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Showing papers by "Moorfields Eye Hospital published in 2014"


Journal ArticleDOI
TL;DR: The initial results of this retinal gene therapy trial are consistent with improved rod and cone function that overcome any negative effects of retinal detachment, and lend support to further assessment of gene therapy in the treatment of choroideremia and other diseases, such as age-related macular degeneration, for which intervention should ideally be applied before the onset ofretinal thinning.

685 citations


Journal ArticleDOI
10 Jan 2014-Eye
TL;DR: The past decade has seen a greater understanding of the molecular biological mechanisms that determine refractive error, giving further support to the belief that myopia is the result of a complex interaction between genetic predisposition and environmental exposures.
Abstract: Myopia is one of the most prevalent disorders of the eye. Higher myopia is associated with comorbidities that increase risks of severe and irreversible loss of vision, such as retinal detachment, subretinal neovascularization, dense cataract, and glaucoma. In recent years, reports from population-based prevalence studies carried out in various geographical areas now give a clear picture of the current distribution of refractive error. The scarcity of data from well-designed longitudinal cohort studies is still yet to be addressed. These studies have confirmed the previous data indicating that prevalence of refractive error varies according to ethnicity and geographic regions, and also point to an increase in myopia prevalence over the past half-century. The problem is particularly pronounced in affluent, industrialised areas of East Asia. Environmental risk factors for myopia related to socioeconomic status and lifestyle have been identified. The past decade has seen a greater understanding of the molecular biological mechanisms that determine refractive error, giving further support to the belief that myopia is the result of a complex interaction between genetic predisposition and environmental exposures. This review summarizes data on the prevalence, incidence, progression, associations, risk factors, and impact from recent epidemiological studies on myopia.

496 citations


Journal ArticleDOI
01 Feb 2014-BMJ Open
TL;DR: For the first time in at least five decades, diabetic retinopathy/maculopathy is no longer the leading cause of certifiable blindness among working age adults in England and Wales, having been overtaken by inherited retinal disorders.
Abstract: Objectives To report on the causes of blindness certifications in England and Wales in working age adults (16–64 years) in 2009–2010; and to compare these with figures from 1999 to 2000. Design Analysis of the national database of blindness certificates of vision impairment (CVIs) received by the Certifications Office. Setting and participants Working age (16–64 years) population of England and Wales. Main outcome measures Number and cause of blindness certifications. Results The Certifications Office received 1756 CVIs for blindness from persons aged between 16 and 64 inclusive between 1 April 2009 and 31 March 2010. The main causes of blindness certifications were hereditary retinal disorders (354 certifications comprising 20.2% of the total), diabetic retinopathy/maculopathy (253 persons, 14.4%) and optic atrophy (248 persons, 14.1%). Together, these three leading causes accounted for almost 50% of all blindness certifications. Between 1 April 1999 and 31 March 2000, the leading causes of blindness certification were diabetic retinopathy/maculopathy (17.7%), hereditary retinal disorders (15.8%) and optic atrophy (10.1%). Conclusions For the first time in at least five decades, diabetic retinopathy/maculopathy is no longer the leading cause of certifiable blindness among working age adults in England and Wales, having been overtaken by inherited retinal disorders. This change may be related to factors including the introduction of nationwide diabetic retinopathy screening programmes in England and Wales and improved glycaemic control. Inherited retinal disease, now representing the commonest cause of certification in the working age population, has clinical and research implications, including with respect to the provision of care/resources in the NHS and the allocation of research funding.

453 citations


Journal ArticleDOI
TL;DR: The BGI produced greater IOP reduction and a lower rate of glaucoma reoperation than the AGV, but the BGI was associated with twice as many failures because of safety issues.

255 citations


Journal ArticleDOI
TL;DR: This article reviews the literature and attempts to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials.
Abstract: Optic neuritis is an inflammatory optic neuropathy that affects many patients with multiple sclerosis (MS) at some point during their disease course Differentiation of acute episodes of MS-associated optic neuritis from other autoimmune and inflammatory optic neuropathies is vital for treatment choice and further patient management, but is not always straightforward Over the past decade, a number of new imaging, laboratory and electrophysiological techniques have entered the clinical arena To date, however, no consensus guidelines have been devised to specify how and when these techniques can be most rationally applied for the diagnostic work-up of patients with acute optic neuritis In this article, we review the literature and attempt to formulate a consensus for the investigation of patients with acute optic neuritis, both in standard care and in research with relevance to clinical treatment trials

234 citations


Journal ArticleDOI
TL;DR: PIOL can masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other neoplasms such as metastatic cancers, and treatment approaches have centered on systemic methotrexate-based chemotherapy, often with cytarabine (Ara-C) and radiotherapy.

175 citations


Journal ArticleDOI
TL;DR: Long-term functional outcome among uveitis patients is good, with BCVA remaining stable for more than 10 years of follow-up, and in cases when vision loss occurs, it is related mainly to retinal changes.

163 citations


Journal ArticleDOI
TL;DR: Native T1 mapping in Fabry disease is a reproducible technique and T1 reduction prior to the onset of LVH is associated with early diastolic and systolic changes measured by echocardiography.
Abstract: Cardiovascular magnetic resonance (CMR) derived native myocardial T1 is decreased in patients with Fabry disease even before left ventricular hypertrophy (LVH) occurs and may be the first non-invasive measure of myocyte sphingolipid storage. The relationship of native T1 lowering prior to hypertrophy and other candidate early phenotype markers are unknown. Furthermore, the reproducibility of T1 mapping has never been assessed in Fabry disease. Sixty-three patients, 34 (54%) female, mean age 48 ± 15 years with confirmed (genotyped) Fabry disease underwent CMR, ECG and echocardiographic assessment. LVH was absent in 25 (40%) patients. Native T1 mapping was performed with both Modified Look-Locker Inversion recovery (MOLLI) sequences and a shortened version (ShMOLLI) at 1.5 Tesla. Twenty-one patients underwent a second scan within 24 hours to assess inter-study reproducibility. Results were compared with 63 healthy age and gender-matched volunteers. Mean native T1 in Fabry disease (LVH positive), (LVH negative) and healthy volunteers was 853 ± 50 ms, 904 ± 46 ms and 968 ± 32 ms (for all p < 0.0001) by ShMOLLI sequences. Native T1 showed high inter-study, intra-observer and inter-observer agreement with intra-class correlation coefficients (ICC) of 0.99, 0.98, 0.97 (ShMOLLI) and 0.98, 0.98, 0.98 (MOLLI). In Fabry disease LVH negative individuals, low native T1 was associated with reduced echocardiographic-based global longitudinal speckle tracking strain (−18 ± 2% vs −22 ± 2%, p = 0.001) and early diastolic function impairment (E/E’ = 7 [6–8] vs 5 [5–6], p = 0.028). Native T1 mapping in Fabry disease is a reproducible technique. T1 reduction prior to the onset of LVH is associated with early diastolic and systolic changes measured by echocardiography.

162 citations


Journal ArticleDOI
TL;DR: It is established that different levels of impaired PLK4 activity result in growth and cilia phenotypes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features.
Abstract: Centrioles are essential for ciliogenesis. However, mutations in centriole biogenesis genes have been reported in primary microcephaly and Seckel syndrome, disorders without the hallmark clinical features of ciliopathies. Here we identify mutations in the genes encoding PLK4 kinase, a master regulator of centriole duplication, and its substrate TUBGCP6 in individuals with microcephalic primordial dwarfism and additional congenital anomalies, including retinopathy, thereby extending the human phenotypic spectrum associated with centriole dysfunction. Furthermore, we establish that different levels of impaired PLK4 activity result in growth and cilia phenotypes, providing a mechanism by which microcephaly disorders can occur with or without ciliopathic features.

160 citations


Journal ArticleDOI
TL;DR: The lack of a clear association of disruption of retinal structure or function in ACHM with age suggests that the window of opportunity for intervention by gene therapy is wider in some individuals than previously indicated.

142 citations


Journal ArticleDOI
01 May 2014-Eye
TL;DR: Major advances in understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process, including in vitro fertilisation techniques.
Abstract: Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations.

Journal ArticleDOI
TL;DR: Foveal cone specialization and pit morphology vary greatly in albinism, and the degree to which retinal anatomy correlates with genotype or visual function remains unclear, and future examination of larger patient groups will provide important insight.
Abstract: Purpose Albinism is associated with disrupted foveal development, though intersubject variability is becoming appreciated We sought to quantify this variability, and examine the relationship between foveal cone specialization and pit morphology in patients with a clinical diagnosis of albinism

Journal ArticleDOI
TL;DR: High-quality evidence from six trials revealed that participants receiving intravitreal anti-VEGF treatment were 2.71 times more likely to gain at least 15 letters of visual acuity at six months compared to participants treated with sham injections.
Abstract: Background Central retinal vein occlusion (CRVO) is a common retinal vascular disorder in which macular edema (ME) may develop, with a consequent reduction in visual acuity. The visual prognosis in CRVO-ME is poor in a substantial proportion of patients, especially those with the ischemic subtype, and until recently there has been no treatment of proven benefit. Macular grid laser treatment is ineffective, and whilst a few recent randomized controlled trials (RCTs) suggest short-term gains in visual acuity with intravitreal steroids for patients with non-ischemic CRVO-ME, there is no established treatment for ischemic CRVO-ME. Anti-vascular endothelial growth factor (anti-VEGF) agents have been used to treat ME resulting from a variety of causes and may represent a treatment option for CRVO-ME.

Journal ArticleDOI
TL;DR: The accumulated effect of repeat dexamethasone pellet implantations improves retinal thickness and resolves ocular inflammation, resulting in restoration of ocular function.

Journal ArticleDOI
TL;DR: An extremely strong MHC risk component in BSCR is defined, and evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum is detected.
Abstract: Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% of cases carry the HLA-A29 allele, which defines the strongest documented HLA association for a human disease. We have conducted a genome-wide association study in 96 Dutch and 27 Spanish cases, and 398 unrelated Dutch and 380 Spanish controls. Fine-mapping the primary MHC association through high-resolution imputation at classical HLA loci, identified HLA-A*29:02 as the principal MHC association (odds ratio (OR) = 157.5, 95% CI 91.6–272.6, P = 6.6 × 10−74). We also identified two novel susceptibility loci at 5q15 near ERAP2 (rs7705093; OR = 2.3, 95% CI 1.7–3.1, for the T allele, P = 8.6 × 10−8) and at 14q32.31 in the TECPR2 gene (rs150571175; OR = 6.1, 95% CI 3.2–11.7, for the A allele, P = 3.2 × 10−8). The association near ERAP2 was confirmed in an independent British case–control samples (combined meta-analysis P = 1.7 × 10−9). Functional analyses revealed that the risk allele of the polymorphism near ERAP2 is strongly associated with high mRNA and protein expression of ERAP2 in B cells. This study further defined an extremely strong MHC risk component in BSCR, and detected evidence for a novel disease mechanism that affects peptide processing in the endoplasmic reticulum.

Journal ArticleDOI
TL;DR: To compare visual outcomes after deep anterior lamellar keratoplasty (DALK) and penetrating ker atoplasty for keratoconus, and to compare additional outcomes relating to factors which may contribute to poor visual outcomes (e.g. astigmatism, graft rejection and failure), a number of electronic databases were searched.
Abstract: Background Keratoconus is an ectatic (weakening) disease of the cornea, which is the clear surface at the front of the eye. Approximately 10% to 15% of patients diagnosed with keratoconus require corneal transplantation. This may be full-thickness (penetrating) or partial-thickness (lamellar). Objectives To compare visual outcomes after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty for keratoconus, and to compare additional outcomes relating to factors which may contribute to poor visual outcomes (e.g. astigmatism, graft rejection and failure). Search methods We searched a number of electronic databases including CENTRAL, PubMed and EMBASE without using any date or language restrictions. We last searched the electronic databases on 31 October 2013. We also handsearched the proceedings of several international ophthalmic conferences. Selection criteria We included all randomised controlled trials (RCTs) comparing the outcomes of DALK and penetrating keratoplasty in the treatment of keratoconus. Data collection and analysis Two authors assessed trial quality and extracted data independently. For dichotomous data (graft failure, rejection, achievement of functional vision) results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). For continuous data (postoperative best corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), keratometric astigmatism and spherical equivalent) results were expressed as mean differences (MDs) and 95% CIs. Main results We identified two completed studies, with a total of 111 participants (n = 30 and n = 81), both conducted in Iran, that met our inclusion criteria. Participants had moderate to severe keratoconus pre-operatively and were randomly allocated to receive either DALK or penetrating keratoplasty. Only one eye of each participant was treated as part of the trials. The smaller study had 12 month follow-up data for all participants. For the larger study, four DALK surgeries had to be abandoned due to technical failure and visual and refractive outcomes were not measured in these participants. Follow-up length for the remaining 77 participants ranged from 6.8 to 36.4 months, with all 77 followed for at least three months post-suture removal. Details of the randomisation procedure were unavailable for the smaller study and so sensitivity analyses were conducted to determine if the results from this study had affected the overall results of the review. Neither of the included studies reported a difference between groups on any of the measures of post-graft visual achievement, keratometric astigmatism or spherical equivalent. A single case of graft failure in a penetrating keratoplasty was reported. No postoperative graft failures were reported in the DALK group of either study. Instances of graft rejection were reported in both groups, in both studies. The majority of these cases were successfully treated with steroids. The data, which related to all cases in each study - given that the four cases that did not go ahead as planned had already technically failed without presence of rejection - showed that rejection was less likely to occur in DALK (odds ratio (OR): 0.33, 95% confidence interval (CI) 0.14 to 0.81, GRADE rating: moderate). Results of the sensitivity analysis indicated that inclusion of the Razmju 2011 study did not bias the results with regards to rejection episodes. While sensitivity analysis showed altered results with regards to failure rates, the data available from the Javadi 2010 study alone had a very wide 95% CI, suggesting an imprecise estimate. Therefore, even after removal of the Razmju 2011 data, it is still difficult to draw conclusions regarding superiority of one technique over another with regards to graft failure. DALK was unable to be completed as planned in four cases and in a further three cases, complications during dissection required further intervention. Other adverse events, of varying severity, were reported in both intervention groups with similar frequency. For both types of surgery, these included postoperative astigmatism, steroid induced ocular hypertension and persistent epithelial defects. In recipients of DALK, one participant had interface neovascularisation (a proliferation of blood vessels where the host and donor cornea come together) and one had wrinkling of Descemet's membrane, the basement membrane separating the corneal stroma from the corneal endothelium. In the penetrating keratoplasty groups, one participant required graft resuturing and one had an atonic pupil, a condition in which the pupil dilates and is non-reactive. Overall, the quality of the evidence was rated as very low to moderate, with methodological limitations, incomplete data analysis and imprecision of findings, as well as high risk of bias in several areas for both studies. Authors' conclusions We found no evidence to support a difference in outcomes with regards to BCVA at three months post-graft or at any of the other time points analysed (GRADE rating: very low). We also found no evidence of a difference in outcomes with regards to graft survival, final UCVA or keratometric outcomes. We found some evidence that rejection is more likely to occur following penetrating keratoplasty than DALK (GRADE rating: moderate). The small number of studies included in the review and methodological issues relating to the two, mean that the overall quality of the evidence in this review is low. There is currently insufficient evidence to determine which technique may offer better overall outcomes - final visual acuity and time to attain this, keratometric stabilisation, risk of rejection or failure, or both, and risk of other adverse events - for patients with keratoconus. Large randomised trials comparing the outcomes of penetrating keratoplasty and DALK in the treatment of keratoconus are needed.

Journal ArticleDOI
TL;DR: This study is the largest prospective series of ocular syphilis in the post-penicillin era and confirms good visual outcomes for treated IOS, irrespective of HIV status or time to presentation.
Abstract: PURPOSE The British Ocular Syphilis Study (BOSS) is the first national prospective epidemiological study of intraocular syphilis (IOS) in light of the global increase in early syphilis (ES). The aims were to ascertain the UK incidence, demographics, clinical features, laboratory data, and posttreatment visual outcomes of patients with IOS. METHODS Prospective study of IOS, reported through the national reporting system (British Ocular Surveillance Unit) from 2009 to 2011. Case definition was any adult presenting with intraocular inflammation in ES. RESULTS A total of 41 new cases (63 eyes) of IOS were reported, giving an annual incidence of 0.3 per million UK adult population. Mean age was 48.7 years (range, 20.6-75.1); 90.2% were male. All had RPR/VDRL titers of ≥1:16. Bilateral ocular involvement occurred in 56%; in unilateral cases, the left eye was more commonly affected (P = 0.009). Mean presenting logMAR visual acuity was 0.52 (20/63 Snellen; range, -0.2 to 2.30 logMAR). Panuveitis was the commonest diagnosis, seen in 41.3%, and isolated anterior uveitis was uncommon (9.5%). Subgroup analysis between HIV-positive and -negative patients found no significant differences in terms of proportion of bilateral disease, presenting or post treatment acuity. HIV-positive patients had higher rates of panuveitis. At final follow-up, 92.1% had visual acuity ≥ 0.3 logMAR (20/40 Snellen) after antibiotic therapy. CONCLUSIONS This study is the largest prospective series of ocular syphilis in the post-penicillin era. It confirms good visual outcomes for treated IOS, irrespective of HIV status or time to presentation. The study identified an unexpected preponderance for left eye involvement in uniocular cases; which is unexplained.

Journal ArticleDOI
TL;DR: People with self‐identified vision impairment are surveyed to determine their use of accessibility features of consumer electronic devices such as smartphones, tablet computers, and e‐book readers.

Journal ArticleDOI
TL;DR: In this article, the authors studied 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.

Journal ArticleDOI
TL;DR: The results demonstrate that the new grading tool for LSCD, the COASTL tool, is reliable and repeatable, and that improvements in the biomarkers used in this tool correlate positively with improvements in visual acuity.
Abstract: Limbal stem cell deficiency (LSCD) is an eye disorder in which the stem cells responsible for forming the surface skin of the cornea are destroyed by disease. This results in pain, loss of vision, and a cosmetically unpleasant appearance. Many new treatments, including stem cell therapies, are emerging for the treatment of this condition, but assessment of these new technologies is severely hampered by the lack of biomarkers for this disease or validated tools for assessing its severity. The aims of this study were to design and test the reliability of a tool for grading LSCD, to define a set of core outcome measures for use in evaluating treatments for this condition, and to demonstrate their utility. This was achieved by using our defined outcome set (which included the Clinical Outcome Assessment in Surgical Trials of Limbal stem cell deficiency [COASTL] tool) to evaluate the 3-year outcomes for allogeneic ex vivo cultivated limbal epithelial transplantation (allo-CLET) in patients who had bilateral total LSCD secondary to aniridia or Stevens-Johnson syndrome. The results demonstrate that our new grading tool for LSCD, the COASTL tool, is reliable and repeatable, and that improvements in the biomarkers used in this tool correlate positively with improvements in visual acuity. The COASTL tool showed that following allo-CLET there was a decrease in LSCD severity and an increase in visual acuity up to 12 months post-treatment, but thereafter LSCD severity and visual acuity progressively deteriorated.

Journal ArticleDOI
TL;DR: Although the studies were too small to provide definitive evidence regarding the relative safety of the surgical procedures, it was noted that there were relatively fewer complications with non-filtering surgery compared to trabeculectomy (17% and 65% respectively).
Abstract: Background Glaucoma is the second commonest cause of blindness worldwide. Non-penetrating glaucoma surgeries have been developed as a safer and more acceptable surgical intervention to patients compared to conventional procedures. Objectives To compare the effectiveness of non-penetrating trabecular surgery compared with conventional trabeculectomy in people with glaucoma. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 8), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to September 2013), EMBASE (January 1980 to September 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to September 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 September 2013. Selection criteria This review included relevant randomised controlled trials (RCTs) and quasi-RCTs on participants undergoing standard trabeculectomy for open-angle glaucoma compared to non-penetrating surgery, specifically viscocanalostomy or deep sclerectomy, with or without adjunctive measures. Data collection and analysis Two review authors independently reviewed the titles and abstracts of the search results. We obtained full copies of all potentially eligible studies and assessed each one according to the definitions in the 'Criteria for considering studies' section of this review. We used standard methodological procedures expected by The Cochrane Collaboration. Main results We included five studies with a total of 311 eyes (247 participants) of which 133 eyes (participants) were quasi-randomised. One hundred and sixty eyes which had trabeculectomy were compared to 151 eyes that had non-penetrating glaucoma surgery (of which 101 eyes had deep sclerectomy and 50 eyes had viscocanalostomy). The confidence interval (CI) for the odds ratio (OR) of success (defined as achieving target eye pressure without eye drops) does not exclude a beneficial effect of either deep sclerectomy or trabeculectomy (OR 0.98, 95% CI 0.51 to 1.88). The odds of success in viscocanalostomy participants was lower than in trabeculectomy participants (OR 0.33, 95% CI 0.13 to 0.81). We did not combine the different types of non-penetrating surgery because there was evidence of a subgroup difference when examining total success. The odds ratio for achieving target eye pressure with or without eye drops was imprecise and was compatible with a beneficial effect of either trabeculectomy or non-penetrating filtration surgery (NPFS) (OR 0.79, 95% CI 0.35 to 1.79). Operative adjuvants were used in both treatment groups; more commonly in the NPFS group compared to the trabeculectomy group but no clear effect of their use could be determined. Although the studies were too small to provide definitive evidence regarding the relative safety of the surgical procedures we noted that there were relatively fewer complications with non-filtering surgery compared to trabeculectomy (17% and 65% respectively). Cataract was more commonly reported in the trabeculectomy studies. None of the five trials used quality of life measure questionnaires. The methodological quality of the studies was not good. Most studies were at high risk of bias in at least one domain and for many, there was lack of certainty due to incomplete reporting. Adequate sequence generation was noted only in one study. Similarly, only two studies avoided detection bias. We detected incomplete outcome data in three of the included studies. Authors' conclusions This review provides some limited evidence that control of IOP is better with trabeculectomy than viscocanalostomy. For deep sclerectomy, we cannot draw any useful conclusions. This may reflect surgical difficulties in performing non-penetrating procedures and the need for surgical experience. This review has highlighted the lack of use of quality of life outcomes and the need for higher methodological quality RCTs to address these issues. Since it is unlikely that better IOP control will be offered by NPFS, but that these techniques offer potential gains for patients in terms of quality of life, we feel that such a trial is likely to be of a non-inferiority design with quality of life measures.

Journal ArticleDOI
TL;DR: The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV) and Africa has the highest incidence rates.

Journal ArticleDOI
TL;DR: Corticosteroid use before diagnosis of AK is highly predictive of a poorer visual outcome, largely due to the initial misdiagnosis of AK as herpetic keratitis.

Journal ArticleDOI
08 Apr 2014-PLOS ONE
TL;DR: In vitro clonal analysis is used to confirm that limbal crypts provide a niche for the resident LESCs and present a three dimensional reconstruction of the LESC niche in which the stem cell is closely associated and maintained by both dendritic pigmented limbal melanocytes and elongated limbal stromal cells.
Abstract: Limbal epithelial stem cells (LESCs) are essential to maintain the transparent ocular surface required for vision. Despite great advances in our understanding of ocular stem cell biology over the last decade, the exact location of the LESC niche remains unclear. In the present study we have used in vitro clonal analysis to confirm that limbal crypts provide a niche for the resident LESCs. We have used high-resolution imaging of the basal epithelial layer at the limbus to identify cells with a morphology consistent with stem cells that were only present within the basal layer of the limbal crypts. These cells are proximal to limbal stromal cells suggesting direct cell-to-cell interaction. Serial block-face scanning electron microscopy (SBFSEM) confirmed that the putative LESCs are indeed in direct contact with cells in the underlying stroma, a contact that is facilitated by focal basement membrane interruptions. Limbal mesenchymal cells previously identified in the human limbus collocate in the crypt-rich limbal stromal area in the vicinity of LESCs and may be involved in the cell-to-cell contact revealed by SBFSEM. We also observed a high population of melanocytes within the basal layer of the limbal crypts. From these observations we present a three dimensional reconstruction of the LESC niche in which the stem cell is closely associated and maintained by both dendritic pigmented limbal melanocytes and elongated limbal stromal cells.

Journal ArticleDOI
TL;DR: The Argus® II is the first retinal prosthesis approved for the treatment of patients blind from retinitis pigmentosa (RP), receiving CE marking in March 2011 and FDA approval in February 2013, and Alpha-IMS followed closely and obtained CE marks in July 2013.
Abstract: Introduction/background The Argus® II is the first retinal prosthesis approved for the treatment of patients blind from retinitis pigmentosa (RP), receiving CE (Conformite Europeenne) marking in March 2011 and FDA approval in February 2013. Alpha-IMS followed closely and obtained CE marking in July 2013. Other devices are being developed, some of which are currently in clinical trials. Sources of data A systematic literature search was conducted on PubMED, Google Scholar and IEEExplore. Areas of agreement Retinal prostheses play a part in restoring vision in blind RP patients providing stable, safe and long-term retinal stimulation. Areas of controversy Objective improvement in visual function does not always translate into consistent improvement in the patient's quality of life. Controversy exists over the use of an external image-capturing device versus internally placed photodiode devices. Growing points The alpha-IMS, a photovoltaic-based retinal prosthesis recently obtained its CE marking in July 2013. Areas timely for developing research Improvement in retinal prosthetic vision depends on: (i) improving visual resolution, (ii) improving the visual field, (iii) developing an accurate neural code for image processing and (iv) improving the biocompatibility of the device to ensure longevity.

Journal ArticleDOI
01 Aug 2014-Eye
TL;DR: The need for more high-quality prospective surgical trials in the management of the childhood glaucoma is highlighted, and this paper highlights the need for collaborative approaches to researching and delivering this care.
Abstract: Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma.

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TL;DR: The results support a role for the RPE in disease pathogenesis and several novel variants are reported, including a highly prevalent substitution in patients of South Asian descent that is associated with earlier-onset disease.

Journal ArticleDOI
TL;DR: Intravitreal injections of bevacizumab are used to treat neovascularization secondary to systemic lupus erythematosus but should be timed with retinal laser photocoagulation to prevent further progression of retinal ischemia.
Abstract: Ischemic retinal vasculitis is an inflammation of retinal blood vessels associated with vascular occlusion and subsequent retinal hypoperfusion. It can cause visual loss secondary to macular ischemia, macular edema, and neovascularization leading to vitreous hemorrhage, fibrovascular proliferation, and tractional retinal detachment. Ischemic retinal vasculitis can be idiopathic or secondary to systemic disease such as in Behcet's disease, sarcoidosis, tuberculosis, multiple sclerosis, and systemic lupus erythematosus. Corticosteroids with or without immunosuppressive medication are the mainstay treatment in retinal vasculitis together with laser photocoagulation of retinal ischemic areas. Intravitreal injections of bevacizumab are used to treat neovascularization secondary to systemic lupus erythematosus but should be timed with retinal laser photocoagulation to prevent further progression of retinal ischemia. Antitumor necrosis factor agents have shown promising results in controlling refractory retinal vasculitis excluding multiple sclerosis. Interferon has been useful to control inflammation and induce neovascular regression in retinal vasculitis secondary to Behcet's disease and multiple sclerosis. The long term effect of these management strategies in preventing the progression of retinal ischemia and preserving vision is not well understood and needs to be further studied.

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TL;DR: Phakic IOL surgery was safer than excimer laser surgical correction for moderate to high myopia as it results in significantly less loss of best spectacle corrected visual acuity (BSCVA) at 12 months postoperatively, however there is a low risk of developing early cataract with phaki IOLs.
Abstract: Background Myopia is a condition in which the focusing power (refraction) of the eye is greater than that required for clear distance vision. There are two main types of surgical correction for moderate to high myopia; excimer laser and phakic intraocular lenses (IOLs). Excimer laser refractive surgery for myopia works by removing corneal stroma to lessen the refractive power of the cornea and to bring the image of a viewed object into focus onto the retina rather than in front of it. Phakic IOLs for the treatment of myopia work by diverging light rays so that the image of a viewed object is brought into focus onto the retina rather than in front of the retina. They can be placed either in the anterior chamber of the eye in front of the iris or in the posterior chamber of the eye between the iris and the natural lens. Objectives To compare excimer laser refractive surgery and phakic IOLs for the correction of moderate to high myopia by evaluating postoperative uncorrected visual acuity, refractive outcome, potential loss of best spectacle corrected visual acuity (BSCVA) and the incidence of adverse outcomes. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 February 2014. Selection criteria We included randomised controlled trials (RCTs) comparing excimer laser refractive surgery and phakic IOLs for the correction of myopia greater than 6.0 diopters (D) spherical equivalent. Data collection and analysis Two authors independently assessed trial quality and extracted data. We performed data analysis. We summarised data for outcomes using odds ratios. We used a fixed-effect model as only three trials were included in the review. Main results This review included three RCTs with a total of 228 eyes. The range of myopia of included patients was -6.0 D to -20.0 D of myopia with up to 4.0 D of myopic astigmatism. The percentage of eyes with uncorrected visual acuity (UCVA) of 20/20 or better at 12 months postoperative was not significantly different between the two groups. Phakic IOL surgery was safer than excimer laser surgical correction for moderate to high myopia as it results in significantly less loss of best spectacle corrected visual acuity (BSCVA) at 12 months postoperatively. However there is a low risk of developing early cataract with phakic IOLs. Phakic IOL surgery appears to result in better contrast sensitivity than excimer laser correction for moderate to high myopia. Phakic IOL surgery also scored more highly on patient satisfaction/preference questionnaires. Authors' conclusions The results of this review suggest that, at one year post surgery, phakic IOLs are safer than excimer laser surgical correction for moderate to high myopia in the range of -6.0 to -20.0 D and phakic IOLs are preferred by patients. While phakic IOLs might be accepted clinical practice for higher levels of myopia (greater than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism), it may be worth considering phakic IOL treatment over excimer laser correction for more moderate levels of myopia (less than or equal to 7.0 D of myopic spherical equivalent with or without astigmatism). Further RCTs adequately powered for subgroup analysis are necessary to further elucidate the ideal range of myopia for phakic IOLs. This data should be considered alongside comparative data addressing long-term safety as it emerges.

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TL;DR: This is the first demonstration of ATP manipulation in vivo and may provide a simple non-invasive route to combating age related tissue decline.