Differences in the neural basis of human amblyopia: The distribution of the anomaly across the visual field

DIFFERENCES IN THE NEURAL BASIS OF HUMAN AMBLYOPIA: THE DISTRIBUTION OF THE ANOMALY ACROSS THE VISUAL FIELD R. F. HESS and J. S. POINTER The Physiological Laboratory, University of Cambridge, Downing Street, Cambridge C52 3EG. England (Receired 24 Ocrober 1984; in revisedform ?6 Jane 1985) Abstract-Spatio-temporal contrast sensitivities to ho~zontally-oriented Gaussian-weighted patches of sinusoidal grating stimuh were determined across the nasal and temporal visual fields of strabismic and non-strabismic. anisometropic amblyopes. The visual field distribution of the amblyopic anomaly differs in strabismic and non-strabismic, anisometropic eyes. In strabismus the peripheral region of one or both hemifields is spared; in non-strabismic, anisometropic cases the loss is evenly distributed across the binocular visual field but is not present in the monocular temporal field. These findings suggest that the non-strabismic forms of amblyopid in humans result from binocular competitive imbaiance in early life. The strabismic results pose two problems for the present competitive model of amblyopia: in strabismus, amblyopia Amblyopia development

is mainly

iimited

Anisometropia Visual field

to central

vision and shows an asymmetric

Binocular

competition

INTRODUCTION

encountered (prevalence I-5.6*/0) non-pathologists ophthalmic condition in which uncorrectable loss of visual function occurs in an eye which was strabismic or anisometropic during the early years of life. Over the past two decades a host of neurophysiological investigations have been undertaken on the developing visual system of animals: monocular deprivation by surgical or refractive procedures has been carried out to understand the neural substrate ofamblyopia and also to unravel the rules that underlie normal visual development (Wiesei and Hub&, 1965; Guiliery, 1972; Ikeda and Wright, 1976: Blakemore, 1978; Eggers and Blakemore. 1978; Singer, 1975; Freeman and Bonds, 1979; Boothe et al., 1982; Cynader, 1982; Harwerth, 1982; Sherman and Spear, 1982). From these studies two models have been proposed, each with different ramifications for our understanding of the development of normal visual function. The first model, proposed by Wiesel and Hubel in 1963 and later supported by the experiments of Guillery (1972). Blakemore (t978), Eggers and Blakemore (197S), Singer (1978), Cynader (1982) and Haruerth (1982), seeks to explain amblyopia solely on the basis of an imbalance between binocular neurona/ inleracfions resulting from the strabismus or anisometropia. The experiments of Guillery (1972) and others suggest that these interactions are of a local, possibly single cell, nature. The alternative model, originally put forward by Ikeda and Wright (1976) and lkeda and Tremain (1978), argues that strabismic and anisometropic amblyopia have a common neural basis: this model maintains that the Amblyopia

is a commonly

Contrast

distribution.

sensitivity

Strabismus

Visual

cortical competitive imbalance has developed from the direct, non-competitive deprivation effects produced by the blurred retinal image present in early life. Ikeda and her co-workers argue that the initial reason behind the competitive imbalance in the cortex originates from the retina and that the anomaly’s distribution is limited to the central field because it is here that the ganglion cells are most affected by blur, i.e. where those with the smallest receptive fields are located. Since these animal studies purport to model the human condition, it is of some importance to know the psychophysjcal details that bear upon these issues for humans with amblyopia. The question as to how the anomaly is distributed across the binocular and monocular fields of vision is of particular relevance in connection with the evaluation of these two conflicting animal models. A number of psychophysical studies have been carried out on humans with amblyopia but these have mainly concentrated on central vision and used rather large stimulus field sizes (Gstalder and Green, 1971; Mitchell er al,. 1973: Levi and Harwerth, 1977; Hess and Howell, 1977; Sjiistrand, 1978; Hagemans and van der Wildt. 1975; Bradley and Freeman, 1981; Rentschler et al., 1981). Our knowledge of the distribution of the amblyopic anomaly across the visual field is incomplete, being documented mainly in terms of visual acuity (Kirschen and Ftom, 1978; Thomas, 1978; Avetisov. 1979; Hess and Jacobs, 1979; Jacobson and Sandberg, 1980; Sireteanu and Fronius, 1981). Here we investigate the distribution of the ambtyopic anomaly in strabismic and non-strabismic anisometropic ambiyopia using stimuli of different

1571

1578

R. F. HESS and J. S PCUNTER

spatial and temporal frequencres which are well localized in space and time. In order to evaluate these two current animal models of the human amblyopic condition we investigated two features: firstly, whether the visual field distribution of the anomaly is similar in strabismic and non-strabismic. anisometropic amblyopia; and secondly, whether it involves both the binocular and monocular visual fields. Our results indicate that the distribution of the anomaly in human amblyopia is different in strabismic and non-strabismic forms of the anomaly. 4lETHODS General

procedures

Monocular detection thresholds were measured for sinusoidal grating stimuli varying in spatial and temporal frequency using a temporal, twoalternative, forced-choice (2 AFC) technique. A staircase procedure driven by the subject’s responses and controlled by computer determined the detection threshold. Each trial consisted of two presentations (denoted by auditory tones) one of which contained the stimulus while the other was a blank field of the same space-averaged luminance. The average of 6-8 reversals of the staircase constituted one mean. Each datum consisted of the average of at least two means. Stimuli were presented in the centre of a Joyce Electronics (Cambridge, U.K.) raster display (P4 phosphor) at a mean luminance of 100 cd/m* and at a frame rate of 200 Hz. The display screen was surrounded by a large luminance-matched field (40 deg vertically x 60deg horizontally). The room was artificially illuminated. The display screen’s contrast linearity was measured, and found to hold up to 98% contrast. A fixation light of adjustable intensity was used to direct subject fixation so that eccentric regions could be tested. The viewing distance was 3.7 m. Refractive errors were fully corrected prior to testing. When the monocular visual field was tested slightly different viewing conditions prevailed. The subject sat at a distance of 0.93 m from the display with the head restrained by a rotatable dental bite. The horizontal extents of the binocular and monocular visual fields were plotted for each subject: this facilitated the choosing of appropriate eccentricities for the examination of the extreme binocular and adjacent monocular fields. Since the stimulus was extremely eccentric under these conditions we went to some lengths to ensure that any off-axis refractive error was corrected. A specially constructed spectacle frame accommodated additional laterally-located lenses which could be centred and aligned perpendicular to the eccentric viewing axis. In this way central vision, which was used for fixation, could be optically corrected independently of eccentric vision. Stimulus

were used to measure contrast detection thresholds. This orientation ensured that any functional unsteadiness of the amblyopic eye (predominately in the horizontal plane: Schor and Hallmark, 1978) did nor interfere with our measurements by introducing retinal image smear. These patterns were digitally generated using a PDPI l/34 laboratory computer. The contrast of each stimulus was weighted with GausSian functions of space and time (s. _I’.t). This ensured that the stimuli were well localized spatially and temporally and that eccentric detection was not differentially biased to the edge of the stimulus proximal to the fovea. The luminance distribution of each stimulus is specified by r;(.r,y,t) = L,[I + CG (.r,y,t).sin(2rrf,r).cos(2n/;t)]

where L, indicates the space averaged luminance, C the contrast variable and f, and f; the spatial and temporal frequencies. The spread function is given by G(x,y,t) = expt - (x/S,)’ - (v/S,)’ -

Subjects

Seventeen amblyopic subjects were tested in detail during this study (Table 2) and we display representative results from eight subjects here. Each subject underwent a full orthoptic and ophthalmic examination, the relevant details from which are listed in Table 2. We sought to examine “mild”, “moderate” and “severe” classes of strabismic and anisometropic amblyopia: in the anisometropic group we included hyperopes and myopes. It should be noted that in our solely strabismic group only half exhibited small degrees of eccentric fixation. Table

grating patterns

I. Stimulus

Spatial frequency Wdeg)

details

Spatial Gaussian spreads* (dcg)

Full-field flicker 0.8 1.6 3.2 6.3 10.0 *Note: angular

sinusoidal

(t/.S,)‘l. (2)

The term spread signifies the distance in time or space that the Gaussian falls from I to I!e. The overall spread function is the product of the horizontal, vertical and time gaussians having spreads S,, S,”and S,. Full-field flicker and five spatial frequencies (0.8, 1.6, 3.2,6.4, 10.0 c/deg) were used in conjunction with two temporal frequencies (I,8 Hz). The appearance of some of these stimuli on the display screen at highly suprathreshold contrast are shown (Plate I), and a list of their corresponding spatial (circular, s =_v) Gaussian spreads is given (Table I).

3.7m.

Horizontally-oriented

(I)

subtense at viewing frequency: spread 250 msec).

Temporal

(temporal

4 2 ?

I 0.5 0.3 distance of 8 HZ

I or

Amblyopic Table 2. Amblyopic

SubJect group

Sex

hge 0’)

Class’

PW.

m

33.25

HA

P T.

f

23.25

H ‘S-A

A.W.

m

33.83

HIS-A

S.E-R.

f

29.50

H/S

TO.

m

41.08

H,‘S

C.D

f

39.00

M/S-A

SubJect

lKey

(Table ?(a). (b). (c)l: H = hyperopic;

Table

across

the visual

Clirwal

Class

Aae (yr)

M.K.

f

32.25

H/A

R.C.

m

22.75

H/S

R.H.

m

27.83

H/S

N.S.

Ill

28.83

M/A

L.C.

m

35.91

M/S

A.F.

f

35.41

M/S

Subject

Sex

Age (yr)

Class

C.G

m

11.66

H/S-A

R.J.

f

23.91

H/S-A

C.F.

m

29.08

HIS

S.T.

f

SO.58

H/S

J.S.

f

42.41

M/S-A

Clinical

data

Central fixation Rx-R +0.75 DS:6’5+ L +4.75’-1.25 x 50:6,9+ Presents with L. ESOpT. no etc. tixn. Rx-R +4.00 DS:6/5+ L +5.50/-0.25 x 85:6,9+ Unsteady etc. tixn. (co.5 deg). small R.EXOT and R/L Rx-R +1.75/-1.50x ll5:6!9 L plano:6:5+ Res. int. R.EXOT, no ccc. fixn. Rx-R + 1.50/-1.50 x 15:6/6 L +0.25,‘-0.25 x 165:6/j+ (Alt.) R.EXOT and R/L Rx-R +I.OO/-0.50 x 160:6/6L +0.75/-0.50x 170:6/j+ Res. variable L.EXOT and R/L, no etc. lixn. Rx-R -0.25 DS:6/5+ L -5.00/-1.50x 60:6/12

2 (ctd). (b) Moderate

Sex

lj7Y

field

(a) mild (n = 6. 33.32 + 5 90 yr): 6 I2 or better Snellen acult)

M = myopic; A = anisometropic

Subject

Table

deficit

amblyopia;

First uorn

data

Central tixn. Rx-R +4.50/-0.50 x 135:6/36 L +0.75 DS:6/5 5deg R.ESOT. no etc. fixn. Rx-R +O.SO/-I.00 x 120: 6/24-t L -0.25/-1.00 x 55:6/5 5de.g R.EXOT and L/R. no etc. tixn. Rx-R plano/-0.50 x 140:6/24+ L piano/-0.75 x 90:6/5 Central fixn. Rx-R pIanoi-0.50 x 105:6/S L -1.75/-3.00x 10:6,‘24 I5 deg L.EXOT and L/R, no etc. fixn. Rx-R -l.SO/-0.75 x 180:6/5+ L - l.SO/-0.50 x 180:6/24 0.75 deg etc. lixn. (part accm.) R.ESOT Rx-R -l.25/-1.00 x 10:6/18 L -2.50/-1.50 Y 170:6/5

trt: present Rx

Rx age 3 yr: occln therapy. constantly

present

No Rx worn: no surgery.orthopt~

First Rx mid-teens: surgery Rx worn constantly

Rx

trt

R age 7 yr: present

First Rx age 2 yr: 25 deg dew.- no surgery. occln. thernpy only: present Rx used selectiwly First Rx age 6 yr: surgery 22 yr: no present Rx

R age I2 yr, L age

S = strabismic amblyopia

(n = 6, 30.50 & 4.59 yr): 6/18-6/60 Clinical

hlstory

First Rx age IO yr: no orthoptlc used selectively

Snellen

acuity Clinical

hlstory

First Rx early teens: no surgeryiorthoptic present Rx

trt: no

First Rx age 6 yr: occln. therapy: no present Rx

First Rx age 3 yr: surgery and occln. therapy: no present Rx

First Rx age 25 yr: no surgery:orthoptx present Rx

trt: no

First Rx age 24yr: no surgeryjorthoptic present Rx worn constantly

trt:

First Rx age 3 yr: occln. worn constantly

Rx

therapy:

present

2 (ctd). (c) Severe (n = 5, 32.73 f 12.09 vr): worse than 6160 Snellen acuity Clinical

data

Presents with L.ESO/IT, 0.5 deg etc. tixn. Rx-R plano:6/5 L +3.50/-1.00 x 90:3/60 Central fixn. small R.ESOT Rx-R +7.00 DS:3/60 L plano:6/5 + 15 dcg ccc. fixn., (consec.) L.EXOT Rx-R +4.50/-0.50 x 180:6/S+ L +4.25 DS:2/60 IOdeg ccc. fixn., L.ESOT Rx-R -0.251-0.50 x IlO:6/5+ L +O.SO DS: l/60 Presents with R.EXOpT. no ccc. fixn. Rx-R - 5.00 DS:2/60 L + l.OO/-0.75 x 15:6/5+

Clinical

history

First Rx age 6 yr: occln. therapy: no present Rx

First Rx age 8 yr: occln. therapy:

First Rx age 6 yr: surgery Rx worn constantly

no present Rx

L age 8 yr: present

First Rx age 5 yr: occln. therapy: worn constantly

present

No Rx as child: no surgery:orthoptic present Rx used selectively

Rx

trt:

l5JO

R. F. Hess and J. S.

Initlallq we measured &he spatial and temporal sensitivity function of the amblyopic eye for central viewing (0 deg eccentricity). This facilitated the chotce of appropriate spatial and temporal frequencies for the examination of the peripheral visual field. RESULTS In this study we investigated the visual field distribution of the amblyopic anomaly for the detection of a variety of spatio-temporal grating stimuli. The binocular and monocular fields of vision were assessed separately for representatives of clinically recognised forms of amblyopia. These included subjects with only strabismus, with only anisometropia (hy peropic and myopic forms) and those with strabismus and anisometropia. We found no evidence of a detection anomaly in the normal fixating eye of these subjects for either fovea1 or eccentrically located stimuli: consequently, we adopted the procedure of comparing the normal and fellow amblyopic eye of each subject in the subsequent analysis.

The srrabismic binocular visual field

Two cases of strabismus (subjects S.E-B. and T.O.: results not shown here) were observed in which no detection anomaly was found for foveally located stimuli of between 0.8-iO,Oc[deg. We verified that this was also true for peripherally located stimuli of varying spatial (0.8-lO.Oc/deg) and temporal (I, 8 and 32 Hz) frequency. The Snellen acuity in each of these subjects was only slightly reduced below 616, yet they complained of difficulty when using their amblyopic eye in everyday situations. The occurrence of an ambiyopic perceptuai anomaly in a straoismic eye without an associated loss in contrast detection for foveally presented targets is known (Hess ez al., 1978). These results confirm the normality of the peripheral fields of vision for detection in these cases. Within the moderate and severe classes of Snellen acuity loss associated with strabismus, fovea1 contrast detection anomalies have been well documented (Gstalder and Green, 1971; MitchelI e( al., 1973; Levi and Harwerth, 1977; Hess and Howell, 1977; Thomas, 1978; SjiSstrand, 1978; Hagemans and van der Wifdt, 1978; Bradley and Freeman, 1981; Rentschler et al., 1981). In Figs l-3 we examine how the detection anomaly varies as a function of the eccentricity of the stimulus in the horizontal visual field. AS already described, the stimulus was well localized in space being presented in a temporal time, and (sigma = 250 msec) and spatial (see Table I) Gaussian envelope. Contrast thresholds in the figures are compared for two different spatial and temporal frequencies in a number of representive cases. In each case the results for the normal eye (open symbols) are compared with those from the fellow amblyopic eye (solid symbols). Each experimental run consisted of alternate testing of the normal and amblyopic eye at

POIVTER

each eccentricity: to minimise any training effect, the testing was undertaken in counterbalanced order al each nasal and temporal eccentricity. Each datum in the figures represents the average of at feast two threshold determinations which in turn were derived from 6 to 8 staircase reversals: in most cases resufts were repeated on another occasion. In cases where eccentric fixation was present the results have been plotted such that zero eccentricity on the abscissa corresponds to the fovea of the amblyopic eye. In Fig. l(a) subject R.C. (an hyperopic 5deg esotrope) exhibits a contrast detection anomaly whose distribution across the visual field is spatial frequency dependent. Although the detection anomaly is similar for foveally presented stimuli of 3.2 and &4c/deg (both presented at 1 Hz) the eccentricity dependence of the anomaly varies with spatial frequency. At 3.2c/deg the difference between contrast detection of the normal and fellow amblyopic eye decreases as the stimulus is directed more eccentrically into the temporal hemifield, whereas it increases for more eccentric stimulation in the nasal hemifield. Hence at this mid-spatial frequency there is a naso-temporal asymmetry in the visual field distribution of the contrast detection anomaly. These results should be compared to the result obtained at a higher spatial frequency (6.4 c/de@. At this spatial frequency the detection anomaly seen for fovea1 stimulation decreases for both nasalfy and temporally located stimuli. A stight but opposite (i.e. contrary to that seen for 3.2 c/deg) naso-temporal asymmetry is now seen in the distribution of the detection anomaly. When the temporal modulation is changed from I to 8 Hz contrast reversal [Fig. I(b)], the slight nasotemporal asymmetry previously seen for 3.2 cideg at 1 Hz disappears; the detection anomaly is now more evently distributed across the central 20deg and disappears at 25 deg. The naso-temporaI asymmetry in the detection of the 6.4cjdeg stimulus at I Hz remains for 8 Hz temporal modulation. In Fig. 2 results from a similar experiment are presented for a myopic 15 deg exotrope (L.C.). For both spatial frequencies (3.2 and 6.4c/deg) at 1 Hz temporal modulation [Fig. 2(a)j, a strong nasotemporal asymmetry is seen in the distribution of the detection anomaly across the visual field. Detection thresholds are normal beyond 7.5-10 deg in the temporal field but progressively more abnormal for more eccentrically located stimuli in the nasal field. Thus the detection anomaly is restricted to the fovea and the nasal visual field. For 8 Hz temporal modulation [Fig. 2(b)] a similar though reduced asymmetry is seen for the distribution of the detection anomaly at both spatial frequencies. The detection responses in the temporal field are now also anomalous but to a lesser extent than those in the nasal field. The detection results from a more severe exampie of strabismic amblyopia (subject C.F., a hyperopic exotrope) are displayed in Fig. 3. In this case the detection anomaly is severe even at low to medium

Plate I. A selection of the horizontally-oriented sinusoidal grating stimuli used in this study are displayed here at a supra-threshold contrast level. Note that the relative angular extent of the circularly-symmetric Gaussian window was dependent upon grating spatial frequency (Table I). The horizontal bar indicates I deg.

1581

Amblyopic

deficit across

the visual

field

1583

STRABISMIC SF = 3-2 c/d TF = 8 n2

SF= 6.4 cfd TF.

r#r 109

10

I

*

I

,

1_

10

5

0

5

10

Tk+-’

(Twnporol)

(Nasal) VISUAL

Fig.

1.

2s

I -2s

l/(r1 20 15

10

ECCENTRICIll

0

s

I 10

II] 1s

20 (Nasal)

I

(f*mpoml

FIELO

ilk 5

( DEC)

sensitivity vs visual field eccentricity-(a) I Hz results, (b) 8 Hz results: subject R.C., strabismic; esotrope. moderate acuity deficit (6/24+). Symbols: + ambtyopic eye, 0 normaf fellow eye. Error bars indicate & I SD.

Contrast

hyperopic

STRABISMK SF=3.2cld

SF 2 3.2 cid TF i 8Hz

TF = 1 t4x 1

1L

i

VISUAL Fig.

2.

Contrast

sensitivity

FIELD

ECCENTRICIYY

( OEGI

vs visual field eccentricity: subject L.C., myopic acuity deficit (6/24).

strabismic;

exotrope.

moderate

25

I5R.t

R F HE_TSand J S

PCWTFR

anomaly on visual field eccentrtctty is affected bk SICIT factors as the type of strabismus. the severtty (III amblyopia and the spatio-temporal frequent;. of the test stimulus. Thus there is not a unique dtjcrlptlon of the variation of the detection anomaly with visuai field eccentricity in strabismic amblyopia, other than that it is always absent in some peripheral parts ofthe binocular visual field.

spatial frequencies (0.8 and 3.2 c deg) and a large amount (15 deg) of eccentric fixation was present. (The results have been adjusted so that the fovea1 results correspond to Odeg eccentricity: because of this. only limited results remain for stimuli falling in the nasal field.) Since the detection thresholds in the amblyopic eye do not show any fall off with eccentricity, the detection anomaly is greatest within the central IOdeg and gradually reduces with eccentricity. These results show no obvious naso-temporal asymmetry in the distribution of the amblyopic eye’s detection threshold out to IOdeg. A change in the temporal stimulation from 1 to 8 Hz does not alter this picture [compare Fig. 3(a) and (b)]. These results suggest that there is a great deal of variation in the distribution of the detection anomaly across the visual field within the strabismic classification of ambiyopia. For mild and moderate amblyopias (corrected Snellen acuity 6160 or better) the distribution of the anomaly depends upon the spatial and temporal frequency of the stimulus used in its assessment. In general these results (Figs l-3) are representative of results obtained using similar methods on other strabismic individuals and suggest that, in amblyopia associated with a strabismus, the detection anomaly is greatest in the central field, being much reduced in nasal and temporal regions. The exact nature of the dependency of the detection

The anisometropic

binocular cisual fielri

The distribution of the detection anomaly across the visual field in amblyopic subjects with anisometropia and strabismus is displayed in Figs 4 and 5. These results both concern anisometropes with a hyperopic refraction who have eccentric fixation and a microtropia. These results are similar to those already described for amblyopes with a strabismus alone. The detection anomaly at 0.8, 3.2 and 6.4 c/deg exhibits a strong naso-temporal asymmetry, with the temporal field being spared in this case of an exodeviation (Fig. 4: A.W.) and the nasal field being spared in this case of an esodeviation (Fig. 5: C.G.). When temporal modulation is changed from I to 8 Hz this asymmetry in the visual field distribution of the anomaly is not greatly affected [compare Figs 4(a) and (b), 5(a) and (b)]. Figures 6 to 8 display results for hyperopic and myopic anisometropes who do not have any mea-

STRABISMIC

CF

SF = 0.8

> c > ;lx

I

’ -25

1

20

c/d

TFSIHZ

4

I

ti

15

IO

I

5

I

0

4

I

5

1

10

1

15

,

1

20

25 J

’

25 I

20 I

15

10

5

0

5

10

SF n 3.2cJd

15

20

SF=

25

3.2

c/d

TF - BHZ

r-l : ;

O\ O-0

,o

‘0

1 ’ (Temporal

(Nosal

) VISUAL

Fig. 3. Contrast

sensitivity

1

FIELO

2c

20 I

15 I

tlrmporol

I

ECCENTRlCIrV

10 4

5I

01

5I

loI

1s I

t DEG 1

vs visual field eccentricity: subject C.F., hyperopic acuity deficit Q/60).

20 I

(Nasal)

strabismic;

exotrope,

severe

is

Amblyopic STRABISMIC

deficit across

I ANISOMETROPE SF = 3.2 c/d TF -

A.W.

/

,’

I llr

100 -

7

1585

the visual field

SF.

3.2

TF=

snz

c/d

loo -

0

G 10c F z ; 5

5 ’ 25

20

IS

IO

5

0

5

IO

I5

20

25

1-I

14 20

25

AW.

tlcmporai)

I Nosal VISUAL

Fig. 4. Contrast

STRABISMIC

sensitivity

I

IO

0

1

I

‘,

ECCENTRICITY

1

5

’

5

’

10

’

15

I

( DE

TF i 6 Hz

I Nasal

strabismic

anisometrope;

I ANISOMETROPE SF-0,6c/d

5

IA

20

15

1

I

1

I

I

I

10

5

o

5

IO

15

(Ttmporal)

I

I

25

(Nasal VISUAL

Fig. 5. Contrast

Hz

20

sensitivity

1

FIELD

’

(Nasal)

~Tcmpaol) ECCENTRICITY

I

25

SF.6.Lcld

G)

vs visual field eccentricity: subject A.W.. hyperopic exotrope, mild acuity deficit (6/9).

TF=l

’

20

I

/I

ITrmporol

FIELD

1

IS

I t 1

( DEG)

vs visual field eccentricity: subject CC.. hyperopic micro-esotrope. severe acuity deficit (3160).

strabismic

anisometrope;

)

IiS6

R.

F. HESSand

J. S.

PDISTEK

ANISOMETROPE P w.

I

PW

SF*l,§c/d TF=lH(r

SF-

’

2s

20

15

(imporal

IO

5

0

5

10

1s

)

20 (Nasal

VISUAL

Fig. 6. Contrast sensitivity

vs

’

20

15

(lmlpomi

FIELD

ta

J

0

5

x)

15

cld

20

(Nosot

1

ECCENTRICITY

I

(DEGI

visual field eccentricity: subject P.W., hyperopic anisometrope; no deviation, mild acuity deficit (6/9+).

I “Y

2s

1

3.2

TF=IHz

/:\ 0

I

SF ml.6

,

p

.

SF=1,6cld TFS El+2

F-0,

1

I

I

1

10

I5

20

J 25

I

I

SF 83.2 TF=

SF m 3.2 c td

Cld

TF=

1Ur

6tiX

1

2

2

t Temporal

(NOWI1 1

1 VISUAL

Fig. 7. Contrast

FlELo

20

(1*rnforoi ECCENTRICITY

15 1

10

5

0

s

-i!rk-is

10

(Nasal

(DEG)

sensitivity YS visual field eccentricity: subject M.K., hyperopic anisometrope; deviation. moderate acuity deficit (6:361.

no

1

Amblyopic

deficit across

surable strabismus or eccentric fixation. Subjects P.W. (Fig. 6) and M.K. (Fig. 7) are both hyperopes and exhibit a detection anomaly whose distribution is quite different from any of the results so far discussed. The relative contrast threshold loss in essentially independent of locus of assessment in the binocular visual field. The central and peripheral regions of the amblyopic field. at least out to Zjdeg (the extent of our initial measurements), are similarly reduced in sensitivity compared with normal vision. No large naso-temporal asymmetry is present and the form of both of these sets of results does not appear to depend upon the spatio-temporal stimuli used in the investigation. In Fig. 8 qualitatively similar results are seen for a subject (N.N.) with anisometropia of the myopic form. These results, in which the sensitivity to 3 different spatial (I .6, 3.2 and 6.4 c/deg)

the visual

[sy?

field

and :! different temporal (I, 8 Hz) frequencies arc compared, also show that although a slight nasotemporal asymmetry exists the detection anomaly seen for central vision is never reduced at any peripheral eccentricity. The naso-temporal asymmetry is now present without any indication of peripheml sparing, quite unlike that seen in the strabismic results (Figs l-3). This finding can be generalized to the extent that it is independent of spatial (1.6. 3.2 and 6.4c:deg) and temporal (I.8 Hz) frequency. Figure 9 summarizes the results of all 17 of the subjects tested. The magnitude of the fovea1 deficit for contrast sensitivity is plotted against the minimum peripheral deficit (out to 30 dcg). Results arc shown for 3 different spatial frequencies and for subjects with a strabismus (open symbols). anisometropia {solid symbols) and both (half-solid sym-

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R. F. Hiss and J. S. POINTER

1588

amblyopic detection anomaly across the visual tieId is clearly different between subjects who manifest ;i strabismus and those that do not. It seems that it is the presence or absence of the strabismus. not the anisometropia, that determines whether or not the peripheral field is spared in amblyopia. Comparison

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In the experiments described so far detection thresholds have been measured as a function of eccentricity for two or three representative spatial and temporal frequencies. For each of these stimuli the form of the fall off of detection thresholds with eccentricity has been investigated for normal and fellow amblyopic eyes. In this investigation the central 25 deg of the binocular visual field has been tested. It is of obvious interest to know whether these conclusions are equally valid for more eccentric regions of the visual field. For example, is the detection anomaly in the more anomalous hemifield for strabismics, and in both hemitields for non-strabismic anisometropes, present over the entire visual field, i.e. both in the binocular and the monocular regions? At extreme eccentricities the visual field changes from being binocular to monocular: consequently, if amblyopia has developed from binocular competitive interactions the detection anomaly may only be present in the binocular visual field. In Fig. IO contrast detection is plotted for a normal subject (J.P.) as a function of the spatial frequency of

I 00 DEFKIT

Fig. 9. The fovea1 contrast sensitivity deficit is plotted against the minimal contrast sensitivity deficit at any eccentricity within the central 30deg.

bols). The straight lines represent the two extreme predictions, namely mainly a central loss (dashed line) and an evenly distributed loss (solid line). The results of subjects with a strabismus (independent of whether they had an accompanying anisometropia) tend to fulfill the first prediction whereas nonstrabismic anisometropes tend to fulfill the second. Thus the overall form of the distribution of the

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the stimulus (temporal modulation I Hz) in three different regions of the visual field. Stimuli were presented in a fixed Gaussian patch (X and J sigma = 10 deg) in space. with a Gaussian envelope in time (D = 250 msec). The two eyes of this normal subject were compared for each of three eccentric zones after a careful refraction at each eccentricity. In the top right frame of the figure the location of the grating stimulus within the field of vision is diagrammatically illustrated. Stimulus A was centered on the fovea (0 deg eccentricity); stimulus B was located at the most eccentric part of the binocular visual field (centred at a 50-55 deg temporal field eccentricity, its most eccentric edge being 2.5 deg within the binocular zone); and stimulus C was located in the least eccentric part of the monocular visual field (centred at a 65-70 deg temporal field eccentricity, its least eccentric edge being 2.5 deg within the monocular crescent). This alignment precision with our amblyopic subjects ensured that any fixation nystagmus exhibited by the amblyopic eye did not displace the stimulus across the binocular/monocular boundary. For the normal observer (Fig. IO) the fovea1 contrast detection function is similar for each eye and has the expected form (curve A); there is a peak sensitivity of around 200 located near 3 c/deg, a low spatial frequency fall off (slope = -0.5) and a high frequency fall off. The contrast detection function is also similar for both eyes when the stimulus is located in the eccentric part of the binocular field (at 50-55 deg eccentricity), although now the function has beon displaced to a lower sensitivity and to lower spatial frequencies (curve B). The peak sensitivity of around 50 occurs near 0.4 c/deg, but there is a similar low spatial frequency fall off (slope = -0.5) and a high spatial frequency fall off extrapolating to a much reduced acuity of around 6.5c/deg. In the least eccentric part of the monocular visual field (65-70 deg eccentricity) a similar contrast threshold function is obtained, although shifted even further down and further to the left (curve C). The peak sensitivity of 30 is obtained near 0.2 c/deg and the extrapolated acuity is now reduced to around 3 c/deg. These results for normal vision suggest that, at least for medium spatial frequencies, the slope of the fall off in detection threshold across the binocular visual field is further increased within the more eccentric monocular field. In Figs 11-13, for three amblyopic subjects, the results of a similar comparison between the normal and the amblyopic eye’s detection response in these three regions of the visual field are compared. The results of one strabismic and two non-strabismic anisometropic amblyopes are shown. In the case of R.C., a strabismic amblyope (Fig. I I), the detection anomaly which involves all spatal frequencies tested (0. I-IO c/deg) for central fixation (0 deg eccentricity) is absent for stimuli located in either the eccentric part of the binocular field or in the monocular field of vision. The normal and fellow amblyopic eyes

1591

exhibit similar thresholds across spatial frequency for these eccentrically located stimuli, irrespective of whether they stimulated the monocular or binocular fields of vision. These results extend the findings of R.C. which are displayed in Fig. I. They suggest that the equilization ofsensitivity in normal and amblyopic eyes seen to occur at 2&25 deg temporaily in Fig. I(a) for 3.2 cideg is also true at 55 deg in the binocular field for lower spatial frequencies. Thus this elimination of the detection anomaly in the strabismic eye occurs as a function of eccentricity and not because of a transition from the binocular to the monocular visual field. This finding should be compared with results obtained under similar conditions for the two nonstrabismic anisometropes. The results for P.W., a hyperopic anisometrope, are shown in Fig. 12, and those for N.N., a myopic anisometrope, are shown in Fig. 13. In each of these cases the contrast detection deficit is present for centrally fixated stimuli and also for stimuli presented at a very eccentric locus of the binocular visual field. Within the spatial frequency range that is common to these two widely disparate regions, the detection deficits are comparable. This supports and extends the previous results (P.W., Fig. 6; N.N., Fig. 8) relating to the variation of the detection anomaly at selected spatial frequencies over the central 25 deg of the visual field. Notice that for each type of refractive anisometrope the detection anomaly which had been maintained over 5655 deg of the binocular visual field disappears at all spatial frequencies when the least eccentric region of the monocular visual field is tested (65-70 deg eccentricity). The sensitivity in the monocular visual field of the amblyopic eye is normal for stimuli between 0.1-2 c/deg, a spatial frequency region for which anomalous responses occur within the binocular visual field.

DISCUSSION

Ambfyopic Dimal loss The results of this study can be considered on two different levels. At the microscopic level, the results suggest that there is considerable variation in the contrast detection anomaly in different individuals with amblyopia. The details of the distribution of the anomaly across the visual field depend upon such factors as the spatial and temporal frequency of the stimulus, the type of amblyopia, the severity of amblyopia and whether it is assessed in the monocular or binocular visual field. The finding of such a large variation in turn underlines the inadequacy of using a large-field grating to investigate amblyopia. So, for example, the hemifield asymmetry of the anomaly in mild-moderate strabismic amblyopia could well explain the apparent conflict in the literature concerning the effect of different grating field sizes in amblyopia (Hess, 1977; Hagemans and van

R. F HESS and J S. POIVTER

1978). The cases reported by Hess (1977) were of a more severe form and exhibited a symmetrical acuity loss (Hess and Jacobs. 1979). If the cases examined by Hagemans and van der Wildt (1975) exhibited a strong asymmetry in the distribution of the anomaly this might explain their finding of a strong dependence of amblyopia on the field size of the stimulus. A further factor which might have contributed to some of the present confusion in this literature is the use of the traditional clinical strabismic/anisometropic classification. In place of this, the present results suggest that a more adequate would be along strabismic/nonclassification strabismic lines. Such a division takes into account amblyopes the fact that some anismotropic (especially those with a hyperopic refraction) have microtropias and eccentric fixation. These individuals have previously been classified as anisometropes yet the present psychophysical assessment of the distribution of their anomaly, as well as the results of an earlier study of the anomaly (Hess et al., 1980), suggest a strabismic-like response. All of these findings argue that in future the psychophysical analysis of amblyopia should be more refined in both the localization of the stimulus (in space, and also in spatial and temporal frequency) and in the clinical details of the type of amblyopia studied. At the macroscopic level, the present results suggest that the overall features of the distribution of the amblyopic detection anomaly across the visual field differ in strabismic and in non-strabismic, anisometropic, amblyopes. In strabismic subjects, including those with anisometropia, the detection anomaly involves only the more central part of the visual field. In mild cases of strabismic amblyopia the paracentral and peripheral areas in one hemifield are spared. Similar asymmetries in the visual acuity of esotropic 1981) and exotropic and Fronius, (Sireteanu (Nawratzki and Jampolsky, 1958) amblyopes have been reported previously. In severe cases of strabismic amblyopia the detection anomaly is more symmetrically distributed but still involves mainly the central region of the visual field (i.e. within the central 30 deg). The extent of the central field that is affected depends upon the spatial and temporal frequency of the stimulus and should not be considered in terms of a fixed area. This predominantly central field loss in strabismic amblyopia is also apparent from earlier acuity and contrast sensitivity studies (Kirschen and Flom, 1978; Thomas, 1978; Avetisov, 1979; Hess and Jacobs, 1979; Sireteanu and Fronius, 1981). This finding for strabismic amblyopes contrasts with the result found in non-strabismic, anisometropic amblyopes. For these cases, the detection anomaly involves both central and peripheral regions of the visual field. Although the threshold loss may be slightly different in each hemified it does not vary greatly as a function of eccentricity within the binocular field. Furthermore, the form of the loss does not dzr Wildt.

vary greatly with either the spatio-temporal teristics

of the stimulus

or the severity

chxaiof visual loss.

This detection anomaly. which is evenly distnbuted across the binocular visual field, is not present in the monocular visual field. These findings lend support to the notion that there is a fundamental difference in the neural basis of strabismic and non-strabismic. anisometropic amblyopia, a proposal previously put forward on the basis of the different threshold behaviour of these two types of amblyopia at different luminances (Hess et nl., 1980) and contrast levels (Hess et al., 1983).

Relecance 10 animal models

The present results argue that strabismic and nonstrabismic, anismometropic amblyopia are likely to have different neural bases. They suggest that nonstrabismic anisometropic amblyopia probably involves underlying competitive neuronal interactions known to be important in the developing animal visual system (Wiesel and HUM, 1965; Guillery, 1972; Blakemore, 1978; Eggers and Blakemore, 1978; Singer, 1978; Cynader, 1982; Sherman and Spear, 1982): this follows from the even distribution of the anomaly across the binocular visual field. Since the anisometropic anomaly is not present in the monocular visual field, any direct, non-competitive and permanent deprivation effect (e.g. from blur) must be slight. This conclusion argues against one aspect of the highly original proposal put forward by tkeda and Wright (1976) on the basis of their animal models of strabismic and non-strabismic, anisometropic amblyopia. They proposed that these two forms of amblyopia had a common neural basis and that the direct, non-competitive effects of image blur initiated the competitive imbalance in the cortex. Our results do not bear directly upon this second issue, namely the reason behind the competitive imbalance. This aspect of Ikeda and Wright’s proposal may be correct if one postulates that blur produces a competitive imbalance at the cortex by reducing retinal neuronal activity without having any permanent effects. However, it can only be applied to the results from the anisometropic amblyopes because blur would affect contrast sensitivity at any one spatial frequency equally across the whole visual field. Thus, if the resultant neural loss passively followed the attenuated stimulation due to blur, the effects at any one spatial frequency should not be restricted to the central field, but it should involve the whole field over which the stimulus can be detected. Although these results in non-strabismic, anisometropic humans are consistent with the notion that competitive neuronal interactions underly amblyopia, and thus fit in well with our current concept of binocular competition and its importance in the development of the animal visual system (Wiesel and Hubel, 1965; Guillery, 1972; Blakemore, 1978; Cynader, 1982; Sherman and Spear. 1982) the results for

I593

Amblyopic deficit across the visual field strabismic humans with amblyopia are less clear cut. Specifically, there are two findings from the present human strabismic study and from previous strabismic animal studies (Ikeda and Wright. 1976; Ikeda et al., 1977: Ikeda and Jacobson, 1977) which are more difficult to understand in terms of our present concept of binocular competition. Firstly. strabismic amblyopia involves mainly the central region of the visual field: why should competitive influences involve only central vision? Secondly, strabismic amblyopia is asymmetrically distributed across the central field: it is difficult to understand why binocular competitive influences should exhibit such asymmetries. One could speculate that in strabismus any image displacement would result in less correlated responsivity between left and right eye inputs to binocular neurones which have smaller receptive fields 1981). Competitive and Fronius, (Sireteanu influences should in turn affect the neurones with the smallest receptive fields most and those with the largest receptive fields least. Therefore the resultant amblyopia should extend evenly and symmetrically over the central field for high spatial frequency stimuli and not be present over any of the visual field for low spatial frequency stimuli. The present results do not substantiate this speculation. Another possibility is that the upper limit of disparity may increase with eccentricity for neurones with receptive fields of a given size. This would ensure that any absolute image displacement would produce less imbalance between the monocular inputs of peripherally located neurones. Until this information is known for spatially extended targets it remains one possible explanation of how a competitive model might account for the visual loss being restricted to the centre of the visual field as a result of strabismus. The asymmetric nature of the loss is more difficult to explain in terms of a competitive model. We have gone to some lengths to ensure that this asymmetry cannot be accounted for by monocular eccentric fixation of the amblyopic eye. There has been a recent attempt to determine whether amblyopia is mainly a spatial frequency or retinal locus specific deficit (Bradley et al., 1984). The present results clearly point to a retinal locus specific deficit underlying amblyopia. In strabismus, it is centrally (central 30 deg) located and asymmetrically distributed within the visual field. In anisometropia, it is restricted to the binocular field of vision.

Acknowledgemenrs-The authors wish to acknowledge the financial support of the Medical Research Council of Great Britain and the Wellcome Trust. We thank several of our colleagues for helpful discussions. Special thanks are due to Ruth Banks, Chief Orthoptist, Addenbrooke’s Hospital, Cambridge, who undertook an orthoptic examination upon all subjects prior to their participation in the study and to an anonymous referee who suggested the inclusion of Fig. 9. The patience of our subjects is gratefully acknowledged. R.F.H., is a Wellcome Senior Lecturer.

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Bradley A., Freeman R. D. and Applegate R. (1984) IS amblyopia spatial frequency or retinal locus specific? Vision Res. 25, 41-54.

Cynader M. S. (1982) Competitive neuronal interactions -underlying amblyopia. Human Neurobiol. I, 3i39. Eeeers H. M. and Blakemore C. 11918) Phvsioloeical basis -if anisometropic amblyopia. Sc‘ience: N. 2. 201: X&261. Freeman R. D. and Bonds A. B. (1919) Cortical plasticity in monocularly deprived immobilized kittens depends on eye movement. Science, N. Y. 206, 1093-1095. Gstalder R. J. and Green D. Cl. (1971) Laser interferometric acuity in amblyopia. J. Pediaf. Ophthal. 8, Z-256. Guillery R. W. (1912) Binocular competition in the control of geniculate cell growth. J. camp. Neural. 144, Ill-121. Hagemans K. H. and Wildt G. J. van der (1978) The influence of the stimulus width on the contrast sensitivity function in amblyopia. Incesr. Ophthal. cisual Sci. 18, 842-841.

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K;lr>
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G .ind F!om

d~fTcrrntretindl :lw.

l_e\r D. 11. and Har\\erth R. S 11977~ Spario-temporal mt
in strabismic

Sci. 17, 577-581

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