Losses of hemi®eld contrast sensitivity in patients with pituitary adenomaand normal visual acuity and visual ®eld

V. Porciattia, d,*, P. Ciavarellaa, M.R. Ghiggib, V. D'Angeloc, S. Padovanoa, M. Grifaa, G. Morettia

aDivision of Ophthalmology, Hospital Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, ItalybDivision of Endocrinology, Hospital Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, ItalycDivision of Neurosurgery, Hospital Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy

dInstitute of Neurophysiology, CNR, Pisa, Italy

Accepted 20 January 1999

Abstract

Objective: To detect early losses of contrast sensitivity (CS) in patients with pituitary adenomas, before the occurrence of visual acuity

and visual ®eld defects.

Methods: CS has been evaluated in both hemi®elds of 28 patients with different kinds of pituitary adenoma (mainly intrasellar) and normal

visual acuity and visual ®eld, as well as in 15 age-matched controls. Two different stimuli were used: a coarse (0.3 c/deg) dynamic (10 Hz)

grating and a ®ner (2 c/deg) static grating.

Results: On average, CS and/or hemi®eld asymmetry were reduced in patients, whereas perimetric sensitivity was normal. CS losses were

more frequent for 2 c/deg static-, as compared with 0.3 c/deg, 10 Hz stimuli. However selective losses for either stimuli were also found. CS

losses did not correlate with anatomical measurements (size, chiasm involvement) of tumors as established by MRI scans.

Conclusions: CS evaluation may provide a simple and effective tool for early detection and monitoring of visual dysfunction in patients

with pituitary adenoma. The lack of correlation between CS losses and chiasm involvement suggests causes different from chiasmal

compression for visual dysfunction. q 1999 Elsevier Science Ireland Ltd. All rights reserved.

Keywords: Contrast sensitivity; Pituitary adenoma; Magnocellular pathway; Parvocellular pathway

1. Introduction

It is well known that pituitary tumors may cause a typical

pattern of visual loss, primarily characterized by reduced

visual acuity and bitemporal hemianopsia (chiasmal

syndrome: Goldstein and Sherman, 1993; Ikeda and Yoshi-

moto, 1995; Trevino, 1995). Chiasmal syndrome, however,

occurs only when tumors have already progressed substan-

tially. Typically, most of patients with pituitary adenoma

seek care for causes different from vision loss. Clinical

visual symptoms may be absent even in cases of very

large (2.5±4 cm) tumors (Auer et al., 1996). Still, surgical

treatment of pituitary tumors is usually prescribed when the

visual ®eld is affected (Cohen et al., 1985; Wormington,

1989; Glaser, 1990).

A suitable visual test, in patients with pituitary adenoma,

should be sensitive enough to; (i) signal dysfunction of the

visual pathway before the onset of a chiasmal syndrome; (ii)

follow up the course of the disease and the effect of a ther-

apy and (iii) establish upper limits of dysfunction beyond

which surgical reduction of the tumor could be considered.

A possibility in this direction is offered by the evaluation of

contrast sensitivity (CS) to sinusoidal gratings. It is known

that CS, as compared with visual acuity, is a more compre-

hensive evaluation of the visual function (Campbell and

Robson, 1968; Shapley, 1990). In addition, in many neuro-

logical disorders involving the visual pathway, CS has been

reported to be earlier and more severely affected than visual

acuity (Bodis-Wollner, 1972; Lorance et al., 1987). CS can

be measured independently for the right or the left hemi-

®eld, in order to evaluate the CS asymmetry between hemi-

®elds (expected to be speci®cally impaired in chiasmal

dysfunction).

A further possibility offered by CS is that of using a set of

stimuli with spatio-temporal characteristics suitable to

emphasize vision subserved by either the parvocellular or

the magnocellular subsystems of the visual pathway (Meri-

gan and Maunsell, 1993; Van Essen and Gallant, 1994). The

Clinical Neurophysiology 110 (1999) 876±886

CLINPH 986631388-2457/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved.

PII: S1388-2457(99)00024-3

* Corresponding author. Tel.: 1 39-50-540-770; fax: 1 39-50-540-080.

E-mail address: porciatt@in.pi.cnr.it (V. Porciatti)

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886 877

Table 1

Summary of clinical features of patientsa

Patient Age Sex Tumor size Chiasm involv. Stalk deviat. Hormon secret. Previous therapy Visual acuity Visual ®eld MD

1. BoAn 29 F 2 1 1 ± BC 1.0 2 0.12

1.0 0.23

2. BrVe 32 F 1 5 1 GH ± 1.0 2 1.81

1.0 2 1.97

3. CaAm 40 F 1 1 1 GH Oct 1.0 1.05

1.0 1.25

4. CaMa 38 M 1 1 1 ± ± 0.9 2 1.42

0.9 2 2.37

5. CiMi 58 M 2 1 3 GH ± 1.0 4.04

1.0 3.5

6. CoAm 47 F 2 1 1 GH Oct 0.95 1.08

0.95 2 0.26

7. DiDo 42 F 3 1 4 ± BC 1.0 0.75

1.0 0.07

8. FiBa 29 M 2 4 2 ± NS1 1.0 2 1.05

1.0 2 0.68

9. FrDa 25 M 1 1 1 ACTH NS1 1.0 2 1.65

1.0 2 3.01

10. GiEl 30 F 2 2 1 ± BC 1.0 2 3.57

1.0 2 2.23

11. GuMi 69 M 2 1 1 ± ± 1.0 3.17

0.95 2.18

12. InDo 40 F 2 5 1 ± ± 0.95 2 1.93

0.65 2 2.4

13. IrGi 34 F 3 3 1 ± BC 1.0 2 0.16

1.0 0.14

14. LoPa 24 F 1 1 1 Prol BC 1.0 0.76

1.0 1.27

15. LoMG 26 F 2 1 1 Prol Cab 1.0 2 2.64

NS1 1.0 2 2.59

16. MaAn 46 F 1 5 1 Prol Cab 0.95 2 4.95

0.95 2 6.60

17. MaGi 42 M 3 1 1 ± NS1 ± ±

1.0 2 0.85

18. MiSi 30 F 2 1 4 Prol Cab 1.0 2 0.30

1.0 2 1.76

19. NuEl 30 F 1 1 4 GH Oct 1.0 0.35

NS1 1.0 2 0.70

20. PePa 23 F 2 1 4 GH NS1 1.0 2 0.15

1.0 2 1.99

21. RuAn 58 M 1 1 1 GH Oct 0.75 2 0.96

NS2 1.0 2 3.36

22. SaLo 31 F 2 1 1 ± BC 1.0 2 0.23

1.0 2 0.13

23. SeLu 29 M 1 5 1 GH NS2 1.0 2 1.9

1.0 2 2.23

24. ScGi 49 F 1 5 2 GH Oct 1.0 2 5.97

NS1 1.0 2 5.49

25. TiPa 34 F 1 1 1 Prol BC 1.0 0.61

Cab 1.0 0.88

26. ToCi 23 F 1 1 1 ± ± 1.0 2 1.08

1.0 2 2.09

27. TuFi 38 F 2 1 3 ± ± 1.0 2 4.81

1.0 2 4.99

28. VeLn 25 F 1 5 3 Prol BC 0.9 0.87

1.0 2 0.40

a GH, growth hormone; ACTH, adreno-cortico-trophic-hormone; Prol, prolactin; BC, bromocriptine 1.3 mg/day (patient #1), 2.5 mg/day (patient #13), 5.0

mg/day (patients #7, 10, 22, 28), 7.5 mg/day (patient #14); Cab, cabergoline 1.0 mg/day; Oct, octreotide 0.3 mg/day; NS1, one neurosurgery session; NS2, two

neurosurgery sessions.

P/M systems originate from retinal ganglion cells with

different soma size (small/large), relay to different laminae

of the lateral geniculate nucleus (parvocellular/magnocellu-

lar) and then project to different layers of the striate cortex

(4Cb /4Ca ). P and M systems also display very different

functional characteristics. Neurons of the P system respond

well to stimuli of low temporal- and high spatial frequency,

whereas those of the M system do it for stimuli of high

temporal- and low spatial frequency. It has been shown in

the monkey, that selective lesions of the parvocellular lami-

nae of the lateral geniculate nucleus do not alter the CS for

stimuli of high temporal- and low spatial frequency (which

emphasize the activity of the M system) (Merigan et al.,

1991). By contrast, selective lesions of the magnocellular

laminae of the lateral geniculate nucleus do not alter the CS

for stimuli of low temporal- and high spatial frequency

(which emphasize the activity of the P system) (Merigan

and Maunsell, 1990). So, evaluating the CS for stimuli

with the above characteristics in patients with pituitary

adenoma may help to detect early dysfunction, involving

primarily P or M ®bers. A differential interaction of P and

M ®bers with pituitary tumors may be expected, since ®ber

retinotopy at chiasmal level is reported to be very compli-

cated in primates (Poliak, 1957; Hoyt and Luis, 1963; Reese

and Cowey, 1990; Naito, 1994).

This study reports results obtained in a group of patients

with different kinds of pituitary adenomas. It will be shown

that most of them have substantial losses of CS in presence

of normal visual acuity and visual ®eld. CS losses are poorly

correlated to both the size of the adenoma and the way the

tumor impinges on the optic chiasm, suggesting that chiasm

compression is not the sole source for visual dysfunction.

CS may be selectively altered for stimuli emphasizing the

function of either the P or the M pathway, in keeping with

the notion of segregation of the two subsystems at the level

of the optic chiasm in primates. Part of these results have

been published previously in abstract form (Porciatti et al.,

1997a, b).

2. Methods

2.1. Subjects

Twenty-eight subjects (8 males, 20 females) attending the

Division of Endocrinology of the Hospital Casa Sollievo

della Sofferenza, San Giovanni Rotondo, Italy, were

included in the study. Their age ranged from 23 to 69

years (mean age 36.5, SD 11.7). All cases were diagnosed

having pituitary adenoma, on the basis of standard clinical

criteria and MRI (Asa et al., 1993; Schubiger, 1996). MRI

scans (2 mm resolution, T1-weighted sagittal/coronal spin-

echo sequences before/after Gd enhancement) were also

used to establish the size of the tumor, as well as the way

it impinges on the optic chiasm and/or deviates the pituitary

stalk (Kucharczyk and Davis, 1986; Elster, 1993; Schubi-

ger, 1996). Adenomas were divided into 3 groups, according

their size (Asa et al., 1993; Schubiger, 1996): (1) intrasellar

microadenoma, less than 1 cm; (2) intrasellar macroade-

noma, 1 cm or more and (3) extrasellar macroadenoma.

Five categories of chiasm involvement could be established:

(1) none; (2) indentation; (3) dislocation; (4) compression;

(5) empty sella. Pituitary stalk deviation exerted by adeno-

mas was de®ned as: (1) none; (2) on axis but tilted back-

wards; (3) tilted rightwards (4) tilted leftwards.

Sixteen subjects had secretory tumors (Growth hormone,

n � 9; Prolactin, n � 6; ACTH, n � 1) while 12 had non-

functioning adenomas. Subjects, when necessary, were on

adequate medical therapy with dopamine or somatostatine

agonists (Johnston et al., 1981; Warnet et al., 1989; Ezzat et

al., 1992; Malarkey, 1993; Webster et al., 1994). Eight

subjects had had previous microsurgical transsphenoidal

debulking of the tumor. All patients had a standard ophthal-

mological examination, including Humphrey static perime-

try (program 30-2). All patients had good visual acuity and

visual ®eld, according standard criteria (Sponsel et al.,

1995) in both eyes, except subject #17 whose right eye

was blind due to a previous trauma.

A summary of clinical details of patients is reported in

Table 1. Fifteen normal control subjects, age- and sex-

matched with the patients' group, were also included in

the study. All subjects had no or small refractive errors,

which were suitably corrected for the viewing distance.

All experiments followed the tenets of the declaration of

Helsinky. Informed consent was obtained after the aims

and the experimental techniques were fully explained. The

experiments had the approval of the local ethical committee.

2.2. Visual stimuli

Visual stimuli were vertical sinusoidal gratings, gener-

ated electronically and displayed on a 17 0 0 black and

white monitor (Eizo Flexscan 5500, Jokogawa, Japan) at a

frame rate of 60 Hz, 800 £ 600 pixels, mean luminance 100

cd/sqm. Two kinds of stimuli were used: a coarse, dynamic

grating (0.3 c/deg, sinusoidally modulated in counterphase

at 10 Hz: de®ned as M-stimulus) and a ®ner (2 c/deg), static

grating: de®ned as P-stimulus. These spatio-temporal condi-

tions are close to those at which the CS for dynamic and

static gratings, respectively, is reported to be highest

(Robson, 1966). The system (Mangoni, Pisa, Italy) allowed

presentation of stimuli in the right or left hemi®eld as well

as ®ne adjustment of contrast by speci®c pushbuttons along

a dB scale (de®ned as 20 log10 contrast). Luminance linear-

ization by gamma correction was provided by the factory.

Patterned and unpatterned hemi®elds were equiluminant.

Subjects ®xated monocularly at a small square placed in

the stimulus center from 57 cm distance (visual ®eld 24:5 £32 deg) with natural pupils (measured with a ruler to be in

the range 4±5 mm in all subjects). The stimulus was

occluded to the non-®xating eye by means of a frosted lens.

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886878

2.3. Psychophysical technique

Sensitivity estimates were obtained with the method of

ascending limits. The experimenter decreased the contrast

of the stimulus until the observer reported that the stimulus

was no longer visible. The contrast was further lowered by

4±8 dB, and then increased in small steps (1 dB) until the

subject reported seeing it, to yield threshold. Subjects were

given adequate time for learning the procedure and the

different kind of stimuli (M-/P-stimulus, Right/Left visual

®eld) whose sequence was randomly chosen. For each

condition, at least 12 measures (divided in two blocks)

were made, to verify consistency of responses. Additional

measures were made when necessary to keep test-retest

reliability within 2 dB. The method of ascending limits

may be considered non-optimal in terms of precision and

progressive shift in threshold due to perceptual learning.

However, the present procedure represented a good compro-

mise between precision, reliability, time constraints and

feasibility in a clinical context.

3. Results

3.1. Normal controls

Sensitivity estimates obtained in normal observers (15

eyes of 15 subjects) from either hemi®eld for M- and P-

stimuli are summarized in the histograms of Fig. 1. For

both kind of stimuli, the contrast sensitivity is of the

order of 42 dB, and there is no signi®cant asymmetry

between the right or left hemi®eld. Filled symbols between

histograms represent the full-®eld contrast sensitivity

(average of two hemi®elds) and the 95% con®dence limits

of normality.

3.2. Patients

Examples of CS measured in subjects #8 and 10 are

reported in Fig. 2. Both subjects had an intrasellar, non-

secerning tumor whose anatomical characteristics are

reported in Table 1. Patient #8 underwent a surgical reduc-

tion of the tumor 2 years before. In both patients, the visual

acuity and visual ®eld were normal. Further details of the

two subjects are reported in Table 1. It can be noted that the

two subjects show different kinds of CS loss. In both eyes of

subject #8, the CS is below the 95% con®dence limits of

normality (white boxes) for the M-, but not for P-stimulus.

In addition, the CS is signi®cantly (t test, P , 0:05) asym-

metric between hemi®elds for both M- and P-stimuli in the

left eye and for the M-stimulus in the right eye. In subject

#10 the CS loss, on average, is greater for the P- than for the

M-stimulus. CS asymmetry between hemi®elds is signi®-

cant for both M- and P-stimuli in the left eye and for the P-

stimulus in the right eye. It is interesting that in subject #8,

but not subject #10, the sign of hemi®eld asymmetry is eye-

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886 879

Fig. 1. Average monocular contrast sensitivities (histograms ^ SEM) eval-

uated from the right and left hemi®eld of 15 normal subjects for M (0.3 c/

deg, 10 Hz counterphase modulation) and P (2 c/deg, static) stimuli. The

®lled symbols between histograms represent the full-®eld (average of two

hemi®elds) contrast sensitivity and their 95% con®dence limits.

Fig. 2. Contrast sensitivities (histograms ^ SEM) evaluated in two repre-

sentative subjects with pituitary adenoma and normal visual acuity and

visual ®eld. The white boxes represent the 95% con®dence limits of

normality.

dependent. Overall, histograms in Fig. 2 are representative

of the heterogeneity of ®ndings in patients, indicating that:

(i) CS mean losses may be of different extent for the M- and

the P-stimulus; (ii) signi®cant hemi®eld asymmetries may

be found in presence of normal full-®eld CS; (iii) the sign of

hemi®eld asymmetry may or may not be eye-dependent.

Results obtained in the whole group of patients are summar-

ized below.

3.3. Comparison between CS and clinical measurements of

vision

In Fig. 3, individual CS mean losses (average of the right

and left hemi®eld) are compared to losses of visual acuity.

Visual acuity losses have been transformed in dB values in

order to compare data on the same scale. It is readily

apparent that in the great majority of eyes CS losses may

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886880

Fig. 3. Loss (deviation from the normal mean) of full-®eld contrast sensitivity plotted against corresponding loss of visual acuity for stimuli of M- (left) and P-

(right) type. Data have been obtained from individual eyes of the patient group.

Fig. 4. Loss (deviation from the normal mean) of full-®eld contrast sensitivity plotted against corresponding loss of perimetric sensitivity for stimuli of M-

(left) and P- (right) type. Data have been obtained from individual eyes of the patient group.

be found in presence of normal visual acuity, for both M-

and P-stimuli.

In Fig. 4, CS mean losses are compared with visual ®eld

losses (Humphrey Program 30-2, Mean Deviation). This is a

meaningful comparison, since CS and perimetric sensitivity

are evaluated approximately over the same region of the

visual ®eld. It can be noted that, on average, CS losses

evaluated in individual eyes tend to be larger than peri-

metric losses. For statistical evaluation, sensitivities of the

two eyes have been averaged and used as a single entry. In

addition, subjects who had received surgical treatment (#8,

9, 15, 18-21, 23-24) were distinguished from those who had

received medical treatment only. A two-way ANOVA was

performed. The factors were Treatment (no surgery,

surgery) and Test (Humphrey MD, M-stimulus mean loss,

P-stimulus mean loss). The results are summarized in Fig. 5

as histograms. Signi®cant effects were Surgery:

F�1; 83� � 4:2, P � 0:04 and Test: F�2; 80� � 4:56,

P � 0:001. Post-hoc comparisons (Student-Neuman-Keuls,

P , 0:05) indicated that contrast sensitivity losses (for both

M- and P-stimuli) were, in patients undergoing surgery,

larger than those of patients receiving medical treatment

only. In addition, contrast sensitivity losses (for both the

M- and P-stimuli) were larger than those evaluated with

the Humphrey perimeter. These latter losses did not signi®-

cantly differ from zero.

Fig. 6 compares CS hemi®eld asymmetry evaluated in

individual eyes with corresponding perimetric hemi®eld

asymmetry. This latter measure is not currently available

on standard perimeters. Perimetric asymmetry has been

computed by ®rst averaging deviations of all tested points

in each hemi®eld (n � 19), and then subtracting the aver-

aged values. For both contrast and perimetric asymmetries,

data have been recti®ed to positive values to normalize the

sign of asymmetry. As shown in Fig. 6, the asymmetry in

sensitivity between hemi®elds tends to be somehow larger

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886 881

Fig. 5. Comparison between average losses of perimetric sensitivity and

full-®eld contrast sensitivity (M- and P-stimuli) in the patient group. Histo-

grams represent the mean sensitivity loss (1SEM) of patients (average of

the two eyes). Cross-hatched and open histograms represent patients who

underwent surgery (n � 8) or medical treatment only (n � 20), respec-

tively.

Fig. 6. Contrast sensitivity hemi®eld asymmetry plotted against perimetric hemi®eld asymmetry for stimuli of the M- (left) and P- (right) type. Data have been

obtained from individual eyes of the patient group.

for CS measurements than for perimetric measurements.

As for CS mean losses, a two-way ANOVA statistics

was performed on data obtained by averaging measures

of the two eyes, and distinguishing subjects receiving

surgical or medical treatment. Factors were Treatment

(no surgery, surgery) and Test (perimetric asymmetry, M-

stimulus asymmetry, P-stimulus asymmetry). Data are

summarized in Fig. 7. The only signi®cant effect was

Test: F�2; 83� � 4:09, P � 0:02. Post-hoc comparisons

(Student-Neuman-Keuls, P , 0:05) indicated that P-, but

not M-stimulus, asymmetry was larger that perimetric

asymmetry. In addition, P-stimulus asymmetry was larger

than M-stimulus asymmetry.

A further question to ask was whether the sign of CS

asymmetry was consistent with the model: temporal-hemi-

®eld CS , nasal-hemifield CS, signaling speci®c dysfunc-

tion of the crossed projection. For both the M- and P-stimuli,

the number of eyes in which hemi®eld asymmetry ®tted the

model was comparable to that of eyes with inconsistent

asymmetry (M-stimulus: 32/55 vs. 23/55; P-stimulus: 27/

55 vs. 28/55).

3.4. Comparison between losses with M- and P-stimuli

In Fig. 8, CS losses (both mean loss and hemi®eld asym-

metry) evaluated with the M-stimulus are compared with

those evaluated with the P-stimulus. Dashed lines, repre-

senting upper limits of normality, divide diagrams in 4

sectors. Data points falling in the lower left sector are within

the normal range, whereas data points in the upper right

sector indicate eyes in which the CS is altered for both the

M- and P-stimuli. Data points falling in upper left, or lower

right, sectors indicate eyes in which CS is altered selectively

for the P- or M-stimulus, respectively. It can be noted in Fig.

8 that: (i) many eyes show selective impairment of CS (in

particular hemi®eld asymmetry) and (ii) losses occurring for

the P-stimulus are more frequent than those for the M-

stimulus.

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886882

Fig. 7. Comparison between average perimetric asymmetry and contrast

sensitivity asymmetry (M- and P-stimuli) in the patient group. Histograms

represent the mean asymmetry (1SEM) of patients (average of the two

eyes). Cross-hatched and open histograms represent patients who under-

went surgery (n � 8) or medical treatment only (n � 20), respectively.

Fig. 8. Abnormalities detected with M- and P- stimuli for average contrast sensitivity (left) and hemi®eld asymmetry (right) measurements. Vertical and

horizontal dotted lines represent the upper limits of normality for M- and P- stimuli, respectively. Numbers within diagrams correspond to the eyes with

abnormal vision for the P-stimulus only (upper left), M-stimulus only (bottom right) or both stimuli (upper right).

3.5. Association between CS and anatomical measurements

of tumor

A question to ask was whether CS losses were associated

to the anatomical dimensions of adenomas and the extent to

which they interact with the optic chiasm. These anatomical

measures have been obtained from MRI scan (see Section 2

and Table 1). Adenomas were divided into 3 groups, accord-

ing to their size (Asa et al., 1993; Schubiger, 1996): (1)

intrasellar microadenoma, less than 1 cm; (2) intrasellar

macroadenoma, 1 cm or more and (3) extrasellar macroa-

denoma. In Fig. 9, CS mean losses are plotted against corre-

sponding size of adenomas. It can be noted in Fig. 9 that CS

losses are rather independent of the size of adenoma. A two-

way ANOVA was performed on data obtained by averaging

measures of the two eyes. Factors were Tumor size (1±3)

and Stimulus (M, P). No signi®cant effects were found.

A more stringent comparison is between CS mean losses

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886 883

Fig. 9. Loss of full-®eld contrast sensitivity as a function of adenoma size: (1) intrasellar microadenoma , 1 cm; (2) intrasellar macroadenoma . 1 cm and (3)

extrasellar macroadenoma.

Fig. 10. Loss of full-®eld contrast sensitivity as a function of chiasm involvement: (1) none; (2) indentation; (3) dislocation; (4) compression and (5) empty

sella.

and the extent with which adenomas impinge on the optic

chiasm. From MRI scans it was possible to de®ne 5 cate-

gories of chiasm involvement: (1) none; (2) indentation; (3)

dislocation; (4) compression and (5) empty sella (see section

2 and Table 1). In Fig. 10, CS losses of individual eyes have

been plotted as a function of degree of chiasm involvement.

As shown in Fig. 10, there is no apparent relationship

between CS loss and the extent of chiasmal involvement.

In particular, CS losses found in group 1 (no direct chiasm

involvement) may be equal to, or even larger than, those of

groups with de®nite chiasm involvement.

MRI scans were also used to establish 4 categories of

pituitary stalk deviation exerted by adenomas: (1) none;

(2) on axis but tilted backwards; (3) tilted rightwards and

(4) tilted leftwards (Table 1). There was no signi®cant rela-

tionship between CS loss and pituitary stalk deviation (one-

way ANOVA, not shown in ®gures).

3.6. Association between CS losses and hormonal levels

Since CS losses were poorly correlated to either tumor

size or the way it impinges on the optic chiasm, we asked the

question of whether psychophysical measures depended on

hormonal levels. Patients with secretory adenomas (n � 16)

were divided into two groups: (1) growth-hormone secern-

ing, n � 9 and (2) prolactin secerning, n � 6. Patient no. 9

was excluded, since he was the only representative with

elevated ACTH. At time of testing, growth-hormone level

ranged from 1 to 13 mU/l (mean: 7.4, SD 5), and prolactin

from 0.8 to 115 mU/l (mean: 40.2, SD 45.8). There was no

statistically signi®cant correlation (Pearson) between CS

mean loss/CS hemi®eld asymmetry and the levels of growth

hormone and prolactin.

3.7. Association between CS losses and disease duration

A further question to ask was whether the amount of CS

loss, independently of its anatomical/biochemical causes,

was associated to disease duration. Known duration (time

between ®rst diagnosis and CS testing) ranged between 1

and 84 months (mean: 15.5, SD 18.3). There was no statis-

tically signi®cant correlation (Pearson) between CS mean

loss/CS hemi®eld asymmetry and disease duration.

4. Discussion

The aim of this study was to establish whether the

contrast sensitivity for selected stimuli presented in either

hemi®eld was a suitable test to detect dysfunction of the

visual pathway in patients with pituitary adenoma, before

the onset of a chiasmal syndrome, which represents a rather

late stage in tumor progression (Goldstein and Sherman,

1993; Ikeda and Yoshimoto, 1995; Trevino, 1995). Chias-

mal syndrome, primarily de®ned on the basis of a typically

abnormal visual ®eld, is currently used as a hallmark for

surgical treatment (Cohen et al., 1985; Wormington, 1989;

Glaser, 1990).

Contrast sensitivity measurements have been previously

reported to be impaired in patients with chiasmal compres-

sion and visual complaints (Bodis-Wollner and Diamond,

1976; Kupersmith et al., 1982; Plant, 1985; Lorance et al.,

1987; Grochowicki et al., 1990). The present results indicate

that pituitary adenomas can cause signi®cant dysfunction of

the visual pathway in many patients without chiasmal

compression and normal visual acuity and visual ®eld. In

particular, the comparison between CS losses (both average

loss and hemi®eld asymmetry) and perimetric losses is

meaningful, since both measurements have been obtained

from the same region of the visual ®eld. On average, CS is

signi®cantly altered when perimetric sensitivity is not. In

addition, CS is more altered in previously operated patients

as compared with those receiving medical treatment only.

That CS is able to signal different levels of subclinical visual

dysfunction is of potential interest for both better under-

standing of chiasmal disorders and therapeutical follow-up

of patients. Overall, our data extend previous results show-

ing that CS may be earlier and more severely affected than

visual acuity and/or visual ®eld in many neurological disor-

ders involving the visual pathway (Bodis-Wollner, 1972;

Lorance et al., 1987).

Merigan and Maunsell (1990) and Merigan et al. (1991)

using conditions comparable with those used in the present

study, were able to induce selective CS losses for either M-

or P-stimuli in the monkey with lesion of speci®c laminae of

the lateral geniculate body. Given the overall similarity

between the monkey- and human visual system, it is likely

that the stimuli we have used are adequate to show, at least

in part, differential impairment of P- and M-subsystems. As

shown by our results, CS losses were found for both M- and

P-stimuli. However, several eyes showed selective loss of

CS for one of the two stimuli. This may suggest primary

involvement of either the M- or the P-pathway, in keeping

with the notion of segregation of M- and P-®bers at the level

of the optic chiasm in primates (Reese and Cowey, 1989;

Naito, 1994). A non-uniform damage may depend on the

heterogeneous ways tumors affect the optic chiasm. On

average, CS losses (in particular hemi®eld asymmetry) for

P-stimuli were more frequent than those for the M-stimuli.

This may suggest overall higher vulnerability of P-®bers, as

compared with M-®bers, in chiasmal disease (Reese and

Cowey, 1989).

Psychophysical visual dysfunction in presence of normal

visual acuity and Bjerrum campimetry, in patients with

tumors extending in the suprasellar region, has been

reported for foveally-presented (0.25 deg) ¯ash stimuli

(Gutowsky et al., 1997). Losses were uniform for chromatic,

luminance and temporal sensitivities, indicating unspeci®c

dysfunction of the magno- and parvocellular pathways. Our

results are in keeping with the above ®ndings, in that pitui-

tary adenomas can cause substantial visual dysfunction

which is not detectable with routine examinations. In addi-

V. Porciatti et al. / Clinical Neurophysiology 110 (1999) 876±886884

tion, they extend them indicating that losses may be

detected at earlier stages. Although the psychophysical tech-

niques used in the present and the Gutowsky et al. (1997)

study were different, the overall amount of sensitivity loss is

of the same order. Contrary to the Gutowsky et al. (1997)

results, however, our data suggest differential and speci®c

vulnerability of the magno- and parvocellular pathways.

This discrepancy may well depend on the different contin-

gent of ®bers subserving foveal and more peripheral regions

of the visual ®eld (Reese and Ho, 1988; Naito, 1989, 1994;

Plant and Perry, 1990).

It is interesting that signi®cant CS losses have been found

in many cases in which the size of adenoma was small

enough not to establish any direct or major involvement

of the optic chiasm. This ®nding strongly suggests that

chiasmal compression per se is not the primary cause of

visual dysfunction in our patient sample. Also, interference

with inferior vessels of the optic chiasm (Bergland and Ray,

1969) is unlikely. Hence, other possibilities have to be taken

into account.

At the present stage, the sources of visual dysfunction are

mainly matter of speculation. Our data appear to exclude

hormonal levels and disease duration as signi®cant factors.

Pharmacological treatment might play a role. However,

dopamine agonists are reported to induce positive effects

on the CS of normal subjects (Domenici et al., 1985). An

adverse chemical effect on CS exerted by substances asso-

ciated with developing tumor cannot be excluded. These

include growth factors, proteases, as well as toxic metabo-

lites. Possibly, multiple factors contribute to CS losses in

pituitary adenomas. Gutowsky et al. (1997) also suggested

multifactorial causes for foveal dysfunction in patients with

suprasellar tumors. A better understanding of pathophysio-

logical mechanisms in patients with pituitary adenomas

might be provided by longitudinal studies of patients. Preli-

minary results (Porciatti et al., 1997b) show that some

patients of the same sample, followed-up during the course

of pharmacological treatment, showed clear improvement

of CS loss and CS asymmetry. The improvement could be

selective for either M- or P-stimulus, and occurred at

constant visual acuity, visual ®eld and tumor size as

assessed by MRI scans.

Independently of the mechanisms responsible for visual

dysfunction, the present results suggest that CS evaluation

may provide a simple and effective tool for early detection

and monitoring of visual dysfunction in patients with pitui-

tary adenoma. In prospective, this could offer the possibility

for earlier surgery, before severe damage of the visual path-

way has occurred.

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