Aim Mutation in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). In this study, we identified the strength of the CFH Y402H gene variant association in a UK AMD cohort and tested the hypothesis that this variant may influence the biological response of choroidal neovascularisation (CNV) following photodynamic therapy (PDT) for CNV. Methods A total of 557 cases with AMD and 551 normal controls were genotyped for the CFH Y402H (1277 C/T) variant using the 5 0 nuclease TaqMan assay for allelic discrimination. The CFH gene association for AMD, for the different CNV subtypes and for patients needing PDT was estimated. Twenty-seven PDT-treated patients were followed up for 15 months with ETDRS-derived vision, clinical examination, and fundus angiography. Individuals with different CFH genotypes were then analysed for any association with visual change following PDT. Results The risk association for AMD with the CFH CC genotype (odd ratio (OR) ¼ 3.62, P c o0.0001) was similar to that reported in other Caucasian cohorts. The magnitude and strength of this association was stronger in AREDS stages 2-4 (ORs ¼ 4.48, 2.69, and 5.17). ORs for the risk of predominantly classic CNV were significantly raised for both the CC (OR ¼ 17.87, Po0.0001) and CT (OR ¼ 9.06, P ¼ 0.0002) genotypes. The number of patients carrying the high-risk C allele was 70.4% in those requiring PDT as compared to 52.3% in the non-PDT group (OR ¼ 2.16, P ¼ 0.011), and presence of the CC genotype significantly increased the risk of PDT (OR ¼ 5.48, P ¼ 0.015). The degree of visual loss following PDT was significantly higher in the CFH CC genotype group (P ¼ 0.038); 50% of CC cases (n ¼ 13) and 45% of the CT cases (n ¼ 12) lost 15 or more ETDRS letters at final follow-up. Conclusion In this UK cohort of AMD patients, the CFH Y402H variant was significantly enriched in patients with predominantly classic CNV. Patients homozygous for the CFH Y402H genotype seem to have worse visual acuity after PDT.
Significant positive and negative associations exist between HLA alleles and AMD. HLA polymorphisms influence the development of AMD, possibly via modulating choroidal immune function.
The burden of disease in diabetes eye care has reached gargantuan proportions in the 21st century. There are an estimated 552 million people globally who will live with diabetes by the year 2030, with half of this population eventually developing diabetic retinopathy. 1 As such, we are approaching a landmark in history where radical changes in the way we practice ophthalmology will be required to maintain delivery of high quality care to these patients. The examination of the human retina was only made possible in 1851, when Hermann von Helmholtz first held up a lens to a patient's eye using a naked candle as a source of illumination. 2 To this day, ophthalmologists round the world use the same physical principles to perform a retinal examination. The evolution of the ophthalmic examination has occurred in a gradual step-wise fashion, following the developments of its time; for example, the invention of electricity allowing for more powerful light sources, and modern optical lenses that offer a wider field-of-view of the retina. However, it has been the more recent exponential leaps in digital technology that 629983D STXXX10.
Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography.
Objective To evaluate the relationship, over time, between central graft thickness and visual acuity following Descemet's stripping endothelial keratoplasty (DSEK). Methods A retrospective analysis of 70 consecutive cases of DSEK. All donor lenticules were dissected manually. Serial postoperative measurements of central graft and total corneal thicknesses were made using anterior segment optical coherence tomography. Visual acuity, refraction and patient demographics were collected from case notes. The correlation between central graft thickness and visual acuity at serial time points was calculated. Results The median age at surgery was 75 years (lower quartile (LQ) 66, upper quartile (UQ) 83, range 36-90 years). Nineteen eyes were excluded from statistical analysis, leaving 51 eyes of 46 patients remaining. Last follow-up occurred a median of 12 months postoperatively (LQ 6, UQ 23, range 4-38 months). The median preoperative visual acuity was 0.71 logarithm of the minimum angle of resolution (logMAR), improving to 0.34 logMAR postoperatively (p<0.001, n=43). Median graft thickness decreased from 209 μm at day 1 to 142 μm at last follow-up (p<0.001). No statistically significant correlation was found between central total corneal thickness and visual acuity at any time point. Except for a single time point, no statistically significant correlation was found between central graft thickness and visual acuity. Conclusion There is no clear association between central graft, or total corneal, thickness and visual acuity following DSEK.
The pro-inflammatory homozygous IL8 -251AA genotype is an important risk factor for AMD. This may have implications for future therapy with biological agents that could target this cytokine.
Intracameral mydriasis was clinically effective in most patients undergoing cataract surgery and might be associated with an improved patient experience and a more streamlined preoperative flow. Mydrane represents a licensed alternative to the off-label use of other intracameral mydriatic agents, but was not judged to be a cost-effective intervention for routine use in this particular setting.
Age-related Macular Degeneration (AMD) is a common, irreversible blinding condition that leads to the loss of central vision. AMD has a complex aetiology with both genetic as well as environmental risks factors, and share many similarities with Alzheimer's disease. Recent findings have contributed significantly to unravelling its genetic architecture that is yet to be matched by molecular insights. Studies are made more challenging by observations that aged and AMD retinas accumulate the highly pathogenic Alzheimer's-related Amyloid beta (Aβ) group of peptides, for which there appears to be no clear genetic basis. Analyses of human donor and animal eyes have identified retinal Aβ aggregates in retinal ganglion cells (RGC), the inner nuclear layer, photoreceptors as well as the retinal pigment epithelium. Aβ is also a major drusen constituent; found correlated with elevated drusen-load and age, with a propensity to aggregate in retinas of advanced AMD. Despite this evidence, how such a potent driver of neurodegeneration might impair the neuroretina remains incompletely understood, and studies into this important aspect of retinopathy remains limited. In order to address this we exploited R28 rat retinal cells which due to its heterogeneous nature, offers diverse neuroretinal cell-types in which to study the molecular pathology of Aβ. R28 cells are also unaffected by problems associated with the commonly used RGC-5 immortalised cell-line, thus providing a well-established model in which to study dynamic Aβ effects at single-cell resolution. Our findings show that R28 cells express key neuronal markers calbindin, protein kinase C and the microtubule associated protein-2 (MAP-2) by confocal immunofluorescence which has not been shown before, but also calretinin which has not been reported previously. For the first time, we reveal that retinal neurons rapidly internalised Aβ1-42, the most cytotoxic and aggregate-prone amongst the Aβ family. Furthermore, exposure to physiological amounts of Aβ1-42 for 24 h correlated with impairment to neuronal MAP-2, a cytoskeletal protein which regulates microtubule dynamics in axons and dendrites. Disruption to MAP-2 was transient, and had recovered by 48 h, although internalised Aβ persisted as discrete puncta for as long as 72 h. To assess whether Aβ could realistically localise to living retinas to mediate such effects, we subretinally injected nanomolar levels of oligomeric Aβ1-42 into wildtype mice. Confocal microscopy revealed the presence of focal Aβ deposits in RGC, the inner nuclear and the outer plexiform layers 8 days later, recapitulating naturally-occurring patterns of Aβ aggregation in aged retinas. Our novel findings describe how retinal neurons internalise Aβ to transiently impair MAP-2 in a hitherto unreported manner. MAP-2 dysfunction is reported in AMD retinas, and is thought to be involved in remodelling and plasticity of post-mitotic neurons. Our insights suggest a molecular pathway by which this could occur in the senescent eye leading to complex diseases such ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.