A Static Perimetric Technique Believed to Test Receptive Field Properties

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The operative steps are: (1) The tumor is outlined in ink, then a second line is drawn 3 mm outside the first. (2) A sketch of the tumor area is prepared for the pathologist, numbering each part of the border, the tumor, and the base layer. (3) The tumor, its border, and the base layer are excised, each is placed in its own bottle of fixative, numbered to cor­ respond with the sketch, and the tissue and sketch are sent to the pathology laboratory. (4) The wound is lightly dressed and the pa­ tient is returned to his room to await the

AUGUST, 1970

pathology report. (5) If the report indicates that the tumor has been completely excised, the area is then covered with a skin graft. In a series of 293 cases with up to 10 years of followup, only one patient has had a recurrence. REFERENCES

1. Reese, A. B. : Tumors of the Eye, 2nd ed. New York, Harper & Row, 1963, p. 14. 2. Mohs, F. E. : Chemosurgical treatment of cancer of the eyelid: A microsurgical controlled method of excision. Arch. Ophth. 39:43, 1948.

A STATIC P E R I M E T R I C T E C H N I Q U E BELIEVED T O TEST R E C E P T I V E FIELD P R O P E R T I E S III.

CLINICAL TRIALS

ROBERTO N. SUNGA, M.D.

AND JAY M. ENOCH, P H . D .

St. Louis, Missouri

In papers I and II of this series,1'2 a psychophysical technique described by Westheimer3·4 was confirmed and extended, and the method adapted to the Haag-Streit Goldmann perimeter. This technique is believed to reflect retinal receptive field properties. The method allows the examiner to evaluate the extent and nature of spatial interactive properties, both summative and inhibitory, at any point in the visual field. At this time, the analysis has been limited to points in the vi­ sual field located within 15 degrees of the central fovea. Receptive field size (discussed in the preFrom the Department of Ophthalmology, Wash­ ington University School of Medicine, and the Oscar Johnson Institute, 660 South Euclid Avenue, St. Louis, Missouri. This research has been sup­ ported in part by NIH Research Grants NB 02168 and NB 03639, and Career Development Award NB-K3-15138 (Dr. Enoch) from the National In­ stitute of Neurological Diseases and Blindness, Bethesda, Maryland. Dr. Sunga is now located at the Philippine Eye Research Institute, University of the Philippines, Manila, Philippines. Reprint requests to Jay M. Enoch, Ph.D., De­ partment of Ophthalmology, Washington Univer­ sity School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110.

vious two papers) exceeds by orders of mag­ nitude the angle subtended by the individual retinal receptor—even in the fovea. While some evidence for limited interreceptor neural interaction exists,5 the latter may be considered only as contributory in terms of the functions evaluated in this study. Thus, the more extensive interactive events giving rise to "Westheimer-type" functions most probably occur central to the photoreceptor. A priori, it was assumed that differences in response would be found when comparing the effects of photoreceptor lesions with pa­ thology ocurring in diseases of inner retinal layers. Assuming differences between inner retinal pathology and outer retinal pathology are established, it is desirable to determine the loci within the retina giving rise to spe­ cific changes in the measured functions. If the technique evaluated in this paper reflects retinal receptive field properties, it then be­ comes important to determine the nature of the measured functions when patients with postganglion cell lesions are studied. In addition, there are other meaningful is­ sues that need to be considered. For exam-

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pie, it is necessary to define the types of changes which occur in different forms of eye pathology. With remission of disease, we must determine whether there is full or par­ tial recovery of function. It will be of inter­ est to learn if the area of interaction changes during pathology, and to predict resultant vi­ sual dysfunction. METHODS

Preliminary study leading to the develop­ ment of the clinical technique has been de­ scribed in papers I and II of this report.1'2 Briefly, the procedure is as follows : Standard kinetic fields are first obtained on the patient. One or more points located in the area of relative scotoma are selected for evaluation, and an equivalent control point or points are chosen in a more normal part of the same field, or in the sec­ ond eye, or in the eye of a normal subject. As noted in the first paper, points located within a few degrees of the blind spot are not chosen, and a simple sphere refraction is conducted within the cupola in order to minimize blur. In some, but not all cases, mydriasis and cycloplegia are induced. Once the point to be examined is chosen, the stimulus array is assembled, and the fixation point set.' The stimulus array consists of three fields. The first (Field I) is set at a fixed luminance level above the (periodically flashed stimulus) static threshold measured at the point to be tested. The test stimulus (Field I) is small in diameter (gener­ ally the smallest visible: e.g., Goldmann 0, I, or II), and is flashed repetitively at the rate of 70 msec every one-half second. A non-flashing back­ ground (Field II) is centered on this target. The size of Field II is varied in steps, and at each step, the background field luminance (Bn) is determined which first makes the test field (Field I) just invis­ ible, and then just visible again. The process is re­ peated six or more times per size background. These two fields are superimposed on the standard cupola background (Field I I I ) . The pantograph arm of our perimeter (equipped with static and flicker attachments) projects the flashing test field. An added projector provides the background field (Field I I ) . ' A fixation projector supplies the necessary fixation point, and an avail­ able telemicroscope is clamped to the cupola to allow centering of the stimulus array. By turning a knob controlling a neutral density wedge, the patient varies the luminance of the background field. He is instructed to turn the knob until the flashing field disappears, then loosen his hold on the control. The wedge setting is recorded. The examiner can also translate the wedge indepen­ dently, and often he overrides the setting of the

245

subject so that no position sense is imparted by the knob setting. The subject is then instructed to turn the knob in the counter direction until the small flashing test field is again just visible, and again, just invisible. Usually, larger background fields are presented first, because subjects find the task easier. Back­ ground field size is reduced in steps to a size ap­ proximately equal to the test field size. Order of presentation does not seem to be a significant vari­ able, unless the lesion is central to the ganglion cell layer. Since the task is simple, only a few training settings are required prior to the initiation of test­ ing.

In figures presented below, log back­ ground field area has been plotted on the abscissa and log background luminance neces­ sary to make the flashing field disappear (higher value—open symbols) and reappear (lower value—filled symbols) is indicated on the ordinate. The initial fall in the curve for smaller backgrounds is interpreted as summa­ tion, and the succeeding rise in threshold with increased background area is termed inhibi­ tion.1 The total area over which neural inter­ action takes place is regarded as an estimate of receptive field size. RESULTS

In ocular diseases believed to affect the choroid, the pigment epithelium, and the ret­ inal receptors the functions reported in this study are usually unaltered except for general associated loss in sensitivity. Diseases of the inner retina show the loss of the inhibition component. In optic neuritis and diseases of the optic pathway, added variables result in differing response functions. This study must be regarded as introduc­ tory or preliminary, because there are lim­ ited numbers of patients in certain classes of eye disease important in this analysis. In order to minimize fixation problems, patients were accepted for study only if visual acuity in the eye manifesting an anomaly was 20/80 or better. The results of testing these patients are described in terms of those whose pathology produced a response func­ tion unaltered in shape from that pre-estab­ lished as the basic response, and those in

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tO

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60

Fig. 1 (Sunga and Enoch). Kinetic fields of left eye of patient (J.B.) with nonspecific choroiditis showing a large area of relative scotoma of varying densities. The areas showing lines having different orientations represent zones of relative scotoma. The area with multiple dots includes the blind spot.

whom the curve was found to be altered from the basic response function. Unaltered basic response function—Dis­ eases in which no change was found in the essential shape of the basic response function were divided into two groups. Group I con­ sisted of pathology generally associated with the choroid or outer retinal layers, including nonspecific choroiditis, histoplasmosis, angioid streaks with macular lesion, defects in the pigment epithelium, flecked retina syndrome, early tapetoretinal degeneration, and choroidal cyst. Pathology classified as Group II was that in which the site of pathology was not defined. This included low grade amblyopia (20/40), either strabismic or aniseimetropic. No diseases ordinarily considered to origi­ nate in inner retinal or optic pathway pathol­ ogy are found in Groups I and II. In patients studied whose ocular pathol­ ogy was classified as Group I or II, there

was, as a rule, a loss of visual sensitivity as measured by tests of kinetic or static perimetry or visual acuity. Plotting of data, as shown in Figure 9, paper II, 2 generally re­ sulted in overlapping of functions (log Bn vs log area Field II ) having essentially iden­ tical interactive areas (receptive field size). On the basis of these findings, we con­ cluded that in these cases, if a signal is ini­ tiated in the retinal areas tested, despite the influence of the pathological lesion(s) pres­ ent, it is processed as it might be in the nor­ mal subject in terms of the response mecha­ nisms herein evaluated. GROUP I CASE REPORTS

Cases illustrating Group I diseases, pa­ thology generally associated with choroid or outer retinal layers, are as follows : ChoroiditL·, nonspecific—This patient, a Cauca­ sian man, aged 34, whose visual acuity was

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RE :20/20, LE :20/30, gave a history of scintillating scotomas in both eyes of four to five years' dura­ tion. In both posterior poles, there were irregular, blanching pigmented and depigmented choroidal le­ sions mainly juxtapapillary and some around the macula. In the left eye, kinetic fields (Fig. 1) showed a large peripapillary relative scotoma of varying density with a small tail below and to the right of the macula. Westheimer functions were measured in the left eye at 10° eccentricity on the 45° half-meridian (A in Fig. 1, normal field), and within the scotoma on the 135° and 180° half-meridians (B and C). All measured basic response functions (Fig. 2) showed normal descending (summation) and as­ cending (inhibition) arms. The test-retest reliability of this subject was excellent. Static thresholds for the flashing Goldmann target size I at the 10° ec­ centricities were 1.3 log units on the 45° half-me­ ridian or radius, and 1.1. and 1.0 log units on the 135° and 180° half-meridians, respectively. The lat­ ter values indicate that more light (less density filter) was required for static threshold in areas of relative field loss. The Westheimer type response functions were determined using the flashing Goldmann size I target set at 1.0 log unit above threshold as the test field (Field I ) . Histoplasmosis—The visual acuity of this Cauca­ sian man, age 35, was RE :20/20, LE :20/30. In his left eye, there was a punched out, deep chorioretinal lesion just temporal to the macula with a corre­

3.0

4.0

247

sponding relative scotoma on the kinetic field (Fig. 3). A presumed diagnosis of histoplasmo­ sis was made on the basis of a positive skin test and the appearance of the fundus lesion. Figure 4 shows the response patterns obtained within the normal field (A on Fig. 3) and within the relative scotoma (B). Both measured Westhei­ mer functions revealed normal summation and inhi­ bition limbs. Thresholds for the test flash (Goldmann size I) at 5° eccentricities were 1.2 log unit on the 180° meridian and 1.0 log unit on the 0° meridian. Defects in the pigment epithelium—Visual acuity was 20/20 in both eyes in this Negro woman, age 65. On routine examination, the posterior pole of both fundi of this patient revealed numerous small, round, yellowish-white spots which (with the con­ tact lens) appeared to be defects in the pigment ep­ ithelium. Since there were no field changes, West­ heimer functions were arbitrarily taken centrally and at 10° eccentricity. Both patterns were normal. Flecked-retina syndrome—Visual acuity was 20/20 in both eyes of this Caucasian man, age 35. Both posterior polar regions contained many small, whitish, deep retinal spots. Dark adaptation and ki­ netic fields were normal. Westheimer functions de­ termined arbitrarily at 5° and 10° eccentricities were normal. Angiod streaks with macular lesion—This pa­ tient, a Caucasian man, age 37, whose visual acuity was RE:20/20, LE:20/80, had a positive family

Area of Test Field

I

C % 10" on ίβΟ° meridian B 110° on 135°meridian

2.0

3.0

1.0

2.0

A Ξ fO° on 45° meridian

dB. *. AB=GoWmannsizer.1.0IJU. "·* above threshold

0.0

1.0

<**', V ^ *v'

2.0 3.0 4.0 LOG BACKGROUND AREA (Minutes of Arc) 2

5.0

Fig. 2 (Sunga and Enoch). Westheimer functions of the patient with nonspecific choroiditis. Data were obtained within the normal field (A in Fig. 1) and within the scotoma area (B and C). All three curves showed normal summation and inhibition arms.

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No scotoma for l / 4 e

330 Relat Intel». He 4 1 0 1X II III IV V

«1

X X

Fig. 3 (Sunga and Enoch). This figure shows an area of relative scotoma (lines of differing orienta­ tions) temporal to the macula in left eye of patient (C.S.) with presumed histoplasmosis. The area with multiple dots represents the blind spot. 3.0r

1I

4.0r

62.0

3.0-

1„

2.0

Area of Test Field

Eccentricity From Fovea 5° on 180° meridian ΔΒ 1.2 LU. f threshold 5°on 0° meridian ABIOLU. f threshold

1

C.S. ΔΒ Goldmann size I

0.0

1.0

2.0 3.0 4.0 LOG BACKGROUND AREAflVïnutes of Arc)2

5.0

Fig. 4 (Sunga and Enoch). In this patient with presumed histoplasmosis, even in an area of relative scotoma (B in Fig. 3), the response functions were similar to that in the normal field area (A).

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history of pseudoxanthoma elasticum. He developed blurred vision in the left eye three months prior to examination. Both posterior poles showed promi­ nent angioid streaks with a bull's eye appearance at the left macula. There was a corresponding rela­ tive, central scotoma in the left eye (Fig. 5). Response functions were measured in the same eye within the relative scotoma at 2° and 5° eccen­ tricities on the 0° half-meridian or radius (A and B in Fig. 5). The response patterns again showed a descending and an ascending arm similar to a nor­ mal curve (Fig. 6). Early tapetoretinal degeneration—For the last 12 years, this patient a Caucasian man, age 34, whose visual acuity was RE:20/40, LE:20/30, had had gradually progressing night blindness. Fundus ex­ amination showed some optic nerve pallor, attenua­ tion of the vessels and mild pigmentary changes. There was absence of the rod segment on dark ad­ aptation. Kinetic fields revealed a large ring sco­ toma with concentric contraction of Goldmann isopters I/2e and I/4e (Fig. 7). Westheimer functions were measured foveally, and at 3° eccentricity on the 270° half-meridian or radius (A and B, Fig. 7) and both curves showed normal summation and inhibition components. A second patient, a Caucasian man, age 21, whose visual acuity was RE: 20/20, LE: 20/25, also reported decreased night vision, in this case of two years duration. His fundi showed pallor of the

249

disks, attenuation of the arteries, and pigment changes compatible with retinitis pigmentosa. Ki­ netic fields revealed slight concentric contraction of Goldmann I/4e. Cone thresholds measured by dark adaptation were essentially normal, but there was loss of the rod component. Westheimer functions were arbitrarily measured at 5° and 10° eccentrici­ ties, and both showed a normal pattern. Choroidal cyst—In this patient, a Caucasian man, age 71, whose visual acuity was R E : 20/30, L E : 20/20, Fundus examination showed a large choroidal cyst (about 2 to 3 disk diameters) temporal to the macula. Fluorescein studies confirmed the presence of a choroidal cystic lesion. There was a large rela­ tive scotoma corresponding to the area of the le­ sion. Westheimer functions measured within the rela­ tive scotoma area (at 5° eccentricity on the 180° half-meridian) and in an area of the normal field (0° half-meridian) were similar and both showed patterns having a normal shape. GROUP II CASE REPORTS

Cases illustrating Group II pathology in which the site was not denned—low-grade ambylopia, either strabismic or aniseimetropic—are as follows :

Fig. S (Sunga and Enoch). This is the kinetic field of the left eye of a patient (R.M.) who had angiod streaks with a macular lesion. The area with vertical lines represents the blind spot.

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Area of Test Field 3.0 Eccentricity from Fowea -i

Ï

I1

I

S

2.0

A

2e

B

5°

US R.M. ΔΒ: 1.0 L.U. above Threshold 1.0-

2-

§ ^i

1.0

2.0

4.0

3.0

Log Background Area (Minutes of Arc) Field H

5.0

2

Fig. 6 (Sunga and Enoch). Normal response functions within the area of relative scotoma (at 2° and 5° eccentricities on the 0° half-meridian, A and B, Fig. 5) in a patient with angoid streaks and macular lesions. Strabismic ambylopia—In this Caucasian boy, age 10, whose visual acuity was RE : 20/20, LE : 20/40, orthoptic examination revealed 9Δ estropia and 8Δ right hypertropia with constant suppression of the left eye when both eyes were exposed. Fundus ex­ amination was normal. The threshold for the flashing test field (Gold­ mann size 0) was 1.4 log units in the right eye and 1.2 log units in the left eye. Response functions were measured with the test flash set at 1.0 log unit above threshold. Measured central functions in both the normal and amblyopic eye showed normal sum­ mation and inhibition arms. Anuometropic amblopia—This patient, a Cauca­ sian man, age 23, whose visual acuity was RE: 20/20, L E : 20/40, had always had poorer vision in the left eye. Refraction showed R E : +1.00 DS and LE: —2.00 DS. Fundus and orthoptic exami­ nation were normal. The Westheimer functions measured centrally in both eyes were similar and showed normal summa­ tion and inhibition arms. Test flash (Goldmann size 0) thresholds: R E : 1.7 log units and L E : 1.0 log unit.

Basic response function unaltered or show­ ing loss of inhibition arm—Diseases in this category may also be divided into two groups :

Group III consists of central serous retinopathy and senile macular degeneration. Group IV consists of ocular hypertension and glaucoma. The conditions listed in Group III are normally categorized as outer retinal dis­ eases (Group I ) . In each, one patient among those tested showed loss of inhibition, the re­ mainder exhibited unaltered functions. It is tentatively assumed that the two exceptions either had a somewhat different form of the basic condition, or added complications in­ volving the entire retina, or were not prop­ erly categorized. In these two cases, the di­ agnosis of the referring ophthalmologist has been questioned. It was felt that in the case of the fifth patient in Group III, his age (58 years) and observed retinal changes were not consistent with central serous retinopathy. It was suggested, in the second case de­ scribed under macular degeneration, that this patient had senile disciform type of retinal

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2S1

degeneration. It is not appropriate here to gory, Westheimer type functions were ob­ enter into the complex discussion relative to tained at arbitrary locations in the field the categorization of central serous retinop- (since no visual field defect was evident), athy and disciform degeneration of the mac­ and in the latter two classes, testing was con­ ula. It is important to indicate that a degree ducted at points in the field where relative of ambiguity exists, and a broader sample of defects were present. The measured func­ patients with macular lesions needs to be tions in the latter two categories showed tested. Interestingly, the fifth patient de­ ' changes in visual sensitivity, but only in well scribed, who showed inhibition loss during established glaucoma was there evidence of an active phase of his disease, exhibited re­ alteration in the Westheimer type functions. covery of that response characteristic during In patients with well established glaucoma, there was clear cut evidence of loss of the remission of the disease. Patients with ocular hypertension and inhibition arm. Graded loss was evident as glaucoma may be divided in three categories one moved from a part of the visual field from the point of view of this report, (a) where no defect was present, into an area of steroid induced ocular hypertension without relative field defect. The obvious conclusion field change, (b) patients having a history of arising from these studies is that alterations ocular hypertension exhibiting their initial in the function measured in these studies is a glaucomatous field defects, and (c) well es­ late sign in glaucoma, and is not the result of tablished glaucoma patients having long­ simple ocular hypertension. As will be seen when Group V is considstanding relative field loss. In the first cate­

Fig. 7 (Sunga and Enoch). A large ring scotoma in the right eye of a patient (R.S.) with retinitis pigmentosa.

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Fig. 8 (Sunga and Enoch). Static fields of a patient with central serous retinopathy in the right eye. Westheimer functions were measured centrally in the left eye (A), and centrally and at 3°, and 5° (B, C, and D) in the right eye.

PERIMETRIC ANALYSIS

VOL. 70, NO. 2

ered, the changes noted are the same as those found in inner retinal disease. Recovery of inhibition loss (or field defect) was not ob­ served in patients with glaucoma under con­ trol, but since patients having inhibition loss due to other conditions have shown recovery, this change in visual response may still be reversible. This is a problem which must be pursued. The authors consider individuals with well established glaucoma as falling in Group V, i.e., those patients with diseases of the inner retina. It is generally accepted that glaucomatous field loss is largely associated with events which occur at or near the optic nerve head. The function measured in this study reflects neural interactive processes. While some neural interactive phenomena such as the blue arcs of the retina may originate at points along the axons of the ganglion cells, it is believed that the bulk of the phenomena measured herein occurs at a synaptic level. Presumably events affecting axon character­ istics, in time, also influence the cell body and the dendrites. This may well explain

253

why Westheimer functions do not seem to be altered early in glaucoma. Obviously an enlarged sample will be needed to clarify this issue. Group III

CASE REPORTS

Cases illustrating Group III, are those with basic response function unaltered or showing loss of inhibition. Four cases with central serous retinopathy and unchanged functions are described first: A 42-year-old Caucasian woman whose visual acuity was 20/20 in both eyes developed blurred and distorted central vision in the right eye a month be­ fore examination. In her right eye, there was a slight macular edema and mottling. Kinetic fields were normal. Static fields revealed a slight depres­ sion of sensitivity centrally, with the greatest dip recorded at 5° eccentricity (Fig. 8). The central foveal theshold for theflashingtest field (Goldmann size 0) was 1.0 log unit in the right eye and 1.5 log units in the left eye. Test field luminance was set at 1.0 log unit above threshold. The two central functions were essentially the same (Fig. 9, A and B) and showed both descending and ascending limbs. Functions were also measured in the right eye at 3° and 5° eccentricities on the 180° half-meridian and the functions were again un­ altered (Figs. 9-C and D).

4 . 0 r Area of Central Test Field ( A and B) J Area of Test Relds(C and D)

3.0 r

Y

I I» I

I

3.0OS Î0

2.0 B * O.D. central L

o 3° on 180' ■ meridian

D · meridian

0.0

1.0

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2.0 3.0 4.0 LOG BACKGROUND AFOUMinutes of Arc) 2

50

Fig. 9 (Sunga and Enoch). The response functions were normal even in areas of depressed sensitivity (B, C, and D) in a patient who had central serous retinopathy.

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AUGUST, 1970

4.0 Area of Test Field

is

2.0

3.0-

1.0

2.0-

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CE (8-9-68) — Central Fixation ΔΒ« Goldmann size 0:1.0L.U, above threshold

0.0

1.0

4r

3.0 r

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r

2.0

1.0

2.0 3.0 4.0 2 LOG BACKGROUND AREA(Minute of Arc)

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Area of Test Field

8

I

CE (11-12-68) Central Fixation ΔΘ ■ Goldmann size 0:1.0 L.U. 2above threshold

1.0

_L

2.0 3.0 4.0 Log Background Area (Minutes of Arc) 2 Field S

5.0

Fig. 10 (Sunga and Enoch). Top: This figure illustrates the loss of the inhibition arm in the right eye of a patient who had central serous retinopathy. The summation arm was normal. The response function in the unaffected eye showed a normal pattern. Bottom : Recovery from the loss of inhibition arm by same patient. Essentially similar patterns were measured in both central foveas.

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PERIMETRIC ANALYSIS

In a second patient with central serous retinopathy who showed unchanged Westheimer type func­ tion, blurred and distorted vision had developed in one eye. The right eye of this Caucasian woman, age 32, was normal with visual acuity of 20/20. Vi­ sual acuity of the left eye was 20/50, and there was edema and elevation of the macula with some pig­ ment mottling. Static fields revealed a slight sensi­ tivity loss centrally in the left eye. Westheimer functions measured in the central retina in both eyes revealed normal summation and inhibition arms. A third patient with central serous retinopathy, a Caucasian man, age 52, had normal vision in his left eye (visual acuity 20/20), but visual acuity in his right eye was 20/30. He complained of blurred central vision, and showed distortions when tested with the Amsler grid. Slight pigment mottling and edema of the macula were present at the time of fundus examination. Kinetic fields were normal. The diagnosis was central serous retinopathy. Westheimer functions measured centrally in both eyes showed normal summation and inhibition arms. In a fourth patient, a Negro man, age 21, the left eye was normal but visual acuity in the right eye was 20/25. About three weeks before the mea­ surement of the response functions, this patient de­ veloped blurred central vision in the right eye and it showed a slight macular edema. Kinetic fields taken three weeks after the onset of symptoms were normal. At that time, Westheimer type re­ sponse functions measured centrally were normal in both eyes. Loss of inhibition—In a fifth patient with central serous retinopathy, a Caucasian man, age 58, the left eye was normal, but visual acuity in the right eye was 20/40. The patient became aware of a cen­ tral scotoma in the right eye a few months before data were obtained for this study. Examination of the right fundus showed elevation of the macula with pigment mottling, depigmentation and drusen. The left eye was normal. There was a small relative central scotoma in the right eye. Westheimer functions were measured centrally in both eyes. The threshold for the flashing field (Goldmann size 0) was 1.0 log unit in the right eye and 1.8 log units in the left eye. With the test field set at 1.0 log unit above threshold, the measured functions in the left eye were normal. In the right eye the summation arm was normal but there was loss of inhibition (Fig. 10, top). That is, the initial drop in the function was present, but the rise was missing (Fig. 10, top, A ) . Three months later the vision improved to 20/25 in the right eye and the macular edema subsided. At this time, both measured central functions were almost identical (Fig. 10, bottom) and showed both summation and inhibition arms. This is clear evi­ dence of recovery following loss of the inhibition arm. Static thresholds for Goldmann size 0 mea­ sured foveally were R E : 1.6 log units and L E : 1.8 log units. Macular degeneration, unchanged function—The patient, a Caucasian man, age 65, had noticed

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progressive blurring of vision in both eyes for a paeriod of two years prior to the measurement of the Westheimer functions. Visual acuity was R E : 20/400, L E : 20/80. Both fundi showed moderate choroidal sclerosis, pigment mottling and depigmen­ tation in the macula. Kinetic fields revealed relative central scotomas in both eyes. A Westheimer func­ tion was determined centrally in the left eye and the pattern was normal (Fig. 11). Macular degeneration, changed function—This patient, a Caucasian woman, age 67, showed loss of inhibition on testing. She complained of progressive deterioration of vision in both eyes for the past two years; visual acuity was R E : 20/200, L E : 20/40. Fundus examination showed greyish cystoid eleva­ tions in the macular area with drusen scattered in the posterior poles. Fluorescein angiography re­ vealed dye retention which appeared to conform to the greyish cystic retinal elevations and probably representing serous detachment of the pigment epi­ thelium. Kinetic fields showed a relative central scotomata in the left eye. Figure 12 represents the measured central func­ tion in the left eye, which showed a normal de­ scending limb but loss of the inhibition arm. The threshold for the flashing Goldmann size I was 1.2 log units. Response functions were measured at two levels of test field luminance (1.0 and 0.5 log unit above threshold). Raising the threshold only trans­ lated the function upward an equivalent distance on the graph. GROUP IV CASE REPORTS

Cases illustrating Group IV pathology consisted of patients with ocular hyperten­ sion and glaucoma. Observations in these pa­ tients are as follows : Elevated IOP, corticosteroid induced, no field loss—In this Caucasian woman, age 39, visual acuity was normal in both eyes. Because elevated intraocular pressures were measured on some occa­ sions, the patient was considered to be glaucomasuspect. The angles were open and kinetic fields were normal. The patient's right eye was main­ tained on topical corticosteroids for six weeks (dexamethasone, 0.1%, 1 drop 4 times daily) and her IOP rose to 52 mm Hg. At that time quantita­ tive fields were normal. When IOP was highest, Westheimer functions were arbitrarily measured in her right eye at 5°, 10°, and 15° eccentricities on the 330° half-merid­ ian. All data were normal. Like the patient just described, this Caucasian woman, age 75, was also glaucoma-suspect and was also a high responder when topical corticosteroids were administered. Visual acuity was 20/25 in both eyes. Quantative fields at the height of the pressure rise (RE: 46 mm Hg) were normal. When pres­ sures rose to this height, Westheimer functions were again determined at 5°, 10°, and 15° eccen­ tricities, and were normal. Glaucoma with early field loss—On June 6, 1968,

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Area of Test Field

3 0

I S3 2.0 1.0 L.U. above threshold

I I 10 . 5

2F.Z. ΔΒ : Goldmann size 0 Central Fovea

§

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_|_

_L

_L

2.0 3.0 4.0 5.0 Log Background Area (Minutes of Arc) 2 Field H Fig. 11 (Sunga and Enoch). Normal central Westheimer-type function in a patient with macular degeneration. 1.0

3.0r

1

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4.0r Area of Test Flash

3.0 ΔΒ Luminance above threshold

I

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1.0 LU.

1.0

2.0

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0.0L

1.0

2.0 3.0 4.0 LOG BACKGROUND AREA(Minutes of Arc) 2

5.0

Fig. 12 (Sunga and Enoch). Loss of inhibition arm of the function in a patient with macular degenera­ tion. Measurements were made with the test flash luminance set at two values above the static threshold (1.0 and 0.5 log units) and both functions were similar.

Fig. 13 (Sunga and Enoch). Top: Enlargement of the blind spot to Goldmann I/3e in the right eye of a patient (H.D.) who had chronic simple glaucoma. Bottom: Baring of the blind spot and slight superior depression in same patient four months later. Westheimer functions measured at the edge of, and outside of the I/3e isopter were still normal in this case. Multidotted area represents the blind spot to I/4e.

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kinetic fields of this patient, a Caucasian man, age 74, with chronic simple glaucoma revealed enlarge­ ment of the blind spots (Fig. 13, top). His visual acuity was R E : 20/20, L E : 20/30. Four months later there was slight depression superiorly to Goldmann I/3e (Fig. 13, bottom). The angles were open and pressures were controlled under pilocarpine. Westheimer functions were taken at the edge of the I/3e isopter (Fig. 13, bottom, A) at 10° eccentric­ ity on the 90° half-meridian or radius and outside this isopter (B, 15° eccentricity). Both measured response functions were normal. Measurements were not taken in the region immediately surround­ ing the blind spot.1 Glaucoma with well-established field loss—Since 1965, this 77-year-old Caucasian woman (visual acuity RE : 20/40, LE : 20/20) has had borderline to poor outflow facility. Both angles were open. A Bjerrum scotoma was first noted in the right eye in 1965. It progressed slowly for two years until it be­ came stable (Fig. 14). Response functions measured within the I/3e isopter at 10° eccentricity on 270° half-meridian (A in Fig. 14) showed normal summation and inhibi­ tion arms. At the same eccentricity outside this isopter (B, 90° half-meridian), the functions showed a normal summation arm, but there was absence of the inhibition arm (Fig. 15). Thresholds for the flashing test field (Goldmann size I) were 1.0 log unit at 10° eccentricity on the 270° half-meridian and 0.7 log unit on the 90° half-meridian. Response functions were measured with the test flash set at 0.7 log unit above the threshold. In a second glaucomatous patient with well-es­ tablished field loss, visual acuity was R E : 20/20, L E : 20/25. In 1966, this Negro man, age 48, no­ ticed halos around lights, and he was diagnosed as having chronic simple glaucoma. Examination showed open angles with marked cupping of both disks. Kinetic fields revealed extensive field loss in the left eye and a dense inferior Bjerrum scotoma in the right eye (Fig. 16). 3% carbachol, 1% epinephrine (Glaucon), and acetazolamide (Diamox) were prescribed. He was discharged with controlled pressures. Within the normal field in the right eye, at 5° eccentricity on the 90° half-meridian (A in Fig. 16), the measured Westheimer functions were es­ sentially normal. At the same eccentricity on the 165° half-meridian and outside the I/2e isopter (B), the summation arm of the function was nor­ mal, but there was loss of the inhibition arm (Fig. 17). Thresholds for the test flash (Goldmann size I) were 1.3 log units on the 90° half-meridian and 1.0 log unit on the 165° half-meridian. Test flash luminance was set at 1.0 log unit above thresh­ old. In a third patient, a Caucasian woman, age 64, with well-established field loss, visual acuity was RE: 20/20, LE: 20/30. She was diagnosed as hav­ ing chronic simple glaucoma. Both disks showed moderate cupping. In the left eye, there was enlarge­ ment of the blind spot with field loss superiorly. Westheimer functions measured in an area of field

AUGUST, 1970

loss (10° eccentricity on the 90° half-meridian) showed typical loss of inhibition and normal sum­ mation. In the normal part of the visual field (same eccentricity on the 0° half-meridian) unaltered pat­ terns were recorded. Like the patient just described, this 48-year-old glaucoma patient, a Caucasian man whose visual acuity was 20/20 in both eyes, showed marked depression superiorly with a questionable nasal step when kinetic fields were measured. Response func­ tions within the normal field (7° eccentricity on the 240° half-meridian) and at the edge of the I/2e isopter (7° eccentricity on the 60° half-meridian) showed normal summation and inhibition arms. Within the area of relative field loss (10° eccen­ tricity on the 60° half-meridian) there was loss of inhibition but a retention of normal summation. Loss of inhibition component and reduc­ tion in size of receptive fields—As in the cases previously described, patients with this type of visual response deficit may be cate­ gorized in two classes : Group V included cases demonstrating pathology generally as­ sociated with inner retinal layers. This group included patients with glaucoma with well established field loss (see Group I V ) , and pa­ tients with retinal edema following retinal artery embolism. Group VI included cases in which the site of retinal pathology was undefined ; one had macula edema following photocoagulation of choroidal angioma. In sites of relative visual field loss asso­ ciated with inner retinal layer pathology, there was a loss of the inhibition component of the function evaluated in this study. Concommittant was a reduction in receptor field size. When the authors speak of inner reti­ nal pathology altering the measured re­ sponse function, they tentatively mean that portion of the retina supplied by the central retinal artery. The fact that the modified tech­ nique described in paper II 2 of this series did not result in inhibition arm loss in normals, even when the test field (Field I) was set at 0.5 log units above static threshold, supports the notion that the functional losses reported are real. Since the test level above threshold was held constant in the test and control area (rather than test field luminance, see Fig. 8 in paper I I ) , 2 this finding is not simply a test level artifact. In addition, when possible, the

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Fig. 14 (Sunga and Enoch). Advanced field loss in right eye of a patient (G.B.) who had chronic simple glaucoma. 3.0

!

K

Area of Test Field

1 β 2.0

"s! δ^

5

10

8

i

270" Meridian

G.B. ΔΒ - Goldmann Eccentricity : 7

90 s Meridian 0.7 LU. above threshold

1.0

2.0 3.0 4.0 Log Background Area (Minutes of Arc)z Field IT

5.0

Fig. IS (Sunga and Enoch). Within the I/3e isopter (at A in Fig. 14), Westheimer functions were still normal. Outside of this isopter, (B), the summation arm was normal but there was loss of the inhibition

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AUGUST, 1970

ΙΙ/4Θ

Fig. 16 (Sunga and Enoch). Another patient (C.J., right eye) with chronic simple glaucoma who had advanced visual field defects. Functions were measured at 5° eccentricities on the 90° (A) and 165° (B) half-meridians or radii. test field luminance level (Βτ) was raised to a higher level (Fig. 12) in order to deter­ mine whether a functional change could be elicited. In no case did such a maneuver re­ sult in reappearance of the inhibition arm. It is interesting that the summation arm of the function has not been significantly al­ tered in any form of pathology considered thus far. That part of the response function does not change as the luminance setting of the test field approaches the absolute threshold.1 Louise Sloan6 has shown that summation, measured in the more standard way is generally unaltered in retinal pathol­ ogy. Her work contradicts earlier findings by Dubois-Poulson and Magis.7 Fankhauser and Enoch,8 among others, demonstrated that blurred retinal imagery affects summa­ tion—a fact confirmed for Westheimer type functions in the first paper of this series.1

Wilson9 recently presented evidence suggest­ ing that summation is altered in all areas where relative field loss occurs. The func­ tions measured in this study, while not iden­ tical in nature, do not lend support to Wil­ son's findings. If systematic changes occur in summation in this study, they must be subtle. It is important for us to determine why this response characteristic is so much less subject to change. Similarly, we must seek to understand why the functional change which takes place between light and dark adapted states in both the photopic and scotopic systems1 becomes seemingly blocked in inner retinal pathology. What is altered —what recovers? The fact that these changes do occur in inner retinal pathology does locate the phenomenon in the inner ret­ ina, and supports Westheimer's contention that the properties considered are retinal.

3.0

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Area of Test Field 2.0-

3-

90° Meridian 1.0

C.J. ΔΒ ·' Goldmann size I 5" Eccentricity from Fovea

1.0

Z

'

Q

—·

—

Meridian

W

165°

· 1.0 L.U. above threshold

_L _l _L 4.0 2.0 3.0 Log Background Area (Minutes of Arc)2 Field I I

I 5.0

Fig. 17 (Sunga and Enoch). Like G.B., this patient with chronic simple glaucoma had loss of the inhibition arm in the area of relative field loss (B in Fig. 16) and normal functions in the area in his field still exhibited essentially normal responses (A in Figure 16).

GROUP V CASE REPORT

Inner retinal layer pathology—In a Caucasian woman, age 44, whose visual acuity was R E : 20/20, LE : HM, retinal edema followed retinal ar­ tery embolism. About four months before the mea­ surement of the Westheimer functions, the patient developed clouding of her vision in the left eye which progressed rapidly. There was pain on move­ ment of the eye. A diagnosis of optic neuritis was given at that time and with steroids, the pain sub­ sided but there was no improvement of vision. Three weeks before the measurements, she began to notice fogginess below the fixation point in the right eye. There was no accompanying pain. Fundus examination revealed a large area of retinal edema superior-temporal to the macula with emboli involv­ ing the superior-temporal and inferior-temporal arteries. In the left eye, the disk was markedly ele­ vated with venous engorgement and flame-shaped hemorrhages. Kinetic fields showed a large scotoma corresponding to the area of retinal edema (Fig. 18). Within the normal right field, at 5" eccentricity on the 0° half-meridian (A in Fig. 18) the mea­ sured function showed normal descending and as­ cending arms (Fig. 19). Outside the I/2e isopter at the same eccentricity (B, Fig. 18), the summation arm was normal but there was loss of inhibition. The threshold for the test flash outside this isopter was only 0.5 log unit and the test flash luminance

was therefore set at this level. Within the more normal area of the field, response functions were measured at two levels of test flash luminance (0.5 and 1.0 log unit). The patient died before added testing could be conducted. GROUP VI CASE REPORT

Site of retinal pathology undefined—Macular edema followed photocoagulation of a choroidal an­ gioma in this Caucasian man, age 27, whose visual acuity was RE : 20/20, LE : 20/70. Routine refrac­ tion revealed the vision in this patient's left eye to be somewhat poorer than the right eye, and further examination revealed a large choroidal angioma temporal to the macula. Immediately following pho­ tocoagulation of the angioma, the macula became elevated and edematous. Kinetic fields at the time showed a temporal arcuate defect. The response functions were measured centrally in both eyes (Fig. 20, top). Data on the right eye were normal. In the left eye, the summation arm was normal, but there was loss of the inhibition arm. The response functions were measured with the test flash (Goldmann size 0) set at 1.0 log unit above thresholds. The thresholds for the test flash were 1.8 log units in the right eye and 1.0 log unit in the left eye. These data are also plotted in Figure 9 in paper II in this series.' Two months after the photocoagulation, West­ heimer functions were again measured centrally in

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AUGUST, 1970

Fig. 18 (Sunga and Enoch). Kinetic fields of right eye of patient (A.T.) with retinal edema following retinal arterial emboli. The figure shows a dense scotoma inferiorly (dotted area) and some relative loss superiotemporally, RE. both eyes (Fig. 20, bottom). Both functions were similar. As in the case of a patient with central se­ rous retinopathy, there was clear evidence of recov­ ery of function. Kinetic fields at this time still showed the same arcuate defect in the left eye.

An attempt to localize the site of loss of the inhibition component—The data reported up to this point fall into two general catego­ ries. Unaltered Westheimer-type functions were obtained in diseases of the outer retina, and the inhibition component was appar­ ently missing in diseases of the inner retina, or retinal areas supplied by retinal (as op­ posed to the choroidal) vessels. The fact that summation is not altered, but inhibition changes suggests that the two processes need not be mediated at th same point. From the point of view of understanding the physiol­ ogy (as well as the pathology and differential diagnosis) of the situation, more informa­ tion is needed regarding the loci of these neural interactions. Unfortunately, there is

no disease that seems to attack just the hori­ zontal, bipolar, and/or amacrine cells. Be­ cause an essentially normal ERG ß-wave has often been recorded in absolute glaucoma, changes in that disease may be limited to the ganglion cell layer, or at least to units central to the point(s) where the ß-wave is gener­ ated. During a search of the literature for evi­ dence of a condition manifesting pathology localized in the inner nuclear layer, Dr. Rob­ ert Moses called the authors' attention to a very interesting paper by Ehinger.10 In the course of a discussion of the distribution of adrenergic endings in the retina, Ehringer noted that cats on very high doses of reserpine, a catecholamine depleting agent, exhib­ ited marked photophobia. It has been shown that most adrenergic endings found in the cat retina are located in a plexus at the inner nuclear and inner plexiform layers. Photo-

VOL. 70, NO. 2

phobia may be possibly associated with a general loss of inhibition. The role of the iris in this situation is undefined. Since patients with hypertension are often placed on high dose levels of reserpine, guanethidine (Ismelin) and similar antiadrenergic drugs, four patients receiving high dosage of these drugs were studied. How­ ever, the reader must distinguish between high dose level and toxic level, and recognize the fact that the ratio of dose level pre­ scribed: body weight in the patients exam­ ined, was measurably far less than Ehringer administered to his cats. The four men tested were being followed at the Hypertension Clinic of the Veterans Hospital in St. Louis. All of.them were under high dosage of guanethidine with a total dose varying from 46 to 609 g at the time of the examination. These hypertensive cases became Group VII in this study. The patients examined had normal acuity and kinetic visual fields, and no visual symp­ toms. No alterations were found in the func­

3.0 r

263

PERIMETRIC ANALYSIS

4.0r

Area o f

Tes

tions measured centrally and at 5°, 10°, and 15°. Both summation and inhibition arms were present. This finding may or may not be significant. If loss of inhibition were found, it would have been meaningful. A negative finding also may indicate that dose levels administered to patients were not suf­ ficiently great to induce changes. While these data are inconclusive, the experiment is pre­ sented as a possible approach for other in­ vestigators in pursuit of questions raised in this study. Optic neuritis and diseases of the optic pathways—Group VIII diseases included papilledema, chiasmal lesions, optic neuritis, and cortical lesions. The characteristics of the patients in Group VIII were the most interesting and puzzling of the entire group. Initially, in cases of optic neuritis, the data indicated a loss of summation but retention of inhibi­ tion, and in individuals with optic pathway lesions, a loss of both summation and inhibi­ tion. While exciting from a diagnostic point

* ^ d

^

i -si

I

iK

Eccentricity From Fovea and ΔΒ Luminance above threshold

3.0-

IS!

5°onO° -o meridian AB=1.0LU. 5°onQ" f meridian *AB=0.5LU.

2.0

ΔΒ= Goldmann size I 0.0

_ § _ _ .n 5C'on 90" meridian AB=0.5L.U.

ψζ::ζ: :--.--:

*»■ Λ -»' ■&.■ ~

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10

2.0 3.0 4.0 LOG BACKGROUND AREA (Minutes of Arc)2

5.0

Fig. 19 (Sunga and Enoch). In this case with retinal edema (B in Figure 18, 5° eccentricity on the 90° half-meridian), there was loss of the inhibition arm of the function within the area of the rela­ tive scotoma. In an area of normal field (A), the functions showed normal summation and inhibition arms.

AMERICAN JOURNAL OF OPHTHALMOLOGY

264

3.0

4.0

AUGUST, 1970

Area of Test Field

1 O.D.

3.0

8

I 2.0

f.O LU. above threshold

LA. (9-13-68) &B'·Goldmann size 0 Central Fovea

1.0

2.0

3.0

5.0

4.0

Log Background Area (Min. of Arc) Field I I

2

Area of Test Field

SOD OS L.A. (11-12-68) Central Fovea ΔΒ-Goldmonn size 0:1.0 LU. above threshold

I 1.0

_L

X

2.0 3.0 4.0 Log Background Area (Minutes of Arc) 2 Field H

5.0

Fig. 20 (Sunga and Enoch). Top: This Westheimer function shows loss of the inhibition arm in the left eye of a patient with macular edema following photocoagulation of a choroidal angioma temporal to the macula. Bottom : These data show recovery of the inhibition function in the same patient. The functions were measured approximately three months after the photocoagulation of a choroidal angioma temporal to the macula. At this time, the macula edema had subsided.

VOL. 70, NO. 2

PERIMETRIC ANALYSIS

of view, these data made little sense in terms of all that which has been discussed in this and in the two previous papers of this series. If the interaction described above was taking place in the retina, how could such profound events be taking place at more central points? Hence, as far as possible, these pa­ tients have been studied in depth. While all details have not been worked out, a fairly consistent set of findings is emerging. These cases exhibit added variables that are impor­ tant in and of themselves, and these variables are treated in the fourth paper in this series.11 Frumkes and Sturr, 12 and Battersby and Wagman, 13 have also conducted studies in which this problem is considered to some de­ gree. In patients with optic neuritis, a surpris­ ing effect was found—not always restricted to the area of relative field loss. After each brief rest period there was a relatively rapid loss in visual sensitivity. For example, if one was determining their static perimetric re­ sponse (the Weber fraction) at a point in a relative scotoma area, the threshold would rise a log unit or more in a remarkably short period of time. Blinking, head movements, saccades, etc., could partially restore sensi­ tivity (depending on duration and extent). This effect was not simply local adaptation or Troxler's effect, for it made little differ­ ence whether the static stimulus was pre­ sented steadily or successively flashed (70 msec flash every half second). To evaluate this response characteristic, the static peri­ metric value was measured repeatedly as a function of time from a starting point fol­ lowing a brief rest period. Measuring Westheimer type functions in these patients proved to be difficult. If a small background field (Field I I ) was pre­ sented first and then progressively larger test fields were employed, these patients showed retention of summation and loss of inhibi­ tion. If a large-size background field target was presented first, and then followed by successively smaller backgrounds (the usual order of presentation), there was essentially

265

normal inhibition and a loss of summation! Most simply stated, these patients exhibited a form of saturation or visual fatigue re­ sponse. By combining the two sets of data, a relatively normal pattern could be defined when Westheimer type functions were mea­ sured. The one patient studied who exhibited mild papilledema exhibited normal Westhei­ mer type functions on repeated trials. Another patient, whose condition has still not been clearly defined, also exhibited sum­ mation loss with inhibition retained. He was referred to the experimenters as a possible case of optic neuritis. He had a vertically oriented, but not quite straight-line scotoma on the right side of his right field covering an area of about 5°. When taking a kinetic field, if one slowed the movement of the spot of light at any point in the general central area, in either eye, the target disappeared. The condition varied some from visit to visit. There were marked deficits in local ad­ aptation (Troxler's effect) in the entire cen­ tral area, making the measurement of static fields very difficult. In the central right half of his field in the more normal eye, there was no field defect, but there was a more marked local adapting region. While homonymous, the scotoma area in the one eye and the more marked or rapid local adaptation defect in the second eye were only partially congruent. There seems to be a general debilative effect coupled with a possible early postchiasmal lesion. This patient had good fixation, and static local adaptation fields were obtained on him using a stop watch.14 Vari­ ance was remarkably limited, and his re­ sponse time was rapid and consistent. This is another fascinating variable, and this case is worthy of detailed study. When measuring Westheimer type functions on this patient, retention of inhibition and loss of summa­ tion was noted. Again by reversing the order of background field presentations, a rela­ tively normal summation arm was deter­ mined. His loss of summation was therefore presumed to be artifactual.

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In the limited number of chiasmal lesions and striate cortex lesions studied, a perfectly flat Westheimer type function was obtained ! In one case, following pituitary surgery, the measured function returned to normal form. In another case, apprehension concerning impending surgery was high and all data un­ satisfactory. In a third case, the patient was somewhat less than the best possible ob­ server. In normal field areas, unaltered func­ tions were obtained without exception. We have been unable to bring the latter two pa­ tients back for further study. In still another patient, recovering from a stroke involving the occipital cortex, visual responses measured in the recovering field area generally resembled those encountered in the cases of optic neuritis. In unaffected parts of the field, Westheimer type functions were normal. In areas of the field showing a relative scotoma, unreliable data having high variance were obtained. With recovery, a normal Westheimer type function was re­ corded. The authors believe that further study of temporal variables in these cases is indicated. Interestingly, many of the threshold values obtained when testing these patients were re­ corded when the background field luminance (Bn) value was relatively small. One often had the feeling that the static threshold was being repeatedly determined, i.e., the back­ ground field (Field I I ) was hardly visible against the cupola background. Observations of the flashing field often followed a saccade, a blink,· etc. This is the highest possible threshold (or the lowest possible sensitivity) condition. As shall be seen in the following part of this paper,11 cupola luminance proved to be an important factor in such cases.

AUGUST, 1970

GROUP V I I I CASE REPORTS

Group VII cases include diseases of the optic pathway. Papilledema—On neurologic workup, this Cauca­ sian woman, age 30, whose visual acuity was RE : 20/25, LE : 20/15, was diagnosed as having pseudotumor cerebri. Examination of the fundus showed elevation of both sides from about 2 to 4 D with slight peripapillary edema. Kinetic field tests re­ vealed enlargement of the blind spots. Westheimer type functions were arbitrarily measured at 5° and 10° eccentricities and both curves showed normal summation and inhibition arms. Optic neuritis—In this Caucasian woman, age 35, visual acuity in both eyes was 20/20. About a year prior to examination, the patient had an episode of seeing a "spot" before the right eye and a similar episode in the left eye a month prior to the exami­ nation. Except for a partial star figure in the left macula, ophthalmic examination was essentially negative. Figure 21 shows the kinetic fields of the right eye. There was an inferonasal quadrant defect to Goldmann II/4e connecting with the blind spot. The defect appeared infero-altitudinal to I/4e· In the left eye, the I/4e isotoper was normal but with I/2e, there was a cecocentral scotoma with a break­ through inferiorly. Westheimer functions were measured at 7° eccentricities on the 15° and 135° half-meridians or radii RE and both response functions were normal. Data were also taken on the 270° half-meridian at 5°, 7°, and 10° eccentricities and all these functions showed a normal inhibition arm, but there was progressive depression of the summation arm. The usual order of background size presentations was used when measuring these functions, i.e., from the largest size (in this case, equivalent to Goldmann target size IV) to the smallest. When the order of the background size presentation was reversed, measurement at 5° ec­ centricity on the 270° half-meridian showed the summation arm was normal, but this time there was loss of the inhibition arm (Fig. 22). Added re­ sponse data on this patient are presented in the fourth paper in this series." Optic neuritis—Visual acuity was 20/20 in both eyes of this Caucasian man, age 34. Since 1963 the patient had had recurrent episodes of blurred vision in both eyes. Fields had shown a small central rela­ tive scotoma, RE, and a superior scotoma, LE. Ex­ amination of the fundus revealed right primary optic atrophy, and temporal pallor of the left disk.

Fig. 22 (Sunga and Enoch). Westheimer functions measured at 5° eccentricity on the 270° halfmeridian (C in Fig. 21) show normal inhibition but depressed summation when the usual background size series was presented (largest to smallest size). When the reverse order of background size targets was presented, there was normal summation but absent inhibition.

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VOL. 70, NO. 2

Fig. 21 (Sunga and Enoch). Kinetic fields of right eye of a patient (D.L.) with optic neuritis. Westheimer functions were measured at 7° eccentricities on the 15° (B), and 135° (A) half-meridians and 5° (C), 7° (D) and 10° eccentricities on the270° half-meridian.

Background Field Presentation

2.0

From largest to smallest size (size Y I l o l l )

1.0

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i

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Fig. 23 (Sunga and Enoch). Kinetic fields of right eye of a second patient (E.K.) with optic neuritis. Background Field Presentation 3.0

2.0

I

I

I -J

S

1.0-

From largest to smallest size (size Y I toll)

i Area of Test Field

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E.K.: Δθ Goldmann size I I 7* on 90" Meridian

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PERIMETRIC ANALYSIS

269

Fig. 25 (Sunga and Enoch). Kinetic fields obtained in the left eye of a patient (C.T.) with chiasmal meningioma. There was a large temporal scotoma of varying density (cross-hatched and dotted areas). The blind spot is included within the dotted areas. The right eye showed temporal hemianopic field loss. There was a small relative scotoma superiorly, RE (Fig. 23) on kinetic fields. Left kinetic fields were normal. Westheimer type functions were measured at 7° on the 90° half-meridian and at the same ec­ centricity on the 270° half-meridian. However, at 90° there was normal inhibition but depressed summation when the usual order of background sizes were pre­ sented (from largest to smallest size). Reversing the order of background size presentations (Fig. 24) again resulted in a function with relatively nor­ mal summation but absent inhibition. Optic neuritis—Visual acuity was 20/20 in both eyes in this patient who, in December, 1967, com­ plained of inability to see the end of words. His ophthalmologist noted a small scotoma, RE. He also developed right temporal headaches. When seen in October, 1968, static fields revealed

an absolute defect from fixation up to 7° and de­ pressed sensitivity from 7° to 11° temporally in the right eye. The rest of the findings were essen­ tially negative. Diagnosis was possible optic neuri­ tis. Repeat fields showed the absolute scotoma to be vertically oriented (but not quite a straight cut) just temporal to fixation and extending about 5° temporally. Between the scotoma and the blind spot, the target disappeared when the movement of the test spot was slowed. The same phenomenon was present also in the left eye. Further testing indi­ cated that there was marked disturbance in local adaptation in both fields." Westheimer functions showed marked variance and there was loss in sum­ mation if large backgrounds were presented first, and a loss of inhibition if small targets were pre­ sented initially. Diagnosis is uncertain at this time,

Fig. 24 (Sunga and Enoch). As in Figure 22, the measured function obtained when the usual order of background size presentations was used showed normal inhibition, but loss of summation. There was a reversal of the function (normal summation but absent inhibition) when the backgrounds were presented from the smallest to the largest area.

AMERICAN JOURNAL OF OPHTHALMOLOGY

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4.0r Area of Test Field C.T. ΔΒ= Goldmann size I : 0.8 L.U. above threshold

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3.0 Eccentricity From Fovea . X?" NASAL « on 0"meridian

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2.0 10° on 210° meridian

0.0

1.0

2.0 3.0 4.0 LOG BACKGROUND AREA(Minutes of Arc) 2

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I

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ΔΒ* Goldmann size 1:0.8 L.U. above threshold fO'on 210'meridian

Nov. 6 1.0 July 31

_L

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5.0

Fig. 26 (Sunga and Enoch). Top: Functions were measured in the left eye within the normal field (A) and within the relative scotoma (B) in a patient with chiasmal meningioma. The function measured within the scotoma was completely flat. Bottom: Recovery of both summation and inhibition arms of the Westheimer functions four months after surgery in the left eye of a patient who had chiasmal meningioma. The kinetic fields in the left eye had improved to normal. Both sets of data were obtained at point B in Figure 25.

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but it is generally agreed that the pathology is cen­ on the 150° half-meridian, the measured functions tral to the retina. There was generalized depression were normal. However, at the same eccentricity on of sensitivity with a small left scotoma (about 1° the 330° half-meridian (right side of the field) the just to the right of the fixation) noted on one occa­ responses were so very erratic that the functions could not be taken reliably. About two weeks later, sion. Chiasmal meningioma—Visual acuity was R E : the Westheimer type response functions were again 20/25, LE : 20/50 in this Caucasian woman, age 30, measured. This time the measured responses at 10° when she noticed gradual blurring of vision, and eccentricity on the 330° half-meridian were nor­ was found to have temporal pallor of the disks. She mal ! In addition, kinetic fields were normal. She underwent surgery for chiasmal meningioma. Three had exhibited marked recovery. weeks after surgery, kinetic fields showed temporal SUMMARY hemianopsia in the right eye and a large relative temporal field defect in the left eye (Fig. 25). Clinical trials were conducted of an ex­ Basic response functions were measured in the left eye at 10° eccentricities in the normal field (0° perimental procedure believed to test recep­ half-meridian or radius, A in Fig. 25) and within tive field properties. The receptive field is the scotoma (210° half-meridian, B). The data taken within the normal field area revealed an es­ composed of a summative area located about sentially normal response curve, while within the the test point, and this, in turn, is sur­ scotoma, the response function was completely flat rounded by an inhibitory zone. That part of (Fig. 26, top). Four months after surgery, kinetic fields still the surrounding visual field (or retina) showed a temporal hemianopic cut in the right eye which influences response at the test point but in the left eye the fields became normal. At this has been termed the receptive field. time, functions again were measured at 10° eccen­ Pathology of the choroid, pigment epithe­ tricity on the 210° half-meridian in the left eye and the curve showed recovery to a normal pattern lium, and receptor cell layer locally reduces (Fig. 26, bottom). retinal sensitivity, but does not alter the Chiasmal meningioma—Visual acuity was 20/20 in both eyes in this Caucasian boy, age 16, who form of the function measured in this study. showed a completely flat function. He had had Inner retinal pathology apparently blocks the episodes of vertigo, headaches and right arm numb­ inhibition component of the receptor field. ness. Kinetic fields showed right congruous superior quadrant-anopsia. Westheimer functions measured On this basis, perimetric differentiation of within the normal field (at 3° eccentricity on the inner retinal pathology from outer retinal 225° half-meridian) were normal. Outside the I/2e pathology can be made at any point in the isopter (at the same eccentricity on the 45° halfmeridian), the measured response functions were visual field. In cases of optic neuritis and completely flat. Four months later, repeat fields in visual pathway pathology, added variables were done and showed essentially identical findings. were observed to complicate the picture. This time, however, the responses outside the I/2e isopter were so erratic that the functions could not They induce recognizable artifacts in the be plotted. measured function. It will be important to Hemianopsia—homonymous hemianopsia, with further delineate the origins of the compo­ macula sparing compatible with occipital lobe le­ sion, was seen in this Negro woman, age 47, whose nents comprising the receptive field, and to visual acuity in both eyes was 20/30. This is an­ study added cases in several disease catego­ other patient with a time varying change in static ries. thresholds. When admitted in November, 1968, she Since no evidence for an increase in re­ had severe headaches, vomiting and lethargy. Ex­ amination revealed slight right-sided motor weak­ ceptive field size has been found in pathol­ ness. EEG showed moderate slow dysrhythmia with ogy, and since the question is really one of definite left posterior triangle localization. Her vi­ sion at that time was 20/20 in both eyes. Multiple the presence of summation and inhibition, it cotton wool exudates and hypertensive vascular may be possible to shorten the basic test changes were present in both posterior polar re­ procedure for speedier first order clinical as­ gions. Kinetic fields revealed right-sided relative sessment. homonymous hemianopsia with macula sparing. Repeat fields were performed two months later ADDENDUM and showed recovery to normal limits to Goldmann III/4e and I/4e. She had inconsistent responses Two important papers by Dowling and when the right side of both fields were being tested. Werblin have recently appeared.15'16 They At that time, Westheimer type functions were mea­ sured. Within the normal field at 10° eccentricity combine an analysis of the cells and inter-

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connections present in the mudpuppy retina15 and intracellular recordings from all types of retinal neural units in this same species.16 The very large dimensions of the cellular components in this species have al­ lowed such an analysis to be made for a first time. Werblin 17 has used a stimulus distribu­ tion somewhat similar to that employed in this (and Westheimer's and Crawford's) study. He notes that a basic response pattern similar to that recorded here is first observed at the bipolar cell level. That is, he records what he calls sensitization effects when annu­ lar stimuli are employed. He notes that the mudpuppy's retina is "wired" in a somewhat similar manner to that of humans, although areas of interaction, etc., may be different. This work presents an important contribu­ tion in the attempt to define the retinal locus of the Westheimer function. The implication is that the neural organization studied first occurs at the outer plexiform layer with the horizontal cells playing an important role. This inference does not limit such activity to that level. ACKNOWLEDGMENTS

We thank the many members of the staff of the Department of Ophthalmology, Washington Uni­ versity School of Medicine, who referred patients to our attention. In particular, the help provided by Drs. Andrew Gay and Maxwell Rachlin was most valuable. We also thank Dr. Mitchell Perry, of the Hypertension Clinic, Barnes Hospital, St. Louis, for his assistance. REFERENCES

1. Enoch, J., Sunga, R., and Bachmann, E. : A static perimetric technique believed to test receptive field properties : I. Extension of the Westheimer

AUGUST, 1970

experiments on spatial interaction. Am. J. Ophthl. 70:113, 1970. 2. Enoch, J., Sunga, R., and Bachmann, E. : A static perimetric technique believed to test receptive field properties: II. Adaptation of the method to the quantitative perimeter. Am. J. Ophth. 70:126, 1970. 3. Westheimer, G. : Spatial interaction in the human retina during scotopic vision. J. Physiol. 181:881, 1965. 4. Westheimer, G. : Spatial interaction in human cone vision. J. Physiol. 190:139, 1967. 5. Brown, K. T. and Murakami, M. : Rapid ef­ fects of light and dark adaptation upon the recep­ tive field organization of S-potentials and late re­ ceptor potentials. Vis. Res. 8:1145, 1968. 6. Sloan, L., and Brown, D. J. : Area and lumi­ nance of test object as variables in projection perimetry. Vis. Res. 2 :525, 1962. 7. Dubois-Poulson, A., and Magis, C. : La notion de sommation spatiale en physio-pathologic oculaire. Mod. Prob. Ophth. 1:218,1957. 8. Fankhauser, F., and Enoch, J. M. : The effects of blur on perimetric thresholds. Arch. Ophth. 68:130, 1962. 9. Wilson, M. D. : Spatial and temporal summa­ tion in impaired regions of the visual field. J. Phy­ siol. 189:189, 1967. 10. Ehinger, B. : Adrenergic neurones in the ret­ ina. Life Sciences. 5:129, 1966. 11. Sunga, R., and Enoch, J. M. : Further peri­ metric analysis of patients with lesions of the vi­ sual pathways. Am. J. Ophth. 70:1970. In press. 12. Frumkes, T., and Sturr, J. : Spatial factors determining visual excitability. J. Opt. Soc. 58:1657,1968. 13. Battersby, W., and Wagmann, I. : Neural limitations of visual excitability. IV. Spatial deter­ minants of retrochiasmal interaction. Am. J. Phy­ siol. 203 :359, 1962. 14. Bay, E. : Disturbances of visual perception and their examination. Brain 76:515, 1953. 15. Dowling, J. and Werblin, F.: Organization of the retina of the mudpuppy, necturus maculosus. I. Synaptic structure. J. Neurophysiol. 32 :315, 1969. 16. Werblin, F. and Dowling, J. : Organization of the retina of the mudpuppy, necturus maculosus. II. Intracellular recording. J. Neurophysiol. 32:339, 1969. 17. Werblin, F.: Personal communication.