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Wang S, Li J, Yan Z, Jiang Q, Li K. Intravitreal conbercept for chronic central serous chorioretinopathy with occult CNV: a retrospective clinical study based on multimodal ophthalmic imaging. Front Med (Lausanne) 2025; 12:1550543. [PMID: 40201323 PMCID: PMC11975556 DOI: 10.3389/fmed.2025.1550543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Accepted: 03/13/2025] [Indexed: 04/10/2025] Open
Abstract
Purpose This study aimed to evaluate the therapeutic efficacy and safety of intravitreal conbercept in patients with chronic central serous chorioretinopathy (cCSC) complicated by occult choroidal neovascularization (CNV), and to explore its potential in improving visual function and various ophthalmic parameters. Methods This retrospective, longitudinal, comparative study included 50 patients diagnosed with cCSC and occult CNV. Patients underwent intravitreal conbercept injections and were monitored over a six-month period. Comprehensive ophthalmic evaluation included best-corrected visual acuity (BCVA), central macular thickness (CMT), subretinal fluid (SRF) status, subfoveal choroidal thickness (SFCT), and optical coherence tomography angiography (OCTA). OCTA parameters such as foveal avascular zone (FAZ) area and CNV lesion characteristics were analyzed pre- and post-treatment. Patients were categorized based on changes in CNV lesion size to identify prognostic factors influencing treatment response. Results Significant improvements were observed in mean BCVA from baseline (0.78 ± 0.50 vs. 0.32 ± 0.31, p < 0.01) in all 50 eyes of the patients, except for one eye. Additionally, there were significant improvements in CMT, SRF status, SFCT, FAZ area, and CNV lesion size post-treatment (p < 0.05). Pearson correlation analysis indicated a positive correlation between baseline BCVA and CMT (r = 0.3615, p = 0.0116). Changes in BCVA post-treatment correlated with alterations in CMT, SRF diameter, and CNV lesion size. Patients with a favorable treatment response had significantly lower baseline CMT (312.17 ± 57.39 vs. 428.86 ± 114.54, p < 0.05) and CNV vessel diameter (17.46 ± 2.72 vs. 24.84 ± 4.02, p < 0.01) compared to those with unfavorable responses. Conclusion Intravitreal conbercept injection was found to be safe and effective in improving BCVA and various ophthalmic parameters in patients with cCSC complicated by occult CNV, with no significant adverse effects observed during the study period. Baseline CMT, SRF diameter, CNV lesion size, and mean CNV vessel diameter were identified as valuable indicators for assessing treatment response and prognosis. These findings provide important insights for the clinical management and prognostic evaluation of cCSC patients with occult CNV, highlighting the utility of multimodal imaging in assessing treatment outcomes.
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Affiliation(s)
| | | | | | - Qin Jiang
- Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China
| | - Keran Li
- Department of Ophthalmology, The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China
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Sun Y, Zhang W, Hu B, Sun B, Zhang T, Yu S, Yuan G, Dai R, Fan K, Wang L, Cheng P, An G, An L, Wang F, Chen W, Zhang J, Zhou X, Wang F, Ye J, Huang X, Peng X, Li J, Wu M, Wan G, Zhong J, Ha S, Ke X, Liang J, Qi H, Yin H, Qian T, Qu J, Shi X, Hou J, Miao H, Yao Y, Jin E, Deng X, Zhang J, Shi X, Liu J, Ma J, Liu J, Tao Y, Liu B, Li X, Zhao M. Treat-And-Extend Versus Pro Re Nata Regimen of Intravitreal Conbercept Injection for Neovascular Age-Related Macular Degeneration: Results from COCOA, a Prospective, Open-Label, Multicenter, Randomized Phase IV Clinical Trial. Semin Ophthalmol 2025:1-7. [PMID: 40079155 DOI: 10.1080/08820538.2025.2467853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 02/08/2025] [Accepted: 02/11/2025] [Indexed: 03/14/2025]
Abstract
PURPOSE To evaluate and contrast the effectiveness and safety of two conbercept treatment protocols-a three-dose treat-and-extend (3+T&E) regimen and a three-dose pro re nata (3+PRN) regimen-in Chinese patients diagnosed with neovascular age-related macular degeneration (nAMD). METHODS Eligible patients, who had not undergone anti-VEGF intraocular injections within 3 months prior to enrollment, were randomly assigned to either the 3+T&E or 3+PRN regimen. The 3+T&E group received at least three monthly injections, with subsequent visit intervals extended based on disease activity assessment. The primary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to week 48, using a predefined noninferiority threshold. RESULTS Among 501 participants (249 in 3+T&E, 252 in 3+PRN), approximately half had prior anti-VEGF treatment. At 48 weeks, both regimens showed significant BCVA improvements (+9.9 for 3+PRN, +8.6 for 3+T&E; p = .208), with comparable rates of ≥15-letter gains (32.12% for 3+PRN, 30.77% for 3+T&E; p = .827). The 3+PRN group received fewer injections (mean 6.4 vs. 6.9 in 3+T&E; p = .028) but had shorter intervals between injections (6.93 weeks vs. 7.46 weeks in 3+T&E; p = .010). Drug-related adverse events occurred in 5% of patients, with ocular events evenly distributed and minimal cardiovascular events reported. CONCLUSION Both 3+T&E and 3+PRN conbercept regimens effectively improved visual and anatomical outcomes in Chinese nAMD patients. The 3+T&E regimen was noninferior to 3+PRN in improving BCVA from baseline to week 48. The 3+T&E regimen enabled longer injection intervals while 3+PRN regimen with less injections is more cost-effective while maintaining a comparable safety profile. Treatment plan tailored to an individual patient's situation appears necessary.
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Affiliation(s)
- Yaoyao Sun
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Wenfang Zhang
- Department of Ophthalmology, The Second Hospital of Lanzhou University, Lanzhou, China
| | - Bojie Hu
- Tianjin Medical University Eye Hospital, Tianjin, China
| | - Bin Sun
- Department of Ophthalmology, Shanxi Eye Hospital, Taiyuan, Shanxi, People's Republic of China
| | - Tonghe Zhang
- Department of Retina and Vitreous, The Second People's Hospital of Jinan, Jinan, People's Republic of China
| | - Suqin Yu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai, China
| | - Gongqiang Yuan
- Shandong Eye Hospital, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China
| | - Rongping Dai
- Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Ke Fan
- Henan Eye Institute, Henan Eye Hospital, Henan Branch of National Clinical Research Center for Ocular Diseases, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Lifei Wang
- Department of Ophthalmology, Hebei Eye Hospital, Xingtai, Hebei, China
| | - Pei Cheng
- Department of Ophthalmology, the First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China
| | - Gang An
- Department of Ophthalmology, Jinzhou Central Hospital, Jinzhou, China
| | - Liangbao An
- Department of Ophthalmology, Shenyang He Eye hospital, Shenyang, China
| | - Fang Wang
- Department of Ophthalmology, Shanghai Tenth People's Hospital, Shanghai, China
| | - Weiqi Chen
- Department of Ophthalmology, Xiangguang Chinese University and Shantou International Eye Center, Shantou, China
| | - Jie Zhang
- Department of Ophthalmology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu Province, People's Republic of China
| | - Xiyuan Zhou
- Department of Ophthalmology, The Second Affiliated Hospital of Chongqing University, Chongqing, China
| | - Feng Wang
- Department of Ophthalmology, Second Affiliated Hospital of Xi 'an Jiaotong University, Xi'an, China
| | - Jian Ye
- Department of Ophthalmology, Chinese People's Liberation Army Army Special Medical zh Center, Chongqing, China
| | - Xionggao Huang
- Department of Ophthalmology, Army Specialty Medical Center, Third Military Medical University, Chongqing, China
| | - Xiaoyan Peng
- Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing Tongren Eye Center, Capital Medical University, Haikou, People's Republic of China
| | - Jun Li
- Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, Shandong, China
| | - Miaoqin Wu
- Department of Ophthalmology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Zhejiang, China
| | - Guangming Wan
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jingxiang Zhong
- Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Jieyang, China
| | - Shaoping Ha
- Department of Ophthalmology, Ning Xia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China
| | - Xiao Ke
- Medical Research Center, Chengdu Kanghong Biotechnology Inc, Chengdu, Sichuan, China
| | - Jianhong Liang
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Huijun Qi
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Hong Yin
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Tong Qian
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jinfeng Qu
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Xuan Shi
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jing Hou
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Heng Miao
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Yuou Yao
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Enzhong Jin
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Xun Deng
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jian Zhang
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Xiaoqing Shi
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jun Liu
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jie Ma
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jia Liu
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Ye Tao
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Bin Liu
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Xiaoxin Li
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
| | - Mingwei Zhao
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
- Beijing Key Laboratory of Ocular Disease and Optometry Science, Beijing, China
- College of Optometry, Peking University Health Science Center, Beijing, China
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Li S, Pan J, Xu Y, Dai Z, Fang Q. Exploring the factors influencing the timely intravitreal anti-VEGF treatment in patients with diabetic macular edema: a qualitative interview study using the COM-B model. BMC Health Serv Res 2025; 25:302. [PMID: 39994645 PMCID: PMC11849149 DOI: 10.1186/s12913-025-12379-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 02/05/2025] [Indexed: 02/26/2025] Open
Abstract
PURPOSE To explore the factors influencing the untimely receipt of intravitreal anti-vascular endothelial growth factor (VEGF) injections in patients with diabetic macular edema (DME), based on the capability, opportunity, and motivation-behavior (COM-B) model. DESIGN An exploratory qualitative study was conducted with semi-structured interviews with DME patients who had received at least one injection of anti-VEGF therapy within one year. The COM-B model was utilized to guide both data collection and analysis. RESULTS Themes and subthemes were identified. Psychological capability for timely intravitreal anti-VEGF treatment included lack of relevant knowledge and choice of more convenient treatments. Social opportunity included no mention of intravitreal anti-VEGF therapy and effective doctor-patient communication; physical opportunity included unavailability of anti-VEGF and high treatment costs. Reflective motivation included lack of confidence in the efficacy and unmet expectations; automatic motivation included fear of injections, and fear of blindness. CONCLUSION This study identified the facilitators and barriers that influenced the timely intravitreal anti-VEGF injections, which lays the foundation for the development of future interventions.
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Affiliation(s)
- Shu Li
- Shanghai Jiao Tong University School of Nursing, Shanghai, China
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiani Pan
- Department of Nursing, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Xu
- Department of Nursing, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhengyue Dai
- Shanghai Jiao Tong University School of Nursing, Shanghai, China
| | - Qiong Fang
- Shanghai Jiao Tong University School of Nursing, Shanghai, China.
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Beirão S, Pereira PMR, Fernandes R, Tomé JPC. Photosensitizer formulations in photodynamic therapy of age-related macular degeneration. Eur J Med Chem 2025; 283:117105. [PMID: 39642690 DOI: 10.1016/j.ejmech.2024.117105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 11/22/2024] [Accepted: 11/23/2024] [Indexed: 12/09/2024]
Abstract
Age-related macular degeneration (AMD) is a progressive degenerative disease that leads to visual impairment, predominantly affecting the elderly. Despite significant advancements in treatment, a definitive cure remains elusive. Current therapeutic strategies only slow down disease progression, inhibiting abnormal blood vessels growth, and preserving or improving vision. Among these strategies, photodynamic therapy (PDT) has emerged as a promising treatment, particularly for neovascular form, the most severe form of the disease. Although several photosensitizers (PS) have been developed, only one has received clinical approval for use in AMD. This treatment involves the intravenous administration of a photosensitizing agent that preferentially accumulates in the abnormal blood vessels beneath the macula. Upon activation by targeted laser light, the PS triggers photochemical reactions, leading to vascular occlusion and the reduction of choroidal neovascularization. This review provides a comprehensive overview of both experimental and clinical studies on PDT for AMD, discussing the current state of research, challenges in treatment optimization, and potential future directions to enhance this therapeutic approach.
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Affiliation(s)
- Sandra Beirão
- Centro de Química Estrutural, Institute of Molecular Sciences & Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, nº 1, 1049-001, Lisboa, Portugal; University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; University of Coimbra, Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal
| | - Patrícia M R Pereira
- Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA
| | - Rosa Fernandes
- University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal; University of Coimbra, Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
| | - João P C Tomé
- Centro de Química Estrutural, Institute of Molecular Sciences & Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, nº 1, 1049-001, Lisboa, Portugal.
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Wazan LE, Widhibrata A, Liu GS. Soluble FLT-1 in angiogenesis: pathophysiological roles and therapeutic implications. Angiogenesis 2024; 27:641-661. [PMID: 39207600 DOI: 10.1007/s10456-024-09942-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Accepted: 08/19/2024] [Indexed: 09/04/2024]
Abstract
Fine-tuning angiogenesis, the development of new blood vessels, is essential for maintaining a healthy circulatory and lymphatic system. The small glycoprotein vascular endothelial growth factors (VEGF) are the key mediators in this process, binding to their corresponding membrane-bound VEGF receptors (VEGFRs) to activate angiogenesis signaling pathways. These pathways are crucial throughout human life as they are involved in lymphatic and vascular endothelial cell permeability, migration, proliferation, and survival. Neovascularization, the formation of abnormal blood vessels, occurs when there is a dysregulation of angiogenesis and can result in debilitating disease. Hence, VEGFRs have been widely studied to understand their role in disease-causing angiogenesis. VEGFR1, also known as Fms-like tyrosine kinase-1 (FLT-1), is also found in a soluble form, soluble FLT-1 or sFLT-1, which is known to act as a VEGF neutralizer. It is incorporated into anti-VEGF therapy, designed to treat diseases caused by neovascularization. Here we review the journey of sFLT-1 discovery and delve into the alternative splicing mechanism that creates the soluble receptor, its prevalence in disease states, and its use in current and future potential therapies.
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Affiliation(s)
- Layal Ei Wazan
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia
- Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia
| | - Ariel Widhibrata
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia
| | - Guei-Sheung Liu
- Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Level 7, 32 Gisborne Street, East Melbourne, VIC, 3002, Australia.
- Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, VIC, Australia.
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
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Chen S, Liu Y, Zhang Y, Guo X, Bai T, He K, Zhu Y, Lei Y, Du M, Wang X, Liu Q, Yan H. Bruton's tyrosine kinase inhibition suppresses pathological retinal angiogenesis. Br J Pharmacol 2024. [PMID: 39374939 DOI: 10.1111/bph.17344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2024] [Revised: 06/25/2024] [Accepted: 08/22/2024] [Indexed: 10/09/2024] Open
Abstract
BACKGROUND AND PURPOSE Pathological retinal angiogenesis is a typical manifestation of vision-threatening ocular diseases. Many patients exhibit poor response or resistance to anti-vascular endothelial growth factor (VEGF) agents. Bruton's tyrosine kinase (BTK) controls the proliferation and function of immune cells. Therefore, we examined the anti-inflammatory and anti-angiogenic effects of BTK inhibition on retinal angiogenesis. EXPERIMENTAL APPROACH Retinal neovascularisation and vascular leakage in oxygen-induced retinopathy in C57/BL6J mice were assessed by whole-mount retinal immunofluorescence. PLX5622 was used to deplete microglia and Rag1-knockout mice were used to test the contribution of lymphocytes to the effects of BTK inhibition. The cytokines, activation markers, inflammatory and immune-regulatory activities of retinal microglia/macrophages were detected using qRT-PCR and immunofluorescence. NLRP3 was detected by western blotting, and the effects of BTK inhibition on the co-culture of microglia and human retinal microvascular endothelial cells (HRMECs) were examined. KEY RESULTS BTK inhibition suppressed pathological angiogenesis and vascular leakage, and significantly reduced retinal inflammation, which involved microglia/macrophages but not lymphocytes. BTK inhibition increased anti-inflammatory factors and reduced pro-inflammatory cytokines that resulted from NLRP3 inflammasome activation. BTK inhibition suppressed the inflammatory activity of microglia/macrophages, and acted synergistically with anti-VEGF without retinal toxicity. Moreover, the supernatant of microglia incubated with BTK-inhibitor reduced the proliferation, tube formation and sprouting of HRMECs. CONCLUSION AND IMPLICATIONS BTK inhibition suppressed retinal neovascularisation and vascular leakage by modulating the inflammatory activity of microglia and macrophages. Our study suggests BTK inhibition as a novel and promising approach for alleviating pathological retinal angiogenesis.
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Affiliation(s)
- Siyue Chen
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Yuming Liu
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Yutian Zhang
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Xu Guo
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Tinghui Bai
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Kai He
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Yanfang Zhu
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Yi Lei
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
| | - Mei Du
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
- Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Xiaohong Wang
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
- Department of Pharmacology, Tianjin Key Laboratory of Inflammation Biology, the Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Qiang Liu
- Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hua Yan
- Department of Ophthalmology, Tianjin Medical University General Hospital, Ministry of Education International Joint Laboratory of Ocular Diseases, Tianjin Key Laboratory of Ocular Trauma, Tianjin Institute of Eye Health and Eye Diseases, China-UK "Belt and Road" Ophthalmology Joint Laboratory, Tianjin, China
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Cui M, Su Q, Yip M, McGowan J, Punzo C, Gao G, Tai PWL. The AAV2.7m8 capsid packages a higher degree of heterogeneous vector genomes than AAV2. Gene Ther 2024; 31:489-498. [PMID: 39134629 PMCID: PMC11600122 DOI: 10.1038/s41434-024-00477-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 08/03/2024] [Accepted: 08/06/2024] [Indexed: 09/15/2024]
Abstract
Recombinant adeno-associated virus (rAAV) vectors are currently the only proven vehicles for treating ophthalmological diseases through gene therapy. A wide range of gene therapy programs that target ocular diseases are currently being pursued. Nearly 20 years of research have gone into enhancing the efficacy of targeting retinal tissues and improving transgene delivery to specific cell types. The engineered AAV capsid, AAV2.7m8 is currently among the best capsids for transducing the retina following intravitreal (IVT) injection. However, adverse effects, including intraocular inflammation, have been reported following retinal administration of AAV2.7m8 vectors in clinical trials. Furthermore, we have consistently observed that AAV2.7m8 exhibits low packaging titers irrespective of the vector construct design. In this report, we found that AAV2.7m8 packages vector genomes with a higher degree of heterogeneity than AAV2. We also found that genome-loaded AAV2.7m8 stimulated the infiltration of microglia in mouse retinas following IVT administration, while the response to genome-loaded AAV2 and empty AAV2.7m8 capsids produced much milder responses. This finding suggests that IVT administration of AAV2.7m8 vectors may stimulate retinal immune responses in part because of its penchant to package and deliver non-unit length genomes.
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Affiliation(s)
- Mengtian Cui
- Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA
| | - Qin Su
- Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA
| | - Mitchell Yip
- Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA
| | - Jackson McGowan
- Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA
| | - Claudio Punzo
- Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA
- Department of Ophthalmology and Visual Sciences, UMass Chan Medical School, Worcester, MA, USA
| | - Guangping Gao
- Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA.
- Department of Microbiology, UMass Chan Medical School, Worcester, MA, USA.
| | - Phillip W L Tai
- Horae Gene Therapy Center, UMass Chan Medical School, Worcester, MA, USA.
- Department of Microbiology, UMass Chan Medical School, Worcester, MA, USA.
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8
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Sheth JU, Stewart MW, Narayanan R, Anantharaman G, Chandran K, Lai TYY, Chakravarthy U, Das T. Macular neovascularization. Surv Ophthalmol 2024:S0039-6257(24)00095-X. [PMID: 39222802 DOI: 10.1016/j.survophthal.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/22/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Neovascularization of the macula, a common complication of many chorioretinal diseases such as neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and pathologic myopia, results from increased synthesis of vascular endothelial growth factor (VEGF) by the retinal pigment epithelium and/or Müller cells because of localized ischemia and inflammation. The Consensus on Neovascular AMD Nomenclature (CONAN) study group acknowledged that these vessels may originate from either the choriocapillaris or the retinal microvasculature, prompting them to propose the term 'macular neovascularization' (MNV) to include intraretinal, subretinal, and sub-pigment epithelial neovascularization localized to the macula. MNV frequently appears as a grey-green macular lesion with overlying intraretinal thickening and/or subretinal exudation, causing metamorphopsia, reduced central vision, relative central scotoma, decreased reading speed, and problems with color recognition. Multimodal imaging with optical coherence tomography (OCT), OCT angiography, dye-based angiographies, fundus autofluorescence, and multiwavelength photography help establish the diagnosis and aid in selecting an appropriate treatment. The standard of care for MNV is usually intravitreal anti-vascular endothelial growth factor injections, though thermal laser photocoagulation, verteporfin photodynamic therapy, and vitreoretinal surgery are occasionally used. We discuss the etiology and clinical features of MNV, the role of multimodal imaging in establishing the diagnosis, and the available therapeutic options.
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Affiliation(s)
- Jay U Sheth
- Department of Vitreoretinal Services, Shantilal Shanghvi Eye Institute, Mumbai, India.
| | | | - Raja Narayanan
- Anant Bajaj Retina Institute, Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
| | | | - Kiran Chandran
- Department of Vitreoretinal Services, Giridhar Eye Institute, Cochin, India
| | - Timothy Y Y Lai
- Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong, Hong Kong
| | - Usha Chakravarthy
- Department of Ophthalmology and Vision Science, Queen's University of Belfast, Belfast, United Kingdom
| | - Taraprasad Das
- Department of Vitreoretinal Services, Shantilal Shanghvi Eye Institute, Mumbai, India; Anant Bajaj Retina Institute, Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
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9
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Wang D, Chen Y, Li J, Wu E, Tang T, Singla RK, Shen B, Zhang M. Natural products for the treatment of age-related macular degeneration. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 130:155522. [PMID: 38820665 DOI: 10.1016/j.phymed.2024.155522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Revised: 02/08/2024] [Accepted: 03/07/2024] [Indexed: 06/02/2024]
Abstract
BACKGROUND Age-related macular degeneration (AMD) is a chronic retinal disease that significantly influences the vision of the elderly. PURPOSE There is no effective treatment and prevention method. The pathogenic process behind AMD is complex, including oxidative stress, inflammation, and neovascularization. It has been demonstrated that several natural products can be used to manage AMD, but systematic summaries are lacking. STUDY DESIGN AND METHODS PubMed, Web of Science, and ClinicalTrials.gov were searched using the keywords "Biological Products" AND "Macular Degeneration" for studies published within the last decade until May 2023 to summarize the latest findings on the prevention and treatment of age-related macular degeneration through the herbal medicines and functional foods. RESULTS The eligible studies were screened, and the relevant information about the therapeutic action and mechanism of natural products used to treat AMD was extracted. Our findings demonstrate that natural substances, including retinol, phenols, and other natural products, prevent the development of new blood vessels and protect the retina from oxidative stress in cells and animal models. However, they have barely been examined in clinical studies. CONCLUSION Natural products could be highly prospective candidate drugs used to treat AMD, and further preclinical and clinical research is required to validate it to control the disease.
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Affiliation(s)
- Dongyue Wang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
| | - Yi Chen
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China
| | - Jiakun Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China; Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China
| | - Erman Wu
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China
| | - Tong Tang
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China
| | - Rajeev K Singla
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China; School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab-144411, India.
| | - Bairong Shen
- Joint Laboratory of Artificial Intelligence for Critical Care Medicine, Department of Critical Care Medicine and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, PR China.
| | - Ming Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
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10
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Cheng S, Zhang S, Huang M, Liu Y, Zou X, Chen X, Zhang Z. Treatment of neovascular age-related macular degeneration with anti-vascular endothelial growth factor drugs: progress from mechanisms to clinical applications. Front Med (Lausanne) 2024; 11:1411278. [PMID: 39099595 PMCID: PMC11294244 DOI: 10.3389/fmed.2024.1411278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 07/08/2024] [Indexed: 08/06/2024] Open
Abstract
Neovascular age-related macular degeneration (nARMD) is an important cause of visual impairment and blindness in the elderly, with choroidal neovascularization in the macula as the main pathological feature. The onset of nARMD is closely related to factors including age, oxidative stress, and lipid metabolism. Vascular endothelial growth factor (VEGF) is an important factor contributing to nARMD as well as choroidal neovascularization and retinal leakage formation. At present, anti-VEGF therapy is the only treatment that improves vision and halts disease progression in most patients, making anti-VEGF drugs a landmark development for nARMD treatment. Although intravitreal injection of anti-VEGF drugs has become the first-line treatment for nARMD, this treatment has many shortcomings including repeated injections, poor or no response in some patients, and complications such as retinal fibrosis. As a result, several new anti-VEGF drugs are being developed. This review provides a discussion of these new anti-VEGF drugs for the treatment of nARMD.
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Affiliation(s)
| | | | | | | | | | - Xiaoming Chen
- Department of Ophthalmology, The First Affiliated Hospital of Yangtze University, Jingzhou, China
| | - Zuhai Zhang
- Department of Ophthalmology, The First Affiliated Hospital of Yangtze University, Jingzhou, China
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11
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Kulbay M, Wu KY, Nirwal GK, Bélanger P, Tran SD. The Role of Reactive Oxygen Species in Age-Related Macular Degeneration: A Comprehensive Review of Antioxidant Therapies. Biomedicines 2024; 12:1579. [PMID: 39062152 PMCID: PMC11274723 DOI: 10.3390/biomedicines12071579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/26/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024] Open
Abstract
This review article delves into the intricate roles of reactive oxygen species (ROS) in the pathogenesis of age-related macular degeneration (AMD). It presents a detailed analysis of the oxidative stress mechanisms that contribute to the development and progression of these diseases. The review systematically explores the dual nature of ROS in ocular physiology and pathology, underscoring their essential roles in cellular signaling and detrimental effects when in excess. In the context of AMD, the focus is on the oxidative impairment in the retinal pigment epithelium and Bruch's membrane, culminating in the deterioration of macular health. Central to this review is the evaluation of various antioxidant strategies in the prevention and management of AMD. It encompasses a wide spectrum of antioxidants, ranging from dietary nutrients like vitamins C and E, lutein, and zeaxanthin to pharmacological agents with antioxidative properties. The review also addresses novel therapeutic approaches, including gene therapy and nanotechnology-based delivery systems, aiming to enhance antioxidant defense mechanisms in ocular tissues. The article concludes by synthesizing current research findings, clinical trial data, and meta-analyses to provide evidence-based recommendations. It underscores the need for further research to optimize antioxidant therapies, considering individual patient factors and disease stages. This comprehensive review thus serves as a valuable resource for clinicians, researchers, and healthcare professionals in ophthalmology, offering insights into the potential of antioxidants in mitigating the burden of AMD.
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Affiliation(s)
- Merve Kulbay
- Department of Ophthalmology & Visual Sciences, McGill University, Montréal, QC H4A 3S5, Canada;
| | - Kevin Y. Wu
- Division of Ophthalmology, Department of Surgery, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; (K.Y.W.)
| | - Gurleen K. Nirwal
- Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
| | - Paul Bélanger
- Division of Ophthalmology, Department of Surgery, University of Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; (K.Y.W.)
| | - Simon D. Tran
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3A 1G1, Canada
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12
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Wang D, Wu K, Li X, Chen L, Huang W. Prognostic factors for intravitreal conbercept in the treatment of choroidal neovascularization secondary to pathological myopia. Int Ophthalmol 2024; 44:253. [PMID: 38907787 DOI: 10.1007/s10792-024-03177-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 06/15/2024] [Indexed: 06/24/2024]
Abstract
PURPOSE To identify risk factors influencing visual outcomes in patients with pathological myopia-associated choroidal neovascularization (PM-CNV) following intravitreal injections of conbercept. METHODS A total of 86 eyes from 86 patients received intravitreal conbercept in a 1 + PRN regimen. After the initial injection, patients were followed for 12 months. They were categorized into two groups based on their 12-month visual acuity change: those who achieved greater than a one-line improvement in BCVA (improved group; n = 65) and those who experienced a one-line or lesser improvement or a decrease in BCVA (non-improved group; n = 21). RESULTS Over the 12-month period, the mean BCVA in the improved group significantly improved from 0.82 to 0.41 LogMAR. In the non-improved group, BCVA changed from 1.24 to 1.09 LogMAR. Similarly, the mean CRT decreased from 426.21 μm at baseline to 251.56 μm at 12 months in the improved group, and from 452.47 to 382.45 μm in the non-improved group. Multivariable logistic regression analyses revealed that older age (OR 1.287; 95% CI 1.019-1.625; P = 0.034), poorer baseline BCVA (OR 6.422; 95% CI 1.625-25.384; P = 0.008), the presence of subfoveal CNV (OR 4.817; 95% CI 1.242-18.681; P = 0.023), and organized interlacing patterns of CNV morphology (OR 5.593; 95% CI 1.397-22.392; P = 0.015) emerged as independent risk factors correlated with worsened visual prognosis following intravitreal conbercept injections. CONCLUSIONS Conbercept demonstrates significant efficacy and safety in treating PM-CNV. Key factors influencing visual recovery post-treatment include older age, poorer baseline BCVA, the presence of subfoveal CNV, and organized interlacing patterns of CNV morphology.
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Affiliation(s)
- Dingding Wang
- Ophthalmology Department, Huizhou Municipal Central Hospital, Huizhou, 516000, Guangdong, China.
| | - Kunfang Wu
- Ophthalmology Department, Huizhou Municipal Central Hospital, Huizhou, 516000, Guangdong, China
| | - Xiang Li
- Ophthalmology Department, Huizhou Municipal Central Hospital, Huizhou, 516000, Guangdong, China
| | - Lili Chen
- Ophthalmology Department, Huizhou Municipal Central Hospital, Huizhou, 516000, Guangdong, China
| | - Wangbin Huang
- Ophthalmology Department, Huizhou Municipal Central Hospital, Huizhou, 516000, Guangdong, China
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Xie H, Ju H, Lu J, Wang X, Peng H. Comparative study on the efficacy of Conbercept and Aflibercept in the treatment of neovascular age-related macular degeneration. Sci Rep 2024; 14:11997. [PMID: 38796619 PMCID: PMC11128006 DOI: 10.1038/s41598-024-62536-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/17/2024] [Indexed: 05/28/2024] Open
Abstract
This study compares the effectiveness of Conbercept and Aflibercept in treating neovascular age-related macular degeneration (nAMD). Conducted at the First Affiliated Hospital of Chongqing Medical University's Ophthalmology Department (May 2020-May 2023), this prospective study enrolled 159 nAMD patients. Participants were randomly divided into two groups: one receiving 0.5 mg Conbercept and the other 2 mg Aflibercept intravitreal injections. Over 12 months, the study, employing a Treat-and-Extend (T&E) regimen, assessed Best-Corrected Visual Acuity (BCVA), Central Retinal Thickness (CRT) changes and injection frequency. Of the 159 patients, 137 (149 eyes) completed the study. No significant age difference was found between the groups (P = 0.331). After 12 months, BCVA improved similarly in both groups (Conbercept: 52.8 ± 18.9, Aflibercept: 52.0 ± 19.7 letters; P = 0.820). CRT reduction was also comparable (Conbercept: 246.3 ± 82.8 µm, Aflibercept: 275.9 ± 114.3 µm; P = 0.079). Injection frequencies averaged 6.9 ± 0.7 (Conbercept) and 6.7 ± 0.7 (Aflibercept; P = 0.255). Subtype analysis revealed Type 1 MNV had higher baseline BCVA and lower CRT, with more frequent injections compared to other types. Both Conbercept and Aflibercept are clinically similar in efficacy for nAMD, with the T&E regimen proving therapeutically effective and potentially reducing patient costs. Anti-VEGF treatment efficacy varies across nAMD subtypes, indicating a potential benefit in tailored treatments for specific subtypes.Clinical trial registration number NCT05539235 (Protocol Registration and Results System).
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Affiliation(s)
- Hao Xie
- Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Chongqing, China
- Department of Clinical Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, China
| | - Huan Ju
- Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Chongqing, China
- Department of Clinical Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, China
| | - Jing Lu
- Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Chongqing, China
- Department of Clinical Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, China
| | - Xing Wang
- Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Chongqing, China.
- Department of Clinical Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, China.
| | - Hui Peng
- Department of Ophthalmology, the First Affiliated Hospital of Chongqing Medical University, No.1, Youyi Road, Chongqing, China.
- Department of Clinical Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, China.
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14
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Roshanshad A, Moosavi SA, Arevalo JF. Association of the Complement Factor H Y402H Polymorphism and Response to Anti-Vascular Endothelial Growth Factor Treatment in Age-Related Macular Degeneration: An Updated Meta-Analysis. Ophthalmic Res 2024; 67:358-386. [PMID: 38754401 DOI: 10.1159/000539377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 04/17/2024] [Indexed: 05/18/2024]
Abstract
INTRODUCTION Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to several causes, including genetic factors. We evaluated the effects of Complement Factor H (CFH) rs1061170/Y402H polymorphism on the response to anti-VEGF therapy among AMD patients. METHODS PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were used for a literature search. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated to assess the effects of CFH Y402H polymorphism on the response to anti-VEGF therapy in AMD. I2 was used to present the amount of heterogeneity. We used STATA version 14.0 software. RESULTS Twenty-five papers reporting data for 4,681 patients were included in this study. Better response to anti-VEGF therapy was seen in T over C (OR = 1.25, 95% CI = 1.04-1.50), TT over CC (OR = 1.60, 95% CI = 1.06-2.4), and TT + TC over CC (OR = 1.68, 95% CI = 1.23-2.28) genotypes. There was no significant difference in the three other genetic models (TT vs. TC, TT vs. TC + CC, TC vs. TT + CC). In Asians, no significant difference was observed in all six genetic models. Ranibizumab and bevacizumab had similar efficacy; however, conbercept was more effective in homozygous genotypes. The literature indicated that TT and TC genotypes and T allele were associated with a better functional response, while the CC genotype and C alleles had a better anatomical response. The combination of risk alleles in ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents. CONCLUSION In patients with AMD, the CFH Y402H is a predictor of the response to anti-VEGF agents and should be considered in the treatment plan.
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Affiliation(s)
- Amirhossein Roshanshad
- MPH Department, Shiraz University of Medical Sciences, Shiraz, Iran
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Ali Moosavi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - J Fernando Arevalo
- Retina Division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Kumar A, Ferro Desideri L, Ting MYL, Anguita R. Perspectives on the currently available pharmacotherapy for wet macular degeneration. Expert Opin Pharmacother 2024; 25:755-767. [PMID: 38738427 DOI: 10.1080/14656566.2024.2354921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Accepted: 05/09/2024] [Indexed: 05/14/2024]
Abstract
INTRODUCTION Wet age-related macular degeneration (w-AMD) is a leading cause of visual impairment globally, with its prevalence expected to rise alongside increasing life expectancy. The current standard treatment involves frequent intravitreal injections of anti-VEGF agents, which although revolutionary, pose significant burdens on both patients and healthcare services. AREAS COVERED This review explores current and emerging pharmaceutical treatments for w-AMD, focusing on their pharmacokinetics, pharmacodynamics, efficacy, and safety. Promising developments include extending treatment intervals with newer anti-VEGF agents like brolucizumab and faricimab, biosimilars offering cost-effective options, and exploring innovative drug delivery methods such as subretinal gene therapy. Combination therapies, gene therapies, and novel agents like KSI-301 and OPT-302 show potential for improving treatment outcomes and reducing treatment burden. EXPERT OPINION While current treatments for w-AMD have significantly advanced with the advent of anti-VEGF therapies, their limitations in terms of treatment burden and incomplete responses have spurred research into diverse alternative approaches. These innovative strategies offer hope for improving patient outcomes and reducing healthcare burdens, suggesting a promising future for w-AMD management.
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Affiliation(s)
- Aneeta Kumar
- Royal Free London Hospital NHS Foundation Trust, London, UK
| | - Lorenzo Ferro Desideri
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department for BioMedical Research, University of Bern, Bern, Switzerland
- Bern Photographic Reading Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | | | - Rodrigo Anguita
- Bern Photographic Reading Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
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Sun C, Zhang S, Xu N, Liu K, Wei F, Zhang X, Zhang J, Gao S, Yu Y, Ding X. Topical Ophthalmic Liposomes Dual-Modified with Penetratin and Hyaluronic Acid for the Noninvasive Treatment of Neovascular Age-Related Macular Degeneration. Int J Nanomedicine 2024; 19:1887-1908. [PMID: 38414529 PMCID: PMC10898604 DOI: 10.2147/ijn.s446425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/07/2024] [Indexed: 02/29/2024] Open
Abstract
Introduction Since intrinsic ocular barrier limits the intraocular penetration of therapeutic protein through eye drops, repeated intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are the standard therapy for neovascular age-related macular degeneration (nAMD), which are highly invasive and may cause particular ocular complications, leading to poor patient compliance. Methods Using Penetratin (Pen) as the ocular penetration enhancer and hyaluronic acid (HA) as the retina-targeting ligand, a dual-modified ophthalmic liposome (Penetratin hyaluronic acid-liposome/Conbercept, PenHA-Lip/Conb) eye drop was designed to non-invasively penetrate the ocular barrier and deliver anti-VEGF therapeutic agents to the targeted intraocular tissue. Results PenHA-Lip effectively penetrates the ocular barrier and targets the retinal pigment epithelium via corneal and non-corneal pathways. After a single topical administration of conbercept-loaded PenHA-Lip (PenHA-Lip/Conb), the intraocular concentration of conbercept peaked at 18.74 ± 1.09 ng/mL at 4 h, which is 11.55-fold higher than unmodified conbercept. In a laser-induced choroidal neovascularization (CNV) mouse model, PenHA-Lip/Conb eye drops three times daily for seven days inhibited CNV formation and progression without any significant tissue toxicity and achieved an equivalent effect to a single intravitreal conbercept injection. Conclusion PenHA-Lip efficiently and safely delivered conbercept to the posterior eye segment and may be a promising noninvasive therapeutic option for nAMD.
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Affiliation(s)
- Chen Sun
- Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China
| | - Shuyue Zhang
- Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China
| | - Nan Xu
- Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China
| | - Kun Liu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200040, People's Republic of China
| | - Fang Wei
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200040, People's Republic of China
| | - Xiaoqian Zhang
- Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China
| | - Jigang Zhang
- Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China
| | - Shen Gao
- Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai, 200433, People's Republic of China
| | - Yuan Yu
- Department of Pharmacy, Naval Medical University, Shanghai, 200433, People's Republic of China
| | - Xueying Ding
- Clinical Research Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People's Republic of China
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Pece A, Fossataro F, Maione G, Liuzzi R. Structural and clinical changes in previously treated type 1 macular neovascularization in non-responder AMD eyes switched to brolucizumab. Eur J Ophthalmol 2024; 34:245-251. [PMID: 37150939 DOI: 10.1177/11206721231174491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/09/2023]
Abstract
PURPOSE To examine structural and clinical changes in previously treated type 1 macular neovascularization (MNV) in non-responder age-related macular degeneration (nAMD) eyes switched to brolucizumab. Subretinal hyper-reflective material (SHRM), intraretinal (IRF) and subretinal fluid (SRF) presence, fibrovascular-pigment epithelium detachment (PED) height and central macular thickness (CMT) variation were analyzed using optical coherence tomography (OCT). METHODS In this prospective study all patients underwent a complete ophthalmological evaluation including structural OCT at baseline (T0), one month (T1), three (T2), four (T3) and six months after switching to brolucizumab treatment (T4). Non-responder criterion was the persistence of IRF and SRF. Moreover, CMT and BCVA had shown worsening or no improvement before switching to brolucizumab. Clinical function and structural activity biomarkers were measured at each visit and changes were analyzed. P value <0.05 was considered statistically significant. RESULTS Twenty eyes of twenty patients were enrolled. All the structural variables examined during the follow-up showed significant reductions. Decreases in IRF, SRF and PED were already significant at T1 (p < 0.05). SHRM was significantly reduced at T2 (p < 0.05). Structural biomarkers were absent at T3. At T4, all biomarkers remained stable while SHRM was no longer detectable in 18 patients. Changes in visual acuity from baseline to T4 were not significant. CONCLUSION This short-term experience highlights that brolucizumab might be considered an effective treatment option in nAMD with type 1 MNV, as it can promote a reduction of structural activity biomarkers.
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Affiliation(s)
- Alfredo Pece
- Department of Ophthalmology, Melegnano Hospital, Milan, Italy
| | | | - Giulio Maione
- Department of Ophthalmology, Melegnano Hospital, Milan, Italy
| | - Raffaele Liuzzi
- Institute of Biostructure and Bioimaging, National Research Council of Italy, Napoli, Italy
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Gao L, Song Y, Sun X, Zhang J, Liu Y, Chen Y, Wu Z, Jian Y, Liu X, Lv L, Chen S, Wang YS, Chen N, Ke X, Zhang F. Safety and efficacy of intravitreal injection of conbercept for the treatment of patients with choroidal neovascularization secondary to pathological myopia: Results from the SHINY study. Acta Ophthalmol 2023. [PMID: 38009430 DOI: 10.1111/aos.15810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 11/07/2023] [Indexed: 11/28/2023]
Abstract
PURPOSE To evaluate the safety and efficacy of intravitreal injections of 0.5 mg conbercept in patients with choroidal neovascularization secondary to pathological myopia (pmCNV). METHODS The 177 pmCNV patients were randomly assigned in a 3:1 ratio to receive conbercept or sham injection, respectively. The conbercept group receive conbercept intravitreal injections administered on a pro re nata (PRN) basis after 3 monthly loading doses. The sham group received three consecutive monthly sham injections and then one conbercept injection followed by PRN conbercept intravitreal injections. RESULTS At month 3, the mean BCVA for the two groups were improved by 12.0 letters (conbercept group, from 54.05 letters to 66.05 letters) and 0.6 letters (sham group, from 49.77 letters to 50.33 letters), respectively (p < 0.001). The mean central retinal thickness (CRT) at month 3 in the two groups decreased 62.0 μm (conbercept group, from 348.90 μm to 286.18 μm) and 4.4 μm (sham group, from 347.86 μm to 343.47 μm) (p < 0.001). At month 9, the mean BCVA improved by 13.3 letters in the conbercept group and 11.3 letters in the sham group. The mean CRT decreased 73.6 μm in the conbercept group and 55.9 μm in the sham group (p < 0.001). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival haemorrhage and increased intraocular pressure. CONCLUSION Intravitreal injections of 0.5 mg conbercept provided improvement in visual and anatomical outcomes in pmCNV patients with low rates of ocular and nonocular safety events.
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Affiliation(s)
- Liqin Gao
- Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China
| | - Yanping Song
- Department of Ophthalmology, Chinese PLA General Hospital of Central Theater Command, Wuhan, China
| | - Xiaodong Sun
- Department of Ophthalmology, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai General Hospital, Shanghai, China
| | - Junjun Zhang
- Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, China
| | - Yuling Liu
- Department of Ophthalmology, Peking University Third Hospital, Beijing, China
| | - Youxin Chen
- Department of Ophthalmology, Peking Union Medical College Hospital, Beijing, China
| | - Zhifeng Wu
- Department of Ophthalmology, Wuxi No.2 People's Hospital, Nanjing Medical University, Wuxi, China
| | - Ye Jian
- Department of Ophthalmology, Daping Hospital and Institute of Surgery Research, Army Medical University, Chongqing, China
| | - Xiaoling Liu
- National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China
| | - Lin Lv
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China
| | - Shaojun Chen
- Department of Ophthalmology, He Eye Specialist Hospital, Chongqing, China
| | - Yu-Sheng Wang
- Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Nan Chen
- Department of Ophthalmology, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, China
| | - Xiao Ke
- Medical Research Center, Chengdu Kanghong Biotechnology Inc, Chengdu, China
| | - Feng Zhang
- Department of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, China
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Ke X, Jiang H, Li Q, Luo S, Qin Y, Li J, Xie Q, Zheng Q. Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration. Mol Ther 2023; 31:3308-3321. [PMID: 37752703 PMCID: PMC10638048 DOI: 10.1016/j.ymthe.2023.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/31/2023] [Accepted: 09/23/2023] [Indexed: 09/28/2023] Open
Abstract
The upregulation of vascular endothelial growth factor (VEGF) is strongly associated with the development of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD). Currently, the standard treatment for nAMD involves frequent intravitreal injections of anti-VEGF agents, which inhibit the growth of new blood vessels and prevent leakage. However, this treatment regimen places a significant burden on patients, their families, and healthcare providers due to the need for repeated visits to the clinic for injections. Gene therapy, which enables the sustained expression of anti-VEGF proteins after a single injection, can dramatically reduce the treatment burden. KH631 is a recombinant adeno-associated virus 8 vector that encodes a human VEGF receptor fusion protein, and it is being developed as a long-term treatment for nAMD. In preclinical studies using non-human primates, subretinal administration of KH631 at a low dose of 3 × 108 vg/eye resulted in remarkable retention of the transgene product in the retina and prevented the formation and progression of grade IV CNV lesions. Furthermore, sustained transgene expression was observed for more than 96 weeks. These findings suggest that a single subretinal injection of KH631 has the potential to offer a one-time, low-dose treatment for nAMD patients.
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Affiliation(s)
- Xiao Ke
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China; Chengdu Kanghong Pharmaceuticals Group Co Ltd, Chengdu, China
| | - Hao Jiang
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China; Therapeutic Proteins Key Laboratory of Sichuan Province, Chengdu, China
| | - Qingwei Li
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China; Therapeutic Proteins Key Laboratory of Sichuan Province, Chengdu, China
| | - Shuang Luo
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China; Therapeutic Proteins Key Laboratory of Sichuan Province, Chengdu, China
| | - Yingfei Qin
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China
| | - Jing Li
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China
| | - Qing Xie
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China; Therapeutic Proteins Key Laboratory of Sichuan Province, Chengdu, China
| | - Qiang Zheng
- Chengdu Origen Biotechnology Co., Ltd, Chengdu, China; Chengdu Kanghong Pharmaceuticals Group Co Ltd, Chengdu, China; Therapeutic Proteins Key Laboratory of Sichuan Province, Chengdu, China.
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20
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Guo H, Li W, Nie Z, Zhang X, Jiao M, Bai S, Duan N, Li X, Hu B. Microinvasive pars plana vitrectomy combined with internal limiting membrane peeling versus anti-VEGF intravitreal injection for treatment-naïve diabetic macular edema (VVV-DME study): study protocol for a randomized controlled trial. Trials 2023; 24:685. [PMID: 37875997 PMCID: PMC10594908 DOI: 10.1186/s13063-023-07735-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 10/16/2023] [Indexed: 10/26/2023] Open
Abstract
BACKGROUND Diabetic macular edema (DME) is the main cause of vision loss in diabetic patients. Currently, anti-vascular endothelial growth factor (VEGF) intravitreal injection stands as the first-line therapy for DME. However, some patients exhibit insufficient response to anti-VEGF agents and often require multiple injections, imposing psychological and economic burdens. While microinvasive pars plana vitrectomy (PPV) has been shown to be safe and effective in treating refractory DME, scant research has explored its application to treatment-naïve DME. The purpose of this study is to determine whether early PPV combined with internal limiting membrane (ILM) peeling can lessen the therapeutic burden of DME patients, prevent vision loss, and maintain long-term stabilization of diabetic retinopathy. METHODS This is a single-center, prospective, parallel-group, non-inferiority randomized controlled trial involving 102 DME participants. Participants will be randomly assigned to either the study group (PPV combined with ILM peeling) or the control group (conbercept intravitreal injection (IVC)) at a 1:1 ratio, with a scheduled follow-up at 12 months post-operation. Comparative analysis of results between the two groups will be conducted at months 1, 3, 6, and 12 after the intervention. The primary outcomes involve evaluating the changes in central subfield thickness (CST) and best corrected visual acuity (BCVA). The secondary outcomes include assessment of optical coherence tomography (OCT) and OCT angiography (OCTA) biomarkers, re-treatment and adverse events rates, diabetic retinopathy (DR) development, cost-effectiveness analysis, and vision-related quality of life (VRQL). DISCUSSION Some patients do not respond well to anti-VEGF drugs and repeated intravitreal injections increase the treatment burden for patients. The VVV study aims to explore whether PPV combined with ILM peeling could become an initial treatment option for treatment-naïve DME patients. TRIAL REGISTRATION ClinicalTrials.gov NCT05728476. Registered on 15 February 2023.
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Affiliation(s)
- Haoxin Guo
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Wenbo Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Zetong Nie
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Xiang Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Mingfei Jiao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Siqiong Bai
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Naxin Duan
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Xiaorong Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Bojie Hu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China.
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Song L, Luo C, Zheng Y, Sha X. Clinical outcomes of different regimens of intravitreal Conbercept for the treatment of choroidal neovascularization secondary to pathological myopia. Int Ophthalmol 2023; 43:3445-3452. [PMID: 37561252 DOI: 10.1007/s10792-023-02655-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Accepted: 02/19/2023] [Indexed: 08/11/2023]
Abstract
PURPOSE To assess the clinical outcomes of two intravitreal injection regimens of Conbercept used to treat choroidal neovascularization secondary to pathological myopia (PM-CNV). METHODS A total of 72 eyes of 72 patients were treated: 39 eyes received a single injection followed by treatment pro re nata (1 + PRN); 33 eyes first received 3 consecutive monthly injections (3 + PRN) then followed by PRN. After initial injection, patients were followed up for 12 months. RESULTS The mean age of 72 patients was 45.3 ± 5.1 years, with the mean diopter of -10.62 ± 3.24D. The best corrected visual acuity (BCVA) was 0.86 ± 0.23 LogMAR with 1 + PRN and 0.90 ± 0.19 LogMAR with 3 + PRN at baseline (P = 0.422), 0.36 ± 0.07 and 0.33 ± 0.05 LogMAR at month 3 (P = 0.026); and 0.33 ± 0.03 and 0.32 ± 0.02 LogMAR at month 12 (P = 0.096). The central retinal thickness (CRT) was 333.5 ± 22.7 μm with 1 + PRN and 341.2 ± 20.9 μm with 3 + PRN at baseline (P = 0.139), 281.53 ± 10.28 and 273.15 ± 13.24 μm at month 3 (P = 0.004); 266.83 ± 8.14 and 264.91 ± 9.27 μm at month 12 (P = 0.350). The number of injections in the 1 + PRN group was significantly lower than that observed in the 3 + PRN group (2.15 ± 1.06 versus 3.36 ± 0.74; P < 0.001). During the follow-up, no serious ocular complications and adverse reactions related to Conbercept and injections occurred. CONCLUSIONS Both injection regimens resulted in similar visual outcomes in PM-CNV patients. The 1 + PRN regimen had fewer injections and might be more suitable in this patient population.
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Affiliation(s)
- Li Song
- Ophthalmology Department, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
| | - Chunyun Luo
- Ophthalmology Department, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Yu Zheng
- Ophthalmology Department, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
| | - Xiangyin Sha
- Ophthalmology Department, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China.
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Sun Z, Li S, Wang W, Zhang M, Liu W, Ji Z, Wang J, Sun Y, Liu M, Liu C. Treatment of filtration bleb dysfunction after glaucoma surgery by needle revision of filtration bleb combined with conbercept. Medicine (Baltimore) 2023; 102:e34591. [PMID: 37653819 PMCID: PMC10470796 DOI: 10.1097/md.0000000000034591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2023] [Revised: 07/07/2023] [Accepted: 07/13/2023] [Indexed: 09/02/2023] Open
Abstract
Filtration surgery (Trabeculectomy) is the main treatment for glaucoma. The scarring of the filtration bleb and obstruction of the outflow of aqueous humor through the filtration channel are the main reasons of the surgery failure. The objective of this study was to determine the clinical efficacy of needle revision of filtration blebs combined with subconjunctival injection of conbercept on the functional bleb formation in glaucoma patients with eye pressure out of control after trabeculectomy. A total of 48 eyes with poor filtration bleb function after trabeculectomy for glaucoma were treated with needle revision of filtration bleb combined with subconjunctival injection of conbercept. After the treatment, the patients were followed up for 3 months during which visual acuity, intraocular pressure, slit lamp and ultrasound biomicroscope examinations were performed. Intraoperative and postoperative complications were recorded. The visual acuity and intraocular pressure were significantly improved after the needle revision of filtration blebs. Among the 48 eyes, 39 eyes still had functional blebs at the end of the follow-up period, and filtration blebs failed in 9 eyes 2 to 8 weeks after the removal of the needle. The survival rate of filtration blebs at 3 months after needle revision was (79.06 ± 3.42%), and 81.25% (39/48) of the eyes showed good formation rate of functional bleb at the last follow-up. Three months after needle revision, there was local scar formation in some filtration blebs. Part of the filtration blebs showed mild thickening of the local subconjunctival tissue, and the filtration bleb was slightly raised and diffuse, showing a multi-cavity and thin-walled shape in some blebs. Ultrasound biomicroscopy examination showed relative structural manifestations. Subconjunctival hemorrhage occurred in 43 patients during and after the operation. Low intraocular pressure occurred in 8 patients with the lowest pressure of 5 mm Hg. Choroidal edema was observed in 3 patients. Five patients had intraoperative conjunctival hemorrhage in the anterior chamber, and hyphema occurred. All complications were self-limited and resolved without surgical intervention. Needle revision of filtration bleb combined with anti-VEGF drugs is a safe and effective method for the treatment of filtration bleb dysfunction after surgery of glaucoma.
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Affiliation(s)
- Zhonghua Sun
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
| | - Shanshan Li
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
| | - Wen Wang
- Operating Room, The Fourth People’s Hospital of Jinan, Jinan, China
| | - Miaomiao Zhang
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
| | - Wei Liu
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
| | - Zhen Ji
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
| | - Jianrong Wang
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
| | - Yan Sun
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
| | - Mingkun Liu
- Department of Clinical Medicine, Shandong First Medical University, Jinan, China
| | - Cuijuan Liu
- Department of Ophthalmology, The Jinan Second People’s Hospital, Jinan, China
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23
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Zhan HQ, Zhou JL, Zhang J, Wu D, Gu CY. Conbercept combined with laser photocoagulation in the treatment of diabetic macular edema and its influence on intraocular cytokines. World J Diabetes 2023; 14:1271-1279. [PMID: 37664482 PMCID: PMC10473943 DOI: 10.4239/wjd.v14.i8.1271] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/19/2023] [Accepted: 07/14/2023] [Indexed: 08/11/2023] Open
Abstract
BACKGROUND The prevalence of diabetes mellitus (DM) in China is high, and the base is broad. Diabetic retinopathy (DR) is a critical condition affecting the life and health of a nation and its economic development. DR is a common complication of DM. AIM To investigate the efficacy of laser photocoagulation combined with intravitreal injection of conbercept for treating macular edema. METHODS Overall, 130 patients with diabetic macular edema (DME) hospitalized in The Third People's Hospital of Changzhou from January 2019 to June 2022 were retrospectively included. According to the treatment plan, 130 patients with DME were categorized into an observation and a control group, with 65 patients in each group. The control group received laser photocoagulation, and the observation group received laser photocoagulation with intravitreal injection of conbercept. Observe changes in vision, cytokines in the eye and so on. RESULTS The total efficacy rate in the observation group (93.85%) was higher than that in the control group (78.46%) (P < 0.05). In both groups, the best corrected visual acuity correction effect improved after treatment, and the observation group was superior to the control group (P < 0.05). Retinal thickness and central macular thickness improved after treatment, and the observation group was superior to the control group (P < 0.05). The levels of vascular endothelial growth factor, interleukin-6, soluble intercellular adhesion molecule-1, and basic fibroblast growth factor in both groups improved after treatment, and the observation group was superior to the control group (P < 0.05). CONCLUSION In patients with macular edema, combining laser photocoagulation and intravitreal injections of conbercept for DME is a more effective and safer strategy to improve vision, and lower intraocular cytokine levels.
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Affiliation(s)
- Hui-Qin Zhan
- Department of Ophthalmology, The Third People’s Hospital of Changzhou, Changzhou 213001, Jiangsu Province, China
| | - Ji-Lin Zhou
- Department of Ophthalmology, The Third People’s Hospital of Changzhou, Changzhou 213001, Jiangsu Province, China
| | - Jun Zhang
- Department of Ophthalmology, The Third People’s Hospital of Changzhou, Changzhou 213001, Jiangsu Province, China
| | - De Wu
- Department of Ophthalmology, The Third People’s Hospital of Changzhou, Changzhou 213001, Jiangsu Province, China
| | - Chun-Yan Gu
- Department of Ophthalmology, The Third People’s Hospital of Changzhou, Changzhou 213001, Jiangsu Province, China
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24
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Wang X, Wang P. Spectral-domain optical coherence tomography combined with electroretinography in the assessment of conbercept for neovascular age-related macular degeneration: a preliminary study. Front Neurosci 2023; 17:1179421. [PMID: 37179553 PMCID: PMC10166866 DOI: 10.3389/fnins.2023.1179421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 03/31/2023] [Indexed: 05/15/2023] Open
Abstract
Objective To observe the effect of three consecutive intravitreal injections of conbercept in the treatment of neovascular age-related macular degeneration (nAMD), to investigate the correlation between retinal anatomy and retinal function by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), to evaluate the short-term clinical efficacy of conbercept in the treatment of nAMD, and to explore the value of ERG as a predictor of treatment efficacy. Method A retrospective investigation was conducted on 36 patients (36 eyes) treated with intravitreal injections of conbercept at 0.5 mg a month for three consecutive courses. Data collected included the best corrected visual acuity (BCVA), central retinal thickness (CRT), retinal pigment epithelium (RPE) elevation volume in 1 mm-diameter (1RV), 3 mm-diameter (3RV), and 6 mm-diameter circles around the fovea (6RV), amplitude density and latency of the P1 wave in the multifocal electroretinography (mf-ERG) R1 ring and amplitude and latency in full-field electroretinography (ff-ERG) at baseline and monthly. The paired t test was used to compare the difference between pre- and posttreatment. Pearson correlation analysis was used to analyze the correlation between macular retinal structure and function. The difference was significant when p < 0.05. Results At 12 weeks, the BCVA, CRT, 1RV, 3RV, 6RV, the P1 wave amplitude density of the mf-ERG R1 ring and the ff-ERG amplitude parameters were all significantly improved (p < 0.001). The BCVA in logMAR was positively correlated with CRT; 1RV, 3RV, and 6RV were negatively correlated with the amplitude density and latency of the mf-ERG R1 ring P1 wave. There were no severe ocular or systemic complications during the follow-up period. Conclusion Conbercept is useful for the short-term treatment of nAMD. It can safely improve the visual acuity of affected eyes and restore the structure and function of the retina. ERG could serve as an objective indicator of function for evaluating the efficacy of and determining the need for retreatment during nAMD treatment.
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Affiliation(s)
| | - Peng Wang
- Chongqing Key Laboratory of Ophthalmology, Department of Ophthalmology, Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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25
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Nhàn NTT, Maidana DE, Yamada KH. Ocular Delivery of Therapeutic Agents by Cell-Penetrating Peptides. Cells 2023; 12:1071. [PMID: 37048144 PMCID: PMC10093283 DOI: 10.3390/cells12071071] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 03/28/2023] [Accepted: 03/30/2023] [Indexed: 04/05/2023] Open
Abstract
Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural and physiological complexity of the eye. CPPs may be tailored to overcome this challenge, facilitating cellular uptake and delivery to the targeted area. Retinal diseases occur at the posterior pole of the eye; thus, intravitreal injections are needed to deliver drugs at an effective concentration in situ. However, frequent injections have risks of causing vision-threatening complications. Recent investigations have focused on developing long-acting drugs and drug delivery systems to reduce the frequency of injections. In fact, conjugation with CPP could deliver FDA-approved drugs to the back of the eye, as seen by topical application in animal models. This review summarizes recent advances in CPPs, protein/peptide-based drugs for eye diseases, and the use of CPPs for drug delivery based on systematic searches in PubMed and clinical trials. We highlight targeted therapies and explore the potential of CPPs and peptide-based drugs for eye diseases.
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Affiliation(s)
- Nguyễn Thị Thanh Nhàn
- Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA;
| | - Daniel E. Maidana
- Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, IL 60612, USA;
- Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago, IL 60612, USA
| | - Kaori H. Yamada
- Department of Pharmacology and Regenerative Medicine, University of Illinois College of Medicine, Chicago, IL 60612, USA;
- Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, Chicago, IL 60612, USA;
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26
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Li H, Niu Y, Rong A, Bi Y, Xu W, Cui H. Effect of Adjunctive Intravitreal Conbercept Injection at the End of 25G Vitrectomy on Severe Proliferative Diabetic Retinopathy: 6-Month Outcomes of a Randomised Controlled Trial. Ophthalmol Ther 2023; 12:1173-1180. [PMID: 36752956 PMCID: PMC10011228 DOI: 10.1007/s40123-023-00664-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 01/20/2023] [Indexed: 02/09/2023] Open
Abstract
INTRODUCTION This study aimed to evaluate the effect of pre-operative versus pre-operative plus post-operative intravitreal conbercept (IVC) injection on severe proliferative diabetic retinopathy (PDR). METHODS This was a prospective, comparative and randomised study. A total of 84 patients who underwent vitrectomy for severe PDR were included in this study. Patients were randomly divided into control (41 eyes) and experiment (43 eyes) groups. Patients in the experiment group received adjunctive pre-operative and post-operative IVC injection, whereas patients in the control group only received pre-operative IVC injection. The incidence of post-operative vitreous haemorrhage (POVH), best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were determined. RESULTS The incidence of early POVH was significantly different between the two groups, but no significant difference was observed between groups at 3 and 6 months. In the experiment group, the BCVA was significantly improved 1 month after surgery when compared with the control group (p 0.019). There was no marked difference in the mean post-operative BCVA at 3 and 6 months between groups (p 0.063 and 0.082). CRT was significantly lower in the experiment group than in the control group at 1 and 3 months after surgery (p 0.037 and 0.041), but there was no significant difference at 6 months (p 0.894). CONCLUSION Additional IVC injected at the end of surgery improves the POVH and BCVA at the early stage after surgery in severe PDR, but this benefit is absent at 6 months. Further studies are needed to investigate the effect of IVC at the end of vitrectomy. TRIAL REGISTRATION chictr.org.cn identifier: ChiCTR2200060735. Retrospectively registered, register date: 9 June 2022.
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Affiliation(s)
- Houshuo Li
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Shanghai, 200065, China
| | - Yunli Niu
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Shanghai, 200065, China
| | - Ao Rong
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Shanghai, 200065, China
| | - Yanlong Bi
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Shanghai, 200065, China
| | - Wei Xu
- Department of Ophthalmology, Tongji Hospital, School of Medicine, Tongji University, 389 Xincun Road, Shanghai, 200065, China
| | - Hongping Cui
- Department of Ophthalmology, Shanghai East Hospital, School of Medicine, Tongji University, 150 Jimo Road, Shanghai, 200120, China.
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Shu Y, Ye F, Liu H, Wei J, Sun X. Predictive value of pigment epithelial detachment markers for visual acuity outcomes in neovascular age-related macular degeneration. BMC Ophthalmol 2023; 23:83. [PMID: 36869310 PMCID: PMC9983272 DOI: 10.1186/s12886-023-02797-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 01/27/2023] [Indexed: 03/05/2023] Open
Abstract
BACKGROUND To determine the predictive value of quantitative morphological parameters for pigment epithelial detachment (PED) of neovascular age-related macular degeneration (nAMD) patients. METHODS One eye from each of 159 patients with nAMD were studied. Polypoidal choroidal vasculopathy (PCV) group included 77 eyes, and non-PCV group 82. Patients received conbercept 0.05 ml (0.5 mg) in a 3 + ProReNata (PRN) treatment regimen. Correlations between retinal morphologic parameters at baseline and best-corrected visual acuity (BCVA) gain at 3 or 12 months after treatment (structure-function correlations) were assessed. Optical coherence tomography (OCT) scans were used to assess retinal morphologic features including intraretinal cystoid fluid (IRC), subretinal fluid (SRF), PED or PED type (PEDT), and vitreomacular adhesion (VMA). Greatest height (PEDH) and width of PED (PEDW), and volume of PED (PEDV) at baseline were also measured. RESULTS For non-PCV group, BCVA gain from 3 or 12 months after treatment was negatively correlated with PEDV at baseline (r = -0.329, -0.312, P = 0.027, 0.037). BCVA gain at 12 months after treatment was negatively correlated with PEDW at baseline (r = -0.305, P = 0.044). For PCV group, there were no correlations with PEDV, PEDH, PEDW, and PEDT in BCVA gain between baseline and 3 or 12 months after treatment (P > 0.05). SRF, IRC, VMA at baseline did not correlate with short-term and long-term BCVA gain in patients with nAMD (P > 0.05). CONCLUSION For patients with non-PCV, PEDV at baseline was negatively correlated with short-term and long-term BCVA gain, and PEDW was negatively correlated with long-term BCVA gain. On the contrary, quantitative morphological parameters for PED at baseline had no correlation with BCVA gain in patients with PCV.
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Affiliation(s)
- Yiyang Shu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Fuxiang Ye
- Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haiyun Liu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China. .,National Clinical Research Center for Eye Diseases, Shanghai, China. .,Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai, China. .,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China. .,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.
| | - Jin Wei
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Xiaodong Sun
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.,National Clinical Research Center for Eye Diseases, Shanghai, China.,Shanghai Key Laboratory of Ocular Fundus Disease, Shanghai, China.,Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.,Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
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Gautam M, Gupta R, Singh P, Verma V, Verma S, Mittal P, Karkhur S, Sampath A, Mohan RR, Sharma B. Intracameral Drug Delivery: A Review of Agents, Indications, and Outcomes. J Ocul Pharmacol Ther 2023; 39:102-116. [PMID: 36757304 DOI: 10.1089/jop.2022.0144] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023] Open
Abstract
An intracameral (IC) injection directly delivers the drug into the anterior chamber of the eye. This targeted drug delivery technique overcomes the ocular barriers and offers a high therapeutic concentration of medication at the desired site and consequently better clinical outcomes. IC drug delivery is a safe and effective modality with many advantages over topical delivery. These include excellent bioavailability, reduced systemic risk, and minimal ocular toxicity. Agents delivered via IC injection have shown promising results against infection, inflammation, ocular hypertension, and neovascularization. Current literature shows that IC antibiotics, including cefuroxime, vancomycin, and moxifloxacin, are routinely used for prophylaxis of endophthalmitis. Other drugs available for IC use are steroids, anesthetics, mydriatics, miotics, antivascular endothelial growth factor, antiglaucoma, and alkylating agents. Introduction of sustained-release devices containing dexamethasone or Bimatoprost in anterior chamber via IC route has the potential in treating ocular inflammation and raised intraocular pressure. The complications such as hemorrhagic occlusive retinal vasculitis and toxic anterior segment syndrome have been documented with IC prophylaxis but are rare. In this review, we provide an overview of available IC drugs, their pharmacokinetics, the spectrum of activity, dosage and preparation, prophylactic and therapeutic usage, clinical efficacy, and safety profiles.
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Affiliation(s)
- Megha Gautam
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Rituka Gupta
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Priti Singh
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Vidhya Verma
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Sunil Verma
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Parul Mittal
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Samendra Karkhur
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Ananyan Sampath
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
| | - Rajiv R Mohan
- Department of Ophthalmology and Molecular Medicine, University of Missouri, Columbia, Missouri, USA
| | - Bhavana Sharma
- Department of Ophthalmology, All India Institute of Medical Sciences, Bhopal, India
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Radke NV, Mohamed S, Brown RB, Ibrahim I, Chhablani J, Amin SV, Tsang CW, Brelen ME, Raichand NS, Fang D, Zhang S, Dai H, Chen GLJ, Cheung CMG, Hariprasad SM, Das T, Lam DSC. Review on the Safety and Efficacy of Brolucizumab for Neovascular Age-Related Macular Degeneration From Major Studies and Real-World Data. Asia Pac J Ophthalmol (Phila) 2023; 12:168-183. [PMID: 36971706 DOI: 10.1097/apo.0000000000000602] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 02/01/2023] [Indexed: 03/29/2023] Open
Abstract
Frequent antivascular endothelial growth factor injections in neovascular age-related macular degeneration (nAMD) often lead to poor compliance and suboptimal outcomes. A longer-acting agent has been a pressing unmet need until recently. Brolucizumab, an antivascular endothelial growth factor agent, is a single-chain antibody fragment approved by the US Food and Drug Administration (FDA) on October 8, 2019, for treating nAMD. It delivers more molecules at equivalent volumes of aflibercept, thus achieving a longer-lasting effect. We reviewed literature published in English between January 2016 and October 2022 from MEDLINE, PubMed, Cochrane database, Embase, and Google scholar using the keywords: "Brolucizumab, real-world data, intraocular inflammation (IOI), safety, and efficacy". Brolucizumab showed reduced injection frequency, better anatomic outcomes, and noninferior vision gains compared with aflibercept in HAWK and HARRIER studies. However, post hoc studies on brolucizumab revealed a higher-than-expected incidence of IOI, leading to the early termination of 3 studies: MERLIN, RAPTOR, and RAVEN for nAMD, branch retinal vein occlusion, and central retinal vein occlusion, respectively. Contrastingly real-world data showed encouraging outcomes in terms of fewer IOI cases. The subsequent amendment of the treatment protocol resulted in reduced IOI. Thereafter US FDA approved its use in diabetic macular edema on June 1, 2022. Based on major studies and real-world data, this review shows that brolucizumab is effective for treating naive and refractory nAMD. The risk of IOI is acceptable and manageable, but proper preinjection screening and high-vigilance care of IOI are needed. More studies are warranted to evaluate further the incidence, best prevention, and treatment measures for IOI.
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Affiliation(s)
- Nishant V Radke
- The C-MER Drugs and Medical Devices Research and Development Center, Shenzhen, China
- The C-MER (Shenzhen), Dennis Lam Eye Hospital, Shenzhen, Guangdong, China
| | - Shaheeda Mohamed
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Ilyana Ibrahim
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
| | - Jay Chhablani
- University of Pittsburgh, UPMC Eye Centre, Pittsburgh, PA
| | - Shivam V Amin
- Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL
| | - Chi-Wai Tsang
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Marten E Brelen
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Dong Fang
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
| | - Shaochong Zhang
- Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, China
| | - Hong Dai
- Department of Ophthalmology, Beijing Hospital, Beijing, China
| | - Guy Li Jia Chen
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | | | - Seenu M Hariprasad
- Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL
| | - Taraprasad Das
- Anant Bajaj Retina Institue-Srimati Kanuri Santhamma Centre for Vitreoretinal Disease, L V Prasad Eye Institute, Hyderabad, Telangana, India
| | - Dennis S C Lam
- The C-MER Drugs and Medical Devices Research and Development Center, Shenzhen, China
- The C-MER International Eye Research Center of The Chinese University of Hong Kong (Shenzhen), Shenzhen, China
- The C-MER Dennis Lam and Partners Eye Center, C-MER International Eye Care Group, Hong Kong, China
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Zhu W, Hao Y, Yuan Z, Huang C, Liu J, Ma Y. Long-Term Outcomes of High-Dose Conbercept Treatment for Myopic Choroidal Neovascularization and Idiopathic Choroidal Neovascularization. Ophthalmic Res 2023; 66:636-644. [PMID: 36746135 DOI: 10.1159/000529342] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 01/09/2023] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The aim of the study was to report 2-year outcomes of intravitreal injection of high-dose conbercept (1 mg 2 + PRN scheme) for subjects with myopic choroidal neovascularization (mCNV) and idiopathic choroidal neovascularization (iCNV) by optical coherence tomography angiography follow-up. METHODS A total of 38 subjects (38 eyes) were enrolled in this retrospective study, which were divided into group A (mCNV, 20 subjects, 20 eyes) and group B (iCNV, 18 subjects, 18 eyes). All subjects received 1.0 mg of conbercept intravitreally at diagnosis and again 35 days later. Additional conbercept injection was administered upon findings of decreased best-corrected visual acuity (BCVA); metamorphosis aggravation, macular hemorrhage, or edema; increased central retinal thickness (CRT); or leakage observed by fluorescein angiography. The BCVA, CRT, and CNV areas of the two groups were evaluated at baseline and at 1, 2, 4, 6, 12, and 24 months after surgery. RESULTS The BCVA of group A improved from 0.31 ± 0.16 logMAR at baseline to 0.12 ± 0.03 logMAR at the final follow-up (p < 0.001), while in group B the corresponding improvement was from 0.33 ± 0.16 logMAR at baseline to 0.12 ± 0.03 logMAR at the final follow-up (p < 0.001). Visual acuity improved in 17 subjects in group A and 15 in group B, while it remained stable in 3 subjects in each of groups A and B. CRT decreased from 311.83 ± 30.95 μm in group A and 351.17 ± 37.09 μm in group B preoperation to 229.56 ± 5.75 μm and 227.67 ± 4.98 μm at 24-month follow-up, respectively (p < 0.001 in groups A and B). Metamorphopsia was improved in subjects in groups A and B. CNV had disappeared in the two groups at the last postoperative visit. The BCVA, CRT, and CNV areas showed no statistical differences between the two groups at 6-, 12-, and 24-month follow-up (p > 0.05). CONCLUSION Intravitreal injection of conbercept (1 mg 2 + PRN scheme) is effective for treating patients with mCNV or iCNV, which can improve and stabilize vision as well as dramatically alleviate metamorphopsia.
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Affiliation(s)
- Wei Zhu
- Department of Ophthalmology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China,
| | - Yanlei Hao
- Department of Ophthalmology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Zhongfang Yuan
- Department of Ophthalmology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Chunmei Huang
- Department of Ophthalmology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jiehui Liu
- Department of Ophthalmology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yan Ma
- Department of Ophthalmology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
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THE REPORTING QUALITY OF NONINFERIORITY TRIALS USING INTRAVITREAL VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS. Retina 2023; 43:243-253. [PMID: 36695797 DOI: 10.1097/iae.0000000000003649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 10/06/2022] [Indexed: 01/26/2023]
Abstract
PURPOSE Noninferiority trials (NIFTs) are widely used to study intravitreal vascular endothelial growth factor inhibitors for the treatment of ocular diseases. Thus, this trial design deserves greater attention. We aimed to comprehensively assess the methodological and reporting quality of NIFTs in the field of neovascular ocular diseases. METHODS We identified NIFTs using antivascular endothelial growth factor agents published before February 2020 from PubMed and Web of Science. Two independent authors extracted and double-checked predefined elements related to the quality of design and reporting. The characteristics and reporting of NIFTs were described with frequencies and percentages. We summarized important factors that were potentially biased the results of NIFTs and provided point-to-point recommendations. RESULTS In total, 34 studies involving 15,190 subjects and 51 pairs of noninferiority comparisons were identified. Areas of concern that could potentially affect the qualities of NIFTs included the absence of justification for the selection of noninferiority margins (61.8%), the use of unusually wide noninferiority margins (26.5%), the lack of outcome confirmation provided by the intention-to-treat and per-protocol analyses (64.7%), the presence of postrandomization exclusions >10% (52.9%), and not declaring the compensatory benefits (35.3%). Moreover, industry-sponsored NIFTs were more likely to draw positive results (P = 0.036). CONCLUSION NIFTs of antivascular endothelial growth factor therapies commonly achieved noninferiority of the tested intervention. However, the methodologies and reporting limitations may affect the confidence of the results. Thus, more awareness must be created among investigators for better adherence to guidelines and recommendations while designing, conducting, and reporting on NIFTs.
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Sun J, Nie H, Pan P, Jiang Q, Liu C, Wang M, Deng Y, Yan B. Combined Anti-Angiogenic and Anti-Inflammatory Nanoformulation for Effective Treatment of Ocular Vascular Diseases. Int J Nanomedicine 2023; 18:437-453. [PMID: 36718193 PMCID: PMC9884055 DOI: 10.2147/ijn.s387428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 01/16/2023] [Indexed: 01/24/2023] Open
Abstract
Background Ocular vascular diseases are the major causes of visual impairment, which are characterized by retinal vascular dysfunction and robust inflammatory responses. Traditional anti-angiogenic or anti-inflammatory drugs still have limitations due to the short-acting effects. To improve the anti-angiogenic or anti-inflammatory efficiency, a dual-drug nanocomposite formulation was proposed for combined anti-angiogenic and anti-inflammatory treatment of ocular vascular diseases. Methods CBC-MCC@hMSN(SM) complex nanoformulation was prepared by integrating conbercept (CBC, an anti-angiogenic drug) and MCC950 (MCC, an inhibitor of inflammation) into the surface-modified hollow mesoporous silica nanoparticles (hMSN(SM)). CBC-MCC@hMSN(SM) complex nanoformulation was then characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, zeta potentials, and nitrogen adsorption-desorption measurement. CBC and MCC release profile, cytotoxicity, tissue toxicity, anti-angiogenic effects, and anti-inflammatory effects of CBC-MCC@hMSN(SM) were estimated using the in vitro and in vivo experiments. Results CBC-MCC@hMSN(SM) complex had no obvious cytotoxicity and tissue toxicity and did not cause a detectable ocular inflammatory responses. CBC-MCC@hMSN(SM) complex was more effective than free CBC or MCC in suppressing endothelial angiogenic effects and inflammatory responses in vitro. A single intraocular injection of CBC-MCC@hMSN(SM) complex potently suppressed diabetes-induced retinal vascular dysfunction, choroidal neovascularization, and inflammatory responses for up to 6 months. Conclusion Combined CBC and MCC nanoformulation provides a promising strategy for sustained suppression of pathological angiogenesis and inflammatory responses to improve the treatment outcomes of ocular vascular diseases.
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Affiliation(s)
- Jianguo Sun
- Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People’s Republic of China
| | - Huiling Nie
- The Affiliated Eye Hospital and The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, People’s Republic of China
| | - Panpan Pan
- Department of Chemistry, Fudan University, Shanghai, People’s Republic of China
| | - Qin Jiang
- The Affiliated Eye Hospital and The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, People’s Republic of China
| | - Chang Liu
- Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People’s Republic of China
| | - Min Wang
- Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People’s Republic of China
| | - Yonghui Deng
- Department of Chemistry, Fudan University, Shanghai, People’s Republic of China,Department of Gastroenterology and Hepatology, Zhongshan Hospital, Institute of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China,Correspondence: Yonghui Deng; Biao Yan, Email ;
| | - Biao Yan
- Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, People’s Republic of China
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Li S, Guo L, Zhou P, Tang J, Wang Z, Zhang L, Zhao M, Qu J. Comparison of efficacy and safety of intravitreal ranibizumab and conbercept before vitrectomy in Chinese proliferative diabetic retinopathy patients: a prospective randomized controlled trial. EYE AND VISION (LONDON, ENGLAND) 2022; 9:44. [PMID: 36451252 PMCID: PMC9714121 DOI: 10.1186/s40662-022-00316-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Accepted: 11/05/2022] [Indexed: 12/05/2022]
Abstract
BACKGROUND To compare the efficacy and safety of preoperative intravitreal injections of ranibizumab and conbercept in Chinese proliferative diabetic retinopathy (PDR) patients. METHODS This prospective randomized controlled trial enrolled 90 eyes of 80 patients with PDR. Forty-four eyes of 40 patients that received intravitreal ranibizumab (IVR) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVR group. Forty-six eyes of 40 patients that received intravitreal conbercept (IVC) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVC group. Intraoperative and postoperative indices were assessed for further comparison between the two groups. RESULTS There were no statistically significant differences in all surgery indices, including intraoperative indices (surgery time, P = 0.225; intraoperative bleeding, P = 0.808; endodiathermy use, P = 0.693; incidence of iatrogenic retinal breaks, P = 0.740; relaxing retinotomy, P = 0.682; retinal reattachment, P = 0.682 and silicone oil tamponade, P = 0.814) and postoperative indices (postoperative vitreous hemorrhage (VH), P = 0.808; neovascular glaucoma (NVG), P = 0.964; recurrent retinal detachment, P = 0.531; postoperative fibrovascular proliferation progression, P = 0.682 and reoperation, P = 0.955) between the two groups. There were no statistically significant differences in best-corrected visual acuity (BCVA) at each follow-up visit (P = 0.939, 0.669, 0.741 and 0.717, respectively) or in central retinal thickness (CRT) (P = 0.976, 0.699, 0.551 and 0.686, respectively). As for safety profile, both groups had no ocular or system adverse events during the observation period. CONCLUSIONS IVR and IVC as a pretreatment of vitrectomy had similar efficacy and safety profile for Chinese PDR patients. TRIAL REGISTRATION Registered at ClinicalTrials.gov ( NCT05414149 ).
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Affiliation(s)
- Siying Li
- grid.411634.50000 0004 0632 4559Department of Ophthalmology, Peking University People’s Hospital, Beijing, China ,Eye Diseases and Optometry Institute, Beijing, China ,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China ,grid.11135.370000 0001 2256 9319College of Optometry, Peking University Health Science Center, Beijing, China
| | - Lili Guo
- grid.411634.50000 0004 0632 4559Department of Ophthalmology, Peking University People’s Hospital, Beijing, China ,Eye Diseases and Optometry Institute, Beijing, China ,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China ,grid.11135.370000 0001 2256 9319College of Optometry, Peking University Health Science Center, Beijing, China
| | - Pingping Zhou
- grid.452866.bDepartment of Ophthalmology, The First Affiliated Hospital of Jiamusi University, Jiamusi City, Heilongjiang Province China
| | - Jiyang Tang
- grid.411634.50000 0004 0632 4559Department of Ophthalmology, Peking University People’s Hospital, Beijing, China ,Eye Diseases and Optometry Institute, Beijing, China ,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China ,grid.11135.370000 0001 2256 9319College of Optometry, Peking University Health Science Center, Beijing, China
| | - Zongyi Wang
- grid.411634.50000 0004 0632 4559Department of Ophthalmology, Peking University People’s Hospital, Beijing, China ,Eye Diseases and Optometry Institute, Beijing, China ,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China ,grid.11135.370000 0001 2256 9319College of Optometry, Peking University Health Science Center, Beijing, China
| | - Linqi Zhang
- grid.411634.50000 0004 0632 4559Department of Ophthalmology, Peking University People’s Hospital, Beijing, China ,Eye Diseases and Optometry Institute, Beijing, China ,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China ,grid.11135.370000 0001 2256 9319College of Optometry, Peking University Health Science Center, Beijing, China
| | - Mingwei Zhao
- grid.411634.50000 0004 0632 4559Department of Ophthalmology, Peking University People’s Hospital, Beijing, China ,Eye Diseases and Optometry Institute, Beijing, China ,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China ,grid.11135.370000 0001 2256 9319College of Optometry, Peking University Health Science Center, Beijing, China
| | - Jinfeng Qu
- grid.411634.50000 0004 0632 4559Department of Ophthalmology, Peking University People’s Hospital, Beijing, China ,Eye Diseases and Optometry Institute, Beijing, China ,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, China ,grid.11135.370000 0001 2256 9319College of Optometry, Peking University Health Science Center, Beijing, China
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Li X, Qu J, Su G, Yu S, Zhang Y, Sadda SV. The comparison of two different strategies of intravitreal conbercept for polypoidal choroidal vasculopathy in Chinese patients results from a 48-week randomized phase 4 study: STAR study. Acta Ophthalmol 2022; 101:e327-e337. [PMID: 36259089 DOI: 10.1111/aos.15272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 09/21/2022] [Accepted: 09/30/2022] [Indexed: 11/29/2022]
Abstract
PURPOSE To compare a treat-and-extend (TAE) strategy with a fixed dosing regimen of intravitreal conbercept (IVC) for the management of treatment-naïve polypoidal choroidal vasculopathy (PCV) patients. METHODS 249 patients with treatment-naïve PCV were randomized 1:1 to fixed dosing regimen with injections every 12 weeks (3 + Q12W) group or treat-and-extend regimen(3 + TAE) group. Patients received 3 monthly intravitreal injections of 0.5 mg conbercept as loading dose in both groups. The 3 + Q12W patients were monitored monthly and received mandated injections every 12 weeks; the 3 + TAE patients were monitored and treated monthly until the resolution of exudative disease activity; the interval between visits was then individualized according to study protocol. Visual and anatomical outcomes were compared between the two groups. RESULTS At 48 weeks, there was no significant difference between the 3 + Q12W group and 3 + TAE group in mean BCVA improvement (p = 0.421), mean changes in central retinal thickness (CRT) (p = 0.818), maximum retinal thickness (MRT) (p = 0.448), pigment epithelial detachment (PED) height (p = 0.221), PED volume (p = 0.076), branching vascular network (BVN) area (p = 0.615), polypoidal lesion number (p = 0.701), polypoidal lesion area (p = 0.424), rates of patients who avoided vision loss of ≥15 ETDRS letters (p = 0.397) or complete polypoidal lesion regression rate (43.8% vs. 41.8%, p = 0.814). The 3 + Q12W group had more decreased retinal haemorrhage area (p = 0.014) and fewer mean numbers of injections comparing with 3 + TAE group (6.6 vs. 9.4, p < 0.001). Mean maximum extension interval between injections after loading injections was 9.6 ± 2.0 weeks for 3 + TAE group, with 27.8% of patients achieving an extension interval of 12 weeks and 61.1% patients 8 weeks or more. CONCLUSIONS Both 3 + Q12W and 3 + TAE regimens of IVC could result in improvement in visual and anatomical outcomes in PCV patients.
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Affiliation(s)
- Xiaoxin Li
- Xiamen Eye Center of Xiamen University, Xiamen, China.,Department of Ophthalmology, Peking University People's Hospital, Beijing, China
| | - Jinfeng Qu
- Department of Ophthalmology, Peking University People's Hospital, Beijing, China
| | - Guanfang Su
- Department of Ophthalmology, The Second Hospital of Jilin University, Jilin, China
| | - Suqin Yu
- Department of Ophthalmology, Shanghai General Hospital of Shanghai Jiao Tong University, Shanghai, China
| | - Yongjin Zhang
- Department of Ophthalmology & Visual Science, Eye and ENT Hospital of Fudan University, Shanghai, China
| | - Srini Vas Sadda
- Doheny Image Reading Center, Doheny Eye Institute, University of California Los Angeles (UCLA) Affiliated, Los Angeles, California, USA.,Department of Ophthalmology, David Geffen School of Medicine at University of California Los Angeles, California, Los Angeles, USA
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Toutounchian S, Ahmadbeigi N, Mansouri V. Retinal and Choroidal Neovascularization Antivascular Endothelial Growth Factor Treatments: The Role of Gene Therapy. J Ocul Pharmacol Ther 2022; 38:529-548. [PMID: 36125411 DOI: 10.1089/jop.2022.0022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Neovascularization in ocular vessels causes a major disease burden. The most common causes of choroidal neovascularization (CNV) are age-related macular degeneration and diabetic retinopathy, which are the leading causes of irreversible vision loss in the adult population. Vascular endothelial growth factor (VEGF) is critical for the formation of new vessels and is the main regulator in ocular angiogenesis and vascular permeability through its receptors. Laser therapy and antiangiogenic factors have been used for CNV treatment. Bevacizumab, ranibizumab, and aflibercept are commonly used anti-VEGF agents; however, high costs and the need for frequent intraocular injections are major drawbacks of anti-VEGF drugs. Gene therapy, given the potency of one-time treatment and no need for frequent injections offers the real possibility of such a lasting treatment, with fewer adverse effects and higher patient quality of life. Herein, we reviewed the role of gene therapy in the CNV treatment. In addition, we discuss the advantages and challenges of current treatments compared with gene therapy.
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Affiliation(s)
- Samaneh Toutounchian
- Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Naser Ahmadbeigi
- Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Vahid Mansouri
- Gene Therapy Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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Shen Y, Wang H, Xu X, Chen C, Zhu S, Cheng L, Fang J, Liu K, Xu X. Metabolomics study of treatment response to conbercept of patients with neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Front Pharmacol 2022; 13:991879. [PMID: 36199690 PMCID: PMC9527301 DOI: 10.3389/fphar.2022.991879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 08/31/2022] [Indexed: 11/23/2022] Open
Abstract
Background: Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are major causes of blindness in aged people. 30% of the patients show unsatisfactory response to anti-vascular endothelial growth factor (anti-VEGF) drugs. This study aims to investigate the relationship between serum metabolome and treatment response to anti-VEGF therapy. Methods: A prospective longitudinal study was conducted between March 2017 and April 2019 in 13 clinical sites in China. The discovery group were enrolled from Shanghai General Hospital. The validation group consisted of patients from the other 12 sites. Participants received at least one intravitreal injection of 0.5 mg anti-VEGF drug, conbercept, and were divided into two groups - responders and non-responders. Serum samples of both groups were processed for UHPLC-MS/MS analysis. We constructed principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models to investigate the metabolic differences between two groups using SIMCA-P. Area under curve (AUC) was calculated to screen the biomarkers to predict treatment response. Metabolites sub-classes and enriched pathways were obtained using MetaboAnalyst5.0. Results: 219 eyes from 219 patients (nAMD = 126; PCV = 93) were enrolled. A total of 248 metabolites were detected. PCA and PLS-DA models of the discovery group demonstrated that the metabolic profiles of responders and non-responders clearly differed. Eighty-five differential metabolites were identified, including sub-classes of diacylglycerophosphocholines, lysophosphatidylcholine (LPC), fatty acids, phosphocholine, etc. Responders and non-responders differed most significantly in metabolism of LPC (p = 7.16 × 10^-19) and diacylglycerophosphocholine (p = 6.96 × 10^-17). LPC 18:0 exhibited the highest AUC, which is 0.896 with 95% confidence internal between 0.833 and 0.949, to discriminate responders. The predictive accuracy of LPC 18:0 was 72.4% in the validation group. Conclusions: This study suggests that differential metabolites may be useful for guiding treatment options for nAMD and PCV. Metabolism of LPC and diacylglycerophosphocholine were found to affect response to conbercept treatment. LPC 18:0 was a potential biomarker to discriminate responders from non-responders.
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Affiliation(s)
- Yinchen Shen
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Hanying Wang
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Xiaoyin Xu
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Chong Chen
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Shaopin Zhu
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Lu Cheng
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
| | - Junwei Fang
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
- *Correspondence: Kun Liu, ; Junwei Fang,
| | - Kun Liu
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
- *Correspondence: Kun Liu, ; Junwei Fang,
| | - Xun Xu
- Department of Ophthalmology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- National Clinical Research Center for Eye Diseases, Shanghai, China
- Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
- Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China
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Tolentino MJ, Tolentino AJ. Investigational drugs in clinical trials for macular degeneration. Expert Opin Investig Drugs 2022; 31:1067-1085. [PMID: 35962560 DOI: 10.1080/13543784.2022.2113375] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Intravitreal anti-vascular endothelial growth factor (VEGF) injections for exudative age-related macular degeneration (eAMD) are effective and safe but require frequent injections and have nonresponding patients. Geographic atrophy/dry AMD (gaAMD) remains an unmet medical need . New therapies are needed to address this leading cause of blindness in the increasing aged population. AREAS COVERED This paper reviews the pathogenesis of macular degeneration, current and failed therapeutics, therapies undergoing clinical trials and a rationale for why certain AMD therapies may succeed or fail . EXPERT OPINION VEGF- inhibitors reduce both vascular leakage and neovascularization. Experimental therapies that only address neovascularization or leakage will unlikely supplant anti-VEGF therapies. The most promising future therapies for eAMD, are those that target, more potently inhibit and have a more sustained effect on the VEGF pathway such as KSI-301, RGX-314, CLS-AX, EYEP-1901, OTX-TKI. GaAMD is a phenotype of phagocytic retinal cell loss. Inhibiting phagocytic activity of retinal microglial/macrophages at the border of GA and reducing complement derived activators of microglial/macrophage is the most promising strategy. Complement inhibitors (Pegcetacoplan and Avacincaptad pegol) will likely obtain FDA approval but will serve to pave the way for combined complement and direct phagocytic inhibitors such as AVD-104.
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Affiliation(s)
- Michael J Tolentino
- University of Central Florida, FL, USA.,Blue Ocean Clinical Research, Lakeland, FL, USA.,Aviceda Therapeutics, Cambridge, MA, USA
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Karasavvidou EM, Tranos P, Panos GD. Brolucizumab for the Treatment of Degenerative Macular Conditions: A Review of Clinical Studies. Drug Des Devel Ther 2022; 16:2659-2680. [PMID: 35971530 PMCID: PMC9375562 DOI: 10.2147/dddt.s378450] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 08/04/2022] [Indexed: 12/13/2022] Open
Abstract
Age-related macular degeneration (AMD), diabetic retinopathy and retinal vein occlusion represent some of the commonest degenerative conditions that lead to severe vision impairment in the developed countries. The gold standard treatment of complications associated with these conditions is the intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents. Brolucizumab is a newly developed, humanised, single-chain fragment of a monoclonal antibody binding all VEGF-A isoforms, which was recently approved for the treatment of neovascular AMD. Intravitreal brolucizumab promises to reduce treatment burden for nAMD patients by achieving comparable therapeutic outcomes with fewer clinic visits. Promising also appears its use for the treatment of more challenging maculopathies like diabetic macular oedema (DMO). The aim of this review is to describe the special pharmacological properties of brolucizumab and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of degenerative macular disorders.
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Affiliation(s)
| | | | - Georgios D Panos
- Department of Ophthalmology, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK
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Prognostic Factor Study of Macular Edema Recurrence in Retinal Vein Occlusion after Conbercept Treatment: A Post Hoc Analysis of the FALCON Study. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:3616044. [PMID: 35936375 PMCID: PMC9355755 DOI: 10.1155/2022/3616044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Revised: 07/04/2022] [Accepted: 07/13/2022] [Indexed: 11/18/2022]
Abstract
Objective The study was aimed at exploring the potential predictive factors associated with the recurrence of macular edema (ME) secondary to vein occlusion (RVO) after intravitreal antivascular endothelial growth factor (VEGF) loading treatment in the FALCON study. Methods This is a post hoc analysis of 30 patients with central RVO and 30 patients with branch RVO. All patients received a monthly administration of intravitreal conbercept during the 3-month loading phase and pro re nata (PRN) treatment during the 6-month follow-up period. Based on the recurrence of ME at the first follow-up visit, patients were classified into the recurrence group or nonrecurrence group. The primary endpoint was to explore the risk factors for recurrence among baseline characteristics, fluorescein angiography (FA) patterns, and optical coherence tomography (OCT). Results In general, 38 patients (64.4%) experienced ME recurrence at the first follow-up visit (3 months), regardless of disease type (p = 0.32). Significant improvements in VA were noted in both the nonrecurrence and recurrence groups (p < 0.001), however, without significant between-group differences (p = 0.1). A significant reduction in CRT in both groups (p < 0.001) was identified, and patients without recurrence showed a greater reduction in CRT compared with those with recurrence (p < 0.001). In addition, logistic regression analyses indicated the corrections of ME recurrence with baseline macular volume and the disruption of the outer limiting membrane at the fovea. Conclusion This study suggested that OCT parameters, including baseline macular volume and outer limiting membrane disruption, and reduction in CRT after loading therapy were more predictive of ME recurrence than FA patterns or visual changes following conbercept loading therapy.
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Jia H, Lu B, Yuan Y, Yuan F, Li L, Song Y, Rong A, Zhou M, Wang F, Sun X. A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration. Front Med (Lausanne) 2022; 9:852519. [PMID: 35795633 PMCID: PMC9251380 DOI: 10.3389/fmed.2022.852519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
Purpose To compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD). Methods This was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of -5 letters. Results From July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, -1.169 letters; 95% confidence interval (CI): -6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups. Conclusion These findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months. Clinical Trial Registration ClinicalTrials.gov, identifier NCT02802657.
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Affiliation(s)
- Huixun Jia
- National Clinical Research Center for Ophthalmic Diseases, Shanghai, China
- Department of Ophthalmology, School of Medicine, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
| | - Bing Lu
- National Clinical Research Center for Ophthalmic Diseases, Shanghai, China
- Department of Ophthalmology, School of Medicine, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
| | - Yuanzhi Yuan
- Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Fei Yuan
- Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Lei Li
- Department of Ophthalmology, Fudan University Eye and ENT Hospital, Fudan University, Shanghai, China
| | - Yanping Song
- Department of Ophthalmology, Central Theater Command General Hospital, Wuhan, China
| | - Ao Rong
- Department of Ophthalmology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Minwen Zhou
- National Clinical Research Center for Ophthalmic Diseases, Shanghai, China
- Department of Ophthalmology, School of Medicine, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
| | - Fenghua Wang
- National Clinical Research Center for Ophthalmic Diseases, Shanghai, China
- Department of Ophthalmology, School of Medicine, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
| | - Xiaodong Sun
- National Clinical Research Center for Ophthalmic Diseases, Shanghai, China
- Department of Ophthalmology, School of Medicine, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, Shanghai, China
- Shanghai Key Laboratory of Fundus Diseases, Shanghai, China
- Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
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An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma. Eye (Lond) 2022; 36:1154-1167. [PMID: 34974541 PMCID: PMC9151779 DOI: 10.1038/s41433-021-01766-w] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/19/2021] [Accepted: 09/07/2021] [Indexed: 12/26/2022] Open
Abstract
In the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelial growth factor (VEGF) drug injections may lose the initial vision gains in vision. Protracted regular treatment schedules represent a high burden not only for patients and families, but also healthcare professionals, systems, and ultimately society too. There has been a clear need for longer-acting therapies that reduce the frequency, and therefore the burden, of treatment interventions. Several longer-acting interventions for nAMD, diabetic macular oedema, retinal vein occlusion, uveitis and glaucoma have either been developed or are in late-phase development, some of which employ novel mechanisms of actions, and all of which of promise longer (≥3 month) treatment intervals. This review delivers an overview of anti-VEGF agents with longer durations of action, DARPins, bispecific anti-VEGF/Ang2 therapies, anti-PDGF and anti-integrin therapy, Rho-kinase inhibitors, the Port Delivery System, steroids, gene therapy for retina and uveitis, and for glaucoma, ROCK inhibitors, implants and plugs, and SLT laser and MIGS. The review also refers to the potential of artificial intelligence to tailor treatment efficacy with a resulting reduction in treatment burden.
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Disulfiram Exerts Antifibrotic and Anti-Inflammatory Therapeutic Effects on Perimysial Orbital Fibroblasts in Graves' Orbitopathy. Int J Mol Sci 2022; 23:ijms23095261. [PMID: 35563653 PMCID: PMC9104881 DOI: 10.3390/ijms23095261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 05/03/2022] [Accepted: 05/06/2022] [Indexed: 12/12/2022] Open
Abstract
Fibrosis of extraocular muscles (EOMs) is a marker of end-stage in Graves’ orbitopathy (GO). To determine the antifibrotic and anti-inflammatory therapeutic effects and the underlying molecular mechanisms of disulfiram (DSF) on perimysial orbital fibroblasts (pOFs) in a GO model in vitro, primary cultures of pOFs from eight patients with GO and six subjects without GO (NG) were established. CCK-8 and EdU assays, IF, qPCR, WB, three-dimensional collagen gel contraction assays, cell scratch experiments, and ELISAs were performed. After TGF-β1 stimulation of pOFs, the proliferation rate of the GO group but not the NG group increased significantly. DSF dose-dependently inhibited the proliferation, contraction, and migration of pOFs in the GO group. Additionally, DSF dose-dependently inhibited fibrosis and extracellular matrix production markers (FN1, COL1A1, α-SMA, CTGF) at the mRNA and protein levels. Furthermore, DSF mediates antifibrotic effects on GO pOFs partially through the ERK-Snail signaling pathway. In addition, DSF attenuated HA production and suppressed inflammatory chemokine molecule expression induced by TGF-β1 in GO pOFs. In this in vitro study, we demonstrate the inhibitory effect of DSF on pOFs fibrosis in GO, HA production, and inflammation. DSF may be a potential drug candidate for preventing and treating tissue fibrosis in GO.
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Combined drug triads for synergic neuroprotection in retinal degeneration. Biomed Pharmacother 2022; 149:112911. [DOI: 10.1016/j.biopha.2022.112911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 11/23/2022] Open
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Sarkar A, Jayesh Sodha S, Junnuthula V, Kolimi P, Dyawanapelly S. Novel and investigational therapies for wet and dry age-related macular degeneration. Drug Discov Today 2022; 27:2322-2332. [PMID: 35460893 DOI: 10.1016/j.drudis.2022.04.013] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 03/13/2022] [Accepted: 04/13/2022] [Indexed: 12/13/2022]
Abstract
Age-related macular degeneration (AMD) is a macular degenerative eye disease, the major cause of irreversible loss of central vision. In this review, we highlight current progress and future perspectives of novel and investigational therapeutic strategies in the drug pipeline, including anti-vascular endothelial growth factor (VEGF) agents, bispecific antibodies, biosimilars, small molecules, gene therapy, and long-acting drug delivery strategies for both dry and wet AMD. We anticipate that biologics with dual functionalities and combined therapies with long-acting capabilities will lead the wet AMD pipeline. Sustained-release platforms also show potential. However, significant breakthroughs are yet to be made for dry AMD. The personalized approach might be well suited in the scenario of diverse genetic variations in both conditions. Teaser: AMD is the leading cause of global blindness in the developed world. This article highlights investigational therapeutics, such as antibodies, Bi-specifics, small molecules, biosimilars, gene therapy and long-acting strategies (Port Delivery System), for this condition.
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Affiliation(s)
- Aira Sarkar
- Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Srushti Jayesh Sodha
- Department of Pharmaceutical Sciences, University of the Sciences, Philadelphia, PA 19104, USA
| | | | - Praveen Kolimi
- Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA
| | - Sathish Dyawanapelly
- Department of Pharmaceutical Science and Technology, Institute of Chemical Technology, Mumbai, 400019, India.
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Efficacy and Safety of Antivascular Endothelial Growth Factor (Anti-VEGF) in Treating Neovascular Age-Related Macular Degeneration (AMD): A Systematic Review and Meta-analysis. J Immunol Res 2022; 2022:6004047. [PMID: 35465351 PMCID: PMC9033403 DOI: 10.1155/2022/6004047] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 03/02/2022] [Indexed: 01/23/2023] Open
Abstract
This study is aimed at assessing the efficacy and safety of antivascular endothelial growth factor (anti-VEGF) inhibitors in treating age-related macular degeneration (AMD). PubMed, Embase, and Cochrane library were searched. Weighted mean difference (WMD) and relative risk (RR) with 95% confidence interval (CI) were applied to assess outcomes. Eighteen randomized controlled trials involved 8,847 neovascular AMD patients were selected for the meta-analysis. Pegaptanib (WMD: 6.70;
) and ranibizumab (WMD: 17.80;
) were associated with greater BCVA changes than control after 1 year. Bevacizumab was linked with less changes in central macular thickness after 1 year compared to control (WMD: -38.50;
), but more changes compared to ranibizumab (WMD: 10.69;
). The incidence of gain of 15 or more letter visual acuity after 1 year was increased when compared with bevacizumab versus control (RR: 7.80;
), pegaptanib versus control (RR: 2.83;
), and ranibizumab versus control (RR: 3.92;
). Moreover, ranibizumab was associated with more BCVA changes and an increased incidence of gain of 15 or more letter visual acuity after 2 years compared with control (RR: 5.77;
). This study found that most anti-VEGF inhibitors provided better efficacy than non-anti-VEGF intervention, and the treatment effectiveness among various anti-VEGF agents was equally effective.
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An J, Zeng Y, Liu H, Huang L, Yao J, Hou E, Zhang X. Corneal neovascularization inhibition and wound healing impregnability of conbercept on rabbit cornea after penetrating keratoplasty. Cutan Ocul Toxicol 2022; 41:98-104. [PMID: 35373690 DOI: 10.1080/15569527.2022.2050745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Jianbin An
- The Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yue Zeng
- Baoding NO.1 Central Hospital, Baoding, China
| | - Huan Liu
- Division of Ocular Injuries, Department of Ophthalmology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
- Hebei OPO Eye Bank, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Liying Huang
- Division of Ocular Injuries, Department of Ophthalmology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
- Hebei OPO Eye Bank, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jia Yao
- Division of Ocular Injuries, Department of Ophthalmology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
- Hebei OPO Eye Bank, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Enchong Hou
- Division of Ocular Injuries, Department of Ophthalmology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
- Hebei OPO Eye Bank, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaorong Zhang
- Division of Ocular Injuries, Department of Ophthalmology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
- Hebei OPO Eye Bank, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
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Musiał-Kopiejka M, Polanowska K, Dobrowolski D, Krysik K, Wylęgała E, Grabarek BO, Lyssek-Boroń A. The Effectiveness of Brolucizumab and Aflibercept in Patients with Neovascular Age-Related Macular Degeneration. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19042303. [PMID: 35206485 PMCID: PMC8872595 DOI: 10.3390/ijerph19042303] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/28/2022] [Accepted: 02/15/2022] [Indexed: 11/16/2022]
Abstract
Age-related macular degeneration (AMD) is a progressive, chronic disease of the central area of the retina, which, if untreated, leads to blindness. This study aimed to compare the effectiveness of therapy using anti-VEGF drugs, namely brolucizumab and aflibercept, in patients with neovascular AMD (nAMD) during a monitoring period lasting around 20 weeks. The analysis consisted of 40 patients diagnosed with neovascular age-related macular degeneration, with 20 patients receiving aflibercept (Eylea, Bayer) at a dose of 2 mg/50 µL into the vitreous chamber at the following intervals—3 doses, 4 weeks apart, followed by a fourth dose after 8 weeks. The remaining 20 patients received brolucizumab (Beovu, Novartis) at a dose of 6 mg/50 µL, administered in the following schedule—3 initial doses, 4 weeks apart, with the administration of a fourth dose decided for each patient individually by the doctor, depending on disease activity, assessed through imaging tests. To evaluate treatment effectiveness, the following measurements were used: ‘read distance and near visual acuity’ for each eye separately using the Snellen chart; and non-invasive retinal imaging techniques—optical coherence tomography (OCT) and OCT angiography (OCTA). In patients treated using brolucizumab, during the observation period, statistically significant differences were found in the following parameters: flow area (p = 0.0277); select area (p = 0.0277); FOVEA (p = 0.0073); visus (p = 0.0064). In brolucizumab-treated patients, changes in OCT and OCTA, indicating an improvement, were already visible after the first injection of the drug, whereas in the aflibercept-treated group, changes were only visible after the fourth injection. We found a higher effectiveness of brolucizumab therapy compared to aflibercept in patients with nAMD during an observations period lasting 20 weeks. Our observations are significant, although they require further research.
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Affiliation(s)
- Magdalena Musiał-Kopiejka
- Trauma Centre, Department of Ophthalmology, St. Barbara Hospital, 41-200 Sosnowiec, Poland; (M.M.-K.); (K.P.); (D.D.); (K.K.)
| | - Katarzyna Polanowska
- Trauma Centre, Department of Ophthalmology, St. Barbara Hospital, 41-200 Sosnowiec, Poland; (M.M.-K.); (K.P.); (D.D.); (K.K.)
| | - Dariusz Dobrowolski
- Trauma Centre, Department of Ophthalmology, St. Barbara Hospital, 41-200 Sosnowiec, Poland; (M.M.-K.); (K.P.); (D.D.); (K.K.)
- Chair and Clinical Department of Ophthalmology, Division of Medical Science in Zabrze, Medical University of Silesia in Katowice, 40-760 Katowice, Poland;
- Department of Ophthalmology, District Railway Hospital, 40-760 Katowice, Poland
| | - Katarzyna Krysik
- Trauma Centre, Department of Ophthalmology, St. Barbara Hospital, 41-200 Sosnowiec, Poland; (M.M.-K.); (K.P.); (D.D.); (K.K.)
- Department of Ophthalmology, Faculty of Medicine in Zabrze, University of Technology, Academy of Silesia in Katowice, 41-800 Zabrze, Poland
| | - Edward Wylęgała
- Chair and Clinical Department of Ophthalmology, Division of Medical Science in Zabrze, Medical University of Silesia in Katowice, 40-760 Katowice, Poland;
- Department of Ophthalmology, District Railway Hospital, 40-760 Katowice, Poland
| | - Beniamin Oskar Grabarek
- Department of Histology, Cytophysiology and Embryology, Faculty of Medicine, University of Technology, Academy of Silesia in Katowice, 41-800 Zabrze, Poland;
| | - Anita Lyssek-Boroń
- Trauma Centre, Department of Ophthalmology, St. Barbara Hospital, 41-200 Sosnowiec, Poland; (M.M.-K.); (K.P.); (D.D.); (K.K.)
- Department of Ophthalmology, Faculty of Medicine in Zabrze, University of Technology, Academy of Silesia in Katowice, 41-800 Zabrze, Poland
- Correspondence:
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Next-generation anti-VEGF agents for diabetic macular oedema. Eye (Lond) 2022; 36:273-277. [PMID: 34373607 PMCID: PMC8807622 DOI: 10.1038/s41433-021-01722-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 07/16/2021] [Accepted: 07/26/2021] [Indexed: 02/03/2023] Open
Abstract
The treatment and outcomes of diabetic macular oedema (DMO) have improved with the introduction of intravitreal injections. However, real-world data reveal that the burden of DMO treatment causes large gaps in outcomes between randomized clinical trials and daily clinical practice. Long-lasting intravitreal drugs and devices for DMO might reduce this disparity by achieving optimal treatment due to more feasible injection regimens. In this manuscript, we cover pharmacodynamics, preliminary results from clinical trials, and safety behavior about brolucizumab, faricimab, conbercept, KSI-301, and port-delivery system WR42221. These treatments might present the first step to control the global epidemic of diabetic eye disease in real life.
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Zhang Y, Gao S, Li X, Huang X, Zhang Y, Chang T, Cai Z, Zhang M. Efficacy and Safety of Anti-Vascular Endothelial Growth Factor Monotherapies for Neovascular Age-Related Macular Degeneration: A Mixed Treatment Comparison. Front Pharmacol 2022; 12:797108. [PMID: 34992542 PMCID: PMC8724554 DOI: 10.3389/fphar.2021.797108] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 11/29/2021] [Indexed: 02/05/2023] Open
Abstract
Background: We aimed to evaluate the comparative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD). Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost <15 letters in BCVA, the mean change in central retinal thickness, and the number of injections within 12 months. Results: Twenty-seven trials including 10,484 participants and eighteen treatments were identified in the network meta-analysis. The aflibercept 2 mg bimonthly, ranibizumab 0.5 mg T&E, and brolucizumab 6 mg q12w/q8w regimens had better visual efficacy. Brolucizumab had absolute superiority in anatomical outcomes and a relative advantage of safety, as well as good performance of aflibercept 2 mg T&E. The proactive regimens had slightly better efficacy but a slightly increased number of injections versus the reactive regimen. Bevacizumab had a statistically non-significant trend toward a lower degree of efficacy and safety. Conclusion: The visual efficacy of four individual anti-VEGF drugs is comparable. Several statistically significant differences were observed considering special anti-VEGF regimens, suggesting that brolucizumab 6 mg q12w/q8w, aflibercept 2 mg bimonthly or T&E, and ranibizumab 0.5 mg T&E are the ideal anti-VEGF regimens for nAMD patients. In the current landscape, based on the premise of equivalent efficacy and safety, the optimal choice of anti-VEGF monotherapies seems mandatory to obtain maximal benefit.
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Affiliation(s)
- Yun Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.,Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Sheng Gao
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.,Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Xun Li
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.,Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Xi Huang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.,Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.,Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Tiancong Chang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.,Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
| | - Zhaolun Cai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Meixia Zhang
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.,Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu, China
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Emerging Treatment Modalities for Neovascular Age-Related Macular Degeneration: A Systematic Overview. Adv Ther 2022; 39:5-32. [PMID: 34724151 DOI: 10.1007/s12325-021-01949-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 10/06/2021] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Neovascular age-related macular degeneration (nAMD) represents a leading cause of irreversible visual loss affecting the quality of life of millions of elderly patients worldwide. Although the introduction of intravitreal injections with anti-vascular endothelial growth factors (anti-VEGF) agents has revolutionized the management of nAMD, their effectiveness and ultimate success are limited by several therapeutic challenges. Consequently, real-world efficacy appears significantly inferior to that reported by randomized controlled trials. Therefore, further innovative, long-term treatment options are essential to improve the prognosis and outcome of nAMD therapy. METHODS Emerging pharmacological therapies for nAMD and those currently in clinical trials are reviewed and their mechanism of action, safety, and efficacy are discussed. The evidence presented herein has been collected from online databases PubMed, Cochrane library, and the ClinicalTrials.gov site. RESULTS A number of promising technologies and novel anti-VEGF therapies are currently being tested and some have already reached phase III trials. Anti-VEGF agents with enhanced durability and possibly efficacy, gene therapy, angiogenic targets, alternative drug delivery routes such as sustained delivery implants, drug carriers, and encapsulated cell technology are currently being explored. We briefly discuss the potential value of these options. CONCLUSION Several options may optimize future nAMD management. On the basis of current, albeit limited evidence, the most promising technology to reach clinical practice soon appears to be the sustained drug delivery options, which may improve visual outcome and reduce the socioeconomic burden of nAMD.
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