Choroidal Neovascularization Size Research Articles

H-151, a Selective STING Inhibitor, Has Potential as a Treatment for Neovascular Age-Related Macular Degeneration.

The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) stimulator of interferon gene (STING) pathway is a crucial cascade in the inflammatory response initiated by the recognition of cytosolic double-stranded DNA (dsDNA). The aim of this study was to evaluate the effect of STING inhibitor in murine choroidal neovascularization (CNV). To investigate whether the cGAS-STING pathway is activated during CNV, CNV was induced using laser photocoagulation in male C57BL/6J mice. The expression of change of cGAS and STING during CNV development was confirmed by Western-blotting. H-151, a potent STING palmitoylation antagonist, was used as a STING inhibitor. H-151 was administered intravitreally immediately after laser induction. To confirm the role of the cGAS-STING pathway in CNV formation, we evaluated CNV size and performed fundus fluorescein angiography. The expression levels of cGAS and STING were significantly upregulated in the RPE-choroid complex after CNV induction, and dsDNA merged with cGAS was observed in CNV lesions. Intravitreal administration of H-151 suppressed CNV development and fluorescent leakage from neovessels. In CNV lesions, the high expression of STING and cGAS was observed in infiltrating F4/80+ macrophages. H-151 administration attenuated downstream signals of the cGAS-STING pathway, including the phosphorylation of nuclear factor-κB, and downregulated the expression of interleukin 1β. These findings support that the inhibition of cGAS-STING pathway treats abnormal ocular angiogenesis.

Oral Metformin Inhibits Choroidal Neovascularization by Modulating the Gut-Retina Axis.

Emerging data indicate that metformin may prevent the development of age-related macular degeneration (AMD). Whereas the underlying mechanisms of metformin's anti-aging properties remain undetermined, one proposed avenue is the gut microbiome. Using the laser-induced choroidal neovascularization (CNV) model, we investigate the effects of oral metformin on CNV, retinal pigment epithelium (RPE)/choroid transcriptome, and gut microbiota. Specific pathogen free (SPF) male mice were treated via daily oral gavage of metformin 300mg/kg or vehicle. Male mice were selected to minimize sex-specific differences to laser induction and response to metformin. Laser-induced CNV size and macrophage/microglial infiltration were assessed by isolectin and Iba1 immunostaining. High-throughput RNA-seq of the RPE/choroid was performed using Illumina. Fecal pellets were analyzed for gut microbiota composition/pathways with 16S rRNA sequencing/shotgun metagenomics, as well as microbial-derived metabolites, including small-chain fatty acids and bile acids. Investigation was repeated in metformin-treated germ-free (GF) mice and antibiotic-treated/GF mice receiving fecal microbiota transplantation (FMT) from metformin-treated SPF mice. Metformin treatment reduced CNV size (P < 0.01) and decreased Iba1+ macrophage/microglial infiltration (P < 0.005). One hundred forty-five differentially expressed genes were identified in the metformin-treated group (P < 0.05) with a downregulation in pro-angiogenic genes Tie1, Pgf, and Gata2. Furthermore, metformin altered the gut microbiome in favor of Bifidobacterium and Akkermansia, with a significant increase in fecal levels of butyrate, succinate, and cholic acid. Metformin did not suppress CNV in GF mice but colonization of microbiome-depleted mice with metformin-derived FMT suppressed CNV. These data suggest that oral metformin suppresses CNV, the hallmark lesion of advanced neovascular AMD, via gut microbiome modulation.

Crocetin inhibits choroidal neovascularization in both in vitro and in vivo models

Choroidal neovascularization (CNV) is the primary pathogenic process underlying wet age-related macular degeneration, leading to severe vision loss. Despite current anti-vascular endothelial growth factor (VEGF) therapies, several limitations persist. Crocetin, a major bioactive constituent of saffron, exhibits multiple pharmacological activities, yet its role and mechanism in CNV remain unclear. Here, we investigated the potential effects of crocetin on CNV using in vitro and in vivo models. In human umbilical vein endothelial cells, crocetin demonstrated inhibition of VEGF-induced cell proliferation, migration, and tube formation in vitro, as assessed by CCK-8 and EdU assays, transwell and scratch assays, and tube formation analysis. Additionally, crocetin suppressed choroidal sprouting in ex vivo experiments. In the human retinal pigment epithelium (RPE) cell line ARPE-19, crocetin attenuated cobalt chloride-induced hypoxic cell injury, as evidenced by CCK-8 assay. As evaluated by quantitative PCR and Western blot assay, it also reduced hypoxia-induced expression of VEGF and hypoxia-inducible factor 1α (HIF-1α), while enhancing zonula occludens-1 expression. In a laser-induced CNV mouse model, intravitreal administration of crocetin significantly reduced CNV size and suppressed elevated expressions of VEGF, HIF-1α, TNFα, IL-1β, and IL-6. Moreover, crocetin treatment attenuated the elevation of phospho-S6 in laser-induced CNV and hypoxia-induced RPE cells, suggesting its potential anti-angiogenic effects through antagonizing the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Our findings indicate that crocetin may hold promise as an effective drug for the prevention and treatment of CNV.

NR4A1 deletion promotes pro-angiogenic polarization of macrophages derived from classical monocytes in a mouse model of neovascular age-related macular degeneration

BackgroundNeovascular age-related macular degeneration causes vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Cx3cr1−/− mice display alterations in non-classical monocytes and microglia with increased CNV size, suggesting that non-classical monocytes may inhibit CNV formation. NR4A1 is a transcription factor that is necessary for maturation of non-classical monocytes from classical monocytes. While Nr4a1−/− mice are deficient in non-classical monocytes, results are confounded by macrophage hyper-activation. Nr4a1se2/se2 mice lack a transcriptional activator, resulting in non-classical monocyte loss without macrophage hyper-activation.Main bodyWe subjected Nr4a1−/− and Nr4a1se2/se2 mice to the laser-induced CNV model and performed multi-parameter flow cytometry. We found that both models lack non-classical monocytes, but only Nr4a1−/− mice displayed increased CNV area. Additionally, CD11c+ macrophages were increased in Nr4a1−/− mice. Single-cell transcriptomic analysis uncovered that CD11c+ macrophages were enriched from Nr4a1−/− mice and expressed a pro-angiogenic transcriptomic profile that was disparate from prior reports of macrophage hyper-activation.ConclusionsThese results suggest that non-classical monocytes are dispensable during CNV, and NR4A1 deficiency results in increased recruitment of pro-angiogenic macrophages.

Therapeutic Benefit of Melatonin in Choroidal Neovascularization During Aging Through the Regulation of Senescent Macrophage/Microglia Polarization.

This study aimed to investigate the age-dependent anti-angiogenic capability of melatonin in choroidal neovascularization (CNV) and to explore the underlying molecular mechanisms. In the present study, a laser-induced CNV model was established in both young (three months of age) and old (18 months of age) mice, and the size of CNV lesions and vascular leakage was detected by morphological and imaging examination. Next, Western blot and immunostaining were used to observe the levels of M2 markers, senescence-related markers, and molecules involved in IL-10/STAT3 pathway. Additionally, colivelin was used to study the effect of IL-10/STAT3 pathway activation on the expression of M2 markers and senescence-related markers by Western blot and immunostaining. Finally, the effects of colivelin on melatonin-induced reduction of CNV size and vascular leakage in mice at different ages were assessed using morphological and imaging examination. Our results revealed that aging promoted M2 macrophage/microglia polarization, and aggravated CNV and vascular leakage. Melatonin significantly inhibited the M2 polarization of senescent macrophage/microglia and reduced the CNV area and vascular leakage. Moreover, melatonin markedly suppressed IL-10/STAT3 pathway activation in the macrophage/microglia of old mice, and STAT3 activator colivelin reversed the suppressive effect of melatonin on M2 polarization of senescent macrophage/microglia and laser-induced CNV in old mice. Our data demonstrated that melatonin significantly prevented the M2 polarization of senescent macrophage/microglia by inhibiting the IL-10/STAT3 pathway, and eventually attenuated senescence-associated CNV. These findings suggested that melatonin could serve as a promising therapeutic agent to treat CNV and other age-related ocular diseases.

Attenuation of Laser-Induced Choroidal Neovascularization by Blockade of Prostaglandin D2 Receptor 2.

The purpose of this study was to investigate the impact of prostaglandin D2 (PGD2) receptor 2 (DP2) on choroidal neovascularization (CNV) formation in mice. Using a laser-induced CNV model, the CNV size of wild-type (WT) mice treated with DP2 antagonist (CAY10471 or OC000459) was compared with that of untreated mice. Vascular endothelial growth factor (VEGF) and MCP-1 levels were also compared between the two groups. Similar experiments were performed comparing DP2 knockout (DP2KO) mice with WT mice (8 and 56 weeks old). The number of infiltrating macrophages to laser spots was also compared between the WT and DP2KO mice. We administered a DP2 antagonist to 15-methyl PGD2 (a DP2 agonist)-stimulated ARPE-19 cells and measured VEGF secretion by enzyme-linked immunosorbent assay. Tube formation assay was performed on human umbilical vein endothelial cells with or without a DP2 antagonist. CNV sizes were significantly smaller in mice treated with CAY10471 or OC000459 than in those treated with vehicle. Similarly, the CNV size of DP2KO mice was significantly smaller than that of WT mice. The number of macrophages at laser spots in DP2KO mice was significantly lower than that in WT mice. The VEGF concentration of lasered DP2KO mice's eyes was significantly lower than that of lasered WT mice' eyes. DP2 antagonist treatment suppressed VEGF secretion in ARPE-19 cells under 15-methyl PGD2 stimulation. The tube formation assay suggested that lumen formation was inhibited by a DP2 antagonist. DP2 blockade attenuated choroidal neovascularization. Drugs targeting DP2 are potentially a novel treatment for age-related macular degeneration.

CD11c+ macrophages are pro-angiogenic and necessary for experimental choroidal neovascularization.

Patients with neovascular AMD (nAMD) suffer vision loss from destructive angiogenesis, termed choroidal neovascularization (CNV). Macrophages are found in CNV lesions from nAMD patients. Additionally, Ccr2-/- mice, which lack classical monocyte-derived macrophages, show reduced CNV size. However, macrophages are highly diverse cells that can perform multiple functions. We performed single-cell RNA-sequencing on immune cells from wildtype and Ccr2-/- eyes to uncover macrophage heterogeneity during the laser-induced CNV mouse model of nAMD. We identified 12 macrophage clusters, including Spp1+ macrophages. Spp1+ macrophages were enriched from wildtype lasered eyes and expressed a pro-angiogenic transcriptome via multiple pathways, including vascular endothelial growth factor signaling, endothelial cell sprouting, cytokine signaling, and fibrosis. Additionally, Spp1+ macrophages expressed the marker CD11c, and CD11c+ macrophages were increased by laser and present in CNV lesions. Finally, CD11c+ macrophage depletion reduced CNV size by 40%. These findings broaden our understanding of ocular macrophage heterogeneity and implicate CD11c+ macrophages as a potential therapeutic target for treatment-resistant nAMD patients.

DCZ19931, a novel multi-targeting kinase inhibitor, inhibits ocular neovascularization

Neovascularization is a prominent cause of irreversible blindness in a variety of ocular diseases. Current therapies for pathological neovascularization are concentrated on the suppression of vascular endothelial growth factors (VEGF). Despite the remarkable efficacy of anti-VEGF drugs, several problems still exist, including ocular complications and drug resistance. Thus, it is still required to design novel drugs for anti-angiogenic treatment. This study aimed to investigate the anti-angiogenic effects of a small molecule multi-target tyrosine kinase inhibitor, DCZ19931, on ocular neovascularization. The results showed that administration of DCZ19931 at the tested concentrations did not cause obvious cytotoxicity and tissue toxicity. DCZ19931 could reduce the size of choroidal neovascularization (CNV) lesions in laser-induced CNV model and suppress ocular neovascularization in oxygen-induced retinopathy (OIR) model. DCZ19931 could suppress VEGF-induced proliferation, migration, and tube formation ability of endothelial cells, exhibiting similar anti-angiogenic effects as Ranibizumab. DCZ19931 could reduce the levels of intercellular cell adhesion molecule-1 (ICAM-1) expression in vivo and in vitro. Network pharmacology prediction and western blots revealed that DCZ19931 exerted its anti-angiogenic effects through the inactivation of ERK1/2-MAPK signaling and p38-MAPK signaling. In conclusion, this study indicates that DCZ19931 is a promising drug for anti-angiogenic therapy for ocular diseases.

GPx4 reduces laser‐induced choroidal neovascularization by inhibiting ferroptosis

AbstractPurpose: To investigate the protective effects of glutathione peroxidase 4 (GPx4) in laser‐Induced age‐related macular degeneration (AMD) animal model.Methods: In this study, Norway brown rats were used to establish a laser‐induced AMD model. To investigate the protective role of GPx4, rats received laser photocoagulation and intravitreal injection of GPx4 (25 μg/eye) or PBS on the same day. The size and vascular leakage of choroidal neovascularization (CNV) were measured on 7 and 14 days after lasing by using OCT and FA. Immunohistochemical staining of the choroidal flat mounts with CD31 were used to assess angiogenesis.Results: Compared with PBS group, intravitreal injection of GPx4 decreased the CNV size of 0.083 ± 0.121, P = 0.07 on day 7 and 0.11 ± 0.135 (p &lt; 0.05) on day 14. By leakage grading, the CNV lesion with pathologically significant leakage (grade 2a and 2b) was reduced in GPx4 group (2%) and increased in PBS group (25.6%) from day 7 to day 14. The immunostaining with CD31 showed smaller lesions in GPx4 group than PBS group.Conclusions: This study showed that GPx4 inhibited CNV formation and providing a novel molecular target against ferroptosis for wet AMD treatment.

Absence of Gut Microbiota Is Associated with RPE/Choroid Transcriptomic Changes Related to Age-Related Macular Degeneration Pathobiology and Decreased Choroidal Neovascularization.

Studies have begun to reveal significant connections between the gut microbiome and various retinal diseases, including age-related macular degeneration (AMD). As critical supporting tissues of the retina, the retinal pigment epithelium (RPE) and underlying choroid play a critical role in retinal homeostasis and degeneration. However, the relationship between the microbiome and RPE/choroid remains poorly understood, particularly in animal models of AMD. In order to better elucidate this role, we performed high-throughput RNA sequencing of RPE/choroid tissue in germ-free (GF) and specific pathogen-free (SPF) mice. Furthermore, utilizing a specialized laser-induced choroidal neovascularization (CNV) model that we developed, we compared CNV size and inflammatory response between GF and SPF mice. After correction of raw data, 660 differentially expressed genes (DEGs) were identified, including those involved in angiogenesis regulation, scavenger and cytokine receptor activity, and inflammatory response—all of which have been implicated in AMD pathogenesis. Among lasered mice, the GF group showed significantly decreased CNV lesion size and microglial infiltration around CNV compared to the SPF group. Together, these findings provide evidence for a potential gut–RPE/choroidal axis as well as a correlation with neovascular features of AMD.

Comparative transcriptome analysis of human and murine choroidal neovascularization identifies fibroblast growth factor inducible-14 as phylogenetically conserved mediator of neovascular age-related macular degeneration.

Visual outcome of patients with neovascular age-related macular degeneration has significantly improved during the last years following the introduction of anti-vascular endothelial growth factor (VEGF) therapy. However, about one third of patients show persistent exudation and decreasing visual acuity despite recurrent anti-VEGF treatment, which implies a role of other, still unknown proangiogenic mediators. The present study applied transcriptional profiling of human and mouse (C57BL/6J wildtype) choroidal neovascularization (CNV) membranes each with reference to healthy control tissue to identify yet unrecognized mediators of CNV formation. Key factors were further investigated by immunohistochemistry as well as by intravitreal inhibition experiments and multiplex protein assays in the laser-induced CNV mouse model. Transcriptional profiles of CNV membranes were characterized by enhanced activation of blood vessel development, cytoskeletal organization, and cytokine production, with angiogenesis and wound healing processes predominating in humans and activation of immune processes in mice. Besides several species-specific factors, 95 phylogenetically conserved CNV-associated genes were detected, among which fibroblast growth factor inducible-14 (FN14), a member of the tumor necrosis factor (TNF) receptor family, was identified as a key player of CNV formation. Blocking the pathway by intravitreal injection of a FN14 decoy receptor modulated the cytokine profile - most notably IL-6 - and led to a significant reduction of CNV size in vivo. This study characterizes the transcriptome of human and mouse CNV membranes in an unprejudiced manner and identifies FN14 as a phylogenetically conserved mediator of CNV formation and a promising new therapeutic target for neovascular AMD. This study was funded by the Helmut Ecker Foundation and the Volker Homann Foundation.

Comparison of Intraocular Cytokine Levels of Choroidal Neovascularization Secondary to Different Retinopathies.

Purpose: To investigate and compare the aqueous concentrations of vascular endothelial growth factor (VEGF) and other inflammatory cytokines in various choroidal neovascularization (CNV) diseases and types.Methods: This observational study included 127 naive eyes with CNV and 43 control eyes with cataracts. Aqueous humor (AH) samples were obtained prior to intravitreal anti-VEGF injection or cataract surgery. Multiple inflammatory cytokines, including VEGF, interleukin (IL) 6, IL-8, IL-10, interferon-inducible protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels, were measured using a multiplex bead assay. The angiogenesis index was defined as the ratio of IP-10 to MCP-1. In addition, the relationship among AH cytokine levels, central macular thickness (CMT), and CNV size on optical coherence tomography angiography (OCTA) was evaluated.Results: Except in the myopic CNV group (P = 0.452), the AH concentration of VEGF was significantly higher in all other CNV groups than in the control group (P < 0.05 for all comparisons). IL-8, IL-10, IP-10, and MCP-1 levels (P < 0.05 for all groups) were significantly higher in all CNV diseases except those with neovascular central serous chorioretinopathy. The angiogenesis index was significantly higher in all CNV diseases (P < 0.05 for all comparisons). The VEGF level may be associated with the size of the CNV on OCTA (p = 0.043).Conclusions: The level of intraocular inflammatory cytokines varied among different CNV diseases and CNV types. Therefore, the angiogenesis index may be a more sensitive indicator of angiogenesis.

Tetrahedral framework nucleic acids-based delivery of microRNA-155 inhibits choroidal neovascularization by regulating the polarization of macrophages

Choroidal neovascularization (CNV) is a common pathological feature of various eye diseases and an important cause of visual impairment in middle-aged and elderly patients. In previous studies, tetrahedral framework nucleic acids (tFNAs) showed good carrier performance. In this experiment, we developed microRNA-155-equipped tFNAs (T-155) and explored its biological effects on CNV. Based on the results of in-vitro experiments, T-155 could regulate macrophages into the antiangiogenic M1 type. Then, we injected T-155 into the vitreous of laser-induced CNV model mice and found that T-155 significantly reduced the size and area of CNV, inhibited blood vessel leakage. In summary, we prove that T-155 could regulate the inflammatory process of CNV by polarizing macrophages, thereby improving the symptoms of CNV. Thus, T-155 might become a new DNA-based drug with great potential for treating CNV.

Immunosenescence in Choroidal Neovascularization (CNV)-Transcriptional Profiling of Naïve and CNV-Associated Retinal Myeloid Cells during Aging.

Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1GFP/+ mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.

Guardians of the eye: new tales about retinal microglia and other ocular macrophages.

Guardians of the eye: new tales about retinal microglia and other ocular macrophages.

Development of Intraretinal Fluid in Neovascular Age-Related Macular Degeneration During Anti–Vascular Endothelial Growth Factor Treatment

To identify the risk factors of intraretinal fluid (IRF) development during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (AMD). Retrospective cohort study. A total of 425 treatment-naïve patients with neovascular AMD who completed 24 months of follow-up were enrolled. All patients were treated with an initial series of 3 monthly loading doses of anti-VEGF injections, followed by further injections as required. Baseline characteristics were evaluated using multivariate modeling to determine the potential risk factors for IRF development. IRF occurred in 40.2% (171/425 eyes) of all participants during the maintenance phase after the loading injections. The development of IRF during follow-up negatively affected visual outcomes regardless of the presence of IRF at baseline. Multivariate analysis showed that larger areas of choroidal neovascularization (odds ratio [OR] 1.360; P < .001), the presence of IRF at baseline (OR 5.469; P < .001), and the presence of fibrovascular pigment epithelial detachment (OR 2.043; P=.022) were associated with an increased risk of IRF during follow-up. Type 1 (OR 2.005; P = .037) and type 2 macular neovascularization (MNV) (OR 2.643; P = .009) were also associated with a higher risk of IRF than aneurysmal type 1 MNV/polypoidal choroidal vasculopathy. The development of IRF during anti-VEGF treatment for neovascular AMD has additional negative effects on visual outcomes regardless of the presence of IRF at baseline. Baseline risk factors, including choroidal neovascularization size, presence of IRF at baseline, presence of fibrovascular pigment epithelial detachment, and MNV subtype may influence the development of IRF during anti-VEGF treatment.

3-year follow-up of half-dose verteporfin photodynamic therapy for central serous chorioretinopathy with OCT-angiography detected choroidal neovascularization

To assess the 3-year outcome of half-dose verteporfin photodynamic therapy (PDT) in central serous chorioretinopathy (CSC) with optical coherence tomography angiography (OCT-A) detected choroidal neovascularization (CNV), we performed a retrospective, interventional study. Patients were divided into 2 groups according to the fluorescein angiography: point source leakage in group 1 and diffuse oozing in group 2. Data were collected from patients including changes of best-corrected visual acuity (BCVA), size of CNV, central macular thickness (CMT), choroidal thickness (CT), reabsorption of subretinal fluid (SRF), sessions of half-dose PDT, and the number of intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF). There was a total of 34 eyes in 32 patients included. The mean sessions of half-dose PDT was 1.50 ± 0.75. The mean number of IVI of anti-VEGF was 1.38 ± 3.34. BCVA improved from 0.38 ± 0.33 to 0.20 ± 0.22 (p < 0.001). Mean CMT was significantly reduced along with reduced CT and increased size of CNV. SRF was totally reabsorbed in 31 eyes. Patients in group 1 had significant less sessions of PDT and better final BCVA. In conclusion, half-dose PDT treatment was effective for CSC with CNV. Patients with diffuse oozing in FA may fare less well with half-dose PDT.

Guanabenz and Clonidine, α2-Adrenergic Receptor Agonists, Inhibit Choroidal Neovascularization.

Neovascular age-related macular degeneration (AMD) with choroidal neovascularization (CNV) is a leading cause of blindness in elderly people. Anti-vascular endothelial growth factor (anti-VEGF)-drugs are used to treat AMD patients; however, some patients are resistant to these therapies. The purpose of this study was to investigate the anti-angiogenic effects of α2-adrenergic agonists, including guanabenz and clonidine. We evaluated the anti-angiogenic effects of α2-adrenergic agonists in human retinal microvascular endothelial cells (HRMECs). A proliferation assay was conducted, and the migration ratio was evaluated. In a laser-induced CNV model, guanabenz and clonidine were delivered via intraperitoneal injection or implantation of an osmotic pump device. Fourteen days following CNV induction, CNV lesion size and fundus fluorescein angiography (FFA) were evaluated. Guanabenz and clonidine inhibited VEGF-induced retinal endothelial cell growth and migration. In the CNV model mice, CNV lesion sizes were reduced by intraperitoneal administration of guanabenz or clonidine. Data, including body weight, systolic blood pressure, and heart rate showed that guanabenz (0.5 and 2.0 mg/kg/day) had little effect on these parameters; conversely, a high dose of clonidine (1.0 mg/kg/day) did affect these parameters. Additionally, clonidine did not affect CNV size, but continuous administration of guanabenz attenuated both CNV size and leakage from neovessels. Our study suggests a key role for α2-adrenergic receptors during CNV formation. Therefore, we suggest that α2-adrenergic receptor agonists may represent novel therapeutic drugs for patients with neovascular AMD.

Intravitreal conbercept for choroidal neovascularisation secondary to pathological myopia in a real\u2010world setting in China

BackgroundTo evaluate the 12-month efficacy and safety of intravitreal conbercept for myopic choroidal neovascularization (CNV).MethodsA retrospective, observational study. Thirty-four eyes of 34 pathologic myopic patients with CNV were treated with intravitreal conbercept (IVC) 0.5 mg with a follow up of 12 months. After the first injection, administration of conbercept followed a pro re nata (PRN) regimen. Outcomes included best corrected visual acuity (BCVA), central retinal thickness (CRT), CNV size, the total number of treatments, and adverse events.ResultsThe mean patient age was 55.88 ± 16.17 years, and the mean eye spherical equivalent was − 8.72 ± 3.75 D. The mean number of IVC over 12 months was 2.12 ± 0.69. Overall, best-corrected visual acuity(BCVA)improved from 0.86 ± 0.33 logMAR at baseline to 0.44 ± 0.32 logMAR at month 12 (p < 0.001), mean improvement of vision was 4.12 ± 2.69 lines. Mean central retinal thickness reduced from 285.9 ± 104.6 µm at baseline to 192.1 ± 97.5 µm at month 12 (p < 0.001). Mean CNV size decreased from 0.52 ± 0.38 mm2 at baseline to 0.31 ± 0.19 mm2 at 12 months (p < 0.05). All the 34 eyes had reduced or stable size of CNV. Thirty-two eyes (94.12 %) showed the absence of CNV leakage at the end of the study period. No severe systemic or ocular adverse events were observed.ConclusionsIntravitreal conbercept 0.5 mg was safe and effective for treatment of myopic CNV over 12 months in a real-world setting.

Characteristics of treatment-naïve quiescent choroidal neovascularization detected by optical coherence tomography angiography in patients with age-related macular degeneration

To determine the characteristics of eyes with treatment-naïve quiescent choroidal neovascularization (CNV) detected by optical coherence tomography angiography (OCTA). Thirty-eight eyes of 37 treatment-naïve consecutive patients (30 men, 7 women, average 69.8 years) were studied. Quiescent CNVs were detected by OCTA (RTVue XR Avanti, Optovue, Fremont, CA) in all eyes. Swept-source OCT (SS-OCT; DRI-OCT, Topcon, Japan) confirmed the absence of exudation. The symptoms, visual acuity, CNV size, and status of the fellow eye were evaluated. Patients were followed longitudinally and the length of follow-up period and development of exudation were recorded for each patient. We also investigated patients' medical records from their referral hospitals in search of prior exudation. All eyes with quiescent CNV were diagnosed at the initial visit with sub-retinal pigment epithelium CNVs, i.e., type 1 CNV, from the OCT and OCTA images. Prior exudation was confirmed in 15 eyes (39.5%) from their medical records of the referral hospitals. Symptoms were present in 18 eyes (47.3%). An exudative CNV was present in 12 of the fellow eyes. Exudation developed in 12 eyes (31.6%) during an average follow-up period of 25.1 months. One-half of the eyes had a prior exudation. The CNV at the baseline in eyes that developed exudation during the follow-up period was larger than eyes without exudation; however, the difference was not significant (0.59±0.47 vs 0.48±0.32 mm2, P = 0.50). Quiescent CNVs will develop exudation in approximately 30% of the eyes during a mean 2-year follow-up period. These findings must be remembered when investigating quiescent CNVs that could not be distinguished from eyes with former active CNV and naturally deactivate CNV.