Visual field defects in esotropic cats: a developmental consequence of the squint

Visual field defects in esotropic cats: a developmental consequence of the squint

ELSEVIER Behavioural Brain Research 74 (1996) 161-166 BEHAVIOURAL BRAIN RESEARCH Research report Visual field defects in esotropic cats: a develop...

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ELSEVIER

Behavioural Brain Research 74 (1996) 161-166

BEHAVIOURAL BRAIN RESEARCH

Research report

Visual field defects in esotropic cats: a developmental consequence of the squint M. Di Stefano *, C. Gargini, F. Romano Dipartimento di Fisiologia e Biochimica, Universitgt degli Studi di Pisa, Via S. Zeno 31, 56127, Pisa, Italy

Received 7 July 1994; revised 21 January 1995; accepted 11 February 1995

Abstract

In nine adult cats with surgically induced esotropia (squint-angle ranging between 8° and 32°), the extent of binocular and monocular visual fields was behaviourally assessed by the food-perimetry method. Results indicate that: (1) The extention of both the nasal and the temporal hemifield of the esotropic eye is narrowed. (2) Field losses are largest in the cats with severe esotropia (> 15°); yet the relationship between rate of impairment scored in each animal and individual angles of squint is not linear. (3) In the cats with severe esotropia, the visual field of the non-deviated eye is also narrowed. (4) We suggest that field deficits reflect a stop in the developmental expansion of the immature visual field as a consequence of ocular misalignment. Keywords: Cat; Esotropia; Perimetry;Orienting response; Nasal-field;Temporal-field;Development

1. Introduction

Behavioural studies of the visual field in cats raised with unilateral convergent strabismus (esotropia) provide controversial results. Kalil [14] and Ikeda and Jacobson [10] reported that in esotropic cats there is an almost complete suppression of the nasal field of the deviated eye, whereas Berman and Murphy [-2] found that the esotropic eye retains a normal visual field. The field deficit has been ascribed to either structural changes in the projections from the deviated eye [12] or to a functional inhibition of their cortical representation [13,15]. However, the strict resemblance between the strabismic visual field of adult esotropes and the immature visual field of kittens with normal eye alignment [22], is worth to be considered. Restriction of the visual field extension could be interpreted as a developmental consequence of ocular misalignment. In this light, field losses may simply reflect a stop in development of the corresponding retinal projections. The reported alterations in anatomy [11,12] and visual function [ 3 , 4 ] o f

* Corresponding author. Fax: + 39 50 552183. e-mail: [email protected] 0166-4328/96/$09.50© 1996ElsevierScienceB.V. All rights reserved SSDI 0166-4328(95)00145-X

the esotropic pathway might parallel the developmental arrest. We have re-examined the occurrence of visual field defects in esotropic animals preceding the study of their electrophysiological correlates (Di Stefano and Gargini, in preparation). Our behavioural data, that are in general agreement with earlier results [10,14,23] indicate not only a loss of the nasal field, but also demonstrate a temporal field loss in esotropic animals. Furthermore, our results provide additional information about the relationship between the extent of the field deficit and the angle of ocular deviation.

2. Methods

Nine cats were used in this experiment. All the animals were born and raised in the laboratory animal colony. In each cat unilateral convergent strabismus was induced within the 4th postnatal week that is before the onset of the critical period of neural plasticity. The esotropic deviation was produced by resecting, under ketamine anesthesia (40 mg/kg body weight, i.m.), the tendon of the lateral rectus muscle of the right eye.

M. Di Stefano et al./Behavioural Brain Research 74 (1996) 161-166

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2.1. Eye

alignment

different assessments. For each cat the averaged values are reported in Table 1. Two cats died before the recording session. In these animals the ocular deviation was evaluated by close comparison of their corneal reflex photographies to that of the other cats in which the angle of squint was measured during the electrophysiological recordings.

Despite of the nearly identical procedure to produce the squint, each cat developed a different angle of inward deviation. The angle of esodeviation was firstly assessed in the awake animals by corneal reflex photography [ 19] and was further measured during the electrophysiological experiment after the period of perimetric testing at ages ranging from 9 to 14 months. The methods used to estimate ocular misalignment in the anaesthetized, paralysed animals are reported in detail elsewhere [ 5 ]. There was generally a very good agreement between the two

2.2.

Perimetry

In the 9 strabismic cats, the extent of binocular and monocular visual fields was measured when they had reached adulthood (7-12 months of age), using the food

Table 1 Percentage of positive orienting responses Deviated eye:

Nasal field (left)

Temporal field (right)

Cat

Squint (°)

45 °

30 °

15 °



15 °

30 °

45 °

60 °

75 °

90 °

1 2 3 4 5 6 7 8 9

8 9.2 11.5 12 15 18 28.5 29.2 32

62.8 56 51.7 46.5 47.5 6.7 5.7 0 10

86.5 91.7 90.8 84.5 88.5 14 18.8 11.8 17

85 91.8 93 87.5 90.7 59.6 60.3 54.6 53

88.5 91 90.5 91.5 93.5 69.9 73 68 75.9

100 100 100 100 100 94 92 91.5 94.5

100 100 100 100 100 100 100 100 100

100 100 100 100 100 98 94 92 100

99 98.5 98.5 96 95.5 82 85.2 79 77

93.5 89 91.5 95 93.5 56.2 60 58 56.2

58 49 62 53.5 52.5 33.5 35 39 42.5

Non-deviated eye:

Temporal field (left)

Nasal field (right)

Cat

Squint (°)

90 °

75 °

60 °

45 °

30 °

15 °



15 °

30 °

45 °

1

8

2 3 4 5 6 7 8 9

9.2 11.5 12 15 18 28.5 29.2 32

96 94 97.5 95.2 92.4 89.5 87.2 91.3 88

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 94 92 91.5 94.5

100 100 100 100 100 100 100 100 100

100 100 98 100 100 72.5 75.5 71.3 76.2

100 100 100 100 100 100 100 100 I00

100 100 100 100 100 100 100 100 100

62 71 62.5 67.5 72.5 63.5 59.5 58.5 59

Both eyes:

Left field

Right field

Cat

Squint (°)

90 °

75 °

60 °

45 °

30 °

15 °



15 °

30 °

45 °

60 °

75 °

90 °

1 2 3 4 5 6 7 8 9

8 9.2 11.5 12 15 18 28.5 29.2 32

88 90 87.5 87.2 88.3 86.3 86.2 86.5 85.5

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

100 100 100 100 100 100 100 100 100

60.5 61 58 61.3 63.5 59.5 59.2 60 57.5

33 32.5 34.5 34.2 35 31.5 32.5 34.3 31.5

25.5 27.2 24.5 27.3 29.2 23.3 26.2 31.5 27.5

M. Di Stefano et al./Behavioural Brain Research 74 (1996) 161-166

perimetry method, as firstly described by Sprague and Meikle [24]. On a semicircular table that served as a perimeter, the left and right visual fields were represented. Each hemifield, extending from 0 ° to 90 ° was subdivided in six sectors corresponding to 15, 30, 45, 60, 75 and 90 degrees of visual angle as measured for a viewing distance of 47 cm. At such a distance the cat was held steady, its head gently restrained, by an experimenter sitting at its back. A second experimenter sat directly opposite the cat. Cats were trained to fixate straight ahead, toward the midline of the perimeter, at position 0 ° where the second experimenter displayed the fixation stimulus, a small piece of meat held by forceps on the table. Testing stimuli (morsels of food as above described) were not presented unless stable fixation was obtained; this condition was aided by tapping the forceps against the edge of the table at position 0 °. When the experimenter sitting in front of the animal was assured of the cat's central fixation he introduced from beneath the table the testing stimulus on one of the six positions of either hemifield and at the same time he removed the stimulus presented in the midline. If the cat oriented its eyes and head toward the peripheral stimulus he was released and allowed to eat the piece of meat on the point of presentation. The cat's immediate reaction to the stimulus was scored as a positive response, whereas delayed moving and/or orientation toward a position other than the correct one was counted as an error. Responses to the 0 ° position were tested in the following way: when the cat's fixation was surely directed to the centre of the perimeter, the experimenter removed the fixation stimulus and introduced the testing stimulus at the same central position. Cats were tested during several daily sessions under binocular and monocular viewing conditions. The animals were initially trained with both eyes open. When they became familiar with the testing procedure, one eye was occluded by an opaque contact lens and monocular training with both the normal and the deviated eye was performed. Orienting responses were scored after about 3 weeks of training that was the time needed to obtain a stable performance under either viewing conditions. Each daily session consisted of 3 trials for each position of the two hemifields and 3 trials for the 0 ° position. Overall, in each cat we scored 156 orienting responses in the binocular condition, and 180 responses for each eye under monocular viewing. The order of presentation of stimuli at the different eccentricities in the two hemifields followed a semi-random schedule analogous to that used by Simoni and Sprague [21]. Different sequences were used in the different testing sessions. Four blank trials were randomly introduced in each sequence. On blank trials the attention of the cat was directed centrally toward the fixation stimulus. Then the fixation stimulus was removed but no testing stimulus

163

was presented. During blank trials all animals remained initially still looking at the central position and then they moved randomly on the table in search of the stimulus.

3. Results

Table 1 shows the results obtained by perimetry testing. For each animal are reported the percentages of positive orienting responses scored at each eccentricity under binocular and monocular viewing. The cats are ordered by angle of squint from smallest to largest. 3.1. Esotropic eye Inspection of the data reveals that in each nasal sector and in the temporal field > 45 ° the response level of the deviated eye of all animals is below 100%. The largest decrease of responsiveness is present in cats with severe strabismus. The relation between angle of squint and loss of responsiveness in the two hemifields, is shown in Fig. 1. For each cat the angle of squint is plotted as a function of the 'nasal loss' (Fig. 1A) and of the 'temporal loss' (Fig. 1B). 'Nasal loss' corresponds to the percentage of negative orienting reactions averaged across the three nasal sectors. 'Temporal loss' represents the mean percentage of errors scored at the periphery of the temporal field (60 °, 75 ° and 90 ° of eccentricity) where the response level is below 100%. As shown, the failure of orienting in the nasal field is mild (25%-30% of negative responses) for the five cats with an angle of squint < 15°, whereas it is twice larger (60-67% of negative responses) for the four animals with angle of squint > 15°. In all animals the loss of responsiveness in the temporal field is less pronounced than in the nasal region; yet it is largest in the four cats with severe squint (39%-41% vs. 20-24% of negative responses). At each nasal and temporal eccentricity the response rate of two groups of animals (cats with squint > 15° vs. cats with squint <15 ° ) was compared by the Mann-Whitney test performed on the percent values submitted to the arcsine transformation. Statistical comparisons have shown that at all test angles, but 30 ° in the temporal hemifield, the loss of orienting reactions is significantly greater for the group of cats with largest squint (Mann-Whitney test: at 0 ° and at each eccentricity in the nasal hemifield z=2.5, P < 2 % ; at 15 °, 60 °, 75 ° and 90 ° in the temporal hemifield, z = 2.4, P < 2%; at 45 ° in the temporal hemifield z = 2.2, P < 5%). The extent of the visual field through the strabismic eye of the two groups of animals is represented in Fig. 2. In the very strabismic animals (cats 6-9) the extension of the visual field is severely reduced in both the nasal and the temporal regions, whereas in the less strabismic

164

M. Di Stefano et al./BehaviouralBrain Research 74 (1996) 161-166 DEVIATED EYE

NASAL LOSS

A

IO0

Nasal f it=it[

~"

0"

15"

T~ mnc*ra[ f i e l d

~o z o ,,,

75

O O 7

O

t~ p..

O

50

*o D

<15"

z

O OO 0

t~

25

>15"

O

W

cl z 2~ .

0

,

,

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5

0

I

,

,

10

,

i

I

. . . .

15

t

. . . .

20

I

. . . .

25

L

. . . .

50

35

ANGLE OF SQUINT (deg)

Fig. 2. Extension of the visual field through the deviated eye. At each stimulus position the length of the corresponding line is proportional to the mean percentage of correct responses scored in cats with esotropia <15 ° vs. cats with esotropia >15 ° (stippled field). Full length indicates 100% of positive reactions.

TEMPORAL LOSS

13

NON DEVIATED EYE

100

Temporol ~ . l a

ew

~5°

0*

1S*

~.,o.ol flel d

75

~9 ud z 50

*o

o

%

o

z

<15"

UJ

25

o

UJ

OZ

©

(9

O

>15'

Fig. 3. Extension of the visual field through the non-deviated eye. Conventions as in Fig. 1.

2~ , , , I

. . . .

5

I

10

. . . .

I

15

. . . .

I

20

. . . .

I

25

. . . .

l l l l ~

30

35

ANGLE OF SQUINT (deg)

Fig. 1. Relationship between the individual angles of squint and the loss of performance scored in each cat in the nasal (A) and in the temporal hemifield (B). Each 'nasal loss' value corresponds to the mean percentage of negative responses recorded in the nasal field. Each 'temporal loss' value represents the mean percentage of errors scored at the 60°, 75° and 90° of eccentricity in the temporal field.

m u s ( M a n n - W i t n e y test: at 0 °, z = 2 . 5 , P < 2 % ; at 30 °, z = 2 . 7 , P < l % ; at 90 °, z = 2 . 5 , P < 2 % ) . At 45 °, in the nasal hemifield the level of response of all a n i m a l s is b e l o w 100%, r a n g i n g between 58.5 a n d 72%, a n d the difference between the two g r o u p s of cats is n o t significant. 3.3. Both eyes

cats (cats 1 - 5 ) the visual field loss is restricted to the p e r i p h e r a l p o r t i o n of the n a s a l field. 3.2. Non-deviated eye

In m i l d e s o t r o p i c cats the extent of the visual field t h r o u g h the n o n - d e v i a t e d eye (Fig. 3) is r o u g h l y c o m p a rable to t h a t m e a s u r e d in n o r m a l a d u l t a n i m a l s [ 1 0 , 2 0 , 2 7 ] . In cats with severe squint the response rate at the central p o s i t i o n a n d at 30 ° a n d 90 ° in the t e m p o r a l field, is significantly lower t h a n in cats with m i l d strabis-

As c o m p a r e d to p e r i m e t r i c m e a s u r e m e n t s p e r f o r m e d in n o r m a l l y r e a r e d cats 1-20,21] the b i n o c u l a r field seems to be n a r r o w e d in esotropes. I n all animals, in fact, the response level d r o p s b e l o w 40% (range 35-27.3%) at 75 ° a n d 90 ° of eccentricity in the right hemifield, t h a t is in the e x t r e m e p o r t i o n of the visual field ipsilaterally to the d e v i a t e d eye (Fig. 4). In this s a m e region of the field, however, the cats show a larger n u m b e r of orienting responses when they are m o n o c u l a r l y tested t h r o u g h the d e v i a t e d eye (mean 62%, range 93.5-35%). This observa-

M. Di Stefano et aL/Behavioural Brain Research 74 (1996) 161-166

BOTH EYES Left

h

r"

°o O~



.....

~nifield

t.la o

,o ' O

o

Fig. 4. Extensionof the binocularvisualfield.Conventionsas in Fig. 1. tion suggests that the loss of most peripheral portion of the binocular field may be attributed to the fixation habit of the esotropic animals that favours the nondeviated eye [9,11,25]. In fact, if strabismic cats adopt a prevalent fixation through the non-deviated eye, one may expect that under binocular testing they can fail to localize stimuli presented in the temporal region of the strabismic eye.

4. Discussion

In agreement with earlier reports [10,14,23], present results confirm that in esotropic cats the visual field of the deviated eye is restricted both in the nasal and in the temporal region. Our findings indicate that the extent of nasal and temporal losses bears no direct relation to the angle of squint although the extension of the visual field is differentially impaired by mild and severe esotropia. Among the nine cats, which displayed very different degrees of strabismus, we assessed only two different rates of impairment: (1) small nasal deficit and nearly normal extension of the temporal hemifield when the squint-angle was 15° or less; (2) severe restriction of both the nasal and the temporal hemifield when the strabismus magnitude was 18° or more. Thus, in the cats with large misalignment the size of the esotropic field is significantly smaller than in mild esotropic cats. In addition, in these very strabismic animals is also present a consistent reduction of the visual field of the non-deviated eye. The deficit of the non-deviated visual field that we found in adult esotropes with food-perimetry confirms the results of Siretenau [23] obtained in strabismic kittens with a different method. The striking similarity in size between the monocular field of immature cats (3-4 weeks old) with normal ocular alignment [22] and the esotropic field of adult strabismic cats suggests the possibility that field deficits

!65

are the result of a developmental arrest of the visual field at an immature stage. It is known that the extent of the visual field is not complete at birth and, in kittens [22] as well as in human infants [16] the full size is reached during the postnatal life through a gradual expansion. The growth of the two hemifields is, however, asymmetric, since the nasal field attains more slowly than the temporal field the adult-like extension [ 17,22]. Given the difference in time of development between the two hemifields, a stop or a delay in their postnatal expansion would lead to a more pronounced reduction of the nasal than the temporal field in adult animals. Indeed, in cats reared with neonatal esotropia the nasal region of the strabismic field is always reduced. Our results suggest however that there are limits of image misalignment beyond which the expansion of both hemifields of the esotropic eye become severely impaired and also the visual field of the non-deviated eye is affected. Although the neural mechanisms underlying postnatal development of the visual field are still unclear [16], the impaired field expansion might parallel a stop or a delay in the functional maturation of retinal afferents. There is evidence that the normal development of visual pathways is driven by activity-dependent processes depending on normal patterns of use of the eyes [ 18]. It is likely that in esotropia the neural activity through the strabismic pathway is decreased, as suggested by delayed transmission [6,7] and impaired visual effectiveness [3,4] of the strabismic input. Therefore, if activity-dependent signals are reduced during postnatal development the functional maturation of esotropic afferents may be perturbed. The greater susceptibility of the ipsilateral retinal pathway to any imbalance in visual stimulation of the two eyes in the early life [ 1,15] may explain why the deficit is limited to the nasal field in mild esotropia. It is interesting that a nasal loss analogous to that occurring in mild esotropes has been found in cats reared with unequal alternating monocular exposure [26]. Severe misalignment has a more deleterious effect on the extension of both deviated and nondeviated visual fields. It may be expected that the absence of synchronous neuronal activity in both eyes perturbs the general mechanism that strengthens co-activated inputs. As a consequence, the development of afferents from both eyes may be impaired. Based on anatomical evidence it has been recently claimed [8] that esotropic deviation impedes functional maturation of deviated as well as non-deviated Y projections. This supports our finding that the non-deviated visual field is restricted in cats with severe squint and it is in line with electrophysiological and behavioural studies reporting that visual effectiveness of the non-strabismic eye is far from normal [3,9]. In conclusion we suggest that field deficits observed in cats reared with ocular misalignment may reflect the impaired postnatal development of the visual field which retains the extension of immature animals.

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M. Di Stefano et al./Behavioural Brain Research 74 (1996) 161-166

Acknowledgment We wish to thank Mrs. Giovanna Bresciani whose constant care to the kittens made this work possible. This experiment was partially supported by the research grant RS 60% (91).

References [ 1] Bisti, S. and Carmignoto G., Monocular deprivation in kittens affects differently crossed and uncrossed visual pathway, Vision Res., 26 (1986) 875-884. [2] Berman, N. and Murphy H.E., The critical period for alteration in cortical binocularity resulting from divergent and convergent strabismus, Dev. Brain Res., 2 (1982) 181-202. [3] Chino, Y.M., Shansky, M.S., Jankowski, W.L. and Banser, F.A., Effects of rearing kittens with convergent strabismus on development of receptive-field properties in striate cortex neurons, J. Neurophysiol., 50 (1983) 265-286. I-4] Crewther, D.P. and Crewther, S.G., Neural site of strabismic amblyopia in cats: spatial frequency deficit in primary cortical neurons, Exp. Brain Res., 79 (1990) 615-622. [5] Di Stefano M., Lepore F., Ptito M., Bedard S., Marzi C.A. and Guillemot J.P., Binocular interactions in the lateral suprasylvian visual area of stabismic cats following section of the corpus callosum, Eur. J. Neurosci., 3 (1991) 1016-1024. [6] Freeman, R. D. and Tsumoto, T., An electrophysiological comparison of convergent and divergent strabismus in the cat: electrical and visual activation of single cortical cells. J. Neurophysiol., 49 (1983) 238-253 [7] Freeman, R.D., Sclar, G. and Ohzawa, L., An electrophysiologlcal comparison of convergent and divergent strabismus in the cat: visual evoked potentials. J. Neurophysiol., 49 (1983) 227-237 [8] Garraghty, P.B., Roe, A.W., Chino, Y.M. and Sur, M., Effect of convergent strabismus on the development of physiologically identified retino-geniculate axons in cats, J. Comp. Neurol., 289 (1989) 202-212. [9] Holopigian, K. and Blake, R., Spatial vision in strabismic cats, J. Neurophysiol., 50 (1983)287-296. [10] Ikeda A. and Jacobson S.G., Nasal field loss in cats reared with

convergent squint: behavioural studies, J. Physiol. (Lond.), 270 (1977) 367-381. [ 11 ] Ikeda, H. and Wright, M.J., Properties of LGN cells in kittens reared with convergent squint: a neurophysiological demonstration of amblyopia, Exp. Brain Res., 25, (1976) 63-77. [12] Ikeda, H. Plaint, G.T. and Tremain, K.E., Nasal field loss in kittens reared with convergent squint: neurophysiological and morphological studies of the lateral geniculate nucleus, J. Physiol. (Lond.), 270 (1977) 345-366. [13] Jones, K.R., Kalil, R.E. and Spear, P.D., Effects of strabismus on responsivity, spatial resolution and contrast sensitivity of cat lateral geniculate neurons, J. Neurophysiol., 52 (1984) 538-552. [ 14] Kalil, R.E., Visual fields defects in strabismic cats, Invest. Ophthalmol. Visual Sci., 14, Suppl.: (1977) 163. [15] Kalil R.E., Spear P.D. and Lagsetmo A., Response properties of striate cortex neurons in cats raised with divergent or convergent strabismus, J Neurophysiol., 52 (1984) 514-537. [ 16] Mohn,G. and Van Hof-Van Duin, J., Development of the binocular and monocular visual fields of human infants during the first year of life, Clin. Vision Sci., 1 (1986) 51-64. [17] Mohn, G. and Van Hof-Van Duin, J., The development of the binocular and monocular visual field in fullterm and preterm human infants, Invest. Ophthalmol. Visual Sci., (1985) Suppl. 24. [18] Shatz C.J., Impulse activity and patterning of connections during CNS development, Neuron, 5 (1990) 745-756. [19] Sherman, SM., Development of interocular alignment in cats, Brain Res., 37 (1972) 187-203. [20] Sherman, M.S., Visual fields defects in monocularly and binocularly deprived cats, Brain Res., 49 (1973) 25-45. [21 ] Simoni A. and Sprague J.M., Perimetric analysis of binocular and monocular visual fields in Siamese cats, Brain Res., 111 (1977) 189-196. [22] Sireteanu, R. and Maurier, D., The development of the kittens visual field, Vision Res., 22 (1982) 1105-1112 [23] Sireteanu, R., Restricted visual fields in both eyes of kittens raised with unilateral induced strabismus: relationship to extrastriate cortical binocularity, Clin. Vision Sci., 6 (1991) 277-287 [24] Sprague, J.M. and Meikle T.H., The role of the superior colliculus in visually guided behaviour, Exp. Neurol., 11 (1965) 115-146. [25] Treiman, K.E. and Ikeda, H., Relationship between amblyopia LGN cell 'shrinkage' and cortical ocular dominance in cats, Exp. Brain Res., 47 (1982) 119-129. [26] Tumosa, N., Tieman, S.B. and Hirsh H.V.B., Visual field deficits in cats reared with unequal alternating monocular exposure, Exp. Brain Res., (1982) 119-129 [27] Van Hof-van Duin, J., Visual field measurements in monocularly deprived and normal cats, Exp. Brain Res., 30 (1977) 353-368.