Assessment of choroidal blood flow using laser speckle flowgraphy

Background/aims There is considerable interest in novel techniques to quantify choroidal blood flow (CBF) in humans. In the present study, we investigated a novel technique to measure CBF based on laser speckle flowgraphy (LSFG) in healthy subjects. Methods This study included 31 eyes of 31 healthy, non-smoking subjects aged between 19 and 74 years. A commercial LSFG instrument was used to measure choroidal vessel diameter (CVD) and relative flow volume (RFV) in choroidal vessels that were identified on fundus photos, an approach that was used previously only for retinal vessels. The reproducibility and the effect of isometric exercise on these parameters were investigated. The latter was compared with measurement of subfoveal CBF using laser Doppler flowmetry (LDF). Results Intraclass correlation coefficients for CVD and RFV were higher than 0.8 indicating excellent reproducibility. During isometric exercise, we observed an increase in ocular perfusion pressure of approximately 60% (P<0.001). The increase in RFV and CBF was lower, but also highly significant versus baseline (at minute 6 of isometric exercise: RFV 10.5%+/- 4.2%, CBF 8.3%+/- 3.6%;P< 0.001 each) indicating choroidal autoregulation. Conclusion LSFG may be a novel approach to study blood flow in choroidal vessels. Data are reproducible and show good agreement with LDF data

Evaluation of flicker induced hyperemia in the retina and optic nerve head measured by Laser Speckle Flowgraphy

Purpose The coupling between neural activity and blood flow is a physiological key principle of ocular blood flow regulation. The current study was performed to investigate whether Laser speckle flowgraphy (LSFG), a commercially available technique for measuring blood flow, is capable to assess flicker-induced haemodynamic changes in the retinal and optic nerve head (ONH) circulation. Methods Twenty healthy subjects were included in this cross sectional study. A commercial LSFG instrument was used to measure blood flow at the ONH as well as in retinal vessels before and during stimulation with flickering light. Mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for the ONH and relative flow volume (RFV) a measure of relative blood flow of the respective retinal vessels. Results Stimulation with flicker light increased ONH MBR by +17.5%+/- 6.6% (p<0.01). In retinal arteries, flicker stimulation led an increase of +23.8 +/- 10.0% (p<0.05) in total RFV. For retinal veins, an increase of +23.1%+/- 11.0 (p<0.05) in total RFV was observed during stimulation. A higher response was observed in nasal RFV compared to temporal RFV in retinal arteries (nasal: +28.9%+/- 20.0%;temporal: +20.4%+/- 17.6%, p<0.05) and veins (nasal: +28.3%+/- 19.6%;temporal +17.8%+/- 18.9%, p<0.05). Conclusion As shown previously with other techniques, flicker stimulation leads to an increase in retinal and optic nerve head blood flow. Our results indicate that LSFG is an appropriate method for the quantification of retinal and ONH blood flow during visual stimulation and may be used as a non-invasive, easy to use tool to assess neuro-vascular coupling in humans

Ocular Blood Flow Measurements in Healthy White Subjects Using Laser Speckle Flowgraphy

Purpose. To assess the feasibility and reliability of Laser Speckle Flowgraphy (LSFG) to measure ocular perfusion in a sample of healthy white subjects and to elucidate the age-dependence of the parameters obtained. Methods: This cross-sectional study included 80 eyes of 80 healthy, non-smoking white subjects of Western European descent between 19 and 79 years of age. A commercial LSFG instrument was applied to measure ocular blood flow at the optic nerve head (ONH) three successive times before and after pharmacological pupil dilation. The mean blur rate (MBR), a measure of relative blood flow velocity, was obtained for different regions of the ONH. Eight parameters of ocular perfusion derived from the pulse-waveform analysis of MBR including blowout time (BOT) and falling rate (FR) were also recorded. Results Artifact-free LSFG images meeting the quality criteria for automated image analysis were obtainable in 93.8% without pupil dilation and in 98.8% with pharmacological pupil dilation. Measurements of MBR showed excellent repeatability with intraclass correlation coefficients >= 0.937 and were barely affected by pupil dilation. The majority of pulse-waveform derived variables exhibited equally high repeatability. MBR-related blood flow indices exhibited significant age dependence (p<0.001). FR (r = 0.747, p<0.001) and BOT (r = -0.714, p<0.001) most strongly correlated with age. Conclusions: LSFG represents a reliable method for the quantitative assessment of ocular blood flow in white subjects. Our data affirms that the LSFG-derived variables FR and BOT may be useful biomarkers for age-related changes in ocular perfusion

Novel Approaches for Imaging-Based Diagnosis of Ocular Surface Disease

Imaging has become indispensable in the diagnosis and management of diseases in the posterior part of the eye. In recent years, imaging techniques for the anterior segment are also gaining importance and are nowadays routinely used in clinical practice. Ocular surface disease is often synonymous with dry eye disease, but also refers to other conditions of the ocular surface, such as Meibomian gland dysfunction or keratitis and conjunctivitis with different underlying causes, i.e., allergies or infections. Therefore, correct differential diagnosis and treatment of ocular surface diseases is crucial, for which imaging can be a helpful tool. A variety of imaging techniques have been introduced to study the ocular surface, such as anterior segment optical coherence tomography, in vivo confocal microscopy, or non-contact meibography. The present review provides an overview on how these techniques can be used in the diagnosis and management of ocular surface disease and compares them to clinical standard methods such as slit lamp examination or staining of the cornea or conjunctiva. Although being more cost-intensive in the short term, in the long term, the use of ocular imaging can lead to more individualized diagnoses and treatment decisions, which in turn are beneficial for affected patients as well as for the healthcare system. In addition, imaging is more objective and provides good documentation, leading to an improvement in patient follow-up and education

Role of nitric oxide in optic nerve head blood flow regulation

Background/Aim: Autoregulation is the ability of a vascular bed to keep its blood flow stable despite changes in perfusion pressure. While several studies have investigated choroidal blood flow (ChBF) regulation and the mechanisms behind it, only few data are available for the optic nerve head (ONH). The aim of the present project was to investigate whether the regulatory behavior of the ONH differs from that of the choroid. Further, the role of nitric oxide (NO) in ONH blood flow regulation during changes in ocular perfusion pressure (OPP) was assessed. Material and Methods: The present project consisted of three studies in healthy volunteers. In the first study, choroidal and ONH blood flow in response to an experimental increase and decrease in OPP was compared. In addition, two three-way crossover, double-masked, placebo controlled studies were performed in which subjects received an unspecific NO synthase (NOS) inhibitor (L-NMMA), an alpha-receptor agonist (phenylephrine) or placebo. During infusion of these substances, OPP was increased by isometric exercise in one study and in the other study OPP was decreased by an artificial increase in intraocular pressure (IOP). In all studies, blood flow was assessed using laser Doppler flowmetry. Results: The response in blood flow to provocation was less pronounced than the response in OPP, indicating for blood flow regulation in the choroid as well as in the ONH. ChBF regulated better than optic nerve head blood flow (p =0.023) during isometric exercise. ONH blood flow regulated better than ChBF (p = 0.001) during artificial IOP increase. Administration of an NOS inhibitor significantly decreased ONH blood flow at rest (p < 0.01). In contrast, inhibition of NOS did not alter the pressure/flow relationship in the ONH during isometric exercise or experimental increase in IOP (p = 0.37 and p = 0.49, respectively). Conclusion: ONH blood flow regulation is complex and differs from that of the choroid. During isometric exercise, the choroid regulates its blood flow better than the ONH while the opposite is the case during artificial increase in IOP. NO is an important regulator of basal vascular tone in the ONH. In contrast, it does not seem to be involved in the regulatory processes during experimental manipulation in OPP.Problemstellung/Ziel: Autoregulation ist die Fähigkeit eines Gefäßbettes den Blutfluss trotz Änderungen des Perfusionsdruckes konstant zu halten. Es konnte bereits gezeigt werden, dass die Choroidea über solche regulatorische Kapazität verfügt. Für das Gefäßsystem der Papille sind derzeit nur wenige Daten verfügbar. Das Ziel des vorliegenden Projektes war es zu untersuchen, ob es Unterschiede in der Blutflussregulation in der Choroidea und der Papille während Änderungen des okulären Perfusionsdrucks gibt. Weiters wurde getestet, ob Stickstoffmonoxid (NO) in die Regulation des Blutflusses in der Papille während Änderungen des okulären Blutflusses involviert ist. Methoden: Im Rahmen des vorliegenden Projektes wurden drei klinische Studien an gesunden Probanden durchgeführt. Ziel der ersten Studie war der Vergleich zwischen choroidalem und papillärem Blutfluss während Veränderungen des OPP. Weiters wurden zwei doppelblinde, plazebo-kontrollierte, dreifach cross-over, Studien durchgeführt, in denen die Probanden einen unspezifischen NO-Synthase Inhibitor (L-NMMA), einen Alpha-Rezeptor Agonisten (Phenylephrine) oder Plazebo erhielten. Während der Verabreichung dieser Substanzen wurde entweder der OPP durch isometrische Übung erhöht oder durch experimentelle Erhöhung des Intraokulardrucks gesenkt. In allen Studien wurde der Blutfluss mittels Laser Doppler Flowmetry gemessen. Ergebnisse: Der Anstieg des Blutflusses in der Choroidea und in der Papille war geringer als der Anstieg des okulären Perfusionsdruckes. Dies weist auf das Vorhandensein von Autoregulation in beiden Gefäßbetten hin. Während isometrischer Übung war der choroidale Blutfluss besser reguliert als der papilläre, (p =0.023), während experimenteller Erhöhung des Intraokulardruckes war dies umgekehrt (p = 0.001). Verabreichung eines NO-Synthase Inhibitors führte zu einer signifikanten Reduktion des basalen papillären Blutflusses. (p < 0.01). Hemmung der NO-Synthase führte zu keiner Veränderung im Verhalten des papillären Blutflusses während isometrischer Übung oder experimenteller Erhöhung des Intraokulardrucks (p = 0.37 bzw. p = 0.49). Schlussfolgerung: Die Regulation des Blutflusses in der Papille ist komplex und unterscheidet sich von der der Choroidea. Während isometrischer Übung scheint die Choroidea ihren Blutfluss über einen weiteren Bereich des Perfusionsdruckes stabil zu halten als die Papille, während experimenteller Erhöhung des Augeninnendrucks ist dies umgekehrt. NO hat eine bedeutende Funktion in der Regulation des basalen Blutflusses in der Papille, scheint jedoch nicht an der Blutflussregulierung während Veränderungen des OPP beteiligt zu sein.submitted by Doreen SchmidlAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheWien, Med. Univ., Diss., 2012OeBB(VLID)188346

Novel approaches for imaging-based diagnosis of ocular surface disease

Imaging has become indispensable in the diagnosis and management of diseases in the posterior part of the eye. In recent years, imaging techniques for the anterior segment are also gaining importance and are nowadays routinely used in clinical practice. Ocular surface disease is often synonymous with dry eye disease, but also refers to other conditions of the ocular surface, such as Meibomian gland dysfunction or keratitis and conjunctivitis with different underlying causes, i.e., allergies or infections. Therefore, correct differential diagnosis and treatment of ocular surface diseases is crucial, for which imaging can be a helpful tool. A variety of imaging techniques have been introduced to study the ocular surface, such as anterior segment optical coherence tomography, in vivo confocal microscopy, or non-contact meibography. The present review provides an overview on how these techniques can be used in the diagnosis and management of ocular surface disease and compares them to clinical standard methods such as slit lamp examination or staining of the cornea or conjunctiva. Although being more cost-intensive in the short term, in the long term, the use of ocular imaging can lead to more individualized diagnoses and treatment decisions, which in turn are beneficial for affected patients as well as for the healthcare system. In addition, imaging is more objective and provides good documentation, leading to an improvement in patient follow-up and education.Published versionThis research was funded by the Medical Scientific Fund of the Mayor of the City of Vienna, Project No. 17059

Retinal neurovascular coupling in diabetes

Neurovascular coupling, also termed functional hyperemia, is one of the physiological key mechanisms to adjust blood flow in a neural tissue in response to functional activity. In the retina, increased neural activity, such as that induced by visual stimulation, leads to the dilatation of retinal arterioles, which is accompanied by an immediate increase in retinal and optic nerve head blood flow. According to the current scientific view, functional hyperemia ensures the adequate supply of nutrients and metabolites in response to the increased metabolic demand of the neural tissue. Although the molecular mechanisms behind neurovascular coupling are not yet fully elucidated, there is compelling evidence that this regulation is impaired in a wide variety of neurodegenerative and vascular diseases. In particular, it has been shown that the breakdown of the functional hyperemic response is an early event in patients with diabetes. There is compelling evidence that alterations in neurovascular coupling precede visible signs of diabetic retinopathy. Based on these observations, it has been hypothesized that a breakdown of functional hyperemia may contribute to the retinal complications of diabetes such as diabetic retinopathy or macular edema. The present review summarizes the current evidence of impaired neurovascular coupling in patients with diabetes. In this context, the molecular mechanisms of functional hyperemia in health and disease will be covered. Finally, we will also discuss how neurovascular coupling may in future be used to monitor disease progression or risk stratification.Published versionThis work was funded by the Austrian Science Foundation FWF Project KLIF721