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To identify correlations between the vascular characteristics of macular neovascularization (MNV) obtained by optical coherence tomography angiography (OCTA) and distinct retinal fluid volumes in neovascular age-related macular degeneration (nAMD).In this prospective interventional study, 54 patients with treatment-naïve type 1 or 2 nAMD were included and treated with intravitreal aflibercept. At baseline and month 1, each patient underwent a SD-OCT volume scan and volumetric flow scan using a swept-source OCTA. A deep learning algorithm was used to automatically detect and quantify fluid in OCT scans. Angio Tool, a National Cancer Institute algorithm, was used to skeletonize MNV properties and quantify lesion size (LS), vessel area (VA), vessel density (VD), total number of endpoints (TNE), total number of junctions (TNJ), junction density (JD), total vessel length (TVL), average vessel length (AVL) and mean-e-lacunarity (MEL). Subsequently, linear regression models were used to investigate a correlation between OCTA parameters and fluid quantifications.The median amount of fluid within the central 6-mm EDTRS ring was 173.7 nl at baseline, consisting of 156.6 nl of subretinal fluid (SRF) and 2.3 nl of intraretinal fluid (IRF). Fluid decreased significantly in all compartments to 1.76 nl (SRF) and 0.64 nl (IRF). The investigated MNV parameters did not change significantly after the first treatment. There was no significant correlation between MNV parameters and relative fluid decrease after anti-VEGF treatment. Baseline fluid correlated statistically significant but weakly with TNE (p = 0.002, RMacular neovascularization parameters at baseline and month 1 played only a minor role in the exudation process in nAMD. None of the MNV parameters were correlated with the treatment response.

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.

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.

To develop and validate a deep learning model to automatically segment three structures using an anterior segment optical coherence tomography (AS-OCT): The intraocular lens (IOL), the retrolental space (IOL to the posterior lens capsule) and Berger's space (BS; posterior capsule to the anterior hyaloid membrane).An artificial intelligence (AI) approach based on a deep learning model to automatically segment the IOL, the retrolental space, and BS in AS-OCT, was trained using annotations from an experienced clinician. The training, validation and test set consisted of 92 cross-sectional OCT slices, acquired in 47 visits from 41 eyes. Annotations from a second experienced clinician in the test set were additionally evaluated to conduct an inter-reader variability analysis.The AI model achieved a Precision/Recall/Dice score of 0.97/0.90/0.93 for IOL, 0.54/0.65/0.55 for retrolental space, and 0.72/0.58/0.59 for BS. For inter-reader variability, Precision/Recall/Dice values were 0.98/0.98/0.98 for IOL, 0.74/0.59/0.62 for retrolental space, and 0.58/0.57/0.57 for BS. No statistical differences were observed between the automated algorithm and the inter-reader variability for BS segmentation.The deep learning model allows for fully automatic segmentation of all investigated structures, achieving human-level performance in BS segmentation. We, therefore, expect promising applications of the algorithm with particular interest in BS in automated big data analysis and real-time intra-operative support in ophthalmology, particularly in conjunction with primary posterior capsulotomy in femtosecond laser-assisted cataract surgery.

PURPOSE To investigate the effects of vitrectomy (Vy) with or without same time cataract surgery and membrane plus internal limiting membrane peeling (MP+ILMP) on retinal oxygenation and choroidal volume and their role on postoperative outcome. METHODS Thirty-two eyes were included in this prospective clinical study. All patients received 23 gauge Vy+MP+ILMP without endotamponade. Additional cataract surgery was performed in 14 patients. Follow-up visits were scheduled at day 1, week 1, month 1 and month 3. At each visit, best corrected visual acuity (BCVA) using ETDRS charts (except at day 1), oxygenation of retinal vessels using the Oxymap T1, and optical coherence tomography (OCT, Heidelberg Spectralis) was performed. RESULTS Mean BCVA increased significantly from 73 ± 11 letters to 77 ± 7 letters at month 3 (p = 0.02). Mean central retinal thickness (CRT) decreased from 456 ± 84 µm at baseline to 418±58µm (p = 0.01 baseline versus month 3). In the cataract surgery group, CRT was higher at month 3 than in the group without (400 ± 58 µm versus 441 ± 51 µm; p = 0.007). There was no statistically significant difference in choroidal volume or oxygenation of retinal vessels between groups (additional cataract surgery versus vitrectomy alone). Oxygenation of retinal arteries tended to decrease at day 1 followed by an increase, but the changes did not reach the level of significance (p = 0.29 baseline versus month 3). Oxygenation of retinal veins increased significantly (p = 0.02 baseline versus month 1; p = 0.04 baseline versus month 3, accordingly). There was a significant negative correlation (Spearman correlation coefficient rs = -0.35, p = 0.047) between visual acuity and oxygenation of retinal veins at month 3. No statistically significant correlation was found between CRT and oxygenation of neither retinal arteries nor veins. Choroidal volume (CV) of the central mm did not change significantly during the study period (baseline: 0.203 ± 0.04 mm3 , median: 0.206, month 3: 0.205 ± 0.04 mm3 , p = 0.54). There was no statistically significant effect of choroidal volume at baseline on postoperative clinical outcomes (change in BCVA estimate [95% CI]: 7 [-76; 90], p = 0.86; change in CRT: 147 [-577; 871], p = 0.68). CONCLUSION Oxygen saturation may affect the visual acuity outcome but not the CRT in patients after vitrectomy for epiretinal membrane. Choroidal thickness had no statistically significant influence on the study outcomes. Further studies are needed to evaluate if the measurement of retinal oxygenation may be helpful in the decision for surgery.

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.

BACKGROUND/AIMS To explore whether the existence and pattern of distribution of macular haemorrhage or exudate can be valuable diagnostic markers for macular neovascularization type 3 (MNV3) in patients with neovascular age-related macular degeneration. METHODS Eighty-three eyes of 83 consecutive treatment naive patients with stage 3 MNV3 were enrolled. The diagnosis was based on fluorescein angiography (FA) and optical coherence tomography (OCT). Subretinal and intraretinal haemorrhage and dense exudates were evaluated on colour fundus photography. Fluorescein angiography (FA) images and OCT scans were used to identify the axial location of the haemorrhage. 83 patients with MNV1 and 83 with MNV2 were included as two control groups. RESULTS In the MNV3 group, 62 (75%) eyes had intraretinal haemorrhage and 52 (63%) had dense exudates. 73 (88%) eyes had intraretinal haemorrhage and/or dense exudates. 41 (49%) had both pathologies. The intraretinal haemorrhage was flame shaped over the lesion and punctate or semi-punctate further away from it and directed to the fovea. No subretinal haemorrhage was noticed. In the MNV1 and MNV2 groups, 11 (13%) and 24 (29%) eyes had subretinal haemorrhage or dense exudates, respectively. No intraretinal haemorrhage was seen in the two control groups. The prevalence of exudates and haemorrhage (irrespective of its location) was greater in MNV3 than in MNV1 or 2 (p

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.

Purpose The pathophysiology of diabetic neurodegeneration and microvasculopathy remains controversial. Neurosensory layer thickness and corneal nerve fibre loss represent potential biomarkers of neuropathy. The purpose of this cross-sectional study was to determine the correlation between these neurodegenerative features and their association with retinal microvascular integrity in patients with type II diabetes without retinopathy. Methods Nerve fibre length (NFL), density (NFD) and branch density (NBD) were assessed using corneal confocal microscopy. Spectralis optical coherence tomography (OCT) was used for peripapillary retinal nerve fibre layer (RNFL), and macular RNFL, ganglion cell (GCL), inner plexiform (IPL) and inner nuclear layer (INL) thicknesses. Parafoveal vessel density (PVD) was determined using OCT angiography. Results We analysed 118 eyes of 61 patients. Peripapillary RNFL, macular RNFL, GCL, IPL and INL were 101 ± 8, 29 ± 3, 43 ± 4, 36 ± 3 and 36 ± 3 μm. NFL, NFD and NBD were 12.3 ± 4.4 mm/mm2 , 17.8 ± 7.4/mm2 and 26.7 ± 15.2/mm2 . Corneal nerve fibre variables were neither associated with inner retinal thicknesses nor PVD. A significant positive correlation was found between macular GCL, IPL and peripapillary RNFL with deep capillary plexus PVD (p ≤ 0.05). Conclusion Our results indicate that corneal and retinal neurodegeneration are independent changes early in type II diabetes and that distinct retinal, but not corneal neurodegenerative features, are associated with retinal microvascular perfusion.

Purpose To evaluate the relationship of neuroretinal layer thickness with sensitive measures of cardiovascular autonomic neuropathy in diabetic patients with non‐proliferative diabetic retinopathy (NPDR). Methods Twenty‐seven eyes of 27 patients with type 1 diabetes presenting with mild‐to‐moderate NPDR were compared to 27 healthy control (HC) eyes matched for age and gender. The total macular volume (TMV) and the volumes of individual neurosensory layers in the macula were analysed from spectral domain optical coherence tomography using automated layer segmentation. Cardiovascular autonomic regulation was assessed by short‐term power spectrum analysis of heart rate variability (HRV) before, during and after an orthostatic challenge. Results The patients had an age of 46 ± 12 years and diabetes since 28 ± 9 years. Diastolic and mean arterial pressure was lower in the patients compared to HCs. TMV (r = 0.58, p = 0.002), inner plexiform layer volume (IPLV; r = 0.39, p = 0.047) and inner nuclear layer volume (INLV; r = 0.60, p = 0.001) were associated with reduced recovery of low‐frequency (LF) spectral power of HRV after orthostatic load in diabetic patients but not in HCs. The response of LF spectral power during the orthostatic manoeuvre was blunted in patients compared to HCs (p = 0.02). Diabetes duration was negatively associated with TMV and INLV, whereas IPLV was significantly reduced in eyes with moderate NPDR compared to HCs. Conclusion The results indicate a correlation between inner retinal tissue loss and diminished autonomic regulation in type 1 diabetic patients with mild‐to‐moderate NPDR. The observed changes can be interpreted as congruent early signs of retinal and systemic neuropathy in diabetes.

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

Purpose To evaluate detailed changes in retinal layer thickness in spectral-domain optical coherence tomography (SD-OCT) images during a 1-year follow-up of patients treated for diabetic macula oedema (DME). Methods Post hoc analysis of retinal layer thickness changes applying the automated layer segmentation of SD-OCT images in eyes with DME that were randomly assigned to receive pro re nata (PRN) treatment with either 0.5 mg ranibizumab or 8 mg triamcinolone. In each patient, seven retinal layers were segmented in 49 scans covering a 20° × 20° area of the macula at baseline and after 1 year of treatment. Changes in individual layer thickness were correlated with visual acuity (VA) and compared between treatment arms. Results Twenty-five patients (seven female, 60.2 ± 15.1 years) were evaluated. Thickness decrease of retinal nerve fibre layer (RNFL) was associated with a gain in VA over 12 months (r > 0.54; p

Purpose We aimed to determine the correlation between optical coherence tomography (OCT)‐ and demographic features and baseline best corrected visual acuity (BCVA) in treatment‐naïve patients with retinal vein occlusion (RVO). Methods This was a cross‐sectional posthoc analysis of OCT images that included RVO patients from two prospective, open‐label, multicentre studies. The morphological grading was done manually, in the standardized setting of a reading centre. Main outcome measure was the estimated difference in Early Treatment Diabetic Retinopathy Study letters associated with each individual biomarker. Results Included were 381/301 treatment‐naïve patients with BRVO/CRVO. For BRVO, statistically significant correlations with BCVA were seen for a 100 µm increase in central subfield thickness (CST; −3.1 letters), intraretinal cysts at centre point (CP; +4.1), subretinal fluid (SRF) at CP (+3.0) and hyperreflective foci (HRF) at the central B‐scan (−2.2). In CRVO, a 100 µm increase in CST was associated with a loss of −3.4 letters. In the total cohort, 100 µm increase in CST, SRF at CP and HRF at the central B‐scan correlated with a difference of −3.2,+3.2 and −2.0 letters. A 10‐year increase in age and female gender yielded a −2.0 and −2.5 letter decrease in the total cohort. Adjusted multiple R 2 for the respective group was 18.3%/26.3%/23.5%. Conclusions Of all parameters studied, only CST and age were consistently associated with worse BCVA in treatment‐naïve RVO patients. Morphology on OCT explained only a modest part of functional loss in this patient cohort.