Abstracts from the 21st Pupil Colloquium



P.D.R. Gamlin and R.J. Clarke

Pupil Dynamics in Rhesus Monkeys

To investigate the characteristics of the pupil plant in the Rhesus monkey, we have examined pupilloconstriction elicited by electrical microstimulation of the Edinger-Westphal nucleus (EW) or the pupillomotor fibers of the oculomotor nerve (OMN). Alert rhesus monkeys fixated a dim laser spot on a tangent screen while the pupil diameter of both eyes was measured under infrared lighting using ISCAN RK-406 pupillometry systems. A microelectrode was lowered under physiological guidance either to the EW or the OMN. Microstimulation was carried out over a wide range of parameters. In response to brief stimulus trains, the pupil constricted with a latency of 80-120 ms. Shorter latencies were associated with higher stimulation currents. Peak pupilloconstriction occurred approximately 300-500ms after stimulation and showed an exponential return to baseline with a time constant of approximately 300-600ms. These characteristics indicate that the pupil plant acts as a low pass filter and explain the sluggishness of pupillary responses. While a first-order model of the pupil plant with a time constant of approximately 350 ms approximates these results, a third-order model is required to provide a more complete description.


Vision Science Research Center, University of Alabama at Birmingham,

Birmingham, AL 35294, USA. Phone (205) 934 5533 Fax (205) 934 5725







Shinji OONO, Maki MATSUO, Shigeto HARA

Accommodation, convergence and pupil dynamics in phoriamyopia

Purpose: Some patients with exodeviation control it with accommodation. This is called phoriamyopia, or pseudomyopia. Phoriamyopia is accompanied by not only accommodation but pupil constriction with convergence to orthophoria. The phenomenon is similar to near reaction in normal subjects. We recorded simultaneously three reactions, namely accommodation, pupil constriction and convergence which are induced on phoriamyopia. We also compared these reactions with near reaction in normal subjects, to investigate differences between them.

Patients and methods: We studied 4 patients with phoriamyopia and 7 normal subjects. Normal subjects were orthophoria and had sufficient fusional amplitude. Accommodation was continuously recorded with a modified autorefractometer (Nidek AR-15). The pupil reaction was recorded by monitoring the CRT of the autorefractometer. Convergence was recorded with a DC electro-oculograph.

Results: Fusional amplitude in phoriamyopia patients was insufficient (2) or absent (2). Accommodative convergence in phoriamyopia and near reaction in normal subjects occurred in the same order, namely, 1., convergence; 2., accommodation; and 3., miosis. However, the accommodation latency time from the beginning of convergence to control exodeviotion in phoriamyopia (78± 11msec) was shorter than that in near reaction of normal subjects (131± 37msec), that was statistically signifficant. The latency time of miosis from the convergence was 308± 40msec in phoriamyopia and 359± 79msec in near reaction, respectively, that was statistically insignifficant. The latency times of miosis from accommodation was therefore 230± 48msec in phoriamyopia and 228± 53msec in near reaction, respectively, that was statistically insignifficant. The result suggested that the miosis induced in both phoriamyopia and near reaction ocurs more closely related to accommodation than convergence.

Conclusions and discussion: It was confirmed that phoriamyopia is accompanied by not only accommodation but pupil constriction. Three reactions in phoriamyopia appear to mimic near reaction in normal subjects. However, the latency time of accommodation from the convergence in phoriamyopia was much shorter than that of near reaction. This suggests that accommodation initiates accommodative convergence in phoriamyopia, but convergence does in near reaction.

Keywords: phoriamyopia, convergence, accommodation, miosis, near reaction

Department of Ophthalmology, Saga Medical School

Nabeshima, Saga 849, Japan



C. Kriegbaum, H. Wilhelm, B. Wilhelm and F. Schaeffel

Binocular balance of the near reaction

Accommodation and pupillary near reaction are usually thought to be equal in both eyes. We tested for interocular differences.

Methods: By means of real time (25 Hz) infrared video retinoscopy and simultaneous pupillography, refraction and pupillary diameter were recorded during fixation of a target at distances of 50, 33, 25, and 20 cm in 45 emmetropic (refractions not ex-ceeding ±0.75 dpt) subjects between 6 and 39 years. Measurements were performed during monocular fixation, one eye covered by an infrared light transmitting filter. Accommodation and pupillary near responses of the leading (LE) and non-leading eye (NE) and, additionally, of the uncovered eye ("direct near response") and covered eye ("consensual near response") were compared.

Results: 20 cm target distance (Mean values ± standard deviations):

20 cm target distance

LE dir.

NE dir.

LE cons.

NE cons.

Refraction during near fixation [dpt]





Pupillary near response [ mm ]





Pupil diameter during near fixation [ mm ]





Statistics (Student t-test for paired samples): Significant differences between direct and consensual accommodation (LE p_0.005; NE p_0.05) and between pupil diameter during near fixation (LE only, p_0.01). Otherwise no significant differences. — The results obtained for the longer viewing distances showed similar interocular differences.

Conclusions: There are no significant differences of accommodation and pupillary near response between the leading and non-leading eye in normal subjects under monocular viewing conditions. However, there are small but significant differences between direct and consensual accommodation, both for the leading and non-leading eye. This finding indicates that there are slight interocular differences in accommodation. An artifact by the infrared transmitting filter could be excluded. The pupillary near reaction is highly variable among individuals. Significant differences were only found between the pupillary diameter of the covered and uncovered leading eye. The near vision system is not perfectly balanced, which may contribute to the development of asthenopia or amblyopia.



University Eye Hospital, Dept. of Pathophysiology of Vision and Neuro-ophthalmology, D-72076 Tübingen

Phone +497071 294786, Fax +497071 295038, e-mail wilhelm@uni-tuebingen.de





Barbur J L, Cole V & Harlow A J

Separation of pupil light reflex response components

We have developed and applied new techniques for isolating different components in the pupil light reflex (PLR) response. The aim is to understand abnormal pupil responses and in particular why lesions to the primary visual cortex cause a reduction in PLR amplitude for most stimulus conditions.

The test pattern consists of an area of 9ox 9o divided into smaller square elements of variable size. In order to achieve local luminance contrast masking, we employed spatial modulation of the luminance of each check in the array and varied systematically the amplitude of random luminance modulation (RLM). The spatial modulation is dynamic, the luminance of each check changing randomly every 83 ms, but the space averaged luminance of the stimulus remains constant and equal to that of the surrounding background (see Barbur et al, Proc. Roy. Soc. Lond. B, 258, 327-334, 1994). In addition, the mean luminance of the test pattern can also be modulated independently in the same sequence, causing random, temporal changes in the mean light flux level of the stimulus. Results In normal subjects the results show that the PLR amplitude decreases asymptotically to a steady level as the spatial modulation amplitude is increased. No such decrease is observed when the stimulus is restricted to cortically blind spatial modulation amplitude is increased. No such decrease is observed when the stimulus is restricted to cortically blind regions of the visual field. When temporal modulation of light flux level is also employed, the remaining PLR amplitude can be abolished completely in both normal subjects and hemianopes. The results obtained suggest that there are at least two components involved in mediating the pupil light reflex response with different spatial properties. These components may also be associated with different pathways since the use of spatial modulation fails to cause a reduction in PLR amplitude in subjects with damaged primary visual cortex.

City University, Applied Vision Research Centre, Department of Optometry & Visual Science, 311-321 Goswell Road, London EC1V 7DD. Tel. +44-171-4778000 Fax +44- 171-4778355, e-mail: J.L.Barbur@city.ac.uk








Harlow A J, Cole V, & Barbur J L

Methods for isolating pupil colour responses in the periphery of the visual field

We have investigated new techniques for isolating pupil colour responses (PCR) from afferent pupil light reflex (PLR) signals when coloured stimuli are presented in the periphery of the visual field. Under such conditions the response of the pupil is dominated largely by rod driven PLR signals. The aim was to establish whether pure PCRs can be isolated and elicited in subjects with damaged primary visual cortex who show coarse residual discrimination of colour when large visual stimuli are employed (Brent et al, Proc. R. Soc. Lond. B., 256, 1994). Pupil responses to large chromatic stimuli (i.e., a 9 deg square, presented 12 deg in the periphery) were measured in normal subjects and in patients with damaged primary visual cortex. The test pattern consisted of an array of checks defined by luminance contrast. Initial findings prompted the development of two luminance masking techniques. Firstly, local luminance masking was achieved by employing spatial modulation of the luminance of each check in a large array that formed the test pattern, every 83 ms (Barbur et al, Proc. Roy. Soc. Lond. B, 258, 327-334, 1994). Spatial modulation does not change the mean luminance of the pattern. Secondly, the mean luminance of the pattern elements that formed the coloured stimulus was also modulated independently, in the same sequence, causing random, temporal modulation of the mean light flux over the pattern. In normal subjects, the spatial masking technique can reduce the amplitude of PLR responses elicited with achromatic stimuli, but it has little or no effect on the PCR amplitude when the stimuli are presented in the periphery of the visual field. The temporal modulation technique, on the other hand, eliminates the PLR response to achromatic stimuli, and it also reduces the response amplitude to chromatic stimuli, but it fails to abolish completely these responses. When the maximum effective level of temporal masking is employed, the observed PCR amplitudes become similar to those that can be elicited with chromatic stimuli restricted to the central foveal region. Similar results were obtained in cortically blind subjects who show coarse discrimination of stimulus colour, but the residual PCRs were of reduced amplitude. Spatiotemporal modulation techniques can be used to isolate PCR signals from accompanying PLR responses. The results also suggest that some residual chromatic processing as demonstrated psychophysically or objectively using the pupil colour response remains even in the absence of V1.

City University, Applied Vision Research Centre, 311-321 Goswell Road, London EC1V OHB. Tel. 071-477800 Ext 4342. Fax 071-4778355 e-mail: J.L.Barbur@city.ac.uk




Kenneth D. Cocker, Merrick J. Moseley and Alistair R. Fielder

Pupillary Responses to Pattern and Light in Delayed Visual Maturation

Infants with Delayed Visual Maturation type 1 (DVM-1) fail to develop normal vision for several months after birth yet have no apparent neurological or ophthalmic abnormalities. Recovery begins between three and five months after birth and can complete within a few days. The nature of the underlying defect is unknown, though both cortical and subcortical pathways have been implicated. Can the neurological mechanism(s) which underlie DVM-1 be further elucidated by an examination of pupil function? Specifically, by the use of stimuli which differentially activate cortical (responses to pattern) and subcortical (responses to luminance) mechanisms.

Our subjects were a male infant with DVM-1 and his unaffected monozygotic twin. Twin I failed to feed and thrive but was neurologically and ophthalmologically normal. Twin II developed normally. Behavioural Grating Acuity (BGA), measured using acuity cards, showed that at 17 weeks. Twin I had no measurable visual acuity whilst that of Twin I fell within the normal range at 3.8 cy/deg.

Pupillometry was undertaken on Twin I at 17 weeks. Responses were initially recorded to a 0.1 cy/deg high contrast grating and a 1.3 log unit luminance increment. Full details of the recording protocol can be found elsewhere (Cocker et al. Invest. Ophthalmol. Visual Sci. 35(5):2620-2625). Twin I showed no pattern response but a robust light response (40% constriction in area, 280ms latency). No BGA could be measured until 19.6 weeks when it was recorded as 1.8 cy/deg. At this time pupil responses to pattern were found to be present to stimuli up to 1.2 cy/deg (the 'pupil acuity'). At 20 and 22 weeks Twin I had BGAs of 3.6 and 4.9 cy/deg and pupil acuities of 3.8 cy/deg. Twin II had a BGA of 4.9 cy/deg and a pupil acuity of 3.8 cy/deg at 22.5 weeks.

In our DVM-1 subject, pupillary responses to pattern were initially absent and subsequently developed in a manner comparable to acuity measured behaviourally. The initial absence of a pattern response accompanied by a normal reaction to light suggest that DVM-1 results from dysfunction within the visual cortex.

Department of Ophthalmology, The University of Birmingham, Birmingham and Midland Eye Hospital, Church Street, Birmingham, U.K. B3 2NS. Tel: ++44 121 507 2445 Fax: ++44 121 233 9213 email: k.d.cocker@bham.ac.uk






H. Krastel, Chr. Reisser, E. Alexandridis

Relative defects of the afferent pupil and of subjective ganzfeld brightness sensations in traumatic and sinugenous optic nerve conditions

Objective: Optic nerve involvement deserves consideration in midfacial lesions of e.g. traumatic or inflammatory origin. Its detection may, however, suffer from facial and anterior ocular segment pathology by weakening the diagnostic specificity of conventional tests of visual function. It is for this reason that we applied subjective brightness sensation and swinging flashlight test, since both types of examination do not need a focussed retinal image.

Methods: A simple interocular comparative estimation of subjective brightness may indicate optic nerve (and/or retinal) affection. A diffusor (frosted glass goggles or even a simple sheet of white paper) is placed in front of the eyes. Alternating illumination of right and left visual field, respectively, is provided by a penlight. In cases where pupil light responses are amenable to examination, the swinging flashlight test serves to check for afferent defects objectively.

Clinical observations: Our series of clinical observations comprised 11 traumatic, 2 neoplastic, 4 inflammatory and 5 postsurgical conditions. Subjective interocular brightness comparison turned out to be the more sensitive indicator of visual sensory malfunction in those cases, where the patient`s general condition permitted appropriate subjective responding.

Conclusion: Both of these quick and handy bedside checks of optic nerve (and retinal) function, the sensory and the pupillomotor test, should be performed at first visit: they help to identify those patients in need of a more thorough examination of retina and optic nerve.



Im Neuenheimer Feld 400

D 69120 Heidelberg

Tel +49-6221 566613 or ++608

Fax. +49-6221 565422





Aki Kawasaki*, Paula Moore**, and Randy Kardon**

Does the Relative Afferent Pupillary Defect

Change Over Time in Normal Subjects ?

Purpose: To better define the fluctuations in repeated measurements of the relative afferent pupillary defect (RAPD) over time.

Methods: We used computerized infrared pupillometry to test 17 normal subjects four times over a three year period. For each testing session, an RAPD and its 95% confidence interval (representing short-term variability) was determined for each subject. We compared the change in log unit RAPD between testing sessions to the short-term variability estimated for each test (95% confidence interval). If the change in RAPD exceeded the short-term variability, we assumed this represented a component of long-term variability.

Results: Of the 17 normal subjects who had their RAPD quantified at four sessions, the mean RAPD was 0.01 log units, but was as high as 0.32 log units. The average short-term variability or 95% confidence interval was 0.1 log units (RAPD±0.05 log units). Of the 17 normal subjects who were tested four times over three years, 7 always had an RAPD in the same eye. The change in RAPD between any two sessions was relatively small (median change=0.038 log units; maximum change=0.282 log units), and exceeded the short-term variability in 38% of comparisons (46/120). This residual difference not accounted for by short-term variability was considered to be the long-term component of RAPD variability and was very small (median=0.06 log units).

Conclusions: The major component for inaccuracy in RAPD quantification derives from short-term variability. Long-term variability in the RAPD may exist in normal subjects, but its contribution is minor. These results will help define what should be considered a significant change in RAPD over time in patients with disease of the pregeniculate visual system.

Supported by a VA Merit Review Grant, Zeiss-Humphrey Corp., and a private grant from the Midwest Eye Institute, Methodist Hospital Propriety Interest: None

* Midwest Eye Institute of Methodist Hospital, Indianapolis, Indiana and

** Department of Ophthalmology, University of Iowa and Veterans Administration Hospital, Iowa City, Iowa





Shiro Usui, Kazutsuna Yamaji, Yutaka Hirata

Evaluation of the Autonomic Nervous Activity in Micro Gravity using Pupillary Flash Response

Since man's first exploration into space about 35 years ago, we have been getting more opportunities to stay in space. However, the effects caused by such different environment in space on the human body especially on the autonomic nervous system (ANS) are still remained as a main problem. Since the pupil is innervated by the ANS, it has the potential as a possible monitor for the ANS activity. In the previous study[1], we made the first attempt to measure pupillary flash responses during the parabolic flight which can realize a short period hyper- and micro-gravity in order to examine the effect of the gravitational change in the ANS.

In neuro-ophthalmology, dynamic parameters of the pupillary flash response such as initial pupil diameter (Dinit), latency (L), constriction amount (deltaD), maximum constriction and dilation velocity (Vcmax, Vdmax) and maximum acceleration in constriction(Acmax) have been utilized for the diagnosis of autonomic nervous diseases. However, there still exist some aspects to be improved in the conventional method. This study proposed a new method to evaluate the ANS activity by improving the conventional method based on the analysis of the model for human pupillary muscle plant[2] and on consideration of the effect of the range nonlinearity[3]. We pointed out that the parasympathetic nervous activity can be evaluated by referring either Vcmax or Acmax whereas all the parameters are referred in the conventional method. On the other hand, it was shown that there is no parameter that reflects mainly the sympathetic nervous activity. Therefore, for its evaluation, we have introduced a new dynamic parameter named "recovery amount" which is defined as the difference of the pupil diameter between initial state (Dinit) and around 2.5sec after the flash stimulus, where according to the model analysis, parasympathetic nervous activity does not have any contribution on the dynamics of the response.

Validity of the proposed method was confirmed by applying it to the flash response of the subjects whose autonomic nervous activity had been modified by either the parasympatholytic(scopolamine) or sympathomimetic(epinephrine) drugs.

The application of the proposed method to the parabolic flight data for 3 subjects led us to the conclusion that during both hyper- and micro-gravitational period, the parasympathetic nervous activity was suppressed for all of the subjects.



[1] Usui, S., Hirata, Y and Nagaoka, S. : Pupillary Light Response during a Parabolic Flight, Proceeding of 40th International Congress of Aviation and Space Medicine, Tokyo, p.141, 1992. June

[2] Usui, S. and Hirata, Y. : Estimation of Autonomic Nervous Activity using the Inverse Dynamic Model of the Pupil Muscle Plant, Annals of Biomedical Engineering, vol.23, 1995. July (in press)

[3] Usui, S., and Stark, L. : A Model for Nonlinear Stochastic Behavior of the Pupil, Biol. Cybern., vol.45, pp.13-21, 1982


Shiro USUI , Ph.D; BPEL, Dept. of Information and Computer Sciences, Toyohashi University of Technology, Tenpaku, Toyohashi 441, Japan

Tel & Fax : +81-532-46-7806 E-mail: usui@bpel.tutics.tut.ac.jp


Franz Thoss, Bengt Bartsch, and Getaneh Bekele

On Relations between Visual and Pupillary Threshold

Under stationary conditions the course of the pupillary threshold as a function of adaptation illumination is very similar to the course of the visual threshold. In both cases we found at low illuminations, due to the rods, a constant value and an increase up to an inflection. A second plateau and a further increase at higher illuminations are due to the cones. For a central stimulus of 30 degrees the pupillographic threshold is higher than the visual threshold by a factor of about five; for all of 30 degrees the pupillographic threshold is higher than the visual threshold by a factor of about five for all adaptation states. At a definite state of adaptation the threshold is not constant, but fluctuates. A direct continuous registration of these fluctuations is impossible because of the time-consuming nature of threshold measurement. The calculation of the most important frequencies is still possible on the basis of a very simple measurement: It is enough to find out, whether a constant stimulus at a definite time is above or below the threshold. The only condition is that the sum of the "times above the threshold" should be nearly equal to the sum of the "times below the threshold". This investigation is possible for both visual and pupillometric thresholds. The comparison of the spectra of these thresholds shows, that in both cases very low frequencies (periods of more than 100 seconds) are predominating. In addition the pupillographic threshold shows oscillations with durations of about one minute. Hypotheses concerning the origin of the fluctuations are discussed.

Carl Ludwig Institute of Physiology, University of Leipzig, Liebigstr.27

D-04103 Leipzig, Phone ++49 341 97 15528, FAX ++49 341 97 15509





Peter A. Howarth

Noise in the Pupillary System

The pupil of the human eye is constantly changing size, even in the absence of variation in the light flux reaching the retina. This "noise" is generally termed "hippus" and its frequency spectrum has been shown to be 1/f-like over a range of frequencies from around 1/5 Hz to 4-5 Hz. A 1/f function is one whre the amplitudes of the oscillations are inversively proportiona to their frequencies, and the function is linear when amplitude and frequency are plotted on logarithmic scales.

The frequency spectrum of hippus has previously been shown to have the same slope irrespective of ambient (steady) light level and pupil size. The present experiment was designed to answer the question of how light-generated signals from the retina and the noise signals interacted when the light varied. It was hypothesised that the presence of a light-generated signal would dampen the larger changes in pupil size; as these occur at lower frequencies it was expected that the frequency spectrum of the hippus would then be altered.

Twenty subjects each performed ten trials viewing a steady light, and ten trials viewing a sinusoidally-modulated light of frequency 1 Hz. Pupil size was sampled sixty times per second, using an infra-red video-based Micromeasurements pupillometer. Trials lasted 10 seconds, and were blink-free. Fourier analysis was performed on the data to produce the pupil spectra.

The 1Hz component caused by the pupillary response to the light was digitally removed, and the spectra of the with-signal and without-signal trials were compared. Although the with-signal amplitudes were consistently lower than the without-signal amplitudes - as one would expect given the reduction in pupil size seen in response to a flickering light - the slopes of the functions were indistinguishable, and this result does not support the hypothesis proposed. The pupillary response to the varying light seems to be superimposed upon the noise signal (or vice versa) rather than interacting with it as expected.

Department of Human Sciences

Loughborough University


LE11 3TU


Tel. +44 509- 263171

Fax +44 509-610724

e-mail: P.Howarth@lut.ac.uk






Josef Grünberger, L. Linzmayer, E.M. Madja, A. Reitner and H. Walter

Pupillary Dilatation Test and Fourier-Analysis of Pupillary Oscillations in Encephalomyelitis Disseminata Patients


For the investigation of encephalomyelitis disseminata patients the pupillary receptor test which was based on a hypersensitivity on pupillary dilatation response to the topical application of the cholinergic antagonist, tropicamide, was used.

Further a new technique for measurement of central nervous activation, the Fourier -Analysis of pupillary oscillations without and under the influence of a cognitive task was carried out. We investigated 29 patients aged between 31 and 60 years, diagnosed (and well defined) as encephalomyelitis disseminata, and compared their results to those of 18 normal controls with only small differences in age. All patients had to pass a complete ophthalmological examination to exclude any anterior segment disease. The patients were investigated by means of a computerassisted TV pupillometer from the Whittaker Corporation. We measured the pupillary diameter (left eye) 7 times. The patients and the normal controls received by topical application 0.01 % tropicamide solution in the left eye. The encephalomyelitis disseminata group had, after 40 minutes, a pupillary dilatation of 31.9 %, as compared to their baseline. At the same measurement time, the control group showed only 16.5 % dilatation ( p 0.001, Newman Keuls). Under the influence of a cognitive task, the normal controls revealed higher amplitudes than the encephalomyelitis disseminata patients (p 0.05, Newman Keuls), reflecting a lower capacity for cognitive activation in the encephalomyelitis disseminata group.

Department of Psychiatry, University of Vienna, Evangelical Hospital, Vienna, Department of Ophthalmology, University of Vienna. Austria.

Tel. +43-140400-3570, Fax +43-140400-3560





A. Reitner, I Baumgartner, CH. Thuile, R. Baradaran Dilmaghani, E. Ergun,

S. Kaminski, J. Lukas, P. Dal-Bianco

Mydriatic Effect of 0.01% Tropicamide in Alzheimer Patients and its Relation to Mind Scores, Corneal Parameters and Tear Film


Using infrared pupillography we measured 34 patients (20 m, 14 f, age 69+/- 11, history of Alzheimer´s disease 2-5 years ) suffering from Alzheimer’s disease ( AAMI / CROOK-criteria) and 20 healthy, age matched controls. All measurements were repeated after 4 weeks.

At their first visit pupil diameters were determined before and after unilateral tropicamide application; measurements were taken in 15 minutes intervals for up to 90 minutes. At the second visit additional parameters like Schirmer’s test, Meibomien gland evaluation, endothelial cell counts, pachymetry of the cornea, and tonometry were collected. Mind tests, neurological examination, MRI, CCT, Carotide Duplex scan, EEG and blood tests were done in the neurological department before starting our study.

In Alzheimer patients , we found an average pupil dilation in the treated eye of 18.6 +/- 12 % after 45 minutes. There was no further increase of pupillary diameter between 45 and 90 minutes. However, mydriasis of up to 50% was also observed in healthy controls. When data of repeated measurements were compared for each patient, intraindividual variation was high. Furthermore, patients with poorest mind scores showed the highest degree of mydriasis (p=0,01). However, these correlations could not be verified in repeated measurements. We were unable to detect significant correlations between any of the corneal and tear film parameters and the dilating effect of tropicamide.

Our data reveal that there is pupil dilation after the use of tropicamide 0.01% eye drops in Alzheimer patients. This effect can be found in healthy normals too. Repeated measurements show marked intraindividual variation. Anterior segment abnormities in though asymptomatic patients (e.g. tear film deficiences) seem to have no influence on this testing procedure.

Univ. Eye Clinic Vienna, Dept. A

Univ. Clinic, Dept. for Neurology, Vienna

Tel. +43- 1317 2933

Fax +43- 1317 2934






Michael Boettcher, W. Luedtke

Concentration effect correlation between pupil diameter and serum levels of psychotropics


The influence of psychotropics on the pupillary light reflex was investigated in 4 studies with chlorprothixene, levomepromazine, amitriptyline and promethazine in healthy male volunteers.

3 different oral formulations of chlorprothixene (film coated tablet, suspension, aequous solution) and an i.v. formulation were applied in dosages of 100mg each to 8 volunteers (vol.). 100mg levomepromazine were given as an i.v. formulation (4 vol.). 75 mg amitripytyline (7 vol.) and 100mg of promethazine (12 vol.) were applied orally.

Dynamic light evoked pupillometry was used to determine pupil diameter (PD) before and on several occasions after drug administration. Initial PD as well as reflex amplitude were recorded and used for further evaluations. Serum drug concentrations were determined by HPLC and correlated with pharmacodynamic effects on PD.


Chlorprothixene: The relationship between serum levels and adjusted reflex amplitude (comparison to preadministration values) could be depicted as a sigmoidal curve. Within the concentration range from 10 to 80 µg/l this model allows to estimate serum levels from pupillometric parameters. A pharmacokinetic-pharmacodynamic model (3-compartments) was calculated for the aequous solution and i.v. formulation.

Levomepromazine: The correlation of concentration and effect follows the course of a clockwise hysteresis loop, thus reflecting phases of increasing and decreasing serum levels with their corresponding effects.

Promethazine: After promethazine a threshold phenomenon was observed: concentrations below 19 µg/l did not affect reflex amplitude while above this value relatively small elevations of serum levels resulted in large reductions of this parameter.

Amitriptyline: A counter-clockwise hysteresis like concentration effect correlation was also found after amitriptyline. A slight reduction of reflex amplitude within the first 6 hours after administration was followed by an increase for at least 24 hours.


The concentration effect relationship between pupil reaction and serum levels can be used to characterize psychoactive drugs.



Department of Clinical Pharmacology


Neurather Ring 1 51063 Köln

Tel.: 0221 - 6472671 Fax.: 0221 - 6472353




E. Szabadi and C.M. Bradshaw

The human iris is innervated by both the sympathetic (noradrenergic) and the parasympathetic (cholinergic) systems. Antidepressants have multiple effects at the cholinergic and noradrenergic neuroeffector junctions: they block both post-junctional muscarinic cholinorceptors and a1-adrenoceptors, and they block the uptake of noradrenaline into sympathetic nerve terminals. While the blockade of post-junctional receptors results in the antagonism of the effects of both endogenously-released and exogenously-applied acetylcholine and noradrenaline, noradrenaline uptake blockade results in the potentiation of the effects of noradrenaline. The net effect of an antidepressant reflects the balance between these three major effects of the drug at the cholinergic and noradrenergic synapses: while muscarinic receptor blockade and uptake blockade result in mydriasis, a1-adrenoceptor blockade results in miosis.

The kinetic parameters of the light reflex reflect the activation of the parasympathetic and sympathetic inputs to the iris in a characteristic fashion: while the latency and amplitude of the response are mainly due to the activation of the cholinergic parasympathetic input, the redilatation is also influenced by the activation of the sympathetic input.

The effects of single doses of desipramine, ciclazindole, reboxetine, trazodone, amoxapine, fluvoxamine, binodaline and fengabine were studied in small groups (6-12) of healthy male volunteer subjects.

In some experiments, solutions (10-30 µl) of a cholinoceptor agonist (pilocarpine hydrochloride 0.004-0.02 M) an adrenoceptor agonist (noradrenaline hydrochloride 0.2 M; methoxamine hydrochloride 0.02-0.04 M; tyramine hydrochloride 0.072 M) were instilled into the conjunctival sac of one eye; the same volume of artificial tear was applied to the fellow eye.

Pupil diameter was measured either by photography or by infrared television pupillometry. Pupil photography was carried out in an evenly illuminated room using a camera and a fast time-course flash gun mounted at 1.5 m from the headrest. Pupil diameter was measured with a millimetre rule on the projected enlarged photographic negative. Television pupillometry was carried out in the dark using a binocular infrared television pupillometer (Applied Science Laboratories, Waltham, MA. USA). The pupillary light reflex was evoked by a series of 12 green (565 nm) light stimuli (intensities ranging from 5.3 x 10-5 to 3.5 mW/cm2; duration 200 ms separated by intervals of 20 s). Each response was recorded by computer for further analysis.


Resting pupil diameter. The antidepressants had variable effects on resting pupil size. Desipramine, ciclazindole, reboxetine caused mydriasis, trazodone and amoxapine caused miosis, and fluvoxamine, binodaline and fengabine had no effect. Amitriptyline usually had no effect, however, both small miosis and mydriasis could be observed occasionally.

Pilocarpine-evoked miosis was consistently antagonised by amitriptyline, and was affected to a much lesser extent by desipramine, consistent with the relatively high affinity of amitriptyline for muscarinic cholinorceptors. This response was not affected by fluvoxamine and amoxapine, antidepressants with little affinity for muscarinic cholinoceptors.

Adrenoceptor agonist-evoked mydriasis. Noradrenaline-evoked mydriasis could be potentiated by both desipramine and amitriptyline. Desipramine was more potent, consistent with the higher potency of this drug as an inhibitor of the noradrenaline-uptake mechanism. Methoxamine-evoked mydriasis was antagonised by amitriptyline, desipramine and ciclazindole, consistent with the blockade of a1-adrenoceptors by these drugs. Tyramine-evoked mydriasis was antagonised by amitriptyline and desipramine, indicating that these antidepressants effectively blocked the uptake of tyramine and thus prevented its pharmacological effect.

Kinetics of the pupillary light reflex. Desipramine and reboxetine increased the latency, reduced the amplitude and shortened the recovery time of the light reflex response. The effects on the latency and amplitude are consistent with the anticholinergic, and the effect on the recovery time with the sympathomimetic (uptake blockade) effect of the antidepressants. Thus the pupillary light reflex response can be used to reveal the interaction of antidepressants with both cholinergic and adrenergic mechanisms.

Prof. E. Szabadi

Department of Psychiatry

University of Nottingham

Queen's Medical Centre

Nottingham NG7 2UH

Tel. +44-115-970-9336

Fax +44-115-970-9495




Markus Diel, Wilhelm H., Wehner H.-D., Wannek U.

The influence of acute alcohol ingestion on the pupillary light reflex

To detect alcohol or drug abuse in car drivers by means of pupillography during traffic controls is presently being discussed in various circles. Therefore, we tested the influence of alcohol on pupillary behaviour.

Method: 10 healthy volunteers aged between 21 and 26 years were examined by means of infrared video pupillography. 30 light reactions were recorded before, 20, 40, 60, 90, 120, 150 and 180 minutes after ingestion of an individual dose of ethanol (g pure ethanol = body mass [kg] x 0.7 + 30%). Blood alcohol levels were determined. Pupillography was performed with a video system sampling at 25 Hz.

The pupillograms were evaluated by means of curve fitting.

5 volunteers were retested under the same conditions but without alcohol.

Results: A blood alcohol concentration between 0.60 and 1.43 per mille was obtained. One volunteer who reached only 0.34 %0 was excluded from the study. The most significant effect could be demonstrated with latency time; only little influence was seen on baseline pupillary diameter (Table 1). Controls showed a decrease in latency time from 369 ms to a mean value of 354 ms (slightly significant after 40 and 90 minutes, probably due to an adaptation effect). The other parameters were not significantly changed in the control group.

Time (min)









Latency (ms)









Constriction time (ms)









2/3 Redilation time (ms)









Baseline diameter (mm)


5.94 ±0.24

5.99 ±0.25

6.02 ±0.32*

5.88 ±0.39

5.94 ±0.27

5.98 ±0.35

5.88 ±0.35

Constriction amplit. (mm)

1.03 ±0.24

0.86 ±0.38*

0.95 ±0.33

0.92 ±0.33

0.87 ±0.33*

0.79 ±0.32*

0.81 ±0.28*

0.79 ±0.26*

Table 1: Mean parameters (± standard deviation) of the pupillary light reaction under alcohol.

Asterisks indicate significant difference as compared to the 0-value in the first column according to t-test for paired samples.

Discussion: Alcohol increases the latency time of the pupillary light reflex significantly. Baseline diameter shows only slight increase with a peak after 60 minutes. Several dynamic parameters of the light reaction change under acute alcohol influence, but not all of them significantly over the whole range of time. After initial decrease of constriction time, there are maxima after one and two hours.

Redilation time is shortened and the constriction amplitude reduced. The increase in latency time must be considered as an influence on the synaptic transmission in the pupillary pathways. Theoretically, a decreased light sensitivity of the retina could play a role, because the constriction amplitude decreases. However, the effect on latency time is much more pronounced and there is no electroretinographic evidence reported for this assumption. Additionally, according to a report by Kömpf et al. (EUNOS meeting, Antwerp 1995) the latency time of saccades increases after alcohol ingestion as well.

However, all the observed effects are subtle and always related to the initial parameters in the same individual.

According to our results, pupillography in acute alcohol ingestion is of scientific interest but not a useful screening method for traffic control purpose.


University Eye Hospital, Dept. of Pathophysiology of Vision and Neuro-ophthalmology

(Director: Prof. E. Zrenner)

D-72076 Tübingen

Telefon +497071 294786

Telefax +497071 295038









Peter Rößger

The Pupil Diameter as an Instrument to Measure Mental Workload in Ergonomics

Following the research of for example Beatty (1982, Task-Evoked Pupillary Responses, Processing Load...) on pupil diameter and mental workload (mwl) some experiments were made. The main problem concerning the application of pupil measures in ergonomics is the handling of other influences, for example brightness or the distance of fixation. The results show, that there is no interaction between the influences brightness and mwl, the distance has no influence on the pupil if it is bigger than 50 cm, and if decisions have to be made, the pupil diameter raises with difficulty. Some perspectives of application will be discussed.

TU Berlin

Institut für Arbeitswissenschaft

Sekb. Ro 1-4

Rohrdamm 20/20

D- 13629 Berlin

Tel. +4930-38006-132

Fax +4930-38006-123

e-mail: arbwb.kf.tu-berlin.de





Bitsios, P., Szabadi, E, Bradshaw, C.M.


It has been shown that the eye-blink response evoked by a sudden noise ('acoustic startle') is enhanced when the subject anticipates an aversive stimulus, e.g. a mild electric shock ('fear-potentiated startle') (Grillon et al. 1991). We examined whether the threat of an electric shock, as used in the fear-potentiated startle paradigm, would affect the pupillary light reflex. Light stimuli (0.086 mW cm-2, 200 ms, 565 nm) were generated by a light-emitting diode, and pupil diameter was monitored by computerized binocular infrared television pupillometry in the dark. Twelve healthy volunteers (8 males, 4 females; 18-26 years) participated in one experimental session. The first (adaptation) phase of the session consisted of 12 blocks of 3 light stimuli; in the second phase, 6 'safe' blocks (shock-box disconnected) and 6 'threat' blocks (shock-box connected) alternated; a mild electric shock was delivered 2 s before the fourth 'threat' block. At the end of each block, subjects rated their anxiety using visual analogue scales. Two-factor ANOVA (condition x block) showed that in the threat condition there was an increase in initial pupil diameter, a decrease in light reflex amplitude and an increase in anxiety ratings (P<0.001). All these effects decreased across the blocks (P<0.01), consistent with habituation. The increase in initial pupil diameter and the decrease in the amplitude of the pupillary light reflex are consistent with both increased sympathetic and decreased parasympathetic activity in the threat condition.

Grillon C et al. (1991) Psychophysiology, 28, 588-595

Department of Psychiatry University of Nottingham Queen's Medical Centre Nottingham NG7 2UH

Tel. +44-115-970-9336

Fax +44-115-970-9495





Josef Grünberger, L. Linzmayer, R. Wytek, and M. Grünberger

Determination of reliability and validity of the pupillary oscillations hypothesis and the use of the cognitive pupillary oscillations hypothesis in patients with neurotic disorders and organic brain syndrome


Pupillary oscillations seem to reflect central nervous activation. Therefore we analysed pupillary oscillations during the recording period of static pupillometry for determination of the pupillary diameter of the left eye (described by the autors in 1992) which lasted for 25.6 s. For the computerassisted measurement a Whittaker 1050 TV-Pupillometer was used. Before calculating the Fourier analysis, blinks have to be identified and eliminated by means of a new technique which is called "smoothing". Using the Fourier analysis, the spectrum was divided into 5 frequency bands (0.0-0.2; 0.21-0.4; 0.41-0.60; 0.61-0.80; 0.81-1 Hz ). We were also interested in the total spectrum.

Under the influence of a cognitive test (simple calculations) changes of the heigth of amplitudes of pupillary oscillations reflecting central nervous activation can be observed. (Cognitive pupillary oscillations-hypothesis).

In healthy young and elderly subjects a re-test reliability of 0.75-0.85 could be calculated. Also the data after FFT ( Fast Fourier Transform ) of pupillary oscillations of two populations of patients ( n=509 and 396 respectively ) showed a high stability. The validity of the method was determined by means of a procedure similar to the cross validation. The use of the "cognitive pupillary oscillations hypothesis" for differential diagnosis between patients with neurotic disorders ( ICD 9: 300 ) ( n=73 ) and patients with organic brain syndrom ( ICD 9: 290 , ICD 291.2 ) ( n=34 ) is be shown. During a cognitive task patients with neurotic disorders demonstrated higher amplitudes than patients with organic brain syndrom. Thus, in the latter group a lower activation could be observed.

Section of Clinical Psychodiagnostics of the Psychiatric University Clinic, Vienna.

Tel. +43-140400-3570

Fax +43-140400-3560






Sharon L. Merritt(a), Andrew P. Keegan(a), Ali M. Oroujeh(a), Robert C. Basner(b), James A. Christon(b)

Full-size and desktop pupillometers: A comparison of two methods

Excessive daytime sleepiness has recently been recognized as a significant health problem that can result from poor sleep habits as well as sleep disorders and treatment for other chronic diseases, i. e. medication side effects. Pupil motility, a reflection of wakefulness, has been used clinically as an objective measure of physiologic sleepiness. A normally alert person can sit quietly in the dark for up to 15 minutes while maintaining a stable pupil size. In contrast, in people who are excessively sleepy, the pupil oscillates and decreases in size as wakefulness decreases. Microcomputer-based pupillometry is a non-invasive method that can be used to capture real time pupil diameter data in situations that may unmask physiologic sleepiness. Recent technologic advances have made possible the development of portable equipment that can be used in virtually any clinical setting where the measure of physiologic sleepiness is of interest.

As part of our on-going program of research, the first purpose of this study was to compare the measures of pupil size and reaction to light obtained between a full size pupillometer built at Mayo Clinic and those obtained from a desktop portable model (PupilscreenR) built by Fairville Medical Optics, Inc. Pupil diameter data were collected from normal control subjects during the Alertness Level Test (ALT) where the subjects are instructed to try to stay awake for 10 minutes, and during customized light stimulus testswhere responses to mixed frequency light stimuli are recorded (PLR). Data were collected from the same individuals without any history of a sleep disorder on two different days, but at the same time of day and under the same historical sleep conditions. As the second part of this study, we incorporated PupilscreenR into a sleep disorders clinical assessment to evaluate pre-posttreatment sleepiness in patients with obstructive sleep apnea.

Characteristics of the systems and data obtained from the two pupillometers are compared in the presentation. Visual inspection of data indicated that the pupil diameter measures obtained from the two systems were similar (Figure 1) as were the absolute size and frequency characteristics calculated from the same data. Relative determinism values, a non-linear measure of wakefulness, were calculated from recurrence plot data and indicated that the subjects would be classified similarly by the two systems relative to their level of alertness.









Repeatability data obtained with PupilscreenR from two subjects during the ALT and PLR tests indicate that the measures of pupil diameter obtained over time are relatively consistent when the testing conditions are similar. Pupil diameter data obtained with PupilscreenR from obstructive sleep apnea patients at diagnosis, and nights 1 and 2 of continuous positive airway pressure treatment indicate that pupillometry holds promise as a method for assessing the effectiveness of this treatment in decreasing physiologic sleepiness. The portability of PupilscreenR may favor its use in a variety of clinical applications where measures of physiologic sleepiness are of interest.

Center for Narcolepsy Research(a), University of Illinois at Chicago,

College of Nursing, 845 S. Damen Ave M/C 802,

Chicago, Il 60612-7350

Phone (312) 996-5175 Fax: (312) 996-7008

The Center for Sleep and Ventilatory Disorders(b) (M/C 722), College of Medicine, University of Illinois Hospital, 1740 W. Taylor St., Room 814E,

Chicago, IL 60612-7233.

Supported in part by Mr. J. A. Piscopo.

PupilscreenR was loaned to the Center from Fairville Medical Opitcs, Inc



Barbara Wilhelm, H. Lüdtke, P. Streicher, M. Adler

Public relations and methodical considerations -

introducing pupillography as an objective test of vigilance into Germany

Pupillary behaviour in fatigue was described and analized by Loewenfeld and Lowenstein from the sixties on and was used intensively by Robert E. Yoss in the diagnosis and management of narcolepsy. Since then, amazingly few scientists and clinicians have worked with this method, which there may be quite a few reasons for. Today, the technical preconditions would allow a much more wide spread use of pupillography in the diagnosis of fatigue than can can be found actually. The need for such a method seems to be stronger than ever because fatigue is an increasing problem in our civilized societies. One reason is the high number of patients with sleep apnea syndrome, the most common form of hypersomnia. The diagnosis and therapy management of sleep disorders is time-consuming and intensive depending on sleep laboratories and subjective tests. On the other hand there is a great number of insomniacs whose fatigue cannot be measured by Multiple Sleep Latency Test (MSLT) which otherwise is a widely used method to measure daytime sleepiness. Also in these patients, pupillography as an objective method would be of high diagnostic value. In Germany, public institutions have only just begun to pay attention to fatigue related accidents and other risks for public health caused by sleep disorders or stressing life style with poor sleep habits. Even among people working in sleep medicine and sleep research pupillography and fatigue related changes of pupil behaviour in darkness are not known. Therefore, one part of our work has to be missionary concerning the information of neurologists, psychiatrist and other colleagues on the one, and politicians and insurances on the other hand. Problems often start with the question how to get enough patients with hypersomnias into an eye hospital...

Method: Spontaneous pupillary behaviour in darkness is recorded over a period of 10 minutes by means of infrared video pupillography. The system consists of an infrared sensitive video camera, connected to a frame grabber card in a 80386 personal computer and an image processing software for 25Hz real time analysis, additional software for off-line analysis based on Fast Fourier Transformation. Simultaneous recording of pupil size, accommodation and vergence allows to tell whether a change in pupil size is spontaneous or related to accommodative changes or simply instable fixation. In a normal alert subject pupil dilates in darkness and maintains that diameter stable over a long period of time, whereas in an excessivley sleepy person the average pupil size decreases with time and fatigue waves appear with a latency depending on the intensity of sleepiness. To provide complete darkness and protection against acustic stimuli during the measurement is of great importance.


Concerning the influence of eye lashes and any form of ptosis, algorithms have to be used that are based on the horizontal pupil diameter. Problems can arise by disturbances of the tear film or lid closure as a consequence of extreme daytime sleepiness. The first can simply be solved by artificial tears, the second could be solved by lid cratch but this means an extreme irritation probably influencing the pupillary behaviour itself.

As we have come close to a mobile application of the method, pupillography could be helpful as a screening method for hypersomnias and as a therapy control in any kind of sleep disorder in future. Furthermore, pupillography could even detect acute vigilance problems in certain risk groups like pilots, bus drivers or operators in nuclear power plants.

Supported by Fortüne program of the University of Tübingen.


University Eye Hospital, Dept. of Pathophysiology of Vision and Neuro-ophthalmology

(Director: Prof. E. Zrenner)

D-72076 Tübingen

Telefon +497071 294786

Telefax +497071 295038





Mario Zulauf, Andreas Schötzau, Stephanie Turtschi, Brigitta Henzi, Phillip Hendrickson, Josef Flammer

Pupil perimetry with the Octopus 1–2–3: The optimal stimulus interval

Purpose: To evaluate if shorter than 3–second inter-stimulus intervals are feasible in pupil perimetry.

Materials and Methods: The measurements were performed on a modified Octopus 1–2–3 which measures the pupil area at a rate of 50 Hz and is remotely controlled by a personal computer. Twenty healthy eyes of 10 subjects completed 3 similar programs, each testing 4 times the pupillary light reflex at 27 test locations within 27 degrees of polar eccentricity with the following parameter settings: Stimulus size Goldmann V (1.72°), stimulus duration 100 ms, background illumination 3.14 apostilbs (asb), stimulus intensity in the center = 16.3 asb (_14 dB), in all other test locations = 410 asb (_0 dB), and inter-stimulus intervals of A) = 3 seconds, B) = 2 s, or, C) = 1.5 s. As outcome parameters, amplitude of pupil area decrease during pupil contraction, the latency time of the onset of pupillary contraction, the velocity of pupil area change during stimulus presentation, and the number of missing values of the amplitudes and latencies were investigated.

Results: The amplitude averaged 162, 170 and 161 pixels with the inter-stimulus interval of 3, 2 and 1.5 seconds, respectively. A contraction of 160 pixels corresponds to a change in pupil diameter of 3.57 mm to 3.27 mm. The latency average 321.8 ms, 314.6 ms, and 311.6 ms, with each interval, respectively. The pupil area change during stimulus presentation averaged 16.6 pixels/second, 17.9 pixels/second and 16.0 pixels/second, i.e., the average pupil was still dilating during stimulus presentation. Of the 2160 pupillary light reactions, 23.6%, 20.8% and 21.1% amplitudes and 14.7%, 13.2% and 14.0% latencies were not quantified.

Conclusion: As the three measurement conditions with inter-stimulus intervals of 1.5 s, 2 s and 3 s rendered comparable results, the authors recommend 1.5 s. All volunteers tested prefered this short interval.


The authors have no proprietary interest in the hardware or software mentioned.


Supported by The Commission for the Promotion of Applied Research, Bern, Switzerland, grant # 2569.1.


University Eye Clinic


CH-4012 Basel - Switzerland

Fax: ++ 41 (61) 321-7763

Phone: ++ 41 (61) 321-7777





Andreas Schötzau, Mario Zulauf, Sarah Michel Stöckli, Birgitta Henzi, Phillip Hendickson, Josef Flammer

Pupil perimetry with the Octopus 1–2–3: Optimal parameter describing the pupillary light reflex (PLR) to distinguish glaucoma from normal

Purpose: To investigate outcome parameters in pupil perimetry other than the commonly employed latency time of the pupillary light reflex and amplitude of the constriction.

Materials and methods: The measurements were performed on a modified Octopus 1–2–3 which measures the pupil area at a rate of 50 Hz and is remotely controlled by a personal computer. Program specifications: Stimuli exciting 5 times a pupillary light reflex at 33 test locations within 27 degrees of polar eccentricity; stimulus parameters: Goldmann size V(1.7°), background illumination 3 apostilb (asb), stimulus duration 100 ms, inter-stimulus interval = 1.5 s, stimulus intensity 16.3 asb (_14 dB) in the center , 129.7 asb (_5 dB) up to polar eccentricity of 8.5 degrees and 410 asb (_0 dB) beyond 8.5 degrees. An algorithm describes the pupillary light reflex with six different parameters, i.e., the contractile state before the onset of the PLR, the latency time of the PLR, the contraction velocity, the time of maximal contraction, the amplitude of contraction, and, the redilation velocity. Twenty glaucomatous eyes of twenty subjects (not treated with miotics) were compared with 20 eyes of healthy subjects, which were matched for age and gender. Refraction and visual acuity was similar in both groups, but intraocular pressures averaged 18.2 and 14.6 mm Hg, respectively. In standard perimetry (program G1x, stage 1 + 2=33 test locations), Mean Defect (MD) averaged 1.1 dB and 1.8 dB (both within normal limits), Loss Variance (LV) 9.5 dB2 and 15.3 dB2 (both beyond normal limits), i.e., a very challenging data set where glaucomatous subjects were familiar and normal subjects were not familiar with the test.

Discriminant analysis was calculated on the mean of the medians of each test location of the latency time and the contraction amplitude only. A stepwise logistic regression analysis was performed, entering all 30 test locations and the 6 mentioned parameters into the model.

Results: In standard perimetry, discriminant analysis on the indices log MD and log LV revealed a sensitivity = 77% and a specificity = 35% (N:S.). In pupil perimetry, discriminant analysis on the means of the medians of all 33 test locations including the parameters amplitude, contraction velocity and latency revealed a sensitivity = 56% and a specificity of 67% (N.S.). The results of the stepwise logistic regression analysis will be presented and may lead to new vistas on analyzing pupil perimetry results.


Conclusions: The applied discriminant analysis was not able to distinguish the two groups properly in either perimetry and calls for new ways to analyze perimetric results.



The authors have no proprietary interest in the hardware or software mentioned.


Supported by The Commission for the Promotion of Applied Research, Bern, Switzerland, grant # 2569.1.


University Eye Clinic


CH-4012 Basel - Switzerland

Fax: ++ 41 (61) 321-7763

Phone: ++ 41 (61) 321-7777



P.A. Moore, R.H. Kardon

Functional Visual Field Loss: Comparison of Visual and Pupil Perimetry

Purpose. To evaluate the diagnostic capability of pupil perimetry in patients with suspected functional visual field loss.

Methods. Pupil and visual perimetry were compared in 17 patients with suspected functional visual field loss and in 2 patients with suspected functional visual field loss and in 2 patients with peripheral field loss due to confirmed retinal or optic nerve disease. Pupil contraction amplitude and visual threshold were compared at the same 76 locations (program 30-2) by linking a Humphrey automated perimeter to a computerized infrared pupillometer.

Results. Functional visual field loss took the form of either peripheral constriction, scotomata or homonymous field defects. Functional patients showed normal pupil perimetry with the greatest contraction amplitudes in the center of the visual field, gradually decreasing towards the periphery. In contrast, patients with proven loss of the peripheral visual field due to retinitis pigmentosa or optic disc drusen showed no pupil response in the periphery. Pupil contraction can also be reduced in the periphery of a normal visual field due to either supra nuclear inhibition, small pupil size, autonomic neuropathy or systemic drugs with anticholinergic effects on the pupillary sphincter.

Conclusions. Pupil perimetry can objectively substantiate functional field loss when focal pupillary responses are normal but visual threshold is not. Supported by a VA Merit Review Grant and Zeiss-Humphrey Corp. Propriety Interest: None

University of Iowa Hospital and the Veterans Administration Medical Center. Iowa City, Iowa.







How Does the Pupil Respond to Exponentially Increasing Light?


PURPOSE: The pupil response to light is of primary concern in pupil research. I investigated dynamic and quasi-static behaviors of the human pupil in response to exponentially (logarithmically linear) increasing light, as the retinal photoreceptors are thought to be log-converters.

METHODS: Stimulator: The light stimulus was presented by a 1-channel 15° angle Maxwellian-view stimulator. The light source was a 'superbright' red-emitting diode (peak wavelength 653.5 nm, half-width 19.5 nm); and its light output was linearized by pin-photodiode feedback technique1. Stimulus: The exponential (log-linear) function was generated in a computer and sent to the stimulator via a 12-bit DAC. A stimulus of 3-log-unit amplitude with 0.64-Td initial light level and 640-Td final level was given. The stimulus increasing time (rise time) has 12 steps from 0 second (step input) to 4 minutes! (quasi-static input): that is 0, 0.25, 0.5, 1, 2, 4, 8, 16, 32, 64, 128, and 256 sec. An ample time interval was preserved between each trial in order for the stimulated eye to re-adapt to the initial light level. Pupil measurement Pupil area of the stimulated eye was measured by our ’bright-pupil’ infrared TV-pupillometer that can measure a large (even dilated) pupil accurately2. Subjects: Five paid male students (22-23 yr old) with normal color vision were used. The subject was asked to fixate a cross-hair target in the center of the Maxwellian-view path.

RESULTS: With stimuli of 0-1 sec rise times, responses showed downward curves, and the pupil constriction was large in amplitude. For 2-8 sec stimuli, the responses were linearly constricting, showing the ratio of change in the pupil area with respect to that of stimulus be constant. And for stimuli of rise times longer than 16 sec, the responses exhibited upward curves, and the pupil constriction was moderate.

CONCLUSION: To a log-linear input light of 3-log unit amplitude, the human pupillary light reflex system responds transiently exhibiting an overshoot when its rise time is between 0 sec and 1 sec; linearly when it is within 2 and 8 sec; and adaptively when it is longer than 16 sec.


(1) T. Watanabe et al., Vision Res. 32, 953-961 (1992)

(2) T. Watanabe et al., Rev. Sci. Instrum. 61, 36-41 (1990).

Address: Tokyo Science University Faculty of Science and Technology

2641 Yamazaki, Noda, Chiba 278, Japan

Phone: +81-471-24-1501; Fax: +81-471-25-8651



Aki Kawasaki, M.D.* and Randy H. Kardon, M.D., PhD.**

The Relative Afferent Pupillary Defect Within a Day

Purpose. To minimize the short-term variability of the pupillary light response, a computerized relative afferent pupillary defect (RAPD) test has been designed to derive a single RAPD measurement and its associated 95% confidence interval. We studied whether this confidence interval would reliably contain the range of RAPD due to moment-to moment fluctuations of the pupillary light reflex if we repeated several computerized determinations of the RAPD within the same day using pupillography.

Methods. 5 normal subjects were tested 5 times, each identical test immediately following the other. This was done at three times in a single day (total of 15 RAPD tests). Pupillary responses were recorded with infrared pupillography in response to a computer-controlled alternating light. Eighty light alternations (stimulus pairs) were given in each RAPD test. The stimulus light was given at equal intensity for each eye and then attenuated in one eye, followed by the other, by 0.3 log-units and then by 0.6 log-units . The RAPD and its 95% confidence interval were determined from linear regression by identifying the right or left log-unit attenuation at which the difference in pupillary contraction amplitude between right-eye and left-eye stimulation was equal to zero.

Results. Preliminary results showed that at each of the three daytime sessions, 4 of 5 RAPDs determined within minutes of each other fell within the predicted 95% confidence interval. Differences between the outlying RAPD and the outerlimit of the 95% confidence interval derived from the first test was typically within 0.04 log-units. There was no significant defference in the size of the 95% confidence interval within or between the three testing sessions.

Conclusions. The machine-determined RAPD provides an accurate assessment of relative afferent pupillary asymmetry and its 95% confidence interval determined from a single RAPD test can accurately estimate its repeatability.

* Midwest Eye Institute of Methodist Hospital, Indianapolis, Indiana

** Department of Ophthalmology, University of Iowa and Veterans Administration Hospital, Iowa City, Iowa




Mario Zulauf, Andreas Schötzau, Birgitta Henzi, Phillip Hendrickson

Pupil Perimetry and Swiss Cheese.

Purpose: To evaluate the common grounds of Pupil Perimetry and Swiss Cheese. Manufacturing as in both, the hole and not the surrounding is of primary interest.

Methods: Swiss Pupil Perimeters were compared with Swiss Cheese Factories in a randomized, double–blind, crossover design to estimate the influence of the environment on either result.

Results: Both, Swiss Pupil Perimetry and Swiss Cheese Munfacturing, render a more reproducible and larger size of the hole, i.e., pupil, if performed in a Swiss Alpine surrounding compared with the city climate of a mid-sized town, i.e., Basel. Best results were obtained during sunset when the sun’s last rays were saluted by the tunes of Alp Horns.

Conclusions: It is highly recommended to relax on a meadow and to listen to Alp Horns.



The authors have no proprietary interest in the hardware, software, and, Alp Horns mentioned.


Supported by The Commission for the Promotion of Applied Research, Bern, Switzerland, grant # 2569.1 and The Foundation to Elucidate the Misteries of Swiss Chees Holes, unrestricted grant #1291.08.01, c/o Swiss Cheese Union, Burgdorf, Emmental - Switzerland.


University Eye Clinic


CH-4012 Basel - Switzerland

Fax: ++ 41 (61) 321-7763

Phone: ++ 41 (61) 321-7777



R.H. Kardon, Paula Moore

Comparison of Pupil Perimetry and Visual Perimetry in Patients with Visual Loss: Update and New Directions

Purpose: To compare the pupil and visual field in 300 patients with pregeniculate and postgeniculate visual loss

Methods: Visual threshold perimetry (Humphrey program 30-2) was performed on the same day as pupil perimetry in each eye of patients with damage to either the pregeniculate or postgeniculate visual pathway. The same 76 locations within the 30 degree field were tested by both methods. In normal subjects, spatial summation was studied and a new method of pupil threshold determination was used to compare visual and pupil responses for target sizes of 0.9, 1.7, 3.0, 4.0, and 5.0 degrees.

Results: Good correlation was found between the visual and pupil fields in patients with anterior ischemic optic neuropathy, retinal diseases, and postgeniculate damage. Poor correlation was seen in optic neuritis, early glaucoma, and intracranial compression of the visual pathway. Spatial summation was complete for the pupillary system over the size range studied, but didn't change much for the visual system at sizes greater than 1.7 degrees.

Conclusion: Comparison of pupil perimetry with visual perimetry may be helpful in understanding the cause and location of the damage. Differences between the two may result from differences in susceptibility to damage of pupillary ganglion cells, their decrease in number, or segregation of pupillary and visual fibers within the anterior visual pathway toward the chiasm.

Supported by a VA Merit Review Grant, Zeiss-Humphrey Corp., and a private grant from the Midwest Eye Institute, Methodist Hospital

University of Iowa Hospital and the Veterans Administration Medical Center. Iowa City, Iowa





Helmut Wilhelm, B. Wilhelm, U. Schmidt, R. Schmid

Contralateral relative afferent pupillary defect without visual impairment in a thalamic lesion — pupillographic analysis

Relative afferent pupillary defects (RAPD) without visual field loss have been reported in patients with lesions close to the pretectal area or lateral geniculate nucleus (LGN) (1-3). We had the opportunity to examine such a patient clinically, as well as by means of pupillography and pupil perimetry.

Case report: A 21 year old woman suffered from a sudden onset of ataxia, upbeat nystagm, convergence nystagm, and paresis and vertical gaze palsy. MRI showed an acute right sided ischemic medial thalamic lesion (about 8 mm in diameter) and, additionally, an older left sided lesion (5 mm) of the left thalamus. Her only risk factor were moderate elevated antiphospholipid antibodies. She recovered completely. 4 years later she was examined in our department because of red eyes caused by allergy against contact lens rinsing fluid. A marked right sided RAPD of 0.9 log units (determined by means of neutral density filters) was found. Visual acuity was 1.2 (24/20) both sides after the conjunctival inflammation had normalised, visual fields, examined by automated threshold and suprathreshold grid perimetry with very dens grid (240 test spots), did not show any interocular difference. Neither did VECP and colour vision. Her optic discs were normal. MRI showed both thalamic lesions unchanged.

Pupillographic results: The RAPD could be demonstrated convincingly both direct and consensually with stimuli of different size. The consensual reactions differed more than the direct reactions. No naso-temporal asymmetry could be shown, neither in 10 and 20° hemifield stimulation nor in pupil perimetry.

Discussion: It is unlikely that the right thalamic lesion caused the RAPD. It is distant to the LGN and bracchium of the superior colliculus, and it is on the wrong side, if we consider the previous reports (1-3). The left sided lesion, however, is located in the pulvinar, close to the LGN and bracchium. It seems to disturb the pupillomotor input from the right eye to the dorsal midbrain on the left side. This would mean that the pupillomotor pathway crosses more or less completely. Then the right pretectum gets its input from the left eye and vice versa! This assumption could also explain RAPDs in optic tract and retrogeniculate lesions. An asymmetrical chiasmal crossing of the pupillomotor fibres may theoretically cause such a finding, however, this would lead to a marked difference in pupillomotor sensitivity between nasal and temporal hemifield even in normal subjects.

Our knowledge concerning the pupillary pathways has not improved very much since the beginning of this century. RAPD in near geniculate and tract lesions, pupillary hemiakinesia in retrogeniculate lesions and even contraction anisocoria cannot be explained sufficiently by the common model of the pupillary pathway with a direct retinal-pretectal projection. We suggest the presence of a second crossing of previously uncrossed fibres on the suprageniculate plane based on computer modelling of the pupillary pathway.


Dr. H. Wilhelm


D- 72076 Tübingen

Phone +497071 294786

Fax + 497071 295038



1. Eliott D, Cunningham EJ, Miller NR. Fourth nerve paresis and ipsilateral relative afferent pupillary defect without visual sensory disturbance. A sign of contralateral dorsal midbrain disease. J Clin Neuro Ophthalmol 1991;11(3):169-72.

2. Ellis CJ. Afferent pupillary defect in pineal region tumour. J Neurol Neurosurg Psychiatry 1984;47(7):739-41.

3. Johnson RE, Bell RA. Relative afferent pupillary defect in a lesion of the pretectal afferent pupillary pathway. Can J Ophthalmol 1987;22(5):282-4.





Wolfgang Fink (*), H. Wilhelm, B. Wilhelm

A model for the pupillary pathway based on neural network theory

From the viewpoint of neural network theory we introduce a model for the pupillary pathway which can easily be handled computationally and analytically.

Methods: In order to model the binocular pupillary reactions we use a feed-forward typed network, namely a multilayered perceptron consisting of four neural layers, which can be identified as follows: the four retinal halfplanes act as input neurons of the input layer. The following two hidden layers denote the left & right lateral geniculate nucleus (LGN)/thalamus complex and the left & right pretectum. Finally the nuclei Edinger-Westphal represent the output units of the output layer, which control the binocular pupillary reactions quasi-directly.

The neural couplings connecting the neural layers can be adjusted according to neuroanatomical conditions, e. g., chiasmal crossing etc..

Results/Discussion: It is possible to calculate the pupillary reactions analytically as a function of external and internal parameter sets. The stimulation of the four retinal halfplanes by incoming light forms the external parameter set, whereas the set of neural coupling strengths between the neural layers mentioned above represents the internal parameter set.

Although this model is a simple approach it reveals a wide variety of pupillary reactions and is capable of explaining many clinical findings: Several lesions, e. g., lesions of the intercalated neurons between afferent and efferent pupillary pathways can be simulated within the model and the corresponding pupillary reactions such as anisocoria or relative afferent pupillary defects can be calculated analytically.

Furthermore predictions made by the model may give rise to new experiments, which on their part might verify the model again and, if need be, adjust it.

Due to its neural network structure the model described above can easily be extended to much more complex pupillary pathways, while retaining its computational and analytical calculability.

(*) Institut fuer Theoretische Physik, Auf der Morgenstelle 14, D 72076 Tübingen

University Eye Hospital,

Dept. of Pathophysiology of Vision and Neuro-ophthalmology

D-72076 Tübingen

Telefon +497071 294786

Telefax +497071 295038





H. Stanley Thompson, Randy H. Kardon

Adie's Syndrome: Denervation and Re-innervation of the Iris Sphincter Demonstrated by Infrared Videographic Transillumination.

Purpose. To use a new transillumination technique to look at the behavior of the iris sphincter in Adie's syndrome.

Methods. The irises of 10 patients with Adie's syndrome were recorded with a video apparatus a) using diffuse, frontal white light and a color slit lamp video camera b) using a black and white video camera sensitive to the near infrared.

For transillumination, white light from a source rich in infrared energy was passed through a fiberoptic transilluminator held against the lower lid and directed through the lower half of the globe towards the posterior pole of the eye. The eye was then viewed from the front with infrared light pouring out of the pupil and transilluminating the iris and anterior segment.

Results. We made the following observations:

1. Iris sphincter segments that responded normally to light and to near could be seen to contract and darken.

2. Iris sphincter segments that failed to react to light did not contract and darken.

3. Many of these denervated iris sphincter segments had apparently been re-innervated by nerves serving the ciliary muscle, as they could be seen to contract and darken with a near effort, but not to light.

4. After low dose pilocarpine (0.05% or 0.1%), all denervated or re-innervated segments with supersensitivity could be seen to contract and darken.

5. After a further miotic dose of pilocarpine (1%) all sphincter segments contracted and darkened with the exception of rare segments that appeared to be atrophic.

Conclusions. In patients with Adie's syndrome the characteristic signs of segmental denervation and re-innervation of the iris sphincter can be seen better with videographic infrared transillumination than by looking at the front surface of the iris with a slit lamp in the usual way. This method is also useful for identifying which segments of the sphincter demonstrate cholinergic supersensitivity.

H. Stanley Thompson, M.D. and Randy H. Kardon, M.D., Ph.D.,

Dept. Ophthalmology, Neuro-ophthalmology Unit, University of Iowa and Veterans Administration Hospital, Iowa City, Iowa.





Hans Borgmann, J. Berg, J. Eckert

Pupil size in cataract surgery with and without prostaglandin inhibitors

In a prospective study 2327 cataract extractions were evaluated, 767 eyes were treated before with flurbiprofen, 1650 eyes were operated without treatment.

The evaluation was concentrated on the behaviour of the pupil during surgery dependent on the size before surgery. Because it is uncomfortable to do phacoemulsification through a pupil smaller than 5 mm, this size was defined as the lower limit.

The results show that 9 mm pupils do not come into the critical range. In 8,7 and 6 mm pupils there is a clear difference between treated and not-treated eyes the latter become smaller in a higher percentage.

H. Borgmann

Hospital of the Order of St. John

Department of Ophthalmology

Johanniterstr. 3-5

D 53113 Bonn

Tel +49228-543 2500

Fax +49228-543 2513






Harry J. Wyatt

Pupil dilation, convectin, and anterior segment kinetics

I have reported on techniques developed to quantify the "form" of the pupil — i.e. its shape and placement in the eye [ARVO (1994); Vision Research (1995) 35: 2021]. The techniques involve photography with a modified slit-lamp and digitization of the pupil margin. Digitizing the limbus provides a globe-fixed coordinate system. (The first Purkinje image of the illumination source is also digitized in some cases.) The pupil is then represented as a circular Fourier series. Using these techniques, I have been studying the nature of pharmacologic pupil dilation.

Results comparing the fully-dilated to the natural pupil are in agreement with Walsh (1988; Ophthal. Physiol. Opt. 8: 178): there are small shifts of the center. In contrast, the process of dilation may be more interesting than the product: during dilation, substantial asymmetries occur. (Note that "asymmetry" is used here to indicate asymmetric form of a single pupil, not anisocoria.) At the onset of a typical dilation, one side of the pupil shifts maximally, while the opposite side remains nearly stationary. The pupil also becomes elongated; however, unlike "sector" or "focal" dilation, the elongation is usually not in the direction of maximal shift, but more nearly perpendicular to it. The direction of maximal shift is invariably downwards, and also contains an idiosyncratic horizontal component which is somewhat nasal on average. Late in dilation, the pupil center returns to near its initial position, and pupil shape returns to near-circularity.

Since the final pupil form is relatively symmetrical, it is difficult to explain the transient asymmetries on the basis of intrinsic iris properties. One possibility is that the drug arrives asynchronously at the sphincter muscle. To test this, a 2-dimensional model has been developed; simulated dilations can, indeed, approximate observed pupil behavior.

What might cause such asynchrony? Two further experiments examined this: (1) Drugs were administered while subjects' heads were inverted. 1-2 minutes later, the eye was flushed with sterile saline and subjects sat upright for the rest of the session. Dilation in these subjects resembled the normal, upright situation. (2) Drugs were administered while subjects sat normally. 1-2 minutes later, the eye was flushed and subjects' heads were placed in a head-rolled position for the rest of the session. Dilation in these subjects differed dramatically from the normal situation, and the changes correlated approximately with head position.


These results suggest a gravitational influence occuring after the cornea. I propose that convectional flow of aqueous humor, described by Ehrlich (1888) and analyzed by Türk (1906, 1911), plays a major role in anterior segment pharmacokinetics. It may also play an important role in general transport in the anterior segment.


Suny College of Optometry

100 E. 24th Street

New York, NY 10010 (USA)

Tel. +1-212-7805163

Fax +1-212-7805174

e-mail: WYATTHJ@aol.com




Michael C. Koss, Ph.D

Analysis of miosis produced by McN-A-343 in anesthetized cats

McN-A-343 is a selective M1 muscarinic agonist that stimulates muscarinic transmission in sympathetic ganglia. In preliminary experiments, we observed that i.v. McN-A-343 produced miosis in cats in the presence of nicotinic ganglionic blockade. This project was undertaken to ascerUse of uninitialized value in concatenation (.) or string at E:\listplex\SYSTEM\SCRIPTS\filearea.cgi line 455, line 731. tain the site(s) and mechanism of action of this McN-A-343 induced miosis with special reference to possible muscarinic transmission in the ciliary ganglion.

Cats were anesthetized with pentobarbital (36 mg/kg, i.p.) and one superior cervical ganglion (SCG) was removed. Bilateral pupillary dose-response curves in response to i.v. McN-A-343 (6.25-1600 µg/kg) were generated during infusion of the nicotinic ganglionic blocker, hexamethonium (C6; 1mg/kg/min). Bilateral nictitating membrane (NM) responses also were recorded. Experiments were repeated in animals pretreated with M1 muscarinic receptor antagonist, pirezepine (50 mg/kg) and in animals with one ciliary ganglion removed. In other experiments, direct stimulation of preganglionic parasympathetic input and recordings of ciliary nerve activity were undertaken.

McN-A343 produced a dose-related miosis that was not antagonized by either pirenzepine or by removal of the ciliary ganglion but was reversed by atropine (1mg/kg, i.v.). In contrast, concentration of the NM was antagonized by pirenzepine and was dependent on an intact SCG. In addition, McN-A-343 failed to facilitate postganglionic ciliary nerve activity although an effect was clearly seen with the nicotinic ganglionic stimulant (DMPP). A residual miosis to preganglionic ciliary nerve stimulation also was not seen in animals pretreated with C6 (as observed with the NM). Drug-induced pupillary constriction appears to be due to a direct effect of McN-A-343 on the sphincter muscle and not to M1 muscarinic receptor activation. Taken together, the results suggest a lack of muscarinic transmission in the parasympathetic ciliary ganglion. This contrasts with sympathetic ganglia where muscarinic transmission (via M1 muscarinic receptors) is so clearly demonstrated. Supported by NIH grant EY09344.

Dept. of Pharmacology, Univ. Oklahoma College of Medicine, Oklahoma City,OK 73190. Phone (409) 271-2107; FAX (405) 271-3415.