Diagnosis, Treatment, and Follow-up of Patients With AMD
Diagnosis, Treatment, and Follow-up of Patients With AMD
Age-related macular degeneration (AMD) is an irreversible pathology that is the principal cause of serious loss of central vision and legal blindness among people over 60 years of age. There are two forms of AMD: the dry, or atrophic form, and the wet, neovascular form. The latter is less frequent but is the cause of approximately 80–90% of cases of serious loss of vision in a short time period. Early diagnosis is therefore essential to permit intervention as promptly as possible. Currently, the most effective therapy for neovascular AMD uses the new class of anti-VEGF drugs, and ranibizumab is today's 'gold standard' for this treatment. The Progetto LUCE (LUCE Project) consists of an advisory board of retinal disease specialists in Lombardy, Italy, whose task is to propose a consensus for the diagnosis, treatment and follow-up of neovascular AMD patients treated with ranibizumab on the basis of a review of the scientific evidence and Italian national health service regulations and the clinical experience of the advisory board members.
Age-related macular degeneration (AMD) is the principal cause of serious loss of central vision and legal blindness among people over 60 years of age. It is therefore extremely important from the social and healthcare viewpoints, with its heavy impact on public health. The incidence of AMD is respectively 2.5, 6.7 and 10.8% among people aged 65, 70 and 75 years. This incidence, and the progression of all the forms of AMD, rise significantly with age, and it is forecast that by 2020 there will be a 107% increase among people aged 85 or over.
There are two forms of AMD: the non-neovascular, dry, or atrophic, form and the neovascular, wet or exudative form. The wet form is less frequent, but causes approximately 80–90% of cases of serious loss of vision; these patients have choroidal neovascularization (CNV), also widely referred to as age-related neovascular macular degeneration (AMDn).
AMDn causes the choroidal capillaries to proliferate and penetrate the Bruch membrane, reaching the retinal pigment epithelium (RPE) and sometimes reaching the subretinal space. These new capillaries are abnormally permeable, allowing accumulation of serum and blood under the RPE and/or the neurosensory retina. In the final stages of AMD, fibrotic metaplasia and disc-shaped scars form and become organized, causing permanent sight loss. In patients with wet AMD the first sign is metamorphopsias, then central or paracentral scotomas, and slight or heavy permanent loss of vision; progression may be slow or fast depending on the type of lesion.
In patients with AMD the complex formed by the choroidal new vessels and the fibrous tissue can destroy the photoreceptors within 3–24 months; thus, if not treated, the disease can lead to loss of central vision within 2 years. There are also more aggressive forms leading to values just below the level of legal blindness in a few months. There is a 50% probability of AMDn becoming bilateral within 5 years.
Early diagnosis is therefore obviously essential in order to take action as promptly as possible to obtain the best result from therapy. Basic diagnostic investigations are retinal fluorescein angiography (fluoroangiography [FAG]), indocyanine green angiography (ICG), and optical coherence tomography (OCT). Treatment for AMDn is aimed at the patient's quality of life, improving visual acuity so as to facilitate independence and the activities of daily living, and to prevent the disease progressing by stopping further leakage from the lesion. Treatment must be well tolerated and suited to the patient's needs. Treatment options include laser photocoagulation, photodynamic therapy, dietary supplements and visual rehabilitation.
The most effective approach today, for neovascular AMD, involves intravitreal injection of a drug that inhibits vascular endothelial growth factors (anti-VEGF). Laser photocoagulation and photodynamic therapy are used less and less, and only for retinal angiomatous proliferation (RAP) and polypoidal forms, either singly or with drug injections.
VEGF-A is a key factor in the angiogenesis cascade. New vessel formation is closely regulated in time and space, governed by numerous growth factors and opposed by a group of inhibitors. VEGF-A has now been identified as the most important, though not the only mediator of ocular angiogenesis – physiological or pathological – and is produced by the RPE cells.
In summary, antiangiogenic treatment has a series of main effects:
Of the anti-VEGF drugs available today, ranibizumab is considered the 'gold standard' for the treatment of AMDn. This drug is also indicated for diabetic macular edema and edema secondary to retinal vein occlusion. Ranibizumab is a humanized monoclonal antibody fragment with high binding affinity for all the VEGF-A isoforms. Its low molecular weight – only 48 kDa, means it penetrates the retinal wall but its systemic half-life is short, and its vitreal half-life is around 9 days.
Ranibizumab is backed by a broad development program that provides an excellent level of clinical evidence of its efficacy and safety. Phase I/II studies confirmed that it is well tolerated and improves visual acuity in most patients, compared with controls. Three phase III trials for registration, MARINA, ANCHOR and PIER, have provided further evidence of its efficacy and safety.
The Progetto LUCE (LUCE Project) is an advisory board made up of retinal disease experts in Lombardy, Italy, and its aim is to propose a consensus on the diagnosis, treatment and follow-up of patients with AMDn treated with ranibizumab; this will be based on a review of the published scientific evidence, national health service regulations and, above all, the clinical experience of the board members.
Abstract and Introduction
Abstract
Age-related macular degeneration (AMD) is an irreversible pathology that is the principal cause of serious loss of central vision and legal blindness among people over 60 years of age. There are two forms of AMD: the dry, or atrophic form, and the wet, neovascular form. The latter is less frequent but is the cause of approximately 80–90% of cases of serious loss of vision in a short time period. Early diagnosis is therefore essential to permit intervention as promptly as possible. Currently, the most effective therapy for neovascular AMD uses the new class of anti-VEGF drugs, and ranibizumab is today's 'gold standard' for this treatment. The Progetto LUCE (LUCE Project) consists of an advisory board of retinal disease specialists in Lombardy, Italy, whose task is to propose a consensus for the diagnosis, treatment and follow-up of neovascular AMD patients treated with ranibizumab on the basis of a review of the scientific evidence and Italian national health service regulations and the clinical experience of the advisory board members.
Introduction
Age-related macular degeneration (AMD) is the principal cause of serious loss of central vision and legal blindness among people over 60 years of age. It is therefore extremely important from the social and healthcare viewpoints, with its heavy impact on public health. The incidence of AMD is respectively 2.5, 6.7 and 10.8% among people aged 65, 70 and 75 years. This incidence, and the progression of all the forms of AMD, rise significantly with age, and it is forecast that by 2020 there will be a 107% increase among people aged 85 or over.
There are two forms of AMD: the non-neovascular, dry, or atrophic, form and the neovascular, wet or exudative form. The wet form is less frequent, but causes approximately 80–90% of cases of serious loss of vision; these patients have choroidal neovascularization (CNV), also widely referred to as age-related neovascular macular degeneration (AMDn).
AMDn causes the choroidal capillaries to proliferate and penetrate the Bruch membrane, reaching the retinal pigment epithelium (RPE) and sometimes reaching the subretinal space. These new capillaries are abnormally permeable, allowing accumulation of serum and blood under the RPE and/or the neurosensory retina. In the final stages of AMD, fibrotic metaplasia and disc-shaped scars form and become organized, causing permanent sight loss. In patients with wet AMD the first sign is metamorphopsias, then central or paracentral scotomas, and slight or heavy permanent loss of vision; progression may be slow or fast depending on the type of lesion.
In patients with AMD the complex formed by the choroidal new vessels and the fibrous tissue can destroy the photoreceptors within 3–24 months; thus, if not treated, the disease can lead to loss of central vision within 2 years. There are also more aggressive forms leading to values just below the level of legal blindness in a few months. There is a 50% probability of AMDn becoming bilateral within 5 years.
Early diagnosis is therefore obviously essential in order to take action as promptly as possible to obtain the best result from therapy. Basic diagnostic investigations are retinal fluorescein angiography (fluoroangiography [FAG]), indocyanine green angiography (ICG), and optical coherence tomography (OCT). Treatment for AMDn is aimed at the patient's quality of life, improving visual acuity so as to facilitate independence and the activities of daily living, and to prevent the disease progressing by stopping further leakage from the lesion. Treatment must be well tolerated and suited to the patient's needs. Treatment options include laser photocoagulation, photodynamic therapy, dietary supplements and visual rehabilitation.
The most effective approach today, for neovascular AMD, involves intravitreal injection of a drug that inhibits vascular endothelial growth factors (anti-VEGF). Laser photocoagulation and photodynamic therapy are used less and less, and only for retinal angiomatous proliferation (RAP) and polypoidal forms, either singly or with drug injections.
VEGF-A is a key factor in the angiogenesis cascade. New vessel formation is closely regulated in time and space, governed by numerous growth factors and opposed by a group of inhibitors. VEGF-A has now been identified as the most important, though not the only mediator of ocular angiogenesis – physiological or pathological – and is produced by the RPE cells.
In summary, antiangiogenic treatment has a series of main effects:
Inhibition of the growth and extension of new vessel formation;
Regression of the neovascularization;
Stabilization of the endothelial membranes and reduction of the permeability of the CNV microcirculation;
Reduction of the diffusion of protein and lipid molecules into extravascular spaces, reduction of edema and restoration of the normal central macular thickness.
Of the anti-VEGF drugs available today, ranibizumab is considered the 'gold standard' for the treatment of AMDn. This drug is also indicated for diabetic macular edema and edema secondary to retinal vein occlusion. Ranibizumab is a humanized monoclonal antibody fragment with high binding affinity for all the VEGF-A isoforms. Its low molecular weight – only 48 kDa, means it penetrates the retinal wall but its systemic half-life is short, and its vitreal half-life is around 9 days.
Ranibizumab is backed by a broad development program that provides an excellent level of clinical evidence of its efficacy and safety. Phase I/II studies confirmed that it is well tolerated and improves visual acuity in most patients, compared with controls. Three phase III trials for registration, MARINA, ANCHOR and PIER, have provided further evidence of its efficacy and safety.
The Progetto LUCE (LUCE Project) is an advisory board made up of retinal disease experts in Lombardy, Italy, and its aim is to propose a consensus on the diagnosis, treatment and follow-up of patients with AMDn treated with ranibizumab; this will be based on a review of the published scientific evidence, national health service regulations and, above all, the clinical experience of the board members.
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