Reader and Industry Forum
Corneal Infiltrative Events: More Common Than You Think
By Derek Cunningham, OD, FAAO
In your August 2011 issue, I read the Point/Counterpoint column on Corneal Infiltrative Events by Joseph P. Shovlin, OD, FAAO, and Michael S. Mayers, OD, FAAO, with much interest. I felt that some pertinent information was not presented, as it is not published in the peer-reviewed literature or in eyecare-related trade publications.
Lessons From MAUDE
One example comes from inspection of the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database, which contains a plethora of information on adverse events in users of contact lenses and lens care solutions that may not be captured in clinical trials and retrospective chart reviews.
Based on an in-depth review of MAUDE reports from Jan. 1, 2007 to Aug. 31, 2011, there is evidence that supports Dr. Shovlin's standpoint regarding an increase in likely non-infectious infiltrative events as well as the role of misdiagnosis and a self-limiting nature in their under-reporting. This is especially true for events of contact lens-associated infiltrative keratitis (CLAIK).
There are a large number of MAUDE reports from the specified time period in which the condition as diagnosed has a nonviral infectious etiology (e.g., mild bacterial keratitis, “a little infection,” micropunctate ulcers), yet characteristics and clinical course do not support a bacterial, fungal, or parasitic etiology, including bilateral involvement, recurrence with re-exposure to care solution after resolution even when new lenses and care solutions are used, previous diagnosis of viral infection such as epidemic keratoconjunctivitis (EKC; ‘pink eye'), and complete resolution without intervention.
Second, while not mentioned by Dr. Shovlin, numerous MAUDE reports list a diagnosis of viral infection (e.g., “viral dots on the cornea,” “pink eye,” or herpetic ulcer), allergies, or Thygeson's superficial punctate keratopathy (SPK) that is either later diagnosed as a corneal infiltrative event (CIE)/keratitis or the diagnosis is not supported by the clinical course, such as recurrence with re-exposure to care solution. This ambiguity in diagnosis is highlighted in a section from a continuously updated eMedicine report (Ventocilla, 2011) that states:
“A problem associated with the use of chemical disinfection systems and seen with increasing frequency is the development of small, gray, epithelial, granular opacities that resemble the epithelial opacities of Thygeson superficial punctate keratopathy. The round, gray-white granules appear to be on the surface of the epithelium and are scattered randomly across the cornea. They are similar to Thygeson superficial punctate keratopathy, but they tend to be small and stain less intensely with fluorescein. These opacities are associated with symptoms of foreign body sensation, tearing, photophobia, lens intolerance, and conjunctival injection. The symptoms resolve over a few days after the chemical disinfecting solution is discontinued.”
This description is highly similar to that of CLAIK.
Third, several MAUDE reports state that medical attention was not sought and/or symptoms cleared with simple cessation of multipurpose solution (MPS) use, confirming the self-limiting nature of some of these events and possibly explaining why they have not been captured in studies. Additionally, more than 20 MAUDE reports by eyecare practitioners (ECPs) testify that multiple patients (two to 60 cases in each report) have presented to their practice experiencing the exact same signs and symptoms while using a certain MPS, most commonly in combination with one silicone hydrogel contact lens material.
While Dr. Mayers is correct that there is little support for an increase in “sterile” infiltrative events in the peer-reviewed literature, the implication that only a few isolated reports/ECPs have noticed an increase in CIEs is, in my opinion, not supported by the overabundance of MAUDE reports about the very same MPS. The MAUDE database showed 212 reports (confirmed fungal, amoebic, or bacterial infection and suspicious reports not included) of at least 411 patients who experienced an inflammatory event, mostly bilateral CIEs, while using the implicated MPS.
Initial evaluation of those practitioners who reported cases appears relatively impartial. Twenty-five ECPs (optometrists and ophthalmologists) reported multiple patients. The manufacturer submitted all reports except for those from two ECPs. Seventeen ECPs reported multiple patients in one Medical Device Reporting (MDR)—two ECPs reported “several,” one reported “multiple,” one reported “some,” and 13 reported between two and 60 patients. Eight ECPs reported events in 36 patients over 26 MDRs. Almost 40 ECPs reported a single patient in one MDR.
More Investigation is Needed
Although open clinician reporting databases often lack validation controls, they are still our best source for tracking national prevalence data for relatively infrequent events. Well-controlled single or multiple site clinical studies typically lack N numbers to identify clear trends due to enrollment issues or budget constraints.
There is a clear need for further study on this issue. More clinical research needs to be done to better understand the perceived national increase in infiltrative events. CLS
BioSciences assisted with gathering study data for this article.
For references, please visit www.clspectrum.com/references.asp and click on document #198.
|Dr. Cunningham is the director of Research and Optometry at Dell Laser Consultants in Austin, Texas. He is also a consultant or advisor to AMO, Allergan, Alcon, B+L, Ista Pharmaceuticals, Reichert, RPS, and Vistakon and has received research funding from Alcon.|