Ranibizumab for Neovascular Age-Related Macular Degeneration

Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins

The Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) study was a randomized, double-blind, sham-controlled clinical trial to determine whether intravitreal administration of ranibizumab (an anti-vascular endothelial growth factor [VEGF] agent) prevents vision loss and improves mean visual acuity in patients with minimally classic or occult choroidal neovascularization related to age-related macular degeneration (AMD). Ranibizumab therapy was associated with clinically and statistically significant benefits in visual acuity and the amount of angiographic leakage from choroidal neovascularization during two years of follow-up, with low rates of serious adverse events.

Author(s):  
Alan D. Penman ◽  
Kimberly W. Crowder ◽  
William M. Watkins

In this chapter, report 1 of the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) study details the one-year results of two double-masked, placebo-controlled, randomized clinical trials to determine whether photodynamic treatment with verteporfin reduces the risk of vision loss in patients with age-related macular degeneration (AMD) due to subfoveal choroidal neovascularization (CNV) measuring 5400 µm or less in greatest linear dimension with evidence of classic CNV and best-corrected visual acuity of approximately 20/40 to 20/200. At the month-12 examination, 61% of eyes assigned to verteporfin compared with 46% of eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline). Verteporfin therapy was found to be safe and effective in reducing the risk of vision loss, and the authors recommended verteporfin therapy for treatment of patients with predominantly classic CNV from AMD.


2013 ◽  
Vol 5 ◽  
pp. CMT.S8921 ◽  
Author(s):  
Michael W. Stewart

The treatment of exudative age-related macular degeneration (AMD) has been completely transformed by the development of drugs that bind vascular endothelial growth factor (VEGF). The antibody-based VEGF inhibitors bevacizumab and ranibizumab usually prevent the enlargement of choroidal neovascular membranes, reduce vascular permeability, and improve visual acuity. The newest VEGF inhibitor, aflibercept, is a soluble fusion protein that binds all isoforms of VEGF-A, VEGF-B, and placental growth factor with high affinity. Preclinical studies demonstrated aflibercept's ability to prevent experimental neovascularization and tumor growth in animal models. In phase 3 trials for exudative AMD, patients who received aflibercept avoided moderate vision loss and experienced improved visual acuity comparable to those who received ranibizumab. Additionally, patients who were treated with aflibercept 2 mg every 8 weeks (after 3 monthly loading doses) had similar visual results to those treated every 4 weeks. When treated as needed during the second year of the trials, patients were able to last an average of 3 months between aflibercept injections. Since its regulatory approval, aflibercept has also been found to perform well as a salvage therapy for eyes that respond incompletely to ranibizumab and bevacizumab. Because aflibercept can be administered less frequently than ranibizumab, it promises to decrease the frequency of patients’ visits to physicians’ offices in addition to the overall cost of AMD therapy.


2018 ◽  
Vol 103 (4) ◽  
pp. 469-474 ◽  
Author(s):  
Florentina Joyce Freiberg ◽  
Stephan Michels ◽  
Alyson Muldrew ◽  
Jason Slakter ◽  
Denis O’Shaughnessy ◽  
...  

PurposeTo report the incidence and features of retinal microvascular abnormalities (MVAs) occurring secondary to stereotactic radiotherapy (SRT) in a randomised double-masked sham-controlled clinical trial at 21 European sites.MethodsTwo hundred and thirty participants with neovascular age-related macular degeneration (AMD) treated with at least three intravitreal antivascular endothelial growth factor (anti-VEGF) injections prior to enrolment, and demonstrating a continuing need for re-treatment. Interventions: 16 Gy, 24 Gy or sham SRT. All three groups received pro re nata anti-VEGF injections if the lesion was judged to be active at review visits. Colour fundus images from baseline and 6 months and fluorescein angiograms from baseline and annual visits were graded for measures of morphological outcome and safety using a prespecified protocol with accompanying definitions to distinguish RT-related MVA from non-specific retinal vessel abnormalities that are known to occur in neovascular AMD. The main outcome measure was MVA detected by months 12, 24 and 36 after enrolment.ResultsThe frequency of MVAs in the combined SRT arms was 0% in year 1, 13.1% in year 2 and 30.3% in year 3. The area of MVA was small and the mean change in visual acuity in year 2 was similar in a subset of SRT eyes with MVAs, versus those without MVAs. MVA was considered to have possibly contributed to vision loss in 2 of 18 cases with MVA in year 2, and 5 of 37 cases in year 3.ConclusionTreatment with SRT is associated with development of subtle MVAs that have little or no impact on visual outcome. These findings can help clinicians recognise the retinal MVAs that occur in response to SRT.


2020 ◽  
Vol 77 (5) ◽  
pp. 779-780 ◽  
Author(s):  
Anu Kauppinen

AbstractProlonged life expectancies contribute to the increasing prevalence of age-related macular degeneration (AMD) that is already the leading cause of severe vision loss among the elderly in developed countries. In dry AMD, the disease culminates into vast retinal atrophy, whereas the wet form is characterized by retinal edema and sudden vision loss due to neovascularization originating from the choroid beneath the Bruch’s membrane. There is no treatment for dry AMD and despite intravitreal injections of anti-vascular endothelial growth factor (VEGF) that suppress the neovessel formation, also wet AMD needs new therapies to prevent the disease progression and to serve patients lacking of positive response to current medicines. Knowledge on disease mechanisms is a prerequisite for the drug development, which is hindered by the multifactorial nature of AMD. Numerous distinguished publications have revealed AMD mechanisms at the cellular and molecular level and in this multi-author review, we take a bit broader look at the topic with some novel aspects.


2019 ◽  
Vol 4 (1) ◽  
pp. e000398 ◽  
Author(s):  
Saira Khanna ◽  
Rahul Komati ◽  
David A Eichenbaum ◽  
Ishani Hariprasad ◽  
Thomas A Ciulla ◽  
...  

Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.


2019 ◽  
Vol 30 (5) ◽  
pp. 1082-1090
Author(s):  
Jordi Monés ◽  
Marc Biarnés ◽  

Importance: To provide new insights into aflibercept effect in non-naive-treated patients with neovascular age-related macular degeneration. Purpose: To assess the efficacy of intravitreal aflibercept in patients with neovascular age-related macular degeneration without optimal response to previous anti-vascular endothelial growth factor A therapy. Design: Single-arm, multi-centre, prospective study. Participants: Patients ⩾50 years with active neovascular age-related macular degeneration, best-corrected visual acuity between 20/32 and 20/320 with suboptimal response to ranibizumab or bevacizumab. Methods: Aflibercept was administered monthly (3-first months), and bimonthly thereafter until month 8. Anatomical and functional outcomes were assessed. Main outcome measure: Percentage of eyes without intra or subretinal fluid on optical coherence tomography after 3-monthly loading doses of aflibercept. Results: A total of 46 patients were included. At week 12, 45.7% (95% confidence interval: 31.5%–60.1%) of eyes showed no fluid on optical coherence tomography. The mean (standard deviation) best-corrected visual acuity increased from 65.1 (8.3) to 69.6 (8.1) letters (+4.5 (5.8) p < 0.0001) and was stabilized at week 40 as compared to baseline. Mean central macular thickness decreased from 430 (119) µm to 323 (100) µm at week 12 (–107 (90) µm, p < 0.0001) and was reduced at week 40 (–46 (111) µm, p = 0.0056). At week 40, 21.7% (95% confidence interval: 9.8%–33.7%) had no fluid. There was a case of presumed noninfectious endophthalmitis that was successfully managed. Conclusion: Almost half of patients presented no fluid on optical coherence tomography at week 12, and there was a clinically significant improvement in best-corrected visual acuity. At week 40, one in five patients did not show intra or subretinal fluid, central macular thickness decreased and best-corrected visual acuity was stabilized compared to baseline.


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