Nocturnal Intraocular Pressure Research Articles

The Benefit of Nocturnal IOP Reduction in Glaucoma, Including Normal Tension Glaucoma.

Nocturnal intraocular pressure (IOP) profiling has shown that the peak IOP usually occurs at night, particularly in patients with glaucoma. Multiple studies have demonstrated that these nocturnal IOP elevations drive glaucomatous progression, often despite stable daytime IOP. Existing vascular dysregulation and decreased nighttime blood pressure compound the damage via low ocular perfusion pressure while elevated nocturnal IOP disrupts axonal transport. These findings are consistent with studies that indicate lowering nocturnal IOP is important for slowing glaucoma progression. Many of the current treatment options lower nighttime IOP significantly less than daytime IOP. Non-invasive IOP-lowering treatments that effectively lower nocturnal IOP remain an unmet need in the treatment of glaucoma.

Effect of Ambient Lighting on Intraocular Pressure Rhythms in Rats.

The purpose of this study was to determine the effects of ambient lighting on intraocular pressure (IOP) rhythmicity and variability. IOP was continuously recorded by wireless telemetry from rats under light/dark (LD), dark/light (DL), asymmetric (6L18D and 18D6L), constant dark (DD), and constant light (LL) cycles. In some DD experiments, 1-hour light pulses were presented at varying times. IOP rhythmicity and variability were respectively quantified via cosinor analysis and peak detection algorithms that identified transient and sustained fluctuations. Rat IOP peaked at night and troughed during the day with LD amplitude of 8.7 ± 3.4mm Hg. Rhythmicity persisted in DD and LL with a free-running period of 24.1 ± 0.3 and 25.2 ± 0.4 hours, respectively. Peak-to-trough amplitude was approximately 60% smaller in LL, often disappeared after 1 to 2 weeks as daytime IOP drifted 2.6 ± 1.5mm Hg higher, and returned to approximately 60% larger in LD. Rhythmicity was similarly impacted but resynchronized to DL over 4 to 6days. Rhythmicity was unaltered by short photoperiods (6L18D), but the nocturnal IOP elevation was markedly shortened by long photoperiods (18L6D) and temporarily lowered to daytime levels by light pulses during the subjective night. Transient and sustained event rate, amplitude, interval, and energy content were nearly identical in LD, DD, and LL. Aqueous humor dynamics of rat eyes are intrinsically configured to set IOP at daytime levels. Circadian clock input modulates these dynamics to elevate IOP at night. Light at night blocks this input, sending IOP back to daytime levels. Effects of abnormal lighting on IOP rhythmicity may contribute to pressure-related ocular neuropathies.

Susceptibility of optic nerve head in children with posture-related elevation of intraocular pressure

Background/AimsThis work aimed to investigate changes in optic nerve head (ONH) morphometry based on Bruch membrane opening in children with extensive nocturnal intraocular pressure (IOP) elevations.MethodsThe course of Bruch membrane opening-based optic nerve head (ONH) morphometry was analysed in thirty-two patients younger than 18 years with evaluable SD-OCT examinations of the ONH and nocturnal posture-dependent IOP elevation above 25 mmHg. Longitudinal changes in neuroretinal rim tissue, as measured by Bruch Membrane opening minimum rim width (BMO-MRW) and peripapillary retinal nerve fiber layer (RNFL) thickness, were assessed.ResultsOne year after the 24 h IOP measurement, global BMO-MRW (− 1.61 ± 16.8 µm, n.s.; p = 0.611) and RNFL (+ 0.64 ± 3.17 µm; n.s.; p = 0.292) measurements were not significantly different from the baseline. No significant BMO-MRW reduction (− 3.91 ± 24.3 µm; n.s. p = 0.458) or deviation in RNFL thickness (+ 1.10 ± 3.52 µm) was observed at the four-year follow-up. Absolute IOP values measured in the supine position did not correlate with changes in global BMO-MRW or RNFL thickness.ConclusionPosture-dependent IOP elevations do not seem to influence retinal nerve fibre layer thickness or Bruch membrane opening-based morphometric data in childhood.

Posture-related fluctuations of intraocular pressure in healthy children with suspicion of glaucoma

PurposeCurrently, there are no specific data on the circadian course of intraocular pressure (IOP) in children, especially for IOP measurements in the supine position. The study aimed to characterize the diurnal and nocturnal IOP fluctuations in supine and sitting positions in patients less than 18 years of age.MethodsSeventy-nine eyes of 79 patients under 18 years of age with suspicious optic nerve heads or ocular hypertension could be included in this study. All included patients showed an inconspicuous retinal nerve fiber layer thickness and Bruch’s membrane minimum rim width by coherence tomography. IOP measurements during the 24-h IOP profile were retrospectively evaluated. Measurements were taken at 10:00, 16:00, 20:00, and 23:00 h in the sitting position and at 6:00 h in the morning in the supine position using iCare rebound tonometry on 2 consecutive days.ResultsThirty-four of 79 children (43.0%) had peak nocturnal IOP values > 25 mmHg. The mean daily IOP was 18.8 ± 5.6 mmHg, and the mean daily fluctuation was 6.1 ± 4.0 mmHg. At 6 am, supine measurements were elevated to 25.1 ± 8.0 mmHg. Extensive fluctuations with values > 40 mmHg in the nocturnal supine measurement occurred in a relevant share of patients (n = 5).ConclusionThere appear to be relevant diurnal and nocturnal IOP fluctuations in healthy children (< 18 years). Nocturnal IOP measurements in supine patients with risk factors for glaucoma may provide important additional information to identify critical patients for further follow-up.

Efficacy of selective laser trabeculoplasty on lowering intraocular pressure fluctuations and nocturnal peak intraocular pressure in treated primary open-angle glaucoma patients

PurposeTo investigate the efficacy of adjunctive selective laser trabeculoplasty (SLT) in reducing 24-h intraocular pressure (IOP) fluctuations and nocturnal IOP peaks.MethodsIn this prospective interventional case series, 157 medically treated eyes of 157 patients with primary open-angle glaucoma (POAG) who were assigned SLT to further reduce IOP were consecutively included. Each patient had a complete glaucoma work-up and 24-h IOP monitoring (6 measurements, including one in the supine position) taken before and on average 6 months after SLT. The main outcome measures were the reduction of 24-h IOP fluctuations and nocturnal peak IOP. Secondary outcome measures were success rates, factors influencing the reduction of high 24-h IOP fluctuations and nocturnal peak IOP, complications, and severe adverse events.ResultsMedicated mean 24-h IOP (mmHg) was statistically significantly reduced from 15.1 ± 2.6 to 13.8 ± 2.4 (P < 0.001) and IOP fluctuations from 6.5 ± 2.7 to 5.4 ± 2.6 (P < 0.001) 6 months after SLT. Ninety-four eyes (59.9%) initially had high IOP fluctuations (more than 5 mmHg). These were reduced from 8.1 ± 2.3 to 5.6 ± 2.7 at 6 months (P < 0.001). Fifty-two eyes (55.3%) had fluctuations below 5 mmHg post-SLT which was defined as success. Fifty-one patients (32.5%) had nocturnal IOP peaks. In these cases, nocturnal IOP was reduced by 19.2% from 20.1 ± 3.4 to 16.2 ± 3.3 mmHg at 6 months (P = 0.001).ConclusionsThe current study demonstrates that adjunctive SLT not only reduces mean 24-h IOP in treated POAG patients, but also has an additional benefit in reducing IOP fluctuations and nocturnal peak IOP.Trial registrationClinical trial registration: NCT02959242.

Suppression of trabecular meshwork phagocytosis by norepinephrine is associated with nocturnal increase in intraocular pressure in mice

Intraocular pressure (IOP) is an important factor in glaucoma development, which involves aqueous humor (AH) dynamics, with inflow from the ciliary body and outflow through the trabecular meshwork (TM). IOP has a circadian rhythm entrained by sympathetic noradrenaline (NE) or adrenal glucocorticoids (GCs). Herein, we investigated the involvement of GC/NE in AH outflow. Pharmacological prevention of inflow/outflow in mice indicated a diurnal outflow increase, which was related to TM phagocytosis. NE showed a non-self-sustained inhibition in phagocytosis of immortalized human TM cells, but not GC. The pharmacological and reverse genetic approaches identified β1-adrenergic receptor (AR)-mediated exchange proteins directly activated by cyclic adenosine monophosphate (EPAC)-SHIP1 signal activation by ablation of phosphatidylinositol triphosphate, regulating phagocytic cup formation. Furthermore, we revealed the phagocytosis involvement in the β1-AR-EPAC-SHIP1-mediated nocturnal IOP rise in mice. These suggest that TM phagocytosis suppression by NE can regulate IOP rhythm through AH outflow. This discovery may aid glaucoma management.

Melatonin, circadian rhythms and glaucoma: current perspective.

Melatonin, circadian rhythms and glaucoma: current perspective.

Twenty-Four-Hour Intraocular Pressure Control with Omidenepag Isopropyl 0.002% in Patients with Glaucoma and Ocular Hypertension.

PurposeTo clarify the intraocular pressure (IOP)-lowering effect of a selective prostanoid EP2 receptor agonist, omidenepag isopropyl (OMDI) during a 24-hour period.Patients and MethodsSubjects aged ≥20 years and with diagnosed, untreated primary open-angle glaucoma or ocular hypertension were enrolled. IOP measurements were performed every 4 hours over a 24-hour period using a Goldmann applanation tonometer (GAT) and Icare PRO tonometer (PRO). The baseline 24-hour IOP was measured in untreated subjects. After the baseline measurements, participants were given OMDI 1 drop once daily at night for 4 weeks. At week 4, the IOP measurement was repeated under the same conditions. Diurnal (9 am, 1 pm, 5 pm) and nocturnal (9 pm, 1 am, 5 am) IOP measurements were compared between baseline and treatment with OMDI. Safety measures included adverse events, slit-lamp biomicroscopy, visual acuity, heart rate and blood pressure.ResultsOf 27 participants enrolled, 25 patients (20 males and 5 females, average age 52.2 ± 8.5 years) completed the study. In the sitting position, the baseline diurnal and nocturnal mean IOPs (GAT) were 19.1 ± 2.1 mmHg and 18.2 ± 2.6 mmHg, respectively, the diurnal and nocturnal mean IOP reduction from baseline were –2.8 ± 2.6 mmHg (p < 0.0001) and –3.3 ± 2.9 mmHg (p < 0.0001), respectively, mean 24-hour IOP (GAT) was significantly lower with the OMDI treatment (−3.1 ± 2.5 mmHg, p < 0.0001). In the supine position, the baseline nocturnal mean IOP (PRO) was 17.99 ± 2.22 mmHg, and the nocturnal mean IOP reduction from baseline was −1.78 ± 2.37 mmHg (p = 0.0009) after 4 weeks of the treatment. Nine adverse events were observed in 8 patients including mild conjunctival hyperemia (n = 8) and mild iritis (n=1). There were no significant effects on systemic safety.ConclusionOnce daily OMDI treatment was able to produce stable 24-hour IOP reduction.

Short- and long-term agreement and reproducibility of 48-hours intraocular pressure measurements in glaucoma patients

BackgroundGlaucomatous eyes often show strong intraocular pressure (IOP) fluctuations and individual measurements at different time points are necessary for personalized therapy. To survey IOP variations 48-hours diurnal and nocturnal IOP measurements were performed on two consecutive days. Aims of this study were to investigate the short-term repeatability of 48-hours measurements within one patient’s IOP profile and long-term repeatability between two separate IOP profiles of the same patient.MethodsA retrospective cohort study was performed evaluating data of 90 glaucoma patients in a German university medical center between 2006 and 2013. All patients underwent two separate diurnal IOP profiles of 48 h. IOP was measured at 8 am, 2 pm, 6 pm, 9 pm using Goldmann applanation tonometry and at 12 midnight using Perkins tonometry in supine position on two consecutive days. Intraclass correlation coefficients (ICC) were calculated to evaluate agreement for the same time points (each time point agreement) and for consecutive measurements within the IOP profiles (between time point agreement). ICC ≤ 0.4 was defined as poor agreement, 0.4–0.75 as moderate and ≥ 0.75 as excellent. Differences between time points were investigated by Bland Altman plots.ResultsEach time point measurements of profile 1 showed moderate to excellent agreement (ICCs 0.62–0.93). There was a moderate to excellent agreement for measurements between time points of profile 1 (ICCs day one 0.57–0.86, day two 0.71–0.90). Profile 2 was performed at a median interval of 12.0 months (quartiles 11.0 to 21.0). Each time point agreements within profile 2 showed ICCs from 0.23 to 0.81. It showed moderate to excellent agreement for changes between time points (ICCs 0.53–0.94). Day two demonstrated ICCs from 0.74 to 0.88. Long term IOP repeatability (over both pressure profiles) showed moderate to good agreement (ICCs 0.39–0.67).ConclusionsShort and long-term agreement of IOP measurements evaluated by diurnal IOP profiles is moderate to good. Due to mostly moderate agreements, which we believe represent IOP fluctuations, we conclude that it is necessary to perform 48-hours IOP profiles to gain a better overview of the individual IOP fluctuations.

24-h intraocular pressure patterns measured by Icare PRO rebound in habitual position of open-angle glaucoma eyes.

To measure the 24-h intraocular pressure (IOP) by Icare PRO rebound in healthy and primary open-angle glaucoma (POAG) eyes and compare it with non-contact tonometry (NCT). Thirty POAG patients, who were under IOP-lowering treatment, and 30 healthy subjects were included. Participants were hospitalized overnight for the 24-h IOP measurement. IOPs were measured by Icare PRO and NCT according to a standard protocol every 2h during 24h. The 24-h IOP curve and IOP-related parameters were compared between Icare PRO and NCT groups in POAG and healthy eyes. The IOPs measured by Icare PRO in habitual position increased notably at 22:00 in the normal group and at 20:00 in the POAG group, reached peak at 0:00, stayed high until 4:00, and then decreased in both groups (all p < 0.05). The POAG patients had higher mean 24-h IOP, peak IOP, IOP fluctuation, and greater IOP change from supine to sitting position in the nocturnal period than those in the normal subjects even after adjusting for eyes, age, gender, CCT, and axial length (all p < 0.05). The Icare PRO provides a well-tolerated approach for 24-h IOP monitoring in habitual position. Twenty-four-hour IOP in habitual position is more sensitive for detecting high nocturnal IOP peaks and greater IOP fluctuation for POAG patients.

Short-term Evaluation of Negative Pressure Applied by the Multi-Pressure Dial System to Lower Nocturnal IOP: A Prospective, Controlled, Intra-subject Study.

IntroductionThe purpose of this study was to investigate the short-term safety and feasibility of negative pressure application by the Multi-Pressure Dial (MPD) System to lower nocturnal intraocular pressure (IOP) in subjects with open-angle glaucoma (OAG).MethodsA prospective, controlled, intra-subject study of 22 eyes from 11 subjects at a single site was performed. All subjects had a history of OAG and were currently using a topical prostaglandin. For each subject, the eye with the highest IOP in the supine position was selected as the treatment eye (TE) and the contralateral eye served as the control eye (CE). The negative pressure for the TE was set to 60% of the baseline IOP value with no negative pressure in the CE. IOP measurements were collected at three prespecified time points overnight in the supine position with active negative pressure. The primary outcome measure was mean IOP with the application of negative pressure.ResultsAt the three overnight time points, the mean (± standard deviation) baseline IOP prior to negative pressure application was 22.2 ± 2.5 mmHg in the TE and 21.8 ± 2.5 mmHg in the CE. With the application of 60% negative pressure to the TE and no active negative pressure to the CE, the mean IOP was 14.2 ± 2.2 and 19.5 ± 2.4 mmHg, respectively. The mean percentage IOP reduction in the TE was 35% (p < 0.001). There were two minor adverse events, both unrelated to device wear, and there were no IOP spikes ≥ 10 mmHg.ConclusionThe MPD can safely and effectively lower nocturnal IOP in the supine position. The MPD holds promise as a potential new, non-invasive treatment option for the control of nocturnal IOP.

A Randomized, Phase 2 Study of 24-h Efficacy and Tolerability of Netarsudil in Ocular Hypertension and Open-Angle Glaucoma.

IntroductionPharmacotherapy to lower intraocular pressure (IOP) is a mainstay of treatment aimed at delaying progression of visual field loss in ocular hypertension (OHT) and open-angle glaucoma (OAG), but some topical treatments are less effective in controlling IOP at night. Peak IOP may be related to glaucoma progression and can occur outside office hours. A phase 2 study was conducted to evaluate the IOP-lowering efficacy of netarsudil across the diurnal and nocturnal periods.MethodsThis was a randomized, double-masked, single-center, vehicle-controlled, 9-day study. After washout of any prior ocular hypotensive agents, 12 patients with OHT or OAG underwent baseline IOP assessment at 15:00, 18:00, 21:00, 00:00, 03:00, 06:00, 09:00, and 12:00 h on day 1/day 2. Participants were then randomized in a 2:1 ratio to netarsudil ophthalmic solution 0.02% (n = 8) or vehicle (n = 4) for 7 days of self-administered dosing each evening. IOP was assessed at the same time points on day 8/day 9. All measurements were conducted with a Perkins tonometer in habitual positions by day (seated) and at night (supine).ResultsBaseline mean 24-h IOP was 22.4 mmHg in the netarsudil group and 22.9 mmHg in the vehicle group. Netarsudil was associated with a reduction in mean nocturnal IOP (measurements at 21:00, 00:00, 03:00, 06:00 h) of 3.5 mmHg, which was significant relative to baseline nocturnal IOP (P < 0.001) and the reduction in the vehicle group (0.4 mmHg; P < 0.001 vs. netarsudil). Reduction in mean diurnal IOP with netarsudil (3.5 mmHg) was the same as the nocturnal reduction and statistically significant versus baseline (P < 0.001) and the vehicle group (0.9 mmHg; P < 0.01). The magnitude of IOP reductions with netarsudil was consistent at each time point assessed over the 24-h period. No adverse events were reported.ConclusionNetarsudil exhibited consistent IOP-lowering efficacy over a 24-h period in this short-term study.Trial RegistrationClinicaltrials.gov identifier: NCT02874846.

&lt;p&gt;Overnight Safety Evaluation of a Multi-Pressure Dial in Eyes with Glaucoma: Prospective, Open-Label, Randomized Study&lt;/p&gt;

PurposeTo investigate the safety and tolerability of the multi-pressure dial (MPD) worn overnight for seven consecutive days.DesignProspective, open-label, randomized, single-site study.SubjectsTwenty eyes of 10 subjects with open-angle glaucoma were fitted with an MPD and randomized to negative pressure application of −10 mmHg in one eye (study eye) worn overnight for 7 consecutive days.MethodsSafety measures included best-corrected visual acuity (BCVA), intraocular pressure (IOP) changes from baseline during and after negative pressure application, slit lamp and dilated fundus exam findings, and rate of adverse events. Subjective assessments were completed daily by the subjects during the 7-day study period and immediately following the study period.ResultsPrior to the 7-day testing period, application of 10 mmHg negative pressure reduced mean IOP from 18.2 ± 3.8 mmHg to 14.0 ± 2.1 mmHg (p<0.01), a 22% reduction. After 7 days of consecutive nightly wear, repeat IOP measurements with the application of negative pressure showed a decrease in mean IOP from 16.9 ± 4.3 mmHg to 13.5 ± 3.7 mmHg. The observed IOP reduction was in addition to the subjects’ current treatment regimen. There were no statistically significant changes in IOP, BCVA from baseline following the 7-day period of nightly wear with the application of negative pressure. The patient-reported outcomes were favorable.ConclusionThe MPD can safely and comfortably be worn overnight. The decrease in IOP of >20% in addition to current therapy is both clinically and statistically significant. The MPD shows promise as a potential new treatment option for nocturnal IOP control.

Continuous intraocular pressure monitoring in patients with obstructive sleep apnea syndrome using a contact lens sensor.

PurposeTo 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.MethodProspective, 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.ResultsThe 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.ConclusionsPeriods 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.

Correlation Between Office-Hour and Peak Nocturnal Intraocular Pressure in Patients Treated with Prostaglandin Analogs

To test the hypothesis that the correlation between office-hour intraocular pressure (IOP) and peak nocturnal IOP is weakened after using a prostaglandin analog. Before-and-after study. Twenty-four-hour IOP data obtained in a sleep laboratory of 51 patients (22 patients with open-angle glaucoma and 29 patients with ocular hypertension) were reviewed. Patients had no IOP-lowering medication upon study entry and were then treated with prostaglandin monotherapy for 4weeks. Measurements of IOP were taken every 2 hours in the sitting and supine positions during the diurnal/wake period (7:30 AM-9:30 PM) and in the supine position during the nocturnal/sleep period (11:30 PM-5:30 AM). Individual and average IOP readings during office hours (9:30 AM-3:30 PM) and peak IOP during the nocturnal/sleep hours were analyzed using the Pearson correlation coefficient and linear regression. There were statistically significant correlations for all the paired variables for the analyses. Average office-hour IOP had a higher correlation with peak nocturnal IOP than individual office-hour IOP. After the treatment with prostaglandin analog, the correlation between average office-hour IOP and nocturnal peak IOP in the sitting position (r= 0.373) and the supine position (r= 0.386) were reduced from the sitting baseline (r= 0.517) and the supine baseline (r= 0.573) in right eyes. Similar change patterns appeared in left eyes. There is a correlation between office-hour IOP reading and peak nocturnal IOP under no IOP-lowering treatment as well as under prostaglandin monotherapy. The strength of correlation was weaker under the treatment compared with baseline.

Relationship between nocturnal intraocular pressure-related peak recorded by contact lens sensor and disease progression in treated glaucomatous eyes.

Purpose:The aim of this study is to study the association between Nocturnal Intraocular Pressure (IOP) related Peak recorded by a Contact Lens Sensor (CLS) and glaucoma progression in treated glaucomatous eyes.Methods:Institutional study in which forty glaucoma patients were recruited from glaucoma clinic. A total of 19 patients were labeled as progressors on current anti-glaucoma treatment despite controlled day time IOP whereas twenty one patients were clinically stable showing no progression. Worse eye of each patient was selected for placement of CLS. The timing of the highest signal (IOP related peak) was noted in 24 hour CLS graph and if it fell within the time frame of 11 pm to 5 am, it was labeled as 'nocturnal IOP related peak'.Results:Progressors were found to be significantly more prone to night spike than Non Progressors (χ2 = 6.812; n = 40; P = 0.009), thus, showing a definite association between the two. Association between Nocturnal IOP related peak and various other variables like age, gender, mean daytime IOP and systemic illness was studied. A positive correlation was established between female gender and Nocturnal IOP related spike with a significantly higher proportion of females showing night spike than their male counterparts (χ2 = 5.763; n = 40; P = 0.016). Other parameters did not show any significant relationship with Nocturnal IOP related spike.Conclusion:Dynamic 24 hour recording by CLS is beneficial in detecting nocturnal IOP-related peak, and thus, can potentially improve the clinical care of glaucoma patients, especially those showing progression.

Circadian Rhythm and Glaucoma: What do We Know?

The current understanding of circadian regulation disorders and their involvement in glaucoma pathophysiology are poorly understood, yet they may have a substantial impact on the onset and progression of glaucoma. Herein, we review and summarize all the available literature on circadian rhythm disorder and glaucoma to uncover the impact on glaucoma risk, and we highlight future research and potential novel targets for glaucoma management. A review of the relevant literature was performed through PubMed through August 1, 2019. Within a normal circadian rhythm, intraocular pressure (IOP) peaks at night, whereas blood pressure (BP) troughs at night. High nocturnal IOP coupled with low nocturnal systemic BP results in low ocular perfusion pressure and potential for unobserved damage to retinal tissues and the optic nerve. Circadian-related melatonin and sleep disorders also result in changes in IOP and ocular perfusion pressure that lead to the progression of glaucoma. In addition, impaired perception of light input due to glaucoma can subsequently lead to abnormal serum levels of melatonin, resulting in circadian rhythm misalignment. This disruption of the circadian rhythm also contributes to sleep and mood disorders, common in individuals with glaucoma. As regards treatment, glaucoma medications that lower nocturnal IOP without influencing nocturnal BP or diminishing circadian variation seem most effective. Glaucoma progression is influenced by multiple physiological factors regulated by the circadian rhythm. Progression of the disease may also cause physiological changes that lead to circadian-related issues. Further research is warranted on the diurnal cycle, melatonin-mediated processes, and their influence on glaucoma management.

Application of rebound self-tonometry for measurements in a supine position

Diurnal or nocturnal fluctuations of intraocular pressure (IOP), which are especially common in glaucoma patients, often require hospitalization of the patient in order to be detected. This is often inconvenient for the patient. Therefore, this study evaluated the usefulness of arebound tonometer (RT) designed for IOP self-tonometry (RT-Home) in an outpatient department, especially in the supine position and out of office hours. Over a period of 6months unselected open-angle glaucoma patients were equipped with aRT-home device for one night each. At the beginning IOP values measured by medical personnel (RT-Home(o)) were compared with IOP measured by the patient (RT-Home(p)), as well as measured by applanation tonometry according to Goldmann (GAT). Patients also completed aquestionnaire regarding subjective comfort during use of the RT-Home. The RT-Home(o) showed abias of -1.1 mm Hg (-7.9 to 5.7 mm Hg) compared to GAT and RT-Home(p) showed abias of -1.6 mm Hg (-8.9 to 5.9 mm Hg) compared to GAT. The measurement differences between GAT and RT-Home(o) as well as RT-Home(p) showed a stong correlation with the IOP and the central corneal thickness (IOP: r = 0.481, P > 0.0001, RT-Home(o) vs. GAT; corneal thickness: r = 0.612, P < 0.0001, RT-Home(o) vs. GAT). The RT-Home(p) in a supine position showed significantly elevated IOP levels than during the day (P < 0.0001). The RT-Home showed no qualitative differences between measurements in supine and sitting positions. The RT-Home is effective and precise for use in an outpatient department to gain ageneral overview over patients' IOP out of office hours and also in the supine position. In the long term it seems possible that RT-Home can avoid hospitalization for diurnal and nocturnal IOP evaluation especially of young, mobile patients; however, interpretation of the data always requires professional knowledge.

Lentiviral Vector-Mediated Expression of Exoenzyme C3 Transferase Lowers Intraocular Pressure in Monkeys.

Primary open-angle glaucoma (POAG) is considered a lifelong disease characterized by optic nerve deterioration and visual field damage. Although the disease progression can usually be controlled by lowering the intraocular pressure (IOP), therapeutic effects of current approaches do not last long. Gene therapy could be a promising method for persistent treatment of the disease. Our previous study demonstrated that gene transfer of exoenzyme C3 transferase (C3) to the trabecular meshwork (TM) to inhibit Rho GTPase (Rho), the upstream signal molecule of Rho-associated kinase (ROCK), resulted in lowered IOP in normal rodent eyes. In the present study, we show that the lentiviral vector (LV)-mediated C3 expression inactivates RhoA in human TM cells by ADP ribosylation, resulting indisruption of the actin cytoskeleton and altered cell morphology. In addition, intracameral delivery of the C3 vector to monkey eyes leads to persistently lowered IOP without obvious signs of inflammation. This is the first report of using a vector to transduce the TM of an alive non-human primate with a gene that alters cellular machinery and physiology. Our results in non-human primates support that LV-mediated C3 expression in the TM may have therapeutic potential forglaucoma, the leading cause of irreversible blindness in humans.

The evaluation of intraocular pressure fluctuation in glaucoma subjects during submaximal exercise using an ocular telemetry sensor.

Purpose:To evaluate the effect of acute submaximal exercise on intraocular pressure (IOP) fluctuations in open-angle glaucoma (OAG) subjects using an ocular telemetry sensor (OTS, Sensimed TriggerFish®).Methods:Twelve OAG subjects aged 45–65 years with no medical limitation for exercise were included in this prospective study. A submaximal exercise test was performed using a cycle ergometer for 20 min during which OTS voltages and metabolic parameters were recorded continuously. IOP voltages taken before, during, and after exercise were compared using the Friedman test and correlations with the metabolic parameters were evaluated using the Spearman analysis.Results:In two subjects, the OTS stopped functioning after a few hours. Median OTS measurements were 37.60 mVeq 10 min before exercise [interquartile range (IQR) 137.27], 51.75 (IQR 121.2), 62.35 (IQR 123.72), 54.6 (IQR 141.3), and 59.7 mVeq (IQR 196.7) during exercise (4 time points, 5 min apart), and 50.7 (IQR 147.35) and 64.2 mVeq (IQR 103.25) 10 and 30 min after exercise and the change was statistically non-significant (P = 0.66). No correlations were found between OTS and metabolic parameters measured at the same time points (P > 0.05). Nocturnal acrophase pattern was detected in five subjects (50%), diurnal acrophase in two patients, and double-hump in two patients. Median IOP voltages in the morning, afternoon/evening, and night were 335.84, 149.15, and 341.38 mVeq, respectively (P < 0.001).Conclusion:Continuous IOP monitoring did not reveal a remarkable voltage change in OAG patients during or immediately after exercise, but nocturnal IOP peaks in half of the patients.