The Evidence Supporting Ranibizumab in the Treatment of Neovascular Age-related Macular Degeneration

2013 ◽  
Vol 07 (02) ◽  
pp. 102
Author(s):  
Simon P Kelly ◽  
Winfried Amoaku ◽  
◽  

The efficacy and safety of ranibizumab in neovascular age-related macular degeneration (AMD) or ‘wet AMD’ has been demonstrated in the large phase III ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, EXCITE and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab. Various head-to-head studies have compared the anti-angiogenic treatments for wet AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab and raised concern about an increased risk of ocular and systemic adverse events (AEs) in patients receiving bevacizumab compared with those receiving ranibizumab. Studies such as SAILOR and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with few serious ocular and systemic AEs.

2019 ◽  
Vol 12 (3) ◽  
pp. 102-112
Author(s):  
I. E. Ioshin ◽  
T. Anoprieva

Age-related macular degeneration (AMD) is a chronic progressive disease regarded as a leading cause of vision impairment in elderly people in industrial countries. Neovascular AMD is characterized by an increased risk of severe vision loss. Intravitreal injections of anti-VEGF medication has become a standard of treatment of neovascular AMD. Clinical trials demonstrate that the use of anti-VEGF helps stabilize the vision in at least 90 % of patients, while 30 to 40 % gain three or more lines of vision (15 ETDRS letters). However, observational studies suggest that there are barriers diminishing the efficacy of anti-VEGF treatment in routine clinical practice. Finding an optimal dosing regimen for anti-VEGF therapy that could maintain treatment efficacy with a lower number of injections and fewer monitoring visits could be a solution. The review discusses the evidence base regarding anti-VEGF dosing principles and analyzes current dosing regimens with regard to their benefits and limitations.


2019 ◽  
Vol 3 (2) ◽  
pp. 90-93
Author(s):  
Rami Gabriel ◽  
Jaime Toledo-Corral ◽  
Maria Cristina Kenney ◽  
Mitul Mehta

Purpose: This study employed a prospective survey to evaluate whether maternal family history or paternal family history is more likely to be found in patients with age-related macular degeneration (AMD). Methods: Family history of AMD was ascertained through a survey questionnaire of 346 patients who were confirmed by an ophthalmologist to have AMD. To compare proportions of maternally and paternally transmitted disease, the data were treated as pair matched and analyzed using the modified chi-squared McNemar test. Probands with either parent deceased before age 60 were excluded. Further analysis was conducted by grouping wet-AMD and dry-AMD patients. Results: Of the 346 surveys conducted, 91 (26.3%) reported at least 1 parent affected with AMD. Probands were 65.9% women and 44.1% men. The mean ± SD age for men was 74.3 ± 6.3 years and for women 72.7 ± 7.7 years. The average age of proband fathers was 75.0 ± 6.9 years and of proband mothers 80.1 ± 6.0 years. Probands with AMD had a higher proportion of affected mothers than fathers with an odds ratio (OR) of 3.00 and a 95% CI of 1.73 to 5.44, P = .0001. For wet AMD, the OR was 4.0 (95% CI 1.46 to 13.6) and for dry AMD, the OR was 2.6 (95% CI 1.35 to 5.4). Conclusions: Our results indicate that individuals with maternal history of AMD may be at a significantly increased risk for developing AMD than if their father had the disease. Owing to limitations in sample size and discrepancies in lifespan between sexes, further studies will be needed to generalize results. The maternal proclivity in our study sample correlates with literature describing a mitochondrial component in the disease process, soliciting further exploration into mitochondrial etiology and larger hereditary studies.


2021 ◽  
pp. 112067212110026
Author(s):  
Pablo Gili ◽  
Leyre Lloreda Martín ◽  
José-Carlos Martín-Rodrigo ◽  
Naon Kim-Yeon ◽  
Laura Modamio-Gardeta ◽  
...  

Purpose: To identify the association between single-nucleotide polymorphisms (SNPs) in CFH, ARMS2, HTRA1, CFB, C2, and C3 genes and exudative age-related macular degeneration (AMD) in a Spanish population. Methods: In 187 exudative AMD patients and 196 healthy controls (61% women, mean age 75 years), 12 SNPs as risk factors for AMD in CFH (rs1410996, rs1061170, r380390), ARMS2 (rs10490924, rs10490923), HTRA1 (rs11200638), CFB (rs641153), C2 (rs547154, rs9332739), and C3 (rs147859257, rs2230199, rs1047286) genes were analyzed. Results: The G allele was the most frequent in CFH gene (rs1410996) with a 7-fold increased risk of AMD (OR 7.69, 95% CI 3.17–18.69), whereas carriers of C allele in CFH (rs1061170) showed a 3-fold increased risk for AMD (OR 3.22, 95% CI 1.93–5.40). In CFH (rs380390), the presence of G allele increased the risk for AMD by 2-fold (OR 2.52, 95% CI 1.47–4.30). In ARMS2 (rs10490924), the T-allele was associated with an almost 5-fold increased risk (OR 5.49, 95% CI 3.23–9.31). The A allele in HTRA1 (rs11200638) was more prevalent in AMD versus controls (OR 6.44, 95% CI 3.62–11.47). In C2 gene (rs9332739) the presence of C increased risk for AMD by 3-fold (OR 3.10, 95% CI 1.06–9.06). Conclusion: SNPs in CFH, ARMS2, HTRA1, and C2 genes were associated in our study with an increased risk for exudative AMD in Spanish patients.


2021 ◽  
pp. 112067212110183
Author(s):  
Laurent Kodjikian ◽  
Carl Joe Mehanna ◽  
Salomon-Yves Cohen ◽  
François Devin ◽  
Sam Razavi ◽  
...  

Anti-vascular endothelial growth factor (VEGF) agents have transformed the management of patients with neovascular age-related macular degeneration (nAMD) over the past two decades. However, as more long-term real-world data become available, it is clear that treatment outcomes are inferior to those reported in large, controlled clinical trials. This is largely driven by undertreatment, that is, not maintaining a consistent injection frequency to achieve sustained VEGF suppression, whether due to patient non-compliance, an important injection burden, or non/incomplete anatomical response. Newer therapeutic advances under evaluation hold promise in achieving more, for less. We review the latest drugs currently in or having successfully finished phase III clinical trials, and determine their potential place in the management of patients with nAMD in Europe.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessandro Arrigo ◽  
Emanuela Aragona ◽  
Ottavia Battaglia ◽  
Andrea Saladino ◽  
Alessia Amato ◽  
...  

AbstractOuter retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p < 0.01). We detected completely formed ORT in 26/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (p < 0.01). ORT took 18 ± 8 months (range 3–35 months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (p < 0.01). We also described pigment accumulations simulating ORT, which were detected in 16/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (p < 0.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and Müller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility.


Author(s):  
Liv Tybjærg Nordestgaard ◽  
Anne Tybjærg-Hansen ◽  
Ruth Frikke-Schmidt ◽  
Børge Grønne Nordestgaard

Abstract Context To enable prevention and treatment of age-related macular degeneration(AMD), understanding risk factors for AMD is important. Objective We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein(HDL) cholesterol, and low levels of low-density lipoprotein(LDL) cholesterol, are associated with increased risk of AMD. Design and Setting From the Danish general population, we studied 106,703 and 16,032 individuals in the Copenhagen General Population Study(CGPS) and the Copenhagen City Heart Study(CCHS) with median follow-up of respectively 9 and 32 years. Main Outcome Measures 1,787 AMD in CGPS and 206 in CCHS. Results Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40(95%CI:1.20-1.63) and 1.22(1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18(1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L(39 mg/dL) higher HDL, and 1 mmol/L(39mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19(1.07-1.32), and 1.05(1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Conclusion Elevated plasma apolipoprotein A1 and HDL cholesterol, and lower LDL cholesterol, are associated with increased risk of age-related macular degeneration.


2019 ◽  
Vol 20 (20) ◽  
pp. 5049 ◽  
Author(s):  
Ibuki ◽  
Shoda ◽  
Miwa ◽  
Ishida ◽  
Tsubota ◽  
...  

Background: Age-related macular degeneration (AMD) is the leading cause of blindness and can be classified into two types called atrophic AMD (dry AMD) and neovascular AMD (wet AMD). Dry AMD is characterized by cellular degeneration of the retinal pigment epithelium, choriocapillaris, and photoreceptors. Wet AMD is characterized by the invasion of abnormal vessels from the choroid. Although anti-vascular endothelial growth factor (VEGF) therapy has a potent therapeutic effect against the disease, there is a possibility of chorio-retinal atrophy and adverse systemic events due to long-term robust VEGF antagonism. We focused on hypoxia-inducible factor (HIF) regulation of VEGF transcription, and report the suppressive effects of HIF inhibition against ocular phenotypes in animal models. Many of the known HIF inhibitors are categorized as anti-cancer drugs, and their systemic side effects are cause for concern in clinical use. In this study, we explored food ingredients that have HIF inhibitory effects and verified their effects in an animal model of AMD. Methods: Food ingredients were screened using a luciferase assay. C57BL6/J mice were administered the Garcinia cambogia extract (Garcinia extract) and hydroxycitric acid (HCA). Choroidal neovascularization (CNV) was induced by laser irradiation. Results: Garcinia extract and HCA showed inhibitory effects on HIF in the luciferase assay. The laser CNV model mice showed significant reduction of CNV volume by administering Garcinia extract and HCA. Conclusions: Garcinia extract and HCA showed therapeutic effects in a murine AMD model.


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