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      Differences in clinical characteristics and treatment outcomes of submacular hemorrhage caused by age-related macular degeneration and retinal macroaneurysms: A multicenter survey from the Japan Clinical Retina Study (J-CREST) group

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          Abstract

          Purpose

          To evaluate the clinical characteristics, treatment trends, and visual prognosis of submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) and retinal arterial macroaneurysm (RAM).

          Methods

          This retrospective study enrolled 187 Japanese patients with SMH at 10 institutions from 2015 to 2018. Medical records including SMH etiology, best-corrected visual acuity (BCVA), fundus photographs, optical coherence tomography images, and selected treatments were analyzed.

          Results

          Major causes of SMH were typical nAMD (tnAMD) (18%), polypoidal choroidal vasculopathy (PCV) (50%) and RAM (29%). Age, male/female ratio, baseline BCVA, central retinal thickness, and involved retinal layers were significantly different between etiologies (all P<0.0001). Treatment with anti-vascular endothelial growth factor drugs with and without intravitreal gas injection was chosen for half of eyes in the tnAMD and PCV groups, whereas vitrectomy was performed in 83.7% of eyes with RAM. The final BCVA improved significantly from baseline in the PCV and RAM groups (P = 0.0009, P<0.0001) and final BCVA was significantly better in the PCV group at a level similar to the other groups (P = 0.0007, P = 0.0008). BCVA improvement from baseline was significantly greater in the RAM group compared with the tnAMD (P = 0.0152) and PCV (P = 0.017) groups. Multivariate analysis revealed better final BCVA was significantly associated with younger age (P = 0.0054), better baseline BCVA (P = 0.0021), RAM subtype (P = 0.0446), and no tnAMD (P = 0.001).

          Conclusions

          The characteristics of, and treatment strategy for, SMH were different between the underlying diseases. Anti-vascular endothelial growth factor treatment with or without expansile gas was mainly chosen for SMH in tnAMD and PCV, whereas vitrectomy with gas was the most common treatment for RAM, and the higher rate for vitrectomy might result in the greater BCVA improvement in the RAM group than in the other groups. Final BCVA was better in PCV, RAM, and tnAMD, in that order, because patients with PCV were younger and had better baseline BCVA.

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          Most cited references30

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          Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease?

          Neovascular age-related macular degeneration (nAMD) is the commonest cause of severe visual impairment in older adults in Caucasian white populations. Polypoidal choroidal vasculopathy (PCV) has been described as a separate clinical entity differing from nAMD and other macular diseases associated with subretinal neovascularization. It remains controversial as to whether or not PCV represents a sub-type of nAMD. This article summarizes the current literature on the clinical, pathophysiological and epidemiological features and treatment responses of PCV and compares this condition to nAMD. Patients with PCV are younger and more likely Asians, and eyes with PCV lack drusen, often present with serosanguinous maculopathy or hemorrhagic pigment epithelial detachment, and have differing responses to photodynamic therapy and anti-vascular endothelial growth factor (VEGF) agents. There are also significant differences in angiographic and optical coherence tomography features between PCV and nAMD. Histopathological studies suggest differences in the anatomical details of the associated vascular abnormalities in the retina and choroids and the relative role of VEGF. There is emerging evidence of common molecular genetic determinants involving complement pathway and common environmental risk factors (e.g. smoking). Such information could further assist clinicians involved in the care of elderly patients with these conditions.
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            Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study

            Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed.
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              • Article: not found

              EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy.

              To assess the effects of verteporfin photodynamic therapy (PDT) combined with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. In this multicenter, double-masked, primarily indocyanine green angiography-guided trial, 61 Asian patients were randomized to verteporfin PDT (standard fluence), ranibizumab 0.5 mg, or the combination. Patients were administered with verteporfin PDT/placebo and initiated with three consecutive monthly ranibizumab/sham injections starting Day 1, and re-treated (Months 3-5) as per predefined criteria. The primary endpoint was the proportion of patients with indocyanine green angiography-assessed complete regression of polyps at Month 6. Secondary endpoints included mean change in best-corrected visual acuity at Month 6 and safety. At Month 6, verteporfin combined with ranibizumab or alone was superior to ranibizumab monotherapy in achieving complete polyp regression (77.8% and 71.4% vs. 28.6%; P < 0.01); mean change ± standard deviation in best-corrected visual acuity (letters) was 10.9 ± 10.9 (verteporfin PDT + ranibizumab), 7.5 ± 10.6 (verteporfin PDT), and 9.2 ± 12.4 (ranibizumab). There were no new safety findings with either drug used alone or in combination. Verteporfin PDT combined with ranibizumab 0.5 mg or alone was superior to ranibizumab monotherapy in achieving complete regression of polyps in this 6-month study in patients with symptomatic macular polypoidal choroidal vasculopathy. All treatments were well tolerated over 6 months.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Writing – original draft
                Role: ConceptualizationRole: Data curationRole: Validation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: Data curation
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 September 2022
                2022
                : 17
                : 9
                : e0274508
                Affiliations
                [1 ] Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Japan
                [2 ] Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
                [3 ] Department of Ophthalmology, Sapporo City General Hospital, Sapporo, Japan
                [4 ] Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
                [5 ] Department of Ophthalmology, Tokushima University Graduate School, Tokushima, Japan
                [6 ] Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
                [7 ] Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
                [8 ] Department of Ophthalmology, Fukui University Graduate School of Medical Sciences, Yoshida, Japan
                [9 ] Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan
                [10 ] Department of Ophthalmology, Nara Medical University, Kashihara, Japan
                National Yang-Ming University Hospital, TAIWAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-2566-5506
                https://orcid.org/0000-0001-9913-1905
                https://orcid.org/0000-0003-0807-8817
                Article
                PONE-D-22-04349
                10.1371/journal.pone.0274508
                9522260
                36173964
                76f8eed3-9e9a-462c-a0f1-b4f10c5582f0
                © 2022 Kimura et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 February 2022
                : 28 August 2022
                Page count
                Figures: 2, Tables: 4, Pages: 12
                Funding
                The authors received no specific funding for this work.
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                Biology and Life Sciences
                Anatomy
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