scholarly journals Therapeutic Effects of Fenofibrate Nano-Emulsion Eye Drops on Retinal Vascular Leakage and Neovascularization

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1328
Author(s):  
Li Huang ◽  
Wentao Liang ◽  
Kelu Zhou ◽  
Ronald A. Wassel ◽  
Zachary D. Ridge ◽  
...  
Keyword(s):  
Macular Edema ◽  
Vision Loss ◽  
Vascular Leakage ◽  
Age Related Macular Degeneration ◽  
Inflammatory Factors ◽  
Diabetic Patients ◽  
Therapeutic Effects ◽  
Eye Drops ◽  
Age Related ◽  
Nano Emulsion

Macular edema caused by retinal vascular leakage and ocular neovascularization are the leading causes of severe vision loss in diabetic retinopathy (DR) and age-related macular degeneration (AMD) patients. Oral administration of fenofibrate, a PPARα agonist, has shown therapeutic effects on macular edema and retinal neovascularization in diabetic patients. To improve the drug delivery to the retina and its efficacy, we have developed a nano-emulsion-based fenofibrate eye drop formulation that delivered significantly higher amounts of the drug to the retina compared to the systemic administration, as measured by liquid chromatography–mass spectrometer (LC-MS). The fenofibrate eye drop decreased leukocytes adherent to retinal vasculature and attenuated overexpression of multiple inflammatory factors in the retina of very low-density lipoprotein receptor knockout (Vldlr−/−) mice, a model manifesting AMD phenotypes, and streptozotocin-induced diabetic rats. The fenofibrate eye drop also reduced retinal vascular leakage in these models. The laser-induced choroidal neovascularization was also alleviated by the fenofibrate eye drop. There were no detectable ocular toxicities associated with the fenofibrate eye drop treatment. These findings suggest that fenofibrate can be delivered efficiently to the retina through topical administration of the nano-emulsion eye drop, which has therapeutic potential for macular edema and neovascularization.

scholarly journals Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1869
Author(s):  
Majid Khan ◽  
Aamir A. Aziz ◽  
Noah A. Shafi ◽  
Tayeb Abbas ◽  
Arshad M. Khanani
Keyword(s):  
Clinical Trials ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Tyrosine Phosphatase ◽  
Vascular Diseases ◽  
Vascular Leakage ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Vascular Endothelial ◽  
Age Related

This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

scholarly journals Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress

2021 ◽  
Vol 14 (8) ◽  
pp. 1260-1273
Author(s):  
Zi-Yan Cai ◽  
◽  
Ke Liu ◽  
Xuan-Chu Duan ◽  
◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vision Loss ◽  
Eye Diseases ◽  
The Body ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Classical Pathway ◽  
Age Related ◽  
Important Relationship

Age-related eye diseases, including cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), are the leading causes of vision loss in the world. Several studies have shown that the occurrence and development of these diseases have an important relationship with oxidative stress in the eye. The Keap1-Nrf2-ARE pathway is a classical pathway that resists oxidative stress and inflammation in the body. This pathway is also active in the development of age-related eye diseases. A variety of drugs have been shown to treat age-related eye diseases through the Keap1-Nrf2-ARE (Kelch-like ECH-Associating protein 1- nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway. This review describes the role of oxidative stress in the development of age-related eye diseases, the function and regulation of the Keap1-Nrf2-ARE pathway, and the therapeutic effects of drugs associated with this pathway on age-related eye diseases.

scholarly journals Treatment Efficacy and Compliance in Patients with Diabetic Macular Edema Treated with Ranibizumab in a Real-Life Setting

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Anne-Laurence Best ◽  
Franck Fajnkuchen ◽  
Sylvia Nghiem-Buffet ◽  
Typhaine Grenet ◽  
Gabriel Quentel ◽  
...  
Keyword(s):  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Vision Loss ◽  
Real Life ◽  
Treatment Compliance ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Real Life Setting ◽  
The Mean

Purpose. To assess real-life efficacy of ranibizumab and treatment compliance of patients with vision loss secondary to diabetic macular edema (DME). Methods. A retrospective study was conducted in DME patients treated with ranibizumab. Patients were monitored every 4 weeks for visual acuity (VA) and central retinal thickness (CRT) by SD-OCT. All patients received a loading dose of 3 monthly injections followed by retreatments on an as-needed basis. The primary endpoint was the change in VA at M12. Patient compliance to the follow-up and the correlation between the injection number and VA were also investigated. Compliance was compared to that of neovascular age-related macular degeneration (nAMD) patients. Results. Seventy-two eyes of 55 consecutive DME patients were included. At baseline, the mean VA was 56.5 letters and CRT was 470 μm. At M12, the mean VA was 63.4 letters (p<0.0001), 31.1% of patients had a VA > 70 letters, the mean VA change was +6.9 letters, and the mean CRT was 361.9 μm (p=0.0001) after a mean number of 5.33 intravitreal injections. In patients who received ≥7 injections, the VA gain and final VA were significantly higher than in patients who received <7 injections. At M12, 25.45% of DME patients were lost to follow-up versus 16.8% of nAMD patients (n=55). Discussion/Conclusion. Our study confirms the real-life efficacy of ranibizumab in DME at M12 and the need for a large number of injections to achieve better visual outcomes. We also showed a trend to a lower compliance in diabetic versus nAMD patients.

Quality-Adjusted Life Years in Macular Edema: The Benefit of Anti-VEGF Agents in a Tertiary Center in Greece

2021 ◽  
Author(s):  
Nikolaos Theodore Voutsas ◽  
Eleni Papageorgiou ◽  
Alexandra Tantou ◽  
Evangelia Tsironi ◽  
Maria Kotoula
Keyword(s):  
Macular Edema ◽  
Time Horizon ◽  
Vision Loss ◽  
Hospital Setting ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Life Years ◽  
Tertiary Center

Abstract Introduction: Diabetic macular edema (DME), wet age-related macular degeneration (AMD) and macular edema due to central retinal vein occlusion (CRVO) are leading causes of vision loss, currently managed with anti-vascular endothelial growth factor injections (anti-VEGF). Aim of this study was to calculate QALYs in patients with DME, AMD and CRVO treated with anti-VEGF agents (QALYs+) in a Greek tertiary hospital setting and compare them to theoretical QALYs that the patients would have without treatment (QALYs-). Material and Methods: The study included 143 treatment-naive patients with macular edema due to DM (n=57), AMD (n=79) and CRVO (n=7), who received anti-VEGF injections as monotherapy according to the Treat-and-Extend (T&E) protocol. The anti-VEGF agents were ranibizumab and aflibercept in equivalent fractions. QALYs where calculated by the formula QALY = Utility Value * Time, where “time” refers to the follow-up period of the study. For QALYs-, we assumed that visual acuity remained unchanged during this period.Results: Mean follow-up time was 1+1.3 years in the DME group, 1.3 + 1.2 years in the AMD group and 0.5 +1 years in the CRVO group. For patients with DME, QALYs- were 0.75, and QALYs+ were 0.78 (QALY difference +0.033, p=0.439). For patients with AMD, QALYs- were 0.95 and QALYs+ were also 0.95 (QALY difference 0, p=0.45). QALYs- of patients with CRVO were 0.77, and QALYs+ were 0.80 (QALY difference +0.032, p=0.09).Discussion/Conclusion: QALYs+ were identical to QALYs- in patients with AMD and QALYs+ were minimally higher than QALYs- in patients with DME and CRVO in this specific Greek setting for a time horizon between 0.5 and 1.3 years. Possible explanations are the short time horizon used in this analysis and the inclusion of data from the better-seeing eye (BSE).

scholarly journals Pattern of Cystoid Macular Edema in Erbil

2019 ◽  
Vol 3 (1) ◽  
pp. 80-94
Author(s):  
Muhsen Al-jubouri ◽  
Ahmed Joma
Keyword(s):  
Diabetic Retinopathy ◽  
Cataract Surgery ◽  
Macular Edema ◽  
Teaching Hospital ◽  
Cystoid Macular Edema ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Teaching Hospitals ◽  
Cataract Operation ◽  
Age Related

Cystoid Macular Edema (CME) in its various forms can be considered one of the leading causes of central vision loss in the developed world. It is not a disease itself, It represents a common pathologic sequel of the retina and occurs in a variety of pathological conditions such as, diabetic retinopathy, central or branch retinal vein occlusion, intraocular inflammation and following cataract extraction. This study was done to investigate the pattern of CME in patient attending Erbil Teaching Hospitals. This is a hospital base prospective study that included 61 patients (75 eyes) conducted at Erbil Teaching Hospital and Rigor Teaching Hospital for six months. All patients underwent a comprehensive assessment including medical and ophthalmic history and detailed ophthalmic examination including slit lamp examination, intraocular pressure measurement (IOP), Best corrected visual acuity (BCVA), dilated fundus examination and Optical Coherence Tomography (OCT) examination. It was found that of the 61 patients 32 (52.5%) were females and 29 (47.5%) were males. The mean age (56.4±10.8) years. Out of the 75 eyes included in the study, 41 eyes (54.66%) had diabetic retinopathy, 10 (13.34%) eyes had CME following cataract operation (Irvine-Gass syndrome), 8 eyes (10.67%) had BRVO, 6 eyes (8%) were had CRVO, 5 eyes (6.66%) had Age related Macular Degeneration, 3 eyes (4%) with uveitis, and 2 (2.67%) had Retinitis Pigmentosa. The average macular thickness was (415.6± 107). It was concluded that diabetic retinopathy is the most common predictive factor of CME, followed by cataract surgery. CME is more severe in diabetic retinopathy, CRVO and after cataract surgery.

scholarly journals Topical Nonsteroidal Anti-Inflammatory Drugs for Macular Edema

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Andrea Russo ◽  
Ciro Costagliola ◽  
Luisa Delcassi ◽  
Francesco Parmeggiani ◽  
Mario R. Romano ◽  
...  
Keyword(s):  
Macular Edema ◽  
Age Related Macular Degeneration ◽  
Therapeutic Effects ◽  
Retinal Diseases ◽  
Clinical Use ◽  
Drug Penetration ◽  
Age Related ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Topical Nsaids

Nonsteroidal anti-inflammatory drugs (NSAIDs) are nowadays widely used in ophthalmology to reduce eye inflammation, pain, and cystoid macular edema associated with cataract surgery. Recently, new topical NSAIDs have been approved for topical ophthalmic use, allowing for greater drug penetration into the vitreous. Hence, new therapeutic effects can be achieved, such as reduction of exudation secondary to age-related macular degeneration or diabetic maculopathy. We provide an updated review on the clinical use of NSAIDs for retinal diseases, with a focus on the potential future applications.

Anti-Vegf in Management of Macular Edema in Retinal Disease

2017 ◽  
Vol 71 (1) ◽  
pp. 15-19
Author(s):  
Natasha T Shekerinov ◽  
Vesna Dimovska Jordanova ◽  
Milco Bogoev
Keyword(s):  
Visual Acuity ◽  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Vision Loss ◽  
Vascular Occlusion ◽  
Retinal Disease ◽  
Age Related Macular Degeneration ◽  
Blood Retinal Barrier ◽  
Anti Vegf ◽  
Age Related

Abstract Aim. To present new opportunities, clinical implications and benefits of the available VEGF therapy as a treatment of macular edema, which is a result of venous vascular occlusions, diabetic macular edema in diabetic retinopathy and age-related macular degeneration. Background. The pathophysiology of macular edema is complex and various processes are involved in its development. It is actually an abnormal retinal capillary permeability and a disorder in the blood retinal barrier, which only increases the vascular permeability. This causes an expansion of the extracellular spaces, which leads to fluid accumulation, which additionally leads to macular thickening and eventual vision loss. Methods. The studies included 40 patients, of whom17 was diagnosed with macular edema in diabetic retinopathy and were treated with anti-VEGF therapy. Also, there were 11 patients diagnosed with wet form of AMD, and 12 cases diagnosed with macular edema secondary to vein occlusion. This retrospective study of 18 months monitored the effects of visual acuity on Snellen chart and the effects of macula anatomy using Optical Coherent tomography /OCT/. All patients received intravitreal injection of Bevacizumab /Avastin/ of 1.25mg /0.04ml/ and were evaluated monthly or every 4 to 8weeks. We monitored the potential ocular and systematic side effects in all our cases. Results. In the first group which included patients with edema due to venous vascular occlusion improvement of visual acuity in 58.33% patients, 25.0% showed no change in visual acuity and 16.66% showed slight worsening of 0.029 and regression of CMT entirely to 393.22 after 4.6 intravitreal injections on average. In the second group there was no improvement of VA 0.172 and reducing central macular thickness for 218.34μm by 5.6 intravitreal applications. The third group, 17 patients with macular edema due to diabetic retinopathy had stabilization of visual acuity, i.e. slight improvement in 8 of them by 0.14; and, in 9 and improvement of 0.21 and regression CMT, an average of 174.3 μm. Although it has been shown that benefit of intravitreal use of Bevacizumab and improvement of visual acuity has not been always change hand in hand with the reduction of macular edema, the need for this kind of treatment in certain cases are needed to maintain stable CMT and VA in such patients. Conclusion. Over the last few years monoclonal antibodies have become a standard therapy in treatment of wet form of AMD. Switch on anti-VEGF drugs has shown significant results in clinical and visual out-comes in patients with changes of the macula as a result of other disease. In fact, they caused a revolution in the treatment of refractory macular edema.

Region of Interest based Predictive Algorithm for Subretinal Hemorrhage Detection using Faster R-CNN

2021 ◽  
Author(s):  
Sai Ganesh N ◽  
Suchetha M ◽  
Rajiv Raman ◽  
Edwin Dhas D
Keyword(s):  
Neural Network ◽  
Convolutional Neural Network ◽  
Macular Edema ◽  
Vision Loss ◽  
Region Of Interest ◽  
Performance Comparison ◽  
Age Related Macular Degeneration ◽  
Subretinal Hemorrhage ◽  
Predictive Algorithm ◽  
Age Related

Abstract Macular Edema (ME) is an essential sort of macular issues caused due to the storing of fluid underneath the macula. Age-related Macular Degeneration (AMD) and Diabetic Macular Edema (DME) are the two customary visual contaminations that can lead to fragmentary or complete vision loss. This paper proposes a deep learning-based predictive algorithm that can be used to detect the presence of a Subretinal hemorrhage. This method initially detects the presence of Subretinal hemorrhage, and it then segments the Region of Interest (ROI) by a semantic segmentation process. The segmented ROI is applied to a predictive algorithm which is derived from the Fast Region Convolutional Neural Network (Fast R-CNN) algorithm, that can categorize the Subretinal hemorrhage as responsive or non-responsive. The dataset, provided by a medical institution, comprised of Optical Coherence Tomography (OCT) images of both pre and post-treatment images, was used for training the proposed Faster Region Convolutional Neural Network (Faster R-CNN). We also used the Kaggle dataset for performance comparison with the traditional methods that are derived from the Convolutional Neural Network (CNN) algorithm. The evaluation results using the Kaggle dataset and the hospital images provide an average sensitivity, selectivity, and accuracy of 85.3%, 89.64%, and 93.48% respectively. Further, the proposed method provides a time complexity in testing as 2.64s, which is less than the traditional schemes like CNN, R-CNN, and Fast R-CNN.

scholarly journals Role of amyloid β-peptide in the pathogenesis of age-related macular degeneration

2021 ◽  
Vol 6 (1) ◽  
pp. e000774
Author(s):  
Minwei Wang ◽  
Shiqi Su ◽  
Shaoyun Jiang ◽  
Xinghuai Sun ◽  
Jiantao Wang
Keyword(s):  
Mitochondrial Dysfunction ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cell Structure ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Peptide ◽  
Age Related

Age-related macular degeneration (AMD) is the most common eye disease in elderly patients, which could lead to irreversible vision loss and blindness. Increasing evidence indicates that amyloid β-peptide (Aβ) might be associated with the pathogenesis of AMD. In this review, we would like to summarise the current findings in this field. The literature search was done from 1995 to Feb, 2021 with following keywords, ‘Amyloid β-peptide and age-related macular degeneration’, ‘Inflammation and age-related macular degeneration’, ‘Angiogenesis and age-related macular degeneration’, ‘Actin cytoskeleton and amyloid β-peptide’, ‘Mitochondrial dysfunction and amyloid β-peptide’, ‘Ribosomal dysregulation and amyloid β-peptide’ using search engines Pubmed, Google Scholar and Web of Science. Aβ congregates in subretinal drusen of patients with AMD and participates in the pathogenesis of AMD through enhancing inflammatory activity, inducing mitochondrial dysfunction, altering ribosomal function, regulating the lysosomal pathway, affecting RNA splicing, modulating angiogenesis and modifying cell structure in AMD. The methods targeting Aβ are shown to inhibit inflammatory signalling pathway and restore the function of retinal pigment epithelium cells and photoreceptor cells in the subretinal region. Targeting Aβ may provide a novel therapeutic strategy for AMD.

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