For many years, eye care providers have debated the most effective management approach for acute bacterial keratitis (BK). While virtually all of us accept the tenet that liberal dosing of topical, broad-spectrum antibiotics is crucial to success, the question of whether adjunctive topical corticosteroids provide any benefit has fueled debate.

Proponents of corticosteroid use claim that these agents help to curb leukocyte recruitment and activation, minimize the structural complications of local inflammation, and potentially reduce stromal loss and opacification.¹

Critics of steroids, on the other hand, cite the potential for superinfection in cases of resistant organisms, as well as hampering the re-epithelialization process.¹ Let’s take a fresh look at this debate in light of results from a new clinical trial.

A Look at SCUT
Until recently, the evidence to support corticosteroid use for BK was either anecdotal or retrospective in nature.^2-6 The literature lacked a well-executed, large-scale, prospective clinical trial to determine the benefits––if any––of incorporating steroids into the therapeutic management of BK.

But then in 2007, recruitment began for such a study: the Steroids for Corneal Ulcers Trial, or SCUT. Its fundamental purpose: “To determine whether adding topical steroids to antibiotic treatment improves the outcomes of bacterial corneal ulcers, especially visual acuity.”⁷ The published report of this pilot study, which evaluated 42 individuals with culture-confirmed BK, appeared in the February 2009 issue of Archives of Ophthalmology.⁷

In the SCUT, all subjects received 0.5% moxifloxacin every hour while awake for 48 hours, and then were randomized to receive either topical steroids or placebo in conjunction with antibiotic therapy. The steroid regimen was q.i.d. for the first week, b.i.d. for the second week, once daily for the third week, and then discontinued.

All patients were seen daily until re-epithelialization was achieved. For purposes of visual acuity and scarring, they were evaluated at the initial visit, at three weeks and at three months.

Compared to those in the placebo group, patients in the steroid group required more time to achieve complete re-epithelialization––by an average difference of about two days––even after adjusting for initial defect size.⁷ There were four adverse events reported in the placebo group, including two corneal perforations. No adverse advents were documented in the steroid group.

Regarding visual acuity, there was no statistical difference between the steroid and placebo groups at three weeks or three months––although there was a trend favoring the steroid group.⁷ Likewise, there was no statistically significant difference in scar size at three weeks or three months. But again, the trend favored reduced scarring in the steroid group.

SCUT Follow-Up Study
Overall, the outcome of the SCUT pilot study seemed to be a blow to proponents of steroid use in BK. But ultimately the authors concluded that, based upon statistical analysis, their sample size was far too small. They called for a larger trial of at least 360 patients to reassess the outcomes––particularly visual acuity.

In the February 2012 issue of Archives of Ophthalmology, the SCUT authors published the results of this proposed large-scale trial.⁸ Five hundred individuals were enrolled in the SCUT follow-up study, which adhered to the exact same protocol as outlined in the original design––250 patients were randomly selected to receive corticosteroids and 250 patients were administered a placebo.

A multiple linear regression model of the data revealed that the additional use of steroids offered no significant improvement in best-corrected visual acuity at three months when compared with placebo.⁸ Likewise, there was no statistically significant difference in scar/infiltrate size at three weeks, time to re-epithelialization, or adverse events between the two groups. “The results of the SCUT demonstrate no obvious benefit in using corticosteroids in the overall study population; also, no apparent serious safety concerns were observed,” the authors concluded.⁸

Impressions and Limitations
Like the pilot study, the SCUT follow-up appears to discourage the use of corticosteroids when managing bacterial corneal infections. Indeed, several editorial columns published in the wake of the SCUT echoed this sentiment.^9-11

However, careful scrutiny uncovers several shortcomings associated with this study:

• The corticosteroid regimen was extremely conservative. The SCUT researchers employed prednisolone sodium phosphate 1% as the trial medication. Seasoned clinicians know that this drug exhibits weak anti-inflammatory capabilities––especially when compared to today’s other popular choices, such as prednisolone acetate 1% or difluprednate 0.05%. Likewise, the initial dosing (q.i.d. for one week) could be considered sparse by most standards.

In clinical practice, we tend to favor a more aggressive regimen of prednisolone acetate 1%, dosed hourly while awake and initiated as early as 24 hours after the commencement of broad-spectrum antibiotic therapy.

Should you use a topical steroid to help treat this corneal ulcer? Research from the SCUT may provide a definitive answer.

Of course, this can vary based upon the severity of the ulcer as well as the time required to confirm the cultures and antibiotic susceptibilities.

• The SCUT researchers did not consider subjective measures of improvement, such as patient comfort and functional visual recovery time. Arguably, any study must have a primary outcome criterion. For SCUT, it was visual acuity at three months. Secondary outcomes included infiltrate/scar size, re-epithelialization and corneal perforation.

But, the researchers did not consider quality of life issues, such as overall patient comfort during the healing process or short-term visual recovery during the first week of therapy.

Such factors are critically important to patients and clinicians alike, because both pain and fear of vision loss are the greatest emotional stressors commonly associated with corneal ulcers.

Our clinical experience suggests that both comfort and short-term visual recovery can be enhanced significantly by the use of corticosteroids.

• One of the most significant findings of the SCUT was buried within the discussion section, where many readers could have overlooked it. The SCUT researchers reported no overall difference in three-month visual acuity scores or safety concerns between the steroid and placebo groups.

However, a single paragraph in the concluding section of the publication reads: “An intriguing finding of the study was that pre-specified subgroup analyses demonstrated a benefit in three-month visual acuity using corticosteroids in ulcers with greatest severity at presentation. Corticosteroid
treatment was associated with a benefit in visual acuity compared with the placebo group in the subgroups with the worst visual acuity and central ulcer location at baseline.”⁸

In other words, those cases of BK in which vision was most threatened and recovery most tenuous were the very instances in which corticosteroids seemed to yield the greatest therapeutic benefit.

Many cases of BK in the study were non-central; these cases would be expected to have low visual morbidity and good visual recovery, either with or without steroid use.

For our part, the urge to employ corticosteroids in BK is almost always dictated by severity, location and potential threat to the patient’s vision.

The recent SCUT report certainly did not end the debate over corticosteroid use in BK management. No doubt, additional research will follow. And while the perceived message from this study may have been that “steroids don’t help corneal ulcers,” we are encouraged by the fact that no harm came to those in the steroid arm. It’s also reassuring to note that, in the most severe cases, there was indeed some long-term benefit to employing corticosteroids in BK.⁸

For nearly two decades, we have initiated adjunct steroid use for patients with BK, and we can attest that patients treated in this fashion fared significantly better than those who had been treated with antibiotics alone.

So, we will continue to advocate for the judicious use of corticosteroids––along with appropriate antibiotic therapy––in cases of potentially sight-threatening corneal infections.

1. Wilhelmus KR. Indecision about corticosteroids for bacterial keratitis: An evidence-based update. Ophthalmology. 2002 May; 109(5):835-44.
2. Suwan-Apichon O, Reyes JM, Herretes S, et al. Topical corticosteroids as adjunctive therapy for bacterial keratitis. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005430.
3. Wang JC, Su D, Lim L. Contact lens microbial keratitis and prior topical steroid use: a disaster in the making? Ann Acad Med Singapore. 2004 Jul;33(4):484-8.
4. Miedziak AI, Miller MR, Rapuano CJ, et al. Risk factors in microbial keratitis leading to penetrating keratoplasty. Ophthalmology. 1999 Jun;106(6):1166-70; discussion 1171.
5. Stern GA, Buttross M. Use of corticosteroids in combination with antimicrobial drugs in the treatment of infectious corneal disease. Ophthalmology. 1991 Jun;98(6):847-53.
6. Garber JM. Steroids’ effects on the infectious corneal ulcer. J Am Optom Assoc. 1980 May;51(5):477-83.
7. Srinivasan M, Lalitha P, Mahalakshmi R, et al. Corticosteroids for bacterial corneal ulcers. Br J Ophthalmol. 2009 Feb;93(2):198-202.
8. 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.
9. Topical steroids don’t help ulcers. Rev Optom. 2011 Nov;148(11):6.
10. Bankhead C. Topical steroids no help for eye ulcers. October 11, 2011. Available at: www.medpagetoday.com/Ophthalmology/GeneralOphthalmology/28977. Accessed August 28, 2012.
11. Lietman TM. Topical steroids for bacterial corneal ulcers: What have we learned from the SCUT? Topics in Ocular Antiinfectives. 2012 Feb;27:1-4.