Holger Lüdtke

Mathematical procedures in data recording and processing of pupillary fatigue waves

Spontaneous pupillary behaviour in darkness provides information about a subjects 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 pupils 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.

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 ≤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.

Pupillographic sleepiness testing in hypersomniacs and normals

Abstract · 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.

How do spontaneous pupillary oscillations in light relate to light intensity

Characteristics of light-induced pupillary oscillations at constant light intensities have been investigated sparsely compared to sleepiness-related pupillary oscillations in darkness. This study presents the first controlled analysis of light-induced pupillary oscillations and their relationship to illumination. Pupillary oscillations of alert subjects were recorded by infrared video pupillography in different background lighting. Although showing obvious relationships of mean frequency and amplitude to light intensity, there were considerable inter- and intra-individual differences in the appearance of light-induced oscillations. As they looked rather similar to sleepiness waves, the question remains to identify light-induced oscillations in day light and to differentiate them from sleepiness-related oscillations.

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.

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

Abstract · 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.

The prevalence of relative afferent pupillary defects in normal subjects.

Background: Observational and pupillographic studies of small numbers of normal subjects have shown that a small (<0.3 log units) relative afferent pupil defect (RAPD) is present in a minority. We have extended the investigation of the prevalence of RAPD to a larger number of normal subjects. Methods: A total of 102 subjects were examined by observation and pupillography. The swinging flashlight test was performed using neutral density filters for quantification. During the pupillographic procedure, light-emitting diodes were placed in front of each eye, alternately flashing for 2.5 seconds with a 0.5 second break. A binocular real-time pupillometer recorded the direct and consensual pupillary responses. After artefact detection and removal, the amplitudes of pupillary response were determined and plotted against stimulus intensity. The means of the direct and the consensual responses were used for automated calculation of RAPD. Results: By observation, there was no RAPD in 87 (85%) subjects; there was an RAPD of 0.15 log units in 13 (13%), and an RAPD of 0.3 log units in 2 (2%). By pupillography, there was an RAPD of 0.07 log units in 53 (52%) subjects, an RAPD between 0.08 and 0.22 log units in 43 (42%) subjects, and an RAPD between 0.23 and 0.39 log units in 6 (6%) subjects. Conclusions: Observation and pupillographic measurements of the swinging light test in a large normal subject cohort has confirmed that an RAPD is present in a small minority but that it does not exceed 0.39 log units. The RAPD in these subjects may be explained by inaccuracy of measurement or by asymmetries in the connections between visual pathways and pretectal nuclei in the midbrain.

The effect of caffeine on spontaneous pupillary oscillations

Caffeine stimulates the central nervous system, but the duration and extent of its influence on the pupil are not known. The aim of this study was to determine whether caffeine could have an effect on pupillary sleepiness waves, measured with the Pupillographic Sleepiness Test (PST) during routine clinical PST testing, where the caffeine dose‐response of a participant cannot be registered before recording.

Short-Term Reproducibility and Variability of the Pupillographic Sleepiness Test

The pupillographic sleepiness test (PST) measures the amplitude of the fluctuations of pupil size in the dark, which reflects the level of central nervous system activation and thus alertness. The aim of this study was to assess the short‐term reproducibility and variability of the results obtained with the PST in normal healthy subjects.