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Sheth JU, Stewart MW, Narayanan R, Anantharaman G, Chandran K, Lai TYY, Chakravarthy U, Das T. Macular neovascularization. Surv Ophthalmol 2025; 70:653-675. [PMID: 39222802 DOI: 10.1016/j.survophthal.2024.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 08/22/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Neovascularization of the macula, a common complication of many chorioretinal diseases such as neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and pathologic myopia, results from increased synthesis of vascular endothelial growth factor (VEGF) by the retinal pigment epithelium and/or Müller cells because of localized ischemia and inflammation. The Consensus on Neovascular AMD Nomenclature (CONAN) study group acknowledged that these vessels may originate from either the choriocapillaris or the retinal microvasculature, prompting them to propose the term 'macular neovascularization' (MNV) to include intraretinal, subretinal, and sub-pigment epithelial neovascularization localized to the macula. MNV frequently appears as a grey-green macular lesion with overlying intraretinal thickening and/or subretinal exudation, causing metamorphopsia, reduced central vision, relative central scotoma, decreased reading speed, and problems with color recognition. Multimodal imaging with optical coherence tomography (OCT), OCT angiography, dye-based angiographies, fundus autofluorescence, and multiwavelength photography help establish the diagnosis and aid in selecting an appropriate treatment. The standard of care for MNV is usually intravitreal anti-vascular endothelial growth factor injections, though thermal laser photocoagulation, verteporfin photodynamic therapy, and vitreoretinal surgery are occasionally used. We discuss the etiology and clinical features of MNV, the role of multimodal imaging in establishing the diagnosis, and the available therapeutic options.
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Affiliation(s)
- Jay U Sheth
- Department of Vitreoretinal Services, Shantilal Shanghvi Eye Institute, Mumbai, India.
| | | | - Raja Narayanan
- Anant Bajaj Retina Institute, Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
| | | | - Kiran Chandran
- Department of Vitreoretinal Services, Giridhar Eye Institute, Cochin, India
| | - Timothy Y Y Lai
- Department of Ophthalmology and Visual Sciences The Chinese University of Hong Kong, Hong Kong
| | - Usha Chakravarthy
- Department of Ophthalmology and Vision Science, Queen's University of Belfast, Belfast, United Kingdom
| | - Taraprasad Das
- Department of Vitreoretinal Services, Shantilal Shanghvi Eye Institute, Mumbai, India; Anant Bajaj Retina Institute, Srimati Kanuri Santhamma Centre for Vitreoretinal Diseases, L V Prasad Eye Institute, Hyderabad, India
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2
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Mano F, LoBue S, Tailor P, Olsen TW. Incisional choroidal surgery. Surv Ophthalmol 2025; 70:595-615. [PMID: 39222800 DOI: 10.1016/j.survophthal.2024.08.002] [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: 05/07/2024] [Revised: 08/22/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
The choroid is a thin layer of highly vascular uveal tissue enclosed externally by sclera and internally by neurosensory retinal tissue. The choroid is a "middle layer" ocular tissue with anatomically challenging surgical access. The primary functional role of the choroid is to provide rapid, oxygenated, and nutrient-rich blood flow to both the highly metabolic retinal pigment epithelium and outer retina (i.e. photoreceptors) while simultaneously removing waste products. Historically, incisional choroidal surgery (ICS) has involved tumor biopsy or excision, removal of choroidal neovascular complex or autologous choroidal translocations; however, ICS also holds unique potential for novel and innovative approaches to address macular pathology. Using large-animal surgical studies, researchers have explored ICS with the objective of finding safer and more effective techniques to reduce surgical risks such as bleeding, tissue contraction, and scar tissue formation. We explore the relevant anatomy and embryology, existing surgical techniques, discuss the implications for retinal drug delivery, define ICS guiding principles, and offer a rationale for implementation of ICS into a vitreoretinal surgical practice. We also identify other future challenges and anticipate future innovations that will advance ICS.
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Affiliation(s)
- Fukutaro Mano
- Kindai University, Osaka, Japan; Mayo Clinic, Rochester, MN, USA
| | - Stephen LoBue
- LoBue Laser and Eye Medical Center, Murrieta, CA, USA; Mayo Clinic, Rochester, MN, USA
| | | | - Timothy W Olsen
- Chair Emeritus, Emory University, Atlanta, GA, USA; Mayo Clinic, Rochester, MN, USA; EyeMacular Regeneration, Inc., Rochester, MN, USA; iMacular Regeneration, LLC, Rochester, MN, USA.
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Birner K, Coulibaly LM, Schrittwieser J, Steiner I, Mohamed H, Schürer‐Waldheim S, Gumpinger M, Bogunovic H, Schmidt‐Erfurth U, Reiter GS. Normative prospective data on automatically quantified retinal morphology correlated to retinal function in healthy ageing eyes by two microperimetry devices. Acta Ophthalmol 2025; 103:423-431. [PMID: 39731225 PMCID: PMC12069971 DOI: 10.1111/aos.17434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Accepted: 12/15/2024] [Indexed: 12/29/2024]
Abstract
PURPOSE The relationship between retinal morphology, as assessed by optical coherence tomography (OCT), and retinal function in microperimetry (MP) has not been well studied, despite its increasing importance as an essential functional endpoint for clinical trials and emerging therapies in retinal diseases. Normative databases of healthy ageing eyes are largely missing from literature. METHODS Healthy subjects above 50 years were examined using two MP devices, MP-3 (NIDEK) and MAIA (iCare). An identical grid, encompassing 45 stimuli was used for retinal sensitivity (RS) assessment. Deep-learning-based algorithms performed automated segmentation of ellipsoid zone (EZ), outer nuclear layer (ONL), ganglion cell layer (GCL) and retinal nerve fibre layer (RNFL) from OCT volumes (Spectralis, Heidelberg). Pointwise co-registration between each MP stimulus and corresponding location on OCT was performed via registration algorithm. Effect of age, eccentricity and layer thickness on RS was assessed by mixed effect models. RESULTS Three thousand six hundred stimuli from twenty eyes of twenty patients were included. Mean patient age was 68.9 ± 10.9 years. Mean RS for the first exam was 28.65 ± 2.49 dB and 25.5 ± 2.81 dB for MP-3 and MAIA, respectively. Increased EZ thickness, ONL thickness and GCL thickness were significantly correlated with increased RS (all p < 0.001). Univariate models showed lower RS with advanced age and higher eccentricity (both p < 0.05). CONCLUSION This work provides reference values for healthy age-related EZ and ONL-thicknesses without impairment of visual function and evidence for RS decrease with eccentricity and increasing age. This information is crucial for interpretation of future clinical trials in disease.
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Affiliation(s)
- Klaudia Birner
- Department of Ophthalmology and OptometryMedical University of ViennaViennaAustria
| | - Leonard M. Coulibaly
- Department of Ophthalmology and OptometryMedical University of ViennaViennaAustria
| | | | - Irene Steiner
- Center for Medical Data Science, Institute of Medical StatisticsMedical University of ViennaViennaAustria
| | - Hamza Mohamed
- Department of Ophthalmology and OptometryMedical University of ViennaViennaAustria
| | | | - Markus Gumpinger
- Department of Ophthalmology and OptometryMedical University of ViennaViennaAustria
| | - Hrvoje Bogunovic
- Aritificial Intelligence Institute, Center for Medical Data ScienceMedical University of ViennaViennaAustria
| | | | - Gregor S. Reiter
- Department of Ophthalmology and OptometryMedical University of ViennaViennaAustria
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4
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Baillif S, Nahon-Esteve S, Pace-Loscos T, Pagès G, Dufies M. Aqueous humor mediator levels as biomarkers of anti-VEGF response in age-related macular degeneration. Cytokine 2025; 190:156921. [PMID: 40147376 DOI: 10.1016/j.cyto.2025.156921] [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: 10/10/2024] [Revised: 02/08/2025] [Accepted: 03/12/2025] [Indexed: 03/29/2025]
Abstract
PURPOSE To monitor intraocular mediator dynamics in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with anti-VEGF intravitreal injections (IVIs) to identify individual mediator patterns correlating with treatment response. DESIGN Interventional, monocentric, prospective, clinical study. PARTICIPANTS Treatment-naïve nAMD patients. METHODS Aqueous humor samples (100-200 μL) were collected by clear cornea paracentesis at baseline (before the first anti-VEGF IVI) and before the second and third anti-VEGF IVIs. The levels of 13 intraocular mediators were measured (VEGF-A, VEGF-C, PlGF, IL-1β, IL-6, IL-10, IL-18, CXCL1, CXCL5, CXCL7, CXCL8, MIP-1α and TNFα) using multiplex arrays. MAIN OUTCOMES MEASURES The primary endpoint was the changes in intraocular inflammatory mediator levels between baseline and month 3. Secondary endpoints were the changes in best-corrected visual acuity (BCVA) and Central Retinal Thickness (CRT) between baseline and month 4. RESULTS Fifteen eyes were included in the study. BCVA remained stable throughout the study (p = 0.07). CRT, foveal thickness, and the presence of intraretinal and subretinal fluid significantly decreased after anti-VEGF IVIs (p < 0.0001, p < 0.0001, p < 0.001 and p < 0.001, respectively). After anti-VEGF IVIs, VEGF-A levels significantly decreased (p < 0.0001). No significant differences in all other mediator levels were observed. Three patients had baseline VEGF-A levels ≤50 pg/mL: they showed higher baseline IL-6 levels (p = 0.05), and elevated IL-6 (p = 0.03), PlGF (p = 0.02), VEGF-C (p = 0.005), IL-8 (p = 0.04), and TNFα (p = 0.013) levels after the first IVI. Good clinical responders had significantly higher baseline VEGF-A levels (p = 0.007). Patients who required a fourth IVI within 8 weeks of the loading dose had higher baseline TNFα levels (p = 0.05); higher MIP-1α levels after the first IVI (p = 0.045); and elevated TNFα (p = 0.026) and IL-8 (p = 0.029) levels after the second IVI. CONCLUSIONS The aqueous humor levels of the studied mediators remained stable after anti-VEGF IVIs, except for a significant decrease in VEGF-A levels in all patients. Patients with low baseline intraocular VEGF-A levels (i.e., ≤50 pg/mL) showed an intraocular inflammatory profile with elevated IL-6, PlGF, VEGF-C, IL-8 and TNFα levels. Treatment response correlated with high baseline VEGF-A levels. An interval > 8 weeks between the third and fourth anti-VEGF IVIs was associated with a pro-angiogenic/pro-inflammatory environment.
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Affiliation(s)
- Stéphanie Baillif
- Department of Ophthalmology, Pasteur 2 University Hospital, Université Côte-d'Azur, Nice, France; Roca Therapeutics, Nice, France.
| | - Sacha Nahon-Esteve
- Department of Ophthalmology, Pasteur 2 University Hospital, Université Côte-d'Azur, Nice, France
| | - Tanguy Pace-Loscos
- Centre Antoine Lacassagne, Department of Epidemiology, Biostatistics and Health Data, Nice, France
| | - Gilles Pagès
- Roca Therapeutics, Nice, France; France Institute for Research on Cancer and Aging (IRCAN), Université Côte d'Azur, CNRS UMR 7284 and INSERM U1081, Nice, France
| | - Maeva Dufies
- Roca Therapeutics, Nice, France; France Institute for Research on Cancer and Aging (IRCAN), Université Côte d'Azur, CNRS UMR 7284 and INSERM U1081, Nice, France
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5
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Luan R, Xu S, Xu M, Wang M, Huang X, Wang J, Li Q, Gong Y, Liu J, Shao Y, Li X. Targeting BMP4 as a therapeutic strategy for neovascularization and fibrosis in age-related macular degeneration. Exp Eye Res 2025; 255:110348. [PMID: 40118134 DOI: 10.1016/j.exer.2025.110348] [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: 12/08/2024] [Revised: 02/14/2025] [Accepted: 03/18/2025] [Indexed: 03/23/2025]
Abstract
This study investigates the role of bone morphogenetic protein-4 (BMP4) in age-related macular degeneration (AMD), with a focus on its effects on subretinal fibrosis and choroidal neovascularization (CNV). Using a mouse model of laser-induced CNV, we found that BMP4 expression was significantly elevated in CNV lesions. BMP4 was shown to promote fibroblast proliferation and their differentiation into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA). Additionally, BMP4 promoted the transition of endothelial progenitor cells (EPCs) into endothelial cells (ECs), a process that was modulated by mitochondrial function. Intravitreal administration of Noggin, a BMP4 inhibitor, significantly reduced CNV lesion volume and decreased the expression of CD31 and α-SMA, suggesting a decrease in neovascularization and fibrosis. These findings underscore BMP4's critical role in AMD pathogenesis by driving both angiogenesis and fibrosis. Targeting BMP4 with Noggin presents a promising therapeutic approach for AMD, addressing both neovascularization and fibrosis in a single intervention, and highlights BMP4 as a potential novel target for AMD therapy.
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Affiliation(s)
- Rong Luan
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Shuzhan Xu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Manhong Xu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Manqiao Wang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Xinyuan Huang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Jie Wang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Qingbo Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Yi Gong
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China
| | - Juping Liu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China.
| | - Yan Shao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China.
| | - Xiaorong Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 384300, China.
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Chandak S, Gurudas S, Pakeer RM, Kazantzis D, Ghanchi F, Grabowska A, Talks SJ, Pearce I, McKibbin M, Kotagiri A, Menon G, Burton BJ, Gale R, Sivaprasad S. Factors associated with achieving various visual acuity outcomes during loading doses of aflibercept 2 mg for treatment naïve exudative age-related macular degeneration: PRECISE Study Report 7. Eye (Lond) 2025; 39:1553-1561. [PMID: 39984700 DOI: 10.1038/s41433-025-03687-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/08/2025] [Accepted: 02/05/2025] [Indexed: 02/23/2025] Open
Abstract
PURPOSE To identify demographic and baseline OCT characteristics that are predictive of VA outcomes after the first and post-loading injections in patients treated with 2 mg aflibercept. METHODS This study evaluated VA outcomes in 1999 eyes of 1862 patients with nAMD initiated on aflibercept therapy. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA outcome defined as VA ≥ 68 ETDRS letters (Snellen ≥ 6/12) and poor VA outcome of <54 ETDRS letters (Snellen < 6/18) or a loss of ≥5 ETDRS letters after first and post-loading injections were analysed using logistic regression via generalised estimating equations. RESULTS The mean age was 79.3 (SD 7.8) years, 1126 (60.5%) were females, and predominantly white ethnic background (1772 [95.2%]). The mean presenting VA was 58.0 (SD 14.5) ETDRS letters. After the loading phase, 930/1994 (46.6%) eyes achieved VA ≥ 68 ETDRS letters, and 457 (22.9%) attained VA < 54 ETDRS letters. Increasing age, non-white ethnicity, and baseline VA < 54 letter score is associated with VA < 54 letters. The OCT parameters associated with reduced odds of VA ≥ 68 ETDRS letters and increased odds of VA < 54 ETDRS letters after first and post-loading phase included fovea-involving intraretinal fluid, all types of macular neovascularisation (MNV) versus type 1 MNV, fovea-involving MNV (vs. non-foveal MNV), subfoveal MNV complex, increased central subfield thickness, foveal presence of subretinal hyper-reflective material, atrophy, fibrosis, ungradable or ellipsoid zone and/or external limiting membrane loss. CONCLUSION This study could provide individual-level visual prognosis about their post-loading VA based on demography, VA and OCT characteristics at presentation.
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Affiliation(s)
- Swati Chandak
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
| | - Sarega Gurudas
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
- Institute of Ophthalmology, University College, London, UK
| | - Raheeba Mohammed Pakeer
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
| | - Dimitrios Kazantzis
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
| | - Faruque Ghanchi
- Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Anna Grabowska
- King's College Hospital NHS Foundation Trust, London, UK
| | | | - Ian Pearce
- The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust, Liverpool, UK
| | | | - Ajay Kotagiri
- South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK
| | - Geeta Menon
- Frimley Health NHS Foundation Trust, Surrey, UK
| | | | - Richard Gale
- York Teaching Hospital NHS Foundation Trust, York, UK
| | - Sobha Sivaprasad
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK.
- Institute of Ophthalmology, University College, London, UK.
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Beretta F, Zucchiatti I, Sacconi R, Fantaguzzi F, Lingardo S, Bandello F, Querques G. Two-Years Real-World Experience of a Tertiary Center with Intravitreal Brolucizumab Switch for Treatment of Exudative Neovascular Age-Related Macular Degeneration. Ophthalmol Ther 2025; 14:1325-1335. [PMID: 40249498 PMCID: PMC12069189 DOI: 10.1007/s40123-025-01141-y] [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: 02/21/2025] [Accepted: 03/31/2025] [Indexed: 04/19/2025] Open
Abstract
INTRODUCTION To analyze visual and anatomical outcomes in patients switched to brolucizumab and previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for exudative neovascular age-related macular degeneration (nAMD). These outcomes were was assessed in the real-world setting of a tertiary center with a follow-up period of 2 years. METHODS This retrospective longitudinal study included 29 eyes of 24 patients with exudative nAMD previously treated with at least three injections of another intravitreal anti-VEGF molecule. The eyes were then treated with brolucizumab for at least 24 months following the switch. A pro re nata ("as needed") therapeutic regimen was followed in our clinic between January 2021 and June 2024, during which time clinical and anatomical parameters were evaluated, and possible adverse events were recorded. RESULTS After 24 months of treatment with brolucizumab, patients showed a significant reduction in central macular thickness (P = 0.001) and choroidal thickness (P < 0.001). Visual acuity remained stable during the follow-up period. "Poor responders" had longer disease duration and had received more injections before the switch than "good responders." Adverse events included one subretinal hemorrhage and one intraocular inflammation across 302 injections. CONCLUSIONS Treatment with brolucizumab is effective in patients previously treated with other therapeutic molecules. The best outcomes were achieved in patients who switched therapy to brolucizumab early in their disease. Treatment with brolucizumab in this population demonstrated an acceptable risk profile, with only one intraocular inflammatory event out of 302 intravitreal injections.
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Affiliation(s)
- Federico Beretta
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Ilaria Zucchiatti
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Riccardo Sacconi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Federico Fantaguzzi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Stefano Lingardo
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Francesco Bandello
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giuseppe Querques
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
- Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
- Department of Ophthalmology, University Vita-Salute-IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
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8
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Spooner K, Broadhead G, Fraser-Bell S, Hong T, Wong JG, Chang AA. Real-World 10-Year Outcomes of Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration: A Meta-Analysis. Clin Exp Ophthalmol 2025. [PMID: 40411432 DOI: 10.1111/ceo.14559] [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: 04/10/2024] [Revised: 04/04/2025] [Accepted: 05/09/2025] [Indexed: 05/26/2025]
Abstract
BACKGROUND This study examines the long-term effectiveness of anti-VEGF therapy in managing neovascular age-related macular degeneration (nAMD). Despite the well-established short-term improvements of anti-VEGF therapy, there is limited data on its continued efficacy over extended periods. This meta-analysis synthesises real-world data to evaluate anti-VEGF therapy's long-term outcomes systematically. METHODS We conducted a comprehensive literature review across PubMed, EMBASE and Cochrane databases, focusing on studies that reported outcomes of anti-VEGF treatment for nAMD over a decade. The analysis included pooling baseline patient characteristics, study designs, sample sizes and changes in visual acuity (VA) over 10 years. RESULTS Our search produced 12 observational studies encompassing 7509 eyes, with 1274 completing 10-years of follow-up. The most substantial improvement in VA was observed in the first year following the initiation of anti-VEGF therapy. On average, there was a decline of 8.11 letters in VA after 10 years from baseline (95% CI -10.83 to -5.39, p < 0.01). In some cases, VA reverted to baseline levels after 10 years; in others, it declined significantly below baseline. Meta-regression showed that mean VA change was greater in those with a lower baseline VA and those treated with a higher number of injections over 10-years(p < 0.01). CONCLUSION Our findings suggest that the mean visual acuity of eyes treated for nAMD deteriorates progressively over the long-term from two years after starting treatment. Regular injections appear crucial for preserving maximum vision. While our analysis did not identify an increased incidence of serious ocular adverse events, the long-term impact of anti-VEGF therapy on geographic atrophy remains unclear and warrants further investigation.
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Affiliation(s)
- Kimberly Spooner
- Cureos Research, Sydney, Australia
- Save Sight Institute, University of Sydney, Sydney, Australia
- Graduate School of Health, The University of Technology, Sydney, Australia
| | - Geoffrey Broadhead
- Cureos Research, Sydney, Australia
- Save Sight Institute, University of Sydney, Sydney, Australia
- Canberra Eye Surgeons, Canberra, Australia
| | - Samantha Fraser-Bell
- Save Sight Institute, University of Sydney, Sydney, Australia
- Sydney Eye Hospital, Sydney, Australia
- Royal North Shore Hospital, St Leonards, Australia
- Sydney Retina Clinic, Sydney, Australia
| | - Thomas Hong
- Cureos Research, Sydney, Australia
- Sydney Retina Clinic, Sydney, Australia
| | - James G Wong
- Save Sight Institute, University of Sydney, Sydney, Australia
- Sydney Eye Hospital, Sydney, Australia
- Sydney Retina Clinic, Sydney, Australia
- Strathfield Retina Clinic, Sydney, Australia
| | - Andrew A Chang
- Cureos Research, Sydney, Australia
- Save Sight Institute, University of Sydney, Sydney, Australia
- Sydney Eye Hospital, Sydney, Australia
- Sydney Retina Clinic, Sydney, Australia
- Strathfield Retina Clinic, Sydney, Australia
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9
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Heloterä H, Kostanek J, Liukkonen M, Siintamo L, Linna-Kuosmanen S, Watala C, Blasiak J, Kaarniranta K. Serum RNA Profile Reflects Fluid Status and Atrophic Retinal Changes in Neovascular Age-Related Macular Degeneration. Int J Mol Sci 2025; 26:4852. [PMID: 40429992 PMCID: PMC12112293 DOI: 10.3390/ijms26104852] [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: 03/10/2025] [Revised: 04/23/2025] [Accepted: 04/30/2025] [Indexed: 05/29/2025] Open
Abstract
The increasing prevalence of age-related macular degeneration (AMD), a disease that can result in the loss of central vision, is an emerging problem worldwide due to aging societies. Growing patient numbers create a challenge for the healthcare system. Understanding the mechanisms of AMD pathogenesis will aid in early, personalized, and efficient intervention, helping to mitigate this issue. Current diagnostic methods rely on optical coherence tomography and angiography imaging, which identify existing damages, but do not provide information on the mechanisms behind them. In the present work, we demonstrate a difference in the serum RNA profile between neovascular AMD (nAMD) patients and controls. Moreover, the RNA profile of nAMD patients corresponded with anatomical changes in the retinal fluid compartments as well as atrophic changes of the retina. We followed two independent ways to control false positive leads, and when these approaches were combined, thioredoxin-related transmembrane protein 4 (TMX4) was observed to be differentially expressed by both approaches. This finding opens a new pathway in AMD studies, which are limited due to restricted access to live human target material and the limited value of animal models of human AMD.
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Affiliation(s)
- Hanna Heloterä
- Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland; (H.H.); (M.L.)
| | - Joanna Kostanek
- Department of Haemostatic Disorders, Medical University of Lodz, 90-419 Lodz, Poland; (J.K.)
| | - Mikko Liukkonen
- Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland; (H.H.); (M.L.)
| | - Leea Siintamo
- Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland; (H.H.); (M.L.)
| | - Suvi Linna-Kuosmanen
- A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland;
| | - Cezary Watala
- Department of Haemostatic Disorders, Medical University of Lodz, 90-419 Lodz, Poland; (J.K.)
| | - Janusz Blasiak
- Faculty of Medicine, Collegium Medicum, Mazovian Academy in Plock, 09-402 Plock, Poland;
| | - Kai Kaarniranta
- Department of Ophthalmology, University of Eastern Finland, 70210 Kuopio, Finland; (H.H.); (M.L.)
- Department of Ophthalmology, Kuopio University Hospital, 70210 Kuopio, Finland
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10
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Oertel J, Fischer D, Tarhan M, Meller D, Hammer M. Fundus autofluorescence lifetimes in age-related macular degeneration versus healthy controls in a pseudophakic population. Acta Ophthalmol 2025. [PMID: 40365784 DOI: 10.1111/aos.17519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025]
Abstract
PURPOSE To check whether prolonged fundus autofluorescence (FAF) lifetimes in age-related macular degeneration (AMD) could be an artefact resulting from lens fluorescence. METHODS Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in pseudophakic intermediate AMD as well as healthy controls. The median values of FAF lifetimes in the centre, the inner and the outer ring of the ETDRS grid, obtained as amplitude-weighted mean of the lifetimes from a three-exponential fit of the fluorescence decay over time in two spectral channels, as well as peak emission wavelengths (PEW) were compared between patients and controls. The age dependence of FAF lifetime was checked per group. In the patient cohort, FAF lifetimes of individuals with and without subretinal drusenoid deposits (SDD) were compared. RESULTS Forty-four AMD patients (mean age 80.0 ± 6.0 years) and 26 controls (mean age 73.0 ± 10.2 years) were included. The FAF lifetimes of a subgroup of patients (N = 25, mean age 76.3 ± 5.6 years), age-matched to the controls, were significantly longer than those of the controls (all grid areas and spectral channels p < 0.001). FAF lifetimes increased with age in the controls (p = 0.006-0.03), but not in the patients. Patients with SDD had longer FAF lifetimes than those without (p = 0.003-0.068). PEW neither showed significant group differences nor age dependence. CONCLUSIONS Although long fluorescence lifetimes of the lens can affect FAF lifetime measurements, prolonged FAF lifetimes in AMD are specific to the disease and not a lens artefact as shown in pseudophakic eyes. The effect of AMD on the lifetimes outweighs that of age. Patients with SDD, who have a higher risk of AMD progression, also show longer FAF lifetimes.
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Affiliation(s)
- Jana Oertel
- Department of Ophthalmology, University Hospital Jena, Jena, Germany
| | - Dominik Fischer
- Department of Ophthalmology, University Hospital Jena, Jena, Germany
| | - Melih Tarhan
- Department of Ophthalmology, University Hospital Jena, Jena, Germany
| | - Daniel Meller
- Department of Ophthalmology, University Hospital Jena, Jena, Germany
| | - Martin Hammer
- Department of Ophthalmology, University Hospital Jena, Jena, Germany
- Center for Medical Optics and Photonics, University of Jena, Jena, Germany
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11
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Overbey K, Romano F, Ding X, Bennett CF, Stettler I, Garg I, Ploumi I, Vingopoulos F, Yuan M, Razavi P, Finn M, Laíns I, Patel NA, Kim L, Wu D, Eliott D, Husain D, Vavvas D, Miller JW, Miller JB. Choriocapillaris impairment in dry AMD: insights from swept-source OCT angiography and associations with structural biomarkers. Br J Ophthalmol 2025:bjo-2024-326416. [PMID: 40360203 DOI: 10.1136/bjo-2024-326416] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 04/24/2025] [Indexed: 05/15/2025]
Abstract
AIMS To assess choriocapillaris flow deficit percentage (CCFD%) across stages of dry age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS This cross-sectional, observational study included 270 eyes (182 patients), classified as early (70 eyes), intermediate (121 eyes) and geographic atrophy (GA, 79 eyes).Participants underwent a complete examination including macular 6×6 mm SS-OCTA scans (PLEX Elite 9000). Scans were reviewed and analysed for subretinal drusenoid deposits (SDDs), retinal pigment epithelium (RPE) atrophy size, incomplete RPE and outer retinal atrophy (iRORA) and drusen volume (3 mm). CCFD% was calculated after compensation and binarisation using Phansalkar's method (r=4-15 pixels) in various early treatment for diabetic retinopathy study sectors. Linear mixed-effects models adjusted for age evaluated associations with AMD stages and other imaging biomarkers. RESULTS CCFD% progressively increased with advancing dry AMD stages. Intermediate AMD eyes showed higher CCFD% than early AMD ones across all regions (p<0.001). GA eyes exhibited significantly higher CCFD% compared with early (p<0.001) and intermediate AMD eyes (p<0.001).SDDs were significantly associated with higher CCFD% in early (p<0.01) and intermediate AMD (p<0.05) for almost all regions examined, but not in GA (p>0.05). iRORA presence in iAMD and larger RPE atrophy in GA correlated with increased CCFD% (p<0.001). CONCLUSIONS This study provides a comprehensive reference database for CCFD% across the stages of dry AMD using SS-OCTA. CCFD% increased with AMD severity, iRORA, SDDs, particularly in early and intermediate stages, and RPE atrophy size. Our findings support CCFD% as a valuable biomarker for clinical and research applications, warranting longitudinal studies to validate its prognostic value.
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Affiliation(s)
- Katherine Overbey
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
| | - Francesco Romano
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Xinyi Ding
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Cade F Bennett
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
| | - Isabella Stettler
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
| | - Itika Garg
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Ioanna Ploumi
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
| | - Filippos Vingopoulos
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Melissa Yuan
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Peyman Razavi
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
| | - Matthew Finn
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
| | - Inês Laíns
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Nimesh A Patel
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Leo Kim
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - David Wu
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Dean Eliott
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Deeba Husain
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Demetrios Vavvas
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - Joan W Miller
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
| | - John B Miller
- Harvard Retinal Imaging Lab, Massachusetts Eye and Ear, Boston, MA, USA
- Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA
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12
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Chandak S, Gurudas S, Pakeer Muhammed R, Keskin A, Thottarath S, Ghanchi F, Grabowska A, Talks SJ, Pearce I, McKibbin M, Kotagiri A, Menon G, Burton BJL, Gale R, Sivaprasad S. Visual outcome following initiation of first injection versus after three monthly doses of aflibercept 2 mg for treatment naïve age-related macular degeneration to inform clinical trial designs: PRECISE Report No. 6. Eye (Lond) 2025:10.1038/s41433-025-03797-z. [PMID: 40355704 DOI: 10.1038/s41433-025-03797-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 03/29/2025] [Accepted: 03/31/2025] [Indexed: 05/14/2025] Open
Abstract
PURPOSE To study the outcome of the first dose versus three monthly doses of 2 mg aflibercept in the initiation phase of neovascular age-related macular degeneration (nAMD) to inform future clinical trial design on novel durable agents. These agents may take time to act and so initial dosing with aflibercept 2 mg is required for immediate effect. METHODS Visual acuity (VA) outcomes and associations with baseline VA and OCT characteristics were analysed using logistic regression via generalised estimating equations. In addition, VA outcomes based on different combinations of eligibility criteria were assessed. RESULTS A total of 1999 eyes of 1862 patients were analysed. The mean age was 79.3 (SD 7.8) years. The mean presenting VA was 58.0 (SD 14.5) ETDRS letter score. A statistical difference in VA was found after first injection (visit 2, 61.6, SD 14.3 ETDRS letter score) and after three monthly injections (visit 4, 62.7, SD 14.9 ETDRS letter score) (P < 0.001). Lower baseline VA and OCT features suggestive of structural changes in the fovea are associated with lower VA after both first and post- initiating doses. Eyes with baseline VA > / = 54 letters alone had similar VA outcomes to eyes with both VA > / = 54 letters and central subfield thickness (CST) of <500 microns. CONCLUSION Mean VA outcomes after three monthly anti-VEGF injections are significantly better than after the first initiating dose. However, baseline OCT characteristics associated with VA in these two timepoints are not clinically different.
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Affiliation(s)
- Swati Chandak
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
| | - Sarega Gurudas
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
- Institute of Ophthalmology, University College, London, UK
| | - Raheeba Pakeer Muhammed
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
| | - Ayse Keskin
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
| | - Sridevi Thottarath
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK
| | - Faruque Ghanchi
- Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Anna Grabowska
- King's College Hospital NHS Foundation Trust, London, UK
| | | | - Ian Pearce
- The Royal Liverpool and Broadgreen University Hospitals NHS Foundation Trust, Liverpool, UK
| | | | - Ajay Kotagiri
- South Tyneside and Sunderland NHS Foundation Trust, Sunderland, UK
| | - Geeta Menon
- Frimley Health NHS Foundation Trust, Surrey, UK
| | | | - Richard Gale
- York Teaching Hospital NHS Foundation Trust, York, UK
| | - Sobha Sivaprasad
- National Institute of Health Research Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, UK.
- Institute of Ophthalmology, University College, London, UK.
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13
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Hoshino J, Matsumoto H, Numaga S, Nakamura K, Akiyama H. Two-year outcomes of treat-and-extend regimen with intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration. Jpn J Ophthalmol 2025:10.1007/s10384-025-01204-4. [PMID: 40347367 DOI: 10.1007/s10384-025-01204-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/24/2025] [Indexed: 05/12/2025]
Abstract
PURPOSE We previously reported 1-year outcomes of a treat-and-extend (TAE) regimen with intravitreal faricimab (IVF) for treatment-naïve neovascular age-related macular degeneration (nAMD). Herein, we evaluated the second-year results of this TAE regimen with IVF in eyes completing the first-year treatment. STUDY DESIGN Retrospective, interventional case series. METHODS We retrospectively studied 30 eyes with treatment-naïve nAMD that had completed the initial year of treatment, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), total number of injections over 2 years, and intended injection interval at the last visit. RESULTS Twenty-five eyes completed the 2-year IVF treatment. There was no significant difference between pre-treatment and 2 years post-treatment BCVA. FT and CCT both showed significant reductions, maintained during the 2-year study period. The total number of injections was 10.1 ± 1.2 over the 2 years. The intended injection interval at the last visit was 13.0 ± 3.4 weeks. Of 5 eyes not completing 2 years of IVF treatment, 4 were switched to other anti-vascular endothelial growth factor (VEGF) agents due to persistent fluids despite IVF at 8-week intervals. In the remaining eye, IVF treatment was discontinued due to suspected faricimab-related intraocular inflammation. CONCLUSIONS The TAE regimen with IVF for treatment-naïve nAMD was effective during a 2-year period for improving exudative changes and maintaining visual acuity. Although IVF was found to be a relatively safe treatment for nAMD, there were cases requiring a switch to other anti-VEGF agents due to inadequate fluid control effect.
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Affiliation(s)
- Junki Hoshino
- Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Hidetaka Matsumoto
- Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
| | - Saki Numaga
- Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Kosuke Nakamura
- Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan
| | - Hideo Akiyama
- Department of Ophthalmology, Gunma University Graduate School of Medicine, 3-39-15 Showa-machi, Maebashi, Gunma, 371-8511, Japan
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14
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Saito M, Mitamura M, Ito Y, Endo H, Katsuta S, Ishida S. Inter-Relationships Between the Deep Learning-Based Pachychoroid Index and Clinical Features Associated with Neovascular Age-Related Macular Degeneration. J Clin Med 2025; 14:3245. [PMID: 40364275 PMCID: PMC12072645 DOI: 10.3390/jcm14093245] [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: 04/04/2025] [Revised: 04/29/2025] [Accepted: 05/06/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: To investigate the impact of pachychoroid on the clinical features of neovascular age-related macular degeneration (nAMD) in Japan using the deep learning-based Hokkaido University pachychoroid index (HUPI), which has a high discriminative ability for pachychoroid. Methods: This retrospective observational study examined 124 eyes of 111 treatment-naïve nAMD patients, including 44 eyes with type 1 macular neovascularization (MNV), 26 eyes with type 2 MNV, and 54 eyes with polypoidal choroidal vasculopathy (PCV). HUPI was calculated for each eye from EDI-OCT choroidal images using our modified LeNet that had learned the image patterns of pachychoroid. Differences in HUPI between nAMD types and inter-relationships between nAMD parameters, including HUPI, were evaluated. Results: The mean HUPI was 0.53 ± 0.30 for type 1 MNV, 0.33 ± 0.23 for type 2 MNV, and 0.61 ± 0.3 for PCV, with significant differences between any two of the three groups (p < 0.05, for each). Round-robin multiple regression analysis for nAMD parameters showed the close associations of the HUPI with choroidal vascular hyperpermeability (CVH) and subretinal fluid (SRF) (p = 0.017 and p < 0.001 for each) and the clear division of nAMD parameters into the following two groups: one including intraretinal fluid and type 1 and type 2 MNV and the other including SRF, CVH, polypoidal lesions, and HUPI. Conclusions: HUPI revealed that eyes with type 1 MNV and PCV had more pachychoroid-like features than eyes with type 2 MNV. HUPI was tightly associated with CVH and SRF but not MNV per se in nAMD parameters, reinforcing the pathoetiological concept of differentiating pachychoroid from typical nAMD.
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Affiliation(s)
- Michiyuki Saito
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan
| | - Mizuho Mitamura
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan
| | - Yuki Ito
- Department of Ophthalmology, Teine Keijinkai Hospital, Sapporo 006-8555, Japan
| | - Hiroaki Endo
- Department of Ophthalmology, Teine Keijinkai Hospital, Sapporo 006-8555, Japan
| | - Satoshi Katsuta
- Department of Ophthalmology, Teine Keijinkai Hospital, Sapporo 006-8555, Japan
| | - Susumu Ishida
- Department of Ophthalmology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-8638, Japan
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15
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Yang HS, Jeon S. Clinical implication of aberrant choroidal feeding artery in type 1 macular neovasculopathy. Sci Rep 2025; 15:15966. [PMID: 40335557 PMCID: PMC12059174 DOI: 10.1038/s41598-025-01094-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Accepted: 05/02/2025] [Indexed: 05/09/2025] Open
Abstract
Type 1 macular neovascularization (MNV) is the most common type of MNV located in the sub-retinal pigment epithelium (RPE). Although type 1 MNV harbors significant clinical variabilities, the underlying pathomechanism has not been fully elucidated yet. The present study evaluated the characteristics of the choroidal feeding artery in 51 eyes with type 1 MNV using a multimodal imaging composite. In most cases (88.2%), a clear, visible connection between the MNV and choroidal artery was not confirmed. A seamless connection between the MNV and the underlying choroidal feeding artery was found in six of 51 eyes (11.8%). Patients with this aberrant choroidal feeding artery showed large pigment epithelial detachments (PED; P < 0.001) and sub-RPE deposits (P < 0.001) more frequently. Patients with aberrant choroidal feeding arteries achieved a dry macula of a similar percentage (P = 0.680) with more frequent anti-vascular endothelial growth factor injections (P = 0.005) and a switch to brolucizumab (P = 0.042) during a similar follow-up period (P = 0.305). Type 1 MNV with aberrant choroidal feeding arteries showed distinct characteristics from unimpeded blood flow (Large PED and sub-RPE deposits), suggesting that the aberrant choroidal arteries serve not only as a source of blood flow but also contribute to the development of MNV by arteriogenesis.
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Affiliation(s)
- Hyun Seung Yang
- Department of Ophthalmology, Seoul Shinsegae Eye Center, Seoul, Republic of Korea
- Biomedical Imaging Research Institute, Seoul Shinsegae Eye Center, Seoul, Republic of Korea
- Department of Applied Bioengineering, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea
| | - Sohee Jeon
- Keye Eye Center, 326 Teheran-ro, Gangnam-gu, Seoul, Republic of Korea.
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16
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Xiaodong L, Xia C, Xuewei Q, Dandan W, Yi Y, Zhilin L. Sustainable Practices in Anti-VEGF Therapy: A 15-Year Bibliometric Analysis of Ranibizumab for Age-Related Macular Degeneration. J Ophthalmol 2025; 2025:8891531. [PMID: 40365539 PMCID: PMC12074854 DOI: 10.1155/joph/8891531] [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: 12/02/2024] [Accepted: 04/12/2025] [Indexed: 05/15/2025] Open
Abstract
Objective: A bibliometric analysis was performed in the domain of ranibizumab and age-related macular degeneration (AMD) to delineate current trends in international research dynamics and to provide a visual representation of research hotspots and challenges associated with ophthalmic drugs over the past 15 years. This study also evaluates the sustainability of ranibizumab therapy through reduced injection burden, cost-effectiveness compared to alternative treatments, and long-term outcomes that minimize healthcare resource utilization. Method: In this cross-sectional study, bibliometrics analyzed data retrieved and extracted from the Web of Science Core Collection (WOSCC) database to analyze the evolution and thematic trends in the delivery of studies from January 1, 2008, to September 2, 2023, for ranibizumab and AMD studies. A total of 2691 articles on the field were assessed for specific characteristics such as the year of publication, journal, author, institution, country/region, citation, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed using VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. Results: From 2008 to 2023, the cumulative number of articles published globally increased from 1 to 2,691, with the highest number of articles published in 2020 (255 papers). RETINA THE JOURNAL OF RETINAL AND VITREOUS DISEASES published the most manuscripts (285 papers) and was cited (6496 citations), followed by OPHTHALMOLOGY (193 papers) and GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY (163 papers). OPHTHALMOLOGY was the most cited (20,865 citations), with the United States (786 papers, 38,014 citations), Univ Sydney (98 papers, 5245 citations), and Kim, Jong Woo (56 papers, 550 citations) being the most productive and influential institutions, countries, and authors, respectively. Five clusters were formed by summarizing the top 100 keywords, which marked the emerging frontier of ranibizumab and AMD-related research. Further discussion of the five clusters of research is to assist the researcher in determining the scope of the research topic and planning the direction of the research. Conclusion: Over the past two decades, there has been a notable increase in the number of publications and citations pertaining to ranibizumab and AMD across various countries, institutions, and authors. This study elucidates current trends, global collaboration patterns, foundational knowledge, research hotspots, and developmental trajectories within the realm of ranibizumab-related AMD research. Key advancements in AMD treatment with ranibizumab over the last 15 years have centered on less frequent injection schedules, extended drug efficacy, and enhanced safety profiles.
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Affiliation(s)
- Li Xiaodong
- Department of Ophthalmology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Chen Xia
- Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Qin Xuewei
- Department of Ophthalmology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Wu Dandan
- Department of Ophthalmology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Yang Yi
- Department of Ophthalmology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, China
| | - Li Zhilin
- Department of Ophthalmology, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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17
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Jaggi D, Berger LE, Zweifel S, Becker MD, Michels S, Stalder O, Lincke JB, Habra O, Wolf S, Zinkernagel MS. Comparison of treatment routine using aflibercept: Strict vs. relaxed retreatment regimen (TOLERANT study)-A non-inferiority, randomized controlled trial. Acta Ophthalmol 2025. [PMID: 40326420 DOI: 10.1111/aos.17514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 04/23/2025] [Indexed: 05/07/2025]
Abstract
PURPOSE This trial evaluated the noninferiority of a relaxed compared to a strict treat-and-extend treatment strategy in patients with neovascular Age-related macular degeneration (AMD). METHODS Multicenter, randomized, controlled, phase IV, non-inferiority clinical trial. Patients with treatment-naïve nAMD were randomized 1:1 to a relaxed or strict treat-and-extend treatment regimen. Aflibercept 2 mg/0.05 mL was used. In the relaxed regimen, up to 100 μm subfoveal subretinal fluid was tolerated, vs. no tolerance of any fluid in the strict regimen. The primary outcome was the change in best corrected visual acuity (BCVA; ETDRS letters) from baseline to the end of the study at week 104 and its difference between the two treatment arms, with a 5-letter non-inferiority margin. RESULTS We randomized 150 patients. The full analysis showed non-inferiority of the relaxed treatment, with a mean difference of -0.12 letters (95%-CI: -3.45 to infinity, H0; mean. diff. ≤ 5 letters: p = 0.008), and a visual acuity gain of 7.3 (4.82; 9.78) vs. 7.01 (3.67; 10.36) letters in the strict vs. relaxed regimen, respectively. Many patients deviated from the protocol due to Covid-19. Per-protocol analysis showed a mean difference of -1.78 letters (95%-CI: -6.61 to infinity, H0; mean. diff. ≤ 5 letters: p = 0.136). Fewer injections were needed in the relaxed regimen, with a mean difference of -2.34 (95%-CI: -4.11 to -0.56, p = 0.01). CONCLUSION Tolerating up to 100 μm subfoveal subretinal fluid achieves good visual outcomes in our 24-month follow-up period, in patients treated with aflibercept for nAMD, with significantly fewer injections needed.
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Affiliation(s)
- Damian Jaggi
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
| | - Lieselotte E Berger
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
| | - Sandrine Zweifel
- Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Matthias D Becker
- Spross Research Institute, Department of Ophthalmology, Zürich City Hospital, Zürich, Switzerland
- Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany
| | | | | | - Joel-Benjamin Lincke
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
| | - Oussama Habra
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
| | - Sebastian Wolf
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
| | - Martin S Zinkernagel
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of BioMedical Research, University of Bern, Bern, Switzerland
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18
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Yoon JM, Noh H, Nam SW, Ham DI. Peripheral retinal and choroidal thickness of eyes with reticular pseudodrusen. Graefes Arch Clin Exp Ophthalmol 2025:10.1007/s00417-025-06842-5. [PMID: 40319159 DOI: 10.1007/s00417-025-06842-5] [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: 09/10/2024] [Revised: 03/26/2025] [Accepted: 04/22/2025] [Indexed: 05/07/2025] Open
Abstract
PURPOSE This study aimed to investigate the peripheral retinal and choroidal thicknesses in eyes with reticular pseudodrusen (RPD). METHODS Imaging data of ultrawide-field swept-source optical coherence tomography taken from 40 patients with age-related macular degeneration (AMD) were analyzed. Thirty-nine eyes of 20 patients had RPD (RPD group) and 39 eyes of 20 patients had no RPD (control group). Eyes with RPD were divided into localized/intermediate and diffuse types according to the fundus distribution. The retinal and choroidal thicknesses were measured at the fovea and six peripheral points in each eye, and the results were statistically analyzed. RESULTS The mean ages were 78.0 ± 6.1 years in the RPD group and 74.4 ± 7.2 years in the control group. The RPD group showed a thinner retina only at the nasal point (p = 0.002) than the control group. The choroid was significantly thinner in the RPD group than in the control group at most peripheral points, except for the far temporal and far inferior points. Diffuse and localized/intermediate types of RPD eyes showed no significant difference in choroidal thickness, except at the nasal point, which was thinner in the diffuse type (p = 0.049). CONCLUSION In eyes with RPD, most peripheral retinal thicknesses were not different from those of eyes with AMD without RPD; however, most peripheral choroidal thicknesses were thinner regardless of the fundus distribution status of the RPD. Nasal choroidal thickness may be associated with RPD severity.
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Affiliation(s)
- Je Moon Yoon
- Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hoon Noh
- Hangil Eye Hospital, Incheon, Republic of Korea
| | - Seung Wan Nam
- Good Morning Light Eye Clinic, Ulsan, Republic of Korea
| | - Don-Il Ham
- Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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Feo A, Ramtohul P, Govetto A, Borrelli E, Sacconi R, Corradetti G, Querques G, Romano MR, Rosenfeld PJ, Spaide RF, Freund KB, Sadda S, Sarraf D. En face OCT: Breakthroughs in understanding the pathoanatomy of retinal disease and clinical applications. Prog Retin Eye Res 2025; 106:101351. [PMID: 40054600 DOI: 10.1016/j.preteyeres.2025.101351] [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: 10/03/2024] [Revised: 03/03/2025] [Accepted: 03/04/2025] [Indexed: 03/16/2025]
Abstract
En face optical coherence tomography (OCT) is a practical and informative imaging modality to noninvasively visualize distinct retinal and choroidal layers by providing coronal images using boundary-specific segmentation. Ongoing research with this method is generating breakthroughs in the illustration of new perspectives of retinal disease. The clinical value of en face OCT as an advanced retinal imaging tool is growing steadily and it has unveiled many new insights into the pathoanatomy of retinal disorders. Moreover, this modality can capture various en face OCT biomarkers that correspond to different cell or tissue subtypes, which were previously only identified through histological or electron microscopy methods, underscoring the significance of this technique in providing valuable pathoanatomical information. In this comprehensive review, we will systematically summarize the en face OCT findings across a broad spectrum of retinal diseases, including disorders of the vitreoretinal interface and retinal vascular system (e.g. paracentral acute middle maculopathy or PAMM and diabetic retinopathy), in addition to the en face OCT features of other conditions such as age-related macular degeneration, pachychoroid disease spectrum, myopic degeneration, uveitis and inflammatory disorders, inherited retinal dystrophies, and drug toxicity. We will discuss and highlight the unique clinical and pathoanatomical findings uncovered with en face OCT of each these diseases mentioned above.
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Affiliation(s)
- Alessandro Feo
- Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute, University of California of Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele-Milan, 20072, Italy
| | - Prithvi Ramtohul
- Ophthalmology Department, Hopital Nord, Aix-Marseille University, Marseille, France; Vitreous Retina Macula Consultants of New York, New York, NY, United States
| | - Andrea Govetto
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele-Milan, 20072, Italy; Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, Bergamo, Italy
| | - Enrico Borrelli
- Department of Surgical Sciences, University of Turin, Turin, Italy; Department of Ophthalmology, "City of Health and Science" Hospital, Turin, Italy
| | - Riccardo Sacconi
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Giulia Corradetti
- Department of Ophthalmology, Doheny Eye Institute, University of California Los Angeles, Los Angeles, CA, United States
| | - Giuseppe Querques
- School of Medicine, Vita-Salute San Raffaele University, Milan, Italy; Division of Head and Neck, Ophthalmology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Mario R Romano
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele-Milan, 20072, Italy; Department of Ophthalmology, Eye Unit Humanitas Gavazzeni-Castelli, Via Mazzini 11, Bergamo, Italy
| | - Philip J Rosenfeld
- Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, United States
| | - Richard F Spaide
- Vitreous Retina Macula Consultants of New York, New York, NY, United States
| | - K Bailey Freund
- Vitreous Retina Macula Consultants of New York, New York, NY, United States; Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY, United States
| | - SriniVas Sadda
- Department of Ophthalmology, Doheny Eye Institute, University of California Los Angeles, Los Angeles, CA, United States
| | - David Sarraf
- Retinal Disorders and Ophthalmic Genetics Division, Stein Eye Institute, University of California of Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States; Greater Los Angeles VA Healthcare Center, Los Angeles, CA, United States.
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20
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Janmohamed IK, Mushtaq A, Kabbani J, Harrow S, Nadarajasundaram A, Ata A, Monye H, Jarrar Z, Hannan S, Membrey L. 1-Year real-world outcomes of faricimab in previously treated neovascular age-related macular degeneration. Eye (Lond) 2025; 39:1344-1348. [PMID: 39863706 PMCID: PMC12044001 DOI: 10.1038/s41433-025-03616-5] [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: 10/05/2024] [Revised: 12/23/2024] [Accepted: 01/13/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND AND OBJECTIVES Faricimab, a bispecific antibody targeting VEGF-A and angiopoietin-2, has shown promise in treating neovascular age-related macular degeneration (nAMD). This study evaluates 1-year outcomes of faricimab in treatment-experienced nAMD patients. METHODS This single-centre retrospective cohort study included patients previously treated for nAMD who switched to faricimab between November 2022 and March 2024. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and treatment intervals were assessed at baseline, 6, and 12 months. RESULTS One hundred eighty-four patients (215 eyes) were included. Patients had received a median of 18 (interquartile range [IQR] 10-28.5) anti-VEGF injections per eye over an average of 5.02 ± 11.82 years before switch. An average of 8.63 ± 2.2 faricimab injections were administered per eye over an average follow-up of 12.19 ± 2.70 months. Median BCVA decreased from 70 ETDRS letters (IQR 55-76) at baseline to 62 (IQR 47-76) at 12 months (p = 0.0038). Median CMT improved from 259.5 μm (IQR 223-299.75) at baseline to 232 μm (202.0-272.5) at 12 months (p < 0.0001). At the last follow-up, 40.2% of eyes were dry on OCT. The median dosing interval doubled from 4 weeks (IQR 4-4) to 8 weeks (IQR 6-10) with faricimab (p < 0.0001). 47.4% and 16.3% of eyes achieved treatment intervals of ≥8-12 weeks and ≥12 weeks, respectively. Three events of uveitis were noted following the loading phase. CONCLUSIONS This real-world study demonstrates that faricimab maintains vision and achieves significant anatomical improvements in treatment-experienced nAMD patients. The extended treatment intervals could significantly reduce the burden on patients and healthcare resources.
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Affiliation(s)
| | | | - Jamil Kabbani
- Kingston Hospital Eye Department, Kingston, London, UK
| | | | | | - Anibe Ata
- Maidstone Hospital Eye Department, Hermitage Lane, Maidstone, UK
| | - Henrietta Monye
- Maidstone Hospital Eye Department, Hermitage Lane, Maidstone, UK
| | | | - Shabeeba Hannan
- Maidstone Hospital Eye Department, Hermitage Lane, Maidstone, UK
| | - Luke Membrey
- Maidstone Hospital Eye Department, Hermitage Lane, Maidstone, UK
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21
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Hafner M, Asani B, Eckardt F, Siedlecki J, Schworm B, Priglinger SG, Schiefelbein J. Deep-Learning-Assisted Analysis of Early Biomarker Changes in Treatment-Naïve Patients with Neovascular AMD Under Intravitreal Faricimab. Ophthalmol Ther 2025; 14:1025-1037. [PMID: 40133689 PMCID: PMC12006649 DOI: 10.1007/s40123-025-01125-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Accepted: 03/04/2025] [Indexed: 03/27/2025] Open
Abstract
INTRODUCTION Artificial intelligence (AI)-driven biomarker segmentation offers an objective approach to assessing neovascular age-related macular degeneration (nAMD). In addition, faricimab, a bispecific VEGF and Ang-2 inhibitor, presents new potential in disease management. This study applies an AI-based segmentation algorithm to quantify key optical coherence tomography (OCT) biomarkers and assess the short-term efficacy of intravitreal faricimab in treatment-naïve patients. METHODS This retrospective analysis includes 40 eyes from 38 treatment-naïve patients with nAMD treated with faricimab at LMU University Hospital Munich between January 2023 and September 2024. Patients received 4-monthly intravitreal injections. Biomarkers of disease activity, including central retinal thickness (CRT), intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM) and fibrovascular pigment epithelium detachment (fvPED), were quantified using a deep learning-based semantic segmentation algorithm. Best-corrected visual acuity (BCVA) and OCT imaging data were analyzed at baseline (mo0) and after 1 (mo1), 2 (mo2) and 3 months (mo3). RESULTS AI-driven analysis revealed significant reductions in key biomarkers. CRT decreased from 433.6 (IQR: 306.6) µm at mo0 to 241.5 (IQR: 130.8) µm at mo3 (p < 0.0001). IRF and SRF volumes were reduced by > 99% from mo0 to mo3 (both p < 0.0001). BCVA improved from 0.60 (IQR: 0.30) logMAR at mo0 to 0.40 (IQR: 0.33) logMAR at mo3 (p < 0.0001). Correlation analysis identified IRF and SHRM reductions as the strongest predictors of visual improvement. CONCLUSION This study demonstrates the potential of AI-assisted biomarker analysis for precise disease monitoring in nAMD. Faricimab significantly reduced disease activity biomarkers and improved visual acuity in treatment-naïve patients, reinforcing its efficacy in early disease control. Future studies should explore long-term outcomes and further integrate AI-driven biomarker evaluation in clinical practice.
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Affiliation(s)
- Michael Hafner
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany.
| | - Ben Asani
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Franziska Eckardt
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Jakob Siedlecki
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Benedikt Schworm
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Siegfried G Priglinger
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Johannes Schiefelbein
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
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Tanaka K, Omori T, Oguchi Y, Itagaki K, Kato Y, Honjo J, Norikawa K, Sugano Y, Mukai R, Ishida Y, Machida T, Sekine H, Sekiryu T. HTRA1 and complement activation in neovascular age-related macular degeneration. Jpn J Ophthalmol 2025; 69:453-459. [PMID: 39937341 DOI: 10.1007/s10384-024-01153-4] [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: 03/17/2024] [Accepted: 10/30/2024] [Indexed: 02/13/2025]
Abstract
PURPOSE To investigate the relationship between high temperature requirement A (HTRA1) and the local complement system, we measured HTRA1 and complement activation products in the aqueous humor of patients with neovascular age-related macular degeneration (nAMD). STUDY DESIGN Surveys (cross-sectional studies). METHODS One hundred twenty-one eyes of 121 patients with nAMD and 55 control eyes were enrolled. HTRA1, complement activation products (C3a and C4a), and proinflammatory cytokines (vascular endothelial growth factor [VEGF] and monocyte chemoattractant protein-1) were measured. Genotyping of ARMS2 A69S, in linkage disequilibrium with the HTRA1 gene, was performed in all patients and controls. RESULTS The respective GG, GT, and TT genotypes for ARMS2 A69S were distributed as follows: 23 (19.0%), 54 (44.6%), and 44 (36.4%) in nAMD patients, and 26 (47.3%), 22 (40.0%), and 7 (12.7%) in controls, (p < 0.001). HTRA1 concentrations in the aqueous humor were higher in nAMD (994 pg/ml; interquartile range, 743-1450) than controls (794 pg/ml; 490-1325). The difference in the HTRA1 concentrations in the aqueous humor between each genotype of ARMS2 A69S was not significant (GG genotype: 857 pg/ml; 508-1115, GT genotype: 957 pg/ml; 758-1474, TT genotype: 1,141 pg/ml; 757-1663, p = 0.1417). VEGF and C3a concentrations in the eyes with the risk allele (T allele) were significantly higher than those with the non-risk allele (p = 0.0400 and p = 0.0197, respectively). HTRA1 concentration was correlated with only the VEGF concentration (ρ = 0.3651, p < 0.0001). CONCLUSION Concentrations of HTRA1 in the aqueous humor were not increased in patients with the ARMS2 risk allele and did not correlate with C3a and C4a concentrations. HTRA1 concentrations in aqueous humor do not reflect local complement activation in nAMD.
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Affiliation(s)
- Keiichiro Tanaka
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan.
| | - Tomoko Omori
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Yasuharu Oguchi
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Kanako Itagaki
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Yutaka Kato
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Junichiro Honjo
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Koki Norikawa
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Yukinori Sugano
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Ryo Mukai
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Yumi Ishida
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Takeshi Machida
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Hideharu Sekine
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
| | - Tetsuju Sekiryu
- Department of Ophthalmology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima, Fukushima, 960-1247, Japan
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Ţurcaş C, Nicoară SD. A comprehensive review of structure-function correlations in age-related macular degeneration: Contributions of microperimetry. Surv Ophthalmol 2025; 70:426-450. [PMID: 39828006 DOI: 10.1016/j.survophthal.2025.01.009] [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: 10/28/2024] [Revised: 01/11/2025] [Accepted: 01/13/2025] [Indexed: 01/22/2025]
Abstract
Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness worldwide. High-resolution imaging techniques have been pivotal in characterizing the morphological alterations in the retina and in identifying structural biomarkers with prognostic significance. In clinical practice, visual function is primarily assessed through visual acuity testing, which, however, does not completely reflect the functional deficits experienced by patients. Microperimetry provides a more comprehensive evaluation of macular function, enabling a direct correlation with retinal structure. We examine the current literature on the correlation between morphological biomarkers - identified via optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence - and retinal sensitivity, as assessed by microperimetry. By encompassing all stages of AMD, we explore the association between retinal sensitivity and a broad spectrum of structural parameters, including distinct drusen phenotypes, hyperreflective foci, the integrity and thickness of various retinal layers, the junctional zone of geographic atrophy, exudative features of neovascular AMD, choriocapillaris flow deficits, and diverse patterns of autofluorescence, among numerous other relevant structural markers. By offering a deeper understanding of the structure-function correlations in disease progression, we provide critical up-to-date insights into the underlying mechanisms of AMD. Moreover, as novel therapeutic strategies continue to emerge, these correlations may serve as more robust endpoints for future clinical trials.
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Affiliation(s)
- Cristina Ţurcaş
- Doctoral School, "Iuliu Hațieganu" University of Medicine and Pharmacy, Emil Isac 13, Cluj-Napoca 400023, Romania; Department of Ophthalmology, "Iuliu Hațieganu" University of Medicine and Pharmacy, Victor Babeș 8, Cluj-Napoca 400012, Romania.
| | - Simona Delia Nicoară
- Department of Ophthalmology, "Iuliu Hațieganu" University of Medicine and Pharmacy, Victor Babeș 8, Cluj-Napoca 400012, Romania; Ophthalmology Clinic, Emergency County Hospital, Clinicilor 3-5, Cluj-Napoca 400006, Romania.
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Wykoff CC, Jackson TL, Price CF, Baldwin ME, Leitch IM, Slakter J. Sozinibercept Combination Therapy for Neovascular Age-related Macular Degeneration: Phase 2b Study Subgroup Analysis by Lesion Type. Ophthalmic Surg Lasers Imaging Retina 2025; 56:287-296. [PMID: 39999360 DOI: 10.3928/23258160-20250108-04] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/27/2025]
Abstract
BACKGROUND AND OBJECTIVE The purpose of this study was to evaluate the angiographic predictors of response to the anti-vascular endothelial growth factor-C/-D agent, sozinibercept. PATIENTS AND METHODS Prespecified and post hoc subgroup analyses of a phase 2b, randomized, double-masked, sham-controlled trial of 240 participants with treatment-naïve neovascular age-related macular degeneration, comparing monthly intravitreal sozinibercept 0.5 mg or 2 mg, plus ranibizumab 0.5 mg, versus monthly ranibizumab monotherapy. RESULTS Visual acuity benefits at week 24 were greatest in participants with occult lesions receiving 2 mg sozinibercept combination therapy (+15.65 [n = 53] letters versus +9.62 [n = 51] with ranibizumab monotherapy; least squares mean difference +6.03; P = 0.0009). A composite analysis of occult and minimally classic lesions excluding retinal angiomatous proliferation (n = 175/240) also favored sozinibercept over control (+16.08 versus +10.34 letters; +5.74; P = 0.0002). Structural outcomes mirrored sozinibercept visual acuity benefits, with less leakage and smaller lesions on multimodal imaging. CONCLUSION Angiographic lesion characteristics were found to predict the response to sozinibercept combination therapy. [Ophthalmic Surg Lasers Imaging Retina 2025;56:287-296.].
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Funatsu R, Terasaki H, Mihara N, Sonoda S, Shiihara H, Miyake S, Imatsuji H, Sakamoto T. IDENTIFICATION OF LEAKAGE SITES IN CENTRAL SEROUS CHORIORETINOPATHY USING OPTICAL COHERENCE TOMOGRAPHY AND THE ASSESSMENT OF THE CHARACTERISTICS OF THE BIOMARKERS. Retina 2025; 45:893-900. [PMID: 39841922 DOI: 10.1097/iae.0000000000004404] [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] [Indexed: 01/24/2025]
Abstract
PURPOSE To identify optical coherence tomography-based imaging biomarkers that can localize focal leakage points without fluorescein angiography in central serous chorioretinopathy (CSC). METHODS This retrospective case-control study analyzed 119 consecutive patients (123 eyes) with CSC between April 2018 and February 2024, comprising 66 eyes with focal-leakage type and 57 eyes with diffuse-leakage type. We assessed leakage sites using optical coherence tomography, and the proportions of optical coherence tomography findings were compared between focal-leakage and diffuse-leakage types. RESULTS Hyporeflective lucency signs were observed in 27 eyes (40.9%) with focal-type CSC, while no such signs were detected in diffuse-type CSC cases (0.0%; P < 0.001). In focal-type CSC, these signs were exclusively localized to leakage points, with no occurrence in other areas within serous retinal detachment. Microrips of retinal pigment epithelium and subretinal hyperreflective material were identified in 23 (34.8%) and 47 eyes (71.2%) with focal-type CSC, respectively, and also in eyes with diffuse-type CSC (5.3% and 19.3%, respectively; P < 0.001 for both comparisons). CONCLUSION Only the hyporeflective lucency sign is present exclusively in focal leakage points of fluorescein angiography. Our findings suggested that the hyporeflective lucency sign may serve as a potential therapeutic target in CSC.
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Affiliation(s)
- Ryoh Funatsu
- Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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26
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Riedl S, Birner K, Schmidt-Erfurth U. Artificial intelligence in managing retinal disease-current concepts and relevant aspects for health care providers. Wien Med Wochenschr 2025; 175:143-152. [PMID: 39992600 PMCID: PMC12031981 DOI: 10.1007/s10354-024-01069-1] [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: 07/06/2024] [Accepted: 12/18/2024] [Indexed: 02/26/2025]
Abstract
Given how the diagnosis and management of many ocular and, most specifically, retinal diseases heavily rely on various imaging modalities, the introduction of artificial intelligence (AI) into this field has been a logical, inevitable, and successful development in recent decades. The field of retinal diseases has practically become a showcase for the use of AI in medicine. In this article, after providing a short overview of the most relevant retinal diseases and their socioeconomic impact, we highlight various aspects of how AI can be applied in research, diagnosis, and disease management and how this is expected to alter patient flows, affecting also health care professionals beyond ophthalmologists.
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Affiliation(s)
- Sophie Riedl
- Department of Ophthalmology and Optometry, Laboratory of Ophthalmic Image Analysis, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Klaudia Birner
- Department of Ophthalmology and Optometry, Laboratory of Ophthalmic Image Analysis, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Ursula Schmidt-Erfurth
- Department of Ophthalmology and Optometry, Laboratory of Ophthalmic Image Analysis, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
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Blasiak J, Pawlowska E, Helotera H, Ionov M, Derwich M, Kaarniranta K. Potential of autophagy in subretinal fibrosis in neovascular age-related macular degeneration. Cell Mol Biol Lett 2025; 30:54. [PMID: 40307700 PMCID: PMC12044759 DOI: 10.1186/s11658-025-00732-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 04/11/2025] [Indexed: 05/02/2025] Open
Abstract
Age-related macular degeneration (AMD) is an eye disease that can lead to legal blindness and vision loss. In its advanced stages, it is classified into dry and neovascular AMD. In neovascular AMD, the formation of new blood vessels disrupts the structure of the retina and induces an inflammatory response. Treatment for neovascular AMD involves antibodies and fusion proteins targeting vascular endothelial growth factor A (VEGFA) and its receptors to inhibit neovascularization and slow vision loss. However, a fraction of patients with neovascular AMD do not respond to therapy. Many of these patients exhibit a subretinal fibrotic scar. Thus, retinal fibrosis may contribute to resistance against anti-VEGFA therapy and the cause of irreversible vision loss in neovascular AMD patients. Retinal pigment epithelium cells, choroidal fibroblasts, and retinal glial cells are crucial in the development of the fibrotic scar as they can undergo a mesenchymal transition mediated by transforming growth factor beta and other molecules, leading to their transdifferentiation into myofibroblasts, which are key players in subretinal fibrosis. Autophagy, a process that removes cellular debris and contributes to the pathogenesis of AMD, regardless of its type, may be stimulated by epithelial-mesenchymal transition and later inhibited. The mesenchymal transition of retinal cells and the dysfunction of the extracellular matrix-the two main aspects of fibrotic scar formation-are associated with impaired autophagy. Nonetheless, the causal relationship between autophagy and subretinal fibrosis remains unknown. This narrative/perspective review presents information on neovascular AMD, subretinal fibrosis, and autophagy, arguing that impaired autophagy may be significant for fibrosis-related resistance to anti-VEGFA therapy in neovascular AMD.
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Affiliation(s)
- Janusz Blasiak
- Faculty of Medicine, Collegium Medicum, Mazovian Academy in Plock, 09-402, Plock, Poland.
| | - Elzbieta Pawlowska
- Department of Pediatric Dentistry, Medical University of Lodz, 92-217, Lodz, Poland
| | - Hanna Helotera
- Department of Ophthalmology, University of Eastern Finland, 70210, Kuopio, Finland
| | - Maksim Ionov
- Faculty of Health Sciences, Mazovian Academy in Plock, 09-402, Plock, Poland
| | - Marcin Derwich
- Department of Pediatric Dentistry, Medical University of Lodz, 92-217, Lodz, Poland
| | - Kai Kaarniranta
- Department of Ophthalmology, University of Eastern Finland, 70210, Kuopio, Finland
- Department of Ophthalmology, Kuopio University Hospital, 70210, Kuopio, Finland
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Moshtaghion SMM, Locri F, Reyes AP, Plastino F, Kvanta A, Morillo-Sanchez MJ, Rodríguez-de-la-Rúa E, Gutierrez-Sanchez E, Montero-Sánchez A, Lucena-Padros H, André H, Díaz-Corrales FJ. VEGF in Tears as a Biomarker for Exudative Age-Related Macular Degeneration: Molecular Dynamics in a Mouse Model and Human Samples. Int J Mol Sci 2025; 26:3855. [PMID: 40332529 PMCID: PMC12027898 DOI: 10.3390/ijms26083855] [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: 03/18/2025] [Revised: 04/09/2025] [Accepted: 04/10/2025] [Indexed: 05/08/2025] Open
Abstract
Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid-retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid-RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization.
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Affiliation(s)
- Seyed Mohamad Mehdi Moshtaghion
- Department of Integrative Pathophysiology and Therapies, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Junta de Andalucía, CSIC, University of Seville, University Pablo de Olavide, 41092 Seville, Spain; (A.P.R.); (A.M.-S.)
| | - Filippo Locri
- Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 17177 Stockholm, Sweden; (F.L.); (F.P.); (A.K.); (H.A.)
| | - Alvaro Plaza Reyes
- Department of Integrative Pathophysiology and Therapies, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Junta de Andalucía, CSIC, University of Seville, University Pablo de Olavide, 41092 Seville, Spain; (A.P.R.); (A.M.-S.)
| | - Flavia Plastino
- Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 17177 Stockholm, Sweden; (F.L.); (F.P.); (A.K.); (H.A.)
| | - Anders Kvanta
- Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 17177 Stockholm, Sweden; (F.L.); (F.P.); (A.K.); (H.A.)
| | - Maria Jose Morillo-Sanchez
- Department of Ophthalmology, Virgen Macarena University Hospital, 41009 Seville, Spain; (M.J.M.-S.); (E.R.-d.-l.-R.); (E.G.-S.)
| | - Enrique Rodríguez-de-la-Rúa
- Department of Ophthalmology, Virgen Macarena University Hospital, 41009 Seville, Spain; (M.J.M.-S.); (E.R.-d.-l.-R.); (E.G.-S.)
- Department of Surgery, Ophthalmology Area, University of Seville, 41009 Seville, Spain
| | - Estanislao Gutierrez-Sanchez
- Department of Ophthalmology, Virgen Macarena University Hospital, 41009 Seville, Spain; (M.J.M.-S.); (E.R.-d.-l.-R.); (E.G.-S.)
- Department of Surgery, Ophthalmology Area, University of Seville, 41009 Seville, Spain
| | - Adoración Montero-Sánchez
- Department of Integrative Pathophysiology and Therapies, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Junta de Andalucía, CSIC, University of Seville, University Pablo de Olavide, 41092 Seville, Spain; (A.P.R.); (A.M.-S.)
| | - Helena Lucena-Padros
- Department of Maternofetal Medicine, Genetics and Reproduction, Institute of Biomedicine of Seville, CSIC, Virgen del Rocio University Hospital, University of Seville, 41013 Seville, Spain;
| | - Helder André
- Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 17177 Stockholm, Sweden; (F.L.); (F.P.); (A.K.); (H.A.)
| | - Francisco J. Díaz-Corrales
- Department of Integrative Pathophysiology and Therapies, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Junta de Andalucía, CSIC, University of Seville, University Pablo de Olavide, 41092 Seville, Spain; (A.P.R.); (A.M.-S.)
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Kataoka K, Gale R, Li X, Şermet F, Qian CX, Cheung CMG, Tsilimbaris MK, Kozak I. Simultaneous GA and CNV/MNV: incidence, characteristics, and treatments. Graefes Arch Clin Exp Ophthalmol 2025:10.1007/s00417-024-06721-5. [PMID: 40229571 DOI: 10.1007/s00417-024-06721-5] [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: 09/16/2024] [Revised: 12/05/2024] [Accepted: 12/12/2024] [Indexed: 04/16/2025] Open
Abstract
PURPOSE Understanding the clinical characteristics and underlying mechanisms of simultaneous geographic atrophy (GA) and choroidal neovascularization (CNV)/macular neovascularization (MNV) is necessary for the long-term management of late age-related macular degeneration (AMD) in clinical practice. METHODS The authors reviewed the literature on the incidence, risk factors, and clinical characteristics of simultaneous GA and CNV/MNV and developed consensus recommendations for the diagnosis, assessment, and management of simultaneous GA and CNV/MNV in clinical practice. RESULTS The incidence rate of CNV/MNV in eyes with GA is reported as 7.4% per patient-year or 13.8% in 4.1 years, while that of macular atrophy (MA) subsequent to CNV/MNV is reported as 24.4% to 37% in 24 months. Recent studies using optical coherence tomography angiography (OCT-A) revealed the presence of subclinical CNV/MNV in 11% to 16% of eyes with GA. Fundus autofluorescence is used to detect MA; optical coherence tomography (OCT) and OCT-A are useful for detecting MA, especially around the fovea, with OCT-A offering high sensitivity and specificity in the detection of both MA and CNV/MNV. GA and CNV/MNV share the genetic risk factors of HTRA1, complement factor H, complement factors 3 and 2, and ARMS2, and clinical risk factors of large drusen, cuticular drusen, intraretinal hyperreflective foci, and subretinal drusenoid deposits, suggesting that simultaneous GA and CNV/MNV represents a continuum of AMD. Anti-vascular endothelial growth factor therapy for CNV/MNV is reported to have no impact on the speed or magnitude of MA development or enlargement. An association has been observed between CNV subtype and MA progression, with the latter being slower in the presence of type 1 CNV/MNV. CONCLUSIONS These findings suggest there is a high probability of coexistence of GA and CNV/MNV and that they should not be considered separately. Future clinical studies should assess the two conditions simultaneously using OCT and OCT-A. KEY MESSAGES What is known Owing to differences in their clinical characteristics, geographic atrophy (GA) and choroidal neovascularization (CNV)/macular neovascularization (MNV) have historically been regarded as two separate entities; however, several cases of coexistent GA and CNV/MNV have been reported recently in the published literature. What is new The findings of this review confirm that GA and CNV/MNV share common genetic risk factors and clinical characteristics, and suggest that these two entities are part of a continuum of late-stage age-related macular degeneration (AMD). The potential for GA and CNV/MNV to coexist should be considered in any discussion of the long-term management of late AMD; moreover, clinicians should assess for CNV/MNV in patients with GA, and for GA in those with CNV/MNV, using multimodal imaging.
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Affiliation(s)
| | - Richard Gale
- Hull York Medical School, University of York and York Teaching Hospital NHS Foundation Trust, York, UK
| | - Xiaoxin Li
- Eye Center and Eye Institute of Peking University People's Hospital, Beijing, China
| | - Figen Şermet
- Ophthalmology Department, Ankara University School of Medicine, Ankara, Turkey
| | - Cynthia X Qian
- Department of Ophthalmology, University of Montreal, Montreal, Canada
| | - Chui Ming Gemmy Cheung
- Singapore Eye Research Institute, National Eye Centre, Singapore, Singapore
- Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | | | - Igor Kozak
- Moorfields Eye Hospital Centre, Abu Dhabi, United Arab Emirates.
- University of Arizona-Tucson, Tucson, AZ, USA.
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Grün M, Rothaus K, Ziegler M, Lange C, Lommatzsch A, Faatz H. The Vascular Architecture of Macular Neovascularization in Age-Related Macular Degeneration as a Predictor of Therapy Requirements: A 3-Year Longitudinal Analysis. Diagnostics (Basel) 2025; 15:982. [PMID: 40310357 PMCID: PMC12025654 DOI: 10.3390/diagnostics15080982] [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: 03/03/2025] [Revised: 04/08/2025] [Accepted: 04/11/2025] [Indexed: 05/02/2025] Open
Abstract
Background: Anti-Vascular Endothelial Growth Factor (VEGF) therapy is an effective therapy for improving and stabilizing the vision of patients with neovascular age-related macular degeneration (nAMD). However, the treatment requirements, particularly the number of intraocular injections, can vary significantly among patients. This study aimed to analyze the vascular characteristics of macular neovascularizations (MNVs) to identify potential biomarkers that could predict the required injection frequency throughout the disease course. Methods: In all patients, the initial diagnosis of nAMD was confirmed using optic coherence tomography (OCT), fluorescein angiography, and OCT angiography (OCTA). MNVs detected using OCTA were subjected to quantitative vascular analysis of their area, total vascular length (sumL), fractal dimension (FD), and flow density. These results were then correlated with the number of intravitreal anti-VEGF treatments administered during the first 3 years of treatment. Additionally, the relationship between the parameters and visual acuity progression was analyzed. Results: A total of 68 treatment-naïve eyes were included in the study, comprising 31 eyes with type 1 MNV, 19 eyes with type 2 MNV, and 18 eyes with type 3 MNV. The average MNV area at baseline was 1.11 mm2 ± 1.18 mm2, the mean total vascular length was 12.95 mm ± 14.24 mm, the mean fractal dimension was 1.26 ± 0.14, and the mean flow density was 41.19 ± 5.87. On average, patients in our cohort received 19.8 ± 8.5 intravitreal injections (IVIs). A significant correlation was found between the number of administered IVIs in the first 3 treatment years and the MNV area (p < 0.005), sumL (p < 0.005), and FD (p < 0.05), while no correlation was found with flow density. Additionally, there was no significant association between MNV type and treatment requirements, nor between MNV vascular architecture and visual acuity progression. Conclusions: The results suggest that the specific vascular structure of untreated MNV may serve as a predictor of long-term treatment demand. With the emergence of new drug classes and advancements in imaging techniques, these parameters could offer valuable insights for forecasting treatment requirements.
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Affiliation(s)
- Michael Grün
- Department of Ophthalmology at St. Franziskus Hospital, 48145 Münster, Germany
| | - Kai Rothaus
- Department of Ophthalmology at St. Franziskus Hospital, 48145 Münster, Germany
| | - Martin Ziegler
- Department of Ophthalmology at St. Franziskus Hospital, 48145 Münster, Germany
| | - Clemens Lange
- Department of Ophthalmology at St. Franziskus Hospital, 48145 Münster, Germany
- Department of Ophthalmology, Freiburg University Hospital, 79106 Freiburg, Germany
| | - Albrecht Lommatzsch
- Department of Ophthalmology at St. Franziskus Hospital, 48145 Münster, Germany
- Achim Wessing Institute for Diagnostic Ophthalmology, Duisburg-Essen University, 45147 Essen, Germany
| | - Henrik Faatz
- Department of Ophthalmology at St. Franziskus Hospital, 48145 Münster, Germany
- Achim Wessing Institute for Diagnostic Ophthalmology, Duisburg-Essen University, 45147 Essen, Germany
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31
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Hafner M, Eckardt F, Siedlecki J, Schworm B, Herold TR, Asani B, Priglinger SG, Schiefelbein JB. Deep learning assisted analysis of biomarker changes in refractory neovascular AMD after switch to faricimab. Int J Retina Vitreous 2025; 11:44. [PMID: 40217505 PMCID: PMC11992866 DOI: 10.1186/s40942-025-00669-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 04/04/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Artificial intelligence (AI)-driven biomarker segmentation offers an objective and reproducible approach for quantifying key anatomical features in neovascular age-related macular degeneration (nAMD) using optical coherence tomography (OCT). Currently, Faricimab, a novel bispecific inhibitor of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), offers new potential in the management of nAMD, particularly in treatment-resistant cases. This study utilizes an advanced deep learning-based segmentation algorithm to analyze OCT biomarkers and evaluate the efficacy and durability of Faricimab over nine months in patients with therapy-refractory nAMD. METHODS This retrospective real-world study analyzed patients with treatment-resistant nAMD who switched to Faricimab following inadequate responses to ranibizumab or aflibercept. Automated segmentation of key OCT biomarkers - including fibrovascular pigment epithelium detachment (fvPED), intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), choroidal volume, and central retinal thickness (CRT) - was conducted using a deep learning algorithm based on a convolutional neural network. RESULTS A total of 46 eyes from 41 patients completed the nine-month follow-up. Significant reductions in SRF, fvPED, and choroidal volume were observed from baseline (mo0) to three months (mo3) and sustained at nine months (mo9). CRT decreased significantly from 342.7 (interquartile range (iqr): 117.1) µm at mo0 to 296.6 (iqr: 84.3) µm at mo3 and 310.2 (iqr: 93.6) µm at mo9. The deep learning model provided precise quantification of biomarkers, enabling reliable tracking of disease progression. The median injection interval extended from 35 (iqr: 15) days at mo0 to 56 (iqr: 20) days at mo9, representing a 60% increase. Visual acuity remained stable throughout the study. Correlation analysis revealed that higher baseline CRT and fvPED volumes were associated with greater best-corrected visual acuity (BCVA) improvements and longer treatment intervals. CONCLUSIONS This study highlights the potential of AI-driven biomarker segmentation as a precise and scalable tool for monitoring disease progression in treatment-resistant nAMD. By enabling objective and reproducible analysis of OCT biomarkers, deep learning algorithms provide critical insights into treatment response. Faricimab demonstrated significant and sustained anatomical improvements, allowing for extended treatment intervals while maintaining disease stability. Future research should focus on refining AI models to improve predictive accuracy and assessing long-term outcomes to further optimize disease management. TRIAL REGISTRATION Ethics approval was obtained from the Institutional Review Board of LMU Munich (study ID: 20-0382). This study was conducted in accordance with the Declaration of Helsinki.
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Affiliation(s)
- Michael Hafner
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany.
| | - Franziska Eckardt
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Jakob Siedlecki
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Benedikt Schworm
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Tina R Herold
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Ben Asani
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Siegfried G Priglinger
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
| | - Johannes B Schiefelbein
- Department of Ophthalmology, LMU University Hospital, LMU Munich, Mathildenstraße 8, 80336, Munich, Germany
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Cui Y, Poudel S, Xu N, Zhou K, Cheng R, Liang W, Yuan T, Zhao L, Qin C, Stevens KG, Duerfeldt AS, Hu J, Xu Q, Ma JX. Sustained release of a novel non-fibrate PPARα agonist from microparticles for neuroprotection in murine models of age-related macular degeneration. J Control Release 2025; 380:910-926. [PMID: 39961437 DOI: 10.1016/j.jconrel.2025.02.037] [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: 11/26/2024] [Revised: 01/28/2025] [Accepted: 02/14/2025] [Indexed: 02/23/2025]
Abstract
Prior research has demonstrated the therapeutic potential of peroxisome proliferator-activated receptor α (PPARα) agonist fenofibrate on diabetic retinopathy. In the present study, a novel non-fibrate PPARα agonist, A190, was designed with higher potency and selectivity than fenofibrate in PPARα agonism. A190 was encapsulated in biodegradable microparticles (A190-MP) to ensure sustained drug release, with detection in the retina up to 6 months following a single intravitreal injection. A190-MP alleviated retinal dysfunction as shown by electroretinography in Vldlr-/- (wet-AMD model) and Abca4-/-/Rdh8-/- (dry-AMD model) mice. A190-MP also attenuated the decreases in cone photoreceptor density and outer nuclear layer thickness as demonstrated by optical coherence tomography and histology. Moreover, A190-MP reduced vascular leakage and neovascularization in Vldlr-/- mice, suggesting an anti-inflammatory and anti-angiogenic effect. A190-MP upregulated expression of PPARα, PGC1α, and TOMM20 in the retina of Vldlr-/- and Abca4-/-/Rdh8-/- mice. A190-MP also improved retinal mitochondrial function as shown by Seahorse analysis using retinal biopsy. In vitro, A190 attenuated oxidative stress and preserved cell viability in a photoreceptor-derived cell line exposed to 4-HNE and improved mitochondrial function, via a PPARα-dependent mechanism. These findings revealed sustained therapeutic effects of A190-MP in wet and dry AMD models, through improving mitochondrial function by activating PPARα.
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Affiliation(s)
- Yi Cui
- Department of Ophthalmology, Fujian Medical University Union Hospital, Fuzhou 350001, China; Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America
| | - Sagun Poudel
- Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, United States of America
| | - Nuo Xu
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America; Department of Ophthalmology, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, China
| | - Kelu Zhou
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America
| | - Rui Cheng
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America
| | - Wentao Liang
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America
| | - Tian Yuan
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America
| | - Long Zhao
- Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, United States of America
| | - Chaolong Qin
- Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, United States of America
| | - Katelyn G Stevens
- Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, United States of America
| | - Adam S Duerfeldt
- Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, United States of America
| | - Jianzhang Hu
- Department of Ophthalmology, Fujian Medical University Union Hospital, Fuzhou 350001, China.
| | - Qingguo Xu
- Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23298, United States of America; Department of Ophthalmology, Pediatrics, Biomedical Engineering, Center for Pharmaceutical Engineering, and Institute for Structural Biology, Drug Discovery & Development (ISB3D), Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, United States of America.
| | - Jian-Xing Ma
- Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27101, United States of America.
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Kleefeldt N, Kuehnel S, Reiser L, Goebel W, Hillenkamp J, William A. [Morphological and functional changes of secondary macular neovascularization in central serous chorioretinopathy under anti-VEGF treatment]. DIE OPHTHALMOLOGIE 2025:10.1007/s00347-025-02221-x. [PMID: 40199756 DOI: 10.1007/s00347-025-02221-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 01/18/2025] [Accepted: 02/28/2025] [Indexed: 04/10/2025]
Abstract
BACKGROUND Investigation of the morphological changes by optical coherence tomography angiography (OCT-A) and the development of visual acuity in secondary macular neovascularization (sMNV) in central serous chorioretinopathy (CCS) during anti-vascular endothelial growth factor (VEGF) treatment. PATIENTS AND METHODS Retrospective study of all treatment-naïve eyes with respect to anti-VEGF treatment, in which sMNV in CCS was detected by fluorescein angiography (FA) and OCT‑A and which were treated at the University Eye Hospital Würzburg between July 2021 and the end of December 2022. All patients were treated according to a pro re nata injection regimen (PRN regimen) and followed up for 1 year. RESULTS In the study 20 eyes from 16 patients with sMNV in CCS were included. Using FA the sMNV could be confirmed in 35% of cases and using OCT‑A in 100% of cases. Morphologically, the sMNV was clearly demarcated by OCT‑A as "sea-fan"-like in 10 eyes and filamentous in 10 eyes. The decrease in area of the sMNV from 0.94 ± 1.2 mm2 at baseline to 0.72 ± 0.82 mm2 at 12 months was not statistically significant (p = 0.12). During the observational period an average of 8.7 ± 1.6 intravitreal injections (IVOM) were administered (5-12 IVOM, median 9 IVOM). DISCUSSION Both FA and OCT‑A were used to detect sMNV in CCS, with OCT‑A providing more reliable detection of sMNV than FA. With OCT‑A two different types of sMNV could be detected: 1) the "sea-fan" type and 2) the filamentous MNV type. Within the first year of treatment sMNV in CCS requires a comparable number of IVOMs as the treatment of neovascular age-related macular degeneration.
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Affiliation(s)
- Nikolai Kleefeldt
- Augenklinik Würzburg, University Hospital Würzburg, Joseph-Schneider-Str. 11, 97080, Würzburg, Deutschland
| | - Sophia Kuehnel
- Augenklinik Würzburg, University Hospital Würzburg, Joseph-Schneider-Str. 11, 97080, Würzburg, Deutschland
| | - Lukas Reiser
- Augenklinik Würzburg, University Hospital Würzburg, Joseph-Schneider-Str. 11, 97080, Würzburg, Deutschland
| | - Winfried Goebel
- Augenklinik Würzburg, University Hospital Würzburg, Joseph-Schneider-Str. 11, 97080, Würzburg, Deutschland
| | - Jost Hillenkamp
- Augenklinik Würzburg, University Hospital Würzburg, Joseph-Schneider-Str. 11, 97080, Würzburg, Deutschland
| | - Antony William
- Augenklinik Würzburg, University Hospital Würzburg, Joseph-Schneider-Str. 11, 97080, Würzburg, Deutschland.
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Boberg-Ans S, Arnold-Vangsted F, Scheel-Bech AB, Boberg-Ans LC, Arnold-Vangsted A, Jakobsen C, Stokbro K, Subhi Y. A Systematic Review and Meta-Analysis Association Between Periodontitis and Age-Related Macular Degeneration: Potential for Personalized Approach. J Pers Med 2025; 15:145. [PMID: 40278325 PMCID: PMC12028726 DOI: 10.3390/jpm15040145] [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: 02/25/2025] [Revised: 03/24/2025] [Accepted: 04/03/2025] [Indexed: 04/26/2025] Open
Abstract
Background/Objectives: Periodontitis is a chronic inflammatory disease that leads to systemic low-grade inflammation. Systemic low-grade inflammation has been found in patients with age-related macular degeneration (AMD). In this systematic review and meta-analysis, we evaluated the association between periodontitis and AMD. Methods: We searched 11 scientific literature databases on 16th December 2024 for studies of a diagnosis of periodontitis and prevalent or incident AMD. Eligible studies underwent a qualitative review and meta-analysis of the association. Study selection, data extraction, and risk of bias within studies were made in duplicate by two authors and conferred with a senior author. Results: Seven studies eligible for review included in total 149,217 individuals. Across the seven studies, different study designs, diagnoses and definitions of periodontitis, and diagnosis and definitions of AMD were employed. Our meta-analysis showed an association between periodontitis and AMD with an odds ratio of 1.42 (95% CI: 1.12 to 1.78; p = 0.003). Conclusions: Periodontitis is significantly associated with AMD. Unlike genetic predisposition and high age, which are important risk factors of AMD that cannot be modified, periodontitis is a risk factor that can be treated and potentially eliminated, thus allowing for a personalized approach for risk elimination in AMD. Attention should be given to the dental health of patients at risk of AMD.
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Affiliation(s)
| | | | - Anna Bonde Scheel-Bech
- Department of Ophthalmology, Rigshospitalet, 2600 Glostrup, Denmark; (A.B.S.-B.); (A.A.-V.)
| | - Lars Christian Boberg-Ans
- Department of Ophthalmology, University Hospital of Southern Denmark, 7100 Vejle, Denmark;
- Department of Ophthalmology, Innlandet Hospital Trust, 2406 Elverum, Norway
| | - Andreas Arnold-Vangsted
- Department of Ophthalmology, Rigshospitalet, 2600 Glostrup, Denmark; (A.B.S.-B.); (A.A.-V.)
- Department of Ophthalmology, University Hospital of Southern Denmark, 7100 Vejle, Denmark;
| | - Christian Jakobsen
- Department of Oral and Maxillofacial Surgery, Odense University Hospital, 5200 Odense, Denmark; (C.J.); (K.S.)
| | - Kasper Stokbro
- Department of Oral and Maxillofacial Surgery, Odense University Hospital, 5200 Odense, Denmark; (C.J.); (K.S.)
- Department of Clinical Research, University of Southern Denmark, 5200 Odense, Denmark
| | - Yousif Subhi
- Department of Ophthalmology, Rigshospitalet, 2600 Glostrup, Denmark; (A.B.S.-B.); (A.A.-V.)
- Department of Clinical Research, University of Southern Denmark, 5200 Odense, Denmark
- Department of Clinical Medicine, University of Copenhagen, 2200 Copenhagen, Denmark
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35
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Eastline M, Said S, Bosch MM, Knecht-Bosch P. Exit Strategy for Treatment of Neovascular Age-Related Macular Degeneration in a Real-World Setting: Wishful Thinking? Klin Monbl Augenheilkd 2025; 242:398-404. [PMID: 39909072 DOI: 10.1055/a-2511-5899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2025]
Abstract
INTRODUCTION To analyze our outcome for patients with neovascular age-related macular degeneration (nAMD) treated with aflibercept in a treat-and-extend regimen pursuing an exit strategy (with best possible adherence to the "Bern" exit criteria) over 6 years in a real-world setting. The primary objective of the study was to investigate the proportion of patients who were able to achieve and maintain treatment exit. METHODS This is a retrospective chart review study of treatment-naïve patients diagnosed with nAMD receiving intravitreal aflibercept injections performed at our department with at least 2 years of follow-up visits. The primary outcome was the percentage of patients able to achieve and maintain the treatment exit regarding intravitreal anti-VEGF injections. Further outcome measures were best-corrected visual acuity (BCVA), incidence of recurrence after treatment cessation, duration of therapy, and number and intervals of injections. RESULTS There were 31 eyes of 25 patients included in this retrospective study. The observation period was from September 1, 2017 to August 31, 2023. Of all included patient eyes, 22.6% (n = 7) reached exit criteria. Of all the "exit" patients, 28.6% (n = 2) suffered from disease relapse and therapy was restarted at a mean (± SD) of 41.5 ± 12.5 weeks (range: 29 to 54 weeks). Regarding the eyes that met treatment exit, 5 of 31 (16.1%) had no disease recurrence in the observed study period. The median BCVA (Snellen decimal; ± interquartile range: IQR) changed from 0.63 (0.27) at baseline to 0.63 (0.4) in the first year, 0.63 (0.3) in the second year, 0.63 (0.46) in the third year, 0.63 (0.3) in the fourth year, 0.63 (0.4) in the fifth year, and 0.4 (0.04) in the sixth year. The median number of injections (± IQR) per eye in the first year of treatment was 8 (2), in the second year 5 (2), in the third year 5 (2.5), in the fourth year 5 (1), in the fifth year 3 (0.8), and in the sixth year 3 (0). Extension of the treatment interval after the loading phase in weeks was achieved up to a median (± IQR) of 5.8 (4) in the first year, 8.4 (6) in the second year, 8 (5.7) in the third year, 9.4 (5.6) in the fourth year, 7 (6.9) in the fifth year, and 8.4 (3.1) in the sixth year of observation. DISCUSSION Our study indicates a lower rate of patients reaching exit criteria with a treat-and-extend regimen compared to clinical study settings, and a similar recurrence rate of nAMD after treatment cessation. Nonadherence to a strict treat-and-extend protocol might influence the result.
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Affiliation(s)
| | - Sadiq Said
- Eye Clinic Wettingen, Switzerland
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Martina Monika Bosch
- Eye Clinic Wettingen, Switzerland
- Department of Ophthalmology, University Hospital Zurich, Switzerland
| | - Pascal Knecht-Bosch
- Eye Clinic Wettingen, Switzerland
- Department of Ophthalmology, University Hospital Zurich, Switzerland
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Pauleikhoff D, Yu S, Bachmeier I, Armendariz BG, Bormann E, Pauleikhoff L. Hyperreflective material evolution patterns during long term anti-VEGF therapy in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 2025; 263:957-964. [PMID: 39710708 PMCID: PMC12095329 DOI: 10.1007/s00417-024-06712-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 11/25/2024] [Accepted: 12/05/2024] [Indexed: 12/24/2024] Open
Abstract
This retrospective, real-life cohort was analyzed to detect the frequency of different HRM evolution patterns and their correlation with MNV types, morphological and functional changes in exudative nAMD under long-term anti-VEGF therapy. We evaluated optical coherence tomography (OCT) volume scans in 143 eyes of 94 nAMD patients (start of anti-VEGF therapy 2009-2018, therapy until the last visit) and recorded the VA at all visits. HRM evolution patterns were differentiated: pattern 1 = no HRM, pattern 2 = subretinal HRM resolved during follow-up, pattern 3 = persistent subretinal HRM with new HRM-boundary remodeling [BR], pattern 4 = persistent subretinal HRM without HRM-BR. Pattern 1 was observed in 58 eyes (40.6%), 33 eyes (23.1%) showed pattern 2, 39 eyes (27.3%) pattern 3 and 13 eyes (9.1%) pattern 4. HRM pattern correlated with type 1-3 MNV (p = 0.02), especially pattern 1 with type 1 MNV and pattern 3 with type 2 MNV. Over time, a change of MNV types could be observed only from type 2 into type 1 MNV (p = 0.0001). Some eyes with HRM pattern 3 changed during follow-up into pattern 4, which was often associated with the presence of macular atrophy (p = 0.0001) and demonstrated a reduced mean VA compared to pattern 1-3 at baseline (p = 0.0001), year 1 (p = 0.0001) and final visit (p = 0.02).In this study, we characterized different HRM evolution patterns in a real-world dataset and demonstrated their associations with MNV transformation during long term anti-VEGF therapy. The HRM patterns may provide prognostic value with morphological and functional implications.
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Affiliation(s)
- Daniel Pauleikhoff
- Dep. of Ophthalmology, St. Franziskus Hospital, Hohenzollernring 74, 48155, Münster, Germany.
| | - Siqing Yu
- F. Hoffmann-La Roche Ltd, Pharma Research and Early Development, Basel, Switzerland
| | - Isabel Bachmeier
- F. Hoffmann-La Roche Ltd, Pharma Research and Early Development, Basel, Switzerland
| | | | - Eike Bormann
- Institute of Biostatistics and Clinical Research, University Muenster, Muenster, Germany
| | - Laurenz Pauleikhoff
- Dep. of Ophthalmology, Faculty of Medicine, University of Hamburg, Hamburg, Germany
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Faes L, Bijon J, Bacci T, Freund KB. Review of type 3 macular neovascularization in age-related macular degeneration: no DRAMA (Deep Retinal Age-related Microvascular Anomalies). Eye (Lond) 2025; 39:870-882. [PMID: 39394372 PMCID: PMC11933695 DOI: 10.1038/s41433-024-03343-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2024] [Revised: 08/24/2024] [Accepted: 09/11/2024] [Indexed: 10/13/2024] Open
Abstract
Type 3 macular neovascularization (MNV) is a unique form of neovascular age-related macular degeneration (AMD) that presents distinct pathogenetic features, clinical manifestations, and prognostic considerations when compared to types 1 and 2 MNV. Insights gained from clinicopathological correlations, bridging in vivo examination techniques with ex vivo histological analysis, have significantly enhanced our comprehension of this MNV phenotype, shaped current management strategies and influenced future directions for therapeutics. The particularities of type 3 MNV, which may largely stem from its origin from the retinal vasculature, are critically important for predicting the disease course. Our current understanding suggests that type 3 MNV occurs in response to retinal pigment epithelium (RPE) disruption and photoreceptor loss when neovessels originating from the deep capillary plexus are accompanied by activated Müller glia as they infiltrate sub-retinal pigment epithelium basal laminar deposits. Dysregulation of angiogenic and angiostatic factors are thought to play a key role in its pathogenesis. The prognosis for type 3 MNV is likely bilateral involvement and progression towards macular atrophy. It may be imperative for practitioners to distinguish type 3 MNV from other mimicking pathologies such as intraretinal microvascular anomalies, which are also part of the type 3 disease spectrum. For instance, deep retinal age-related microvascular anomalies (DRAMA) may present with similar features on multimodal imaging yet may necessitate distinct management protocols. Distinguishing between these conditions may be vital for implementing tailored treatment regimens and improving patient outcomes in the diverse landscape of AMD phenotypes in the future.
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Affiliation(s)
- Livia Faes
- Vitreous Retina Macula Consultants of New York, New York, USA
| | - Jacques Bijon
- Vitreous Retina Macula Consultants of New York, New York, USA
| | - Tommaso Bacci
- Ophthalmology Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena University Hospital, Siena, Italy
| | - K Bailey Freund
- Vitreous Retina Macula Consultants of New York, New York, USA.
- Department of Ophthalmology, NYU Grossman School of Medicine, New York, NY, USA.
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Romano F, Bennett C, Ding X, Miller JB. Reply to Comment on: "Associations Between Contrast Sensitivity, OCT Features, and Progression From Intermediate to Late AMD". Am J Ophthalmol 2025; 272:187-188. [PMID: 39814094 DOI: 10.1016/j.ajo.2025.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Accepted: 01/06/2025] [Indexed: 01/18/2025]
Affiliation(s)
- Francesco Romano
- Harvard Retinal Imaging Lab (F.R, C.B, X.D, J.B.M), Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA; Retina Service, Department of Ophthalmology (F.R, X.D, J.B.M), Massachusetts Eye and Ear, Boston, Massachusetts, USA
| | - Cade Bennett
- Harvard Retinal Imaging Lab (F.R, C.B, X.D, J.B.M), Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA
| | - Xinyi Ding
- Harvard Retinal Imaging Lab (F.R, C.B, X.D, J.B.M), Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA; Retina Service, Department of Ophthalmology (F.R, X.D, J.B.M), Massachusetts Eye and Ear, Boston, Massachusetts, USA
| | - John B Miller
- Harvard Retinal Imaging Lab (F.R, C.B, X.D, J.B.M), Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA; Retina Service, Department of Ophthalmology (F.R, X.D, J.B.M), Massachusetts Eye and Ear, Boston, Massachusetts, USA.
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Tillmann A, Turgut F, Munk MR. Optical coherence tomography angiography in neovascular age-related macular degeneration: comprehensive review of advancements and future perspective. Eye (Lond) 2025; 39:835-844. [PMID: 39147864 PMCID: PMC11933389 DOI: 10.1038/s41433-024-03295-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/09/2024] [Accepted: 08/05/2024] [Indexed: 08/17/2024] Open
Abstract
Optical coherence tomography angiography (OCTA) holds promise in enhancing the care of various retinal vascular diseases, including neovascular age-related macular degeneration (nAMD). Given nAMD's vascular nature and the distinct vasculature of macular neovascularization (MNV), detailed analysis is expected to gain significance. Research in artificial intelligence (AI) indicates that en-face OCTA views may offer superior predictive capabilities than spectral domain optical coherence tomography (SD-OCT) images, highlighting the necessity to identify key vascular parameters. Analyzing vasculature could facilitate distinguishing MNV subtypes and refining diagnosis. Future studies correlating OCTA parameters with clinical data might prompt a revised classification system. However, the combined utilization of qualitative and quantitative OCTA biomarkers to enhance the accuracy of diagnosing disease activity remains underdeveloped. Discrepancies persist regarding the optimal biomarker for indicating an active lesion, warranting comprehensive prospective studies for validation. AI holds potential in extracting valuable insights from the vast datasets within OCTA, enabling researchers and clinicians to fully exploit its OCTA imaging capabilities. Nevertheless, challenges pertaining to data quantity and quality pose significant obstacles to AI advancement in this field. As OCTA gains traction in clinical practice and data volume increases, AI-driven analysis is expected to further augment diagnostic capabilities.
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Affiliation(s)
- Anne Tillmann
- Augenarzt Praxisgemeinschaft Gutblick, Pfäffikon, Switzerland
| | - Ferhat Turgut
- Augenarzt Praxisgemeinschaft Gutblick, Pfäffikon, Switzerland
- Department of Ophthalmology, Stadtspital Zürich, Zürich, Switzerland
- Department of Ophthalmology, Semmelweis University, Budapest, Hungary
| | - Marion R Munk
- Augenarzt Praxisgemeinschaft Gutblick, Pfäffikon, Switzerland.
- Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, 3010, Bern, Switzerland.
- Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60208, USA.
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Lee CH, Bae K, Yoon CK, Park UC, Park KH, Lee EK. CLINICAL COURSE AND PROGNOSTIC FACTORS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION WITH SUBRETINAL FLUID. Retina 2025; 45:714-723. [PMID: 39689291 DOI: 10.1097/iae.0000000000004368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
PURPOSE To investigate the clinical course and prognostic factors of age-related macular degeneration without macular neovascularization (MNV) in patients presenting with pigment epithelial detachment (PED) and the associated subretinal fluid (SRF). METHODS Morphological characteristics of spectral-domain optical coherence tomography images were analyzed to determine anatomic outcomes. Factors associated with the progression to late AMD, defined as complete retinal pigment epithelium and outer retinal atrophy (cRORA) or MNV, were investigated. RESULTS Fifty eyes of 41 patients were included in this study. The most common SRF location was the angle of the PED (56%), and there was a significant decrease in SRF thickness and PED height and width over the follow-up period. Eleven (22%) eyes developed cRORA, and seven (14%) eyes developed MNV during a mean period of 52.1 months. Multivariate analysis revealed that hyperreflective foci and MNV in the fellow eye were associated with the development of cRORA, and higher PED height was a significant factor associated with the development of MNV. CONCLUSION In patients with AMD, SRF can be accompanied by PED in the absence of MNV. Notably, patients with this characteristic entity can progress to late AMD, including cRORA and MNV, in a significant proportion of cases.
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Affiliation(s)
- Chang Hwan Lee
- Department of Ophthalmology, Kangwon National University College of Medicine, Kangwon National University Hospital, Chuncheon, Korea ; and
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kunho Bae
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Chang Ki Yoon
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Un Chul Park
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Kyu Hyung Park
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
| | - Eun Kyoung Lee
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
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Nam KT, Yun C. Long-term visual outcomes of patients with neovascular age-related macular degeneration treated with anti-VEGF therapy lost to follow-up. Graefes Arch Clin Exp Ophthalmol 2025:10.1007/s00417-025-06798-6. [PMID: 40111518 DOI: 10.1007/s00417-025-06798-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 01/27/2025] [Accepted: 03/09/2025] [Indexed: 03/22/2025] Open
Abstract
PURPOSE To evaluate the long-term visual outcomes of patients with neovascular age-related macular degeneration (AMD) who were lost to follow-up (LTFU) during treatment compared with those with continuous follow-up (CFU). METHODS A retrospective study was conducted on patients diagnosed with neovascular AMD who received anti-VEGF therapy from 2010 to 2022. The patients were classified into the long-term LTFU group (LTFU for more than 6 months), the short-term LTFU group (LTFU for 2 months to less than 6 months), and the CFU group. We conducted a comparative analysis of baseline characteristics, factors related to visual prognosis, and differences in the occurrence of severe vision loss. RESULTS A total of 169 patients were classified into 43 in the long-term LTFU group, 57 in the short-term LTFU group, and 69 in the CFU group. The mean follow-up duration was 57.12 ± 31.68 months. There was no significant difference in baseline visual acuity (logMAR) among the long-term LTFU, short-term LTFU, and CFU groups (0.76 ± 0.54, 0.68 ± 0.51, and 0.72 ± 0.54, respectively; P = 0.734). The final visual acuity was significantly lower in the long-term LTFU group (1.12 ± 0.79) compared with the short-term LTFU group (0.65 ± 0.62) and the CFU group (0.65 ± 0.56) (P < 0.001), and the change in visual acuity was significantly greater in the long-term LTFU group (0.36 ± 0.69) compared with the short-term LTFU group (-0.03 ± 0.64) and the CFU group (-0.07 ± 0.58) (P = 0.001). Long-term LTFU was significantly associated with changes in visual acuity from the baseline to the final visit (P = 0.002) and severe vision loss (P = 0.002). CONCLUSION In patients with neovascular AMD, those LTFU for more than six months during treatment had worse long-term visual outcomes compared to those with regular follow-up or shorter LTFU durations.
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Affiliation(s)
- Ki Tae Nam
- Department of Ophthalmology, Jeju National University Hospital, Jeju, Korea
| | - Cheolmin Yun
- Department of Ophthalmology, Korea University College of Medicine, 123, Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do, Seoul, Korea.
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Lazrak A, Bonnafous M, Jean-Charles A, Ouamrane K, Tabouillot A, Chaoui-Boudghane Y, Merle H. Exploring Clinical Features of Polypoidal Choroidal Vasculopathy in Black Patients: A Cross-Sectional Study and a Comprehensive Review. Ophthalmol Retina 2025:S2468-6530(25)00114-9. [PMID: 40120679 DOI: 10.1016/j.oret.2025.02.030] [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: 10/15/2024] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/25/2025]
Abstract
OBJECTIVE This study aimed to evaluate the clinical and angiographic presentation of polypoidal choroidal vasculopathy (PCV) in a large cohort of Black patients. DESIGN We conducted a descriptive cross-sectional analysis. PARTICIPANTS Out of 283 patients followed for PCV in our department, 167 cases were confirmed by indocyanine green angiography (ICGA). The remaining patients lacked ICGA imaging. Among the 167 confirmed cases, 57 patients were excluded due to significant ophthalmological comorbidities, leaving 160 affected eyes in 110 patients for analysis. METHODS We reviewed the most recent retinophotography, OCT, fluorescein, and ICGA images in our database. All analyzed patients were followed and underwent their examinations at the University Hospital Center of Martinique, a referral center in Fort de France primarily serving a Black population. An exploratory analysis of choroidal features was made in those who underwent enhanced depth imaging spectral-domain OCT. In parallel, a literature review on PCV was performed to contextualize our findings. MAIN OUTCOME MEASURES We measured visual acuity, sex ratio, patient age, characteristics of exudative phenomena, polyp location, and PCV type according to Kawamura classification. RESULTS Most patients were women (62.7%), with an average age of 72.2 ± 10.1 years. Among the 160 eyes, 81.9% exhibited idiopathic type 2 PCV and 52.4% showed peripapillary polyp distribution. The mean visual acuity was 0.29 ± 0.3 logarithm of the minimum angle of resolution. Soft drusen were present in 15% of eyes, and 44.5% of patients had bilateral involvement. Black patients seem to have distinctive PCV characteristics compared with other ethnic groups, with a low incidence of macular polyps (23.1%), a high incidence of peripapillary polyps (52.4%), and high incidence of bilateral involvement (42.8%). CONCLUSIONS This is the largest series of Afro-descendant patients with PCV ever described in the literature. Polypoidal choroidal vasculopathy in our population is primarily type 2 PCV according to Kawamura's classification, predominantly affecting women, often bilateral, with a preferentially extramacular location of the polyps. These observations may be explained by the fact that PCV in these patients is not the result of neovascularization but rather linked to a generalized disease of the choroid, such as pachychoroid. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.
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Affiliation(s)
- Adam Lazrak
- Department of Ophthalmology, University Hospital Center of Martinique, Pierre Zobda-Quitman Hospital, Fort de France, France.
| | - Martin Bonnafous
- Department of Ophthalmology, University Hospital Center of Martinique, Pierre Zobda-Quitman Hospital, Fort de France, France
| | - Albert Jean-Charles
- Department of Ophthalmology, University Hospital Center of Martinique, Pierre Zobda-Quitman Hospital, Fort de France, France
| | - Katia Ouamrane
- Department of Ophthalmology, University Hospital Center of Martinique, Pierre Zobda-Quitman Hospital, Fort de France, France
| | - Alizée Tabouillot
- Department of Ophthalmology, University Hospital Center of Martinique, Pierre Zobda-Quitman Hospital, Fort de France, France
| | - Yanice Chaoui-Boudghane
- Department of Ophthalmology, University Hospital Center of Martinique, Pierre Zobda-Quitman Hospital, Fort de France, France
| | - Harold Merle
- Department of Ophthalmology, University Hospital Center of Martinique, Pierre Zobda-Quitman Hospital, Fort de France, France
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Matagrin B, Fenniri I, Chirpaz N, Billant J, Agard E, Chudzinski R, Burillon C, Dot C. SIRE: Short interval in real life Does intensive anti-VEGF treatment in the first year predict subsequent treatment burden in exudative age-related macular degeneration? Eye (Lond) 2025:10.1038/s41433-025-03734-0. [PMID: 40114029 DOI: 10.1038/s41433-025-03734-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 01/20/2025] [Accepted: 02/19/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Anti-VEGF's have changed the prognosis of exudative age-related macular degeneration (AMD). Ranibizumab and aflibercept have proven their functional efficacy, but their use has revealed in real life a wide variety of patient profiles with varied responses to treatment. This work focused on patients receiving "intensive" IVT treatment with a sustained injection rhythm, also referred to as having a high treatment burden. OBJECTIVE The main objective of this work was to determine, in real-life conditions, the proportion of patients receiving "intensive" treatment among those being followed for exudative AMD. Secondary objectives were to analyse the long-term functional outcomes of these patients, their anatomical characteristics, and the evolution of their treatment regimen. METHOD A retrospective descriptive single-centre real-life study was conducted on patients treated for exudative AMD with intensive treatment (intervals of less than 8 weeks during the first year of treatment). A subgroup analysis compared patients who exceeded Q8 during follow-up (Group 1) versus patients remaining in intensive treatment (Group 2). RESULTS A total of 301 records were analysed, with 24.9% of the eyes (n = 75) considered under intensive treatment. The mean age was 84 years ( ± 7.5), and 61% were men. Type 1 choroidal neovascularization (CNV) accounted for 64% of our cohort, type 2 CNV represented 29.3%, and type 3 was involved in 6.7%. The mean follow-up was 5.6 years ( ± 3.6), with an average number of 41 IVT ( ± 26.7). Visual acuity was maintained at 0.53 ( ± 0.2) baseline vs. 0.61 ( ± 0.2) after 5 years of follow-up (p = 0.02). Central retinal thickness (CRT) and subretinal fluid (SRF) were significantly reduced during our follow-up, and PED height remained stable. Almost half of the eyes (44%) had an extension of their interval ( > Q8) beyond the first year; however, this objective was achieved on average after 4.5 years of treatment. The visual acuity of Group 2 ( < Q8), despite receiving more injections, was superior to that of Group 1 ( > Q8) with baseline values of 0.57 ( ± 0.2) and 0.48 ( ± 0.2) (p = 0.161) respectively, and at 5 years 0.79 ( ± 0.2) and 0.54 ( ± 0.2) (p = 0.026). Similarly, CRT, PED height, and SRF were higher in Group 2. The distribution of neovascular types showed more type 2 in Group 1 (45.5% vs. 16.7%). CONCLUSION Patients requiring intensive treatment represent about ¼ of our AMD patient population. Despite the high treatment burden, these patients maintain their visual acuity at 5 years. An extension of intervals is observed in nearly half of the patients, occurring late. Intensive treatment during the first year appears to be predictive of a future hight treatment burden.
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Affiliation(s)
- B Matagrin
- Department of Ophthalmology, CHU E. Herriot, Lyon, France.
| | - I Fenniri
- Department of Ophthalmology, CHU E. Herriot, Lyon, France
| | - N Chirpaz
- Department of Ophthalmology, CHU E. Herriot, Lyon, France
| | - J Billant
- Department of Ophthalmology, CHU E. Herriot, Lyon, France
- Department of Ophthalmology, Desgenettes Military Hospital, Lyon, France
- French Military Academy of Val-de-Grâce, Paris, France
| | - E Agard
- Department of Ophthalmology, Desgenettes Military Hospital, Lyon, France
- French Military Academy of Val-de-Grâce, Paris, France
| | - R Chudzinski
- Department of Ophthalmology, CHU E. Herriot, Lyon, France
| | - C Burillon
- Department of Ophthalmology, CHU E. Herriot, Lyon, France
| | - C Dot
- Department of Ophthalmology, CHU E. Herriot, Lyon, France
- Department of Ophthalmology, Desgenettes Military Hospital, Lyon, France
- French Military Academy of Val-de-Grâce, Paris, France
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Gu Z, Luo X, Sun R, Xi T, Zhang C. Long-term effects of the COVID-19 lockdown on the structural and functional outcomes of neovascular AMD patients in Suzhou, China. PLoS One 2025; 20:e0319677. [PMID: 40112264 PMCID: PMC11925463 DOI: 10.1371/journal.pone.0319677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Accepted: 02/05/2025] [Indexed: 03/22/2025] Open
Abstract
BACKGROUND Timely anti-vascular endothelial growth factor (VEGF) therapy is essential for visual function in neovascular age-related macular degeneration (nAMD). The coronavirus pandemic has led to unprecedented delays in anti-VEGF intravitreal therapy because of the need to reduce hospital attendance. OBJECTIVES To assess the long-term impact of COVID-19 pandemic-related delays in intravitreal anti-VEGF therapy on nAMD patients. METHODS This was a retrospective study of 98 patients (102 eyes) with nAMD whose anti-VEGF treatments were interrupted for > 8 weeks due to the COVID-19 pandemic. Best-corrected visual acuity (BCVA), central retinal thickness (CRT) and anatomical characteristics on spectral domain optical coherence tomography (SD-OCT) were measured at baseline, at the last follow-up visit before treatment interruption (V0), at the first visit after the COVID-19 lockdown had ended (V1), at the six-month follow-up (V-6 months) and at the final visit at the 1-year follow-up (V-final). The control group included nAMD patients who had completed at least three anti-VEGF treatments and received consecutive follow-up with timely anti-VEGF treatments for one year. RESULTS After one year of regular follow-up and standardized treatment, the treatment-interrupted group (TIG) had significantly worse visual acuity than the treatment-continuous group (TCG) (0.71 ± 0.38 vs. 0.52 ± 0.32, p < 0.001); however, there was no significant difference between the groups in the mean CRT (273.95 ± 112.96 µm vs. 261.43 ± 90.66 µm, p > 0.05). Furthermore, subgroup analysis revealed that, compared with those before treatment interruption, the BCVA of the TIG patients slightly improved, but the mean CRT and related activity indices returned to baseline values according to OCT imaging (all p > 0.05). Multiple linear regression analysis revealed that longer treatment interruption was associated with greater deterioration in visual acuity (p = 0.009). CONCLUSION Treatment interruption for more than 8 weeks had a sustained negative impact on visual acuity in treated eyes one year later. For nAMD patients, continuous treatment, regardless of the underlying regimen, remains critical.
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Affiliation(s)
- Zheyao Gu
- Department of Ophthalmology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China
| | - Xiangying Luo
- Department of Ophthalmology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China
| | - Ruizhu Sun
- Department of Ophthalmology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China
| | - Ting Xi
- Department of Ophthalmology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China
| | - Chunyuan Zhang
- Department of Ophthalmology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, China
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Hosoda S, Sakurada Y, Fukuda Y, Kotoda Y, Kikushima W, Kashiwagi K. Short-Term Outcomes of Three Consecutive Monthly Loading Administrations of Aflibercept 8 Mg for Treatment-Naïve Exudative Age-Related Macular Degeneration. Pharmaceuticals (Basel) 2025; 18:438. [PMID: 40143214 PMCID: PMC11945045 DOI: 10.3390/ph18030438] [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: 02/16/2025] [Revised: 03/09/2025] [Accepted: 03/19/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: The aim was to investigate the short-term outcomes of three consecutive monthly aflibercept 8 mg administrations for treatment-naïve eyes with exudative age-related macular degeneration (AMD). Methods: Twenty-one eyes with exudative AMD were included (type 1 macular neovascularization: eleven eyes; type 2 macular neovascularization, four eyes; and polypoidal choroidal vasculopathy (PCV), six eyes). All eyes received three consecutive monthly administrations of aflibercept 8 mg (114.3 mg/mL) at an injection volume of 0.07 mL. Indocyanine green angiography (ICGA) was performed on eyes with PCV at baseline and at the 3-month visit. Results: The best-corrected visual acuity significantly (BCVA) improved from 0.31 ± 0.38 (baseline) to 0.25 ± 0.38 at the 3-month visits (p = 0.035). Dry macula achieved 62% and 100% at the 1-month and 3-month visits, respectively. Central retinal thickness and subfoveal choroidal thickness significantly decreased by 55.7% and 19.8%, from 341 ± 112 (baseline) to 190 ± 64 (3-month visits) and from 192 ± 50 (baseline) to 154 ± 51 (3-month visits), respectively (both p < 0.001). Complete regression of polypoidal lesions was seen in five (83.3%) eyes out of six on ICGA at the 3-month visit. No systemic adverse events were noted, and one eye developed a retinal pigment epithelial tear one month after the first injection. Conclusions: Three consecutive monthly administrations of aflibercept (8 mg) were safe and effective for resolving exudation and polyp regression, with significant BCVA improvement in treatment-naïve eyes with exudative AMD.
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Affiliation(s)
| | - Yoichi Sakurada
- Department of Ophthalmology, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan; (S.H.); (Y.F.); (Y.K.); (W.K.); (K.K.)
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46
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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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Pauleikhoff L, Ziegler M, Bachmeier I, Yu S, Armendariz BG, Pauleikhoff D. Retinal sensitivity above macular neovascularization under anti-VEGF therapy in exudative neovascular age-related macular degeneration. BMC Ophthalmol 2025; 25:123. [PMID: 40075283 PMCID: PMC11899697 DOI: 10.1186/s12886-025-03946-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 02/24/2025] [Indexed: 03/14/2025] Open
Abstract
PURPOSE Growth of macular neovascularization (MNV) associated with development of complete retinal pigment epithelial and outer retina atrophy (cRORA) been observed in eyes neovascular age-related macular degeneration (nAMD) under effective anti-vascular endothelial growth factor (VEGF) therapy. We aimed to evaluate the influence of the presence of MNV on the sensitivity of the overlaying retina both in patients with or without cRORA and to generate hypotheses about their association. METHODS Pilot study on nAMD patients undergoing long-term anti-VEGF therapy that had also undergone microperimetry testing. Area of MNV and, if present, associated cRORA were identified on optical coherence tomography (OCT) volume scans and transposed onto en-face near-infrared images. Mesopic microperimetry performed at the same visit was then superimposed. Retinal sensitivity above the MNV and the surrounding retina were compared, excluding areas of cRORA. RESULTS Twenty-six eyes (19 f, 7 m; age 79.3 ± 5.7 y; fu 4.0 ± 1.8 y; 7.4 ± 2.5 inj./y) were classified into a no cRORA (n = 11) and a cRORA group (n = 15). In the no cRORA group, mean retinal sensitivity above the MNV did not differ from the surrounding retina (20.9 ± 2.8 vs. 22.0 ± 2.4, p = 0.33), while in the cRORA group, a lower sensitivity above the MNV in comparison to the surrounding retina was observed (16.2 ± 3.4 vs. 19.9 ± 2.0, p = 0.001). CONCLUSION In the absence of cRORA, retinal sensitivity above the MNV did not differ significantly from that of the surrounding retina. These results could indicate a possible nutritional function of the MNV to the overlying retina in cases where no cRORA is present.
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Affiliation(s)
- Laurenz Pauleikhoff
- Department of Ophthalmology, Faculty of Medicine, University of Hamburg, Hamburg, Germany
| | - Martin Ziegler
- Dep. of Ophthalmology, St. Franziskus Hospital, Muenster, Germany
| | - Isabel Bachmeier
- F. Hoffmann-La Roche Ltd, Pharma Research and Early Development, Basel, Switzerland
| | - Siqing Yu
- F. Hoffmann-La Roche Ltd, Pharma Research and Early Development, Basel, Switzerland
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Imazeki M, Takeuchi M, Yasukawa T, Terasaki H, Yamamoto Y, Jujo T, Wakuta M, Matsubara H, Mitamura Y, Kato A, Kondo M, Kimura K, Takagi H, Gomi F, Sakamoto T. Predictors of Disengagement and Loss to Follow-Up of Intravitreal Injection for Neovascular Age-Related Macular Degeneration in a Real-World Clinical Setting: Post Hoc Analysis of the Multicenter Survey from the Japanese Clinical Retinal Study (J-CREST) Group. J Clin Med 2025; 14:1803. [PMID: 40142610 PMCID: PMC11943445 DOI: 10.3390/jcm14061803] [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: 02/03/2025] [Revised: 02/27/2025] [Accepted: 03/05/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: In a recent study, we investigated anti-VEGF treatment strategies for three subtypes of neovascular age-related macular degeneration (nAMD)-typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)-among a large cohort of Japanese patients. To further explore these findings, we conducted a post hoc analysis of this cohort to identify factors associated with the discontinuation of anti-VEGF therapy for nAMD in a real-world clinical setting. Methods: We collected medical records of patients newly diagnosed with nAMD who initiated intravitreal anti-VEGF antibody injection therapy. Patients were divided into two groups: those who continued anti-VEGF therapy for one year and those who discontinued treatment. Baseline best-corrected visual acuity, optical coherence tomography (OCT) findings, injection regimen, and the type of anti-VEGF antibody drug used were analyzed using univariate and multivariate analyses. Results: A total of 667 treatment-naïve nAMD patients initiated anti-VEGF agents and followed the therapy for 1 year. The one-year dropout rate in this study was 13%. Logistic regression analysis revealed that poor initial visual acuity and a PRN treatment regimen were significantly associated with higher odds of dropout. Age, gender, systemic factors, and the choice of intravitreal injection did not show any significant differences. Conclusions: Poor initial visual acuity and PRN treatment regimens may increase the risk of treatment dropout and should be carefully monitored.
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Affiliation(s)
- Masaya Imazeki
- Department of Ophthalmology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan;
| | - Masaru Takeuchi
- Department of Ophthalmology, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan;
| | - Tsutomu Yasukawa
- Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan; (T.Y.); (A.K.)
| | - Hiroto Terasaki
- Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan; (H.T.); (T.S.)
| | - Yuki Yamamoto
- Department of Ophthalmology, Hyogo Medical University, 1-1, Mukogawacho, Nishinomiya 663-8501, Japan; (Y.Y.); (F.G.)
| | - Tatsuya Jujo
- Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8511, Japan;
| | - Makiko Wakuta
- Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, 1-1-1, Minami-Kogushi, Ube 755-8505, Japan; (M.W.); (K.K.)
| | - Hisashi Matsubara
- Department of Ophthalmology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan; (H.M.); (M.K.)
| | - Yoshinori Mitamura
- Department of Ophthalmology, Institute of Biomedical Sciences, Tokushima University Graduate School of Medicine, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan;
| | - Aki Kato
- Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan; (T.Y.); (A.K.)
| | - Mineo Kondo
- Department of Ophthalmology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu 514-8507, Japan; (H.M.); (M.K.)
| | - Kazuhiro Kimura
- Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, 1-1-1, Minami-Kogushi, Ube 755-8505, Japan; (M.W.); (K.K.)
| | - Hitoshi Takagi
- Kawasaki-Tama Eye Clinic, 2428, Noborito, Kawasaki 214-0014, Japan;
| | - Fumi Gomi
- Department of Ophthalmology, Hyogo Medical University, 1-1, Mukogawacho, Nishinomiya 663-8501, Japan; (Y.Y.); (F.G.)
| | - Taiji Sakamoto
- Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima 890-8544, Japan; (H.T.); (T.S.)
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Birner K, Reiter GS, Steiner I, Zarghami A, Sadeghipour A, Schürer-Waldheim S, Gumpinger M, Bogunović H, Schmidt-Erfurth U. Structure-Function Correlation of Deep-Learning Quantified Ellipsoid Zone and Retinal Pigment Epithelium Loss and Microperimetry in Geographic Atrophy. Invest Ophthalmol Vis Sci 2025; 66:26. [PMID: 40067294 PMCID: PMC11918028 DOI: 10.1167/iovs.66.3.26] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/09/2025] [Indexed: 03/20/2025] Open
Abstract
Purpose The purpose of this study was to define structure-function correlation of geographic atrophy (GA) on optical coherence tomography (OCT) and functional testing on microperimetry (MP) based on deep-learning (DL)-quantified spectral-domain OCT (SD-OCT) biomarkers. Methods Patients with GA were prospectively examined by SD-OCT (Spectralis, 97 B-scans) and two microperimetry devices (MP3 and MAIA) in two combined test runs each. DL-algorithms measured the ellipsoid-zone thickness (EZT), ellipsoid-zone loss (EZL), hyper-reflective-foci (HRF) volume, drusen-volume (DV), and retinal-pigment-epithelium loss (RPEL) area. Pointwise co-registration was established between all stimuli and the location on OCT. A multivariable mixed-effect model with variable selection was used to identify pointwise retinal sensitivity (PWS) changes for each biomarker, accounting for age and eccentricity. Results Three thousand six hundred stimuli points were collected and correlated with 1940 OCT B-scans in 20 eyes of 20 patients. PWS was significantly lower in stimuli with EZL without RPEL (-2.81, 95% confidence interval [CI] = -3.72 to -1.91 decibel [dB], 0 degrees, P < 0.0001) and in areas with both EZL and RPEL (-10.03, 95% CI = -10.96 to -9.11 dB, 0 degrees, P < 0.0001) compared to areas without any atrophy. Increased EZT had a significant positive effect on PWS (0.34, 95% CI = 0.32 to 0.36 dB/µm, P < 0.0001). Structure-function correlations were consistent throughout all levels of eccentricity with P < 0.001. Drusen and HRF volume, but not age, were associated with reduced PWS. Conclusions Functional impairment by MP was associated with defined morphological changes as quantified by DL on OCT. PR degeneration seen as EZL alone impairs the function on MP examinations. The combination of DL-based SD-OCT biomarker assessment and MP appear suited for evaluation of retinal function beyond visual acuity for disease monitoring.
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Affiliation(s)
- Klaudia Birner
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Gregor S. Reiter
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Irene Steiner
- Center for Medical Data Science, Institute of Medical Statistics, Medical University of Vienna, Vienna, Austria
| | - Azin Zarghami
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | | | - Simon Schürer-Waldheim
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Markus Gumpinger
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Hrvoje Bogunović
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Ursula Schmidt-Erfurth
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
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50
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Chaikitmongkol V, Tadadoltip W, Patikulsila D, Srisomboon T, Narongchai C, Choovuthayakorn J, Watanachai N, Kunavisarut P, Sangkaew A, Upaphong P, Bressler NM. Recurrent polypoidal lesions after achieving inactive polypoidal choroidal vasculopathy following 1-year fixed-dosing aflibercept treatments. Asia Pac J Ophthalmol (Phila) 2025; 14:100176. [PMID: 40032076 DOI: 10.1016/j.apjo.2025.100176] [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: 09/06/2024] [Revised: 02/17/2025] [Accepted: 02/23/2025] [Indexed: 03/05/2025] Open
Abstract
PURPOSE Polypoidal choroidal vasculopathy (PCV) may have frequent recurrences after fluid resolution, but time to recurrence is unclear. This study explored time to first polypoidal recurrence after 1-year fixed-dosing aflibercept treatments. DESIGN Retrospective cohort study. METHODS Treatment-naïve PCV eyes treated between April 2015 to May 2019 were identified and included with criteria including: (1) received fixed-dosing 2 mg aflibercept in the first year, (2) became "inactive" (absence of both intraretinal and subretinal fluid on OCT) at post-treatment year-1 (PTY1) and managed as needed (PRN) thereafter, (3) FU ≥ 12 months after PTY1. Fundus photography, indocyanine green angiography (ICGA), and OCT graded to identify timing and risk factors for recurrence (defined as fluid on OCT). RESULTS Of 37 study eyes [37 patients; median age was 64 years (IQR 59-69); median aflibercept injection number was 8 (IQR 8-8); median FU 38 months (IQR, 30-50 months)]; 18 eyes (49 %) had recurrence during FU. Fourteen (78 %) of 18 had recurrence within 12 months after PTY1 visit. Risk factors for recurrence included: incomplete polypoidal regression on post-treatment ICGA [P = .004, Hazard ratio (HR) = 4.4, 95 % confidence interval (CI) 1.6-11.9] and PED with internal heterogeneous reflectivity on post-treatment OCT (P = .04, HR = 2.7, 95 % CI 1.1-6.9). CONCLUSIONS Nearly half of inactive PCV eyes following 1-year fixed-dosing aflibercept treatments had recurrent polypoidal lesions. Eyes with high-risk features for recurrence, some of which can be detected with OCT without the need for ICGA, may warrant close monitoring.
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Affiliation(s)
- Voraporn Chaikitmongkol
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Wantip Tadadoltip
- Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Direk Patikulsila
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Titipol Srisomboon
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Ophthalmology, Nakornping Hospital, Chiang Mai, Thailand
| | - Chanusnun Narongchai
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Ophthalmology, Lanna Hospital, Chiang Mai, Thailand
| | - Janejit Choovuthayakorn
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Nawat Watanachai
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Paradee Kunavisarut
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Apisara Sangkaew
- Retina Division, Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Phit Upaphong
- Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Neil M Bressler
- Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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