Macular
Degeneration
Macular degeneration, also known as age-related
macular degeneration (AMD or ARMD), 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.[1] 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. Genetic factors and smoking also play a role.[1] It is due to damage to
the macula of
the retina.
Diagnosis is by a complete eye exam. The 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 the change of
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. There is no cure or
treatment that returns vision already lost. In the wet form, anti-VEGF medication is 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.[5] 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 2020, it affects more than 190 million people globally with
the prevalence expected to increase to 288 million people by 2040 as the
proportion of elderly persons in the population increases. It is equally seen in males and females and it
is more common in those of European or North American ancestry. 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
Normal vision
The same view with
age-related macular degeneration
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 one
-
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.
Risk factors
Key risk factors are age,
race/ethnicity, smoking, and family history.
Advanced age is the strongest predictor of AMD, particularly over age 50.
Race and ethnicity
AMD by race and age from
National Eye Institute data
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, Caucasian individuals are more than 6 times more
likely to develop AMD than Black or Hispanic individuals. Thus, caucasun background
is a major risk factor for AMD.
In Caucasian (White) skin,
there is a specific group of polymorphic genes (with single nucleotide
alterations) that encode for enzymes and transcription factors responsible for
the early steps (including the first step, formation of L-DOPA from the amino
acid tyrosine) 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 result in an
increase in 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 eighty.
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 were 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.
Exposure to UV light from
sunlight is possibly associated with an increased risk of developing AMD,
although evidence is weaker than other causes.
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 is a highly heritable
condition. Recurrence ratios for
siblings of an affected individual are three- to sic times 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. Variants of
these genes give rise to different kinds of dysfunction in these processes.
Over time, this results in accumulation of intracellular and extracellular
metabolic debris. This can cause scarring of the retina or breakdown of its
vascularization.
The list of genetic
variations association with AMD include 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
where identified gene variants are found are designated:
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
Specific genes
Polymorphisms in genes for
complement system proteins: variation in the genes for the complement system
proteins factor H (CFH), factor B (CFB) and factor 3 (C3), 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 (Y402H)
results in reduced ability of the protein to localize 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 (encoding a secreted
serine protease), was identified.
Six mutations of the gene
SERPING1 (Serpin Peptidase Inhibitor, Clade G (C1 Inhibitor), 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 screen on 402 AMD
patients and revealed a statistically significant correlation between mutations
in fibulin-5 and incidence of the disease.
Mitochondrial-related gene
polymorphisms such as that in the MT-ND2 molecule, predicts wet AMD.
Pathophysiology
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 path ophysiological
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 metabolizing 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.
Stages
In AMD there is a
progressive accumulation of characteristic yellow deposits, called drusen
(buildup of extracellular proteins and lipids), in the macula (a part of the
retina), between the retinal pigment epithelium and the underlying choroid.
This accumulation is believed to damage the retina over time. Amyloid beta,
which builds up in the brains of Alzheimer's disease patients, is one of the
proteins that accumulate in AMD, which is a reason why AMD is sometimes called
"Alzheimer's of the eye" or "Alzheimer's of the retina". AMD can be divided into 3 stages: early,
intermediate, and late, based partially on the extent (size and number) of
drusen.
Most people with these early changes (referred
to as age-related maculopathy) still have good vision. People with drusen may
or may not develop AMD. In fact, the majority of people over age 60 have drusen
with no adverse effects. The risk of developing symptoms is higher when the
drusen are large and numerous, and associated with the disturbance in the
pigmented cell layer under the macula. Large and soft drusen are thought to be
related to elevated cholesterol deposits.
Early AMD
Early AMD is diagnosed based
on the presence of medium-sized drusen, about the width of an average human
hair. Early AMD is usually asymptomatic.
Intermediate AMD
Intermediate AMD is
diagnosed by large drusen and/or any retinal pigment abnormalities.
Intermediate AMD may cause some vision loss, but, like early AMD, it is usually
asymptomatic.
Recently, subgroups of
intermediate AMD have been identified, which have a very high risk of
progression toward late AMD. This subgroup (depending on the precise
definitions) is termed nascent GA and/or iRORA (incomplete retinal pigment
epithelium and outer retinal atrophy). These 'high-risk' subgroups of intermediate
AMD can be used to inform patients of their prognosis. In addition, these can
be applied in clinical trials as endpoints.
Late AMD
In late AMD, enough retinal
damage occurs that, in addition to drusen, people will also begin to experience
symptomatic central vision loss. The damage can either be the development of
atrophy or the onset of neovascular disease. Late AMD is further divided into
two subtypes based on the types of damage: Geographic atrophy and Wet AMD (also
called Neovascular AMD).
Dry AMD
Dry AMD (also called
nonexudative AMD) is a broad designation, encompassing all forms of AMD that
are not neovascular (wet AMD). This includes early and intermediate forms of
AMD, as well as the advanced form of dry AMD known as geographic atrophy. Dry
AMD patients tend to have minimal symptoms in the earlier stages; visual
function loss occurs more often if the condition advances to geographic
atrophy. Dry AMD accounts for 80–90% of cases and tends to progress slowly. In
10–20% of people, dry AMD progresses to the wet type.
Geographic atrophy
Geographic atrophy (also
called atrophic AMD) is an advanced form of AMD in which progressive and
irreversible loss of retinal cells leads to a loss of visual function. There
are multiple layers that make up the retina, and in geographic atrophy, there
are three specific layers that undergo atrophy: the choriocapillaris, retinal
pigment epithelium, and the overlying photoreceptors.
The three layers that
undergo atrophy in geographic atrophy are all adjacent to each other. The
photoreceptors are the most superficial and they are the cells that are
responsible for converting energy from the light from the outside world into an
electrical signal to be sent to the brain. There are several functions of the
retinal pigment epithelium. One of the main functions of the retinal pigment epithelium
is to minimize oxidative stress. It does so by absorbing light, and thus
preventing it from getting to the underlying layers. The layers underlying the
retinal pigment epithelium are very vascularlized so they have very high oxygen
tension. Thus, if light was to get to those layers, many free radicals would
form and cause damage to nearby tissues. The deepest layer that undergoes
atrophy in geographic atrophy is called the choriocappilaris. It is a capillary
network that provides nutrients to the retinal pigment epithelium.
The pathophysiology of
geographic atrophy is still uncertain. Some studies questioned whether it was
due to a deficient retinal pigment epithelium, leading to increased oxidative
stress. Other studies have looked for
inflammatory causes of damage. Thus far,
the medical community is still not certain. Recent studies have begun to look
at each layer individually. They found that decreased blood flow in the
choriocapillaris precedes atrophy of the retinal pigment epithelium and the
overlying photoreceptors. Since the
choriocapillaris is a vascular layer, this may be used as an argument for why
geographic atrophy could be a disease due to decreased blood flow.
Wet AMD
Neovascular or exudative
AMD, the "wet" form of advanced AMD, causes vision loss due to
abnormal blood vessel growth (choroidal neovascularization) in the
choriocapillaris, through Bruch's membrane. It is usually, but not always,
preceded by the dry form of AMD. The proliferation of abnormal blood vessels in
the retina is stimulated by vascular endothelial growth factor (VEGF). Because
these blood vessels are abnormal, these are also more fragile than typical
blood vessels, which ultimately leads to blood and protein leakage below the
macula. Bleeding, leaking, and scarring from these blood vessels eventually
cause irreversible damage to the photoreceptors and rapid vision loss if left
untreated.
Diagnosis
Super resolution microscopic
investigation of human eye tissue affected by AMD.
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 may include the following clinical examinations as well as
procedures and tests:
The transition from dry to
wet AMD can happen rapidly, and if it is left untreated can lead to legal
blindness in as little as six months. To prevent this from occurring and to
initiate preventive strategies earlier in the disease process, dark adaptation
testing may be performed. 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.
00000In 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 may include the following in addition to the above tests:
Preferential hyperacuity
perimetry changes (for wet AMD). Preferential hyperacuity perimetry is a test
that detects drastic changes in vision and involves the macula being stimulated
with distorted patterns of dots and the patient identification of where in the
visual field this occurs.
In wet macular degeneration,
angiography can visualize the leakage of bloodstream behind the macula.
Fluorescein angiography allows for the identification and localization of
abnormal vascular processes.
Histology
Pigmentary changes in the
retina – In addition to the pigmented cells in the iris (the colored part of
the eye), there are pigmented cells beneath the retina. As these cells break
down and release their pigment, dark clumps of released pigment may appear. 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. Normal retinal reception
and image transmission are sometimes possible in a retina when high
concentrations of drusen are present. This
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
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 2023, 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 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. These specific micronutrient supplementations
were associated with a lower risk of progression to more severe forms of AMD
and greater visual acuity at 5 years. 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
Ranibizumab(1), aflibercept2),
brolucizumab(3) and faricimab(4) are approved VEGF inhibitors for the treatment
of CNV in wet AMD. All four drugs are
administered via intravitreal injection, meaning they are injected directly
into the eye. Bevacizumab is another VEGF inhibitor that has been shown to have
similar efficacy and safety as the previous two drugs, however, is not
currently indicated for AMD. AMD can
also be treated with laser coagulation therapy.
A randomized control trial
found that bevacizumab and ranibizumab had similar efficacy and reported no
significant increase in adverse events with bevacizumab. A 2014 Cochrane
review found that the systemic safety of bevacizumab and ranibizumab are
similar when used to treat neovascular AMD, except for gastrointestinal
disorders. Bevacizumab however is not
FDA approved for treatment of macular degeneration. A controversy in the UK
involved the off-label use of cheaper bevacizumab over the approved, but expensive,
ranibizumab. Ranibizumab is a smaller
fragment, Fab fragment, of the parent bevacizumab molecule specifically
designed for eye injections. Other
approved antiangiogenic drugs for the treatment of neo-vascular AMD include
pegaptanib and aflibercept.
These anti-VEGF agents may
be administered monthly or adaptively. For adaptive anti-VEGF treatment, two
approaches are conventionally applied. In the case of pro re nata, the patient
comes at fixed intervals, but treatment is only administered if an activity is
detected (i.e., presence of fluid). In the case of treat-and-extend, the
patients always receive treatment, but the interval to the next visit is
extended if the lesion was inactive. Recently, researchers have started to apply AI
algorithms to predict the future need for treatment. But these approaches have not been validated
for clinical use as of today.
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. A 2007 Cochrane review found that laser
photocoagulation of new blood vessels in the choroid outside of the fovea is
effective and economical method, but that the benefits are limited for vessels
next to or below the fovea.
Photodynamic therapy has
also been used to treat wet AMD. The drug verteporfin is administered
intravenously; light of a certain wavelength is then applied to the abnormal
blood vessels. This activates the verteporfin destroying the vessels.
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 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, similar to the way 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. First clinical
trials are being prepared as of January 2021.
Adaptive devices
Josef Tal, an Israeli
composer who was affected by macular degeneration, checks a manuscript using a
CCTV desktop unit.
Because peripheral vision is
not affected, people 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.
Adaptive devices can help
people read. These include magnifying glasses, special eyeglass lenses,
computer screen readers, electronic glasses, and TV systems that enlarge the
reading material.
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.).
Video cameras can be fed
into standard or special-purpose computer monitors, and the image can be zoomed
in and magnified. These systems often include a movable table to move the
written material.
Accessible publishing
provides larger fonts for printed books, patterns to make tracking easier,
audiobooks and DAISY books with both text and audio.
Epidemiology
Disability-adjusted life
year for macular degeneration and other (sense organ diseases) per 100,000
inhabitants in 2004.
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 under 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.
Research
Association with other
age-related diseases
Studies indicate drusen
associated with AMD are similar in molecular composition to amyloid beta (Aβ)
plaques and deposits in other age-related diseases such as Alzheimer's disease
and atherosclerosis. This suggests that similar pathways may be involved in the
etiologies of AMD and other age-related diseases.
Genetic testing
Genetic testing can help
identify whether a patient with AMD is at a greater risk of developing the
condition and can inform disease progression. Genetic testing can also allow researchers to
identify whether patients are more or less likely to respond to treatments,
such anti-VEGF medication or complement inhibitors. However, there remain several challenges to
using predictive tools which incorporate genetic variation in clinical
practice. the way that different genetic variants Therefore, there is increasing interest in
understanding the functional consequences of rare mutations, which often have
more pronounced effects. Genetic testing
to guide clinical management is not currently recommended.
Stem cell transplant
See also: Stem cell therapy
for macular degeneration.
Cell based therapies using
bone marrow stem cells as well as retinal pigment epithelial transplantation
are being studied. A number of trials
have occurred in humans with encouraging results.
Genome editing
CRISPR-Cas9 genome editing
may be used to treat wet age-related macular degeneration caused by VEGFA.
Scientists described an approach in which engineered lentiviruses are injected
into the affected anatomical regions for transient editing that could reduce
the area of choroidal neovascularization by 63% without inducing undesired
off-target edits or anti-Cas9 immune responses.
RPE and L-DOPA in
amelioration of wet AMD
The retinal pigment
epithelium (RPE) has an essential role in the eye. It secretes a large variety
of factors including at least 22 proteins important in maintaining the
structure, function and micro-environments on the two sides of the RPE. (The
two sides of the RPE include the choroid side, where blood vessels form and
bring nourishment to the eye, and the photoreceptor side, with rods and cones
that receive light signals.) In particular, the RPE secretes vascular
endothelial growth factor (VEGF) at its basement membrane, with the VEGF
reaching the choriocapillaris to maintain proper blood vessel formation in the
choroid region.
Many factors, including
genetic factors, hypoxia, oxidative stress and inflammatory stressors, may
cause pathologic over-production of VEGF by the RPE. This over-production
causes excess blood vessel formation in the choroid region (the
choriocapillaris), which is a major cause of wet AMD.
Artificial
intelligence for prediction
Research is exploring if
artificial intelligence can help in predicting wet AMD early enough to make
prevention possible. A study tested an AI model for predicting whether people
with wet AMD in one eye would develop it in the other within six months.
Compared to doctors and optometrists the AI model predicted the development
more accurately.
Other types
There are a few other (rare)
kinds of macular degeneration with similar symptoms but unrelated in etiology
to Wet or Dry age-related macular degeneration. They are all genetic disorders
that may occur in childhood or middle age.
Vitelliform macular
dystrophy
Sorsby's fundus dystrophy is
an autosomal dominant, retinal disease characterized by sudden acuity loss
resulting from untreatable submacular neovascularization. Stargardt's disease (juvenile macular
degeneration, STGD) is an autosomal recessive retinal disorder characterized by
juvenile-onset macular dystrophy, alterations of the peripheral retina, and
subretinal deposition of lipofuscin-like material.
Similar symptoms with a very
different etiology and different treatment can be caused by epiretinal membrane
or macular pucker or any other condition affecting the macula, such as central
serous retinopathy.
Jan Ricks Jennings, MHA, LFACHE
Senior Consultant
Senior Management
Resources, LLC
JanJenningsBlog.Blogspot.com
724.733.0509 Office
412.913.0636 Cell
January 18, 20023
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