Intravitreal bevacizumab for treatment-naive patients with subfoveal occult choroidal neovascularization secondary to age-related macular degeneration: a 12-month follow-up study.
ABSTRACT The aim of this study was to assess the 12-month efficacy of intravitreal bevacizumab (IVB) injection for occult choroidal neovascularization secondary to age-related macular degeneration.
In this retrospective, interventional case series, 68 treatment-naïve patients with age-related macular degeneration, affected by subfoveal occult choroidal neovascularization showing recent disease progression, were monitored during the IVB protocol. The patients received 1 initial IVB injection (1.25 mg/0.05 mL), and they underwent further retreatment on a monthly basis only when necessary, according to a standardized as-required regimen, until no significant signs of choroidal neovascularization activity were present. Main outcome measures were the modifications in best-corrected visual acuity and in central retinal thickness measured by optical coherence tomography.
With respect to baseline, at the 12-month check, mean best-corrected visual acuity increased from 0.82 to 0.45 logMAR (P < 0.01) and mean central retinal thickness decreased from 517.0 microm to 306.5 microm (P < 0.01). To achieve these benefits, the required mean IVB number was lowered from 3.87 in the first 6 months to 1.085 in the second 6 months. A better final best-corrected visual acuity was correlated with greater best-corrected visual acuity (P < 0.005) and lesser central retinal thickness (P < 0.05) at baseline.
In patients with age-related macular degeneration complicated by progressive occult choroidal neovascularization, first-line IVB administration represents a useful therapeutic option, especially considering its lower cost in comparison with other antiangiogenic drugs.
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ABSTRACT: In Western countries, therapeutic management of patients affected by choroidal neovascularization (CNV) secondary to different typologies of macular degeneration represents a major health care problem. Age-related macular degeneration is the disease most frequently associated with CNV development. Schematically, CNVs can be distinguished into classic and occult subtypes, which are characterized by variable natural history and different responsiveness to some therapeutic procedures. At present, the dramatic vision loss due to CNV can be mainly treated by two interventional strategies, which are utilizable in either single or combined modalities: photodynamic therapy with verteporfin (PDT-V), and intravitreal administration of drugs acting against vascular endothelial growth factor. The combined use of PDT-V and anti-angiogenic drugs represents one of the most promising strategies against neovascular macular degeneration, but it unavoidably results in an expensive increase in health resource utilization. However, the positive data from several studies serve as a basis for reconsidering the role of PDT-V, which has undergone a renaissance prompted by the need for a more rational therapeutic approach toward CNV. New pharmacogenetic knowledge of PDT-V points to exploratory prospects to optimize the clinical application of this intriguing photothrombotic procedure. In fact, a Medline search provides data regarding the role of several single nucleotide polymorphisms (SNPs) as genetic predictors of CNV responsiveness to PDT-V. Specifically, correlations between SNPs and different levels of PDT-V efficacy have been detected by examining the gene variants influencing (i) thrombo-coagulative pathways, i.e. methylenetetrahydrofolate reductase (MTHFR) 677C>T (rs1801133), factor V (F5) 1691G>A (rs6025), prothrombin (F2) 20210G>A (rs1799963), and factor XIII-A (F13A1) 185G>T (rs5985); (ii) complement activation and/or inflammatory processes, i.e. complement factor H (CFH) 1277T>C (rs1061170), high-temperature requirement factor A1 (HTRA1) promoter -512G>A (rs11200638), and two variants of the C-reactive protein (CRP) gene (rs2808635 and rs876538); and (iii) production and bioavailability of vascular endothelial growth factor (VEGFA -2578C>A [rs699947] and rs2146323). This article critically evaluates both the clinical plausibility and the opportunity to utilize the most important SNP-response interactions of PDT-V for an effective upgrade of the current anti-CNV therapeutic scenario. In addition, the pharmacogenetics of a very severe post-PDT-V adverse event, i.e. a decrease in acute vision, is briefly discussed. A comprehensive appraisal of the findings reviewed in this article should be carefully considered to design future trials aimed at verifying (after proper genotypic stratification of the enrolled patients) whether these innovative pharmacogenetic approaches will be able to improve the multifaceted interventional management of neovascular macular degeneration.Molecular diagnosis & therapy 08/2011; 15(4):195-210. · 1.69 Impact Factor
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ABSTRACT: Vascular endothelial growth factor (VEGF) is a naturally occurring glycoprotein in the body that acts as a growth factor for endothelial cells. It regulates angiogenesis, enhances vascular permeability, and plays a major role in wet age-related macular degeneration. The consistent association between choroidal neovascularization and increased VEGF expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of this disorder. Blockade of VEGF activity is currently the most effective strategy for arresting choroidal angiogenesis and reducing vascular permeability, which is frequently the main cause of visual acuity deterioration. In recent years, a number of other molecules have been developed to increase the efficacy and to prolong the durability of the anti-VEGF effect. Aflibercept (EYLEA®; Regeneron Pharmaceutical Inc and Bayer), also named VEGF Trap-eye, is the most recent member of the anti-VEGF armamentarium that was approved by the US Food and Drug Administration in November 2011. Because of its high binding affinity and long duration of action, this drug is considered to be a promising clinically proven anti-VEGF agent for the treatment of wet maculopathy. This article reviews the current literature and clinical trial data regarding the efficacy and the pharmacological properties of VEGF-Trap eye and describes the possible advantages of its use over the currently used "older" anti-VEGF drugs. For this review, a search of PubMed from January 1989 to May 2013 was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, VEGF-Trap eye in wet AMD, VEGF-Trap eye in diabetic retinopathy, VEGF-Trap eye in retinal vein occlusions, aflibercept. Studies were limited to those published in English. Two Phase III clinical trials, VEGF Trap-eye Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, comparing VEGF Trap-eye to ranibizumab demonstrated the noninferiority of this novel compound. The clinical equivalence of this compound against ranibizumab is maintained even when the injections are administered at 8-week intervals, which indicates the potential to reduce the risk of monthly intravitreal injections and the burden of monthly monitoring.Drug Design, Development and Therapy 01/2013; 7:711-22. · 3.49 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: This study reviews differences in both ocular and systemic safety between intravitreal bevacizumab and ranibizumab in the setting of neovascular age-related macular degeneration. RECENT FINDINGS: Serious adverse events associated with either bevacizumab and ranibizumab injections are generally rare. However, acute intraocular inflammation (AII) tends to occur more frequently following bevacizumab injection. Systemic absorption of bevacizumab is greater than with ranibizumab, and many studies have shown an increased risk of systemic adverse events in patients receiving bevacizumab compared with those receiving ranibizumab. SUMMARY: Although rare, adverse events with off-label use of bevacizumab are more common than with ranibizumab. Continued study into long-term safety of the two agents is warranted.Current opinion in ophthalmology 03/2013; · 2.49 Impact Factor