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Background With FA and SD-OCT, different types of CNV in exudative AMD may be differentiated: type 1 CNV (within the sub-RPE space, typically corresponding to angiographically occult CNV), type 2 CNV (within the subretinal space, typically corresponding to angiographically classic CNV) and type 3 NV (intraretinal retinal angiomatous proliferation). OCT-angiography (OCT-A) is a new method to visualize vasculature based on flow characteristics. A correlation of type 1 and 2 CNV was performed. Methods Thirty-six eyes (17 type 1 CNV, 9 combined type 1 and 2 CNV, and 10 type 2 CNV) of 36 patients were examined by FA, SD-OCT and OCT-A. Standardized OCT-A segmentations were performed at the level of mid-choroid, choriocapillaris (CC), RPE and outer retina. On these images the size and demarcation of CNV lesions were classified: “not distinguishable”, “minor” or “sharp” demarcation. Furthermore, the size of the different CNV subtypes was determined and compared. Results Both types of CNV were visible in OCT-A. They could be detected on the slabs “mid-choroid”, “CC” and “RPE”. While type 1 CNV showed most often a minor demarcation from the surrounding vasculature, type 2 CNV showed nearly always a sharp demarcation. In addition, type 2 CNV extended into the slab “outer retina” and were much smaller than type 1 CNV. Conclusions Different types of CNV in exudative AMD can be visualized and differentiated with OCT-A. Type 1 CNV were larger with minor demarcation from the surrounding vasculature and were visible on the slab “mid-choroid”, “CC” and “RPE”. In contrast, type 2 CNV demonstrated a sharp demarcation from the surrounding vasculature reaching the slab “outer retina”.

BackgroundBrolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to brolucizumab therapy in previously anti-vascular endothelial growth factor (anti-VEGF)-treated patients.MethodsPatients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated including best-corrected visual acuity (BCVA (logMAR)), foveal centre point (FCP (µm)), central subfield retinal thickness (CSRT (µm)) and macular volume (mm³).ResultsSixty-three eyes of 57 patients with nAMD (52.6% females) with a mean (±SD) age of 79.5±6.7 years were included. Mean change of BCVA was 0.03±0.14 logMAR (p=0.115). Significant reductions were recorded for FCP with a mean (±SD) change of −66.81±72.63 µm, −66.76±60.71 µm for CSRT and −0.27±0.24 mm³ for macular volume (all p<0.001). Intraocular inflammation was observed in seven eyes of seven patients, including one case of retinal vasculitis.ConclusionsThe results of the SHIFT study indicate that switch to brolucizumab may represent a treatment option in patients with nAMD poorly responsive to other anti-VEGF agents. Further long-term analyses appear prudent to assess efficacy and safety of brolucizumab in a routine clinical setting.

AimsTo investigate the efficacy of a bi-modality deep convolutional neural network (DCNN) framework to categorise age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) from colour fundus images and optical coherence tomography (OCT) images.MethodsA retrospective cross-sectional study was proposed of patients with AMD or PCV who came to Peking Union Medical College Hospital. Diagnoses of all patients were confirmed by two retinal experts based on diagnostic gold standard for AMD and PCV. Patients with concurrent retinal vascular diseases were excluded. Colour fundus images and spectral domain OCT images were taken from dilated eyes of patients and healthy controls, and anonymised. All images were pre-labelled into normal, dry or wet AMD or PCV. ResNet-50 models were used as the backbone and alternate machine learning models including random forest classifiers were constructed for further comparison. For human-machine comparison, the same testing data set was diagnosed by three retinal experts independently. All images from the same participant were presented only within a single partition subset.ResultsOn a test set of 143 fundus and OCT image pairs from 80 eyes (20 eyes per-group), the bi-modal DCNN demonstrated the best performance, with accuracy 87.4%, sensitivity 88.8% and specificity 95.6%, and a perfect agreement with diagnostic gold standard (Cohen’s κ 0.828), exceeds slightly over the best expert (Human1, Cohen’s κ 0.810). For recognising PCV, the model outperformed the best expert as well.ConclusionA bi-modal DCNN for automated classification of AMD and PCV is accurate and promising in the realm of public health.

Proliferative diabetic retinopathy (PDR) the sequel of diabetic retinopathy (DR), a frequent complication of diabetes mellitus (DM), is the leading cause of blindness in the working-age population. The current screening process for the DR risk is not sufficiently effective such that often the disease is undetected until irreversible damage occurs. Diabetes-associated small vessel disease and neuroretinal changes create a vicious cycle resulting in the conversion of DR into PDR with characteristic ocular attributes including excessive mitochondrial and retinal cell damage, chronic inflammation, neovascularisation, and reduced visual field. PDR is considered an independent predictor of other severe diabetic complications such as ischemic stroke. A “domino effect” is highly characteristic for the cascading DM complications in which DR is an early indicator of impaired molecular and visual signaling. Mitochondrial health control is clinically relevant in DR management, and multi-omic tear fluid analysis can be instrumental for DR prognosis and PDR prediction. Altered metabolic pathways and bioenergetics, microvascular deficits and small vessel disease, chronic inflammation, and excessive tissue remodelling are in focus of this article as evidence-based targets for a predictive approach to develop diagnosis and treatment algorithms tailored to the individual for a cost-effective early prevention by implementing the paradigm shift from reactive medicine to predictive, preventive, and personalized medicine (PPPM) in primary and secondary DR care management.

AimTo assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA).MethodsSingle-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss’ κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated.ResultsFifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between WF-OCTA and UWF-FA was high in the superotemporal (κ=0.98) and inferotemporal (κ=0.94) and weak in the superonasal (κ=0.24) and inferonasal quadrants (κ=0.42). On UWF-FA, 63% of NVEs (n=153) were located in the temporal quadrants with 93% (n=142) of them being detected on WF-OCTA scans.ConclusionThe high reliability of non-invasive WF-OCTA imaging in detecting PDR can improve clinical examination with the potential to replace FA as a single diagnostic tool.

Focal choroidal excavation (FCE) is defined as an area of concavity in choroid detected on optical coherence tomography. These are mostly present in macular region without evidence of accompanying scleral ectasia or posterior staphyloma. Though initially considered to be congenital, increasing number of cases have been identified in association with other choroidal pathologies such as central serous choroidopathy, choroidal neovascularisation, polypoidal choroidal vasculopathy, choroiditis, choroidal tumours. In this review article, we aim to elaborate on the morphology, pathogenesis and differential diagnosis of FCE and specifically discuss the spectrum of diseases with known association along with the impact of their treatment on FCE

PurposeTo evaluate the role of right-angled vessels (RAVs) during disease progression in macular telangiectasia type 2 (MacTel).MethodsIn this study, 100 eyes of 52 patients and 52 eyes of 26 age-related controls were examined using fundus photography, spectral-domain optical coherence tomography (SD-OCT), OCT angiography (OCT-A) and fundus fluorescein angiography (FFA). Two masked readers graded fundus photographs of patients’ eyes into five disease stages according to Gass and Blodi, and evaluated all eyes for the presence of RAVs. If RAVs were present, their course and origin (arterial vs venous) was evaluated with OCT-A and FFA, respectively. Additionally, we looked for morphological correlates of these vessels on SD-OCT scans. Neovascular eyes were analysed for the presence of RAVs and for morphological changes on formation of neovascularisations (NVs).ResultsIn OCT-A, RAVs were already detectable in eyes with early stages (1 to 2), could be tracked from superficial to outer retinal layers and were shown to form anastomoses in the outer retina with disease progression. These vessels were of both arterial and venous origin as shown by early phase FFA. Dilated capillaries and RAVs in OCT-A corresponded to hyper-reflective alterations of the outer retina on SD-OCT scans. In 19/19 eyes, NVs were associated with the presence of RAVs, and RAVs were shown to directly connect to neovascular complexes and to undergo morphological changes upon NV formation.ConclusionsThe results emphasise the role of RAVs during disease progression from an early stage on and demonstrate their involvement in the development of secondary NVs in MacTel.

BackgroundTo evaluate the prevalence, risk factors and treatment of retinopathy of prematurity (ROP) in Turkey and to establish screening criteria for this condition.MethodsA prospective cohort study (TR-ROP) was performed between 1 April 2016 and 30 April 2017 in 69 neonatal intensive care units (NICUs). Infants with a birth weight (BW)≤1500 g or gestational age (GA)≤32 weeks and those with a BW>1500 g or GA>32 weeks with an unstable clinical course were included in the study. Predictors for the development of ROP were determined by logistic regression analyses.ResultsThe TR-ROP study included 6115 infants: 4964 (81%) with a GA≤32 weeks and 1151 (19%) with a GA>32 weeks. Overall, 27% had any stage of ROP and 6.7% had severe ROP. A lower BW, smaller GA, total days on oxygen, late-onset sepsis, frequency of red blood cell transfusions and relative weight gain were identified as independent risk factors for severe ROP in infants with a BW≤1500 g. Of all infants, 414 needed treatment and 395 (95.4%) of the treated infants had a BW≤1500 g. Sixty-six (16%) of the treated infants did not fulfil the Early Treatment for Retinopathy of Prematurity requirements for treatment.ConclusionsScreening of infants with a GA≤34 weeks or a BW<1700 g appears to be appropriate in Turkey. Monitoring standards of neonatal care and conducting quality improvement projects across the country are recommended to improve neonatal outcomes in Turkish NICUs.Trial registration number NCT02814929, Results.

Retinal neovascularisation (RNV) is manifested in various retinal pathological conditions, often leading to irreversible blindness. The oxygen‐induced retinopathy (OIR) mouse model proves to be a useful tool for understanding RNV pathogenesis. In this model, retinal vascular phenotype undergoes two distinct stages: neovascular formation, followed by spontaneous regression. While microglial functions in the neovascular formation stage have been extensively studied, their behaviors and roles during regression remain unclear. In this study, we characterise the spatiotemporal dynamics and molecular heterogeneity of retinal microglia across both stages. During RNV formation, microglia exhibit an outer‐to‐inner and central‐to‐midperipheral migration pattern, whereas a reversed migration trend is observed during regression. We confirm a highly glycolytic microglia (HGM) subpopulation during RNV formation and demonstrate its pro‐angiogenic role by targeting a highly expressed pyruvate kinase M2 (Pkm2), a crucial enzyme for glycolysis. Importantly, we find that microglia exhibit enhanced phagocytic activity during regression, constituting a distinct phagocytosis‐associated microglia (PAM) subtype, expressing mannose receptor C‐type 1 (Mrc1/CD206). Altogether, our findings reveal stage‐specific microglial functional dynamics, providing novel insights into RNV pathogenesis and intervention.

AimsTo identify single-nucleotide polymorphisms (SNPs) associated with central serous chorioretinopathy (CSCR) by a systematic review and meta-analysis, and to compare the association profiles between CSCR, neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).MethodsWe searched the EMBASE, PubMed and Web of Science for genetic studies of CSCR from the starting dates of the databases to 12 September 2020. We then performed meta-analyses on all SNPs reported by more than two studies and calculated the pooled OR and 95% CIs. We also conducted sensitivity analysis and adopted the funnel plot to assess potential publication bias.ResultsTotally 415 publications were reviewed, among them 10 were eligible for meta-analysis. We found 10 SNPs that have been reported at least twice. Meta-analysis and sensitivity analysis confirmed significant associations between CSCR and six SNPs in three genes, namely age-related maculopathy susceptibility 2 (ARMS2) (rs10490924, OR=1.37; p=0.00064), complement factor H (CFH) (rs800292, OR=1.44; p=7.80×10−5; rs1061170, OR=1.34; p=0.0028; rs1329428, OR=1.40; p=0.012; and rs2284664, OR=1.36; p=0.0089) and tumour necrosis factor receptor superfamily, member 10a (TNFRSF10A) (rs13278062, OR=1.34; p=1.44×10−15). Among them, only TNFRSF10A rs13278062 showed the same trend of effect on CSCR, nAMD and PCV, while the SNPs in ARMS2 and CFH showed opposite trends in the SNP associations.ConclusionsThis study confirmed the associations of ARMS2, CFH and TNFRSF10A with CSCR, and revealed that ARMS2, CFH and TNFRSF10A may affect different phenotypic expressions of CSCR, nAMD and PCV.