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Lim G, Kim KT, Kim DY, Chae JB, Seo EJ. Early optical coherence tomography biomarkers for tailored frequency of intravitreal aflibercept in neovascular age-related macular degeneration. Sci Rep 2025; 15:8911. [PMID: 40087500 PMCID: PMC11909171 DOI: 10.1038/s41598-025-93962-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Accepted: 03/11/2025] [Indexed: 03/17/2025] Open
Abstract
Intravitreal anti-vascular endothelial growth factor (VEGF) injections are essential for treating neovascular age-related macular degeneration (nAMD), but patient responses vary significantly, complicating standardized regimens. This study identifies early optical coherence tomography (OCT) biomarkers and best-corrected visual acuity (BCVA) as predictors of injection frequency in a one-year treat-and-extend (T&E) regimen to optimize individualized treatment. A retrospective analysis of treatment-naïve nAMD patients receiving intravitreal aflibercept was conducted. Patients underwent three initial monthly loading injections, followed by a modified T&E regimen. OCT parameters and BCVA were assessed at baseline, during, and after the loading phase to identify associations with injection frequency and recurrence intervals. Post-loading central subfield thickness (CST) significantly predicted injection frequency (p < 0.001) and recurrence timing (p = 0.013), while baseline CST and BCVA showed no correlation. BCVA remained similar between high- and low-treatment-need groups despite differing injection frequencies. Type 2 macular neovascularization responded more rapidly to treatment than type 1, reflecting varying dynamics. CST after the loading phase is a reliable predictor of treatment needs within one year, superior to baseline biomarkers. Early response monitoring during loading enables personalized anti-VEGF therapy, minimizing overtreatment and preserving vision, underscoring the value of individualized management in nAMD.
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Affiliation(s)
- Gyeongsoo Lim
- Department of Ophthalmology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Kyung Tae Kim
- Department of Ophthalmology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Dong Yoon Kim
- Department of Ophthalmology, Seoul Top Eye Center, Cheongju, Korea
| | - Ju Byung Chae
- Department of Ophthalmology, Seoul Top Eye Center, Cheongju, Korea
| | - Eoi Jong Seo
- Department of Ophthalmology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea.
- Department of Ophthalmology, College of Medicine, Chungbuk National University, 776, Sunhwan-1-Ro, Seowon-Gu, Cheongju, 28644, Korea.
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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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Parravano M, Viola F, Nicolò M, Vujosevic S, Bianchino L, Sicari E, Villa G, Lanzetta P. Real-world evidence of anti-VEGF therapies in patients with neovascular age-related macular degeneration in Italy: The RADIANCE study. Eur J Ophthalmol 2025:11206721241310628. [PMID: 39901532 DOI: 10.1177/11206721241310628] [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: 02/05/2025]
Abstract
PURPOSE Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, particularly neovascular AMD (nAMD). This study aimed to investigate the real-world treatment patterns, effectiveness, and safety of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies for anti-VEGF naïve nAMD patients in Italy. METHODS RADIANCE is a retrospective, observational, multicenter cohort study conducted at 13 clinical sites across Italy. The study enrolled all consecutive patients with nAMD, naïve to any intraocular anti-VEGF treatment and who initiated therapy with aflibercept, ranibizumab, or bevacizumab between January 2017 and November 2018. The primary objective of this study was to evaluate changes in visual acuity (VA) 52 weeks after initiating treatment with anti-VEGF. RESULTS A total of 405 patients were enrolled; of these, 263 patients had at least two VA measurements and were included in the completer analysis (CA) set. At 52 weeks, the median VA change from baseline in the CA set was +1 letter, with 41.1% showing ≥ 5-letter improvement. Stratified by anti-VEGF agent, no statistically significant differences were observed. Overall, patients received a median of 5.0 (25th-75th percentile 3-6) injections of the initial anti-VEGF agent during the first year. Patients receiving ≥ 6 injections in the first year showed better VA outcomes. Undertreatment was evident at decreasing injection frequency over time. CONCLUSION The results of the RADIANCE study suggest an overall moderate effectiveness after 1 year of treatment with anti-VEGF in naïve patients with nAMD in Italy. Real-world outcomes demonstrated suboptimal treatment with no significant differences among anti-VEGF agents.
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Affiliation(s)
| | - Francesco Viola
- Ophthalmology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Massimo Nicolò
- Clinica Oculistica-DiNOGMi, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Stela Vujosevic
- Department of Biomedical, Surgical, and Dental Sciences, University of Milan, Milan, Italy
- Eye Clinic, IRCCS MultiMedica, Milan, Italy
| | | | | | | | - Paolo Lanzetta
- Department of Medicine-Ophthalmology, University of Udine, Udine, Italy
- IEMO, Istituto Europeo di Microchirurgia Oculare, Udine-Milan, Italy
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Schoumacher M, Lambert V, Campas M, Blaise P, Locht B, Thys M, Duchateau E, Cavalier E, Rakic JM, Noël A, de Tullio P. Opportunities, challenges, and difficulties in NMR-based metabolomics applied to neovascular age-related macular degeneration (nAMD) patient follow-up. Front Mol Biosci 2025; 11:1449226. [PMID: 39935708 PMCID: PMC11811626 DOI: 10.3389/fmolb.2024.1449226] [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: 06/14/2024] [Accepted: 12/12/2024] [Indexed: 02/13/2025] Open
Abstract
Introduction This study applies NMR-based metabolomics to investigate neovascular age-related macular degeneration (nAMD), addressing challenges in patient management, disease progression evaluation, and treatment response assessment. A two-year follow-up of 29 nAMD patients undergoing treatment provided 231 time points for analysis. Methods Over the two-year period, 11 males and 18 females (aged 61-92 years) were monitored, yielding 231 time points. At each time point, blood samples for NMR metabolomics analysis, clinical measurements (e.g., lactate, glucose levels, HDL/LDL cholesterol, and blood pH), and optical coherence tomography (OCT) images were collected to evaluate the progression of choroidal neovascularization. 1H-NMR metabolomic analysis led to the quantification of over 60 metabolites and of the major lipoprotein fractions. Both multivariate and univariate statistical approaches tailored for longitudinal data were employed to identify biomarkers correlating metabolomic changes with ocular alterations during disease progression. Results and Discussion Despite a rigorous analytical workflow enabling precise quantification of over 60 metabolites and the application of advanced statistical tools for longitudinal data, achieving consistent results across the cohort proved challenging. The dataset's heterogeneity, reflecting real-world clinical practice, complicated the derivation of global conclusions. Personalized analyses on a patient-by-patient basis successfully identified individual correlation models, but a universal model remained elusive. This study highlights the inherent challenges of translating findings from controlled settings into clinical practice, where factors such as visit frequency, treatment variability, and disease heterogeneity limit data uniformity. We emphasize the importance of experimental design in longitudinal studies, particularly when dealing with incomplete and variable datasets. We are therefore confident that, considering both the challenges and difficulties identified in this work and the preliminary results presented here, it is possible to develop predictive and individualized models for monitoring patients with nAMD. Such models could greatly assist clinicians in providing better care for these patients.
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Affiliation(s)
- M. Schoumacher
- Clinical Metabolomics Group (CliMe), Center for Interdisciplinary Research on Medicines, Université de Liège, Liège, Belgium
- Department of Medical Chemistry, University Hospital of Liège, Liège, Belgium
| | - V. Lambert
- Department of Ophthalmology, University Hospital of Liège, Liège, Belgium
| | - M. Campas
- Clinical Metabolomics Group (CliMe), Center for Interdisciplinary Research on Medicines, Université de Liège, Liège, Belgium
| | - P. Blaise
- Department of Ophthalmology, University Hospital of Liège, Liège, Belgium
| | - B. Locht
- Department of Ophthalmology, University Hospital of Liège, Liège, Belgium
| | - M. Thys
- Department of Ophthalmology, University Hospital of Liège, Liège, Belgium
| | - E. Duchateau
- Department of Ophthalmology, University Hospital of Liège, Liège, Belgium
| | - E. Cavalier
- Clinical Metabolomics Group (CliMe), Center for Interdisciplinary Research on Medicines, Université de Liège, Liège, Belgium
- Department of Medical Chemistry, University Hospital of Liège, Liège, Belgium
| | - J.-M. Rakic
- Department of Ophthalmology, University Hospital of Liège, Liège, Belgium
| | - A. Noël
- Laboratory of Tumor and Development Biology, GIGA, Université de Liège, Liège, Belgium
| | - P. de Tullio
- Clinical Metabolomics Group (CliMe), Center for Interdisciplinary Research on Medicines, Université de Liège, Liège, Belgium
- Department of Medical Chemistry, University Hospital of Liège, Liège, Belgium
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Hayek G, Reglodi D, Goetz C, Perone JM, Csutak A. Ranibizumab treatment improves the reading speed of patients with neovascular age-related macular degeneration: A nonrandomized clinical trial using the Radner reading chart. J Fr Ophtalmol 2025; 48:104350. [PMID: 39504678 DOI: 10.1016/j.jfo.2024.104350] [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: 02/28/2024] [Revised: 04/30/2024] [Accepted: 05/24/2024] [Indexed: 11/08/2024]
Abstract
PURPOSE Intravitreal injections with anti-vascular endothelial growth factor (VEGF) drugs can slow progression in neovascular age-related macular degeneration (nAMD). Best spectacle-corrected visual acuity (BSCVA) and/or central retinal thickness (CRT) are common barometers of efficacy of this treatment. However, BSCVA does not accurately measure reading ability, which is often severely impacted by nAMD. Since most studies on the effect of intravitreal anti-VEGF injections on reading ability in nAMD have limitations, we conducted an open-label nonrandomized non-blinded self-controlled clinical trial using Radner Charts, a standardized, validated tool for measuring reading ability. METHODS Patients newly diagnosed with active nAMD and scheduled to undergo induction ranibizumab treatment (monthly treatments for 3months) were recruited by convenience sampling in 2010-2013 at a university hospital. The primary outcome was change in Radner Chart-determined reading speed (maximum words/minute [wpm]) at 3months (1month post-third injection) relative to baseline. Secondary outcome measures were 3-month change in BSCVA and CRT. Treatment-induced effects on wpm, BSCVA, and CRT were determined with Wilcoxon tests. Spearman correlations between these variables were evaluated. RESULTS The injections significantly improved wpm (48 to 75), BSCVA (+9 letters), and CRT (357 to 224μm) (all P<0.0001). BSCVA, but not CRT, correlated with wpm at baseline and 3months (P=0.0004 and 0.03, respectively). BSCVA and CRT were not correlated, unless change in these variables was considered, possibly because of a non-linear relationship. CONCLUSION Anti-VEGF treatment significantly improved reading ability. Whether BSCVA can serve as a clinically meaningful assessment of reading ability requires further research. Baseline variables may not help to identify patients with poor reading speed responses to treatment.
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Affiliation(s)
- G Hayek
- Ophthalmology Department, Metz-Thionville Regional Hospital Center, Mercy Hospital, Metz, France; Ophthalmology Department, Medical School, University of Pécs, Pécs, Hungary.
| | - D Reglodi
- Anatomy Department, Medical School, University of Pécs, Pécs, Hungary
| | - C Goetz
- Clinical Research Support Unit, Metz-Thionville Regional Hospital Center, Mercy Hospital, Metz, France
| | - J-M Perone
- Ophthalmology Department, Metz-Thionville Regional Hospital Center, Mercy Hospital, Metz, France
| | - A Csutak
- Ophthalmology Department, Medical School, University of Pécs, Pécs, Hungary
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Han JM, Han J, Ko J, Jung J, Park JI, Hwang JS, Yoon J, Jung JH, Hwang DDJ. Anti-VEGF treatment outcome prediction based on optical coherence tomography images in neovascular age-related macular degeneration using a deep neural network. Sci Rep 2024; 14:28253. [PMID: 39548212 PMCID: PMC11568167 DOI: 10.1038/s41598-024-79034-6] [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: 08/21/2024] [Accepted: 11/05/2024] [Indexed: 11/17/2024] Open
Abstract
Age-related macular degeneration (AMD) is a major cause of blindness in developed countries, and the number of affected patients is increasing worldwide. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard therapy for neovascular AMD (nAMD), and optical coherence tomography (OCT) is a crucial tool for evaluating the anatomical condition of the macula. However, OCT has limitations in accurately predicting the degree of functional and morphological improvement following intravitreal injections. Artificial intelligence (AI) has been proposed as a tool for predicting the treatment response of nAMD based on OCT biomarkers. Our study focuses on the development and assessment of an AI model utilizing the DenseNet201 algorithm. The model aims to predict anatomical improvement based on OCT images before, and during anti-VEGF therapy. The training process involves two scenarios: (1) using only preinjection OCT images and (2) utilizing both OCT images before and during anti-VEGF therapy for model training. The outcomes of our investigation, involving 2068 images from a cohort of 517 Korean patients diagnosed with nAMD, indicate that the AI model we introduced surpassed the predictive performance of ophthalmologists. The model exhibited a sensitivity of 0.915, specificity of 0.426, and accuracy of 0.820. Notably, its predictive capabilities were further enhanced with the inclusion of additional OCT images taken after the first and second injections during the loading phase. The treatment prediction performance of the model was the highest when using all input modalities (before injection, and after the first and second injections) and concatenation-based fusion layers. This study highlights the potential of AI in assisting individualized and tailored nAMD treatment.
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Affiliation(s)
- Jeong Mo Han
- Kong Eye Hospital, Seoul, Korea
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea
| | - Jinyoung Han
- Department of Applied Artificial Intelligence, Sungkyunkwan University, Seoul, Korea
- Department of Human-Artificial Intelligence Interaction, Sungkyunkwan University, Seoul, Korea
| | - Junseo Ko
- Department of Applied Artificial Intelligence, Sungkyunkwan University, Seoul, Korea
| | - Juho Jung
- Department of Applied Artificial Intelligence, Sungkyunkwan University, Seoul, Korea
| | - Ji In Park
- Department of Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Korea
| | | | - Jeewoo Yoon
- Department of Applied Artificial Intelligence, Sungkyunkwan University, Seoul, Korea
| | - Jae Ho Jung
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea
| | - Daniel Duck-Jin Hwang
- Department of Ophthalmology, Hangil Eye Hospital, 35 Bupyeong-daero, Bupyeong-gu, Incheon, 21388, Korea.
- Lux Mind, Incheon, Korea.
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Śpiewak D, Drzyzga Ł, Dorecka M, Wyględowska-Promieńska D. Summary of the Therapeutic Options for Patients with Dry and Neovascular AMD. J Clin Med 2024; 13:4227. [PMID: 39064267 PMCID: PMC11278184 DOI: 10.3390/jcm13144227] [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: 05/06/2024] [Revised: 07/15/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness worldwide and a severe medical and social problem. The steadily increasing number of patients is related to the aging of the population. So far, many factors affecting the development of AMD have been identified, which can be divided into non-modifiable, including genetic factors, age, and sex, and modifiable or environmental factors, such as smoking, poor diet, and hypertension. Early stages of age-related macular degeneration are characterized by fundus drusen and abnormalities in the retinal pigment epithelium. In late stages, geographic atrophy and choroidal neovascularization (CNV) are observed. The treatment of AMD, especially its advanced forms, is very challenging. Intensive research has made it possible to treat advanced stages of the dry form of AMD with pegcetacoplan and avacincaptad pegol, new drugs approved for use in the US. Pegcetacoplan targets the C3 and avacincaptad pegol targets the C5, the pivotal proteins of the complement cascade. The drugs are administered by intravitreal injection. The gold standard for neovascular AMD (nAMD) consists of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs such as bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab. Treatment can be administered according to the fixed, pro-re-nata, and treat-and-extend regimens. The latter seems to have the best effect on improving visual acuity (VA) and the maximum therapeutic benefit. The search continues for the best ways to deliver intravitreal drugs. Current methods include sustained-release implants and hydrogel platforms for drug release, while the most promising future pathways for treating dry and nAMD are stem cell and gene therapy.
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Affiliation(s)
- Dorota Śpiewak
- Department of Ophthalmology, Prof. K. Gibiński University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland
- Clinical Ophthalmology Center Okolux, 40-754 Katowice, Poland
| | - Łukasz Drzyzga
- Department of Ophthalmology, Prof. K. Gibiński University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland
- Clinical Ophthalmology Center Okolux, 40-754 Katowice, Poland
| | - Mariola Dorecka
- Department of Ophthalmology, Prof. K. Gibiński University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland
- Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-287 Katowice, Poland
| | - Dorota Wyględowska-Promieńska
- Department of Ophthalmology, Prof. K. Gibiński University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland
- Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-287 Katowice, Poland
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Grassi MO, Viggiano P, Borrelli E, Boscia G, Molfetta T, Malerba MG, D'Addario M, Giancipoli E, Alessio G, Boscia F. Comparative Study on Anti-VEGF in Wet Age-Related Macular Degeneration in the Setting Based on Lean Methodology from the Bari Intravitreal Injection Registry (BIVIR). Ophthalmol Ther 2024; 13:1619-1634. [PMID: 38619788 PMCID: PMC11109068 DOI: 10.1007/s40123-024-00927-w] [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: 09/18/2023] [Accepted: 02/29/2024] [Indexed: 04/16/2024] Open
Abstract
INTRODUCTION Optimizing treatment protocols for wet age-related macular degeneration (wAMD) is an ongoing challenge, as it involves a delicate balance between achieving therapeutic efficacy and minimizing invasive procedures' frequency. This study aimed to apply the Lean methodology and evaluate the effectiveness of this new setting on intravitreal therapy for wAMD, employing different anti-vascular endothelial growth factors (VEGF) drugs (bevacizumab, brolucizumab, aflibercept, ranibizumab), drawing data from the Bari Intravitreal Injections Registry (BIVIR). METHODS This was a retrospective, monocentric, nonrandomized, comparative study. Lean methodology was employed to design the new setting and the BIVIR collected information from electronic medical records. Clinical data of four groups, stratified based on the first-line anti-VEGF agents used, were compared. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes were compared between the four groups at 3 and 12 months. RESULTS Out of 4990 eyes and 41,323 intravitreal injections (IVs) recorded in BIVIR, 1421 eyes of 1182 patients were included. The mean number of IVs in first year was 6.1 ± 2.5, with no significant differences among the four subgroups. The mean change in BCVA was + 6.2 letters [95% confidence interval (CI) 5.6-6.8] after two IVs, and + 5.9 (95% CI 5.1-6.8) letters after three IVs; at three months, brolucizumab was associated with a greater mean increase in BCVA than bevacizumab (p = 0.050); aflibercept (p = 0.044) and ranibizumab p = 0.047). At the 1-year follow-up, the mean change was + 6.3 letters (95% CI 5.4-7.2), brolucizumab and ranibizumab were associated with a superior improvement in BCVA compared to aflibercept (p = 0.033). Regarding the CRT, a significant reduction was observed in the subgroup treated with brolucizumab at the 3-month follow-up, compared to bevacizumab (p = 0.003), aflibercept (p = 0.015), and ranibizumab (p < 0.001); Aflibercept exhibited a superior effect than ranibizumab (p = 0.001). At 1-year follow-up, aflibercept resulted in a more significant reduction of macular thickness compared to ranibizumab (p = 0.016) while no significant differences were observed among the other drugs. CONCLUSIONS Our practical experience showed the effectiveness of the new setting in the treatment of wAMD. This comparative study at 1 year suggested a predominant brolucizumab efficacy on functional outcomes. In addition, brolucizumab and aflibercept appeared to have similar efficacy in fluid control.
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Affiliation(s)
- Maria Oliva Grassi
- DIBRAIN Department, University of Bari, Piazza Giulio Cesare, 11, Bari, Italy.
| | - Pasquale Viggiano
- DIBRAIN Department, University of Bari, Piazza Giulio Cesare, 11, Bari, Italy
| | - Enrico Borrelli
- Vita-Salute San Raffaele University Milan, Milan, Italy
- IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giacomo Boscia
- DIBRAIN Department, University of Bari, Piazza Giulio Cesare, 11, Bari, Italy
| | - Teresa Molfetta
- DIBRAIN Department, University of Bari, Piazza Giulio Cesare, 11, Bari, Italy
| | | | - Maria D'Addario
- DIBRAIN Department, University of Bari, Piazza Giulio Cesare, 11, Bari, Italy
| | - Ermete Giancipoli
- UOC Oftalmologia, Dipartimento di Scienze Mediche e Chirurgiche, University of Foggia, Foggia, Italy
| | - Giovanni Alessio
- DIBRAIN Department, University of Bari, Piazza Giulio Cesare, 11, Bari, Italy
| | - Francesco Boscia
- DIBRAIN Department, University of Bari, Piazza Giulio Cesare, 11, Bari, Italy
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Ghosh AK, Nikumbh US, Shukla CK, Laul RS, Dixit A, Mahapatra SK, Nayak S, Shah UM, Parwal S, Venkatapathy N, Radhakrishnan N, Kelgaonkar A, Saxena S, Mishra D, Dave VP, Khan P, Saswade MR, Shantilal MS, Ramasamy K, Sreekanta S, Rajurkar M, Doshi M, Behera S, Patel P, Dhawan S, Lakhwani L. Efficacy, Safety and Immunogenicity of Sun's Ranibizumab Biosimilar in Neovascular Age-Related Macular Degeneration: A Phase 3, Double-Blind Comparative Study. Ophthalmol Ther 2024; 13:1369-1382. [PMID: 38530568 DOI: 10.1007/s40123-024-00883-5] [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: 12/05/2023] [Accepted: 01/04/2024] [Indexed: 03/28/2024] Open
Abstract
INTRODUCTION The study aimed to evaluate comparability in terms of efficacy, safety and immunogenicity of Sun's ranibizumab biosimilar with reference ranibizumab in patients with neovascular age-related macular degeneration (nAMD). METHODS This prospective, randomised, double-blind, two-group, parallel-arm, multicentre, phase 3 comparative study included patients with nAMD ≥ 50 years, randomised (in a 2:1 ratio) in a double-blind manner to receive 0.5 mg (0.05 mL) intravitreal injection of either Sun's ranibizumab or reference ranibizumab in the study eye every 4 weeks until week 16 (total of four doses). RESULTS Primary endpoint results demonstrated equivalence in the proportion of patients who lost fewer than 15 letters from baseline best-corrected visual acuity (BCVA) to the end of week 16 (99% of patients in Sun's ranibizumab and 100% in reference ranibizumab; p > 0.9999), with the proportional difference (90% confidence interval) at -1% (-2.51, +0.61) lying within a pre-specified equivalence margin. Visual acuity improved by 15 or more letters in 43% of Sun's ranibizumab group and 37% of the reference ranibizumab group (p = 0.4267). The mean increase in BCVA was 15.7 letters in Sun's ranibizumab group and 14.6 letters in the reference ranibizumab group (p < 0.001 within both groups and p = 0.5275 between groups). The mean change in central macular thickness was comparable between groups (p = 0.7946). Anti-ranibizumab antibodies were found in one patient of the reference ranibizumab group, while neutralising antibodies were not found in any patients. Both products were well tolerated. CONCLUSION Sun's ranibizumab biosimilar is found to be therapeutically equivalent to reference ranibizumab in patients with nAMD. There were no additional safety or immunogenicity concerns. TRIAL REGISTRATION CTRI/2020/09/027629, registered on 07 September 2020.
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Affiliation(s)
- Asim K Ghosh
- Regional Institute of Ophthalmology, Kolkata, India
| | - Usha S Nikumbh
- B. J. Govt. Medical College and Sassoon General Hospital, Pune, India
| | | | - Rohit S Laul
- Chopda Medicare & Research Centre Pvt. Ltd, Nashik, India
| | - Abhishek Dixit
- Sankat Mochan Nethralaya and Dental Care, Varanasi, India
| | - Santosh K Mahapatra
- JPM Rotary Club of Cuttack Eye Hospital & Research Institute, Cuttack, India
| | | | | | | | | | | | | | | | | | | | - Perwez Khan
- Department of Ophthalmology, GSVM Medical College, Kanpur, India
| | | | | | - Kim Ramasamy
- Aravind Eye Hospital & Postgraduate Institute of Opthalmology, Coimbatore, India
| | | | - Mandodari Rajurkar
- India Clinical Research, Sun Pharma Laboratories Ltd, Sun House, Plot Number 201 B/1, Western Express Highway, Goregaon (East), Mumbai, 400063, India.
| | - Maulik Doshi
- Ex Sun Pharma Laboratories Limited, Mumbai, India
| | - Sapan Behera
- Ex Sun Pharma Laboratories Limited, Mumbai, India
| | - Piyush Patel
- Ex Sun Pharma Laboratories Limited, Mumbai, India
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10
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Song YY, Seong HJ, Kim JT, Lee SC, Lee MW. Features of optical coherence tomography angiography in age-related macular degeneration with residual fluid after three loading doses of aflibercept. EYE AND VISION (LONDON, ENGLAND) 2024; 11:4. [PMID: 38297400 PMCID: PMC10832073 DOI: 10.1186/s40662-023-00372-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 12/25/2023] [Indexed: 02/02/2024]
Abstract
BACKGROUND To identify the macular neovascularization (MNV) features in exudative age-related macular degeneration (AMD) patients who exhibited residual fluid after receiving three loading doses of aflibercept. METHODS Patients were classified into two groups: Group 1, which did not exhibit intraretinal fluid (IRF) and subretinal fluid (SRF), and Group 2, which did exhibit IRF and/or SRF. Optical coherence tomography angiography (OCTA) features were assessed and compared between the groups. RESULTS A total of 101 eyes were enrolled; 65 for Group 1 and 36 for Group 2. No significant differences were found in baseline MNV size (2.94 ± 2.51 µm2 vs. 2.22 ± 2.26 µm2, P = 0.178) or vessel density (47.1 ± 15.4 % vs. 41.3 ± 10.5%, P = 0.052) between Groups 1 and 2. There were significant differences in the presence of loops (52.3% vs. 75%, P = 0.026) and peripheral arcades (29.2% vs. 55.6%, P < 0.001) at baseline between the two groups. In Group 1, there was a significant reduction in the presence of branching (P < 0.001) and loops (P = 0.016) after treatment. In Group 2, only the presence of branching decreased significantly (P < 0.001) after treatment. Multivariable analysis revealed that the presence of a peripheral arcade (B = 4.77, P = 0.001) was significantly associated with residual fluid. CONCLUSIONS Although responding to treatment, the presence of loops and peripheral arcades in exudative AMD patients may contribute to residual fluid following the three loading doses of aflibercept. The peripheral arcade, in particular, may play a more significant role in the presence of residual fluid.
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Affiliation(s)
- Yong-Yeon Song
- Department of Ophthalmology, Konyang University Hospital, Konyang University College of Medicine, #1643 Gwanjeo-dong, Seo-gu, Daejeon, Republic of Korea
| | - Hyun-Je Seong
- Department of Ophthalmology, Konyang University Hospital, Konyang University College of Medicine, #1643 Gwanjeo-dong, Seo-gu, Daejeon, Republic of Korea
| | - Jung-Tae Kim
- Department of Ophthalmology, Konyang University Hospital, Konyang University College of Medicine, #1643 Gwanjeo-dong, Seo-gu, Daejeon, Republic of Korea
| | - Sung-Chul Lee
- Department of Ophthalmology, Konyang University Hospital, Konyang University College of Medicine, #1643 Gwanjeo-dong, Seo-gu, Daejeon, Republic of Korea
| | - Min-Woo Lee
- Department of Ophthalmology, Konyang University Hospital, Konyang University College of Medicine, #1643 Gwanjeo-dong, Seo-gu, Daejeon, Republic of Korea.
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11
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Garay-Aramburu G, Rodriguez-Feijoo D, Aldazabal-Echeveste M, Del Barrio Z, Eiras-Fernández A, Piñero DP, Larrauri-Arana A. Predictors of stoppage and recurrence of choroidal neovascularization with a Treat- Extend-Stop protocol: 4-year follow-up. J Fr Ophtalmol 2023; 46:1204-1211. [PMID: 37658033 DOI: 10.1016/j.jfo.2023.02.021] [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: 11/30/2022] [Revised: 02/09/2023] [Accepted: 02/12/2023] [Indexed: 09/03/2023]
Abstract
OBJECTIVE To analyze the long-term results of treatment of active age-related macular degeneration (AMD) with anti-vascular endothelial growth factor (VEGF) agents using the treat-extend-stop (TES) approach, defining predictive factors for stoppage of the treatment and recurrences in a real-world setting. METHODS Data from 191 eyes treated with intravitreal injections for choroidal neovascularization due to AMD were retrospectively reviewed. Changes in best-corrected visual acuity (BCVA) and membrane activity (optical coherence tomography) were recorded and evaluated over a 48-month follow-up. Logistic regression analysis was used to determine predictors of treatment stoppage and recurrences after stoppage. RESULTS BCVA improvement was found in 70.5% of eyes at 48 months, and remaining signs of activity in 27.9%. Disease inactivity was achieved in 69 eyes (31.9%), with a relapse of the membrane in 29 of these eyes (42.0%). Significant independent predictors of treatment stoppage were found: no foveal membrane, inactive membrane at 12, 24, 36 and 48 months, extension interval>8 weeks at 12 and 24 months,>15 injections at 24 months, and baseline BCVA>61 letters. Concerning recurrent membranes, only the presence of membrane activity at 36 months and baseline BCVA>61 letters were independent predictors. CONCLUSIONS Anti-VEGF treatment of AMD using the TES protocol allows for successful visual restoration in most patients, with more likely disease inactivity in those eyes with better baseline BCVA, maintaining signs of membrane inactivity during the first two years of follow-up and requiring fewer injections.
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Affiliation(s)
- G Garay-Aramburu
- Department of Ophthalmology, Begiker-Ophthalmology Research Group, Biocruces Bizkaia Health Research Institute. Facultad de Medicina, Campus de Vitoria-Gasteiz, University of the Basque Country, UPV/EHU, Avenida Montevideo 18, 48013 Bilbao, Bizkaia, Spain
| | | | | | - Z Del Barrio
- Department of Ophthalmology, Araba University Hospital, Araba, Spain
| | - A Eiras-Fernández
- Department of Ophthalmology, Araba University Hospital, Araba, Spain
| | - D P Piñero
- Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.
| | - A Larrauri-Arana
- Department of Ophthalmology, Araba University Hospital, Araba, Spain; Universidad del País Vasco-Euskal Herriko Unibertsitatea, Vitoria-Gasteiz, Araba, Spain
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12
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Usui Y, Iwanishi H, Sumioka T, Ichikawa K, Miyajima M, Usui-Kusumoto K, Reinach PS, Okada Y, Saika S. Engineered Knockout of TRPA1 Inhibits Laser-Induced Choroidal Neovascularization Along With Associated TGFβ1 Expression and Neutrophil Infiltration. J Transl Med 2023; 103:100256. [PMID: 37797886 DOI: 10.1016/j.labinv.2023.100256] [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: 03/08/2022] [Revised: 07/20/2023] [Accepted: 08/28/2023] [Indexed: 10/07/2023] Open
Abstract
We examined the effects of gene ablation and chemical inhibition of transient receptor potential ankyrin 1 (TRPA1) on the growth of experimental argon laser-induced choroidal neovascularization (CNV) in mice. CNV was induced in the eyes of 6- to 8-week-old TRPA1-null (knockout [KO]) and wild-type (WT) mice by argon laser irradiation. Gene expression analysis was performed in laser-injured tissues at days 1 and 3. CNV growth was evaluated at day 14. Reciprocal bone marrow transplantation was performed between each genotype to identify the components responsible for either recipient tissue or bone marrow-derived inflammatory cells. Our results show that laser irradiation successfully induced CNV growth at the site of laser injury. The size of induced CNV was significantly smaller in KO mice than in WT mice at day 14, as determined by angiography with fluorescein isothiocyanate-dextran. Invasion of neutrophils, but not macrophages, was suppressed in association with suppression of the expression of transforming growth factor β1 and interleukin 6 in laser-irradiated KO tissue. Bone marrow transplantation indicated that the genotype of the recipient mouse, but not of inflammatory cells, is attributable to the KO phenotype. Systemic administration of a TRPA1 antagonist also reduced the CNV in a WT mouse. In conclusion, TRPA1 signaling in local cells is involved in growth of laser-induced CNV. The phenotype was not attributable to vascular endothelial cells and inflammatory cells. Blocking TRPA1 signal may therefore be a potential treatment strategy for CNV-related ocular diseases.
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Affiliation(s)
- Yuta Usui
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Hiroki Iwanishi
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
| | - Takayoshi Sumioka
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Kana Ichikawa
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Masayasu Miyajima
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Keiko Usui-Kusumoto
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Peter Sol Reinach
- Department of Ophthalmology and Optometry, Wenzhou Medical University School, Wenzhou, People's Republic of China
| | - Yuka Okada
- Department of Ophthalmology, Wakayama Medical University Kihoku Hospital, Wakayama, Japan
| | - Shizuya Saika
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
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13
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Nichani PAH, Popovic MM, Dhoot AS, Pathak A, Muni RH, Kertes PJ. Treat-and-extend dosing of intravitreal anti-VEGF agents in neovascular age-related macular degeneration: a meta-analysis. Eye (Lond) 2023; 37:2855-2863. [PMID: 36859600 PMCID: PMC10517126 DOI: 10.1038/s41433-023-02439-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 11/04/2022] [Accepted: 02/01/2023] [Indexed: 03/03/2023] Open
Abstract
Intravitreal injections of antiangiogenic agents are pivotal in treating neovascular age-related macular degeneration (nAMD). The comparative efficacy and safety of treat-and-extend (T&E) versus bimonthly, monthly, and pro re nata (PRN) dosing remains unclear. A systematic review and meta-analysis of English-language RCTs reporting on efficacy and/or safety outcomes of dosing regimens of anti-VEGF agents in nAMD was performed. Best-corrected visual acuity (BCVA, ETDRS letters) at last follow-up represented the primary endpoint, while central subfield thickness (CSFT, μm), injection burden, and ocular adverse events were secondary endpoints. A random effects meta-analysis was performed, and 95% confidence intervals were calculated. Across six RCTs, 781 T&E-, 663 monthly-, 130 PRN-, and 123 bimonthly treated eyes were included. Mean changes in BCVA and CSFT at last follow-up were similar between T&E versus monthly (WMD, -0.62 letters; 95% CI, -2.12 to 0.87; P = 0.41; WMD, 5.30 microns; 95% CI, -10.67 to 21.26; P = 0.52, respectively), bimonthly (WMD, 1.68 letters; 95% CI, -3.55 to 6.91; P = 0.53; WMD, -18.91 microns; 95% CI, -46.41 to 8.60; P = 0.18, respectively), and PRN (BCVA WMD, 1.08 letters; 95% CI, -2.95 to 5.11; P = 0.60) regimens. T&E was associated with a reduced injection burden versus monthly (WMD, -4.52 injections; 95% CI, -6.66 to 2.39; P < 0.001) but higher injection burden versus PRN (WMD, 1.81 injections; 95% CI, 1.12 to 2.51; P < 0.001) dosing. There was no significant difference in safety outcomes amongst comparators. There was no significant difference in efficacy and safety between T&E, bimonthly, monthly, and PRN dosing. T&E resulted in fewer injections versus monthly and fewer clinic visits versus PRN.
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Affiliation(s)
- Prem A H Nichani
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada
| | - Marko M Popovic
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada
| | - Arjan S Dhoot
- Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada
- Institute of Biomedical Engineering, Faculty of Applied Science and Engineering, University of Toronto, Toronto, ON, Canada
| | - Ananya Pathak
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, ON, Canada
| | - Rajeev H Muni
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada
- Department of Ophthalmology, St. Michael's Hospital/Unity Health Toronto, Toronto, ON, Canada
- Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, ON, Canada
| | - Peter J Kertes
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada.
- Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, ON, Canada.
- John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
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14
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Usui Y, Iwanishi H, Sumioka T, Ichikawa K, Miyajima M, Usui-Kusumoto K, Reinach PS, Okada Y, Saika S. WITHDRAWN: Engineered knockout of TRPA1 inhibits laser-induced choroidal neovascularization along with associated TGFb1 expression and neutrophil infiltration. J Transl Med 2023:100232. [PMID: 37567390 DOI: 10.1016/j.labinv.2023.100232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2023] [Revised: 07/20/2023] [Accepted: 07/20/2023] [Indexed: 08/13/2023] Open
Affiliation(s)
- Yuta Usui
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Hiroki Iwanishi
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Takayoshi Sumioka
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Kana Ichikawa
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Masayasu Miyajima
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Keiko Usui-Kusumoto
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
| | - Peter Sol Reinach
- Ophthalmology and Optometry, Wenzhou Medical University School, Wenzhou, China
| | - Yuka Okada
- Department of Ophthalmology, Wakayama Medical University Kihoku Hospital, Wakayama, Japan
| | - Shizuya Saika
- Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan
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15
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Rotenstreich Y, Sher I, Lawrence M, Mangelus M, Ingerman A, Barak Y. A Novel Device for Suprachoroidal Drug Delivery to Retina: Evaluation in Nonhuman Primates. Transl Vis Sci Technol 2023; 12:3. [PMID: 37289173 PMCID: PMC10257339 DOI: 10.1167/tvst.12.6.3] [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: 12/12/2022] [Accepted: 04/04/2023] [Indexed: 06/09/2023] Open
Abstract
Purpose Evaluation of distribution and tolerance of suprachoroidal injection of indocyanine green (ICG) in nonhuman primates (NHPs) using a novel suprachoroidal (SC) delivery technology. Methods Three live and three euthanized African green monkeys were injected with 150 or 200 µL ICG/eye into the SC space of both eyes, 2.5 mm posterior to the limbus in the inferior quadrant, utilizing a novel SC injector. Eyes were analyzed by imaging of scleral flatmounts. Live animals were observed for 24 hours for general health. Ophthalmic evaluation included slit-lamp biomicroscopy, tonometry, fundus imaging, confocal laser ophthalmoscopy, and spectral-domain optical coherence tomography (SD-OCT) before and at 10 minutes and 1, 3, and 24 hours post-injection. Results SC dosing was successfully performed in all eyes. Infrared fundus imaging demonstrated ICG distribution throughout the posterior segment, reaching the macula within 24 hours post-injection. No inflammation, intravitreal penetration, SC blebs, retinal detachment, or hemorrhages were detected. No significant changes were observed in retinal thickness by SD-OCT (P = 0.267, ANOVA). A mild, statistically insignificant elevation in intraocular pressure was observed within 10 minutes post-injection (mean ± standard error: 7.28 ± 5.09 mmHg; P = 0.061) and was spontaneously resolved within the first hour after dosing. Conclusions Suprachoroidal injection of 150 to 200 µL ICG dye was successfully performed and well tolerated in NHP eyes, with rapid distribution into the macular region and throughout the posterior pole. Translational Relevance This novel SC drug delivery system may potentially provide safe and effective delivery of therapeutics to the posterior pole region in humans.
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Affiliation(s)
- Ygal Rotenstreich
- The Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel
- The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Ifat Sher
- The Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel
- The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
- TELEM Rubin Excellence in Biomedical Research Program, Sheba Medical Center, Tel Hashomer, Israel
| | | | | | | | - Yoreh Barak
- Department of Ophthalmology, Rambam Health Care Campus, Haifa, Israel
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16
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Nawash B, Ong J, Driban M, Hwang J, Chen J, Selvam A, Mohan S, Chhablani J. Prognostic Optical Coherence Tomography Biomarkers in Neovascular Age-Related Macular Degeneration. J Clin Med 2023; 12:jcm12093049. [PMID: 37176491 PMCID: PMC10179658 DOI: 10.3390/jcm12093049] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/13/2023] [Accepted: 04/19/2023] [Indexed: 05/15/2023] Open
Abstract
Optical coherence tomography has revolutionized the diagnosis and management of neovascular age-related macular degeneration. OCT-derived biomarkers have the potential to further guide therapeutic advancements with anti-vascular endothelial growth factor; however, the clinical convergence between these two tools remains suboptimal. Therefore, the aim of this review of literature was to examine the current data on OCT biomarkers and their prognostic value. Thirteen biomarkers were analyzed, and retinal fluid had the strongest-reported impact on clinical outcomes, including visual acuity, clinic visits, and anti-VEGF treatment regimens. In particular, intra-retinal fluid was shown to be associated with poor visual outcomes. Consistencies in the literature with regard to these OCT prognostic biomarkers can lead to patient-specific clinical decision making, such as early-initiated treatment and proactive monitoring. An integrated analysis of all OCT components in combination with new efforts toward automated analysis with artificial intelligence has the potential to further improve the role of OCT in nAMD therapy.
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Affiliation(s)
- Baraa Nawash
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Joshua Ong
- Michigan Medicine, University of Michigan, Ann Arbor, MI 48104, USA
| | - Matthew Driban
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Jonathan Hwang
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Jeffrey Chen
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Amrish Selvam
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Sashwanthi Mohan
- Ophthalmology, Medcare Hospital LLC, Dubai P.O. Box 215565, United Arab Emirates
- Education and Research, Rajan Eye Care Hospital Pvt Ltd., Chennai 600042, India
| | - Jay Chhablani
- Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
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17
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Lüke JN, Alquoqa H, Alsamman A, Aljabary B, Schaub F, Heindl LM. Retrospective analysis of OCT parameters after intravitreal anti-VEGF inhibitors in neovascular AMD patients in a real-world setting. Int Ophthalmol 2023; 43:13-25. [PMID: 35781595 PMCID: PMC9902313 DOI: 10.1007/s10792-022-02383-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 06/14/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of the present study was to evaluate changes of best corrected visual acuity (BCVA), retinal nerve fiber layer thickness (RNFL), total macular volume (TMV), intraocular pressure (IOP) and central retinal thickness (CRT) after intravitreal injection of ranibizumab, bevacizumab and aflibercept in patients with neovascular age-related macular degeneration (nAMD) in a clinical real world setting. METHODS In a retrospective clinical study design, 120 patients (80 women and 40 men) were analyzed after being diagnosed with nAMD within 8 years (2010-2018). Every patient received at least 6 anti-VEGF injections in a Pro-Re-Nata or Treat-and-Extend regimen. OCT parameters (RNFL, TMV, CRT) and visual acuity (BCVA) were assessed at first diagnosis, at treatment day and during the course. RESULTS Intraretinal fluid was reduced significantly in a magnitude of 88-64 µm (CRT) and 0.75-0.55 mm3 (TMV). Apart from a significant reduction immediately after the therapy start (post-3 injections) with ranibizumab (- 1.4 µm, p = 0.03), RNFL thickness remained constant. A slight improvement in visual acuity of 0.06 logMAR could initially be observed. If further injections were required, only stabilization was achieved compared to baseline visual acuity. CONCLUSION The changes of OCT parameters CRT, TMV, and RNFL as well as the stabilization of functional results (BCVA) as illustrated in this study comparing effects of different anti-VEGF-agents provide evidence for the transferability of former results to a clinical real-world setting.
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Affiliation(s)
- Jan Niklas Lüke
- Department of Ophthalmology, Faculty of Medicine and University Hospital, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
| | | | | | | | - F Schaub
- Department of Ophthalmology, Faculty of Medicine and University Hospital, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
- Universitätsmedizin Rostock, Klinik und Poliklinik für Augenheilkunde, Rostock, Germany
| | - L M Heindl
- Department of Ophthalmology, Faculty of Medicine and University Hospital, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
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CHARACTERISTICS OF AGE-RELATED MACULAR DEGENERATION SHOWING A POOR RESPONSE TO THREE LOADING DOSES OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR. Retina 2023; 43:8-15. [PMID: 36161992 DOI: 10.1097/iae.0000000000003628] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 09/17/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE To analyze the clinical features of refractory age-related macular degeneration patients associated with the response to three consecutive loading doses of anti-vascular endothelial growth factor. METHODS A retrospective chart review was performed on typical exudative age-related macular degeneration patients treated by three consecutive anti-vascular endothelial growth factor injections. The patients were divided into a group without residual fluid on optical coherence tomography images (Group 1) and a group with residual fluid (Group 2). We analyzed qualitative and quantitative morphologic features of optical coherence tomography and optical coherence tomography angiography. We performed univariate and multivariate logistic regression analyses to identify factors associated with the treatment response. RESULTS We enrolled a total of 90 patients (Group 1: n = 60, Group 2: n = 30). Under optical coherence tomography, the choroidal thickness differed significantly between groups 1 and 2 (246.60 ± 67.67 vs. 286.90 ± 40.92 µ m, P = 0.001). Under optical coherence tomography angiography, the presence of branching (48.3% vs. 73.3%, P = 0.024), loops (31.7% vs. 66.7%, P = 0.002), and a peripheral arcade (40.0% vs. 76.7%, P = 0.001) differed significantly. Logistic regression analysis showed that the initial CT (B = 0.012; P = 0.007), presence of loops (B = 1.289; P = 0.015), and peripheral arcade (B = 1.483; P = 0.008) significantly affected the anti-vascular endothelial growth factor treatment response. CONCLUSION A thicker choroid and the presence of loops and a peripheral arcade were significantly associated with a poorer response to three loading anti-vascular endothelial growth factor injections in typical exudative age-related macular degeneration patients.
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19
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Hashimoto Y, Okada A, Matsui H, Yasunaga H, Aihara M, Obata R. Recent trends in anti-vascular endothelial growth factor intravitreal injections: a large claims database study in Japan. Jpn J Ophthalmol 2023; 67:109-118. [PMID: 36508060 PMCID: PMC9742668 DOI: 10.1007/s10384-022-00969-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 10/20/2022] [Indexed: 12/14/2022]
Abstract
PURPOSE To clarify recent trends in the use of intravitreal injections of anti-vascular endothelial growth factor (VEGF) in Japan. STUDY DESIGN Retrospective cohort study. METHODS We used the DeSC database, a large-scale claims database for Japan, for entries between April 2014 and March 2021. We counted the number of anti-VEGF drug injections (aflibercept, ranibizumab, brolucizumab, and pegaptanib) administered every year, calculated the sex- and age-adjusted injection rates, and stratified these rates according to sex, age categories, anti-VEGF drugs, and diagnoses. We also calculated the number of injections administered within one year after the first injection according to the diagnoses. RESULTS In total, 164,451 cases of anti-VEGF injections were identified. The sex- and age-adjusted rates of anti-VEGF injections per 1000 person-years increased from 7.9 in 2014 to 16.1 in 2020. Men were approximately twice as likely to receive anti-VEGF injections than women. The 70-79, 80-89, and ≥90 age categories had the highest rates, accounting for approximately 80%. Neovascular age-related macular degeneration had the highest rate, accounting for 60-70% over the study period. Aflibercept was the most commonly used drug, accounting for approximately 80% over the study period. The average number of injections within one year after the first injection was 4.4 for neovascular age-related macular degeneration, 2.7 for branch retinal vein occlusion, 3.1 for central retinal vein occlusion, and 3.5 for diabetic macular edema in 2020. CONCLUSION These findings can be used as a benchmark for the clinical practice of anti-VEGF therapy.
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Affiliation(s)
- Yohei Hashimoto
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan ,Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Akira Okada
- Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroki Matsui
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
| | - Hideo Yasunaga
- Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033 Japan
| | - Makoto Aihara
- Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryo Obata
- Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Current and Novel Therapeutic Approaches for Treatment of Neovascular Age-Related Macular Degeneration. Biomolecules 2022; 12:biom12111629. [PMID: 36358978 PMCID: PMC9688017 DOI: 10.3390/biom12111629] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/10/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
Age-related macular degeneration AMD is one of the leading causes of blindness in the elderly population. An advanced form of AMD known as neovascular AMD (nAMD) is implicated as the main attributor of visual loss among these patients. The hallmark feature of nAMD is the presence of neovascular structures known as choroidal neovascular membranes (CNVs), along with fluid exudation, hemorrhages, and subretinal fibrosis. These pathological changes eventually result in anatomical and visual loss. A type of proangiogenic factor known as vascular endothelial growth factor (VEGF) has been known to mediate the pathological process behind nAMD. Therefore, therapy has transitioned over the years from laser therapy that ablates the lesions to using Anti-VEGF to target the pathology directly. In this work, we provide an overview of current and emerging therapies for the treatment of nAMD. Currently approved Anti-VEGF agents include ranibizumab, aflibercept, and brolucizumab. Bevacizumab, also an Anti-VEGF agent, is used to manage nAMD even though this is an off-label use. While Anti-VEGF agents have provided a favorable prognosis for nAMD, they are associated with a substantial financial burden for patients and the healthcare system, due to their high cost as well as the need for frequent repeat treatments and visits. Emerging therapies and studies aim to extend the intervals between required treatments and introduce new treatment modalities that would improve patients’ compliance and provide superior results.
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Sakamoto T, Shimura M, Kitano S, Ohji M, Ogura Y, Yamashita H, Suzaki M, Mori K, Kozawa M, Yap PS, Kaneko T, Ishibashi T, for the MERCURY Study Group
OhHideyasuSugimotoMasahikoKogoJiroTakagiHitoshiMitamuraYoshinoriImaizumiHirokoKusuharaSentaroOgataNahokoTakamuraYoshihiroMurakamiTomoakiTakeuchiMasaruToriyamaYuichiHiranoTakaoYoshidaShigeoHisatomiToshioIshikawaKeijiroHirakataAkitoOkamotoFumikiAbeSachiNishiKatsuhiroSawadaOsamuNozakiMiho. Two-year visual and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY). BMJ Open Ophthalmol 2022; 7:e001069. [PMCID: PMC9621165 DOI: 10.1136/bmjophth-2022-001069] [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] [Indexed: 11/06/2022] Open
Abstract
Objective We report the 2-year visual and psychological outcomes of the MERCURY study, examining the long-term effectiveness and safety of ranibizumab and subsequent therapy in Japanese patients with diabetic macular oedema with impaired visual acuity (VA) in the real-world setting. Methods and analysis This was a 24-month, phase 4, open-label, single-arm, multicentre, prospective, observational study. Following an initial dose of ranibizumab (0.5 mg) by intravitreal injection (0.05 mL), treatment was administered as needed after month 1. The primary treated eye (PTE) was the first eye that received a ranibizumab injection. Results In total, 209 patients were enrolled; 192 (91.9%) and 174 (83.3%) completed months 12 and 24, respectively. In the PTE set, mean±SD changes in best-corrected VA (BCVA) from baseline to months 12 (primary endpoint) and 24 were −0.08±0.35 (p=0.015) and −0.13±0.30 (p<0.001) logarithmic minimum angle of resolution, respectively. Mean±SD central subfoveal thickness (CSFT) changes from baseline to months 12 and 24 were −102.3±146.1 µm (p<0.001) and −103.6±157.2 µm (p<0.001), respectively. Patients receiving three injections during the first 2 months had greater BCVA improvements throughout the study than those receiving 1–2 consecutive injections. Overall, 91 (43.5%) and 130 (62.2%) patients had ocular and non-ocular adverse events, respectively. At month 24, the mean±SD Hospital Anxiety and Depression Scale (HADS)-Anxiety and HADS-Depression scores decreased by 0.44±3.75 (p=0.196) and 0.19±3.38 (p=0.541), respectively. Conclusions At 24 months after initiation of ranibizumab and subsequent treatment, patients showed significant BCVA and CSFT improvements. Long-term treatment was considered safe and tolerable and did not lead to worsened psychological status.
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Affiliation(s)
- Taiji Sakamoto
- Department of Ophthalmology, Kagoshima University, Kagoshima, Japan
| | - Masahiko Shimura
- Department of Ophthalmology, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan
| | - Shigehiko Kitano
- Diabetes Center, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Masahito Ohji
- Department of Ophthalmology, Shiga University of Medical Science, Otsu, Japan
| | - Yuichiro Ogura
- Genentech Inc, South San Francisco, California, USA (present affiliation),Department of Ophthalmology and Visual Science, Nagoya City University, Nagoya, Japan
| | - Hidetoshi Yamashita
- Department of Ophthalmology and Visual Sciences, Yamagata University, Yamagata, Japan
| | - Makoto Suzaki
- Medical Division, Novartis Pharma K.K, Minato-ku, Tokyo, Japan
| | - Kimie Mori
- Medical Division, Novartis Pharma K.K, Minato-ku, Tokyo, Japan
| | - Masanari Kozawa
- Medical Division, Novartis Pharma K.K, Minato-ku, Tokyo, Japan
| | - Poh Sin Yap
- Novartis Corporation Sdn. Bhd, Selangor, Malaysia
| | - Takeumi Kaneko
- Medical Division, Novartis Pharma K.K, Minato-ku, Tokyo, Japan
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22
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Victor AA, Putri YM. Pro re nata versus fixed aflibercept regimen for neovascular age-related macular degeneration: a systematic review and meta-analysis. Int J Retina Vitreous 2022; 8:67. [PMID: 36138445 PMCID: PMC9503225 DOI: 10.1186/s40942-022-00416-x] [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: 06/29/2022] [Accepted: 09/01/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Aflibercept is a relatively new anti-VEGF used to treat neovascular age-related macular degeneration (AMD). The purpose of this review is to evaluate the effect of pro re nata (PRN) and fixed regimen (bimonthly) of aflibercept injection for neovascular AMD on visual outcomes at 12 months of follow-up. METHODS We conducted a systematic search in PubMed (MEDLINE), Embase, Scopus, and Web of Science, EBSCOHost, and ClinicalTrials.gov databases. Number of injections, number of hospital visit, mean change of best corrected visual acuity (BCVA), mean change of central macular thickness (CMT), and adverse effects of the included studies were evaluated. Meta-analysis were performed using Review Manager 5.4. RESULTS Four studies were selected for meta-analyses synthesis (3 RCT, 1 retrospective study). A total of 197 eyes in PRN group and 241 eyes in the fixed group. All four studies favored fixed regimen with standardized mean difference of 0.56 (95% CI 0.36-0.75, I2 = 0%, p < 0.00001). There was no significant difference in CMT between both group with SMD of 0.17 (95% CI - 0.14-0.48, I2 = 26%, p = 0.28). CONCLUSION The present meta-analysis shows that bimonthly injection of aflibercept for neovascular AMD is superior compared to PRN injection, shown by better improvement in BCVA at 12 months follow-up. However, high risk of bias downgrade the certainty of evidence.
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Affiliation(s)
- Andi Arus Victor
- Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
| | - Yan Martha Putri
- Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia
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The impact of retinal fluid tolerance on the outcomes of neovascular age-related macular degeneration treated using aflibercept: A real-world study. PLoS One 2022; 17:e0271999. [PMID: 35900984 PMCID: PMC9333245 DOI: 10.1371/journal.pone.0271999] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 07/05/2022] [Indexed: 11/19/2022] Open
Abstract
This study investigated the impact of retinal fluid tolerance on retinal thickness and visual acuity in patients with neovascular age-related macular degeneration after 18 months of treatment using intravitreal aflibercept. This retrospective study was based on the medical records of 90 eyes presenting persistent or recurrent retinal fluid retention after 3 months of aflibercept loading injections. We defined the fluid tolerance ratio as the sum of fluid-tolerance duration divided by the total duration of retinal fluid observed throughout the follow-up period. Eyes were categorized into strict, intermediate, and relaxed group based on their fluid tolerance ratio (= 0, <30%, > = 30%, respectively). The mean total follow-up time was 556 days. The relaxed group required fewer injections than the strict group (4.92 vs 7.50 injections, P < 0.01) and presented a similar reduction in retinal thickness (-57.50 vs -71.65 μm, P = 0.83). Nonetheless, the two groups were similar in terms of final visual acuity (logarithm of the minimum angle of resolution 0.72 vs 0.70, P = 0.95) and visual gains (4.21 vs -1.12 letters, P = 0.56). These results indicate that in the setting of limited medical resources, a fluid-tolerant approach provides comparable gains in visual acuity. Reducing the number of injections may also improve adherence to therapy.
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Schroeder M, Westborg I, Fluur C, Olsen R, Lövestam‐Adrian M. Exploration of real-world outcomes and treatment patterns in patients treated with anti-vascular endothelial growth factors for neovascular age-related macular degeneration in Sweden. Acta Ophthalmol 2022; 100:e928-e935. [PMID: 34543528 DOI: 10.1111/aos.15025] [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: 01/19/2021] [Accepted: 08/31/2021] [Indexed: 11/29/2022]
Abstract
PURPOSE To analyse and compare the number and interval of anti-vascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD), as well as the visual development in patients followed up for one to three years in clinical practice and during different index periods. METHODS This observational study included treatment-naïve eyes with nAMD from the Swedish Macula Register that started treatment between 2007 and 2017, stratified by different index periods (2007-2010, 2011-2013, 2014-2015 and 2016-2017) and by follow-up cohorts for each index period of one, two or three years (cohorts 1-3). Their intravitreal anti-VEGF treatment was assessed by number of injections, injection intervals, visual acuity (VA) and near VA change. RESULTS From the earliest index period 2007-2010 to the latest 2016-2017, the number of injections increased for the comparable follow-up time; 6.2 ± 1.4 versus 8.3 ± 2.0 injections after 1 year of treatment, 4.8 ± 1.6 versus 6.7 ± 2.4 during year 2. The last injection interval was 73 ± 34 days after 1, 71 ± 33 after 2 and 67 ± 32 after 3 years of follow-up for the index period 2014-2015. For the same period, the percentage of eyes with at least two consecutive 12-16 weeks of injection interval over 1-, 2- and 3-year follow-up increased from 5.2%, 15.0%, to 17.5% respectively. Baseline VA for eyes indexed 2016-2017 increased and presented with 62.1 ± 13.4 letters compared with 57.7 ± 13.5 letters in 2007-2010; p < 0.0001. CONCLUSIONS From the earliest to the latest index periods, the number of injections increased for the comparable follow-up time. Accordingly, baseline VA and near VA and their outcomes improved continuously.
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Affiliation(s)
- Marion Schroeder
- Divison of Ophthalmology Department of Clinical Sciences Lund Lund University Skane University Hospital Lund Sweden
| | - Inger Westborg
- Department of Neuroscience, Ophthalmology Uppsala University Uppsala Sweden
| | | | | | - Monica Lövestam‐Adrian
- Divison of Ophthalmology Department of Clinical Sciences Lund Lund University Skane University Hospital Lund Sweden
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Genetic Association Analysis of Anti-VEGF Treatment Response in Neovascular Age-Related Macular Degeneration. Int J Mol Sci 2022; 23:ijms23116094. [PMID: 35682771 PMCID: PMC9181567 DOI: 10.3390/ijms23116094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/26/2022] [Accepted: 05/27/2022] [Indexed: 02/01/2023] Open
Abstract
Anti-VEGF treatment for neovascular age-related macular degeneration (nAMD) has been FDA-approved in 2004, and since then has helped tens of thousands of patients worldwide to preserve vision. Still, treatment responses vary widely, emphasizing the need for genetic biomarkers to robustly separate responders from non-responders. Here, we report the findings of an observational study compromising 179 treatment-naïve nAMD patients and their reaction to treatment after three monthly doses of anti-VEGF antibodies. We show that established criteria of treatment response such as visual acuity and central retinal thickness successfully divides our cohort into 128 responders and 51 non-responders. Nevertheless, retinal thickness around the fovea revealed significant reaction to treatment even in the formally categorized non-responders. To elucidate genetic effects underlying our criteria, we conducted an undirected genome-wide association study followed by a directed replication study of 30 previously reported genetic variants. Remarkably, both approaches failed to result in significant findings, suggesting study-specific effects were confounding the present and previous discovery studies. Of note, all studies so far are greatly underpowered, hampering interpretation of genetic findings. In consequence, we highlight the need for an extensive phenotyping study with sample sizes exceeding at least 15,000 to reliably assess anti-VEGF treatment responses in nAMD.
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26
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Rocha JV, Marques AP, Macedo AF, Afonso-Silva M, Laires P, Almeida AS, Fernandes J, Pardal M, Santana R. Trends, geographical variation and factors associated with the use of anti-VEGF intravitreal injections in Portugal (2013-2018): a retrospective analysis of administrative data. BMJ Open 2022; 12:e055478. [PMID: 35387817 PMCID: PMC8987746 DOI: 10.1136/bmjopen-2021-055478] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
AIMS The arrival of anti-vascular endothelial growth factor (anti-VEGF) therapies represented a treatment shift for several ophthalmological disorders and led to an increasing number of patients undergoing intravitreal injections. The aims of this observational study were to assess the expansion of anti-VEGF intravitreal injections in the Portuguese National Health System (NHS) and to identify factors correlated with geographical variations in episode rates. METHODS Administrative database on discharge from Portuguese NHS hospitals was analysed for annual values and rates of intravitreal anti-VEGF injections at a national and regional level, between 2013 and 2018. RESULTS The number of episodes of anti-VEGF treatment and patients treated increased 16% and 9% per year, respectively, between 2013 and 2018. During the study period around 72% of patients were treated in the Metropolitan areas of Lisbon and Porto and in the Central region. Intravitreal anti-VEGF treatment rates in 2018 were 560 per 100 000 population and presented high variability between municipalities. Higher anti-VEGF treatment rates at the municipality level were associated with shorter distances between their residence and the hospital. At the hospital level, higher ratio of ophthalmologists and higher organisational level were associated with higher anti-VEGF treatment rates. CONCLUSION The number of episodes and patients treated with anti-VEGF injections has been growing in recent years. Proximity to healthcare, more access to ophthalmologists and hospitals with higher organisational levels are associated with higher anti-VEGF treatment rates. Improving access is crucial to reduce regional discrepancies and ensure optimal treatment frequency, which may improve health outcomes.
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Affiliation(s)
- João Victor Rocha
- National School of Public Health, NOVA University Lisbon, Lisboa, Portugal
- Comprehensive Health Research Centre, National School of Public Health, NOVA University Lisbon, Lisboa, Portugal
| | - Ana Patricia Marques
- National School of Public Health, NOVA University Lisbon, Lisboa, Portugal
- Comprehensive Health Research Centre, National School of Public Health, NOVA University Lisbon, Lisboa, Portugal
| | | | | | - Pedro Laires
- National School of Public Health, NOVA University Lisbon, Lisboa, Portugal
- HE&OR, Novartis Farma, Produtos Farmacêuticos SA, Porto Salvo, Portugal
| | - Ana Sofia Almeida
- Medical Affairs, Novartis Farma, Produtos Farmacêuticos SA, Porto Salvo, Portugal
| | - Julieta Fernandes
- Medical Affairs, Novartis Farma, Produtos Farmacêuticos SA, Porto Salvo, Portugal
| | - Marisa Pardal
- HE&OR, Novartis Farma, Produtos Farmacêuticos SA, Porto Salvo, Portugal
| | - Rui Santana
- National School of Public Health, NOVA University Lisbon, Lisboa, Portugal
- Comprehensive Health Research Centre, National School of Public Health, NOVA University Lisbon, Lisboa, Portugal
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Matonti F, Korobelnik JF, Dot C, Gualino V, Soler V, Mrejen S, Delyfer MN, Baillif S, Streho M, Gascon P, Creuzot-Garcher C, Kodjikian L. Comparative Effectiveness of Intravitreal Anti-Vascular Endothelial Growth Factor Therapies for Managing Neovascular Age-Related Macular Degeneration: A Meta-Analysis. J Clin Med 2022; 11:1834. [PMID: 35407439 PMCID: PMC8999505 DOI: 10.3390/jcm11071834] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/09/2022] [Accepted: 03/16/2022] [Indexed: 12/11/2022] Open
Abstract
Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) have become the standard of care for age-related macular degeneration (AMD). Although most pivotal trials have used monthly injections, alternative strategies that enable the injections to be administered on a more flexible schedule, including pro re nata (PRN) and treat-and-extend (T&E) regimens, are being applied more frequently. This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. To this end, a systematic review of published randomized studies was conducted from the MEDLINE and EMBASE databases and the Cochrane library, and a meta-analysis was applied to the obtained data using single-means modeling to compare the efficacy and maintenance among the different available treatments and regimens at Years 1 and 2. Quality analysis identified the best-informed data for modeling purposes. Overall, 47 relevant publications were retrieved for the analysis. Superior efficacy, meaning that there were observed improvements in visual acuity (VA) and central retinal thickness (CRT), occurred with monthly versus PRN regimens, yet a higher IVI number was also observed. Conversely, the T&E regimens displayed similar efficacy to the monthly regimens, but with a reduced IVI number. Aflibercept T&E exhibited similar efficacy to ranibizumab T&E, but with significantly lower IVI numbers at both Year 1 (p < 0.0001) and Year 2 (p = 0.0011). Though all of the regimens resulted in maintained efficacy between Years 1 and 2, the required IVI number varied. The retrieved data did not enable other regimens or newer anti-VEGF agents such as brolucizumab to be compared. In conclusion, the T&E regimens were shown to be the most efficient, optimizing durable effectiveness whilst minimizing the IVI number in newly diagnosed exudative AMD, with aflibercept requiring the lowest IVI number.
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Affiliation(s)
- Frédéric Matonti
- Centre Monticelli Paradis, 433 Bis Rue Paradis, 13008 Marseille, France;
- National Center for Scientific Research (CNRS), Timone Neuroscience Institue (INT), Aix Marseille University, 13008 Marseille, France
- Groupe Almaviva Santé, Clinique Juge, 13008 Marseille, France
| | - Jean-François Korobelnik
- Department of Ophthalmology, Bordeaux University Hospital, 33000 Bordeaux, France; (J.-F.K.); (M.-N.D.)
- INSERM, BPH, UMR1219, Bordeaux University, 33000 Bordeaux, France
| | - Corinne Dot
- Department of Ophthalmology, Desgenettes Military Hospital, 69003 Lyon, France;
| | - Vincent Gualino
- Clinique Honoré Cave, Department of Ophthalmology, 82000 Montauban, France;
- Unité de Rétine, Ophthalmology Department, Hôpital Pierre-Paul Riquet, Toulouse University Hospital, 31300 Toulouse, France;
- Place Baylac, TSA 40031, CEDEX 9, 31059 Toulouse, France
- Ophthalmology Department, AP-HP, Hôpital Lariboisière, Université de Paris, 75014 Paris, France
| | - Vincent Soler
- Unité de Rétine, Ophthalmology Department, Hôpital Pierre-Paul Riquet, Toulouse University Hospital, 31300 Toulouse, France;
- University Toulouse III, 31000 Toulouse, France
- CERCO UMR 5549, Centre National de la Recherche Scientifique, 31000 Toulouse, France
| | - Sarah Mrejen
- Centre d’Imagerie et de Laser, 75015 Paris, France;
- Centre Hospitalier National Ophtalmologique des 1520, 75012 Paris, France
| | - Marie-Noëlle Delyfer
- Department of Ophthalmology, Bordeaux University Hospital, 33000 Bordeaux, France; (J.-F.K.); (M.-N.D.)
- INSERM, BPH, UMR1219, Bordeaux University, 33000 Bordeaux, France
| | - Stéphanie Baillif
- Department of Ophthalmology, Pasteur 2 University Hospital, Côte d’Azur University, 06108 Nice, France;
| | - Maté Streho
- Explore Vision Centre, 75001 Paris, France;
- Department of Ophthalmology, Lariboisière Hospital, 75010 Paris, France
| | - Pierre Gascon
- Centre Monticelli Paradis, 433 Bis Rue Paradis, 13008 Marseille, France;
- Department of Ophthalmology, Aix-Marseille University, Hôpital Nord, Chemin des Bourrely, 13008 Marseille, France
| | | | - Laurent Kodjikian
- Department of Ophthalmology, Croix-Rousse University Hospital, Hospices Civils de Lyon, 69002 Lyon, France;
- UMR-CNRS 5510 Matéis, University of Lyon, 69622 Villeurbanne, France
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Scondotto G, Sultana J, Vadalà M, Avitabile T, Cillino S, Foti SS, Labbate L, Longo A, Mirabelli E, Puzo MR, Rapisarda C, Ibanez Toro P, Trombetta CJ, Trifirò G, Virgili G. Assessment of intravitreal anti-VEGF drugs and dexamethasone for retinal diseases in real world setting: A multi-centre prospective study from Southern Italy. Eur J Ophthalmol 2022; 32:3064-3073. [PMID: 35075918 DOI: 10.1177/11206721211073402] [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: 11/17/2022]
Abstract
Describe drug utilisation and clinical outcomes of intravitreal anti-VEGF drug and dexamethasone use in the real-world setting in Southern Italy using data from multi-centre study of retinal disease. Clinical data of retinal disease patients treated with anti-VEGF drugs and dexamethasone implant in 6 out-patient ophthalmology centres from Southern Italy were collected by means of an electronic case report form. Patients receiving at least one intravitreal injection/implant of the study drugs were followed for up to two years and described in terms of demographics and clinical characteristics. Drug utilisation patterns were described. A sign-rank test was used to compare clinical data on visual acuity and other ophthalmic parameters from baseline at different follow-up times for each indication. Data from 1327 patients was collected. Most patients were diagnosed with age-related macular degeneration (AMD) (660, 49.7%), followed by diabetic macular oedema (423, 31.9%), retinal vein occlusion (164, 12.3%), and myopic choroidal neovascularization (80, 6.0%). Patients were followed for a median of 10.3 months (interquartile range: 3.6 - 24.7 months). Mean patient age was 69.7 (±10.9) years and 54.2% were males. Ranibizumab (55.4%) and aflibercept (27.5%) were the most commonly used drugs. Baseline visual acuity significantly improved by about 0.05 to 0.1 logMAR at all follow-up times for AMD and RVO but less consistently for the other diseases. Intravitreal ranibizumab use accounted for half of all treatment for retinal diseases in a Southern Italian out-patient setting. Patients treated with anti-VEGF drugs for AMD and RVO in Southern Italy experienced significant improvement in VA.
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Affiliation(s)
- Giulia Scondotto
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, 18980University of Messina, Messina, Italy
| | - Janet Sultana
- Pharmacy Department, Mater Dei Hospital, Malta.,College of Medicine and Health, University of Exeter, Exeter, Malta
| | - Maria Vadalà
- Institute of European and Mediterranean Science and Technology (IEMEST), Palermo, Italy
| | - Teresio Avitabile
- Department of Ophthalmology, A. O. U. Policlinic-Vittorio Emanuele, Catania, Italy
| | - Salvatore Cillino
- Department of Biomedicine, Neuroscience and Advanced Diagnostic, Ophthalmology Section, University of Palermo, Palermo, Italy
| | - Saveria Serena Foti
- Academic spin-off "INSPIRE - Innovative Solutions For Medical Prediction And Big Data Integration In Real World Setting" - Azienda Ospedaliera Universitaria "G. Martino" Messina, Italy
| | - Luca Labbate
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, 18980University of Messina, Messina, Italy
| | - Antonio Longo
- Department of Ophthalmology, A. O. U. Policlinic-Vittorio Emanuele, Catania, Italy
| | - Eliana Mirabelli
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, 18980University of Messina, Messina, Italy
| | - Maria Rosalia Puzo
- Assistance and Pharmaceutical Services Office, Personal Policies Department, Basilicata Region, Potenza, Italy
| | - Carlo Rapisarda
- Department of Ophthalmology, A. O. U. Policlinic-Vittorio Emanuele, Catania, Italy
| | - Patricia Ibanez Toro
- Assistance and Pharmaceutical Services Office, Personal Policies Department, Basilicata Region, Potenza, Italy
| | - Costantino J Trombetta
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, 18980University of Messina, Messina, Italy
| | - Gianluca Trifirò
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Gianni Virgili
- Department of Neuroscience, Psychology, Drug Research and Clinical Health, University of Florence, Florence, Italy.,Centre for Public Health, Queen's University of Belfast (UK), Belfast, UK
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29
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To investigate treat and extend versus pro re nata regimen in neovascular age-related macular degeneration: results from the IDEM study. Graefes Arch Clin Exp Ophthalmol 2022; 260:2149-2156. [PMID: 35020019 DOI: 10.1007/s00417-021-05543-z] [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: 04/18/2021] [Revised: 12/17/2021] [Accepted: 12/27/2021] [Indexed: 11/04/2022] Open
Abstract
PURPOSE The purpose of this study is to report the 24-month outcomes of a pro re nata (PRN) compared with a treat and extend (T&E) regimen in patients previously treated for neovascular age-related macular degeneration (nAMD). METHODS This was a 2-year prospective, single-center study. Previously treated patients for nAMD were randomized into two regimen groups: T&E and PRN groups. Main outcome measured was change in best corrected visual acuity (BCVA) from baseline to month 24. Secondary outcomes encompassed anatomical features such as central retinal thickness (CRT), number of intravitreal injections (IVI), and visits required. RESULTS A total of 124 eyes received the T&E (n = 61) or PRN (n = 63) regimen. At month 24, the mean BCVA change was -4.4 early treatment diabetic retinopathy study (ETDRS) letters (T&E) and -3.4 ETDRS letters (PRN), with a difference of +1.1 ETDRS letters (95% CI [-2.25]; p = 0.006). The mean change in CRT was -10.6 µm (T&E) and -7.9 µm (PRN), with a difference of +2.6 µm (95% CI [+19.2]; p = 0.004). The T&E group had received a mean of +4.6 more injections (95% CI [-7.06; -2.12]; p < 0.001) at month 24. CONCLUSION There was statistically proven non-inferiority between the PRN and T&E regimens in terms of visual and anatomical outcomes at 24 months, with significantly more IVI administered in the T&E regimen.
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Yeung L, Hsieh YT, Yang CH, Chen LJ, Chen SJ, Cheng CK, Sheu SJ, Tsai CY, Wu TT, Wu WC, Chen SN. Management of neovascular age-related macular degeneration: Taiwan expert consensus. J Formos Med Assoc 2021; 120:2061-2071. [PMID: 34274193 DOI: 10.1016/j.jfma.2021.06.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 04/20/2021] [Accepted: 06/18/2021] [Indexed: 11/22/2022] Open
Abstract
Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss. The present consensus provides suggestions on diagnosis, evaluation, treatment, and follow-up strategies for nAMD from a panel of 11 practicing ophthalmologists. The experts suggest that the baseline visit for nAMD management should include a comprehensive ophthalmologic examination via a multimodal approach consisting of visual and anatomical evaluation. Patients diagnosed with nAMD should be subjected to treatment with the goal of maintaining visual function while diminishing anatomical disease activity and minimizing treatment burden. Currently, anti-VEGF therapy is the main treatment strategy for nAMD, and evaluation involving comprehensive ophthalmologic examination within 1 month of completion of the loading phase comprising three monthly injections is recommended to guide subsequent management. Either a treat-and-extend or pro re nata regimen can be considered for the maintenance phase of anti-VEGF therapy, and the regimen should be chosen and adjusted according to disease activity, reimbursement criteria, financial burden, and patient preferences. In the event of inactive nAMD or poor treatment outcomes, after thorough evaluation and patient education, anti-VEGF therapy may be stopped. The consensus provides practical nAMD management guidelines for ophthalmologists and fellow healthcare professionals.
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Affiliation(s)
- Ling Yeung
- Department of Ophthalmology, Chang Gung Memorial Hospital, Keelung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yi-Ting Hsieh
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chang-Hao Yang
- Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan; Department of Ophthalmology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Lee-Jen Chen
- Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Shih-Jen Chen
- Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Cheng-Kuo Cheng
- Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
| | - Shwu-Jiuan Sheu
- Department of Ophthalmology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan; Department of Ophthalmology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-Yao Tsai
- School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan
| | - Tsung-Tien Wu
- School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Chi Wu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Ophthalmology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - San-Ni Chen
- Department of Ophthalmology, Changhua Christian Hospital, Changhua, Taiwan; College of Medicine, Chung-Shan Medical University, Taichung, Taiwan; Department of Optometry, College of Nursing and Health Science, Da-Yeh University, Changhua, Taiwan.
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Kinoshita T, Mori J, Hatanaka A, Shimizu M, Imaizumi H. Visual Outcome and Treatment Frequency of Anti-VEGF Therapy Using the Treat-and-Extend and Treatment Cessation Regimen for Exudative Age-Related Macular Degeneration and Pachychoroid Neovasculopathy. Clin Ophthalmol 2021; 15:4405-4418. [PMID: 34795473 PMCID: PMC8593600 DOI: 10.2147/opth.s334641] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Accepted: 09/27/2021] [Indexed: 12/14/2022] Open
Abstract
Purpose To report the results of anti-vascular endothelial growth factor (VEGF) therapy using treat-and-extend (TAE) and treatment cessation regimens for exudative age-related macular degeneration (AMD) and pachychoroid neovasculopathy (PN). Methods We retrospectively studied 101 treatment-naïve eyes of 101 patients with exudative AMD and PN that underwent anti-VEGF therapy using TAE and treatment cessation regimen with a follow-up period of ≥12 months. Best-corrected visual acuity (BCVA), treatment frequency, and number of eyes with successful treatment cessation were measured. Successful treatment cessation was defined as dry macula retention without treatment for >16 weeks after the last injections. Factors related to the successful treatment cessation were evaluated. Results BCVA was maintained at the last visit with a mean follow-up period of 49.9 ± 26.9 months. The injection number decreased from 6.8 ± 2.31 at the first year to 3.7 ± 3.64 at the fifth year. At the last visit, 48 (47.5%) eyes were being treated at an interval of ≥12 weeks or were under treatment cessation. Successful treatment cessation during the follow-up period and at the last visit were achieved in 56 (55.4%) and 27 (26.7%) eyes, with a median treatment-free period of 66 and 126 weeks, respectively. Good early treatment response and a small recurrence number were associated with successful treatment cessation at the last visit. Conclusion Patients with good early response to treatment and fewer recurrences may achieve treatment cessation. This information could help physicians predict the achievement of treatment cessation for a considerable period.
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Affiliation(s)
- Takamasa Kinoshita
- Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan
| | - Junya Mori
- Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan
| | - Akira Hatanaka
- Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan
| | - Miho Shimizu
- Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan
| | - Hiroko Imaizumi
- Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan
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Teo KYC, Nguyen V, Barthelmes D, Arnold JJ, Gillies MC, Cheung CMG. Extended intervals for wet AMD patients with high retreatment needs: informing the risk during COVID-19, data from real-world evidence. Eye (Lond) 2021; 35:2793-2801. [PMID: 33239765 PMCID: PMC7688202 DOI: 10.1038/s41433-020-01315-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 10/28/2020] [Accepted: 11/10/2020] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND/OBJECTIVE Some clinicians may be forced to temporarily extend treatment intervals in neovascular age-related macular degeneration (nAMD) eyes with frequent retreatments to reduce the number of visits during the COVID-19 pandemic. To provide an indication of what these outcomes may be, we studied eyes with active lesions with unplanned treatment interval extensions before the pandemic occurred. METHODS We compared eyes with active disease despite ≤6 weekly injections whose next injection was extended to ≥7 weeks and those whose intervals were not extended. We identified 1559 (16%) of 9602 eyes from the Fight Retinal Blindness! (FRB!) registry (2013 and 2018) that fit this criteria. Eyes were further stratified into four groups by the mean interval over the following 6 months: (1) ≤6 weeks (81%), (2) 7-9 weeks (9%), (3) 10-12 weeks (5%) and (4) >12 weeks (5%). RESULTS There was a significant loss in VA in eyes extended to >12 weeks compared to the non-extended group (adjusted VA change, mean (95% CI): ≤6 weeks, 0.4 (-1.5 to 2.2), versus >12 weeks, -4.7 (-7.4 to -2.1), letters, p = 0.03 and a threefold increase in relative risk of losing ≥15 letters (absolute risk (14% versus 4%, p < 0.01)). CONCLUSION Mean VA remained stable for 6 months in eyes requiring frequent treatment despite retreatment interval extension up to 10-12 weeks. There was a significant short-term risk to vision when retreatment interval was extended beyond 12 weeks, hence extensions to this level should be considered cautiously. These data may be useful for physicians who are considering reducing visits to mitigate the risk of COVID-19.
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Affiliation(s)
- Kelvin Yi Chong Teo
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
- Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
- Save Sight Institute, University of Sydney, Sydney, NSW, Australia
| | - Vuong Nguyen
- Save Sight Institute, University of Sydney, Sydney, NSW, Australia
| | - Daniel Barthelmes
- Save Sight Institute, University of Sydney, Sydney, NSW, Australia
- University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | | | - Mark C Gillies
- Save Sight Institute, University of Sydney, Sydney, NSW, Australia
| | - Chui Ming Gemmy Cheung
- Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
- Duke-NUS Medical School, National University of Singapore, Singapore, Singapore.
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Topical Triamcinolone Acetonide-Loaded Liposome Formulation Used as an Adjuvant to Intravitreal Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration. Pharmaceutics 2021; 13:pharmaceutics13091491. [PMID: 34575567 PMCID: PMC8471461 DOI: 10.3390/pharmaceutics13091491] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/19/2021] [Accepted: 07/20/2021] [Indexed: 01/01/2023] Open
Abstract
Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the antiangiogenic (ranibizumab (RBZ)) and anti-inflammatory (triamcinolone acetonide (TA)) agents used to treat vitreoretinal diseases. One of the strategies includes liposomes. This study evaluated the safety and efficacy of a topical triamcinolone-loaded liposome formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment- naïve patients with neovascular age-related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) groups. Patients from the RBZ-TALF group were instructed to apply TALF for 12 months after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in the case of nAMD reactivation. Regarding safety, non-ocular abnormalities were observed during TALF therapy. Concerning efficacy, non-significant differences were identified in terms of visual acuity or central foveal thickness when the RBZ-PRN and RBZ-TALF groups were compared. It is worth noting that the average number of RBZ injections was significantly lower in the RBZ-TALF group (2.5 ± 1.4 vs. 6.1 ± 1.3 IVTs; p = 0.0004). Therefore, TALF used as an adjuvant to RBZ reduces the need for RBZ-IVT retreatment with optimal visual and anatomic results.
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Kim JH, Kim JW, Kim CG. Five-Year Reactivation After Ranibizumab or Aflibercept Treatment for Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy. J Ocul Pharmacol Ther 2021; 37:525-533. [PMID: 34520251 DOI: 10.1089/jop.2021.0051] [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: 11/13/2022] Open
Abstract
Purpose: To evaluate 5-year reactivation after ranibizumab or aflibercept treatment for neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). Methods: This retrospective study included 192 patients (192 eyes) who had been diagnosed with neovascular AMD or PCV and treated with ranibizumab or aflibercept. The incidence and timing of lesion reactivation during the 5-year follow-up period were evaluated, and the factors associated with reactivation were also investigated. Results: During the follow-up period, lesion reactivation was noted in 156 patients (81.3%) at a mean of 9.5 ± 10.5 months after the third antivascular endothelial growth factor injection. The incidence of reactivation was 59.9% during the first 12 months, 33.7% during ≥12 and <24 months, 11.8% during >24 and ≤36 months, 15.5% during >36 and ≤48 months, and 5.3% during >48 and ≤60 months. There was a significant difference in the incidence among the 5 periods (P < 0.001). The proportion of PCV was significantly higher in patients experiencing reactivation (51.9%) than in those who did not (30.6%) (P = 0.021). Conclusions: During the 5-year follow-up, lesion reactivation was noted in approximately four-fifths of the patients. The incidence of lesion reactivation was highest during the first 12 months and decreased thereafter. The incidence was higher in patients with PCV than in those with neovascular AMD, especially after 12 months.
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Affiliation(s)
- Jae Hui Kim
- Department of Ophthalmology, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, South Korea.,Kim's Eye Hospital Data Center, Seoul, South Korea
| | - Jong Woo Kim
- Department of Ophthalmology, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, South Korea
| | - Chul Gu Kim
- Department of Ophthalmology, Kim's Eye Hospital, Konyang University College of Medicine, Seoul, South Korea
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Bilgic A, Kodjikian L, Mathis T, Sudhalkar AA, Vasavada SA, Bhojwani DM. SINGLE INJECTION RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN PATIENTS WITH WET AGE-RELATED MACULAR DEGENERATION: Incidence and Characteristics. Retina 2021; 41:1901-1910. [PMID: 33411472 DOI: 10.1097/iae.0000000000003106] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
PURPOSE To determine the incidence of complete resolution of choroidal neovascular membrane-associated exudation with a single antivascular endothelial growth factor injection in treatment-naive wet age-related macular degeneration patients and its associated characteristics. METHODS Retrospective, observational study of naive wet age-related macular degeneration patients who received antivascular endothelial growth factor therapy with ranibizumab/aflibercept and demonstrated complete resolution of retinal exudation with a single injection. Complete resolution was defined as the total disappearance of the intraretinal fluid, cysts, and subretinal fluid and a return of retinal thickness to <250 μm on spectral-domain optical coherence tomography. All relevant data were collected. Follow-up was scheduled on Days 1, 7, and 30 postoperatively and then monthly, with at least 9 visits mandatory per year if the macula remained fluid free. Appropriate statistical analyses were performed. RESULTS Sixty-three patients (29 men; mean age 67.25 ± 4.40 years) were identified. The mean baseline and final-corrected distance visual acuity was 20/160 and 20/45, respectively. Patients completed a mean of 10.9 follow-up visits per year. Smaller choroidal neovascular membranes (<200 μm), early presentation, better presenting corrected distance visual acuity, subfoveal choroidal neovascular membranes, absence of blood/fibrosis, and use of aflibercept (2 mg) favored resolution with one injection. CONCLUSION A subset (13.76%; 63/458, 95% confidence intervals: 10.73-17.25) of patients with treatment-naive wet age-related macular degeneration demonstrates resolution of choroidal neovascular membrane-associated exudation with a single antivascular endothelial growth factor injection, sustained over 2 years or more. This can lower therapy costs, treatments, office visits, and the potential risk of geographic atrophy.
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Affiliation(s)
| | - Laurent Kodjikian
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
- Laboratoire UMR-CNRS 5510 Matéis, Université Lyon 1, Villeurbane, France
| | - Thibaud Mathis
- Service d'Ophtalmologie, Hôpital Universitaire de la Croix-Rousse, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
- Laboratoire UMR-CNRS 5510 Matéis, Université Lyon 1, Villeurbane, France
| | - Aditya A Sudhalkar
- Alphavision Augenzentrum, Bremerhaven, Germany
- Sudhalkar Eye Hospital and Retina Centre, Baroda, India ; and
- Raghudeep Eye Hospital, Ahmedabad, India
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Kim KT, Chae JB, Lee S, Seo EJ, Kim DY. Analyses of the effects of persistent subretinal fluid on visual/anatomic outcomes according to the type of macular neovascularization during the relaxed treat-and-extend protocol in age-related macular degeneration patients. BMC Ophthalmol 2021; 21:294. [PMID: 34376158 PMCID: PMC8356423 DOI: 10.1186/s12886-021-02063-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/26/2021] [Indexed: 11/10/2022] Open
Abstract
Background To analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients. Methods Patients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type. Results Seventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type. Conclusions Using a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.
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Affiliation(s)
- Kyung Tae Kim
- Department of Ophthalmology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, 776, Sunhwan-1-Ro, Seowon-Gu, Cheongju, 28644, South Korea
| | - Ju Byung Chae
- Department of Ophthalmology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, 776, Sunhwan-1-Ro, Seowon-Gu, Cheongju, 28644, South Korea
| | - Seungheon Lee
- Department of Ophthalmology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, 776, Sunhwan-1-Ro, Seowon-Gu, Cheongju, 28644, South Korea
| | - Eoi Jong Seo
- Department of Ophthalmology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, 776, Sunhwan-1-Ro, Seowon-Gu, Cheongju, 28644, South Korea
| | - Dong Yoon Kim
- Department of Ophthalmology, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, 776, Sunhwan-1-Ro, Seowon-Gu, Cheongju, 28644, South Korea.
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Stattin M, Ahmed D, Graf A, Haas AM, Kickinger S, Jacob M, Krepler K, Ansari-Shahrezaei S. The Effect of Treatment Discontinuation During the COVID-19 Pandemic on Visual Acuity in Exudative Neovascular Age-Related Macular Degeneration: 1-Year Results. Ophthalmol Ther 2021; 10:935-945. [PMID: 34374028 PMCID: PMC8351565 DOI: 10.1007/s40123-021-00381-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 07/23/2021] [Indexed: 01/08/2023] Open
Abstract
Introduction To evaluate the effect of a 9-week treatment deferral due to healthcare restrictions caused by Austria’s first governmental lockdown associated with the coronavirus disease 2019 (COVID-19) pandemic on visual acuity (VA) in eyes compromised by exudative neovascular age-related macular degeneration (nAMD) after 1 year. Methods Retrospective data collection of 98 eyes (98 patients) with a treatment discontinuation at a tertiary eye care center (Clinic Landstraße, Vienna Healthcare Group, Austria) between March 16 and May 4, 2020. Prior to the lockdown, patients received multiple intravitreal injections (IVI) of anti-vascular endothelial growth factor with a personalized treatment interval for 3 years on average and at least three IVI after the lockdown. Results When the treatment interval doubled to 117.6 ± 31.4 days in spring 2020, patients lost 2.2 ± 4.6 ETDRS letters (p = 0.002) on average before reinitiating therapy. In total, 4.1 ± 8.1 letters (p < 0.0001) were lost despite continuous individual re-treatment over the course of the next year. In a univariate analysis, the extended interval time remained statistically significant (p < 0.0001), indicating a larger VA reduction within intervals with increasing interval time in days. Conclusion The short-term treatment interruption had a persistent negative impact on the VA course of eyes under therapy after 1 year. Continuous therapy independent of the underlying treatment regimen remains of utmost importance in exudative nAMD. Our data should create awareness to regulators regarding future decisions despite the global pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00381-y. Age-related macular degeneration (AMD) is the leading cause of legal blindness in developed countries. Wet AMD refers to the existence of new vessel growth in the macular, the part of the retina with the highest concentration of photoreceptors and hence the best visual acuity. The gold standard therapy of wet AMD consists of repeated injections of an antibody against new vessel formation into the eye to stabilize the disease. The sudden break of a treatment regimen for an individual person has never been investigated as it is ethically not acceptable. The coronavirus disease 2019 (COVID-19) pandemic and its associated lockdown led to an emerging situation in spring, 2020. We were forced by governmental restrictions to minimize contact with the most vulnerable patient cohort—the elderly. As an initial consequence, the Medical Retina Unit of Department of Ophthalmology (Clinic Landstraße, Vienna Healthcare Group, Austria) postponed appointments of patients with only one eye afflicted by wet AMD. This study examined the effect of a short-term treatment deferral caused by the first national COVID-19 lockdown in eyes of patients with ongoing therapy of wet AMD in Austria. The break led to a persistent visual loss despite re-treatment, which was still evident after 1 year. Our findings provide further support for an adequate and permanent therapy of wet AMD and regard intravitreal injections as urgent standard of care. It should be taken into consideration by authorities in future pandemic planning.
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Affiliation(s)
- Martin Stattin
- Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria.,Medical Retina Unit, Clinic Landstraße, Department of Ophthalmology, Vienna Healthcare Group, Juchgasse 25, 1030, Vienna, Austria
| | - Daniel Ahmed
- Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria.,Medical Retina Unit, Clinic Landstraße, Department of Ophthalmology, Vienna Healthcare Group, Juchgasse 25, 1030, Vienna, Austria
| | - Alexandra Graf
- Center for Medical Statistic, Informatics, and Intelligent Systems, Medical University of Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Anna-Maria Haas
- Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria.,Medical Retina Unit, Clinic Landstraße, Department of Ophthalmology, Vienna Healthcare Group, Juchgasse 25, 1030, Vienna, Austria
| | - Stefan Kickinger
- Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria.,Medical Retina Unit, Clinic Landstraße, Department of Ophthalmology, Vienna Healthcare Group, Juchgasse 25, 1030, Vienna, Austria
| | - Michael Jacob
- Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria
| | - Katharina Krepler
- Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria.,Medical Retina Unit, Clinic Landstraße, Department of Ophthalmology, Vienna Healthcare Group, Juchgasse 25, 1030, Vienna, Austria
| | - Siamak Ansari-Shahrezaei
- Karl Landsteiner Institute for Retinal Research and Imaging, Vienna, Austria. .,Medical Retina Unit, Clinic Landstraße, Department of Ophthalmology, Vienna Healthcare Group, Juchgasse 25, 1030, Vienna, Austria. .,Medical School, Sigmund Freud University Vienna, Campus Prater Freudplatz 3, 1020, Vienna, Austria. .,Department of Ophthalmology, Medical University of Graz, Auenbruggerplatz 1, 8036, Graz, Austria.
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Kaiser PK, Wykoff CC, Singh RP, Khanani AM, Do DV, Patel H, Patel N. RETINAL FLUID AND THICKNESS AS MEASURES OF DISEASE ACTIVITY IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. Retina 2021; 41:1579-1586. [PMID: 33949342 PMCID: PMC8297539 DOI: 10.1097/iae.0000000000003194] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
PURPOSE Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration, as evidenced by clinical trials that have used these features for inclusion criteria, retreatment criteria, and outcome measures of the efficacy of intravitreal injections of anti-vascular endothelial growth factor agents. METHODS A literature review of anatomical measures of disease activity was conducted. RESULTS Treatment goals for neovascular age-related macular degeneration include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. The change in retinal thickness has been found to correlate with the change in the visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity, whereas the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice. CONCLUSION Retinal thickness and retinal fluid are common anatomical measures of disease activity in neovascular age-related macular degeneration. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in neovascular age-related macular degeneration.
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Affiliation(s)
- Peter K. Kaiser
- Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Charles C. Wykoff
- Retina Consultants of Texas, Retina Consultants of America, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas;
| | - Rishi P. Singh
- Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Arshad M. Khanani
- Sierra Eye Associates, Reno, Nevada
- University of Nevada, Reno School of Medicine, Reno, Nevada
| | - Diana V. Do
- Byers Eye Institute, Stanford University, Palo Alto, California; and
| | - Hersh Patel
- Novartis Pharmaceuticals, East Hanover, New Jersey
| | - Nikhil Patel
- Novartis Pharmaceuticals, East Hanover, New Jersey
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Choi YJ, Yoo WS, Cho YW, Choi YJ, Chung IY. One-year Outcomes of a Treat-and-extend of Ranibizumab for Naive Exudative Age-related Macular Degeneration: Retrospective Analysis. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2021. [DOI: 10.3341/jkos.2021.62.7.939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Purpose: This study investigated the 1-year outcomes of a treat-and-extend regimen of ranibizumab for exudative age-related macular degeneration and examined the clinical results when drug treatment was changed within the same period. Methods: This retrospective analysis included 32 eyes first diagnosed with wet age-related macular degeneration and treated for more than 1 year with a treat-and-extend regimen of ranibizumab, as well as 24 eyes treated by changing from ranibizumab to aflibercept within the same period. The injection number, maximum injection interval, change in central retinal thickness, and best-corrected visual acuity were assessed in all eyes. Results: In 32 eyes that received a treat-and-extend regimen of ranibizumab, the mean best-corrected visual acuity improved from 59.46 ± 15.13 to 68.00 ± 12.48 at 12 months (p < 0.0001). The mean central retinal thickness decreased from 409 ± 141 μm to 273 ± 89 μm at 12 months (p < 0.0001). The average number of injections per year was 7.2 ± 0.85. One complication related to the 12 months of injections was a tear in the retinal pigment epithelium; no systemic complications were observed. Of 24 eyes that underwent a change in medication, the rate of maintenance or improvement in initial visual acuity was 83% (10 eyes). The central retinal thickness was initially 371.58 ± 109.96 μm, but improved to 290.33 ± 58.66 μm in 12 eyes that received three injections of aflibercept. Conclusions: At 1 year, good outcomes were obtained using treat-and-extend ranibizumab for exudative age-related macular degeneration. When the treatment was changed to aflibercept within the same period, vision was often maintained and short-term anatomical improvement was evident.
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40
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Liefers B, Taylor P, Alsaedi A, Bailey C, Balaskas K, Dhingra N, Egan CA, Rodrigues FG, Gonzalo CG, Heeren TF, Lotery A, Müller PL, Olvera-Barrios A, Paul B, Schwartz R, Thomas DS, Warwick AN, Tufail A, Sánchez CI. Quantification of Key Retinal Features in Early and Late Age-Related Macular Degeneration Using Deep Learning. Am J Ophthalmol 2021; 226:1-12. [PMID: 33422464 DOI: 10.1016/j.ajo.2020.12.034] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 12/28/2020] [Accepted: 12/28/2020] [Indexed: 02/01/2023]
Abstract
PURPOSE We sought to develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD). DESIGN Development and validation of a deep-learning model for feature segmentation. METHODS Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2712 B-scans. A deep neural network was trained with these data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by 4 independent observers. The main outcome measures were Dice score, intraclass correlation coefficient, and free-response receiver operating characteristic curve. RESULTS On 11 of 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared with 0.61 ± 0.17 for the observers. The mean intraclass correlation coefficient for the model was 0.66 ± 0.22, compared with 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively because of a lack of data. Free-response receiver operating characteristic analysis demonstrated that the model scored similar or higher sensitivity per false positives compared with the observers. CONCLUSIONS The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials.
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Ang JL, Wright AF, Dhillon B, Cackett P. Choroidal neovascularisation in a predicted female choroideraemia carrier treated with intravitreal anti-vascular endothelial growth factor. Eur J Ophthalmol 2021; 31:4-10. [PMID: 33884923 DOI: 10.1177/1120672120965495] [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: 11/15/2022]
Abstract
PURPOSE To report a case of choroidal neovascularisation and leakage in a myopic female predicted to be a choroideraemia carrier treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS Case report. RESULTS A female magazine editor presented with sudden decrease in vision in her right eye, with Snellen visual acuities (VAs) of 1/60 and 3/60 in the right and left eyes respectively. She was diagnosed with choroidal neovascularisation (CNV) formation and subretinal haemorrhage in her right eye. This is on a background of previous presentations, the first of which was 20 years ago for declining left eye vision. She was subsequently found to be a predicted choroideraemia carrier. However, she also has high myopia, and it is unclear whether the predicted choroideraemia carrier status or high myopia is the main underlying cause of her CNV, although we believe that the former is more likely. The first episode of CNV in her right eye was treated successfully with intravitreal anti-VEGF. However, she experienced four further CNV reactivations in her right eye, all of which were treated successfully with anti-VEGF. At her last follow-up visit to date, Snellen VAs were 6/9 and 3/60 in her right and left eye respectively. CONCLUSION This is a unique case of CNV formation in a predicted choroideraemia carrier who also has co-existent high myopia. Prompt treatment of CNV activity with anti-VEGF has been efficacious in prevention of subretinal fibrosis and irreversible vision loss and allowed the patient to continue working in her chosen career.
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Affiliation(s)
| | - Alan F Wright
- MRC Institute of Genetics and Molecular Medicine, Edinburgh, UK
| | - Baljean Dhillon
- Princess Alexandra Eye Pavilion, Edinburgh, UK.,The University of Edinburgh, Edinburgh, UK
| | - Peter Cackett
- Princess Alexandra Eye Pavilion, Edinburgh, UK.,The University of Edinburgh, Edinburgh, UK
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42
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Li X, Zhu Q, Egger A, Chang L, Wolf S, Song Y, Zhang J, Dong F, Xu X, Weisberger A. Two different treatment regimens of ranibizumab 0.5 mg for neovascular age-related macular degeneration with or without polypoidal choroidal vasculopathy in Chinese patients: results from the Phase IV, randomized, DRAGON study. Acta Ophthalmol 2021; 99:e336-e345. [PMID: 33377611 PMCID: PMC8247421 DOI: 10.1111/aos.14588] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 06/09/2020] [Accepted: 07/21/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE To evaluate the efficacy and safety of monthly and pro re nata (PRN, guided by visual acuity stabilization and disease activity criteria) ranibizumab regimens in Chinese patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). METHODS This double-masked study randomized nAMD patients (1:1) to ranibizumab monthly from baseline to Month (M) 11 to a PRN regimen from M12 to M23 (monthly group, n = 167) versus ranibizumab three monthly doses followed by a PRN regimen up to M23 (PRN group, n = 166). Subgroups were assessed based on the presence/absence of PCV (indicated by indocyanine green angiography). RESULTS Of 334 randomized patients, 41.7% had PCV at baseline. Mean average best-corrected visual acuity (BCVA) change from M3 to M4 through M12 was 3.3 letters with monthly and 1.7 letters with PRN (mean difference: 1.6; 95% CI: -2.95, -0.20, primary end-point). Mean change in BCVA from baseline (monthly/PRN, 53.8/53.7) to M12 and M24 was 12.3 and 11.3 letters in monthly and 9.6 and 9.3 letters in PRN group. Corresponding values for patients with PCV/without PCV were 12.7/12.1 letters (M12) and 12.3/10.6 letters (M24) in monthly and 9.4/9.4 letters (M12) and 9.7/8.7 letters (M24) in PRN groups. The mean number of injections was 11.4 (monthly) and 8.2 (PRN) from Day 1 to M11 and 4.8 (monthly) and 5.0 (PRN) from M12 to M23. No new safety findings were reported. CONCLUSIONS The study results support the use of either ranibizumab monthly or PRN regimens in Chinese patients with nAMD, regardless of presence of PCV.
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Affiliation(s)
- Xiaoxin Li
- Peking University People's HospitalBeijingChina
| | - Qi Zhu
- China Novartis Institutes for Biomedical Research Co., Ltd.ShanghaiChina
| | | | - Liu Chang
- China Novartis Institutes for Biomedical Research Co., Ltd.ShanghaiChina
| | - Sebastian Wolf
- Department Ophthalmology, InselspitalBern University HospitalUniversity of BernBernSwitzerland
| | - Yanping Song
- Wuhan General Hospital of Guangzhou Military CommandWuhanChina
| | - Junjun Zhang
- West China HospitalSichuan UniversityChengduChina
| | | | - Xun Xu
- Shanghai First People's HospitalShanghaiChina
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43
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Fursova AZ, Zabanova VE, Gamza YA, Tarasov MS, Vasilyeva MA, Nikulich IF, Derbeneva AS. [Ophthalmic safety profile of antiangiogenic therapy]. Vestn Oftalmol 2021; 137:114-122. [PMID: 33881272 DOI: 10.17116/oftalma2021137021114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Antiangiogenic therapy with inhibitors of vascular endothelial growth factor (anti-VEGF) has not only fundamentally changed the treatment outcomes of vasoproliferative eye diseases, but also became the most common ophthalmic surgical manipulation. At the same time, in 36-48% of bilateral lesions there is a need to perform injections in both eyes, making relevant the issues of safety and prevention of severe complications that threaten irreversible loss of visual function. The article reviews the results of randomized clinical trials and real clinical practice, analyzes the incidence and causes of its most dangerous complication - endophthalmitis, characterizes the clinical course depending on the type of drug used, and considers the possibility of reducing the risk of this complication occurring. Special attention is paid to the safety profile of a new VEGF inhibitor - brolucizumab - which has received registration for the treatment of neovascular age-related macular degeneration (nAMD). Specialists dealing with retinal pathologies acknowledge the need to monitor the state of the anterior and posterior parts of the eye in order to detect the signs of intraocular inflammation as quickly and early as possible. Drug efficacy, treatment regimen, duration of action and safety are the main characteristics that should determine the personalized approach in each clinical case.
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Affiliation(s)
- A Zh Fursova
- Novosibirsk State Region Hospital, Novosibirsk, Russia.,Novosibirsk State Medical University, Novosibirsk, Russia
| | - V E Zabanova
- Novosibirsk State Region Hospital, Novosibirsk, Russia.,Novosibirsk State Medical University, Novosibirsk, Russia
| | - Yu A Gamza
- Novosibirsk State Region Hospital, Novosibirsk, Russia.,Novosibirsk State Medical University, Novosibirsk, Russia
| | - M S Tarasov
- Novosibirsk State Region Hospital, Novosibirsk, Russia.,Novosibirsk State Medical University, Novosibirsk, Russia
| | - M A Vasilyeva
- Novosibirsk State Region Hospital, Novosibirsk, Russia
| | - I F Nikulich
- Novosibirsk State Region Hospital, Novosibirsk, Russia.,Novosibirsk State Medical University, Novosibirsk, Russia
| | - A S Derbeneva
- Novosibirsk State Region Hospital, Novosibirsk, Russia.,Novosibirsk State Medical University, Novosibirsk, Russia
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Wong DT, Berger AR, Bourgault S, Chen J, Colleaux K, Cruess AF, Dookeran RI, Gauthier D, Hurley B, Kapusta MA, Kertes PJ, Qian CX, Samad A, Sheidow T, Whelan JH. Imaging Biomarkers and Their Impact on Therapeutic Decision-Making in the Management of Neovascular Age-Related Macular Degeneration. Ophthalmologica 2021; 244:265-280. [PMID: 33823520 DOI: 10.1159/000516108] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 03/09/2021] [Indexed: 11/19/2022]
Abstract
These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.
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Affiliation(s)
- David T Wong
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Alan R Berger
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Serge Bourgault
- Department of Ophthalmology, Université Laval, Québec, Québec, Canada
| | - John Chen
- Department of Ophthalmology, McGill University, Montréal, Québec, Canada
| | - Kevin Colleaux
- Department of Ophthalmology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Alan F Cruess
- Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Ravi I Dookeran
- Department of Ophthalmology, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Danny Gauthier
- Department of Ophthalmology, Université de Montréal, Montréal, Québec, Canada
| | - Bernard Hurley
- Department of Ophthalmology, University of Ottawa, Ottawa, Ontario, Canada
| | - Michael A Kapusta
- Department of Ophthalmology, McGill University, Montréal, Québec, Canada
| | - Peter J Kertes
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Cynthia X Qian
- Department of Ophthalmology, Université de Montréal, Montréal, Québec, Canada
| | - Arif Samad
- Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Thomas Sheidow
- Department of Ophthalmology, Western University, London, Ontario, Canada
| | - James H Whelan
- Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada
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Mitchell P, Rodríguez FJ, Joussen AM, Koh A, Eter N, Wong DT, Korobelnik JF, Okada AA. MANAGEMENT OF RETINAL PIGMENT EPITHELIUM TEAR DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY. Retina 2021; 41:671-678. [PMID: 33346626 PMCID: PMC7989608 DOI: 10.1097/iae.0000000000003083] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti-vascular endothelial growth factor (VEGF) therapy. METHODS Literature searches were performed using MEDLINE/PubMed databases (cut-off date: August 2019). RESULTS Three key recommendations were made based on existing literature and clinical experience: 1) Multimodal imaging with color fundus photography, optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence imaging, optical coherence tomography-angiography, and/or fluorescein angiography are recommended to diagnose RPE tear and assess risk factors. Retinal pigment epithelium tears can be graded by size and foveal involvement. 2) Patients at high risk of developing RPE tear should be monitored after each anti-VEGF injection. If risk factors worsen, it is not yet definitively known whether anti-VEGF administration should be more frequent, or alternatively stopped in such patients. Prospective research into high-risk characteristics is needed. 3) After RPE tear develops, anti-VEGF treatment should be continued in patients with active disease (as indicated by presence of intraretinal or subretinal fluid), although cessation of therapy should be considered in eyes with multilobular tears. CONCLUSION Although evidence to support the assumption that anti-VEGF treatment contributes to development of RPE tear is not definitive, some data suggest this link.
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Affiliation(s)
- Paul Mitchell
- Department of Ophthalmology, Centre for Vision Research, Westmead Institute for Medical Research, the University of Sydney, Sydney, Australia
| | - Francisco J. Rodríguez
- Fundación Oftalmologica Nacional, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | | | - Adrian Koh
- Eye and Retina Surgeons, Camden Medical Centre, Singapore
| | - Nicole Eter
- Department of Ophthalmology, University of Münster Medical Center, Münster, Germany
| | - David T. Wong
- Unity Health Toronto, St. Michael's Hospital, University of Toronto, Canada
| | - Jean-François Korobelnik
- Service d'ophtalmologie, CHU Bordeaux, Bordeaux, France
- University of Bordeaux, INSERM, Bordeaux Population Health Research Center, Team LEHA, UMR 1219, Bordeaux, France; and
| | - Annabelle A. Okada
- Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan
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Gascon P, Ramtohul P, Delaporte C, Kerever S, Denis D, Comet A. Aflibercept in real-life for the treatment of age-related macular degeneration using a treat and extend protocol: The Armada study. Eur J Ophthalmol 2021; 32:356-363. [PMID: 33779324 DOI: 10.1177/11206721211005703] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
PURPOSE To report the visual and anatomic outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with aflibercept under a standardized Treat and Extend (T&E) protocol for up to 3 years of follow-up in "real-life" practice. METHODS This retrospective, observational, multicenter study included patients with treatment-naïve nAMD and at least 12 months of follow-up. T&E regimen adjustment was initiated after loading phase. At each visit best-corrected visual acuity (BCVA) and optical coherence tomography parameters were performed. RESULTS One hundred and thirty-six eyes of 115patients had at least 1 year of follow-up with 114 and 82 eyes completing at least 2 and 3 years of follow-up, respectively (mean follow-up duration: 2.7 ± 1.3 years). Mean age was 78.6 ± 8.6 years old and 52% were women. Mean BCVA increased from 60.6 ± 18.7 letters at diagnosis to 66.9 ± 16.2 letters at 1 year (+6.3 letters, p = 0.003) and remained stable throughout the follow-up period (63.1 ± 20.3 letters (+2.5, p = 0.1) and 64.0 ± 20.1 letters (+3.4, p = 0.27) at 2 and 3 years, respectively). The mean central retinal thickness decreased significantly from 358.2 ± 87.9 µm at baseline to 302 ± 71.7 µm at 12 months and maintained stable after 36 months of follow-up (297.1 ± 76 µm, p < 0.0001). Mean number of injections was 6.6 ± 2.2, 4.8 ± 1.9, and 5.6 ± 1.7 at 1, 2, and 3 years, respectively. Mean cumulative number of 16.4 ± 5.6 injections after 3 years. Mean treatment interval was 6.8 ± 2.5 weeks at 1 year. Eight-week and 12-week treatment interval were achieved in 59.5% and 19.1%, 65.8%, and 36.8% and 69.5% and 41.5% at 1, 2, and 3 years, respectively. CONCLUSIONS Our study demonstrated that intravitreal injections of aflibercept initiated under a standardized T&E for patients with treatment-naïve nAMD allow for significant visual improvement at 12 months, which was maintained over a 3-year follow-up period.
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Affiliation(s)
- Pierre Gascon
- Ophthalmology Department, Hopital Nord, Aix-Marseille University, Marseille, France.,Institut de Neurosciences de la Timone, Aix-Marseille University, Marseille, France
| | - Prithvi Ramtohul
- Ophthalmology Department, Hopital Nord, Aix-Marseille University, Marseille, France
| | - Charles Delaporte
- Ophthalmology Department, Hopital Nord, Aix-Marseille University, Marseille, France
| | - Sébastien Kerever
- ECSTRA Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Centre, UMR 1153, INSERM, Paris, France.,University of Paris VII Denis Diderot, Paris, France
| | - Danièle Denis
- Ophthalmology Department, Hopital Nord, Aix-Marseille University, Marseille, France
| | - Alban Comet
- Ophthalmology Department, Hopital Nord, Aix-Marseille University, Marseille, France
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47
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Sharma S, Gupta V, Maiti A, Natesh S, Saxena S, Dave V, Parmar V, Sampangi R, Murthy H, Dharwadkar S, Yadav NK, Joshi S, Mayor R, Ratra D, Basu S, Goel N, Chaturvedi A, Patel R, Jose V. Safety and efficacy of Razumab™ (world's first biosimilar ranibizumab) in wet age-related macular degeneration: a post-marketing, prospective ASSET study. Int J Retina Vitreous 2021; 7:24. [PMID: 33762008 PMCID: PMC7992797 DOI: 10.1186/s40942-021-00293-w] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Accepted: 03/09/2021] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Razumab™ (world's first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD. METHODS This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks. RESULTS Of the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost < 15 letters from baseline visual acuity. In the ITT and PP populations, 31.20% and 32.76% patients, respectively, showed improved visual acuity by ≥ 15 letters. Significant improvements in BCVA (mean difference: 8.8, 9.2, p < 0.001 for ITT, PP) and VFQ-25 (8.5, 9.2, p < 0.001 for ITT, PP) were seen; CRT reduced significantly (125 µm, 119.3 µm, p < 0.001 for ITT, PP). CONCLUSION Razumab™ (world's first biosimilar ranibizumab) was well-tolerated without new safety concerns and significantly improved visual acuity in wet AMD patients. Trial registration CTRI/2016/03/006739. Registered 18 March 2016-Prospectively registered, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739.
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Affiliation(s)
- Shashikant Sharma
- Medical Affairs, Intas Pharmaceuticals Ltd, Ahmedabad, Gujarat, India.
| | - Vishali Gupta
- Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aniruddha Maiti
- Susrut Eye Foundation & Research Centre, Kolkata, West Bengal, India
| | | | - Sandeep Saxena
- Department of Ophthalmology, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Vivek Dave
- L V Prasad Eye Institute, Hyderabad, Telangana, India
| | - Vimal Parmar
- PBMA's H. V. Desai Eye Hospital, Pune, Maharashtra, India
| | - Raju Sampangi
- Gurushree Hi-Tech Multi Speciality Hospital, Bangalore, Karnataka, India
| | - Hemanth Murthy
- Retina Institute of Karnataka, Bangalore, Karnataka, India
| | - Sandhya Dharwadkar
- K.R. Hospital, Mysore Medical College & Research Institute, Mysore, India
| | | | | | - Rahul Mayor
- Dr. Shroff's Charity Eye Hospital, New Delhi, India
| | | | - Soumyava Basu
- L V Prasad Eye Institute, Bhubaneswar, Odisha, India
| | - Neha Goel
- ICARE Eye Hospital & Post Graduate Institute, Noida, Uttar Pradesh, India
- Eye7 Chaudhary Eye Centre, New Delhi, India
| | - Alok Chaturvedi
- Medical Affairs, Intas Pharmaceuticals Ltd, Ahmedabad, Gujarat, India
| | - Ronak Patel
- Department of Biostatistics and Programming, Lambda Therapeutic Research Ltd., Ahmedabad, Gujarat, India
| | - Vinu Jose
- Clinical Development & Medical Affairs, Intas Pharmaceuticals Ltd. (Biopharma), Ahmedabad, Gujarat, India
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Greenlee TE, Wang VY, Kang H, Ohlhausen ME, Chen AX, Hom GL, Conti TF, Briskin I, Babiuch AS, Singh RP. CONSEQUENCES OF LAPSES IN TREATMENT WITH VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN ROUTINE CLINICAL PRACTICE. Retina 2021; 41:581-587. [PMID: 32658164 DOI: 10.1097/iae.0000000000002888] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
PURPOSE Evaluating outcomes in patients receiving intravitreal antivascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration whom experience a lapse in treatment. METHODS A retrospective chart review evaluating 3,304 patients ≥18 years who experienced treatment lapses ≥3 months compared with control counterparts. Demographic information, macular thickness as measured by central subfield thickness, and visual acuity were collected at baseline, the first postlapse appointment, and at 3, 6, and 12 months after the lapse for the study group. RESULTS Lapse (n = 241) and control patients (n = 241) had similar baseline visual acuity and central subfield thickness (Early Treatment Diabetic Retinopathy Study: 58.9 ± 20.2 [20/63] vs. 59.2 ± 20.1 [20/63]; central subfield thickness: 252.4 ± 63.2 µm vs. 259.8 ± 66.2 µm, P = 0.21). Analysis revealed that lapse patients experienced a significant increase in central subfield thickness after lapse when compared with controls (279.4 ± 86.9 µm vs. 253.7 ± 65.9 µm, P < 0.01), which normalized on resumption of treatment (259.1 ± 79 µm vs. 246.8 ± 57.6 µm, P = 0.06). Study patients also experienced loss in the visual acuity after lapse when compared with controls (52.9 ± 23.6 Early Treatment Diabetic Retinopathy Study [20/100] vs. 59.9 ± 20.8 [20/63] Early Treatment Diabetic Retinopathy Study, P < 0.01) that did not recover through 12 months of follow-up. CONCLUSION Patients with neovascular age-related macular degeneration who have lapses in care are at risk for poorer outcomes. Although macular thickness normalizes on resumption of treatment, their decline in the visual acuity does not recover.
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Affiliation(s)
- Tyler E Greenlee
- Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
| | - Victoria Y Wang
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Hannah Kang
- Case Western Reserve University College of Arts and Sciences, Cleveland, Ohio; and
| | - Marc E Ohlhausen
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Andrew X Chen
- Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Grant L Hom
- Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Thais F Conti
- Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
| | - Isaac Briskin
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
| | - Amy S Babiuch
- Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
| | - Rishi P Singh
- Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
- Case Western Reserve University School of Medicine, Cleveland, Ohio
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49
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Müller PL, Liefers B, Treis T, Rodrigues FG, Olvera-Barrios A, Paul B, Dhingra N, Lotery A, Bailey C, Taylor P, Sánchez CI, Tufail A. Reliability of Retinal Pathology Quantification in Age-Related Macular Degeneration: Implications for Clinical Trials and Machine Learning Applications. Transl Vis Sci Technol 2021; 10:4. [PMID: 34003938 PMCID: PMC7938003 DOI: 10.1167/tvst.10.3.4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 12/22/2020] [Indexed: 11/24/2022] Open
Abstract
Purpose To investigate the interreader agreement for grading of retinal alterations in age-related macular degeneration (AMD) using a reading center setting. Methods In this cross-sectional case series, spectral-domain optical coherence tomography (OCT; Topcon 3D OCT, Tokyo, Japan) scans of 112 eyes of 112 patients with neovascular AMD (56 treatment naive, 56 after three anti-vascular endothelial growth factor injections) were analyzed by four independent readers. Imaging features specific for AMD were annotated using a novel custom-built annotation platform. Dice score, Bland-Altman plots, coefficients of repeatability, coefficients of variation, and intraclass correlation coefficients were assessed. Results Loss of ellipsoid zone, pigment epithelium detachment, subretinal fluid, and drusen were the most abundant features in our cohort. Subretinal fluid, intraretinal fluid, hypertransmission, descent of the outer plexiform layer, and pigment epithelium detachment showed highest interreader agreement, while detection and measures of loss of ellipsoid zone and retinal pigment epithelium were more variable. The agreement on the size and location of the respective annotation was more consistent throughout all features. Conclusions The interreader agreement depended on the respective OCT-based feature. A selection of reliable features might provide suitable surrogate markers for disease progression and possible treatment effects focusing on different disease stages. Translational Relevance This might give opportunities for a more time- and cost-effective patient assessment and improved decision making as well as have implications for clinical trials and training machine learning algorithms.
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Affiliation(s)
- Philipp L. Müller
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Institute of Ophthalmology, University College London, London, UK
- Department of Ophthalmology, University of Bonn, Bonn, Germany
| | - Bart Liefers
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Tim Treis
- BioQuant, University of Heidelberg, Heidelberg, Germany
| | - Filipa Gomes Rodrigues
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Institute of Ophthalmology, University College London, London, UK
| | - Abraham Olvera-Barrios
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Institute of Ophthalmology, University College London, London, UK
| | - Bobby Paul
- Barking, Havering and Redbridge University Hospitals NHS Trust, Romford, UK
| | | | - Andrew Lotery
- University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Clare Bailey
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | - Paul Taylor
- Institute of Health Informatics, University College London, London, UK
| | - Clarisa I. Sánchez
- Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands
- Informatics Institute, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands
| | - Adnan Tufail
- Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Institute of Ophthalmology, University College London, London, UK
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Sivaccumar J, Sandomenico A, Vitagliano L, Ruvo M. Monoclonal Antibodies: A Prospective and Retrospective View. Curr Med Chem 2021; 28:435-471. [PMID: 32072887 DOI: 10.2174/0929867327666200219142231] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 11/12/2019] [Accepted: 11/19/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Monoclonal Antibodies (mAbs) represent one of the most important classes of biotherapeutic agents. They are used to cure many diseases, including cancer, autoimmune diseases, cardiovascular diseases, angiogenesis-related diseases and, more recently also haemophilia. They can be highly varied in terms of format, source, and specificity to improve efficacy and to obtain more targeted applications. This can be achieved by leaving substantially unchanged the basic structural components for paratope clustering. OBJECTIVES The objective was to trace the most relevant findings that have deserved prestigious awards over the years, to report the most important clinical applications and to emphasize their latest emerging therapeutic trends. RESULTS We report the most relevant milestones and new technologies adopted for antibody development. Recent efforts in generating new engineered antibody-based formats are briefly reviewed. The most important antibody-based molecules that are (or are going to be) used for pharmacological practice have been collected in useful tables. CONCLUSION The topics here discussed prove the undisputed role of mAbs as innovative biopharmaceuticals molecules and as vital components of targeted pharmacological therapies.
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Affiliation(s)
- Jwala Sivaccumar
- Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Napoli, Italy
| | - Annamaria Sandomenico
- Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Napoli, Italy
| | - Luigi Vitagliano
- Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Napoli, Italy
| | - Menotti Ruvo
- Istituto di Biostrutture e Bioimmagini, CNR, Via Mezzocannone 16, 80134 Napoli, Italy
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