scholarly journals An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma

Eye ◽  
2022 ◽  
Author(s):  
Faruque Ghanchi ◽  
Rupert Bourne ◽  
Susan M. Downes ◽  
Richard Gale ◽  
Christina Rennie ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Late Phase ◽  
Rho Kinase ◽  
Diabetic Macular Oedema ◽  
Negative Consequences ◽  
Regular Treatment ◽  
Anti Vegf ◽  
Age Related ◽  
Phase Development ◽  
Long Acting

AbstractIn the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelial growth factor (VEGF) drug injections may lose the initial vision gains in vision. Protracted regular treatment schedules represent a high burden not only for patients and families, but also healthcare professionals, systems, and ultimately society too. There has been a clear need for longer-acting therapies that reduce the frequency, and therefore the burden, of treatment interventions. Several longer-acting interventions for nAMD, diabetic macular oedema, retinal vein occlusion, uveitis and glaucoma have either been developed or are in late-phase development, some of which employ novel mechanisms of actions, and all of which of promise longer (≥3 month) treatment intervals. This review delivers an overview of anti-VEGF agents with longer durations of action, DARPins, bispecific anti-VEGF/Ang2 therapies, anti-PDGF and anti-integrin therapy, Rho-kinase inhibitors, the Port Delivery System, steroids, gene therapy for retina and uveitis, and for glaucoma, ROCK inhibitors, implants and plugs, and SLT laser and MIGS. The review also refers to the potential of artificial intelligence to tailor treatment efficacy with a resulting reduction in treatment burden.

scholarly journals Rho-Kinase Inhibitors for the Treatment of Refractory Diabetic Macular Oedema

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1683
Author(s):  
Milagros Mateos-Olivares ◽  
Luis García-Onrubia ◽  
Fco. Javier Valentín-Bravo ◽  
Rogelio González-Sarmiento ◽  
Maribel Lopez-Galvez ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Oedema ◽  
Standard Therapy ◽  
Vision Loss ◽  
Therapeutic Potential ◽  
Rho Kinase ◽  
Diabetic Macular Oedema ◽  
New Drugs ◽  
Anti Vegf

Diabetic macular oedema (DMO) is one of the leading causes of vision loss associated with diabetic retinopathy (DR). New insights in managing this condition have changed the paradigm in its treatment, with intravitreal injections of antivascular endothelial growth factor (anti-VEGF) having become the standard therapy for DMO worldwide. However, there is no single standard therapy for all patients DMO refractory to anti-VEGF treatment; thus, further investigation is still needed. The key obstacles in developing suitable therapeutics for refractory DMO lie in its complex pathophysiology; therefore, there is an opportunity for further improvements in the progress and applications of new drugs. Previous studies have indicated that Rho-associated kinase (Rho-kinase/ROCK) is an essential molecule in the pathogenesis of DMO. This is why the Rho/ROCK signalling pathway has been proposed as a possible target for new treatments. The present review focuses on the recent progress on the possible role of ROCK and its therapeutic potential in DMO. A systematic literature search was performed, covering the years 1991 to 2021, using the following keywords: “rho-Associated Kinas-es”, “Diabetic Retinopathy”, “Macular Edema”, “Ripasudil”, “Fasudil” and “Netarsudil”. Better insight into the pathological role of Rho-kinase/ROCK may lead to the development of new strategies for refractory DMO treatment and prevention.

scholarly journals Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1170
Author(s):  
Arunbalaji Pugazhendhi ◽  
Margaret Hubbell ◽  
Pooja Jairam ◽  
Balamurali Ambati
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Rho Kinase Inhibitors ◽  
Age Related ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

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 Vasospastic angina: pathophysiology and clinical significance

2020 ◽  
Vol 19 (1) ◽  
pp. 99-105
Author(s):  
B. I. Geltser ◽  
M. M. Tsivanyuk ◽  
V. N. Kotelnikov ◽  
R. S. Karpov
Keyword(s):  
Kinase Inhibitors ◽  
Magnesium Deficiency ◽  
Coronary Artery Spasm ◽  
Rho Kinase ◽  
Diagnosis And Treatment ◽  
Vasospastic Angina ◽  
Coronary Smooth Muscle ◽  
Provocation Tests ◽  
Life Threatening ◽  
Long Acting

The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.

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 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.

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 Vasospastic angina: pathophysiology and clinical significance

2020 ◽  
Vol 19 (1) ◽  
pp. 99-105
Author(s):  
B. I. Geltser ◽  
M. M. Tsivanyuk ◽  
V. N. Kotelnikov ◽  
R. S. Karpov
Keyword(s):  
Kinase Inhibitors ◽  
Magnesium Deficiency ◽  
Coronary Artery Spasm ◽  
Rho Kinase ◽  
Diagnosis And Treatment ◽  
Vasospastic Angina ◽  
Coronary Smooth Muscle ◽  
Provocation Tests ◽  
Life Threatening ◽  
Long Acting

The review discusses an analysis of the literature on various aspects of the pathogenesis, diagnosis and treatment of vasospastic angina (VA). Data on the prevalence of coronary artery spasm (CAS) in various populations, as well as risk factors and triggers, are presented. We considered pathophysiological mechanisms of CAS, including hyperreactivity of coronary smooth muscle cells, endothelial dysfunction, nonspecific inflammation, oxidative stress, magnesium deficiency, autonomic imbalance, etc. The relationship of CAS with coronary atherosclerosis and thrombosis is emphasized. Modern recommendations for the diagnosis and treatment of VA are presented. Invasive verification of CAS is performed by pharmacological provocation tests with certain contraindications. Calcium antagonists and their combination with long-acting nitrates play a key role in the treatment of VA. Medications with a prospect for use in VA are Rho-kinase inhibitors, ATP-sensitive potassium channel activators, alpha-1 blockers. The management of patients with refractory VA and the prospects for endovascular treatment are discussed. It was noted that patients with multi-vessel VA are more likely to develop life-threatening arrhythmias and sudden death.

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.

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