Management of Wet Age-Related Macular Degeneration - Literature review Example

Management of Wet Age Related Macular Degeneration Lecturer: Introduction Wet macular degeneration is the damage and breakdown of the retina where abnormal growth of blood vessels results in leakage and bleeding underneath and into the retina (Heier, 2011). Apart from degeneration of retinal pigments in cells, wet age-related macular degeneration is characterized by growth of new blood vessels from the tiny blood vessels within the choroid. The fresh and abnormal vessels break past Bruch’s membrane into the macular part of retina. These vessels are delicate and prone to leaking blood and fluid capable of damaging the rods and cones and cause damaging in the macula inflicting vision loss. An individual develops Age-related Macular Degeneration (AMD) when cells of the macula malfunction and the body begins a process of developing fresh blood vessels in order to repair the problem. However, the new blood vessels develop in the wrong place and result in swelling and bleeding under the macular that causes a lot of damage macular and scarring. The blood vessels and scarring damage vision and can result in lesions in an individual’s centre field of sight. AMD is the primary cause of blindness in developed nations and the degenerative disease mainly incorporate laser, photodynamic therapy (PDT) and the administration of ant vascular endothelial growth factors (AEGF) (Ashton Acton, 2012). The aim of this review is to summarize the prevailing treatment options of endovascular AMD and the triggers of wet AMD. Triggers of Wet AMD Apart from Age-related macular degeneration being associated with aging, aging is not the sole factor since genetics and environmental factor play a role; even though, it is unclear what causes lack of proper functioning of retinal pigment epithelium. The pathogenesis of AMD is incompletely understood with evidence indicating that AMD represents a complex disease brought about by various genetic as well as environmental factors. Nevertheless, age is the strongest risk factors because on the cellular and molecular levels various changes occur as an individual grows old and the changes have been identified on the outer retina. It is believed that alterations in RPE (Retinal Pigment Epithelium) as well as Bruch’s membrane have a role in the pathogenic cascade (Alberti, 2001).This condition has strong genetic risk factors and environmental risk factors such as smoking. Genetics Studies implicate many genes in AMD although most of the studies are inconclusive; nevertheless, increased risk of AMD is reported in carriers of certain alleles. Therefore, these alleles are casually related to the condition because of their close position to the unknown genetic variants, this is also true for certain alleles that probably flag unidentified causative agent. However, mutations in some genes are rare and the role of such mutations in age-related macular degeneration is unknown. First-degree relatives of individuals with the condition tend to have increased risk of developing age-related macular degeneration (Paulus & de Jong, 2007). Smoking Studies show reproducible evidence that consistently associates smoking to age-related macular degeneration with analysis showing relative risk to age-related macular degeneration is 2.4 in current smokers compared to individuals who never smoke who had insignificant risk of 1.29 in former smokers. Smoking can decrease concentration of macular pigment by up to 50% and the nicotine in the plasma activates retinal phospholipase that cause formation of arachidonic acid that promote inflammatory mediators (Paulus & de Jong, 2007). Light-induced Toxic effects There is weak epidemiologic evidence regarding the excessive contact with light associated with AMD because it is challenging to measure human’s lifetime exposure to light. However, it seems that the shorter the wavelength and higher the intensity of light the higher the chance of experiencing a photo chemically induced light damage. All light, even the ambient natural light can destroy the retina if the exposure is long enough; however, in humans light-induced damage relies on duration of exposure, age, unknown genetic factors, the wavelength and the level of oxygenation within the retina (Paulus & de Jong, 2007). Treatment strategies Laser Photocoagulation This was the initial laser therapy for wet AMD began in the 1980s with clinical trials indicating that mid to long-term success of the treatment compared to no intervention in individuals with AMD. However, this method of managing wet AMD is associated with high risk of early loss of vision related to the damage of photoreceptors. Therefore, considering the new pharmacological treatment for wet AMD, this method is no longer acknowledged as the initial treatment of subfoveal lesions (Fuchsjà & Schmidt-Erfurth, 2007). Photodynamic Therapy Photodynamic therapy (PDT) employs intravenously infused photosensitising dye and because of the AMD it offers the ability to avoid non-selective tissue damage. This mechanism helps maintain integrity of the photoreceptor and the functions of the retina and various clinical studies prove to be efficient with the largest success being in the classical lesions. However, although this method of managing AMD is shown to slow the rate of loss of the visual field, it rarely improves the visual acuity of the individual after treatment. In patients with severe detachment of the RPE, accompanying therapy includes the risk of mechanical rips; moreover, owing to the mean decrease in vision after treatment, this form of therapy is not acknowledged as a standalone practice but rather applied in conjunction with pharmacological adjuncts (Fuchsjà & Schmidt-Erfurth, 2007). Nevertheless, PDT used together with Intravitreal Triamcinolone Corticosteriod poses inhibitory effect to vascular permeability, swelling and appearance of vascular endothelial growth factor. The various clinical trials show that combination of PDT Intravitreal Steroids has beneficial and addictive influences on visual acuity, reduction of the size of lesion, retreatment frequency and foveal thickness. However to use this regimen in managing AMD, the well-known side effects of corticosteroids have to be taken into account (Fuchsjà & Schmidt-Erfurth, 2007). Anti-antiangiogenic treatments Vascular Endothelial growth factor (VEGF) remains an essential cytokine for development of chorodial neovascularisation by increasing vascular permeability resulting in angiogenesis Various studies as well as clinical studies show that VEGF is has a role in developing from dry to exudative age-related Macular Degeneration (Fuchsjà & Schmidt-Erfurth, 2007). Pegaptanib (macugen) Mucagen is considered an extremely choosy blocker of VEGF 165 which has a vital duty in blood-retina obstacle breakdown. This inhibits angiogenesis as well as pathological leakages and is selected based on the notion of eliminating pathogenical stimulus and preserving physiological structure of macular areas to ensure that photoreceptors function and recover (Fuchsjà & Schmidt-Erfurth, 2007). Mucagen therapeutic benefits do not necessarily exceed the effect of monotherapy PDT; however, frequent re-treatment regimen using re-injections every six weeks is necessary for a minimum of two years (Fuchsjà & Schmidt-Erfurth, 2007). Ranibizumab This is a recombinant and improved anti-VEGF-A which is a neutralizing antibody fragment that targets the various VEGF isoforms. This antibody has a short half-life that is between two and four days, which results in rapid clearance as well as better systematic safety. Various studies performed to investigate the efficiency as well as safety concerns of this drugs show that ranibizumab results in maintenance of vision within 3 lines in about 95% of treated eyes. Improvement of visual acuity was evident in 34-42% of treated eyes and these benefits were sustained for a period of two years. These benefits form the basis for its approval by US FDA (Food and Drug Agency) in treating the various lesions within neovascular AMD. Anti-VEGF substances were the initial substances to achieve formidable and consistent improvement in visual acuity owing to their selective capability and strategy in eliminating pathogenical stimulus while sparing the structure of macular area (NHS Choices, 2013). This makes ranibizumab to be recommended as an essential therapy in AMD by experts in many nations. Bevacizumab This is a full-length recombinant and humanized antibody that binds to the various VEGF isoforms and was originally acknowledged in treatment of metastatic colorectal cancer. Although the drug is available due to the low costs, it has not undergone prospective randomized clinical tests in order to evaluate its efficiency and safety in a reliable manner. Similar to ranibizumab, bevacizumab decreases vascular permeability as well as angiogenesis and; even though, there are no random multicentre trials necessary in comparing the use of bevacizumab with approved therapy offered by ranibizumab results from small series of interventions appear promising. Intravenous and intravitreal administration of bevacizumab are valued in the treatment of neovascular AMD with intravitreal administration of bevacizumab reported in retrospective analysis of data in patients considered non-responders to other treatments. Intravitreal is shown to be safe and tolerated because within three months of treatment, visual acuity improved significantly as retinal thickness reduced with 94% of the eyes having stable or improved visual acuity. Although Bevacizumab may provide effective and cheap treatment in neovascular AMD, direct comparison with other forms of treatments is essential in elucidating this therapeutic approach. Recent meta-analysis did not show any relevant evidence for beneficial outcomes of surgical procedures like removal of subfoveal, macular translocation or even transplantation of pigment epithelium (Fuchsjà & Schmidt-Erfurth, 2007). Discussion It has been shown that until recently, the only valued and available option for patients with AMD was the laser treatment that decreases incidences of severe vision loss within patients. AMD is a leading cause of blindness in individuals above the age of 65 years with many patients showing dry form; nevertheless, the wet type is shown various patients. Macular photocoagulation demonstrates the benefit of laser photocoagulation in treatment of choroidal neovascularization; even though severe visual loss results regardless of having a laser treatment. PDT involves intravenous administration of photosensitizing drug accompanied with the application of non-lethal laser light to affected tissues to incite local reaction within the abnormal vascular membranes (Tuo, 2012). PDT never affects the retina and thus offers a potential treatment without immediate loss of centre of vision induced by the thermal laser (Alfaro, 2006). Unfortunately, PDT is only beneficial for patients with mainly classic lesions; as well, of all the patients who receive PDT close to 34% have a stable visual acuity. Pegaptanib and ranibizumab being endothelial growth factor inhibitors are licensed to treat wet AMD (Joint Formulary Committee, 2013). Ranibizumab play inhibitory role in CNV and decreases vascular permeability through binding VEGF and intravitreal ranibizumab decreases the risk of losing visual acuity and enhances it compared to non-treatment and PDT. Some high-quality studies show that finest timing for ranibizumab in taking care of wet AMD within the three months. Although there are many treatment options available in management of AMD, no single treatment is shown to permanently arrest the progress of the condition or even offer significant improvements; however, the various therapies offer some unique results. Wet macular degeneration can be treated through photocoagulation or PDT in trying to preserve the remaining vision. From the study it is clear the common treatment options for wet AMD include laser photocoagulation and PDT as well as the intravitreal injections containing inhibitors of VEGF-A. Nevertheless, anti-VEGF interventions in wet AMD have come under scrutiny; even though, they have transformed management of the condition by increasing visual acuity compared to the traditional therapies (Mitchell et al, 2011). Revised guidelines and conclusion Although there have been significant improvements in therapeutic approaches aimed at treating exudative AMD; however, it has to be considered that with current technologies symptoms of wet AMD are only targeted. Therefore, to intervene at an early time during the disease progression or even to prevent the sight-threatening forms of AMD, there is need for complete understanding regarding the procedures that result in AMD and end-stage neovascularisation (Mitchell et al, 2011). The studies indicate that AMD is partially genetic and although the findings be essential in identifying people with high risk of developing AMD, it may also be useful in providing new pathways in treating the disease. Moreover, to fully understand the condition there is need to consider AMD as a complex multifactor disease since studies show gene-gene as well as gene-environment interactions have a role in the risk of the disease. Regarding gene-gene interactions, there are various conclusions with some studies showing weak interactions; moreover, genetic and environmental factors need to be studied in order to comprehend people’s risk regarding AMD. References Alberti, W. E. Age-related macular degeneration: current treatment concepts ; with 33 tables. Berlin [u.a.], Springer. 2001. Alfaro, D. V. Age-related macular degeneration a comprehensive textbook. Philadelphia, Lippincott Williams & Wilkins. 2006. Ashton Acton, P. Macular Degeneration: New Insights for the Healthcare Professional: 2012 Edition ScholarlyBrief. ScholarlyEditions. 2012. FuchsjÃ, G., & Schmidt-Erfurth, U. M. Management of Wet Age-related Macular Degeneration. 2007. Heier, J. S. 100 questions & answers about macular degeneration. Sudbury, Mass, Jones and Bartlett Publishers. 2011. Joint Formulary Committee. British National Formulary (Bnf) 65. Pharmaceutical Pr.2013. Mitchell, P, Annemans, L, White, R, Gallagher, M, & Thomas, S. Cost Effectiveness of Treatments for Wet Age-Related Macular Degeneration, Pharmacoeconomics, 2011, 29, 2, pp. 107-131. NHS Choices, Treating macular degeneration. 2013. Available from: http://www.nhs.uk/Conditions/Macular-degeneration/Pages/Treatment.aspx Paulus T.V.M de Jong. Age-related Macular degeneration. 2007. Available from http://www.nejm.org/doi/full/10.1056/NEJMra062326#t=citedby Read More