Morphological changes of macular neovascularization during long-term anti-VEGF-therapy in neovascular age-related macular degeneration.

PURPOSE: To analyze the morphological changes of macular neovascularization (MNV) in exudative neovascular age-related macular degeneration under long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy in a retrospective cohort study. METHODS AND PATIENTS: We evaluated 143 nAMD eyes of 94 patients (31 male, 63 female; initial age 55-97 y, mean age 75.9 ± 7.5 y), who started anti-VEGF therapy (IVAN pro re nata (PRN) protocol) between 2009-2018 and received ongoing therapy until the last recorded visit (mean follow-up 5.3 ± 2.9 y, range 1-14 y). The mean total number of injections was 33.3 ± 19.8 with 7.0 ± 2.3 injections/year. MNV size and, if present, associated complete retinal pigment epithelium (RPE) and outer retina atrophy (cRORA) size were measured on optical coherence tomography (OCT) volume scans at the initial visit and for each year of follow-up. MNV and cRORA were identified on B-scans and their respective borders were manually transposed onto the en-face near infrared image and measured in mm2. RESULTS: MNV enlarged through follow-up, with a mean growth rate of 1.24 mm2 / year. The mean growth in MNV size was independent of initial MNV size, age, gender, MNV subtypes or number of injections per year. Nevertheless, a great interindividual variation in size and growth was observed. cRORA developed in association with increasing MNV size and its incidence increased linearly over follow-up. cRORA lesions also showed continuous growth by a rate of 1.22 mm2 / year. CONCLUSIONS: Despite frequent long-term anti-VEGF therapy, we observed ongoing MNV growth. This is consistent with the concept that the development of MNV may be a physiological biological repair mechanism to preserve RPE and photoreceptor function, provided hyperpermeability and fluid exudation are controlled. Whether recurring low VEGF levels or other factors are responsible for MNV growth remains controversial.

Pachychoroid neovasculopathy versus macular neovascularization in age-related macular degeneration with and without shallow irregular pigment epithelial detachment.

To compare the choroidal neovascular features of individuals with pachychoroid neovasculopathy (PNV) and neovascular age-related macular degeneration (nAMD) with and without shallow irregular pigment epithelial detachment (SIPED). Using optical coherence tomography angiography, the choroidal neovascular complexes of 27 patients with PNV, 34 patients with nAMD and SIPED, and 15 patients with nAMD without SIPED were analyzed with FIJI and AngioTool software. PNV compared to nAMD with SIPED had a greater vessel percentage area (P = 0.034), junction density (P = 0.045), average vessel length (P < 0.001), and fractal dimension (P < 0.001). PNV, compared to nAMD without SIPED, had a greater total vessel length (P = 0.002), total number of junctions (P < 0.001), junction density (P = 0.034), and fractal dimension (P = 0.005). nAMD with SIPED, compared to nAMD without SIPED, had greater vessel area, total number of junctions, total vessel length, and average vessel length (all P values < 0.001). Patients with nAMD plus SIPED and individuals with nAMD without SIPED have similar fractal dimension values (P = 0.703). Biomarkers of choroidal neovascular complexity, such as fractal dimension, can be used to differentiate PNV from nAMD with or without SIPED.

Characterization of Vascular Morphology of Neovascular Age-Related Macular Degeneration by Indocyanine Green Angiography.

Age-related macular degeneration (AMD) is a leading cause of blindness among older individuals, and its prevalence is rapidly increasing due to the aging population. Choroidal neovascularization (CNV) or wet AMD, which accounts for 10%-20% of all AMD cases, is responsible for an alarming 80%-90% of AMD-related blindness. Current anti-VEGF therapies show suboptimal responses in approximately 50% of patients. Resistance to anti-VEGF treatment in CNV patients is often associated with arteriolar CNV, while responders tend to have capillary CNV. While fluorescein angiography (FA) is commonly used to assess leakage patterns in wet AMD patients and animal models, it does not provide information about CNV vascular morphology (arteriolar CNV vs. capillary CNV). This protocol introduces the use of indocyanine green angiography (ICGA) to characterize lesion types in laser-induced CNV mouse models. This method is crucial for investigating the mechanisms and treatment strategies for anti-VEGF resistance in wet AMD. It is recommended to incorporate ICGA alongside FA for comprehensive assessment of both leakage and vascular features of CNV in mechanistic and therapeutic studies.

FITC-Labeled RGD Peptides as Novel Contrast Agents for Functional Fluorescent Angiographic Detection of Retinal and Choroidal Neovascularization.

The development of choroidal neovascularization (CNV) is a crucial factor in the pathophysiology and prognosis of exudative age-related macular degeneration (AMD). Therefore, the detection of CNV is essential for establishing an appropriate diagnosis and treatment plan. Current ophthalmic imaging techniques, such as fundus fluorescent angiography and optical coherence tomography, have limitations in accurately visualizing CNV lesions and expressing CNV activity, owing to issues such as excessive dye leakage with pooling and the inability to provide functional information. Here, using the arginine-glycine-aspartic acid (RGD) peptide's affinity for integrin αvß3, which is expressed in the neovascular endothelial cells in ocular tissues, we propose the use of fluorescein isothiocyanate (FITC)-labeled RGD peptide as a novel dye for effective molecular imaging of CNV. FITC-labeled RGD peptides (FITC-RGD2), prepared by bioconjugation of one FITC molecule with two RGD peptides, demonstrated better visualization and precise localization of CNV lesions than conventional fluorescein dyes in laser-induced CNV rodent models, as assessed using various imaging techniques, including a commercially available clinical fundus camera (Optos). These results suggest that FITC-RGD2 can serve as an effective novel dye for the diagnosis of neovascular retinal diseases, including AMD, by enabling early detection and treatment of disease occurrence and recurrence after treatment.

Renally Clearable Ultraminiature Chain-Like Gold Nanoparticle Clusters for Multimodal Molecular Imaging of Choroidal Neovascularization.

Currently, available gold nanoparticles (GNPs) typically accumulate in the liver and spleen, leading to concerns for their long-term biosafety. To address this long-standing problem, ultraminiature chain-like gold nanoparticle clusters (GNCs) are developed. Via self-assembly of 7-8 nm GNP monomers, GNCs provide redshifted optical absorption and scattering contrast in the near-infrared window. After disassembly, GNCs turn back to GNPs with a size smaller than the renal glomerular filtration size cutoff, allowing their excretion via urine. A one-month longitudinal study in a rabbit eye model demonstrates that GNCs facilitate multimodal molecular imaging of choroidal neovascularization (CNV) in vivo, non-invasively, with excellent sensitivity and spatial resolution. GNCs targeting αv ß3  integrins enhance photoacoustic and optical coherence tomography (OCT) signals from CNV by 25.3-fold and 150%, respectively. With excellent biosafety and biocompatibility demonstrated, GNCs render a first-of-its-kind nanoplatform for biomedical imaging.

Detection of Choroidal Neovascularization Using Optical Tissue Transparency.

Purpose: Optical tissue transparency (OTT) provides a tool for visualizing the entire tissue block. This study provides insights into the potential value of OTT with light-sheet fluorescence microscopy (LSFM) in detecting choroidal neovascularization (CNV) lesions. Methods: OTT with LSFM, hematoxylin and eosin (H&E) staining of paraffin sections, choroidal flatmount immunofluorescence, and optical coherence tomography angiography (OCTA) were used to obtain images of CNV. We determined the rate of change as (Data of week 1 - Data of week 2)/Data of week 1 × 100%. Finally, we compared the rate of change acquired from OTT with LSFM and the other methodologies. Results: We found that OTT with LSFM can realize three-dimensional (3D) visualizations of the entire CNV. The results showed that the decline in the rate of change from week 1 to week 2 after laser photocoagulation was 33.05% with OTT, 53.01% with H&E staining, 48.11% with choroidal flatmount, 24.06% with OCTA (B-scan), 18.08% with OCTA (en face), 10.98% with OCTA (3D reconstruction), and 7.74% with OCTA (vessel diameter index). Conclusions: OTT with LSFM will continue to be an invaluable resource for investigators to detect more visualized and quantified information regarding CNV. Translational Relevance: OTT with LSFM now serves as a tool for detecting CNV in mice, and it may undergo human clinical trials in the future.

Pachychoroid neovasculopathy has clinical properties that differ from conventional neovascular age-related macular degeneration.

To determine the clinical properties of pachychoroid neovasculopathy (PNV) that differ from conventional neovascular age-related macular degeneration (nAMD) and suggest that they are different clinical entities. To accomplish this, we reviewed the medical records of 100 consecutive patients diagnosed with nAMD. All of the patients were Japanese, and their mean age was 75.5 years. There were 72 men and 28 women. For the bilateral cases, only the right eye was analyzed. An eye was diagnosed with PNV when a macular neovascularization (MNV) was detected just above the dilated choroidal vessels. The Indocyanine green angiographic (ICGA) and en face optical coherence tomographic (OCT) images were used to assess the vertical symmetry of the medium and large choroidal vessels. The subfoveal choroidal thickness (SCT) was also measured manually in the OCT images. After reclassification, there were 29 (29%) patients with typical nAMD (25 with type 1 MNV, 4 with type 2 MNV), 43 (43%) with PNV, 21 (21%) with polypoidal choroidal vasculopathy, and 7 (7%) with retinal angiomatous proliferation. Of the 43 PNV, 17 (39.5%) had polypoidal lesions and 26 (60.5%) had no polypoidal lesions. The percentage of eyes with vertical asymmetry of the medium and large choroidal vessels was significantly greater in the 35 PNV (81.4%) than in the 16 non-PNV (28.1%; P < 0.01) cases. The mean SCT was significantly thicker in the PNV eyes than in the non-PNV eyes (298 ± 96 µm vs. 228 ± 82 µm; P < 0.01). The response of PNV to anti-vascular endothelial growth factor treatments was better than that of non-PNV eyes [higher dry macula rate after the loading period (90.9% vs. 59.1%), fewer total number of injections (11.0 ± 2.9 vs. 13.4 ± 3.2), and longer treatment intervals for the anti-VEGF therapy (8.4 ± 3.1 vs. 13.4 ± 3.2 weeks) at 2 years (all P < 0.01)]. These differences in the morphology and response to anti-VEGF treatments suggest that PNV is a separate clinical entity to conventional nAMD.

Multimodal imaging of laser-induced choroidal neovascularization in pigmented rabbits.

This study aimed to demonstrate longitudinal multimodal imaging of laser photocoagulation-induced choroidal neovascularization (CNV) in pigmented rabbits. Six Dutch Belted pigmented rabbits were treated with 12 laser lesions in each eye at a power of 300 mW with an aerial diameter spot size of 500 µm and pulse duration of 100 ms. CNV progression was monitored over a period of 4 months using different imaging techniques including color fundus photography, fluorescein angiography (FA), photoacoustic microscopy (PAM), and optical coherence tomography (OCT). All treated eyes developed CNV with a success rate of 100%. The margin and morphology of CNV were detected and rendered in three dimensions using PAM and OCT. The CNV was further distinguished from the surrounding melanin and choroidal vessels using FDA-approved indocyanine green dye-enhanced PAM imaging. By obtaining PAM at 700 nm, the location and density of CNV were identified, and the induced PA signal increased up to 59 times. Immunohistochemistry with smooth muscle alpha-actin (αSMA) antibody confirmed the development of CNV. Laser photocoagulation demonstrates a great method to create CNV in pigmented rabbits. The CNV was stable for up to 4 months, and the CNV area was measured from FA images similar to PAM and OCT results. In addition, this study demonstrates that contrast agent-enhanced PAM imaging allows for precise visualization and evaluation of the formation of new blood vessels in a clinically-relevant animal model of CNV. This laser-induced CNV model can provide a unique technique for longitudinal studies of CNV pathogenesis that can be imaged with multimodal imaging.

Graph Attention U-Net for Retinal Layer Surface Detection and Choroid Neovascularization Segmentation in OCT Images.

Choroidal neovascularization (CNV) is a typical symptom of age-related macular degeneration (AMD) and is one of the leading causes for blindness. Accurate segmentation of CNV and detection of retinal layers are critical for eye disease diagnosis and monitoring. In this paper, we propose a novel graph attention U-Net (GA-UNet) for retinal layer surface detection and CNV segmentation in optical coherence tomography (OCT) images. Due to retinal layer deformation caused by CNV, it is challenging for existing models to segment CNV and detect retinal layer surfaces with the correct topological order. We propose two novel modules to address the challenge. The first module is a graph attention encoder (GAE) in a U-Net model that automatically integrates topological and pathological knowledge of retinal layers into the U-Net structure to achieve effective feature embedding. The second module is a graph decorrelation module (GDM) that takes reconstructed features by the decoder of the U-Net as inputs, it then decorrelates and removes information unrelated to retinal layer for improved retinal layer surface detection. In addition, we propose a new loss function to maintain the correct topological order of retinal layers and the continuity of their boundaries. The proposed model learns graph attention maps automatically during training and performs retinal layer surface detection and CNV segmentation simultaneously with the attention maps during inference. We evaluated the proposed model on our private AMD dataset and another public dataset. Experiment results show that the proposed model outperformed the competing methods for retinal layer surface detection and CNV segmentation and achieved new state of the arts on the datasets.

Choroidal neovascularization removal with photo-mediated ultrasound therapy.

BACKGROUND: Age-related macular degeneration (AMD) is a major cause of irreversible central vision loss. The main reason for lost vision due to AMD is choroidal neovascularization (CNV). In the clinic, current treatments for CNV include photodynamic therapy, laser photocoagulation, and anti-vascular endothelial growth factor (VEGF) therapy. PURPOSE: This study evaluates a novel treatment technique combining synchronized nanosecond laser pulses and ultrasound bursts, namely photo-mediated ultrasound therapy (PUT) as a potential treatment method for CNV, for its efficacy and safety in the treatment of CNV via the experiments in a clinically-relevant rabbit model in vivo. METHODS: CNV was created by subretinal injection of Matrigel and vascular endothelial growth factor (M&V) in 10 New Zealand white rabbits. Six rabbits were used in the PUT group. In the control groups, two rabbits were treated by laser-only, and two rabbits were treated by ultrasound-only. The treatment efficacy was evaluated through fundus photography and fluorescein angiography (FA) longitudinally for up to 4 weeks. Rabbits were sacrificed for histopathology 3 months after treatment to examine the safety of PUT. RESULTS: The fluorescein leakage on FA was quantified to longitudinally evaluate treatment outcome. Compared with baseline, the relative intensity index was reduced by 26.57% ± 8.66% at 3 days after treatment, 27.24% ± 6.21% at 1 week after treatment, 27.79% ± 2.61% at 2 weeks after treatment, and 32.12% ± 3.23% at 4 weeks after treatment, all with a statistically significant difference of p < 0.01. The comparison between the relative intensity indexes from the two control groups (laser-only treatment and ultrasound-only treatment) did not show any statistically significant difference at all time points. Safety evaluation at 3 months with histopathology demonstrated that the PUT did not result in morphologic changes to the neurosensory retina. CONCLUSIONS: This study introduces PUT for the first time for the treatment of CNV. The results demonstrated good efficacy and safety of PUT to treat CNV in a clinically-relevant rabbit model. With a single session of treatment, PUT can safely reduce the leakage of CNV for at least 1 month after treatment.

Characteristics and response of subretinal hyperreflective material to anti-vascular endothelial growth factor in myopic choroidal neovascularization.

This retrospective study evaluated the characteristics and response of subretinal hyperreflective material (SHRM) to anti-vascular endothelial growth factor (VEGF) treatment in eyes with myopic choroidal neovascularization (CNV). The visual acuity (VA) was assessed at 3, 6, and 12 months after initiating anti-VEGF treatment in 116 patients (119 eyes) with SHRM and myopic CNV. Multimodal imaging, including color fundus photography, fluorescein angiography (FA), and optical coherence tomography angiography (OCT-A), were performed. We compared type 2 neovascularization (NV) (n = 64), subretinal hyperreflective exudation (SHE) (n = 37), NV with hemorrhage (n = 15), and fibrosis (n = 3). The type 2 NV group, and NV with hemorrhage groups showed significant VA improvement after 12 months of treatment (p < 0.05 in both groups); the SHE group failed to show improvement (p = 0.366). All groups showed a significant reduction in central foveal thickness after 12 months of treatment (all p < 0.05). The SHE group had a significantly higher incidence of interrupted ellipsoid zone than the other groups (p < 0.05). Myopic CNV can present as SHRM on OCT-A. Visual prognoses vary in different SHRM types. OCT-A and FA may help predict the outcomes of different subtypes of myopic CNV. SHE is predictive of outer retinal layer atrophy in patients with various SHRM types.

Clinical implications of choroidal vascular brightness using ultra-widefield indocyanine green angiography in polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is characterized by choroidal vascular abnormalities including polypoidal lesion and branching vascular networks. Not only choroidal structural changes, but also choroidal hyperpermeability and congestion are also thought to be involved in pathogenesis of PCV. We investigated choroidal vascular brightness intensity (CVB) using ultra-widefield indocyanine green angiography (UWF-ICGA) images and analyzed its association with clinical features in patients with PCV. In this study, 33 eyes with PCV and 27 eyes of age-matched controls were included. CVB was measured by extracting the enhanced pixels of choroidal vessels after the reference brightness across the images was adjusted to be uniform. Associations between choroidal vascular features and the clinical features of PCV were also determined. The mean CVB was higher in PCV than control eyes, regardless of the segmented region (all p < 0.001). CVB was also higher at the posterior pole than at the periphery, and the inferior quadrants were brighter than the superior quadrants in both the PCV and control group (all p < 0.05). In affected eyes, CVB was higher than in unaffected fellow eyes at the posterior pole, whereas there was no difference at the periphery. Posterior pole CVB correlated significantly with subfoveal choroidal thickness (r = 0.502, p = 0.005), polyp number (r = 0.366 p = 0.030), and the greatest linear dimension (r = 0.680, p = 0.040). Greatest linear dimension was positively correlated with CVB at posterior pole (p = 0.040), whereas SFCT or CVD in all regions didn't show the significant correlation. The UWF ICGA results showed an increase in CVB at the inferior quadrants and posterior pole, suggesting venous outflow congestion in PCV eyes. CVB might provide more substantial information on the phenotype than other choroidal vascular features.

An ImageJ macro tool for OCTA-based quantitative analysis of Myopic Choroidal neovascularization.

Myopic Choroidal neovascularization (mCNV) is one of the most common vision-threatening com- plications of pathological myopia among many retinal diseases. Optical Coherence Tomography Angiography (OCTA) is an emerging newer non-invasive imaging technique and is recently being included in the investigation and treatment of mCNV. However, there exists no standard tool for time-efficient and dependable analysis of OCTA images of mCNV. In this study, we propose a customizable ImageJ macro that automates the OCTA image processing and lets users measure nine mCNV biomarkers. We developed a three-stage image processing pipeline to process the OCTA images using the macro. The images were first manually delineated, and then denoised using a Gaussian Filter. This was followed by the application of the Frangi filter and Local Adaptive thresholding. Finally, skeletonized images were obtained using the Mexican Hat filter. Nine vascular biomarkers including Junction Density, Vessel Diameter, and Fractal Dimension were then computed from the skeletonized images. The macro was tested on a 26 OCTA image dataset for all biomarkers. Two trends emerged in the computed biomarker values. First, the lesion-size dependent parameters (mCNV Area (mm2) Mean = 0.65, SD = 0.46) showed high variation, whereas normalized parameters (Junction Density(n/mm): Mean = 10.24, SD = 0.63) were uniform throughout the dataset. The computed values were consistent with manual measurements within existing literature. The results illustrate our ImageJ macro to be a convenient alternative for manual OCTA image processing, including provisions for batch processing and parameter customization, providing a systematic, reliable analysis of mCNV.

Deep Learning for Diagnosing and Segmenting Choroidal Neovascularization in OCT Angiography in a Large Real-World Data Set.

Purpose: To diagnose and segment choroidal neovascularization (CNV) in a real-world multicenter clinical OCT angiography (OCTA) data set using deep learning. Methods: A total of 105,66 OCTA scans from 3135 eyes, including 4701 with CNV and 5865 without, were collected in five eye clinics. Both 3 × 3-mm and 6 × 6-mm scans of the central and temporal macula were included. Scans with CNV were collected from multiple diseases, and scans without CNV were collected from both healthy controls and those with multiple diseases. No scans were removed during training or testing due to poor quality. The trained hybrid multitask convolutional neural network outputs a CNV diagnosis and membrane segmentation, respectively. Results: The model demonstrated a highly accurate CNV diagnosis (area under receiver operating characteristic curve = 0.97), achieving a sensitivity of 95% at 95% specificity. The model also correctly segmented CNV lesions (F1 score = 0.78 ± 0.19). Additionally, model performance was comparable on both high-definition 3 × 3-mm scans and low-definition 6 × 6-mm scans. The model did not suffer large performance variations under different diseases. We also show that a subclinical lesion in a patient with neovascular age-related macular degeneration can be monitored over a multiyear time frame using our approach. Conclusions: The proposed method can accurately diagnose and segment CNV in a large real-world clinical data set. Translational Relevance: The algorithm could enable automated CNV screening and quantification in the clinic, which will help improve CNV diagnosis and treatment evaluation.

[Diagnosis and clinical features of non-exudative macular neovascularization]. / Diagnostika i klinicheskie osobennosti neekssudativnoi makulyarnoi neovaskulyarizatsii.

Macular neovascularization (MNV) is the process of new abnormal blood vessels formation in the choroid and/or retina. The widespread adoption of optical coherence tomography angiography (OCTA) has significantly expanded the possibilities of not only detecting pathological blood flow before the development of exudation and deterioration of visual acuity, but also determining its characteristics. The purpose of this review is to substantiate the criteria for choosing terminology and diagnostic markers of MNV. The term "non-exudative MNV" refers to type 1 neovascularization without intraretinal or subretinal exudation detected on repeated OCT scans in the course of at least 6 months. This type of MNV may include previously untreated, non-exudative membranes with a low tendency to exudate, as well as previously treated membranes that have become inactive or dormant and no longer require anti-angiogenic therapy. The criterion for dividing the non-exudative form of MNV into inactive (with a low growth rate and vascular density (VD) at baseline) and subclinical (with a high growth rate and VD) is the time of its activation, generally recognized as 6 months. The diagnostic criteria is the visualized "double layer" sign on OCT scans (retinal pigment epithelium and Bruch's membrane), as well as patterns of neovascular membranes of varying sizes, morphology and localization on OCTA scans. The cumulative risk of conversion from subclinical to exudative at two years of follow-up is 13.6 times higher than in eyes without detectable neovascularization, which highlights the importance of frequent monitoring in this healthy eye population for early detection of MNV signs.

Optical coherence tomography biomarkers for myopic choroidal neovascularization treated with anti-vascular endothelial growth factor.

In recent years, optical coherence tomography (OCT) biomarkers for specific retinal diseases have been found to be associated with treatment outcome and disease recurrence. The main purposes of this study were to identify OCT biomarkers for myopic choroidal neovascularization (mCNV) treated with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF). OCT features in 43 eyes of 39 patients with mCNV treated with anti-VEGF with at least 1 year of follow-up were retrospectively analyzed. Eyes with subretinal hyperreflective material (SHM) in baseline spectral-domain OCT (SD-OCT) had significantly more visual improvement than eyes without SHM at month 6 (p = 0.007) and had a trend of more visual improvement than eyes without SHM (p = 0.058) at month 12. Eyes with subretinal fluid (SRF) at baseline had significantly more central retinal thickness (CRT) decrease than patients without SRF at month 6 and 12 (p = 0.012 and 0.006 respectively). In univariate regression analysis, dome-shaped macula (DSM), SRF in baseline OCT image and fuzzy border of mCNV when entering pro re nata (PRN) injection protocol tended to have higher risk of disease recurrence in 1 year (odds ratio: 14.86 (p = 0.003), 3.75 (p = 0.049) and 22.92 (p < 0.001) respectively). However, they were not significant in multivariate regression analysis. OCT biomarkers at baseline could provide prognostic information for mCNV management.

Outer nuclear layer recovery as a predictor of visual prognosis in type 1 choroidal neovascularization of neovascular age-related macular degeneration.

To investigate the changes in outer nuclear layer (ONL) thickness during anti-vascular endothelial growth factor (VEGF) treatment in type 1 choroidal neovascularization (CNV) and its impact on vision. Type 1 CNV eyes (n = 94) were retrospectively compared to normal control eyes (n = 35). Along with best-corrected visual acuity (BCVA), the location of CNV, foveal ONL thickness, and subretinal fluid height were measured using optical coherence tomography (OCT) and analyzed. Visual outcome and OCT biomarkers were compared. As a result, the CNV group had thinner foveal ONL and worse BCVA compared to the control group. ONL thickness recovered partially along with visual improvement following 3 monthly initial loading doses of aflibercept injections, and it correlated with the final BCVA during the 1-year follow-up. Eyes achieved foveal ONL recovery over + 10 µm had lower subfoveal CNV (45.5%) and showed better visual outcomes than eyes with stationary ONL or suboptimal ONL recovery (76.0%, p = 0.012). In conclusion, type 1 CNV eyes that recovered foveal ONL thickness at initial loading of anti-VEGF demonstrated good final visual outcome during the 1-year follow-up. Monitoring the foveal ONL thickness during early anti-VEGF treatment can give information about the visual outcomes in type 1 CNV.

Morphological prognosis prediction of choroid neovascularization from longitudinal SD-OCT images.

BACKGROUND: Choroid neovascularization (CNV) has no obvious symptoms in the early stage, but with its gradual expansion, leakage, rupture, and bleeding, it can cause vision loss and central scotoma. In some severe cases, it will lead to permanent visual impairment. PURPOSE: Accurate prediction of disease progression can greatly help ophthalmologists to formulate appropriate treatment plans and prevent further deterioration of the disease. Therefore, we aim to predict the growth trend of CNV to help the attending physician judge the effectiveness of treatment. METHODS: In this paper, we develop a CNN-based method for CNV growth prediction. To achieve this, we first design a registration network to rigidly register the spectral domain optical coherence tomography (SD-OCT) B-scans of each subject at different time points to eliminate retinal displacements of longitudinal data. Then, considering the correlation of longitudinal data, we propose a co-segmentation network with a correlation attention guidance (CAG) module to cooperatively segment CNV lesions of a group of follow-up images and use them as input for growth prediction. Finally, based on the above registration and segmentation networks, an encoder-recurrent-decoder framework is developed for CNV growth prediction, in which an attention-based gated recurrent unit (AGRU) is embedded as the recurrent neural network to recurrently learn robust representations. RESULTS: The registration network rigidly registers the follow-up images of patients to the reference images with a root mean square error (RMSE) of 6.754 pixels. And compared with other state-of-the-art segmentation methods, the proposed segmentation network achieves high performance with the Dice similarity coefficients (Dsc) of 85.27%. Based on the above experiments, the proposed growth prediction network can play a role in predicting the future CNV morphology, and the predicted CNV has a Dsc of 83.69% with the ground truth, which is significantly consistent with the actual follow-up visit. CONCLUSION: The proposed registration and segmentation networks provide the possibility for growth prediction. In addition, accurately predicting the growth of CNV enables us to know the efficacy of the drug against individuals in advance, creating opportunities for formulating appropriate treatment plans.

Intravitreal aflibercept for idiopathic choroidal neovascularisation in paediatric age.

A boy in early adolescence presented with a 1-week history of visual acuity impairment in his right eye (RE). Fundus examination of the RE revealed an elevated yellow-greyish lesion in the inferior temporal juxtafoveolar area. Findings on optical coherence tomography, fluorescein angiography and optical coherence tomography angiography were compatible with active choroidal neovascularisation (CNV). In the absence of a primary ocular pathology and a potential systemic secondary cause, it was assumed an idiopathic aetiology of CNV. The child was treated with intravitreal injections of aflibercept, showing good anatomical and functional responses. No complications were recorded after the injections. CNV in children is a rare ocular condition that can lead to permanent visual acuity impairment. Although the therapeutic approach remains controversial, anti-vascular endothelial growth factor intravitreal injections represent a safe and effective therapeutic option for CNV in children.

Review for Diagnostics of the Year: Inflammatory Choroidal Neovascularization - Imaging Update.

Inflammatory choroidal neovascularization (iCNV) is a rare complication of uveitis but is a major cause of vision compromise in affected patients. Fluorescein angiography (FA) has been the gold standard for diagnosis. However, it is an invasive modality and when used alone, it might be difficult to distinguish iCNV from inflammatory lesions. Optical coherence tomography (OCT) is a noninvasive and rapid imaging modality that can provide additional features to diagnose iCNV. OCT angiography (OCTA) uses intrinsic motion contrast to visualize flow and is useful to distinguish iCNV from inflammatory lesions. However, its role in evaluating iCNV activity and treatment response is still unclear and more studies are required to reach consensus. In conclusion, the use of data from multimodal imaging is necessary to identify and promptly treat iCNV, thus preserving patient vision.