Age Related Macular Degeneration
Disease Details
Family Health Simplified
- Description
- Age-related macular degeneration (AMD) is an eye disease that causes loss of central vision due to damage to the macula, the part of the retina responsible for detailed vision.
- Type
- Age-related macular degeneration (AMD) is primarily a multifactorial condition rather than a single-gene disorder. It has a complex inheritance pattern influenced by both genetic and environmental factors. Genetic predisposition plays a significant role, with multiple genes, including those involved in the complement system (like CFH and ARMS2), contributing to the risk. However, it is not inherited in a straightforward Mendelian manner (e.g., autosomal dominant or recessive) but rather through a combination of genetic susceptibility and external factors such as age, smoking, and diet.
- Signs And Symptoms
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Early or intermediate AMD may be asymptomatic, or it may present with blurred or decreased vision in one or both eyes. This may manifest initially as difficulty with reading or driving (especially in poorly lit areas). Other symptoms of AMD include distortion of vision and blind spots (especially in and around the central visual field).Other signs and symptoms of macular degeneration include:
Distorted vision in the form of metamorphopsia, in which a grid of straight lines appears wavy and parts of the grid may appear blank: Patients often first notice this when looking at things like miniblinds in their home or telephone poles while driving. There may also be central scotomas, shadows or missing areas of vision
Slow recovery of visual function after exposure to bright light (photostress test)
Visual acuity drastically decreasing (two levels or more), e.g.: 20/20 to 20/80
Blurred vision: Those with nonexudative (dry) macular degeneration may be asymptomatic or notice a gradual loss of central vision, whereas those with exudative (wet) macular degeneration often notice a rapid onset of vision loss (often caused by leakage and bleeding of abnormal blood vessels).
Trouble discerning colors, specifically dark ones from dark ones and light ones from light ones
A loss in contrast sensitivity
Formed visual hallucinations and flashing lights have also been associated with severe visual loss secondary to wet AMD Macular degeneration by itself will not lead to total blindness. For that matter, only a small number of people with visual impairment are totally blind. In almost all cases, some vision remains, mainly peripheral. Other complicating conditions may lead to such an acute condition (severe stroke or trauma, untreated glaucoma, etc.), but few macular degeneration patients experience total visual loss.The area of the macula constitutes only about 2.1% of the retina, and the remaining 97.9% (the peripheral field) remains unaffected by the disease. Even though the macula provides such a small fraction of the visual field, almost half of the visual cortex is devoted to processing macular information.In addition, people with dry macular degeneration often do not experience any symptoms but can experience gradual onset of blurry vision in one or both eyes. People with wet macular degeneration may experience acute onset of visual symptoms. - Prognosis
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Age-related macular degeneration (AMD) is a progressive eye condition affecting the macula, the central part of the retina, leading to central vision loss. The prognosis varies:
1. **Dry AMD**: This is the more common form and progresses slowly. Individuals may retain some degree of vision, particularly peripheral vision, for many years.
2. **Wet AMD**: This less common but more severe form can lead to rapid vision loss. Early detection and treatment can help slow down the progression and preserve vision.
Overall, regular eye exams and timely intervention are crucial in managing AMD and mitigating its impact on vision. - Onset
- Age-related macular degeneration (AMD) typically has an onset after the age of 50. The condition affects the central part of the retina, known as the macula, and can lead to loss of central vision. While the exact age can vary, it is most commonly diagnosed in individuals aged 60 and older.
- Prevalence
- The prevalence of age-related macular degeneration (AMD) varies by age and population. In general, it affects approximately 1 in 10 people over the age of 65 and about 1 in 4 people over the age of 75.
- Epidemiology
- The prevalence of any age-related macular degeneration is higher in Europeans than in Asians and Africans. There is no difference in prevalence between Asians and Africans. The incidence of age-related macular degeneration and its associated features increases with age and is low in people <55 years of age. Smoking is the strongest modifiable risk factor. As of 2008, age-related macular degeneration accounts for more than 54% of all vision loss in the white population in the US. An estimated 8 million Americans are affected with early age-related macular degeneration, of whom over 1 million will develop advanced age-related macular degeneration within the next 5 years. In the UK, age-related macular degeneration is the cause of blindness in almost 42% of those who go blind aged 65–74 years, almost two-thirds of those aged 75–84 years, and almost three-quarters of those aged 85 years or older.
- Intractability
- Age-related macular degeneration (AMD) is currently considered intractable in the sense that there is no cure. However, certain treatments can help manage symptoms and slow the progression of the disease. These treatments include anti-VEGF injections for wet AMD, lifestyle changes, nutritional supplements, and low vision aids. Early detection and ongoing monitoring are crucial for managing the condition effectively.
- Disease Severity
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Age-related macular degeneration (AMD) is classified into three stages based on disease severity:
1. **Early AMD**: Characterized by medium-sized drusen (yellow deposits beneath the retina). Vision is generally not affected at this stage.
2. **Intermediate AMD**: Larger drusen and/or pigment changes in the retina. Some people may notice mild visual changes, but many do not experience significant vision impairment.
3. **Late AMD**: Further divided into two types:
- *Dry AMD (Geographic Atrophy)*: Gradual breakdown of light-sensitive cells and supporting tissue in the central retinal area, leading to vision loss.
- *Wet AMD (Neovascular)*: Abnormal blood vessels grow under the retina and leak blood or fluid, causing rapid and severe vision loss.
Early detection and monitoring are essential to manage and possibly slow the progression of AMD. - Healthcare Professionals
- Disease Ontology ID - DOID:10871
- Pathophysiology
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The pathogenesis of age-related macular degeneration is not well known, although some theories have been put forward, including oxidative stress, mitochondrial dysfunction, and inflammatory processes.
The imbalance between the production of damaged cellular components and degradation leads to the accumulation of harmful products, for example, intracellular lipofuscin and extracellular drusen. Incipient atrophy is demarcated by areas of retinal pigment epithelium (RPE) thinning or depigmentation that precede geographic atrophy in the early stages of AMD. In advanced stages of AMD, atrophy of the RPE (geographic atrophy) and/or development of new blood vessels (neovascularization) result in the death of photoreceptors and central vision loss.
In the dry (nonexudative) form, drusen accumulates between the retina and the choroid, causing atrophy and scarring to the retina. In the wet (exudative) form, which is more severe, blood vessels grow up from the choroid (neovascularization) behind the retina which can leak exudate and fluid and also cause hemorrhaging.
Early work demonstrated a family of immune mediators was plentiful in drusen. Complement factor H (CFH) is an important inhibitor of this inflammatory cascade, and a disease-associated polymorphism in the CFH gene strongly associates with AMD. Thus an AMD pathophysiological model of chronic low grade complement activation and inflammation in the macula has been advanced. Lending credibility to this has been the discovery of disease-associated genetic polymorphisms in other elements of the complement cascade including complement component 3 (C3).A powerful predictor of AMD is found on chromosome 10q26 at LOC 387715. An insertion/deletion polymorphism at this site reduces expression of the ARMS2 gene though destabilization of its mRNA through deletion of the polyadenylation signal. ARMS2 protein may localize to the mitochondria and participate in energy metabolism, though much remains to be discovered about its function.
Other gene markers of progression risk includes tissue inhibitor of metalloproteinase 3 (TIMP3), suggesting a role for extracellular matrix metabolism in AMD progression. Variations in cholesterol metabolising genes such as the hepatic lipase, cholesterol ester transferase, lipoprotein lipase and the ATP-binding cassette A1 correlate with disease progression. The early stigmata of disease, drusen, are rich in cholesterol, offering face validity to the results of genome-wide association studies. - Carrier Status
- Age-related macular degeneration (AMD) is not typically associated with a simple carrier status like some genetic diseases. It is a complex condition influenced by both genetic and environmental factors. There is no single gene that determines carrier status for AMD. Instead, risk factors include age, family history, smoking, diet, and genetic variations in multiple genes, such as those related to the complement system.
- Mechanism
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Age-related macular degeneration (AMD) is a complex eye disease that primarily affects the macula, the central part of the retina responsible for sharp central vision. Here are the mechanisms and molecular pathways involved:
1. **Mechanism:**
- **Dry AMD:** It is characterized by the gradual breakdown of light-sensitive cells in the macula and the retinal pigment epithelium (RPE). Yellow deposits called drusen accumulate under the retina, leading to a slow decline in vision.
- **Wet AMD:** This form involves abnormal blood vessel growth (neovascularization) under the retina. These new blood vessels can leak fluid or blood, causing rapid and severe damage to the macula.
2. **Molecular Mechanisms:**
- **Oxidative Stress:** Reactive oxygen species (ROS) damage cellular structures in the retina and RPE, contributing to cell death and AMD progression.
- **Inflammation:** Chronic inflammation, regulated by components like complement factor H (CFH), C3, and other immune mediators, plays a significant role in AMD pathogenesis.
- **Angiogenesis:** In wet AMD, vascular endothelial growth factor (VEGF) promotes the formation of abnormal blood vessels. Anti-VEGF therapies are often used to treat this process.
- **Lipid Metabolism:** Dysregulated lipid transport and accumulation, involving proteins like apolipoprotein E (ApoE), are believed to contribute to drusen formation.
- **Genetic Factors:** Variants in several genes, including CFH, ARMS2, and HTRA1, have been implicated in increasing the risk of developing AMD.
- **Mitochondrial Dysfunction:** Impaired mitochondrial function leads to reduced energy production and increased oxidative stress, fostering retinal cell degeneration. - Treatment
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Age-related macular degeneration (AMD) is a common eye condition that can cause vision loss in people over 50. There are two main types: dry and wet AMD. Treatment options vary depending on the type and severity.
1. **Dry AMD**:
- **Lifestyle Changes**: Nutritional supplements with vitamins C and E, zinc, copper, and beta-carotene can slow progression.
- **Monitoring**: Regular eye exams to monitor progression.
- **Low Vision Aids**: Devices to help improve vision.
2. **Wet AMD**:
- **Anti-VEGF Injections**: Medications like ranibizumab, aflibercept, or bevacizumab are injected into the eye to help reduce abnormal blood vessel growth.
- **Photodynamic Therapy (PDT)**: A light-sensitive drug is used in combination with a laser to destroy abnormal blood vessels.
- **Laser Surgery**: High-energy lasers are used to seal abnormal blood vessels.
Early detection and treatment are essential for preserving vision. - Compassionate Use Treatment
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Age-related macular degeneration (AMD) is a common eye condition and a leading cause of vision loss among people age 50 and older. Regarding compassionate use treatment and off-label or experimental treatments:
1. **Compassionate Use Treatment**:
- Compassionate use, also known as expanded access, allows patients with serious or life-threatening conditions to gain access to investigational treatments when no comparable or satisfactory alternative therapy options are available. This might include drugs or treatments currently in clinical trials that have not yet been approved by regulatory agencies like the FDA.
2. **Off-Label Treatments**:
- **Avastin (Bevacizumab)**: Originally approved for cancer treatment, it is often used off-label for AMD due to its anti-angiogenic properties, similar to approved drugs like Lucentis (Ranibizumab) and Eylea (Aflibercept).
- **Triamcinolone Acetonide**: This corticosteroid may be used off-label to reduce macular edema associated with AMD.
3. **Experimental Treatments**:
- **Gene Therapy**: Research is ongoing into using gene therapy to introduce genes that can help treat or prevent AMD.
- **Stem Cell Therapy**: Studies are exploring the potential of stem cell transplantation to replace damaged retinal cells.
- **Combination Therapies**: Combining anti-VEGF therapy with other treatments, such as radiation or other drugs, to improve outcomes.
- **New Anti-VEGF Agents**: Investigational drugs that target VEGF or other pathways to reduce abnormal blood vessel growth and leakage.
- **Complement Inhibitors**: Experimental drugs targeting the complement pathway, which is part of the immune system believed to contribute to the progression of AMD.
Patients should discuss these options with their healthcare providers to understand the potential benefits and risks and to determine the best course of action for their specific situation. - Lifestyle Recommendations
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For age-related macular degeneration (AMD), here are some lifestyle recommendations:
1. **Diet**: Consume a diet rich in leafy green vegetables, fish, fruits, and nuts. Foods high in antioxidants, such as vitamins C and E, beta-carotene, and zinc, can be beneficial.
2. **Exercise**: Engage in regular physical activity to improve overall health and maintain optimal blood flow.
3. **Smoking**: Avoid smoking, as it significantly increases the risk of AMD and accelerates its progression.
4. **Sun Protection**: Wear sunglasses with UV protection to shield your eyes from harmful UV rays.
5. **Healthy Weight**: Maintain a healthy weight to reduce the risk of chronic conditions that can affect eye health.
6. **Blood Pressure and Cholesterol**: Keep blood pressure and cholesterol levels in check, as high levels can contribute to AMD.
7. **Regular Eye Exams**: Have regular eye check-ups to monitor eye health and detect any early signs of AMD.
8. **Supplements**: Consider specific supplements if recommended by your healthcare provider, such as the AREDS2 formulation, which has been shown to reduce the risk of advanced AMD in some individuals.
Implementing these lifestyle changes can help manage and potentially reduce the risk of AMD progression. - Medication
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For age-related macular degeneration (AMD), there are several medications that can be used to slow the progression of the disease, especially in its wet form.
1. **Anti-VEGF Drugs**: These drugs inhibit the growth of abnormal blood vessels in the retina and include:
- Ranibizumab (Lucentis)
- Aflibercept (Eylea)
- Bevacizumab (Avastin)
- Brolucizumab (Beovu)
2. **Photodynamic Therapy (PDT)**: Verteporfin (Visudyne) is used in combination with laser treatment to target abnormal blood vessels.
3. **AREDS and AREDS2 Supplements**: High-dose formulations of antioxidants and zinc based on the Age-Related Eye Disease Studies (AREDS and AREDS2) can reduce the risk of progression in the intermediate and late stages of dry AMD.
Always consult with a healthcare professional for diagnosis and treatment options suitable for individual cases. - Repurposable Drugs
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Repurposing existing drugs for age-related macular degeneration (AMD) is an area of active research. Some drugs that have shown potential include:
1. **Statins:** These are traditionally used to lower cholesterol but have been investigated for their potential protective effects on retinal health.
2. **Metformin:** Commonly used for type 2 diabetes, it has anti-inflammatory properties and may reduce the risk of developing AMD.
3. **Aspirin:** While there is mixed evidence, low-dose aspirin has been studied for its anti-inflammatory effects that could potentially benefit AMD patients.
4. **Antioxidants:** Certain antioxidant compounds, such as those found in AREDS (Age-Related Eye Disease Study) supplements, are being examined for their potential to slow progression in AMD.
Further clinical trials are needed to confirm the efficacy and safety of these repurposed medications for AMD. - Metabolites
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Age-related macular degeneration (AMD) is associated with various metabolic changes. Some metabolites linked to AMD include:
1. Lipids: Elevated levels of certain lipids, such as cholesterol and lipoproteins, have been implicated in AMD.
2. Homocysteine: Increased levels of homocysteine are associated with a higher risk of AMD.
3. Antioxidants: Lower levels of antioxidants like lutein and zeaxanthin are often observed in AMD patients.
The abbreviation "nan" typically refers to not a number in data analysis, which is not directly related to AMD unless in the context of missing or undefined values in a dataset concerning the disease. If you meant something else by "nan," please provide more context. - Nutraceuticals
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For age-related macular degeneration (AMD), certain nutraceuticals have shown promise in supporting eye health and potentially slowing the progression of the disease. Key nutraceuticals include:
1. **Antioxidants**: Vitamins C and E, lutein, and zeaxanthin are antioxidants that protect the retina from oxidative stress.
2. **Zinc and Copper**: Essential minerals that support overall eye health and are included in the AREDS2 (Age-Related Eye Disease Study 2) supplement formulation.
3. **Omega-3 Fatty Acids**: Particularly DHA and EPA, which may reduce inflammation and support retinal health.
These supplements, particularly in formulations based on the AREDS2 study recommendations, may help reduce the risk of progression to advanced AMD in individuals with intermediate disease. Always consult with a healthcare provider before starting any new supplement regimen. - Peptides
- Peptides and nanoparticles (nanotechnology) are emerging areas of research in the treatment of age-related macular degeneration (AMD). Peptide-based therapies may target specific pathways involved in the disease process, potentially reducing inflammation and abnormal blood vessel growth associated with AMD. Nanoparticles can be used to deliver drugs more effectively to the retina, improving the efficacy and reducing the side effects of treatments. These advanced approaches are still largely in the experimental or early clinical trial stages but hold promise for future AMD therapies.