Mechanisms and Evolution of Antimicrobial Resistance in Ophthalmology: Surveillance, Clinical Implications, and Future Therapies

Antimicrobial resistance (AMR) is a growing global health concern with profound implications for ophthalmology, where it compromises the management of ocular infections such as bacterial keratitis, conjunctivitis, endophthalmitis, and postoperative complications. Resistance in common ocular pathogens, including <i>Staphylococcus aureus</i> (<i>S. aureus</i>), <i>Streptococcus pneumoniae</i> (<i>S. pneumoniae</i>), <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>), and coagulase-negative staphylococci (CoNS) emerge through genetic mutations, horizontal gene transfer, and biochemical mechanisms such as enzymatic degradation, target modification, efflux pumps, and reduced membrane permeability. Biofilm formation further complicates eradication on the ocular surface and interior. The key drivers of resistance include inappropriate or prolonged topical antibiotic use, routine prophylaxis in ocular surgery, subtherapeutic dosing, and cross-resistance with systemic antimicrobials. The rise in multidrug-resistant strains, particularly methicillin-resistant <i>S. aureus</i>, fluoroquinolone-resistant <i>P. aeruginosa</i>, and drug-resistant <i>S. pneumoniae</i> has been linked to delayed treatment response, increased healthcare costs, and sight-threatening outcomes. Recent advances in rapid diagnostics, molecular assays, and point-of-care testing support earlier and more precise detection of resistance, enabling timely therapeutic decisions. Promising strategies to address AMR in ophthalmology include antimicrobial stewardship, novel drug delivery platforms, and alternative approaches such as bacteriophage therapy and antimicrobial peptides. Emerging tools, including genomic surveillance, artificial intelligence (AI)-driven resistance prediction, and personalized antimicrobial regimens, further expand opportunities for innovation. Collectively, this review synthesizes current evidence on AMR in ocular disease, summarizing patterns of resistance, underlying mechanisms, and clinical consequences, while highlighting strategies for mitigation and underscoring the need for global awareness and collaboration among clinicians, researchers, and policymakers to safeguard vision.