COMMENTARY

Treating Bacterial Keratitis in Developing Countries

Brianne N. Hobbs, OD

Disclosures

January 12, 2017

Prospective, Randomized Clinical Trial of Povidone-Iodine 1.25% Solution Versus Topical Antibiotics for Treatment of Bacterial Keratitis

Isenberg SJ, Apt L, Valenton M, et al
Am J Ophthalmol. 2016 Oct 27. [Epub ahead of print]

Corneal scarring is the most common cause of preventable blindness in children in the developing world.[1,2] Malnutrition, particularly vitamin A deficiency, predisposes children to corneal infections. Topical antibiotics to treat these infections are often unavailable or cost-prohibitive in developing areas. Lack of treatment commonly results in permanent visual impairment.

There is a great need for a topical treatment that is widely effective, inexpensive, easy to produce, and has minimal side effects. Povidone-iodine ophthalmic solution is already used extensively in preoperative and postoperative contexts, and it is effective against all bacteria, viruses, and fungi in vitro. There is no known bacterial resistance to povidone-iodine, and it rarely causes allergic reactions. Povidone-iodine seems like a good candidate to treat bacterial keratitis. A research team recently evaluated the effectiveness of povidone-iodine in replacing more expensive and difficult to obtain antibiotics in the setting of developing countries.

Study Summary

Isenberg led a group of researchers who investigated the utility of using povidone-iodine as a replacement for antibiotics for the treatment of bacterial keratitis in two developing countries, India and the Philippines.

They randomly assigned 172 subjects with confirmed bacterial keratitis to either 1.25% povidone-iodine ophthalmic solution or the control antibiotic, which was either ciprofloxacin 0.3% (in India) or neomycin-polymyxin B-gramicidin (in the Philippines). To qualify for inclusion in the study, a diagnosis of bacterial keratitis with onset <14 days prior with no previous treatment was required. Corneal ulcer size in the treatment groups ranged from 2 mm to 8 mm in diameter, with a median corneal ulcer size of 2.75 mm2. Patients were admitted to the hospital for the duration of their treatment to ensure compliance.

The povidone-iodine ophthalmic solution was equally effective or, in some cases, superior to traditional topical antibiotics.

The primary outcome measure was the interval of time from treatment initiation to "presumed cure," defined as a closed epithelial defect with no inflammation. The patient was classified as "recovering" when the epithelial defect was <1 mm2 with minimal inflammation. No significant difference was found between the treatment groups in the number of patients achieving recovering status. In the Philippines, the 10-day probability of presumed cure was 91% in the povidone-iodine group and 86% in the neomycin-polymyxin B-gramicidin group. The median interval to presumed cure was 7 days in both the povidone-iodine group and the antibiotic group in the Philippines. The most common causative organism was Moraxella species in the Philippines and Streptococcus pneumoniae in India. In India, povidone-iodine was superior in both the median interval to ulcer resolution and overall cure rate. The cure rate at 10 days was 38% for the povidone-iodine group and 14% for the ciprofloxacin group in India. No significant difference was found in the treatment effects for gram-positive vs gram-negative organisms. The drop-out rate was similar in the two groups, potentially indicating that povidone-iodine's tolerability is similar to topical antibiotics. Povidone-iodine can cause temporary discoloration and stinging upon insertion, but the lower concentration (1.25%) helped to minimize discomfort.

Viewpoint

This finding is of incredible clinical importance and could dramatically reduce corneal scarring and visual impairment in developing countries.

Povidone-iodine can be produced from powders or solutions that are available worldwide. It is extremely inexpensive to prepare. In Kenya, a 5-mL bottle of the solution costs less than $0.10 (US dollars) to prepare.[3] Coupled with its broad range of effectivity against bacteria, viruses, and fungi, povidone-iodine seems to be an excellent alternative to topical antibiotics in developing countries.

From a public health perspective, the implications of this trial could have profound effects on the economic productivity, healthcare costs, and quality-of-life measures of developing countries.

It is important to realize that this study is not advocating for the replacement of antibiotics with povidone-iodine in locations such as the United States, where fourth-generation fluoroquinolones are available. Fourth-generation fluoroquinolones would likely perform superiorly to ciprofloxacin and neomycin-polymyxin B-gramicidin. However, this class of antibiotics is not typically available in the developing world, so they are not a viable treatment option.

This trial had a very specific purpose—to identify an effective, readily available alternative to topical antibiotics for the developing world—and it achieved that goal.

Abstract

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