Antimicrobial & Antiviral Therapy

Antibacterial Therapy

Antibiotic choice in ophthalmology tracks the clinical scenario closely. The likely organisms, and the tissue penetration required to reach them, differ sharply between surface infection, corneal infection, and intraocular infection.

Bacterial Conjunctivitis

Chloramphenicol remains first-line for uncomplicated bacterial conjunctivitis in many countries, including the UK and Sweden, owing to its broad spectrum, low cost, and good tolerability. Its use is tempered by a rare but serious risk: with systemic exposure, chloramphenicol carries an idiosyncratic risk of aplastic anemia. The risk from topical ophthalmic use specifically is very low, estimated at roughly 1 in 224,000 courses, but it remains a genuine prescribing consideration, especially for prolonged or repeated courses.

Bacterial Keratitis

Bacterial keratitis (corneal ulcer) needs broader, deeper coverage than simple conjunctivitis. Fourth-generation fluoroquinolones (moxifloxacin, gatifloxacin) are the empirical first-line choice in most guidelines. They provide excellent gram-positive and gram-negative coverage, including Pseudomonas and Staphylococcus aureus, with good corneal penetration. Resistance is a real and growing concern. In ocular Staphylococcus aureus isolates, fluoroquinolone resistance arises primarily through mutations in topoisomerase IV (the parC/parE subunits, the primary gram-positive target) and secondarily in DNA gyrase (the primary gram-negative target); efflux pump upregulation contributes as well. That pattern is why culture and sensitivity testing matters for cases that don't respond to empirical treatment.

Fusidic acid (Fucithalmic) is a narrower-spectrum option. It is active primarily against gram-positive organisms, useful for staphylococcal blepharoconjunctivitis, but inactive against Pseudomonas. Its viscous gel formulation extends contact time enough to allow twice-daily dosing. Topical azithromycin (AzaSite) is formulated in DuraSite, a polycarbophil-based mucoadhesive polymer that prolongs ocular surface contact time and sustains drug release. Azithromycin also concentrates intracellularly in polymorphonuclear cells, giving it enhanced activity against intracellular pathogens like Chlamydia trachomatis.

Endophthalmitis and Vancomycin

The Endophthalmitis Vitrectomy Study (EVS) established the standard empirical intravitreal regimen for bacterial endophthalmitis: vancomycin (1 mg/0.1 mL) for gram-positive coverage plus ceftazidime (2.25 mg/0.1 mL) for gram-negative coverage. Ceftazidime was chosen over amikacin as the gram-negative agent specifically because amikacin carries a risk of macular infarction. Vancomycin's broader ophthalmic role is treating methicillin-resistant Staph aureus (MRSA) and coagulase-negative staphylococcal infections; it is not a routine first-line choice for ordinary bacterial conjunctivitis.

Doxycycline: An Anti-Inflammatory, Not Just Antimicrobial, Use

Oral doxycycline treats rosacea-associated blepharitis and meibomian gland dysfunction, but the mechanism that matters clinically here is not primarily antibacterial. At sub-antimicrobial doses (e.g., 40 mg modified-release), tetracyclines inhibit bacterial lipases and matrix metalloproteinase-9 (MMP-9) and reduce inflammatory cytokines in meibomian secretions. That anti-inflammatory effect operates at doses too low to meaningfully disrupt the ocular microbiome.

Endophthalmitis Prophylaxis: Povidone-Iodine

Povidone-iodine 5% is the best-evidenced agent for reducing endophthalmitis risk before intravitreal injection. It works as a slow-release iodine reservoir: it gradually liberates free molecular iodine (I₂), the actual antimicrobial species, which oxidizes and denatures microbial proteins, lipids, and nucleic acids. The result is rapid, broad-spectrum bactericidal, fungicidal, and viricidal activity on the conjunctival surface.

Antiviral Therapy

Topical acyclovir 3% ointment is first-line for HSV epithelial (dendritic or geographic) keratitis. As a nucleoside analogue, it is selectively phosphorylated by HSV-encoded thymidine kinase, a step that only happens efficiently in infected cells, before it inhibits viral DNA polymerase. Trifluridine (trifluorothymidine), a fluorinated thymidine analogue, works through a related but distinct mechanism. It is phosphorylated by host cellular kinases as well as viral thymidine kinase; the monophosphate inhibits thymidylate synthase and the triphosphate is incorporated into viral DNA, producing faulty DNA. Because its activation does not depend on viral thymidine kinase alone, trifluridine retains activity against some thymidine-kinase-deficient, acyclovir-resistant HSV strains.

For systemic herpetic eye disease, HSV and varicella-zoster virus (VZV) alike, oral valacyclovir is generally preferred over oral acyclovir itself. Valacyclovir is a prodrug: intestinal and hepatic valacyclovir hydrolase converts it to acyclovir and valine, achieving three to five times higher plasma acyclovir levels than dosing acyclovir directly. That higher bioavailability supports an effective three-times-daily regimen, simplifying treatment of herpes zoster ophthalmicus and HSV prophylaxis.

CMV Retinitis

CMV retinitis is the most common serious ocular opportunistic infection in patients with HIV/AIDS. Ganciclovir, given orally as valganciclovir, intravenously, or intravitreally, is first-line. It requires phosphorylation by the CMV-encoded kinase UL97 before it can inhibit the CMV DNA polymerase (UL54). When resistance emerges, typically through UL97 mutations that block that initial phosphorylation step, foscarnet becomes the alternative: as a pyrophosphate analogue, it inhibits viral DNA polymerase directly and needs no viral kinase activation at all. Foscarnet is also useful for acyclovir-resistant HSV/VZV for the same reason. Intravitreal cidofovir is an older third option, but it carries significant ocular toxicity risk, most notably a high rate of uveitis and ocular hypotony from direct cidofovir toxicity to the ciliary body epithelium, which reduces aqueous production. Systemic cidofovir also requires co-administration of probenecid to block its renal tubular secretion and limit nephrotoxicity.

Antifungal Therapy

Azole antifungals (voriconazole, fluconazole) inhibit the cytochrome P450-dependent enzyme lanosterol 14-alpha-demethylase, blocking synthesis of ergosterol, an essential fungal cell membrane component, and disrupting membrane integrity. Voriconazole covers Aspergillus and resistant Fusarium strains better than older azoles. It also has an advantage specific to fungal keratitis: unlike natamycin (below), it penetrates the cornea well and achieves therapeutic aqueous concentrations, which makes it preferred for deep stromal or endothelial fungal involvement, Candida keratitis especially, or cases that fail natamycin. It can be delivered topically, as 1% drops prepared from IV solution, or by direct intrastromal injection.

Natamycin 5% ophthalmic suspension is first-line instead for filamentous fungal keratitis (Fusarium, Aspergillus), often following trauma involving vegetable matter. It is a polyene macrolide that binds ergosterol in the fungal cell membrane. Its major limitation is poor corneal penetration: it does not reach therapeutic concentration in the deep stroma or anterior chamber, which is exactly why deep or endothelial fungal disease favors voriconazole instead. Candida keratitis responds better to azoles than to natamycin.

Antiparasitic and Prophylactic Agents

Acanthamoeba Keratitis

Acanthamoeba treatment has to address both the organism's active trophozoite form and its highly resistant cyst form. That's why standard therapy is a combination: a biguanide (PHMB or chlorhexidine, which disrupts the amoebal cell membrane) together with a diamidine agent (propamidine/Brolene or hexamidine, which carries cysticidal activity). The combination is used long-term, often months, because the cyst form resists shorter courses.

Ocular Toxoplasmosis

Reactivation toxoplasmic retinochoroiditis is treated with an antiparasitic regimen rather than a conventional antibiotic course. The classic combination is oral pyrimethamine plus sulfadiazine, with folinic acid (leucovorin) added for a different reason than treating the infection itself: it protects the bone marrow from pyrimethamine's antifolate effect. Trimethoprim-sulfamethoxazole has become a widely used alternative regimen, and clindamycin is often substituted when a patient has a sulfa allergy. No single regimen has been shown to outperform the others in outcome studies, so the choice usually comes down to allergy history and tolerance for side effects.

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