International Journal of Molecular Sciences

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Prof. Dr. Hsiaoming Chao

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1. Department of Chinese Medicine, School of Chinese Medicine, China Medical University, Taichung 404, Taiwan
2. Institute of Pharmacology, Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
3. Department of Ophthalmology, Shin Kong Hospital, Taipei 105, Taiwan
Interests: neuroprotection in retinal ischemia; vitreoretinal surgery
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Prof. Dr. Robert Casson

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1. Machine Learning Division, Ophthalmic Research Laboratory, University of Adelaide, Adelaide, SA 5005 Australia
2. Department of Ophthalmology, Royal Adelaide Hospital, Adelaide, SA 5000, Australia
Interests: glaucoma; retinal cell biology; neuroprotection; ophthalmic epidemiology; translational ophthalmic
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Dr. Hsi-Kung Kuo

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1. Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung City, Taiwan
2. School of Medicine, Chang Gung University, Taoyuan City, Taiwan
Interests: uveitis; nonarteritic anterior ischemic optic neuropathy; vitreoretinal surgery
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Special Issue Information

Dear Colleagues,

Retinal vascular occlusion, normal tension glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are associated with retinal ischemia and can threaten vision. The incidence rates of these diseases are as follows: 0.0018% for central retinal artery occlusion (CRAO); 4% for primary open-angle glaucoma (in urban areas); 2.9% for sight-threatening diabetic retinopathy (type 2 diabetes); and 0.36% for AMD (age ≥40).

The aim of this Special Issue is to evaluate the protective effects and underlying mechanisms of complementary medicine or therapies against retinal ischemia. Recent advancements in retinal research have addressed several subtopics: neuroprotection in retinal ischemia (e.g., anti-VEGF agents such as faricimab, protectants like modified cerebrolysin, acupuncture, stem cells, gene therapy, and retinal chips); femtosecond-assisted phacovitrectomy; Artisan lenses in IOL dislocation; Artiflex lenses in moderate myopia; exozymes in Harada disease with associated dry eye; and comparison of silicon oil versus scleral buckles in capsulotomized pseudophakic eyes with inferior break-induced inferior retinal detachment (RD).

In macular surgery, recent topics include the use of amniotic membranes or ILM flaps in macular holes with or without RD, as well as electrophysiological and pathological evaluations using techniques such as EOG, multifocal ERG, flash ERG, VEP, microperimetry, and OCT-A.

Please note that purely clinical studies are not suitable for submission to International Journal of Molecular Sciences (IJMS). However, clinical or preclinical model studies that incorporate biomolecular experiments are welcome.

Prof. Dr. Hsiaoming Chao
Prof. Dr. Robert Casson
Dr. Hsi-Kung Kuo
Guest Editors

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16 pages, 1057 KB

Open AccessArticle

Combined Therapy Versus Fortified Anti-VEGF Monotherapy in Type C Polypoidal Choroidal Vasculopathy: Long-Term Outcomes and Exploratory Biomarker Insights

by Windsor Wen-Jin Chao, Howard Wen-Haur Chao and Hsiao-Ming Chao

Int. J. Mol. Sci. 2026, 27(3), 1224; https://doi.org/10.3390/ijms27031224 - 26 Jan 2026

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Abstract

While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of the standard one) anti-VEGF combined with PDT versus fortified anti-VEGF monotherapy and to investigate biomolecular profiles and disease relationships among PCV, neovascular age-related macular degeneration (nvAMD), and central serous chorioretinopathy (CSCR). The goal was to identify novel pathways to inform future therapeutic strategies, including hypoxia-inducible factors (HIF)-1α inhibitors. This retrospective cohort study included 23 eyes with indocyanine green-confirmed type C PCV. One eye treated with transpupillary thermotherapy was not included in the following two groups. Patients received either combined therapy (PDT + fortified-dose anti-VEGF; n = 12) or fortified-dose anti-VEGF monotherapy (n = 10). Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary outcomes included injection burden and recurrence. Exploratory analyses examined aqueous biomarkers, including VEGF, placental growth factor (PlGF), β-catenin, HIF-1α, and Wnt1 across PCV, CSCR, and nvAMD to identify novel therapeutic targets. Significant (p = 0.003/p = 0.005) median CRT reduction was similar (p = 0.468) between groups (combined/monotherapy: 137.5 µm/106.5 µm). BCVA (median [Q1, Q3]) change in logarithm of the minimum angle of resolution (LogMAR) was not statistically significant (p = 0.279), with 0.25 [0.00, 0.98] in the combined group versus 0.00 [−0.03, 0.28] in the monotherapy group. Treatment burden of anti-VEGFs per person per year was lower with combined therapy (1.16 ± 0.47# PDT + 2.81 ± 0.92# anti-VEGF injections) compared with monotherapy (4.61 ± 1.49# injections). Six eyes demonstrated recurrence at a mean of 15.5 months. Incomplete regression of polyps and branching vascular networks was observed in all eyes. Exploratory biomarker analysis revealed significantly (p < 0.05) higher VEGF and PlGF levels in nvAMD compared with PCV. nvAMD also demonstrated significantly (p < 0.05) higher β-catenin and lower HIF-1α levels relative to PCV and CSCR, while no significant biomarker differences were observed between PCV and CSCR. Combined therapy or monotherapy with fortified anti-VEGFs reduced treatment burden and achieved significant anatomical improvement but did not yield superior functional outcomes, highlighting the therapeutic difficulty of type C PCV. Biomarker profiling revealed shared hypoxia-related mechanisms between PCV and CSCR, with elevated HIF-1α compared to nvAMD indicating a “preliminary” possible role for HIF-1α inhibitors. Differential expression of these biomarkers highlights additional molecular pathways that may inform future targeted interventions. Full article

(This article belongs to the Special Issue Molecular Insight into Retinal Diseases: 2nd Edition)

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