Contact Lens-Related MK: What can Epidemiologic Studies Tell Us?

Serina Stretton, BSc, PhD Serina is a science writer for the Vision CRC and the Institute for Eye Research in Sydney, Australia and has written and contributed to a broad range of research papers in the fields of optometry, clinical science and public health.

Eye & Contact Lens 29(IS):S85-89

In 2003, Fiona Stapleton published an insightful appraisal of the range of epidemiologic studies used to assess the incidence and risk factors for contact lens-related microbial keratitis. Over the past year or so, several large-scale studies designed to measure the absolute and relative risk of infection with currently marketed contact lenses, and in particular silicone hydrogels were initiated. These include single-centre hospital-based surveillance [1] and case-control[2, 3] studies in the UK, and multi-centre population-based surveillance [4] and case-control studies [5] from Australia and New Zealand (see editorial) and a cohort study from the United States. An understanding of the relative merits and limitations of these study designs will help when evaluating the differences and similarities between studies. Publication of results from Morgan et al.’s studies [1, 2] and the imminent publication of results from other studies suggest that it is timely to summarise Stapleton’s review of the advantages and disadvantages of the different study designs used for determining risks associated with new lens types and wear modalities.

Stapleton begins by summarising what is known of the incidence of infection and visual loss, as well as the risk factors associated with infection arising from conventional hydrogel contact lens wear. These data in the main are derived from several large surveillance, cohort and case-control studies from a range of countries.[6-16] Overall the rate of infection with daily wear of conventional hydrogels is 4 per 10,000 and with extended wear is approximately 4 to 5-fold greater (Table 1). The rate of visual loss with conventional hydrogel is rare and has been estimated at 1 per 300 wearers per decade for extended wear and 1 per 25,000 wearers per decade for daily wear [17]. Specific risk factors that have been identified by multivariable analysis of epidemiologic study data are overnight wear, smoking, and poor lens care and lens case hygiene. Among overnight wearers, the risk of infection increases with longer periods of continuous overnight use and lower socioeconomic status, and among daily wearers, male gender and poor hygiene (infrequent disinfection) are associated with a greater risk.

Most of the surveillance and case-control studies of microbial keratitis associated with conventional hydrogel lens wear have used clinical definitions of microbial keratitis because of the absence of any single defining feature of corneal infection. These definitions usually involve the presence of an epithelial defect with underlying infiltration of the corneal stroma that require treatment with intensive antibiotics and a corneal scrape. Such definitions represent only the severe presentations of microbial keratitis and exclude more mild conditions that may not require treatment at a tertiary referral centre.

To overcome the limitations of a clinical definition, Morgan et al. [1, 2] have applied a clinical severity matrix originally described by Aasuri et al. [18] to collect information on the relative severity of lens-related keratitis. Practitioners are required to score each parameter (Table 2) on a 0 to 3 scale, and cumulative scores greater than 8 indicate a likely case of severe keratitis. This scale allows researchers to collect more detailed information on the incidence and spectrum of severity of microbial keratitis without the need to differentiate between infected and ‘sterile’ ulcers, and it is likely that presumed sterile keratitis most likely represents the non-severe (score < 8) events in the Aasuri et al. matrix.

When assessing the impact of contact lens wear, a cohort is any group of wearers that has worn the same lens type(s) or used the same lens wear modality over a given period. Annualised incidence is calculated from the proportion of wearers who develop infection and relative risk is determined by comparing the incidence between groups exposed to different lens types or wear modalities, using the group with the lowest risk as the referent. For contact-lens related studies, wearers are fitted with a lens that may or may not be currently marketed and are followed over a defined period [16, 19, 20]. Although this is a simple study design, large sample sizes are required when assessing the incidence of rare diseases such as lens-related microbial keratitis, and because studies are usually conducted during the early exposure period ie immediately after a subject is fitted with a new lens, it is not possible to tease out any effects of duration of wear on the incidence of disease. The published cohort studies examining the performance of silicone hydrogel lenses [19-21] do not have sufficient sample sizes to detect rare complications such as microbial keratitis and therefore no assumptions on the relative safety of silicone hydrogels can be made from these studies.

When considering the conclusions drawn from cohort studies, a range of issues need to be considered. Volunteers, such as those who participate in pre-market clinical trials, may not be representative of the general population. Although the chance of capturing all disease events in clinical trials is high, there is also the potential for bias to be introduced by the selection and treatment of subjects. Strict inclusion criteria exclude subjects who are not ideal candidates for contact lens wear and subjects are usually highly motivated and have a heightened awareness of the impact of poor lens hygiene or non-compliance with instructions. In particular, subjects in clinical trials are closely monitored by practitioners with specific expertise in contact lens practice. Bias can also be introduced by the differences in the types of subject that volunteer for clinical trials and in subjects that discontinue from a trial. For example, subjects remaining towards the end of a clinical trial may be “successful” lens wearers who have a lower incidence of lens-related complications compared to those who discontinue.

Surveillance studies measure the number of new cases of infection over time in a large well-defined population and therefore overcome some of the potential limitations of cohort studies that are associated with rarity of disease or bias introduced by selection of highly motivated or compliant subjects. These studies can only be conducted on marketed lenses and involve active participation of all relevant practitioners in the defined region.

Surveillance studies that examine the incidence of infection from multiple centres rely on all practitioners in that population to report all cases of infection and therefore require high practitioner response rates and adherence to a uniform definition of disease. Surveillance studies that examine all patients attending a single centre (such as a large acute care hospital) are more likely to have a higher capture rate than multi-centre studies, but may not be as reflective of the general population.

A key factor that affects calculations of incidence in surveillance studies is the strategies employed to measure the size of the population at risk (denominator) and the penetrance of contact lens types in that population. One strategy is to conduct lens wear surveys from a sample of the population by telephone, and to extrapolate the results to the whole region using census data (see editorial). Other approaches use lens sales data and/or surveys of contact lens fitters in a population to estimate the number of new and existing lens wearers [1, 10].

Surveillance studies that are conducted over periods of rapid change in the penetrance of a particular lens type, such as has been seen with silicone hydrogels, also need to address how this change may affect calculations of incidence.


Case-control

Case-control studies are more complicated study designs that require careful consideration of the subjects selected for controls. Cases and controls are to be derived from the same population and need to be collected concurrently. Relative risk is calculated by comparing the ratio of cases to controls in a test group (a particular lens type) to the ratio of cases to controls in a group with the lowest risk. In most lens-related studies, cases are collected from hospital departments [2, 3, 7, 12] and controls are collected from lens wearers attending the same hospital for non-lens related conditions [2, 3, 7, 12] as well as from the general community in the catchment area for the hospital [2, 3, 7]. Controls derived from the general community are needed as hospital-based controls may not always be reflective of the general lens wearing community.

Risk factors for lens-related infection and their respective importance are assessed by analysis of written or verbal surveys from all subjects participating in the study and if large numbers of subjects refuse to be surveyed, the applicability of risk factor data may be limited.


Discussion

The incidence of rare complications of lens wear such as microbial keratitis, are best suited to large population-based surveillance studies; however, the quality of these studies is dependent on capturing the full spectrum of disease (numerator) from mild to severe cases, and on the methods used to derive the size of the population at risk (denominator). Cohort studies are also used to determine the incidence of disease, and are most useful for studies that focus on common complications associated with lens wear rather than rare diseases such as microbial keratitis. Prospective case-control studies are ideal for assessing relative risk of disease but give no indication of incidence. In these types of studies it is essential that the appropriate controls are used.

Data from the population-based surveillance studies conducted in the 1980s and 1990s indicate that the absolute risk of infection with conventional hydrogel lenses has remained stable for at least a decade, for both daily and extended wear. The contact lens market has changed dramatically since these studies have been published, with the introduction and increase in popularity of daily disposable lens wear, and more recently silicone hydrogel lenses. Moreover, the need for revised definitions of lens-related keratitis that better reflect the spectrum of disease is now recognised.

Morgan et al.’s surveillance [1] and case-control [2] studies of microbial keratitis among contact lens wearers attending the Royal Eye Hospital in Manchester is the first of several studies soon to be published on the incidence and relative risk of infection with silicone hydrogel lenses. Morgan et al.'s data and preliminary analysis from some of the other studies [3-5] indicate that wearing silicone hydrogel lenses for up to 30 consecutive nights of wear, does not increase the risk of infection above the established rate of infection with conventional hydrogel extended wear, and that the risk factors for infection remain essentially the same; overnight wear, male gender, smoking and lens care hygiene. 


References 

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