{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:00:15Z","timestamp":1792058415625,"version":"4.4.0"},"reference-count":116,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fight for Sight, Denmark"},{"name":"Ophthalmologist Else Bruntse\u2019s foundation"},{"DOI":"10.13039\/100019562","name":"Synoptik Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019562","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100020035","name":"A.P. 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Their compact size, high solubility, stability, and ability to access cryptic epitopes distinguish them from conventional monoclonal Abs (mAbs) and larger Ab fragments. These properties are particularly attractive in ophthalmology, where molecular size, tissue penetration, and formulation constraints critically influence therapeutic performance. This narrative review summarizes the structural features, engineering strategies, immunogenicity considerations, and production platforms of sdAbs, with a focus on ocular applications. Preclinical studies demonstrate promising efficacy in retinal vascular diseases through targeting of VEGFA, ANG2, TNF\u03b1, and complement components, as well as in inflammatory and anterior segment disorders. SdAbs can be formatted as multimeric or Fc-fused constructs to extend intraocular half-life or delivered via gene therapy vectors as a sustained intraocular \u201cbiofactory\u201d approach. Notably, recent work demonstrates the feasibility of vector-encoded sdAbs targeting complement C3 in vivo. While challenges remain regarding immunogenicity, pharmacokinetics, and regulatory pathways, the approval of several sdAb-based drugs in other fields underscores their clinical potential. SdAbs represent a promising next-generation modality for ocular therapeutics, enabling innovative strategies beyond conventional antibody formats.<\/jats:p>","DOI":"10.3390\/ijms27115080","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:23:21Z","timestamp":1780622601000},"page":"5080","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Promise of Single-Domain Antibodies as Ocular Therapeutics: A Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5393-3918","authenticated-orcid":false,"given":"Thomas Stax","family":"Jakobsen","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Ophthalmology, Rigshospitalet, 2600 Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9158-1665","authenticated-orcid":false,"given":"Karoline","family":"Kaptain","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Regional Hospital G\u00f8dstrup, 7400 Herning, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3058-7960","authenticated-orcid":false,"given":"Kathrine","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke Lentz","family":"Adsersen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2896-0439","authenticated-orcid":false,"given":"Lars","family":"Aagaard","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Louise","family":"Askou","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-6350","authenticated-orcid":false,"given":"Thomas J.","family":"Corydon","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"},{"name":"Department of Ophthalmology, Aarhus University Hospital, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-019-0592-z","article-title":"Development of therapeutic antibodies for the treatment of diseases","volume":"27","author":"Lu","year":"2020","journal-title":"J. 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