{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:14:05Z","timestamp":1760058845243,"version":"build-2065373602"},"reference-count":57,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AMD Therapeutics LLC"},{"name":"NeoVascularX, Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Exudative age-related macular degeneration (AMD) is a disease of choroidal neovascularization that causes blindness. Current treatments to preserve vision in this prevalent and blinding condition are repeat intraocular injections of anti-vascular endothelial growth factor medicines for a patient\u2019s lifetime to preserve and prevent vision loss leading to blindness. Rifampicin, a small-molecule antibiotic, has previously been reported to exhibit anti-angiogenic properties and a topical safety profile that is well-tolerated. Based on this evidence, we investigated the feasibility of formulating rifamycin as an ophthalmic drop capable of delivering therapeutic concentrations to the posterior segment of the eye. Methods: Inhibition of neovascularization by administration of rifampicin was analyzed in the rat oxygen-induced retinopathy (OIR) and mouse laser-induced choroidal neovascularization (CNV) models. Pharmacokinetic (PK) studies were conducted in mice, rats, and rabbits by dosing various formulations containing rifampicin, and the compound was quantified by LC\/MS analysis. Results: Results from dose escalation studies in the mouse laser-induced CNV model suggested the minimum effective dose of rifampicin required for inhibiting neovascularization in subretinal tissues to be 0.7 mg\/kg, which is substantially lower than the 20 mg\/kg dosage approved for infectious disease treatments. The previous studies did not report the minimum effective dose in the anti-angiogenesis effects. The effective area under the concentration-time curve (AUC) in the sub-retina was evaluated as 0.27 h\u00b7ng\/mg. In rabbits, rifampicin was delivered to the sub-retina by a single topical application of various formulations in a dose-dependent manner. The topical application of the formulations containing 1% rifampicin, which was well-tolerated in clinical trials previously reported for ocular trachoma, achieved subretinal delivery approximately 2\u201332 times greater than the effective AUC. Plasma exposure of the compound by the topical application was evaluated to range approximately 0.5\u201310 ng\/mL. Conclusions: Rifampicin was delivered to the sub-retina in rabbits with an efficiency greater than the effective dose required for inhibiting neovascularization. Limited amounts of plasma exposure by the topical application were detected. These results suggested the therapeutic potential of the rifampicin formulations for the topical treatment of exudative macular degeneration.<\/jats:p>","DOI":"10.3390\/ph18050655","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:35:13Z","timestamp":1746185713000},"page":"655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of Rifampicin Eye Drops for the Treatment of Exudative Age-Related Macular Degeneration"],"prefix":"10.3390","volume":"18","author":[{"given":"Valory Anne S.","family":"Vailoces","sequence":"first","affiliation":[{"name":"School of Medicine & Health Sciences, George Washington University, Washington, DC 20052, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Tolentino","sequence":"additional","affiliation":[{"name":"Department of Biology, University of California Berkeley, Berkeley, CA 94720, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6104-5737","authenticated-orcid":false,"given":"Jose Fernando","family":"Arevalo","sequence":"additional","affiliation":[{"name":"Retina Division, Wilmer Eye Institute, Department of Ophthalmology at Johns Hopkins Bayview Medical Center, Johns Hopkins University, Baltimore, MD 21287, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron A.","family":"Adelman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, School of Medicine, Yale University, New Haven, CT 06510, USA"},{"name":"Department of Ophthalmology, Mayo Clinic, Jacksonville, FL 32224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Bhisitkul","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of California San Francisco, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana V.","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quan Dong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA 94303, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4914-7356","authenticated-orcid":false,"given":"Michael J.","family":"Tolentino","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, School of Medicine, University of Central Florida, Orlando, FL 32827, USA"},{"name":"Department of Ophthalmology, Orlando College of Osteopathic Medicine, Winter Garden, FL 34787, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6512-7203","authenticated-orcid":false,"given":"Masaki","family":"Tanito","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shimane University Faculty of Medicine, Shimane 693-8501, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Serizawa","sequence":"additional","affiliation":[{"name":"AMD Therapeutics LLC, Palo Alto, CA 94306, USA"},{"name":"NeoVascularX, Inc., Palo Alto, CA 94306, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1001\/jama.2023.26074","article-title":"Review of Age-Related Macular Degeneration","volume":"331","author":"Fleckenstein","year":"2024","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fleckenstein, M., Keenan, T.D.L., Guymer, R.H., Chakravarthy, U., Schmitz-Valckenberg, S., Klaver, C.C., Wong, W.T., Chew, E.Y., Fleckenstein, M., and Keenan, T.D.L. 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