Analysis of continuous 24-hour intraocular pressure patterns in glaucoma.
ABSTRACT: To present a method to analyze circadian intraocular pressure (IOP) patterns in glaucoma patients and suspects undergoing repeated continuous 24-hour IOP monitoring.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.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).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.).
Project description:BACKGROUND:The aim of this article was to study the circadian intraocular pressure (IOP)-related effects of ocular hypotensive medications using a contact lens sensor (CLS). DESIGN:This is a university-based prospective, randomized, crossover trial. PARTICIPANTS:A total of 23 patients with primary open-angle glaucoma participated. METHODS:Patients underwent ambulatory recording of IOP-related patterns for 24 h in one eye during 3 monthly sessions using a CLS. Patients were untreated in session 1 (S1), were randomized to one of four classes of glaucoma drops for S2 and had a prostaglandin analogue add-on for S3. MAIN OUTCOME MEASURES:Changes in IOP-related patterns were defined using (i) slopes from wake/sitting to sleep/supine; (ii) cosinor rhythmometry modelling; and (iii) area under receiver operating curve (AUC) of sleep period. RESULTS:Mean patient age was 63.8 ± 11.8 years. Positive linear slopes were seen from wake/sitting to sleep/supine at S1 (17.1 ± 14.2 mVeq/h) and S2 (5.5 ± 23.9 mVeq/h) and negative slopes at S3 (-1.9 ± 29.4 mVeq/h) (S1-S2, P = 0.01; S1-S3, P = 0.02). In the prostaglandin group, slopes changed significantly with introduction of drops (S1-S2, P < 0.024), whereas they did not in a mixed group combining the three other classes (S1-S2, P = 0.060). Overall, cosinor amplitudes were 98.4 ± 46.5 mVeq (S1), 113.0 ± 35.6 mVeq (S2) and 109.6 ± 58.3 mVeq (S3) (S1-S2, P = 0.23; S1-S3, P = 0.66; S2-S3, P = 0.93). AUC were 91.8 ± 63.0 mVeq (S1), 76.3 ± 102.7 mVeq (S2) and 19.9 ± 135.8 mVeq (S3). Differences between sessions were not statistically significant (S1-S2, P = 0.541; S1-S3, P = 0.083; S2-S3, P = 0.092). CONCLUSIONS:Prostaglandin analogues, but not other medications, seem to flatten the IOP-related increase at transition of the wake/sitting to the sleep/supine period, but do not seem to have an effect on acrophase and amplitude.
Project description:To compare estimates of 24-hour intraocular pressure (IOP) peak timing and variation obtained using a contact lens sensor (CLS) and using a pneumatonometer.Laboratory data collected from 30 healthy volunteers (ages, 20-66 years) in a randomized, controlled clinical trial were analyzed. Participants were housed for 24 hours in a sleep laboratory. One randomly selected right or left eye was fitted with a CLS that monitored circumferential curvature in the corneoscleral region related to the change of IOP. Electronic output signals of 30 seconds were averaged and recorded every 5 minutes. In the contralateral eye, habitual IOP measurements were taken using a pneumatonometer once every two hours. Simulated 24-hour rhythms in both eyes were determined by cosinor fitting. Simulated peak timings (acrophases) and simulated data variations (amplitudes) were compared between the paired eyes.Bilateral change patterns of average 24-hour data for the group were in parallel. The simulated peak timing in the CLS fitted eye occurred at 4:44 AM ± 210 min (mean ± SD) and the IOP peak timing in the contralateral eye at 4:11 AM ± 120 min (P=0.256, Wilcoxon signed-rank test). There was no significant correlation between the simulated data variations in the paired eyes (P=0.820, linear regression).The 24-hour CLS data showed a simulated peak timing close to the 24-hour IOP peak timing obtained using the pneumatonometer. However, the simulated variations of 24-hour data in the paired eyes were not correlated. Estimated 24-hour IOP rhythms using the two devices should not be considered interchangeable.
Project description:To characterize the 24-h habitual-position intraocular pressure (IOP) patterns of optic disc phenotypes (ODPs) in untreated normal-tension glaucoma (NTG) and the relationships between nocturnal IOP elevation and various clinical factors.Prospective, cross-sectional, observational study.Eighty-two NTG patients with focal ischemic (FI) ODP and 82 age- and disease severity-matched NTG patients with myopic glaucomatous (MG) ODP were recruited prospectively over 3 years. The IOP was recorded 11 times over a 24-hour (h) period by a single ophthalmologist using a hand-held tonometer (TonoPen®XL). A cosinor model was used to describe the 24-h IOP rhythm. Associations between nocturnal IOP elevation and both ocular and demographic variables were evaluated using the generalized estimating equation (GEE).Mean habitual-position IOP was significantly higher during nighttime than daytime in the FI group (16.44 vs. 14.23 mmHg, P < 0.001), but not in the MG group (15.91 vs. 15.70 mmHg, P = 0.82). The FI group also exhibited a significantly higher peak IOP during sleeping hours (P = 0.01) and lower trough IOP during the 24-h period than the MG group (P < 0.01). The MG group showed a significantly higher peak IOP during waking hours than the FI group (P < 0.01). Therefore, 24-h IOP fluctuation range was significantly higher in the FI group than the MG group (P = 0.013). In the FI group, peak habitual-position IOP and the highest frequency of IOP peaks occurred during sleeping hours (12 AM-6 AM). By contrast, IOP peaks in the MG group occurred during morning hours (8 AM-12 PM). The FI group showed an overall nocturnal acrophase in habitual-position IOP, with 45 patients (54.9%) having a nocturnal acrophase; 10 (12.2%), a diurnal acrophase; and 27 (32.9%), no evident acrophase. By contrast, the MG group showed no evident peak in habitual-position IOP, with 9 patients (10.9%) having a nocturnal acrophase; 43 (52.4%), a diurnal acrophase; and 30 (36.6%), no evident acrophase. In multivariate modeling using the GEE, ODP (P < 0.001) and spherical equivalent (SE, P = 0.001) were independently associated with nocturnal IOP elevation.Based on 24-h habitual-position IOP data, FI is associated with significant nocturnal IOP elevation, while no such nocturnal IOP elevation is observed in MG ODP. In untreated NTG, there are also significant differences in the 24-h IOP pattern between FI and MG ODPs.
Project description:PURPOSE:To analyse nocturnal intraocular pressure (IOP) fluctuations in patients with obstructive sleep apnea syndrome (OSAS) using a contact lens sensor (CLS) and to identify associations between the OSAS parameters determined by polysomnographic study (PSG) and IOP changes. METHOD:Prospective, observational study. Twenty participants suspected of having OSAS were recruited. During PSG study, IOP was monitored using a CLS placed in the eye of the patient. The patients were classified according to the apnea-hypopnea index (AHI) in two categories, severe (>30) or mild/moderate (<30) OSAS. We evaluated several parameters determined by the IOP curves, including nocturnal elevations (acrophase) and plateau times in acrophase (PTs) defined by mathematical and visual methods. RESULTS:The IOP curves exhibited a nocturnal acrophase followed by PTs of varying extents at which the IOP remained higher than daytime measurement with small variations. We found significant differences in the length of the PTs in patients with severe OSAS compared to those with mild/moderate disease (P = 0.032/P = 0.028). We found a positive correlation between PTs and OSAS severity measured by the total number of apneic events (r = 0.681/0.751 P = 0.004/0.001) and AHI (r = 0.674/0.710, P = 0.004/0.002). Respiratory-related arousal and oxygen saturation also were associated significantly with the IOP PT length. CONCLUSIONS:Periods of nocturnal IOP elevation lasted longer in severe OSAS patients than those with mild/moderate OSAS and correlate with the severity of the disease. The length of the nocturnal PT is also associated to respiratory parameters altered in patients with OSAS.
Project description:Twenty-four-hour intraocular pressure (IOP) patterns may provide more information regarding rates of visual field progression than office-hour measurements. However, little is known about the added value of 24-hour monitoring when stratifying glaucoma risk based on rates of progression.To test the hypothesis that 24-hour IOP-related patterns recorded with a contact lens sensor (CLS) correlate with prior rates of visual field progression.A multicenter, retrospective cohort study was conducted at 50 ophthalmology care centers in 13 countries. Participants included 445 patients (445 eyes) with treated, manifest open-angle glaucoma. The study was conducted from November 8, 1999, to September 17, 2016.Twenty-four-hour recordings of IOP-related patterns were prospectively collected with a CLS system. Retrospective visual field data of patients who underwent at least 3 prior reliable visual field tests were examined.Association between CLS variables and rates of visual field mean deviation (MD) change.Of the 445 patients included, 238 (53.5%) were women and 394 (88.5%) were white. The mean (SD) age and MD values at the time of CLS recording were 68.9 (11.2) years and -9.0 (7.0) dB. The mean rate of MD change was -0.46 (0.5) dB/y in 5.2 (3) years of follow-up. After adjusting for baseline MD severity, age, and treatment, the following CLS variables were associated with fast visual field progression: mean peak ratio while awake (β = -0.021; 95% CI, -0.04 to -0.003), number of long peaks during sleep (β = 0.036; 95% CI, 0.005 to 0.067), night bursts ocular pulse frequency SD (β = 0.027; 95% CI, 0.004 to 0.051), and night bursts ocular pulse amplitude SD (β = 19.739; 95% CI, 1.333 to 38.145). Regression models including CLS variables had better fit than Goldmann IOP when testing the association with rates of progression.Results of this study indicate that 24-hour CLS recordings may be associated with prior rates of visual field progression of glaucoma. This association appears to be better than Goldmann mean IOP measured multiple times during office hours. Therefore, the CLS may be useful to assess the risk of future functional loss, even in situations when insufficient historical visual field information is available.
Project description:To study performance of a contact lens sensor (CLS) for 24-hour monitoring of IOP-related short-term patterns and compare with IOP obtained by pneumatonometry.Prospective clinical trial. Thirty-one healthy volunteers and 2 glaucoma patients were housed for 24 hours in a sleep laboratory. One randomly selected eye was fitted with a CLS (Triggerfish, Sensimed, Switzerland), which measures changes in ocular circumference. In the contralateral eye, IOP measurements were taken using a pneumatonometer every two hours with subjects in the habitual body positions. Heart rate (HR) was measured 3 times during the night for periods of 6 minutes separated by 2 hours. Performance of CLS was defined in two ways: 1) recording the known pattern of IOP increase going from awake (sitting position) to sleep (recumbent), defined as the wake/sleep (W/S) slope and 2) accuracy of the ocular pulse frequency (OPF) concurrent to that of the HR interval. Strength of association between overall CLS and pneumatonometer curves was assessed using coefficients of determination (R2).The W/S slope was statistically significantly positive in both eyes of each subject (CLS, 57.0 ± 40.5 mVeq/h, p<0.001 and 1.6 ± 0.9 mmHg/h, p<0.05 in the contralateral eye). In all, 87 CLS plots concurrent to the HR interval were evaluated. Graders agreed on evaluability for OPF in 83.9% of CLS plots. Accuracy of the CLS to detect the OPF was 86.5%. Coefficient of correlation between CLS and pneumatonometer for the mean 24-h curve was R2 = 0.914.CLS measurements compare well to the pneumatonometer and may be of practical use for detection of sleep-induced IOP changes. The CLS also is able to detect ocular pulsations with good accuracy in a majority of eyes.ClinicalTrials.gov NCT01390779.
Project description:To detect and quantify eye blinks during 24-hour intraocular pressure (IOP) monitoring with a contact lens sensor (CLS).A total of 249 recordings of 24-hour IOP patterns from 202 participants using a CLS were included. Software was developed to automatically detect eye blinks, and wake and sleep periods. The blink detection method was based on detection of CLS signal peaks greater than a threshold proportional to the signal amplitude. Three methods for automated detection of the sleep and wake periods were evaluated. These relied on blink detection and subsequent comparison of the local signal amplitude with a threshold proportional to the mean signal amplitude. These methods were compared to manual sleep/wake verification. In a pilot, simultaneous video recording of 10 subjects was performed to compare the software to observer-measured blink rates.Mean (SD) age of participants was 57.4 ± 16.5 years (males, 49.5%). There was excellent agreement between software-detected number of blinks and visually measured blinks for both observers (intraclass correlation coefficient [ICC], 0.97 for observer 1; ICC, 0.98 for observer 2). The CLS measured a mean blink frequency of 29.8 ± 15.4 blinks/min, a blink duration of 0.26 ± 0.21 seconds and an interblink interval of 1.91 ± 2.03 seconds. The best method for identifying sleep periods had an accuracy of 95.2 ± 0.5%.Automated analysis of CLS 24-hour IOP recordings can accurately quantify eye blinks, and identify sleep and wake periods.This study sheds new light on the potential importance of eye blinks in glaucoma and may contribute to improved understanding of circadian IOP characteristics.
Project description:BACKGROUNDCircadian timing of treatments can largely improve tolerability and efficacy in patients. Thus, drug metabolism and cell cycle are controlled by molecular clocks in each cell and coordinated by the core body temperature 24-hour rhythm, which is generated by the hypothalamic pacemaker. Individual circadian phase is currently estimated with questionnaire-based chronotype, center-of-rest time, dim light melatonin onset (DLMO), or timing of core body temperature (CBT) maximum (acrophase) or minimum (bathyphase).METHODSWe aimed at circadian phase determination and readout during daily routines in volunteers stratified by sex and age. We measured (a) chronotype, (b) every minute (q1min) CBT using 2 electronic pills swallowed 24 hours apart, (c) DLMO through hourly salivary samples from 1800 hours to bedtime, and (d) q1min accelerations and surface temperature at anterior chest level for 7 days, using a teletransmitting sensor. Circadian phases were computed using cosinor and hidden Markov modeling. Multivariate regression identified the combination of biomarkers that best predicted core temperature circadian bathyphase.RESULTSAmong the 33 participants, individual circadian phases were spread over 5 hours, 10 minutes (DLMO); 7 hours (CBT bathyphase); and 9 hours, 10 minutes (surface temperature acrophase). CBT bathyphase was accurately predicted, i.e., with an error less than 1 hour for 78.8% of the subjects, using a new digital health algorithm (INTime), combining time-invariant sex and chronotype score with computed center-of-rest time and surface temperature bathyphase (adjusted R2 = 0.637).CONCLUSIONINTime provided a continuous and reliable circadian phase estimate in real time. This model helps integrate circadian clocks into precision medicine and will enable treatment timing personalization following further validation.FUNDINGMedical Research Council, United Kingdom; AP-HP Foundation; and INSERM.
Project description:Study Objectives:To examine associations between 24-hour rest-activity patterns and body mass index (BMI) among community-dwelling US adults. Rest-activity patterns provide a field method to study exposures related to circadian rhythms. Methods:Adults (N = 578) wore an actigraph on their nondominant wrist for 7 days. Intradaily variability and interdaily stability (IS), M10 (most active 10-hours), L5 (least active 5-hours), and relative amplitude (RA) were derived using nonparametric rhythm analysis. Mesor, acrophase, and amplitude were calculated from log-transformed count data using the parametric cosinor approach. Results:Participants were 80% female and mean (standard deviation) age was 52 (15) years. Participants with higher BMI had lower values for magnitude, RA, IS, total sleep time (TST), and sleep efficiency. In multivariable analyses, less robust 24-hour rest-activity patterns as represented by lower RA were consistently associated with higher BMI: comparing the bottom quintile (least robust) to the top quintile (most robust 24-hour rest-activity pattern) of RA, BMI was 3-kg/m2 higher (p = .02). Associations were similar in magnitude to an hour less of TST (1-kg/m2 higher BMI) or a 10% decrease in sleep efficiency (2-kg/m2 higher BMI), and independent of age, sex, race, education, and the duration of rest and/or activity. Conclusions:Lower RA, reflecting both higher night activity and lower daytime activity, was associated with higher BMI. Independent of the duration of rest or activity during the day or night, 24-hour rest, and activity patterns from actigraphy provide aggregated measures of activity that associate with BMI in community-dwelling adults.
Project description:PURPOSE:To assess the short-term day-to-day reproducibility of 24-hour intraocular pressure (IOP) curves in various respects in untreated primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. METHODS:47 subjects with POAG and 34 subjects with OHT underwent IOP measurements every 2 hours in both eyes for consecutive 48 hours by a non-contact tonometer (NCT). IOP values at each time point were recorded. Mean IOP, peak IOP, time difference of peak IOP between two days and IOP fluctuation were also calculated. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to evaluate reproducibility. RESULTS:ICCs of the entire IOP values for a complete 24-hour curve were 0.577 and 0.561 in POAG and OHT patients, respectively. ICCs of IOP values at different time points ranged from 0.384 (10am) to 0.686 (4am) in POAG patients and from 0.347 (6am) to 0.760 (4am) in OHT patients. ICCs of mean IOP, peak IOP and IOP fluctuation were respectively 0.832, 0.704, 0.367 in POAG patients and 0.867, 0.816 0.633 in OHT patients. Only 37.23% and 35.29% of the peak IOP time points appeared within the time difference of 2 hours in POAG and OHT patients, respectively, while 53.19% and 48.53% appeared within 4 hours in POAG and OHT patients, respectively. CONCLUSION:A 24-hour IOP curve in a single day is not highly reproducible in short-term and has limited use for evaluating individual IOP condition. Mean IOP and peak IOP for a 24-hour IOP curve are useful parameters in clinical follow-up, while IOP value at a certain time point, IOP fluctuation and peak IOP time point should be interpreted with caution.