Not All Keratitis is Created Equal: It is The Visual Outcome that is Important

Robin L. Chalmers, OD, FAAO, Clinical Trial Consultant, Atlanta, GA, USA Robin Chalmers, OD, FAAO has studied symptoms and complications associated with contact lens wear over her career. A graduate of UC Berkeley School of Optometry, she was a director of clinical research at CIBA Vision for 15 years. In 2000 she became an independent clinical trial consultant specializing in dry eye and contact lens epidemiology.

Recently, a few epidemiology studies have been conducted that estimate the incidence of keratitis with use of silicone hydrogel and other types of soft lenses.  Most of the studies have measured the rate of keratitis in general with many types of contact lenses in Australia and the UK.  The two US studies are Food and Drug Administration (FDA) mandated studies that have been charged specifically with measuring the annual  incidence of microbial keratitis with silicone hydrogel lenses (lotrafilcon A1 and balafilcon A2) when used for continuous wear (overnight for up to 30 nights in a row). 

A quick review of the terms in Table 1 helps to clarify the difference between keratitis and microbial keratitis.  These precise definitions will help the reader understand whether only infectious or inflammatory events are being measured in each study; or whether they are being treated as a continuum of events that includes all types of corneal inflammation. The more general term “keratitis” includes a range of conditions, from minor inflammation such as asymptomatic infiltrates up to the very severe inflammation associated with a corneal infection. 

Table1: Definitions related to keratitis*

Morgan, Efron and colleagues studied rates of keratitis of all severity in their recent work out of Manchester, England.3-5  The most recent publication from this one center study demonstrated the difficulty in determining the precise diagnosis, but it estimated that of the 111 corneal infiltrative events that they studied, 12 (10.1%) could be classified as microbial keratitis and only 3 (2.7%)of them could be classified unambiguously.5  The studies recently presented by Stapleton, Keay and Edwards in Australia and by Dart and Radford in London are using a “presumed microbial keratitis” study criterion that will include frank corneal infections but may also include events that may not be proven to be infectious.  (Presented at the Association for Research in Vision and Ophthalmology meeting May 2006; not yet published)

On the other hand, the studies that were designed to study rates of microbial keratitis are much more specific, including in that rate only cases with clear link to causation by microorganisms.  The FDA studies of lotrafilcon A1 and balafilcon A2 have measured the rate of microbial keratitis, per se.  Because microbial keratitis is a subset of keratitis in general, it follows that the rate of microbial keratitis will be lower than the rate for general keratitis and that the risk factors may be distinct for each condition. The contact lens clinical community should expect differing results from these well-respected research teams due to differences in healthcare models in the US and other countries, the varied epidemiological approaches and clinical definitions being utilized.

One approach that was utilized in the CIBA Vision study of lotrafilcon A1, is to study all corneal inflammation that occurred during a year and later determine which events fit the clinical and biological pattern consistent with corneal infection.  In that study 2.6% of lens wearers per year experienced a symptomatic infiltrative event while using their lenses primarily on a continuous wear basis of up to 30 nights wear.  Also, 0.036% of lens wearers per year of wear had microbial keratitis that involved a reduction in visual acuity and 0.14% lens wearers per year had microbial keratitis without any effect on acuity.  The relative proportion of microbial keratitis to symptomatic corneal infiltrative events with lotrafilcon A lenses in this study (overall rate MK 0.176%/overall rate symptomatic infiltrates 2.6% = 6.8%) is slightly lower but similar to that reported for all lens types by Efron et al (10.1%)5.     

For clinicians, the practical implications of these rates must be extrapolated from these data.  For example, if a practitioner has 500 patients in continuous wear silicone hydrogels, he or she could expect to see approximately one person per month with symptomatic infiltrates but would not be likely to have any patients with microbial keratitis.  Larger practices or tertiary referral centers will be most likely to encounter patients with more serious conditions.  But all practitioners must be prepared to make real-time differential diagnoses in order to best manage their patients.

The purpose of epidemiology studies is to determine whether the benefit of a treatment such as wearing lenses round the clock is warranted by the rate of microbial keratitis and the sequelae from those events.  The estimation of benefit to risk must be made compared to other methods of refractive correction.  LASIK and overnight ortho-keratology are the next two most popular non-spectacle methods for refractive correction after contact lenses. 

In a recent invited review of the first 50 cases of microbial keratitis from ortho-keratology reported in the literature, Watt and Swarbrick6 report that 54% of the patients had a final best corrected acuity of 20/40 or worse in the affected eye.  Although it is impossible to determine an overall rate of infection from this case series, it is clear that the vision outcomes once an infection does occur are worse with ortho-keratology compared to contact lenses, where 2 of the 10 cases lost any acuity and one of those lost only 2 lines of acuity1.  Table 2 shows the rates of loss of best corrected visual acuity with LASIK from studies published in the last 18 months.7-11  The loss of best-corrected acuity associated with LASIK ranges in the best situation from 0.6% (at one of the most prestigious hospitals in the UK) to 7%.  These rates do not compare well to the 0.036% reported by Schein with lotrafilcon A lenses in a well-controlled prospective study1.  On balance, it seems that for the outcome of greatest interest, correctable visual acuity, LASIK and ortho-keratology seem to carry substantially higher risk compared to silicone hydrogel and other types of soft lenses.   

Table 2: The reported loss of best corrected
visual acuity with LASIK from recent published studies

References

1. Schein, OD, McNally JJ, Katz J, Chalmers RL, Tieksch JM, Alfonso E, Bullimore M,
   O’Day D, Shovlin J.  The Incidence of Microbial Keratitis Among Wearers of a 30-Day Silicone Hydrogel Extended-Wear Contact Lens.  Ophthalmology 2005 112(12)2172-9.
2. Summary of Safety and Effectiveness Data. Purevision (balafilcon A) Soft Contact Lenses – P980006/S004B. 10-12-2001. Rockville, Maryland, U. S. Food and Drug Administration.
3. Morgan PB, Efron N, Hill EA, Raynor MK, Whiting MA, Tollo AB.  Incidence of keratitis of varying severity among contact lens wearers.  2005 Br J Ophthalmol 89430-6.
4. Morgan PB, Efron N, Brennan NA, Hill EA.  Risk factors for the development of corneal infiltrative events associated with contact lens wear.  Invest Ophthalmol Vis Sci 2005 46:9:3136-43.
5. Efron N, Morgan PB.  Can subtypes of contact-lens associated corneal infiltrative events be clinically differentiated?  Cornea 2006;(5)540-44.
6. Watt K, Swarbrick HA. Microbial keratitis in overnight orthokeratology: review of the first 50 cases.  Eye Contact Lens. 2005 Sep;31(5):201-8.
7. Spadea L, Sabetti L, D'Alessandri L, Balestrazzi E.  Photorefractive keratectomy and LASIK for the correction of hyperopia: 2-year follow-up.  J Refract Surg. 2006 Feb;22(2):131-6.
8. Esquenazi S, Bui V.  Long-term refractive results of myopic LASIK complicated with intraoperative epithelial defects.  J Refract Surg. 2006 Jan-Feb;22(1):54-60.
9. Gailitis RP.  Comparison of LASIK outcomes with the Alcon LADARVision4000 and the VISX STAR S2 excimer lasers using optimized nomograms.  J Refract Surg. 2005 Nov-Dec;21(6):683-90.
10. Beer MH, Hjortdal JO, Ehlers N. Efficacy and safety of laser-assisted in situ keratomileusis for myopia.  Ugeskr Laeger. 2005 Nov 7;167(45):4291; author reply 4291-2
11. Watson SL, Bunce C, Allan BD.  Improved safety in contemporary LASIK.  Ophthalmology. 2005 Aug;112(8):1375-80.