Publications by authors named "Reinhard Told"

39 Publications

Impact of large choroidal vessels on choriocapillaris flow deficit analyses in optical coherence tomography angiography.

PLoS One 2021 3;16(8):e0254955. Epub 2021 Aug 3.

Vienna Clinical Trial Center (VTC), Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: To investigate the impact of large choroidal vessels (LCV) on Choriocapillaris (CC) flow deficit (FD) analyses with swept-source optical coherence tomography angiography (SS-OCTA).

Design: Prospective, cross-sectional study.

Methods: Macular 6x6mm SS-OCTA scans were obtained from intermediate age-related macular degeneration (iAMD) and healthy eyes. Images were captured and processed according to most common standards and analyzed for percentage of flow-deficits (FD%) within four 1x1mm squares at the corners of each image. Choroidal thickness (CT), iris color and refraction error were considered as potential influential factors for LCV visibility. A linear mixed model and logistic regression models were calculated for statistical evaluation.

Results: Sixty-nine iAMD and 49 age-matched healthy eyes were enrolled. LCV were visible in at least one sector in 52% of iAMD and 47% of healthy eyes. Within the iAMD group FD% were significantly lower in areas containing LCV (p = 0.0029). Increasing CT resulted in an odds ratio decrease of LCV (OR: 0.94, p<0.0001). Below a CT value of ≤118μm LCV could be expected with a sensitivity of 86% and a specificity of 85%.

Conclusions: LCV can significantly affect CC FD analyses of SS-OCTA images. Their visibility is negatively associated with CT. The impact of LCV should be taken into account when performing CC FD assessments, especially in patients where reduced CT is to be expected and inclusion of affected areas should be considered carefully.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254955PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330935PMC
August 2021

Three-dimensional assessment of para- and perifoveal photoreceptor densities and the impact of meridians and age in healthy eyes with adaptive-optics optical coherence tomography (AO-OCT).

Opt Express 2020 Nov;28(24):36723-36739

An adaptive optics optical coherence tomography (AO-OCT) system is used to assess sixty healthy eyes of thirty subjects (age 22 to 75) to evaluate how the outer retinal layers, foveal eccentricity and age effect the mean cone density. The cone mosaics of different retinal planes (the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST), and the full en-face plane (FEF)) at four main meridians (superior, nasal, inferior, temporal) and para- and perifoveal eccentricities (ecc 2.5° and 6.5°) were analyzed quantitatively. The mean overall cone density was 19,892/mm at ecc 2.5° and 13,323/mm at ecc 6.5°. A significant impact on cone density was found for eccentricity (up to 6,700/mm between ecc 2.5° and 6.5°), meridian (up to 3,700/mm between nasal and superior meridian) and layer (up to 1,400/mm between FEF and IS/OS). Age showed only a weak negative effect. These factors as well as inter-individual variability have to be taken into account when comparing cone density measurements between healthy and pathologically changed eyes, as their combined effect on density can easily exceed several thousand cones per mm even in parafoveal regions.
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http://dx.doi.org/10.1364/OE.409076DOI Listing
November 2020

Retinal vessel diameters, flicker-induced retinal vasodilation and retinal oxygen saturation in high- and low-risk pregnancy.

Acta Ophthalmol 2021 Sep 16;99(6):628-636. Epub 2020 Dec 16.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

Purpose: To compare retinal vascular parameters between high-risk and low-risk pregnant women over time during pregnancy.

Methods: In a longitudinal study, we included pregnant women with normal blood pressure and normal body mass index (BMI, group 1), pregnant women with systemic hypertension and/or overweight (group 2) and age-matched nonpregnant healthy women (group 3). Using the dynamic vessel analyser (DVA) we investigated flicker-induced vasodilation in retinal arteries (FLA) and veins (FLV), central retinal arterial and vein equivalent (CRAE, CRVE), arterio-venous ratio (AVR) and retinal arterial and venous oxygen saturation (SartO , SveinO ). Study visits were scheduled 2nd trimester (TP 2), 3rd trimester (TP 3) and postpartum (PP).

Results: Data from 29 women in group 1, 25 women in group 2 and 33 women in group 3 were included for analysis. FLA, FLV, CRAE, CRVE, AVR and SveinO were altered in group 2 (p-values between < 0.001 and 0.009). At TP 3 the differences between groups were most pronounced. In contrast, there were only minor differences between group 1 and 3. Changes in retinal parameters were independently associated with systemic blood pressure and BMI.

Conclusions: The present analysis indicates that flicker-induced retinal vasodilation, retinal vessel diameters and retinal oxygen saturation are altered in high-risk pregnant women. Hence, these parameters are candidate biomarkers for pregnancy complications, a hypothesis that deserves further study.
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http://dx.doi.org/10.1111/aos.14696DOI Listing
September 2021

Intraretinal microvascular changes after ERM and ILM peeling using SSOCTA.

PLoS One 2020 1;15(12):e0242667. Epub 2020 Dec 1.

Department of Ophthalmology and Optometry, Vienna Trial Center (VTC), Medical University of Vienna, Vienna, Austria.

Background: To prospectively investigate retinal vascular changes in patients undergoing epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling using swept source optical coherence tomography angiography (SSOCTA).

Methods: Consecutive patients were grouped based on ERM severity and followed using SSOCTA up to month 3 after surgical intervention. Superficial and deep foveal avascular zone (s/dFAZ) as well as foveal and parafoveal vessel density (VD) were correlated with ERM severity and visual acuity. Differences between groups were evaluated.

Results: Significant correlations were found between ERM severity and baseline sFAZ, dFAZ and best corrected visual acuity (BCVA), central retinal subfield thickness (CST) and ΔCST (r = -0.52, r = -0.43, r = -0.42, r = 0.58, r = 0.39; all p<0.05). Vascular flow parameters did not correlate with age, peeling size, pseudophakia or CST, but correlated with intraretinal cysts presence. No associations of BCVA with any of the OCTA parameters across time were found. Significant differences between ERM severity groups 1 and 2 were found for sFAZ at baseline (p = 0.005) and at the 3-month follow-up (p = 0.014), and for dFAZ at baseline (p = 0.017). Superficial foveal and parafoveal VD were not significantly different between groups (all p>0.05).

Conclusions: This study clearly shows that ERM severity based on ERM staging has to be taken into account when undertaking studies in patients with idiopathic ERM using SSOCTA. Further, specific changes in the superficial and deep retinal vasculature in eyes undergoing ERM and ILM peeling were found. However, the clinical usefulness and prognostic value for post-surgical treatment BCVA of the SSOCTA-derived variables (sFAZ and dFAZ area, as well as foveal and parafoveal VD) used remains questionable.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242667PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707569PMC
January 2021

Identification of microvascular and morphological alterations in eyes with central retinal non-perfusion.

PLoS One 2020 10;15(11):e0241753. Epub 2020 Nov 10.

Department of Ophthalmology and Optometry, Vienna Clinical Trial Centre (VTC), Medical University of Vienna, Vienna, Austria.

Purpose: To evaluate the characteristics and morphological alterations in central retinal ischemia caused by diabetic retinopathy (DR) or retinal vein occlusion (RVO) as seen in optical coherence tomography angiography (OCTA) and their relationship to visual acuity.

Methods: Swept-source optical coherence tomography (SSOCT) and OCTA (Topcon, Triton) data of patients with central involving retinal ischemia were analyzed in this cross-sectional study. The following parameters were evaluated: vessel parameters, foveal avascular zone (FAZ), intraretinal cysts (IRC), microaneurysms (MA), vascular collaterals in the superficial (SCP) and deep plexuses (DCP), hyperreflective foci (HRF), epiretinal membrane (ERM), external limiting membrane (ELM) and ellipsoid zone (EZ) disruption, as well as the disorganization of retinal inner layers (DRIL). Best-corrected visual acuity (BCVA), age, gender, disease duration and ocular history were also recorded.

Results: 44 eyes of 44 patients (22 with RVO, 22 with DR) were analyzed. The mean age was 60.55 ± 11.38 years and mean BCVA 0.86 ± 0.36 (Snellen, 6m). No significant difference was found between DR subgroups (non proliferative vs. proliferative). Between RVO subgroups (CRVO vs. BRVO) a significant difference was found in term of collateral vessel of the DCP (p = 0.014). A pooled DR and RVO group were created and compared. Significantly more MAs (p = 0.007) and ERM (p = 0.007) were found in the DR group. Statistically significant negative correlation was demonstrated between FAZ and BCVA (p = 0.45) when analyzing all patients with retinal ischemia.

Conclusion: This study has shown that the best predictor of visual outcome in center involved ischemic diseases is the size of FAZ. Besides the presence of MAs and ERM, all other OCT and OCTA parameters were present in a similar extent in DR and RVO group despite the completely different disease origins. Our results suggest that as soon as retinal ischemia in the macular region is present, it has a similar appearance and visual outcome independently of the underlying disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241753PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654769PMC
December 2020

LONGITUDINAL CHANGES IN QUANTITATIVE AUTOFLUORESCENCE DURING PROGRESSION FROM INTERMEDIATE TO LATE AGE-RELATED MACULAR DEGENERATION.

Retina 2021 Jun;41(6):1236-1241

Department of Ophthalmology and Optometry, Christian Doppler Laboratory for Ophthalmic Image Analysis, Vienna Reading Center, Medical University of Vienna, Vienna, Austria.

Purpose: To prospectively investigate the development of quantitative autofluorescence (qAF) during progression from intermediate to late age-related macular degeneration (AMD).

Methods: Quantitative autofluorescence images from patients with intermediate AMD were acquired every three months with a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) using a built-in autofluorescence reference. The association between changes in longitudinal qAF and progression toward late AMD was assessed using Cox regression models with time-dependent covariates.

Results: One hundred and twenty-one eyes of 71 patients were included, and 653 qAF images were acquired. Twenty-one eyes of 17 patients converted to late AMD (median follow-up: 21 months; 12 eyes: atrophic AMD; nine eyes: neovascular AMD). The converting patients' mean age was 74.6 ± 4.4 years. Eleven eyes in the converting group (52.4%) were pseudophakic. The presence of an intraocular lens did not affect the qAF regression slopes (P > 0.05). The median change for atrophic AMD was -2.34 qAF units/3 months and 0.78 qAF units/3 months for neovascular AMD. A stronger decline in qAF was significantly associated with an increased risk of developing atrophic AMD (hazard ratio = 1.022, P < 0.001). This association, however, was not present in the group progressing toward neovascular AMD (hazard ratio = 1.001, P = 0.875).

Conclusion: The qAF signal declines with progression to atrophy, contrary to developing neovascularization. Quantitative autofluorescence may allow identification of patients at risk of progressing to late AMD and benefits individualized patient care in intermediate AMD.
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http://dx.doi.org/10.1097/IAE.0000000000002995DOI Listing
June 2021

Retinal vessel architecture in retinopathy of prematurity and healthy controls using swept-source optical coherence tomography angiography.

Acta Ophthalmol 2021 Mar 4;99(2):e232-e239. Epub 2020 Aug 4.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: To determine microvascular changes in children with a history of retinopathy of prematurity (ROP) and in a control group of full-term children.

Methods: In a cross-sectional study, 30 eyes of 15 children aged 6-8 years with a history of ROP were evaluated with swept-source optical coherence tomography angiography (SS-OCTA). Twenty-eight eyes of 22 age-matched full-term children served as a healthy control group. The foveal avascular zone (FAZ), vessel density (VD) and choroidal vascular flow area (VFA) were evaluated on OCTA and correlated with central retinal thickness (CRT), visual acuity (VA), birth weight (BW), gestational age (GA) and ROP stages.

Results: Twenty-two eyes of 14 children with a history of ROP (stage 1-3) and 25 eyes of 19 full-term children were available for evaluation. In the ROP group, the gestational age was 27 ± 2 weeks and birth weight was 781 ± 164 g. In the ROP group, CRT was higher in the central ETDRS segment (mean difference [95% CI]: 32.8 µm [18.7; 47.0], p = 0.0002) compared to the controls. Smaller mean FAZ area (-0.12 [-0.19; -0.04], p = 0.004) and perimeter (-662 [-1228; -96], p = 0.03) was found in comparison to the control group. An oval shape of the FAZ was observed among patients with a history of ROP. The mean central VD of the superficial plexus was 28 ± 8/23 ± 8% and of the deep plexus 7 ± 7/3 ± 5% (ROP group/control group; p > 0.05). No statistically significant difference was found regarding the choroidal VFA. Only weak correlation of FAZ and VD with function was observed.

Conclusions: Swept-source optical coherence tomography angiography imaging revealed significant microvascular anomalies in children with a history of ROP indicating disturbance of early morphological development of the central retina.
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http://dx.doi.org/10.1111/aos.14557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984179PMC
March 2021

Profiling neovascular age-related macular degeneration choroidal neovascularization lesion response to anti-vascular endothelial growth factor therapy using SSOCTA.

Acta Ophthalmol 2021 Mar 24;99(2):e240-e246. Epub 2020 Jul 24.

Department of Ophthalmology and Optometry, Vienna Clinical Trial Center (VTC), Medical University of Vienna, Vienna, Austria.

Purpose: To identify the changes in distinct vascular parameters of choroidal neovascularization (CNV) in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD) during the primary response to anti-VEGF therapy using aflibercept.

Methods: Patients were prospectively followed during the first 3 months according to a standardized protocol with mandatory visits at days 7 and 14 after each anti-VEGF treatment up to day 90. Fourteen eyes were seen in addition at days 1 and 3 post-initial injection. Aflibercept was administered at baseline (BL), day 30 and 60. 6 × 6mm SSOCTA (PlexElite, Zeiss) images were acquired. Using the semi-automated AngioTool, CNV area, vessel area, vessel density (VD), the number of junctions, junctions density, total vessel length, average vessel length, total number of endpoints and lacunarity were assessed.

Results: Thirty-two consecutive patients presenting with treatment-naïve, SSOCTA-positive CNV lesions were included. Close follow-up showed a characteristic neovascular response curve with a dynamic decrease in lesion size within days and a reactive increase following 2 weeks after initial treatment. An undulating pattern was seen for all neovascular parameters except for vascular density, with variable statistical significance. Due to a flattening of the therapeutic response as early as after the second treatment, CNV lesion size and most of the related parameters had an increase in activity above baseline values at the end of the loading phase. Lesion size was the leading feature of reactivation by a mean increase of 19.3% after three monthly aflibercept injections. Subgroup analysis based on lesion size revealed a significant correlation between best-corrected visual acuity and quantitative change in lesion size over time, but not baseline size.

Conclusions: Using SSOCTA, a morphologic neovascular response pattern can be identified in anti-VEGF treatment of CNV. A synchronized early decrease and consecutive reactivation in a large spectrum of neovascular biomarkers including size and internal structure are visualized in a qualitative and quantitative manner. SSOCTA analyses allow new insights in CNV morphology changes and therapeutic response.
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http://dx.doi.org/10.1111/aos.14554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984400PMC
March 2021

Subretinal Drusenoid Deposits and Photoreceptor Loss Detecting Global and Local Progression of Geographic Atrophy by SD-OCT Imaging.

Invest Ophthalmol Vis Sci 2020 06;61(6):11

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Purpose: To investigate the impact of subretinal drusenoid deposits (SDD) and photoreceptor integrity on global and local geographic atrophy (GA) progression.

Methods: Eighty-three eyes of 49 patients, aged 50 years and older with GA secondary to age-related macular degeneration (AMD), were prospectively included in this study. Participants underwent spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging at baseline and after 12 months. The junctional zone and presence of SDD were delineated on SD-OCT and FAF images. Linear mixed models were calculated to investigate the association between GA progression and the junctional zone area, baseline GA area, age, global and local presence of SDD and unifocal versus multifocal lesions.

Results: The area of the junctional zone was significantly associated with the progression of GA, both globally and locally (all P < 0.001). SDD were associated with faster growth in the overall model (P = 0.039), as well as in the superior-temporal (P = 0.005) and temporal (P = 0.002) sections. Faster progression was associated with GA baseline area (P < 0.001). No difference was found between unifocal and multifocal lesions (P > 0.05). Age did not have an effect on GA progression (P > 0.05).

Conclusions: Photoreceptor integrity and SDD are useful for predicting global and local growth in GA. Investigation of the junctional zone is merited because this area is destined to become atrophic. Photoreceptor loss visible on SD-OCT might lead to new structural outcome measurements visible before irreversible loss of retinal pigment epithelium occurs.
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http://dx.doi.org/10.1167/iovs.61.6.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415285PMC
June 2020

Relationship between morphological and vascular alterations in geographic atrophy using a multimodal imaging approach.

Acta Ophthalmol 2020 Sep 17;98(6):e700-e708. Epub 2020 Feb 17.

Department of Ophthalmology, Medical University of Vienna, Vienna, Austria.

Purpose: To assess geographic atrophy (GA) using a multimodal imaging approach, focusing on alterations at the level of the retinal pigment epithelium (RPE) and the choriocapillaris (CC) layers, by lesion demarcation, and assessment of morphological alterations within the atrophic area and in the transition zone.

Methods: Fifty-seven eyes of 34 patients with atrophic age-related macular degeneration (AMD) were included in this prospective, observational, cross-sectional study. Multimodal imaging using wide-field polarization-sensitive optical coherence tomography (PS-OCT), optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF) was performed. The images were overlaid and used to analyse and compare alterations in the retina and the CC.

Results: Mean atrophic lesion size was 8.15 mm (range: 2.23-17.23 mm ). In 52 of 57 eyes (91%), OCT-A displayed focal hypodense areas at the CC level in the transition zone of GA, as well as increased focal depolarizing material (e.g. melanin-containing structures) showed in PS-OCT en face depolarizing material maps. These regions of increased depolarizing material at the transition zone corresponded to the hypodense areas on OCT-A scans. All 57 eyes presented with abnormal FAF patterns at the transition zone. All 57 eyes showed distinct alterations of CC flow pattern architecture. Six eyes (11%) demonstrated reduced and three eyes (5%) a complete loss of CC flow pattern architecture across the entire area of GA, while 48 of 57 eyes (84%) presented with irregular mixed patterns of different focal alterations of CC flow architecture within the area of GA. Reduced CC patterns exceeding GA lesion margins into the transitional zone were found in all eyes.

Conclusions: Optical coherence tomography angiography images revealed different degrees of flow impairment within the atrophic lesion area and its transition zone. Alterations in RPE morphology and tissue integrity resulting in accumulation of depolarizing material, such as melanin, could result in misinterpretation of OCT-A imaging in areas in the shadow of depolarizing material. These changes seem to be partially independent from autofluorescence altering processes.
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http://dx.doi.org/10.1111/aos.14352DOI Listing
September 2020

SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY, FLUORESCEIN ANGIOGRAPHY, AND INDOCYANINE GREEN ANGIOGRAPHY COMPARISONS REVISITED: Using a Novel Deep-Learning-Assisted Approach for Image Registration.

Retina 2020 Oct;40(10):2010-2017

Department of Ophthalmology and Optometry, Vienna Clinical Trial Center (VTC), Medical University of Vienna, Vienna, Austria.

Purpose: To compare area measurements between swept source optical coherence tomography angiography (SSOCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA) after applying a novel deep-learning-assisted algorithm for accurate image registration.

Methods: We applied an algorithm for the segmentation of blood vessels in FA, ICGA, and SSOCTA images of 24 eyes with treatment-naive neovascular age-related macular degeneration. We trained a model based on U-Net and Mask R-CNN for each imaging modality using vessel annotations and junctions to estimate scaling, translation, and rotation. For fine-tuning of the registration, vessels and the elastix framework were used. Area, perimeter, and circularity measurements were performed manually using ImageJ.

Results: Choroidal neovascularization lesion size, perimeter, and circularity delineations showed no significant difference between SSOCTA and ICGA (all P > 0.05). Choroidal neovascularization area showed excellent correlation between SSOCTA and ICGA (r = 0.992) and a Bland-Altman bias of -0.10 ± 0.24 mm. There was no significant difference in foveal avascular zone size between SSOCTA and FA (P = 0.96) and an extremely small bias of 0.0004 ± 0.04 mm and excellent correlation (r = 0.933). Foveal avascular zone perimeter was not significantly different, but foveal avascular zone circularity was significantly different (P = 0.047), indicating that some small cavities or gaps may be missed leading to higher circularity values representing a more round-shaped foveal avascular zone in FA.

Conclusion: We found no statistically significant differences between SSOCTA and FA and ICGA area measurements in patients with treatment-naive neovascular age-related macular degeneration after applying a deep-learning-assisted approach for image registration. These findings encourage a paradigm shift to using SSOCTA as a first-line diagnostic tool in neovascular age-related macular degeneration.
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http://dx.doi.org/10.1097/IAE.0000000000002695DOI Listing
October 2020

INVESTIGATING A GROWTH PREDICTION MODEL IN ADVANCED AGE-RELATED MACULAR DEGENERATION WITH SOLITARY GEOGRAPHIC ATROPHY USING QUANTITATIVE AUTOFLUORESCENCE.

Retina 2020 Sep;40(9):1657-1664

Department of Ophthalmology and Optometry, Vienna Clinical Trial Center (VTC), Medical University of Vienna, Vienna, Austria; and.

Purpose: To investigate geographic atrophy (GA) progression using quantitative autofluorescence (qAF) in eyes with solitary GA.

Methods: Forty-three eyes of 26 patients (age 79.7 ± 7.2 years; 28 women; 16 pseudophakic) underwent spectral-domain optical coherence tomography and qAF imaging at baseline and after 12 months. The junctional zone (AJZ) and a nonaffected 300-µm-wide control area (AC) were delineated on spectral-domain optical coherence tomography scans and transferred to the qAF image. Linear mixed models were calculated to investigate the association between GA progression and qAF, age, and baseline GA area. Mixed model analyses of variance were used to investigate differences in qAF between areas.

Results: Quantitative autofluorescence of the three inferior sections of both the AJZ (P = 0.028; P = 0.014 and P = 0.032) and the AC (P = 0.043; P = 0.02 and P = 0.028) were significantly associated with GA progression after 12 months. However, qAF measurements were not associated with GA progression in the overall model (P > 0.05). Mean qAF was significantly lower in the AJZ and growth area (AG12) than in the AC (both P ≤ 0.001).

Conclusion: The authors report a statistically significant association between GA growth area and qAF measurements at specific retinal locations and a significant difference in qAF between the GA border and unaffected areas outside the lesion. Quantitative autofluorescence measurements may be limitedly useful for predicting GA progression.
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http://dx.doi.org/10.1097/IAE.0000000000002653DOI Listing
September 2020

Longitudinal Association Between Drusen Volume and Retinal Capillary Perfusion in Intermediate Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2019 06;60(7):2503-2508

Vienna Clinical Trial Center (VTC), Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: To evaluate vascular changes in the superficial and deep retinal capillary plexus (SCP, DCP) and their association with drusen volume changes in intermediate age-related macular degeneration (iAMD).

Methods: Patients with iAMD were examined at baseline and 12 months thereafter. Drusen volume was extracted from 20° × 20° OCT scans using a 3-mm ETDRS grid using a customized algorithm with manual correction. Vessel density (VD) and flow area (FA) were extracted from 3 × 3 mm SD-OCT-A scans after manual correction of the segmentation. Associations were investigated using multiple regression models.

Results: We used 31 eyes of 31 patients for evaluation. The mean age at baseline was 74.9 ± 5.4 years; 26 patients were female. Baseline visual acuity (VA) was 0.05 ± 0.08 logMAR (Snellen equivalent approximately 20/22). The initial mean 3-mm central drusen volume was 0.144 ± 0.136 mm3. A significant association with the signal strength index was consistently found, therefore all capillary measurements were corrected. VD in the same area was 49.88% ± 7.38% and 55.43% ± 9.31% for the SCP and DCP, respectively. The baseline FA resulted in 3.292 ± 0.218 mm2 and 3.433 ± 0.224 mm2 for the SCP and DCP, respectively. No association was found between changes in drusen volume and FA or VD after 12 months (all P > 0.05). VA worsened (P = 0.013) and the foveal FA of the SCP increased significantly (P = 0.014).

Conclusions: No significant association was found between the increase in drusen volume in iAMD and capillary retinal perfusion over a 12-month follow-up. Although VA decreased statistically over this time period, the foveal FA of the SCP increased.
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http://dx.doi.org/10.1167/iovs.18-26237DOI Listing
June 2019

Impact of Drusen Volume on Quantitative Fundus Autofluorescence in Early and Intermediate Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2019 05;60(6):1937-1942

Vienna Clinical Trial Center (VTC), Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Purpose: Drusen volume (DV) and quantitative autofluorescence (qAF) are potential indicators of progression in age-related macular degeneration (AMD). This prospective and observational study examined the association between DV and qAF of the retinal pigment epithelium.

Methods: Eighty-eight eyes of 52 patients with early and intermediate AMD were included. The mean follow-up was 9.2 ± 5.6 months, resulting in 312 examinations. DV was extracted from 6 × 6-mm spectral-domain optical coherence tomography scans. qAF was measured using a rotated Delori pattern. The associations between qAF and DV, age, sex, and lens status were investigated using linear mixed models.

Results: Patients' mean age was 75.6 ± 5.0 years (range, 61.0-83.4 years). Sixty-eight eyes (77.3%) were from females. No significant association between DV and qAF was found, neither within the total outer Early Treatment Diabetic Retinopathy Study (ETDRS) grid nor for ETDRS segments six to nine (all P > 0.05). Sex and lens status were not associated with qAF (P = 0.429 and P = 0.213, respectively). A significant association between age and qAF (P = 0.025) was found, indicating a decrease of qAF with age.

Conclusions: Quantification of DV and fundus autofluorescence did not reveal any correlation in early and intermediate AMD. qAF decreased with age, whereas DV increased in about half of the patients. This finding is a quantitative corroboration that fundus autofluorescence and the buildup of drusen are not correlated processes in AMD.
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http://dx.doi.org/10.1167/iovs.19-26566DOI Listing
May 2019

Repeatability and reliability of quantitative fundus autofluorescence imaging in patients with early and intermediate age-related macular degeneration.

Acta Ophthalmol 2019 Jun 13;97(4):e526-e532. Epub 2018 Dec 13.

Department of Ophthalmology and Optometry, Vienna Trial Center (VTC), Medical University of Vienna, Vienna, Austria.

Purpose: Quantification of fundus autofluorescence has only recently become available. We report our findings on the evaluation of the repeatability and reliability of quantitative fundus autofluorescence (qAF) measurements in patients with early and intermediate age-related macular degeneration (AMD), using the first approved and commercially available instrument.

Methods: A total of 43 eyes of 22 patients (aged between 52 and 84 years) diagnosed with early and intermediate AMD were included. All eyes were imaged at day 1, 3 months and 6 months using a modified scanning laser ophthalmoscope, equipped with an internal fluorescent reference. Mean qAF values were calculated for the fovea and for each concentric ring of the Delori pattern. Repeatability and reliability were calculated using Bland-Altman analysis and intraclass correlation (ICC).

Results: The mean patient age was 73.5 ± 7.9 years. Sixteen patients (73%) were female. qAF repeatability of the eight segments in the middle ring of the Delori pattern (qAF ) for between sessions was ±8.2%. Agreement at 3- and 6-month follow-up in eyes without retinal changes was ±8.3% and ±9.8%, respectively. Reliability of qAF was high for all images acquired [ICC = 0.98 (CI: 0.96-0.99), 0.97 (0.93-0.99) and 0.98 (0.92-0.99)]. Agreement at 3- and 6-month follow-up in eyes with retinal changes was ±18.1% and ±20.2%, respectively. Intraclass correlation (ICC) was slightly lower in eyes with retinal changes at 0.93 (0.84-0.97) and 0.96 (0.91-0.98), respectively.

Conclusions: Quantitative autofluorescence shows excellent repeatability and reliability as well as follow-up agreement in patients with early and intermediate AMD without retinal changes. This is relevant when conducting longitudinal studies using qAF.
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http://dx.doi.org/10.1111/aos.13987DOI Listing
June 2019

Comparison of SD-Optical Coherence Tomography Angiography and Indocyanine Green Angiography in Type 1 and 2 Neovascular Age-related Macular Degeneration.

Invest Ophthalmol Vis Sci 2018 05;59(6):2393-2400

Department of Ophthalmology and Optometry, Vienna Clinical Trial Center, Medical University of Vienna, Vienna, Austria.

Purpose: The purpose of this study is to compare the ability of spectral domain optical coherence tomography angiography (SD-OCTA) and indocyanine green angiography (ICGA) to detect and measure lesion area in patients with type 1 and 2 choroidal neovascularization (CNV).

Methods: Types 1 and 2 neovascular AMD (nAMD) were included in this prospective and observational case series. ETDRS best-corrected visual acuity (BCVA), ophthalmic examination with funduscopy, OCTA (AngioVue), fluorescein angiography (FA), ICGA, and OCT (Spectralis) were performed. CNV measurements were done manually by two experienced graders using the systems' innate region selection tools.

Results: Forty eyes of 39 consecutive patients with nAMD were included. Mean age was 77 ± 6.4 years, ETDRS BCVA was 67 ± 13 letters, and 11 eyes were treatment naïve. Nineteen CNV lesions were classified as type 1 and 21 as type 2. ICGA was able to identify CNV in all eyes. By contrast, OCTA detected CNV in 95% of type 1 and 86% of type 2 nAMD eyes. Mean overall CNV area (CNV-A) was 2.8 ± 2.7 mm2 in ICGA and 2.1 ± 2.7 mm2 in OCTA. Both lesion types CNV-A appeared significantly smaller in OCTA compared with ICGA (P < 0.01). Bland-Altman plot revealed a mean difference (bias) between OCTA and ICGA CNV-A of 0.76 ± 1.74 mm2. Intraclass correlation coefficient (ICC) for CNV-A was 0.91 and 0.93 for ICGA and OCTA, respectively. ICGA CNV-A in the four OCTA-negative eyes (median 4.7 mm2) was not significantly different from the 36 OCTA-positive eyes (median 1.7 mm2).

Conclusions: Type 1 and 2 CNV-A were significantly smaller in OCTA than in ICGA. OCTA was generally less successful in detecting CNV than ICGA in patients who were included into this study based on FA and OCT. However, OCTA detected all type 1 lesions except for one, indicating that the SD-OCTA signal is limited by detection limits of blood flow velocity rather than lesion type. Further efforts are needed pushing the limits of lowest detectable and fastest distinguishable flow until OCTA can deliver realistic qualitative and quantitative imaging of type 1 and 2 CNV for diagnosis and monitoring.
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http://dx.doi.org/10.1167/iovs.17-22902DOI Listing
May 2018

Method comparison of two non-invasive dual-wavelength spectrophotometric retinal oximeters in healthy young subjects during normoxia.

Acta Ophthalmol 2018 Aug 28;96(5):e614-e618. Epub 2018 Feb 28.

Department of Ophthalmology and Optometry, Vienna Clinical Trial Center (VTC), Medical University of Vienna, Vienna, Austria.

Purpose: Spectrophotometric retinal oximetry is a non-invasive technology for measuring oxygen saturation in arterioles and venules (SaO , SvO ). We compared two commercially available systems: the Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) and the Dynamic Vessel Analyzer (DVA, Imedos, Jena, Germany).

Methods: Twenty healthy adults were included after giving informed consent. Two measurement cycles 30 min apart, including Oxymap T1, DVA, arterialized capillary blood draw of the earlobe (ScO ) and peripheral oxygen saturation using finger pulse oximetry (SpO ) were scheduled.

Results: SaO (p > 0.0004) but not SvO (p < 0.05) was statistically significantly different between the retinal oximeters used. Agreement between devices using repeated SO measurements resulted in a standard deviation (SD) of differences of 3.5% in retinal arterioles and 4.8% in venules. Bland-Altman plot using the mean of a participant's two measurements from each device showed an average mean difference of 4.4% (95% confidence limits of agreement: -8.6 to 17.4) and -3.3% (95% confidence limits of agreement: -28.8 to 22.2) for SaO and SvO , respectively. Comparison of mean SaO and SvO with mean ScO and SpO indicated that SO measurements were generally higher in ScO and SpO .

Conclusion: This study shows very good repeatability for both devices, which is consistent with the literature. However, it does not show sufficient concordance between SaO measurements from both devices, indicating that patients should be followed by one device only. Differences in absorbance wavelengths used and image post-processing may explain the differences.
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http://dx.doi.org/10.1111/aos.13719DOI Listing
August 2018

2018 Update on Intravitreal Injections: Euretina Expert Consensus Recommendations.

Ophthalmologica 2018 1;239(4):181-193. Epub 2018 Feb 1.

Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.

Intravitreal injections (IVI) have become the most common intraocular procedure worldwide with increasing numbers every year. The article presents the most up-to-date review on IVI epidemiology and techniques. Unfortunately, important issues related to pre-, peri- and postinjection management lack randomized clinical trials for a final conclusion. Also, a great diversity of approaches exists worldwide. Therefore, expert consensus recommendations on IVI techniques are provided.
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http://dx.doi.org/10.1159/000486145DOI Listing
June 2018

Effects of Intravitreal Dexamethasone Implants on Retinal Oxygen Saturation, Vessel Diameter, and Retrobulbar Blood Flow Velocity in ME Secondary to RVO.

Invest Ophthalmol Vis Sci 2017 10;58(12):5022-5029

Department of Ophthalmology, Medical University of Vienna, MUV, Vienna, Austria.

Purpose: To investigate the effects of intravitreal 0.7 mg dexamethasone implants (Ozurdex) on arterial and venous oxygen saturation, retinal vessel diameter, and retrobulbar blood flow velocity in patients with macular edema (ME) due to retinal vein occlusion (RVO).

Methods: This prospective, nonrandomized clinical trial included 40 eyes of 40 patients with ME due to RVO. Measurements of arterial and venous oxygen saturation and retinal vessel diameters were performed using the Dynamic Vessel Analyzer. The main outcome measure was the retinal arteriovenous oxygen difference, calculated as the difference between arterial and venous oxygenation. Color Doppler imaging was performed for measuring peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) in ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCAs). Follow-up was monthly for 6 months following an initial dexamethasone implant injection. As statistical analysis, a mixed model was performed to investigate the effect treatment.

Results: The arteriovenous oxygen difference showed a significant increase (P < 0.01). Arterial oxygenation and vessel diameter did not respond to the treatment (P > 0.05), while the venous oxygen saturation and diameter decreased significantly (P < 0.01) compared to baseline. The retrobulbar blood flow velocities PSV, EDV, and RI showed no change in the OA, CRA, and PCA (P > 0.05).

Conclusions: In patients with RVO, intravitreal dexamethasone treatment leads to an increase in arteriovenous oxygen saturation difference indicating improved retinal oxygenation. Arterial oxygenation and vessel diameter showed no response, whereas venous oxygenation and vessel diameter decreased after treatment.
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http://dx.doi.org/10.1167/iovs.17-22229DOI Listing
October 2017

Psychophysical Vision Simulation of Diffractive Bifocal and Trifocal Intraocular Lenses.

Transl Vis Sci Technol 2016 Oct 17;5(5):13. Epub 2016 Oct 17.

Department of Clinical Pharmacology, Center of Medical Physics and Biomedical Engineering, Medical University Vienna, Austria.

Purpose: The visual performance of monofocal, bifocal, and trifocal intraocular lenses was evaluated by human individuals using a vision simulator device. This allowed investigation of the visual impression after cataract surgery, without the need actually to implant the lenses.

Methods: The randomized, double-masked, three-way cross-over study was conducted on 60 healthy male and female subjects aged between 18 and 35 years. Visual acuity (Early Treatment Diabetic Retinopathy Study; ETDRS) and contrast sensitivity tests (Pelli-Robson) under different lighting conditions (luminosities from 0.14-55 cd/m, mesopic to photopic) were performed at different distances.

Results: Visual acuity tests showed no difference for corrected distance visual acuity data of bi- and trifocal lens prototypes ( 0.851), but better results for the trifocal than for the bifocal lenses at distance corrected intermediate ( 0.021) and distance corrected near visual acuity ( 0.044). Contrast sensitivity showed no differences between bifocal and trifocal lenses at the distant ( = 0.984) and at the near position ( 0.925), but better results for the trifocal lens at the intermediate position ( 0.043). Visual acuity and contrast sensitivity showed a strong dependence on luminosity ( 0.001).

Conclusions: At all investigated distances and all lighting conditions, the trifocal lens prototype often performed better, but never worse than the bifocal lens prototype.

Translational Relevance: The vision simulator can fill the gap between preclinical lens development and implantation studies by providing information of the perceived vision quality after cataract surgery without implantation. This can reduce implantation risks and promotes the development of new lens concepts due to the cost effective test procedure.
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http://dx.doi.org/10.1167/tvst.5.5.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072543PMC
October 2016

Total Retinal Blood Flow in a Nonhuman Primate Optic Nerve Transection Model Using Dual-Beam Bidirectional Doppler FD-OCT and Microsphere Method.

Invest Ophthalmol Vis Sci 2016 Mar;57(3):1432-40

Center for Medical Physics and Biomedical Engineering Medical University of Vienna, Vienna, Austria.

Purpose: We validated noninvasive Doppler-optical coherence tomography (OCT) blood flow measurements against the terminal microsphere method in a surgical induced optic nerve transection nonhuman primate model.

Methods: In 6 nonhuman primates, total retinal blood flow (TRBF) was measured with a custom-built dual-beam bidirectional Doppler Fourier Domain (FD)-OCT. Peripapillary retinal nerve fiber layer thickness (RNFLT) was measured by Spectralis spectral-domain (SD)-OCT. Measurements were performed every 10 to 15 days before and after unilateral optic nerve transection (ONT) until RNFLT was reduced by more than 40% from baseline. Before the animals were killed, TRBF was measured using the microsphere technique.

Results: A significant correlation between all arterial and venous Doppler OCT TRBF measurements was found in ONT and contralateral control eyes (both P < 0.01, n = 6). The Bland-Altman analysis showed a bias of 0.57 in the ONT group and 0.02 in the contralateral control group. Also, excellent agreement was observed between Doppler OCT and microsphere measurements (P < 0.01, r = 0.976, bias = 0.54). After ONT, TRBF and RNFLT decreased by -51% ± 42% and -44% ± 2% (n = 5), respectively. In the contralateral control eyes, TRBF and RNFLT were unchanged.

Conclusions: Very good accordance was found between TRBF measurements, obtained with dual-beam bidirectional Doppler FD-OCT and the microsphere method. It also was possible to monitor changes over time in TRBF after ONT with Doppler OCT. These findings highlight the accuracy and potential of noninvasive Doppler OCT to provide valuable information for detecting early changes in ocular disease in future.
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http://dx.doi.org/10.1167/iovs.16-19140DOI Listing
March 2016

Relation of retinal blood flow and retinal oxygen extraction during stimulation with diffuse luminance flicker.

Sci Rep 2015 Dec 17;5:18291. Epub 2015 Dec 17.

Department of Clinical Pharmacology Medical University of Vienna Waehringer Guertel 18-20, 1090 Vienna, Austria.

Cerebral and retinal blood flow are dependent on local neuronal activity. Several studies quantified the increase in cerebral blood flow and oxygen consumption during activity. In the present study we investigated the relation between changes in retinal blood flow and oxygen extraction during stimulation with diffuse luminance flicker and the influence of breathing gas mixtures with different fractions of O2 (FiO2; 100% 15% and 12%). Twenty-four healthy subjects were included. Retinal blood flow was studied by combining measurement of vessel diameters using the Dynamic Vessel Analyser with measurements of blood velocity using laser Doppler velocimetry. Oxygen saturation was measured using spectroscopic reflectometry and oxygen extraction was calculated. Flicker stimulation increased retinal blood flow (57.7 ± 17.8%) and oxygen extraction (34.6 ± 24.1%; p < 0.001 each). During 100% oxygen breathing the response of retinal blood flow and oxygen extraction was increased (p < 0.01 each). By contrast, breathing gas mixtures with 12% and 15% FiO2 did not alter flicker-induced retinal haemodynamic changes. The present study indicates that at a comparable increase in blood flow the increase in oxygen extraction in the retina is larger than in the brain. During systemic hyperoxia the blood flow and oxygen extraction responses to neural stimulation are augmented. The underlying mechanism is unknown.
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http://dx.doi.org/10.1038/srep18291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682144PMC
December 2015

Compromised Optic Nerve Blood Flow and Autoregulation Secondary to Neural Degeneration.

Invest Ophthalmol Vis Sci 2015 Nov;56(12):7286-92

Devers Eye Institute Legacy Research Institute, Portland, Oregon, United States.

Purpose: To test the hypothesis that optic nerve head (ONH) blood flow (BF) and autoregulation compromise are consequences of optic nerve degeneration induced by surgical optic nerve transection (ONT).

Methods: In both eyes of five nonhuman primates, peripapillary retinal nerve fiber layer thickness (RNFLT) was measured by spectral-domain optical coherence tomography. Optic nerve head BF and dynamic autoregulation responses to a rapid manometric IOP increase (from 10-40 mm Hg) were measured by Laser Speckle Flowgraphy. The measurements were conducted every 10 to 15 days before and after unilateral ONT. Post-ONT measurements were repeated until RNFLT in the ONT eye was reduced by more than 40% of baseline value.

Results: After ONT, RNFLT, and ONH BF progressively declined over time (P < 0.0001 and P = 0.02, respectively). Longitudinal changes between the two were highly correlated (P < 0.0001). When data was grouped by test session, the first significant decreases for RNFLT and BF were found 13 ± 0.8 and 24 ± 3.2 days post ONT, respectively (P < 0.05, both). At the final time point (55 ± 0.5 days post ONT), RNFLT, and BF were reduced by 44% ± 2.0% and 38 ± 5.0% from baseline, respectively. Dynamic autoregulation analysis showed marginal increased response time in post-ONT eyes (P = 0.05). Control eyes showed no longitudinal changes for any parameter.

Conclusions: The close association between RNFLT loss and ONH BF decrease following optic nerve degeneration demonstrated a clear cause and effect relationship. Increased BF response time appears to be a sign of dynamic autoregulation dysfunction in this ONT model.
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http://dx.doi.org/10.1167/iovs.15-17879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642604PMC
November 2015

Antioxidative capacity of a dietary supplement on retinal hemodynamic function in a human lipopolysaccharide (LPS) model.

Invest Ophthalmol Vis Sci 2014 Dec 18;56(1):403-11. Epub 2014 Dec 18.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.

Purpose: Beneficial effects of dietary supplements in age-related macular degeneration (AMD) are related to antioxidative properties. In the Age-Related Eye Disease Study 1 (AREDS 1), a reduced progression to late stage AMD was found using vitamin C, E, zinc, and β-carotene. We showed previously that the AREDS 1 formulation restores the O2-induced retinal vasoconstrictor response of retinal vessels in a human endotoxin (lipopolysaccharide [LPS]) model.

Methods: We hypothesized that the abnormal O2-induced retinal red blood cell (RBC) flow response can be modulated by a different formulation (vitamin C, E, and zinc, lutein/zeaxanthin, selenium, taurine, Aronia extract, and omega-3 free fatty acids). A total of 43 healthy subjects was included in this randomized, double masked, placebo-controlled parallel group study. The reactivity of retinal arterial and venous diameter, RBC velocity, and flow to 100% O2 breathing was investigated in the absence and presence of 2 ng/kg LPS. Between the two study days was a 14-day period of daily dietary supplement intake.

Results: The decrease in retinal arterial diameter, RBC velocity, and flow during 100% O2 breathing was diminished significantly after LPS infusion. Dietary supplement intake for 14 days almost restored the response of retinal hemodynamic parameters to 100% O2 after LPS administration. This effect was significant for retinal arterial diameter (P = 0.03 between groups), and RBC velocity and flow (each P < 0.01 between groups).

Conclusions: The present data indicate restoring of the RBC flow response to 100% O2 after LPS administration. This is likely due to an amelioration of endothelial dysfunction resulting from oxidative stress, a factor involved in AMD pathophysiology. (ClinicalTrials.gov number, NCT00914576.).
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http://dx.doi.org/10.1167/iovs.14-15581DOI Listing
December 2014

Effect of increased oxygen tension on flicker-induced vasodilatation in the human retina.

J Cereb Blood Flow Metab 2014 Dec 24;34(12):1914-8. Epub 2014 Sep 24.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

In the retina, blood flow and neural activity are tightly coupled. Stimulation of the retina with flickering light is accompanied by an increase in blood flow. The current study seeks to investigate whether an increase in oxygen tension modulates flicker (FL)-induced vasodilatation in the human retina. A total of 52 healthy volunteers were included. Via a breathing mask, 100% oxygen (O(2)) was administered in one, a mixture of 8% carbon dioxide and 92% oxygen (C/O) in a second cohort. Retinal vessel diameters were measured with a Vessel Analyzer and FL responses were assessed before and during the breathing periods. At baseline, FL stimulation increased retinal vessel diameters by +3.7±2.3% in arteries and by +5.1±3.7% in veins. Breathing of C/O led to a decrease in arterial (-9.0±6.9%) and venous (-11.3±5.9%) vessel calibers. Flicker response was increased to 5.7±2.5% in arteries and to 8.6±4.1% in veins. Breathing of pure O2 induced a vasoconstriction of vessel diameters by -14.0±5.3% in arteries and -18.4±7.0% in veins and increased FL responses in arteries (+6.2±2.8%) and veins (+7.2±3.1%). Systemic hyperoxia increases FL-induced retinal vasodilatation in the retina. The mechanism by which oxygen modulates the hyperemic response to FL stimulation remains to be elucidated.
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http://dx.doi.org/10.1038/jcbfm.2014.161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269745PMC
December 2014

Regulation of retinal oxygen metabolism in humans during graded hypoxia.

Am J Physiol Heart Circ Physiol 2014 Nov 12;307(10):H1412-8. Epub 2014 Sep 12.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria; and

Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O₂ in 88% N₂ as well as breathing 15% O₂ in 85% N₂. Oxygen saturation in a retinal artery (SO₂art) and an adjacent retinal vein (SO₂vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O₂ breathing, respectively. SO₂art as well as SO₂vein decreased during both 12% O₂ breathing (SO₂art: -11.2 ± 4.3%, P < 0.001; SO₂vein: -3.9 ± 8.5%, P = 0.012) and 15% O₂ breathing (SO₂art: -7.9 ± 3.6%, P < 0.001; SO₂vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O₂: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O₂: -2.8 ± 18.9%, P = 0.65; 15% O₂: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia.
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http://dx.doi.org/10.1152/ajpheart.00479.2014DOI Listing
November 2014

Retinal oxygen metabolism during normoxia and hyperoxia in healthy subjects.

Invest Ophthalmol Vis Sci 2014 Jul 11;55(8):4707-13. Epub 2014 Jul 11.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.

Purpose: To characterize retinal metabolism during normoxia and hyperoxia in healthy subjects.

Methods: Forty-six healthy subjects were included in the present study, and data of 41 subjects could be evaluated. Retinal vessel diameters, as well as oxygen saturation in arteries and veins, were measured using the Dynamic Vessel Analyzer. In addition, retinal venous blood velocity was measured using bidirectional laser Doppler velocimetry, retinal blood flow was calculated, and oxygen and carbon dioxide partial pressures were measured from arterialized capillary blood from the earlobe. Measurements were done during normoxia and during 100% oxygen breathing.

Results: Systemic hyperoxia caused a significant decrease in retinal venous diameter (-13.0% ± 4.5%) and arterial diameter (-12.1% ± 4.0%), in retinal blood velocity (-43.4% ± 7.7%), and in retinal blood flow (-57.0% ± 5.7%) (P < 0.001 for all). Oxygen saturation increased in retinal arteries (+4.4% ± 2.3%) and in retinal veins (+19.6% ± 6.2%), but the arteriovenous oxygen content difference significantly decreased (-29.4% ± 19.5%) (P < 0.001 for all). Blood oxygen tension in arterialized blood showed a pronounced increase from 90.2 ± 7.7 to 371.3 ± 92.7 mm Hg (P < 0.001). Calculated oxygen extraction in the eye decreased by as much as 62.5% ± 9.5% (P < 0.001).

Conclusions: Our data are compatible with the hypothesis that during 100% oxygen breathing a large amount of oxygen, consumed by the inner retina, comes from the choroid, which is supported by previous animal data. Interpretation of oxygen saturation data in retinal arteries and veins without quantifying blood flow is difficult. (ClinicalTrials.gov number, NCT01692821.).
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http://dx.doi.org/10.1167/iovs.14-14593DOI Listing
July 2014

Flicker-induced retinal vasodilatation is not dependent on complement factor H polymorphism in healthy young subjects.

Acta Ophthalmol 2014 Nov 26;92(7):e540-5. Epub 2014 May 26.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.

Purpose: The complement factor H (CFH) tyrosine 402 histidine (Y402H, rs1061170) variant is known to be significantly associated with age-related macular degeneration (AMD). Whether this genetic variant may impact retinal blood flow regulation is largely unknown. This study investigated whether flicker-induced vasodilation, an indicator for the coupling between neural activity and blood flow, is altered in subjects carrying the rs1061170 risk allele.

Methods: One hundred healthy subjects (aged between 18 and 45 years) were included in this study. Retinal blood flow regulation was tested by assessing retinal vessel calibres in response to stimulation with diffuse flicker light. Retinal vascular flicker responses were determined with a Dynamic Vessel Analyzer (DVA). In addition, genotyping for rs1061170 was performed.

Results: Eighteen subjects were homozygous for the risk allele C, 50 were homozygous for the ancestral allele T, and 31 subjects were heterozygous (CT). One subject had to be excluded from data evaluation, as no genetic analysis could be performed due to technical difficulties. Baseline diameters of retinal arteries (p = 0.39) and veins (p = 0.64) were comparable between the three groups. Flicker-induced vasodilation in both retinal arteries (p = 0.38) and retinal veins (p = 0.62) was also comparable between the three studied groups.

Conclusions: Our data indicate that homozygous healthy young carriers of the C risk allele at rs1061170 do not show abnormal flicker-induced vasodilation in the retina. This suggests that the high-risk genetic variant of CFH polymorphism does not impact neuro-vascular coupling in healthy subjects.
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http://dx.doi.org/10.1111/aos.12433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4225479PMC
November 2014

Retinal hemodynamic effects of antioxidant supplementation in an endotoxin-induced model of oxidative stress in humans.

Invest Ophthalmol Vis Sci 2014 Apr 7;55(4):2220-7. Epub 2014 Apr 7.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.

Purpose: The Age-Related Eye Disease Study 1 (AREDS 1) has shown that nutritional supplementation with antioxidants and zinc modifies the natural course of AMD. It is presumed that the supplements exert their beneficial effects by ameliorating oxidative stress due to the scavenging of reactive oxygen species (ROS). We have shown in a human model that under oxidative stress induced by administration of lipopolysaccharide (LPS) the vasoconstrictor response of retinal vessels to oxygen breathing is diminished. This reduced vascular response to hyperoxia was previously shown to be normalized by the AREDS 1 supplements. In the present study, we tested the hypothesis that the response can also be restored by a different antioxidant formulation.

Methods: This randomized, double-masked, placebo-controlled parallel group study included 40 healthy volunteers. On each study day, retinal red blood cell (RBC) flow and the reactivity of retinal RBC flow to hyperoxia were investigated in the absence and presence of 2 ng/kg LPS. Between the two study days, subjects received either the supplement or placebo for 14 days.

Results: Before supplementation LPS reduced retinal arterial vasoconstriction (P < 0.001) and reactivity of retinal RBC flow (P = 0.03) in response to 100% oxygen breathing. Two weeks of supplementation did not affect baseline retinal RBC flow, but normalized the LPS-induced change in the response to hyperoxia. The arterial vasoconstrictor response during LPS and 100% oxygen breathing was 4.1 ± 1.0% after administration of placebo and 10.6 ± 0.9% after supplementation (P = 0.005). The response of RBC flow to 100% oxygen breathing during LPS was 52.2 ± 2.1% after administration of placebo and 59.5 ± 2.0% after supplementation (P = 0.033).

Conclusions: Our data show that the supplement used in the present study can normalize the response of retinal RBC flow to hyperoxia under LPS administration. This indicates that supplementation can prevent endothelial dysfunction induced by oxidative stress, which is assumed to play a role in the pathophysiology of AMD. (ClinicalTrials.gov number, NCT00914576.).
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http://dx.doi.org/10.1167/iovs.13-13784DOI Listing
April 2014

Interaction between leukocytes and erythrocytes in the human retina: effects of pentoxifylline on hyperoxia-induced vasoconstriction during increased neutrophil counts.

Microvasc Res 2014 Mar 18;92:85-90. Epub 2014 Jan 18.

Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. Electronic address:

Purpose: Pentoxifylline, a nonselective phosphodiesterase inhibitor, shows vasodilator effects in certain vascular beds and reduces blood viscosity. We have previously shown that under states of vasoconstriction an interaction between circulating erythrocytes and leukocytes may play a role in the control of blood flow. The reason for this observation is not entirely clear but may be related to a mechanical interaction between red and white blood cells. In the present study we hypothesized that pentoxifylline may alter this interaction during oxygen-induced vasoconstriction.

Methods: 24 healthy male subjects participated in this double masked, randomized, placebo-controlled 2 way cross over trial. In order to increase white blood cell count (WBC) count, 300 μg of G-CSF was administered intravenously. Vasoconstriction of retinal vessels was induced by oxygen inhalation. 400mg of pentoxifylline or placebo was infused at two different study days. White blood cell flux was assessed with the blue-field entoptic technique. Vessel calibers were measured with a dynamic vessel analyzer (DVA) and red blood cell velocity (RBCV) was determined with laser Doppler velocimetry (LDV). Retinal blood flow was calculated based on retinal vessel diameters and RBCV.

Results: Administration of G-CSF induced a significant increase in WBC, both in the placebo and the pentoxifylline group (p<0.01 for both groups). Retinal vessel diameter, RBCV, calculated retinal blood flow and white blood cell flow were not altered by administration of pentoxifylline. Hyperoxia induced a pronounced decrease in retinal blood flow parameters. No difference was observed between groups during oxygen breathing in vessel diameters (p=0.54), RBCV (p=0.34), calculated retinal blood flow (p=0.3) and white blood cell flow (p=0.26).

Conclusion: Our data indicate that short time administration of pentoxifylline does not alter the oxygen-induced effect on ocular blood flow parameters during leukocytosis. Whether long-term treatment could improve retinal blood flow under states of vasoconstriction remains to be investigated.
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http://dx.doi.org/10.1016/j.mvr.2014.01.004DOI Listing
March 2014
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