Macular Degeneration Affects The Macula

Macular degeneration (धब्बेदार अध:पतन), also known as age-related macular degeneration (AMD or ARMD), is a medical condition that may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, 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. Exercising, eating well, and not smoking may reduce the risk of macular degeneration. There is no cure or treatment that restores the vision already lost. 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.

Macular degeneration Meaning

It is a degenerative condition affecting the central part of the retina (the macula) and resulting in distortion or loss of central vision.

Macular degeneration Symptoms

Early or intermediate AMD (Age-related Macular Degeneration) 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 Symptoms

Signs and other 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 (photo stress test).
• Visual acuity drastically decreases (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.

Not lead to total blindness

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 (a severe stroke or trauma, untreated glaucoma, etc), but few macular degeneration patients experience total visual loss.

Macula remains unaffected

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. 

Dry and Wet Macular degeneration

In addition, people with dry macular degeneration often do not experience any symptoms but can experience a gradual onset of blurry vision in one or both eyes. People with wet macular degeneration may experience acute onset of visual symptoms.

Risk factors of Macular degeneration

Key risk factors are age, race/ethnicity, smoking, and family history. 

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.

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 (high blood pressure): In the ALIENOR study 2013, early and late AMD was not significantly associated with systolic or diastolic blood pressure (BP), hypertension, or use of antihypertensive medications, but elevated pulse pressure [(PP) systolic BP minus diastolic BP] 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.
• A digital screen does not radiate harmful energy against human eyes, but staring at the screen for a long time without pauses does increase eye strain. There is no evidence to support the claim that exposure to digital screens contributes to the risk of macular degeneration.

Genetics

AMD (Age-related Macular Degeneration) 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 (1, 6, and 10) as explaining at least 50% of the risk. These genes have roles regulating the immune response, inflammatory processes, and homeostasis of the retina. 

List of genetic variations

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 which 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 include:

• Complement Factor H (CFH) on chromosome 1 at location 1q31.3
• HTRA serine peptidase 1/Age Related Maculopathy Susceptibility 2 (HTRA1/ARMS2) on chromosome 10 at location 10q26
• Complement Factor B/Complement Component 2 (CFB/CC2) on chromosome 6 at 6p21.3

Macular degeneration Diagnosis

Diagnosis of age-related macular degeneration depends on signs in the macula, not necessarily vision. Early diagnosis of AMD can prevent further visual deterioration and potentially improve vision.

Diagnosis of dry (or early stage) AMD

It may include the following clinical examinations as well as procedures and tests:

• A dark adaptometer can detect subclinical AMD at least three years earlier than it is clinically evident.
• There is a loss of contrast sensitivity, so that contours, shadows, and color vision are less vivid. The loss, in contrast, sensitivity can be quickly and easily measured by a contrast sensitivity test like Pelli Robson performed either at home or by an eye specialist.
• When viewing an Amsler grid, some straight lines appear wavy and some patches appear blank
• When viewing a Snellen chart, at least 2 lines decline
• In dry macular degeneration, which occurs in 85–90 percent of AMD cases, drusen spots can be seen in Fundus photography
• Using an electroretinogram, points in the macula with a weak or absent response compared to a normal eye may be found
• Farnsworth-Munsell 100 hue test and Maximum Color Contrast Sensitivity test (MCCS) for assessing color acuity and color contrast sensitivity
• Optical coherence tomography is now used by most ophthalmologists in the diagnosis and the follow-up evaluation of the response to treatment with antiangiogenic drugs.

Diagnosis of wet (or late-stage) AMD

This may include the following in addition to the above tests:

• Preferential hyperacuity perimetry changes (for wet AMD). 
• In wet macular degeneration, angiography can visualize the leakage of the bloodstream behind the macula. Fluorescein angiography allows for the identification and localization of abnormal vascular processes.

Histology

• As these cells break down and release their pigment, dark clumps of released pigment and later, areas that are less pigmented may appear
• Exudative changes: hemorrhages in the eye, hard exudates, subretinal/sub-RPE/intraretinal fluid
• Drusen, tiny accumulations of extracellular material that build up on the retina. While there is a tendency for drusen to be blamed for the progressive loss of vision, drusen deposits can be present in the retina without vision loss. Some patients with large deposits of drusen have normal visual acuity. If normal retinal reception and image transmission are sometimes possible in a retina when high concentrations of drusen are present, then, even if drusen can be implicated in the loss of visual function, there must be at least one other factor that accounts for the loss of vision.

Management of Macular degeneration

Treatment of AMD varies depending on the category of the disease at the time of diagnosis. In general, treatment is aimed at slowing down the progression of AMD. As of 2018, there are no treatments to reverse the effects of AMD. Early-stage and intermediate-stage AMD is managed by modifying known risk factors such as smoking cessation, management of hypertension and atherosclerosis, and making dietary modifications. 

For intermediate-stage AMD, management also includes antioxidant and mineral supplementation. Advanced-stage AMD is managed based on the presence of choroidal neovascularization (CNV): dry AMD (no CNV present) or wet AMD (CNV present). No effective treatments exist for dry AMD. The CNV present in wet AMD is managed with vascular endothelial growth factor (VEGF) inhibitors. Daily use of an Amsler grid or other home visual monitoring tools can be used to monitor for the development of distorted vision, which may be a sign of disease progression.

Dietary supplements

The age-related eye disease studies 1 and 2 (AREDS) showed that those with bilateral early or intermediate AMD, or intermediate AMD in one eye and advanced AMD in the other eye may benefit from specific vitamin and mineral supplementation. The specific vitamins and minerals in AREDS-1 are:

• Vitamin C (500 mg), 
• Zinc (80 mg), 
• Vitamin E (400 IU), 
• Copper (2 mg), and 
• Beta-carotene (15 mg).

In the AREDS-2 formulation, lutein (10 mg) and zeaxanthin (2 mg) replaced beta-carotene due to the risk of lung cancer in smokers taking beta-carotene. There is no evidence that micronutrient supplementation prevents AMD progression in those with severe disease or prevents disease onset in those without AMD.

Dry AMD

There is no cure for dry AMD. While there is increasing academic and pharmaceutical interest in developing complement inhibitors to treat ophthalmic inflammation, with several clinical trials underway for dry AMD, the first such agent to complete Phase 3 trials in AMD (the anti-factor D agent, lampalizumab) did not significantly improve the rate of disease progression. Nevertheless, strategies targeting different aspects of the complement system are ongoing.

Wet AMD

The American Academy of Ophthalmology practice guidelines do not recommend laser coagulation therapy for macular degeneration but state that it may be useful in people with new blood vessels in the choroid outside of the fovea who don’t respond to drug treatment. There is strong evidence that laser coagulation will result in the disappearance of drusen but does not affect choroidal neovascularization. 

Photodynamic therapy

Photodynamic therapy has also been used to treat wet AMD. The drug verteporfin is administered intravenously; the light of a certain wavelength is then applied to the abnormal blood vessels. This activates the verteporfin destroying the vessels.

Cataract surgery

Cataract surgery could improve visual outcomes for people with AMD, though there have been concerns about surgery increasing the progression of AMD. A randomized controlled trial found that people who underwent immediate cataract surgery (within two weeks) had improved visual acuity and better quality of life outcomes than those who underwent delayed cataract surgery (6 months).

Radiotherapy

Radiotherapy has been proposed as a treatment for wet AMD but the evidence to support the use of modern stereotactic radiotherapy combined with anti-VEGF is currently uncertain and is awaiting the results of ongoing studies.

Nucleoside reverse transcription inhibitors

Nucleoside reverse transcription inhibitors like they are used in anti-HIV therapy was associated with a reduced risk of developing atrophic macular degeneration. This is because Alu elements undergo L1 (protein)-mediated reverse transcription in the cytoplasm resulting in DNA synthesis. 

Adaptive devices

Because peripheral vision is not affected, persons with macular degeneration can learn to use their remaining vision to partially compensate. Assistance and resources are available in many countries and every state in the U.S. Classes for “independent living” are given and some technology can be obtained from a state department of rehabilitation.

Helps in reading

Adaptive devices can help people read. These include:

• Magnifying glasses,
• Special eyeglass lenses,
• Computer screen readers,
• Electronic glasses, and
• TV systems. 

Computer screen readers such as JAWS or Thunder work with standard Windows computers. Also, Apple devices provide a wide range of features (voice-over, screen readers, Braille, etc).

Research in Macular degeneration

Types of Macular Degeneration

Macular degeneration is a condition that affects the macula, a small but critical part of the retina responsible for central vision. There are two main types of macular degeneration:

1. Dry macular degeneration: Also known as atrophic macular degeneration, this is the most common form of the condition, accounting for about 90% of cases. Dry macular degeneration usually progresses slowly, and there is currently no cure for this type of disease.
2. Wet macular degeneration: Also known as neovascular macular degeneration, this type accounts for about 10% of cases. It occurs when abnormal blood vessels grow beneath the retina, which can leak blood and fluid, causing scarring and rapid loss of central vision. Wet macular degeneration can progress rapidly, and if left untreated, it can cause severe vision loss.

Both types of macular degeneration can cause symptoms such as blurry vision, distorted vision, and difficulty seeing in low-light conditions. However, early detection and treatment can help slow the progression of the disease and preserve vision. Regular eye exams are crucial for detecting macular degeneration in its early stages.

Reference: https://en.wikipedia.org/wiki/Macular_degeneration