Macular Degeneration
Disease Details
Family Health Simplified
- Description
- Macular degeneration is an eye condition that causes deterioration of the central portion of the retina, leading to vision loss.
- Type
- Macular degeneration, specifically age-related macular degeneration (AMD), is generally not considered to have a single clear pattern of genetic transmission. However, it is known to be influenced by multiple genetic and environmental factors. Some genetic variants, particularly those in the CFH and ARMS2 genes, have been associated with an increased risk of developing AMD. It is considered a complex, multifactorial disease with polygenic inheritance.
- 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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Macular degeneration, specifically age-related macular degeneration (AMD), generally has a variable prognosis depending on its type and progression rate. There are two primary forms: dry AMD and wet AMD.
Dry AMD:
- Prognosis: This is the more common and less severe form. It typically progresses slowly, resulting in gradual vision loss over years. Some patients may maintain functional central vision for a long time.
Wet AMD:
- Prognosis: This is less common but more severe. It can cause rapid and significant vision loss. However, early detection and treatment, such as anti-VEGF injections, can help manage the condition and slow its progression.
Overall, the prognosis can vary widely, and regular monitoring by an eye care professional is essential for optimal management. - Onset
- Macular degeneration, also known as age-related macular degeneration (AMD), typically has an onset in individuals who are 50 years old or older. It is a progressive condition affecting the central part of the retina (the macula), leading to loss of central vision.
- Prevalence
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Macular degeneration is a common eye disorder, particularly among older individuals. The prevalence varies by region and population, but in the United States, it affects approximately 11 million people. Globally, it is estimated that around 196 million people will be affected by 2020, with that number expected to increase to 288 million by 2040.
Dry macular degeneration is more prevalent than the wet form, accounting for about 85-90% of cases. The disease primarily affects individuals over the age of 50, and the risk increases significantly with age. - 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
- Macular degeneration, particularly its advanced forms like wet age-related macular degeneration (AMD), can be challenging to manage and is often considered intractable in the sense that there is no cure. However, various treatments, such as anti-VEGF injections, laser therapy, and lifestyle changes, can help slow its progression and alleviate symptoms.
- Disease Severity
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Disease severity in macular degeneration varies depending on the type and stage of the condition. It typically progresses through several stages:
1. **Early Stage:** Often asymptomatic, characterized by the presence of medium-sized drusen (yellow deposits) beneath the retina.
2. **Intermediate Stage:** Some vision loss might occur, with larger drusen and/or pigment changes in the retina.
3. **Advanced Stage:**
- **Dry AMD:** More severe vision loss due to the thinning of the macula.
- **Wet AMD:** Rapid and severe vision loss resulting from abnormal blood vessels growing under the retina and leaking fluid or blood.
The severity can be monitored through regular eye exams and imaging tests such as optical coherence tomography (OCT). - Healthcare Professionals
- Disease Ontology ID - DOID:4448
- 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
- Macular degeneration does not have a carrier status because it is not a single-gene recessively inherited condition. It is a complex, multifactorial disease influenced by both genetic and environmental factors.
- Mechanism
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Macular degeneration, specifically age-related macular degeneration (AMD), involves the deterioration of the macula, which is a small central portion of the retina responsible for sharp, central vision.
**Mechanism:**
1. **Dry AMD**: This form is more common and is characterized by the thinning of the macula and the presence of drusen, which are yellow deposits beneath the retina. These changes lead to a gradual loss of central vision.
2. **Wet AMD**: This form is less common but more severe. It involves the growth of abnormal blood vessels underneath the retina and macula. These vessels can leak fluid or blood, leading to rapid and severe vision loss.
**Molecular Mechanisms:**
1. **Oxidative Stress**: Oxidative damage to the retinal pigment epithelium (RPE) and photoreceptors is a key factor. Reactive oxygen species (ROS) can cause cellular damage, contributing to the degeneration process.
2. **Inflammation**: Chronic inflammation plays a crucial role. Activation of the complement system, particularly components like C3 and factor H, has been implicated in the development of AMD.
3. **Genetic Factors**: Variants in genes such as CFH (complement factor H), ARMS2 (age-related maculopathy susceptibility 2), and HTRA1 (HtrA serine peptidase 1) have been associated with increased risk. These genes influence immune responses and extracellular matrix composition.
4. **Lipid Metabolism**: Dysfunctional lipid metabolism and accumulation of lipofuscin and drusen in the retina contribute to AMD. Components like cholesterol and apolipoproteins in drusen deposits disrupt retinal function.
5. **Angiogenesis in Wet AMD**: VEGF (vascular endothelial growth factor) plays a crucial role in new blood vessel formation. Overexpression of VEGF leads to the growth of abnormal, leaky blood vessels underlying the macula in wet AMD.
In summary, the mechanisms of macular degeneration involve a complex interplay of genetic, environmental, and molecular factors, including oxidative stress, inflammation, lipid dysregulation, and abnormal angiogenesis. - Treatment
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There is currently no cure for macular degeneration, but several treatments can help slow its progression and improve vision. The treatments vary based on whether it is the dry or wet form of the disease.
For dry macular degeneration:
- Nutritional supplements (like AREDS and AREDS2 formulas) containing vitamins C, E, zinc, copper, lutein, and zeaxanthin may slow progression.
- Regular monitoring by an eye care professional.
For wet macular degeneration:
- Anti-VEGF (Vascular Endothelial Growth Factor) injections, such as ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin), can reduce abnormal blood vessel growth and leakage.
- Photodynamic therapy (PDT) uses a light-activated drug to destroy abnormal blood vessels.
- Laser photocoagulation is used to seal leaky blood vessels.
Regular eye exams and early detection are essential for managing macular degeneration effectively. - Compassionate Use Treatment
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Compassionate use treatments for macular degeneration, particularly for those with severe forms or who have not responded to standard therapies, might include access to investigational drugs that are still under clinical research.
Off-label treatments for macular degeneration include medications like Avastin (bevacizumab), originally approved for cancer treatment but used off-label for age-related macular degeneration (AMD), similar to other anti-VEGF (vascular endothelial growth factor) therapies.
Experimental treatments currently under research may include:
- Gene therapy, aiming to correct genetic mutations causing macular degeneration.
- Stem cell therapy, aiming to replace damaged retinal cells.
- New anti-VEGF drugs or delivery systems, such as long-acting implants or eye drops.
- Complement inhibitors targeting the inflammatory pathway involved in AMD.
Each of these approaches is at various stages of research and clinical testing, and their availability and efficacy may depend on regulatory approvals and ongoing clinical trials. - Lifestyle Recommendations
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### Lifestyle Recommendations for Macular Degeneration
1. **Healthy Diet:**
- **Nutrient-Rich Foods:** Consume foods high in vitamins C and E, zinc, lutein, zeaxanthin, and omega-3 fatty acids. Leafy green vegetables, fatty fish, nuts, and fruits are particularly beneficial.
- **Balanced Diet:** Focus on a balanced diet to maintain overall health, which can positively affect eye health.
2. **Regular Exercise:**
- **Physical Activity:** Engage in regular physical activities to promote good circulation, which can help keep the blood vessels in your eyes healthy.
3. **Protective Eyewear:**
- **Sunglasses:** Wear sunglasses that block ultraviolet (UV) rays to protect your eyes from harmful UV radiation.
4. **Avoid Smoking:**
- **Quit Smoking:** Smoking is a major risk factor for macular degeneration, so quitting can significantly reduce your risk.
5. **Maintain a Healthy Weight:**
- **Weight Management:** Keeping a healthy weight can reduce the risk of cardiovascular diseases, which may impact macular degeneration.
6. **Regular Eye Exams:**
- **Routine Check-ups:** Have regular eye examinations, especially if you have a family history of macular degeneration. Early detection can help manage the condition better.
7. **Control Blood Pressure:**
- **Blood Pressure Management:** High blood pressure can damage blood vessels in the eyes, so managing it is crucial.
8. **Reduce Screen Time:**
- **Limit Prolonged Use:** Take breaks from screens to prevent eye strain, following the 20-20-20 rule: every 20 minutes, look at something 20 feet away for at least 20 seconds.
### Note:
- These recommendations can help manage macular degeneration risk and slow its progression. Always consult healthcare professionals for personalized advice. - Medication
- For macular degeneration, a common treatment involves medications that inhibit vascular endothelial growth factor (anti-VEGF). These medications, such as ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin), are typically administered via intravitreal injection to slow or prevent further vision loss.
- Repurposable Drugs
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Macular degeneration, particularly age-related macular degeneration (AMD), is a leading cause of vision loss in the elderly. Repurposable drugs that have shown potential in the treatment or management of macular degeneration include:
1. **Metformin**: Commonly used to treat type 2 diabetes, research has suggested it may have a protective effect against age-related macular degeneration due to its anti-inflammatory and anti-aging properties.
2. **Statins**: These cholesterol-lowering drugs have been investigated for their potential in reducing the risk or slowing the progression of macular degeneration due to their anti-inflammatory and lipid-lowering effects.
3. **Aspirin**: Low-dose aspirin has been studied for its potential benefits in AMD, though results have been mixed regarding its efficacy and safety.
These drugs are not specifically approved for AMD, but they hold potential for repurposing in managing the disease. Always consult healthcare professionals before considering any treatment options. - Metabolites
- Macular degeneration is a condition that affects the central part of the retina called the macula, leading to vision loss. Specific metabolites associated with macular degeneration include lipid metabolites and inflammatory markers. Abnormalities in these metabolites can contribute to the pathogenesis of the disease by promoting oxidative stress and inflammation in retinal cells.
- Nutraceuticals
- Nutraceuticals like antioxidants (e.g., vitamins C and E), zinc, lutein, and zeaxanthin may benefit individuals with macular degeneration. They can slow the progression of the disease, especially in its intermediate and late stages. The Age-Related Eye Disease Study (AREDS) formula is commonly recommended. Consult with a healthcare provider before starting any supplements.
- Peptides
- Research indicates that peptide-based therapies are being explored for the treatment of macular degeneration, specifically aimed at inhibiting factors that contribute to disease progression, such as vascular endothelial growth factor (VEGF). Nanotechnology offers promising advancements in drug delivery systems for macular degeneration, including nanoparticle-based delivery methods that enhance the precision and efficiency of treatments, potentially improving outcomes and reducing side effects.