- Email: [email protected]
Motion Perception Thresholds In Areas of Glaucomatous Visual Field Loss
VisionRes., Vol.37,No.3, pp.355–364,1997 Copyright@ 1996ElsevierScienceLtd.All rightsreserved Printedin GreatBritain PII: S0042-6989(96)00136-8 0042-6989/97 $17.00+ 0.00
Pergamon
Motion Perception Thresholds In Areas of Glaucomatous Visual Field Loss CHARLES F. BOSWORTH,* PAMELA A. SAMPLE,*~ROBERT N. WEINREB* Received 24 October 1995; in revised form 13 March 1996
This study examined whether one can differentiate between areas of known visual field 10SSand areas of known relative field sparing in eyes with primary open angle glaucoma using motion coherence thresholds. Two visual field locations from patients with primary open angle glaucoma (n= 14), which differed significantly in sensitivity, were selected for presentation of a motion stimulus. In the area of visual field loss mean threshold was 17.4 ~ 4.1 dB (1.74 + 0.41 log units relative to the brightest stimulus). In the area of relative field sparing mean threshold was 27.0 + 3.6 dB (2.70 i 0.36 log units). Motion coherence thresholds were significantly poorer for the area of visual field loss compared to the area of relative field sparing (P <0.0032, two-tailed paired t-test). This result suggests that a perimetric type motion test should be evaluated for early detection of glaucoma. Copyright 01996 Elsevier Science Ltd Psychophysics
Motion perception
Gkaucoma
Perimetry
INTRODUCTION
Functional testing of the visual field in clinical practice may not indicateloss of sensitivityuntil late in the course of glaucoma.Automatedperimetry,the most widely used clinical test, may not detect glaucomatous visual field loss until there is a considerableloss of optic nerve fibers (Quigleyet al., 1989).Clearly a more sensitivefunctional test is desirable. Becausethere is evidencethat glaucomatousdamage is more apparent when isolating certain visual functions, this may be one way to create a more sensitivefunctional test. Tests which isolate one aspect of vision and which have shown differences between normal and glaucomatous eyes include short wavelength automated perimetry which measures short-wavelengthsensitivity(Sample & Weinreb, 1990, 1992;Sample et al., 1993, 1994;Johnson et al., 1993a,b), high pass resolution perimetry which measures visual resolution (Frisen, 1993), temporalmodulation perimetry which measures temporal processing (Tyler, 1981; Casson et al., 1993; Tyler et al., 1994), and pattern discrimination perimetry which measures form perception (Drum et al., 1987). The ability of these tests to detect glaucoma earlier supports the conclusion that glaucomatous damage is more apparent when isolating certain visual functions. By isolating one particular aspect of visual function to
prevent spared visual systems from compensating for those compromised by glaucoma, the diagnostic sensitivity of a visual function test should subsequently increase. Sensitivity might also be improved by testing eccentric locationswhere glaucomatousdamage is likely to occur in the earliest stages of the disease. A good diagnostictest for glaucoma,however, shouldnot only be highly sensitive, but must also be easy for patients and operators to use reliably. Thus, a successful test for the early detection of glaucoma should isolate one particular aspect of visual function, test eccentric locations, and should be easy to use reliably. One possible diagnostic technique, which can satisfy the above criteria for a successful glaucoma test, uses video displays to measure motion perception (Fitzke et al., 1987, 1989; Silverman et al., 1990; Bullimore et al., 1993; Watkins & Buckingham, 1991; Joffe et al., 1991; Trick et al., 1995;Johnsonet al., 1995;Scholl& Zrenner, 1995). Testing motion perception with random-dot kinematograms, one of the methods previously employed, reduces possible interactions with other visual systems such as form perception, and limits the observer’s ability to make displacement judgments or direction discriminations based upon positional or orientationalcues (Nakayama & Tyler, 1980). Evidence indicates that random dot kinematograms are processed primarily through the larger diameter magnocellular retinal ganglion cells (Shapley et al., 1981; Livingstone & Hubel, 1988; Schiller & Malpeli, 1987). Thus, two justifications for developing motion tests have been developed because of their ability to assess magnocellular function (see Discussion).
*Departmentof Ophthalmology,Universityof California, San Diego, CA 92093-0946,U.S.A. ~To whom all correspondence should be addressed [EmaiZ [email protected]]. 355
356
C. F. BOSWORTHet al.
TABLE 1. Visual field locations of the relatively spared and deficit test positions and the correspondingvisual field thresholds and motion thresholds for each patient Spared position Subjects 1 2 3 4 5 6 7 8 9 10 11 12* 13 14
Deficit position
Location
Visual function threshold (dB)
Motion threshold (% coherence)
Location
Visual function threshold (dB)
Motion threshold (% coherence)
– 12, –12 –18, +06 +06, –18 – 12, –06 +06, +12 – 18, –06 –06, –18 –06, –18 –06, –18 –13, –13 –12, +12 –06, –12 –06, –06 – 18, +20
28.7 28.5 37.0 20.8 29.6 26.5 25.0 27.0 24.5 25.2 27.0 25.0 24.7 28.0
30 10 50 30 70 30 30 40 40 30 60 30 50 30
– 12, +12 – 18, –06 +06, +18 –12, +06 +06, –12 –18, +06 –06, +18 –06, +18 –06, +18 –13, +13 – 12, –12 –06, +12 –06, +06 –18, –12
14.3 24.0 12.0 16.0 14.3 18.6 17.5 18.6 19.8 21.3 24.3 17.5 12.7 18.4
40 20 70 60 70 40 70 60 50 100 60 — 70 40
*Subjectexcluded from final data analysis for failing visibility verification.
Several studiesusing video displaysto measuremotion sensitivity have found foveal motion deficits in patients with either glaucoma (Fitzke et al., 1987, 1989; Silverman et al., 1990;Watkins & Buckingham, 1991;Joffe et al., 1991; Bullimore et al., 1993; Trick et al., 1995; Johnson et al., 1995; Scholl & Zrenner, 1995), ocular hypertension (Fitzke et al., 1987, 1989; Watkins & Buckingham, 1991; Trick et al., 1995; Johnson et al., 1995; Scholl & Zrenner, 1995), or retinitis pigmentosa (Turano & Wang, 1992).Silvermanand colleaguesusing a random-dot kinematogram (Silverman et al., 1990), found a 70% elevation of foveal motion coherence thresholdsin primary open angle glaucomapatients and a 44% elevation in ocular hypertensiveswhen compared to age-matched normal controls. Trick and colleagues (Trick et al., 1995), found significant elevations in glaucoma patients’ motion thresholds for both low (4.2 deg/see) and high (12.5 deg/see) velocity randomdot kinematograms. Bullimore and colleagues (Bullimore et al., 1993),found that 10 of 15 glaucomapatients had Dmin values outside the normal range, but that coherence thresholds and DM,Xdid not discriminate between normals and patients. They also noted that patients suspected of having glaucoma were not significantly different from normal controls on any of their dependent measures: Dmi,, D~~~, or coherence thresholds. The aim of the current study was to determine if a random-dot kinematogram can differentiate between areas of known field loss and known relativefield sparing in the same eye with primary open angle glaucomausing smaller eccentrically placed targets. If the test can differentiate between these locations, it could suggest that a perimetric type motion test may be worth evaluating for early detection of glaucomatousdamage.
METHODS
Subjects Subjects for this study (n = 14) were primary open angle glaucoma patients as determined by the following criteria: 1. intraocular pressures >24 mm Hg on at least two separate occasions determined by Goldmann applanation tonometry; 2. open angleswith abnormaloptic discsbased on cup/ disc asymmetry between the two eyes of 0.2 or more, localized rim defects, disc hemorrhages, or vertical cup/disc >0.6 with excavation determined by indirect ophthalmoscopythrough dilated pupils; and 3. previously documented characteristic standard visual field loss determined by program 24-2 using a Humphrey Visual Field Analyzer 640, with corrected pattern standard deviations outside 95$70 confidencelimits or glaucoma hemifieldtest results outside the 99.5!Z0confidencelimits. For this study, reliability indices were set at 25% or less for fixation losses, false positive errors, and false negative errors. Each subject had a location of relative sparing corresponding to the location of their deficit in the quadrant either superior or inferior to it (Table 1). In this design, each patient served as his/her own control. Their mean age (~ SD) was 70.6 ~ 9.1 yr. This study was approved by the Human Subjects Committee of the University of California, San Diego and was undertaken with the understandingand consent of each subject. Random-dot motion display Our display is a modified version of the foveally centered, 60x 60 deg display employed by Silverman et al. (1990).The motion stimuluswas produced on a Barco
MOTION PERCEPTIONIN GLAUCOMA
357
358
C. F. BOSWORTHet al.
TABLE 2. Normal subjects’ (n= 4) average threshold in percent coherence for the different step sizes tested (1, 2, 3, 4, 5, and 6 pixels) at the fovea, 15 deg eccentricity, 30 deg eccentricity, and across the three field locations Location of presentation Fovea Fifteen Thirty Average
1 pixel 15.0 * 22.5 k 42.5 ~ 26.6 +
10.0 5.0 9.6 14.4
2 pixels 22.5 ~ 25.0 k 25.0 t 22.5 ~
9.6 5.8 10.0 13.2
3 pixels 27’.5~ 15.0 ~ 25.0 t 22.5 k
CCID monitor with 1024x 768 lines of resolution and a refresh rate of 75 Hz. Each pixel subtended 0.31 mm (7.35 min arc at the viewing distance of 16.5 cm). The monitor was driven by a Power PC 8100 Macintosh computer using a Raster Ops 24xli video card. Seven frames were shown in rapid successionto create the motion stimulus.Within each of these frames, 20 dots were randomly placed within a circular test region of 7.3 deg of visual angle. These dots moved at a constant velocity of 8.2 degJsec in random directions to create “noise”. A percentage of the dots were then displaced together in one of four cardinal directions(right, left, up, down) to create the coherent motion signal which the patients were to detect. The randomly chosen signal dots remained the same for all seven frames of the display and had the same spatial displacementas the noise. While it has been reported that this could create streaming for signal dots positioned on a flickering noise which is randomly positioned, each frame (Falzett & Lappin, 1983), Watamaniuk et al. (1995) demonstrated that a signal of this nature embedded in a surroundof vectored motion is not significantlyinfluencedby nonmotioncues (Watamaniuket al., 1995).We chose to defineour signal in this way because it can allow detection of single dot paths (Watamaniuk et al., 1995). This increased the number of step changes available, while allowing for a lower spatial frequency which would favor the magnocellular pathway. The signal ranged in strength from 10 to 1009%coherence (Fig. 1). Threshold was the percent coherence a subject needed to correctly identify the direction of motion at least 62.5% of the time. Percent coherence was selected as our dependent measure because Silverman and colleagues reported a 44% elevation in the motion coherence thresholds of ocular hypertensive. Because early glaucoma is usually characterized by localized, peripheral visual field loss, we designed the stimulusto stimulatethe short-rangemotion pathways at different eccentric locations. We selected stimulus parameters based on findings from a variety of laboratories (Braddick, 1974; McKee & Nakayama, 1984; Williams & Sekuler, 1984; Baker & Braddick, 1985a,b; Bischof & Groner, 1985; Van de Grind & Keonderink, 1987; Derrington & Goddard, 1989; Snowden & Braddick, 1989, 1991; Satoshi & Cavanagh, 1990; Nawroot & Sekuler, 1990; Cleary &Braddick, 1990), and we verified the effectiveness with these parameters for stimuli placed within the central 30 deg visual field. Therefore, the parameters of the current stimulus were
12.6 5.8 10.0 13.2
4 pixels 17.5 t 20.0 i 25.0 i 20.8 +
5.0 0.0 5.8 9.8
5 pixels 20.0 ~ 25.5 + 35.5 ~ 27.0 +
8.2 19.1 12.9 13.8
6 pixels 30.0 + 32.5 f 27.5 k 30.0 ~
20.0 18.9 17.1 18.3
within known ranges for testing the motion systemwhile still allowing glaucoma patients with impaired vision to perceive the display. The stimulus parameters were as follows. Stimulus contrast. The area surrounding the circular test region was a uniform gray background rather than one filled with random noise, because the latter may test regions larger than those definedby the target (Nawroot & Sekuler, 1990). The uniform gray background had a luminance of 26.43 cd/m2. The dot luminance was 59.23 cd/m2 giving a contrast of 38.3%. This contrast is below an upper cutoff of 50%, above which visual persistence can impair motion perception in a seven frame display (Cleary & Braddick, 1990; Derrington & Goddard, 1989), and it is above a contrast level of 30%, below which motion perception exhibits contrast dependence (Van De Grind& Keonderink, 1987). Region size. We chose a region size of 7.3 deg because it can cover four points on program 24-2 and because field size must be >2.5 deg in diameter for our displacement value of 29.4 min arc (Baker & Braddick, 1985a). A foveal field size of 2.5 deg or larger includes ~max values > zg.o min arc due to the recruitment of eccentric motion detectors (Baker & Braddick, 1985a). D max is the maximum displacementover which coherent motion can be perceived. Number of frames. A stimulus comprising seven frames creates six dot displacements, which is within the optimumrange of four to.six displacements(Snowden & Braddick, 1989). Frame duration. The optimum exposure time per frame is between 10 and 80 msec (Baker & Braddick, 1985b). We chose an exposure time of 60 msec. Inter-stimulus-interval(ISI). An 1S1of zero prevents motion reversal (reporting movement in the correct plane, but opposite direction) (Satoshi & Cavanagh, 1990). Dot size. A dot size of 29.4 min (4 pixels) was large enough for patients to accurately see the display in the peripheral visual field. Dot density. Dot density was set at 0.83 dots/deg to reduce the likelihood of mismatching (Williams & Sekuler, 1984). The lower probability of mismatching in the current stimulus allowed us to use larger dot sizes and displacements to facilitate testing patients with reduced vision in the peripheral field. This density gave 20 dots per stimulus. Dot displacement size (pilot study). To set the parameter of dot displacement, pilot work was needed.
359
MOTION PERCEPTIONIN GLAUCOMA
TABLE3. The parameters involvedin motiondisplays showingthe optimumranges reported in the literature or determinedby pilot studies, and the actual settings chosen for this motion perimetry test Parameter Dot displacement Contrast Frame duration Number of steps 1S1 Dot density Dot size and number Region size Viewing distance Coherence range
Optimumrange
Settings
Pilot study 30% < x < 50% 10 msec < x <80 msec 42.5 deg Refraction available Independentvariable
29.4 min arc 38.3% 60 msec Six steps =Zero 0.83 dots/deg 29.4 min arc and 20 dots 7.3 deg 16.5cm G1OO%Coherence
Braddick originally proposed that D~aXwas 15 min arc for short-range apparent motion at the fovea (Braddick, 1974). Other studies later showed higher D~,X values with increasingeccentricity(Baker & Braddick, 1985a,b; McKee & Nakayama, 1984). To determine the optimal dot displacement for the perception of coherent motion within the central 30 deg of visual field,we presented the target foveally and at two retinal locations along the superiorvertical meridian (15 and 30 deg eccentricity)to subjects with normal eyes (n= 4; mean age 29.0 ~ 8.4 yr). These subjects had a normal ophthalmological exam with intraocular pressures <21 mm Hg, normal optic discs, and no visual field loss. The motion display for this pilot study was identicalto the one used for the actual testing of glaucoma patients except for dot displacementsize (1, 2, 3, 4, 5, or 6 pixels) and region position(fovea, 15 deg, or 30 deg)which were independentvariables.The results indicatedthat a 4 pixel displacement generated the lowest average threshold across the tested retinal locations. A displacement of 4 pixels (29.4 min arc) was therefore chosen (Table 2). Avoiding grating cues at high coherence levels. Visual persistence can affect motion perception by causing alpha-stripes (Cleary & Braddick, 1990; Snowden & Braddick, 1991; Bischof & Groner, 1985).Alpha-stripes (Snowden & Braddick, 1991) are illusions which occur when a dot travels repeatedly over the same path generating the perception of stripes. To avoid alphastripes, the dots were displaced perpendicularly to their direction of movement as they wrapped around the screen. In addition, a larger dot displacement and a smaller display size helped break down this alphastriping effect because a large number of dots wrap around during each stimuluspresentation.For a summary of the current testing parameters and the optimal ranges suggested in the experimentalliterature see Table 3.
locating a group of four points on the Humphrey standard visual field with at least two points outside the 5% confidencelimits on the pattern deviation plot. This was the locationof visual field loss where the motion stimulus was presented. This location was then required to have a matching group of four points in the quadrant either superior or inferior to it, at the same eccentric location, with no abnormalpoints on the corrected pattern standard deviation.This was the location of relative sparingwhere the motion stimulus was presented (Table 1 and Fig. 2). Four subjects had an inferior field defect. Eight subjects had a superiorfield defect. See Table 1 for a listing of the field locationsof the spared and deficittest positions and the corresponding visual field thresholds and motion thresholds for each patient. The order of presentation (area of visual field loss vs area of relative sparing) was randomized across subjects to preclude learning and fatigue effects.
Testprocedures The subject sat in a darkened room with a patch placed over the nontest eye. The subject’s chin rested in a chin rest while he/she viewed the screen through proper refraction for the test distance of 16.5 cm. The subject focusedon a black fixation“x” in the center of the display and adapted for 2 min to the background illumination. During this time, a camera was focused on the test eye so that fixationcould be monitored by the test administrator on a separate video display system. Trials where fixation was lost were aborted and retested later in the program. The testing procedure was then explained to the subject. The sessionbegan with a foveal practice test consisting of 12 presentationsall at 100% coherence. The patient’s performance on these trials was observed by the test administrator to make sure that the patient properly understoodthe task. After completingthe foveal practice, anotherpractice stimuluswith two coherencelevels (40% Test locations and 70’%)was randomly presented in the area of relative Each subject had a location of relative sparing sparing and the area of visual field loss at 2 sec intervals. corresponding to the location of their deficit in the This practice ended after 48 responseswith one of three quadrant either superior or inferior to it. The two test results which determined the make-up of the actual locations on opposite sides of the horizontal meridian motion test: were matched for eccentricity: one an area of relative visual field sparing and the other an area of visual field 1. If the patients got > 62.5% of their direction loss. The testing locations were determined by first discriminationresponsescorrect at 40% coherence,
360
C. F. BOSWORTHet al.
. . .,
.0 . . *6 .,
. . * *
. . * ●
* . . . ●. ●.
,.:
●.
.
.,
.
●*
.* ,,
. . .,
“:.
* *● .. *● ● . .1: . . . . ., . . *, ,. ““ . ●.,* ●“●. A. . . . . . ●*.● ●. * “* ● * ● * ● “ ,$: .* *,,● ,.**** ● * ., ,. ●
“ V
4.
.
. . ,.
D. . .
.
●
*
.,
.,
0 ● ● * O* , . ● O ,. ,. ., ,.
0 ● ●● ●● t ~ . ●
●. ●. . . ●* . . 8. * . ● , . . , ● , . 8* . . , . . . ., ,. . . ,. ● . .* ., *. . . ,, ,, ,. ., ,, .**. .,.. ., ., ..;. ●● ✎o ✌;
.. ,
✎✌ ●4 . .
● ✎✎ ✌✌ ✌✎ . . ,. . . , .
● ✎ ✎ ✎ ✌✎ ✌✎ ✎ ✎ 0 .
~
✌ ✌ ✌✌ . . . . ✎ ✎ .
.
s.
.
.-
*
●* ● , ,. . ● ,.
SC *4 .,
.0
●. ●0
.6
.
●● * .
●
c ,. ,, ,, *,
.. .. ,, ..
., ,, ., ,.
.. ,. .* ..
.
●O
. . .. . .. , ● ,,: ,, .* ,. ,** ● , .-.
●●
., * ,.
●✎ ✃ ✎ ✎ **( ✎✎ . . ., . . ., . . 1. . .
0::. ,. :: .,. . ,,.,,. ,.,,,. ., ,:, . ,. ,., . . , . . ..,,.,.. ●
*.:
.4-
9*. ,. ., ,, ,. . . . .
., . . ,. , . ., ,. ,. ,. ,, , . . ,, . . ,. . . ., . . ,. ,. . , ., . . . . .* * :: ,, ., . . ., . ● , . , . ● . .
. ● ,. , . ,. ,. .*
., 0, ,, $s , , .* . . ,, . . ., . . .* ,, . . ., ., . ● .0 ,. . .
., ,. ,. .* o.
● ●
*
,. ,. *. ,, . . ,. ., ,. . . ,. ●
.
●
o .,: . , ,,:,,:
,,: ,
*
●●
.
.
.
● ☛✍ ●☛ ✎✎
94 .. ,,:
. .
:::: ., .~:o*: ,. ,. ..:,,*.** ,. ,,:
.
.
●
,.;
.
--
*
.. ,9 ,. .*: ,.
. . .
. . . . ., .
,
**** ● . ● . ,, , . ,, *. , . . ●* , , ● *● . . . . . . . , . . . . ** ●. , , . . ,. , ., ,. ,. . ,. , . . ● * ,. . ● . ,, ●. . . . . . ,. ,. ., ,. ,. . ,. ,, ,, ., ,, ● * , . . . . . .0 ✌ ● ✎ ☛✎ 0 . , , ● ● ● ● ● .0 . ● ● J ,. .* ☛ ✎✌ ✎✌ ● ✎ ✎✌ ✎✌ ✌✌ ● O 0 .,, ,, ,. . . ● . ● . 4 ,.: ..:,,: .: ,.: . . ● O . ● . . . ●* ● . ● , ●
9, *. . . . . ● ☛ ✎ ✎ ✎ ✎ ✌✎ . . ●. ● . ,. ,, ., ., ., ... 0.
.4 ,, .,
.
.
.
,
. .
.
. . : : :: ..: .*: o
● ☛ ✎✎ ✎ ✎ ✎☛ ✌✎ ✎✌ ✌ ✎ ✎✎ ✎ ✎ ✎✌ ✎ ✎ ✎✌
✎
,:
:
● ●
i
.,
.
,
:
:
.*:
.,.
,
.
/,
. .
‘a
U3
UY
m
e=
m.,
● ✎✌
.,
. . ,, .0
,. ● .,1: . ..~., .*:
1 .: ,.: , . .
. . ., . .* ● .,
,. . . ● . .0,
,
●
●
●
✚✚
.$:;;::: ,..,.,,. o, * ,. ......,, . . ... * . . ., . .
●
☛
●
1
☛
✎ ✌ ✎ ▼ ✎✎ ● ✎ ., . . ., ., ● .
✎✌ ✎✎ ● ✎ ✎✎ ., ., . . , , ● .
.
.
☛☛☛ ✎
0.0
●
✎
●
✎
.*
.*,
●4
●
,, .a ., e, ,, . . ,. . . . . ,, . . ,. ,. c , .; ., ,, , D . . ,, ., ,,
m
02
UY
●
. .
~
,,.0
m
Cn
●✎ ✌✌ ✌✎ ✌✎ . s, . . ,, . .
,,,..*, .:,. , Iill? ..O
. .
.,
0
.
☛✌ ● ✌ ●✎ ● ✎ $$.
llcl 1+
● *
..,.
*
,0 . .
., . .
.
✎
.
✎● ✎● ✎ ✎ ✎✎ . . . . ., .*
-}.
MOTIONPERCEPTIONIN GLAUCOMA
361
Foveal Practice at 100940
~
40 0/0 Coherence Practice
\ 10YO-60Y0 Coherence
f
~
~
&
~40y0100yo~ Coherence
r
END TESTING
J
I
Coherence
I
& $ \ +’ b
Stimulus is Considered Unseen :C ~
ENDTESTING
Threshold Reached
................... ++ Threshold Not Reached FIGURE3. A flow chart showing how the program determines which coherence range to test for each subject, given hisiher response at each stage of the program. At each stage the subject must get 62.59Zof their direction discrimination responses correct to reach threshold. Dashed arrows leading from a given stage of the program indicate what happens if threshold is not reached, solid arrows indicate what happensif performanceis equal to or better than threshold.This procedurewas followedby the program for each of the two independentlocations (see text for complete description).
they were given a motiontest which had a coherence coherence, they were given a visibility verification range of 10–60%.If, however,a thresholdvalue was test. If the patient could correctly identify 70% of unobtainable in this range, stimuli from 7O–1OOYO the verificationtargets, the motion test was set to a coherence were added until threshold was detercoherence range of 40–100% (Fig. 3). mined. The visibility verify test was randomly presented in 2. If the patients reached threshold at 70% coherence, each of the two test locationsfor 60.0 msec to determine but did not at the 40% coherence level, they were if the patient could see a static version of the stimulus. given a motion test which had a coherence range of The time between presentations was randomly varied 40–100%.If a sub-thresholdvalue was unobtainable from 2000 to 5000 msec, and the patient responded by in this range, stimuli at 10-30?7 were added. pressing any key on the computerkeyboard.If the subject 3. If the patients got <62.5% of their direction discrimination responses correct even at 70% did not respond within 500 msec of stimulus offset, the
362
—
C. F. BOSWORTHet al.
120
1
100-r
80E ~ 5 0 $
4
/ ●*
60-
Threshold (62.5 % Correct)
..-4 b .s * .4,
++
● ’
b+’ 20.
I
10%
2070
I 30%
i
I
I
doyo
50’?-”.
60%’.
1
7f)%
1
80Y.
I
90%
I
1
100%
YOCoherence FIGURE4. This graph showsmean percent correct (with SE)for each coherencelevel in the area of deficit (dashedcurve) vs the area of sparing (solid curve) across subjects (n = 13). The solid horizontal line denotes the threshold criterion of 62.5%.
stimuluswas considered unseen. Testing proceeded only if the patient correctly identified70% of the static targets in both locations. One patient failed the visibility test in the deficit location and was excluded from the data analysis. For all testing, the subject reported which direction (left, right, up, down) he/she thought the dots were moving in a four alternativeforced-choiceparadigm.The test administratorpressed an arrow key correspondingto the direction indicated by the subject. The patient could respond at any time during the stimuluspresentationor at the end of the presentation. The program gave a 2 sec delay before presenting the next stimulus. Subjectswere informed that they could pause and rest at any time during the test. Because the method of constant stimuli was used the whole procedure lasted ca 45 min and only one eye was tested for each subject.
area of relative field sparing it was 38.6Y0coherence + 15.1% (Table 1 and Fig. 4). We did not find evidence for motion reversal. Reversed responses never exceeded chance (25’%0) at either location. DISCUSSION
The sensitivityof a motion test to diagnose glaucoma may be attributed to its isolation of one particular aspect of visual processing, the motion system. This prevents sparing in other visual systems from compensating for disease related damage (Silverman et al., 1990; Bullimore et al., 1993; Joffe et al., 1991). There are two approaches which argue the merits of testing motion perception because of its isolation of the motion system. The first concludes, from reports of selective damage to larger optic nerve fibers (Quigley et al., 1987), that glaucoma must selectively damage the magnocellularpathway because its cells are, on average, RESULTS of the largest diameter. However, as Johnson (1994) Mean (t SD) visual field threshold for the area of points out, these histological results, upon which this visual field loss was 17.4 dB~ 4.1 dB or 1.741 log units conclusion has been made, show an “overall amount of relative to the maximum brightness OdB (OdB = loss present for all optic nerve fibers irrespective of their 10000 asb) and for the area of relative sparing was diameter”.This leads to a secondjustificationfor motion 27.0 dB~3.6 dB or 2.70 log units. Motion coherence testing. Because all visual functions may be comprothresholds for these two locations were significantly mised by glaucoma, some functions may be comprodifferent, t(lz)= 3.67, PsO.0032, two-tailed paired. The mised more than others depending on the individual. mean motion threshold~ SD acrosssubjectsin the area of Thus, a battery of tests which isolate different visual visual field loss was 57.7’%coherence + 20.0%. In the functionsmay be needed for early detection of glaucoma
MOTION PERCEPTIONIN GLAUCOMA
across patients. Regardless of which theory is correct, they do provide justification for continued investigation into the effects of glaucoma on motion perception. For motion perimetry to become a successful diagnostic tool for glaucoma detection, it must be able to reliably differentiate between normal and glaucomatous eyes. However, considerableoverlap between glaucoma patients and normal controls has been found in motion thresholds (Bullimore et al., 1993). This could be the result of using relatively large, foveally fixated fields of random dots which might allow both normal and pathogenic regions of the visual field to contribute to glaucomapatients’ motion percept. Joffe et al., in a 1991 ARVO abstract, used a small 3 deg display size at multiple retinal locations and found that glaucoma patients had specificlocations of marked sensitivityloss (Joffeet al., 1991).To maximizethe sensitivityof motion threshold perimetry, it may be necessary to use smaller display regions. The stimulus used in this study was designed to function at discrete retinal locations across the central 30 deg of the visual field. Longitudinalstudy of a large number of primary open angle glaucoma, normal, and suspect eyes, and testing multiple retinal locations using a staircase procedure to shorten test time are necessary before the diagnostic and clinical utility of this test can be determined. Our results indicate that this motion test successfully differentiated between areas of known visual field loss and locationsof a known relative sparingin patientswith glaucoma.The resultssuggestthat the ability of a motion display to test discrete retinal locations across the visual field may be importantfor detectingearly motion deficits in glaucoma patients. REFERENCES Baker, L.C. & Braddick,O. J. (1985a).Eccentricity-dependentscaling of the limits for short-range apparent motion perception. Vision Research, 25, 803–812.
Baker, L. C. & Braddick, O. J. (1985b). Temporal properties of the short range process in apparent motion.Perception, 14, 181–192. Bischof, W. F. & Groner, M. (1985). Beyond the displacement limit: an analysis of short-range processes in apparent motion. Vision Research, 25, 839–847.
Braddick, O. J. (1974). A short-range process in apparent motion. VisionResearch, 14, 519–527. Bullimore, M. A., Wood, J. M. & Swenson, K. (1993). Motion perception in glaucoma. Investigative Ophthalmology and Visual Science, 34, 3526-3533.
Casson, E. J., Johnson, C. A. & Shapiro, L. R. (1993). Longitudinal comparison of temporal-modulationperimetry with white-on-white and blue-on-yellow perimetry in ocular hypertension and early glaucoma. Journal of the Optical Socie~ of America, 10, 1792– 1806.
Cleary, R. & Braddick, O. J. (1990). Masking of low frequency information in short-range apparent motion. Vision Research, 30, 317-327.
Derrington, M. A. & Goddard, A. P. (1989). Failure of motion discrimination at high contrasts: evidence for saturation. Vision Research, 29, 1767–1776.
Drum, B., Breton, M. & Massof, R. (1987). Pattern discrimination perimetry: a new concept in visual field testing. Documents in Ophthalmology, 49, 433440.
Falzett, M. & Lappin, J. S. (1983).Detection on spatial forms in space and time. Vision Research, 23, 181–189.
363
Fitzke, F. W., Poinoosawmy,D., Ernst, W. & Hitchings, R. A. (1987). Peripheraldisplacementthresholdsin normals, ocular hypertensive and glaucoma. In Greve E. L. & Heijl A. (Eds), Seventh International Visual Field Symposium (pp. 447452). Dordrecht: Martinus Nijhoff. Fitzke, F. W., Poinoosawmy,D., Nagasubramanian,S. & Hitchings, R. A. (1989). Peripheral displacement thresholds in glaucoma and ocular hypertension.In Heijl A. (Ed.), Perimetric update (pp.399– 405). Amsterdam: Kugler and Ghedini Publications. Frisen, L. (1993). High-pass resolution perimetry: a clinical review. Documents in Ophthalmology, 83, 1-25.
Joffe, K. M., Raymond,J. E. & Crichton,A. (1991).Motionperimetry in glaucoma. ARVO Abstracts. Investigative Ophthalmology and Visual Science, 32 (suppl.), 1103. Johnson, C. A. (1994). Selective versus nonselective losses in glaucoma.Journal of Glaucoma, 3 (suppl. 1), s32-s44. Johnson, C. A., Adams, A. J., Casson, E. J. & Brandt, J. D. (1993a). Blue-on-yellowperimetry can predict the development of glaucomatous visual field loss. Archives in Ophthalmology, 111, 645–650. Johnson, C. A., Adams, A. J., Casson, E. J. & Brandt, J. D. (1993b). Progression of early glaucomatous visual field loss for blue-onyellow color perimetry and standard white-on-white automated perimetry. Archives in Ophthalmology, 111, 651-656. Johnson, C. A., Marshall, D. & Eng, K. M. (1995). Displacement threshold perimetry in glaucoma using a Macintosh computer system and a 21 inch monitor. In Heijl, A. (Ed.), Perimetric update (Pp. 103-110). Amsterdam: Kugler and Ghedini Publications. Livingstone,M. S. & Hubel, D. H. (1988).Segregationof form, color, movement, and depth: anatomy, physiology, and perception. Science, 240, 74&749.
McKee, S. P. & Nakayama, K. (1984). The detection of motion in the peripheral visual field. Vision Research, 24, 25–32. Nakayama, K. & Tyler, C. W. (1980). Psychophysical isolation of movement sensitivity by removal of familiar position cues. Vision Research, 21, 427433.
Nawroot,M. & Sekuler,R. (1990).Assimilationand contrast in motion perception: explorations in cooperativity. Vision Research, 30, 1439-1451.
Quigley, H. A., Dunkelberger,G. R. & Green, W. R. (1989). Retinal ganglioncell atrophycorrelated with automatedperimetry in human eyes with glaucoma.American Journal of Ophthalmolo~, 107, 453. Quigley,H. A., Sanchez,R. M., Dunkelberger,G. R., L’Hernault,N. L. & Babinski, T. A. (1987). Chronic glaucoma selectively damages large optic nerve fibers. Investigative Ophthalmology and Visual Science, 28, 913–920.
Sample,P. A., Madrid, M. E. & Weinreb, R. N. (1994).Evidencefor a variety of functional defects in glaucoma-suspect eyes. Glaucoma, 3, S5-S17.
Sample,P. A., Taylor,J. D.N., Martinez, G., Lusky,M. & Weinreb, R. N. (1993).Short-wavelengthcolor visual fieldsin glaucomasuspects at risk. American Journal of Ophthalmology, 115, 225–233. Sample, P. A. & Weinreb, R. N. (1990). Color perimetry for assessment of primary open-angleglaucoma.Investigative Ophthalmology and Visual Science, 31, 1869–1875.
Sample, P. A. & Weinreb, R. N. (1992). Progressivecolor visual field loss in eyes with primary open angle glaucoma. Investigative Ophthalmology and Visual Science, 33, 2068–2071.
Satoshi, S. & Cavanagh, P. (1990). Isi produces reverse apparent motion. Vision Research, 30, 757–768. Schiller, P. H. & Malpeli, J. G. (1987).Functionalspecificityof lateral geniculate nucleus laminae of the rhesus monkey. Journal of Neurophysiology, 41, ‘78%797.
Scholl, H. P. N. & Zrenner, E. (1995). Motion thresholds of colored stimuli of different luminance contrasts are increased in ocular hypertension and early primary-open-angle-glaucoma (POAG). Color Vision Deficiencies, 13, 73-85.
Shapley, R. M., Kaplan, E. & Soodak, R. (1981). Spatial summation and contrast sensitivity of X and Y cells in the lateral geniculate nucleus of the macaque. Nature, 292, 543–545. Silverman, S. E., Trick, G. L. & Harr, W. M. Jr. (1990). Motion perception is abnormal in primary open-angleglaucoma and ocular
364
C. F. BOSWORTHet al.
hypertension. Investigative Ophthalmology and Visual Science, 31, 722–729.
Snowden,R. J. & Braddick, O. J. (1989).The combinationof motion signals over time. Vision Research, 29, 1621–1630. Snowden,R. J. & Braddick,O. J. (1991).The temporal integrationand resolution of velocity signals. Vision Research, 31, 907–914. Trick, G. L., Steinman, B. S. & Amyot, M. (1995). Motionperception deficits in glaucomatous optic neuropathy. Vision Research, 35, 2225–2233.
Turano, K. & Wang, X. (1992). Motion thresholds in retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 33,
motion in moving random-dotpatterns. Optical S“ociey of America A. Optics and Imagescience, 4, 1643-1642. Watamaniuk, S. N. J., McKee, S. P. & Grzywacz, N. M. (1995). Detecting a trajectory embedded in random-directionmotion noise. VisionResearch, 35, 65–77. Watkins, R. & Buckingham,T. (1991).Motionperception hyperacuity is abnormal in primary open-angle glaucoma and ocular hypertension. ARVO Abstracts. Investigative Ophthalmology and Visual Science, 32 (suppl.), 1103. Williams, D. W. & Sekuler, R. (1984). Coherent global motion precepts from stochastic local motions. Vision Research, 24, 55–62.
2411–2422.
Tyler, C. W. (1981).Specificdeficits of flicker sensitivity in glaucoma and ocular hypertension. Investigative Ophthalmology and Visual Science, 20, 204-212.
Tyler, C. W., Hardage, L. & Stamper, R. L. (1994). The temporal visiogram in ocular hypertension and its progression to glaucoma. Glaucoma, 3, S65–S72. Van de Grind, W. A., Keonderink,J. J. & Van Doom, A. J. (1987). Influenceof contrast on foveal and peripheral detection of coherent
Acknowledgements—The authors wish to thank Scott Hancher, Department of Ophthalmology, UCSD, for developing the motion program used in this study. This study was supportedby National Eye Institute Grant EY08208(Dr Sample).
Pergamon
Motion Perception Thresholds In Areas of Glaucomatous Visual Field Loss CHARLES F. BOSWORTH,* PAMELA A. SAMPLE,*~ROBERT N. WEINREB* Received 24 October 1995; in revised form 13 March 1996
This study examined whether one can differentiate between areas of known visual field 10SSand areas of known relative field sparing in eyes with primary open angle glaucoma using motion coherence thresholds. Two visual field locations from patients with primary open angle glaucoma (n= 14), which differed significantly in sensitivity, were selected for presentation of a motion stimulus. In the area of visual field loss mean threshold was 17.4 ~ 4.1 dB (1.74 + 0.41 log units relative to the brightest stimulus). In the area of relative field sparing mean threshold was 27.0 + 3.6 dB (2.70 i 0.36 log units). Motion coherence thresholds were significantly poorer for the area of visual field loss compared to the area of relative field sparing (P <0.0032, two-tailed paired t-test). This result suggests that a perimetric type motion test should be evaluated for early detection of glaucoma. Copyright 01996 Elsevier Science Ltd Psychophysics
Motion perception
Gkaucoma
Perimetry
INTRODUCTION
Functional testing of the visual field in clinical practice may not indicateloss of sensitivityuntil late in the course of glaucoma.Automatedperimetry,the most widely used clinical test, may not detect glaucomatous visual field loss until there is a considerableloss of optic nerve fibers (Quigleyet al., 1989).Clearly a more sensitivefunctional test is desirable. Becausethere is evidencethat glaucomatousdamage is more apparent when isolating certain visual functions, this may be one way to create a more sensitivefunctional test. Tests which isolate one aspect of vision and which have shown differences between normal and glaucomatous eyes include short wavelength automated perimetry which measures short-wavelengthsensitivity(Sample & Weinreb, 1990, 1992;Sample et al., 1993, 1994;Johnson et al., 1993a,b), high pass resolution perimetry which measures visual resolution (Frisen, 1993), temporalmodulation perimetry which measures temporal processing (Tyler, 1981; Casson et al., 1993; Tyler et al., 1994), and pattern discrimination perimetry which measures form perception (Drum et al., 1987). The ability of these tests to detect glaucoma earlier supports the conclusion that glaucomatous damage is more apparent when isolating certain visual functions. By isolating one particular aspect of visual function to
prevent spared visual systems from compensating for those compromised by glaucoma, the diagnostic sensitivity of a visual function test should subsequently increase. Sensitivity might also be improved by testing eccentric locationswhere glaucomatousdamage is likely to occur in the earliest stages of the disease. A good diagnostictest for glaucoma,however, shouldnot only be highly sensitive, but must also be easy for patients and operators to use reliably. Thus, a successful test for the early detection of glaucoma should isolate one particular aspect of visual function, test eccentric locations, and should be easy to use reliably. One possible diagnostic technique, which can satisfy the above criteria for a successful glaucoma test, uses video displays to measure motion perception (Fitzke et al., 1987, 1989; Silverman et al., 1990; Bullimore et al., 1993; Watkins & Buckingham, 1991; Joffe et al., 1991; Trick et al., 1995;Johnsonet al., 1995;Scholl& Zrenner, 1995). Testing motion perception with random-dot kinematograms, one of the methods previously employed, reduces possible interactions with other visual systems such as form perception, and limits the observer’s ability to make displacement judgments or direction discriminations based upon positional or orientationalcues (Nakayama & Tyler, 1980). Evidence indicates that random dot kinematograms are processed primarily through the larger diameter magnocellular retinal ganglion cells (Shapley et al., 1981; Livingstone & Hubel, 1988; Schiller & Malpeli, 1987). Thus, two justifications for developing motion tests have been developed because of their ability to assess magnocellular function (see Discussion).
*Departmentof Ophthalmology,Universityof California, San Diego, CA 92093-0946,U.S.A. ~To whom all correspondence should be addressed [EmaiZ [email protected]]. 355
356
C. F. BOSWORTHet al.
TABLE 1. Visual field locations of the relatively spared and deficit test positions and the correspondingvisual field thresholds and motion thresholds for each patient Spared position Subjects 1 2 3 4 5 6 7 8 9 10 11 12* 13 14
Deficit position
Location
Visual function threshold (dB)
Motion threshold (% coherence)
Location
Visual function threshold (dB)
Motion threshold (% coherence)
– 12, –12 –18, +06 +06, –18 – 12, –06 +06, +12 – 18, –06 –06, –18 –06, –18 –06, –18 –13, –13 –12, +12 –06, –12 –06, –06 – 18, +20
28.7 28.5 37.0 20.8 29.6 26.5 25.0 27.0 24.5 25.2 27.0 25.0 24.7 28.0
30 10 50 30 70 30 30 40 40 30 60 30 50 30
– 12, +12 – 18, –06 +06, +18 –12, +06 +06, –12 –18, +06 –06, +18 –06, +18 –06, +18 –13, +13 – 12, –12 –06, +12 –06, +06 –18, –12
14.3 24.0 12.0 16.0 14.3 18.6 17.5 18.6 19.8 21.3 24.3 17.5 12.7 18.4
40 20 70 60 70 40 70 60 50 100 60 — 70 40
*Subjectexcluded from final data analysis for failing visibility verification.
Several studiesusing video displaysto measuremotion sensitivity have found foveal motion deficits in patients with either glaucoma (Fitzke et al., 1987, 1989; Silverman et al., 1990;Watkins & Buckingham, 1991;Joffe et al., 1991; Bullimore et al., 1993; Trick et al., 1995; Johnson et al., 1995; Scholl & Zrenner, 1995), ocular hypertension (Fitzke et al., 1987, 1989; Watkins & Buckingham, 1991; Trick et al., 1995; Johnson et al., 1995; Scholl & Zrenner, 1995), or retinitis pigmentosa (Turano & Wang, 1992).Silvermanand colleaguesusing a random-dot kinematogram (Silverman et al., 1990), found a 70% elevation of foveal motion coherence thresholdsin primary open angle glaucomapatients and a 44% elevation in ocular hypertensiveswhen compared to age-matched normal controls. Trick and colleagues (Trick et al., 1995), found significant elevations in glaucoma patients’ motion thresholds for both low (4.2 deg/see) and high (12.5 deg/see) velocity randomdot kinematograms. Bullimore and colleagues (Bullimore et al., 1993),found that 10 of 15 glaucomapatients had Dmin values outside the normal range, but that coherence thresholds and DM,Xdid not discriminate between normals and patients. They also noted that patients suspected of having glaucoma were not significantly different from normal controls on any of their dependent measures: Dmi,, D~~~, or coherence thresholds. The aim of the current study was to determine if a random-dot kinematogram can differentiate between areas of known field loss and known relativefield sparing in the same eye with primary open angle glaucomausing smaller eccentrically placed targets. If the test can differentiate between these locations, it could suggest that a perimetric type motion test may be worth evaluating for early detection of glaucomatousdamage.
METHODS
Subjects Subjects for this study (n = 14) were primary open angle glaucoma patients as determined by the following criteria: 1. intraocular pressures >24 mm Hg on at least two separate occasions determined by Goldmann applanation tonometry; 2. open angleswith abnormaloptic discsbased on cup/ disc asymmetry between the two eyes of 0.2 or more, localized rim defects, disc hemorrhages, or vertical cup/disc >0.6 with excavation determined by indirect ophthalmoscopythrough dilated pupils; and 3. previously documented characteristic standard visual field loss determined by program 24-2 using a Humphrey Visual Field Analyzer 640, with corrected pattern standard deviations outside 95$70 confidencelimits or glaucoma hemifieldtest results outside the 99.5!Z0confidencelimits. For this study, reliability indices were set at 25% or less for fixation losses, false positive errors, and false negative errors. Each subject had a location of relative sparing corresponding to the location of their deficit in the quadrant either superior or inferior to it (Table 1). In this design, each patient served as his/her own control. Their mean age (~ SD) was 70.6 ~ 9.1 yr. This study was approved by the Human Subjects Committee of the University of California, San Diego and was undertaken with the understandingand consent of each subject. Random-dot motion display Our display is a modified version of the foveally centered, 60x 60 deg display employed by Silverman et al. (1990).The motion stimuluswas produced on a Barco
MOTION PERCEPTIONIN GLAUCOMA
357
358
C. F. BOSWORTHet al.
TABLE 2. Normal subjects’ (n= 4) average threshold in percent coherence for the different step sizes tested (1, 2, 3, 4, 5, and 6 pixels) at the fovea, 15 deg eccentricity, 30 deg eccentricity, and across the three field locations Location of presentation Fovea Fifteen Thirty Average
1 pixel 15.0 * 22.5 k 42.5 ~ 26.6 +
10.0 5.0 9.6 14.4
2 pixels 22.5 ~ 25.0 k 25.0 t 22.5 ~
9.6 5.8 10.0 13.2
3 pixels 27’.5~ 15.0 ~ 25.0 t 22.5 k
CCID monitor with 1024x 768 lines of resolution and a refresh rate of 75 Hz. Each pixel subtended 0.31 mm (7.35 min arc at the viewing distance of 16.5 cm). The monitor was driven by a Power PC 8100 Macintosh computer using a Raster Ops 24xli video card. Seven frames were shown in rapid successionto create the motion stimulus.Within each of these frames, 20 dots were randomly placed within a circular test region of 7.3 deg of visual angle. These dots moved at a constant velocity of 8.2 degJsec in random directions to create “noise”. A percentage of the dots were then displaced together in one of four cardinal directions(right, left, up, down) to create the coherent motion signal which the patients were to detect. The randomly chosen signal dots remained the same for all seven frames of the display and had the same spatial displacementas the noise. While it has been reported that this could create streaming for signal dots positioned on a flickering noise which is randomly positioned, each frame (Falzett & Lappin, 1983), Watamaniuk et al. (1995) demonstrated that a signal of this nature embedded in a surroundof vectored motion is not significantlyinfluencedby nonmotioncues (Watamaniuket al., 1995).We chose to defineour signal in this way because it can allow detection of single dot paths (Watamaniuk et al., 1995). This increased the number of step changes available, while allowing for a lower spatial frequency which would favor the magnocellular pathway. The signal ranged in strength from 10 to 1009%coherence (Fig. 1). Threshold was the percent coherence a subject needed to correctly identify the direction of motion at least 62.5% of the time. Percent coherence was selected as our dependent measure because Silverman and colleagues reported a 44% elevation in the motion coherence thresholds of ocular hypertensive. Because early glaucoma is usually characterized by localized, peripheral visual field loss, we designed the stimulusto stimulatethe short-rangemotion pathways at different eccentric locations. We selected stimulus parameters based on findings from a variety of laboratories (Braddick, 1974; McKee & Nakayama, 1984; Williams & Sekuler, 1984; Baker & Braddick, 1985a,b; Bischof & Groner, 1985; Van de Grind & Keonderink, 1987; Derrington & Goddard, 1989; Snowden & Braddick, 1989, 1991; Satoshi & Cavanagh, 1990; Nawroot & Sekuler, 1990; Cleary &Braddick, 1990), and we verified the effectiveness with these parameters for stimuli placed within the central 30 deg visual field. Therefore, the parameters of the current stimulus were
12.6 5.8 10.0 13.2
4 pixels 17.5 t 20.0 i 25.0 i 20.8 +
5.0 0.0 5.8 9.8
5 pixels 20.0 ~ 25.5 + 35.5 ~ 27.0 +
8.2 19.1 12.9 13.8
6 pixels 30.0 + 32.5 f 27.5 k 30.0 ~
20.0 18.9 17.1 18.3
within known ranges for testing the motion systemwhile still allowing glaucoma patients with impaired vision to perceive the display. The stimulus parameters were as follows. Stimulus contrast. The area surrounding the circular test region was a uniform gray background rather than one filled with random noise, because the latter may test regions larger than those definedby the target (Nawroot & Sekuler, 1990). The uniform gray background had a luminance of 26.43 cd/m2. The dot luminance was 59.23 cd/m2 giving a contrast of 38.3%. This contrast is below an upper cutoff of 50%, above which visual persistence can impair motion perception in a seven frame display (Cleary & Braddick, 1990; Derrington & Goddard, 1989), and it is above a contrast level of 30%, below which motion perception exhibits contrast dependence (Van De Grind& Keonderink, 1987). Region size. We chose a region size of 7.3 deg because it can cover four points on program 24-2 and because field size must be >2.5 deg in diameter for our displacement value of 29.4 min arc (Baker & Braddick, 1985a). A foveal field size of 2.5 deg or larger includes ~max values > zg.o min arc due to the recruitment of eccentric motion detectors (Baker & Braddick, 1985a). D max is the maximum displacementover which coherent motion can be perceived. Number of frames. A stimulus comprising seven frames creates six dot displacements, which is within the optimumrange of four to.six displacements(Snowden & Braddick, 1989). Frame duration. The optimum exposure time per frame is between 10 and 80 msec (Baker & Braddick, 1985b). We chose an exposure time of 60 msec. Inter-stimulus-interval(ISI). An 1S1of zero prevents motion reversal (reporting movement in the correct plane, but opposite direction) (Satoshi & Cavanagh, 1990). Dot size. A dot size of 29.4 min (4 pixels) was large enough for patients to accurately see the display in the peripheral visual field. Dot density. Dot density was set at 0.83 dots/deg to reduce the likelihood of mismatching (Williams & Sekuler, 1984). The lower probability of mismatching in the current stimulus allowed us to use larger dot sizes and displacements to facilitate testing patients with reduced vision in the peripheral field. This density gave 20 dots per stimulus. Dot displacement size (pilot study). To set the parameter of dot displacement, pilot work was needed.
359
MOTION PERCEPTIONIN GLAUCOMA
TABLE3. The parameters involvedin motiondisplays showingthe optimumranges reported in the literature or determinedby pilot studies, and the actual settings chosen for this motion perimetry test Parameter Dot displacement Contrast Frame duration Number of steps 1S1 Dot density Dot size and number Region size Viewing distance Coherence range
Optimumrange
Settings
Pilot study 30% < x < 50% 10 msec < x <80 msec 4
29.4 min arc 38.3% 60 msec Six steps =Zero 0.83 dots/deg 29.4 min arc and 20 dots 7.3 deg 16.5cm G1OO%Coherence
Braddick originally proposed that D~aXwas 15 min arc for short-range apparent motion at the fovea (Braddick, 1974). Other studies later showed higher D~,X values with increasingeccentricity(Baker & Braddick, 1985a,b; McKee & Nakayama, 1984). To determine the optimal dot displacement for the perception of coherent motion within the central 30 deg of visual field,we presented the target foveally and at two retinal locations along the superiorvertical meridian (15 and 30 deg eccentricity)to subjects with normal eyes (n= 4; mean age 29.0 ~ 8.4 yr). These subjects had a normal ophthalmological exam with intraocular pressures <21 mm Hg, normal optic discs, and no visual field loss. The motion display for this pilot study was identicalto the one used for the actual testing of glaucoma patients except for dot displacementsize (1, 2, 3, 4, 5, or 6 pixels) and region position(fovea, 15 deg, or 30 deg)which were independentvariables.The results indicatedthat a 4 pixel displacement generated the lowest average threshold across the tested retinal locations. A displacement of 4 pixels (29.4 min arc) was therefore chosen (Table 2). Avoiding grating cues at high coherence levels. Visual persistence can affect motion perception by causing alpha-stripes (Cleary & Braddick, 1990; Snowden & Braddick, 1991; Bischof & Groner, 1985).Alpha-stripes (Snowden & Braddick, 1991) are illusions which occur when a dot travels repeatedly over the same path generating the perception of stripes. To avoid alphastripes, the dots were displaced perpendicularly to their direction of movement as they wrapped around the screen. In addition, a larger dot displacement and a smaller display size helped break down this alphastriping effect because a large number of dots wrap around during each stimuluspresentation.For a summary of the current testing parameters and the optimal ranges suggested in the experimentalliterature see Table 3.
locating a group of four points on the Humphrey standard visual field with at least two points outside the 5% confidencelimits on the pattern deviation plot. This was the locationof visual field loss where the motion stimulus was presented. This location was then required to have a matching group of four points in the quadrant either superior or inferior to it, at the same eccentric location, with no abnormalpoints on the corrected pattern standard deviation.This was the location of relative sparingwhere the motion stimulus was presented (Table 1 and Fig. 2). Four subjects had an inferior field defect. Eight subjects had a superiorfield defect. See Table 1 for a listing of the field locationsof the spared and deficittest positions and the corresponding visual field thresholds and motion thresholds for each patient. The order of presentation (area of visual field loss vs area of relative sparing) was randomized across subjects to preclude learning and fatigue effects.
Testprocedures The subject sat in a darkened room with a patch placed over the nontest eye. The subject’s chin rested in a chin rest while he/she viewed the screen through proper refraction for the test distance of 16.5 cm. The subject focusedon a black fixation“x” in the center of the display and adapted for 2 min to the background illumination. During this time, a camera was focused on the test eye so that fixationcould be monitored by the test administrator on a separate video display system. Trials where fixation was lost were aborted and retested later in the program. The testing procedure was then explained to the subject. The sessionbegan with a foveal practice test consisting of 12 presentationsall at 100% coherence. The patient’s performance on these trials was observed by the test administrator to make sure that the patient properly understoodthe task. After completingthe foveal practice, anotherpractice stimuluswith two coherencelevels (40% Test locations and 70’%)was randomly presented in the area of relative Each subject had a location of relative sparing sparing and the area of visual field loss at 2 sec intervals. corresponding to the location of their deficit in the This practice ended after 48 responseswith one of three quadrant either superior or inferior to it. The two test results which determined the make-up of the actual locations on opposite sides of the horizontal meridian motion test: were matched for eccentricity: one an area of relative visual field sparing and the other an area of visual field 1. If the patients got > 62.5% of their direction loss. The testing locations were determined by first discriminationresponsescorrect at 40% coherence,
360
C. F. BOSWORTHet al.
. . .,
.0 . . *6 .,
. . * *
. . * ●
* . . . ●. ●.
,.:
●.
.
.,
.
●*
.* ,,
. . .,
“:.
* *● .. *● ● . .1: . . . . ., . . *, ,. ““ . ●.,* ●“●. A. . . . . . ●*.● ●. * “* ● * ● * ● “ ,$: .* *,,● ,.**** ● * ., ,. ●
“ V
4.
.
. . ,.
D. . .
.
●
*
.,
.,
0 ● ● * O* , . ● O ,. ,. ., ,.
0 ● ●● ●● t ~ . ●
●. ●. . . ●* . . 8. * . ● , . . , ● , . 8* . . , . . . ., ,. . . ,. ● . .* ., *. . . ,, ,, ,. ., ,, .**. .,.. ., ., ..;. ●● ✎o ✌;
.. ,
✎✌ ●4 . .
● ✎✎ ✌✌ ✌✎ . . ,. . . , .
● ✎ ✎ ✎ ✌✎ ✌✎ ✎ ✎ 0 .
~
✌ ✌ ✌✌ . . . . ✎ ✎ .
.
s.
.
.-
*
●* ● , ,. . ● ,.
SC *4 .,
.0
●. ●0
.6
.
●● * .
●
c ,. ,, ,, *,
.. .. ,, ..
., ,, ., ,.
.. ,. .* ..
.
●O
. . .. . .. , ● ,,: ,, .* ,. ,** ● , .-.
●●
., * ,.
●✎ ✃ ✎ ✎ **( ✎✎ . . ., . . ., . . 1. . .
0::. ,. :: .,. . ,,.,,. ,.,,,. ., ,:, . ,. ,., . . , . . ..,,.,.. ●
*.:
.4-
9*. ,. ., ,, ,. . . . .
., . . ,. , . ., ,. ,. ,. ,, , . . ,, . . ,. . . ., . . ,. ,. . , ., . . . . .* * :: ,, ., . . ., . ● , . , . ● . .
. ● ,. , . ,. ,. .*
., 0, ,, $s , , .* . . ,, . . ., . . .* ,, . . ., ., . ● .0 ,. . .
., ,. ,. .* o.
● ●
*
,. ,. *. ,, . . ,. ., ,. . . ,. ●
.
●
o .,: . , ,,:,,:
,,: ,
*
●●
.
.
.
● ☛✍ ●☛ ✎✎
94 .. ,,:
. .
:::: ., .~:o*: ,. ,. ..:,,*.** ,. ,,:
.
.
●
,.;
.
--
*
.. ,9 ,. .*: ,.
. . .
. . . . ., .
,
**** ● . ● . ,, , . ,, *. , . . ●* , , ● *● . . . . . . . , . . . . ** ●. , , . . ,. , ., ,. ,. . ,. , . . ● * ,. . ● . ,, ●. . . . . . ,. ,. ., ,. ,. . ,. ,, ,, ., ,, ● * , . . . . . .0 ✌ ● ✎ ☛✎ 0 . , , ● ● ● ● ● .0 . ● ● J ,. .* ☛ ✎✌ ✎✌ ● ✎ ✎✌ ✎✌ ✌✌ ● O 0 .,, ,, ,. . . ● . ● . 4 ,.: ..:,,: .: ,.: . . ● O . ● . . . ●* ● . ● , ●
9, *. . . . . ● ☛ ✎ ✎ ✎ ✎ ✌✎ . . ●. ● . ,. ,, ., ., ., ... 0.
.4 ,, .,
.
.
.
,
. .
.
. . : : :: ..: .*: o
● ☛ ✎✎ ✎ ✎ ✎☛ ✌✎ ✎✌ ✌ ✎ ✎✎ ✎ ✎ ✎✌ ✎ ✎ ✎✌
✎
,:
:
● ●
i
.,
.
,
:
:
.*:
.,.
,
.
/,
. .
‘a
U3
UY
m
e=
m.,
● ✎✌
.,
. . ,, .0
,. ● .,1: . ..~., .*:
1 .: ,.: , . .
. . ., . .* ● .,
,. . . ● . .0,
,
●
●
●
✚✚
.$:;;::: ,..,.,,. o, * ,. ......,, . . ... * . . ., . .
●
☛
●
1
☛
✎ ✌ ✎ ▼ ✎✎ ● ✎ ., . . ., ., ● .
✎✌ ✎✎ ● ✎ ✎✎ ., ., . . , , ● .
.
.
☛☛☛ ✎
0.0
●
✎
●
✎
.*
.*,
●4
●
,, .a ., e, ,, . . ,. . . . . ,, . . ,. ,. c , .; ., ,, , D . . ,, ., ,,
m
02
UY
●
. .
~
,,.0
m
Cn
●✎ ✌✌ ✌✎ ✌✎ . s, . . ,, . .
,,,..*, .:,. , Iill? ..O
. .
.,
0
.
☛✌ ● ✌ ●✎ ● ✎ $$.
llcl 1+
● *
..,.
*
,0 . .
., . .
.
✎
.
✎● ✎● ✎ ✎ ✎✎ . . . . ., .*
-}.
MOTIONPERCEPTIONIN GLAUCOMA
361
Foveal Practice at 100940
~
40 0/0 Coherence Practice
\ 10YO-60Y0 Coherence
f
~
~
&
~40y0100yo~ Coherence
r
END TESTING
J
I
Coherence
I
& $ \ +’ b
Stimulus is Considered Unseen :C ~
ENDTESTING
Threshold Reached
................... ++ Threshold Not Reached FIGURE3. A flow chart showing how the program determines which coherence range to test for each subject, given hisiher response at each stage of the program. At each stage the subject must get 62.59Zof their direction discrimination responses correct to reach threshold. Dashed arrows leading from a given stage of the program indicate what happens if threshold is not reached, solid arrows indicate what happensif performanceis equal to or better than threshold.This procedurewas followedby the program for each of the two independentlocations (see text for complete description).
they were given a motiontest which had a coherence coherence, they were given a visibility verification range of 10–60%.If, however,a thresholdvalue was test. If the patient could correctly identify 70% of unobtainable in this range, stimuli from 7O–1OOYO the verificationtargets, the motion test was set to a coherence were added until threshold was detercoherence range of 40–100% (Fig. 3). mined. The visibility verify test was randomly presented in 2. If the patients reached threshold at 70% coherence, each of the two test locationsfor 60.0 msec to determine but did not at the 40% coherence level, they were if the patient could see a static version of the stimulus. given a motion test which had a coherence range of The time between presentations was randomly varied 40–100%.If a sub-thresholdvalue was unobtainable from 2000 to 5000 msec, and the patient responded by in this range, stimuli at 10-30?7 were added. pressing any key on the computerkeyboard.If the subject 3. If the patients got <62.5% of their direction discrimination responses correct even at 70% did not respond within 500 msec of stimulus offset, the
362
—
C. F. BOSWORTHet al.
120
1
100-r
80E ~ 5 0 $
4
/ ●*
60-
Threshold (62.5 % Correct)
..-4 b .s * .4,
++
● ’
b+’ 20.
I
10%
2070
I 30%
i
I
I
doyo
50’?-”.
60%’.
1
7f)%
1
80Y.
I
90%
I
1
100%
YOCoherence FIGURE4. This graph showsmean percent correct (with SE)for each coherencelevel in the area of deficit (dashedcurve) vs the area of sparing (solid curve) across subjects (n = 13). The solid horizontal line denotes the threshold criterion of 62.5%.
stimuluswas considered unseen. Testing proceeded only if the patient correctly identified70% of the static targets in both locations. One patient failed the visibility test in the deficit location and was excluded from the data analysis. For all testing, the subject reported which direction (left, right, up, down) he/she thought the dots were moving in a four alternativeforced-choiceparadigm.The test administratorpressed an arrow key correspondingto the direction indicated by the subject. The patient could respond at any time during the stimuluspresentationor at the end of the presentation. The program gave a 2 sec delay before presenting the next stimulus. Subjectswere informed that they could pause and rest at any time during the test. Because the method of constant stimuli was used the whole procedure lasted ca 45 min and only one eye was tested for each subject.
area of relative field sparing it was 38.6Y0coherence + 15.1% (Table 1 and Fig. 4). We did not find evidence for motion reversal. Reversed responses never exceeded chance (25’%0) at either location. DISCUSSION
The sensitivityof a motion test to diagnose glaucoma may be attributed to its isolation of one particular aspect of visual processing, the motion system. This prevents sparing in other visual systems from compensating for disease related damage (Silverman et al., 1990; Bullimore et al., 1993; Joffe et al., 1991). There are two approaches which argue the merits of testing motion perception because of its isolation of the motion system. The first concludes, from reports of selective damage to larger optic nerve fibers (Quigley et al., 1987), that glaucoma must selectively damage the magnocellularpathway because its cells are, on average, RESULTS of the largest diameter. However, as Johnson (1994) Mean (t SD) visual field threshold for the area of points out, these histological results, upon which this visual field loss was 17.4 dB~ 4.1 dB or 1.741 log units conclusion has been made, show an “overall amount of relative to the maximum brightness OdB (OdB = loss present for all optic nerve fibers irrespective of their 10000 asb) and for the area of relative sparing was diameter”.This leads to a secondjustificationfor motion 27.0 dB~3.6 dB or 2.70 log units. Motion coherence testing. Because all visual functions may be comprothresholds for these two locations were significantly mised by glaucoma, some functions may be comprodifferent, t(lz)= 3.67, PsO.0032, two-tailed paired. The mised more than others depending on the individual. mean motion threshold~ SD acrosssubjectsin the area of Thus, a battery of tests which isolate different visual visual field loss was 57.7’%coherence + 20.0%. In the functionsmay be needed for early detection of glaucoma
MOTION PERCEPTIONIN GLAUCOMA
across patients. Regardless of which theory is correct, they do provide justification for continued investigation into the effects of glaucoma on motion perception. For motion perimetry to become a successful diagnostic tool for glaucoma detection, it must be able to reliably differentiate between normal and glaucomatous eyes. However, considerableoverlap between glaucoma patients and normal controls has been found in motion thresholds (Bullimore et al., 1993). This could be the result of using relatively large, foveally fixated fields of random dots which might allow both normal and pathogenic regions of the visual field to contribute to glaucomapatients’ motion percept. Joffe et al., in a 1991 ARVO abstract, used a small 3 deg display size at multiple retinal locations and found that glaucoma patients had specificlocations of marked sensitivityloss (Joffeet al., 1991).To maximizethe sensitivityof motion threshold perimetry, it may be necessary to use smaller display regions. The stimulus used in this study was designed to function at discrete retinal locations across the central 30 deg of the visual field. Longitudinalstudy of a large number of primary open angle glaucoma, normal, and suspect eyes, and testing multiple retinal locations using a staircase procedure to shorten test time are necessary before the diagnostic and clinical utility of this test can be determined. Our results indicate that this motion test successfully differentiated between areas of known visual field loss and locationsof a known relative sparingin patientswith glaucoma.The resultssuggestthat the ability of a motion display to test discrete retinal locations across the visual field may be importantfor detectingearly motion deficits in glaucoma patients. REFERENCES Baker, L.C. & Braddick,O. J. (1985a).Eccentricity-dependentscaling of the limits for short-range apparent motion perception. Vision Research, 25, 803–812.
Baker, L. C. & Braddick, O. J. (1985b). Temporal properties of the short range process in apparent motion.Perception, 14, 181–192. Bischof, W. F. & Groner, M. (1985). Beyond the displacement limit: an analysis of short-range processes in apparent motion. Vision Research, 25, 839–847.
Braddick, O. J. (1974). A short-range process in apparent motion. VisionResearch, 14, 519–527. Bullimore, M. A., Wood, J. M. & Swenson, K. (1993). Motion perception in glaucoma. Investigative Ophthalmology and Visual Science, 34, 3526-3533.
Casson, E. J., Johnson, C. A. & Shapiro, L. R. (1993). Longitudinal comparison of temporal-modulationperimetry with white-on-white and blue-on-yellow perimetry in ocular hypertension and early glaucoma. Journal of the Optical Socie~ of America, 10, 1792– 1806.
Cleary, R. & Braddick, O. J. (1990). Masking of low frequency information in short-range apparent motion. Vision Research, 30, 317-327.
Derrington, M. A. & Goddard, A. P. (1989). Failure of motion discrimination at high contrasts: evidence for saturation. Vision Research, 29, 1767–1776.
Drum, B., Breton, M. & Massof, R. (1987). Pattern discrimination perimetry: a new concept in visual field testing. Documents in Ophthalmology, 49, 433440.
Falzett, M. & Lappin, J. S. (1983).Detection on spatial forms in space and time. Vision Research, 23, 181–189.
363
Fitzke, F. W., Poinoosawmy,D., Ernst, W. & Hitchings, R. A. (1987). Peripheraldisplacementthresholdsin normals, ocular hypertensive and glaucoma. In Greve E. L. & Heijl A. (Eds), Seventh International Visual Field Symposium (pp. 447452). Dordrecht: Martinus Nijhoff. Fitzke, F. W., Poinoosawmy,D., Nagasubramanian,S. & Hitchings, R. A. (1989). Peripheral displacement thresholds in glaucoma and ocular hypertension.In Heijl A. (Ed.), Perimetric update (pp.399– 405). Amsterdam: Kugler and Ghedini Publications. Frisen, L. (1993). High-pass resolution perimetry: a clinical review. Documents in Ophthalmology, 83, 1-25.
Joffe, K. M., Raymond,J. E. & Crichton,A. (1991).Motionperimetry in glaucoma. ARVO Abstracts. Investigative Ophthalmology and Visual Science, 32 (suppl.), 1103. Johnson, C. A. (1994). Selective versus nonselective losses in glaucoma.Journal of Glaucoma, 3 (suppl. 1), s32-s44. Johnson, C. A., Adams, A. J., Casson, E. J. & Brandt, J. D. (1993a). Blue-on-yellowperimetry can predict the development of glaucomatous visual field loss. Archives in Ophthalmology, 111, 645–650. Johnson, C. A., Adams, A. J., Casson, E. J. & Brandt, J. D. (1993b). Progression of early glaucomatous visual field loss for blue-onyellow color perimetry and standard white-on-white automated perimetry. Archives in Ophthalmology, 111, 651-656. Johnson, C. A., Marshall, D. & Eng, K. M. (1995). Displacement threshold perimetry in glaucoma using a Macintosh computer system and a 21 inch monitor. In Heijl, A. (Ed.), Perimetric update (Pp. 103-110). Amsterdam: Kugler and Ghedini Publications. Livingstone,M. S. & Hubel, D. H. (1988).Segregationof form, color, movement, and depth: anatomy, physiology, and perception. Science, 240, 74&749.
McKee, S. P. & Nakayama, K. (1984). The detection of motion in the peripheral visual field. Vision Research, 24, 25–32. Nakayama, K. & Tyler, C. W. (1980). Psychophysical isolation of movement sensitivity by removal of familiar position cues. Vision Research, 21, 427433.
Nawroot,M. & Sekuler,R. (1990).Assimilationand contrast in motion perception: explorations in cooperativity. Vision Research, 30, 1439-1451.
Quigley, H. A., Dunkelberger,G. R. & Green, W. R. (1989). Retinal ganglioncell atrophycorrelated with automatedperimetry in human eyes with glaucoma.American Journal of Ophthalmolo~, 107, 453. Quigley,H. A., Sanchez,R. M., Dunkelberger,G. R., L’Hernault,N. L. & Babinski, T. A. (1987). Chronic glaucoma selectively damages large optic nerve fibers. Investigative Ophthalmology and Visual Science, 28, 913–920.
Sample,P. A., Madrid, M. E. & Weinreb, R. N. (1994).Evidencefor a variety of functional defects in glaucoma-suspect eyes. Glaucoma, 3, S5-S17.
Sample,P. A., Taylor,J. D.N., Martinez, G., Lusky,M. & Weinreb, R. N. (1993).Short-wavelengthcolor visual fieldsin glaucomasuspects at risk. American Journal of Ophthalmology, 115, 225–233. Sample, P. A. & Weinreb, R. N. (1990). Color perimetry for assessment of primary open-angleglaucoma.Investigative Ophthalmology and Visual Science, 31, 1869–1875.
Sample, P. A. & Weinreb, R. N. (1992). Progressivecolor visual field loss in eyes with primary open angle glaucoma. Investigative Ophthalmology and Visual Science, 33, 2068–2071.
Satoshi, S. & Cavanagh, P. (1990). Isi produces reverse apparent motion. Vision Research, 30, 757–768. Schiller, P. H. & Malpeli, J. G. (1987).Functionalspecificityof lateral geniculate nucleus laminae of the rhesus monkey. Journal of Neurophysiology, 41, ‘78%797.
Scholl, H. P. N. & Zrenner, E. (1995). Motion thresholds of colored stimuli of different luminance contrasts are increased in ocular hypertension and early primary-open-angle-glaucoma (POAG). Color Vision Deficiencies, 13, 73-85.
Shapley, R. M., Kaplan, E. & Soodak, R. (1981). Spatial summation and contrast sensitivity of X and Y cells in the lateral geniculate nucleus of the macaque. Nature, 292, 543–545. Silverman, S. E., Trick, G. L. & Harr, W. M. Jr. (1990). Motion perception is abnormal in primary open-angleglaucoma and ocular
364
C. F. BOSWORTHet al.
hypertension. Investigative Ophthalmology and Visual Science, 31, 722–729.
Snowden,R. J. & Braddick, O. J. (1989).The combinationof motion signals over time. Vision Research, 29, 1621–1630. Snowden,R. J. & Braddick,O. J. (1991).The temporal integrationand resolution of velocity signals. Vision Research, 31, 907–914. Trick, G. L., Steinman, B. S. & Amyot, M. (1995). Motionperception deficits in glaucomatous optic neuropathy. Vision Research, 35, 2225–2233.
Turano, K. & Wang, X. (1992). Motion thresholds in retinitis pigmentosa. Investigative Ophthalmology and Visual Science, 33,
motion in moving random-dotpatterns. Optical S“ociey of America A. Optics and Imagescience, 4, 1643-1642. Watamaniuk, S. N. J., McKee, S. P. & Grzywacz, N. M. (1995). Detecting a trajectory embedded in random-directionmotion noise. VisionResearch, 35, 65–77. Watkins, R. & Buckingham,T. (1991).Motionperception hyperacuity is abnormal in primary open-angle glaucoma and ocular hypertension. ARVO Abstracts. Investigative Ophthalmology and Visual Science, 32 (suppl.), 1103. Williams, D. W. & Sekuler, R. (1984). Coherent global motion precepts from stochastic local motions. Vision Research, 24, 55–62.
2411–2422.
Tyler, C. W. (1981).Specificdeficits of flicker sensitivity in glaucoma and ocular hypertension. Investigative Ophthalmology and Visual Science, 20, 204-212.
Tyler, C. W., Hardage, L. & Stamper, R. L. (1994). The temporal visiogram in ocular hypertension and its progression to glaucoma. Glaucoma, 3, S65–S72. Van de Grind, W. A., Keonderink,J. J. & Van Doom, A. J. (1987). Influenceof contrast on foveal and peripheral detection of coherent
Acknowledgements—The authors wish to thank Scott Hancher, Department of Ophthalmology, UCSD, for developing the motion program used in this study. This study was supportedby National Eye Institute Grant EY08208(Dr Sample).