2023 Prentice Medal Award lecture: Ocular surface-related symptoms of discomfort and other stories.

ABSTRACT: I have been fortunate to spend portions of my career in each of private practice, industry, and academia. At some times, these occupations have dictated the research direction, whereas, at others, curiosity has been allowed to dominate. This has resulted in multiple avenues of inquiry (some might say, too many), along which I have traveled with a rich and varied cast of collaborators, who have all taught me a great deal. The privilege of being awarded the Charles F. Prentice medal provides me an opportunity to summarize some of these activities. Beginning with an attempt to use contact lenses to solve a problem for those affected by albinism, the story shifts to addressing some of the wider deficiencies of contact lenses, in particular the consequences of their oxygen permeability and tendency to induce discomfort toward the end of the day. After briefly considering some aspects of meibomian gland function, the narrative concludes with the latest investigations of neurological links between the cornea and migraine.

The validity of point of care tear film osmometers in the diagnosis of dry eye.

PURPOSE: To determine the repeatability of TearLab and I-PEN osmometers in vivo and their accuracy in vitro. DESIGN: Prospective, single-visit study. METHODS: The tear osmolarity of 28 participants was evaluated with TearLab and I-PEN on two occasions in random order, over a 2-h period. Both eyes were measured in a randomised order. Coefficients of repeatability (CoR) were determined for each device, together with the bias and limits of agreement between them. For the in vitro experiment, the osmolarity was measured by both osmometers in five solutions (290, 297, 342, 338 and 383 mOsm/L) at two different temperatures (22 and 37°C) with a total of four consecutive measures. RESULTS: The CoRs for the TearLab and I-PEN in the right and left eyes were 26.2, 21.3, 33.6 and 28.3 mOsm/L, respectively. Across the first and second repeats, TearLab showed consistency of diagnosis for 50% of participants with 29% as dry eye positive, while I-PEN indicated 68% consistency of diagnosis with 57% dry eye positive. The instruments agreed on the diagnosis in 46.5% of cases. In vitro comparison showed that the average measurement errors for TearLab and I-PEN were -10 ± 13 and 31 ± 39 mOsm/L at 22°C, and 4 ± 13 and 20 ± 51 mOsm/L at 37°C. CONCLUSIONS: In vitro, both instruments showed reasonable accuracy and repeatability at mid-range osmolarities, but repeatability generally declined at higher and lower levels. While TearLab accuracy remained consistent across the osmolarity range, measurement errors for I-PEN noticeably increased outside the mid-range. In vivo, both instruments displayed poor repeatability. This casts doubt on the value of utilising either instrument to establish osmolarity as a factor in the diagnosis of dry-eye, according to currently recommended diagnostic guidelines (TFOS DEWS II), if only a single measurement is taken from each eye.

Associations between Binocular Vision Disorders and Contact Lens Dissatisfaction.

SIGNIFICANCE: These data demonstrate that binocular vision disorders (BVDs) contribute to contact lens (CL) dissatisfaction independently of CL discomfort (CLD) in myopic, pre-presbyopic, adult, single-vision CL wearers. PURPOSE: This study aimed to determine whether BVDs contribute to CL dissatisfaction and whether this contribution is independent of CLD. METHODS: Participants attended one clinical visit while wearing their habitual CLs. Symptoms from CLD and BVDs were measured with the Contact Lens Dry Eye Questionnaire-8 (CLDEQ-8) and Convergence Insufficiency Syndrome Survey (CISS), respectively. A comprehensive binocular vision (BV) assessment was performed. The Ocular Surface Disease Index (OSDI) was used to measure CL dissatisfaction from CLD and BVDs based on reported correlations between the CLDEQ-8 and the CISS with the OSDI. Participants were categorized according to their CL comfort status (CLD [≥12 on CLDEQ-8] or non-CLD [<12 on CLDEQ-8]) and BV status (BVD or non-BVD). RESULTS: Seventy-six participants completed the trial, and 19 (25%) were diagnosed with BVD. Those diagnosed with BVD scored higher than did those diagnosed with non-BVD for the OSDI (25.1 ± 12.7 vs. 10.7 ± 7.3, P < .001) and CISS (18.7 ± 7.7 vs. 11.9 ± 5.9, P = .001), but not the CLDEQ-8 (P = .25). Those categorized as having CLD scored higher than did those categorized as having non-CLD for the OSDI (19.0 ± 12.3 vs. 9.3 ± 5.9, P = .003) and CISS (16.1 ± 6.8 vs. 11.0 ± 6.2, P = .001). There were no significant interactions between BV status and CL comfort status for any questionnaire (P > .08). CONCLUSIONS: Higher scores for OSDI in those with CLD or BVD indicate that both conditions contribute to CL dissatisfaction. Higher scores for the CISS in those with CLD suggest a degree of overlap for some BVD symptoms. Nonsignificant differences between BVD and non-BVD for the CLDEQ-8 suggest that BVDs contribute to CL dissatisfaction independently of CLD.

The global prevalence of dry eye disease: A Bayesian view.

PURPOSE: To provide estimates for the prevalence of dry eye disease globally and in sub-groups defined by: diagnostic criterion, sex, geographic location and age, using a Bayesian approach. METHODS: Modelling prevalence as a Beta distribution, estimates were inferred from Bayesian posterior distributions obtained by combing an uninformed prior with likelihood functions generated from all relevant studies reporting dry eye prevalence between 1997 and 2021. RESULTS: Global prevalence of dry eye disease was estimated at 11.59% (standard deviation (SD) = 0.04). For symptomatic disease, the estimate was 9.12% (SD = 0.04), with women 9.5% (SD = 0.05) and men 6.8% (SD = 0.06); prevalence was lowest in North America, 4.6% (SD = 0.03) and highest in Africa, 47.9% (SD = 1.8). For signs, prevalence was 35.2% (SD = 0.3), with woman 34.7% (SD = 0.7) and men 37.6% (SD = 0.7); North America showed the lowest regional prevalence, 3.5%, (SD = 0.4) with Eastern Asia the highest, 42.8% (SD = 0.4). Using TFOS DEWS II diagnostic criteria resulted in a global prevalence of 29.5% (SD = 0.8), with women 28.1% (SD = 1.2) and men 24.9% (SD = 1.4). Prevalence was lowest during the fifth decade, increasing approximately linearly with age thereafter. Estimates for other categories are given in accompanying tables. CONCLUSION: A simple, flexible, yet powerful means of combining data from multiple sources to yield prevalence estimates across a range of circumstances is described, that is compatible with published guidelines for conducting meta-analysis. Estimates can be readily updated as new information emerges, or according to need. Understanding the specific characteristics of studies chosen for inclusion is critical to the validity of the outcome. Although dry eye disease is evidently common, affecting about one in 11 people world-wide, data are sparse for the young and all geographical locations except Eastern Asia.

Filaggrin Expression in the Lid Margin During Contact Lens Wear.

AIM: To investigate the expression of the keratinization-related protein, filaggrin, in the lid margin epithelium of contact lens (CL) wearers compared with nonwearers. METHODS: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience; previous CL wearers; and nonwearers as controls. Impression cytology samples were collected from the lid wiper (LW) area of the central upper lid margin. After fixing, an equal, random sample was selected from each group (n=13) for immunocytochemistry analysis using antihuman primary anybody (mouse filaggrin), then stained with secondary antibody (fluorescein isothiocyanate-conjugated donkey anti-mouse immunoglobulin G horseradish peroxidase) to detect filaggrin. Imaging was performed with the 3i-Vivo 2-photon microscope equipped with a Zeiss 20×-objective and SlideBook-reader software. RESULTS: Sixty-five samples from 65 participants (37 women; mean age±SD: 25.1±4.1 years) were collected. Filaggrin was detected in all 65 randomly selected immunostained marginal epithelium samples. All samples were similar in showing patchy areas of filaggrin immunostaining, regardless of CL wear, symptoms or epithelium morphology. Because the filaggrin immunostaining showed similar patterns across almost all the observed samples, comparison between subject groups was impractical. The presence of filaggrin in the healthy LW was additionally confirmed by an independent laboratory. CONCLUSION: Filaggrin expression seems to be a normal part of epithelial cell differentiation in the lid margin and may not be a useful keratinization/stress biomarker in the marginal epithelium. Investigating other keratinization biomarkers that are not detected in the normal mucocutaneous junction/LW may help to understand the keratinization nature of LW epithelium changes in CL wearers.

Changes in the tarsal conjunctiva viewed by in vivo confocal microscopy are associated with ocular symptoms and contact lens wear.

PURPOSE: To investigate the effect of soft contact lens (CL) wear on the morphology of the epithelial-lamina propria junction as well as the possible association with symptoms of discomfort. METHODS: Ninety-two subjects were recruited, including 60 soft CL wearers, 16 previous wearers, and 16 non-wearers. Additionally, subjects were classified as symptomatic or asymptomatic using the Contact Lens Dry Eye Questionnaire 8 for the CL wearers (a score ≥ 12 was considered symptomatic) and the Dry Eye Questionnaire 5 for the previous wearers and non-wearers (a score ≥ 5 was considered symptomatic). In vivo confocal microscopy of the tarsal conjunctiva was performed on a single occasion. Papillae density, shortest diameter, longest diameter, area, circularity, lumen/wall brightness ratio, irregularity, reflectivity, inhomogeneous appearance of wall and inhomogeneous appearance of rete ridges were evaluated. Effects of CL wear, symptoms and their interaction were analysed using two-way analysis of variance. Correlations were investigated using Spearman's coefficient. Data are presented as mean (standard deviation) or median [interquartile range]. RESULTS: Contact lens wearers, compared to previous wearers and non-wearers, showed higher circularity [0.65 (0.08) vs 0.59 (0.10) vs 0.57 (0.11), p = 0.003]. Subjects with symptoms, compared to asymptomatic participants, showed higher circularity [0.64 (0.08) vs 0.61 (0.10), p < 0.001] and lower irregularity (1.0 [0.7-2.0] vs 1.3 [1.0-2.3], p = 0.009). For previous wearers, those with symptoms showed greater density (135.4 [107.3-183.3] vs 87.5 [85.4-116.7], p = 0.013) and circularity [0.64 (0.07) vs 0.54 (0.10), p = 0.016]. For non-wearers, those with symptoms showed higher circularity [0.65 (0.08) vs 0.50 (0.08), p < 0.001]. DEQ-5 correlated with circularity (ρ = 0.55, p = 0.001). CONCLUSIONS: Soft CL wear modifies papillae of the epithelial-lamina propria junction into a more rounded shape; however, CL cessation appears to resolve this alteration. Additionally, a more rounded papillae shape is associated with ocular symptoms in subjects not actively wearing CLs.

Global Prevalence of Presbyopia and Vision Impairment from Uncorrected Presbyopia: Systematic Review, Meta-analysis, and Modelling.

TOPIC: Presbyopia prevalence and spectacle-correction coverage were estimated by systematic review and meta-analysis of epidemiologic evidence, then modeled to expand to country, region, and global estimates. CLINICAL RELEVANCE: Understanding presbyopia epidemiologic factors and correction coverage is critical to overcoming the burden of vision impairment (VI) from uncorrected presbyopia. METHODS: We performed systematic reviews of presbyopia prevalence and spectacle-correction coverage. Accepted presbyopia prevalence data were gathered into 5-year age groups from 0 to 90 years or older and meta-analyzed within World Health Organization global burden of disease regions. We developed a model based on amplitude of accommodation adjusted for myopia rates to match the regionally meta-analyzed presbyopia prevalence. Presbyopia spectacle-correction coverage was analyzed against country-level variables from the year of data collection; variation in correction coverage was described best by a model based on the Human Development Index, Gini coefficient, and health expenditure, with adjustments for age and urbanization. We used the models to estimate presbyopia prevalence and spectacle-correction coverage in each age group in urban and rural areas of every country in the world, and combined with population data to estimate the number of people with near VI. RESULTS: We estimate there were 1.8 billion people (prevalence, 25%; 95% confidence interval [CI], 1.7-2.0 billion [23%-27%]) globally with presbyopia in 2015, 826 million (95% CI, 686-960 million) of whom had near VI because they had no, or inadequate, vision correction. Global unmet need for presbyopia correction in 2015 is estimated to be 45% (95% CI, 41%-49%). People with presbyopia are more likely to have adequate optical correction if they live in an urban area of a more developed country with higher health expenditure and lower inequality. CONCLUSIONS: There is a significant burden of VI from uncorrected presbyopia, with the greatest burden in rural areas of low-resource countries.

The Effect of Contact Lens Wear on the Cellular Morphology of the Lid Wiper Area.

SIGNIFICANCE: This cross-sectional study presented a link between contact lens wear and changes on the cellular morphology characteristics of the lid wiper (LW) epithelium, which was not visible by LW staining. PURPOSE: The aim of this study was to establish if the duration of contact lens (CL) wear affects the cellular morphology of the LW epithelium. METHODS: This was a cross-sectional study of 100 individuals with different exposures to CL wear: short, moderate, and long experience of CL wear; previous CL wearers; and nonwearers (NWs) as controls. Impression cytology samples were collected from the central upper lid margin (LW area). After fixing, samples were stained with periodic acid-Schiff and haematoxylin for cell morphology analysis and subsequently graded according to the Nelson 0- to 3-point scale. Lid wiper staining was assessed with the aid of lissamine green and graded using the Korb (0- to 3-point) scale. One-way Kruskal-Wallis analysis followed by the Dunn multiple-comparisons test was used for statistical comparison. RESULTS: The Nelson grade for LW epithelium morphology was significantly different between groups (P = .003). Abnormal epithelial morphology as defined by grade 2 or 3 was evident in 66.7% of CL wearers with short experience and 76.5% of CL wearers with moderate experience. This was significantly higher than NWs of whom only 21.5% showed greater than grade 1 (P = .02 and .005, respectively). There was no significant difference between NWs and other groups. Lid wiper staining did not significantly differ between groups (P = .50) or correlate with the Nelson grade (Spearman r = 0.02, P = .08). CONCLUSIONS: Metaplasia of the LW epithelium was significantly greater in the early to moderate stages of CL. This supports the view that mechanical irritation is responsible for LW changes in CL wear. Ceasing CL wear seems to lead to recovery. Lid wiper staining did not reflect the underlying morphological changes.

Measuring Daily Disposable Contact Lenses against Nonwearer Benchmarks.

SIGNIFICANCE: Since becoming a popular form of refractive error correction, contact lenses have aspired to replicate the nonwearer experience. This study assessed how well currently available daily disposable soft lenses have achieved that goal, using a graphical representation to show individual lens behavior relative to benchmarks. PURPOSE: The purpose of this study was to assess comfort, vision, and adverse events during daily disposable contact lens wear, relative to emmetropes and spectacle wearers. METHOD: Three-month clinical studies, where participants either wore one of five daily disposable contact lenses (n = 201), were full-time spectacle wearers with no history of contact lens wear (n = 34), or emmetropic non-contact lens wearers (n = 40). Vision quality and comfort were assessed at the beginning and end of the day (1 to 10). Corneal infiltrative events were recorded. Between-group comparisons were made using a linear mixed model and literature estimates of clinical significance. RESULTS: Initial comfort among emmetropes (mean ± 95% confidence interval, 8.0 ± 0.5) was not significantly different from any of the lens types (range, 7.2 ± 0.4 to 8.0 ± 0.4, all P > .06) or spectacle wearers (7.3 ± 0.5, P = .45). Comfort deteriorated during the day in all groups (P < .05). End-of-day comfort for emmetropes (7.3 ± 0.6) was significantly better, only than lenses B (5.7 ± 0.6, P < .001) and D (6.2 ± 0.5, P = .01). Vision quality for emmetropes (8.6 ± 0.5) was better than spectacle wearers (7.8 ± 0.5, P = .04) and lenses A (7.6 ± 0.4, P = .003) and B (7.5 ± 0.4, P < .001). Corneal infiltrative events occurred in 0% of emmetropes and 2.9% of spectacle wearers and ranged from 2.4 to 7.5% in lens wearers. CONCLUSIONS: Under the conditions of this study, comfort and vision with some contemporary daily disposable contact lenses were indistinguishable from nonwearing emmetropes. Although the contact lens-wearing groups had rates of corneal infiltrative events that were not statistically different from the nonwearers, the study had insufficient power to permit robust conclusions in this respect.

Treatment Practices and Outcomes of Meibomian Gland Dysfunction at a Tertiary Center in Southern India.

OBJECTIVE: To describe the current treatment practices for meibomian gland dysfunction (MGD) at a tertiary eye center, together with the subjective outcomes and compliance behaviors of patients. METHODS: This retrospective cohort study reviewed medical records for MGD severity grading, treatment prescribed, and follow-up schedule. In addition, participants were surveyed to gauge subjective outcomes and treatment adherence. RESULTS: Eight hundred ten patients were diagnosed with "MGD" or "meibomitis" and had a total of 14 different treatment combinations prescribed. In 3.0% of cases, there was no treatment specified. As MGD severity increased, it became more likely that management would be applied and this was also associated with significantly longer treatment durations (P=0.02) and shorter follow-up periods (P<0.001). Posttreatment subjective outcomes and treatment adherence surveys had a response rate of 36.7% and 24.1% respectively. Overall, 53.5% reported sustained improvement, 40.7% no improvement, and 5.7% experienced temporary relief. Although no treatment regimen seemed to be more efficacious than others, patients showed greater adherence when using topical reagents compared with lid hygiene measures (P≤0.002). CONCLUSION: Clinicians, in this large tertiary eye center, use a wide range of treatment regimens to manage MGD. This suggests the need for development of standard management protocols. Whether alone, or in combination, no MGD treatment significantly improved subjective symptoms, a result that may be influenced by compliance behaviors. Use of topical reagents (eye drops or ointment) seemed to be associated with the best compliance. Future focus on more effective MGD treatments is needed to improve practical outcomes.

Temporal Characteristics of Sodium Fluorescein in the Tear Meniscus.

PURPOSE: To observe the emission intensity profile of sodium fluorescein in the human tear film as a function of time and concentration. METHODS: Twenty-two participants with no dry eye signs or symptoms were randomly allocated to receive 1 µL of either a 2 or 10% concentration of fluorescein to one eye. Images of the inferior tear meniscus were captured at regular intervals over 30 minutes and the process repeated for the other eye with the alternate concentration. Fluorescence intensity was quantified on the basis of the grayscale pixel values in the tear meniscus images. The fluorescein-decay profile over time and between concentrations was determined. RESULTS: Peak fluorescence intensity was reached in 3.9 ± 3.0 and 8.7 ± 4.4 minutes after instillation for the 2 and 10% concentrations, respectively. The 10% concentration of fluorescein maintained its peak fluorescence intensity longer than the 2% concentration (about 9 and 2 minutes, respectively). The peak fluorescence intensity was not significantly different between the higher and lower concentrations (44 ± 37 vs. 38 ± 32 units, P = .22). For both concentrations, the observed intensity did not return to baseline levels by the end of the 30-minute observation time. CONCLUSIONS: The fluorescence intensity of fluorescein in a clinical setting varies with time such that both the onset and duration of maximum brightness are concentration dependent. At low concentration (2%), maximum brightness occurs almost immediately after instillation and lasts about 2 minutes. With a higher concentration (10%), the effective working window is delayed for about 7 to 8 minutes. Irrespective of initial concentration, observable fluorescence remains in the tear film beyond 30 minutes post-instillation.

Interpreting the corneal response to oxygen: Is there a basis for re-evaluating data from gas-goggle studies?

When anoxia (0% oxygen) is created within a gas-tight goggle, ocular physiological responses, including corneal swelling, limbal hyperaemia and pH change, are known to vary, depending on the presence or absence of a low, oxygen transmissibility contact lens. A new theory is proposed to account for this discrepancy based on the concept of lid derived oxygen, whereby oxygen originating from the vascular plexus of the palpebral conjunctiva supplements that available to the ocular surface in an open, normally blinking eye, even when the surrounding gaseous atmosphere is anoxic. The effect of a lid derived contribution to corneal oxygenation was assessed by using existing experimental data to model open-eye, corneal swelling behavior as a function of atmospheric oxygen content, both with and without the presence of a contact lens. These models predict that under atmospheric anoxia, contact lens wear results in 13.2% corneal swelling compared with only 5.4% when the lens was absent. Lid derived oxygen acts to provide the ocular surface in the non-contact lens wearing, normally blinking, open-eye with up to 4.7% equivalent oxygen concentration, even within the anoxic environment of a nitrogen filled goggle. Correcting for lid derived oxygen eliminates previously observed discrepancies in corneal swelling behavior and harmonizes the models for the contact lens wearing and gas-goggle cases. On this basis it is proposed that true anoxia at the ocular surface cannot be achieved by atmospheric manipulation (i.e. a gas-goggle) alone but requires an additional presence, e.g. a low, oxygen transmissibility contact lens, to prevent access to oxygen from the eyelids. Data from previously conducted experiments in which the gas-goggle paradigm was used, may have been founded on underestimates of the real oxygen concentration acting on the ocular surface at the time and if so, will require re-interpretation. Future work in this area should consider if a correction for lid derived oxygen is necessary.

Demographic Factors Affect Ocular Comfort Ratings During Contact Lens Wear.

PURPOSE: To determine if rating of ocular comfort during soft contact lens wear is affected by demographic factors. METHODS: Retrospective analysis of ocular comfort ratings during soft contact lens wear extracted from 44 nonrandomized similar clinical trials (n = 986). Subjects wore one of seven daily wear silicone hydrogels (SiHy) in combination with one of nine lens care products (LCP), and two daily disposables lenses. The effects on comfort rating of demographic factors were examined after adjusting for lens and LCP effects using general linear model. RESULTS: Males reported lower comfort on insertion than females (7.9 ± 1.6 vs. 8.1 ± 1.6, p = 0.001). Over 45 years old had higher comfort ratings than those between 26 and 45 or <26 years old at insertion (8.7 ± 1.3 vs. 8.1 ± 1.6 vs. 7.8 ± 1.6, p < 0.001), during the day (8.6 ± 1.2 vs. 8.0 ± 1.6 vs. 8.2 ± 1.2, p < 0.001), and end of day (7.7 ± 1.6 vs. 6.8 ± 2.0 vs. 7.0 ± 1.6, p < 0.001). Neophytes reported lower comfort on insertion (7.3 ± 1.6 vs. 8.2 ± 1.5, p < 0.001) and during day (8.0 ± 1.3 vs. 8.3 ± 1.3, p = 0.020) than experienced wearers. Participants with Rx ≥-3.50D had higher comfort ratings than those with ≤-3.50D on insertion (8.3 ± 1.4 vs. 7.8 ± 1.6, p < 0.001), during the day (8.4 ± 1.3 vs. 8.1 ± 1.3, p = 0.010), and end of day (7.2 ± 1.7 vs. 6.9 ± 1.8, p = 0.046). Comfort during the day was different between participants of different ethnic origin (p = 0.024) with Asians reporting the lowest (8.1 ± 1.3). CONCLUSIONS: Demographic factors such as age, gender, lens wear experience, ethnicity, and refractive status can influence the rating of ocular comfort in clinical studies. The confounding effects of such demographic factors can be controlled by implementing randomization and appropriate multivariable statistical analysis.

Impact of duration of contact lens wear on the structure and function of the meibomian glands.

PURPOSE: To investigate the effects of the duration of contact lens (CL) wear on the meibomian glands (MGs), eyelid and tear film. METHODS: This was a cross-sectional study of CL wearers and non-wearers (NWs) aged between 18 and 35 years. The sample comprised of: (i) Three groups of CL wearers of different duration profiles (short, moderate and long experience of CL wear); (ii) a group of previous CL wearers (PWs) who had ceased wear for at least 6 months prior to the present study; (iii) healthy non-wearers as a control group. Study procedures were conducted in the order from least invasive to most invasive as follows: symptom assessment, lipid assessment, non-invasive break-up time, tear meniscus area, tear osmolarity and evaporation, Phenol red thread, MG expressibility, ocular surface and eyelid assessments, meibography, Marx line and lid wiper assessment using lissamine green. For statistical comparison of continuous data, one-way analysis of variance was used with Bonferroni post-hoc correction, where appropriate. Kruskal-Wallis test and Pearson Chi-Square respectively were used for ordinal and categorical variables. RESULTS: A total of 100 participants (49 males and 51 females; mean age ± SD: 25.4 ± 4.1) were enrolled across the five groups, such that each was composed of 20 age/sex matched individuals. Significant differences between the study groups were found for MG expressibility (p < 0.001), number of plugged orifices (p = 0.001), number of expressed orifices (p < 0.001), MG dropout (p = 0.001), Marx line score (p < 0.001), palpebral redness (p = 0.003), and roughness (p = 0.002), non-invasive break-up time (p < 0.001), Phenol red thread (p = 0.005), and tear meniscus area (p = 0.029). For all these variables, the NW group was statistically different from all other groups. Duration of wear was not a significant factor, except for Marx line score which was different in PWs compared to those with longer experience of CL wear (p = 0.03) CONCLUSION: Alterations to MG morphology and function accompany contact lens wear. Although these changes onset during the first 2 years of wear, prolonged CL exposure beyond this point does not appear to be associated with further modification. Cessation of wear for at up to 6 months does not lead to resolution.

Ocular discomfort responses after short periods of contact lens wear.

PURPOSE: To investigate if contact lens-related discomfort is a function of the time of day at which lenses are worn. METHODS: This was a randomized, crossover, open-label clinical trial where subjective responses, with and without contact lenses, were assessed every 2 hours during five stages (A to E). Each stage began at the time when subjects would normally have inserted their contact lenses (T0). During stage A, no lenses were worn, whereas in stage B, lenses were worn continuously for 12 hours. In stages C to E, lenses were worn for only 4 hours. Contact lenses were inserted at T0 for stage C, but for stages D and E, lenses were not inserted until T0 + 4 and T0 + 8 hours, respectively. Mixed linear models were used for statistical analysis. RESULTS: In the absence of contact lenses, ocular comfort and dryness remained reasonably constant throughout the observation period. Ocular comfort and dryness decreased during 12 hours of continuous lens wear and became significantly worse from the 8-hour time onward compared with insertion (p < 0.023). There were no significant differences in terms of ocular comfort and dryness between any of the 4-hour lens wear stages (p < 0.82). During each 4-hour stage, both comfort and dryness behaved in a similar fashion (p > 0.05) to the first 4 hours of continuous contact lens wear. Comparing the scores of each of these stages with the no-lens response at the corresponding time showed no significant differences for comfort (p > 0.23) or dryness (p > 0.37). CONCLUSIONS: Short periods of wear can be experienced at any time of day without significant change in ocular discomfort and dryness. This suggests that subjective responses at the end of the day are determined by the length of time lenses are in contact with the eye, rather than the time of day at which lenses are worn.

Consequences of wear interruption for discomfort with contact lenses.

PURPOSE: To establish whether increased end-of-day discomfort during soft contact lens wear is associated with short-term changes occurring to the lens itself. METHODS: Twenty-seven subjects wore hydrogel lenses (Focus Dailies; Alcon) bilaterally for 10 hours on two separate days. Comfort was reported using 1-100 numerical rating scales (1 = intolerable discomfort, 100 = lens cannot be felt). Day 1 ratings were taken before lens insertion and at 0.05, 5, and 10 hours post-insertion. Day 2 ratings occurred at similar times, but lenses were removed after the 5-hour assessment and either reinserted (n = 14) or newly replaced (n = 12). An additional rating was taken 5 minutes after re-insertion. Wear then continued to the 10-hour point. In a separate study, 24 different subjects repeated these procedures using a silicone hydrogel lens (AirOptix Aqua; Alcon) with wear taking place on 3 days to permit lens replacement to be with existing as well as new lenses in all subjects. RESULTS: For hydrogel lenses, comfort scores (mean ± 95% CI) reported after 10 hours were 79.4 ± 8.3 when lenses were worn un-replaced, compared with 73.2 ± 9.2 for replacement with the existing lens. When replacement was with a brand new lens, the corresponding values were 72.9 ± 10.9 (un-replaced) versus 69.2 ± 12.8 (new lens replacement). For silicone hydrogel lenses, 10-hour comfort was 90.3 ± 3.2 (un-replaced) versus 92.2 ± 2.9 (replacement with existing lens) versus 90.0 ± 3.3 (replacement with new lens). Differences between replacement conditions were not significant in any case (analysis of variance, p > 0.05). CONCLUSIONS: Final comfort was not influenced by replacing lenses midway through the wearing period. Comfort decrements experienced by users of these daily contact lenses towards the later part of the wearing period are not caused by changes occurring to the lenses on this time scale. Possible alternative etiological factors include a fatigue-like response in one or more ocular tissues or stimulation of ocular surface nociceptors induced by the presence of the contact lens.

Comparison of vision performance of spectacles prescribed to 0.05D versus 0.25D steps.

CLINICAL RELEVANCE: Traditionally, refraction is performed, and spectacles are manufactured in in 0.25D-steps. Trial and spectacle lenses manufactured in smaller increments may allow for a more accurate refraction and prescribed spectacles. BACKGROUND: To determine whether refraction in 0.05D-steps improves the proportion of eyes achieving achieve duochrome equality, and whether spectacles prescribed in 0.05D-steps offer any vision benefits, compared to 0.25D-steps. METHODS: Myopic young adults were enrolled into two prospective studies conducted at different sites. Study 1 comprised 66 participants (refracted under cycloplegia) while Study 2 comprised 51 participants (not cyclopleged). A standard refraction was performed in both studies and a trial frame and trial lenses were used to determine the spherical endpoint of duochrome equality (0.25D-steps first then 0.05D-steps). In Study 2, the cylindrical component was refined in 0.05D-steps before the spherical endpoint in 0.05D-steps. Monocular high-contrast-visual-acuity (HCVA) was measured while wearing the final refractions. Participants in Study 2 wore spectacles manufactured in 0.25D and 0.05D-steps for 7 days each in a randomized, double-masked study. Both spectacles appeared identical. Outcome measures assessed on dispensing and after 7 days of wear comprised monocular acuity-based measurements (HCVA, low-contrast-visual-acuity, vanishing-optotype-acuity, contrast-sensitivity) and subjective ratings. The Quality-of-Vision questionnaire and subjective preference were assessed after 7 days. RESULTS: Both studies showed a higher proportion of eyes achieved duochrome equality (P < 0.001) and better average monocular HCVA (P ≤ 0.006) in 0.05D-steps. Study 2 showed 0.05D-step spectacles provided better average results for all monocular acuity-based measurements (P < 0.006) and were preferred by 65% (P = 0.04) of participants after 7 days (P = 0.04). There were no differences between spectacles for any other measures (P > 0.1). CONCLUSIONS: Refraction performed, and spectacles manufactured in 0.05D-steps for this study improved average acuity-based outcomes and were preferred by most participants to spectacles in traditional 0.25D-steps.

Tear film hTERT and corneal nerve characteristics in dry eye disease.

CLINICAL RELEVANCE: The behaviour of human telomerase reverse transcriptase (hTERT) in tears reflects its role in maintaining the ocular surface homoeostasis, as it is increased after the initial fitting of contact lenses and post-overnight lid closure. BACKGROUND: hTERT has been shown to respond to cellular stress in neurodegenerative diseases and to enhance axonal regeneration after peripheral axotomy in an animal model. This work investigated whether the behaviour of hTERT in the tear film reflects ocular surface inflammation and neuronal changes in the presence of dry eye disease. METHODS: Flush tears were collected from 18 participants with dry eye disease (14 females, 4 males, mean age 34.7 ± 5.2 years) and from 18 healthy participants without dry eye disease (8 females, 10 males, mean age 31.9 ± 5.8 years). Dry eye disease status was defined using the TFOS DEWS II diagnostic criteria. hTERT levels in tears were measured using enzyme-linked immunosorbent assays. Confocal images were taken at the level of the subbasal nerve plexus at the central cornea and at the inferior whorl, and the densities of corneal immune cells were evaluated as well as corneal nerve morphology metrics using a fully automated technique (University of Manchester, United Kingdom). RESULTS: In participants with dry eye disease, hTERT levels were significantly higher compared to controls (median [interquartile range]: 434 [320-600] ng/ml, and 184 [42-390] ng/ml, respectively, p = 0.01). Increased nerve fibre width at the inferior whorl, was seen in those with dry eyes (0.0219 [0.0214-0.0236] mm/mm compared to controls 0.0217 [0.0207 0.0222] p < 0.001), but no significant differences were found in the density of corneal immune cells. CONCLUSIONS: hTERT levels were elevated in participants with dry eye disease, and this was accompanied by increased nerve thickness in the inferior cornea. The hTERT response may reflect the stress induced to the ocular surface and corneal nerves due to having dry eye disease.