The benchmark reports for the risk of microbial keratitis with overnight wear of low Dk or conventional soft contact lenses

Serina Stretton, PhD et al

Science Writer,
The Cooperative Research Centre for Eye Research and Technology

Although the absolute risk of microbial keratitis with wear of soft contact lenses is low, the total number of contact lens wearers world-wide is enormous and it is this large population of wearers that makes the risk of microbial keratitis with lens wear a serious public health concern. The US Food and Drug Administration first approved 30-nights of consecutive lens wear in 1981. In the following decades, the number of lens wearers increased dramatically and so too did the number of reports of contact lens-related microbial keratitis in both professional publications and the general media.

The first population-based studies to estimate the relative and absolute risk of microbial keratitis were conducted in the US by Schein, Poggio and colleagues and were published in 1989.^1,2 As the first population-based studies, they were instrumental in the US Food and Drug Administration’s decision to reduce approval for low Dk soft lenses from 30-nights consecutive wear to 6-nights in 1989. The absolute risk of microbial keratitis was calculated from prospective data collected from surveys of all ophthalmologists practicing within New England over 4 months in 1987. The annualized incidence of microbial keratitis with low Dk soft lenses was estimated to be 4.1 (95% CI, 2.9 – 5.2) per 10,000 daily wearers and 20.9 (95% CI, 15.1 – 26.7) per 10,000 extended wearers. These studies differed from the pre- and post-market studies that had gone before in that they surveyed all cases of infection and were not biased by specific inclusion criteria usually placed on subjects in clinical trials, or by the more intense observation and follow-up that clinical trial subjects receive during enrolment. However despite these differences, the estimated risk of microbial keratitis with soft contact lens wear in Poggio et al.’s study¹ was similar to incidence determined from a compilation of retrospective pre-market study data³ (Table 1).

Over the ensuing decades, there have been several more studies, predominantly from Europe or North America, all reporting remarkably similar rates for microbial keratitis with low Dk soft lenses for both daily and extended wear (Table 1). The most recent study, by Lam et al. reported the annualized incidence of microbial keratitis from Hong Kong.⁴ This is the first report from Asia, and interestingly the incidence of keratitis with daily wear in this study [3.1 (95% CI, 2.1 – 4.0) per 10,000 wearers] was comparable to previous reports, yet the incidence with extended wear was half [9.3 (95% CI, 4.9 – 13.7) per 10,000 wearers] that of previous reports. The reason for this difference in the risk of microbial keratitis with extended wear is most likely because extended wear in Hong Kong was limited to 6-nights of consecutive wear, whereas extended wear in Poggio et al.’s study was up to 30-nights and in Cheng et al. and Nilsson and Montans’ studies^5,6 was defined as up to 14-nights of consecutive wear.

The difficulty in differentiating between microbial keratitis and contact lens induced peripheral ulcer (CLPU) has the potential to cause an over-estimation of the risk of microbial keratitis with contact lens wear. For most of the studies included in this review, the definition for microbial keratitis was based on clinical assessment. This was necessary because practitioners often treat empirically without culturing and in many cases ulceration can be culture negative. Microbial keratitis was defined by Poggio et al.¹, Cheng et al.⁵ and Nilsson and Montan⁶ as an epithelial defect with underlying infiltration of the corneal stroma and by Lam et al.⁴ was defined as a stromal infiltrate (> 1 mm in diameter) but not necessarily with an overlying epithelial defect. However the impact of incorporating sterile events in these studies was likely to be negligible. This is because there were no differences in the incidence of keratitis with daily wear between Seal et al.’s study⁷, which used a culture-proven definition for microbial keratitis, and the other studies.

Schein et al.² were the first to estimate the relative risk of microbial keratitis with low Dk soft lens wear using a case-control study. The advantages of case-control studies are that they are useful for comparing the risk of microbial keratitis between lens types and wear modalities and they also allow the identification of specific risk factors. The most significant findings from Schein et al.’s study were that overnight wear was associated with a far greater risk of microbial keratitis than daily wear, irrespective of the lens type and that more consecutive nights of wear with extended wear lenses was associated with increasing risk. Other factors that were found to be associated with a greater risk were smoking and wearers with a lower lens care index. The lens care index was based on the frequency of daily lens cleaning, rinsing, disinfection and enzyme use as well as the frequency of cleaning the lens case. Subsequent studies have confirmed these risk factors using multivariable analyses of epidemiologic data.^{4, 8, 9} In addition, Stapleton et al.⁹ reported a greater risk of microbial keratitis among daily wearers with male gender and poor lens hygiene, particularly infrequent disinfection. Daily use of hydrogen peroxide systems was associated with the lowest risk. Radford et al.¹⁰ also found an increased risk in daily wearers of disposable lenses was occasional overnight lens use, irregular disinfection and the use of chlorine release systems with poor lens case hygiene. It is also interesting to examine the factors from these studies that were not associated with and increased risk of infection. For both daily and extended wear of low Dk soft lenses, lens age, patient age, history of chronic illness, duration of lens wear or time since the last aftercare visit were all not associated with an increased risk.

The most recent change to the contact lens industry has been the introduction of silicone hydrogel lenses and the US Food and Drug Administration approval for 30-nights consecutive wear. The highly oxygen permeable nature of silicone hydrogel lens materials is expected to contribute to a decreased risk of microbial keratitis with this lens type. The studies described above provide a valuable benchmark for comparison of the risk of microbial keratitis with silicone hydrogels with all lens modalities. However there are other factors that may contribute to a change in risk and these potentially include better differentiation between microbial keratitis and CLPU, changes in the need and frequency for lens hygiene practices and changes in management strategies and access to primary eye care.

References

1. Poggio EC, Glynn RJ, Schein OD, Seddon JM, Shannon MJ, Scardino VA, Kenyon KR. The incidence of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. New Eng J Med 1989;321:779-83.
2. Schein OD, Glynn RJ, Seddon JM, Kenyon KR, The microbial keratitis study group. The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. New Engl J Med 1989;321:773-8.
3. MacRae S, Herman C, Stulting R, Lippman R, Whipple D, Cohen E, Egan D, Wilkinson C, Scott C, Smith R. Corneal ulcer and adverse reaction rates in pre-market contact lens studies. Am J Ophthalmol 1991;111:457-65.
4. Lam D, Houang E, Fan D, Lyon D, Seal D, Wong E, The Hong Kong Microbial Keratitis Study Group. Incidence and risk factors for microbial keratitis in Hong Kong: comparison with Europe and North America. Eye 2002;16:608-18.
5. Cheng KH, Leung SL, Hoekman HW, Beekhuis WH, Mulder PG, Geerards AJ, Kijlstra A. Incidence of contact-lens associated microbial keratitis and its related morbidity. Lancet 1999;354:181-5.
6. Nilsson S, Montan P. The annualized incidence of contact lens induced keratitis in Sweden and its relation to lens type and wear schedule: results of a 3-month prospective study. CLAO J 1994;20:225-30.
7. Seal D, Kirkness C, Bennet H. Population-based cohort study of microbial keratitis in Scotland: incidence and features. Contact Lens Anterior Eye 1999;1999:49-57.
8. Dart JKG, Stapleton F, Minassian D. Contact lenses and other risk factors in microbial keratitis. Lancet 1991;338:651-3.
9. Stapleton F, Dart JKG, Minassian D. Risk factors with contact lens related supperative keratitis. CLAO J 1993;19:204-10.
10. Radford CF, Minassian DC, Dart JKG. Disposable contact lens use as a risk factor for microbial keratitis. Br J Ophthalmol 1998;82:1272-5.