Relationship Between Nocturnal Intraocular Pressure Variations and Sleep Macrostructure.

PURPOSE: The purpose of this study was to characterize the relationships between nocturnal intraocular pressure (IOP) variations and sleep macrostructure in healthy subjects. METHODS: This was a cross-sectional study conducted in a center with shared expertise in chronobiology. Twelve healthy volunteers (22.3 ± 2.3 years) underwent a 24-hour IOP measurement session. The IOP variations of one eye were continuously estimated using a contact lens sensor (CLS) measuring the changes in corneal curvature related to the IOP and not requiring nocturnal awakening for measurements. The CLS measurement characteristics (mean, maximum, minimum, and amplitude) were evaluated across sleep stages (non-rapid eye movement [NREM] sleep [N1, N2, N3], REM) and assessed using polysomnography. The CLS signal measurement changes during sleep stage changes were calculated to evaluate the effects of sleep on IOP. RESULTS: A 24-hour IOP nyctohemeral rhythm was found in all subjects. During the nocturnal period, IOP signal values were significantly lower during wake stages than during REM and NREM N1, N2, and N3 sleep stages (P ≤ 0.04). The IOP signal values were significantly higher during the REM stage than during the NREM stages (P ≤ 0.03) and progressively decreased as NREM sleep deepened (P ≤ 0.04). We found a positive relationship between the micro-arousal index and the nocturnal period CLS signal SD (r = 0.76; P = 0.024) and a negative relationship between sleep efficiency and the nocturnal period CLS signal SD (r = -0.69; P = 0.041). CONCLUSIONS: Sleep micro- and macrostructure and nocturnal IOP variations are closely related in young subjects without sleep disorders. Across sleep stages, IOP is highest during REM sleep and progressively decreases as NREM sleep deepens.

Progression of visual field in patients with primary open-angle glaucoma - ProgF study 1.

PURPOSE: To evaluate the visual field rate of progression of patients with treated ocular hypertension (OHT) and primary open-angle glaucoma (POAG) in clinical practice, using the mean deviation (MD) and the visual field index (VFI). METHODS: Non-interventional cohort study. From a large multicentre database representative of the French population, 441 eyes of 228 patients with treated OHT or POAG followed up at least 6 years with Humphrey 24.2 Sita-Standard visual field examination at least twice a year were identified. From initial data, eyes were classified in five groups: 121 with OHT, 188 with early glaucoma (MD greater than -6 dB), 45 with moderate glaucoma (MD -6 to -12 dB), 41 with advanced glaucoma (MD -12 to -18 dB) and 46 with severe glaucoma (MD less than -18 dB). Rate of progression during the follow-up period was calculated using the trend analysis of the Guided Progression Analysis software. RESULTS: The mean duration of follow-up was 8.4 ± 2.7 years and the mean number of visual field, 18.4 ± 3.5. In eyes with OHT, rate of progression was -0.09 dB/year (-0.17%VFI/year). In eyes with POAG, rate of progression was -0.32 dB/year (-0.83%VFI/year) in eyes with early glaucoma, -0.52 dB/year (-1.81%VFI/year) in moderate glaucoma, -0.54 dB/year (-2.35%VFI/year) in advanced glaucoma and -0.45 dB/year (-1.97%VFI/year) in severe glaucoma. In eyes with POAG, a significant progression (p < 0.05) was detected in 159 of 320 eyes (49.7%) with trend analysis and 117 of 320 eyes (36.6%, likely progression) or 183 of 320 eyes (57.2%, possible and likely progression) with event analysis. CONCLUSIONS: Primary open-angle glaucoma is a progressive disease in the majority of patients despite cautioned treatment and follow-up. The rate of progression varies greatly among subjects.

Association of Nonarteritic Ischemic Optic Neuropathy With Obstructive Sleep Apnea Syndrome: Consequences for Obstructive Sleep Apnea Screening and Treatment.

IMPORTANCE: The prevalence of obstructive sleep apnea syndrome (OSAS) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and its influence on second eye involvement is not well known. OBJECTIVE: To evaluate the prevalence of OSAS in patients with NAION and risk factors of second eye involvement. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, we examined 118 patients with anterior ischemic optic neuropathy referred to a tertiary care center from January 1, 2003, through December 31, 2010. EXPOSURES: Patients underwent polysomnography to detect OSAS and were prospectively followed up to assess the risk of second eye involvement. MAIN OUTCOMES AND MEASURES: The prevalence of OSAS in patients with NAION and the risk of second eye involvement using survival analysis based on the presence of OSAS, indication for ventilation treatment with continuous positive airway pressure, and other potential ocular and systemic confounders. RESULTS: In 89 patients with NAION who underwent polysomnography, 67 (75%) had OSAS. Second eye involvement was found in 10 (13.7%) of 73 patients at 3 years: 8 (15.4%) of 52 patients with OSAS at 3 years and 2 (9.5%) of 21 patients without OSAS at 3 years; P = .04. In multivariate analysis, nonadherence to ventilation treatment with continuous positive airway pressure in patients with severe OSAS increased the risk of second eye involvement (hazard ratio, 5.54; 95% CI, 1.13-27.11; P = .04). CONCLUSIONS AND RELEVANCE: These results suggest that OSAS is common in patients with NAION and that polysomnography should be considered in these patients. These findings also suggest that patients with severe OSAS who are nonadherent to ventilation treatment with continuous positive airway pressure have an increased risk of second eye involvement.

The impacts of blended learning design in first year medical studies.

In the first year of medical studies in France, students prepare for a highly selective entrance exam limited by numerus clausus into the second year. We have discontinued live lectures, made maximum use of new information and communication technologies and introduced tutorials in an attempt to make the first year more equitable and to personalise teaching. The reform is based on blended learning with flipped classroom organized into a four-week cycles of different activities. Each cycle corresponds to a learning module. The teachers' and students' opinions were analysed to evaluate the reforms and allow teaching methods to be adapted accordingly. The student profiles at registration and success in the exams following the reform are described. The tutorial's notes are correlated to the final scores at the entrance exam. The keys to success seem to be modified by the reform providing greater equality of opportunity between students. The factors associated to success are baccalaureate highest grades, high School Specialisation (maths, physics or earth and life sciences) and repeating the first year class. The use of blended learning allows us to face the increase of student enrolment, and to facilitate the acceptance of these pedagogical methods for both students and teachers.

A case-control study to assess aspirin as a risk factor of bleeding in rhegmatogenous retinal detachment surgery.

PURPOSE: The purpose of this study was to evaluate the hemorrhagic risk factors during the management of primary rhegmatogenous retinal detachment (RD). METHODS: Three hundred and twenty-two patients with (n = 74) or without (n = 248) bleeding (anterior segment, choroidal, intravitreal and/or subretinal) during or after RD surgery were included in this case-control study. Exclusion criteria were: history of trauma, vitreoretinal surgery, diabetic retinopathy, and taking clopidogrel and/or a vitamin K antagonist. Univariate and multivariate analyses were performed to identify risk factors of perioperative bleeding. RESULTS: Aspirin was not significantly associated with bleeding complications during or after surgery (p = 0.8). Scleral buckling (with cryotherapy and gas tamponnade) was performed in 47 % of the cases and pars plana vitrectomy in 53 % of the cases. Independent risk factors of perioperative hemorrhage were the number of cryotherapy impacts (odds ratio =1.12 [1.06; 1.20], 95 % confidence interval), transscleral drainage (OR = 4.22 [1.62; 10.98]), and use of pars plana vitrectomy (OR = 3.39 [1.36; 8.47]). Bleeding complications were associated with a lower single-operation anatomical success rate (74 % vs 84 %, p = 0.03). There was also a trend toward an association between bleeding complications, a higher total number of RD recurrences (0.19 ± 0.5 in the non-bleeding group vs 0.34 ± 0.6, p = 0.06), and a lower final visual acuity (0.5 ± 0.6 logMAR vs 0.7 ± 0.7, p = 0.09). CONCLUSION: This case-control study suggests that aspirin is not a major risk factor of hemorrhagic complications during and after RD surgery. Perioperative bleeding leads to a lower single-operation anatomic success rate.

Multifocal electroretinogram in birdshot chorioretinopathy.

PURPOSE: To characterize multifocal electroretinogram parameters in patients with birdshot chorioretinopathy. METHODS: Twenty-eight patients with birdshot chorioretinopathy consecutively included from 2006 to 2011 were matched to 27 healthy subjects for age, axial length, and lens status. Multifocal electroretinogram was prospectively evaluated using the Vision Monitor system. RESULTS: Birdshot chorioretinopathy eyes differed significantly from healthy eyes by a decrease in mean root mean square values (-24.7%), P1 (-17.3%) and N2 (-27.5%) amplitude, and the P1/N1 ratio (-26.3%) as well as an increase in N1 (8.7%) and P1 (5.4%) implicit time (IT). An effect of the degree of eccentricity (5 zones) was found for root mean square (P < 0.001), P1 (P < 0.001) and N2 (P < 0.001) amplitude, and P1 IT (P < 0.001). Root mean square, the P1/N1 ratio, P1 and N2 amplitudes, P1 and N1 ITs were significantly correlated with visual acuity, mean defect of visual field, foveal threshold, and color vision score. The fluorescein angiographic score was significantly correlated to N1 and N2 amplitudes and N1 IT. CONCLUSION: Amplitudes and ITs of the multifocal electroretinogram parameters are impaired in patients with birdshot chorioretinopathy and are well correlated with other anatomical and functional tests. Periodic testing could guide the immunosuppressive treatment.

Comparison of intraocular pressure measurements with the Reichert Pt100, the Keeler Pulsair Intellipuff portable noncontact tonometers, and Goldmann applanation tonometry.

PURPOSE: The aim of this study was to compare intraocular pressure (IOP) measurements using 2 portable tonometers, the Keeler Pulsair Intellipuff and the Reichert PT100, with Goldmann applanation tonometry (GAT). MATERIALS AND METHODS: Prospective cross-sectional study was conducted on normotensive and hypertensive patients recruited from the outpatient clinic of the University Hospital of Grenoble. IOP was measured using 2 portable noncontact tonometers (NCTs) and GAT in one eye of each patient in a random order. Central corneal thickness was measured with the Accutome PachPen Pachymeter. The Wilcoxon and t tests were used to compare the differences between tonometers, the Pearson and the Spearman correlation tests to evaluate the correlation among the methods, and the Bland-Altman plots to evaluate the agreement among the methods. Intraclass correlation coefficient (ICC) was used to evaluate the agreement among the methods in normotensive and hypertensive patients separately. RESULTS: A total of 137 eyes of 137 patients were included, 104 normotensive and 33 hypertensive eyes. We found an excellent agreement between PT100 and GAT (ICC=0.77) and between Intellipuff and GAT (ICC=0.75) in normotensive patients. We found a fair to good agreement (ICC=0.67) between PT100 and GAT in hypertensive patients. The agreement we found between Intellipuff and GAT was also excellent in hypertensive patients (ICC=0.86). Both NCTs significantly overestimated IOP measurements compared with GAT in normotensive and hypertensive eyes (mean of the differences between PT100 and GAT: 1.3±2.1 and 8.1±4.6 mm Hg in normotensive and in hypertensive patients, respectively (P<0.05), and between Pulsair Intellipuff and GAT: 1.5±1.8 and 2.3±4.8 mm Hg in normotensive and in hypertensive patients, respectively (P<0.05). CONCLUSIONS: The 2 NCTs agree well with GAT in normotensive patients. The Pulsair Intellipuff also agrees well with GAT in hypertensive patients.

Hourly awakening vs continuous contact lens sensor measurements of 24-hour intraocular pressure: effect on sleep macrostructure and intraocular pressure rhythm.

IMPORTANCE: All studies of 24-hour intraocular pressure (IOP) rhythm conducted to date have used repeated IOP measurements requiring nocturnal awakenings, potentially disturbing sleep macrostructure. OBJECTIVE: To evaluate the effects on sleep architecture and IOP rhythm of hourly awakening vs a contact lens sensor (CLS) to continuously monitor IOP without awakening. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study at a referral center of chronobiology among 12 young healthy volunteers, with a mean (SD) age of 22.3 (2.3) years. INTERVENTIONS: Volunteers underwent two 24-hour IOP measurement sessions during a 2-month period. The eye order and session order were randomized. During one session, the IOP of the first eye was continuously monitored using a CLS, and the IOP of the fellow eye was measured hourly using a portable noncontact tonometer (session with nocturnal hourly awakening). During the other session, the IOP of the first eye was continuously monitored using a CLS, and the IOP of the fellow eye was not measured (session without nocturnal awakening). Overnight polysomnography was performed during the 2 sessions. MAIN OUTCOMES AND MEASURES: A nonlinear least squares, dual-harmonic regression analysis was used to model the 24-hour IOP rhythm from the CLS data. Comparisons of acrophase, bathyphase, amplitude, and the midline estimating statistic of rhythm were used to evaluate the effect of hourly awakening on IOP rhythm. To evaluate the effects of hourly awakening on sleep architecture, comparisons of sleep structure were used, including total sleep period, rapid eye movement, wake after sleep onset, absolute and relative total sleep time, and non-rapid eye movement sleep (N1, N2, and N3). RESULTS: A 24-hour IOP rhythm was found in all individuals for the sessions with and without awakening (P < .05). Hourly awakening for nocturnal IOP measurements increased wake after sleep onset (P = .04) but did not seem to change total sleep time, total sleep period, sleep efficiency, or slow-wave and rapid eye movement sleep stage duration (P > .30). Hourly awakening during noncontact tonometer IOP measurements did not seem to alter the mean variables of the 24-hour IOP pattern evaluated using CLS, including signal, maximum signal, minimum signal, acrophase, and bathyphase (P > .15). CONCLUSION AND RELEVANCE: The 24-hour IOP rhythms seem to be unaffected by hourly nocturnal awakening for IOP measurements in young healthy individuals.

Long-term reproducibility of diurnal intraocular pressure patterns in patients with glaucoma.

PURPOSE: To evaluate the long-term reproducibility of diurnal intraocular pressure (IOP) patterns in patients with primary open-angle glaucoma (POAG). DESIGN: Database study. PARTICIPANTS: Ninety-two patients with POAG. METHODS: We reviewed the records of patients with POAG who underwent 4 diurnal IOP curve measurements 6 months apart with Goldmann applanation tonometry recorded in the sitting position at 9 am, 10 am, 11 am, noon, 2 pm, 3 pm, 4 pm, and 5 pm. MAIN OUTCOME MEASURES: Intervisit agreement of IOP by time point and of diurnal IOP curve parameters (mean, standard deviation, range, maximum, maximum hour, minimum, and minimum hour) was assessed using intraclass correlation coefficients (ICCs). Analyses were performed in all eyes and separately in eyes with and without hypotensive medications, and in eyes naïve and non-naïve of filtering surgery. RESULTS: Between-visit agreement of IOP values at each time point was generally poor, with ICCs ranging from 0.26 to 0.77 in all patients (1 of 8 time points with ICC >0.75), from -0.07 to 0.60 in patients without hypotensive medications (zero time points with ICC >0.75), from 0.29 to 0.80 in patients with hypotensive medications (3 time points with ICCs >0.75), from 0.21 to 0.68 in filtering surgery-naïve patients (zero time points with ICC >0.75), and from 0.21 to 0.87 in patients with previous filtering surgeries (5 time points with ICCs >0.75). The predictive value of the first diurnal IOP curve to estimate the risk of IOP fluctuations during the 3 subsequent curves was limited (only 6.4% of the patients with an IOP range ≥30% of the mean IOP on the first curve presented similar fluctuations on the 3 subsequent curves; 77.1% of the patients who did not have an IOP range ≥30% of the mean IOP on the first curve had an IOP range ≥30% of the mean IOP on at least 1 of the 3 subsequent curves). CONCLUSIONS: Patients with POAG do not manifest a reproducible diurnal IOP pattern from month to month. A single diurnal IOP curve in patients with POAG poorly characterizes IOP fluctuations and has limited value in clinical practice.

Anterior segment biometry using spectral-domain optical coherence tomography.

PURPOSE: To compare the anterior chamber and anterior chamber angle measurements obtained with spectral-domain anterior segment optical coherence tomography (AS-OCT) and time-domain AS-OCT. METHODS: The anterior chamber of healthy participants was imaged with spectral-domain AS-OCT (Casia SS-1000; Tomey, Nagoya, Japan) and time-domain AS-OCT (Visante; Carl Zeiss Meditec, Dublin, CA). Central corneal thickness (CCT), anterior chamber depth (ACD), angle opening distance at 500 and 750 µm (AOD 500 and AOD 750), trabecular iris space area at 500 and 750 µm (TISA 500 and TISA 750), and scleral spur angle were measured. The intraclass correlation coefficients (ICCs) were calculated. The Pearson correlation test was used to evaluate the correlation between the measurements and Bland-Altman plots to evaluate the agreement. RESULTS: One hundred one eyes of 101 healthy participants were analyzed. Excellent repeatability was found with both devices for CCT, AOD 500, AOD 750, TISA 750, and scleral spur angle (ICC = 0.90 to 0.98 and 0.89 to 0.97, respectively) and excellent to moderate repeatability was found for TISA 500 (ICC = 0.68 to 0.97 and 0.70 to 0.93, respectively). For all parameters, Casia and Visante measurements were significantly correlated (r = 0.76 to 0.98; P < .02). ACD measured with the Casia was significantly larger (mean difference = 0.12 ± 0.08 mm; P < .0001), and the scleral spur angle measured with the Casia was significantly lower (mean difference = 4.85° ± 5.30°; P < .01). There were nonsignificant differences between the devices for the other parameters (P > .06). CONCLUSIONS: Both Casia and Visante AS-OCT demonstrate high repeatability. Except for the ACD and scleral spur angles, the two devices show good agreement.

Structure-function relationships with spectral-domain optical coherence tomography retinal nerve fiber layer and optic nerve head measurements.

PURPOSE: To evaluate the regional structure-function relationship between visual field sensitivity and retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements using spectral-domain optical coherence tomography (SD-OCT). METHODS: Prospective cross-sectional study conducted on patients with glaucoma, suspected glaucoma, and healthy subjects. Eyes were tested on Cirrus OCT and standard achromatic perimetry. RNFL thickness of 12 peripapillary 30° sectors, neuroretinal rim thickness extracted from 36 neuroretinal rim scans, and Bruch membrane opening minimum rim width (BMO-MRW)-a recently defined parameter-extracted from 36 neuroretinal rim scans were obtained. Correlations between peripapillary RNFL thickness, neuroretinal rim thickness, all six sectors of BMO-MRW, and visual field sensitivity in the six corresponding areas were evaluated using logarithmic regression analysis. Receiver operating curve areas were calculated for each RNFL, ONH, and macular ganglion cell analysis parameter. RESULTS: We included 142 eyes of 142 subjects. The correlations (r(2)) between RNFL thickness, Cirrus-based neuroretinal rim thickness, BMO-MRW and visual field sensitivity ranged from 0.07 to 0.60, 0.15 to 0.49, and 0.24 to 0.66, respectively. The structure-function correlations were stronger with BMO-MRW than with Cirrus-based neuroretinal rim thickness. The largest areas under the receiver operating curve were seen for rim area (0.926 [95% confidence interval 0.875, 0.977]; P < 0.001) in eyes with glaucoma and for average RNFL (0.863 [0.769, 0.957]; P < 0.01) in eyes with suspected glaucoma. CONCLUSIONS: The structure-function relationship was significantly stronger with BMO-MRW than other ONH SD-OCT parameters. The best diagnostic capabilities were seen with rim area and average RNFL.

Twenty-four-hour rhythm of ocular perfusion pressure in non-arteritic anterior ischaemic optic neuropathy.

PURPOSE: In non-arteritic anterior ischaemic optic neuropathy (NAAION) patients, circulatory insufficiency within the optic nerve has previously been hypothesized to be related to nocturnal systemic hypotension. The main objective of this prospective cohort study was to investigate the nyctohemeral variations in ocular perfusion pressure (OPP) in NAAION patients. METHODS: In 20 patients with NAAION, the intraocular pressure (IOP) was measured using the Tono-Pen XL(™) electronic tonometer every hour for 24 hr. Blood pressure (BP) was evaluated over 24 hr. Mean OPP was calculated with the following formula: OPP sitting position = (0.74 × mean BP) - IOP and OPP lying position = (0.84 × mean BP) - IOP. A nonlinear least squares dual-harmonic regression analysis approach was used to model the 24-hr rhythms of OPP data. RESULTS: On average, a 24-hr amplitude of 4.7 ± 2.6 mmHg was found for OPP. The patients were classified as either having a diurnal OPP rhythm (i.e. with a diurnal acrophase, 10% of the cases), a nocturnal OPP rhythm (45%) or absence of OPP rhythm (45%). Four patients had a nocturnal reduction in OPP (mean, -11%). CONCLUSION: The physiological nocturnal rhythm of OPP was maintained in 45% of the NAAION patients. The nocturnal reduction in OPP seen in 20% of the patients was within the range of OPP where optic nerve blood flow autoregulation is still fully operative. A high prevalence of obstructive sleep apnoea syndrome in our population (71%) may explain the low frequency of systemic nocturnal hypotension.

Effect of overnight wear of the Triggerfish(®) sensor on corneal thickness measured by Visante(®) anterior segment optical coherence tomography.

PURPOSE: To evaluate the effect of overnight wear of the Triggerfish(®) contact lens sensor (CLS) on central corneal thickness (CCT) using the Visante(®) anterior segment optical coherence tomography (AS-OCT). METHODS: Twelve healthy subjects were studied in a sleep laboratory. An ophthalmic examination including ultrasonic CCT, corneal topography, specular microscopy and AS-OCT CCT was performed. Starting at 7 pm, the Triggerfish(®) CLS was fitted on one randomly selected eye. Similar AS-OCT measurements were taken on both eyes every 2 hr from 8 pm to 8 am. The CLS was removed just after the 8 am measurement session. Measurements were repeated at 9 am. RESULTS: Twenty-four eyes of 12 subjects were studied (mean age, 22.1 ± 2.4 years; four men/eight women). CCT significantly increased during the night in both CLS and control eyes (p < 0.01). The maximal change was +4.4 ± 1.7% in the CLS eyes and +2.9 ± 1.8% in the control eyes (p < 0.05). Throughout the night, CCT significantly increased more in eyes with CLS than in control eyes (p < 0.05). There were significantly more corneal curvature irregularities after overnight wear of the CLS than in the control eye: +1.63 Dioptre (D) versus -0.02 D in the 3-mm central zone and +3.17 D versus +0.01 D in the 5-mm central zone (p < 0.01). CONCLUSION: CCT and corneal curvature irregularities increased slightly but significantly more in eyes with the Triggerfish(®) CLS than in control eyes during overnight wear. Further studies are required to determine whether the corneal curvature changes modify the signal recorded by the sensor.

Principles and applications of molecular biology techniques for the microbiological diagnosis of acute post-operative endophthalmitis.

The systematic microbiological evaluation of endophthalmitis allows the confirmation of the infectious nature of the disease and the possible adaptation of treatment at the individual level and, at the collective level, the epidemiological characterization of the bacterial spectrum of endophthalmitis. Long reserved for research, the use of molecular biology techniques to complement conventional culture techniques has become important for the diagnosis of endophthalmitis in recent years. These new diagnostic techniques are particularly useful for the microbiological study of bacteria that are difficult or impossible to grow because of their intrinsic properties, their presence in only a small inoculum, their sequestration on prosthetic materials, or their inactivation by prior antibiotic treatment. These techniques are based on the polymerase chain reaction (PCR), which allows the amplification and detection of extracted bacterial deoxyribonucleic acid (DNA) that is initially present in minute quantities in an ocular sample. In practice, these conventional or real-time PCRs allow either the a priori detection of bacterial DNA (universal PCR) or the identification of a specific DNA fragment of a bacterial genus or species (specific PCR). New techniques of PCR will allow more rapid bacterial identification and also characterization of genotypic properties, such as genes of virulence or antibiotic resistance.

Continuous response of optic nerve head blood flow to increase of arterial blood pressure in humans.

PURPOSE: This study investigates the effect of increased ocular perfusion pressure (OPP) on optic nerve head (ONH) hemodynamics. METHODS: In 21 healthy subjects, the increase in arterial blood pressure (BP), measured continuously using a pneumatic transcutaneous sensor, was produced by isometric exercise consisting of 2 minutes of hand-gripping. ONH blood flow parameters-namely the velocity (Vel), number (Vol), and flux (F) of red blood cells-were measured using the laser Doppler flowmeter (LDF). RESULTS: In those 14 healthy subjects who exhibited a similar increase in BP to handgrip superior to 30% of baseline BP, group average increases of BP and OPP amounted to 34% ± 3% (SEM) and 43% ± 3%, respectively. The increase in F of 19% ± 8%, resulting from an increase in Vel (17% ± 7%) and Vol (6% ± 7%), was significantly less than predicted for a passive autoregulatory response, as revealed also by the increase in vascular resistance (R = OPP/F). Spearman test of linear correlations between F and time during handgrip led to the identification of one group of eight subjects (with a stable F) and one group of six subjects (with an increase in F). A closed-loop gain (G) of the regulatory process, defined as G = 1 - {(F - Fbl)/Fbl}/{(OPP - OPPbl)/OPPbl}, was found to be rather independent from the OPP, with an average value 0.7 ± 0.07. G was 0.83 ± 0.06 for the group of eight subjects with stable F and 0.3 ± 0.15 for the group of six subjects with F increasing with the OPP. CONCLUSIONS: The continuous recording of both BP and LDFs represents a novel and more precise approach to the characterization of ONH hemodynamics during isometric exercise, especially useful in the future for patients with ocular diseases. The efficiency of the ONH blood flow autoregulation appears to vary significantly between healthy subjects. (ClinicalTrials.gov number, NCT00874913.).