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Clinical presentations range from interstitial keratitis, conjunctivitis, episcleritis, and scleritis to anterior, intermediate, and posterior uveitis; acute syphilitic posterior placoid chorioretinitis; retinitis; retinal vasculitis; neuroretinitis; optic neuritis; exudative retinal detachment; and optic nerve dysfunction. These manifestations may occur at any stage of infection and are frequently nonspecific, contributing to diagnostic delays. Diagnosis requires a high index of suspicion and is established by combined non-treponemal and treponemal serologic testing, with cerebrospinal fluid analysis when neurosyphilis is suspected. Multimodal imaging, including optical coherence tomography, fluorescein angiography, fundus autofluorescence, and visual field testing, enhances the detection of subclinical and atypical diseases. Management mandates prompt intravenous penicillin G, with adjunctive corticosteroids to mitigate Jarisch\u2013Herxheimer reactions and control inflammation; ceftriaxone or doxycycline serve as alternatives for penicillin-allergic patients. Long-term follow-up with serial serologies and neurologic evaluation is essential to detect relapse or progression to neurosyphilis. Despite effective therapy, diagnostic delays contribute to irreversible visual loss in a significant proportion of cases. This review integrates current knowledge on ocular syphilis, emphasizing its varied presentations and the importance of early recognition to prevent vision-threatening complications, and calls for multidisciplinary, mechanism-based research to optimize outcomes. We conducted a literature search in Pubmed and Embase for articles published between 2000 and 2025, using the terms \u201cocular syphilis,\u201d \u201csyphilitic uveitis,\u201d and \u201cneurosyphilis,\u201d with a focus on epidemiology, clinical features, diagnostics, therapeutics, and co-infections.<\/jats:p>","DOI":"10.3390\/pathogens14090852","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T09:31:12Z","timestamp":1756373472000},"page":"852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Syphilis and the Eye: Clinical Features, Diagnostic Challenges, and Evolving Therapeutic Paradigms"],"prefix":"10.3390","volume":"14","author":[{"given":"Zizhen","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1359-8198","authenticated-orcid":false,"given":"Yaru","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3124-1101","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"},{"name":"Department of Ophthalmology, Zhongshan Torch Development Zone People\u2019s Hospital, Zhongshan 528436, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Ohno-Matsui","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koju","family":"Kamoi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo 113-8510, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/cid\/ciaa180","article-title":"Prevalence of Self-reported Neurologic and Ocular Symptoms in Early Syphilis Cases","volume":"72","author":"Quilter","year":"2020","journal-title":"Clin. 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