Macular degeneration


Macular degeneration, also known as age-related macular degeneration, is a medical condition which may result in blurred or no vision in the center of the visual field. Early on, there are often no symptoms. Some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual hallucinations may also occur.
Macular degeneration typically occurs in older people, and is caused by damage to the macula of the retina. Genetic factors and smoking may play a role. The condition is diagnosed through a complete eye exam. Severity is divided into early, intermediate, and late types. The late type is additionally divided into "dry" and "wet" forms, with the dry form making up 90% of cases.
The difference between the two forms is categorized by the change in the macula. Those with dry-form AMD have drusen, cellular debris in their macula that gradually damages light-sensitive cells and leads to vision loss. In wet-form AMD, blood vessels grow under the macula, causing blood and fluid to leak into the retina.
Exercising, eating well, and not smoking may reduce the risk of macular degeneration. No cure or treatment restores the vision already lost. In the wet form, anti–vascular endothelial growth factor injected into the eye or, less commonly, laser coagulation or photodynamic therapy may slow worsening. Dietary antioxidant vitamins, minerals, and carotenoids do not appear to affect the onset; however, dietary supplements may slow the progression in those who already have the disease.
Age-related macular degeneration is a main cause of central blindness among the working-aged population worldwide. As of 2022, it affects more than 200 million people globally with the prevalence expected to increase to 300 million people by 2040 as the proportion of elderly persons in the population increases. It is more common in those of European or North American ancestry, and is about equally common in males and females. In 2013, it was the fourth most common cause of blindness, after cataracts, preterm birth, and glaucoma. It most commonly occurs in people over the age of fifty and in the United States is the most common cause of vision loss in this age group. About 0.4% of people between 50 and 60 have the disease, while it occurs in 0.7% of people 60 to 70, 2.3% of those 70 to 80, and nearly 12% of people over 80 years old.

Signs and symptoms

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. Other symptoms of AMD include distortion of vision and blind spots.
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
  • Visual acuity drastically decreasing., e.g.: 20/20 to 20/80
  • Blurred vision: Those with nonexudative macular degeneration may be asymptomatic or notice a gradual loss of central vision, whereas those with exudative macular degeneration often notice a rapid onset of vision loss.
  • 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 blind. In almost all cases, some vision remains, mainly peripheral. Other complicating conditions may lead to such an acute condition, 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% 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.

Risk factors

The pathogenesis of age-related macular degeneration is intricately linked to gene-environment interactions. Key risk factors are age, race/ethnicity, smoking, and family history. Advanced age is the strongest predictor of AMD, particularly over 50.

Race and ethnicity

As illustrated by the Figure in this section, derived from data presented by the National Eye Institute of the United States, among those over 80 years of age, white individuals are more than 6-fold more likely to develop AMD than Black or Hispanic individuals. Thus, white background is a major risk factor for AMD.
In Caucasian skin, there is a specific group of polymorphic genes that encode for enzymes and transcription factors responsible for the early steps of the melanin synthesis pathway. Many of these enzymes and transcription factors are reviewed by Markiewicz and Idowu. Also, as reviewed by Sturm et al. "increasing intracellular concentrations of either tyrosine or L-DOPA both increase melanogenesis" or formation of the black pigment melanin. Thus there appears to be an association between reduced L-DOPA production and white skin. As suggested by the Figure and information in this section, reduced L-DOPA, resulting in white skin, appears to be associated with an increased risk of macular degeneration for white individuals over the age of 80.

Environment and lifestyle

  • Smoking: Smoking tobacco increases the risk of AMD by two to three times that of someone who has never smoked, and may be the most important modifiable factor in its prevention. A review of previous studies found "a strong association between current smoking and AMD.... Cigarette smoking is likely to have toxic effects on the retina."
  • Hypertension : In the ALIENOR study 2013, early and late AMD were not significantly associated with systolic or diastolic blood pressure, hypertension, or use of antihypertensive medications, but elevated pulse pressure was significantly associated with an increased risk of late AMD.
  • Atherosclerosis
  • High cholesterol: Elevated cholesterol may increase the risk of AMD
  • Obesity: Abdominal obesity is a risk factor, especially among men
  • Fat intake: Consuming high amounts of certain fats, including saturated fats, trans fats, and omega-6 fatty acids, likely contributes to AMD, while monounsaturated fats are potentially protective. In particular, omega-3 fatty acids may decrease the risk of AMD.
  • Exposure to UV light from sunlight may be associated with an increased risk of developing AMD, although evidence for this is weaker than for other causes.
  • There is no evidence to support the claim that exposure to digital screens contributes to the risk of macular degeneration.

    Genetics

AMD is a highly heritable condition. Recurrence ratios for siblings of an affected individual are three- to six-fold higher than in the general population. Genetic linkage analysis has identified 5 sets of gene variants at three locations on different chromosomes as explaining at least 50% of the risk. These genes have roles regulating the immune response, inflammatory processes and homeostasis of the retina. Variants of these genes give rise to different kinds of dysfunction in these processes. Over time, this results in the accumulation of intracellular and extracellular metabolic debris. This can cause scarring of the retina or breakdown of its vascularization.
The list of genetic variations associated with AMD includes complement factors, apolipoprotein E, fibroblast growth factor 2, DNA excision repair protein, and age-related maculopathy susceptibility protein 2.
Although genetic testing can lead to the identification of genetic variation that can predispose to AMD, the complex pathogenesis of the condition prevents the use of these tests in routine practice. Nevertheless, they can be useful in selecting patients for clinical trials and analyzing their response to treatment. The three loci where identified gene variants are found are designated:
  • Complement factor H on chromosome 1 at location 1q31.3
  • HTRA serine peptidase 1/Age Related Maculopathy Susceptibility 2 on chromosome 10 at location 10q26
  • Complement factor B/complement component 2 on chromosome 6 at 6p21.3

    Specific genes

  • Polymorphisms in genes for complement system proteins: Variation in the genes for the complement system proteins factor H, factor B and factor 3, among others, are strongly associated with a person's risk for developing AMD. CFH is involved in inhibiting the inflammatory response. The mutation in CFH results in reduced ability of the protein to localise to and protect tissues such as the retina from complement overactivation. Absence of the complement factor H-related genes R3 and R1 protects against AMD. Two independent studies in 2007 showed a certain common mutation Arg80Gly in the C3 gene, which is a central protein of the complement system, is strongly associated with the occurrence of AMD. The authors of both papers consider their study to underscore the influence of the complement pathway in the pathogenesis of this disease.
  • In two 2006 studies, another gene that has implications for the disease, called HTRA1, was identified.
  • Six mutations of the gene SERPING1 are associated with AMD. Mutations in this gene can also cause hereditary angioedema.
  • Fibulin-5 mutation: Rare forms of the disease are caused by genetic defects in fibulin-5, in an autosomal dominant manner. In 2004, Stone et al. performed a screening on 402 AMD patients and revealed a statistically significant correlation between mutations in fibulin-5 and the incidence of the disease.
  • Mitochondrial-related gene polymorphisms such as that in the MT-ND2 molecule, predicts wet AMD.