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Advances in the Diagnosis and Management of Age-Related Macular Degeneration: 3rd Edition

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Ophthalmology".

Deadline for manuscript submissions: 20 August 2026 | Viewed by 1548

Special Issue Editor

Prof. Dr. Tsutomu Yasukawa

E-Mail Website
Guest Editor
Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Interests: age-related macular degeneration; drug delivery system; retina; ophthalmology; choroid
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Age-related macular degeneration (AMD) is a major cause of legal blindness in developed nations. AMD is classified into two types: neovascular and non-neovascular (atrophic) AMD. Recent advances in imaging and therapeutic approaches have improved visual outcomes in eyes with neovascular AMD; that is, anti-vascular endothelial growth factor (VEGF) therapy has become the first-line treatment, supported by multimodal imaging with optical coherence tomography (OCT), fundus photography, fluorescein and indocyanine green angiography, OCT angiography, etc. Photodynamic therapy (PDT) is seldom used at this moment, especially in Western countries; despite this, PDT is still useful in the treatment of polypoidal choroidal vasculopathy and other pachychoroid diseases, which are predominant phenotypes in Asia. Future candidates of new treatment modalities include drug delivery for bioactive proteins, such as anti-VEGF agents, stem-cell-derived retinal pigment epithelial cell or photoreceptor transplant, gene therapy to produce soluble VEGF receptors, neurotrophic factors (e.g., pigment epithelium-derived factor), etc. New drugs have targeted even atrophic AMD, exemplified by complement inhibitors. In spite of these challenging approaches, this sight-threatening disease should be prevented via the use of prophylactic approaches, including antioxidant supplementation.

We previously launched the Special Issue “Advances in the Diagnosis and Management of Age-Related Macular Degeneration” Volume 1 and Volume 2 (https://www.mdpi.com/journal/jcm/special_issues/INK8O7U28B, https://www.mdpi.com/journal/jcm/special_issues/T1BG4AF421), in which various important novel findings and review articles were published and attracted significant attention. Because of the substantial need for and special interest in this field, we decided to launch “Advances in the Diagnosis and Management of Age-Related Macular Degeneration: 3rd Edition” as a sequel to the previous Special Issue.

This Special Issue will recruit original works or reviews regarding the recent status and advances in the diagnosis as well as management of neovascular and non-neovascular AMD.

Prof. Dr. Tsutomu Yasukawa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • age-related macular degeneration
  • angiography
  • anti-vascular endothelial growth factor therapy
  • geographic atrophy
  • macular neovascularization
  • multimodal imaging
  • ophthalmology
  • optical coherence tomography
  • photodynamic therapy
  • retinal pigment epithelium

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Related Special Issue

Published Papers (3 papers)

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Research

13 pages, 594 KB  
Article
Assessing the Validity of the Fellow Eye as an Internal Control in Early-Phase Clinical Trials for Myopic Chorioretinal Atrophy
by Norimichi Nagano, Eisaku Kanemori, Yoshio Hirano, Takahiro Hojo, Yukinori Sakaeda, Takaaki Yuguchi, Soichiro Kuwayama, Shuntaro Ogura, Masayo Kimura, Hiroshi Morita, Kohei Uemura and Tsutomu Yasukawa
J. Clin. Med. 2026, 15(8), 2997; https://doi.org/10.3390/jcm15082997 - 15 Apr 2026
Viewed by 237
Abstract
Background/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as [...] Read more.
Background/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as an internal control in early-phase clinical trials for myopic CRA. Methods: This exploratory and methodological retrospective study included eight patients (16 eyes) with myopic CRA who visited the Department of Ophthalmology at Nagoya City University Hospital between January 2010 and August 2023. Atrophic areas in both eyes were measured, and the longitudinal changes were analyzed. Three mixed-effects models were compared to assess the impact of inter-individual and inter-ocular variability on atrophic area progression. Subsequently, fixed-effects and mixed-effects models were compared using the Akaike Information Criterion (AIC). Finally, the square root of the variance ratio was calculated to quantify the contribution of inter-ocular variability to atrophic area progression. Results: In all eyes, the square root of the atrophic area increased over time. The model including random intercepts and slopes for each eye nested within patients had the lowest AIC of 69.4, suggesting that accounting for both inter-individual and inter-ocular variability improved model accuracy. The mixed-effects model had a lower AIC than the fixed-effects model, indicating a better fit. The square root of the variance ratio was 0.34 in the mixed-effects model, indicating that the inter-ocular variability was lower than the inter-individual variability, though it remained appreciable. Conclusions: This study quantitatively supports the feasibility and methodological validity of inter-ocular comparison designs for early-phase clinical trials in myopic CRA. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration: 3rd Edition)
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13 pages, 2059 KB  
Article
Five-Year Changes in Pachydrusen with Late-Phase Hyperfluorescence on Indocyanine Green Angiography
by Hiroyuki Kamao, Katsutoshi Goto, Kenichi Mizukawa, Ryutaro Hiraki, Atsushi Miki and Shuhei Kimura
J. Clin. Med. 2026, 15(8), 2836; https://doi.org/10.3390/jcm15082836 - 9 Apr 2026
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Abstract
Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This [...] Read more.
Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA–hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration: 3rd Edition)
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15 pages, 1940 KB  
Article
Characterization of the Effects of a Humanin Fragment Peptide (HNF14) in Age-Related Macular Degeneration
by Sonali Nashine and M. Cristina Kenney
J. Clin. Med. 2026, 15(5), 1686; https://doi.org/10.3390/jcm15051686 - 24 Feb 2026
Viewed by 457
Abstract
Background: Age-related macular degeneration (AMD) is a leading cause of vision loss and is strongly associated with mitochondrial dysfunction in retinal pigment epithelial cells. Mitochondrial-derived peptides, including Humanin and its analogs, have demonstrated cytoprotective effects in AMD-related cellular models. However, the effects of [...] Read more.
Background: Age-related macular degeneration (AMD) is a leading cause of vision loss and is strongly associated with mitochondrial dysfunction in retinal pigment epithelial cells. Mitochondrial-derived peptides, including Humanin and its analogs, have demonstrated cytoprotective effects in AMD-related cellular models. However, the effects of shorter Humanin-derived fragments in disease-specific mitochondrial models remain incompletely characterized. Methods: Transmitochondrial retinal pigment epithelial cybrid cell lines containing mitochondria from AMD patients or age-matched normal donors were treated with HNF14, a 14-amino acid Humanin fragment peptide. Cellular metabolic activity, cytotoxicity, oxidative stress, apoptotic signaling, inflammatory markers, angiogenic factor expression, and amyloid-β1–42-induced apoptosis were evaluated using biochemical assays, protein analyses, and live-cell imaging approaches. Results: HNF14 treatment was associated with improved metabolic activity and reduced cytotoxicity in AMD cybrids, with minimal effects in normal cybrids. HNF14 significantly reduced intracellular and mitochondrial oxidative stress, suppressed apoptotic and inflammatory markers, and decreased VEGF-A protein expression in AMD cybrids. In addition, HNF14 attenuated amyloid-β1–42-induced apoptotic signaling in AMD cybrids. These effects were selective for cybrids containing AMD-derived mitochondria. Conclusions: This study demonstrates that HNF14 mitigates mitochondrial and cellular stress responses in AMD transmitochondrial cybrid cells. The findings indicate that a short Humanin-derived fragment retains cytoprotective activity in a disease-specific mitochondrial context and support further investigation of mitochondrial-derived peptides as modulators of mitochondrial dysfunction relevant to AMD pathophysiology. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Age-Related Macular Degeneration: 3rd Edition)
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