Approach
Treatment of infectious keratitis should be aimed at eliminating the causative agent, minimising corneal scarring, and preserving the function of the eye. Ideally, corneal scrapings should be sent for cultures and sensitivity prior to initiating treatment. Unless specific historical or clinical evidence suggests otherwise, microbial keratitis should be assumed to be bacterial. Even in non-bacterial infectious keratitis, epithelial defects should prompt the use of broad-spectrum topical antibacterials or ointment for prophylaxis. Contact lens use should be discontinued while the eye is inflamed. Oral analgesics and other pain medicine should be given as needed. A topical cycloplegic should be used in the presence of an anterior chamber reaction and photophobia. An eye shield should be placed over eyes when considerable corneal thinning is present. Adjunctive analgesic relief in the form of paracetamol, non-steroidal anti-inflammatory drugs, and opioids may be necessary if pain is severe and/or troubling.
Adjunctive treatment with topical corticosteroids in bacterial corneal ulcers does not seem to provide benefit to the majority of patients in terms of improved visual acuity, infiltrate or scar size, time to re-epithelialisation, and corneal perforation.[4][33] A small subgroup of patients with vision of counting fingers or worse, and those with large, central corneal ulcers may benefit from topical corticosteroid use with improvement in visual acuity.[4][34] Treatment of nocardia ulcers with topical corticosteroids may be associated with poorer outcomes.[4][35][36]
Contact lens wearers should avoid wearing contact lenses until the keratitis is completely healed.[4]
Empirical antibiotic treatment prior to culture results
Empirical treatment consists of topical antibiotics.[4]
Low-risk patients (defined as those with a non-staining peripheral infiltrate <1 mm in diameter and no history of contact lens wear) can use broad-spectrum topical antibiotics such as polymyxin B/trimethoprim or a fluoroquinolone. Moderate-risk patients (defined as those with <2 mm peripheral infiltrate, associated epithelial defect, mild anterior chamber reaction, and moderate discharge) and contact lens wearers should use a broad-spectrum topical fluoroquinolone. High-risk patients (defined as those with a stromal infiltrate diameter ≥2 mm, central infiltrate, moderate to severe anterior chamber reaction, and purulent discharge) are initially treated with a combination regimen of hourly fortified topical antibacterial such as tobramycin or gentamicin, combined with cefazolin or vancomycin.[4] Use of fourth-generation topical fluoroquinolones may be as efficacious and better tolerated compared with fortified antibiotics.[37] The dosing frequency can be tapered down gradually after 4 to 14 days if clinical picture improves.
Systemic antibiotics
Usually not indicated, except in high-risk cases (e.g., pending corneal perforation) or gonococcal infection.[4]
In cases of corneal perforation, intravenous antibiotics (e.g., ceftazidime plus vancomycin) can be used for empiric coverage. If ceftazidime plus vancomycin is not tolerated or is contraindicated, regimens that include a cephalosporin (e.g., cefazolin, cefuroxime) plus a fluoroquinolone such as ciprofloxacin, or ciprofloxacin alone can be considered. The treatment course is typically 3 days.[38] When available, culture results should be used to guide the choice of antibiotic agent.
Systemic fluoroquinolone antibiotics such as ciprofloxacin may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[39]
Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.
In the case of gonococcal eye infection, consultation with an infectious disease specialist should be considered, as well as appropriate antibiotic therapy. See Gonorrhoea infection for more information.
Adjustment according to culture results
After cultures and sensitivity results become available, antimicrobial therapy should be tailored more narrowly or switched to appropriate medicine if the initial assessment is incorrect.[4] With fungal and Acanthamoeba keratitis, the diagnosis is often missed initially.
Herpetic keratitis
Herpetic keratitis is divided into dendritic disease, interstitial keratitis, or disciform (endotheliitis) forms.
Epithelial lesions are usually self-limited and typically treated with topical antivirals such as trifluridine or ganciclovir (with or without epithelial debridement) to shorten the disease duration.[7][40]
[ 
]
For the treatment of herpes simplex virus (HSV) keratitis, ganciclovir ophthalmic gel has been shown to be at least as effective as aciclovir ointment but it is better tolerated and results in lower rates of blurred vision, eye irritation, and punctate keratitis.[41] If a large epithelial defect is present, a broad-spectrum topical antibiotic such as polymyxin B/trimethoprim or a fluoroquinolone should be added.
Interstitial keratitis and disciform keratitis (endotheliitis) are driven by an inflammatory reaction to viral antigen and so are treated with topical corticosteroids. Active infection may also be present and oral antivirals should be used concurrently.[7] If a large epithelial defect is present, and if there is marked inflammation, topical corticosteroids should be replaced by oral corticosteroids and a broad-spectrum topical antibiotic such as polymyxin B/trimethoprim or a fluoroquinolone should be added.
If intraocular pressure is high, as is often the case in herpetic disease, anti-glaucoma therapy must be instituted. Prostaglandin analogues are generally avoided in these patients due to theoretical pro-inflammatory effects.
Contact lens wear should be discontinued during therapy.[4] If corneal thinning >50% is present, an eye shield without an eye patch should be placed over the involved eye.[1][19]
Active herpetic disease should be differentiated from a neurotrophic corneal ulcer, a lesion caused by corneal nerve damage and medication toxicity. Neurotrophic corneal ulcers are treated by ceasing toxic medication, lubrication, and patching.
Patients with recurrent episodes of herpetic infection may benefit from prophylactic antivirals such as aciclovir.[7][40]
Fungal keratitis
Fungal keratitis treatment is generally prolonged and complicated, especially because the correct treatment is often delayed as the diagnosis is missed initially. Topical or oral antifungal therapy is recommended.[12] One Cochrane review has found no evidence that any particular antifungal, or combination of antifungals, is more effective in the management of fungal keratitis. Previous studies showed topical natamycin may be superior compared with topical voriconazole.[42] Fungal keratitis with severe inflammation or stromal infiltrate >2 mm or poor response to topical therapy should be treated with systemic antifungal therapy (e.g., itraconazole, voriconazole).[43][44]
If a corneal ulcer has re-epithelialised but the infiltrate appears active, then epithelial debridement may improve drug penetration.
Contact lens wear should be discontinued during therapy.[4] If corneal thinning >50% is present, an eye shield should be placed without an eye patch over the involved eye.[1][19]
If a large epithelial defect is present, a broad-spectrum topical antibiotic such as polymyxin B/trimethoprim or a fluoroquinolone should be added.
Acanthamoeba keratitis
Treatment of Acanthamoeba keratitis is particularly challenging due to a lack of effective antimicrobial medicines and delays in diagnosis. One or more of the following topical preparations may be tried: polihexanide, chlorhexidine, or neomycin/polymyxin B/gramicidin.[45]
[ ]
Chlorhexidine and polihexanide are not currently commercially available in all countries and may need to be specially compounded from an intravenous solution. Treatment for 2 to 6 months or more is usually required.
If a corneal ulcer has re-epithelialised but the infiltrate appears active, then epithelial debridement may improve drug penetration.
If corneal thinning >50% is present, an eye shield should be placed without an eye patch over the involved eye.[1][19]
If a large epithelial defect is present, a broad-spectrum topical antibiotic such as polymyxin B/trimethoprim or a fluoroquinolone should be added.
Oral itraconazole or topical or systemic voriconazole are often added in severe or recalcitrant cases. The duration of treatment depends on response to therapy and may last 1 to 4 weeks or even longer.[46][47][48]
Non-infectious keratitis
Many of the non-infectious keratitides are treated with topical or systemic corticosteroids. However, corticosteroids are only appropriate under the care of an ophthalmologist who is following the patient very closely. Patients with severe autoimmune keratitis associated with systemic disease may need systemic immunomodulating therapies to control their disease under the care of a uveitis specialist or a rheumatologist. Peripheral ulcerative keratitis can be rapidly progressive and may lead to perforation of the globe requiring emergent surgical intervention.
Marginal keratitis is a self-limiting condition.[49] Symptomatic relief may include ocular lubricants and oral analgesia, use of sunglasses for photophobia and regular lid hygiene for associated blepharitis. Referral to an ophthalmologist may be appropriate for consideration of topical antibiotics (to reduce bacterial load) and topical steroids.
Neurotrophic keratitis is characterised by absence of corneal sensitivity that renders the corneal surface vulnerable to occult injury and decreased reflex tearing. Cenegermin is a recombinant human nerve growth factor formulated as an eye drop that has received marketing authorisation in Europe and the US for the treatment of neurotrophic keratitis. Persistent neurotrophic keratitis may lead to the formation of a neurotrophic corneal ulcer.
Active herpetic disease should be differentiated from a neurotrophic corneal ulcer. Neurotrophic corneal ulcers are treated by ceasing toxic medication, lubrication, and patching.[50]
Ongoing treatment
Topical corticosteroids may minimise corneal scarring that occurs due to stromal inflammation once the infection is controlled, in a small subgroup of patients. In bacterial corneal ulcers, adjunctive treatment with topical corticosteroids does not seem to provide benefit to the majority of patients in terms of improved visual acuity, infiltrate or scar size, time to re-epithelialisation, and corneal perforation.[4][33][34] However, a small subgroup of patients with vision of counting fingers or worse, and those with large, central corneal ulcers may benefit from topical corticosteroid use with improvement in visual acuity. In Nocardia ulcers, corticosteroids may be associated with poorer outcomes.[35][36]
Fungal keratitis should prompt more caution and the use of a topical ophthalmic should be delayed until the inflammatory infiltrate appears inactive.
In Acanthamoeba keratitis, use of topical corticosteroids is controversial due to the ability of the pathogen to enter a cystic phase resistant to most medications. The cysts can survive for months and may be reactivated by corticosteroids. Treatment is generally continued until no change in the scar appearance is observed.
Superficial scarring may be corrected with laser surgery (phototherapeutic keratectomy). Severe scarring requires corneal transplantation (penetrating keratoplasty).
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