[Relative afferent pupillary defect in glaucoma]. / Relativer afferenter Pupillendefekt bei Glaukom.

BACKGROUND: The aim of this retrospective study was to estimate the frequency of relative afferent pupillary defect (RAPD) in glaucoma and whether its occurrence relates to the severity of the visual field defect and its side asymmetry as detected by standard automated perimetry. PATIENTS AND METHODS: Among patients with primary open angle glaucoma examined at the glaucoma unit of our university eye hospital patients were identified in whom a swinging-flashlight test as part of their routine examination was carried out. The central 30° visual field was examined by means of static perimetry using the Tübinger Automatic Perimeter or the Octopus Perimeter. The visual field findings and their side difference were compared between patients with and without RAPD by means of the Wilcoxon rank-sum test. RESULTS: After having taken into consideration the inclusion criteria, 100 glaucoma patients were included in the study, 34 of them had an RAPD (34 %). For the visual field analysis only the data of 85 patients, who received the same perimetric strategy, were used. 25 of them had an RAPD (29 %). The calculated visual field scores in patients with RAPD were significantly higher than those in patients without RAPD (p < 0.01), that means their visual field loss was generally more advanced. Also the side difference in visual field of both eyes was significantly greater in patients with RAPD (p < 0.01). A receiver operating characteristics (ROC) curve showed that the side difference in visual field defect is a good predictor for RAPD with an area under curve (AUC) of 0.81. CONCLUSION: RAPD can be diagnosed in about one third of patients with primary open angle glaucoma. It can be found especially with more advanced visual field defects and visual field defects with greater side asymmetry. Its absence does not mean that there is no visual field defect at all. We advise to include the swinging-flashlight test in glaucoma diagnostics.

Pimecrolimus cream 1% in erosive oral lichen planus--a prospective randomized double-blind vehicle-controlled study.

BACKGROUND: Erosive oral lichen planus (EOLP) is a T-cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option. OBJECTIVES: To investigate the efficacy of pimecrolimus cream 1% (Elidel) compared with vehicle cream in the treatment of EOLP. METHODS: Twenty patients were enrolled in a prospective, double-blind, randomized, vehicle-controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open-label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts. RESULTS: Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP 'composite score' including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus-treated group compared with vehicle (P = 0.025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long-lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL(-1). CONCLUSIONS: Pimecrolimus cream 1% effectively treats EOLP with long-lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.

Daytime variations in central nervous system activation measured by a pupillographic sleepiness test.

Pupil size is regulated exclusively by the autonomic nervous system, and in darkness is proportional to the level of central sympathetic tone. Spontaneous pupillary movements, while at rest in darkness and quiet, were recorded for a period of 11 min, using infrared video pupillography. Thirteen young adults took part in a 30-h experiment lasting from 08.00 h to 14.00 h on the following day. Pupillographic testing and completion of a self-rated scale for the estimate of sleepiness were repeated every two hours. Pupillary unrest index (PUI), as a measure of pupil size instability associated with daytime sleepiness, showed the lowest values at 09.00 h, when pupil size was found to be maximal, and 23.00 h. During the course of the day, amplitude spectrum < or = 0.8 Hz and PUI showed increasing values during the afternoon hours, followed by a decrease during the evening. Daytime variations in the pupillary unrest index in healthy normal subjects were found to be positively correlated with the level of alertness. These findings are similar to the daytime variations found by the MSLT (multiple sleep latency test) in young adults.

[Automated swinging flashlight test in patients with optic nerve diseases]. / Automatisierter Swinging-flashlight-Test bei Patienten mit Sehnervenerkrankungen.

AIM OF THE STUDY: The swinging flashlight test is an objective method to diagnose a lesion of the anterior visual pathways. However, errors and faults may easily alter the test's results. Hence, the value of the swinging flashlight test depends highly on the examiner's skills. Therefore an automated and objective procedure was developed which is independent from the examiner. METHODS: A binocularly measuring instrument adapted for video pupillography was supplied with two arrays of light emitting diodes in front of each eye of the subject. By means of this illumination, pupillary light reflexes are elicited alternately. Pupil size is registered continuously, and after artifact elimination, the response amplitudes of the pupils are determined as a mean of right and left pupil. Responses elicited via right and left eye are compared. By varying the stimulus intensity it is possible to measure the amount of the relative afferent pupillary defect. The procedure was tested in 31 patients with optic nerve disorders. RESULTS: The measurements were easily feasible, stable and reliable. Correlation between the relative afferent pupillary defect detected manually by grey filter compensating and with the automated procedure proved to be high. Both variables correlated highly significant with a Spearman rank coefficient of 0.65. If the clinical test is regarded as the golden standard, the automated swinging flashlight test is able to detect 85% of the relative afferent pupillary defects > or = 0.3 logE and 94% of the defects > or = 0.6 logE. CONCLUSION: The automated swinging flashlight test can be recommended to exclude influences by the examiner or if the exact amount of the relative afferent pupillary defect is desired, e.g. when monitoring therapeutic effects in optic nerve diseases. Furthermore, an automated swinging flashlight test could serve as a screening test.

Spontaneous fluctuations in pupil size are not triggered by lens accommodation.

Fluctuations in pupil size and lens accommodation are measured concurrently under open loop conditions, constant illumination and far fixation. In 12/17 trials no correlation was measured between the fluctuations in pupil size and lens accommodation. For the remaining 5/17 trials no lag was observed between the changes in pupil size and lens accommodation indicating that this correlation does not arise as a consequence of a near response. These observations suggest that under conditions of constant illumination and far fixation, the supranuclear centers controlling the near response are not active.

Pupil perimetry using M-sequence stimulation technique.

PURPOSE: M-sequence stimulation technique allows mapping of the retinal function by multifocal electroretinographic (ERG) recordings. However, the information provided about visual field is limited to retinal function. Optic nerve diseases and diseases of the higher visual pathways usually show normal multifocal ERGs. Using pupillary responses instead of the electrical retinal responses might enhance the diagnostic possibilities of this system. The problems of local ERG recordings are very similar to those encountered in pupil perimetry: Local stimuli have to be dim to avoid or at least reduce stray-light responses. Dim stimuli, close to the absolute threshold, elicit only subtle pupillomotor responses. Therefore, techniques that are able to detect small focal responses are promising. METHODS: Pupillography was done by means of an infrared video camera and real time image processing (50 Hz) using a custom-designed videoboard in a personal computer (486). Recording conditions: The stimulus was presented on a monitor (75 Hz) in 26 cm distance from the patient's eyes. It contained 37 hexagons in a 25 degrees visual field. Each element changed between black (1.6 cd/m2) and white (160 cd/m2) after a binary M-sequence independently from other elements. Four thousand ninety six different stimulus pictures of 120-msec duration were shown during a single pupillogram recording. Thirty-seven local pupillograms were calculated in a cross-correlation of stimulus sequence and the pupil diameter. RESULTS: The pupillomotor fields in normals showed a shape and sensitivity distribution as known from conventional pupil perimetry techniques. Artificial paracentral scotomas (5 degrees) created by masking different locations could be demonstrated convincingly. Even in patients with optic nerve lesions it was possible to demonstrate visual field defects. CONCLUSIONS: Pupil perimetry using the M-sequence technique is a promising method of objective perimetry that may find its entrance into clinical application.

Pupillary light reflexes in patients with Leber's hereditary optic neuropathy.

BACKGROUND: According to a recent pupillographic study, patients with Leber's hereditary optic neuropathy (LHON) show the same pupillary behaviour as normals. Because this raises many questions concerning the real nature of LHON and challenges our concept of the afferent pupillary system, we tried to verify the results of this study. METHODS: Pupillary function was assessed in 34 normal subjects and 40 patients with LHON. Pupillary light reflexes were recorded by means of the Compact Integrated Pupillograph (CIP, AMTech). Under mesopic conditions 200-ms stimuli were presented at two different stimulus intensities. Latency, constriction amplitude and baseline diameter were defined automatically. Pupil light reflexes were compared between LHON patients and normals and between the better and the worse eye in 20 LHON patients with different visual acuities. RESULTS: For both stimuli there were significant differences in latency between LHON patients and controls. The latency of the pupil light reflex proved to be about 20 ms longer for LHON patients, and the amplitude was significantly smaller for the bright stimulus. Within LHON patients, the eyes with the worse visual acuity had a significantly smaller constriction amplitude than the eyes with the better visual acuity. CONCLUSION: The results of our study confirm that LHON really is an optic nerve disease and that the pupillary light reflexes are not normal.

Pupillographic sleepiness testing in hypersomniacs and normals.

BACKGROUND: Pupillary oscillations in darkness are considered to be a sign of sleepiness. The purpose of this pilot study was to ascertain whether pupillary oscillations were more pronounced in patients with hypersomnia than in normals. METHODS: Seven patients (four with sleep apnea syndrome, three with narcolepsy) and seven age-matched controls underwent pupillography for 11 min in complete darkness. The changes in pupil size were analyzed mathematically to determine quantitatively the amount of pupillary instability. RESULTS: Hypersomniacs had much higher amounts of pupillary oscillations in darkness than normals. The differences were significant. Baseline pupil size did not differ significantly between the two groups. CONCLUSION: This study showed that a pupillographic sleepiness test based on the evaluation of spontaneous pupillary changes in darkness is applicable in hypersomniacs and may facilitate therapy control, i.e. diagnostic grading by measuring daytime sleepiness objectively.

Mathematical procedures in data recording and processing of pupillary fatigue waves.

Spontaneous pupillary behaviour in darkness provides information about a subject's level of vigilance. To establish infrared video pupillography (IVP) as a reliable and objective test in the detection and quantification of daytime sleepiness, the definition of numerical parameters is an important precondition characterising spontaneous pupil behaviour adequately for further statistical procedures. The correct measurement of the pupil size, even if the lid or eyelashes are occluding the pupil, is of particular concern when testing vigilance. In this case many edge points of the pupil are detected and a fitting procedure is described that fits these edge points to a circle and excludes outliers. The first step of data preparation consists of a mathematical artefact management consisting of blink detection and elimination, followed by interpolation. Second, a fast Fourier transformation is carried out for frequencies from 0.0 to 0.8 Hz for each time segment of 82 s. Results are given in absolute and relative power of each frequency band per time segment and mean values over the entire record of 11 min. Third, the changes of the mean pupillary diameter per data window against time are shown graphically. An additional parameter referring to the pupil's tendency to instability, the pupillary unrest index (PUI), is defined by cumulative changes in pupil size based on mean values of consecutive data sequences. These mathematical procedures provide a high level of quality in both data collection and evaluation of IVP as an objective test of vigilance. In a pilot study, the pupillary behaviour of two groups were measured. One group rated themselves as alert (ten men), the other group as sleepy (12 men). The power and PUI were compared using the Mann-Whitney U-test. Both parameters show significant differences between the two groups.

Pupillographic assessment of sleepiness in sleep-deprived healthy subjects.

Spontaneous pupillary-behavior in darkness provides information about a subject's level of sleepiness. In the present work, pupil measurements in complete darkness and quiet have been recorded continuously over 11-minute period with infrared video pupillography at 25 Hz. The data have been analyzed to yield three parameters describing pupil behavior; the power of diameter variation at frequencies below 0.8 Hz (slow changes in pupil size), the pupillary unrest index, and the average pupil size. To investigate the changes of these parameters in sleep deprivation, spontaneous pupillary behavior in darkness was recorded every 2 hours in 13 healthy subjects from 19:00 to 07:00 during forced wakefulness. On each occasion, comparative subjective sleepiness was assessed with a self-rating scale (Stanford Sleepiness Scale, SSS). The power of slow pupillary oscillations (< or = 0.8 Hz) increased significantly and so did the values of SSS, while basic pupil diameter decreased significantly. Slow pupillary oscillations and SSS did not correlate well in general but high values of pupil parameters were always associated with high values in subjective rating. Our results demonstrate a strong relationship between ongoing sleep deprivation and typical changes in the frequency profiles of spontaneous pupillary oscillations and the tendency to instability in pupil size in normals. These findings suggest that the results of pupil data analysis permit an objective measurement of sleepiness.

[Pupillography for objective vigilance assessment. Methodological problems and possible solutions]. / Pupillographie zur objektiven Vigilanzprüfung. Methodische Probleme und Lösungsansätze.

To measure vigilance disorders in healthy normals or in patients (narcolepsy, sleep apnea syndrome) is difficult, time-consuming and hardly objective with present methods. Recording and analysis of spontaneous pupillary behaviour in darkness by infrared video pupillography is an objective and time-saving method to measure daytime sleepiness. However, certain external conditions must be satisfied (avoid light, noise, stress) to get reliable results. Spontaneous pupillary oscillations are recorded in darkness over 10 min and data are analyzed by fast Fourier transformation, with additional calculation of the mean pupillary diameter for each time segment (approx. 1 min). While in the alert normal, pupil remains dilated during the measurement in darkness and oscillates with an amplitude below 0.3 mm and a frequency about 1 Hz, there are characteristic changes in fatigue: (1) low-frequency components dominate the spontaneous pupillary oscillations, with an amplitude reaching several millimeters, and (2) pupil diameter decreases with time. Infrared video pupillography could play a role as a screening method and therapy control for hypersonic patients (most frequent: sleep apnea syndrome) with excessive daytime sleepiness. An objective, time-saving method like infrared video pupillography would be useful in sleep medicine and psychiatry when testing the level of vigilance, and in psychology or industrial medicine as well, providing informations about acute vigilance problems in healthy normals.

Habit-specific locus of control scales for drinking, smoking, and eating.

The internal consistencies of three habit-specific locus of control scales measuring drinking, smoking, and eating behavior were evaluated using coefficient alpha. The three scales, along with Rotter's 1-E scale, were administered to 202 undergraduate students. Estimates indicated the scales showed reasonably high internal consistency. Scores on the smoking and drinking scales had the lowest correlations with scores on Rotter's generalized measure. Mean drinking scale scores were lower than those for smoking and eating, suggesting that people judge drinking to be under more personal control. The implications of habit-specific expectancies, particularly with regard to habit disorders, are discussed.

[Pupillography as an objective attention test]. / Pupillographie als objektiver Vigilanztest.

Infrared video pupillography (IVP) allows continuous recording of spontaneous pupillary oscillations in darkness which change characteristically with fatigue. Pupil size in darkness is age-related, has its maximum in the second decade and subsequently decreases during life time. Normally, the pupil oscillates in darkness with a frequency of about 1 Hz and amplitudes of less than 0.3 mm. Excessive daytime sleepiness causes instability of this pupillary behaviour which is constant in alert normals, and so called fatigue waves appear with an amplitude reaching several millimeters. The frequency profile is dominated by slow frequencies below 0.5 Hz, while average pupil size decreases continuously with time. As IVP is an objective and time-saving method it could become an important supplement to test procedures used in sleep medicine and sleep research to measure daytime sleepiness.