Intravitreal anti-VEGF drug delivery systems for age-related macular degeneration

2020 ◽  
Vol 573 ◽  
pp. 118767 ◽  
Author(s):  
Andrea Luaces-Rodríguez ◽  
Cristina Mondelo-García ◽  
Irene Zarra-Ferro ◽  
Miguel González-Barcia ◽  
Pablo Aguiar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Macular Degeneration ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related

Advanced Hydrogels Based Drug Delivery Systems for Ophthalmic Delivery

2020 ◽  
Vol 13 (4) ◽  
pp. 291-300 ◽  
Author(s):  
Srividya Gorantla ◽  
Tejashree Waghule ◽  
Vamshi Krishna Rapalli ◽  
Prem Prakash Singh ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Age Related Macular Degeneration ◽  
Stimuli Responsive ◽  
Duration Of Action ◽  
Age Related ◽  
Aqueous Gels ◽  
Ophthalmic Delivery ◽  
3D Printed

Hydrogels are aqueous gels composed of cross-linked networks of hydrophilic polymers. Stimuli-responsive based hydrogels have gained focus over the past 20 years for treating ophthalmic diseases. Different stimuli-responsive mechanisms are involved in forming polymer hydrogel networks, including change in temperature, pH, ions, and others including light, thrombin, pressure, antigen, and glucose-responsive. Incorporation of nanocarriers with these smart stimuli-responsive drug delivery systems that can extend the duration of action by increasing ocular bioavailability and reducing the dosing frequency. This review will focus on the hydrogel drug delivery systems highlighting the gelling mechanisms and emerging stimuli-responsive hydrogels from preformed gels, nanogels, and the role of advanced 3D printed hydrogels in vision-threatening diseases like age-related macular degeneration and retinitis pigmentosa. It also provides insight into the limitations of hydrogels along with the safety and biocompatibility of the hydrogel drug delivery systems.

scholarly journals Novel delivery systems of active substances for intraocular administration

2021 ◽  
Vol 87 (87(03)) ◽  
pp. 331-338
Author(s):  
Rocío Herrero Vanrell
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
The Elderly ◽  
Delivery Systems ◽  
Posterior Segment ◽  
Age Related Macular Degeneration ◽  
Multifactorial Diseases ◽  
Age Related ◽  
Intraocular Drug Delivery ◽  
Active Substances

Neurodegenerative pathologies affecting the posterior segment of the eye such as diabetic retinopathy, age related macular degeneration and glaucoma are among the main causes of blindness in the world. They have in common that are cronic, multifactorial and in some cases related with the elderly. The treatment of these pathologies require to maintain therapeutic concentrations in the posterior segment thanks to the use of successive intraocular injections which are associated to secondary effects being poor tolerated by patients. Intraocular drug delivery systems emerged as an alternative to frequent injections as they are able to deliver the therapeutic agent in a controlled fashion into the eye after a single administration. Depending on the biomaterial these delivery systems are biodegradable or non biodegradable. Attending to their sizes, drug delivery systems are classified in implants (>1mm), microsystems (1-1000μm) y nanosystems (1-1000nm). Biodegradable microspheres emerge as therapeutic tools of great interest for the treatment of neurodegenerative pathologies as they can encapsulate active substances of distinct nature and provide release profiles tailoring with clinical needs. Furthermore, it is possible to administer different amounts of microspheres which correspond to the most adequated doses of the medicine in a personalized therapy. The simultaneous encapsulation of several active substances in the microspheres are of great interest in the treatment of multifactorial diseases covering different therapeutic targets.

scholarly journals Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Multiple Testing ◽  
Age Related Macular Degeneration ◽  
Patient Specific ◽  
Multiple Testing Correction ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Pathway

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.

scholarly journals Mingjing granule, a traditional Chinese medicine in the treatment of neovascular age-related macular degeneration: study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yamin Li ◽  
Lina Liang ◽  
Torkel Snellingen ◽  
Kai Xu ◽  
Yun Gao ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Case Report Form ◽  
Link Type ◽  
Anti Vegf ◽  
Age Related ◽  
Function Test

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.

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