Circadian Rhythm Of Intraocular Pressure Research Articles

A comparison of the circadian rhythm of intraocular pressure in patients with primary glaucoma and normal individuals

Purpose The aim of this study was to evaluate the 24-h intraocular pressure (IOP) fluctuations in patients with glaucoma and to compare them with normal persons.Patients and methods This is a cross-sectional comparative study of the circadian rhythm of IOP that was conducted on 30 patients diagnosed with primary glaucoma on medical or surgical treatment and 30 normal individuals with no signs of glaucoma. There were three cases of primary angle closure glaucoma, and so they were excluded from the analysis.Results The mean age of all participants was 60.25±12.15 years. The mean age of the normal individuals was 58.60±12.33 years compared with 62.22±11.66 years in patients with primary open angle glaucoma (POAG), with no statistically significant difference (P=0.486). A higher proportion of females (63%) were found in the glaucoma group, though not statistically significant (P=0.138). The mean IOP was higher among the glaucoma group (19.92±6.18 mmHg) than in the normal individuals (14.83±1.75 mmHg), with a statistically significant difference (P=0.001). The mean diurnal variation of IOP in the right eye among the normal individuals (3.6±1.1 mmHg) was significantly lower than in the POAG group (7.11±4.8 mmHg) (P=0.001). Similarly, in the left eye, the mean diurnal variation was significantly higher in the POAG group (6.07±2.25 mmHg) compared with the normal individuals (3.52±1.25 mmHg) (P=0.00). The average peak of IOP among normal individuals and patients with POAG was 19.75±2.0 and 37.56.9 mmHg, respectively, in the right eye (P=0.01) and 20.00 ± 1.6 mmHg and 26.25 ± 2.2 in normal individuals and patients with POAG, respectively, in the left eye (P=0.001). The peak IOP among the POAG group was seen at 6 p.m. and 6 a.m., mostly outside office hours.Conclusion The diurnal variation of IOP was more among patients with glaucoma than normal individuals. The average peak of the IOP was seen only after office hours (9 a.m.–5 p.m.), thus emphasizing the need for 24-h monitoring of IOP. The 24-h measurement would help recognize the IOP spikes and help decide the time of instillation of antiglaucoma medication to avoid further glaucoma progression.

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

Relationship between Myopia and Light Exposure

Epidemiological studies found that the incidence of myopia was increasing year by year and the age of onset of myopia was showing a trend of affecting increasingly younger children. Reducing the occurrence of myopia and controlling the increase of myopia diopter have always been the focus of research on the prevention and control of myopia. Large randomized controlled clinical trials have found that outdoor activities can effectively reduce the incidence of myopia and delay the progression of myopia. Basic experiments also revealed that there were certain connections between light exposure and myopia. We herein review the research progress, limitations and future directions of research on light exposure and myopia. From the perspective of light properties, increasing the intensity of light can slow the progression of myopia and reduce the occurrence of experimentally induced myopia. However, the actual mechanism of action is still unclear. The rhythmic changes of light exposure caused by the light/dark cycle may cause abnormalities in the secretion of melatonin and dopamine, and changes in the circadian rhythm of intraocular pressure and choroidal thickness, thus affecting myopia. The red light, with relatively longer wavelength and forming images behind the retina, tends to induce myopia more easily, while the blue light, with medium and short wavelength and forming images before the retina, tends to delay myopia progression. However, different species respond differently to lights of different wavelengths, and the relationship between light wavelength and myopia needs further investigation. Future research can be done to further explore the mechanism of action of how light exposure changes the progression of myopia, including the following aspects: how light changes dopamine levels, causing changes in downstream signal pathways, and thus controlling the growth of the axial length of the eye; how retinal photoreceptor cells receive light signals of different wavelengths in order to adjust the refractive power of the eyes; and how to design artificial lighting of reasonable intensity, composition and properties, and apply the design in myopia prevention and control.

Circadian rhythm of intraocular pressure in clinically normal donkeys (Equus asinus)

ABSTRACT The present study aimed to report the circadian rhythm of intraocular pressure (IOP) in clinically normal donkeys. A prospective study was conducted on 30 adult donkeys. Measurement of the IOP was made at 2-hr interval starting at 6:00 hr till the next day at 4:00 using applanation tonometry. Measurements were recorded for both eyes and compared for male and female differences. The overall mean (± SEM) IOP measurement was 24.99 ± 0.14 mmHg. The mean (± SEM) IOP of the right and left eyes was 25.59 ± 0.19 and 24.27 ± 0.19 mmHg, respectively. The IOP values of the right and left eyes as well as of male and female values did not change significantly (P > 0.05) at all times. IOP measurements demonstrated diurnal fluctuation during the light phase of the day. The IOP significantly (P < 0.001) increased (27.07 ± 0.42) in the early morning (peak daytime at 8:00 hr) and was significantly (P < 0.001) lower (20.68 ± 0.34) at the mid-light phase (12:00 hr) compared to all evaluation times. The study documented the daily rhythm of IOP in donkeys. The 24-hr variation of IOP measurement should be considered when evaluating IOP in donkeys.

Analysis of the circadian rhythm of intraocular pressure in stable and progressive forms of primary open-angle glaucoma

Purpose. To analyze the daily dynamics and the parameters of intraocular pressure circadian rhythm (IOP CR) in patients with primary open-angle glaucoma (POAG) (stable and progressive forms) and determine chronobiological regularities of glaucoma progression depending on the patterns of restructuring the daily dynamics of IOP CR and body temperature.Material and methods. The study included 75 POAG patients, of which 35 had a stable form (S-POAG) and 40 had a rapidly progressing form (P-POAG). The control group was composed of 80 subjects without POAG. The index of retinal ganglion cell loss measured by optical coherence tomography (OCT) was used as a criterion of POAG progression. IOP was measured by the patients themselves for 72 hours at 7 time points (3 am, 8 am, 11 am, 2 pm, 5 pm, 8 pm, and 11 pm, who used an Icare ONE portable intraocular pressure tonometer for individual use.Results. IOP daily dynamics was distributed differently in the different groups. In S-POAG, the peak values were mainly reached in the morning hours, while the minimum values were observed at night. In P-POAG, the peak values of IOP were contrariwise recorded at night. In both POAG groups, an increase of irregular fluctuation share was noted, which indicated a decrease of the CR contribution to the IOP CR. Moreover, in POAG, a change in the phase ratio between the IOP CR and CR of body temperature was observed. For IOP CR phase violation manifestations, the threshold value of GCS global loss index was determined at 10–15 % according to OCT data.Conclusion. IOP daily dynamics were shown to differ in S-POAG and P-POAG patients. In both groups. Signs of desynchronization were detected. The ganglion retinal cell global loss index can be used to determine phase disturbances of IOP CR.

Twenty-Four-Hour Contact Lens Sensor Monitoring of Aqueous Humor Dynamics in Surgically or Medically Treated Glaucoma Patients

Aim This study assessed the 24 h circadian rhythm of intraocular pressure (IOP) using a contact lens sensor in three groups of patients with open-angle glaucoma. Methods This study was a monocentric, cross-sectional, nonrandomized, prospective, pilot study. Eighty-nine patients were enrolled: 29 patients previously underwent an Ex-PRESS mini glaucoma device procedure (Group 1), 28 patients previously underwent Hydrus microstent implantation (Group 2), and 32 patients were currently being treated medically for primary open-angle glaucoma (Group 3). Circadian rhythm patterns were considered with five circadian indicators: fluctuation ranges, maximum, minimum, acrophase (time of peak value), and bathyphase (time of trough value). A two-tailed Mann–Whitney U-test was used to evaluate differences between groups. Results All subjects exhibited a circadian rhythm and a nocturnal pattern. The signal fluctuation range was significantly smaller in the surgical groups than in the medically treated group (Group 1 vs. Group 3, p=0.003; Group 2 vs. Group 3, p=0.010). Subjects who underwent the Ex-PRESS procedure (Group 1) exhibited significant differences compared with the drug therapy group (Group 3) with regard to the minimum value (p=0.015), acrophase (p=0.009), and bathyphase (p=0.002). The other circadian indicators were not significantly different among groups. Conclusions Patients who underwent IOP-lowering surgery had an intrinsic nyctohemeral rhythm. Both surgical procedures, Ex-PRESS and Hydrus, were associated with smaller signal fluctuations compared with medical treatment.

Periodic analysis using two-way analysis of variance for the circadian rhythm of intraocular pressure in primary open angle glaucoma

The purpose of the article is to investigate the diurnal variation of intraocular pressure (IOP) in glaucoma patients by periodic regression analyses using two-way analysis of variance (ANOVA). Seventy-two open-angle glaucoma patients participated in this study and IOP measurements were taken in this group every 2 h during waking hours. Patients were categorized based on the Glaucoma staging system (GSS) into “severe” (GSS > stage 2) and “less severe” (GSS ≤ stage 2) groups. They were also categorized into high tension (IOP ≥ 19 mmHg) and low tension (IOP < 19 mmHg) groups. Diurnal IOP curves were plotted and analyzed for all patients and for each subgroup by periodic regression analysis with two-way ANOVA. Results showed that all diurnal IOP curves from all patients and all subgroups statistically fitted periodic regression curves within a 24-h period (p < 0.0001, two-way ANOVA for all categories). It is concluded that IOP exhibits a 24-h circadian rhythm in glaucoma patients during waking hours.

Daytime profile of the intraocular pressure and tear production in normal dog

To evaluate the circadian rhythms of intraocular pressure (IOP) and tear production in dog exposed to a natural photoperiod. We used 12 clinically healthy Beagles dog housed under natural photoperiod at indoor temperature and humidity. Intraocular pressure and Schirmer tear test (STT) I were measured every 4 h over a 48-h period in both eyes in each animal. Statistical analysis of the data was performed by one-way repeated-measures anova, Student's t-test, and single cosinor method. On each day, there was a highly significant effect of time on both parameters. A statistically significant difference of STT I values was observed comparing left and right eyes (P < 0.0001). Robust daily rhythms were observed for both parameters, IOP values showed diurnal acrophase (left eye: 09:33 +/- 00:50 h; right eye: 09:25 +/- 00:22 h), while STT I values showed nocturnal acrophase (left eye: 20:27 +/- 00:46 h; right eye: 20:00 +/- 00:05 h). This study has demonstrated circadian rhythms in both IOP and STT I.

Circadian rhythm of intraocular pressure in healthy subjects and glaucoma patients

Abstract Purpose: Intraocular pressure (IOP) varies and depends on many factors. Intraocular pressure variations throughout the nycthemeron (the full 24‐period of a night and a day) are the most interesting for studying. Methods: With present techniques, it is impossible to measure continuously without waking the subject up. Thus, IOP must be hourly measured during 24 hours with a portable tonometer which allows short measurements in any posture, without requiring the subjects or patients to rise during the night. Results: Intraocular pressure depends on a nyctohemeral rhythm, being higher at night than during the day in healthy subjects, with a nocturnal peak value (acrophase). In the same normal individual, several 24‐hour monitorings are identical. Each individual has his own 24‐hour pattern of IOP.In glaucoma patients, however, the 24‐hour rhythm of IOP was reversed, with values being higher during the day (a midday peak in IOP) than during the night. Conclusions: The time course of the nyctohemeral curve of intraocular pressure is considered to play a role in the prognosis of glaucoma and allows to classify the type of glaucoma (POAG, NTG). Lowering of IOP is still the only option that is available for treating patients with glaucoma. Variations encountered in the individual’s nyctohemeral IOP pattern must be taken into consideration to manage the most efficient treatment.

Circadian rhythm of intraocular pressure in cats

To evaluate the rhythm of intraocular pressure (IOP) in healthy domestic cats with no evidence of ocular disease and to analyze the influence of photoperiod, age, gender and ocular diseases on diurnal-nocturnal variations of cat IOP. All animals were Domestic Short-haired cats; 30 were without systemic or ocular diseases, classified as follows: 12 male intact adult cats, five intact adult female, five adult spayed female, and eight male cats; the latter were less than 1 year of age. In addition, five adult cats with uveitis and three adult cats with secondary glaucoma were included. IOP was assessed with a Tono-Pen XL at 3-h intervals over a 24-h period in 12 healthy adult male cats kept under a photoperiod of 12-h light/12-h darkness for 2 weeks. Eight animals from the same group were then kept under constant darkness for 48 h, and IOP was measured at 3-h intervals for the following 24 h. In addition, IOP was assessed at 3 p.m. and 9 p.m. in five intact females, five spayed females, and in eight young cats, as well as in five adult cats with uveitis and three glaucomatous cats. Consistent, daily variations in IOP were observed in animals exposed to a light-dark cycle, with maximal values during the night. In cats exposed to constant darkness, maximal values of IOP were observed at subjective night. Differences of IOP values between 3 p.m. and 9 p.m. (diurnal-nocturnal variations) persisted in intact females, spayed females, and young animals, as well as in uveitic and glaucomatous eyes. The present results indicate a daily rhythm of cat IOP, which appears to persist in constant darkness, suggesting some level of endogenous circadian control. In addition, daily variations of cat IOP seem to be independent of gender, age, or ocular diseases (particularly uveitis and glaucoma).

Circadian Intraocular Pressure Rhythm Is Generated by Clock Genes

The present study in a mouse model was undertaken to reveal the role of the circadian clock genes Cry1 and Cry2 in generation of 24-hour intraocular pressure (IOP) rhythm. IOP was measured at eight time points daily (circadian time [CT] 0, 3, 6, 9, 12, 15, 18, and 21 hours), using a microneedle method in four groups of C57BL/6J mice (groups 1 and 3, wild-type; groups 2 and 4, Cry-deficient [Cry1-/-Cry2-/-]). During the IOP measurements, mice in groups 1 and 2 were maintained in a 12-hour light-dark cycle (LD), whereas mice in groups 3 and 4 were kept in a constant darkness (DD) that started 24 to 48 hours before the measurements. Circadian IOP variations in each group were evaluated by one-way analysis of variance (ANOVA) and Scheffé tests. In wild-type mice living in LD conditions, pressures measured in the light phase were significantly lower than those in the dark phase. This daily rhythm was maintained under DD conditions with low pressure in the subjective day and high pressure in the subjective night. In contrast, Cry-deficient mice did not show significant circadian changes in IOP, regardless of environmental light conditions. These findings demonstrate that clock oscillatory mechanisms requiring the activity of core clock genes are essential for the generation of a circadian rhythm of intraocular pressure.

Variations nycthémérales de la pression intraoculaire et leurs implications cliniques

Intraocular pressure follows a circadian rhythm like many of the body's parameters. These fluctuations in intraocular pressure were recently identified as a risk factor for visual field loss, in addition to intraocular pressure itself. Furthermore, the pressure curve seems to have a different profile in glaucomatous patients: the peak occurs later compared with normal subjects. Better knowledge of pressure fluctuations and their physiological mechanisms is essential for optimal management of glaucomatous patients not only to interpret the single ocular tension recordings, but also to use the available treatments rationally, both drugs and surgery. The authors review different studies that have contributed to the current knowledge on the circadian rhythm of intraocular pressure, aquous humor flow regulation, and the effects of topical hypotensive drugs on the pressure curve.

A comparison of the circadian rhythm of intraocular pressure in primary chronic angle closure glaucoma, primary open angle glaucoma and normal eyes

To evaluate the circadian rhythm of intraocular pressure (IOP) in primary chronic angle closure glaucoma (PCACG), primary open angle glaucoma (POAG), and normal eyes. Cross-sectional study of newly diagnosed patients of POAG (60 eyes), PCACG following laser iridotomy (75 eyes), and age and sex matched normal controls (75 eyes). All subjects underwent applanation tonometry at 7 a.m., 10 a.m., 1 p.m., 4 p.m., 7 p.m., and 10 p.m. by a masked observer. Circadian rhythms were classified based upon the timing and presence of peak pressure. Age and gender in all three groups were comparable. Diurnal IOP fluctuations were significantly higher in PCACG (7.69+3.03 mmHg) and POAG (8.31+2.58 mmHg) groups compared to normal controls (4.83 + 2.46 mmHg). PCACG eyes and controls had similarly timed circadian rhythms, with PCACG eyes having a consistently higher IOP. At 7 and 10 a.m., IOP peaked more often in POAG eyes compared to PCACG eyes. A plateau type of circadian rhythm was most common in normal eyes. The timing of peak IOP could be significantly correlated with the type of primary glaucoma examined. Afternoon peaks were more common in postiridotomy PCACG eyes, similar to the rhythm in normal eyes. Morning peaks were more frequent in POAG eyes. Diurnal fluctuation > 6 mmHg, associated with an IOP of 21 mmHg or more was never seen in a normal eye.

Effects of Ocular Hypotensive Agents on Circadian Rhythms of Intraocular Pressure in Rabbits as Measured by Telemetry System

To establish a telemetry system for measuring intraocular pressure (IOP) in rabbits and to evaluate the effects of topical application of ocular hypotensive agents on the circadian rhythm of IOP.

Melatonin Receptor mRNA and Protein Expression in Xenopus laevis Nonpigmented Ciliary Epithelial Cells

Melatonin is an output signal of the circadian clock, and may regulate diurnal rhythms in ocular tissues. A role for melatonin has been suggested in the circadian changes in intraocular pressure (IOP). Changes in IOP may be due partially to changes in the rate of aqueous humor secretion, which is produced by the nonpigmented epithelium of the ciliary body. To examine the mechanism by which melatonin may influence ciliary epithelium function and perhaps the IOP diurnal rhythm, immunocytochemistry with an antibody directed against the Mel1c melatonin receptor subtype was performed on sections of Xenopus eyes. Melatonin receptor immunoreactivity was observed in the basolateral regions of the nonpigmented epithelial cells of the ciliary body. Receptor immunoreactivity was also observed in cells of the retina, as has been previously reported. Specific immunoreactivity was not observed in the epithelium of the iris or pigmented ciliary epithelium. In situ hybridization of the Xenopus eye revealed expression of Mel1c but not Mel1b receptor mRNA in the nonpigmented ciliary epithelium. These results provide evidence that the nonpigmented epithelia of the ciliary body are direct targets for melatonin, and supports previous work that melatonin may influence the rate of aqueous humor secretion by ciliary epithelium, and perhaps the circadian rhythm of IOP.

Influence of Dehydroepiandrosterone on Rabbit Intraocular Pressure

Purpose: The systemic concentration of dehydroepiandrosterone decreases with age in primates while in humans intraocular pressure (IOP) increases with aging. This study was designed to investigate if a relationship existed between dehydroepiandrosterone and IOP in pigmented rabbits. Methods: Animals were treated unilaterally for 6 weeks with topical 3% dehydroepiandrosterone in 30% 2-hydroxypropyl-beta-cyclodextrin; the contralateral eye received vehicle alone. Drops were applied, and IOP measured, twice daily. Results: Small, but statistically significant, drug-related effects were found. IOP was consistently higher in the afternoon; the afternoon minus morning difference in IOP, however, decreased with time. Topical, radioactive drug application indicated very low level penetration into aqueous humor, iris, corneal epithelium, the rest of the cornea, or bulbar conjunctiva. Conclusion: The small drug-related effects may be due, in large part, to poor intraocular drug penetration. The circadian rhythm of IOP appears to be time-dependent in chronic studies with a gradual loss of IOP difference between a.m. and p.m. readings.

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.

Circadian rhythm of intraocular pressure in the rat.

To define the characteristics of the diurnal variation of intraocular pressure (IOP) in eyes of awake rats, ten male brown Norway rats were entrained to a 12-hour light:12-hour dark (12L:12D) lighting schedule and were conditioned to IOP measurement with the TonoPen XL tonometer while awake, using only 0.5% proparacaine HCl anesthesia. The IOP measurements were performed in 4 experiments: Preliminary-IOP was measured at 6-hour intervals in both eyes of each animal, to determine correlation between right and left eyes; Light:Dark-lighting remained the same as in the preliminary experiment, but the measurement schedule was altered so that measurements were obtained at 4-hour intervals in alternating eyes, over two 24-hour light cycles; Dark:Dark-animals were placed in constant dark (0L:24D) and, after 72 h, measurements were obtained at 4-hour intervals in alternating eyes. Animals were then re-entrained to the previous 12L:12D schedule for 7 days, after which they were returned to constant dark and the experiment was repeated; and Dark:Light-animals were entrained to a reversed light:dark cycle (12D:12L) for 28 days, after which measurements were obtained in the same fashion as in the Light:Dark experiment. Close agreement was found between right- and left-eye IOPs. Animals on a 12L:12D schedule exhibited lowest IOP while the lights were on (19.3 +/- 1.9 mm Hg), and highest (31.3 +/- 1.3 mm Hg) while the lights were off. Pressure changes anticipated the change from light to dark and dark to light. This pattern persisted in constant dark, and was reversed when the cycle was changed to 12D:12L. Brown Norway rats possess a regular rhythm of IOP that is entrained by the cycle of light and dark, and persistence of this rhythm in constant dark establishes it as a circadian rhythm. Furthermore, our results indicate that reliable and physiologically meaningful IOP measurements can be obtained in awake rats using the TonoPen XL tonometer.

Diurnal change of anterior chamber depth in rabbits.

It has been shown that there is a circadian rhythm of intraocular pressure and aqueous humor flow in rabbits. It has also been shown that there is a fluctuation in the volume of the aqueous that can be aspirated from the anterior chamber at different times of day. This finding would suggest that the depth and volume of the anterior chamber of this species also undergoes a circadian rhythm. To confirm this hypothesis, we measured by pachometry the anterior chamber depth in 11 adult New Zealand albino rabbits that had been conditioned to light from 6 a.m. to 6 p.m. and to dark from 6 p.m. to 6 a.m. The measurements were performed at noon and at midnight. The anterior chamber was found to be 4% deeper at midnight than at noon (p < 0.001). This finding suggests that the volume of the anterior chamber would be slightly larger at night than during the day in the rabbit eye. We have no explanation for this finding. However, the difference is too small to have an appreciable effect on the measurement of aqueous dynamics or pharmaceutical effects.

Circadian Rhythm of Intraocular Pressure: A Rat Model

The purpose of this study was to examine whether there is a circadian rhythm of intraocular pressure (IOP) in the Lewis rat. Therefore, 20 Lewis rats (40 eyes) were subjected to an alternating 12-hour-light and 12-hour-dark cycle. Using a Tono-Pen 1, IOP was measured every 2 h between 6 a.m. and 12 midnight and every 3 h between 12 midnight and 6 a.m. for 2 consecutive days. These measurements in the Lewis rat revealed a reproducible circadian rhythm with a peak at 8 p.m. and a trough at 6 a.m. In conclusion, when using the Lewis rat as an animal model in longitudinal studies that involve the IOP, the IOP should be measured at the same time each day to correct for diurnal variations. Additionally, Lewis rats may be a useful model to study the causes of circadian rhythms of IOP and for pharmacologic studies of new glaucoma medications.