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Purpose: To compare detection rates of microaneurysms (MAs) on high‐speed megahertz optical coherence tomography angiography (MHz‐OCTA), fluorescein angiography (FA) and colour fundus photography (CF) in patients with diabetic retinopathy (DR). Methods: For this exploratory cross‐sectional study, MHz‐OCTA data were acquired with a swept‐source OCT prototype (A‐scan rate: 1.7 MHz), and FA and CF imaging was performed using Optos® California. MA count was manually evaluated on en face MHz‐OCTA/FA/CF images within an extended ETDRS grid. Detectability of MAs visible on FA images was evaluated on corresponding MHz‐OCTA and CF images. MA distribution and leakage were correlated with detectability on OCTA and CF imaging. Results: 47 eyes with severe DR (n = 12) and proliferative DR (n = 35) were included. MHz‐OCTA and CF imaging detected on average 56% and 36% of MAs, respectively. MHz‐OCTA detection rate was significantly higher than CF (p < 0.01). The combination of MHz‐OCTA and CF leads to an increased detection rate of 70%. There was no statistically significant association between leakage and MA detectability on OCTA (p = 0.13). For CF, the odds of detecting leaking MAs were significantly lower than non‐leaking MAs (p = 0.012). Using MHz‐OCTA, detection of MAs outside the ETDRS grid was less likely than MAs located within the ETDRS grid (outer ring, p < 0.01; inner ring, p = 0.028). No statistically significant difference between rings was observed for CF measurements. Conclusions: More MAs were detected on MHz‐OCTA than on CF imaging. Detection rate was lower for MAs located outside the macular region with MHz‐OCTA and for leaking MAs with CF imaging. Combining both non‐invasive modalities can improve MA detection. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate neuroretinal integrity in different subtypes of optical coherence tomography (OCT)‐graded partial‐thickness macular holes. Methods: Fovea‐centred SD‐OCT images (Cirrus, Carl Zeiss Meditec AG; Spectralis, Heidelberg Engineering GmbH) and visual acuity (VA) acquired at every visit were analysed by two retina specialists retrospectively in 71 eyes of 65 patients. Partial‐thickness macular holes were classified as lamellar macular hole (LMH), epiretinal membrane foveoschisis (ERMF) or macular pseudohole (MPH). Results: Lamellar macular hole, ERMF and MPH were diagnosed in 33 (47%), 31 (43%) and 7 (10%) eyes with a VA of 0.18 ± 0.25, 0.15 ± 0.2, and 0.06 ± 0.08 (p = 0.323), respectively. Median follow‐up time was 11 (interquartile range 4–32.5), 10 (interquartile range 5–18) and 19 (interquartile range 8–24) months in LMH, ERMF and MPH. In all subgroups, VA remained stable during the follow‐up (p = 0.652, p = 0.915 and p = 1.000). Epiretinal proliferations (EP) were present in 12 LMH and 3 ERMF. At baseline, eyes with EP had significantly worse VA (p < 0.001), wider foveal cavities (p = 0.007) and thinner foveal floors (p < 0.001) compared with eyes without EP. Twelve out of 15 eyes with EP showed exudative cystoid spaces. Among all 71 eyes, 51 remained morphologically and functionally stable during follow‐up. Conclusion: In our study cohort, EP are associated with worse VA and advanced neuroretinal tissue loss presenting with wider foveal cavities and thinner foveal floors. During the follow‐up period, VA remained stable in all entities of partial‐thickness macular holes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 mm2 (range: 2.23–17.23 mm2). 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. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes. Methods: In a prospective, randomized, controlled, double‐blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm‐Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20. Results: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM‐1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM‐1) (weeks 2 and 8) and monocyte chemo‐attractant protein 1 (MCP‐1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time‐points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm) in the Lucentis group. Conclusion: The dexamethasone implant affected the aqueous cytokines and proteins MCP‐1, sICAM‐1, sVCAM‐1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the short‐time effect of intravitreal injections (IVI) of the vascular endothelial growth factor inhibitors ranibizumab and aflibercept on retinal arterial and venous oxygen saturation (SO2a and SO2v), arteriovenous oxygen saturation difference (AVD) and vessel diameter (VDa and VDv) in patients with diabetic macular oedema (DME) and patients with choroidal neovascularization (CNV) due to age‐related macular degeneration. Methods: Uncontrolled prospective observational study in 100 eyes. Retinal vessel oxygen saturation and diameters were assessed using a retinal oximeter before and minutes after IVI of ranibizumab or aflibercept. Results: 40 eyes with CNV and 34 eyes with DME were included in the analysis. At baseline, SO2a and SO2v were significantly higher in DME (p = 0.043 and p = 0.009, respectively). After IVI, SO2a significantly decreased in CNV and DME eyes by 2.6% (p = 0.016) and 4.6% (p = 0.002) and SO2v decreased by 14.0% (p = 0.004) and 12.4% (p = 0.017), respectively. However, a significant increase in AVD was only found in CNV (15.7%, p = 0.001). VDa decreased significantly only in DME by 5.7% (p = 0.010). No medication‐specific disease effect was found and vice versa. Conclusions: The observed changes can be interpreted as signs of increased metabolic demand during the physiological stress after an IVI. The abnormal arterial constriction and the abolished increase in AVD seen only in eyes with DME indicate an impairment of vascular autoregulation and oxygen distribution and a reduced neuroretinal metabolism in the diabetic retina with a significant impact on inner retinal oxygen consumption shortly after IVI. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Spectrophotometric retinal oximetry is a non‐invasive technology for measuring oxygen saturation in arterioles and venules (SaO2, SvO2). 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 (ScO2) and peripheral oxygen saturation using finger pulse oximetry (SpO2) were scheduled. Results: SaO2 (p > 0.0004) but not SvO2 (p < 0.05) was statistically significantly different between the retinal oximeters used. Agreement between devices using repeated SO2 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 SaO2 and SvO2, respectively. Comparison of mean SaO2 and SvO2 with mean ScO2 and SpO2 indicated that SO2 measurements were generally higher in ScO2 and SpO2. Conclusion: This study shows very good repeatability for both devices, which is consistent with the literature. However, it does not show sufficient concordance between SaO2 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. [ABSTRACT FROM AUTHOR]

Purpose To suggest a novel classification of neovascular age-related macular degeneration ( AMD) based on optical coherence tomography angiography ( OCTA) and to correlate morphological characteristics based on optical coherence tomography (OCT)/ OCTA with clinical criteria of disease activity. Methods A total of 88 eyes with neovascular AMD (14 treatment-naïve, 74 eyes following anti-vascular endothelial growth factor treatment (VEGF)) were examined using the AngioVue OCTA system (Optovue, Inc., Fremont, CA, USA) and evaluated based on vascular morphology. Choroidal neovascularization ( CNV)-vessel morphology based on OCTA and associations with retinal layers were described and correlated with clinical markers of disease activity. Results In treatment-naïve CNV, CNV-vessel morphology based on OCTA showed a dense-net configuration ( DN) in 12 of 14 eyes, a loose-net configuration ( LN) in one of 14 eyes and an unidentifiable CNV pattern in one of 14 eyes, whereas in treated CNV, DN was registered in 43.2% (32/74), LN in 27% (20/74), DN with additional LN (mixed type) in 14.9% (11/74) and an unidentifiable CNV pattern in 14.9% (11/74). Clinical correlations revealed a significantly longer disease duration for LN with a median value of 4.3 years compared to DN with 2.0 years (p = 0.009) and for CNV involving the outer retina with 3.1 years compared to CNV not involving the outer retina with 1.9 years (p = 0.051). Conclusion Optical coherence tomography angiography (OCTA) allows identification of distinct CNV-specific vascular patterns at the level of the outer retinal layer and choriocapillaris. Correlation with clinical and functional parameters may be useful to better understand pathophysiological mechanisms and guide efficient therapeutic strategies. [ABSTRACT FROM AUTHOR]

Purpose To investigate the influence of intravitreal dexamethasone implant on inflammatory and angiogenic cytokine levels in the aqueous of patients with retinal vein occlusion ( RVO). Methods Forty eyes of 40 consecutive patients with macular oedema ( ME) due to branch and central retinal vein occlusion ( BRVO/ CRVO) were treated with an intravitreal dexamethasone implant (Ozurdex®) at baseline and evaluated until month 6. Retreatment was performed in case of recurrent ME earliest 4 months after the baseline treatment. Aqueous humour samples were taken at baseline, months 1, 3, 6 and at the time of each retreatment. Concentrations of 29 different cytokines were measured by Luminex® bead assays. The control group comprised healthy patients undergoing cataract surgery. Results At baseline concentrations of interleukin ( IL)-8, angiopoietin ( ANG)-2 and intercellular adhesion molecule ( ICAM)-1 were highly elevated in patients with CRVO compared with controls (p = 0.006; p = 0.02; p = 0.03). Vascular endothelial growth factor ( VEGF) concentrations were upregulated in patients with BRVO and CRVO (p = 0.003; p = 0.001). Retreatment with a dexamethasone implant was necessary after 4 months in 14/8 ( BRVO/ CRVO) patients, 5 months in 5/3 patients and 6 months in one patient ( BRVO). After the initial treatment, macrophage chemo-attractant protein ( MCP)-1 and IL17-E concentrations decreased in BRVO (p < 0.001; p = 0.01) and MCP-1 and IL1- α in CRVO (p = 0.01; p = 0.003). Vascular endothelial growth factor ( VEGF) concentrations did not change during treatment in either group (p = 0.3). A mixed-effect model showed that cytokine concentrations positively correlated with central retinal thickness changes. Conclusions Intravitreal dexamethasone treatment resulted in alterations in the concentrations of pro-inflammatory cytokines MCP-1 and IL17-E in patients with BRVO and MCP-1 and IL1- α in patients with CRVO. These data highlight the important role of inflammatory mediators involved in ME due to RVO. [ABSTRACT FROM AUTHOR]