Stargardt’s disease, a genetic disorder of the retina that causes the body to process vitamin A incorrectly. Byproducts of the vitamin accumulate on the macula, in the back of the eye, eventually resulting in a loss of central vision, as if perpetually looking at the world through an eclipse. Onset is typically in childhood.
Stargardt’s disease
Signs and symptoms
Patients with Stargardt disease usually develop symptoms in the mid-first to the late second decade of life, with age of onset which can be as early as ~6 years of age.
The main symptom of Stargardt disease is
loss of visual acuity, uncorrectable with glasses, which progresses and frequently stabilizes between 20/200 and 20/400.
Other symptoms include
wavy vision,
blind spots (scotomata),
blurriness,
impaired color vision, and
difficulty adapting to dim lighting (delayed dark adaptation).
The disease sometimes causes sensitivity to glare; overcast days offer some relief.
Vision is most noticeably impaired when the macula (center of retina and focus of vision) is damaged, leaving peripheral vision more intact.
Generally, vision loss starts within the first 20 years of life.
Genetics
Stargardt disease is associated with several different genes:
STGD1: The most common form of Stargardt disease is the recessive form caused by mutations in the ABCA4 gene. It can also be associated with CNGB3.
STGD3: There is also a rare dominant form of Stargardt disease caused by mutations in the ELOVL4 gene.
STGD4: Associated with PROM1.
The classification "STGD2" is no longer used.
Pathophysiology
In STGD1, the genetic defect causes malfunction of the ATP-binding cassette transporter (ABCA4) protein of the visual phototransduction cycle. Defective ABCA4 leads to improper shuttling of vitamin A throughout the retina, and accelerated formation of toxic vitamin A dimers (also known as bisretinoids), and associated degradation byproducts.
Vitamin A dimers and other byproducts are widely accepted as the cause of STGD1. As such, slowing the formation of vitamin A dimers might lead to a treatment for Stargardt. When vitamin A dimers and byproducts damage the retinal cells, fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina appear, as a reflecting such damage.
In STGD4, a butterfly pattern of dystrophy is caused by mutations in a gene that encodes a membrane bound protein that is involved in the elongation of very long chain fatty acids (ELOVL4)
Treatment
Currently, there is no treatment for the disease. However, ophthalmologists recommend wearing sunglasses and hats outdoors and blue-light blocking glasses when exposed to artificial light sources, such as screens and lights. Tobacco smoke and second-hand smoke should be avoided. Animal studies also show that high doses of vitamin A can be detrimental by building up more lipofuscin toxin. Dietary non-supplemental vitamin A intake may not further the disease progression. Clinical trials are being conducted with promising early results. The trials may one day lead to treatments that might halt, and possibly even reverse, the effects of Stargardt disease using stem cell therapy, gene therapy, or pharmacotherapy.
The Argus retinal prosthesis, an electronic retinal implant, was successfully fitted to a 67-year-old woman in Italy at the Careggi Hospital in 2016. The patient had a very advanced stage of Stargardt’s disease, and a total absence of peripheral and central visual fields.
Prognosis
The long-term prognosis for patients with Stargardt disease is widely variable although the majority of people will progress to legal blindness.
Stargardt disease has no impact on general health and life expectancy is normal. Some patients, usually those with the late onset form, can maintain excellent visual acuities for extended periods, and are therefore able to perform tasks such as reading or driving.
Epidemiology
STGD1 is the most common form of inherited juvenile macular degeneration with a prevalence of approximately 1 in 10,000 births.
https://www.bloomberg.com/news/articles/2017-09-22/these-two-brothers-are-trying-to-cure-blindness-one-henley-at-a-time
https://en.wikipedia.org/wiki/Stargardt_disease
Stargardt’s disease
Signs and symptoms
Patients with Stargardt disease usually develop symptoms in the mid-first to the late second decade of life, with age of onset which can be as early as ~6 years of age.
The main symptom of Stargardt disease is
loss of visual acuity, uncorrectable with glasses, which progresses and frequently stabilizes between 20/200 and 20/400.
Other symptoms include
wavy vision,
blind spots (scotomata),
blurriness,
impaired color vision, and
difficulty adapting to dim lighting (delayed dark adaptation).
The disease sometimes causes sensitivity to glare; overcast days offer some relief.
Vision is most noticeably impaired when the macula (center of retina and focus of vision) is damaged, leaving peripheral vision more intact.
Generally, vision loss starts within the first 20 years of life.
Genetics
Stargardt disease is associated with several different genes:
STGD1: The most common form of Stargardt disease is the recessive form caused by mutations in the ABCA4 gene. It can also be associated with CNGB3.
STGD3: There is also a rare dominant form of Stargardt disease caused by mutations in the ELOVL4 gene.
STGD4: Associated with PROM1.
The classification "STGD2" is no longer used.
Pathophysiology
In STGD1, the genetic defect causes malfunction of the ATP-binding cassette transporter (ABCA4) protein of the visual phototransduction cycle. Defective ABCA4 leads to improper shuttling of vitamin A throughout the retina, and accelerated formation of toxic vitamin A dimers (also known as bisretinoids), and associated degradation byproducts.
Vitamin A dimers and other byproducts are widely accepted as the cause of STGD1. As such, slowing the formation of vitamin A dimers might lead to a treatment for Stargardt. When vitamin A dimers and byproducts damage the retinal cells, fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina appear, as a reflecting such damage.
In STGD4, a butterfly pattern of dystrophy is caused by mutations in a gene that encodes a membrane bound protein that is involved in the elongation of very long chain fatty acids (ELOVL4)
Treatment
Currently, there is no treatment for the disease. However, ophthalmologists recommend wearing sunglasses and hats outdoors and blue-light blocking glasses when exposed to artificial light sources, such as screens and lights. Tobacco smoke and second-hand smoke should be avoided. Animal studies also show that high doses of vitamin A can be detrimental by building up more lipofuscin toxin. Dietary non-supplemental vitamin A intake may not further the disease progression. Clinical trials are being conducted with promising early results. The trials may one day lead to treatments that might halt, and possibly even reverse, the effects of Stargardt disease using stem cell therapy, gene therapy, or pharmacotherapy.
The Argus retinal prosthesis, an electronic retinal implant, was successfully fitted to a 67-year-old woman in Italy at the Careggi Hospital in 2016. The patient had a very advanced stage of Stargardt’s disease, and a total absence of peripheral and central visual fields.
Prognosis
The long-term prognosis for patients with Stargardt disease is widely variable although the majority of people will progress to legal blindness.
Stargardt disease has no impact on general health and life expectancy is normal. Some patients, usually those with the late onset form, can maintain excellent visual acuities for extended periods, and are therefore able to perform tasks such as reading or driving.
Epidemiology
STGD1 is the most common form of inherited juvenile macular degeneration with a prevalence of approximately 1 in 10,000 births.
https://www.bloomberg.com/news/articles/2017-09-22/these-two-brothers-are-trying-to-cure-blindness-one-henley-at-a-time
https://en.wikipedia.org/wiki/Stargardt_disease
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