{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:22:07Z","timestamp":1775726527501,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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 \u2265 125 \u00b5m 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 \u00b1 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 \u00b5m ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p &lt; 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\u2013hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen.<\/jats:p>","DOI":"10.3390\/jcm15082836","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T07:48:07Z","timestamp":1775720887000},"page":"2836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Five-Year Changes in Pachydrusen with Late-Phase Hyperfluorescence on Indocyanine Green Angiography"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2194-7063","authenticated-orcid":false,"given":"Hiroyuki","family":"Kamao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0114, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katsutoshi","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0114, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Mizukawa","sequence":"additional","affiliation":[{"name":"Shirai Eye Hospital, 1339 Takasecho, Kamitakase, Mitoyo 767-0001, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryutaro","family":"Hiraki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0114, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0114, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuhei","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0114, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0039-6257(99)00072-7","article-title":"Drusen in age-related macular degeneration: Pathogenesis, natural course, and laser photocoagulation\u2013induced regression","volume":"44","author":"Abdelsalam","year":"1999","journal-title":"Surv. 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