New perspectives on

Dramatic changes have taken place in the contact lens market over the past decade and two innovations in particular have had a strong impact on prescribing trends. These are the introduction of daily disposable contact lenses in the mid-1990s and the launch of silicone hydrogel lenses around 2000. These lens types currently represent about 34 per cent and 19 per cent of lens fits in the UK, respectively.1
It might be expected that these new products will be associated with lower levels of ocular complications, as well as providing greater levels of comfort and convenience for contact lens wearers. For example, daily disposable lenses could reduce the risk of problems2 because they obviate the need for lens maintenance and avoid long-term surface spoilation. Silicone hydrogel lenses should minimise clinical problems relating to corneal hypoxia because of their greater capacity to transmit atmospheric oxygen to the ocular surface.3 Despite these significant advances, there have still been case reports of severe keratitis with daily disposable lenses4 and silicone hydrogel lenses.5
Keratitis is an inflammation of the cornea characterised by leukocytic migration into the inflammatory focus. Clinical features can include a combination of the following signs and symptoms: pain, photophobia, mucopurulent discharge, corneal infiltrates, epithelial staining, limbal and conjunctival redness, anterior chamber flare and hypopyon. It has long been recognised that the safety of various forms of contact lens wear are best described by determining the incidence of keratitis among lens wearers.
To fully appreciate this problem from the perspective of the patient, it is necessary to consider the 'clinical journey' experienced in cases of contact lens associated keratitis. Virtually all patients who develop symptomatic forms of this condition, regardless of severity, will cease lens wear and visit their contact lens practitioner or a hospital emergency department. They will be distressed and inconvenienced. To only consider severe or 'microbial' keratitis, and to ignore the less severe or so-called 'sterile' keratitis - as has been the practice in the past6 - is a false distinction for the reasons outlined above. In view of this, we have adopted a new approach to this problem by surveying both non-severe and severe forms of hospital-presenting cases of contact lens-associated keratitis.

Manchester Keratitis Study
A 12-month, prospective, epidemiological study was conducted in which all contact lens wearers presenting with any form of corneal infiltrate or ulcer to the acute referral services of the Royal Eye Hospital, Manchester, were surveyed.7 A clinical severity matrix8 was used to quantify the overall severity of presenting signs and symptoms. This involved the examining clinician scoring the severity of each of the following signs and symptoms on a 0 to 3 scale: level of ocular discomfort, lid swelling, conjunctival redness, infiltrate size, infiltrate shape, fluorescein staining, surrounding corneal haze, endothelial debris, hypopyon and the effect of lens discontinuation. The cumulative score for each event - the 'clinical severity score' - was between 2 (the minimum score relating to the criterion for this study of only including patients exhibiting an infiltrative response) and 22, whereby the higher the score, the more clinically severe the event.
The size of the hospital catchment population and the wearing modalities (daily wear or extended wear) and lens types being used (rigid lenses, silicone hydrogel lenses, daily disposable lenses, and all other hydrogel lenses) in that population were estimated from relevant demographic and market data to facilitate the calculation of incidence.
Over the 12-month survey period, 415 patients who were wearing contact lenses presented to the study centre. Of these, 118 were observed to have a corneal infiltrate or ulcer. Figure 1 shows the distribution of clinical severity scores by lens type/modality. The annual incidence (cases per 10,000 wearers) of hospital-presenting CL-associated keratitis for all wearing modalities and lens types is 21.3 (95 per cent confidence interval 17.8-25.5). Figure 2 displays the incidence of keratitis of all levels of severity for five key wearing modality/lens type combinations. In this figure, the level of severity of keratitis for each combination is indicated in the form of colour banding.
In general, patients wearing lenses on an extended wear basis had about an 8X greater risk of developing keratitis than patients wearing lenses on a daily wear basis (p<0.0001). There was found to be no difference in the incidence of keratitis between hydrogel and silicone hydrogel extended wear lenses. However, there was a significant difference in the distribution of severity between these lens types, with a greater proportion of severe forms of keratitis with hydrogel extended wear lenses (p=0.04).
The key differentiating factor between hydrogel and silicone hydrogel lenses is the superior oxygen performance of silicone hydrogel lenses. This finding of a difference in the severity distribution of keratitis rather than incidence of keratitis suggests that while lens-induced hypoxia does not play a significant role in the initiation of keratitis, it seems to have an important impact on the severity of condition. If only severe cases of keratitis are considered (ie those cases with a severity score greater than 8), then extended wear of hydrogel lenses carries a 5X greater risk than extended wear of silicone hydrogel lenses.
Compared with daily wear rigid lenses, daily wear hydrogel lenses carry a 2.4X increased risk of keratitis (p<0.04). Although the incidence of keratitis with re-usable hydrogel lenses (eg monthly replacement) was higher than that with daily disposable hydrogel lenses, which was in turn higher than that with rigid lenses, these differences were not statistically significant, probably as a result of the limited sample size of our study.

Other risk factors
As part of our hospital survey, we asked patients to complete a questionnaire giving details of lens maintenance systems used, general and ocular health, and various aspects of personal lifestyle. By comparing this information in lens wearers who suffered from keratitis with similar information from lens wearers who did not suffer from keratitis, we were able to identify factors (in addition to lens type, as described above) which rendered lens wearers to be at increased risk of developing keratitis.
Table 1 lists all of the factors investigated, including the magnitude of the increased risk where significant. The factors listed as being 'non-significant' in this table may still be of relevance in contact lens-associated keratitis but possibly were not found to be significant in this study as a result of a lack of statistical power.
The reason why males are at increased risk is not obvious, but may be related to perceived health risks. Males have different attitudes and perceptions relating to health risks than do females, whereby they perceive risks as much smaller and much more acceptable.9 For example, males may be more inclined to undervalue the importance of personal hygiene with respect to contact lens care.
Smoking may be a risk factor for a number of reasons. It is generally considered that smoking is an unhygienic pursuit, which may be linked to a general lack of hygiene with respect to matters relating to contact lens wear and care. Toxins from smoke may either irritate the eyes directly or become absorbed into the contact lens and act as an irritant which compromises the health of the ocular surface10 and pre-disposes the eye to the development of keratitis.
The 'protective' effect of compromised ocular health in lowering the risk of contact lens-associated keratitis may be explained by the precautionary attitude adopted by those with compromised ocular health in that such persons may, for example, cease lens wear, reduce wearing time, or use self-prescribed topical ocular medications to alleviate their condition. Such strategies might have the secondary effect of precluding the development of keratitis.
An alternative explanation is that compromised ocular health may be associated with a general upregulation of the inflammatory status of the eye, so that there is an ever-present resistance to extraneous challenges to the ocular surface which could result in keratitis. These principles can be extended to explain why compromised general health also serves to protect the eye from developing keratitis.
We found an increased risk of developing keratitis in late winter (January to March) compared with the risk in mid-summer (July). We accessed the number of consultations for influenza-like illness to NHS helpline by people aged 15-64 in England during the same time period as our study and found that this number peaked around October and November 2003,11 which is in discordance with the peak incidence of keratitis in our study from January to March 2003. This observation is consistent with the finding of a lower incidence of keratitis in association with compromised general health.

Clinical implications
The Manchester Keratitis Study has served to confirm previous findings as well as highlight new matters of clinical concern to contact lens practitioners. Perhaps most importantly, our study confirms that sleeping in lenses carries about an 8X increased risk of keratitis compared with daily lens wear. However, we have also demonstrated that if a patient chooses to sleep in lenses, then silicone hydrogel lenses are 5X safer than conventional hydrogel lenses.
Practitioners should be mindful of the fact that males and smokers have an increased risk of developing contact lens-associated keratitis, and that perhaps paradoxically, those with compromised ocular and/or general health carry a lower risk. Also, practitioners might expect to see more cases of contact lens-associated keratitis in the late winter.

References
1 Morgan PB and Efron N. Trends in UK contact lens prescribing 2005. optician, 2005; 229: 6004, In press.
2 Solomon OD, Freeman MI, Boshnick EL, et al. A 3-year prospective study of the clinical performance of daily disposable contact lenses compared with frequent replacement and conventional daily wear contact lenses. Contact Lens Assoc Ophthalmol J, 1996;22: 250-257.
3 Sweeney DF. Silicone hydrogels. Continuous wear contact lenses. 2nd ed Oxford: Butterworth-Heinemann, 2004.
4 Hingorani M, Christie C, Buckley RJ. Ulcerative keratitis in a person wearing daily disposable contact lenses. Br J Ophthalmol, 1995;79: 1138.
5 Whiting MA, Raynor MK, Morgan PB, Galloway P, Tole DM, Tullo A. Continuous wear silicone hydrogel contact lenses and microbial keratitis. Eye, 2004; 18: 935-7.
6 Poggio EC, Glynn RJ, Schein OD, et al. The incidence of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. N Engl J Med, 1989;321: 779-783.
7 Morgan PB, Efron N, Hill EA, Raynor MK, Whiting MA, Tullo AB. Incidence of keratitis of varying severity among contact lens wearers. Br J Ophthalmol, 2005 ; 89(4): 430-436.
8 Aasuri MK, Venkata N, Kumar VM. Differential diagnosis of microbial keratitis and contact lens-induced peripheral ulcer. Eye Contact Lens 2003;29(1 Suppl):S60-62.
9 Flynn J, Slovic P and Mertz C. K. Gender, race, and perception of environmental health risks. Risk Anal, 1994; 14: 1101-1108.
10 Basu PK, Pimm PE, Shephard R. J. and Silverman F. The effect of cigarette smoke on the human tear film. Can J Ophthalmol, 1978; 13: 22-6.
11 Scheme European Influenza Sureveillance. http://www.eiss.org Accessed on November 25, 2004.

Professor Nathan Efron and Dr Philip Morgan are director and research manager of Eurolens Research, respectively