scholarly journals Predicting the immediate impact of national lockdown on neovascular age-related macular degeneration and associated visual morbidity: an INSIGHT Health Data Research Hub for Eye Health report

2021 ◽  
pp. bjophthalmol-2021-319383
Author(s):  
Susan P Mollan ◽  
Dun Jack Fu ◽  
Ching-Yi Chuo ◽  
Jacqueline G Gannon ◽  
Wen Hwa Lee ◽  
...  

ObjectivePredicting the impact of neovascular age-related macular degeneration (nAMD) service disruption on visual outcomes following national lockdown in the UK to contain SARS-CoV-2.Methods and analysisThis retrospective cohort study includes deidentified data from 2229 UK patients from the INSIGHT Health Data Research digital hub. We forecasted the number of treatment-naïve nAMD patients requiring anti-vascular endothelial growth factor (anti-VEGF) initiation during UK lockdown (16 March 2020 through 31 July 2020) at Moorfields Eye Hospital (MEH) and University Hospitals Birmingham (UHB). Best-measured visual acuity (VA) changes without anti-VEGF therapy were predicted using post hoc analysis of Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD trial sham-control arm data (n=238).ResultsAt our centres, 376 patients were predicted to require anti-VEGF initiation during lockdown (MEH: 325; UHB: 51). Without treatment, mean VA was projected to decline after 12 months. The proportion of eyes in the MEH cohort predicted to maintain the key positive visual outcome of ≥70 ETDRS letters (Snellen equivalent 6/12) fell from 25.5% at baseline to 5.8% at 12 months (UHB: 9.8%–7.8%). Similarly, eyes with VA <25 ETDRS letters (6/96) were predicted to increase from 4.3% to 14.2% at MEH (UHB: 5.9%–7.8%) after 12 months without treatment.ConclusionsHere, we demonstrate how combining data from a recently founded national digital health data repository with historical industry-funded clinical trial data can enhance predictive modelling in nAMD. The demonstrated detrimental effects of prolonged treatment delay should incentivise healthcare providers to support nAMD patients accessing care in safe environments.Trial registration numberNCT00056836.

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Selwyn M. Prea ◽  
Elsa C. Chan ◽  
Gregory J. Dusting ◽  
Algis J. Vingrys ◽  
Bang V. Bui ◽  
...  

Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet”) form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF). However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.


2019 ◽  
Vol 29 (4) ◽  
pp. 368-378 ◽  
Author(s):  
Zois Papadopoulos

Considerable improvement has been achieved in the way in which exudative age-related macular degeneration is conventionally treated and in the associated visual outcomes and prognosis, thanks to the agents with effects against vascular endothelial growth factor (anti-VEGF). By comparison to earlier treatment approaches that involved the use of lasers, the anti-VEGF agents have made it possible to accomplish more positive visual and anatomical outcomes in cases of exudative age-related macular degeneration. Indeed, owing to their positive effects, anti-VEGF agents have quickly come to be considered the gold standard for the treatment of wet age-related macular degeneration. Aflibercept, the most recently approved intravitreally administered anti-VEGF, seems to mark another milestone in the treatment of wet age-related macular degeneration. This anti-VEGF agent presents a series of singular pharmacodynamic and pharmacokinetic attributes that provide it a number of biological benefits in relation to the treatment of choroidal neovascularization compared to other agents. These attributes include high level of affinity for the VEGF-A factor, an intravitreal half-life of great length, as well as the ability to serve as an antagonist for other growth factors besides VEGF. The impact of Aflibercept on the manner in which exudative age-related macular degeneration is managed was demonstrated by thoroughly reviewing the related literature. The present review article highlights the pharmacology, pharmacokinetics, safety and effectiveness of this anti-VEGF agent as well as the landmark clinical studies that have been carried out to establish this drug as a gold standard in the therapy of neovascular age-related macular degeneration. In addition, studies regarding the outcomes and effectiveness of the various dosage regimens, either as monotherapy or in combination with other agents, are also reviewed.


2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yamin Li ◽  
Lina Liang ◽  
Torkel Snellingen ◽  
Kai Xu ◽  
Yun Gao ◽  
...  

Abstract Background Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. Methods/design This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. Discussion Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.


2021 ◽  
pp. 48-56
Author(s):  
Atsuta Ozaki ◽  
Hisashi Matsubara ◽  
Masahiko Sugimoto ◽  
Manami Kuze ◽  
Mineo Kondo ◽  
...  

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is essential for the treatment of macular diseases such as wet age-related macular degeneration and macular edema. Although continued treatment is needed to maintain good vision, some patients cannot continue such injections for various reasons, including specific phobias. Here, we report a case of a patient with a specific phobia of intravitreal injections who could resume treatment after undergoing combined drug and cognitive-behavioral therapy (CBT). A 74-year-old Japanese man diagnosed with retinal angiomatous proliferation by fluorescein angiography and indocyanine green angiography was treated with intravitreal anti-VEGF injection. However, at 8 months after the first treatment, he became difficult to treat because of a phobia of injections. He was treated with photodynamic therapy, but his macular edema did not improve. After a psychiatric consultation, he was diagnosed with a specific phobia of intravitreal injections. Combined drug and CBT enabled him to resume receiving intravitreal injections. This case demonstrates that a specific phobia of intravitreal injections may benefit from combined drug and CBT. In this regard, some patients with high anxiety and fear of intravitreal injections should be referred to a psychiatrist at an early stage.


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