John H.K. Liu

Circadian rhythm of intraocular pressure.

Although it is well known that intraocular pressure (IOP) in humans varies throughout day and night, no consistent circadian pattern has been established. In laboratory rabbits, however, a consistent circadian rhythm of IOP has been confirmed and further characterized in recent years. The current knowledge about the nocturnal IOP elevation in rabbits is reviewed and the implications for the study of human circadian IOP pattern is discussed.

Laboratory assessment of diurnal and nocturnal ocular perfusion pressures in humans

We estimated diurnal and nocturnal levels of ocular perfusion pressure at rest in both young and older adults in a clinical sleep laboratory. Measurements of blood pressure and intraocular pressure (IOP) were obtained every 2 hours for 24 consecutive hours in 16 healthy young adults (ages 18-25 years) and 16 older adults (ages 47-74 years). In the 16-hour diurnal wake period, blood pressure and IOP were measured after a 5-minute sitting rest. In the 8-hour nocturnal period, measurements were taken with subjects in the supine position. Sitting and supine ocular perfusion pressures in the diurnal and nocturnal periods were calculated respectively based upon the blood pressure and IOP. Ocular perfusion pressure was found to be higher in the older group than in the younger group throughout the 24 hours. The peak of ocular perfusion pressure was in the nocturnal period for both groups. Within each subject group, the average nocturnal ocular perfusion pressure in the supine position was higher than the average diurnal ocular perfusion pressure in the sitting position. The diurnal-to-nocturnal increase of ocular perfusion pressure was larger in the older group than in the younger group.

Intraocular pressure measurements throughout the 24 h.

Purpose of review This review summarizes the relationship of 24 h intraocular pressure (IOP) on the management of glaucoma. Recent findings The 24 h IOP pattern demonstrates nocturnal elevation in the majority of individuals. Prostaglandin analogs and carbonic anhydrase inhibitors lower both diurnal and nocturnal IOPs. Timolol monotherapy and timolol add-on treatment to a prostaglandin analog does not lower IOP during the nocturnal period. Laser trabeculoplasty can reduce nocturnal IOP elevation in medically treated glaucoma patients, even in those without significant reduction of diurnal IOP. Though both IOP and central corneal thickness display a 24 h rhythm with peaks during the nocturnal period, there is no correlation between central corneal thickness and 24 h IOP variation in normals and glaucoma patients. Corneal biomechanical properties (corneal hysteresis and corneal resistance factor) remain relatively stable during the 24 h period and are not associated with 24 h IOP fluctuation. Summary Antiglaucoma therapies differ in their ability to lower IOP throughout the 24 h day. The 24 h IOP pattern is independent of central corneal thickness, corneal hysteresis and corneal resistance factor.

Effects of aging on 24-hour intraocular pressure measurements in sitting and supine body positions.

PURPOSE To evaluate how aging alters 24-hour measurements of intraocular pressure (IOP) in the sitting and supine body positions. METHODS Fifteen older volunteers with healthy eyes (ages, 53-71 years) were each housed for 1 day in a sleep laboratory. An 8-hour accustomed sleep period was assigned to each subject. Every 2 hours, measurements of IOP were taken in the sitting and supine positions. Sitting and supine patterns of 24-hour IOP were compared. Simulated 24-hour IOP rhythms in the same body position were determined using cosine fitting of individual 24-hour data. The average postural IOP effects during the diurnal/wake period and the nocturnal/sleep period were compared. Data from this group of older subjects were compared with previously collected data from 16 healthy younger subjects (ages, 18-25 years) under the same experimental conditions. RESULTS Within each age group, sitting and supine patterns of 24-hour IOP were similar and parallel. Compared to the younger subjects, the phase timing (simulated peak) of 24-hour IOP was significantly delayed for the older subjects in both body positions. The postural IOP effect for the older subjects was 4.7 ± 0.8 and 4.8 ± 0.8 mm Hg during the diurnal and nocturnal periods, respectively. These postural IOP effects were not significantly different from the postural effects in the younger subjects. CONCLUSIONS Although aging can significantly delay the phase timing of the 24-hour IOP pattern toward the diurnal/awake period, it may not affect the postural IOP effect during the diurnal and the nocturnal periods.

Diurnal and nocturnal effects of brimonidine monotherapy on intraocular pressure.

PURPOSE To investigate the effect of brimonidine monotherapy on intraocular pressure (IOP) during the nocturnal/sleep period. DESIGN Prospective, open-label experimental study. PARTICIPANTS Fifteen patients with newly diagnosed open-angle glaucoma or ocular hypertension (ages, 46-72 years). METHODS Baseline data of 24-hour IOP in untreated patients were collected in a sleep laboratory. Measurements of IOP were taken using a pneumatonometer every 2 hours in the sitting and supine body positions during the 16-hour diurnal/wake period and in the supine position during the 8-hour nocturnal/sleep period. Patients were treated afterward with 0.1% brimonidine 3 times per day for 4 weeks, and 24-hour IOP data were collected under the same laboratory conditions. MAIN OUTCOME MEASURES Diurnal and nocturnal IOP means under the brimonidine treatment were compared with the baseline. RESULTS The diurnal IOP mean was significantly lower under the brimonidine treatment than the baseline IOP in both the sitting and supine positions. There was no statistically significant change in IOP under the brimonidine treatment from the baseline during the nocturnal period. CONCLUSIONS Although 0.1% brimonidine monotherapy significantly lowered IOP during the diurnal/wake period, it did not significantly lower IOP during the nocturnal/sleep period. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Comparing Diurnal and Nocturnal Effects of Brinzolamide and Timolol on Intraocular Pressure in Patients Receiving Latanoprost Monotherapy

PURPOSE To compare the diurnal and nocturnal effects of brinzolamide and timolol on intraocular pressure (IOP) in patients already receiving monotherapy with latanoprost. DESIGN Prospective, open-label, and crossover clinical trial. PARTICIPANTS Twenty-six patients with glaucoma or ocular hypertension (ages, 44-79 years) who were receiving treatment with 0.005% latanoprost once every evening. METHODS Baseline data of 24-hour IOP were collected in a sleep laboratory while patients were receiving latanoprost monotherapy. Measurements were taken every 2 hours in the sitting and supine positions during the 16-hour diurnal/wake period and in a supine position during the 8-hour nocturnal/sleep period. Patients were randomly assigned to receive an add-on treatment with either 1% brinzolamide 3 times per day or 0.5% timolol gel forming solution once every morning for 8 weeks, and then crossed over to receive the other add-on treatment. At the end of each add-on treatment period, 24-hour IOP data were collected. MAIN OUTCOME MEASURES Diurnal and nocturnal IOP means were compared among the baseline, the brinzolamide add-on treatment, and the timolol add-on treatment. RESULTS During the diurnal period, the mean IOP under brinzolamide or timolol add-on treatment was significantly lower than the baseline IOP in both the sitting and supine positions. There was no statistical difference between the 2 add-on treatments. During the nocturnal period, the supine IOP under brinzolamide add-on treatment was significantly lower than both the baseline and the timolol add-on treatment. There was no difference in nocturnal IOP between the timolol add-on treatment and the baseline. CONCLUSIONS In patients already receiving the latanoprost monotherapy, adding brinzolamide or timolol significantly reduced IOP during the diurnal period. However, only the brinzolamide add-on treatment had an IOP-lowering efficacy during the nocturnal period.

Monitoring intraocular pressure for 24 h

High intraocular pressure (IOP) is a leading risk factor for glaucoma, and lowering IOP continues to be the only evidence-based treatment for preventing the development of glaucoma or reducing the rate of its progression. There are considerable data showing that the IOP peaks of many glaucoma patients appear outside the usual office hours.1 2 As peak IOP is related to glaucoma progression,3 this suggests that clinicians should take IOP measurements outside office hours into account when planning and prescribing glaucoma treatment. Based on data collected in our sleep laboratory at the University of California, San Diego, the average supine IOP during the nocturnal/sleep period has been found to be significantly higher than the average sitting IOP during the diurnal/wake period in untreated glaucoma patients.4 Our studies compared supine IOP during the nocturnal/sleep period with sitting IOP during the diurnal/wake period to mimic the habitual body positions during the course of our daily activities. Approximately two-thirds of …

Analysis of Continuous 24-Hour Intraocular Pressure Patterns in Glaucoma

PURPOSE To present a method to analyze circadian intraocular pressure (IOP) patterns in glaucoma patients and suspects undergoing repeated continuous 24-hour IOP monitoring. METHODS Forty patients with established (n = 19) or suspected glaucoma (n = 21) underwent ambulatory 24-hour IOP monitoring on two sessions 1 week apart using a contact lens sensor (CLS). The CLS provides its output in arbitrary units (a.u.). A modified cosinor rhythmometry method was adapted to the CLS output to analyze 24-hour IOP patterns and their reproducibility. Nonparametric tests were used to study differences between sessions 1 and 2 (S1 and S2). Patients pursued their routine daily activities and their sleep was uncontrolled. CLS data were used to assess sleep times. RESULTS Complete 24-hour data from both sessions were available for 35 patients. Mean (SD) age of the patients was 55.8 ± 15.5 years. The correlation of the cosinor fitting and measured CLS values was r = 0.38 (Spearman r; P < 0.001) for S1, r = 0.50 (P < 0.001) for S2, whereas the correlation between S1 and S2 cosinor fittings was r = 0.76 (P < 0.001). Repeated nocturnal acrophase was seen in 62.9% of patients; 17.1% of patients had no repeatable acrophase. The average amplitude of the 24-hour curve was 143.6 ± 108.1 a.u. (S1) and 130.8 ± 68.2 a.u. (S2) (P = 0.936). CONCLUSIONS Adapting the cosinor method to CLS data is a useful way for modeling the rhythmic nature of 24-hour IOP patterns and evaluating their reproducibility. Repeatable nocturnal acrophase was seen in 62.9% of patients. (ClinicalTrials.gov number, NCT01319617.).

Increased 24-Hour Variation of Human Intraocular Pressure with Short Axial Length

PURPOSE To characterize 24-hour variation of intraocular pressure (IOP) in healthy young adults based on the axial length of the eye. METHODS Twenty-four-hour IOP data were collected from nine healthy young adults with hyperopia, age range 18 to 25 years, in a sleep laboratory. Every 2 hours, measurements of IOP were taken in the participants after 5 minutes in the supine position and 5 minutes in the sitting position during the 16-hour diurnal/wake period as well when supine in bed during the 8-hour nocturnal/sleep period. Variations in 24-hour IOP in this hyperopia group were analyzed, together with previously collected data under the same laboratory conditions from 32 age-matched subjects with emmetropia or mild myopia (emmetropia group) and 34 subjects with moderate to severe myopia (myopia group). RESULTS Average diurnal sitting IOP was lower in the hyperopia group than in the other two groups. The difference between the diurnal sitting and diurnal supine IOP was larger in the hyperopia group than in the myopia group. In all three groups, the nocturnal supine IOP was higher than the diurnal sitting IOP. This elevation in habitual IOP was most significant in the hyperopia group. The hyperopia group also presented a significant IOP elevation within the nocturnal period. Simulated 24-hour rhythms of supine IOP were detected in all groups with different phase timings, but simulated 24-hour IOP variations were not different. The 24-hour habitual IOP fluctuation (peak minus trough) was inversely correlated to axial length. CONCLUSIONS Shorter eyes had a larger 24-hour IOP variation than longer eyes in healthy young adults.

Intraocular and intracranial pressures during head-down tilt with lower body negative pressure.

BACKGROUND Seven astronauts after 6-mo missions to the International Space Station showed unexpected vision problems. Lumbar punctures performed in the four astronauts with optic disc edema showed moderate elevations of cerebral spinal fluid pressure after returning to Earth. We hypothesized that lower body negative pressure (LBNP) imposed during head-down tilt (HDT) would reduce intraocular pressure (IOP) and transcranial ultrasound pulse amplitude, a noninvasive intracranial pressure (ICP) surrogate. METHODS Participating in this study were 25 normal healthy nonsmoking volunteers (mean age: 36 yr). Subjects were positioned supine (5 min), sitting (5 min), 15° whole body HDT (5 min), and 10 min of HDT with LBNP (25 mmHg). The order of HDT and HDT+LBNP tests was balanced. Right and left IOP, transcranial ultrasound pulse amplitude, arm blood pressure, and heart rate were measured during the last minute (steady state) of each testing condition. RESULTS IOP significantly decreased from supine to sitting posture by 3.2 ± 1.4 mmHg (mean ± SD: N = 25), and increased by 0.9 ± 1.3 mmHg from supine to the HDT position. LBNP during HDT significantly lowered IOP to supine levels. In addition, LBNP significantly reduced transcranial ultrasound pulse amplitudes by 38% as compared to the HDT condition (N = 9). Sitting mean blood pressure (BP) was significantly higher (+5 mmHg) than BP values after 10 min of LBNP during HDT. However, heart rate was not significantly different across all conditions. DISCUSSION These data suggest that short duration exposures to LBNP attenuate HDT-induced increases in IOP and ICP. Macias BR, Liu JHK, Grande-Gutierrez N, Hargens AR. Intraocular and intracranial pressures during head-down tilt with lower body negative pressure.