Bacterial keratitis & endophthalmitis
Pseudomonas aeruginosa is the leading cause of contact-lens-associated bacterial keratitis and a major cause of post-surgical and post-traumatic endophthalmitis. Both are ophthalmic emergencies that can destroy vision within 24 to 48 hours through rapid corneal melting or intraocular spread. Rising multidrug resistance, potent toxins, and biofilm formation on the cornea and contact lenses increasingly blunt standard antibiotic therapy. Lytic bacteriophages suit this niche because they self-amplify at the infection site, kill antibiotic-resistant cells through resistance-independent mechanisms, penetrate biofilm, and can be given as eye-drops or intravitreally with minimal host toxicity.
How phages act here
Mechanism
Anti-pseudomonal phages adsorb to specific surface receptors such as LPS, type IV pili, or exopolysaccharides, inject their genome, replicate, and lyse the cell, releasing progeny that propagate the kill. Because P. aeruginosa is heterogeneous and each phage has a narrow host range, cocktails with complementary receptor targets such as Myoviridae plus Podoviridae broaden coverage and suppress phage-resistant mutants. A standout for ocular disease is biofilm targeting: the phage Clew-1 uses the biofilm exopolysaccharide Psl as its receptor, preferentially replicating within and disrupting corneal biofilm rather than planktonic cells. Phage-antibiotic synergy is central, with phages and sub-lethal antibiotics combining for greater killing and lower resistance, and phages can resensitize bacteria to antibiotics. Engineered and enzyme-based tools such as CRISPR-armed phages, depolymerases, and endolysins are emerging additions.
Where it stands
Current evidence
As of 2026 the direct evidence for phage therapy in Pseudomonas keratitis and endophthalmitis is preclinical but consistent and growing, while human phage therapy for P. aeruginosa at other body sites is well established under compassionate use. Topical phage KPP12 eye-drops cleared P. aeruginosa, preserved corneal transparency, and reduced neutrophil damage in a mouse keratitis model (Fukuda 2012). A two-phage cocktail including broad-host-range phage Phi-R18 prevented and suppressed P. aeruginosa keratitis in a mouse model developed for equine disease (Furusawa 2016). The biofilm-tropic phage Clew-1, which uses the Psl exopolysaccharide as a receptor, reduced bacterial burden in a mouse model of corneal biofilm infection (Walton 2025). No completed registered trial yet targets phage therapy specifically for keratitis or endophthalmitis, but human anti-pseudomonal phage experience, including the cystic fibrosis trial NCT05453578 and synergy cases reviewed by Elfadadny 2025, supports translation, with groups such as Armata Pharmaceuticals advancing P. aeruginosa phage products.
Evidence confidence: medium
The data
Key studies & trials
- Fukuda K, Ishida W, Uchiyama J, et al. Pseudomonas aeruginosa keratitis in mice: effects of topical bacteriophage KPP12 administration. PLoS One. 2012;7(10):e47742. ↗
- Furusawa T, Iwano H, Hiyashimizu Y, et al. Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis. Appl Environ Microbiol. 2016;82(17):5332-9. ↗
- Walton B, Abbondante S, Marshall ME, et al. A biofilm-tropic Pseudomonas aeruginosa bacteriophage uses the exopolysaccharide Psl as receptor. eLife. 2025;13:e102352. ↗
- Elfadadny A, Ragab RF, Abd Alaziz OA, et al. Bacteriophage therapy in clinical practice: case studies of Pseudomonas aeruginosa infections. J Chemother. 2025:1-12. ↗
Who is working on it
Programs & centers
The possibility
Picture an emergency-room kit where a corneal scraping is matched to a personalized phage cocktail within hours, and a drop-on-eye therapy clears a fluoroquinolone-resistant ulcer while sparing the ocular surface. Because biofilm-tropic phages like Clew-1 home in on the exopolysaccharide matrix that shields Pseudomonas on the cornea and on intraocular lenses, intravitreal or topical phages could one day rescue eyes from endophthalmitis that are lost to enucleation today. Combined with antibiotics for synergy and with phage enzymes that dissolve biofilm, this living, self-amplifying medicine could make some of ophthalmology's most aggressive infections routinely curable.