Determination of the Minimal Clinically Important Difference (MCID) for Ocular Subjective Responses.

Purpose: To determine the minimal clinically important difference (MCID) for contact lens (CL)-related subjective responses and explore whether MCID values differ between subjective responses and study designs. Methods: This was a retrospective analysis of data from seven one-week bilateral crossover studies and 14 one-day contralateral CL studies. For comfort, dryness, vision, or ease of insertion, participants rated on a 0-100 visual analogue scale (VAS) and indicated lens preference on a five-point Likert scale featuring strong, slight, and no preferences. For each criterion, four MCID estimates were calculated and averaged: mean VAS score difference for "slight preference," lower limit of 95% confidence interval VAS score difference for "slight preference," difference in mean VAS score difference between "slight" and "no preference" and 0.5 standard deviation of VAS scores. Results: The four calculation methods generated a small range of MCID values. For bilateral studies, the averaged MCID was 7.2 (range 5.4-8.8) for comfort, 8.1 (5.2-10.6) for dryness, 7.1 (5.5-9.3) for vision and 7.6 (6.0-10.5) for ease of insertion. For contralateral studies, the averaged MCID was 6.9 (6.1-7.6) for comfort at insertion and 7.5 (6.8-8.2) for end-of-day comfort. Conclusions: This work demonstrated very similar MCID values across subjective responses and study designs, in a population of habitual soft CL wearers. In all cases, MCID values were on average seven units on a 0 to 100 VAS. Translational Relevance: This work provides MCID values which are important for interpreting ocular subjective responses and planning clinical studies.

End-of-day assessment of asymptomatic versus highly symptomatic soft contact lens wearers.

PURPOSE: To investigate differences in key clinical parameters between asymptomatic and highly symptomatic soft contact lens (CL) wearers after 14 h of wear. METHODS: In this pilot investigation, Phase 1 identified asymptomatic (CLDEQ-8 score ≤ 7) and highly symptomatic (CLDEQ-8 score ≥ 20) subjects after fitting with nelfilcon A CLs. Phase 2 investigated the following over a single nelfilcon A CL-wearing day (14 ± 2 h): blinking characteristics, tear meniscus height (TMH), non-invasive tear break-up time (NIBUT), tear film osmolarity and eyelid margin staining. Parameters for the two groups were compared using linear mixed models and post-hoc testing. The relationship between comfort scores and the clinical parameters was also investigated. RESULTS: Overall, 161 and 42 subjects were enrolled into Phase 1 and 2, respectively. Twenty-five asymptomatic and 17 symptomatic subjects completed Phase 2. Lower eyelid TMH was decreased after 14 h in symptomatic compared with asymptomatic subjects (least square mean [LSM] difference -0.04 mm, 95% CI: -0.07, -0.01). Osmolarity was lower in symptomatic than in asymptomatic subjects at fitting (LSM difference -9.89, 95% CI: -18.91, -0.86). Upper eyelid margin staining was greater after 14 h in symptomatic than in asymptomatic subjects (LSM difference 0.53, 95% CI: 0.01, 1.05) and greater after 14 h than baseline in the symptomatic group (LSM difference 0.61, 95% CI: 0.16, 1.07). There was a significant relationship between comfort and upper eyelid margin staining (r = -0.40, 95% CI: -0.63, -0.11) and blink rate (r = -0.31, 95% CI: -0.57, -0.003). CONCLUSION: The potential parameters most effective in differentiating asymptomatic from symptomatic wearers were upper eyelid margin staining and lower TMH. The parameter with the strongest relationship to comfort was upper eyelid margin staining, where higher comfort scores were associated with lower levels of staining.

The short-term effect of contact lens wear on blink characteristics.

PURPOSE: The aim of this pilot study was to investigate the initial effect of contact lens wear on spontaneous blink characteristics. METHODS: This was a randomised, crossover pilot study. Spontaneous blinking was recorded using a high-speed infrared camera in ten subjects with three different soft contact lenses (spherical hydrogel, spherical silicone hydrogel and toric hydrogel), one rigid contact lens and without contact lenses. Custom semi-automated software was used to determine palpebral aperture height, interblink interval (IBI), blink speed, blink completeness and blink duration. RESULTS: The IBI was significantly greater for non-lens wear compared with the silicone hydrogel [ratio (95% CI): 1.34 (1.16, 1.55), p < 0.0001], toric hydrogel [1.28 (1.10, 1.48), p = 0.0001] and rigid corneal lenses [1.48 (1.27, 1.73), p < 0.0001]. The spherical silicone hydrogel lens showed greater closing-phase speed than non-lens wear [mean difference (95% CI): 27.4 (5.6, 49.1) mm/s, p = 0.006]. Shorter total blink duration was found for non-lens wear compared with any of the lens types [spherical hydrogel: ratio 0.89 (0.81, 0.98), p = 0.01; spherical silicone hydrogel: 0.87 (0.80, 0.95), p = 0.0001; toric hydrogel: 0.90 (0.83, 0.98), p = 0.004; and rigid corneal: 0.88 (0.82, 0.96), p = 0.0004]. Opening-phase speed (p = 0.12) and blink completeness metrics (all p > 0.5) were not influenced by wearing condition. CONCLUSION: This work showed that short-term contact lens wear influenced the palpebral aperture height, IBI, speed and duration of the blink, and the effect is dependent on the contact lens type. The completeness of the blink was not altered by contact lens wear. Future work should be conducted to assess the effect of long-term wear of different contact lens types on blink characteristics. The measurement of spontaneous blinking characteristics represents an immediate, sensitive and non-invasive evaluation of the impact of a contact lens on the ocular surface.

Using face masks with spectacles versus contact lenses.

PURPOSE: To test the hypothesis that various subjective ocular and task-related parameters associated with wearing a face mask would be better in neophyte contact lens (CL) wear compared to habitual spectacle (Sp) wear. METHODS: Thirty participants were randomised to continue in Sp (n = 15) or wear somofilcon A daily disposable CL (n = 15) ('group'). A surgical face mask (Type II R) was worn for at least one hour per day on four or more days per week. After two weeks, participants completed the Quality of Life Impact of Refractive Correction Questionnaire (QIRC), a two-part face mask usability questionnaire and graded ocular-related symptoms using 0-100 visual analogue scales. RESULTS: There was no difference between groups for overall QIRC score but some individual question scores reflected better quality of life in the CL: 'outdoor activities', 'keep fit' and 'able to do things' (all p < 0.05). Differences in favour of the CL were seen for the following in the face mask usability questionnaire: 'breathing', 'heat', 'comfort on ears', 'overall comfort', 'walking', 'driving', 'reading', 'computer use', 'exercising' and 'socialising' (all p < 0.05). Significant differences were also seen for the 0-100 VAS symptoms probing vision quality in favour of the CL: glare, distance and near vision, fogging, restricted field of view and peripheral blur. CONCLUSION: This work supports anecdotal reports that CL are a better vision correction option than Sp when used in conjunction with a face mask. Participants reported a range of benefits to the CL/face mask combination for vision-related symptoms, breathing and heat-related symptoms and a number of day-to-day activities including walking, driving and exercising. All of the benefits relating to the CL are likely to result in improved adherence to face mask use. Overall, the findings of this work suggest that where possible, CL should be the preferred vision correction option for people using face masks.

CLEAR - Effect of contact lens materials and designs on the anatomy and physiology of the eye.

This paper outlines changes to the ocular surface caused by contact lenses and their degree of clinical significance. Substantial research and development to improve oxygen permeability of rigid and soft contact lenses has meant that in many countries the issues caused by hypoxia to the ocular surface have largely been negated. The ability of contact lenses to change the axial growth characteristics of the globe is being utilised to help reduce the myopia pandemic and several studies and meta-analyses have shown that wearing orthokeratology lenses or soft multifocal contact lenses can reduce axial length growth (and hence myopia). However, effects on blinking, ptosis, the function of Meibomian glands, fluorescein and lissamine green staining of the conjunctiva and cornea, production of lid-parallel conjunctival folds and lid wiper epitheliopathy have received less research attention. Contact lens wear produces a subclinical inflammatory response manifested by increases in the number of dendritiform cells in the conjunctiva, cornea and limbus. Papillary conjunctivitis is also a complication of all types of contact lenses. Changes to wear schedule (daily disposable from overnight wear) or lens materials (hydrogel from SiHy) can reduce papillary conjunctivitis, but the effect of such changes on dendritic cell migration needs further study. These changes may be associated with decreased comfort but confirmatory studies are needed. Contact lenses can affect the sensitivity of the ocular surface to mechanical stimulation, but whether these changes affect comfort requires further investigation. In conclusion, there have been changes to lens materials, design and wear schedules over the past 20+ years that have improved their safety and seen the development of lenses that can reduce the myopia development. However, several changes to the ocular surface still occur and warrant further research effort in order to optimise the lens wearing experience.

The association of comfort and vision in soft toric contact lens wear.

PURPOSE: This work set out to investigate if there was an association between subjective comfort and both subjective and measured vision during the use of contemporary daily disposable soft toric contact lenses. METHODS: Thirty-eight habitual soft contact lens wearers wore each of three daily disposable toric lenses for one week in a prospective, crossover, randomised, single-masked study. The following clinical measures were recorded at dispensing and follow-up visits: biomicroscopy scores, lens fitting (including rotation and rotational stability), high and low contrast visual acuity, subjective vision quality and subjective ocular surface comfort. Subjective scores were collected using 0-10 numerical grading scales. Comfort scores were analysed using a linear regression model with age, sex, visit, phase of crossover ('phase'), lens type, lens rotation, lens rotational stability, visual acuity, cylinder power and subjective vision quality as factors of interest and then refined using backward stepwise regression. RESULTS: Thirty six participants (31.1 ± 13.5 years) completed the study. Comfort scores were found to be associated with subjective vision quality (F = 127.0 ; p < 0.0001), phase (F = 7.2; p = 0.001) and lens type (F = 4.9; p = 0.009). Greater comfort scores were observed with greater subjective vision quality scores. Visual acuity was not statistically significant in the model. CONCLUSION: This work suggests that symptoms of ocular discomfort may be more intense if there is also perceived visual compromise in daily disposable soft toric lenses. There was a stronger positive correlation between comfort and subjective vision quality compared with comfort and measured visual acuity.

Characterisation of blink dynamics using a high-speed infrared imaging system.

PURPOSE: Development and validation of a non-invasive imaging system to capture spontaneous blinking and characterise blink dynamics using a custom image analysis algorithm. METHODS: A pilot study investigated the influence of illumination type on blink dynamics. Spontaneous blinking was recorded in eight subjects using a high-speed camera under two illumination conditions: white light and infrared. Custom semi-automated software assessed palpebral aperture height (PAH), blink rate, blink speed, blink completeness and blink duration. The main clinical study compared two different image analysis techniques. Spontaneous blinking was recorded in 20 subjects using a high-speed infrared camera. Blink speed and duration were determined using two techniques: manual tracking and semi-automated tracking. Agreement between the two techniques was assessed using Bland-Altman analysis. Coefficients of repeatability (COR) were calculated for the semi-automated technique. RESULTS: There were significant differences between white light and infrared illumination for PAH (p < 0.0001), blink rate (p = 0.04), closing speed (p = 0.009), opening speed (p < 0.0001) and blink duration (p = 0.0003). The mean differences (95% limits of agreement) between the two techniques were 0.6 mm s-1 (-15.9 to 17.0) closing speed, 1.5 mm s-1 (-6.8 to 9.8) opening speed, 2.4 ms (-6.8 to 11.5) closed phase duration and 5.0 ms (-19.4 to 29.3) total blink duration. COR values were 10.1 mm s-1 closing speed, 3.7 mm s-1 opening speed, 6.7 ms closed phase duration and 11.2 ms total blink duration. CONCLUSIONS: This study has shown that spontaneous blinking can be characterised using a non-invasive imaging system. The semi-automated analysis provides a rapid characterisation of blink dynamics, allowing its application in large-scale trials in a number of clinical areas.

Monitoring ocular discomfort using a wrist-mounted electronic logger.

PURPOSE: To investigate ocular discomfort during contact lens wear using a wrist-mounted electronic 'lens awareness logger' (LAL). METHODS: Thirty symptomatic contact lens wearers wore study contact lenses for three days. On the first two days, two lens types which are known to differ in end-of-day comfort (lens A: senofilcon A and lens B: balafilcon A), were worn as a matching pair (randomised order). On day three, a pair of lens B was worn. On each day, the participant used a LAL. On day one and two, the participant pressed a button on the LAL whenever they became aware of their lenses due to discomfort. On day three, the participant used a multiple click protocol (1 = mild awareness to 3 = severe awareness) to report discomfort. RESULTS: LAL events were similar on days one and two (17.3 vs. 15.8 events per day). There were significantly more LAL events for lens B (21.6 events per day) in comparison with lens A (11.6 events per day) (p = 0.006). The LAL event profile highlighted peaks in awareness following lens application and towards the end of the wearing cycle. Comparison of the LAL event profile for the two lens types showed significant differences in lens awareness, particularly in the first half of the wearing cycle. LAL events on day 3, showed a uniform distribution of single and double clicks through the day, but a marked peak in triple clicks in the last two hours of lens wear. CONCLUSION: The LAL was able to differentiate between the study lenses and demonstrated differences in their LAL event profiles. Lens awareness associated with discomfort appeared to increase not only in frequency, but also in intensity towards the end of the wearing cycle. The ability of the LAL to track lens awareness suggests it is likely to be a useful tool in furthering understanding of ocular discomfort.

The impact of contact lens wear on ocular surface mucins using a novel clinical fluorescence imaging system.

PURPOSE: Fluorescein-labelled wheat germ agglutinin (F-WGA) acts as a marker for ocular surface mucins. This clinical study sought to investigate whether the degree of F-WGA fluorescence observed at the ocular surface differed between symptomatic contact lens wearers, asymptomatic contact lens wearers and non-contact lens wearers, using a novel imaging system. METHODS: Twenty-five participants (10 symptomatic contact lens wearers, 10 asymptomatic contact lens wearers and 5 non-contact lens wearers) attended a single study visit. Photographs of the cornea, bulbar and tarsal conjunctiva were captured following application of F-WGA solution. RESULTS: The imaging system captured high-resolution images of F-WGA fluorescence at the ocular surface. The degree of fluorescence differed between the ocular surface regions (p < 0.001). A significant difference in fluorescence was observed between participant groups for the cornea (p = 0.01), with both the symptomatic and asymptomatic contact lens wearers showing lower fluorescence than the non-lens wearers. F-WGA associated fluorescence appeared diminished in the lid wiper region of the symptomatic lens wearers, compared to the asymptomatic group (p = 0.025). CONCLUSION: The use of F-WGA as a clinical marker for ocular surface mucins allows an improved understanding of their distribution across the ocular surface. Contact lens wear appears to negatively impact mucin density across the ocular surface, with the most marked effect on the cornea. F-WGA fluorescence appeared diminished in the lid wiper region for the symptomatic contact lens wearing group, indicating that mechanical interaction in this region may play a role in the aetiology of contact lens discomfort. Given the ability of F-WGA to disclose mucin distribution across the ocular surface it is likely to be a key clinical tool in furthering our understanding of (i) the aetiology of contact lens related discomfort, (ii) contact lens designs/materials to minimise interaction with the ocular surface and (iii) dry eye disease and other ocular surface diseases.

Characterization of Upper Eyelid Tarsus and Lid Wiper Dimensions.

OBJECTIVES: To measure various dimensions of the upper tarsal plate and the area of upper lid wiper staining. The repeatability of the method of measurement was investigated. METHODS: Thirty-five healthy non-contact lens wearers were enrolled. The following parameters were measured from digital images of the upper eyelid captured with a slitlamp camera: length, height, and total area of the tarsal plate and area of lid wiper staining (lissamine green). Measurements were performed in a randomized and masked fashion on two separate occasions by the same investigator using ImageJ (National Institutes of Health). Coefficients of repeatability (COR) were calculated. RESULTS: The dimensions (mean±SD) of the tarsal plate were 20.6±1.9 mm length, 7.9±0.8 mm height, and 103.3±18.8 mm total area. The area of lid wiper staining was 2.7±2.0 mm. No association was found between tarsal dimensions and lid wiper staining (all P>0.05). Image analysis COR values were 0.6 mm tarsal length, 0.1 mm tarsal height, 1.2 mm tarsal area, and 0.4 mm lid wiper staining. There was no significant difference between repeated measurements for any parameter (all P>0.05). Limits of agreement were narrow for all parameters, indicating good agreement between repeated measurements. CONCLUSIONS: This work has demonstrated that there is a wide range in the dimensions of the upper tarsal plate in an urban UK population. No association was found between the upper tarsal dimensions and lid wiper staining. ImageJ was shown to be a repeatable method to measure the dimensions of the upper tarsal plate and upper lid wiper staining.

Effect of Three Interventions on Contact Lens Comfort in Symptomatic Wearers: A Randomized Clinical Trial.

PURPOSE: To investigate whether carrying out various interventions part way through the day influences comfort in symptomatic daily disposable (DD) contact lens wearers. METHODS: A subject-masked, randomized, controlled clinical trial was conducted in thirty symptomatic soft lens wearers who wore their habitual DD contact lenses bilaterally for 12 h on two separate days. Five hours after lens application, one of the following three interventions or a control was performed on each eye: replacing the existing lens with a new lens; removing and reapplying the same lens; performing a 'scleral swish'; and no action (control). Comfort scores were recorded using SMS text messages every hour following lens application using a 0 (causes pain) to 100 (excellent comfort) scale. Comfort scores before lens application, at 6 mins post-application, and at 6 mins post-intervention were also recorded. RESULTS: There was a significant reduction in comfort from pre-lens application to 6 mins post-application for all groups (all p<0.05). Comfort gradually decreased from 6 mins to 5 h after lens application for each group (p<0.0001) with no significant difference between groups over the 5-h period (p = 0.09). There was no significant difference in comfort 6 mins post-intervention for any group (all p>0.05). After the intervention, comfort continued to decline (p<0.0001) with slightly lower mean scores for the control group compared to the new lens group (p = 0.003). Change in comfort relative to pre-intervention (5 h) was similar for all groups (p = 0.81). There was no difference in comfort at 12 h between groups (p = 0.83). CONCLUSION: This work has confirmed that comfort shows a continual and significant decline over a 12-h wearing period in symptomatic DD contact lens wearers. None of the interventions investigated had any significant impact on end-of-day comfort. These data suggest discomfort in lens wearers is more heavily influenced by changes to the ocular environment rather than to the lens itself. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN10419752 http://www.controlled-trials.com/ISRCTN10419752.

Lid Margin Sensitivity and Staining in Contact Lens Wear Versus No Lens Wear.

PURPOSE: To map the sensitivity and staining of the marginal conjunctiva in soft contact lens (SCL) wearers and nonwearers and to investigate diurnal changes. METHODS: Thirty-five nonwearers and 35 SCL wearers were recruited. Mechanical sensitivity was measured at 8 locations on the ocular surface and adnexa (cornea, marginal, bulbar, and tarsal conjunctivae) using the Cochet-Bonnet aesthesiometer. Lid margin staining (lissamine green) was assessed through image analysis. Measurements were repeated at 12 hours in 11 nonwearers and 10 symptomatic SCL wearers. RESULTS: The marginal conjunctiva was the most sensitive conjunctival region (all P < 0.001). There was no significant difference in sensitivity at 12 hours (all P > 0.05). There was a significant difference in sensitivity between the 2 groups in the morning for the lower lid tarsal conjunctiva (P = 0.003). After 12 hours, the sensitivity of the lower lid marginal conjunctiva was found to be reduced in SCL wearers compared with nonwearers (all P < 0.05). Lower lid margin staining was greater than upper lid margin staining in both groups (all P < 0.05). In the SCL wearers, a significant increase in lower lid margin staining was found at 12 hours compared with the morning (P = 0.04). After 12 hours, lower lid margin staining was significantly greater in SCL wearers compared with nonwearers (P = 0.03). CONCLUSIONS: This work has demonstrated that the marginal conjunctiva is the most sensitive conjunctival region. After 12 hours, symptomatic lens wearers showed decreased sensitivity of the lower marginal conjunctiva and increased lower lid margin lissamine green staining compared with those of the nonwearers.

Mechanical sensitivity of the human conjunctiva.

PURPOSE: The aim of this study was to map the sensitivity of the marginal and other conjunctival regions and to investigate changes in the sensitivity of these regions when determined in the morning and evening. METHODS: Thirty-five healthy, noncontact lens wearers (20 female, 15 male; age 27.7 ± 7.3 years) were enrolled. Mechanical sensitivity was measured at 8 locations on the ocular surface and adnexa (cornea, marginal, bulbar, and tarsal conjunctiva) using a Cochet-Bonnet esthesiometer (0.12-mm diameter filament). A subgroup of 11 subjects (6 female, 5 male; age 28.9 ± 9.9 years) returned after 12 hours when this protocol was repeated. RESULTS: The cornea was found to be the most sensitive region (all P < 0.001). The marginal conjunctiva showed greater sensitivity than did the bulbar and tarsal conjunctiva (all P < 0.001). The temporal marginal conjunctiva was more sensitive than the central marginal conjunctiva (all P < 0.05). No difference in marginal conjunctival sensitivity was found between upper and lower eyelids (all P > 0.05). The upper tarsal conjunctiva was more sensitive than the lower tarsal conjunctiva (P = 0.04). There was no significant difference in the sensitivity determined in the morning and the evening for any of the locations investigated (Bonferroni adjusted, P > 0.006). CONCLUSIONS: This work has demonstrated that the marginal conjunctiva was the most sensitive of all the conjunctival regions and that this does not alter over the course of the day.