Patient-centred outcomes following non-operative treatment or appendicectomy for uncomplicated acute appendicitis in children.

While non-operative treatment has emerged as an alternative to surgery for the treatment of uncomplicated acute appendicitis in children, comparative patient-centred outcomes are not well documented. We investigated these in a feasibility randomised trial. Of 57 randomised participants, data were available for 26. Compared with appendicectomy, children allocated to non-operative treatment reported higher short-term quality of life scores, shorter duration of requiring analgesia, more rapid return to normal activities and shorter parental absence from work. These preliminary data suggest differences exist in recovery profile and quality of life between these treatments that are important to measure in a larger RCT. Trial registration number is ISRCTN15830435.

Teaching cultural safety principles: optometry student perceptions.

CLINICAL RELEVANCE: Providing optometry learners with cultural safety training can improve patient safety and health outcomes among Indigenous Peoples. BACKGROUND: Healthcare practitioners require cultural safety training to provide safe eye care to Indigenous Peoples in Canada. Culturally safe care requires optometrists to critically reflect upon their unconscious biases and power differences that impact patient care. Informed by the cultural safety literature and working directly with learners, revisions were made to first and second-year optometry clinic experience courses in a Canadian Doctor of Optometry program. This descriptive study examined student feedback on curricular changes, focused on enhancing cultural safety. METHODS: An 8-item, anonymous, online survey was offered to all learners (n = 178) enrolled in clinic experience courses at in fall 2021 and winter 2022. The survey addressed student understanding of cultural safety, comfort with self-reflective activities, and course effectiveness in teaching patient-centred care. Six items used a 5-point Likert response scale. Descriptive statistics were analyzed (Wilcoxon and Wilcoxon-Pratt). Two open-ended items were analysed using content analysis for themes. RESULTS: Thirty-three surveys were completed. Overall respondents found the clinic experience courses provided effective training in cultural safety and were of professional value. Comfort engaging in self-reflective activities increased (before: mean response 4.0; after: 4.4), and students made connections with societal problems (overall mean 3.5) and with bias/power differential (overall mean 4.0). Suggested changes to support the learning objectives included increased clinic observation, scaffolding these topics in additional courses, and adding relevant literature (e.g. anti-racism) and guest speakers with Indigenous knowledge and experience. CONCLUSION: Optometry learners were favourable about the inclusion of cultural safety concepts in their clinic experience courses. Their feedback points to areas for improvement including deepening course content, and collaborating with Indigenous Peoples in content, course design, and cross-curricular scaffolding.

Conservative treatment for uncomplicated appendicitis in children: the CONTRACT feasibility study, including feasibility RCT.

BACKGROUND: Although non-operative treatment is known to be effective for the treatment of uncomplicated acute appendicitis in children, randomised trial data comparing important outcomes of non-operative treatment with those of appendicectomy are lacking. OBJECTIVES: The objectives were to ascertain the feasibility of conducting a multicentre randomised controlled trial comparing the clinical effectiveness and cost-effectiveness of a non-operative treatment pathway with appendicectomy for the treatment of uncomplicated acute appendicitis in children. DESIGN: This was a mixed-methods study, which included a feasibility randomised controlled trial, embedded and parallel qualitative and survey studies, a parallel health economic feasibility study and the development of a core outcome set. SETTING: This study was set in three specialist NHS paediatric surgical units in England. PARTICIPANTS: Children (aged 4-15 years) clinically diagnosed with uncomplicated acute appendicitis participated in the feasibility randomised controlled trial. Children, their families, recruiting clinicians and other health-care professionals involved in caring for children with appendicitis took part in the qualitative study. UK specialist paediatric surgeons took part in the survey. Specialist paediatric surgeons, adult general surgeons who treat children, and children and young people who previously had appendicitis, along with their families, took part in the development of the core outcome set. INTERVENTIONS: Participants in the feasibility randomised controlled trial were randomised to a non-operative treatment pathway (broad-spectrum antibiotics and active observation) or appendicectomy. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of eligible patients recruited to the feasibility trial. DATA SOURCES: Data were sourced from NHS case notes, questionnaire responses, transcribed audio-recordings of recruitment discussions and qualitative interviews. RESULTS: Overall, 50% (95% confidence interval 40% to 59%) of 115 eligible patients approached about the trial agreed to participate and were randomised. There was high acceptance of randomisation and good adherence to trial procedures and follow-up (follow-up rates of 89%, 85% and 85% at 6 weeks, 3 months and 6 months, respectively). More participants had perforated appendicitis than had been anticipated. Qualitative work enabled us to communicate about the trial effectively with patients and families, to design and deliver bespoke training to optimise recruitment and to understand how to optimise the design and delivery of a future trial. The health economic study indicated that the main cost drivers are the ward stay cost and the cost of the operation; it has also informed quality-of-life assessment methods for future work. A core outcome set for the treatment of uncomplicated acute appendicitis in children and young people was developed, containing 14 outcomes. There is adequate surgeon interest to justify proceeding to an effectiveness trial, with 51% of those surveyed expressing a willingness to recruit with an unchanged trial protocol. LIMITATIONS: Because the feasibility randomised controlled trial was performed in only three centres, successful recruitment across a larger number of sites cannot be guaranteed. However, the qualitative work has informed a bespoke training package to facilitate this. Although survey results suggest adequate clinician interest to make a larger trial possible, actual participation may differ, and equipoise may have changed over time. CONCLUSIONS: A future effectiveness trial is feasible, following limited additional preparation, to establish appropriate outcome measures and case identification. It is recommended to include a limited package of qualitative work to optimise recruitment, in particular at new centres. FUTURE WORK: Prior to proceeding to an effectiveness trial, there is a need to develop a robust method for distinguishing children with uncomplicated acute appendicitis from those with more advanced appendicitis, and to reach agreement on a primary outcome measure and effect size that is acceptable to all stakeholder groups involved. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15830435. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 10. See the NIHR Journals Library website for further project information.

Appendicitis is usually treated with an operation to remove the appendix. But we have learned, from other research, that some children with appendicitis may not need an operation, and could be treated with antibiotics instead. To find out how these two different treatments compare with one another, we need to do a big study. First, though, we need to see if doing that kind of study would even be possible (or 'feasible'). We carried out a feasibility study that had several parts. First, we did a small study with children who had appendicitis, whereby children were randomly allocated to have either antibiotics or an operation, with an equal chance of having either treatment. Second, we asked parents and health-care staff about why they wanted, or did not want, to take part in that small study. This helped us to understand how to make a bigger future study as acceptable as possible to children, families and surgeons. Third, we asked parents, patients and surgeons what they think are the most important things ­ or 'outcomes' ­ we should look at in future research on children who have appendicitis. From that, we developed a list of outcomes that should be included in our future big study, so we can be certain that the research we do is likely to help parents and surgeons. Overall, we established that a future big study is feasible and we have plenty of information to help us with how to plan it best, so that it has the greatest possible chance of success. We were also guided in all of these steps of the research by a group of parents, children and young people, some of whom had appendicitis and some of whom did not.

CONservative TReatment of Appendicitis in Children: a randomised controlled feasibility Trial (CONTRACT).

OBJECTIVE: To establish the feasibility of a multicentre randomised controlled trial to assess the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy in children with uncomplicated acute appendicitis. DESIGN: Feasibility randomised controlled trial with embedded qualitative study to inform recruiter training to optimise recruitment and the design of a future definitive trial. SETTING: Three specialist paediatric surgery centres in the UK. PATIENTS: Children (aged 4-15 years) with a clinical diagnosis of uncomplicated acute appendicitis. INTERVENTIONS: Appendicectomy or a non-operative treatment pathway (comprising broad-spectrum antibiotics and active observation). MAIN OUTCOME MEASURES: Primary outcome measure was the proportion of eligible patients recruited. Secondary outcomes evaluated adherence to interventions, data collection during follow-up, safety of treatment pathways and clinical course. RESULTS: Fifty per cent of eligible participants (95% CI 40 to 59) approached about the trial agreed to participate and were randomised. Repeated bespoke recruiter training was associated with an increase in recruitment rate over the course of the trial from 38% to 72%. There was high acceptance of randomisation, good patient and surgeon adherence to trial procedures and satisfactory completion of follow-up. Although more participants had perforated appendicitis than had been anticipated, treatment pathways were found to be safe and adverse event profiles acceptable. CONCLUSION: Recruitment to a randomised controlled trial examining the effectiveness and cost-effectiveness of a non-operative treatment pathway compared with appendicectomy for the treatment of uncomplicated acute appendicitis in children is feasible. TRIAL REGISTRATION NUMBER: ISRCTN15830435.

Geographic distribution of corneal staining in symptomatic dry eye.

PURPOSE: To describe the geographic distribution of corneal fluorescein staining across the five corneal zones, among non contact lens wearers who report symptoms of dry eye and determine which corneal zone most frequently exhibited the worst staining. METHODS: Prior studies conducted at the Centre for Ocular Research & Education, Canada, were reviewed for inclusion in the analysis. Each study assessed dry eye symptoms using OSDI and also assessed corneal fluorescein staining in five corneal zones. For each subject, the corneal zones were ranked 1-5 according to their relative staining grade, Rank-1 representing the highest grade. RESULTS: Data from 13 studies and 368 subjects were included. The total number of zones assigned Rank-1 (worst) staining was 449 (across 264 subjects). The inferior zone had the most Rank-1 counts of all zones at 193/43%, which involved 52.5% of all subjects. The nasal zone had 77/17% involving 20.9% of subjects, followed by the temporal (69/15.5%, 18.8% subjects) and superior zones (63/14%, 17.1% subjects). The central zone had the lowest count of Rank-1 designations, at only 47/10.5%, involving 12.8% of subjects. Bayesian analysis was used to generate distributions of the credible proportions of subjects likely to present with staining in a single peripheral zone, with or without central zone staining. It illustrated that staining in a peripheral zone without central staining was more credible. The worst single zone staining was most likely to present in the inferior zone (67.9%), followed by the nasal zone (11.3%), the superior zone (9.2%), and the temporal zone (5.6%). CONCLUSION: In the presence of dry eye symptoms, the inferior zone typically presents the most severe grade of corneal staining, more likely without central zone staining. This knowledge is valuable when developing a strategy to treat dry eye signs, as the inferior corneal zone has the highest grade of staining thus has the potential to exhibit the greatest reduction in staining post-treatment.

Health economics and quality of life in a feasibility RCT of paediatric acute appendicitis: a protocol study.

BACKGROUND: Acute appendicitis is one of the most common acute surgical emergencies in children and accounts for an annual cost of approximately £50 million to the National Health Service. Investigating alternative treatment options offers the best prospect of enhancing the quality of care for patients and potential opportunities for cost savings through better allocative efficiency. A feasibility randomised controlled trial (RCT) comparing a non-operative treatment pathway with appendicectomy for children with acute uncomplicated appendicitis is underway (CONTRACT feasibility RCT). AIMS: The prime objective of this economic substudy conducted alongside the CONTRACT feasibility RCT is to better understand and assess: (1) cost data collection tools and cost drivers by identifying patients' pathways and (2) patient quality of life by assessing alternative paediatric health-related quality of life (HRQoL) instruments. Outcomes from this study will inform a future efficacy RCT assessing the effectiveness and cost-effectiveness of non-operative treatment pathway for the treatment of acute uncomplicated appendicitis in children. METHODS: The economic substudy will use individual-level data and will be conducted from the health system perspective over the study's 6-month follow-up period. Microcosting will include health resource and service use, while potential benefits acquired will be measured using the HRQoL measures, Child Health Utility 9D (CHU-9D) and Euroqol-5 dimensions and 5 levels (EQ-5D-5L). We will assess the appropriateness of using the cost per quality-adjusted life year framework in the future RCT, as well as testing and identifying the most suitable HRQoL instrument. CONCLUSIONS: The outcomes of the investigational economic substudy will be used to inform the design of our future definitive RCT. However, the result from this economic study will also provide a detailed description and account of the issues inherent in paediatric Economic Evaluations Alongside Clinical Trials with an emphasis on costing methods of interventions taking place in secondary care settings. TRIAL REGISTRATION NUMBER: ISRCTN1583043.

Mixed Model Analysis of Between-Subject Variability in Overnight Corneal Swelling and Deswelling With Silicone Hydrogel Lenses.

Purpose: To model between subject variability of corneal swelling (CS) and deswelling after overnight wear of silicone hydrogel (SiHy) contact lenses. Methods: A total of 29 neophyte subjects wore 12 SiHy lenses with central transmissibility range of 31 to 211 Dk/t units on separate nights, in random order, and on one eye only. The contralateral eye served as the control. Central corneal thickness was measured using digital optical pachymetry before lens insertion, immediately after lens removal on waking, then 20, 40 minutes, 1, 2, and 3 hours later. Mixed modelling was conducted for simultaneous analysis of group and between-subject effects of CS and deswelling. Results: The best model for overnight CS versus Dk/t was linear with a random intercept showing constant between-subject differences in CS for different Dk/t values. The best fit for corneal deswelling versus time was a curvilinear random intercept and random slope model. About 90% of the total between-subject deswelling variance in either lens or control eyes was due to the intercept variability with much less (∼10%) being due to the variability of the individual deswelling rate (slope). Subject age, sex, and ametropia were not predictors of individual corneal swelling in the swelling versus Dk/t analysis. Age, however, was a significant (inverse) predictor of the rate of corneal deswelling, only in lens-wearing eyes. Conclusions: A large proportion of variability in corneal swelling is because of subject-specific differences in corneal response to hypoxia. This shows that "low swellers" and "high swellers" actually do exist.

CONTRACT Study - CONservative TReatment of Appendicitis in Children (feasibility): study protocol for a randomised controlled Trial.

BACKGROUND: Currently, the routine treatment for acute appendicitis in the United Kingdom is an appendicectomy. However, there is increasing scientific interest and research into non-operative treatment of appendicitis in adults and children. While a number of studies have investigated non-operative treatment of appendicitis in adults, this research cannot be applied to the paediatric population. Ultimately, we aim to perform a UK-based multicentre randomised controlled trial (RCT) to test the clinical and cost effectiveness of non-operative treatment of acute uncomplicated appendicitis in children, as compared with appendicectomy. First, we will undertake a feasibility study to assess the feasibility of performing such a trial. METHODS/DESIGN: The study involves a feasibility RCT with a nested qualitative research to optimise recruitment as well as a health economic substudy. Children (aged 4-15 years inclusive) diagnosed with acute uncomplicated appendicitis that would normally be treated with an appendicectomy are eligible for the RCT. Exclusion criteria include clinical/radiological suspicion of perforated appendicitis, appendix mass or previous non-operative treatment of appendicitis. Participants will be randomised into one of two arms. Participants in the intervention arm are treated with antibiotics and regular clinical assessment to ensure clinical improvement. Participants in the control arm will receive appendicectomy. Randomisation will be minimised by age, sex, duration of symptoms and centre. Children and families who are approached for the RCT will be invited to participate in the embedded qualitative substudy, which includes recording of recruitment consultants and subsequent interviews with participants and non-participants and their families and recruiters. Analyses of these will inform interventions to optimise recruitment. The main study outcomes include recruitment rate (primary outcome), identification of strategies to optimise recruitment, performance of trial treatment pathways, clinical outcomes and safety of non-operative treatment. We have involved children, young people and parents in study design and delivery. DISCUSSION: In this study we will explore the feasibility of performing a full efficacy RCT comparing non-operative treatment with appendicectomy in children with acute uncomplicated appendicitis. Factors determining success of the present study include recruitment rate, safety of non-operative treatment and adequate interest in the future RCT. Ultimately this feasibility study will form the foundation of the main RCT and reinforce its design. TRIAL REGISTRATION: ISRCTN15830435 . Registered on 8 February 2017.

Relationship between vessel diameter and depth measurements within the limbus using ultra-high resolution optical coherence tomography / Relación entre las mediciones del diámetro y la profundidad de vasos sanguíneos en el limbo obtenidas mediante tomografía de coherencia óptica de ultra-alta resolución

Purpose: To establish a relationship between the diameter and depth position of vessels in the superior and inferior corneo-scleral limbus using ultra-high resolution optical coherence tomography (UHR-OCT). Methods: Volumetric OCT images of the superior and inferior limbus were acquired from 14 healthy subjects with a research-grade UHR-OCT system. Differences in vessel diameter and depth between superior and inferior limbus were analyzed using repeated measured ANOVA in SPSS and R. Results: The mean (± SD) superior and inferior diameters were 29 ± 18μm and 24 ± 18μm respectively, and the mean (± SD) superior and inferior depths were 177 ± 109μm and 207 ± 132μm respectively. The superior limbal vessels were larger than the inferior ones (RM-ANOVA, p = 0.004), and the inferior limbal vessels were deeper than the superior vessels (RM-ANOVA, p = 0.041). There was a positive linear association between limbal vessel depth and size within the superior and inferior limbus with Pearson correlation coefficients of 0.803 and 0.754, respectively. Conclusion: This study demonstrated that the UHR-OCT was capable of imaging morphometric characteristics such as the size and depth of vessels in the limbus. The results of this study suggest a difference in the size and depth of vessels across different positions of the limbus, which may be indicative of adaptations to chronic hypoxia caused by the covering of the superior limbus by the upper eyelid. UHR-OCT may be a useful tool to evaluate the effect of contact lenses on the microvascular properties within the limbus (AU)

Objetivo: Establecer la relación entre el diámetro y la profundidad de los vasos del limbo esclerocorneal superior e inferior mediante tomografía de coherencia óptica de ultra-alta resolución (UHR-OCT). Métodos: Se adquirieron 256 conjuntos de imágenes del limbo superior e inferior en 14 sujetos, mediante UHR-OCT. Se analizaron las diferencias en cuanto a diámetro y profundidad del vaso entre el limbo superior e inferior utilizando ANOVA de medidas repetidas en SPSS y R. Resultados: Los diámetros medios (± DE) superior e inferior fueron de 29μm ± 18μm y 24μm ± 18μm respectivamente, y las profundidades medias (± DE) superior e inferior fueron de 177μm ± 109μm y 207m ± 132μm respectivamente. Los vasos del limbo superior fueron de mayor tamaño que los del limbo inferior (RM-ANOVA, p = 0,004), y los vasos del limbo inferior fueron más profundos que los del limbo superior (RM-ANOVA, p = 0,041). Se produjo una asociación lineal positiva entre la profundidad y el tamaño del vaso dentro del limbo superior e inferior, con coeficientes de correlación de Pearson de 0,803 y 0,754, respectivamente. Conclusión: Este estudio demuestra que UHR-OCT fue capaz de obtener imágenes de las características morfométricas tales como tamaño y profundidad de los vasos del limbo. Los resultados de este estudio sugieren una diferencia de tamaño y profundidad de los vasos en las diferentes posiciones del limbo, que puede ser indicativa de adaptaciones a la hipoxia crónica causada por el cubrimiento del limbo superior por parte del párpado superior. UHR-OCT puede ser una herramienta de utilidad para evaluar el efecto de las lentes de contacto sobre las propiedades microvasculares del limbo esclerocorneal (AU)

Corneal, Conjunctival effects and blood flow changes related to silicone hydrogel lens wear and their correlations with end of day comfort.

PURPOSE: First, to examine how wearing high and low modulus lenses with two different base curves affected lens fit, and the corneal tissue and bulbar conjunctival vascular tissue (bulbar redness and blood velocity). Secondly, to quantify the associations between these baseline and outcome variables and the third purpose was to correlate these variables with end of day comfort. METHODS: Thirty participants wore higher (PureVision (PV) 8.3, 8.6) and lower (Acuvue Advance (AA) 8.3, 8.7) modulus silicone hydrogel lenses for two weeks on a daily wear basis. Lens fitting characteristics were examined. Corneal epithelial thickness was measured and the cornea and conjunctiva were assessed. RBC velocity was estimated from high magnification bulbar conjunctival images. Subjective comfort/dryness was reported by participants using visual analogue scales. RESULTS: AA lenses were rated the most comfortable (ANOVA, p=0.041). The least movement was while using the AA 8.3 base curve lens (Tukey p=0.028). Steep AA and PV lenses showed significantly higher conjunctival staining at the 2 week visit (ANOVA, p=0.029). There was a significant decrease in RBC velocity with both steeper AA lenses vs PV lenses (Tukey, p=0.001). Comparing baseline and 2 week visits, there was a significant negative correlation for the PV 8.3 between comfort and superior bulbar staining (r=-0.53). For both the PV 8.3 and AA 8.3 reduced RBC velocity was correlated with dryness (r=0.61 and r=0.91, respectively). CONCLUSIONS: Physical differences in contact lenses affect structural and vascular functional aspects of the ocular surface and these may be associated with symptoms of dryness.

Relationship between vessel diameter and depth measurements within the limbus using ultra-high resolution optical coherence tomography.

PURPOSE: To establish a relationship between the diameter and depth position of vessels in the superior and inferior corneo-scleral limbus using ultra-high resolution optical coherence tomography (UHR-OCT). METHODS: Volumetric OCT images of the superior and inferior limbus were acquired from 14 healthy subjects with a research-grade UHR-OCT system. Differences in vessel diameter and depth between superior and inferior limbus were analyzed using repeated measured ANOVA in SPSS and R. RESULTS: The mean (± SD) superior and inferior diameters were 29±18µm and 24±18µm respectively, and the mean (± SD) superior and inferior depths were 177±109µm and 207±132µm respectively. The superior limbal vessels were larger than the inferior ones (RM-ANOVA, p=0.004), and the inferior limbal vessels were deeper than the superior vessels (RM-ANOVA, p=0.041). There was a positive linear association between limbal vessel depth and size within the superior and inferior limbus with Pearson correlation coefficients of 0.803 and 0.754, respectively. CONCLUSION: This study demonstrated that the UHR-OCT was capable of imaging morphometric characteristics such as the size and depth of vessels in the limbus. The results of this study suggest a difference in the size and depth of vessels across different positions of the limbus, which may be indicative of adaptations to chronic hypoxia caused by the covering of the superior limbus by the upper eyelid. UHR-OCT may be a useful tool to evaluate the effect of contact lenses on the microvascular properties within the limbus.

Validity and Repeatability of a Novel Dynamic Visual Acuity System.

PURPOSE: In many sports, athletes rely on visual information from the environment to perform. Some literature suggests athletes have superior visual abilities to non-athletes, particularly on tasks representative of the visual demands of their sport, such as dynamic acuity, eye movement accuracy and speed, and peripheral vision. Other literature suggests there is no difference between athletes and non-athletes, at least when standard clinical assessments are employed. A limitation of the literature is that almost none of the research has been conducted with standardized, validated tools. This is partly caused by a lack of readily available tools to measure tasks representative of the visual demands of sport, and available tests have typically not been validated against current clinical standards. The purpose of this study is to examine the validity and repeatability of a novel visual acuity system (moV&; V&MP Vision Suite) recently developed in the Vision & Motor Performance Lab (V&MP). moV& permits the measurement of many visual function parameters including dynamic visual acuity with predictable, random, and jittering target motion. METHODS: Twenty-five participants attended two study visits, separated by a minimum of 2 weeks. At each visit, static and dynamic visual acuity was measured using Snellen, ETDRS, and moV& charts. Static visual acuities were compared to determine the validity of moV&, and both static and dynamic visual acuities were compared between visits to determine the test-retest repeatability. RESULTS: moV& static visual acuities are clinically similar to visual acuities measured with the ETDRS chart (moV&, -0.09 ± 0.13; ETDRS, -0.03 ± 0.11, concordance correlation coefficient 0.726). Additionally, all static, dynamic, and jitter visual acuities demonstrate good test-retest repeatability (Lin's concordance correlation coefficient range 0.451-0.953). CONCLUSIONS: moV& provides good clinical measures of static visual acuity that are comparable to both Snellen and ETDRS measures. Dynamic visual acuity measures demonstrate good test-retest repeatability.

Optical edge effects create conjunctival indentation thickness artefacts.

PURPOSE: Conjunctival compression observed in ultrahigh resolution optical coherence tomography (UHR-OCT) images of contact lens edges could be actual tissue alteration, may be an optical artefact arising from the difference between the refractive indexes of the lens material and the conjunctival tissue, or could be a combination of the two. The purpose of this study is to image the artefact with contact lenses on a non-biological (non-indentable) medium and to determine the origins of the observed conjunctival compression. METHODS: Two-dimensional cross-sectional images of the edges of a selection of marketed silicone hydrogel and hydrogel lenses (refractive index ranging from 1.40 to 1.43) were acquired with a research grade UHR-OCT system. The lenses were placed on three continuous surfaces, a glass sphere (refractive index n = 1.52), a rigid contact lens (n = 1.376) and the cornea of a healthy human subject (average n = 1.376). The displacement observed was analysed using ImageJ. RESULTS: The observed optical displacement ranged between 5.39(0.06) µm with Acuvue Advance and 11.99(0.18) µm with Air Optix Night & Day when the lens was imaged on the glass reference sphere. Similarly, on a rigid contact lens displacement ranged between 5.51(0.03) and 9.72(0.12) µm. Displacement was also observed when the lenses were imaged on the human conjunctiva and ranged from 6.49(0.80) µm for the 1-day Acuvue Moist to 17.4(0.22) µm for the Pure Vision contact lens. CONCLUSIONS: An optical displacement artefact was observed when imaging a contact lens on two rigid continuous surfaces with UHR-OCT where compression or indentation of the surface could not have been a factor. Contact lenses imaged in situ also exhibited displacement at the intersection of the contact lens edge and the conjunctiva, likely a manifestation of both the artefact and compression of the conjunctiva.

Pupil scaling for the estimation of aberrations in natural pupils.

PURPOSE: This study aimed to validate the mathematical Zernike pupil size scaling from bigger pupils to smaller pupils, and vice versa, by comparing the estimates of the Zernike coefficients with corresponding clinical measurements obtained at different pupil sizes. METHODS: The i.Profiler Plus (Carl Zeiss Vision, Inc, USA) was used to obtain measures of wavefront aberrations for two pupil sizes (3 mm and the maximum natural pupil size) from the right eyes of 28 visually normal subjects (mean [±SD] age, 57 [±7] years) whose maximum pupil size was greater than or equal to 5 mm without pharmacological dilation. Zernike coefficients were estimated for a 3-mm pupil size scaling down from the measured data of the maximum natural pupil size and, similarly, for the maximum pupil size scaling up from the measured data of the 3-mm pupil. RESULTS: The differences between the estimated and measured values were not significantly different (repeated-measures analysis of variance; p > 0.05) over the range of pupil sizes examined, irrespective of whether the estimates were made by scaling up from a small pupil or scaling down from a large pupil. However, the difference between the measured and estimated coefficients was more variable and less systematic when scaling to a larger pupil size when compared with scaling to a smaller pupil size. CONCLUSIONS: Estimation of ocular wavefront aberration coefficients either scaling down from large to smaller pupils or scaling up from smaller to large pupils provides estimates that are not significantly different from clinically measured values. However, when scaling up to a larger pupil size, the estimates are more variable. These findings have implications for pupil scaling on an individual basis, such as in cases of refractive surgery or when using pupil scaling to examine a clinical cohort.

Are the fluctuations in dynamic anterior surface aberrations of the human eye chaotic?

The purpose of the study is to measure chaos in dynamic anterior surface aberrations and examine how it varies between the eyes of an individual. Noninvasive tear breakup time and dynamic corneal surface aberrations were measured for two open-eye intervals of 15 s. The maximal Lyapunov exponent (MLE) was calculated to test the nature of the fluctuations of the dynamic anterior surface aberrations. The average MLE for total higher-order aberration (HOA) was found to be small (+0.0102±0.0072) µm/s. No significant difference in MLE was found between the eyes for HOA (t-test; p=0.131). Data analysis was carried out for individual Zernike coefficients, including vertical prism as it gives a direct measure of the thickness of the tear film over time. The results show that the amount of chaos was small for each Zernike coefficient and not significantly correlated between the eyes.

In vivo volumetric imaging of the human corneo-scleral limbus with spectral domain OCT.

The limbus is the structurally rich transitional region of tissue between the cornea on one side, and the sclera and conjunctiva on the other. This zone, among other things, contains nerves passing to the cornea, blood and lymph vasculature for oxygen and nutrient delivery and for waste, CO(2) removal and drainage of the aqueous humour. In addition, the limbus contains stem cells responsible for the existence and healing of the corneal epithelium. Here we present 3D images of the healthy human limbus, acquired in vivo with a spectral domain optical coherence tomography system operating at 1060nm. Cross-sectional and volumetric images were acquired from temporal and nasal locations in the human limbus with ~3µm x 18µm (axial x lateral) resolution in biological tissue at the rate of 92,000 A-scans/s. The imaging enabled detailed mapping of the corneo-scleral tissue morphology, and visualization of structural details such as the Vogt palisades, the blood and lymph vasculature including the Schlemm's canal and the trabecular meshwork, as well as corneal nerve fiber bundles. Non-invasive, volumetric, high resolution imaging reveals fine details of the normal human limbal structure, and promises to provide invaluable information about its changes in health and disease as well as during and after corneal surgery.

Grading bulbar redness using cross-calibrated clinical grading scales.

PURPOSE: To determine the between-scale agreement of grading estimates obtained with cross-calibrated McMonnies/Chapman-Davies (MC-D), Institute for Eye Research (IER), Efron, and Validated Bulbar Redness (VBR) grading scales. METHODS: Modified reference images of each grading scale were positioned on a desk according to their perceived redness (within a 0 to 100 range) as determined in a previous psychophysical scaling experiment. Ten observers were asked to represent perceived bulbar redness of 16 sample images by placing them, one at a time, relative to the reference images of each scale. Only 0 and 100 were marked on the scale, but not the numerical position of the reference images. Perceived redness was taken as the measured position of the placed image from 0 and was averaged across observers. RESULTS: Overall, perceived redness depended on the sample image and the reference scale used (repeated measures ANOVA; P = 0.0008); six sample images had a perceived redness that was significantly different between at least two of the scales. Between-scale correlation coefficients of concordance ranged from 0.93 (IER vs. Efron) to 0.98 (VBR vs. Efron). Between-scale coefficients of repeatability ranged from five units (IER vs. VBR) to eight units (IER vs. Efron) of the 0 to 100 range. CONCLUSIONS: The use of cross-calibrated reference grades for bulbar redness grading scales allows comparison of grading estimates obtained with different scales. Perceived redness is dependent on the dynamic range of the reference images of the scale, with redness estimates generally being found to be higher for scales with a shorter dynamic range.

Outcomes of wavefront-guided laser in situ keratomileusis for hyperopia.

PURPOSE: To determine the impact of wavefront-guided laser in situ keratomileusis (LASIK) for hyperopia on corrected distance visual acuity (CDVA), contrast sensitivity, and higher-order aberrations (HOAs). SETTING: Centre for Contact Lens Research, University of Waterloo, Waterloo, Ontario, Canada. DESIGN: Case series. METHODS: This study comprised patients who had LASIK for hyperopia. The HOAs up to the 4th order (5.0 mm pupil) in right eyes were analyzed. RESULTS: The study enrolled 31 patients. The preoperative mean values were sphere, +2.60 diopters (D) ± 1.15 (SD) (range +1.00 to +5.00 D); astigmatism, -0.87 ± 0.74 D (range 0.00 to -3.75 D); and spherical equivalent (SE), +2.16 ± 1.00 D (range +0.63 to +4.50 D). The postoperative refractive SE was within ±0.50 D in 71.0% of eyes. The uncorrected distance visual acuity was 20/20 or better in 87.2% of eyes. There was no significant change in CDVA or contrast sensitivity (all P>.05). There was a significant change in Zernike coefficients Z(0,4), Z(-1,3), Z(-3,3), and Z(3,3) (range of mean absolute change ± SEM: 0.092 ± 0.013 µm to 0.208 ± 0.018 µm; all P<.001). Coefficients Z(-1,3) and Z(3,3) increased and Z(0,4) and Z(-3,3) decreased in magnitude; each had a reversal of sign. The only significant postoperative association was between low-contrast CDVA and Z(0,4) (r=0.617, P<.001). CONCLUSIONS: Low-contrast CDVA after LASIK surgery for hyperopia was correlated with Z(0,4). There were no significant changes in CDVA or contrast sensitivity. The relative risk for losing low-contrast CDVA increased if more than 1 Zernike term had a sign change.

In vivo volumetric imaging of the human upper eyelid with ultrahigh-resolution optical coherence tomography.

The upper eyelid is a biological tissue with complex structure, essential for the maintenance of an optically clear ocular surface due to its physical (blinking) effect. The Meibomian glands (MGs) are structures that lie beneath the surface of the inner eyelid and are partially responsible for the production of the superficial oily layer of the tear film. The MGs are only superficially visible under magnification when the eyelid is everted. We present for the first time in vivo 3-D images of healthy and inflamed human MGs. Tomograms were acquired from the tarsal plate of everted human eyelids with a 1060-nm ultrahigh-resolution optical coherence tomography (UHOCT) system, with approximately 3 microm x 10 microm (axial x lateral) resolution in biological tissue at the rate of 91,911 A-scans/s. Comparison with histology shows that the UHOCT images reveal a spatial distribution of structures that appear to correspond with the MGs' acini and ducts (in healthy subjects), and accumulation of heterogeneous, highly scattering biological material and clear fluids in the visibly blocked glands. Noninvasive, volumetric high-resolution morphological imaging of the human tarsal area could have a significant impact in the clinical diagnosis of inflammatory and noninflammatory lid pathologies.

Swelling of the human cornea revealed by high-speed, ultrahigh-resolution optical coherence tomography.

PURPOSE: To evaluate the change in thickness of the anterior, stromal, and posterior corneal laminae in response to hypoxia-induced corneal swelling, by means of ultrahigh-resolution optical coherence tomography (UHR-OCT). METHODS: A UHR-OCT system, operating in the 1060-nm range, was used to acquire in vivo cross-sectional images of human cornea with a 3.2x10-microm (axial x lateral) resolution in corneal tissue. Corneal edema was induced by inserting a thick, positive-powered, soft contact lens, over which the eye was closed and patched for 3 hours. Tomograms were acquired from eight non-contact-lens wearers. Baseline images were obtained before inducing corneal edema, immediately after removal of the patch and the lens, and then every 15 minutes for approximately 2 hours. All images were postprocessed with a segmentation algorithm to identify the laminae visible in the image. The apical thickness of the laminae (epithelium [EPI], epithelial-Bowman's membrane [Ep-BM] complex, stroma, and endothelial-Descemet's membrane [En-DM] complex) were determined at each time interval. RESULTS: There was an interaction between time after removal of the hypoxic stimulus and deswelling of the layers (RM-ANOVA; P<0.001). The epithelial and stromal thickness reduced significantly with time (P=0.001; P<0.001, respectively), whereas the Ep-BM and En-DM complexes did not (P>0.50). All layers except the En-DM complex exhibited a biphasic pattern of recovery. CONCLUSIONS: UHR-OCT showed regional differences in swelling due to hypoxic provocation. On removal of the hypoxic stimulus, the rate of recovery varied between layers, and all layers except the En-DM complex exhibited a biphasic recovery.