Bacterial keratitis is the fourth leading cause of blindness worldwide and poses significant consequences due to corneal morbidity and economic hardship.1-6 Ultimately, corneal opacification and scarring caused by both bacterial infection and the host inflammatory response are the major consequences of bacterial corneal ulcers.2,3
So, it’s not surprising that many treating practitioners choose to use topical steroids in an attempt to minimize morbidity. Several predisposing factors can affect the course of the disease and its outcome, including prior health, infecting organism(s), inflammatory consequences and therapeutic choices––just to name a few.1
The pros and cons of using topical corticosteroids for bacterial keratitis have been debated heartily for decades. The main concern is localized immunosuppression, which allows for increased bacterial survival and proliferation.1-4 Some clinicians believe that the “anti-inflammatory” effects of antibiotics are frequently sufficient in the treatment of bacterial ulcers.3 However, many practitioners––without strong scientific rationale––may rely heavily on topical steroids after adequate antibiotic coverage in order to minimize corneal scarring.
A Cochrane systematic review identified just a few studies addressing the appropriateness and timing of topical steroid use for bacterial keratitis; most have limited sample size and applicability.7,8
A 50-year meta-analysis by Kirk Wilhelmus, M.D., did not demonstrate a clear-cut beneficial effect of topical corticosteroid use on the course of bacterial corneal ulcers.1,3 He found three important results: First, steroid use before the diagnosis of bacterial keratitis significantly predisposed eyes with pre-exiting disease to ulcerative keratitis (odds ratio: 2.63). Second, once microbial keratitis occurred, prior steroid use significantly increased the odds of antibiotic treatment failure or other infectious complications (odds ratio: 3.75). And third, the effect of topical steroid use with antibiotics after the onset of bacterial keratitis was unclear.
The long-awaited Steroids for Corneal Ulcers Trial (SCUT) study also has recently provided valuable population-based results to answer the long-standing question on whether to use topical steroids for the treatment of bacterial keratitis. The major advantage that this well-designed study had over previous studies is its sample size.4,6
The SCUT study––a multicenter, double-masked, randomized clinical trial––compared the use of 1% topical prednisolone phosphate to a placebo during the treatment of culture-proven bacterial corneal ulcers. The primary outcome was best-corrected visual acuity at three months. Secondary outcomes were scar size, re-epithelialization rate and significant adverse events, such as perforation.4,5
The authors of the SCUT trial were careful to point out limitations that are commonly seen in prospective trials. The antibiotic (broad spectrum fluoroquinolone) chosen for treating the ulcers in this trial may not have been best agent for all corneal ulcers encountered in this trial.6 For example, an antibiotic with a lower minimum inhibitory concentration (MIC) to the particular organism may yield a better outcome.
Also, the fixed dose of topical steroid may have limited the results in this study, and increasing the dose or frequency of steroid application might have provided different results.
Another critical factor is the timing of steroid initiation.6 The start time was set and determined by enrollment criteria, with a gap of 48 hours before a patient could begin treatment with topical steroid.4,6
The core concepts gained from the SCUT trial are:
1. Steroids used topically offer no significant benefit or major risk in the treatment of bacterial keratitis at three months.
2. Adjunctive steroid therapy may improve visual outcome in severe bacterial keratitis, such as in those caused by Pseudomonas.
3. Steroids should not be used in bacterial infections caused by Nocardia.
4. MIC correlates with clinical results in bacterial corneal ulcers (i.e., a lower MIC to a particular organism is associated with a better visual outcome).5,6
The principles for use when choosing adjunctive therapy (i.e., Pseudomonas ulcers):
• Scrapings for stain and culture are crucial.
• Use adequately dosed bactericidal antibiotics.
• Delay initiation of steroids until a clearly beneficial effect has been determined.
• Continue concurrent use of antibiotic with steroids.
• Delay use of steroids if causative organism is not identified. Use steroids two to five days after appropriate antibiotic therapy.2,3,6
Avoid steroid use if fungal, herpetic, atypical Mycobacterium or Nocardia infection is suspected, or if there is severe thinning, enlarging epithelial defect, poor wound healing (diabetes) or immuno-suppression.2,3,6 The use of topical corticosteroids in Acanthamoeba keratitis remains controversial regarding its appropriateness and timing. One study showed a prolonged course of therapy in treating Acanthamoeba keratitis when initiated, but was not associated with medical treatment failure.9
Future trials likely will deal with frequency, intensity and timing of steroid initiation. In the meantime, the valuable SCUT study can lead us to conclude that steroids are not as effective as some have suggested, nor are they as dangerous as others would lead you to believe.5,6 Topical steroids certainly appear to have a role in select cases of severe bacterial keratitis (Pseudomonas), but not in others (Nocardia).
1. Wilhelmus K. Indecisions about corticosteroids for bacterial keratitis an evidence-based update. Ophthalmol. 2002 May;109(5):835-42.
2. Hindman HB, Sheel B, Patel MD, Jun AS. Rationale for adjunctive topical corticosteroids in bacterial keratitis. Arch Ophthalmol. 2009 Jan;127(1):97-102.
3. Cohen EJ. The case against the use of steroids in the treatment of bacterial keratitis. Arch Ophthalmol. 2009 Jan;127(1):103-4.
4. Srinivasan M, Mascarenhas J, Rajaraman R, et al. SCUT: Study design and baseline characteristics. Arch Ophthalmol, 2011;129 [Epub ahead of print].
5. Srinivasan M, Mascarenhas J, Rajaraman R, et al. Corticosteroids for bacterial keratitis: The Steroids for Corneal Ulcers Trial (SCUT). Arch Ophthalmol. 2012 Feb;130(2):143-50.
6. Lietman TM. Topical steroids for bacterial corneal ulcers: What have we learned from the SCUT? Topics in Ocular Anti-infectives. 2012 Feb;27.
7. Chen A, Prajna L, Srinivasan M, et al. Does in vitro susceptibility testing predict clinical outcomes in bacterial keratitis? Results from the steroids for corneal ulcers trial. IOVS. 2007;48:ARVO e-abstract 4277.
8. Acharya N, Srinivasan M, Mahalakshmi R, et al. Steroids for corneal ulcers treatment. SCUT pilot study results. IOVS. 2006;47:ARVO e-abstract 4752.
9. Hammersmith KM. Diagnosis and management of Acanthamoeba keratitis. Curr Opin Ophthalmol. 2006 Aug;17(4):327-31.