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Show STATE OF THE ART Clinical Applications of Pupillography Helmut Wilhelm, MD, and Barbara Wilhelm, MD Abstract: The development of personal computer- based infrared video instruments has allowed pupillography to enter the clinical arena. Measuring pupil diameter for refractive surgery, distinguishing Horner syndrome from physiologic anisocoria, quantifying the relative afferent pupillary defect, and plotting visual fields by means of graded pupil constriction to focal light stimuli are recent applications in ophthalmology. Pupillography has also been used to determine sleepiness and autonomic effects of new pharmaceuticals. ( JNeuro- Ophthalmol 2003; 23: 42^ 19) Pupil examination is usually done with a flashlight and a pupil gauge, and this is sufficient in most cases. Why then consider using expensive and sometimes complicated instruments? There are some good reasons: ( 1) measurements can be performed more accurately; ( 2) additional parameters can be measured, such as pupil latency time; ( 3) findings can be documented and compared from examination to examination; ( 4) observations are not influenced by examiner bias; ( 5) normal values can be established to distinguish more clearly between pathologic and normal findings; ( 6) new information about pupil behavior can be obtained which allows a better understanding of physiology and pathophysiology. NEW TECHNIQUES Pupillography is now mostly carried out by recording the pupil with an infrared video camera ( 1). The video frames are digitized and transferred to a personal computer, usually with a frame grabber interface. Image processing software detects the pupil on each single frame and University of Tuebingen Medical School, Department of Pathophysiology of Vision and Neuro- ophfhalmology, Eye Hospital, D 72076, Tuebingen, Germany. Address correspondence to Helmut Wilhelm, MD, University of Tuebingen Medical School, Department of Pathophysiology of Vision and Neuro- ophfhalmology, Eye Hospital, D 72076, Tuebingen, Germany; E- mail helmut. wilhelm@ med. uni- tuebingen. de The authors are co- inventors of pupillographic devices for measuring sleepiness ( PST) and for performing the swinging flashlight test ( SWIFT) and therefore receive, in accordance with German laws, a portion of the licensing fees for those instruments. calculates its diameter or area. The processing speed of modern personal computers allows the construction of pu-pillographs that measure the pupil in real time at 25 to 60 times per second, depending on the video frame rate. Advances in image processing technology have resulted in instruments that are easier to handle and more reliable than previous solutions. The standard video frame rate of 25 to 60 Hertz ( Hz) limits temporal resolution to 16.7 to 40 milliseconds ( msec). However, where high temporal resolution is needed, a CCD- array camera ( 2,3) may be an alternative, offering a time resolution of 4 milliseconds, which is sufficient for slow movements like those of the pupil. Commercially available pupillographic devices ( Table 1), which range in price from $ 3,000 to $ 30 000, differ remarkably because each instrument is designed for a special purpose. Some instruments are specialized for very high spatial or temporal resolution; others offer the possibility of stable, continuous, long- term recordings of the pupil size. The bit sampling of the analog to digital data may also limit the ability to resolve small changes in pupil size ( 8- bit sampling is adequate; 10- or 12- bit sampling is optimal). Many instruments come without a standardized light stimulus; some instruments supply a great variety of light stimuli, while others are optimized to compare the light reflexes of both eyes. Most instruments allow the recording of only one pupil at a time; others consist of binocular systems. Because of the possibility of unequal direct and consensual pupil reactions, binocular dual channel pupillometers are best suited for clinical application in neuro- ophthalmology, where swinging flashlight test and measuring of pupillary dilation lag are the most common applications. Some instruments allow simultaneous recording of eye movements; others are capable of recording accommodation based on the intensity profile of the fundus reflex exiting the pupil. CLINICAL APPLICATIONS OF PUPILLOGRAPHY Pupil Diameter in Refractive Surgery In refractive surgery, the pupil diameter in darkness is an important variable when determining the diameter of the ablation zone ( 2,3). Because pupil size may vary, a single measurement obtained by taking photographs with infrared Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 42 J Neuro- Ophthalmol, Vol. 23, No. 1, 2003 STATE OF THE ART JNeuro- Ophthalmol, Vol. 23, No. 1, 2003 6,0- 1 5 3 - 50- 45- 4 0- ) L CHI A f FLA 1 1 1 1 1 1 i i • • s. B * - ~ T ~ T i l l 1 " POULIOGSAM r- - f- • •• i •~ r- i i - i ' i l i i i l l l i < ^ -! sooo FIG. 1 . Normal pupillary response to a short light flash ( 0.2 seconds). The upper graph shows the original pupillogram, the lower part its first derivative. Such recordings have been used in many studies. Typical parameters of evaluation are latency time ( 0 to A), peak time ( 0 to B), constriction time ( A to B), 23 redilation time ( B to C) as temporal parameters, baseline diameter ( pupil size between 0 and A), and constriction amplitude ( difference in size between A and B). Relative amplitudes can be calculated ( constriction amplitude divided by baseline size). Maximum constriction or dilation speed can be obtained from the first derivative of the pupillogram. The terminology of pupillography is not uniform; some authors use the term " latency" instead of " peak time." ( Recorded with the AMTech Compact Integrated Pupillograph ™ Time unit = msec). light could lead to false results- usually an underestimation of pupil diameter. Recording the pupil size over a certain time period and using varying lighting conditions, for at least 10 to 30 seconds, leads to more realistic results with a FIG. 3. Pupil campimetry in right hemianopia. The small columns indicate the averages of four light reflex amplitudes, markedly smaller in the blind right hemifield. ( Recorded with a customized pupillographic campimetry system in our department). lower risk of underestimation. In these applications, it is important to control accommodation to prevent a pupil near contraction. Objective Assessment of Visual Function Although accurate measurement of pupillary response to light offers the potential of an objective assessment of visual function across the anterior visual pathway, interindividual differences have limited this application. Constriction amplitude of the pupillary light reflex ( PLR) is proportional to the logarithm of the retinal light flux for midrange photopic stimuli ( Fig 1) ( 1). Latency is inversely proportional to log light intensity. Therefore, the PLR can j Light left ^ Light right OS O 3 OD ^"' 1>^^~~ V^' right " fboH J left ^ v^~. ) \ y i V V K n " ™ ^ Q3 10 s 20 s FIG. 2. Afferent pupil defect ( present in the OS). Both eyes are stimulated alternately. The constriction amplitude in both eyes is measured and averaged. The arrows show the time when a pupil constriction is expected. The software must recognize that the deflection of the curve indicated at 1 is not a response to the light stimulus because it comes too late. At 2, the pupillogram is overlaid by a blink artifact that has to be eliminated by the evaluating software ( indicated with 2) ( Recorded with the SWIFT binocular pupillograph). The distance between the horizontal grid lines is equivalent to approximately 1 mm. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 43 JNeuro- Ophthalmol, Vol. 23, No. 1, 2003 STATE OF THE ART TABLE 1. Pupillographic Devices* Name of the instrument Manufacturer/ distributor Commercially available Principle Spatial resolution Temporal resolution Online analysis Binocular Light stimulus Other stimulus Application Other features CIP AMTech, http:// www. amtech. de Yes IR line scan 0.01mm 250/ 125/ 50/ 25 Hz Yes No Yes ( Yes) S, LR, ( PS) Horizontal eye movements PST AMTech, http:// www. amtech. de Yes IR video 0.05 mm 25 Hz Yes No No No SW Blink count HEY AMTech, http:// www. amtech. de Yes IR video na 50 Hz No Yes Yes No S, LR Com, SW None SWIFT Steinbeis Transferzentrum, Biomed. Optik, http:// www. stz- biomed. de Yes IR video 0.1 mm 40 ms Yes Yes Yes No Com. None Visual Pathway Binocular Pupillometer Visual Pathways Inc. Prescott, AZ, Ph: + 1 928 778 5002 No IR video and IR reflex 0.025 60 and 100 Hz Yes Yes Yes No S, LR, Com, PP, SW Eye movements Micro-measurements System 9000 Micro-measurements, Keith Sherman. No IR video Variable Up to 60 Hz No Yes Yes Yes S, LR, Com, PP, SW Eye movements Continued on next page be used to measure a proportional change in visual function objectively. Unfortunately, interindividual differences of light reflex parameters are enormous. This is different from pattern visual evoked potentials ( VEP), where a reliable normal range can be defined. However, the VEP is weighted to measure the function primarily of the central retina, whereas the PER is efficient at spatial summation over large areas of the retina. Hence the pupil light reflex in response to a diffuse flash better reflects the global function of the retina ( 4,5). Unlike the VEP, the latency of the PLR is not significantly prolonged in inflammatory optic nerve disease ( 6), and therefore cannot replace the VEP in this function. Because of interindividual differences that have yet to be successfully normalized across subjects, the correlation between parameters of the PLR and the visual field is best suited to comparing the input of the two eyes. Afferent Pupillary Defect Pupillography is well suited to reliable measurement of an afferent pupil defect. The swinging flashlight test, although easy to perform clinically, has its pitfalls. First, physiologic anisocoria or immobility of one pupil may lead to difficulties in interpreting the results of the swinging flashlight test carried out manually. Second, the normal variability of the PLR makes it necessary to compare multiple swings. Yet virtually no examiner is able to remember and mentally average the pupillary responses to more than just a few swings. Most examiners therefore stop testing as soon as the expected result is obtained, long before a sufficient number of swings have been performed to overcome short- term variability. There are several advantages to carrying out the swinging flashlight test automatically ( Fig. 2) ( 7- 10). To obtain a reliable assessment of an afferent pupil defect, one must measure simultaneously in the two eyes to compensate for natural differences in the midbrain decussations of the interneuron of the PLR, asymmetric supranuclear influences on the Edinger- Westphal nucleus, and possibly efferent differences in innervation of the two pupils. A binocular pupillographic device is ideally suited to this task. Additionally, a more exact measurement of the amount of a relative afferent pupillary defect is possible by comparing PLRs at different intensities. It has been shown that the pupil reacts even on changes of pattern, colors, and motion, even if there is no change in light flux ( 11). This phenomenon requires sophisticated stimulation techniques. Testing of higher visual functions objectively may be a future possibility ( 12). A final and most important advantage Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 44 © 2003 Lippincott Williams & Wilkins STATE OF THE ART JNeuro- Ophthalmol, Vol. 23, No. 1, 2003 TABLE 1. Continued ETS- PC III ASL Applied Science Laboratory MA. Yes IR video na 50/ 60 Hz Yes No Yes No S, LR, ( SW) Boston, Eye movements, blink detection Sciscope Pupillometer Sciscope Instrument Company. Martin Van Orsow, Iowa City, IA. Ph: 319- 338- 1107 martin@ sciscope. com Yes IR video Variable na No Yes Yes Audio S, LR, PS, Com None The Eyegaze Development System LC Technologies, http:// www. eyegaze. com Yes IR video 0.5 mm 60 Hz No No No Monitor output S, LR, SW Eye movements PUPILSCREEN II ® Type 10 Fairville Medical Optics, Inc., brock499@ aol. com No ( discontinued) Scanning OpticRam Image Sensor 0.05 mm 10 or 20 Hz Yes Yes Yes No S, LR None PUPILSCAN II ® Type 9 Fairville Medical Optics, Inc., brock499@ aol. com Yes Scanning OpticRam Image Sensor 0.05 mm 10 or 20 Hz Yes No Yes No S, LR None Continued on next page consists in independence from examiner bias and observation inaccuracy. Visual Field Defects Pupil campimetry is an attempt to provide objective measurement of visual field defects ( Fig. 3) ( 13- 17). The basic concept is to stimulate small areas of the retina and elicit a graded constriction of the pupil depending on the integrity of local visual function. Perimetric stimuli must be small and dim to elicit a local visual response rather than one generated from a wider retinal area receiving stray light. The pupillomotor field shows a profile similar to that of the visual field as measured psychophysical^ with standard stimuli: the highest sensitivity is in the center and in the nasal inferior retina ( superior temporal field). Pupillo-graphic visual fields, using M- sequence stimulation, have also allowed reasonable estimation of visual field defects ( 18), but this method requires that the subject not blink during the recording intervals. Alternative methods of objective measurement of the visual field, including multifocal electroretinography and multifocal visual evoked potentials, also have limitations. Multifocal electroretinography can map the visual field only if the lesion is located in the retinal receptors ( 19). Multifocal visual evoked potentials are not quite clinically applicable. The initial published results, although promising, allow only a relatively coarse estimation of visual field defects ( 20); however, the use of additional electrodes seems to improve this technique ( 21). Horner Syndrome Dilation lag, referring to delayed enlargement of the pupil when light is withdrawn, is a characteristic feature of Horner syndrome ( 22). A normal pupil usually dilates within approximately 5 seconds after the room light is switched off; in Horner syndrome, it may take 15 to 20 seconds. This means that the amount of anisocoria increases during the first phase of the pupillary dilation ( 5 to 7 seconds) and decreases in the second phase ( 7 to 15 seconds). In physiologic anisocoria, there is no dilation lag, so pupil size difference remains constant following light withdrawal. The measurement of pupil dilation lag is therefore a useful means of differentiating Horner syndrome from physiologic anisocoria ( Fig. 4) ( 23). However, observing the dynamic movement ( dilation) of the pupils simultaneously in darkness may be clinically difficult. Infrared light is required to optimally visualize the dynamics of dilation of both pupils simultaneously. PupiUography accurately measures the speed Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 45 JNeuro- Ophthalmol, Vol. 23, No. 1, 2003 STATE OF THE ART TABLE 1. Continued Name of the instrument Manufacturer/ distributor Commercially available Principle Spatial resolution Temporal resolution Online analysis Binocular Light stimulus Other stimulus Application Other features PUPILSCAN II ® Model 12 Fairville Medical Optics, Inc., brock499@ aol. com Yes Scanning CMOS Image Sensor m lm 0.05 mm 10 or 20 Hz Yes No Yes No S, LR None PUPILSCAN II ® Model 12A Fairville Medical Optics, Inc., lombart@ lombartinstrument. com Yes Scanning Image m lm 0.05 mm 10 Hz Yes No No No S None CMOS Sensor PUPILSCAN II ® Model 129 Fairville Medical Optics, Inc., brock499@ aol. com No ( under development) Scanning CMOS Image Sensor m lm 0.05 mm 10 or 20 Hz Yes No Yes No S, LR None MonVogl Metrovision http:// www. metrovision. fr Yes IR video 0.05 mm 60 Hz Yes No Yes Monitor S, LR, PR, PP, SW Eye movements Octopus 1- 2 3 Pupil Perimeter Interzeag/ Clement Clark; Ph: 01733 6811 No IR video 0.05 mm 50 Hz No No Yes No LR, PP None P_ SCAN 100 system City University London, http:// www. city. ac. uk/ avrc Yes ( for research projects) IR video 0.01 mm 50- 60 Hz Yes Yes Yes Contrast, color, gratings motion S, LR, PP, SW Eye movements Continued on next page of dilation or the difference between both pupils during dilation ( 24) ( Fig. 4). Pupillography is the only method of reliable diagnosis of dilation lag in binocular Horner syndrome ( 24). Sleepiness Changes in the pupillary diameter in complete darkness can only be caused by accommodation or by innerva-tional changes in the central and peripheral sympathetic system that determine the pupillary baseline diameter. When a subject becomes sleepy, large amplitude slow pupillary oscillations occur ( Fig. 5) ( 25). These " sleepiness waves" correlate well with the time of sleep deprivation ( 26). Differences in these oscillations clearly distinguish between treated and untreated sleep apnea patients, and between normal subjects from those with hypersomnias ( 27- 29). To record these sleepiness waves requires long- term pupillography, typically 11 minutes in darkness and quiet. Droopy eyelids, large eye movements, or dry eyes may cause artifacts or interrupt the measurement. Special instrumentation and software have overcome these problems ( 30). As a result, measuring sleepiness objectively by pupillography has become an accepted procedure in sleep medicine. The " pupillographic sleepiness test" is less time-consuming and personnel- intensive than other objective tests, such as the multiple sleep latency test. In Germany, this pupil test has been applied not only in sleep medicine, but also in industrial and traffic medicine. Autonomic Effects of Pharmaceuticals Any drug that acts on the central nervous system affects the pupillogram ( 31). For most substances, it is difficult to predict which arm of the autonomous nervous system will be most influenced ( 32). Pupil dilation can be observed after either parasympatholytic or sympathomimetic drugs, and pupil constriction after parasympathomimetics or sympatholytics. The pupillogram provides sensitive information on cholinergic or adrenergic effects. The latency of the pupillary light reflex is predominantly regu- Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 46 © 2003 Lippincott Williams & Wilkins STATE OF THE ART JNeuro- Ophthalmol, Vol. 23, No. 1, 2003 TABLE 1. Continued EyeCheck MCJ Inc, http:// www. mcjeyecheck. com Yes na na na na na na na S, LR ( used for drag screening) None Chronos Eye Tracker Chronos Vision/ Skalar Medical http:// www. skalar. nl Yes Infrared CMOS imaging 0.05 mm 50/ 100/ 200/ 400 Hz Yes Yes Synchronous output, A/ D D/ A channel Synchronous output, A/ D D/ A channel S, LR, PS, Com, PP, SW Eye movements Procyon P2000SA Procyon Instruments Ltd., http:// www. procyon. co. uk Yes IR video 0.1 mm 5 Hz Yes Yes Yes ( 3 levels) No S, LR, Com na Procyon P2000SA Procyon Instruments Ltd., http:// www. procyon. co. uk Yes IR video 0.1 mm 25 Hz Yes Yes Yes ( Maxwellian view or closed loop) No S, LR, Com na Mayo Clinic Pupillometer na No IR video variable 60 Hz Yes Yes Yes na S, LR, Com, na SW POWERREF II PlusoptiX AG, http:// www. plusoptix. de Yes IR video 0.16 mm 12,5/ 25/ 50 Hz Yes Yes Yes No S, LR, Com Accommodation, Eye movements Oculus Keratograph Oculus, http:// www. oculus. de Yes IR video 0.04 mm 8 Hz Yes No Yes No S, LR, ( Com) Corneal surface anal sis * Information obtained by E- mail inquiry to Pupil Net: www. jiscmail. ac. uk/ lists/ pupil. html, an internet community of pupil researchers. Other instruments are probably available. Com, comparison of the two eyes; Hz, Hertz; LR, analysis of light reaction; na, not applicable; PP, pupil perimetry; PS, psychosensory reaction; S, measurement of pupil size; SW, sleepiness waves. lated by the parasympathetic system; the dilation speed best reflects the action of the sympathetic system. By blocking the dilator muscle with dapiprazole eye drops, one can determine whether pupil dilation is caused by central inhibition of cholinergic activity. Additionally, by applying the pupillographic sleepiness test, sedative effects of a drag can be assessed objectively ( 32). Psychiatric Disorders Pupillography has also been used to objectively measure emotional responses ( 33). Fear, anger, or stress dilate the pupil, an effect called the " psychosensory pupillary response" ( 34). Psychosensory pupil dilation is often less than 0.3 mm, and can be hidden within the normal, spontaneous oscillations of pupil size, which are of the same magnitude. Therefore, pupillography is necessary to isolate the psychosensory response, mostly by averaging several response reflexes similar to what is done to extract the VEP from the EEG recording. ( Fig. 6). Patients with different psychiatric disorders will display different emotional reactions to stimuli presented to them ( 35). For example, an alcoholic patient will react differently to the smell of whisky if this patient is a recidivist risk after withdrawal therapy ( 36). Pupillographic data exist in a great number of psychiatric patients, ( 34,35) but the data have not been sufficiently confirmed to allow their clinical application. However, the use of pupillography in psychiatric disorders is promising. Alzheimer Disease The initial pupillographic results in Alzheimer disease following the application of diluted tropicamide could not be reproduced and have been dismissed as unreliable ( 37- 40). Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 47 JNeuro- Ophthalmol, Vol. 23, No. 1, 2003 STATE OF THE ART lmm normal Pupil Horner's Pupil Difference I s 5 s FIG. 4. Horner syndrome. The involved pupil dilates more slowly, and the anisocoria increases during dilation. After the time period demonstrated here, the Horner pupil continues to dilate for up to 15 seconds whereas the normal pupil usually reaches its endpoint after 5 to 6 seconds. For clinical purposes, longer recording than here ( 15- 20 seconds) is advisable. ( Recorded with the Procyon ™ binocular pupillograph). | Mf^ ff FIG. 5. Sleepiness test. This patient has obstructive sleep apnea. During the first minute, the pupil size remains stable, but then marked sleepiness waves become obvious. ( Recorded with the AMTech PST ™ pupillograph). Note that the time scale is now longer. 10 Time ( min) FIG. 6. One- digit multiplication task. A small pupil dilation indicates the subject's effort to solve the task. Four curves have been averaged together to eliminate random pupillary movements. The task was given between 0 and 1 second. ( Recorded with a modified AMTech PST ™ pupillograph). 7.0 6.9 6.8 6.7 Multiplication Task - v ^ v r - / tdL f W 1 v p A ^ / V A \ n W\ 1 3 4 Time ( s) Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 48 © 2003 Lippincott Williams & Wilkins STATE OF THE ART JNeuro- Ophthalmol, Vol. 23, No. 1, 2003 Autonomic Neuropathy in Diabetes Mellitus Many authors have advocated using pupillography to diagnose autonomic neuropathy in diabetic patients. However, although significant differences between normal and patients with diabetes and between different groups of patients with diabetes can be demonstrated for a variety of parameters, the great variance of data does not allow a clear statement in an individual case ( 41,42). More information on the history and basics of pupillography can be found in Loewenfeld's The Pupil ( 43). REFERENCES 1. Wilhelm H, Wilhelm B, Liidtke H. Pupillographie: prinzipien und anwendungsmoglichkeiten. Zprakt Augenheilkd 1996; 17: 327- 36. 2. Schnitzler EM, Baumeister M, Kohnen T. Scotopic measurement of normal pupils: Colvard versus video vision analyzer infrared pu-pillometer. J Cataract Refract Surg 2000; 26( 6): 859- 66. 3. Boxer Wachler BS, Krueger RR. Agreement and repeatability of pupillometry using videokeratography and infrared devices. J Cataract Refract Surg 2000; 26( 1): 35^ K). 4. Alexandridis E, Argyropoulos T, Krastel H. The latent period of the pupil light reflex in lesions of the optic nerve. Ophthalmologica 1981; 182( 4): 211- 7. 5. Miiller- Jensen A, Zschocke S. Possibilities of simultaneous analysis of phasic pupillary light reflex and visual evoked potentials. Electroencephalogr Clin Neurophysiol 1979; 47( 2): 239^ 12. 6. Van Diemen HA, Van Dongen MM, Nauta JJ, et al. Pupillary light reflex latency in patients with multiple sclerosis. Electroencephalogr Clin Neurophysiol 1992; 82( 3): 213- 9. 7. Wilhelm B, Liidtke H, Peters T, et al. Automated swinging flashlight test in patients with optic nerve diseases. Klin Monatsbl Au-genheilkd 200l; 2lS( l): 2l- 5. 8. Volpe NJ, Plotkin ES, Maguire MG, et al. Portable pupillography of the swinging flashlight test to detect afferent pupillary defects. Oph-thalmology 2000; 107( 10): 1913- 21; discussion 1922. 9. Fison PN, Garlick DJ, Smith SE. Assessment of unilateral afferent pupillary defects by pupillography. Br J Ophthalmol 1979; 63( 3): 195- 9. 10. Kawasaki A, Moore P, Kardon RH. Long- term fluctuation of relative afferent pupillary defect in subjects with normal visual function. Am J Ophthalmol 1996; 122( 6): 875- 82. 11. Barbur JL, Harlow AJ, Sahraie A. Pupillary response to stimulus structure, color and movement. Ophthalmic Physiol Opt 1992; 12: 137- 41. 12. Barbur JL, Harlow AJ, Weiskrantz L. Spatial and temporal response properties of residual vision in a case of hemianopia. Phil Trans R SocLondB 1994; 343: 157- 66. 13. Kardon RH, Kirkali PA, Thompson HS. Automated pupil perimetry. Pupil field mapping in patients and normal subjects. Ophthalmology 1991 ; 98( 4): 485- 95. 14. Jensen W. Die Fernsehbildanalyse. A description of a method for objective perimetry ( author's transl). Albrecht Von Graefes Arch klin exp Ophthalmol 1976; 201( 2): 183- 91. 15. Alexandridis E, Krastel H. Pupillographische Perimetrie mit dem " Octopus." Fortschr Ophthalmol 1989; 86( 6): 692- 4. 16. Kardon RH, Thompson S. Pupil perimetry: methods of threshold determination and comparison with visual responses. In: Mills RP, Wall M, eds. Proc. of the XI International Perimetric Society Meeting. Amsterdam/ New York: Kugler Publications; 1995. 17. Schmid R, Wilhelm B, Wilhelm H. Naso- temporal asymmetry and contraction anisocoria in the pupillomotor system. Graefes Arch Clin Exp Ophthalmol 2000; 238( 2): 123- 8. 18. Wilhelm H, Neitzel J, Wilhelm B, et al. Pupil perimetry using M- sequence stimulation technique. Invest Ophthalmol Vis Sci 2000; 41( 5): 1229- 38. 19. Sutter EE, Tran D. The field topography of ERG components in man. I. The photopic luminance response. Vision Res 1992; 32: 443- 6. 20. Baseler HA, Sutter EE. M and P components of the VEP and their visual field distribution. Vision Res 1997; 37: 675- 90. 21. Hood DC, Zhang X, Hong JE, et al. Quantifying the benefits of additional channels of multifocal VEP recording. Doc Ophthalmol 2002; 104: 303- 20. 22. Pilley SF, Thompson HS. Pupillary " dilatation lag" in Horner's syndrome. Br J Ophthalmol 1975; 59( 12): 731- 5. 23. Krzizok T, Graf M, Kraus S. Foto- und videografische Messung des Dilatationsdefizits zur Differentialdiagnose des Horner- Syndroms. Ophthalmologe 1995; 92( 2): 125- 31. 24. Smith SA, Smith SE. Bilateral Horner's syndrome: detection and occurrence. J Neurol Neurosurg Psychiatry 1999; 66( 1): 48- 51. 25. Lowenstein O, Feinberg R, Loewenfeld IE. Pupillary movements during acute and chronic fatigue: a new test for the obj ective evaluation of tiredness. Invest Ophthalmol 1963; 2: 138- 57. 26. Wilhelm B, Wilhelm H, Liidtke H, et al. Pupillographie assessment of sleepiness in sleep- deprived healthy subjects. Sleep 1998; 21( 3): 258- 65. 27. Wilhelm H, Liidtke H, Wilhelm B. Pupillographie sleepiness testing in hypersomniacs and normals. Graefes Arch Clin Exp Ophthalmol 1998; 236( 10): 725- 9. 28. Wilhelm B, Luedtke H, Widmaier D, et al. Therapy control in sleep apnea patients by means of a pupillographie sleepiness test. Sleep 1998; 21( suppl): 266. 29. O'Neill WD, Oroujeh AM, Merritt SL. Pupil noise is a discriminator between narcoleptics and controls. IEEE Trans Biomed Eng 1998; 45( 3): 314- 22. 30. Liidtke H, Wilhelm B, Adler M, et al. Mathematical procedures in data recording and processing of pupillary fatigue waves. Vision Res 1998; 38( 19): 2889- 96 31. Bottcher M, Liidtke W, Schafer HG. Konzentrationswirkungsbe-ziehung zwischen dem Pupillendurchmesser und den Serum-spiegeln psychotroper Substanzen. Anasthesiol Intensiv med Not-fallmed Schmerzther 1995; 30: 119. 32. Phillips MA, Bitsios P, Szabadi E, et al. Comparison of the antidepressants reboxetine, fluvoxamine and amitriptyline upon spontaneous pupillary fluctuations in healthy human volunteers. Psycho-pharmacology ( Berl) 2000; 149( l): 72- 6. 33. Steinhauer SR, Hakerem G. The pupillary response in cognitive psychophysiology and schizophrenia. Ann NY Acad Sci 1992; 658 ( 182): 182- 204. 34. Hakerem G. Conceptual stimuli, pupillary dilation and evoked cortical potentials: a review of recent advances. In: Janisse MP, ed. Pupillary Dynam ics and Behavior. New York: Plenum, 1974: 135- 58. 35. Griinberger J, Linzmayer L, Grunberger M, et al. Pupillometry in clinical psychophysiological diagnostics: methodology and proposals for application in psychiatry. Isr J Psychiatry Relat Sci 1992 ; 29: 100- 13. 36. Grunberger J, Linzmayer L, Fodor G, et al. Static and dynamic pupillometry for determination of the course of gradual detoxification of opiate- addicted patients. Eur Arch Psychiatry Clin Neurosci 1990; 240: 109- 12. 37. Scinto LF, Daffner KR, Dressier D, et al. A potential noninvasive neu-robiologic test for Alzheimer's disease. Science 1994; 266: 1051- 4. 38. FitzSimon JS, Waring SC, Kokmen E, et al. Response of the pupil to tropicamide is not a reliable test for Alzheimer disease. Arch Neurol 1997; 54( 2): 155- 9. 39. Kardon RH. Drop the Alzheimer's drop test [ editorial; comment]. Neurology 1998; 50( 3): 588- 91. 40. Wilhelm B, Wilhelm H, Wormstall H, et al. Zur Diagnose der De-menz vom Alzheimer- Typ mittels Pupillentest. Nervenheilkunde 1997; 16: 458- 63. 41. Hreidarsson AB. The pupil of the eye in diabetes mellitus, an indicator of autonomic nervous dysfunction. Dan Med Bull 1992; 39: 400- 8. 42. Smith SE, Smith SA, Brown PM, et al. Pupillary signs in diabetic autonomic neuropathy. Br Med J 1978; 2( 6142): 924- 7. 43. Loewenfeld IE. The Pupil. Boston, MA: Butterworth- Heinemann: 1999. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 49 |
