A Clinical Trial of Povidone-Iodine for the Treatment of Bacterial Corneal Ulcers

Hypothesis to be tested:

Infectious corneal ulceration causes corneal scarring, opacification, and blindness in hundreds of thousands of children annually. In developing countries, it is the number one cause of avoidable blindness in children. While in some cases, the cornea was healthy prior to ulceration, in others; xerophthalmia, trachoma, rubeola, trauma, or some other cause previously compromised the cornea. Even when the ulceration is associated with one of the above etiologies, it is usually the bacterial corneal ulcer that directly leads to blindness in the short-term. In many countries, few of these infections are properly treated with appropriate antimicrobial agents due to a number of factors, including cost, availability, and effectiveness. If a topical antimicrobial agent were readily available in developing countries which is also inexpensive and effective, many of these ulcers could be cured before scarring and blindness result.

The best candidate for such a medication is povidone-iodine ophthalmic solution. It has already been proven the best agent to sterilize the ocular surface before and after eye surgery and to prevent conjunctivitis in newborn babies. It was also shown an effective treatment against bacterial conjunctivitis in children. Povidone-iodine ophthalmic solution can be prepared in a local hospital or clinic by mixing the powder with an ophthalmic saline solution bringing the cost of a 10-ml bottle to less than US $0.10. By contrast, in the Philippines, a 10 ml. bottle of Neosporin ophthalmic solution cost about $4.00 and it may take a few bottles to cure a bacterial corneal ulcer. For far less than a U.S. dollar, a corneal ulcer could be fully cured. Povidone-iodine has the widest antimicrobial spectrum of any known topical medication. It has been shown to be effective against all bacteria, fungi, and viruses. No true resistance to povidone-iodine has ever been demonstrated. Allergic reactions are rare. Thus, if any medication could serve the purpose for this study, it would be povidone-iodine.

The primary research question is whether povidone-iodine ophthalmic solution is effective in healing bacterial corneal ulcers, which, if proven, would have a dramatic effect in reducing pediatric blindness.

The number of subjects was determined from the primary outcome measure of non-inferiority to achieve a minimum of a one-day difference between the control and investigative groups, with povidone-iodine being compared to the control medication at each study site. The control medications are Neosporin ophthalmic solution in Manila and ciprofloxacin ophthalmic solution in the two combined Indian sites (Hyderabad and Tiruchirapalli) for a total of four study arms. The number of recruits was calculated to achieve 90% power for detecting non-inferiority using t-tests with a level of significance of 0.05 for comparing mean time to cure. Cure is defined as closure of the epithelial defect with no inflammatory signs other than minimal injection.