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Purpose Detecting glaucoma damage progression is an essential component of follow-ups in glaucoma patients. It is still unclear which of the currently available and routinely used parameters of glaucoma damage heralds the loss of retinal ganglion cells first. We analysed local hospital data on primary open-angle glaucoma (POAG) patients and looked for correlations between the optical coherence tomography (OCT) structural, OCT angiography (OCTA), and visual field (VF) parameters. Patients and Methods Results of eye examinations of POAG patients at baseline, 6 months, and 12 months were analysed. Inclusion criteria were, apart from the diagnosis of POAG, availability and quality of all modalities of examination data and no surgical intervention on the eyes during the observation period. Data on VF mean defect (MD), OCT peripapillary nerve fibre layer (RNFL), OCT macular ganglion cell layer, and OCTA, peripapillary and in the macula, were parameters of interest. Correlations of structural (OCT and OCTA) on one, and functional parameters (VF MD) on the other side, at baseline and as changing over time (first 6 months vs. second 6 months) were performed. Results All together, data from 78 eyes of 78 POAG patients were included in the analysis. Correlations at baseline were all highly significant (Spearmanʼs r-coefficients between 0.31 and 0.8, all p 0.05). Conclusion Whereas a robust correlation was observed at baseline between the structural (OCT and OCTA) and functional (VF MD) parameters, none of the examination modality could predict a change in the other modalities during the 1-year period. Results confirm the necessity of regularly performing both the structural and functional examinations in our glaucoma patients.

Background Lowering intraocular pressure (IOP) is a mainstay of glaucoma therapy. It is, however, still an open question whether a comparable level of long-term IOP lowering achieved by different medications results in comparable protection for the retinal ganglion cells. The purpose of this study was to retrospectively analyze glaucoma damage progression in two cohorts of primary open-angle glaucoma patients with different and unchanged therapy over a period of 3 years, and the main objective of this study was to determine possible differences in terms of structural [retinal nerve fiber layer thickness (RNFL)] and functional [visual field (VF)] outcome. Patients and Methods The retrospective observational cohort analysis compared two differently treated groups of glaucoma patients with their original, at study entry, topical therapy unchanged over 3 years. The main endpoint was the time course of RNFL thickness and VF mean defect (MD). Results Twenty-one eyes were included in each group. The first group (21 eyes) was on a fixed combination of timolol and dorzolamide twice a day and the second group on one drop of prostaglandin analog, either latanoprost alone (15 eyes) or travoprost alone (6 eyes), in an unchanged regimen over a period of 3 years. IOP in mmHg at baseline and at 36 months was 11.9 ± 2.4 and 13.0 ± 2.1 in the first, and 12.9 ± 3.0 and 14.1 ± 3.2 in the second group, respectively. RNFL thickness values in micrometers were at baseline and at 36 months 77.8 ± 12.3 and 76.6 ± 15.2 in the first, and 77.5 ± 15.2 and 72.8 ± 14.5 in the second group, respectively. VF MD in dB were 1.7 ± 2.5 and 1.2 ± 2.9 in the first, and 0.9 ± 2.3 and 0.7 ± 2.6 in the second group, respectively. Conclusion Both groups had comparable baseline, as well as mean overall IOP. However, the course of IOP levels over time was different in the two groups, showing earlier and more pronounced long-term drift in the prostaglandin analog-treated group. RNFL thickness was comparable at baseline, however, RNFL thinning over time was more pronounced in the prostaglandin analog-treated group. There were no statistical differences between the groups in terms of VF MD at baseline and over time.

Background There is an unmet need for reliable and sensitive measures for better monitoring people with multiple sclerosis (PwMS) to detect disease progression early and adapt therapeutic measures accordingly. Objective To assess reliability of extracted features and meaningfulness of 11 tests applied through a smartphone application (“dreaMS”). Methods PwMS (age 18–70 and EDSS ≤ 6.5) and matched healthy volunteers (HV) were asked to perform tests installed on their smartphone once or twice weekly for 5 weeks. Primary outcomes were test–retest reliability of test features (target: intraclass correlation [ICC] ≥ 0.6 or median coefficient of variation [mCV] < 0.2) and reported meaningfulness of the tests by PwMS. Meaningfulness was self-assessed for each test on a 5-point Likert scale (target: mean score of > 3) and by a structured interview. ClinicalTrials.gov Identifier: NCT04413032. Results We included 31 PwMS (21 [68%] female, mean age 43.4 ± 12.0 years, median EDSS 3.0 [range 1.0–6.0]) and 31 age- and sex-matched healthy volunteers. Out of 133 features extracted from 11 tests, 89 met the preset reliability criteria. All 11 tests were perceived as highly meaningful to PwMS. Conclusion The dreaMS app reliably assessed features reflecting key functional domains meaningful to PwMS. More studies with longer follow-up are needed to prove validity of these measures as digital biomarkers in PwMS.

It has been observed that an intraocular pressure (IOP) altering intervention in one eye is followed by a consensual response in the untreated fellow eye. The underlying mechanisms remain unclear. Involvement of neuronal, cytokine, and hormonal regulation of aqueous humor dynamics, as well as improved treatment adherence or systemic absorption of topically administered medical compounds, have been suggested. Our aim was to investigate the short-term effects of unilateral micropulse transscleral laser therapy on IOP in the fellow eye. All medical records of glaucoma patients who underwent micropulse transscleral laser therapy in a tertiary referral center between May 2019 and February 2023 were collected and analyzed. We found a significant reduction in IOP in the treated eyes, indicating successful treatment. In the fellow eyes, despite not having changed any of the pharmacological IOP-reducing therapies, a significant reduction in IOP from 17.0 ± 5.1 mmHg to 13.5 ± 4.4 mmHg (p < 0.01) was observed. This reduction was, however, short-term and reached statistical significance on the first postoperative day only. Our findings support the concept of consensual inter-eye responses to unilateral IOP changes. Further research is warranted to elucidate the mechanisms underlying this phenomenon.

Arterial hypertension is a global health burden that affects vascular structure and function. Assessment of endothelial function can improve cardiovascular (CV) risk stratification. Exercise treatment reduces over all CV risk and improves vascular health. However, it is still not clear which part of the vascular bed is most sensitive to exercise treatment in patients with CV risk. This study aimed to investigate the effects of an 8-week walking based and supervised high-intensity interval training (HIIT) on macro- and microvascular endothelial function as add-on therapy in patients with arterial hypertension.; Forty patients (mean age 58 ± 7 years) treated for arterial hypertension were randomized in the HIIT (3×/week) or control group (CG) receiving standard physical activity recommendations. Arteriolar (aFID) and venular (vFID) flicker light-induced dilatation for retinal microvascular and flow-mediated dilatation (FMD) for macrovascular endothelial function were assessed. In addition, standardized assessments of patients' characteristics were performed before and after 8 weeks.; Both groups reduced weight and body mass index but only the HIIT group reduced body fat, visceral fat, and increased peak oxygen uptake after 8 weeks. The control group reduced diastolic blood pressure. No blood pressure changes were found in the HIIT group. Arteriolar FID increased in the HIIT group independently of confounders (pre: 2.40 ± 0.98%, post: 3.19 ± 1.31%, p < 0.001) but not in the control group (pre: 3.06 ± 1.50%, post: 2.90 ± 1.46%, p = 0.280). No changes were found for FMD in either group.; Arteriolar FID was found to be a sensitive vascular biomarker to assess exercise-induced microvascular improvements even in a short time setting of an 8-week exercise therapy with HIIT. Short-term exercise training affects microvascular endothelial function but not large artery endothelial function. Thus, retinal aFID appears to be a sensitive biomarker to detect short-term exercise efficacy on a vascular level. Dynamic retinal vessel analysis as a diagnostic approach may prove to be an ideal candidate vascular biomarker to monitor treatment effects of exercise in patients with hypertension on top of standard clinical care and may support clinical decision-making in the future.

IntroductionHypertension is a global healthcare burden that affects the structure and function of the macrocirculation and microcirculation and induces disease-specific end-organ damage. Vascular biomarkers are essential to timely diagnose this end-organ damage to improve cardiovascular (CV) risk stratification and medical decision making. Exercise therapy is an effective means to improve vascular health and reduce overall CV risk. However, it is still not clear whether high-intensity interval training (HIIT) is recommendable for patients with hypertension to reduce blood pressure, increase cardiorespiratory fitness and ameliorate vascular health.Methods and analysisThe ‘Hypertension and retinal microvascular dysfunction’ trial will investigate macrovascular and microvascular impairments in hypertensive patients compared with healthy controls to investigate hypertension-induced end-organ damage by using gold-standard methods as well as newly developed unique retinal microvascular biomarkers. In addition, this trial will investigate the reversibility of retinal end-organ damage by assessing the effects of an 8-week supervised and walking based HIIT on blood pressure, cardiorespiratory fitness as well as macrovascular and microvascular health, compared with a control group following standard physical activity recommendations. Primary outcome will be the arteriolar-to-venular diameter ratio. Secondary outcomes will be arteriolar and venular diameters as well as the flicker-light-induced dilation. Further outcomes will be other retinal microvascular biomarkers, flow-mediated dilation of the brachial artery as well as blood pressure, cardiorespiratory fitness, microalbuminuria, hypertensive retinopathy and classical CV risk markers. Analysis of variance and analysis of covariance will be used to investigate group differences between healthy controls and hypertensive patients and training effects in hypertensive patients, respectively.Ethics and disseminationThe Ethics Committee of Northwestern and Central Switzerland approved this study (EKNZ-2021-00086). All participants will give informed consent.Trial registration numberNCT04763005.

To assess the efficacy of tumor necrosis factor-alpha inhibitors (TNFi) on uveitic macular edema (ME) unresponsive to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).This multicenter retrospective study included patients with uveitic ME persisting despite csDMARDs. The effect of an additional TNFi on central retinal thickness (CRT), best corrected visual acuity (BCVA) and corticosteroid need was evaluated.Thirty-five eyes (26 patients, mean age 42.9 ± 15.2 years) were included. CRT decreased from 425 ± 137 µm to 294 ± 66 µm (The addition of a TNFi resulted in an improvement of CRT and BCVA for up to 4 years in uveitic ME but rescue treatments were needed for some patients.

Several new implant devices have recently been introduced to glaucoma surgery using various techniques for reducing intraocular pressure (IOP). Two implants introduced during the past couple of years, XEN45 and PreserFlo Microshunt, are both designed to control subconjunctival filtration. There are two Swiss multicenter studies that collected the data retrospectively to analyze the efficacy and safety of these two devices separately. In this study, we report the analysis of the combined data subset from the University Hospital of Basel.The XEN45 implantation technique was introduced to Basel University Hospital in 2016 and PreserFlo Microshunt in 2018. Sixty operated patients, thirty in each group, were operated on by one surgeon, clinically followed up, and their data retrospectively analyzed from medical records. Only standalone procedures, without combined phacoemulsification, were considered in this analysis; the lens status, however, was neither an inclusion nor an exclusion criterion. Further inclusion criteria were the diagnosis of open-angle glaucoma, no previous glaucoma surgery, other than laser trabeculoplasty, and complete medical records during the 12 months of follow-up. IOP reduction during a 12-month postoperative period was the primary outcome measure as well as the number of IOP reducing drugs. The number of subsequent surgical interventions and complications/adverse events are descriptively reported.Patient age, gender, ophthalmological diagnosis, and initial preoperative IOP were well balanced between the two groups. Postoperative IOP course was comparable between the two methods for the first 12 months. IOP measurements were taken preoperatively and then on the first postop day, week 1, month 1, and months 3, 6, and 12 for the PreserFlo Microshunt vs. XEN45 (mmHg): 23.6 vs. 24.9, 9.0 vs. 8.9, 11.4 vs. 10.6, 13.0 vs.18.3, 16.8 vs.15.1, 15.9 vs.15.0, and 15.4 vs.14.5, respectively. IOP reducing medications were also comparable between the two groups. The study showed that subsequent interventions were more frequent in the XEN45 (13) than in the PreserFlo Microshunt group (7).Both methods demonstrate satisfactory IOP control within a 12-month postoperative period with practically no serious adverse events/complications, but with relatively high numbers of subsequent interventions (needlings), particularly in the XEN45 group.In den letzten Jahren haben einige neue Glaukomimplantate den Weg auf den Markt und in die Augenkliniken gefunden, mit unterschiedlicher Methodik zur Augendrucksenkung (IOD-Senkung). Zwei dieser Implantate, XEN45 und PreserFlo Microshunt, leiten die Kammerflüssigkeit subkonjunktival ab. Zwei voneinander unabhängige, multizentrische Schweizer Studien befassen sich mit der Effizienz und Sicherheit dieser beiden Methoden. Diese Erhebung berichtet über die Zwischenergebnisse einer retrospektiven Subanalyse, welche die Daten beider Methoden vom Augenspital Basel kombiniert.XEN45-Implantationstechnik wurde in Basel 2016, PreserFlo Microshunt 2018 eingeführt. 60 Patienten wurden von einem Chirurgen operiert, danach klinisch nachkontrolliert und ihre Daten retrospektiv via Aktenstudium analysiert. Es wurden Patienten mit Glaukomoperationen ohne Kombination mit einer Kataraktoperation berücksichtigt; der Linsenstatus (phak/pseudophak) war weder Einschluss- noch Ausschlusskriterium. Einschlusskriterien waren die Diagnose eines Offenwinkelglaukoms, keine vorausgegangene Glaukomchirurgie, außer der Lasertrabekuloplastik, und vollständige klinische Patientenakten während der ersten 12 postoperativen Monate. In den Subgruppen wurden die konsekutiven Daten von jeweils 30 Patienten, welche die o. g. Kriterien erfüllt hatten, eingeschlossen. Analysiert wurden die postoperativen IOD-Werte, Anzahl der drucksenkenden Medikation und die eventuellen nachfolgenden Interventionen.Alter, Geschlechterverteilung, Augendiagnosen und präoperativer IOD waren vergleichbar zwischen den beiden Interventionsgruppen – ebenso wie der postoperative IOD-Verlauf in beiden Gruppen. Die IOD-Werte in mmHg präoperativ/am 1. postoperativen Tag/Woche 1/Monate 1/3/6/12 waren jeweils für PreserFlo Microshunt und XEN45 wie folgt: 23,6 vs. 24,9; 9,0 vs. 8,9; 11,4 vs. 10,6; 13,0 vs. 18,3; 16,8 vs.15,1; 15,9 vs. 15,0; 15,4 vs. 14,5. Die Anzahl der IOD-senkenden Medikamente war postoperativ zwischen den 2 Gruppen ausbalanciert; die Anzahl der nachträglichen Interventionen war höher in der XEN45- (13) als in der PreserFlo-Microshunt-Gruppe (7).Beide Methoden haben während des Beobachtungszeitraums von 12 Monaten eine gute Kontrolle des Augendrucks mit wenigen Nebenwirkungen erbracht. Eine Anzahl an kleineren, nachträglichen Interventionen (Needlings) war in beiden Gruppen notwendig, insbesondere in der XEN45-Gruppe.

BackgroundOcular toxoplasmosis is common across all regions of the world. Understanding of the epidemiology and approach to diagnosis and treatment have evolved recently. In November 2020, an international group of uveitis-specialised ophthalmologists formed the International Ocular Toxoplasmosis Study Group to define current practice.Methods192 Study Group members from 48 countries completed a 36-item survey on clinical features, use of investigations, indications for treatment, systemic and intravitreal treatment with antiparasitic drugs and corticosteroids, and approach to follow-up and preventive therapy.ResultsFor 77.1% of members, unilateral retinochoroiditis adjacent to a pigmented scar accounted for over 60% of presentations, but diverse atypical presentations were also reported. Common complications included persistent vitreous opacities, epiretinal membrane, cataract, and ocular hypertension or glaucoma. Most members used clinical examination with (56.8%) or without (35.9%) serology to diagnose typical disease but relied on intraocular fluid testing—usually PCR—in atypical cases (68.8%). 66.1% of members treated all non-pregnant patients, while 33.9% treated selected patients. Oral trimethoprim–sulfamethoxazole was first-line therapy for 66.7% of members, and 60.9% had experience using intravitreal clindamycin. Corticosteroid drugs were administered systemically by 97.4%; 24.7% also injected corticosteroid intravitreally, almost always in combination with an antimicrobial drug (72.3%). The majority of members followed up all (60.4%) or selected (35.9%) patients after resolution of acute disease, and prophylaxis against recurrence with trimethoprim–sulfamethoxazole was prescribed to selected patients by 69.8%.ConclusionOur report presents a current management approach for ocular toxoplasmosis, as practised by a large international group of uveitis-specialised ophthalmologists.

Background: Risdiplam is an orally administered therapy that modifies pre-mRNA splicing of the survival of motor neuron 2 (SMN2) gene and is approved for the treatment of spinal muscular atrophy. The FIREFISH study is investigating the safety and efficacy of risdiplam in treated infants with type 1 spinal muscular atrophy versus historical controls. The primary endpoint of part 2 of the FIREFISH study showed that infants with type 1 spinal muscular atrophy attained the ability to sit without support for at least 5 s after 12 months of treatment. Here, we report on the safety and efficacy of risdiplam in FIREFISH part 2 over 24 months of treatment. Methods: FIREFISH is an ongoing, multicentre, open-label, two-part study. In FIREFISH part 2, eligible infants (aged 1-7 months at enrolment, with a genetically confirmed diagnosis of spinal muscular atrophy, and two SMN2 gene copies) were enrolled in 14 hospitals in ten countries across Europe, North America, South America, and Asia. Risdiplam was orally administered once daily at 0·2 mg/kg for infants between 5 months and 2 years of age; once an infant reached 2 years of age, the dose was increased to 0·25 mg/kg. Infants younger than 5 months started at 0·04 mg/kg (infants between 1 month and 3 months old) or 0·08 mg/kg (infants between 3 months and 5 months old), and this starting dose was adjusted to 0·2 mg/kg once pharmacokinetic data were available for each infant. The primary and secondary endpoints included in the statistical hierarchy and assessed at month 12 have been reported previously. Here we present the remainder of the secondary efficacy endpoints that were included in the statistical hierarchy at month 24: the ability to sit without support for at least 30 s, to stand alone, and to walk alone, as assessed by the Bayley Scales of Infant and Toddler Development, third edition gross motor subscale. These three endpoints were compared with a performance criterion of 5% that was defined based on the natural history of type 1 spinal muscular atrophy; the results were considered statistically significant if the lower limit of the two-sided 90% CI was above the 5% threshold. FIREFISH is registered with ClinicalTrials.gov, NCT02913482. Recruitment is closed; the 36-month extension period of the study is ongoing. Findings: Between March 13 and Nov 19, 2018, 41 infants were enrolled in FIREFISH part 2. After 24 months of treatment, 38 infants were ongoing in the study and 18 infants (44% [90% CI 31-58]) were able to sit without support for at least 30 s (p

BACKGROUND Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood. METHODS We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA. RESULTS A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P

Background: Type 1 spinal muscular atrophy is a rare, progressive neuromuscular disease that is caused by low levels of functional survival of motor neuron (SMN) protein. Risdiplam is an orally administered, small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein. Methods: We report the results of part 1 of a two-part, phase 2-3, open-label study of risdiplam in infants 1 to 7 months of age who had type 1 spinal muscular atrophy, which is characterized by the infant not attaining the ability to sit without support. Primary outcomes were safety, pharmacokinetics, pharmacodynamics (including the blood SMN protein concentration), and the selection of the risdiplam dose for part 2 of the study. Exploratory outcomes included the ability to sit without support for at least 5 seconds. Results: A total of 21 infants were enrolled. Four infants were in a low-dose cohort and were treated with a final dose at month 12 of 0.08 mg of risdiplam per kilogram of body weight per day, and 17 were in a high-dose cohort and were treated with a final dose at month 12 of 0.2 mg per kilogram per day. The baseline median SMN protein concentrations in blood were 1.31 ng per milliliter in the low-dose cohort and 2.54 ng per milliliter in the high-dose cohort; at 12 months, the median values increased to 3.05 ng per milliliter and 5.66 ng per milliliter, respectively, which represented a median of 3.0 times and 1.9 times the baseline values in the low-dose and high-dose cohorts, respectively. Serious adverse events included pneumonia, respiratory tract infection, and acute respiratory failure. At the time of this publication, 4 infants had died of respiratory complications. Seven infants in the high-dose cohort and no infants in the low-dose cohort were able to sit without support for at least 5 seconds. The higher dose of risdiplam (0.2 mg per kilogram per day) was selected for part 2 of the study. Conclusions: In infants with type 1 spinal muscular atrophy, treatment with oral risdiplam led to an increased expression of functional SMN protein in the blood. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT02913482.).

Purpose To compare measurement of wall-to-lumen ratio (WLR) by means of high-resolution adaptive optics imaging (AO) with intuitive to use retinal vessel wall (VW) analysis (VWA). Moreover, to validate the techniques by comparing WLR of healthy young (HY) with healthy older patients. Methods Ten retinal VW images of 13 HY (24 ± 2 years) and 16 healthy older (60 ± 8 years) were obtained with AO and VWA. The average of five measurements of VW, retinal vessel lumen and WLR of a single vessel from AO and VWA were calculated and compared. Results WLR of AO and VWA images showed high correlations, r = 0.75, t(27) = 5.98, P < .001, but differed systematically (WLR: VWA, 40 ± 7% and AO, 35 ± 9%; P < .001). Comparable patterns were found for VW and vessel lumen. HY showed significantly lower WLR (AO, 31 ± 8% and VWA, 36 ± 8%) compared with healthy older (AO, 39 ± 9% [P = .012]; VWA, 42 ± 5% [P = .013]). Conclusions Assessment of WLR by VWA showed a good correlation with laborious analysis of the microstructure by high-resolution AO. Measurement of WLR in different age groups indicated good validity. Deviations in VW, vessel lumen, and WLR between AO and VWA can be explained by systematic differences in image scale and resolution. Future studies are needed to investigate the clinical relevance of microvascular WLR assessment by retinal VWA and its prognostic value. Translational Relevance Additional assessment of retinal WLR by use of digital VWA to evaluate microstructural remodeling may prove to be a valuable extension to the current use of retinal vessel diameters as biomarkers of cardiovascular risk.

The aim of this study was to investigate, for the first time, the effects of high-intensity interval training (HIIT) on retinal microvascular endothelial function in cardiovascular (CV) risk patients. In the randomized controlled trial, middle-aged and previously sedentary patients with increased CV risk (aged 58 ± 6 years) with ≥ two CV risk factors were randomized into a 12-week HIIT (n = 33) or control group (CG, n = 36) with standard physical activity recommendations. A blinded examiner measured retinal endothelial function by flicker light-induced maximal arteriolar (ADmax) and venular (VDmax) dilatation as well as the area under the arteriolar (AFarea) and venular (VFarea) flicker curve using a retinal vessel analyzer. Standardized assessments of CV risk factors, cardiorespiratory fitness, and retinal endothelial function were performed before and after HIIT. HIIT reduced body mass index, fat mass, and low-density lipoprotein and increased muscle mass and peak oxygen uptake (VO2peak). Both ADmax (pre: 2.7 ± 2.1%, post: 3.0 ± 2.2%, P = .018) and AFarea (pre: 32.6 ± 28.4%*s, post: 37.7 ± 30.6%*s, P = .016) increased after HIIT compared with CG (ADmax, pre: 3.2 ± 1.8%, post: 2.9 ± 1.8%, P = .254; AFarea, pre: 41.6 ± 28.5%*s, post: 37.8 ± 27.0%*s, P = .186). Venular function remained unchanged after HIIT. There was a significant association between ∆-change VO2peak and ∆-changes ADmax and AFarea (P = .026, R2 = 0.073; P = .019, R2 = 0.081, respectively). 12-weeks of HIIT improved retinal endothelial function in middle-aged patients with increased CV risk independent of the reduction in classical CV risk factors. Exercise has the potential to reverse or at least postpone progression of small vessel disease in older adults with increased CV risk under standard medication. Dynamic retinal vessel analysis seems to be a sensitive tool to detect treatment effects of exercise interventions on retinal microvascular endothelial function in middle-aged individuals with increased CV risk.

This review article is focused on the various facets of possible endothelin's role in glaucoma; involvement of endothelin in other ocular, in particular vascular, diseases is not specifically discussed. Endothelin is an ubiquitous molecule that occurs in practically all ocular tissues. Its primary physiological function is regulation of the blood vessel diameter and hence regulation of the blood supply in tissues. It is secreted locally, and exerts its effect also predominantly locally. This limits the value of venous blood sampling for estimation of the endothelin function in a particular patient, or in study cohorts as well. Endothelin is involved in the regulation of intraocular pressure, in the regulation of blood flow and in activation of retinal and optic nerve head astrocytes. All these functions are of high importance when it comes to pathogenesis of glaucoma. Possible future directions for glaucoma treatment should encompass pharmacological antagonism to endothelin, an avenue which is at present hindered by potentially serious side-effects of available endothelin-antagonists.Dieser Review-Artikel fokussiert sich auf verschiedene Aspekte der Endothelinrollen bei einem Glaukom; auf die Beteiligung von Endothelin bei anderen, vor allem vaskulären okulären Erkrankungen wird in diesem Artikel nicht im Detail eingegangen. Endothelin ist ein ubiquitäres Molekül, das in praktisch allen okulären Geweben vorhanden ist. Seine primäre physiologische Rolle ist die Steuerung des Gefäßdurchmessers und somit die Regulierung der Gewebedurchblutung. Sowohl die Sekretion als auch die Effekte des Endothelins finden lokal statt; ein Teil des Endothelins gelangt zwar in die systemische Zirkulation, jedoch ist dieser Teil variabel. Somit ist die Messung des Plasmaendothelinspiegels im venösen Blut nicht ideal für die Einschätzung der Endothelinfunktion, sowohl bei einzelnen Patienten als auch in Studienkohorten. Im Kontext der Glaukompathogenese lassen sich die wichtigsten Funktionen des Endothelins im Auge in Regulation des Augeninnendruckes, Regulation der Durchblutung und Aktivierung der Gliazellen/Astrozyten im hinteren Segment, in der Netzhaut und im Sehnerv einteilen. Bei so einem breiten Spektrum der Funktionen, die direkt bei der Pathogenese des Glaukoms involviert sind, liegt es auf der Hand, dass künftige therapeutische Ansätze beim Glaukom eine pharmakologische Modulation des Endothelins beinhalten sollten. Zu diesem Zweck ist derzeit die entsprechende Anwendung der zur Verfügung stehenden Endothelinantagonisten durch ihr ungünstiges Nebenwirkungsprofil beeinträchtigt.

This review article discusses the relationship between ocular perfusion pressure and glaucoma, including its definition, factors that influence its calculation and epidemiological studies investigating the influence of ocular perfusion pressure on the prevalence, incidence and progression of glaucoma. We also list the possible mechanisms behind this association, and discuss whether it is secondary to changes in intraocular pressure, blood pressure or both. Finally, we describe the circadian variation of ocular perfusion pressure and the effects of systemic and topical medications on it. We believe that the balance between IOP and BP, influenced by the autoregulatory capacity of the eye, is part of what determines whether an individual will develop optic nerve damage. However, prospective, longitudinal studies are needed to better define the role of ocular perfusion pressure in the development and progression of glaucoma.

To analyze pulse wave propagation in the ocular circulation and vessel stiffness in untreated eyes of normal tension primary open-angle glaucoma (NTG) patients.Inferotemporal retinal vessels of 22 NTG eyes and 25 controls were examined with a Retinal Vessel Analyzer. Inferotemporal peripapillary retinal nerve fiber layer thickness was measured by ocular coherence tomography. Phase delay between venous trough and arterial peak was assessed at 3 sites centrifugal from the disc and a choroid-to-retina pulse delay was calculated as an estimation of vessel rigidity.There was choroid-to-retina pulse delay of 0.26±0.08, 0.30±0.11, and 0.33±0.11 seconds, respectively, in NTG eyes at proximal, middle, and distal sites; in control eyes, the corresponding values were 0.28±0.10, 0.35±0.12, and 0.40±0.17 seconds. Average choroid-to-retina pulse delay was shorter in NTG eyes (P=0.028). Retinal nerve fiber layer (inferotemporal) showed an opposite correlation with choroid-to-retina pulse delay in controls (r=-0.48, P=0.019) and in NTG eyes (r=0.47, P=0.032 ).Untreated NTG eyes show stiffer retinal vessels. Vessel rigidity correlates with level of glaucomatous damage.

To analyse a response to the therapy switch from the concomitant application of beta-blocker and topical carbonic anhydrase inhibitor to the fixed combination of timolol and dorzolamide (Cosopt) in glaucoma/ocular hypertensive patients under everyday, office-practice conditions.The data source was a survey among practising ophthalmologists in Switzerland assessing their experience with glaucoma patients/ocular hypertensives put for the first time on the fixed combination of timolol and dorzolamide. A total of 98 patients underwent the therapy switch in at least one eye. The intraocular pressure (IOP) change between the baseline visit before switch to the timolol-dorzolamide fixed combination occurred, and the first follow-up control after the switch, served as an indicator of compliance.The IOP decreased on average from 19.43 +/- 5.64 mmHg to 17.97 +/- 3.58 mmHg (p0.01). The time to the follow-up visit ranged from 4 to 354 days, and the magnitude of IOP change demonstrated a significant dependence on the time to the follow-up visit, also when corrected for baseline IOP level. A total of 87 (85.3%) continued on the timolol-dorzolamide fixed combination therapy after the first control visit. In 68 of these 98 patients the contralateral eyes underwent the same therapy switch, and their IOP followed an identical pattern of behaviour.The average IOP decrease of 1.5 mmHg upon therapy switch to the timolol-dorzolamide fixed combination suggests a better efficacy due to improved compliance. Short-term compliance benefit seems to be more pronounced. The high timolol-dorzolamide fixed combination therapy continuation rate reflects an improvement in compliance and subjectively-perceived convenience.

To investigate the choroidal hemodynamic effects of losartan potassium, a specific angiotensin II subtype AT1 receptor antagonist.In this prospective, randomized, observer-masked, open-label placebo-controlled (lactose), two-period crossover study, the choroidal hemodynamic effects of a single oral 50-mg dose of losartan potassium were evaluated in 12 healthy subjects using choroidal laser Doppler flowmetry.Perfusion pressure and the choroidal laser Doppler flowmetry parameters velocity, volume, and flux did not vary significantly compared with placebo (P = 0.33, 0.31, 0.74, and 0.61, respectively). Correcting choroidal laser Doppler flowmetry parameters for perfusion pressure in a covariance analysis did not change these results.A single oral 50-mg dose of the angiotensin II AT1 receptor antagonist losartan potassium given does not disturb the homeostasis of ocular perfusion pressure or choroidal blood flow in young healthy subjects.

PURPOSE: To evaluate the relationship between the circadian blood pressure rhythm and the retrobulbar blood flow in glaucoma patients. DESIGN: Cross-sectional study. METHODS: Circadian blood pressure measurements and color Doppler imaging (CDI) in the ophthalmic artery as well as the central retinal artery of one randomly selected eye were obtained in 193 primary open-angle glaucoma patients. CDI parameters were compared by means of analysis of covariance between patients with a nocturnal decrease in mean systemic blood pressure (MBP) below 20% of the average daytime MBP (over-dippers), patients with a decrease between 10% to 20% (dippers), and patients with a decrease of less than 10% (nondippers), using age, intraocular pressure (IOP), and MBP during color Doppler measurement as covariates. RESULTS: An analysis of covariance disclosed, after correcting for age, IOP, and MBP during color Doppler imaging, a significantly lower EDV ( P = .0096) and a significantly higher RI ( P = .033) in the central artery of over-dipping glaucoma patients compared with nondippers or dippers. This effect seemed independent of the use of vasoactive drugs. CONCLUSIONS: Glaucoma patients with a marked drop in nocturnal systemic blood pressure seem to have altered retrobulbar blood flow parameters, suggesting that an abnormal systemic blood pressure profile may be the manifestation of some kind of systemic vascular dysregulation relevant for the ocular circulation.

PURPOSE To evaluate the effect of 0.5% timolol maleate on the capillary circulation of the anterior optic nerve head in patients with primary open-angle glaucoma and to compare the results with those obtained in a healthy control group. PATIENTS AND METHODS Twelve patients with nonprogressive glaucoma and 12 age- and sex-matched healthy volunteers were included in this prospective study. Optic nerve head perfusion was examined by the Heidelberg Retina Flowmeter (HRF) in both groups. A 3-week washout period preceded the baseline measurement in the glaucoma group, and ONH blood flow was assessed again after 3 weeks of bilateral topical timolol treatment and 2 hours after timolol application. RESULTS Intraocular pressure decreased significantly with timolol (P < 0.001). The HRF flow values for patients with glaucoma were comparable to those for a control group at baseline (P = 0.25), 3 weeks after timolol therapy (P = 0.09), and 2 hours after timolol instillation (P = 0.15). The glaucoma group showed no statistically significant change in the HRF parameter flow as compared with baseline, either after 3 weeks of timolol treatment or 2 hours after timolol instillation (P = 0.40). The heart rate and arterial systolic and diastolic blood pressure values showed no alteration after timolol therapy. CONCLUSIONS Patients with nonprogressive glaucoma seem not to have an altered optic nerve blood flow as assessed by the HRF, and timolol treatment does not seem to alter the latter blood flow parameter in such patients.

To evaluate the correlation between interocular difference in progression of glaucomatous damage and interocular differences in retrobulbar blood flow.On the basis of a retrospective analysis of visual fields, progressive damage was identified in 20 patients with primary open-angle glaucoma. As a parameter of interocular difference in progression of visual field damage, the angle (gamma) between the regression lines of the visual field index mean defect over time per eye was calculated for each subject. The relationship between the angle gamma and interocular differences in intraocular pressure and retrobulbar color Doppler imaging parameters was analyzed by a multiple linear regression analysis in a stepwise forward approach.With larger interocular differences in progression of glaucomatous damage, lower mean blood flow velocities in the ophthalmic artery (partial r = -.69; P. 0016), higher resistivity indices in the central retinal artery (partial r =.48; P.0456), and higher peak systolic velocities in the ophthalmic artery (partial r =.52; P.0285) were noted in the eyes with more marked progression of damage (multiple r =.71; P. 0099). Interocular differences in progression of visual field damage were not related to intraocular pressure or extent of visual field damage.Independent of the extent of the interocular difference in glaucomatous damage and intraocular pressure, interocular difference in progression of glaucomatous visual field damage correlates with interocular difference in retrobulbar hemodynamic parameters.

OBJECTIVE: To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study. DESIGN: Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics. SETTING: Worldwide, multicenter clinical trial. PATIENTS: Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N=1272). MAIN OUTCOME MEASURES: We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume. RESULTS: Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability. CONCLUSION: These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00289978 clinical trial, phase iii journal article multicenter study randomized controlled trial research support, non-u.s. gov't 2012 Oct imported

Devonshire, Virginia Havrdova, Eva Radue, Ernst Wilhelm O'Connor, Paul Zhang-Auberson, Lixin Agoropoulou, Catherine Haring, Dieter Adrian Francis, Gordon Kappos, Ludwig FREEDOMS study group Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't England Lancet neurology Lancet Neurol. 2012 May;11(5):420-8. doi: 10.1016/S1474-4422(12)70056-X. Epub 2012 Apr 10.; BACKGROUND: Fingolimod 0.5 mg once daily is approved for treatment of relapsing multiple sclerosis (MS). In the phase 3, 2-year FREEDOMS (FTY720 Research Evaluating Effects of Daily Oral therapy in MS) study, fingolimod significantly reduced annualised relapse rates (ARRs) and the risk of confirmed disability progression compared with placebo. We aimed to investigate whether the beneficial treatment effect reported for the overall population is consistent in subgroups of patients with different baseline characteristics. METHODS: We did subgroup analyses of ARRs (primary outcome) and confirmed disability progression (a secondary outcome) over 24 months in the FREEDOMS study, a randomised, double-blind study that included 1272 patients with relapsing-remitting MS who were assigned 1:1:1 to fingolimod (0.5 mg or 1.25 mg) or placebo once daily for 24 months. Subgroups were predefined, predefined and slightly modified, or defined post hoc, by demographic factors (including sex and age), disease characteristics (including baseline disability scores, relapse rates, and lesion parameters), and response to previous therapy (including analyses in patients eligible for fingolimod treatment according to the European label). Data were analysed by intention to treat. The FREEDOMS study is registered with ClinicalTrials.gov, number NCT00289978. FINDINGS: Treatment with fingolimod 0.5 mg was associated with significantly lower ARRs versus placebo across all subgroups except for patients aged over 40 years. ARR ratios ranged from 0.76 (95% CI 0.54-1.09; p=0.13) in patients aged over 40 years to 0.29 (0.16-0.52; p

The main objective of this report is to encourage consistent quality of testing and reporting within and between centres that use colour Doppler imaging (CDI) for assessment of retrobulbar blood flow. The intention of this review is to standardize methods in CDI assessment that are used widely, but not to exclude other approaches or additional tests that individual laboratories may choose or continue to use.

Rapid development of functional neuroimaging techniques have brought about a growing interest for neurovascular coupling in neuroresearch, which, in turn, has prompted similar research in ophthalmology. There are now hints that neurovascular coupling is disturbed in glaucoma. The contact of the nerve terminals to the cortical blood vessels is mostly realized through astrocytes. A major defining property of glaucoma, cupping of the optic disk, implies tissue remodeling of the optic nerve head and involves an astrocytic responses. A malfunction of the astrocytes in glaucoma may lead not only to the hallmark of glaucoma-cupping and death of retinal ganglion cells-but also to an accompanying or even preceding disturbance in ocular neurovascular coupling. This article is a short overview of research published in this field so far.

PURPOSE. To test whether the regularity and short-term changes of retinal vessel diameter are related to the history of cold hands and feet and to nailfold circulatory response to cooling. METHODS. In 13 vasospastic and 13 nonvasospastic young healthy women (based on their history of cold extremities and nailfold capillaroscopy) 20- to 30-second recordings of the ocular fundus was obtained with a retinal vessel analyzer. The spatial regularity of arterioles and venules was analyzed by means of the coefficient of variation of vessel diameter and by exploratory Fourier analysis of spatial frequencies. Temporal variability was analyzed as excursion amplitude of the vessel diameter, as a correlation of means and standard deviations of vessel diameter within a defined time period, and by Fourier analysis of temporal diameter change in the heartbeat frequency range. RESULTS. Mean diameters of selected segments of arterioles (129.9 15.3 and 124.4 24.4 m) and venules (150.8 14.6 and 149.3 19.6 m) were not different between the vasospastic and nonvasospastic groups, respectively. Spatial variability: The coefficient of variation in arterioles was 8.8% 2.8% and 6.1% 1.7%, in venules 3.8% 1.4%, and 3.6% 0.9% in the vasospastic and nonvasospastic groups, respectively (difference by ANOVA, P 0.017). Fourier analysis revealed differences between arterioles in the two groups, with relative Fourier power spectrum amplitudes of spatial frequencies higher in vasospastic eyes (Mann-Whitney P 0.029). Temporal variability: The excursion amplitudes of vessel diameters were comparable in the two groups. Individual coefficients of correlation of successive means and standard deviations of the vessel diameter were 0.11 0.23 and 0.09 0.23 in the nonvasospastic group, and 0.25 0.40 and 0.24 0.22 in the vasospastic group, in the arterioles and venules, respectively (ANOVA: vasospastic versus nonvasospastic; P 0.038). Fourier analysis in the heartbeat frequency range revealed differences in relative power spectrum amplitudes of temporal frequencies between arterioles in the two groups (higher in the vasospastic group, Mann-Whitney P 0.029). CONCLUSIONS. Retinal arterioles in healthy vasospastic women show higher spatial irregularity and an increased vessel diameter variation within the temporal frequency of the heartbeat than do arterioles in nonvasospastic women. (Invest Ophthalmol Vis Sci. 2006;47:4026‐4033) DOI:10.1167/iovs.06-0177

PURPOSE To measure the oscillation phase delay between retinal arterioles and venules in order to analyze pulse wave propagation in the ocular circulation of vasospastic and nonvasospastic subjects and a change thereof during the cold pressor test in another group of healthy subjects. METHODS Twenty-four young, healthy women, 12 vasospastic and 12 nonvasospastic, were analyzed. A retinal vessel analyzer was used to obtain 1-minute recordings of the ocular fundus. A phase delay between the arteriole and venule pulsations was assessed at three sites, one (proximal) in the close retinal vicinity of the disc, one (middle) 1 to 2 disc diameters away from the disc, and a third (distal) 3 to 4 disc diameters away from the disc; and, assuming that venules are counterphased to the choroidal circulation, a choroid-to-retina pulse delay was calculated. In addition, the change in these parameters was analyzed during the modified cold-pressor test in 10 healthy subjects (five women, five men). RESULTS Pulse oscillations in arterioles led those in venules by 95.0 degrees +/- 39.0 degrees , 60.5 degrees +/- 57.5 degrees , and 47.5 degrees +/- 64.0 degrees in vasospastic subjects, and 76.0 degrees +/- 58.0 degrees , 31.5 degrees +/- 60.0 degrees , and 2.5 degrees +/- 80.5 degrees in nonvasospastic subjects in the proximal, middle, and distal measuring sites, respectively. Calculated choroid-to-retina pulse delays in vasospastic subjects were 0.20 +/- 0.10, 0.28 +/- 0.14, and 0.30 +/- 0.11 seconds and in nonvasospastic subjects 0.25 +/- 0.15, 0.35 +/- 0.11, and 0.43 +/- 0.2 seconds at the proximal, middle, and distal measuring sites, respectively. The difference was significant between vasospastic and nonvasospastic subjects (P = 0.033) and among the measuring sites (P = 0.0023). During exposure to cold, the choroid-to-retina pulse delays changed from 0.31 +/- 0.08, 0.40 +/- 0.16, and 0.51 +/- 0.26 seconds to 0.26 +/- 0.12, 0.30 +/- 0.10, and 0.33 +/- 0.14 seconds at the proximal, middle, and distal measuring sites, respectively (P = 0.024 for the change from baseline to cold exposure, and P = 0.022 for measuring sites). CONCLUSIONS Retinal vessels in vasospastic subjects demonstrate an altered pattern of oscillation phase delay between arterioles and venules. Vessels in vasospastic subjects seem to conduct pulse waves faster and are thus stiffer than those in nonvasospastic subjects. The pattern of oscillation demonstrates changes during the cold pressor test in healthy subjects, indicating faster pulse-wave propagation.

Aims: To investigate the source of ocular blood flow alterations in glaucoma. Methods: In 56 patients with open angle glaucoma, blood flow parameters were obtained from both eyes in the ophthalmic and central retinal artery by means of colour Doppler imaging, as well as in the choroidal circulation and the neuroretinal rim of the optic nerve by means of laser Doppler flowmetry. Based on these haemodynamic parameters, a cluster analysis (two groups) was performed and differences with regard to risk factors were assessed between clusters. Results: Ocular blood flow data in the two clusters indicated that the two groups (cluster 1 = 26 patient with higher blood flow values; cluster 2 = 30 patients with lower blood flow values) differed mainly in choroidal and optic nerve blood flow. No differences in sex distribution, propensity to have normal tension glaucoma, age, endothelin-1 plasma levels, visual field damage, intraocular pressure, or systemic blood pressure parameters were observed between the two clusters. However, 12 patients (46%) from the cluster with high ocular blood flow values showed a vasospastic response in nailfold capillaroscopy, while such a response was observed in 24 patients (80%) of the cluster with low ocular blood flow values. This difference in vasospastic propensity was statistically significant (p = 0.0121). Conclusions: Ocular blood flow alterations in glaucoma patients seem, at least partly, to be related to a systemic vascular dysregulation.

Treatment of normal-tension glaucoma has been a subject of debate for several years. Glaucomatous damage cannot be influenced directly, and current treatment modalities in normal-tension glaucoma are aimed at the control of risk factors. Intraocular pressure is a widely accepted risk factor and its reduction can improve the prognosis in normal-tension glaucoma patients. The repeated demonstration of the importance of hemodynamic factors in normal-tension glaucoma has, however, not been paralleled by a comparable progress in the development of therapeutic modalities capable of influencing favorably ocular blood flow. Today, calcium channel blockers seem to be the most promising adjunctive treatment to be considered in patients with glaucomatous optic neuropathy without increased intraocular pressure.

Purpose To assess the impact of vascular dysregulation on choroidal blood flow response to the hand-grip test and the relevance of this response to glaucoma. Methods Eighty healthy volunteers underwent a hand-grip test while choroidal blood flow was measured by means of laser Doppler flowmetry. Blood pressure, heart rate, and intraocular pressure (IOP) were monitored. Choroidal blood flow changes were compared between subjects with a positive history of cold hands and control subjects by means of analysis of variance. The relationship of the vascular response to the level of IOP at which progressive damage occurred was analyzed in 21 patients with primary open-angle glaucoma who had progressive damage despite normal or normalized IOP. Results Blood pressure and heart rate increased and IOP decreased in response to a hand-grip test. Healthy subjects with a positive history of cold hands (n = 36) demonstrated a decrease in choroidal blood flow during the hand-grip test (mean +/- SD: 13.5 +/- 5.8, 12.2 +/- 6.8, and 13.4 +/- 6.9 AU, at baseline, during the test, and 3 minutes after release, respectively), whereas control subjects (n = 44) demonstrated an inverse (12.5 +/- 8.3, 13.7 +/- 9.4, and 11.9 +/- 7.1 AU, respectively) response pattern (P = 0.039). Glaucoma patients with a decrease of at least 10% in choroidal blood flow during the hand-grip test had lower IOP (14.67 +/- 3.83 and 13.50 +/- 2.59 mm Hg in the right and the left eyes, respectively) compared (P = 0.032) with those without such a decrease (16.54 +/- 3.85 and 16.92 +/- 2.95 mm Hg in the right and the left eyes, respectively). Conclusions A hand-grip test elicits a different blood flow response in subjects with vasospasm compared with control subjects. Damage by glaucoma in patients with a decrease in choroidal blood flow during a hand-grip test may progress at a relatively lower IOP.

To assess the variability in choroidal laser Doppler flowmetry (LDF).Five measurements of choroidal blood flow were obtained on 5 days in both eyes of 10 subjects. Reliability, sensitivity, and sample size calculations were performed. Yield, the intensity of the returning light (direct current [DC]) divided by the signal amplification (gain) used during recording, was calculated (yield = DC/gain). The correlation between yield and the LDF parameters velocity, volume, and flux was analyzed. Reliability, sensitivity, and sample size calculations were repeated after correcting for this relationship. The influence of different light-scattering properties on the returning signal was assessed in a model eye.Yield and the LDF parameters, velocity, volume, and flux, correlated significantly in a regression model. After the influence of yield was partialized out, reliability, reproducibility, sensitivity, and statistical power improved markedly. The high reliability of yield in a given eye (87%) suggests, that, besides varying recording settings on different days, individual specific scattering properties within the eye influence LDF measurements. Comparison of model eye data with human data disclosed a low signal-to-noise ratio with decreasing yield. Correcting for yield did not affect the sensitivity to blood flow changes induced by hypercapnia or a suction cup.Tissue-scattering properties alter the characteristics of the returning light, and recording settings affect the outcome of the analysis of the returning light during LDF measurements. Partializing out the influence of yield markedly improves the reproducibility of choroidal LDF.

Purpose: To assess sex difference and parameters possibly accounting for such a difference in healthy subjects evaluated by means of the Langham Ocular Blood Flow (OBF) System. Methods: Pulse amplitude of intraocular pressure (IOP) and pulsatile ocular blood flow (POBF) as measured with the Langham OBF System were assessed in 86 healthy men and 69 healthy women. Results: Compared to men, women showed higher POBF (mean ± SD: 722.6 ± 152.8 versus 647.8 ± 164.9 μL/min; P = .0056) and pulse amplitude (mean ± SD: 2.3 ± 0.7 versus 2.0 ± 0.6 mm Hg; P = .0043) values. Sex difference was still significant after correcting for age, refraction, blood pressure, IOP, and pulse rate. Pulse amplitude correlated negatively with pulse rate, and POBF correlated negatively with IOP. Women had higher readings in pulse amplitude and POBF, even after correcting for age, refraction, IOP, blood pressure, and pulse rate. Conclusions: While using the Langham OBF System, one needs to be aware of sex difference that is independent of other hemodynamic parameters. How the observed difference in POBF is related to ocular blood flow, and how it might influence the preponderance of various ocular diseases in men or women remains to be clarified.

PURPOSE: To evaluate the relationship between ocular perfusion pressure and color Doppler measurements in patients with glaucoma. MATERIALS AND METHODS: Twenty patients with primary open-angle glaucoma with visual field deterioration in spite of an intraocular pressure lowered below 21 mm Hg, 20 age-matched patients with glaucoma with stable visual fields, and 20 age-matched healthy controls were recruited. After a 20-minute rest in a supine position, intraocular pressure and color Doppler measurements parameters of the ophthalmic artery and the central retinal artery were obtained. Correlations between mean ocular perfusion pressure and color Doppler measurements parameters were determined. RESULTS: Patients with glaucoma showed a higher intraocular pressure (P

To test the interocular differences in optic disc topography in normal subjects by means of confocal scanning laser ophthalmoscopy.Topographic measurements of the optic disc were evaluated by means of confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph) in 314 eyes of 157 healthy volunteers. The examination was started randomly either with the right eye or the left eye. Differences between right and left eyes in disc area, cup area, cup volume, cup/disc area ratio, rim area, rim volume, maximum cup depth, cup shape measure, retinal nerve fiber layer thickness, and retinal nerve fiber cross section area for 360 degrees and for the temporal and nasal regions of the optic nerve head were evaluated by means of Student t-test. The same parameters were assessed in a subgroup of 80 elderly (age50 years) healthy subjects. Holm's sequentially rejective method was used for significance correction of multiple comparisons.Significant interocular differences in the average retinal nerve fiber layer thickness (p = 0.0010) and retinal nerve fiber layer cross section area (p = 0.0036) were found, with the right eye showing, on the average, lower values. The left eye showed a larger retinal nerve fiber layer thickness in 94 subjects (59.87%) and a larger retinal nerve fiber cross section area in 101 subjects (64. 33%). In the temporal optic disc area there were no statistically significant differences in topometric data (p0.05). In the nasal area, significant interocular differences in the retinal nerve fiber layer thickness (p = 0.0002) and retinal nerve fiber layer cross section area (p = 0.0003) were found. Similar results were found when the group of subjects older than 50 years was considered.This study demonstrates systematic interocular differences in optic disc topometric data. Such a finding, be it due to methodological or biological reasons, should be taken in consideration in clinical trials.

Objective To evaluate normal choroidal blood flow and its relationship with various factors such as age, systemic blood pressure, and intraocular pressure (IOP). Methods A total of 70 healthy subjects were recruited. Choroidal blood flow was assessed using a method based on laser Doppler flowmetry (LDF) technique. The LDF parameters of velocity, volume, and flux were obtained. The influence of age, mean systemic blood pressure, IOP, smoking, and sex on choroidal hemodynamic parameters was assessed in a multiple linear regression model. The correlations between interocular difference in IOP and interocular differences in the LDF parameters were assessed by means of the Pearson linear correlation factor. Results Velocity decreased significantly ( P = .03) with advancing age of the subjects and volume increased significantly ( P = .02) with increasing IOP. Mean blood pressure, smoking, and sex had no influence on the choroidal LDF parameters. Interocular difference in IOP correlated significantly with interocular difference in volume ( R = 0.34, P Conclusion Choroidal blood flow velocity decreased with increasing age of the subjects, while the volume of moving erythrocytes decreased with lower IOP.

To evaluate the correlation of blood-flow velocities in the ophthalmic artery and corneal temperature in normal subjects and glaucoma patients.Corneal temperature was measured on both eyes by means of the THI-500 non-contact infrared thermometer in 18 healthy volunteers and in 18 age and sex matched open-angle glaucoma patients. In these subjects, blood flow velocity was assessed by means of color Doppler imaging (CDI) in both ophthalmic arteries. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistivity index (RI = [(PSV-EDV)/ PSV]) were computed.Corneal temperature values correlated positively with the ipsilateral values of EDV (R(2) = 0.13, p = 0.028, and R(2) = 0.16, p = 0.017 in the left and the right eyes respectively) and negatively with the ipsilateral values of RI (R(2) = 0.11, p = 0.046 and R(2 ) = 0.11, p = 0.044 in the left and the right eyes respectively) in the ophthalmic artery. In addition, the interocular difference in corneal temperature values were significantly correlated positively with the difference in EDV(R( 2) = 0.30, p = 0. 0005) and negatively with the difference in RI (R( 2) = 0.20; p: 0. 0056). All regression models were statistically comparable between normals and glaucoma patients, as well as between right eyes and left eyes. PSV did not contribute to corneal temperature.The present study suggests that retrobulbar hemodynamics influence corneal temperature, and that this relationship is comparable in normal subjects and glaucoma patients.

The etiology of glaucoma is most probably multifactorial. This study intended to investigate the asymmetry in intraocular pressure (IOP) and that in retinal nerve fiber layer (RNFL) thickness in normal-tension glaucoma patients. Two diurnal tension curves, obtained within 3 months and counting at least five IOP readings each, including an early morning IOP measurement upon awaking, were obtained in 15 normal-tension glaucoma patients. None of the patients received IOP-lowering therapy. IOP asymmetry was present in at least three readings and was always in the same direction. The optic nerve was imaged in both eyes in each patient by means of confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomograph). The interocular difference in RNFL thickness and the RNFL cross-sectional area were correlated with the interocular difference in IOP by means of Spearman’s rank correlation factor. Nine female and 6 male normal-tension glaucoma patients (mean ± SD age was 62.4 ± 16.9 years) were included in this study. Interocular IOP asymmetry varied between 0.30 and 4 mm Hg. Strong negative correlations were found between interocular asymmetry in IOP and interocular asymmetry in RNFL thickness asymmetry (R = –0.652, p = 0.0083) and interocular asymmetry in RNFL cross-sectional area (R = –0.702, p = 0.0034). The present results demonstrate for the first time a more marked thinning of the neuroretinal nerve fiber layer in the eye with the higher IOP in normal-tension glaucoma patients.