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Microbial keratitis associated with overnight orthokeratology: what we need to know.

This month’s edition of Cornea contains reports from five independent centers of microbial keratitis associated with the use of overnight orthokeratology (OOK) with rigid gas permeable contact lenses. These reports also summarize the current literature on this topic which is also limited to case reports and small case series. Several features of these reports, viewed in combination, are striking. First, a majority of the reported infections are central and severe, caused by aggressive organisms such as gram negative rods or acanthamoebae. Second, the majority of cases occurred in children or adolescents. Third, the infections were associated with multiple types/brands of rigid gas permeable contact lenses including those with high permeability and reverse geometry designs, although unfortunately the characteristics of the contact lenses were frequently absent in the reports. The limitations regarding the inferences that one can draw from case series are well known. The reporting of complications in case series tends to occur early in the life of a product or procedure; reported cases are generally severe; and they tend to reflect local rather than national practices. Initial case series, such as those reported here, are not accompanied by control groups or suitable denominators that permit one to make estimates regarding the magnitude of risk that may be associated with a given lens or even with the class of product. How, then, does one reconcile the striking features of the reported cases with these limitations? In my view, this set of circumstances raises a set of specific questions which I believe the relevant industry and the Food and Drug Administration (FDA) have a duty to explore in a timely fashion. First, it is instructive to review the current status in the United States of FDA approval for lenses used for OOK. The first company gaining approval for this indication was Paragon, Inc. which received approval in 2002 for this indication for its Paflufocon A and D rigid gas permeable contact lenses made in a reverse geometry design. Approval was granted based on a premarket study of 218 subjects followed for a minimum of nine months (further details available at. http://www.fda.gov/cdrh/pdf/p870024s043.html). This cohort included just 12 adolescents. No serious adverse events were reported. The FDA advisory panel, in its recommendations for approval, also advised that approval be limited to subjects age 18 and over unless further data documenting safety in younger age groups became available. This recommendation was not followed by the FDAwhich gave its final approval without any age restriction. In 2004, Euclid Systems received approval for its Oprifocon A polymer for the indication of OOK based on a study of 191 patients, all of whom were age 18 or older (further details available at http://www.fda.gov/cdrh/pdf/p010062.html). There were no cases of permanent loss of vision, although one corneal infiltrate was reported, and several subjects had temporary reductions in vision due to superficial keratitis or corneal topographic distortions. The device was not referred to the Advisory Panel for review, and the FDA approved the device without an age restriction. This device was subsequently acquired by Bausch and Lomb, Inc. The case series document the potential for severe microbial keratitis in the setting of OOK and implicate gram negative organisms, particularly pseudomonas species in this context. This potential should surprise nobody. Put simplistically, contact lens-associated microbial keratitis results from a combination of corneal epithelial microtrauma and microbial opportunism. It is well known that overnight wear of a contact lens can potentiate both of these factors. To be effective, an orthokeratology lens must alter the normal morphology of the corneal epithelium. Microbial opportunism is favored by the chronic use of standard contact lens care paraphernalia, epithelial trauma, and the closed eye setting. High