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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]

To compare retinal microvascular perfusion between the eyes of hypertensive patients with and without chronic kidney disease (CKD), the vessel density (VD) and fractal dimension (FD) of the superficial (SVP) and deep retinal vascular plexus (DVP) were analyzed on 6 × 6 mm fovea-centered optical coherence tomography angiography (OCTA) images of patients with hypertension. The retina was divided into an inner ring (IR) and outer ring (OR) according to the Early Treatment of Diabetic Retinopathy Study grid. The glomerular filtration rate (GFR) was determined and CKD was diagnosed (GFR < 60 mL/min/1.73 m2). Ninety-six eyes from 52 patients with hypertension were included in this analysis. Twenty patients (n = 37 eyes) were diagnosed with CKD. The mean age was 69 ± 11.7 years and 60.4 ± 9.2 years in the CKD group and in the control group, respectively. The univariate model revealed a significant difference in VD between patients without and with CKD in the superficial IR (0.36 ± 0.03 vs. 0.34 ± 0.04, p = 0.03), the superficial OR (0.35 ± 0.02 vs. 0.33 ± 0.04, p = 0.02), the deep OR (0.24 ± 0.01 vs. 0.23 ± 0.02, p = 0.003), and the FD in the SVP (1.87 ± 0.01 vs. 1.86 ± 0.02, p = 0.02) and DVP (1.83 ± 0.01 vs. 1.82 ± 0.01, p = 0.006). After adjusting for age and sex, these differences did not remain statistically significant. Similar results were observed for the FD in the SVP and DVP. In our cohort, patients with hypertension and CKD did not differ from patients without CKD in regard to microvascular perfusion status in the macular area as assessed using OCTA. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR), a pathologic change of the human retinal vasculature, is the leading cause of blindness in working-age adults with diabetes mellitus. Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography, has shown potential as a tool for early diagnosis of DR through its ability to visualize the retinal vasculature in all spatial dimensions. Previously introduced deep learning-based classifiers were able to support the detection of DR in OCTA images, but require expert labeling at the pixel level, a labor-intensive and expensive process. We present a multiple instance learning-based network, MIL-ResNet,14 that is capable of detecting biomarkers in an OCTA dataset with high accuracy, without the need for annotations other than the information whether a scan is from a diabetic patient or not. The dataset we used for this study was acquired with a diagnostic ultra-widefield swept-source OCT device with a MHz A-scan rate. We were able to show that our proposed method outperforms previous state-of-the-art networks for this classification task, ResNet14 and VGG16. In addition, our network pays special attention to clinically relevant biomarkers and is robust against adversarial attacks. Therefore, we believe that it could serve as a powerful diagnostic decision support tool for clinical ophthalmic screening. [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 assess the signal composition of cone photoreceptors three-dimensionally in healthy retinas using adaptive optics optical coherence tomography (AO-OCT). Methods: Study population. Twenty healthy eyes of ten subjects (age 23 to 67). Procedures. After routine ophthalmological assessments, eyes were examined using AO-OCT. Three-dimensional volumes were acquired at 2.5° and 6.5° foveal eccentricity in four main meridians (superior, nasal, inferior, temporal). Cone densities and signal compositions were investigated in four different 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 full en-face plane (FEF) combining signals from all mentioned cone layers. Additionally, reliability of a simple semi-automated approach for assessment of cone density was tested. Main outcome measures. Cone density of IS/OS, IS/OS+, COST and FEF. Qualitative depiction and composition of each cone layer. Inter-rater agreement of cone density measurements. Results: Mean overall cone density at all eccentricities was highest at the FEF plane (21.160/mm2), followed by COST (20.450/mm2), IS/OS+ (19.920/mm2) and IS/OS (19.530/mm2). The different meridians and eccentricities had a significant impact on cone density, with lower eccentricity resulting in higher cone densities (p≤.001), which were highest at the nasal, then temporal, then inferior and then superior meridian. Depiction of the cone mosaic differed between all 4 layers regarding signal size and packing density. Therefore, different cone layers showed evident but not complete signal overlap. Using the semi-automated technique for counting of cone signals achieved high inter-rater reliability (ICC >.99). Conclusions: In healthy individuals qualitative and quantitative changes in cone signals are found not only in different eccentricities and meridians, but also within different photoreceptor layers. The variation between cone planes has to be considered when assessing the integrity of cone photoreceptors in healthy and diseased eyes using adaptive optics technology. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [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]

To assess serial section block-face scanning electron microscopy (SBFSEM) for retinal pigment epithelium (RPE) ultrastructure, we determined the number and distribution within RPE cell bodies of melanosomes (M), lipofuscin (L), and melanolipofuscin (ML). Eyes of 4 Caucasian donors (16M, 32F, 76F, 84M) with unremarkable maculas were sectioned and imaged using an SEM fitted with an in-chamber automated ultramicrotome. Aligned image stacks were generated by alternately imaging an epoxy resin block face using backscattered electrons, then removing a 125 nm-thick layer. Series of 249-499 sections containing 5–24 nuclei were examined per eye. Trained readers manually assigned boundaries of individual cells and x,y,z locations of M, L, and ML. A Density Recovery Profile was computed in three dimensions for M, L, and ML. The number of granules per RPE cell body in 16M, 32F, 76F, and 84M eyes, respectively, was 465 ± 127 (mean ± SD), 305 ± 92, 79 ± 40, and 333 ± 134 for L; 13 ± 9; 6 ± 7, 131 ± 55, and 184 ± 66 for ML; and 29 ± 19, 24 ± 12, 12 ± 7, and 7 ± 3 for M. Granule types were spatially organized, with M near apical processes. The effective radius, a sphere of decreased probability for granule occurrence, was 1 μm for L, ML, and M combined. In conclusion, SBFEM reveals that adult human RPE has hundreds of L, LF, and M and that granule spacing is regulated by granule size alone. When obtained for a larger sample, this information will enable hypothesis testing about organelle turnover and regulation in health, aging, and disease, and elucidate how RPE-specific signals are generated in clinical optical coherence tomography and autofluorescence imaging. [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]

Aim To analyse a new grading protocol for clinically significant diabetic macular oedema (CSME) based on spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA). Methods 56 eyes of 40 patients with CSME were examined by Cirrus OCT (Carl Zeiss Meditec), Spectralis HRA and OCT (Heidelberg Engineering) on the same day. Three graders analysed images based on a newly developed grading protocol integrating all relevant information from OCT and FA. The protocol defined four categories: (1) subretinal fluid (category 'S'); (2) the planimetrically measured oedematous area (category 'A'); (3) vitreo-retinal interface abnormalities (category 'V'); and (4) CSME aetiology (category 'E') defining the leakage source. Results The new grading protocol allowed for a detailed characterisation of each individual type of CSME. It defines four aetiological types of CSME and analyses four further categories important in diagnosis and during follow-up in clinical and study settings. Atrophic, a new type of CSME, was described and characteristic combinations of triggers of CSME were revealed. Inter-grader agreement, analysed using Fleiss' κ values for Cirrus OCT and Spectralis OCT, respectively, was good for 'S' (0.9; 0.82), 'A' (1.0; 1.0) and 'E' (range 0.63-0.8; 0.57-0.77), and lower for 'V' (0.25; 0.42). Conclusions The 'SAVE' grading protocol of CSME integrates information from two imaging techniques, OCT and FA. Its clinical approach allows examiners to define and further categorise clinical characteristics to find tailored therapeutic strategies. [ABSTRACT FROM AUTHOR]