Vitrification is now a commonly applied technique for cryopreservation in assisted reproductive technology (ART) replacing, in many cases, conventional slow cooling methodology. This review examines ...evidence relevant to comparison of the two approaches applied to human oocytes and embryos at different developmental stages.
Critical review of the published literature using PubMed with particular emphasis on studies which include data on survival and implantation rates, data from fresh control groups and evaluation of the two approaches in a single setting.
Slow cooling is associated with lower survival rates and compromised development relative to vitrification when applied to metaphase II (MII) oocytes, although the vitrification results have predominantly been obtained using direct contact with liquid nitrogen and there is some evidence that optimal protocols for slow cooling of MII oocytes are yet to be established. There are no prospective randomized controlled trials (RCTs) which support the use of either technique with pronuclear oocytes although vitrification has become the method of choice. Optimal slow cooling, using modifications of traditional methodology, and vitrification can result in high survival rates of early embryos, which implant at the same rate as equivalent fresh counterparts. Many studies report high survival and implantation rates following vitrification of blastocysts. Although slow cooling of blastocysts has been reported to be inferior in some studies, others comparing the two approaches in the same clinical setting have demonstrated comparable results. The variation in the extent of embryo selection applied in studies can lead to apparent differences in clinical efficiency, which may not be significant if expressed on a 'per oocyte used' basis.
Available evidence suggests that vitrification is the current method of choice when cryopreserving MII oocytes. Early cleavage stage embryos can be cryopreserved with equal success using slow cooling and vitrification. Successful blastocyst cryopreservation may be more consistently achieved with vitrification but optimal slow cooling can produce similar results. There are key limitations associated with the available evidence base, including a paucity of RCTs, limited reporting of live birth outcomes and limited reporting of detail which would allow assessment of the impact of differences in female age. While vitrification has a clear role in ART, we support continued research to establish optimal slow cooling methods which may assist in alleviating concerns over safety issues, such as storage, transport and the use of very high cryoprotectant concentrations.
To evaluate the efficacy of a myopia control spectacle lens (DIMS) at slowing the progression of myopia in a population of European children in comparison with 0.01% atropine and combined DIMS and ...atropine.
The study was a non-randomised experimenter-masked prospective controlled observational study of individuals aged 6-18 years with progressing myopia but no ocular pathology. Participants were allocated, according to patient/parent choice, to receive 0.01% atropine eyedrops, DIMS (Hoya® MiyoSmart®) spectacles, combined atropine+DIMS or single vision spectacle lenses (control group). The key outcome variables, cycloplegic autorefraction spherical equivalent refraction (SER) and axial length (AL), were measured at baseline and after three, six, and 12 months.
Of the 146 participants (mean age 10.3y ±3.2), 53 received atropine, 30 DIMS spectacles, 31 atropine+DIMS, and 32 single vision control spectacles. Generalized linear mixed model analysis revealed for SER, whilst controlling for age and SER at baseline, at each stage all treatment groups had significantly reduced progression compared with the control group (p<0.016). For AL, whilst controlling for baseline age and AL, at 6 and 12 months all treatment groups had significantly less progression than the control group (p<0.005). For SER only, in pairwise comparisons at 12 months the atropine+DIMS group had significantly reduced progression compared with the DIMS only and Atropine only groups (p<0.001).
In a European population, DIMS and atropine are effective at reducing myopia progression and axial elongation in progressing myopia and are most successful at reducing myopia progression when used in combination.
Glaucoma is a progressive eye disease and a leading cause of visual disability. Automated assessment of the visual field determines the different stages in the disease process: it would be desirable ...to link these measurements taken in the clinic with patient's actual function, or establish if patients compensate for their restricted field of view when performing everyday tasks. Hence, this study investigated eye movements in glaucomatous patients when viewing driving scenes in a hazard perception test (HPT).
The HPT is a component of the UK driving licence test consisting of a series of short film clips of various traffic scenes viewed from the driver's perspective each containing hazardous situations that require the camera car to change direction or slow down. Data from nine glaucomatous patients with binocular visual field defects and ten age-matched control subjects were considered (all experienced drivers). Each subject viewed 26 different films with eye movements simultaneously monitored by an eye tracker. Computer software was purpose written to pre-process the data, co-register it to the film clips and to quantify eye movements and point-of-regard (using a dynamic bivariate contour ellipse analysis). On average, and across all HPT films, patients exhibited different eye movement characteristics to controls making, for example, significantly more saccades (P<0.001; 95% confidence interval for mean increase: 9.2 to 22.4%). Whilst the average region of 'point-of-regard' of the patients did not differ significantly from the controls, there were revealing cases where patients failed to see a hazard in relation to their binocular visual field defect.
Characteristics of eye movement patterns in patients with bilateral glaucoma can differ significantly from age-matched controls when viewing a traffic scene. Further studies of eye movements made by glaucomatous patients could provide useful information about the definition of the visual field component required for fitness to drive.
Enteric nervous system progenitor cells isolated from postnatal human gut and cultured as neurospheres can then be transplanted into aganglionic gut to restore normal patterns of contractility. These ...progenitor cells may be of future use to treat patients with Hirschprung's disease, a congenital condition characterized by hindgut dysmotility due to the lack of enteric nervous system ganglia. Here we demonstrate that progenitor cells can also be isolated from aganglionic gut removed during corrective surgery for Hirschsprung's disease. Although the enteric nervous system marker calretinin is not expressed in the aganglionic gut region, de novo expression is initiated in cultured neurosphere cells isolated from aganglionic Hirschsprung bowel. Furthermore, expression of the neural markers NOS, VIP and GFAP also increased during culture of aganglionic gut neurospheres which we show can be transplantation into cultured embryonic mouse gut explants to restore a normal frequency of contractility. To determine the origin of the progenitor cells in aganglionic region, we used fluorescence-activated cell sorting to demonstrate that only p75-positive neural crest-derived cells present in the thickened nerve trunks characteristic of the aganglionic region of Hirschsprung gut gave rise to neurons in culture. The derivation of enteric nervous system progenitors in the aganglionic gut region of Hirschprung's patients not only means that this tissue is a potential source of cells for future autologous transplantation, but it also raises the possibility of inducing the differentiation of these endogenous cells in situ to compensate for the aganglionosis.
Purpose
Myopia prevalence has increased in the UK at age 10‐16y, but little is known about younger children. We hypothesise that if the ‘myopia epidemic’ is affecting young children, then there will ...be increasing rates of bilateral reduced unaided vision (V) at vision screenings of children 4–5 years of age.
Methods
Retrospective anonymised data from computerised vision screening at age 4–5 years were analysed from serial cross‐sectional data. Refractive error is not assessed in UK vision screening, so vision was investigated. Data were only included from schools that screened every year from 2015/16 to 2021/22. The criterion used was unaided monocular logMAR (automated letter‐by‐letter scoring) vision >0.20 in both the right and left eyes, so as to maximise the chances of detecting bilateral, moderate myopia rather than amblyopia.
Results
Anonymised raw data were obtained for 359,634 screening episodes from 2075 schools. Once schools were excluded where data were not available for every year and data were cleaned, the final database comprised 110,076 episodes. The proportion (percentage and 95% CI) failing the criterion from 2015/16 to 2021/22 were 7.6 (7.2–8.0), 8.5 (8.1–8.9), 7.5 (7.1–7.9), 7.8 (7.4–8.2), 8.7 (8.1–9.2), 8.5 (7.9–9.0) and 9.3 (8.8–9.7), respectively. The slope of the regression line showed a trend for increasing rates of reduced bilateral unaided vision, consistent with increasing frequency of myopia (p = 0.06). A decreasing linear trendline was noted for children ‘Under Professional Care’.
Conclusions
For children 4–5 years of age, there were signs of reduced vision over the last 7 years in England. Consideration of the most likely causes support the hypothesis of increasing myopia. The increase in screening failures highlights the importance of eye care in this young population.
To assess accuracy and adherence of visual field (VF) home monitoring in a pilot sample of patients with glaucoma.
Prospective longitudinal feasibility and reliability study.
Twenty adults (median 71 ...years) with an established diagnosis of glaucoma were issued a tablet perimeter (Eyecatcher) and were asked to perform 1 VF home assessment per eye, per month, for 6 months (12 tests total). Before and after home monitoring, 2 VF assessments were performed in clinic using standard automated perimetry (4 tests total, per eye).
All 20 participants could perform monthly home monitoring, though 1 participant stopped after 4 months (adherence: 98% of tests). There was good concordance between VFs measured at home and in the clinic (r = 0.94, P < .001). In 21 of 236 tests (9%), mean deviation deviated by more than ±3 dB from the median. Many of these anomalous tests could be identified by applying machine learning techniques to recordings from the tablets' front-facing camera (area under the receiver operating characteristic curve = 0.78). Adding home-monitoring data to 2 standard automated perimetry tests made 6 months apart reduced measurement error (between-test measurement variability) in 97% of eyes, with mean absolute error more than halving in 90% of eyes. Median test duration was 4.5 minutes (quartiles: 3.9-5.2 minutes). Substantial variations in ambient illumination had no observable effect on VF measurements (r = 0.07, P = .320).
Home monitoring of VFs is viable for some patients and may provide clinically useful data.
•Twenty patients with glaucoma performed visual field assessments at home for 6 months.•The data were in good agreement with conventional measurements made in clinic.•Home monitoring may be viable and useful for some patients.•Practical concerns and future directions for home monitoring are also discussed.
Purpose
Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (
STAT1
) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. ...The latter is often characterized by the susceptibility to recurrent
Candida
infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF
STAT1
mutations in a large international cohort of CMC patients.
Methods
STAT1
was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different
STAT1
variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients’ peripheral blood cells (PBMC) after stimulation with interferon (IFN)-α, IFN-γ or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients.
Results
Heterozygous mutations within
STAT1
were identified in 35 of 57 CMC patients (61 %). Out of 39 familial cases from 11 families, 26 patients (67 %) from 9 families and out of 18 sporadic cases, 9 patients (50 %) were shown to have heterozygous mutations within
STAT1
. Thirteen distinct
STAT1
mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five
STAT1
variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients.
Conclusion
STAT1
mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of
STAT1
in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing.
Quantitative magnetic resonance imaging enables quantitative assessment of the healing anterior cruciate ligament or graft post‐surgery, but its use is constrained by the need for time consuming ...manual image segmentation. The goal of this study was to validate a deep learning model for automatic segmentation of repaired and reconstructed anterior cruciate ligaments. We hypothesized that (1) a deep learning model would segment repaired ligaments and grafts with comparable anatomical similarity to intact ligaments, and (2) automatically derived quantitative features (i.e., signal intensity and volume) would not be significantly different from those obtained by manual segmentation. Constructive Interference in Steady State sequences were acquired of ACL repairs (n = 238) and grafts (n = 120). A previously validated model for intact ACLs was retrained on both surgical groups using transfer learning. Anatomical performance was measured with Dice coefficient, sensitivity, and precision. Quantitative features were compared to ground truth manual segmentation. Automatic segmentation of both surgical groups resulted in decreased anatomical performance compared to intact ACL automatic segmentation (repairs/grafts: Dice coefficient = .80/.78, precision = .79/.78, sensitivity = .82/.80), but neither decrease was statistically significant (Kruskal‐Wallis: Dice coefficient p = .02, precision p = .09, sensitivity p = .17; Dunn post‐hoc test for Dice coefficient: repairs/grafts p = .054/.051). There were no significant differences in quantitative features between the ground truth and automatic segmentation of repairs/grafts (0.82/2.7% signal intensity difference, p = .57/.26; 1.7/2.7% volume difference, p = .68/.72). The anatomical similarity performance and statistical similarities of quantitative features supports the use of this automated segmentation model in quantitative magnetic resonance imaging pipelines, which will accelerate research and provide a step towards clinical applicability.
Clinical relevance: Accuracy of tonometers is of vital importance in the detection and treatment of glaucoma.
Background: This study investigates: agreement in intraocular pressure measurements ...between three tonometers and Goldmann applanation tonometry (GAT); inter-optometrist agreement for each tonometer; intra-optometrist agreement for GAT; association between central corneal thickness (CCT) and IOP measurements with each tonometer.
Methods: IOP was measured using: CT-1P Non-Contact Tonometer (NCT) (Topcon Corporation, Tokyo, Japan), Pulsair IntelliPuff (Keeler Ltd., Windsor, UK) and Icare rebound tonometer (Icare, Helsinki, Finland) by two optometrists in a random order. Two GAT readings were obtained by each optometrist in a randomised masked manner. Mean differences, and 95% limits of agreement (LoA) for each measurement were calculated. CCT was measured by CT-1P pachymeter.
Results: Forty-one participants' IOPs were measured. Mean differences (95% LoA) between NCT, Pulsair, Icare compared to GAT for one optometrist were: 0.8 (−5.4 to 6.9) mmHg, −1.7 (−8.2 to 4.8) mmHg, −1.6 (−9.0 to 5.9) mmHg. Mean differences (95% LoA) in inter-optometrist agreement for GAT, NCT, Pulsair and Icare were: 0.3 (−6.7 to 7.3) mmHg, 0.4 (−2.1 to 2.9) mmHg, −0.9 (−3.6 to 1.9) mmHg and −0.2 (−4.9 to 4.5) mmHg, respectively. Mean differences (95% LoA) for intra-optometrist agreement for GAT were 0.2 (4.3 to −4.7) mmHg and 0.1 (3.6 to −3.9) mmHg for each optometrist, respectively. There was a weak positive association between CCT and both GAT (r
2
= 0.11) and NCT (r
2
= 0.12).
Conclusion: Pulsair and Icare may measure IOP lower than GAT. Mean differences for inter-optometrist agreement for all tonometers were < 1 mmHg; Pulsair showed a statistically significant difference. Intra-optometrist agreement for GAT was good. IOP measurements taken by two community optometrists are comparable using tonometers used in community practice.
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