scholarly journals A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015

BMJ Open ◽  
2017 ◽  
Vol 7 (10) ◽  
pp. e018289 ◽  
Author(s):  
William Hollingworth ◽  
Tim Jones ◽  
Barnaby C Reeves ◽  
Tunde Peto
Keyword(s):  
Longitudinal Study ◽  
Diabetic Macular Oedema ◽  
Cost Effective ◽  
Age Related Macular Degeneration ◽  
Geographical Variations ◽  
Anti Vegf ◽  
Age Related ◽  
Eye Disorders ◽  
Effective Care ◽  
Endothelial Growth Factor

ObjectivesHigh-cost antivascular endothelial growth factor (anti-VEGF) medicines for eye disorders challenge ophthalmologists and policymakers to provide fair access for patients while minimising costs. We describe the growth in the use and costs of these medicines and measure inequalities in access.DesignLongitudinal study using Hospital Episode Statistics (2005/2006 to 2014/2015) and hospital prescribing cost reports (2008/2009 to 2015/2016). We used Poisson regression to estimate standardised rates and explore temporal and geographical variations.SettingNational Health Service (NHS) care in England.PopulationPatients receiving anti-VEGF injections for age-related macular degeneration, diabetic macular oedema and other eye disorders.InterventionsHigher-cost drugs (ranibizumab or aflibercept) recommended by the National Institute for Health and Care Excellence or lower-cost drug (bevacizumab) not licensed for eye disorders.Main outcome measuresNational procedure rates and variation between and within clinical commissioning groups (CCGs). Cost of ranibizumab and aflibercept prescribing.ResultsInjection procedures increased by 215% between 2010/2011 and 2014/2015. In 2014/2015 there were 388 031 procedures (714 per 100 000). There is no evidence that the dramatic growth in rates is slowing down. Since 2010/2011 the estimated cost of ranibizumab and aflibercept increased by 247% to £447 million in 2015/2016, equivalent to the entire annual budget of a CCG. There are large inequalities in access; in 2014/2015 procedure rates in a ‘high use’ CCG were 9.08 times higher than in a ‘low use’ CCG. In the South-West of England there was twofold variation in injections per patient per year (range 2.9 to 5.9).ConclusionsThe high and rising cost of anti-VEGF therapy affects the ability of the NHS to provide care for other patients. Current regulations encourage the increasing use of ranibizumab and aflibercept rather than bevacizumab, which evidence suggests is more cost-effective. NHS patients in England do not have equal access to the most cost-effective care.

Automated quantification of macular fluid in retinal diseases and their response to anti-VEGF therapy

2020 ◽  
pp. bjophthalmol-2020-317416
Author(s):  
Martin Michl ◽  
Maria Fabianska ◽  
Philipp Seeböck ◽  
Amir Sadeghipour ◽  
Bilal Haj Najeeb ◽  
...  
Keyword(s):  
Learning Algorithm ◽  
Subretinal Fluid ◽  
Diabetic Macular Oedema ◽  
Age Related Macular Degeneration ◽  
Deep Learning Algorithm ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Automated Quantification ◽  
Endothelial Growth Factor

AimTo objectively assess disease activity and treatment response in patients with retinal vein occlusion (RVO), neovascular age-related macular degeneration (nAMD) and centre-involved diabetic macular oedema (DME), using artificial intelligence–based fluid quantification.MethodsPosthoc analysis of 2311 patients (11 151 spectral-domain optical coherence tomography volumes) from five clinical, multicentre trials, who received a flexible antivascular endothelial growth factor (anti-VEGF) therapy over a 12-month period. Fluid volumes were measured with a deep learning algorithm at baseline/months 1, 2, 3 and 12, for three concentric circles with diameters of 1, 3 and 6 mm (fovea, paracentral ring and pericentral ring), as well as four sectors surrounding the fovea (superior, nasal, inferior and temporal).ResultsIn each disease, at every timepoint, most intraretinal fluid (IRF) per square millimetre was present at the fovea, followed by the paracentral ring and pericentral ring (p<0.0001). While this was also the case for subretinal fluid (SRF) in RVO/DME (p<0.0001), patients with nAMD showed more SRF in the paracentral ring than at the fovea up to month 3 (p<0.0001). Between sectors, patients with RVO/DME showed the highest IRF volumes temporally (p<0.001/p<0.0001). In each disease, more SRF was consistently found inferiorly than superiorly (p<0.02). At month 1/12, we measured the following median reductions of initial fluid volumes. For IRF: RVO, 95.9%/97.7%; nAMD, 91.3%/92.8%; DME, 37.3%/69.9%. For SRF: RVO, 94.7%/97.5%; nAMD, 98.4%/99.8%; DME, 86.3%/97.5%.ConclusionFully automated localisation and quantification of IRF/SRF over time shed light on the fluid dynamics in each disease. There is a specific anatomical response of IRF/SRF to anti-VEGF therapy in all diseases studied.

Comparative effectiveness and harms of intravitreal antivascular endothelial growth factor agents for three retinal conditions: a systematic review and meta-analysis

2018 ◽  
Vol 103 (4) ◽  
pp. 442-451 ◽  
Author(s):  
Allison Low ◽  
Ambar Faridi ◽  
Kavita V Bhavsar ◽  
Glenn C Cockerham ◽  
Michele Freeman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Visual Acuity ◽  
Growth Factor ◽  
Adverse Events ◽  
Meta Analysis ◽  
Diabetic Macular Oedema ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Antivascular Endothelial Growth Factor ◽  
Endothelial Growth Factor

Intravitreal antivascular endothelial growth factor (VEGF) agents are widely used to treat ocular conditions but the benefits and harms of these treatments are uncertain. We conducted a systematic review to compare the effects of aflibercept, bevacizumab and ranibizumab on best-corrected visual acuity (BCVA) changes, quality of life and ocular or systemic adverse events in patients with neovascular age-related macular degeneration (NVAMD), diabetic macular oedema (DME) and central or branch retinal vein occlusion (RVO). We searched published and unpublished literature sources to February 2017 for randomised controlled trials and cohort or modelling studies reporting comparative costs in the USA. Two reviewers extracted data and graded the strength of the evidence using established methods. Of 17 included trials, none reported a clinically important difference (≥ 5 letters) in visual acuity gains between agents. Nine trials provide high-strength evidence of no difference between bevacizumab and ranibizumab for NVAMD. Three trials provide moderate-strength evidence of no difference between bevacizumab and ranibizumab for DME. There was low-strength evidence of similar effects between aflibercept and ranibizumab for NVAMD, aflibercept and bevacizumab for RVO and all three agents for DME. There was insufficient evidence to compare bevacizumab and ranibizumab for RVO. Rates of ocular adverse events were low, and systemic harms were generally similar between groups, although 1 DME trial reported more arterial thrombotic events with ranibizumab versus aflibercept. Overall, no agent had a clear advantage over another for effectiveness or safety. Aflibercept and ranibizumab were significantly less cost-effective than repackaged bevacizumab in two trials. Systematic review registration number: CRD42016034076.

scholarly journals Association between Retinal Thickness Variability and Visual Acuity Outcome during Maintenance Therapy Using Intravitreal Anti-Vascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

2021 ◽  
Vol 11 (10) ◽  
pp. 1024
Author(s):  
Timothy Y. Y. Lai ◽  
Ricky Y. K. Lai
Keyword(s):  
Visual Acuity ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Anti Vegf ◽  
Age Related ◽  
Thickness Variability ◽  
The Mean ◽  
Endothelial Growth Factor

Previous studies based on clinical trial data have demonstrated that greater fluctuations in retinal thickness during the course of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) is associated with poorer visual acuity outcomes. However, it was unclear whether similar findings would be observed in real-world clinical settings. This study aimed to evaluate the association between retinal thickness variability and visual outcomes in eyes receiving anti-VEGF therapy for nAMD using pro re nata treatment regimen. A total of 64 eyes which received intravitreal anti-VEGF therapy (bevacizumab, ranibizumab or aflibercept) for the treatment of nAMD were evaluated. Variability in spectral-domain optical coherence tomography (OCT) central subfield thickness (CST) was calculated from the standard deviation (SD) values of all follow-up visits after three loading doses from month 3 to month 24. Eyes were divided into quartiles based on the OCT CST variability values and the mean best-corrected visual acuity values at 2 years were compared. At baseline, the mean ± SD logMAR visual acuity and CST were 0.59 ± 0.39 and 364 ± 113 µm, respectively. A significant correlation was found between CST variability and visual acuity at 2 years (Spearman’s ρ = 0.54, p < 0.0001), indicating that eyes with lower CST variability had better visual acuity at 2 years. Eyes with the least CST variability were associated with the highest mean visual acuity improvement at 2 years (quartile 1: +9.7 letters, quartile 2: +1.1 letters, quartile 3: −2.5 letters, quartile 4: −9.5 letters; p = 0.018). No significant difference in the number of anti-VEGF injections was found between the four CST variability quartile groups (p = 0.21). These findings showed that eyes undergoing anti-VEGF therapy for nAMD with more stable OCT CST variability during the follow-up period were associated with better visual outcomes. Clinicians should consider adopting treatment strategies to reduce CST variability during the treatment course for nAMD.

Arteriosclerotic Changes after Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs in Patients with Exudative Age-Related Macular Degeneration

2016 ◽  
Vol 235 (4) ◽  
pp. 225-232 ◽  
Author(s):  
Tomoaki Shiba ◽  
Mao Takahashi ◽  
Izumi Yoshida ◽  
Hikari Taniguchi ◽  
Tadashi Matsumoto ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protective Factor ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Vascular Endothelial ◽  
Cumulative Number ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor

Purpose: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). Methods: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. Results: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with Δserum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for ΔCAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for Δmean IMT. Conclusion: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.

Pegaptanib Sodium in the Treatment of Neovascular Age-Related Macular Degeneration

2010 ◽  
Vol 2 ◽  
pp. CMT.S2393
Author(s):  
Giuseppe Querques
Keyword(s):  
Macular Degeneration ◽  
Macular Edema ◽  
Single Agent ◽  
Age Related Macular Degeneration ◽  
Ocular Neovascularization ◽  
Pegaptanib Sodium ◽  
Anti Vegf ◽  
Age Related ◽  
Favorable Safety ◽  
Endothelial Growth Factor

Pegaptanib sodium is a polyethylene-glycolated, 28-nucleotide RNA aptamer that binds selectively to vascular endothelial growth factor (VEGF)165 but not smaller isoforms. Preclinical studies identified VEGF165 as an especially potent promoter of ocular neovascularization and inflammation. Following the pivotal clinical trials demonstrating the efficacy of intravitreal pegaptanib in treating all angiographic subtypes of neovascular age-related macular degeneration (NV-AMD), pegaptanib became the first anti-VEGF therapy to receive regulatory approval for this condition. In view of the importance of VEGF in a variety of tissues, including the cardiovascular system and the retina, concerns have been raised as to the risks that might accompany VEGF inhibition. It is thus of particular note that pegaptanib has proved to have a favorable safety record in treating NV-AMD, with no ocular or systemic safety signals having emerged over more than 4 years of clinical studies. Accordingly, in addition to its use as a single agent, pegaptanib has demonstrated promise in combinatorial regimens that employ nonselective anti-VEGF agents as an initial treatment followed by maintenance therapy with pegaptanib. Pegaptanib has also shown encouraging preliminary results in the treatment of diabetic macular edema, proliferative diabetic retinopathy, and macular edema secondary to retinal venous occlusive conditions.

scholarly journals Current and upcoming anti-VEGF therapies and dosing strategies for the treatment of neovascular AMD: a comparative review

2019 ◽  
Vol 4 (1) ◽  
pp. e000398 ◽  
Author(s):  
Saira Khanna ◽  
Rahul Komati ◽  
David A Eichenbaum ◽  
Ishani Hariprasad ◽  
Thomas A Ciulla ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Disease Process ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Optimal Dosing ◽  
Comparative Review ◽  
Dosing Strategies ◽  
Endothelial Growth Factor

Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.

scholarly journals Ten-year survival trends of neovascular age-related macular degeneration at first presentation

2020 ◽  
pp. bjophthalmol-2020-317161
Author(s):  
Cristina Arpa ◽  
Hagar Khalid ◽  
Shruti Chandra ◽  
Siegfried Wagner ◽  
Katrin Fasler ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Age Related Macular Degeneration ◽  
Visual Outcomes ◽  
Anti Vegf ◽  
Kaplan Meier ◽  
Age Related ◽  
Treatment Naïve ◽  
Mean Trend ◽  
Endothelial Growth Factor ◽  
Good Vision

BackgroundTo describe 10-year trends in visual outcomes, anatomical outcomes and treatment burden of patients receiving antivascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD).MethodsRetrospective cohort study of treatment-naïve, first-affected eyes with nAMD started on ranibizumab before January 1, 2009. The primary outcome was time to best-corrected visual acuity (BCVA) falling ≤35 ETDRS letters after initiating anti-VEGF therapy. Secondary outcomes included time to BCVA reaching ≥70 letters, proportion of eyes with BCVA ≥70 and ≤35 letters in 10 years, mean trend of BCVA and central retinal thickness over 10 years, and mean number of injections.ResultsFor our cohort of 103 patients, Kaplan-Meier analyses demonstrated median time to BCVA reaching ≤35 and ≥70 letters were 37.8 (95% CI 22.2 to 65.1) and 8.3 (95% CI 4.8 to 20.9) months after commencing anti-VEGF therapy, respectively. At the final follow-up, BCVA was ≤35 letters and ≥70 letters in 41.1% and 21%, respectively, in first-affected eyes, while this was the case for 5.4% and 48.2%, respectively, in a patient’s better-seeing eye. Mean injection number was 37.0±24.2 per eye and 53.6±30.1 at patient level (63.1% of patients required injections in both eyes).ConclusionsThe chronicity of nAMD disease and its management highlights the importance of long-term visual prognosis. Our analyses suggest that one in five patients will retain good vision (BCVA ≥70 ETDRS letters) in the first-affected eye at 10 years after starting anti-VEGF treatment; yet, one in two patients will have good vision in their better-seeing eye. Moreover, our data suggest that early treatment of nAMD is associated with better visual outcomes.

scholarly journals Antivascular Endothelial Growth Factor Treatment Might Be Continued Even After Vitrectomy for Endophthalmitis in Neovascular Age-Related Macular Degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. 6-12
Author(s):  
Zofia Michalewska ◽  
Jerzy Nawrocki
Keyword(s):  
Growth Factor ◽  
Macular Degeneration ◽  
Visual Outcome ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Antivascular Endothelial Growth Factor ◽  
Endothelial Growth Factor ◽  
Mean Time

Purpose: This article studies visual outcome and frequency of antivascular endothelial growth factor (anti-VEGF) injections continued in patients with neovascular age-related macular degeneration (AMD) who had an earlier vitrectomy for postinjection endophthalmitis. Methods: A retrospective interventional study was conducted reviewing our database for patients with a diagnosis of endophthalmitis in the course of anti-VEGF injections. Endophthalmitis diagnosis was made on clinical examination of pain, rapid decrease in visual acuity (VA), conjunctival hyperemia, hypopyon, and vitritis. In all eyes, core vitrectomy with intravitreal antibiotics was performed. Spectral-domain optical coherence tomography was performed monthly before and after surgery during follow-up. Anti-VEGF injections were continued after surgery in all cases. Results: Eight eyes with postinjection endophthalmitis were included. Mean VA immediately before endophthalmitis was 20/50 Snellen with a mean of 19 intravitreal anti-VEGF injections ( P = .45). At time of endophthalmitis diagnosis, mean VA was 20/1000 (range, 20/2000-20/200). Mean time from injection to when the patient noted first symptoms was 4.3 days (range, 1-8 days). Mean time from first symptoms to surgery was 12 hours (range, 2.5-26 hours). Final mean VA at the end of follow-up (range, 12-84 months) did not statistically differ from VA at the visit immediately before endophthalmitis diagnosis ( P = .69). Mean frequency of injections after vitrectomy did not significantly differ from the presurgical course of treatment ( P =.97). Conclusions: Anti-VEGF treatment might be continued after vitrectomy for endophthalmitis and results in satisfactory anatomical and visual outcome. Surgery did not influence the frequency of anti-VEGF injections for neovascular AMD.

scholarly journals Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration

2019 ◽  
Vol 5 (2) ◽  
pp. eaau6732 ◽  
Author(s):  
Jaeryung Kim ◽  
Jang Ryul Park ◽  
Jeongwoon Choi ◽  
Intae Park ◽  
Yoonha Hwang ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Therapeutic Strategy ◽  
Vascular Leakage ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Medical Needs ◽  
Anti Vegf ◽  
Age Related ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor

Choriocapillary loss is a major cause of neovascular age-related macular degeneration (NV-AMD). Although vascular endothelial growth factor (VEGF) blockade for NV-AMD has shown beneficial outcomes, unmet medical needs for patients refractory or tachyphylactic to anti-VEGF therapy exist. In addition, the treatment could exacerbate choriocapillary rarefaction, necessitating advanced treatment for fundamental recovery from NV-AMD. In this study, Tie2 activation by angiopoietin-2–binding and Tie2-activating antibody (ABTAA) presents a therapeutic strategy for NV-AMD. Conditional Tie2 deletion impeded choriocapillary maintenance, rendering eyes susceptible to NV-AMD development. Moreover, in a NV-AMD mouse model, ABTAA not only suppressed choroidal neovascularization (CNV) and vascular leakage but also regenerated the choriocapillaris and relieved hypoxia. Conversely, VEGF blockade degenerated the choriocapillaris and exacerbated hypoxia, although it suppressed CNV and vascular leakage. Together, we establish that angiopoietin-Tie2 signaling is critical for choriocapillary maintenance and that ABTAA represents an alternative, combinative therapeutic strategy for NV-AMD by alleviating anti-VEGF adverse effects.

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