. Hum. Genet. 51, 444-446(1992).,

31. The DCCT Research Group, 'Are continuing studies of meta-bolic control and microvascular complications in insulin-dependent diabetes mellitus justified?" N. Engl. J. Med. 318,246-249 (1988).

32. J. D. M. Gass, "Pathogenesis of disciform detachment of theneuroepithelium. II. Idiopathic central serous choroidopa-thy," Am. J. Ophthalmol. 63, 587-596 (1967).

Crognale et al.

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