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Recent advances in optical tissue clearing techniques have revolutionized deep tissue imaging by overcoming these fundamental limitations, enabling high\u2010resolution microscopic examination of intact organ systems. In ophthalmic research, these methodologies provide transformative capabilities for macroscopic three\u2010dimensional visualization, effectively addressing the spatial constraints inherent to conventional two\u2010dimensional histological sections. This paradigm shift has opened new avenues for investigating complex spatial relationships in ocular biology, including vascular network organization, neural connectivity patterns, and dynamic cellular processes. This comprehensive review synthesizes the current literature on tissue clearing methodologies with specific emphasis on ocular applications, systematically examining (1) the unique structural considerations for eye tissue clearing, (2) the established protocols for ocular tissue clearing, (3) the new discoveries in ocular structures through tissue clearing, (4) the imaging acquisition and analysis for cleared eye tissue, and (5) the emerging directions for future technological development. By integrating diverse insights, this review establishes a foundation for the continued refinement of tissue clearing approaches in ocular research, promoting a deeper understanding of eye structure and pathology.<\/jats:p>","DOI":"10.1155\/joph\/2810267","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T06:28:11Z","timestamp":1775111291000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Optical Tissue Clearing for Three\u2010Dimensional Ocular Imaging and 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