All participants who were successfully enrolled in the trials were included in the analysis. As an initial step, demographic variables were retrospectively compared between study groups and the historical controls using t tests and Fisher exact tests based on the scale of the variable. Demographic variables that were significant between groups were included in the multiple logistic regression analysis as a possible confounder. Adverse event data were obtained from both scheduled and unscheduled visits. Rates were reported as the number of first AEs per 100 participant eyes. Because subjects who experience a first event have a greater likelihood of developing a second event,44 only first events were considered in the analysis. Adverse event rates were compared between study groups using multiple logistic regression with a robust estimator of variance.45 The robust estimate of variance takes into account the within-subject correlation caused by the two-eye data, where it considers each subject as a cluster of two observations. Analysis of AE types that resulted in zero frequency cells used Fisher exact test. Any significant result from a Fisher exact test was considered as a trend. A value of p ≤ 0.05 was considered statistically significant. Analysis was performed using STATA version 10.46
Demographic variables, namely age, refractive error, and lens wear experience were not significantly different between the two studies and historical control samples (p ≥ 0.21). However, the distribution of sex was different between the groups (p < 0.01). Sex was therefore included as a possible confounder in the multiple logistic regression. Subject demographics for the studies are detailed in Table 4.
After adjusting for sex, logistic regression analysis revealed that at the 1-month scheduled visit (Table 5), there were significantly fewer mechanical events when lenses were replaced each morning compared with being replaced monthly (1.2 vs 5.2%, p = 0.02). Considering all AEs at the 1-month time point, the rate was significantly lower with morning lens replacement compared with that of the historical control (4 vs 8.9%, p = 0.04). Night lens replacement had an overall AE rate of 7.9%, which was not significantly different from that of the historical control.
The distribution of colony-forming units (CFU) per lens for isolated organisms on handled-only lenses is shown in Fig. 3. The mean bacterial count for the handled-only lenses was 813 CFU/lens. Staphylococcus aureus was isolated from the lenses of 35% of subjects, and 65% of subjects had more than 1000 CFU/lens of gram-positive bacterial contamination. Gram-negative bacteria were isolated from the lens of 5% of subjects.
This study investigated the impact of morning and night lens replacement during CW on ocular AEs. As overnight wear increases the risk and rate of AEs6,47 and, by contrast, daily disposable lens wear is associated with the lowest risk of experiencing a severe microbial keratitis,6 the hypothesis of the current study was exposing the eye to a new lens would reduce AEs. This study indicates that regularly replacing lenses each morning, compared with overnight replacement or monthly lens replacement (control), seems to reduce the overall rate of contact lens–related ocular AEs. Although total CIEs were trending lower with the morning lens replacement modality compared with those of the historical control and had a contributory effect in reducing the overall AE rate, the reduction was driven primarily by mechanical events. The lower mechanical events with morning lens replacement might be related to elimination of overnight debris accumulation behind the lenses soon after waking. Although night lens replacement had a similar trend for lower mechanical events compared with that in the historical control, there seemed to be a higher rate of erosions among neophytes compared with that in experienced wearers in the night replacement group. Stapleton et al. has shown that neophytes have significantly higher levels of lid biota compared with those in experienced wearers and attributed these to increased lid manipulation in neophytes.48 Perhaps neophytes inflicted a minor corneal abrasion during the insertion process, which, coupled with overnight lens wear, resulted in a more marked discrete epithelial loss.
Compared with that in the control group, the incidence of corneal inflammatory AEs in the morning and night replacement schedules showed similar trends for a reduction in events of IK/CLARE and an increase in CLPU. Gram-negative contamination of lenses is frequently involved in IK and CLARE events.20,21 Because increased bacterial load on lenses is one of the risk factors for corneal inflammation, perhaps regular lens replacement refreshes the contact lens surface sufficiently to minimize bacteria becoming more adept at infecting the cornea.9 By contrast, CLPU events are associated with increased gram-positive contamination of lenses17,22,49 associated with an epithelial defect.50 The apparent increase in CLPU events in both replacement groups compared with the control might be caused by the increased handling necessitated by both replacement schedules compared with the minimal handling of the control group. Contact lens–induced peripheral ulcer might be caused by specific members of the normal microbiota that become pathogenic at elevated levels.49 Furthermore, AIK was only recorded in the night replacement group. Sankaridurg51 has suggested that AIK is a precursor to CLARE because similar organisms were isolated with both AIK and CLARE. Perhaps if the lenses were not replaced each evening, there might instead have been an increase in acute red eye responses. In any case, lens contamination related to handling lenses in the evening, just before overnight eye closure, overwhelms the benefit offered by exposing the eye to a new lens.
A previous study showed a reduction in the total counts and frequency of isolation of bacteria recovered from eye swabs of subjects instilling saline drops on waking and before sleep compared with baseline.42 The authors speculated that regular saline and/or lubricant instillation acted as a kind of ocular flush, removing stagnant tears and reducing the levels of microorganisms. In the current study, instillation of lubricant after morning lens replacement compared with no saline instillation did not seem to confer any benefit in terms of reducing the incidence of AEs.
The primary limitation of the study was its short duration of 1-month EW. Although the correlation of AEs between the two eyes was low and was based on the 1-month data of the historical control, we accept that this may not be true if the duration of the study was of a longer duration. However, a previous study has shown that more than 40% of infiltrates occurred in the first month of wear.44 The short trial duration also meant that subjects in the current studies remained highly motivated and, coupled with regular follow-up, permitted documentation of all AEs that occurred during the trial period. An obvious improvement to the study design would be to conduct a year-long trial using an active control, which would control for seasonal variations that might have influenced the rates of bacterially driven AEs. In terms of the analysis, logistic regression has one limitation, that it cannot handle cells with zero frequency. In all such situations, the Fisher exact test was used instead. This was the case for specific events, such as SEAL, IK, and AIK. The p values arising from Fisher exact tests could only be considered as trends and not conclusive.
This study supported the hypothesis that replacing lenses after waking reduces contact lens wear–related complications related to CW. Although AEs are higher with EW, they have not been established as an accurate predictor of risk of microbial keratitis; however, it would be interesting to test whether morning replacement reduces the incidence or severity of microbial keratitis with EW of contact lenses. Unfortunately, replacing lenses at night does not seem to have any beneficial effect perhaps because of the side effects of handling lenses just before overnight eye closure. Lens wearers on an EW/CW schedule should be advised to minimize lens handling before sleep to reduce the risk of complications.6
Received May 2, 2012; accepted August 10, 2012.
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