Choroidal Neovascularization Research Articles

A drug delivery system of HIF-1α siRNA nanoparticles loaded by mesenchymal stem cells on choroidal neovascularization.

Aim: To assess mesenchymal stem cells (MSCs) as carriers for HIF-1αsiRNA-loaded nanoparticles (NPs) for targeted therapy of experimental choroidal neovascularization (CNV).Materials & methods: A poly (lactic-co-glycolic acid) (PLGA)-core/lipid-shell hybrid NP was designed. The transfection efficacy of MSCs with the hybrid NPs was assessed. Mice were intravenously injected with MSCs after laser photocoagulation and CNV was assessed at 7days post-injection.Results & conclusion: The transfection efficiency of hybrid NPs into MSCs was 72.7%. HIF-1α mRNA expression in 661w cells co-cultured with MSC-hybrid-siRNA NPs was significantly lower. Intravenous delivery of MSC-hybrid-siRNA NPs greatly reduced CNV area and length. Intravenous injection of MSC-hybrid-siRNA NPs achieved therapeutic efficacy in reducing CNV area. The MSC-mediated homing enabled targeted inhibition of ocular angiogenesis.

REGULATION OF RETINOGENESIS IN PRENATAL ONTOGENESIS AND ITS DISRUPTION IN AGE-RELATED MACULAR DEGENERATION

One of the main causes of blindness in the elderly in developed countries is age-related macular degeneration (AMD) [1, 2, 3]. Active research is being conducted to identify putative molecular targets for the development of an effective strategy for conservative treatment of both atrophic and neovascular forms of this disease [4, 5, 6], but at the present stage, pharmacotherapy is effective only for some patients, and is insufficient to stop the progression of the disease or eliminate the damage that has already occurred. The most promising and promising potential treatment options are considered to be the introduction of cellular technologies with retinal cell replacement and targeted pharmacotherapy. The aim of this study was to investigate the role of the retinal development inducer, SIRT1 [7, 8, 9], in retinogenesis to justify pharmacological inhibition of this protein as a possible treatment option for neovascular AMD. Using immunohistochemistry and immunocytochemistry, we assessed the expression and subcellular localization of SIRT1 and its innate inhibitor DBC1 in the retina of fetuses, adults, and mice. We also studied SIRT1 in retinal progenitor cells derived from mice and humans, the former having been used in small interfering RNA studies. SIRT1 is widely expressed in the developing and adult retina and is a regulator of key genes in retinal development, namely PAX6, Nestin, and CRX [10, 11, 12]. Moreover, we found that photoreceptor progenitor cells were among the smallest cells in a heterogeneous mouse retinal progenitor cell population [13, 14, 15]. Collectively, these results provide a basis for manipulating SIRT1 expression in small retinal progenitors as a means to increase the yield of photoreceptors for transplantation in retinal degeneration models [16, 17]. Furthermore, SIRT1 was found to be highly expressed in human-derived choroidal neovascular membranes, allowing its activity to be pharmacologically inhibited by the drug nicotinamide as a potent regulator of angiogenic and hypoxic signaling in a human retinal pigment epithelial cell line at both the protein level using angiogenesis arrays and at the RNA level using whole genome microarrays [18, 19]. These results point to the SIRT1 inhibitor, Nicotinamide, as a possible agent for treatment of neovascular AMD. Further studies of Nicotinamide are warranted in animal models of AMD. To the best of our knowledge, this is the first time that a detailed analysis of SIRT1 as a regulator of both retinal development and choroidal neovascularization has been reported.

ENLARGEMENT OF CHOROIDAL NEOVASCULARIZATION BEFORE RECURRENCE AFTER PHOTODYNAMIC THERAPY FOR PACHYCHOROID NEOVASCULOPATHY.

To investigate predictors of recurrent exudation in choroidal neovascularization (CNV) of pachychoroid neovasculopathy after photodynamic therapy (PDT). Consecutive, treatment-naïve, symptomatic patients with pachychoroid neovasculopathy with subfoveal retinal fluid treated with PDT and followed for 18 months were studied retrospectively. Choroidal neovascularization areas were calculated from optical coherence tomography angiography images obtained at various time points after the initial PDT. In 52 eyes, the subfoveal retinal fluid resolved completely three months after PDT; in 23 (44%) eyes, exudation recurred during the 18-month follow-up period. In 29 eyes with no recurrence, the mean baseline square root of the CNV area of 1.91 mm (95% CI, 0.27) decreased significantly ( P = 0.006) to 1.47 mm (95% CI, 0.16) at three months after PDT and decreased further until 12 months after PDT (mean, 1.26 mm; 95% CI, P < 0.001) and was maintained thereafter. In 23 eyes with a recurrence, the square root of the CNV area enlarged significantly ( P = 0.028) from 1.43 mm (95% CI, 0.21) at examination three months before the recurrence to 1.73 mm (95% CI, 0.18) at recurrence. Choroidal neovascularization enlargement during the follow-up period after PDT for pachychoroid neovasculopathy may predict recurrence.

Optimal Humanized Scg3-Neutralizing Antibodies for Anti-Angiogenic Therapy of Diabetic Retinopathy.

Secretogranin III (Scg3) is a diabetic retinopathy (DR)-restricted angiogenic factor identified in preclinical studies as a target for DR therapy. Previously, our group generated and characterized ML49.3, an anti-Scg3 monoclonal antibody (mAb) which we then converted into an EBP2 humanized antibody Fab fragment (hFab) with potential for clinical application. We also generated anti-Scg3 mT4 mAb and related EBP3 hFab. In this study, to identify the preferred hFab for DR therapy, we compared all four antibodies for binding, neutralizing and therapeutic activities in vitro and in vivo. Octet binding kinetics analyses revealed that ML49.3 mAb, EBP2 hFab, mT4 mAb and EBP3 hFab have Scg3-binding affinities of 35, 8.7, 0.859 and 0.116 nM, respectively. Both anti-Scg3 EBP2 and EBP3 hFabs significantly inhibited Scg3-induced proliferation and migration of human umbilical vein endothelial cells in vitro, and alleviated DR vascular leakage and choroidal neovascularization with high efficacy. Paired assays in DR mice revealed that intravitreally injected EBP3 hFab is 26.4% and 10.3% more effective than EBP2 hFab and aflibercept, respectively, for ameliorating DR leakage. In conclusion, this study confirms the markedly improved binding affinities of hFabs compared to mAbs and further identifies EBP3 hFab as the preferred antibody to develop for anti-Scg3 therapy.

Video Color OCT Angiography for Myopic Choroidal Neovascularization

To investigate the myopic macular neovascularization (mMNV) features on dynamic video-color optical coherence tomography (OCT) angiography (OCTA) and the diagnostic rate versus the static, four-segmentations visualization mode. Retrospective cohort study PARTICIPANTS: Fifty-four patients with mMNV METHODS: Sixty-two eyes with high myopia complicated by mMNV were included. Clinical charts, fluorescein angiography and structural OCT were used as standard reference to assess lesion activity. Static and video-color OCTA were then analysed and compared by two independent reviewers. Morphology description of mMNV on video-color OCTA and differences in the proportion of diagnosis between video-colour and static OCTA. 62 eyes from 54 patients (mean age 63,22 years) were enrolled. Thirty-four (55%) mMNV were active and 28 (45%) inactive. Twenty-two (65%) active mMNV presented on video-color OCTA as an interlacing vascular network in the outer retina and the choriocapillaris. A tapered form was the prevalent size (72,7%). In 3 eyes (9%) an abnormal and irregular vascular network (AVN) was disclosed and in 5 (15%) only some blood flow alteration. All the lesions extended both in the outer retinal and the choriocapillaris. Eleven (39%) inactive mMNV presented on video-color OCTA as an interlacing vascular network too, in the outer retina and the choriocapillaris. Eight (29%) had some AVN and 6 (21%) only some blood flow alteration. The diagnostic rate of video-color vs static OCTA was 95% (IC 95% 86% to 99%) vs 77% (IC 95% 86% to 99%, p= 0.0009), and shows an advantage in favour of video-colour OCTA of 15% (CI 95%, 3%-27%) and 22% (CI 95%, 7%-38%) in active and inactive lesions, respectively (p<0.026). Lesion extension within both the outer retina and the choriocapillaris was present in 90% and 69% of cases on dynamic OCTA and static OCTA, respectively, with a proportion difference of 20% (CI 95%, 10%-31%, p= 0.0005). Concordance between the two examiners was high: 0.95 (95%, CI 0.88 to 1.00) and 0.96 (0.91 to 1.00) for active and inactive lesions, respectively. Video color-enhanced OCTA may help in diagnosing mMNV and should be considered by clinicians in addition to structural OCT and static OCTA.

ARTIFICIAL INTELLIGENCE-ENHANCED ANALYSIS OF RETINAL VASCULATURE IN AGE-RELATED MACULAR DEGENERATION.

To investigate associations between quantitative vascular measurements derived from intravenous fluorescein angiography (IVFA) and baseline characteristics on optical coherence tomography (OCT) in neovascular age-related macular degeneration (nAMD) patients. The authors prospectively recruited patients with active choroidal neovascularization secondary to AMD over 50 years old, presenting to a single center in Toronto, Canada from 2017 to 2023. Ultra-widefield IVFA images were processed using the artificial intelligence RETICAD FAassist system to extract quantitative information on blood flow, perfusion, and blood-retinal-barrier (BRB) permeability. Associations between IVFA parameters with functional and anatomical outcomes were examined using univariable and multivariable regression models. Eighty-one nAMD eyes and seven healthy control eyes were included. Compared with healthy controls, BRB permeability in the central and peripheral retina was significantly higher in nAMD patients (P < 0.001). On univariable analysis, BRB permeability measured centrally was significantly associated with central macular thickness (P = 0.035), whereas perfusion and blood flow measured centrally were significantly associated with macular volume (P = 0.043 and 0.037, respectively). On multivariable analysis, BRB permeability remained significantly associated with central macular thickness (P = 0.026). Central BRB permeability measured on IVFA was significantly associated with baseline central macular thickness in nAMD patients. Future work should longitudinally explore associations between IVFA parameters and clinical characteristics in diverse nAMD populations.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AND POOR VISUAL ACUITY.

To investigate the significance of intravitreal anti-vascular endothelial growth factor treatment in patients with neovascular age-related macular degeneration and poor visual acuity. Retrospective study of patients with neovascular age-related macular degeneration with baseline best-corrected visual acuity of ≤20/200. Patients were divided into regular treatment and scarce treatment groups according to whether they underwent consecutive intravitreal anti-vascular endothelial growth factor treatments at intervals of ≤4 months or not. A total of 131 eyes were included: 87 and 44 eyes in the regular treatment and scarce treatment groups, respectively. The regular treatment group showed significantly improved preservation of lesion size at both Years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage. Improvements in visual acuity, reduction in central subfield macular thickness, and maximal height of choroidal neovascularization were significantly favorable in the regular treatment group at Year 1, and central subfield macular thickness was significantly decreased at Year 2. Survival analysis revealed that the regular treatment group had significantly greater preservation of visual acuity and lesion size than that in the scarce treatment group. Maintaining intravitreal anti-vascular endothelial growth factor treatment for patients with neovascular age-related macular degeneration and poor vision showed significant advantages in visual acuity and lesion size stability and reduced the incidence of new subretinal hemorrhage, which suggests preservation of paracentral vision.

“Macular Sinkhole” With Secondary Choroidal Neovascularization

Purpose: To describe a case of an eccentric macular hole (MH) overlying a choroidal cavitation in a nonmyopic eye with secondary choroidal neovascularization (CNV). Methods: A case report is presented. Results: A 101-year-old man was referred for an asymptomatic retinal pigmentary abnormality in the right eye. A fundus examination showed a yellow–orange circular lesion with a white center and mild associated hemorrhage. Optical coherence tomography showed an eccentric full-thickness MH overlying a choroidal cavitation with intraretinal cystic change and subretinal hyperreflective material suggestive of CNV. The patient was treated with intravitreal antivascular endothelial growth factor and had a good response. Conclusions: Typically described as being adjacent to the optic disc and in myopic fundi, eccentric macular choroidal cavitations may be seen in nonmyopic eyes and associated with full-thickness MHs (“macular sinkholes”) and CNV. This case report expands the spectrum of potentially visually significant findings associated with choroidal cavitary disease.

Light-Activated Anti-Vascular Combination Therapy against Choroidal Neovascularization.

Choroidal neovascularization (CNV) underlies the crux of many angiogenic eye disorders. Although medications that target vascular endothelial growth factor (VEGF) are approved for treating CNV, their effectiveness in destroying new blood vessels is limited, and invasive intravitreal administration is required. Additionally, other drugs that destroy established neovessels, such as combretastatin A-4, may have systemic side effects that limit their therapeutic benefits. To overcome these shortcomings, a two-pronged anti-vascular approach is presented for CNV treatment using a photoactivatable nanoparticle system that can release a VEGF receptor inhibitor and a vascular disrupting agent when irradiated with 690nm light. The nanoparticles can be injected intravenously to enable anti-angiogenic and vascular disrupting combination therapy for CNV through light irradiation to the eyes. This approach can potentiate therapeutic effects while maintaining a favorable biosafety profile for choroidal vascular diseases.

The benzoylphenylurea derivative BPU17 acts as an inhibitor of prohibitin and exhibits antifibrotic activity

Inflammation-induced choroidal neovascularization followed by the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) is a cause of neovascular age-related macular degeneration (nAMD). RPE-derived myofibroblasts overproduce extracellular matrix, leading to subretinal fibrosis. We already have demonstrated that benzylphenylurea (BPU) derivatives inhibit the function of cancer-associated fibroblasts. Here, we investigated the anti-myofibroblast effects of BPU derivatives and examined such BPU activity on subretinal fibrosis. A BPU derivative, BPU17, exhibits the most potent anti-myofibroblast activity among dozens of BPU derivatives and inhibits subretinal fibrosis in a mouse model of retinal degeneration. Investigations with primary cultured RPEs reveal that BPU17 suppresses cell motility and collagen synthesis in RPE-derived myofibroblasts. These effects depend on repressing the serum response factor (SRF)/CArG-box-dependent transcription. BPU17 inhibits the expression of SRF cofactor, cysteine and glycine-rich protein 2 (CRP2), which activates the SRF function. Proteomics analysis reveals that BPU17 binds to prohibitin 1 (PHB1) and inhibits the PHB1-PHB2 interaction, resulting in mild defects in mitochondrial function. This impairment causes a decrease in the expression of CRP2 and suppresses collagen synthesis. Our findings suggest that BPU17 is a promising agent against nAMD and the close relationship between PHB function and EMT.

Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis

BackgroundTopical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies.MethodsCochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac.ResultsIn total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported.ConclusionsThis literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

CBX7 promotes choroidal neovascularization by activating the HIF-1α/VEGF pathway in choroidal vascular endothelial cells

Vascular endothelial growth factor (VEGF) signaling is crucial for choroidal neovascularization (CNV), a major pathological feature of neovascular age-related macular degeneration (nAMD). Gene transcription of VEGF is mainly regulated by hypoxia-inducible factor 1-alpha (HIF-1α). The chromobox (CBX) family polycomb protein (Pc) subgroup includes CBX2, CBX4, CBX6, CBX7, and CBX8. CBX4 enhances hypoxia-induced VEGF expression and angiogenesis in hepatocellular carcinoma (HCC) cells by increasing HIF-1α′s transcriptional activity. The objective of the study was to examine the functions of members of the CBX family Pc subgroup in choroidal vascular endothelial cells (CVECs) during CNV. CBX4 and CBX7 expression was up-regulated in hypoxic human choroidal vascular endothelial cells (HCVECs). In HCVECs, CBX7 facilitated HIF-1α transcription and expression, while CBX4 did not. In HCVECs, CBX7 stimulated HIF-1α′s nuclear translocation and transcriptional activity, which in turn stimulated VEGF transcription and expression. The CBX7/HIF-1α/VEGF pathway promoted the migration, proliferation, and tube formation of HCVECs. The CBX7/HIF-1α/VEGF pathway was up-regulated in CVECs and in the mouse model with laser-induced CNV. Mouse CNV was lessened by the blockade of CBX7 through the down-regulation of HIF-1α/VEGF. In conclusion, CBX7 enhanced pro-angiogenic behaviors of hypoxic CVECs by up-regulating the HIF-1α/VEGF pathway, which contributing to the formation of mouse laser-induced CNV.

Vascular Changes and Irreversible Complications in 120° Fundus Using Widefield SS-OCTA in Vogt-Koyanagi-Harada Disease.

To characterize the changes of fundus corresponding to 120° field of view in chronic Vogt-Koyanagi-Harada (VKH) disease in the quiescent phase, and explore the associations with irreversible complications in the fundus utilizing widefield swept source optical coherence tomography angiography (SS-OCTA). Prospective cross-sectional study. Sixty-nine chronic VKH patients (115 eyes) and 55 healthy controls (110 eyes) were included and underwent widefield SS-OCTA. Univariate analyses of variations in retinal and choroidal vessel density (VD), choroidal volume, and choroidal vascularity index (CVI) in VKH patients with different disease durations and the controls were conducted. Logistic regression analysis was employed to identify the associations with irreversible complications including choroidal neovascularization, vasoproliferative tumour of the retina, and chorioretinal atrophy. The Welch's analysis of variance showed lower VD of superficial retina, deep retina, choriocapillaris, and large-sized and medium-sized vessels of the choroid (LMVC), and choroidal volume and CVI in the patients with disease duration > 24 months compared to those with disease duration ≤ 24 months (all P≤0.011). The regression analysis revealed the disease duration (P=0.008; OR=1.02, 95%CI=1.005-1.035) and VD of LMVC (P=0.001; OR=0.707, 95%CI=0.575-0.87) were significantly correlated with the irreversible complications. Chronic VKH patients in the quiescent phase with disease duration > 24 months exhibit more severe decreased VD in each layer of the retina and choroid, reduced choroidal volume and sparse choroidal vascularity compared to those with disease duration ≤ 24 months. Prolonged duration and decreased VD of LMVC were associated with irreversible complications in the fundus.

Targeted 8-arm PEG Nanosystems for Localization of Choroidal Neovascularization Macular Degeneration Model.

8-arm PEG (polyethylene-glycol) is a highly promising nanoplatform due to its small size (<10 nm), ease-of-conjugation (many functionalized variants are readily available with "click-like" properties), biocompatibility, and optical inactivity. This study evaluates 8-arm PEG uptake into cells (in vitro) and localization and clearance in vasculature (in vivo) for targeting of choroidal neovascularization in mice, an animal model of macular degeneration. 8-arm PEG nanoparticles were labeled with fluorescein isothiocyanate (FITC) and functionalized in the absence or presence of pentameric Ar-Gly-Asp (RGD; 4 RGD motifs and a PGC linker), one of the most common peptide motifs used for active targeting. In vitro studies show that RGD-conjugated 8-arm PEG nanoparticles exhibit enhanced cellular uptake relative to non-RGD-conjugated control NPs at 34% ± 9%. Laser-induced choroidal neovascularization (CNV) was performed in a mouse model to measure 8-arm PEG localization and clearance to model macular degeneration lesions in vivo. It was determined that both RGD-conjugated and non-RGD-conjugated (nRGD) 8-arm PEG particles localized to CNV lesions, with a half-life around 24 h. In vivo experiments showed that RGD-conjugated nanoparticles exhibited enhanced localization by 15-20% relative to without RGD controls. Exhibiting a high rate of localization and fast clearance relative to larger nanoparticles, targeted 8-arm PEG nanoparticles with a conjugated RGD-peptide could be a promising modality for macular degeneration diagnosis and therapy.

Clinical Outcomes of Double-dose Aflibercept Treatment for Refractory Wet Age-related Macular Degeneration

Purpose: To evaluate the clinical outcomes and prognostic factors of double-dose aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD).Methods: We reviewed the medical records of nAMD patients treated with a double dose of aflibercept (4 mg/0.1 mL) due to an inadequate response to standard 8-weekly intravitreal injections of 2 mg/0.05 mL aflibercept. The assessment at week 8 after treatment included changes in subretinal/intraretinal fluid (SRF/IRF) and best-corrected visual acuity, with patients showing absence or reduction in SRF/IRF classified as the response group. Baseline factors influencing clinical outcomes were analyzed, including central macular thickness (CMT), central choroidal thickness (CCT), size of choroidal neovascularization (CNV), CNV subtype, and maximum height of SRF and IRF.Results: The study included 95 eyes of 95 subjects, with 61 eyes (64.2%) categorized as the response group following double-dose treatment. Responders exhibited thicker CCT (290.4 μm vs. 194.0 μm, &lt;i&gt;p&lt;/i&gt; &lt; 0.001), thinner CMT (251.2 μm vs 311.1 μm, &lt;i&gt;p&lt;/i&gt; = 0.018), smaller CNV area (2.718 mm&lt;sup&gt;2&lt;/sup&gt; vs. 3.964 mm&lt;sup&gt;2&lt;/sup&gt;, &lt;i&gt;p&lt;/i&gt; = 0.034), and a higher prevalence of type 1 CNV (85.2% vs. 58.8%, &lt;i&gt;p&lt;/i&gt; = 0.011) compared to the non-response group. Multivariate binary logistic regression analysis identified thicker CCT (&lt;i&gt;p&lt;/i&gt; &lt; 0.001, r = 1.016), thinner CMT (&lt;i&gt;p&lt;/i&gt; = 0.014, r = 0.988), smaller CNV area (&lt;i&gt;p&lt;/i&gt; = 0.015, r = 0.662), and type 1 CNV (&lt;i&gt;p&lt;/i&gt; = 0.001, r = 0.061) as factors associated with better anatomical outcomes.Conclusions: Double-dose aflibercept was effective in 64% of patients with refractory nAMD, suggesting it may be considered for those with small CNV areas, thinner CMT, and thicker CCT.

Assessment of retinal blood vessel segmentation using U-Net model: A deep learning approach

Segmentation of retinal blood vessels from fundus images is vital to assist ophthalmologists in diagnosing different eye diseases like Arteriosclerosis, Glaucoma, Diabetic Retinopathy, Hypertension, and Choroidal Neovascularization. Accurate detection and timely treatment of these eye diseases can prevent irreversible impairment of vision. In computer-aided automatic diagnosis, Preprocessing of fundus images is necessary to reduce the uneven retinal image illumination, as well as the undesirable effect arising from the contrast differences between the retinal blood vessels and the background. In this study, the Hessian-based Frangi vesselness filter is proposed to enhance vasculature in fundus images. This approach seeks to extract thin vessels to diminish the intensity disparity between thick and thin vessels. Its accuracy has never, however, been thoroughly evaluated. To verify the effectiveness of the suggested filter for boosting vessel-like structures in the fundus images, an experimental approach is presented in this paper. The ability of the filter to improve vessel-like structures in fundus images is validated, and an experimental technique for evaluating filter performance using the U-Net model is described. Five quantitative performances, namely Accuracy, Recall, Specificity, Precision, and F1 Score measures on the DRIVE, HRF, DIARETDB1, DIARETDB0, CHASEDB1, ORIGA, DRISHTI GS, DRIONS DB, FIRE, and FIOT datasets, were evaluated and quantified in these experiments to validate the efficacy of the proposed filter. The results demonstrated a noteworthy improvement by achieving an Accuracy of 99.79 %, 99.84 %, 99.64 %, 99.72 %, 99.57 %, 99.48 %, 99.77 %, 99.05 %, 99.93 %, and 99.40 % respectively. Empirical evidence supports the advantages of this approach.

A comprehensive review of retinal disease diagnosis and open access datasets: Fundus and OCT images

The rapid advancements in deep learning algorithms and the availability of large, open-access databases of fundus and OCT (optical coherence tomography) images have contributed greatly to advancements in computer-assisted diagnostics and the localization of various disorders affecting the retina. This study offers a comprehensive examination of retinal diseases and various recent applications of deep learning strategies for categorising key retinal conditions, such as diabetic retinopathy, glaucoma, age-related macular degeneration, choroidal neovascularization, retinal detachment, media haze, myopia, and dry eyes. Open-access datasets continue to play a critical role in the advancement of digital health research and innovation within the field of ophthalmology. Thirty open-access databases containing fundus and OCT (optical coherence tomography) pictures, which are often utilised by researchers, were carefully examined in this work. A summary of these datasets was created, which includes the number of images, dataset size, and supplementary items in the dataset, as well as information on eye disease and country of origin. We also discussed challenges and limitations of novel deep learning models. Finally, in conclusion, we discussed some important insights and provided directions for future research opportunities.

Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice.

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex-mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.

Non-exudative choroidal and macular neovascularizations: An overview.

Non-exudative choroidal and/or macular neovascularizations (NV) represent nowadays a common finding in different retinal disorders. The introduction of non-invasive techniques such as structural optical coherence tomography (OCT) and OCT angiography (OCTA) allowed for easy detection and follow-up of non-exudative NVs. Recognized as a distinct entity, these lesions demonstrate a high variability in terms of pathophysiology, morphology, and prognostic implications. In the absence of a consensus regarding correct classification of subtypes of non-exudative NVs, accurate management through strict follow-up strategies and prompt treatment is required. In this review we offer a comprehensive overview of the non-exudative NV spectrum in various retinal diseases aiming to provide a deeper insight into this clinical entity.

Factors Affecting Disease Stability After Intravitreal Brolucizumab Injection for Refractory Neovascular Age-Related Macular Degeneration.

The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12weeks (N = 16) and group 2 with TE ≥ 12weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12weeks. Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8μm; P < 0.05), 4 (224.0 vs. 262.9μm; P < 0.05), and 8weeks (216.8 vs. 331.1μm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12weeks. Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.