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A literature analysis on anti-vascular endothelial growth factor therapy (anti-VEGF) using a bibliometric approach.
Yeung, AWK, Abdel-Daim, MM, Abushouk, AI, Kadonosono, K
Naunyn-Schmiedeberg's archives of pharmacology. 2019;(4):393-403
Abstract
We performed the current study to assess the citation performance of research works on anti-vascular endothelial growth factor (anti-VEGF) therapy. We searched Web of Science (WoS) to identify relevant publications and analyze them with reference to their publication year, journal title, citation count, WoS category, and article type. The bibliometric software (VOSviewer) was used for citation analyses of countries and journals and to generate a term map that visualizes the recurring terms appearing in the titles and abstracts of published articles. The literature search resulted in 7364 articles, with a mean citation count of 26.2. Over half of them (50.2%) were published during the past 5 years. Original articles constituted the majority (67.8%). The publications were mainly classified into WoS categories of ophthalmology (43.2%) and oncology (20.6%). The most prolific ophthalmology and cancer journals were Investigative Ophthalmology & Visual Science (7.3%) and Cancer Research (1.4%), respectively. The correlation between journal impact factor and citation count was weak to moderate (for journals with impact factor up to 5 and 10, respectively), and open-access articles had significantly more citations than non-open-access articles (p < 0.001). The frequently targeted tumors by anti-VEGF therapy included metastatic colorectal cancer (196; 49.2 citations per article (CPA)), breast cancers (167; 37.2 CPA), and renal cell carcinoma (122; 38.2 CPA). The frequently targeted eye pathologies were age-related macular degeneration (828; 18.2 CPA), diabetic macular edema (466; 10.8 CPA), and diabetic retinopathy (358; 31.9 CPA). These results indicate that anti-VEGF therapy has a wide range of applications and its publications are highly cited.
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Dexamethasone and Anti-VEGF Combination Therapy for the Treatment of Diabetic Macular Edema.
Al-Khersan, H, Hariprasad, SM, Salehi-Had, H
Ophthalmic surgery, lasers & imaging retina. 2019;(1):4-7
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Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP).
Li, Z, Zhang, Y, Liao, Y, Zeng, R, Zeng, P, Lan, Y
BMC ophthalmology. 2018;(1):19
Abstract
BACKGROUND Retinopathy of Prematurity (ROP) is one of the most common causes of childhood blindness worldwide. Comparisons of anti-VEGF and laser treatments in ROP are relatively lacking, and the data are scattered and limited. The objective of this meta-analysis is to compare the efficacy of both treatments in type-1 and threshold ROP. METHODS A comprehensive literature search on ROP treatment was conducted using PubMed and Embase up to March 2017 in all languages. Major evaluation indexes were extracted from the included studies by two authors. The fixed-effects and random-effects models were used to measure the pooled estimates. The test of heterogeneity was performed using the Q statistic. RESULTS Ten studies were included in this meta-analysis. Retreatment incidence was significantly increased for anti-VEGF (OR 2.52; 95% CI 1.37 to 4.66; P = 0.003) compared to the laser treatment, while the incidences of eye complications (OR 0.29; 95% CI 0.10 to 0.82; P = 0.02) and myopia were significantly decreased with anti-VEGF compared to the laser treatment. However, there was no difference in the recurrence incidence (OR 1.86; 95% CI 0.37 to 9.40; P = 0.45) and time between treatment and retreatment (WMD 7.54 weeks; 95% CI 2.00 to 17.08; P = 0.12). CONCLUSION This meta-analysis indicates that laser treatment may be more efficacious than anti-VEGF treatment. However, the results of this meta-analysis also suggest that laser treatment may cause more eye complications and increase myopia. Large-scale prospective RCTs should be performed to assess the efficacy and safety of anti-VEGF versus laser treatment in the future.
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Evolving multidimensional pharmacological approaches to CNV therapy in AMD.
Ehrenberg, M, Benny, O
Current eye research. 2018;(2):147-154
Abstract
PURPOSE The leading cause of severe visual loss world-wide is age-related macular degeneration. Although anti-Vascular Endothelial Growth Factor agents have significantly led to the initial pharmacologic reversal of vision loss in many cases of exudative macular degeneration, there still has been recurrence of choroidal neovascularization, and/or the onset of chorioretinal atrophy with fibrosis. MATERIALS AND METHODS In this review we discuss the status of anti- Vascular Endothelial Growth Factor in age-related macular degeneration and describe different studies focused on new potential therapeutic targets beyond anti- Vascular Endothelial Growth Factor. RESULTS Further investigations have elicited that Vascular Endothelial Growth Factor is only one of many angiogenic, and pro-inflammatory factors that bring about the growth and leakage of active choroidal neovascularization. Various new multifaceted strategies, including inhibitors to down-stream targets of endothelial cell division, such as TNP-470, may lead to a more permanent inactivation of choroidal neovascularization. CONCLUSIONS Based on the accumulated results in the treatment of age-related macular degeneration, it is hoped that the appropriate combination of anti-Vascular Endothelial Growth Factor agents with longer-acting and multidimensional pharmaceuticals, such as Methionine Aminopeptidase-2 inhibitors, will more effectively control choroidal neovascularization, prevent atrophy and fibrosis, and reduce the burden of frequent intraocular injections in age-related macular degeneration.
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Management of VEGF-Targeted Therapy-Induced Hypertension.
Caletti, S, Paini, A, Coschignano, MA, De Ciuceis, C, Nardin, M, Zulli, R, Muiesan, ML, Salvetti, M, Rizzoni, D
Current hypertension reports. 2018;(8):68
Abstract
PURPOSE OF REVIEW From a physiological point of view, VEGFs (vascular endothelial growth factors) and their receptors (VEGFR) play a critical role in vascular development angiogenesis, endothelial function, and vascular tone. On the pathological side, VEGF-VEGFR signaling may induce dysregulated angiogenesis, which contributes to the growth and to the spread of tumors, being essential for neoplastic proliferation and invasion. RECENT FINDINGS Pharmacological inhibition of VEGF-VEGFR is now a cornerstone in the treatment of many malignancies; however, treatment with VEGF inhibitors is commonly associated with an increase in blood pressure values. This side effect is strictly connected with the mechanism of action of these medications and might represent an index of therapy efficacy. The optimal management of this form of hypertension is, at present, not clear. Calcium channel blockers and renin-angiotensin system inhibitors probably represent the most appropriate classes of hypertensive dugs for the treatment of this condition; however, no conclusive data are presently available.
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Anti-vascular endothelial growth factor combined with intravitreal steroids for diabetic macular oedema.
Mehta, H, Hennings, C, Gillies, MC, Nguyen, V, Campain, A, Fraser-Bell, S
The Cochrane database of systematic reviews. 2018;(4):CD011599
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Abstract
BACKGROUND The combination of steroid and anti-vascular endothelial growth factor (VEGF) intravitreal therapeutic agents could potentially have synergistic effects for treating diabetic macular oedema (DMO). On the one hand, if combined treatment is more effective than monotherapy, there would be significant implications for improving patient outcomes. Conversely, if there is no added benefit of combination therapy, then people could be potentially exposed to unnecessary local or systemic side effects. OBJECTIVES To assess the effects of intravitreal agents that block vascular endothelial growth factor activity (anti-VEGF agents) plus intravitreal steroids versus monotherapy with macular laser, intravitreal steroids or intravitreal anti-VEGF agents for managing DMO. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Ovid Embase; LILACS; the ISRCTN registry; ClinicalTrials.gov and the ICTRP. The date of the search was 21 February 2018. SELECTION CRITERIA We included randomised controlled trials (RCTs) of intravitreal anti-VEGF combined with intravitreal steroids versus intravitreal anti-VEGF alone, intravitreal steroids alone or macular laser alone for managing DMO. We included people with DMO of all ages and both sexes. We also included trials where both eyes from one participant received different treatments. DATA COLLECTION AND ANALYSIS We used standard methodological procedures recommended by Cochrane.Two authors independently reviewed all the titles and abstracts identified from the electronic and manual searches against the inclusion criteria. Our primary outcome was change in best corrected visual acuity (BCVA) between baseline and one year. Secondary outcomes included change in central macular thickness (CMT), economic data and quality of life. We considered adverse effects including intraocular inflammation, raised intraocular pressure (IOP) and development of cataract. MAIN RESULTS There were eight RCTs (703 participants, 817 eyes) that met our inclusion criteria with only three studies reporting outcomes at one year. The studies took place in Iran (3), USA (2), Brazil (1), Czech Republic (1) and South Korea (1). Seven studies used the unlicensed anti-VEGF agent bevacizumab and one study used licensed ranibizumab. The study that used licensed ranibizumab had a unique design compared with the other studies in that included eyes had persisting DMO after anti-VEGF monotherapy and received three monthly doses of ranibizumab prior to allocation. The anti-VEGF agent was combined with intravitreal triamcinolone in six studies and with an intravitreal dexamethasone implant in two studies. The comparator group was anti-VEGF alone in all studies; two studies had an additional steroid monotherapy arm, another study had an additional macular laser photocoagulation arm. Whilst we judged these studies to be at low risk of bias for most domains, at least one domain was at unclear risk in all studies.When comparing anti-VEGF/steroid with anti-VEGF monotherapy as primary therapy for DMO, we found no meaningful clinical difference in change in BCVA (mean difference (MD) -2.29 visual acuity (VA) letters, 95% confidence interval (CI) -6.03 to 1.45; 3 RCTs; 188 eyes; low-certainty evidence) or change in CMT (MD 0.20 μm, 95% CI -37.14 to 37.53; 3 RCTs; 188 eyes; low-certainty evidence) at one year. There was very low-certainty evidence on intraocular inflammation from 8 studies, with one event in the anti-VEGF/steroid group (313 eyes) and two events in the anti-VEGF group (322 eyes). There was a greater risk of raised IOP (Peto odds ratio (OR) 8.13, 95% CI 4.67 to 14.16; 635 eyes; 8 RCTs; moderate-certainty evidence) and development of cataract (Peto OR 7.49, 95% CI 2.87 to 19.60; 635 eyes; 8 RCTs; moderate-certainty evidence) in eyes receiving anti-VEGF/steroid compared with anti-VEGF monotherapy. There was low-certainty evidence from one study of an increased risk of systemic adverse events in the anti-VEGF/steroid group compared with the anti-VEGF alone group (Peto OR 1.32, 95% CI 0.61 to 2.86; 103 eyes).One study compared anti-VEGF/steroid versus macular laser therapy. At one year investigators did not report a meaningful difference between the groups in change in BCVA (MD 4.00 VA letters 95% CI -2.70 to 10.70; 80 eyes; low-certainty evidence) or change in CMT (MD -16.00 μm, 95% CI -68.93 to 36.93; 80 eyes; low-certainty evidence). There was very low-certainty evidence suggesting an increased risk of cataract in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 4.58, 95% 0.99 to 21.10, 100 eyes) and an increased risk of elevated IOP in the anti-VEGF/steroid group compared with the macular laser group (Peto OR 9.49, 95% CI 2.86 to 31.51; 100 eyes).One study provided very low-certainty evidence comparing anti-VEGF/steroid versus steroid monotherapy at one year. There was no evidence of a meaningful difference in BCVA between treatments at one year (MD 0 VA letters, 95% CI -6.1 to 6.1, low-certainty evidence). Likewise, there was no meaningful difference in the mean CMT at one year (MD - 9 μm, 95% CI -39.87μm to 21.87μm between the anti-VEGF/steroid group and the steroid group. There was very low-certainty evidence on raised IOP at one year comparing the anti-VEGF/steroid versus steroid groups (Peto OR 0.75, 95% CI 0.16 to 3.55).No included study reported impact of treatment on patients' quality of life or economic data. None of the studies reported any cases of endophthalmitis. AUTHORS' CONCLUSIONS Combination of intravitreal anti-VEGF plus intravitreal steroids does not appear to offer additional visual benefit compared with monotherapy for DMO; at present the evidence for this is of low-certainty. There was an increased rate of cataract development and raised intraocular pressure in eyes treated with anti-VEGF plus steroid versus anti-VEGF alone. Patients were exposed to potential side effects of both these agents without reported additional benefit. The majority of the evidence comes from studies of bevacizumab and triamcinolone used as primary therapy for DMO. There is limited evidence from studies using licensed intravitreal anti-VEGF agents plus licensed intravitreal steroid implants with at least one year follow-up. It is not known whether treatment response is different in eyes that are phakic and pseudophakic at baseline.
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[Switching the Treatment Regime from PRN (pro re nata, as needed) to T&E (Treat and Extend) for Intravitreal Therapy with Anti-VEGF Agents in Private Practice or Small Institutions].
Imesch, P, Sarra, GM
Klinische Monatsblatter fur Augenheilkunde. 2018;(1):39-46
Abstract
In everyday practice, intravitreal therapy in an "as needed" regimen (pro re nata, PRN) is less predictable and requires more visits (monitoring and injections taken together) with poorer functional results than with the treat and extend (T&E) regimen. Current literature supports the benefit of a switch. However, practical advice is still missing. This article provides "best practice" recommendations for private practice or smaller institutions for the change from PRN to T&E. The requirements are organisational adjustments, staff training, definition of the scenario triggering the switch (A - functional or anatomical deterioration; B - general switch at a predefined date), counselling of the patients, defining benchmarks for the follow-up of the switch and preparing for higher capacity utilisation during the transition (shorter treatment intervals during the switching phase). Guidance is provided for each phase (a, preparation; b, transition; and c, follow-up).
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Subthreshold diode micropulse laser versus conventional laser photocoagulation monotherapy or combined with anti-VEGF therapy for diabetic macular edema: A Bayesian network meta-analysis.
Wu, Y, Ai, P, Ai, Z, Xu, G
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018;:293-299
Abstract
AIMS: To assess the effects of laser photocoagulation as monotherapy or adjuvant therapy for the treatment of DME. METHODS A search of the Cochrane Library, Pubmed, Embase, and the clinicaltrial.gov registry for randomized clinical trials comparing any two treatments of interest (SDMLP monotherapy, CLP monotherapy, CLP plus anti-VEGF therapy) was performed. Data were collected and pooled by Bayesian network meta-analyses which accounts for both direct and indirect comparisons. The primary outcome was the mean change in best-corrected visual acuity measured by the logarithm of the minimal angle of resolution units. The secondary outcome was the mean change in central macular thickness from baseline to month 12. RESULTS Ranibizumab therapy combined with CLP was more effective than SDMLP alone (MD, -0.396; 95% CrI, -0.746 to -0.062) and CLP alone (MD, -0.621; 95% CrI, -0.823 to -0.431). There was no apparent difference of efficacy between SDMLP alone and CLP alone (MD, -0.225; 95% CrI, -0.501 to 0.058). There was no apparent difference of efficacy between SDMLP alone and Bevacizumab therapy combined with CLP (MD, -0.003, 95% CrI, -0.815 to 0.805). CONCLUSION There was no apparent difference on improving vision between SDMLP monotherapy and CLP monotherapy. The most effective treatment in the network was ranibizumab therapy combined with CLP followed by SDMLP monotherapy, Bevacizumab therapy combined with CLP, and CLP monotherapy in rank order.
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Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy.
Wykoff, CC
Current opinion in ophthalmology. 2017;(3):213-218
Abstract
PURPOSE OF REVIEW Diabetic retinopathy is common and increasing in prevalence. Pharmacologic management of diabetic macular edema (DME) has improved tremendously over the last decade with the use of two families of intravitreally administered medications: antivascular endothelial growth factor-specific agents and corticosteroids. Clinical evaluation of these pharmaceuticals has demonstrated that they can have a substantial impact on diabetic retinopathy severity levels and the underlying retinal vasculature itself. RECENT FINDINGS Phase 3 trials employing ranibizumab, aflibercept, and fluocinolone acetonide enrolling eyes with center-involving DME causing visual acuity loss have demonstrated impressive alteration of the natural history of progressive diabetic retinopathy worsening over time through blunted progression to proliferative diabetic retinopathy, improving diabetic retinopathy severity levels, and slowing progressive retinal nonperfusion, the underlying disease process central to diabetic retinopathy itself. SUMMARY Accumulating data indicate that the threshold to initiate ocular-specific pharmacologic treatment for diabetic retinopathy, previously predominately limited to eyes with visual loss because of center-involved DME or proliferative diabetic retinopathy, is being lowered to earlier stages of diabetic retinopathy. Ongoing clinical trials and secondary analyses continue to further explore the impact and durability of vascular endothelial growth factor blockade and corticosteroids on modification of diabetic retinopathy and the underlying retinal vasculature itself.
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[Analysis of the Cochrane Review: Anti-vascular Endothelial Growth Factor for Prevention of Postoperative Vitreous Cavity Hemorrhage after Vitrectomy for Proliferative Diabetic Retinopathy. Cochrane Database Syst Rev. 2015;8:CD008214.].
Sousa, DC, Leal, I, Costa, J, Vaz-Carneiro, A
Acta medica portuguesa. 2017;(7-8):513-516
Abstract
Postoperative vitreous hemorrhage is a complication following vitrectomy for proliferative diabetic retinopathy, delaying visual recovery and making fundus examination and disease follow-up more difficult. Anti-vascular endothelial growth factor drugs such as bevacizumab, when injected in the vitreous cavity, reduce vascular proliferation and their use has been proposed to reduce the incidence of postoperative vitreous hemorrhage. The authors of this Cochrane systematic review evaluated all randomized controlled trials on the pre- or intraoperative use of anti-vascular endothelial growth factor to reduce postoperative vitreous hemorrhage occurrence after vitrectomy in patients with proliferative diabetic retinopathy. The results suggested that the use of intravitreal bevacizumab was effective in reducing early postoperative vitreous hemorrhage (i.e. at four weeks) occurrence, with a good safety profile. This work aims to summarize and discuss the findings and clinical implications of this Cochrane systematic review.