Prophylaxis of Ocular Infection in the Setting of Intraocular Surgery: Implications for Clinical Practice and Risk Management

**Background** Preoperative prophylaxis is essential to minimize the risk of postoperative infections in ophthalmic surgery, particularly endophthalmitis. The most common causative organisms are coagulase-negative staphylococci (CNS), especially *Staphylococcus epidermidis* and *Staphylococcus aureus*, which originate from the patient's own eyelid and conjunctival flora. Molecular epidemiological techniques have shown that microbes isolated from the vitreous in endophthalmitis cases are genetically indistinguishable from conjunctival organisms in more than 80% of cases. Despite the established efficacy of povidone-iodine (PVI), there is considerable heterogeneity in antiseptic practices across Europe and globally. The European Society of Cataract and Refractive Surgeons (ESCRS) guidelines recommend PVI 5–10% applied for a minimum of 3 minutes before surgery, along with intracameral cefuroxime, which reduced endophthalmitis rates fivefold. However, the routine use of preoperative topical antibiotics is not advisable due to lack of clear benefit and risk of selecting resistant flora. This review aims to highlight recent evidence and controversies in preoperative infection prophylaxis and address medico-legal implications.

**Methods** This is a narrative review based on previously conducted studies; no new studies with human participants or animals were performed. The authors searched and synthesized published literature on antiseptic compounds used for preoperative prophylaxis in intraocular surgery, including PVI, chlorhexidine (CHX), polyhexamethylene biguanide (PHMB), picloxydine, ozone, hypochlorous acid (HOCl), and Biosecur. In vitro and in vivo studies, as well as clinical trials, were reviewed to assess efficacy, safety, and tolerability.

**Key Results** - **Povidone-iodine (PVI):** PVI at 5–10% is the most effective antiseptic, reducing ocular surface flora by nearly 90% (Apt et al., 1984). Lower concentrations (0.6%) used as eye drops for 3 days preoperatively reduced bacterial-growth-positive swab cultures by 82% (from 74% at baseline to 14% after prophylaxis) and eliminated bacterial growth in post-injection needle cultures (0% vs. 2% in controls) (Reibaldi et al., Tognetto et al.). PVI has broad-spectrum activity against bacteria, viruses, fungi, and protozoans, and does not induce antibiotic resistance. - **Chlorhexidine (CHX):** CHX 0.05% or 0.1% is well tolerated and associated with low endophthalmitis rates. Oakley et al. reported an endophthalmitis rate of 0.023% in 4322 intravitreal injections using aqueous CHX 0.1%, comparable to PVI. However, CHX is inactive against *Enterobacteriaceae*, *Pseudomonas aeruginosa*, and spores, and resistance has been reported in methicillin-resistant *S. aureus*. A new formulation (Dropsept, CHX 0.02% with vitamin E) showed in vitro bactericidal activity against *S. aureus*, *S. epidermidis*, and *E. coli*, but no effect on *P. aeruginosa*; it also showed antiviral and amoebicidal activity. In vivo studies are lacking. - **Polyhexamethylene biguanide (PHMB):** PHMB is effective against *Acanthamoeba castellanii*, *S. epidermidis*, and *E. coli*. A randomized trial found PHMB more effective than PVI at reducing microorganisms and extending antisepsis duration. PHMB 0.08% caused reversible corneal punctate keratopathy. No commercial preoperative formulation is available. - **Picloxydine dihydrochloride:** Picloxydine 0.05% showed efficacy against conjunctival bacteria in patients undergoing intravitreal injections, with no microbial growth in 80% of swabs the day after treatment (Budzinskaya et al.). - **Ozone:** Ozonized oil 0.5% in liposomes (Ozodrop) reduced microbial load by >90% in >90% of samples in a clinical study (Spadea et al.). In vitro, it inhibited *S. epidermidis* and *E. coli* after 24 hours, but had no antiviral or antiamoebic activity. - **Hypochlorous acid (HOCl):** HOCl showed bactericidal activity in vitro but was less effective than PVI in a randomized study (Kanclerz et al.), with a higher number of positive conjunctival swabs. However, HOCl caused significantly less discomfort. - **Biosecur:** A liposomal formulation (Oftasecur) containing 0.2% Biosecur showed bactericidal and fungicidal effects in vitro. In vivo, a 4-day prophylactic treatment significantly decreased conjunctival bacterial load in patients undergoing intravitreal injections (Vagge et al.).

**Clinical Implications** Preoperative prophylaxis with antiseptics is crucial to reduce postoperative endophthalmitis, especially given rising antibiotic resistance. PVI remains the gold standard due to its broad spectrum, safety, and lack of resistance induction. CHX is a viable alternative for iodine-allergic patients, but its spectrum is narrower. Newer compounds like ozone, HOCl, and Biosecur show promise but require further validation. From a medico-legal perspective, adherence to evidence-based antiseptic protocols (e.g., PVI use) can reduce liability, as ophthalmic surgery has a high litigation/conviction ratio (83.3%). The review emphasizes that preoperative topical antibiotics do not add clear benefit and may promote resistance, so their routine use is not recommended. Standardized protocols and risk management strategies are essential to minimize healthcare-acquired infections and associated legal disputes.