-
1.
Medication Trends for Age-Related Macular Degeneration.
Cho, YK, Park, DH, Jeon, IC
International journal of molecular sciences. 2021;(21)
Abstract
Age-related macular degeneration (AMD) is central vision loss with aging, was the fourth main cause of blindness in 2015, and has many risk factors, such as cataract surgery, cigarette smoking, family history, hypertension, obesity, long-term smart device usage, etc. AMD is classified into three categories: normal AMD, early AMD, and late AMD, based on angiogenesis in the retina, and can be determined by bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E)-epoxides from the reaction of A2E and blue light. During the reaction of A2E and blue light, reactive oxygen species (ROS) are synthesized, which gather inflammatory factors, induce carbonyl stress, and finally stimulate the death of retinal pigment epitheliums (RPEs). There are several medications for AMD, such as device-based therapy, anti-inflammatory drugs, anti-VEGFs, and natural products. For device-based therapy, two methods are used: prophylactic laser therapy (photocoagulation laser therapy) and photodynamic therapy. Anti-inflammatory drugs consist of corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). Anti-VEGFs are classified antibodies for VEGF, aptamer, soluble receptor, VEGF receptor-1 and -2 antibody, and VEGF receptor tyrosine kinase inhibitor. Finally, additional AMD drug candidates are derived from natural products. For each medication, there are several and severe adverse effects, but natural products have a potency as AMD drugs, as they have been used as culinary materials and/or traditional medicines for a long time. Their major application route is oral administration, and they can be combined with device-based therapy, anti-inflammatory drugs, and anti-VEGFs. In general, AMD drug candidates from natural products are more effective at treating early and intermediate AMD. However, further study is needed to evaluate their efficacy and to investigate their therapeutic mechanisms.
-
2.
Rapid growth of primary uveal melanoma following intravitreal bevacizumab injection: a case report and review of the literature.
Ma, J, Roelofs, KA, Russell, L, Weis, E, Chen, SH
Digital journal of ophthalmology : DJO. 2021;(3):27-30
Abstract
Uveal melanoma size is a significant predictor of tumor metastasis. Although the relationship between antivascular endothelial growth factors (VEGF) and uveal melanoma growth has been studied, results are paradoxical, and the relationship remains controversial. We report the case of a 65-year-old man who presented with elevated intraocular pressure in his right eye, neovascularization of his iris, and significant corneal edema, which obscured the view of the angle. Given his history of proliferative diabetic retinopathy, he was diagnosed with neovascular glaucoma and subsequently received an intravitreal injection of bevacizumab and underwent Ahmed valve insertion. This was complicated by postoperative hyphema. Two and a half months postoperatively, a mass involving the inferior iris and ciliary body became visible, and fine-needle aspiration biopsy confirmed uveal melanoma. Seven weeks after diagnosis, the tumor's largest basal diameter had increased from 2.51 mm to 18.0 mm, and apical height increased from 6.23 mm to 11.0 mm. His right eye was enucleated. Histopathological analysis showed discontinuous invasion next to the Ahmed valve. Tumor progression after injection raises the possibility that in some untreated uveal melanomas, accelerated growth may occur following exposure to anti-VEGF agents.
-
3.
Real-Time Photographic- and Fluorescein Angiographic-Guided Management of Diabetic Retinopathy: Randomized PRIME Trial Outcomes.
Yu, HJ, Ehlers, JP, Sevgi, DD, Hach, J, O'Connell, M, Reese, JL, Srivastava, SK, Wykoff, CC
American journal of ophthalmology. 2021;:126-136
Abstract
PURPOSE To assess the safety and efficacy of as-needed (PRN) intravitreal aflibercept injections (IAI) in managing diabetic retinopathy (DR) guided by the real-time DR severity scale (DRSS) level or panretinal leakage index (PLI) assessment among eyes without diabetic macular edema (DME). DESIGN Prospective, randomized phase 2 trial (PRIME). METHODS A total of 40 eyes with nonproliferative (NPDR) or proliferative DR (PDR) received monthly IAIs until a DRSS improvement of ≥2 steps was achieved and eyes were randomized (1:1) to DRSS-guided or PLI-guided management strategies graded by a central reading center. Main outcome measurements included safety and changes in DRSS and PLI. RESULTS Through week 52, 95% of eyes achieved a DRSS improvement of ≥2 steps. Following DRSS improvement, 97% of eyes required at least 1 PRN IAI. In eyes requiring PRN IAI and completing week 52, 100% and 59% experienced DRSS worsening (P = .01) in the DRSS- and PLI-guided arms, respectively. Through week 52, mean PLI decreased 18.2% (P = .49) and 54.6% (P <.0001), respectively, in the DRSS- and PLI-guided arms. NPDR versus PDR eyes at baseline achieved a DRSS improvement of ≥2 steps after a mean 4.9 and 3.6 IAIs (P = .03). Two eyes developed a PDR event at week 52 following 5 months of quiescence. CONCLUSIONS The randomized PRIME study analyzed 2 imaging-based biomarkers to guide PRN management with IAI of DR without DME: DRSS level and PLI. Within the context of this study with limitations, most patients required IAI re-treatment every 3-4 months, and deterioration of PLI appeared to precede DRSS level worsening. Finally, these findings reaffirm the fact that close clinical follow-up is important even among eyes that achieve substantial DRSS improvements with apparently quiescent disease.
-
4.
Pre-therapeutic Biomarkers for Ranibizumab Therapy among Type 2 Diabetic Patients with Diabetic Macular Edema.
Paine, SK, Bhattacharjee, CK, Bhaduri, G, Pramanik, S, Borah, PK, Mahanta, J, Basu, A, Mondal, LK
Optometry and vision science : official publication of the American Academy of Optometry. 2021;(1):81-87
Abstract
SIGNIFICANCE A differential outcome in randomized controlled trials of anti-vascular endothelial growth factor (anti-VEGF) therapy, including ranibizumab, for diabetic macular edema is a major dilemma for planning, optimizing, and managing clinical usage. The variable outcome of the therapeutics necessitates the importance of finding a predictive biomarker for anti-VEGF therapy to improve subject selection. PURPOSE Our study correlates the baseline pro- and anti-VEGF isoforms and its three receptors (VEGFReceptor1, VEGFReceptor2, and VEGFReceptor3) for circulatory candidate protein molecules among diabetic patients with macular edema, with the clinical outcome of ranibizumab therapy. METHODS This study included 86 individuals who were anti-VEGF naive at the time of ascertainment but have completed the standardized therapy regimen of the clinic. Plasma proteins for pro- and anti-VEGF isoforms and its three receptors were determined in replicate by an enzyme-linked immunosorbent assay. RESULTS The study demonstrated that 56 (65.12%) individuals benefited from the therapy in terms of letter gain (Snellen chart). Baseline plasma soluble VEGF receptor 2 (sVEGFR-2) was significantly higher among responders (65.10 pg/mL; 95% confidence interval, 55.41 to 74.80 pg/mL) compared with nonresponders (46.38 pg/mL; 95% confidence interval, 38.69 to 54.07 pg/mL; PFDR = .03). Diffuse diabetic macular edema with proliferative diabetic retinopathy increases the risk of nonresponse to the therapy by 3.03-fold (PFDR = .04). CONCLUSIONS The present study postulates that diffuse diabetic macular edema with proliferative diabetic retinopathy and baseline circulatory soluble VEGF receptor 2 may be potential candidates as therapy-stratifying markers for ranibizumab treatment among patients with diabetic macular edema.
-
5.
Anti-vascular endothelial growth factor therapy in breast cancer: Molecular pathway, potential targets, and current treatment strategies.
Zhang, M, Liu, J, Liu, G, Xing, Z, Jia, Z, Li, J, Wang, W, Wang, J, Qin, L, Wang, X, et al
Cancer letters. 2021;:422-433
Abstract
As the highest incidence of female malignancy, breast cancer is likewise the leading cause of cancer-related deaths. The development of cancer relies on neo-vascularization, which provides sufficient nutrition and oxygen, and supplies a pathway for distant metastasis. Angiogenesis represents the formation of new blood vessels, and is a principal pathogenetic action in breast cancer. Vascular endothelial growth factor (VEGF) is a major angiogenesis regulator that modulates the maintenance and function of mature vascular networks. Therefore, the VEGF pathway is a promising oncotherapeutic target. This review elaborates an update on the prognostic value of VEGF in breast cancer, summarizes clinical experience and lessons of anti-VEGF therapeutics, meanwhile, provides an overview of biomarkers that predict the effectiveness of anti-angiogenic treatment.
-
6.
Clinical efficacy of anti-vascular endothelial growth factor versus panretinal photocoagulation for patients with proliferative diabetic retinopathy: A protocol for systematic review and meta-analysis.
Lin, Y, Zheng, X, Chen, Q, Wu, R
Medicine. 2021;(17):e25682
-
-
Free full text
-
Abstract
BACKGROUND The argument on the optimal treatment for patients with proliferative diabetic retinopathy (PDR) remains to be resolved. Therefore, the primary objective of the present study was to evaluate the clinical efficacy of anti-vascular endothelial growth factor (anti-VEGF) therapy versus panretinal photocoagulation (PRP) for patients with PDR. METHODS Two independent investigators followed The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and the recommendations of the Cochrane Collaboration to conduct this meta-analysis. The electronic databases of EMBASE, PubMed, Cochrane Library, and Web of Science were searched from the inception to April 2021 using the following key terms: "proliferative diabetic retinopathy," "anti-vascular endothelial growth factor," and "panretinal photocoagulation," for all relevant studies. We identified literature that met the following inclusion criteria: patients with PDR; studies focusing on assessing anti-VEGF therapy and PRP; the following outcome measures must be shown: anatomical outcomes, including complete regression and recurrence of neovascularization, mean change in best corrected vision acuity from baseline to the end of follow-up period. The Cochrane risk of bias tool was used to evaluate the risk of bias of included randomized clinical trials by 2 independent reviewers. RESULTS This protocol will provide a reliable theoretical basis for the following research. TRIAL REGISTRATION NUMBER 10.17605/OSF.IO/UHYDR.
-
7.
Epigallocatechin-3-gallate plays more predominant roles than caffeine for inducing actin-crosslinking, ubiquitin/proteasome activity and glycolysis, and suppressing angiogenesis features of human endothelial cells.
Gallemit, PEM, Yoodee, S, Malaitad, T, Thongboonkerd, V
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2021;:111837
Abstract
A recent expression proteomics study has reported changes in cellular proteome (set of proteins) of human endothelial cells (ECs) induced by caffeine and epigallocatechin-3-gallate (EGCG), the most abundant bioactive compounds in coffee and green tea, respectively. Although both common and differential changes were highlighted by bioinformatics prediction, no experimental validation was performed. Herein, we reanalyzed these proteome datasets and performed protein-protein interactions network analysis followed by functional investigations using various assays to address the relevance of such proteome changes in human ECs functions. Protein-protein interactions network analysis revealed actin-crosslink formation, ubiquitin-proteasome activity and glycolysis as the three main networks among those significantly altered proteins induced by caffeine and EGCG. The experimental data showed predominant increases of actin-crosslink formation, ubiquitin-proteasome activity, and glycolysis (as reflected by increased F-actin and β-actin, declined ubiquitinated proteins and increased intracellular ATP, respectively) in the EGCG-treated cells. Investigations on angiogenesis features revealed that EGCG predominantly reduced ECs proliferation, migration/invasion, endothelial tube formation (as determined by numbers of nodes/junctions and meshes), barrier function (as determined by levels of VE-cadherin, zonula occludens-1 (ZO-1) and transendothelial resistance (TER)), and angiopoietin-2 secretion. However, both caffeine and EGCG had no effects on matrix metalloproteinase-2 (MMP-2) secretion. These data indicate that EGCG exhibits more potent effects on human ECs functions to induce actin-crosslink, ubiquitin-proteasome activity and glycolysis, and to suppress angiogenesis processes that commonly occur in various diseases, particularly cancers.
-
8.
Optical Coherence Tomography Angiography of Macular Perfusion Changes after Anti-VEGF Therapy for Diabetic Macular Edema: A Systematic Review.
Elnahry, AG, Elnahry, GA
Journal of diabetes research. 2021;:6634637
Abstract
BACKGROUND Diabetic macular edema (DME) is a major cause of vision loss in diabetics that is currently mainly treated by antivascular endothelial growth factor (VEGF) agents. The effect of these agents on macular perfusion (MP) is a current concern. Optical coherence tomography angiography (OCTA) is an imaging modality that allows noninvasive high-resolution retinal microvasculature imaging. Several recent studies evaluated the effect of anti-VEGF agents on the MP of DME patients using OCTA. Our aim is to provide a systematic review of these studies. METHODS Multiple databases were searched including PubMed, Ovid Medline, EMBASE, and Google Scholar for relevant studies published between January 2016 and November 2020 which were included in this review. Studies were compared regarding their design, the number of included patients, the machine and scanning protocol used, the inclusion and exclusion criteria, the number of injections given, the type of anti-VEGF agent used, the outcome measures assessed, and the effect of injections on different MP parameters. RESULTS A total of 16 studies were included. The studies assessed various OCTA parameters that define MP including the foveal avascular zone area and superficial and deep vascular density and yielded conflicting results. Seven studies showed stable or improved MP following treatment, while 7 studies showed worsening MP following treatment, and 2 studies showed inconclusive results. This could have been due to differences in study design, inclusion criteria, type of anti-VEGF agents used, treatment duration, and methods of image analysis and vascular density quantification. All identified studies were noncomparative case series, and 14 of them (87.5%) used the RTVue XR Avanti OCTA machine. Only one study compared OCTA to fluorescein angiography findings. CONCLUSION Analysis of MP changes following VEGF inhibition for DME could benefit from a unified scanning protocol and analysis approach that uses similar study designs to eliminate potential sources of bias. This may provide more definitive conclusions regarding the effect of treatment on MP.
-
9.
Patient preferences in retinal drug delivery.
Jacobs, B, Palmer, N, Shetty, T, Dimaras, H, Hajrasouliha, A, Jusufbegovic, D, Corson, TW
Scientific reports. 2021;(1):18996
Abstract
Retinal vascular diseases (RVDs) are often treated with intravitreally (IVT) injected drugs, with relatively low patient compliance and potential risks. Ongoing research explores alternative RVD treatments, including eye drops and oral tablets. This study surveyed RVD patients treated with IVT injections to establish factors influencing low compliance rates while gauging treatment delivery method preferences. Demographics, perspectives, and treatment preferences were collected via IRB-approved, self-administered survey sent to Glick Eye Institute patients treated via IVT injections. Demographics, diagnoses, and treatments were ascertained from respondents' medical records. Gender, age, and number of IVT injections received were used as stratifications. Five-level Likert-style scales and t-tests evaluated responses and stratification comparisons. The most common diagnoses in the respondent population (n = 54; response rate = 5%) were age-related macular degeneration, macular edema, and diabetic retinopathy. Respondents had varying levels of education, income, and age. Most (83%) admitted feeling anxious prior to their first IVT injection, but 80% reported willingness to receive IVT injections indefinitely, with a preference for ophthalmologist visits every 1-3 months. Eye drops would be preferred over IVT injections by 76% of respondents, while 65% preferred oral tablets, due to several perceived negative factors of IVT injections and positive factors for eye drops. Stratified groups did not differ in responses to survey questions. RVD patients will accept IVT injections for vision preservation, but alternative delivery methods like eye drops or oral tablets would be preferred. Thus, development of eye drop and oral therapeutics for RVD treatment is further emphasized by these findings.
-
10.
Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study.
Babiuch, A, Wykoff, CC, Hach, J, Srivastava, S, Talcott, KE, Yu, HJ, Nittala, M, Sadda, S, Ip, MS, Le, T, et al
The British journal of ophthalmology. 2021;(8):1111-1115
Abstract
BACKGROUND/AIMS: Quantifying microaneurysms (MAs) turnover may be an objective measure for therapeutic response in diabetic retinopathy. This study assesses changes in MA counts on ultra-widefield fluorescein angiography (UWFA) in subjects undergoing treatment with intravitreal aflibercept injection (IAI) for proliferative diabetic retinopathy (PDR) in the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy(RECOVERY) study using an automated MA detection platform. METHODS RECOVERY is a prospective study that enrolled 40 subjects with PDR randomised 1:1 to receive 2 mg IAI every 4 weeks(q4wk) or every 12 weeks (q12wk). UWFA images were obtained at baseline, 6 months and 1 year. Images were analysed using an automated segmentation platform to detect and quantify MAs. Zones 1, 2 and 3 correspond to the macula, mid-periphery and far-periphery, respectively. RESULTS The q4wk cohort demonstrated a significant decline in MAs in all zones and panretinally at baseline versus month 6, baseline versus year 1, and month 6 versus year 1 (-20.0% to -61.8%; all p<0.001). In the q12wk cohort, baseline versus month 6 showed a significant decline panretinally (mean: -34.2%; p<0.001) and in zone 3 (mean -44.18%; p<0.001). Addiitonally, baseline to year 1 in the q12wk group demonstrated significant decline panretinally (mean: -47.7%; p<0.001) and in zone 3 (mean: -59.8%; p<0.001). All zones demonstrated significantly decline from month 6 to year 1 in the q12wk group. CONCLUSION Therapy with IAI demonstrates significantly reduced panretinal MA counts in PDR at 1 year in both treatment groups. The use of automated platforms to detect and quantify MAs may provide a novel imaging marker for evaluating disease activity and therapeutic impact. TRIAL REGISTRATION NUMBER NCT02863354.