G. Garhöfer

Diffuse luminance flicker increases blood flow in major retinal arteries and veins.

It has been shown that diffuse luminance flicker increases optic nerve head blood flow. The current study has been performed to quantify changes in retinal blood flow during flicker stimulation. In a group of 11 healthy volunteers, red blood cell velocity and retinal vessel diameters were assessed with bi-directional laser Doppler velocimetry and the Zeiss retinal vessel analyzer before, during and after stimulation with diffuse luminance flicker. Retinal blood flow was calculated for each condition. Flicker stimulation increased retinal blood flow by +59 +/- 20% (p<0.01) in arteries and by +53 +/- 25% (p<0.01) in retinal veins. These results demonstrate that diffuse luminance flicker increases retinal blood flow in the human retina.

Hyperglycemia affects flicker-induced vasodilation in the retina of healthy subjects

Flickering light stimulation of retinal photoreceptors induces retinal vessel dilation in humans. In the present study the effect of high blood glucose levels on this neuro-vascular mechanism was investigated in 12 healthy young male subjects. Blood glucose levels were consecutively increased during 30 min to 100, 200 and 300 mg/dl and kept at the respective level for the following 30 min using hyperglycemic insulin clamps. Eight Hertz flickering light was applied to the fundus at the end of each glucose plateau during continuous retinal vessel diameter measurements with the Zeiss retinal vessel analyser (RVA). During normoglycemia (100 mg/dl) flickering light induced a significant vasodilation of retinal arteries (+2.8+/-0.4%, p<0.0001) and veins (+2.6+/-0.4%, p<0.0001). At 300 mg/dl blood glucose the flicker response in retinal veins was significantly decreased by 55% (p=0.015 versus 100 mg/dl). The modified RVA employed in the present study provides high sensitivity and is capable of studying flicker-induced retinal vasodilation. Using this technique the present study confirms that flickering light stimulation of the human retina induces vasodilation in retinal vessels in healthy subjects. In addition, our data indicate that the retinal vessel response to flickering light stimulation is significantly reduced during hyperglycemia in humans. The relevance of this finding for diabetes-related eye disease remains to be shown.

The ocular hemodynamic response to nitric oxide synthase inhibition is unaltered in patients with early type I diabetes

BackgroundAn impaired ocular hemodynamic response to systemic nitric oxide synthesis inhibition has been demonstrated in patients with long-standing insulin-dependent diabetes mellitus. It is unclear whether this altered responsiveness is already detectable in early uncomplicated type I diabetes.MethodsThe effect of the nitric oxide synthase inhibitor NG-monomethyl-l-arginine (L-NMMA) was studied in 10 male patients with early type I diabetes under euglycemic conditions and 10 healthy matched control subjects in a single (analyst) blinded cohort study design. Changes in ocular hemodynamics (fundus pulsation amplitude, mean flow velocity in the ophthalmic artery) and in pulse rate and mean blood pressure were measured in response to systemic intravenous doses of 1.5, 3, and 6xa0mg/kg L-NMMA.ResultsL-NMMA dose-dependently and significantly decreased fundus pulsation amplitude (−21.0% vs −23.3% in diabetics and controls, respectively), mean flow velocity in the ophthalmic artery (−12.3% vs −10.8%) and pulse rate (−15.4% vs −16.6%) and increased mean arterial pressure (+19.5% vs +14.7%). The ocular and systemic hemodynamic effects of L-NMMA were not different between patients with diabetes and controls.ConclusionThe responsiveness of the choroidal vasculature and the ophthalmic artery to L-NMMA is not altered in early type 1 diabetes. An impaired hemodynamic response to nitric oxide synthesis inhibition in diabetes is therefore not caused by a primary defect but rather due to altered vascular responsiveness secondary to long-standing disease.

Risikofaktoren der altersbedingten Makuladegeneration

SummaryAge-related macular degeneration (AMD) is the leading cause of legal blindness in the industrialized world. Considering the increasing life expectancy and the population pyramid age structure, the prevalence of AMD will increase even more in the following years. Given the facts that the pathophysiology of this disease is still poorly understood and that the therapeutical options today are rather limited, several studies have investigated the cause of AMD. The present review will outline the risk factors for this disease and the results of the latest research.ZusammenfassungDie altersbedingte Makuladegeneration (AMD) stellt heute die häufigste Ursache für Blindheit im rechtlichen Sinn in den Industrienationen dar. Durch die anhaltend steigende Lebenserwartung und die Umstrukturierung der Bevölkerungspyramide ist zu erwarten, dass sich diese Entwicklung nicht nur fortsetzen, sondern sogar verschärfen wird. In Anbetracht dessen und der Tatsache, dass bis heute weder die Pathophysiologie dieser Erkrankung eindeutig geklärt ist noch ausreichende Therapieoptionen zur Verfügung stehen, wurden in den letzten Jahrzehnten zahlreiche Studien über die Ursachen der AMD durchgeführt. In der vorliegenden Übersichtsarbeit werden die Risikofaktoren dieser Krankheit und die bisherigen Forschungsergebnisse näher beleuchtet.

Acute effects of intravenously administered ethanol on retinal vessel diameters and flicker induced vasodilatation in healthy volunteers

There is evidence from several vascular beds that acute alcohol consumption causes ocular hypotension and peripheral vasodilatation. The current study investigated the effects of intravenously administered ethanol on retinal vessel diameters and on flicker induced retinal vasodilatation. For this purpose, ethanol (0.35 g/kg) or placebo (physiologic saline solution) was administered intravenously for 40 min in a randomized, double masked, two way cross-over design to 12 healthy male volunteers. Retinal vessel diameters and flicker induced vasodilatation were measured before administration of ethanol as well as 30, 50, 90 and 130 min after the start of infusion with a retinal vessel analyzer. Intraocular pressure, systemic blood pressure and blood ethanol concentration were determined at the same time points. Intravenous administration of ethanol increased blood ethanol concentration from 0.0 g/l to 0.56+/-0.10 g/l. Ethanol reduced IOP, but did not change ocular perfusion pressure. After cessation of the infusion blood ethanol concentration started to drop reaching a blood ethanol concentration of 0.22+/-0.06 g/l 130 min after the start of infusion. Retinal arterial diameters increased significantly after administration of ethanol by a maximum of +4.2+/-4.0%, whereas no change was observed in retinal veins. Neither arterial nor venous diameters were influenced by administration of placebo. Flicker stimulation induced a significant dilatation in both arterial and venous diameters. Ethanol did not change flicker responses in arteries or in retinal veins. In conclusion, intravenous administration of ethanol increases retinal arterial diameters, whereas venous diameters remained unchanged. Whether this is related to a direct vasodilator effect or to a hitherto unidentified mechanism remains to be clarified.

Strukturelle Endpunkte für Glaukomstudien

BACKGROUNDnStructural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma.nnnOBJECTIVEnIs the evidence strong enough to establish structural endpoints as surrogate endpoints?nnnMATERIAL AND METHODSnReview of current understanding between structure and function in glaucoma.nnnRESULTSnThe introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along axa0circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On axa0microscopic level there is axa0strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required.nnnCONCLUSIONnThe current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phasexa03 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phasexa02 and proof of concept studies.ZusammenfassungHintergrundStrukturelle Endpunkte wurden als Surrogatendpunkte für die Zulassung neuroprotektiver Substanzen bei Glaukom diskutiert.FragestellungIst die Evidenz stark genug, um strukturelle Endpunkte als Surrogatendpunkte zu etablieren?Material und MethodeEs erfolgt eine Zusammenfassung des Verständnisses zwischen Struktur und Funktion bei Glaukom.ErgebnisseDie Einführung der optischen Kohärenztomographie hat die Bildgebung bei Glaukom revolutioniert. Klinisch können sowohl die retinale Nervenfaserschichtdicke entlang eines in der Papille zentrierten Kreises als auch die Ganglienzellschichtdicke im Bereich der Makula gemessen werden, wobei man Letztere in Kombination mit anderen retinalen Schichten quantifiziert. Auf mikroskopischer Ebene gibt es eine starke Korrelation zwischen dem Verlust von Struktur und Funktion. Diese ist aber mit den klinischen Methoden nur ungenügend etabliert. Das gilt insbesondere für den longitudinalen Verlauf der Erkrankung. Zukünftige bildgebende Verfahren, die heute noch nicht klinisch zur Verfügung stehen, könnten das Potenzial haben, ein klareres Verständnis zum Zusammenhang zwischen Struktur und Funktion zu etablieren.DiskussionDie derzeitige Evidenz lässt die Verwendung struktureller Endpunkte als Surrogatendpunkte für Phase-3-Studien bei Glaukom nicht zu. Neuroprotektive Medikamente müssen auf Basis von Gesichtsfelduntersuchungen zugelassen werden, da es sich dabei um den patientenrelevanten Endpunkt handelt. Strukturelle Endpunkte könnten aber in der Zukunft eine wichtige Rolle bei Phase-2-Studien oder Proof-of-concept-Studien spielen.AbstractBackgroundStructural endpoints have been discussed as surrogate endpoints for the approval of neuroprotective drugs in glaucoma.ObjectiveIs the evidence strong enough to establish structural endpoints as surrogate endpoints?Material and methodsReview of current understanding between structure and function in glaucoma.ResultsThe introduction of optical coherence tomography has revolutionized imaging in glaucoma patients. Clinically either the nerve fiber layer thickness can be measured along axa0circle centered in the optic nerve head or the ganglion cell layer thickness can be assessed in the macular region, the latter being quantified in combination with other inner retinal layers. On axa0microscopic level there is axa0strong correlation between structural and functional loss but this relation can only partially be described with currently available clinical methods. This is particularly true for longitudinal course of the disease in glaucoma patients. Novel imaging techniques that are not yet used clinically may have the potential to increase our understanding between structure and function in glaucoma but further research in this field is required.ConclusionThe current evidence does not allow the establishment of structural endpoints as surrogate endpoints for phasexa03 studies in glaucoma. Neuroprotective drugs have to be approved on the basis of visual field data because this is the patient-relevant endpoint. Structural endpoints can, however, play an important role in phasexa02 and proof of concept studies.

Neuerungen in der retinalen Bildgebung

New developments in retinal imaging have revolutionised ophthalmology in recent years. In particular, optical coherence tomography (OCT) provides highly resolved and well reproducible images and has rung in a new era in ophthalmological imaging. The technology was introduced in the early 1990u2009s, and has rapidly developed. There have been improvements in resolution, sensitivity and processing speed. There have also been developments in functional processing. OCT angiography is the first application in routine clinical work.

Pharmakologische Basis der Anti-VEGF Therapie

ZusammenfassungDie vorliegende Übersichtsarbeit versucht unser derzeitiges Wissen bezüglicher der pharmakologischen Basis der derzeit verfügbaren anti-VEGF Therapien zusammenzufassen. Zusätzlich sollen die wichtigsten klinischen Studien und die möglichen Unterschiede zwischen den verschiedenen Behandlungskonzepten besprochen werden.SummaryThis review seeks to summarize our current knowledge on the pharmacological basis of the different currently available anti-VEGF treatments. In addition, results of major clinical trials and the potential differences between the different treatment approaches will be covered.

Das Nahrungsergänzungsmittel VITAMAC® bei Patienten mit trockenem Auge Syndrom – Eine Anwendungsbeobachtung

SummaryBACKGROUND: Dry Eye Syndrome is a highly prevalent ocular condition inducing an inflammatory response on the ocular surface. Given that food supplements including omega 3 fatty acids have been shown to reduce inflammation in several tissues, the current observational case series focuses on the question whether patients satisfaction is improved after treatment with a combination of vitamins and omega 3 fatty acids PATIENTS AND METHODS: 20 patients with Dry Eye Syndrome were included in this observational case series. Patients ingested the food supplement VITAMAC® for 3 months according to the product insert. Patients satisfaction was assessed with the Standard Ocular Surface Diseases Index (OSDI) Questioner before and after a three month administration. Following standard care visual acuity and Schirmer test were measured at baseline and at the end of the observation period. RESULTS: 2 patients discontinued the intake of VITAMAC® and were therefore not included in the analysis. For the remaining 18 patients, the OSDI was improved after administration of VITAMAC® from 19.7 (range 8–33) at baseline to 14.1 (range 1–29) at the end of the observation period (p < 0.01). However, no significant change was observed in the Schirmers test or in terms of visual acuity. CONCLUSIONS: Administration of VITAMAC® day and night capsules improved OSDI, but did not affect Schirmer test or visual acuity. Accordingly, one may formulate the hypothesis that VITAMAC® improves the subjective symptoms of DES, which needs to be tested in an adequately designed clinical trial.ZusammenfassungHINTERGRUND: Das weitverbreitete Trockene Auge Syndrom ist mit Entzündungsreaktionen an der Augenoberfläche assoziiert. In Hinblick darauf, dass Nahrungsergänzungsmittel wie Omega 3 Fettsäuren in verschiedenen Geweben eine Reduktion von Entzündungsreaktionen bewirkt, wurde das Augenmerk bei dieser Studie auf die Patientenzufriedenheit nach Behandlung mit einer Wirkstoffkombination aus Vitaminen und Omega 3 Fettsäuren gelegt. PATIENTEN UND METHODEN: 20 Patienten mit dem Trockenen Auge Syndrom wurden in diese Anwendungsbeobachtung eingeschlossen. Die Patienten nahmen drei Monate lang das Nahrungsergänzungsmittel VITAMAC® entsprechend den Angaben der Gebrauchsinformation ein. Die Patientenzufriedenheit wurde dabei mittels des Standard Ocular Surface Index (OSDI) bestimmt. Dazu beantworteten die Patienten jeweils unmittelbar vor Beginn des Einnahmezyklus und nach einer Verabreichungsdauer von 3 Monate den OSDI Fragebogen. Dem Standardverfahren entsprechend wurden ein Sehtest und ein Schirmertest zur Überprüfung der Tränenproduktionsmenge zu Beginn und am Ende des Beobachtungszeitraums durchgeführt. ERGEBNISSE: 2 Patienten brachen die Einnahme von VITAMAC® ab und wurden daher nicht in die Analyse miteinbezogen. Bei den verbleibenden 18 Patienten verbesserte sich der OSDI nach Verabreichung von VITAMAC® signifikant, von 19,7 (Bereich 8 bis 33) bei Beginn auf 14,1 (Bereich 1 bis 25) am Ende der Beobachtungsperiode (p < 0,01). Hingegen konnten beim Schirmer Test und Sehschärfe keine signifikanten Veränderungen beobachtet werden. ZUSAMMMENFASSUNG: Die Verabreichung von VITAMAC® Tag- und Nacht-Kapseln verbesserte den OSDI deutlich, während bezüglich Schirmer Test und Sehschärfe kein Effekt festgestellt werden konnte. Auf diesen Erkenntnissen basierend kann die Hypothese aufgestellt werden, dass VITAMAC® in der Lage ist, die subjektiven Symptome des Trockenen Auge Syndroms zu verbessern, welche es in einer adäquaten klinischen Studie zu überprüfen gilt.