scholarly journals KSI-301: antibody biopolymer conjugate in retinal disorders

2021 ◽  
Vol 13 ◽  
pp. 251584142110277
Author(s):  
Priya R. Chandrasekaran ◽  
V.G. Madanagopalan
Keyword(s):  
Safety Profile ◽  
Diabetic Macular Oedema ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Duration Of Action ◽  
Medline Search ◽  
Anti Vegf ◽  
Age Related ◽  
Retinal Disorders ◽  
Pubmed Search

KSI-301 is a new intravitreal anti-vascular endothelial growth factor (VEGF) antibody biopolymer conjugate under investigation for the treatment of age-related macular degeneration (AMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). Preclinical and early clinical trials so far have shown promising results in retinal vascular diseases. When using anti-VEGF agents for treatment of retinal disorders, the frequency of injections and follow-up visits has increased the treatment burden, greatly affecting the treatment outcome. There are new anti-VEGF agents in the horizon with extended duration of action, durability, safety profile and efficacy, which seem to address the above issues. PubMed search and Medline search were performed on newer anti-VEGF agents, KSI-301, antibody biopolymer conjugate in retina, KODIAK KSI-301, DAZZLE study, GLEAM study, GLIMMER study, GLOW study and BEACON study. This review article showcases the biophysical properties and ongoing trials related to KSI-301. Moreover, we discuss the efficacy and safety profile of KSI-301 on the basis of the results of available trials.

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.

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.

scholarly journals Development of Anti-VEGF Therapies for Intraocular Use: A Guide for Clinicians

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Pearse A. Keane ◽  
Srinivas R. Sadda
Keyword(s):  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Vascular Endothelial ◽  
Vein Occlusion ◽  
Anti Vegf ◽  
Age Related ◽  
Vessel Growth ◽  
Vessel Networks ◽  
Endothelial Growth Factor ◽  
Made In

Angiogenesis is the process by which new blood vessels form from existing vessel networks. In the past three decades, significant progress has been made in our understanding of angiogenesis; progress driven in large part by the increasing realization that blood vessel growth can promote or facilitate disease. By the early 1990s, it had become clear that the recently discovered “vascular endothelial growth factor” (VEGF) was a powerful mediator of angiogenesis. As a result, several groups targeted this molecule as a potential mediator of retinal ischemia-induced neovascularization in disorders such as diabetic retinopathy and retinal vein occlusion. Around this time, it also became clear that increased intraocular VEGF production was not limited to ischemic retinal diseases but was also a feature of choroidal vascular diseases such as neovascular age-related macular degeneration (AMD). Thus, a new therapeutic era emerged, utilizing VEGF blockade for the management of chorioretinal diseases characterized by vascular hyperpermeability and/or neovascularization. In this review, we provide a guide for clinicians on the development of anti-VEGF therapies for intraocular use.

Novel Long-acting Pharmacotherapy for Exudative Age Related Macular Degeneration

2019 ◽  
Vol 24 (41) ◽  
pp. 4860-4863 ◽  
Author(s):  
Elad Moisseiev ◽  
Anat Loewenstein
Keyword(s):  
Macular Degeneration ◽  
Treatment Strategies ◽  
Pharmacological Action ◽  
Age Related Macular Degeneration ◽  
Duration Of Action ◽  
Novel Technologies ◽  
Anti Vegf ◽  
Age Related ◽  
Novel Drugs ◽  
Long Acting

Exudative age-related macular degeneration (AMD) is a major indication for the administration of intravitreal injections of anti-VEGF agents, which have been established as a very effective pharmacotherapy for this disease. However, treatment with anti-VEGF agents requires several patient visits for monitoring and treatment. Strategies for achieving a longer duration of pharmacological action are currently being developed. These include the development of longer-acting drugs, and of novel technologies to increase the duration of action of administered agents. This manuscript will review the novel drugs and technologies currently being developed for achieving a longer-action pharmacotherapy for exudative AMD.

scholarly journals Management of Wet Age-Related Macular Degeneration in Spain: Challenges for Treat and Extend Implementation in Routine Clinical Practice

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
A. García-Layana ◽  
J. García-Arumí ◽  
M. S. Figueroa ◽  
L. Arias Barquet ◽  
J. M. Ruíz-Moreno ◽  
...  
Keyword(s):  
Delphi Study ◽  
Treatment Strategies ◽  
Steering Committee ◽  
Age Related Macular Degeneration ◽  
Clinical Practices ◽  
Duration Of Action ◽  
Treat And Extend ◽  
Anti Vegf ◽  
Age Related ◽  
Main Routine

Purpose. To ascertain wet AMD (wAMD) management patterns in Spain. Methods. A two-round Delphi study conducted through a questionnaire-based survey designed from literature review and validated by an independent Steering Committee. Results. Forty-nine retina specialists experienced in wAMD participated by answering the two-round study questionnaire. Retina specialists are the main responsible for wAMD diagnosis and monitoring, including visits and associated procedures, with a median time per visit of 15 minutes. Standard treatment strategies are based on anti-VEGF administration, including standard loading dose administration followed by maintenance with aflibercept or ranibizumab (81% of patients). Although treat and extend (T&E) dosing strategy is considered as optimal for wAMD management (78% of the panelists), the main routine healthcare limitations (i.e., visits overload, reduced staff, short visit time, coordination issues, lack of facilities) conduct to self-defined “flexible” strategies, based on T&E and pro-re-nata (PRN) protocols. Conclusion. Proactive treatment patterns (T&E) are the preferred ones by the retina specialists in Spain. However, their proper implementation is difficult due to healthcare resource limitations, as well as organisation and logistic issues. The use of anti-VEGF agents with longer duration of action could facilitate the use of strict T&E approaches according to routine clinical practices.

scholarly journals Intravitreal Bevacizumab in Neovascular Age-Related Macular Degeneration as First Choice: a New Italian Ruling

2020 ◽  
Vol 9 (3) ◽  
pp. 179-184
Author(s):  
Stefano Erba ◽  
Antonio Scialdone ◽  
Giuseppe Casalino
Keyword(s):  
Macular Degeneration ◽  
Safety Profile ◽  
Relevant Literature ◽  
Intravitreal Bevacizumab ◽  
Age Related Macular Degeneration ◽  
First Line ◽  
Regulatory Issues ◽  
Anti Vegf ◽  
Age Related ◽  
First Choice

Background: Intravitreal vascular endothelial growth factor (VEGF) inhibitors represent the mainstay of neovascular age-related macular degeneration (nAMD) treatment. Although bevacizumab has been the first anti-VEGF used in ophthalmology, it is unlicensed for intraocular use. However, the favourable cost-benefit balance has favoured its widespread use. We aimed to present relevant literature regarding the safety profile and the regulatory issues of intravitreal bevacizumab use. Methods: In this narrative review we report relevant studies regarding the safety profile of intravitreal bevacizumab. Expert commentary is provided and an overview of the current scenario and possible future directions discussed. Results: Randomized controlled trials have demonstrated that bevacizumab is not inferior to the licensed anti-VEGF agents showing similar efficacy and safety profiles. However, a significant debate on the regulatory issues of intravitreal bevacizumab used as ‘off label’ first-line treatment in nAMD still persists. Recently, the Regional Health System of Lombardia in Italy decided to only cover the expenses of bevacizumab, forcing clinicians to use bevacizumab as the first choice in the treatment of nAMD. Issues about the practical implications of this decision are discussed. Conclusion: The use of intravitreal bevacizumab as first-line therapy in nAMD remains controversial. Many differences in the regulatory aspects still persist among the European countries and sometimes within the same countries, like Italy. Of note the clinical scenario will be modified in future by the introduction of newly developed anti-VEGF agents and anti-VEGF biosimilars.

scholarly journals Anti-vascular endothelial growth factor treatment for retinal conditions: a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e022031 ◽  
Author(s):  
Ba' Pham ◽  
Sonia M Thomas ◽  
Erin Lillie ◽  
Taehoon Lee ◽  
Jemila Hamid ◽  
...  
Keyword(s):  
Systematic Review ◽  
Visual Acuity ◽  
Treatment Regimen ◽  
Macular Oedema ◽  
Meta Analysis ◽  
Diabetic Macular Oedema ◽  
Intravitreal Bevacizumab ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related

ObjectivesTo evaluate the comparative effectiveness and safety of intravitreal bevacizumab, ranibizumab and aflibercept for patients with choroidal neovascular age-related macular degeneration (cn-AMD), diabetic macular oedema (DMO), macular oedema due to retinal vein occlusion (RVO-MO) and myopic choroidal neovascularisation (m-CNV).DesignSystematic review and random-effects meta-analysis.MethodsMultiple databases were searched from inception to 17 August 2017. Eligible head-to-head randomised controlled trials (RCTs) comparing the (anti-VEGF) drugs in adult patients aged ≥18 years with the retinal conditions of interest. Two reviewers independently screened studies, extracted data and assessed risk of bias.Results19 RCTs involving 7459 patients with cn-AMD (n=12), DMO (n=3), RVO-MO (n=2) and m-CNV (n=2) were included. Vision gain was not significantly different in patients with cn-AMD, DMO, RVO-MO and m-CNV treated with bevacizumab versus ranibizumab. Similarly, vision gain was not significantly different between cn-AMD patients treated with aflibercept versus ranibizumab. Patients with DMO treated with aflibercept experienced significantly higher vision gain at 12 months than patients receiving ranibizumab or bevacizumab; however, this difference was not significant at 24 months. Rates of systemic serious harms were similar across anti-VEGF agents. Posthoc analyses revealed that an as-needed treatment regimen (6–9 injections per year) was associated with a mortality increase of 1.8% (risk ratio: 2.0 [1.2 to 3.5], 2 RCTs, 1795 patients) compared with monthly treatment in cn-AMD patients.ConclusionsIntravitreal bevacizumab was a reasonable alternative to ranibizumab and aflibercept in patients with cn-AMD, DMO, RVO-MO and m-CNV. The only exception was for patients with DME and low visual acuity (<69 early treatment diabetic retinopathy study [ETDRS] letters), where treatment with aflibercept was associated with significantly higher vision gain (≥15 ETDRS letters) than bevacizumab or ranibizumab at 12 months; but the significant effects were not maintained at 24 months. The choice of anti-VEGF drugs may depend on the specific retinal condition, baseline visual acuity and treatment regimen.PROSPERO registration numberCRD42015022041.

scholarly journals Effect of COVID-19 Pandemic on Anti-VEGF Treatment of Medical Retinal Conditions

The Physician ◽  
2020 ◽  
Vol 6 (3) ◽  
pp. 1-9
Author(s):  
Mana Rahimzadeh ◽  
Ramu Muniraju ◽  
Shahrnaz Izadi
Keyword(s):  
Visual Acuity ◽  
Total Duration ◽  
Diabetic Macular Oedema ◽  
District General Hospital ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Anti Vegf ◽  
Age Related ◽  
Long Term Impact ◽  
The Uk

Introduction: Ophthalmology services have been significantly impacted by the COVID-19 pandemic. Frequency of intravitreal anti-vascular endothelial growth factor (Anti-VEGF) injections are important in visual outcomes. Methods: We conducted an audit on intravitreal services in an NHS district general hospital in the UK including all new patients with diabetic macular oedema (CI-DMO) and wet age-related macular degeneration (AMD) who were initiated on intravitreal injection of Aflibercept (EYLEA) between 1st January to 15th July 2020, and had subsequent injections until October 2020. Data on injection dates and visual acuity was extracted, and the total number of all intravitreal injections for all indications between January to September 2020 and the same period in 2019. Delay to treatment was defined as more than 14 days, according to the fixed dosing schedule. Results: We found 31% (n=17) of patients initiated on treatment for wet AMD and 44% (N=11) for CI-DMO had delayed injections.  There was no correlation between total duration of delay and change in best-corrected visual acuity (BCVA). Similarly, we found no association between duration of delay and change in BCVA. The number of intravitreal injections declined during the COVID-19 pandemic by 17.8% compared to 2019. Conclusion: Majority of patients initiated on anti-VEGF injections just before the pandemic or during the pandemic received injections on time. Where there were significant delays to treatment, there was no detected loss in vision over the short term. However, the long-term impact and impact of overall reduction in intravitreal injections are unknown.

A Prospective Review of Patients Receiving Intravitreal Anti-VEGF: How are we doing during the SARS-Cov-2 Pandemic?

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Wong YL ◽  
◽  
Rattanasirivilai P ◽  
Tan TK ◽  
Abugreen S ◽  
...  
Keyword(s):  
Diabetic Macular Oedema ◽  
Age Related Macular Degeneration ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Asian Ethnicity ◽  
Severe Visual Loss ◽  
Anti Vegf ◽  
Age Related ◽  
The Uk ◽  
Wet Amd

Objective: During the SARS-CoV-2 pandemic, service provision of Anti- Vascular Endothelial Growth Factor (anti-VEGF) therapy is continued to prevent severe visual loss. As the majority of the patients requiring intravitreal anti- VEGF are elderly and vulnerable, we aim to assess the safety and efficacy of the delivery of anti-VEGF therapy. Method: A prospective data collection of 337 patients who attended the nurse led injection clinics in the UK during the lockdown period from 30 March 2020 to 1 June 2020. A follow up of all of the attended patients was conducted to assess for diagnosis of SARS-CoV-2. Results: 182 (54%) were female and 155 (46%) male. Majority (95%) were Caucasian and 5% were Asian ethnicity. The indication for anti-VEGF injection include wet age related macular degeneration (wet AMD) (70.9%), Diabetic Macular Oedema (DMO) (17.2%), and Retinal Vein Occlusion (RVO) (11.9%). Mean age was 78.84±9.76 for wet AMD, 67.63±3.26 for RVO and 59.28±14.54 for DMO. More wet AMD patients reported subjective deterioration of vision compared to RVO and DMO (40.2% vs. 37.5% vs. 22.4%) [P=0.04]. Chronic Obstructive Pulmonary Disease (COPD) is more common in the wet AMD group as compared to other groups (P=0.03). Five patients from the study group were tested for SARS-CoV-2, none were positive. Conclusion: Delivery of anti-VEGF therapy is safe with the current precautionary measures despite caring for a vulnerable group of patients. Majority of the wet AMD patients are continuing to attend intravitreal injection appointments.

scholarly journals Anti-VEGF-Resistant Retinal Diseases: A Review of the Latest Treatment Options

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1049
Author(s):  
Josh O. Wallsh ◽  
Ron P. Gallemore
Keyword(s):  
Treatment Options ◽  
Vascular Diseases ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Vascular Endothelial ◽  
Future Directions ◽  
Anti Vegf ◽  
Age Related ◽  
Endothelial Growth Factor ◽  
Topical Medications

Anti-vascular endothelial growth factor (anti-VEGF) therapy currently plays a central role in the treatment of numerous retinal diseases, most notably exudative age-related macular degeneration (eAMD), diabetic retinopathy and retinal vein occlusions. While offering significant functional and anatomic benefits in most patients, there exists a subset of 15–40% of eyes that fail to respond or only partially respond. For these cases, various treatment options have been explored with a range of outcomes. These options include steroid injections, laser treatment (both thermal therapy for retinal vascular diseases and photodynamic therapy for eAMD), abbreviated anti-VEGF treatment intervals, switching anti-VEGF agents and topical medications. In this article, we review the effectiveness of these treatment options along with a discussion of the current research into future directions for anti-VEGF-resistant eyes.

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