[Show abstract][Hide abstract] ABSTRACT: Purpose:
AURA was an international, retrospective, observational study that monitored the real-life use and effectiveness of ranibizumab injections in patients with neovascular age-related macular degeneration (nAMD). This paper reports the findings from the UK.
Patients who started treatment with ranibizumab between January 1, 2009, and August 31, 2009, and had documented follow-up to the end of their treatment and/or monitoring or until August 31, 2011, were retrospectively monitored; the diagnosis and subsequent decision to treat was made by the patient's own physician. Assessments included the change in visual acuity (standardized letter count) during the first and second years after start of ranibizumab therapy and resource utilization.
Four hundred and ten patients from 13 UK centers were analyzed. The mean (standard deviation [SD]) letter score at baseline was 55.0 (17.8). The mean (SD) change in visual acuity from baseline was +6.0 (15.4) letters at year 1 and +4.1 (16.9) at year 2. Most of the patients (86.6%) completed a 3-month loading phase; the visual improvements were numerically higher in these patients. Over 2 years, the mean (SD) number of clinic visits and injections was 18.4 (5.0) and 9.0 (4.7), respectively. Resource use and visual acuity gains were greater than those observed in the global population, which included other countries enrolled in AURA (Canada, France, Germany, Ireland, Italy, the Netherlands, and Venezuela). When patients were stratified according to severity of nAMD (based on letter count at baseline), the mean change in visual acuity score at years 1 and 2 was also higher for the UK than for the global population across all subgroups.
Monitoring and treatment rates were high in the UK, resulting in better visual acuity outcomes compared with other included countries. This suggests that translation of clinical study outcomes into real-life settings is achievable, but at the expense of higher resource utilization than is currently the norm in most developed countries.
Preview · Article · Jan 2016 · Clinical Ophthalmology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To determine the disease course of retinal dystrophy caused by recessive variants in the DRAM2 (damage-regulated autophagy modulator 2) gene.
Sixteen individuals with DRAM2-retinopathy were examined (six families; age range, 19-56 years, includes one pre-symptomatic case). The change in visual acuity over time was studied, and electrophysiology (n = 6), retina-tracking perimetry (n = 1), fundus autofluorescence (FAF) imaging (n = 6), and optical coherence tomography (OCT; n = 12) were performed.
All symptomatic patients presented with central visual loss (15/15) unaccompanied either by nyctalopia or light-hypersensitivity; most (11/15) developed symptoms in the third decade of life. A granular macular appearance, often with associated white/yellow dots, was an early fundoscopic feature. There was an ill-defined ring of hyperautofluorescence on FAF. Optical coherence tomography revealed loss of the ellipsoid zone perifoveally in a 19-year-old pre-symptomatic individual. The central atrophic area enlarged over time and fundoscopy showed peripheral degeneration in seven of the nine individuals that were examined ≥10 years after becoming symptomatic; some of these subjects developed nyctalopia and light hypersensitivity. Electrophysiology revealed generalized retinal dysfunction in three of the five individuals that were tested ≥10 years after becoming symptomatic.
Patients with DRAM2-retinopathy are typically asymptomatic in the first two decades of life and present with central visual loss and a maculopathy. A faint hyperautofluorescent ring on FAF can be a suggestive feature. The retinal periphery is frequently affected later in the disease process. Photoreceptor degeneration is likely to be the primary event and future studies on DRAM2-retinopathy are expected to provide important insights into retinal autophagy.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Aflibercept has the potential advantage of reducing capacity problems by allowing 2 monthly visits for patients with neovascular macular degeneration (nAMD) compared with monthly pro re nata regimens that are the most commonly used in the United Kingdom. This study aimed to report the visual outcomes achieved in routine clinical practice using the VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) protocol at 1 year and compare with trials data and other real-world reports.
Retrospective data analysis from an electronic medical record.
Consecutive series of treatment-naïve patients initiated on aflibercept for nAMD at least 1 year before data extraction.
Data were anonymized and remotely extracted from 16 centers in the United Kingdom that use the same electronic medical record (EMR) system (Medisoft Ophthalmology; Medisoft Limited, Leeds, UK).
Main outcome measures:
The minimum data set defined before first data entry and mandated by the EMR included age, gender, visual acuity, injection episodes, and complications.
The mean age was 80.0 years (median, 81.0 years) and 63.7% were women. During the first year of treatment with aflibercept, 1840 treatment-naïve eyes of 1682 patients received a median of 8 (mean, 7.0) injections at a median of 8 (mean, 7.3) visits. The mean baseline visual acuity was 53.7 letters, improving to 58.8 letters (+5.1-letter gain) at 1 year. In first-treated eyes, the respective figures were 52.7 letters at baseline and 58.2 letters at 1 year, a gain of +5.5 letters. The proportion achieving 70 letters or more increased from 16.4% at baseline to 33.7% at 1 year, and 92% avoided moderate visual loss at 1 year.
The visual acuity outcomes are comparable to randomized trials and better than many previous real-world data collections, with a mean +5.1-letter gain at 1 year compared with +8.4 letters in the integrated analysis of the VIEW 1 and VIEW 2 studies. Early visual gains were maintained through the year. Collection of outcomes beyond clinical trials can have limitations but better reflect the full pool of patients actually treated and are important to determine whether a particular treatment is performing as expected. Such data also have the potential to improve services by setting up a mechanism to compare sites.
[Show abstract][Hide abstract] ABSTRACT: Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.
[Show abstract][Hide abstract] ABSTRACT: This supplement has been sponsored by Bayer HealthCare. Please see acknowledgements for full disclaimer. Prescribing Information can be found in the appendices.
L.GB.COM.05.2015.11280. Date of preparation: June 2015
This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a ‘treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for ≥3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.
[Show abstract][Hide abstract] ABSTRACT: To explore factors that influence decision-making in relation to prenatal diagnostic testing (PDT) for inherited retinal disease (IRD).
Semi-structured interviews were conducted with 50 adults with IRD, selected from a larger sample to provide a diversity of backgrounds and opinions on genetic testing. Interviews were transcribed verbatim and analysed using thematic analysis.
Mostly participants supported PDT, believing that it would provide information to help them prepare for and plan the future care of the child and the potential for early access to emerging therapies. Opposition to PDT stemmed from its use to justify termination of pregnancy, with participants feeling that it was not justified as they retained a good quality of life despite their visual impairment. Participants raised concerns about the risk of PDT and the accuracy of the results. However, most suggested that it should be available as an option for others, but for specific reasons and not as a part of routine care.
The variation in attitudes towards PDT and uncertainty about the risk and accuracy of results suggest that individuals at risk of having a child with IRD should have access to genetic counselling to support decision making.
This article is protected by copyright. All rights reserved.
No preview · Article · Jun 2015 · Prenatal Diagnosis
[Show abstract][Hide abstract] ABSTRACT: Purpose: To identify the genetic basis of macular dystrophy in three affected siblings of a non-consanguineous Caucasian family living in the UK.
Methods: Whole-exome sequencing (WES) was performed using SureSelectXT Human V4 target enrichment reagent followed by paired-end sequencing on a HiSeq2500.The data files were processed on the Galaxy platform, aligned to the human reference genome (hg19/GRCh37) and the reported variants annotated using Annovar. Variants were excluded if they were outside the exon and flanking splice recognition sites, were synonymous or had a minor allele frequency >1% in the exome variant server database. Variants were confirmed by PCR and Sanger sequencing.
Results: Genomic DNA from an affected family member was analysed by WES and the list filtered for prioritization of variants that are in the known RetNet genes. We identified 5 heterozygous and 1 homozygous variant though none segregated with the disease phenotype in the family. WES analysis of a second affected siblingand comparison of the full lists for common variantsidentified 15 homozygous and 4 genes with compound heterozygous variants. It was noted that mutations in one of these candidates MFSD8 (major facilitator superfamily domain-containing protein 8) had recently been reported in 2 families to cause nonsyndromic recessive macular dystrophy (Roosing et al., Ophthalmology, 2014). Sanger sequencing of the MFSD8 variants, c.1006G>C, p.E336Q and c.1394G>A, p.R465Q, in the UK family confirmed that all the affected members were indeed compound heterozygous for the mutations. These results are surprising since all publications to date on mutations in this gene except the one above showed that recessive MFSD8 mutations cause a severe multisystem lysosomal storage disorder, neuronal ceroidlipofuscinosis.
Conclusions: This is the second study and only the third family describing biallelic MFSD8 mutations causing a nonsyndromic eye phenotype, and independently confirms the findings of the recent report.It is worth highlighting that one of these mutations, p.E336Q, exists in a heterozygous state in all three families and may act as a
modifier of disease symptoms resulting in the less severe phenotype.
Commercial Relationships: Mohammed E. Elasrag, None; Martin McKibbin, None; James Poulter, None; Chris Inglehearn, None; Carmel Toomes, None; Manir Ali, None
Support: This research was supported by Egyptian government scholarship for Mr Mohammed Elasrag
[Show abstract][Hide abstract] ABSTRACT: To evaluate the influence of vitreomacular attachment on outcomes after intravitreal aflibercept for neovascular age-related macular degeneration.
In a prospective case series, eyes with neovascular age-related macular degeneration were treated with intravitreal aflibercept, given as 3 consecutive monthly injections, followed by further injection every 2 months. Spectral domain optical coherence tomography images were reviewed at each visit to determine the attachment of the posterior hyaloid. Best-corrected visual acuity and retinal thickness were also recorded. Outcomes at Months 2 and 6 were compared between the eyes with persistent vitreomacular attachment (Stage 1) and those with posterior vitreous detachment (Stages 2 or 3 PVD) at baseline.
At baseline, 30 eyes had Stage 1 PVD and 63 eyes had either Stage 2 or 3 PVD. Although there was a trend for both greater visual acuity gains and reductions in retinal thickness for the eyes with Stages 2 or 3 PVD, this failed to reach significance. Baseline visual acuity and age were negatively associated with visual acuity change, and baseline retinal thickness alone was associated with retinal thickness change.
Visual acuity, retinal thickness, and age at the baseline examination, but not PVD status, are associated with functional and anatomical outcomes after intravitreal aflibercept for neovascular age-related macular degeneration.
[Show abstract][Hide abstract] ABSTRACT: Age-related macular degeneration (AMD) and Alzheimer’s disease (AD) are degenerative, multifactorial diseases involving age-related accumulation of extracellular deposits linked to dysregulation of protein homeostasis. Here, we strengthen the evidence that an nsSNP (p.Ala25Thr) in the cysteine proteinase inhibitor cystatin C gene CST3, previously confirmed by meta-analysis to be associated with AD, is associated with exudative AMD. To our knowledge, this is the first report highlighting a genetic variant that increases the risk of developing both AD and AMD. Furthermore, we demonstrate that the risk associated with the mutant allele follows a recessive model for both diseases. We perform an AMD-CST3 case–control study genotyping 350 exudative AMD Caucasian individuals. Bringing together our data with the previously reported AMD-CST3 association study, the evidence of a recessive effect on AMD risk is strengthened (OR = 1.89, P = 0.005). This effect closely resembles the AD-CST3 recessive effect (OR = 1.73, P = 0.005) previously established by meta-analysis. This resemblance is substantiated by the high correlation between CST3 genotype and effect size across the two diseases (R2 = 0.978). A recessive effect is in line with the known function of cystatin C, a potent enzyme inhibitor. Its potency means that, in heterozygous individuals, a single functional allele is sufficient to maintain its inhibitory function; only homozygous individuals will lack this form of proteolytic regulation. Our findings support the hypothesis that recessively acting variants account for some of the missing heritability of multifactorial diseases. Replacement therapy represents a translational opportunity for individuals homozygous for the mutant allele.
Electronic supplementary material
The online version of this article (doi:10.1007/s00439-015-1552-7) contains supplementary material, which is available to authorized users.
[Show abstract][Hide abstract] ABSTRACT: Purpose: To investigate the molecular basis of retinitis pigmentosa in two consanguineous families of Pakistani origin with multiple affected members.
Methods: Homozygosity mapping and Sanger sequencing of candidate genes were performed in one family while the other was analyzed with whole exome next-generation sequencing. A minigene splicing assay was used to confirm the splicing defects.
Results: In family MA48, a novel homozygous nucleotide substitution in C8orf37, c.244–2A>C, that disrupted the consensus splice acceptor site of exon 3 was found. The minigene splicing assay revealed that this mutation activated a cryptic splice site within exon 3, causing a 22 bp deletion in the transcript that is predicted to lead to a frameshift followed by premature protein truncation. In family MA13, a novel homozygous null mutation in C8orf37, c.555G>A, p.W185*, was identified. Both mutations segregated with the disease phenotype as expected in a recessive manner and were absent in 8,244 unrelated individuals of South Asian origin.
Conclusions: In this report, we describe C8orf37 mutations that cause retinal dystrophy in two families of Pakistani origin, contributing further data on the phenotype and the spectrum of mutations in this form of retinitis pigmentosa.
[Show abstract][Hide abstract] ABSTRACT: To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy.
Multicentre national nAMD database study on patients treated 3-5 years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections.
The study included 12 951 treatment-naive eyes of 11 135 patients receiving 92 976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values <0.001 for comparing differences between 6/12 and 6/12-6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values <0.001-0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12.
All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2 years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients' funding.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Full-text · Article · Feb 2015 · British Journal of Ophthalmology
[Show abstract][Hide abstract] ABSTRACT: A large number of genes can cause inherited retinal degenerations when mutated. It is important to identify the cause of disease for a better disease prognosis and a possible gene-specific therapeutic intervention.
To identify the cause of disease in families with nonsyndromic retinitis pigmentosa.
Patients and family members were recruited for the study and underwent clinical evaluation and genetic analyses.
Identification of sequence variants in genes using next-generation sequencing.
We performed exome sequencing for 4 families, which was followed by Sanger sequencing of the identified mutations in 120 ethnicity-matched patients. In total, we identified 4 BBS2 missense mutations that cause nonsyndromic retinitis pigmentosa. Three siblings of Moroccan Jewish ancestry were compound heterozygotes for p.A33D and p.P134R, and 6 patients belonging to 4 families of Ashkenazi Jewish ancestry were homozygous for either p.D104A or p.R632P, or compound heterozygous for these 2 mutations. The mutations cosegregated with retinitis pigmentosa in the studied families, and the affected amino acid residues are evolutionarily conserved.
Our study shows that BBS2 mutations can cause nonsyndromic retinitis pigmentosa and highlights yet another candidate for this genetically heterogeneous condition.
No preview · Article · Dec 2014 · Jama Ophthalmology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To report the reproducibility, sensitivity, specificity, and predictive value of home monitoring for disease activity in neovascular age-related macular degeneration (ARMD).
Participants were trained to complete three separate home monitoring tasks, designed to identify subtle changes in visual function that may indicate increasing neovascular ARMD disease activity. These included measurement of near acuity and assessments of environmental distortion and overall visual function. The need for repeat intra-vitreal injection, as predicted by home monitoring, was compared to standard clinical assessment involving ETDRS distance acuity, slit lamp examination, and spectral domain ocular coherence tomography.
Although all participants were able to complete the home monitoring tasks, the reproducibility of each of the three tasks was modest. Cohen's kappa was 0.118 (p = 0.54) for the comparison of the outcome of the home monitoring exercise with the gold standard of hospital assessment to determine disease activity. The sensitivity of the home monitoring exercise was 33.3 % (95 % CI 15.2-51.4) and the specificity was 77.8 % (95 % CI 61.8-93.8).
This study suggests that current tests of visual function, which are readily completed at home, cannot replace traditional clinic-based assessments for neovascular ARMD disease activity. Instead, such tests are likely to remain complementary to standard assessment in clinic.
No preview · Article · Nov 2014 · Albrecht von Graæes Archiv für Ophthalmologie
[Show abstract][Hide abstract] ABSTRACT: Purpose
To study the characteristics of second treated eyes in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab in the United Kingdom National Health Service.
Multicenter national nAMD database study.
Twelve thousand nine hundred fifty-one treatment-naïve eyes of 11 135 patients receiving 92 976 ranibizumab injections.
Up to 5 years of routinely collected, anonymized data within electronic medical record systems were extracted remotely from 14 centers. Participating centers exclusively used ranibizumab to treat nAMD (loading phase of 3 monthly injections followed by monthly visits and pro re nata re-treatment). The minimum data set included: age, logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) at baseline and at all subsequent visits, and injection episodes.
Main Outcome Measures
Baseline, change and actual VA over 3 years, and number of treatments and clinic visits.
During the study, 1816 (16.3%) of the 11 135 patients received treatment to the fellow eye. Mean baseline and final VA were 0.66 (standard deviation, 0.32) and 0.65 (0.40) for first treated eyes and 0.41 (0.34) and 0.56 (0.40) for second treated eyes. The rate of VA loss after the loading phase was similar in first and second treated eyes (0.03 and 0.05 logMAR units/year). When fellow eyes with baseline VA worse than 20/200 were excluded to restrict analyses to eyes at risk of nAMD, the rate of second-eye involvement was 14.0% per year (42%/3 years). Mean number of injections/visits in years 1, 2, and 3 were similar for first and second treated eyes (5.6/8.2, 3.9/8.0, 3.8/8.2 and 5.5/8.7, 3.6/9.4, and 3.8/9.1, respectively).
Second treated eyes with nAMD commence treatment with better baseline VA, do not show significant vision gain but maintain better VA than first treated eyes at all time points for at least 3 years, making them the more important eye functionally. These data highlight the high burden of second eye involvement, with almost half of all eyes at risk requiring bilateral treatment by 3 years, and the need for regular monitoring of fellow eyes for best visual outcomes which theoretically may reduce the benefits of extended monitoring regimens.
[Show abstract][Hide abstract] ABSTRACT: Purpose
Retinal dystrophies are genetically heterogeneous, resulting from mutations in over 200 genes. Prior to the development of massively parallel sequencing, comprehensive genetic screening was unobtainable for most patients. Identifying the causative genetic mutation facilitates genetic counselling, carrier testing and prenatal/pre-implantation diagnosis, and often leads to a clearer prognosis. In addition, in a proportion of cases, when the mutation is known treatment can be optimised and patients are eligible for enrolment into clinical trials for gene-specific therapies.
Patient genomic DNA was sheared, tagged and pooled in batches of four samples, prior to targeted capture and next generation sequencing. The enrichment reagent was designed against genes listed on the RetNet database (July 2010). Sequence data were aligned to the human genome and variants were filtered to identify potential pathogenic mutations. These were confirmed by Sanger sequencing.
Molecular analysis of 20 DNAs from retinal dystrophy patients identified likely pathogenic mutations in 12 cases, many of them known and/or confirmed by segregation. These included previously described mutations in ABCA4 (c.6088C>T,p.R2030*; c.5882G>A,p.G1961E), BBS2 (c.1895G>C,p.R632P), GUCY2D (c.2512C>T,p.R838C), PROM1 (c.1117C>T,p.R373C), RDH12 (c.601T>C,p.C201R; c.506G>A,p.R169Q), RPGRIP1 (c.3565C>T,p.R1189*) and SPATA7 (c.253C>T,p.R85*) and new mutations in ABCA4 (c.3328+1G>C), CRB1 (c.2832_2842+23del), RP2 (c.884-1G>T) and USH2A (c.12874A>G,p.N4292D).
Tagging and pooling DNA prior to targeted capture of known retinal dystrophy genes identified mutations in 60% of cases. This relatively high success rate may reflect enrichment for consanguineous cases in the local Yorkshire population, and the use of multiplex families. Nevertheless this is a promising high throughput approach to retinal dystrophy diagnostics.
[Show abstract][Hide abstract] ABSTRACT: This paper investigates the willingness of adults with inherited retinal disease to undergo and pay for diagnostic genetic testing in three hypothetical scenarios and to explore the factors that influence decision making. Fifty patients were presented with three scenarios whereby genetic testing provided increasing information: confirming the diagnosis and inheritance pattern alone, providing additional information on future visual function, and identifying in addition a new treatment which could stabilise their condition. Willingness to pay (WTP) was elicited using an iterative bidding game. Regression analysis was used to investigate the probability of agreeing to and paying for testing. Qualitative data were also reviewed to provide a comprehensive understanding of WTP and decision making. The majority of participants agreed to undergo genetic testing in each of the three scenarios. Scenario 2 was the least acceptable with 78% of participants agreeing to genetic testing. The probability of agreeing to genetic testing decreased with age. Between 72 and 96% of participants reported a WTP for genetic testing. Average WTP was £539, £1516, and £6895 for scenarios 1, 2, and 3 respectively. Older participants and participants with higher incomes were willing to pay more for testing. Qualitative data provided additional detail about the rationale behind participants' decisions. The study suggests that patients with inherited retinal disease were willing to undergo and to pay for diagnostic genetic testing, suggesting that they valued the information it may provide. However, several patients preferred not to receive prognostic information and were less willing to pay for genetic testing that yielded such detail.European Journal of Human Genetics advance online publication, 11 June 2014; doi:10.1038/ejhg.2014.111.
Full-text · Article · Jun 2014 · European journal of human genetics: EJHG
[Show abstract][Hide abstract] ABSTRACT: PurposeThe use of intravitreal vascular endothelial growth factor (VEGF) inhibitor medications has widened considerably to include indications affecting females of reproductive age.Patients and methodsWe present our experiences following intravitreal injection of bevacizumab during the first trimester of unrecognised pregnancies in four women.ResultsAll our patients were inadvertently exposed to bevacizumab within the first trimester when placental growth and fetal organogenesis take place. There were three cases of pregnancy without complication and one case of complicated pregnancy in which there was a significant past obstetric history.Conclusion
This case series provides further insights into intravitreal injection of bevacizumab in early pregnancy. There is insufficient information to suggest that such use is safe, nor is there definitive evidence to suggest that it causes harm. We advise that ophthalmologists discuss pregnancy with women of childbearing age undergoing intraocular anti-VEGF injections. Should a woman become pregnant, counselling is needed to explain the potential risks and benefits, and the limited available data relating to the use of these agents in early pregnancy.Eye advance online publication, 17 January 2014; doi:10.1038/eye.2013.311.
No preview · Article · Jan 2014 · Eye (London, England)
[Show abstract][Hide abstract] ABSTRACT: Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term 'genetic counselling'. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations.European Journal of Human Genetics advance online publication, 8 January 2014; doi:10.1038/ejhg.2013.296.
Preview · Article · Jan 2014 · European journal of human genetics: EJHG