Successful corneal infection management warrants a definitive diagnosis, appropriate treatment based on that diagnosis, and close follow-up to ensure eradication and, thus, the preservation of vision and quality of life.
This article discusses the initial treatments for commonly seen bacterial and viral keratitis, along with rarely seen non-bacterial infections, such as fungal and Acanthamoeba (AK) keratitis. The following rules of engagement are generally considered universal:
• Contact lenses (if applicable) should always be discontinued until the infection has cleared, so wear doesn’t exacerbate signs and symptoms.
• Culture results should be pursued when indicated both initially (before treatment) and upon resistance to the selected treatment regimen.
• Patients should be followed closely to ensure their infection is responding positively to treatment.
• Infection eradication is contingent on identifying the organism responsible for the infection and patient compliance with each prescription. (In severe infections, hospital admission may be required to ensure patient adherence.)
• Patients using an ophthalmic corticosteroid should be followed closely for both IOP monitoring and unexpected worsening of the infection.
• Unless otherwise specified, both dosage and duration of use of treatment(s) is/are relative to each case.
Bacterial ulcerative keratitis
In low-risk bacterial keratitis, fourth-generation ophthalmic broad-spectrum antibiotics should be prescribed initially, in less severe corneal ulcers. This is because they target both gram-positive (e.g., Staphylococcus aureus and Staphylococcus pneumonia) and gram-negative (e.g., Pseudomonas aeruginosa) infections. These antibiotics are gatifloxacin ophthalmic solution, and moxifloxacin hydrocholoride ophthalmic solution.
Large infiltrates or ulcers impacting the visual axis should be treated initially with alternating fortified tobramycin (15 mg/mL) (sometimes substituted by ODs with polymyxin B and trimetho-
prim ophthalmic combination) and vancomycin
(10 mg/mL to 25 mg/mL) every hour around the clock.
Initially, a loading dose of commercially available drops can be used every five-to-10 minutes for the first 30 minutes after scrapes are performed for cultures, followed by hourly application to enhance antibiotic coverage.1 Oral antibiotics may be considered for patients who have deep ulcers or scleral involvement.
Ophthalmic cycloplegic agents are indicated in cases of significant anterior chamber inflammation and may also decrease synechiae formation and reduce eye pain.1 A caveat: Avoid prescribing heavy pain medication, which may interfere with adherence to prescribed medications.
Further, an ophthalmic corticosteroid can be prescribed after at least 48 hours of antibiotic usage in cases of culture-proven bacterial keratitis.2 This is because sterilization generally occurs at 48 hours with fortified antibiotics. Concomitant use of an ophthalmic corticosteroid with an appropriate ophthalmic antibiotic dosage generally results in better visual outcomes for these patients.3 That said, it should be avoided in nocardia infections.4
AK-caused keratitis
Biguanides inhibit membrane function, aromatic diamidines restrict DNA synthesis; aminoglycosides impede protein synthesis; and imidazoles destabilize the cell wall of AK.5 However, aminoglycosides have now shown increased neomycin-resistant strains with an increased preponderance for trophozoite transformation. Concentration of benzalkonium chloride in an antibiotic can be therapeutic.
As a first-line therapy, chlorhexidine 0.02% or polyhexanide (PHMB) 0.02% to 0.06% and a propamidine may be utilized every hour for the first two-to-three days, every hour while awake for the following several days, and four times a day may come weeks later. For pain management, NSAIDs may be utilized, as needed.
Steroids are controversial and may worsen the condition. Therefore, an ophthalmic corticosteroid should be prescribed only after significant anti-amoebic treatment and if deep corneal vascularization, scleritis, or severe anterior chamber inflammation occur.
A cycloplegic can also be utilized to reduce discomfort. Several AK infections are polymicrobial (40% fungal, 12.5% bacterial, and 5% triple).5
Fungal keratitis
The first course of action for this condition is as follows: ophthalmic antifungal agents, oral antifungal agents, and ophthalmic antibiotic agents. Epithelial debridement can be done every 24 to 48 hours to increase ophthalmic drug penetration.
The ophthalmic antifungal agents are natamycin 5% (which is generally used for Fusarium and Aspergillus species-based infections), amphotericin B 0.15% to 0.30%, and voriconazole 1% for yeast-based infections.6 (Voriconazole 1% is being used regularly today. Oral miltefosine has been used in refractory cases.) Ophthalmic fluconazole 2%, econazole 1%, itraconazole 1%, and miconazole 1% may also be used. Note: Because there is a paucity of available treatments, several agents along with natamycin 5% (the only FDA approved antifungal agent) are used.
The oral antifungal agent choices are voriconazole 400 mg two times a day, itraconazole
200 mg once a day (reduce to 100 mg once a day), fluconazole 200 mg two times a day, posaconazole 300 mg two times a day (reduce to 300 mg once a day after day one), miconazole, clotrimazole, and ketoconazole. Liver function in patients using oral antifungal agents must be checked monthly. If significant renal clearance insufficiency is present, coordinated treatment with a nephrologist is encouraged.
Because a bacterial superinfection may occur with fungal keratitis, a fourth-generation ophthalmic broad-spectrum antibiotic is also recommended.
Corticosteroids are contraindicated during active infection, as they will worsen fungal infection.
Herpes simplex keratitis
Herpes simplex keratitis presents as (1) epithelial, (2) stromal, and (3) endothelial disease. Additionally, the condition can result in neurotrophic keratopathy (NK), which can cause corneal dissolution.7
Debridement is only indicated if new epithelial lesions are present with a history of stromal disease.8
1. Epithelial. Dendritic and epithelial geographic keratitis often respond to the initial treatments of an oral antiviral, ganciclovir ophthalmic gel 0.15%, or topical trifluridine.
The oral antiviral drugs are acyclovir 400 mg five times a day; valacyclovir 500 mg three times a day, or famciclovir 250 mg three times a day for 10 days to 14 days. (Typically, herpes simplex infections require about half the standard oral dosing of zoster, as they are more sensitive to antivirals.)
Ganciclovir ophthalmic gel 0.15% should be instilled five-to-six times daily until the ulcer has healed, followed by three-times-a-day dosing for an additional seven days.
Trifluridine can be instilled up to nine times a day and can be decreased to five times a day once the epithelium starts healing, typically after one week.7,9
Prolonged use (beyond 14 to 21 days) of either medication increases corneal toxicity.
2. Stromal. The initial treatment for stromal keratitis without ulceration is an ophthalmic cor-ticosteroid, six-to-eight times daily initially and a prophylactic oral antiviral maintained as long as the ophthalmic corticosteroid is used.
As the immune response lessens, the ophthalmic corticosteroid can be tapered slowly, with a subsequent dose reduction. (Pro tips. Always look for comorbidity, such as a bacterial infection. Also, check for corneal sensitivity in the involved eye sooner vs. later to identify NK.1
Stromal involvement with corneal ulceration requires the cautious use of an ophthalmic corticosteroid and oral antiviral treatment prophylaxis. An oral steroid may be used in severe immune stromal keratitis, necrotizing stromal keratitis, severe diffuse and disciform endotheliitis, linear endotheliitis, and severe iridocyclitis/trabeculitis.
3. Endothelial. This requires an oral antiviral (standard dosing) and an ophthalmic corticosteroid (six-to-eight times daily). Prophylaxis with the oral antiviral is indicated for recurrent herpes simplex keratitis infection/inflammation (two or more episodes) to prevent corneal scarring and neovascularization/lipid deposition following ocular surgical procedures.9
Any resistance of the condition not related to patient non-compliance raises the concern for an immuno-suppression or compromised state. If viral resistance is suspected, a viral culture for polymerase chain reaction and sensitivities should be obtained.
Herpes zoster ophthalmicus
The initial treatment here is a seven-to-10-day course of antiviral oral medications (acyclovir
800 mg, five times daily, valacyclovir 1g, three times daily, or famciclovir, 500 mg, three times daily), initiated within 72 hours of onset for best results.
An adjuvant analgesic and oral steroid may reduce pain, but it’s best to get the patient’s primary care provider involved, as an oral steroid may increase the potential for disseminated disease, especially in diabetic patients.
Frequent use of an artificial tear and the prophylactic use of topical antibiotic ointments, three-to- four-times daily, may be indicated with epithelial involvement. Topical antibiotic ointments for the skin should be avoided, as they often exacerbate skin rashes and delay healing.
An ophthalmic corticosteroid is indicated (as in herpes simplex virus keratitis and kerato-uveitis) with herpes zoster ophthalmicus stromal inflammation and uveitis. Prolonged healing times will be experienced with a premature tapering of topical steroids prior to resolution of inflammatory reactions. Again, monitoring for late-onset complications, such as NK, is also imperative here.
Remain vigilant
Various corneal infections are possible, with viral and bacterial infections the leading causes. Fortunately, we have pharmaceutical options to avoid or reduce the potential for sight-threatening complications. When the discussed initial treatments fail or unusual infections are encountered, ODs should work with a corneal specialist who can provide additional insight. OM
References:
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2. Lin A, Rhee MK, Akpek EK, et al. Bacterial keratitis preferred practice pattern. Ophthalmology. 2019;126(1):P1‐P55. doi: 10.1016/j.ophtha.2018.10.018.
3. Ni N, Srinivasan M, McLeod SD, Acharya NR, Lietman TM, Rose-Nussbaumer J. Use of adjunctive topical corticosteroids in bacterial keratitis. Curr Opin Ophthalmol. 2016;27(4):353-7. doi: 10.1097/ICU.0000000000000273.
4. Green M, Hughes I, Hogden J, Sergio S, Apel A, Stapleton F. High-dose steroid treatment of bacterial keratitis. Cornea. 2019 ; 38(2):135-140. Cornea. 2019;38(2):135-140. doi: 10.1097/ICO.0000000000001794.
5. Somani SN, Ronquilo Y, Moshirfar M. Acanthamoeba Keratitis. Continuing Education Activity. https://www.ncbi.nlm.nih.gov/books/NBK549863/ (Accessed Oct. 1, 2024)
6. Awad R, Ghaith AA, Awad K, Saad MM, Elmassry AA. Fungal Keratitis: Diagnosis, Management, and Recent Advances. Clin Ophthalmol. 2024; 18: 85–106. doi: 10.2147/OPTH.S447138
7. Ahmad B, Gurnani B, Patel BC. Herpes Simplex Keratitis. 2024 Mar 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 31424862.)
8. Wilhelmus KR. The treatment of herpes simplex virus epithelial keratitis.
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9. American Academy of Ophthalmology. Herpes Simplex Virus Keratitis: A Treatment Guideline - 2014. https://www.aao.org/education/clinical-statement/herpes-simplex-virus-keratitis-treatment-guideline (Accessed Oct. 1, 2024)
