[Molecular pathological analysis through the ages]. / Molekularpathologische Untersuchungen im Wandel der Zeit.

BACKGROUND: Molecular pathological examinations of tumor samples encompass a wide range of diagnostic analyses. Especially in recent years, numerous new biomarkers have come to the forefront-the analysis of which is crucial for therapy decisions. OBJECTIVES: Within the field of molecular pathology, the demands of next generation sequencing (NGS)-based requirements have experienced massive growth in recent years. To meet this demand, methods are constantly being adapted and further developed. The following sections aim to illuminate how this trend arises and which analyses are gaining importance. METHODS: The article provides an overview of the essential nucleic acid-based analysis techniques in the field of massive parallel sequencing. Terms such as DNA- and RNA-based techniques, as well as the associated analysis methods, are described, particularly with regard to their use in routine molecular pathological diagnostics. RESULTS: The breadth of genomic sequencing has been steadily growing in recent years, particularly due to the increasing relevance of personalized medicine, along with the rising approvals of targeted therapeutics. This necessitates, among other things, the analysis of new biomarkers. The diagnostics as part of interdisciplinary molecular tumor boards (MTB) are now based on large gene panels (> 1 megabase). Furthermore, through the "Modellvorhaben Genomsequenzierung" § 64e, whole exome or whole genome sequencing has been made available for oncological patients. Given these developments, it is evident that future analyses will require the integration of additional omics fields, such as whole transcriptome analysis, epigenomics, and proteomics. CONCLUSION: The challenges of personalized medicine along with the necessity of simultaneously assessing numerous new biomarkers require the implementation and execution of new techniques in molecular pathology whose complexity is steadily increasing.

Central versus peripheral thickness in the human cornea explained.

PURPOSE: The human cornea is thicker in the periphery than the center and it has been suggested that this must be due to greater numbers of lamellae in the peripheral corneal stroma. The purpose of this study was to use high-resolution ultrastructural imaging to determine if the greater thickness of the peripheral cornea is due to the presence of more lamellae or if there is some other anatomical explanation. METHODS: In this study, full thickness corneas from three human donors were processed for light microscopy (LM) and transmission electron microscopy (TEM). Images were taken in three distinct stromal regions (anterior, middle, and posterior) from the central and peripheral cornea. Stromal thickness was evaluated by LM while TEM was used to evaluate numbers and thicknesses of lamellae, mean collagen fibril diameter, and mean collagen fibril density. RESULTS: Mean stromal thickness was significantly thinner in the central (415 ± 34 µm) compared to the peripheral (536 ± 29 µm) cornea (P = 0.009). Numbers of lamellae were not significantly different between central (246 ± 14) and peripheral (251 ± 14) cornea. Average lamellar thickness was not different across all regions of the cornea, except for the peripheral posterior where the lamellae were approximately 50 % thicker (P < 0.05). Collagen fibril diameters were larger in the peripheral cornea by approximately 30 % when compared to the central cornea, in all regions (P < 0.01). CONCLUSIONS: This study shows that it is an increase peripheral posterior lamellar thickness, rather than an increase in the number of lamellae, that accounts for the increase in corneal stromal thickness in the periphery of the human cornea. While collagen fibril diameters are greater throughout the peripheral stroma, the lamellae in the mid and anterior peripheral stroma are not thicker than centrally.

First proficiency testing for NGS-based and combined NGS- and FISH-based detection of FGFR2 fusions in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma harbours druggable genetic lesions including FGFR2 gene fusions. Reliable and accurate detection of these fusions is becoming a critical component of the molecular work-up, but real-world data on the performance of fluorescence in situ hybridisation (FISH) and targeted RNA-based next-generation sequencing (NGS) are very limited. Bridging this gap, we report results of the first round robin test for FGFR2 fusions in cholangiocarcinoma and contextualise test data with genomic architecture. A cohort of 10 cholangiocarcinoma (4 fusion positive and 6 fusion negative) was tested by the Institute of Pathology, University Hospital Heidelberg, Germany. Data were validated by four academic pathology departments in Germany. Fusion-positive cases comprised FGFR2::BICC1, FGFR2::DBP, FGFR2::TRIM8, and FGFR2::ATE1 fusions. In a second step, a round robin test involving 21 academic and non-academic centres testing with RNA-based NGS approaches was carried out; five participants performed FISH testing in addition. Thirteen of 16 (81%) centres successfully passed the NGS only and 3 of 5 (60%) centres passed the combined NGS + FISH round robin test. Identified obstacles were bioinformatic pipelines not optimised for the detection of FGFR2 fusions and assays not capable of detecting unknown fusion partners. This study shows the benefit of targeted RNA-NGS for the detection of FGFR2 gene fusions. Due to the marked heterogeneity of the genomic architecture of these fusions, fusion partner agnostic (i.e. open) methodological approaches that are capable of identifying yet unknown fusion partners are superior. Furthermore, we highlight pitfalls in subsequent bioinformatic analysis and limitations of FISH-based tests.

Nonpolar Lipids Contribute to Midday Fogging During Scleral Lens Wear.

Purpose: To determine correlations between lipids in the fluid reservoir (FR) and the severity of midday fogging (MDF) in scleral lens (SL) wear. Methods: SL neophytes were recruited to wear custom SL for 4 days, examined after 8 hours on days 1 and 4. Lens vault and MDF were quantified from anterior segment optical coherence tomography (AS-OCT), and the FR was collected and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Relative abundance of lipids was compared to MDF scores using nonparametric correlation testing (Spearman rank). Ocular surface and SL fitting characteristics (lens vault, fitting curves) were likewise compared to MDF. Results: Thirteen participants (26 eyes, 69% female, 28 ± 9 years old) were included in this study. MDF severity after 8 hours of SL wear was 33 ± 29 units on day 1 and 28 ± 24 units on day 4 (r = .94; P < 0.01). Twelve samples were analyzed using LC-MS/MS, and a total of 170 distinct lipid species were detected. The lipid classes with greatest correlation to MDF were the wax esters (r = .73, P = 0.01), cholesteryl esters (r = .59; P = 0.049), and triacylglycerols (r = .64, P = 0.03). Polar lipids were observed abundantly in all samples. None of the measured ocular surface or fitting outcomes were correlated to MDF. Conclusions: Nonpolar lipids were the greatest contributors to MDF among these normal participants. Polar lipids may be due to cellular debris, although they do not appear contributory to MDF.

Anatomical and physiological considerations in scleral lens wear: Intraocular pressure.

Intraocular pressure (IOP) is maintained through complex and interrelated systems which control aqueous production and drainage, and it has been suggested that scleral lens (SL) wear may disrupt these vital homeostatic processes. This review provides an overview of anatomical and physiological processes that control IOP, identifies potential effects of SLs on these regulatory mechanisms, and examines studies that have attempted to quantify the effect of SLs on IOP. Lack of access to the cornea during SL wear makes accurate assessment of IOP challenging; therefore, a range of different assessment techniques and instruments have been employed to quantify IOP during and following SL wear. Some studies have evaluated IOP using standard techniques prior to lens application and following lens removal, or through a large central fenestration. Other studies have utilised instruments that facilitate assessment of IOP on the peripheral cornea or conjunctiva overlying the sclera (e.g. Schiotz, transpalpebral, and pneumatonometry). Two studies have recently evaluated changes in optic nerve structure during SL wear. Conflicting results have been reported on this topic, much of which examines changes in IOP in healthy subjects over limited periods of time. Currently, only a few studies have reported on long-term effects of SL wear on IOP in habitual SL wearers (after lens removal). Future research in this area must not only consider the fact that ocular conditions treated with SLs may potentially alter corneal biomechanical properties which can influence IOP, but also that these properties may be further altered by SL wear. Monitoring other risk factors for glaucoma (permanent alterations in optic nerve physiology, visual field defects) could provide a more comprehensive assessment of potentially increased risk of glaucomatous optic neuropathy due to SL wear. Ongoing clinical assessment of optic nerve structure and function is advisable in patients at risk for glaucoma who require SLs.

Impact of recentrifugation of blood collection tubes on chemistry and immunochemistry analytes after 24 and 72 hours of refrigerated storage on the Roche Cobas 8000 platform.

BACKGROUND: We discovered that blood collection tubes (BCTs) were inadvertently recentrifuged due to improper placement on our automated preanalytical system. This study was undertaken to determine the impact of recentrifugation of blood specimens collected in serum separator (SSTs) and plasma separator (PSTs) tubes after refrigerated storage for 24 and 72 h on the concentrations of chemistry and immunochemistry analytes. METHODS: Blood was collected from 20 volunteers in SSTs and PSTs, centrifuged, and 36 chemistry and 14 immunochemistry analytes were measured at baseline in single-centrifuged tubes on a Roche Cobas 8000 chemistry platform. After baseline testing, the BCTs were refrigerated for 24 or 72 h, recentrifuged and retested. The results were compared to the single-centrifuged tubes for statistical significance. RESULTS: Recentrifugation of BCTs after 24 or 72 h of refrigerated storage showed statistically significant increases in lactate dehydrogenase activity and potassium concentration and statistically significant decreases in glucose (except in SSTs after 24 h of refrigerated storage) and CO2 concentration, but no significant differences in immunochemistry analyte concentrations. CONCLUSION: It may be safe to report most routine chemistry and immunochemistry analyte concentrations from recentrifuged SSTs and PSTs on the Roche Cobas 8000, which may save time and costs associated with recollection and retesting.

Ocular and Nonocular Adverse Events during 3 Years of Soft Contact Lens Wear in Children.

SIGNIFICANCE: Children are being fitted at younger ages with soft contact lenses for myopia control. This 3-year investigation of adverse events related to contact lens wear in 7- to 11-year-old participants helps optometrists understand what to expect when fitting children with soft contact lenses. PURPOSE: The purpose of this article is to report the frequency and type of ocular and nonocular adverse events related to soft contact lens wear in children. METHODS: Seven- to 11-year-old children wore soft contact lenses for 3 years. Adverse events were defined by a slit-lamp examination finding of grade 3 or worse; parental report of a clinically meaningful change (determined by the examiner) in eyes, vision, or health; or a clinically meaningful response (determined by examiner) to a symptom checklist. Adverse events were categorized and reported by examiners and finalized by the Executive Committee. The presence or absence of an infiltrate and a list of diagnoses was determined at the conclusion of the study. RESULTS: The 294 participants wore their contact lenses 73.0 ± 26.5 hours per week, and 220 (74.8%) encountered at least 1 adverse event. Of the 432 adverse events, 75.2% were ocular, and 24.8% were nonocular. Contact lens wear was probably or definitely related to 60.6% of the ocular and 2.8% of the nonocular adverse events. None of the ocular adverse events were serious or severe or caused permanent contact lens discontinuation. The corneal infiltrate incidence was 185 cases per 10,000 patient-years of wear (95% confidence interval, 110 to 294). The incidence of moderate ocular adverse events that were definitely or probably related to contact lens wear was 405 cases per 10,000 patient-years of wear (95% confidence interval, 286 to 557). CONCLUSIONS: The adverse events experienced by 7- to 11-year-old myopic children rarely required meaningful treatment and never led to permanent discontinuation of contact lens wear or loss of best-corrected vision.

A comparison of subjective and objective conjunctival hyperaemia grading with AOS® Anterior software.

CLINICAL RELEVANCE: This study evaluates a commercially available conjunctival hyperaemia grading system, providing validation of an important tool for ocular surface research and clinical trials. BACKGROUND: Bulbar conjunctival hyperaemia is a sign of ocular surface inflammation, and proper measurement is essential to clinical care and trials. The aim of this study was to assess the validity and repeatability of an objective grading system in comparison with subjective grading. METHODS: This study was a retrospective, randomised analysis of 300 bulbar conjunctival images that were collected at an academic institution. The images used were de-identified and collected from the Keratograph K5 and Haag-Streit slitlamp. Six investigators graded the images with either a 0.1 or 0.5 unit scaling using a 0-4 Efron grading scale. Three of the investigators also imported the images into the AOS ® Anterior software and graded them objectively. All measurement techniques were assessed for repeatability and comparability to each other. RESULTS: Mean hyperaemia with the objective system (1.1 ± 0.7) was significantly less than the subjective grading (2.0 ± 0.8) (P < 0.001). Both inter- and intra-subject repeatability of the objective system (0.15) was better than the subjective methods (1.70). CONCLUSION: The results showed excellent repeatability of the AOS ® Anterior objective conjunctival hyperaemia grading software, although they were not found to be interchangeable with subjective scores. This system has value in monitoring levels of hyperaemia in contact lens wearers and patients in clinical care and research trials.

CLEAR - Scleral lenses.

Scleral lenses were the first type of contact lens, developed in the late nineteenth century to restore vision and protect the ocular surface. With the advent of rigid corneal lenses in the middle of the twentieth century and soft lenses in the 1970's, the use of scleral lenses diminished; in recent times there has been a resurgence in their use driven by advances in manufacturing and ocular imaging technology. Scleral lenses are often the only viable form of contact lens wear across a range of clinical indications and can potentially delay the need for corneal surgery. This report provides a brief historical review of scleral lenses and a detailed account of contemporary scleral lens practice including common indications and recommended terminology. Recent research on ocular surface shape is presented, in addition to a comprehensive account of modern scleral lens fitting and on-eye evaluation. A range of optical and physiological challenges associated with scleral lenses are presented, including options for the clinical management of a range of ocular conditions. Future applications which take advantage of the stability of scleral lenses are also discussed. In summary, this report presents evidence-based recommendations to optimise patient outcomes in modern scleral lens practice.

Anatomical and physiological considerations in scleral lens wear: Eyelids and tear film.

Scleral lenses can affect a range of anterior segment structures including the eyelids and the tears. The eyelids, consisting of the outer skin layer, the middle tarsal plate, and the posterior palpebral conjunctiva, provide physical protection and house the meibomian glands and cilia which have important and unique functions. Tears consist of a mix of aqueous, mucus, and lipidomic components that serve vital functions of lubricity, protection, and nourishment to the ocular surface. Both the eyelids and the tear film interact directly with scleral lenses on the eye and can affect but also be impacted by scleral lens wear. The purpose of this paper is to review the anatomy and physiology of the eyelids and tear film, discuss the effects and impacts of the scleral lenses on these structures, and identify areas that require further research.

IOP and Optic Nerve Head Morphology during Scleral Lens Wear.

SIGNIFICANCE: Scleral lenses (SLs) are increasing in scope, and understanding their ocular health impact is imperative. The unique fit of an SL raises concern that the landing zone causes compression of conjunctival tissue that can lead to resistance of aqueous humor outflow and increased intraocular pressure (IOP). PURPOSE: This study aimed to assess changes in optic nerve head morphology as an indirect assessment of IOP and evaluate other IOP assessment methods during SL wear. METHODS: Twenty-six healthy adults wore SL on one randomly selected eye for 6 hours, whereas the fellow eye served as a control. Global minimum rim width (optical coherence tomography) and IOP (Icare, Diaton) were measured at baseline, 2 and 6 hours after SL application, and again after SL removal. Central corneal thickness, anterior chamber depth, and fluid reservoir depth were monitored. RESULTS: Minimum rim width thinning was observed in the test (-8 µm; 95% confidence interval [CI], -11 to -6 µm) and control (-6 µm; 95% CI, -9 to -3 µm) eyes after 6 hours of SL wear (P < .01), although the magnitude of thinning was not significantly greater in the lens-wearing eyes (P = .09). Mean IOP (Icare) significantly increased +2 mmHg (95% CI, +1 to +3 mmHg) in the test eyes (P = .002), with no change in the control eyes. Mean IOP changes with Diaton were +0.3 mmHg (95% CI, -0.9 to +3.2 mmHg) in the test eyes and +0.4 mmHg (95% CI, -0.8 to +1.7 mmHg) in the control eyes. However, Diaton tonometry showed poor within-subject variation and poor correlation with Icare. No clinically significant changes were observed in central corneal thickness or anterior chamber depth. CONCLUSIONS: This study suggests that SLs have a minimal effect on IOP homeostasis in the normal eye during SL wear and an insignificant impact on the optic nerve head morphology in healthy adult eyes.

Effect of High Add Power, Medium Add Power, or Single-Vision Contact Lenses on Myopia Progression in Children: The BLINK Randomized Clinical Trial.

Importance: Slowing myopia progression could decrease the risk of sight-threatening complications. Objective: To determine whether soft multifocal contact lenses slow myopia progression in children, and whether high add power (+2.50 D) slows myopia progression more than medium (+1.50 D) add power lenses. Design, Setting, and Participants: A double-masked randomized clinical trial that took place at 2 optometry schools located in Columbus, Ohio, and Houston, Texas. A total of 294 consecutive eligible children aged 7 to 11 years with -0.75 D to -5.00 D of spherical component myopia and less than 1.00 D astigmatism were enrolled between September 22, 2014, and June 20, 2016. Follow-up was completed June 24, 2019. Interventions: Participants were randomly assigned to wear high add power (n = 98), medium add power (n = 98), or single-vision (n = 98) contact lenses. Main Outcomes and Measures: The primary outcome was the 3-year change in cycloplegic spherical equivalent autorefraction, as measured by the mean of 10 autorefraction readings. There were 11 secondary end points, 4 of which were analyzed for this study, including 3-year eye growth. Results: Among 294 randomized participants, 292 (99%) were included in the analyses (mean [SD] age, 10.3 [1.2] years; 177 [60.2%] were female; mean [SD] spherical equivalent refractive error, -2.39 [1.00] D). Adjusted 3-year myopia progression was -0.60 D for high add power, -0.89 D for medium add power, and -1.05 D for single-vision contact lenses. The difference in progression was 0.46 D (95% CI, 0.29-0.63) for high add power vs single vision, 0.30 D (95% CI, 0.13-0.47) for high add vs medium add power, and 0.16 D (95% CI, -0.01 to 0.33) for medium add power vs single vision. Of the 4 secondary end points, there were no statistically significant differences between the groups for 3 of the end points. Adjusted mean eye growth was 0.42 mm for high add power, 0.58 mm for medium add power, and 0.66 mm for single vision. The difference in eye growth was -0.23 mm (95% CI, -0.30 to -0.17) for high add power vs single vision, -0.16 mm (95% CI, -0.23 to -0.09) for high add vs medium add power, and -0.07 mm (95% CI, -0.14 to -0.01) for medium add power vs single vision. Conclusions and Relevance: Among children with myopia, treatment with high add power multifocal contact lenses significantly reduced the rate of myopia progression over 3 years compared with medium add power multifocal and single-vision contact lenses. However, further research is needed to understand the clinical importance of the observed differences. Trial Registration: ClinicalTrials.gov Identifier: NCT02255474.

Anatomical and physiological considerations in scleral lens wear: Conjunctiva and sclera.

While scleral lenses have been fitted using diagnostic lenses or impression moulding techniques for over a century, recent advances in anterior segment imaging such as optical coherence tomography and corneo-scleral profilometry have significantly improved the current understanding of the anatomy of the anterior eye including the morphometry of the conjunctiva, sclera, and corneo-scleral junction, as well as the ocular surface shape and elevation. These technological advances in ocular imaging along with continual improvements and innovations in scleral lens design and manufacturing have led to a global increase in scleral lens prescribing. This review provides a comprehensive overview of the conjunctiva and sclera in the context of modern scleral lens practice, including anatomical variations in healthy and diseased eyes, the physiological impact of scleral lens wear, potential fitting challenges, and current approaches to lens modifications in order to minimise lens-induced complications and adverse ocular effects. Specific topics requiring further research are also discussed.

Scleral lens wear: Measuring inflammation in the fluid reservoir.

PURPOSE: To measure inflammatory mediators in the scleral lens fluid reservoir (FR) in healthy eyes and to compare them to basal tear samples after 8-hs (8h) and 4-days (4d) of scleral lens (SL) wear. METHODS: Fifteen normal, habitual soft contact lens wearers were fitted with 14.8- or 15.4-mm SLs (Zenlens, Alden Optical, USA). Basal ocular surface tears and FR samples were collected after 8h and 4d of daily SL wear. Levels of interleukin (IL) -4 and -8, matrix metalloproteinase (MMP)-7, -9, and -10, and tissue inhibitor of MMPs (TIMPs) 1-4 were measured in all samples using Luminex assays. Visual acuity, corneal and conjunctival staining, and comfort assessments were completed at the baseline, 8h and 4d time points. RESULTS: MMP-9 and MMP-10 were greater in FR than basal ocular surface tears. After 8h of SL wear, the median concentration of MMP-9 in the FR and basal tears were 62.7 and 15.2 ng/mL, respectively (p = 0.047). Likewise, MMP-10 was significantly greater in FR compared to basal tears, after 8h (25.8 ng/mL vs 2.8 ng/mL, p < 0.001) and 4d (2.1 ng/mL vs17.2 ng/mL, p = 0.047). IL-4 and IL-8 levels were greater in FR but not significantly at 8h (2.2 vs 3.1 ng/mL; and 0.1 vs 0.4 ng/mL, respectively) or 4d (0.9 vs 3.5 ng/mL; 0.0 vs 0.2 ng/mL). MMP-7 was not affected by SL wear after 8h (46.0 basal vs 54.4 ng/mL FR) or 4d (34.2 vs 87.5 ng/mL). Visual acuity, corneal and conjunctival staining did not change; comfort was reduced in SL compared to soft contact lens wear. CONCLUSIONS: This is the first study to compare the FR with the basal ocular surface tears. MMP-9 and MMP-10 were elevated in the FR after several hours of SL wear, suggesting potential clinical implications of SL wear and deserves further investigation.

The official guide to scleral lens terminology.

PURPOSE: In absence of scleral lens standards, this article aims to provide an official definition of terms related to scleral lens fitting and manufacturing, in order to make more uniform the use of appropriate terms when describing, writing or lecturing about scelral lenses. Adoption of a common terminology may also favor more fruitful exchanges between eyecare practitioners and manufacturers. METHODS: A committee of 12 advances scleral lens clinicians met and develop a list of terms related to scleral lens fit and manufacturing. Litterature review was made using PubMed database with the keywords "scleral lenses" and "terminology". Other related publications such as textbooks were also considered valid references. Validation of the terms selected and their suggested definition was made by consultation of other experts in the field, over 2 years. A final version was adopted by the Scleral Lens Education Society late in 2018. RESULTS: This article contains three main sections. Section I provides the definition of a scleral lens. Section II addresses the general terminology habitually applied to contact lens field but in the context of scleral lens usage. Finally, Section III suggests a decription of terms specifically used when fitting or manufacturing scleral lenses. At the end, recommendations are made to manufacturers about the essential elements to provide to eyecare practitioners in order to help them understanding the lens design and to customize their fit. CONCLUSION: A common language is key to advancing the science and clinical practice of scleral lens fitting. The current terminology will help standardize this field, helping eyecare practitioners, educators, speakers and manufacturers to talk with the same language.

Penfigoide gestacional y erupción ampollar en el recién nacido / Bullous pemphygoid and blisters in the newborn

El penfigoide gestacional es una dermatosis rara, que se presenta durante el embarazo. Se caracteriza por una respuesta autoinmune contra las proteínas de los hemidesmosomas, que genera un clivaje entre la epidermis y la dermis tanto de la piel como de las mucosas. Clínicamente, presenta prurito intenso, placas y pápulas eritematosas, que evolucionan a apollas con distribución en el abdomen y los miembros. Como complicaciones, en el feto puede generar parto prematuro y bajo peso para la edad gestacional, con alto riesgo de mortalidad. (AU)

Gestational pemphygoid is a rare, autoimmune dermatosis that occurs during pregnancy. It is characterized by an autoimmune response against hemidesmosome proteins, generating a cleavage between the epidermis and the dermis in the skin and mucous membranes. Clinically it presents with intense pruritus, plaques and erythematous papules that evolve to blisters that are distributed mainly in the abdomen and limbs. The complications are preterm birth and low weight for gestational age, with high risk of mortality. (AU)

Peripheral Refraction and Eye Lengths in Myopic Children in the Bifocal Lenses In Nearsighted Kids (BLINK) Study.

PURPOSE: Provide a detailed assessment of peripheral refractive error and peripheral eye length in myopic children. METHODS: Subjects were 294 children aged 7 to 11 years with -0.75 to -5.00 diopter (D) of myopia by cycloplegic autorefraction. Peripheral refraction and eye length were measured at ±20° and ±30° horizontally and vertically, with peripheral refraction also measured at ±40° horizontally. RESULTS: Relative peripheral refraction became more hyperopic in the horizontal meridian and more myopic in the vertical meridian with increasing field angle. Peripheral eye length became shorter in both meridians with increasing field angle, more so horizontally than vertically with correlations between refraction and eye length ranging from -0.40 to -0.57 (all P < 0.001). Greater foveal myopia was related to more peripheral hyperopia (or less peripheral myopia), shorter peripheral eye lengths, and a consistent average asymmetry between meridians. CONCLUSIONS: Peripheral refractive errors in children do not appear to exert strong local control of peripheral eye length given that their correlation is consistently negative and the degree of meridional asymmetry is similar across the range of refractive errors. The BLINK study will provide longitudinal data to determine whether peripheral myopia and additional peripheral myopic defocus from multifocal contact lenses affect the progression of myopia in children. TRANSLATIONAL RELEVANCE: Local retinal control of ocular growth has been demonstrated numerous times in animal experimental myopia models but has not been explored in detail in human myopia development. These BLINK baseline results suggest that children's native peripheral optical signals may not be a strong stimulus for local growth responses.

A measure of tear inflow in habitual scleral lens wearers with and without midday fogging.

PURPOSE: The purpose of this pilot study was to evaluate tear inflow in a scleral lens system using fluorophotometry, and indirectly assess the exchange of the tear reservoir in habitual scleral lens wearers with the presence or absence of midday fogging (MDF). METHODS: Habitual scleral lens wearers (n=23) and normal scleral lens neophytes (n=10) were recruited. Of the 23 habitual wearers, 11 of them experienced MDF and 12 did not have a diagnosis of MDF. Contact lens-fitting characteristics were evaluated using ocular coherence tomograpy (OCT) and biomicroscopy. High molecular weight fluorescein (FITC) Dextran was instilled into the tear reservoir beneath the scleral lens, and the tear fluid fluorescein concentration was measured using the Fluorotron fluorophotometer. Calculated fluorescein concentrations were plotted over time to measure the fluorescein decay rate of the tear fluid beneath the scleral lens, which was used to calculate the tear exchange rate. RESULTS: There was no significant difference in tear inflow between the MDF group (mean: 0.111%) and the non-MDF group (mean: 0.417%), and there was a high amount of variability seen in the rates (p = 0.26). In addition, there was no significance between the tear reservoir thickness in the MDF (283um) and non-MDF (326um) groups (p = 0.53). CONCLUSIONS: The relationship between the amount of tear exchange during scleral lens wear and the incidence of MDF was not significant. Additional studies are needed to further examine the role of tear exchange in MDF and address the causes of variability to improve measurement techniques with fluorophotometry in the scleral lens system.

The Community In-reach Rehabilitation and Care Transition (CIRACT) clinical and cost-effectiveness randomisation controlled trial in older people admitted to hospital as an acute medical emergency.

Objective: To compare the clinical and cost-effectiveness of a Community In-reach Rehabilitation and Care Transition (CIRACT) service with the traditional hospital-based rehabilitation (THB-Rehab) service. Design: Pragmatic randomised controlled trial with an integral health economic study. Settings: Large UK teaching hospital, with community follow-up. Subjects: Frail older people aged 70 years and older admitted to hospital as an acute medical emergency. Measurements: Primary outcome: hospital length of stay; secondary outcomes: readmission, day 91-super spell bed days, functional ability, co-morbidity and health-related quality of life; cost-effectiveness analysis. Results: A total of 250 participants were randomised. There was no significant difference in length of stay between the CIRACT and THB-Rehab service (median 8 versus 9 days; geometric mean 7.8 versus 8.7 days, mean ratio 0.90, 95% confidence interval (CI) 0.74­1.10). Of the participants who were discharged from hospital, 17% and 13% were readmitted within 28 days from the CIRACT and THB-Rehab services, respectively (risk difference 3.8%, 95% CI −5.8% to 13.4%). There were no other significant differences in any of the other secondary outcomes between the two groups. The mean costs (including NHS and personal social service) of the CIRACT and THB-Rehab service were £3,744 and £3,603, respectively (mean cost difference £144; 95% CI −1,645 to 1,934). Conclusion: The CIRACT service does not reduce major hospital length of stay nor reduce short-term readmission rates, compared to the standard THB-Rehab service; however, a modest (<2.3 days) effect cannot be excluded. Further studies are necessary powered with larger sample sizes and cluster randomisation. Trial registration: ISRCTN 94393315, 25th April 2013