September 1999
Volume 40, Issue 10
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Physiology and Pharmacology  |   September 1999
Elevation of Human Intraocular Pressure at Night under Moderate Illumination
Author Affiliations
  • John H. K. Liu
    From the Departments of Ophthalmology and
  • Daniel F. Kripke
    Psychiatry, University of California, San Diego, La Jolla, California.
  • Rivak E. Hoffman
    From the Departments of Ophthalmology and
  • Michael D. Twa
    From the Departments of Ophthalmology and
  • Richard T. Loving
    Psychiatry, University of California, San Diego, La Jolla, California.
  • Katharine M. Rex
    Psychiatry, University of California, San Diego, La Jolla, California.
  • Brian L. Lee
    From the Departments of Ophthalmology and
  • Steven L. Mansberger
    From the Departments of Ophthalmology and
  • Robert N. Weinreb
    From the Departments of Ophthalmology and
Investigative Ophthalmology & Visual Science September 1999, Vol.40, 2439-2442. doi:
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      John H. K. Liu, Daniel F. Kripke, Rivak E. Hoffman, Michael D. Twa, Richard T. Loving, Katharine M. Rex, Brian L. Lee, Steven L. Mansberger, Robert N. Weinreb; Elevation of Human Intraocular Pressure at Night under Moderate Illumination. Invest. Ophthalmol. Vis. Sci. 1999;40(10):2439-2442.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

purpose. An endogenous elevation of intraocular pressure (IOP) occurs at night in healthy young adults. The authors studied whether or not this IOP elevation can be detected under moderate illumination.

methods. Twenty-five healthy volunteers, ages 18 to 25 years, were housed overnight in a sleep laboratory under a strictly controlled light–dark environment. Intraocular pressure was measured in the supine position every 2 hours, using a pneumatonometer. An 8-hour sleep period was assigned to each volunteer according to individual’s accustomed sleep cycle. In the early part of this assigned period, sleep was encouraged with room lights off. Researchers performed IOP measurements at two time points with the aid of night vision goggles. In the middle to the late part of the assigned period, lights were turned on twice for a 1-hour interval. The light intensity was the same as before the bedtime. At the ending of each light period, IOP was measured under illumination.

results. Average IOP was significantly higher in the assigned sleep period versus outside the period. The trough of mean IOP occurred just before the bedtime, and then IOP gradually increased and peaked at the end of the 8-hour assigned sleep period. The difference between the trough and peak IOP was 3.5 ± 0.7 mm Hg (mean ± SEM, n = 25). Within the assigned sleep period, the average IOP determined under illumination was significantly higher than the average IOP preceding the illumination.

conclusions. Elevation of IOP occurred during the assigned sleep period with two 1-hour light exposures of moderate intensity. Environmental light at night had no significant effect on the nocturnal IOP elevation in healthy young adults.

In a strictly controlled laboratory environment, a consistent elevation of intraocular pressure (IOP) occurred at night in healthy young adults. 1 An endogenous circadian (24-hour) oscillator drove part of the nocturnal IOP elevation. It is well known that environmental light is the primary synchronizer for various circadian rhythms. 2 Intermittent light exposures at night blocked the endogenous IOP elevation in laboratory rabbits. 3 Uncontrolled light exposure at night was noticed in many human IOP studies showing inconsistent nocturnal patterns, 4 suggesting that light could be a confounding factor. Is the endogenous elevation of human IOP at night detectable under moderate illumination? We collected overnight IOP data from a group of healthy young adults who received two 1-hour light exposures of moderate intensity at night. Changes in the nocturnal IOP were compared with previous results when no light exposure was applied. 1  
Methods
The study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board. Twenty-five paid volunteers (ages 18–25 years) were recruited mainly from employees and students of our university. Informed consents were obtained after explanation of the nature and possible consequences of the study. 
Experimental subjects were nonsmoking, healthy individuals with a mean age of 20.7 ± 2.2 years (mean ± SD). They were selected on the basis of having a regular daily sleep cycle close to 2300 to 0700. Myopes with greater than 4 diopters were excluded. There were 17 men and 8 women, including 17 white, 3 Asian or Pacific Islander, 3 Hispanic, 1 African American, and 1 Native American. Each subject had a complete ophthalmic examination demonstrating absence of any eye disease. None of them had a narrow iridocorneal angle under slit lamp examination. Daytime sitting IOP levels measured by the Goldmann tonometer were in the range of 11 to 18 mm Hg (14.8 ± 2.4 mm Hg, mean ± SD). 
Before the laboratory study, subjects were instructed to maintain a daily 8-hour accustomed sleep period (lights off) for 7 days to enhance circadian entrainment. Subjects wore a wrist device (Actillume; Ambulatory Monitoring Inc., Ardsley, NY) to monitor light exposure and physical activity. They were told to abstain from alcohol and caffeine for 3 days and not wear contact lenses for 24 hours. Subjects reported to the laboratory before 1700 and stayed indoors for the entire recording session. Light–dark conditions in each sleep room were strictly controlled. Light intensity (from cool-white fluorescent lights) was held constant at 500 to 1000 lux at eye level when standing. When subjects were in bed lying face-up, light intensity at eye level was at 1000 to 1500 lux in the vertical direction. Onset of darkness in each sleep room was adjusted according to the individual’s sleep cycle. The room was absolutely dark when lights were off. Times for IOP measurements were individualized accordingly. For presentation, clock times were normalized as if each subject had an assigned sleep period from 2300 to 0700. 
Intraocular pressure was measured every 2 hours in each eye using a pneumatonometer (model 30 Classic; Mentor O&O, Norwell, MA). The subjects were instructed to lie down in bed for 5 minutes before IOP measurement. One or two drops of 0.5% proparacaine were applied to the cornea as local anesthetic. A hard-copy record was produced for each IOP measurement. Before the assigned sleep period, measurements of IOP were taken at 1730, 1930, and 2130. Subjects continued their normal indoor activities. No naps were allowed. Food and water were always available. Meal times were not regulated. Room activities were continuously videotaped using infrared cameras. 
Subjects went to bed just before the scheduled lights-off at 2300. Sleep was encouraged. During the 8-hour assigned sleep period, IOP was measured at 2330, 0130, 0330, and 0530. For the first two IOP measurements, subjects were awakened, if necessary, and measurements were taken in near-total darkness. 1 Researchers were equipped with infrared night vision goggles (AN/PVS-7B Dark Invader; Meyers, Redmond, WA) to aid these measurements. Disturbance and subjects’ light exposure were kept to a minimum. One hour before the IOP measurements at 0330 and 0530, lights were turned on by the researchers from outside the room. Subjects were not deliberately awakened. Lighting was at the same intensity as before the bedtime. Subject’s sleep positions were not controlled. Researcher entered the room according to the scheduled times, and the IOP measurements were performed in a few minutes. Night vision goggles were not needed when lights were on. Lights were turned off after the IOP measurements, and the subjects were encouraged to sleep again. When the assigned sleep period ended at 0700, room lights were turned on and subjects were awakened, if necessary. Measurements of IOP were taken again at 0730, 0930, and 1130. Debriefing interviews were conducted to document how the subjects had slept at night. 
Values of IOP from both eyes were averaged, and these averages were used for data analyses. Means of the averages from the 25 subjects at each time point were calculated. Comparisons of IOP were made between different time points and various time blocks. P < 0.05 was regarded as statistically significant. 
Results
In their debriefing interviews, 15 of 25 subjects indicated that they had slept well, despite the on and off light conditions at night. Eight subjects said that they did not sleep well. The other 2 subjects stated that they slept well when the lights were off, but not with lights on. 
The average of all individual IOP data in the 8-hour assigned sleep period was 21.9 ± 0.5 mm Hg (mean ± SEM, n = 25). It was significantly higher (P < 0.001, paired t-test) than the average IOP in the light/wake period (20.4 ± 0.3 mm Hg), which contained 6 time points for the IOP measurement. The profile of the IOP change is presented in Figure 1 . Mean IOP showed a gradual change throughout the recording period, including the two 1-hour light exposures in the assigned sleep period. The trough of mean IOP appeared at 2130 (19.1 ± 0.3 mm Hg), and the peak of mean IOP appeared at 0530 (22.6 ± 0.6 mm Hg). The difference in IOP between the trough and peak was 3.5 ± 0.7 mm Hg (P < 0.001, paired t-test, n = 25). The mean IOP at 0330 was 22.4 ± 0.6 mm Hg, also significantly higher (P < 0.001) than the IOP mean at 2130. During the assigned sleep period with two 1-hour light exposures, IOP continued to increase. The average of IOP determined under illumination at 0330 and 0530 (22.5 ± 0.5 mm Hg) was significantly higher (P < 0.05) than the average of IOP determined under darkness at 2330 and 0130 (21.2 ± 0.6 mm Hg). After the 8-hour assigned sleep period, mean IOP decreased in the morning. 
The profile of IOP change was very similar to the profile previously seen in a group of young adults 1 who had received no light exposures (Fig. 1 , right). Student’s t-test showed no difference (P > 0.05) for the nocturnal IOP elevations (from the IOP at either 1730 or 2130) between these two groups at the 4 time points of IOP measurement in the assigned sleep period. The magnitudes of IOP elevation in the present study for the time periods of 2130 to 0530 and 2130 to 0330 were 8% and 12%, respectively, less than those without light exposures. 1 These small reductions were not statistically significant. Measures of IOP changes by time also showed no difference between the two groups of using the Mann–Whitney rank-sum test. 
Discussion
We observed an uninterrupted IOP elevation at night in this group of healthy young adults. In addition, measured under moderate illumination and without the aid of night vision goggles, we detected a significant IOP elevation toward the end of the 8-hour assigned sleep period. The elevation of IOP at night obviously was not related to pupillary dilation in the darkness, inasmuch as the elevation was detectable under illumination. The peak IOP elevation at night, at 6.5 hours into the accustomed sleep period, could not be blocked by two periods of moderate light exposures. The magnitude of IOP elevation was slightly less (not statistically significant) than the magnitude observed in our previous study. 1 This difference may be due to a minor effect of light exposure and/or individual variations in the nocturnal IOP pattern. 
It has been suggested 5 that a few minutes after nighttime arousal, the nocturnal IOP elevation may not be detectable. In the present study, the endogenous IOP elevation at night was not short-lived and remained for at least a few minutes under moderate illumination when volunteers were awakened for tonometry. It seems that a large portion of the endogenous IOP elevation at night was readily detectable if other experimental conditions, including the circadian entrainment, were well controlled. 
During the two 1-hour light exposures, some light (up to 14.5% in the red wavelength) would pass through the closed eyelids. 6 Because of subjects’ variable sleep positions, however, the amounts of light reaching the retinas were difficult to estimate. Videotape recording showed that many subjects had adjusted their lying down positions, such as turning their heads to the side, which would lessen light exposure. Therefore, the light intensity received by the retina might have been insufficient to affect the body’s circadian pacemaker significantly. 7  
A 2-hour light exposure of 2500 lux (measured outside the eyelid) during the early sleep period significantly lowered the nocturnal IOP elevation. 8 However, exposure to the same light intensity during an entire night’s sleep did not affect the nocturnal slowdown of aqueous humor flow. 9 The present study suggests that a person, sleeping under lights at night, may adjust the body position to lessen the light exposure, thereby maintaining homeostasis in ocular physiology. 
With currently available techniques, it is impossible to measure the steady state IOP in an asleep human while the eyelids are closed. Because of this limitation, we conclude that an awakened young adult at night, while lying in bed, is very likely to have a higher IOP than during daytime hours. This nocturnal IOP elevation can be detected under moderate illumination. 
Figure 1.
 
Elevations of intraocular pressure (IOP) in two groups of healthy young adults housed under different light conditions at night. Left: the present study of 25 subjects with an 8-hour assigned sleep period (2300–0700), including two 1-hour light exposures. Black bars on top of the panel represent the periods of darkness. Intraocular pressure was measured in the supine position using a pneumatonometer. Open circles represent individual IOP data; solid circles represent the means at various time points. Right: a comparable study of 21 subjects received no light exposure at night. 1
Figure 1.
 
Elevations of intraocular pressure (IOP) in two groups of healthy young adults housed under different light conditions at night. Left: the present study of 25 subjects with an 8-hour assigned sleep period (2300–0700), including two 1-hour light exposures. Black bars on top of the panel represent the periods of darkness. Intraocular pressure was measured in the supine position using a pneumatonometer. Open circles represent individual IOP data; solid circles represent the means at various time points. Right: a comparable study of 21 subjects received no light exposure at night. 1
 
The authors thank Richard F. Brubaker for his valuable advice. 
Liu JHK, Kripke DF, Hoffman RE, et al. Nocturnal elevation of intraocular pressure in young adults. Invest Ophthalmol Vis Sci. 1998;39:2707–2712. [PubMed]
Czeisler CA. The effect of light on the human circadian pacemaker. Chadwick DJ Ackrill K eds. Circadian Clocks and Their Adjustment. 1995;254–302. John Wiley & Sons Ciba Foundation Symposium 183. New York.
Lee TC, Kiuchi Y, Gregory DS. Light exposure decreases IOP in rabbits during the night. Curr Eye Res. 1995;14:443–448. [CrossRef] [PubMed]
Liu JHK. Circadian rhythm of intraocular pressure. J Glaucoma. 1998;7:141–147. [PubMed]
Brown B. Diurnal variation of IOP [letter]. Ophthalmology. 1991;98:1485–1486. [PubMed]
Robinson J, Bayliss SC, Fielder AR. Transmission of light across the adult and neonatal eyelid in vivo. Vision Res. 1991;31:1837–1840. [CrossRef] [PubMed]
McIntyre IM, Norman TR, Burrows GD, Armstrong SM. Human melatonin suppression by light is intensity dependent. J Pineal Res. 1989;6:149–156. [CrossRef] [PubMed]
Wildsoet C, Eyeson-Annan M, Brown B, Swann PG, Fletcher T. Investigation of parameters influencing intraocular pressure increases during sleep. Ophthal Physiol Opt. 1993;13:357–365. [CrossRef]
Koskela T, Brubaker RF. The nocturnal suppression of aqueous humor flow in humans is not blocked by bright light. Invest Ophthalmol Vis Sci. 1991;32:2504–2506. [PubMed]
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