color vision defect type and spatial vision in the optic...

Color Vision Defect Type and Spatial Vision in the OpticNeuritis Treatment Trial

Marilyn E. Schneck*^ and Gunilla Haegerstrom-Portnoyf

Purpose. To describe the types of color vision defects present in the acute phase of the diseaseand 6 months into recovery in the 438 participants of the Optic Neuritis Treatment Trial.

Methods. Patients meeting strict eligibility criteria were seen within 8 days of the onset ofsymptoms and then at regular follow-up visits. At the first and 6-month visits (and subsequentannual visits), spatial vision (acuity, contrast sensitivity), visual fields, and color vision weremeasured. Farnsworth-Munsell 100-hue tests were scored by a variant of the method ofquadrant analysis described by Smith et al (AmJ Ophthalmol 1985; 100:176-182).

Results. Most persons show mixed red-green (RG) and blue-yellow (BY) color defects (onetype predominating, accompanied by a lesser defect of the other type). BY defects tend tobe slightly more common in the acute phase of the disease, with slightly more RG defects at6 months. Persons may shift defect type over time. Defect type was not related to any of thespatial vision measures at either test time or to treatment group; however, severity of colordefect was related to both spatial vision measures and treatment group.

Conclusions. Contrary to common clinical wisdom, optic neuritis is not characterized by selec-tive RG defects. Color defect type cannot be used for differential diagnosis of optic neuritis.Invest Ophthalmol Vis Sci. 1997;38:2278-2289.

v-lptic neuritis is an acute, inflammatory, demyelinat-ing disease of the optic nerve that is usually accompa-nied by ocular pain. It affects more women than menand may be associated with multiple sclerosis.1 Al-though the most common presenting symptom isblurred vision or visual field loss, a broad range ofvisual functions are affected. The severity of visual lossvaries from a slight visual field deficit to no light per-ception. The constellation of visual functions affectedalso varies greatly.

Color vision defects are common in optic neuritis,even after resolution of the defects in spatial vision.1"6

The Optic Neuritis Study Group1 reported that 94% ofpatients had abnormal color vision in the acute phase ofthe disease and that about 40% had residual color defectsat 6 months.5 Despite the high frequency of color defectsin optic neuritis, the nature of the defects is not wellcharacterized. It is generally agreed that the color defect

From the *Smith-Kettlewell Eye Research Institute, San Francisco, and the fSchool ofOplometry, University of California at Berkeley, California.Supported by the Smith-Kettlewell Eye Research Institute.Svbmitted for publication April 1, 1997; revised May 27, 1997; accepted May 27,1997.Profxrietary interest category: N.Reprint requests: Marilyn Schneck, Smith-Kettlewell Eye Research Institute, 2232Webster Street, San Francisco, CA 94115-1821.

in optic neuritis resembles acquired rather than congeni-tal color defects, but the type of acquired defect is amatter of disagreement.

Kollner's rule states that blue-yellow (BY) colordefects arise in disorders of the retina, whereas condi-tions affecting the optic nerve result in red-green(RG) color defects.7 Many authors report that opticneuritis produces a type II RG defect.8""15 However,the finding of predominantly RG defects in optic neu-ritis is not universal. BY defects are often reported.2"416

Nonselective (NS) losses—that is, approximatelyequal losses of both the RG and BY color systems—have also been found using various techniques.217"22

The discrepancies among these earlier reportsmay be due to many factors, including differences inthe optic nerve diseases included (due to differencesin inclusion and exclusion and diagnostic criteria),sampling biases due to small sample sizes in an inher-ently variable single disease entity, differences in test-ing times in relation to the time course of the disease,differences in the severity of the disease across studies,and differences in testing or scoring methods.

The recent Optic Neuritis Treatment Trial(ONTT)1'5 longitudinally followed a large, homoge-neous sample of optic neuritis patients. Strict eligibil-

2278Investigative Ophthalmology & Visual Science, October 1997, Vol. 38, No. 11Copyright © Association for Research in Vision and Ophthalmology

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Color Vision in the Optic Neuritis Treatment Trial 2279

ity and exclusion criteria were used, and each partici-pant was tested at fixed times from the time of theinitial acute attack. The Farnsworth-Munsell (FM)100-hue test was included in a large battery of testsfor assessing vision. This data set thus provides anopportunity to explore the sources of variabilityamong earlier studies.

In this article, we describe the results of analysesof the FM 100-hue tests performed at the initial visitduring the acute attack of optic neuritis and at the 6-month visit, at which time spatial vision had recoveredin most patients. The relation between the color visiontest results and spatial vision measures (visual acuity,contrast sensitivity), and visual fields is described. Theresults indicate that optic neuritis does not producea single type of color defect even in this relativelyhomogeneous group. We find that most persons havea mixed color defect, with a predominantly RG or BYdefect and a smaller but substantial defect of the othertype, both during the acute attack and during recov-ery. At the time of the acute attack, a slight majorityof selective color defects were BY; at 6 months, a slightmajority were RG. Some persons changed defect typeover time. The discrepancies among earlier studiesthus most likely reflect true interindividual variationin the nature of the color defect, rather than differ-ences in methodology or spatial vision impairment atthe time of testing.

METHODS

Patients

The ONTT1 used strict criteria for eligibility: age 18to 45 years, visual symptoms of 8 days' duration or less,an acute clinical syndrome consistent with unilateraloptic neuritis as determined by an examining neu-roophthalmologist, relative afferent pupillary defect,and some definable visual field loss. A detailed historyof visual symptoms, pain, and past ocular, neurologic,and systemic disease was obtained, and ocular andvision function examinations were performed.

Initially, 457 patients were recruited into thestudy. Nine were subsequently determined to be ineli-gible and were not enrolled into the study. Ten werelost to follow-up. The results of testing the remaining438 patients are described here. The mean age of thepatients at study entry was 31.8 (±6.7) years. Mostwere women (77.2%). According to the classificationcriteria of Poser et al,23 multiple sclerosis was definitein 5.6%, probable in 7.6%, possible in 19.9%, and notpresent in 66.9% of subjects.

The research was in compliance with the tenetsof the Declaration of Helsinki. Before entry into thestudy, eligible patients were required to sign an in-formed consent form approved by the InvestigationalReview Board at each institution.

Vision Tests

Each patient received full refractive correction. Visualacuity was measured monocularly using a retroillumi-nated ETDRS chart24 at 4 m. Acuity was scored letterby letter and converted to a LogMAR scale for analysis.Visual acuity better than 20/20 (LogMAR < 0.0) wasconsidered normal. Contrast sensitivity was assessedusing Pelli-Robson charts specially made for theONTT25 at 1 m (the ONTT charts have higher contrastthan the now commercially available charts). Scoringwas done in triplet groups of letters. Log contrast sen-sitivity of 1.75 or better was considered normal. Visualfields were measured with a Humphrey Field Analyzerusing the 30-2 program, which assesses the central 30°of visual field. A mean deviation of s 3.00 dB wasconsidered normal. Color vision was assessed usingthe Ishihara pseudoisochromatic plates and the FM100-hue test.26'27 All test centers used a provided stan-dard source, a lamp with two Verilux bulbs designedto achieve a color temperature of 6200° K and provide800 lux. Room lights were off during color testing,and the testing surface was matte black. Here we re-strict our description of color vision to the results ob-tained using the FM 100-hue test.

Protocol

Baseline data were collected within 8 days of presenta-tion of symptoms. Patients were then seen at days 4,15, and 30; at weeks 7, 13, and 19; at months 6 and 12;and then yearly. At each follow-up visit, visual acuity,contrast sensitivity, and visual fields were measured.Color vision was assessed with the FM 100-hue test atbaseline (during the acute attack), at 6 months, andat all subsequent annual visits. Here we consider dataonly from the time of the acute attack and at 6 months.

Analyses of the FM 100-Hue Results

Each FM 100-hue test was scored using a locally devel-oped computer program (K. Huie, personal commu-nication). Each test was scored along three dimen-sions that relate to the severity, type, and selectivity ofthe color defect present. The severity of the defectwas determined by computing the square root of thetotal error score, which is the sum of the error scoreson each individual cap using Kinnear's method.28 Theindividual cap error score is an index of how far thecap is from the position it would occupy in a properlyordered arrangement. The criterion for normal(square root of total error score < 10.5) adopted bythe ONTT was used.

FM 100-hue tests with abnormal scores were fur-ther analyzed to determine defect type and selectivity.Various techniques have been developed to determinethe type and selectivity of color defects measured withdie FM 100-hue test.26'28"31 Farnsworth's original tech-nique involved visual inspection of the polar diagram,


2280 Investigative Ophthalmology & Visual Science, October 1997, Vol. 38, No. 11

GDeutanTritanNon-selective

FIGURE 1. Polar plots of error scores from die Famsworth-Munsell 100—hue test. (A) Farnsworth's original classificationof type of color defect. The shaded regions indicate areas corre-sponding to congenital color defects as labeled. All major erroraxes falling outside die shaded areas are considered nonselec-tive. (B) Classification of acquired error type according to Smidiet al.si Errors falling widiin the darkly shaded zones are consid-ered red-green (R-G); errors falling in die lighdy shaded zonesare considered blue-yellow (B-Y). The error pattern shown isclassified as a selective blue-yellow defect using die lenient butnot die strict criterion (see text). (C) The error pattern shownis classified as a selective blue-yellow defect using die strictcriterion of Smidi et al.*'

plotting the magnitude of the error for each of the85 test caps (Fig. 1). The length of the ray extendingfrom each cap location indicates the error score ofthe individual caps. The color defect is consideredselective when several caps in the same region (ortwo regions at 180° from each other) have significant

errors, provided other regions have few or no errors.The type of defect is defined by the orientation of themajor axis of errors. Zones corresponding to colordefects associated with loss or alteration of each of thecone types (protan, deutan, tritan) have been defined.In this scoring scheme, a major axis falling outsideone of these narrow zones is classified as NS, even ifthe error pattern is highly polarized (Fig. 1A).

More recently, quantitative methods for determin-ing the polarity and axis of error patterns have beendeveloped.26'28"31 The method of Smith et al31 was se-lected for analysis of the ONTT data because it isappropriate for acquired color defects, whereas theother methods were developed for congenital colordefects. Smith et al's technique is a form of quadrantanalysis (Fig. IB). Each of the 85 caps is classified asrepresenting either the RG or BY color system pro-cessing. BY regions include caps 1 to 12, 34 to 54, and76 to 84; RG regions include caps 13 to 33 and 55 to75. The square root of the sum of errors on caps 1 to12, 34 to 54, and 76 to 84 thus yield the BY partialerror score. The square root of the sum of errors oncaps 13 to 33 and 55 to 75 is the RG partial errorscore. Either or both defect types are considered to bepresent when the corresponding partial error scoresexceed the age norms established by the authors.Thus, in this technique, a highly polar error patterncannot be defined as NS on the basis of an orientationfalling outside narrow predetermined regions, whichis a problem with the Farnsworth method. A selectivedefect is considered to be present when the differencebetween the RG and BY partial error scores exceedscriterion values. The criteria for selectivity establishedby Smith et al are based on the 95% confidence limits(two standard deviations [SD]) of their data. This cri-terion is strict: The accumulation of RG errors mustgreatly exceed that of BY errors for an RG defect tobe considered selective, and vice versa. This criterionthus identifies relatively pure defects (i.e., defects hav-ing large accumulations of one error type and a muchsmaller number or lack of errors of the other type).

We have adopted an alternative criterion basedon 0.5 SD from Smith et al's normal mean. We chosethis criterion based on ancillary analyses showing thatthis more lenient criterion classified error patterns asselective versus NS in a manner more consistent withthe amplitude analysis of Knoblauch,29 the analyses ofVingrys and King-Smith,so and visual inspection of thepolar plots.

Figure IB shows an example of an error patternthat would be classified as a selective BY error patternby the 0.5 SD criterion (and by visual inspection), butnot the 2.0 SD criterion. Figure 1C shows an errorpattern in which the difference between BY and RGerror accumulations is sufficient to meet the 2.0 SDcriterion for a selective BY defect. Only 11.4% of theoptic neuritis patients produced patterns with this


Color Vision in the Optic Neuritis Treatment Trial

TABLE l. Pass/Fail Rates on the FM 100-HueTime of Test % Normal % Abnormal % Untestable

Acute attack6 months

6.860.6

54.036.2

39.23.2

high degree of polarity at the acute attack or at 6months. Of course, many more (76.6%) had selectivedefects by the lenient criterion, and results will bediscussed with reference to this criterion. The patternof results and conclusions drawn are independent ofthe criterion used.

RESULTS

During the acute attack of optic neuritis, the vast ma-jority of subjects either failed the FM 100-hue test orhad vision too poor to perform it; only 6.8% had errorscores within normal limits (Table 1). Six monthslater, however, 60.6% passed the test, although a largegroup (39.4%) still had abnormal color vision.

At the time of the acute attack, 39.2% of subjectscould not perform the test. In the analyses describedbelow, subjects who could perform the test at both thetime of the acute attack and 6 months are consideredseparately (group A) from those who could performthe test only at the 6-month visit (group B). The resultsfor the entire sample (group A + group B = Group C)are also presented where appropriate. This separationinto groups allowed us to evaluate the change in colorvision over time.

Color Vision Defect Type

The results of subjects who failed the FM 100-hue testwere analyzed to determine selectivity and type of de-fect using the criterion described above. Table 2 showsthe percentage of subjects with BY, RG, and NS defectsduring the acute attack and at 6 months. At the timeof the acute attack, the frequencies of RG and NSdefects were the same (29.6%). There was a tendencyfor more BY defects (40.8%). At 6 months, there wasa slight tendency for more RG defects than BY defectsamong those in group A; 36.8% had BY defects, 42.1%had RG defects, and 21.1% had NS defects. The

2281

change in the distribution of color defect type frommore BY to more RG failed to reach statistical signifi-cance (P = 0.07). At 6 months, the relative frequenciesof RG, BY, and NS defects for those in groups B andC were similar to those in group A; all groups showslightly more RG than BY defects at 6 months.

The shift in defect type is seen more clearly inFigure 2, which plots the distribution of orientationsof major error axes (derived by Knoblauch'smethod29) for those in group A. There is a preponder-ance of axes in the BY zone at the time of the acuteattack and a shift to a majority of RG axes at 6 months.

Change in Defect Type Over Time

As described above, there is a tendency for more BYdefects at baseline but more RG defects at 6 months.There are several means by which the shift in thedistribution may occur. Persons with BY defects mayimprove and have normal BY scores at 6 months,whereas RG defects remain stable; persons with BYdefects at baseline may develop NS defects (by eitheran increase in the RG partial error score or by a de-crease in the BY partial error score); or persons mayactually shift their defect type (i.e., lose the errors inthe BY zone and acquire errors in the RG zone). Infact, each of these transitions occurred (Table 3).

Of the 98 subjects who had selective BY defects atthe acute attack, 63% (62) improved and passed theFM 100-hue test at 6 months. In 6.1% (6), the initialBY defects became NS at 6 months, and 14.3% (14)who initially had BY defects developed RG defects.

Of the 71 persons who had RG defects at baseline,54.9% (39) improved and were color normal at 6months. This is slightly but not significantly less thanthe improvement rate among those with BY defectsinitially. Of those with initial RG defects, 9.8% (7)became NS, and 15.5% (11) defects developed BYdefects. It thus appears that a patient is approximatelyequally likely to switch from a BY to an RG defect(14.3%) as from an RG to a BY defect (15.5%).

Of the 71 persons who had NS defects at the timeof the acute attack, at 6 months 63.4% (45) improvedand became normal, 9.8% (7) continued to show NSdefects, 9.8% (7) developed selective BY defects, and16.9% (12) developed selective RG defects. Of the 168

TABLE 2. Color Defect Type at Time of Acute Attack and at 6 Months

Time of Test Group BY % (N) RG % (N) NS % (N)TotalNumber


AABC

40.8 (98)36.8 (35)34.9 (22)36.1 (57)

29.6 (71)42.1 (40)38.1 (24)40.5 (64)

29.6 (71)21.1 (20)27.0 (17)23.4 (37)

2409563

158

Group A = testable at both acute attack and at 6 months; group B = only testable at 6 months (not testable at acute attack); group C =all (group A + group B); BY = blue-yellow defect; RG = red-green defect; NS = nonselective defect.



TABLE 3. Changes in Color Vision Between Time of Acute Attack and at 6 Months

Color Vision atAcute Attack

N %(N)BY%(N)RG%(N)N S %(N)U T %(N)Total at 6

months

A' %(N)

100(30)

63.3(62)

54.9(39)

63.4(45)

54.8(92)

61.2(268)

BY %(N)

0

16.3(16)15.5

(11)9.8

(7)13.1

(22)

12.8(56)

Color Vision at 6 Months

RG %(N)

0

14.3(14)19.7(H)16.9(12)14.3

(24)

14.6(64)

NS %(N)

0

6.1(6)

9.8(7)

9.8(7)10.1(17)

8.4(37)

UT %(N)

0

0

0

0

7.7(13)

3(13)

Total atAcuteAttack

6.8(30)

22.4

16.2(71)

16.2(71)

38.3(168)

100%(438)

N = normal; BY = blue-yellow defect; RG = red-green defect; NS = nonselective defect; UT = untestable.

88

25

35 58

I. 85

25

35

FIGURE 2. Frequencies of major axes of the error patternsdetermined by Knoblauch's method encountered at base-line (A) and at 6 months (B) in group A, subjects who couldbe measured at both times. Axes falling within the darklyshaded zones are considered red-green; axes falling in thelightly shaded zones are considered blue-yellow.

persons in group B, at 6 months 54.8% (92) had anormal FM 100-hue test, 13.1% (22) had selective BYdefects, 14.3% (24) had selective RG defects, 10.1%(17) had NS defects, and 7.7% (13) remained untest-able.

The type of defect at baseline does not predictwhether color vision will be normal or abnormal at 6months, nor does it predict the type of defect that willbe present at 6 months. However, if color vision isinitially normal, it will remain normal.

Spatial VisionAll spatial vision measures (contrast sensitivity, visualacuity, foveal threshold, and mean deviation of thevisual fields) showed marked improvement betweenthe time of the acute attack and 6 months (Table 4).Overall (group C), median contrast sensitivity im-proved by 0.55 log unit, acuity by 0.6 log unit, visualfield (mean deviation) by more than 2 log units, andfoveal threshold by almost 3 log units. Even thosewhose vision was good enough to perform the test atbaseline (group A) showed considerable improve-ment in spatial vision at 6 months: acuity improvedby 0.32 log unit (from ~20/32 to 20/15), contrastsensitivity by 0.5 log unit, mean deviation by ~1.4log unit, and foveal threshold by 1.0 log unit. Notsurprisingly, the spatial vision of the vast majority ofthose in group B was too poor to measure at the timeof the acute attack. Group B showed marked improve-ment in spatial vision at 6 months. Nonetheless, acuity,contrast sensitivity, foveal threshold, and mean devia-tion of the visual field were all significantly worse at 6months in group B than in group A (VA: t<2.,aii<.rf) =4.32, P < 0.00001; CS: t = 5.04, P < 0.0001; FT: t =5.48, P < 0.00001; MD: t = 4.28, P < 0.00001).

Relation Between Frequency of Color VisionDefects and Spatial VisionThe frequency of abnormal FM 100-hue test resultswas related to performance on each of the spatial vi-



TABLE 4. Spatial Vision Medians at Time of Acute Attack and at 6 Months

Acute Attack 6 Months

Group Log CSVA

(Log MAR) MD(dB) Fovthd(dB) Log CS VA Log MAR M D (dB)Total

Fov thd (dB) Number

ABC

1.250.051.00

0.22<1.70

0.54

-15.7<-34.0

-26.0

27<0.0

7

1.751.551.55

-0.10-0.06-0.08

-1.67-2.50-1.97

373536

269169438

Log CS = log contrast sensitivity; VA = visual acuity in log MAR (minimum angle of resolution); MD = mean deviation in decibels onthe Humphrey 30-2 visual field; Fov thd = foveal threshold in decibels; group A = testable on the FM 100-hue at both acute attack andat 6 months; group B = only testable at 6 months (not testable at acute attack); group C = all (group A + group B); BY = blue-yellowdefect; RG = red-green defect; NS = nonselective defect.

sion measures. This was true both at the time of theacute attack and at 6 months for all subgroups. Ingeneral, the frequency of abnormal test results in-creased with decreasing acuity (Table 5), mean devia-tion (Table 6), and foveal threshold (Table 7) of thevisual field and contrast sensitivity (Table 8).

Table 5 shows performance on the FM 100-huetest at the two measurement times for the three groupsdefined by acuity. At the acute attack (when most per-sons have abnormal color vision or are untestable),65.8% of persons with normal acuity failed the test.Approximately 90% of persons with visual acuity betterthan 20/50 (but less than 20/20) failed the test at thistime. This frequency is similar to that for persons withpoor (worse than 20/50) acuity (88.2%).

At 6 months, most (77%) of those in group A hadacuity better than 20/20; only 27% of these peoplefailed the FM 100-hue test. Of those in group B, 59%had better than 20/20 acuity at 6 months; less than athird of these people failed the FM 100-hue test at 6months (29.3%). Thus, the failure rate for those with20/20 acuity at 6 months was the same for those withvision initially too poor to test and those whose spatialvision was relatively spared at the acute attack. Veryfew persons had acuity worse than 20/50 at 6 months;all 21 of them failed the FM 100-hue test. Acuity andcolor vision were thus fairly closely related at 6 months(visual acuity better than 20/20, only ~28% are abnor-mal; 20/20 to 20/50, ~58% are abnormal; worse than20/50, 100% are abnormal).

Table 6 shows the relation of mean deviation of

the visual field to FM 100-hue performance. At base-line, the percentage of persons failing the FM 100-hue test was similar for those who had normal or mod-erately reduced visual fields. However, nearly all thosewith severely reduced visual field performance failedthe FM 100-hue test initially. At the 6-month follow-up, performance on the FM 100-hue test was directlyrelated to visual field sensitivity. In all three groups,the percentage of subjects failing the FM 100-hue testincreased with the magnitude of the field loss. Theclose association is somewhat surprising, given thatcolor vision is a foveal task and the field mean devia-tion primarily involves peripheral defects. Less surpris-ing is the fact that the frequency of passing the FM100-hue test also increased with foveal threshold, bothat the time of the acute attack and at 6 months, forall groups (see Table 7).

Contrast sensitivity appears to be even morestrongly related to color vision than the other spatialmeasures (see Table 8). At both baseline and particu-larly at 6 months, most subjects with normal contrastsensitivity (>1.75) had normal FM 100-hue test re-sults. The percentage of subjects with abnormal per-formance on the FM 100-hue test increased with de-creasing contrast sensitivity. Everyone with log con-trast sensitivity less than 1.00 failed the FM 100-huetest.

Of course, the degree of correspondence amongmeasures depends on the criterion level for normaldefined for each measure. A more direct, criterion-free method for evaluating the relation between color

TABLE 5. Relation of FM 100-Hue Performance to Visual Acuity

Baseline

6 months

Group

CABC

>20/20Abnormal FM100-Hue % (N)

65.8 (41)27.0 (207)29.3 (99)27.8 (306)

20/20 > VA^ 20/50Abnormal FM 100-Hue % (N)

89.7 (146)57.9 (57)58.8 (51)58.4 (108)

<20/50Abnormal or NTFM 100-Hue % (N)

88.2 (251)100 (5)100 (16)100 (21)

VA = visual acuity; normal FM 100-hue = square root of total error < 10.5; group A = testable on the FM 100-hue at both acute attackand at 6 months; group B = only testable at 6 months (not testable at acute attack); group C = all (group A + group B).



TABLE 6. Relation of FM 100-Hue Performance to Mean Deviation of the Visual Field

Baseline

6 months

Group

CABC

>20/20Abnormal FM100-Hue % (N)

70.0 (10)27.2 (202)24.7 (97)26.4 (299)

-3.0 < MD^ -10.0Abnormal or NT FM100-Hue % (N)

63.0 (74)54.7 (53)66.0 (50)60.2 (103)

> -10 dbAbnormal or NTFM 100-Hue % (N)

98.2 (347)73.3 (15)95.2 (21)86.1 (36)

MD = mean deviation on the Humphrey visual field; normal FM 100-hue = square root of total error < 10.5; group A = testable atboth acute attack and at 6 months; group B = only testable at 6 months (not testable at acute attack); group C = all (group A + groupB).

vision and spatial vision variables is to determine thecorrelation between the FM 100-hue score and thespatial vision variables. Table 9 shows the correlationcoefficients at baseline. Each of the spatial vision mea-sures are significantly correlated with FM 100-hue per-formance at the time of the acute attack. At baseline,only subjects testable on spatial and color tests areincluded in the analyses. One would expect thestrength of the correlations to be greater if thosewhose vision was too poor to perform the FM 100-huetest had been included.

Correlation analyses show that contrast sensitivityis most strongly correlated with FM 100-hue perfor-mance (53% of variance in color score accounted forby contrast sensitivity). The strength of the correlationwith FM 100-hue performance was similar for acuityand foveal threshold (44% and 42% of the varianceaccounted for, respectively). Mean deviation was theleast well correlated with FM 100-hue performance;this is not surprising, because mean deviation is pri-marily a measure of peripheral vision function,whereas color vision is a foveal task.

Table 10 gives the correlation coefficients for thethree groups at 6 months. The correlation betweenall measures of spatial vision and FM 100-hue perfor-mance for those in group A was lower than at the timeof the acute attack. This is not surprising, given theimprovement on all measures over time and resultantrelative restriction of range of values. Nonetheless,contrast sensitivity continued to show the strongestcorrelation (35% of the variance in color score ac-counted for by contrast sensitivity). The total number

of subjects included in the analyses at 6 months was423, not 438: 13 from group B still could not performthe FM-100 hue test at 6 months, and two additionalpersons were missing one or more spatial vision mea-sures at 6 months.

Relation of Type of Color Vision Defect toSpatial VisionGiven the large improvement in spatial vision betweenbaseline and 6-month tests, it is reasonable to ask whetherthe shift in predominant color defect type from BY to RGbetween the initial and 6-month examination is related tothe improvement in spatial vision that occurs over thisperiod. To address this issue, the relation between colordefect type and spatial vision was determined at baselineand 6 months. A finding of better spatial vision amongsubjects with RG rather than BY defects would be consis-tent with an explanation of changes in spatial vision un-derlying the observed change in color defect type overtime from BY at baseline, when spatial vision is poor, toRG at 6 months, when spatial vision measures have gener-ally recovered.

Table 11 shows the mean of the spatial variablesfor each defect type. At baseline and 6 months, therewas no significant difference in any measure of spatialvision among those with RG, BY, or NS defects. Thisfinding is inconsistent with the improvement in spatialvision being responsible for the change from predomi-nantly BY to RG defects.

DISCUSSIONThe results of the ONTT5 support numerous earlierstudies showing that color vision is significantly im-

TABLE 7. Relation of FM 100-Hue Performance to Foveal Threshold

Time

Baseline

6 months

Group

CABC

>35Abnormal FM100-Hue % (N)

50.0 (32)25.2 (214)24.0 (104)24.8 (318)

35 > Fov thd > 28Abnormal or NTFM 100-Hue % (N)

85.6 (90)71.4 (49)69.8 (43)70.6 (92)

<28Abnormal or NTFM 100-Hue % (N)

99.6 (316)100 (7)100 (21)100 (28)

TotalNumber

438270168438

Fov thd = foveal threshold; normal FM 100-hue = square root of total error < 10.5; group A = testable at both acute attack and 6months; group B = only testable at 6 months (not testable at acute attack); group C = all (group A + group B).



TABLE 8. Relation of FM 100-Hue Performance to Contrast Sensitivity

Baseline

6 months

Group

CABC

LogCS> 1.75Abnormal FM100-Hue % (N)

30.0 (10)18.5 (146)12.8 (47)17.1 (193)

1.75 < LogCS^ 1.00Abnormal or NT FM100-Hue % (N)

89.0 (212)53.7 (121)53.6 (110)53.7 (231)

Log CS < 1.00Abnormal or NTFM 100-Hue % (N)

100 (216)100 (3)100 (11)100 (14)

TotalNumber

438270168238

Log CS = log contrast sensitivity measured with the Pelli-Robson chart; normal FM 100-hue = square root of total error < 10.5; group A= testable at both acute attack and at 6 months; group B = only testable at 6 months (not testable at acute attack); group C = all(group A + group B).

paired in the vast majority of optic neuritis patients atthe time of the acute attack and that residual colorvision defects persist even when spatial vision recovers(i.e., when 20/20 visual acuity is regained).

There is little consensus among previous studiesregarding the type of color defect produced by opticneuritis; BY, RG, and NS defects have been reported.The purposes of the analyses presented here were todetermine the sources of discrepancy in previous re-sults and to establish a more reliable description ofthe color vision loss in optic neuritis.

Most commonly used methods for determiningthe type of color defect use criterion zones definedon the basis of congenital color defects. Thus, patternsfor which most errors are accumulated in a definedprotan, deutan, or tritan zone are considered selec-tive; patterns with major error axes falling outside anyof these zone are considered NS, no matter how polar-ized the error pattern. There is little reason to expectthat disorders of the optic nerve would produce errorpatterns like those produced by loss or alteration ofa particular cone pigment (as occurs in congenitaldichromacy or anomalous trichromacy). For this rea-son, use of these classification schemes can producefalsely NS patterns. Therefore, we chose to use thequadrant analysis of Smith et al,31 in which highlypolarized patterns cannot be classified as NS on thebasis of axis orientation; there are no NS zones. Fur-thermore, we used a relatively lenient criterion forselectivity, reducing the required difference betweenRG and BY partial error scores required to classify atest result as selective. Nonetheless, at both the timeof the acute attack and at 6 months into recovery,many NS defects were observed. This suggests that

TABLE 9. Correlation of Color DefectSeverity With Spatial Vision at Acute Attack

VisualAcuity(log MAR)

LogContrastSensitivity

FovealThreshold(dB)

MeanDeviation(dB loss)

0.660.44

0.730.53

0.650.42

0.570.32

both color mechanisms are affected in most peopleat both measurement times and that the discrepanciesamong earlier studies are not due to scoring criteriaor sample bias, but rather reflect true inhomogeneityin this condition.

There was a nonsignificant tendency for BY de-fects to occur more often at the time of the acuteattack, whereas RG defects were more common at 6months. The change in color defect type does notappear to be related to the degree of spatial visionimpairment at the time of testing. Spatial vision im-proves markedly between the time of die acute attackand 6 months, suggesting that the shift in defect typewas related to the improved spatial vision; however, atneither measurement time was there an associationbetween any of the spatial vision measures (acuity,contrast sensitivity, foveal threshold, or mean devia-tion of the visual field) and color defect type. Therewas, however, a significant direct association betweenthe severity of the spatial vision defect and the likeli-hood of an abnormal FM 100-hue test result. Thesefindings suggest that the discrepancies among earlierstudies were not due to differences in the severity ofthe spatial vision loss between subject groups at thetime of testing, but may be related to when in thecourse of the disease patients were tested.

The type of color defect at the time of the acuteattack was not related to the likelihood of having nor-mal versus abnormal color vision at 6 months. All de-fect types at the time of the acute attack had similarprobabilities of becoming normal at 6 months.

However, there was a relation between the likeli-hood of a color defect at 6 months and treatmentgroup. For those whose color vision was abnormal atthe first visit or whose vision was so poor that colorvision could not be tested, there was a significantlyincreased likelihood of having normal color vision at6 months if given intravenous steroids compared toplacebo and oral steroids. There was no differencein the rate of improvement for those receiving oralsteroids over those given a placebo. This finding wasalso reported by the ONTT trial.5 There was no differ-ence between treatment groups in the relative fre-quencies of each defect type at 6 months.



TABLE 10. Correlation of Color Defect Severity With Spatial Vision at 6 Months

Group(N)

A (270)

B (315)

C (423)

rT2

rr2

rr2

Visual Acuity(log MAR)

0.470.220.240.060.370.14

Log ContrastSensitivity

0.590.350.330.110.480.23

FovealThreshold (dB)

0.570.320.280.080.450.20

Mean Deviation(dB loss)

0.470.220.340.120.420.18

Group A = testable at both acute attack and at 6 months; group B = only testable at 6 months (not testable at acute attack); group C =all (group A + group B).

The shift (not statistically significant) in the distri-bution of defect types from more BY at the time ofthe acute attack to more RG at 6 months does notappear to reflect a generally faster recovery for thosewith BY rather than RG defects. This conclusion issupported by the observation that the rate at whichsubjects shifted from BY to RG defects over 6 monthswas similar to the rate of those switching from RG toBY defects. Subjects with NS defects at. the time of theacute attack were about equally likely to have RG asBY defects at 6 months.

It has been suggested that the defect type in opticneuritis patients is related to the severity and type ofspatial defect and fixation location.32"34 We found noassociation between defect type and spatial vision. Onemay question whether this lack of difference betweengroups can be attributed to our relatively lenient crite-rion for selectivity, which results in mixed (but un-equal) defects being classified as selective. To addressthis issue, we reanalyzed the data using the strict crite-rion used by Smith et al31 (2 SD from normal), whichrequires much larger differences between BY and RGerror scores for classification of a defect as selective.Not surprisingly, this resulted in a much larger propor-tion of tests being classified as NS, both at the time

of the acute attack (84.6% versus 29.6% by the lenientcriterion) and at 6 months (88.4% versus 21.1% bythe lenient criterion; Table 12). By this strict criterion,most subjects had NS defects at the time of the acuteattack and at 6 months.

The pattern of results found using the strict crite-rion resembles that described using the more lenientcriterion. At baseline, selective defects were nearlyfour times more likely to be BY (n = 29) than RG (n= 8). In contrast, at 6 months, RG defects (n = 9)were more common than BY defects (n = 2) in groupA, those who were testable at both times. The changein the distribution of color defect type over time frommore BY to more RG is statistically significant (P =0.003). However, given that the number of subjectswith selective defects is small, these findings may bespurious. In fact, among the 63 people who could betested only at 6 months (group B), BY defects dennedby the strict criterion (n = 4) were about as likely asRG defects (n = 3).

There were no significant differences in acuity,contrast sensitivity, mean deviation, or foveal thresh-olds of the visual field between the defect types de-fined by the strict criterion (Table 13). Although sub-jects with RG defects appeared to have slightly worse

TABLE 11. Relation of Color Defect Type to Spatial Vision (Mean ± Standard Deviation)

Time ofTest Group

DefectType


Visual Acuity(Log MAR)

FovealThreshold

(dB)

MeanDeviation

(dB)

Acute

6 months

BYRGNSBYRGNSBYRGNSBYRGNS

1.06 ± 0.301.03 ± 0.390.98 ± 0.421.54 ± 0.231.43 ± 0.301.58 ± 0.211.69 ± 0.161.34 ± 0.351.39 ± 0.231.52 ± 0.211.39 ± 0.321.49 ± 0.24

0.33 ± 0.370.34 ± 0.360.39 ± 0.43

-0.01 ± 0.180.03 ± 0.24

-0.03 ± 0.140.03 ± 0.200.02 ± 0.210.02 ± 0.150.00 ± 0.190.02 ± 0.230.02 ± 0.15

22.0 ±21.4 ±19.6 ±34.5 ±33.1 ±34.8 ±33.1 ±32.2 ±33.5 ±34.0 ±32.8 ±32.8 ±

10.712.513.04.16.34.05.25.05.04.65.84.8

-16.8 ± 8.9-16.8 ± 9.1-19.0 ± 8.4-4.3 ± 5.9-4.2 ± 6.0-3.9 ± 4.3-4.9 ± 3.7-4.9 ± 4.3-5.9 ± 7.1-4.6 ± 5.1-4.4 ± 5.4-4.4 ± 5.9

BY = blue-yellow defect; RG = red-green defect; NS = nonselective defect; group A = testable at both acute attack and at 6 months;group B = only testable at 6 months (not testable at acute attack); group C = all (group A + group B).



TABLE 12. Color Defect Type at Timeof Acute Attack and at 6 Months:Strict Criterion

Time of Test


Group

AABC

BY%

12.12.16.33.8

(N)

(29)(2)(4)(6)

RG <

3.39.54.87.6

Vc (N)

(8)(9)(3)(12)

NS % (N)

84.6 20388.4 (84)88.9 (53)88.6 (137)

TotalNumber

2409563

158

BY = blue-yellow defect; RG = red-green defect; NS =nonselective defect; group A = testable at both acute attach andat 6 months; group B = only testable at 6 months (not testable atacute attack); group C = all (group A + group B).

spatial vision than those with BY defects, none of thesedifferences is statistically significant, as they are basedon small groups, particularly at 6 months. Marre andMarre32 have suggested that the pattern of color visionloss is related to the retinal area involved and tested;eccentric fixation caused by central visual deficits willresult in impaired RG color vision, with relativelyspared BY color vision, whereas preserved foveal fixa-tion is associated with BY defects due to the greatersusceptibility of the BY system to disease. Prior au-thors5'32 have reported such relations in small samples.The present study does not find strong evidence forsuch an association.

Defect type denned by the strict criterion did notpredict the likelihood of normal color vision at 6months (Table 14). Nineteen of 29 (65.5%) subjectswith highly selective BY defects and 3 of 8 (37.5%)subjects with selective RG defects at the time of theacute attack had normal color vision at 6 months.Interestingly, two subjects with initially highly selectiveBY defects converted to RG defects at 6 months—thatis, they lost their BY defects and acquired RG defects,

suggesting a change in the population of nerve fibersaffected over time.

Menage et al19 followed 30 optic neuritis patientsfor 6 months from the time of the initial acute attack.Color vision was assessed using the FM 100-hue test ateach visit (at presentation, 6 weeks, and 6 months).Most subjects with abnormal FM 100-hue test resultsshowed NS losses at all visits. Group averaging of dataobtained during the acute attack revealed an abnor-mality along the tritan axis; this group "BY defect"was absent at later visits. These results are in goodagreement with those of this larger study.

Conclusions

The results from this study provide no evidence tosupport Kollner's rule stating that RG defects are se-lectively associated with optic neuritis. Rather, the vari-ation among earlier studies, with some reporting pre-dominantly RG, BY, or NS color defects, reflects truevariation among optic neuritis patients. In most in-stances, both the RG and BY color systems are affected,with the degree of the impairment of the two-colorsystems varying both between subjects and within onepatient over time. The color defect type is not depen-dent on spatial vision at the time of die test, but itseems to shift somewhat from a higher proportion ofBY defects in the acute phase of the disease to rela-tively more RG defects at 6 months. Thus, one mustconsider the time of testing relative to onset of symp-toms when evaluating color vision findings in opticneuritis. It is ill advised to use color defect type as adiagnostic tool in optic neuritis.

Acknowledgments

Data were provided by the Optic Neuritis Treatment Trial.The authors thank Dr. Joel Pokorny for helpful discussions.

TABLE 13. Relation of Defect Type to Spatial Vision (Mean ± Standard Deviation): StrictCriterion

Time of Test GroupDefectType


Visual Acuity(Log MAR)

FovealThreshold

(dB)

MeanDeviation

(dB)

Acute attack

6 months

A

A

BYRGNSBYRGNSBYRGNSBYRGNS

1.09 ± 0.270.94 ± 0.531.03 ± 0.361.58 ± 0.001.30 ± 0.331.52 ± 0.351.47 ± 0.141.21 ± 0.321.39 ± 0.271.60 ± 0.161.28 ± 0.321.49 ± 0.27

0.34 ± 0.430.40 ± 0.360.35 ± 0.380.10 ± 0.140.04 ± 0.270.0 ± 0.190.01 ± 0.040.27 ± 0.330.03 ± 0.200.05 ± 0.100.08 ± 0.280.01 ± 0.20

19.0 ± 11.516.6 ± 12.721.6 ± 12.038.5 ± 2.129.9 ± 11.734.3 ± 3.932.3 ± 0.524.3 ± 17.732.7 ± 5.335.4 ± 3.529.1 ± 12.033.9 ± 4.3

16.621.0•17.4-0.09-6.41-3.98-7.4-4.4-5.2-3.7-6.1-4.3

± 8.6± 9.9± 8.8± 2.6± 8.7± 8.7± 5.0± 2.2± 2.2± 5.3± 7.9± 5.2

BY = blue-yellow defect; RG = red-green defect; NS = nonselective defect; group A = testable at both acute attack and at 6 months;group B = only testable at 6 months (not testable at acute attack); group C = all (group A + group B).



TABLE 14. Changes in Color Vision Between Baseline and 6 Months: Strict Criterion

Color Vision atAcute Attack

N %(N)BY%(N)RG%(N)NS%(N)UT%(N)Totals at 6

months

N%(N)

100(30)

65.5(19)37.5(3)

60.6(123)

54.8(92)61.0

(267)

BY %(N)

0

0

0

1.0(2)2.4(4)1.4

(6)

Color Vision at 6 Months

RG %(N)

0

6.9(2)

25.0(2)2.5(5)1.8(3)2.7

(12)

NS %(N)

0

27.6(8)

37.5(3)

35.5(72)33.3(56)31.7

(139)

UT %(N)

0

0

0

0.5(1)7.7

(13)3.2

(14)

Total atAcuteAttack

30

29

8

203

168

438

N = normal; BY = blue-yellow defect; RG = red-green defect; NS = nonselective defect; UT = untestable.

Key Words

color vision, Farnsworth-Munsell 100-hue test, optic neuri-tis, Optic Neuritis Treatment Trial, spatial vision

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