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{{SK}} Fundus flavimaculatus
{{SK}} Fundus flavimaculatus
==Overview==
==Overview==
'''Stargardt's disease'' has been vastly reported as an autosomal [[recessive]] [[genetic disorder|genetic]] form of [[macular degeneration|juvenile macular degeneration]] that causes progressive [[blindness|vision loss]], although several dominant pedigrees have been reported.  It is the most common inherited juvenile macular degeneration.<ref name=mdsupport> [http://www.mdsupport.org/library/stargrdt.html Stargardt's Disease]</ref>
'''Stargardt disease''', or '''fundus flavimaculatus''', is an [[Heredity|inherited]] form of juvenile [[macular degeneration]] that causes progressive [[vision loss]] usually to the point of [[legal blindness]]. Several genes are associated with the disorder. Symptoms, mainly vision loss, typically develop before age 20, and also include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.


==Presentation==
==Characteristics and symptoms==
Those with Stargardt's disease are sensitive to glare; overcast days offer little relief. As the disease progresses, it can cause pain and diminishing sight. Vision is impaired first at the center, leaving peripheral vision intact. Symptoms usually appear before age 20.  Symptoms include wavy vision, blind spots, blurriness, and difficulty adapting to dim lighting.<ref name=mdsupport />
The main symptom of Stargardt disease is loss of visual acuity, which ranges from 20/50 to 20/200.<ref name=Yanoff/>  Other symptoms include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.<ref name=mdsupport/><ref>{{cite web|url=http://www.lowvision.org/stargardts.htm |title=Stargardt's |publisher=Lowvision.org |date=1997-03-03 |accessdate=2012-12-05}}</ref> The disease 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.<ref>{{cite web|title=Stargardt's Disease (Fundus Flavimaculatus)|url=http://www.allaboutvision.com/conditions/stargardts.htm|website=allaboutvision.com|publisher=allaboutvision.com|accessdate=2015-08-30}}</ref>


Some patients are able to drive. Many patients use magnifiers to help them see, and wear sunglasses to slow the development.<ref>[http://www.mdsupport.org/library/stargardt2.html Stargardt's Disease: Information for Patients and Their Families]</ref> Some doctors have recommended colored lenses which filter out the light wavelengths which stimulate rod vision.<ref>[http://www.mdsupport.org/library/stargardt.html Stargardt's Patients Need Special Light Protection]</ref>
==Genetics==
Stargardt disease is associated with several different genes:{{Citation needed|date=August 2015}}
* 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 [[dominance (genetics)|dominant]] form of Stargardt disease caused by mutations in the [[ELOVL4]] gene.
* STGD4: Associated with [[PROM1]].
 
The classification "STGD2" is no longer used.{{Citation needed|date=August 2015}}
 
==Pathophysiology==
In STGD1, the genetic defect is manifest in the [[visual phototransduction]] cycle. The [[ATP-binding cassette transporter]] (ABCA4) is defective and leads to rapid formation of toxic vitamin A dimers (also known as bisretinoids), which then build up in fluorescent granules called [[lipofuscin]] in the [[retinal pigmented epithelium]] of the retina.{{Citation needed|date=August 2015}}
 
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 acid]]s ([[ELOVL4]]).{{Citation needed|date=August 2015}}
 
==Treatment==
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.<ref>[http://www.visionaware.org/blog/visionaware-blog/positive-stem-cell-clinical-trial-results-for-stargardt-disease-and-dry-macular-degeneration-1588/12]</ref>
 
==Prognosis==
The long-term prognosis for patients with Stargardt disease is widely variable although the majority of people will progress to legal blindness.<ref name=Yanoff>{{cite book|last1=Yanoff|first1=Myron|last2=Duker|first2=Jay S.|title=Ophthalmology|year=2008|publisher=Mosby|location=Edinburgh|isbn=978-0323057516|pages=560–562|edition=3rd|ref=harv}}</ref>
 
Stargardt disease has no impact on general health and life expectancy is normal.<ref>[http://disorders.eyes.arizona.edu/handouts/stargardt-disease Stargardt Disease] from The University of Arizona College of Medicine, Department of Ophthalmology and Vision Science. Retrieved Jan 2012</ref>  Some patients are able to drive.{{Citation needed|date=August 2015}}
 
==Epidemiology==
STGD1 is the most common form of inherited juvenile macular degeneration with a prevalence of approximately 1 in 10,000 births.<ref name=mdsupport>[http://www.mdsupport.org/library/stargrdt.html Stargardt Disease]</ref>
 
==Research==
Treatment modalities currently under clinical investigation include cell therapy, gene therapy and oral therapies.  Anecdotal evidence suggests that new technology called esight may help some individuals with Stargardt who retain some visual function, recover vision.<ref>[http://www.esighteyewear.com]</ref>
 
On November 22, 2010, it was announced that [[Ocata Therapeutics|Advanced Cell Technology]],<ref>{{cite web|title=Advanced Cell Technology Receives FDA Clearance For the First Clinical Trial Using Embryonic Stem Cells to Treat Macular Degeneration|url=http://www.advancedcell.com/news-and-media/press-releases/advanced-cell-technology-receives-fda-clearance-for-the-first-clinical-trial-using-embryonic-stem-cel/|publisher=Advanced Cell Technology}}</ref> now called [[Ocata Therapeutics]],  received United States Food and Drug Administration clearance to immediately initiate a Phase I/II multicenter clinical trial using retinal cells derived from human embryonic stem cells (hESCs) to treat patients with Stargardt’s Macular Dystrophy.  In September 2011, [[Ocata Therapeutics|ACT]] announced they were beginning the next stage of treatment for SMD, and Dry AMD as the first stage proved to be safe by an independent board of experts.<ref>{{cite web|url=http://www.advancedcell.com/news-and-media/press-releases/act-receives-approval-from-data-and-safety-monitoring-board-%28dsmb%29-to-treat-next-patients-in-stem-cell-clinical-trials/index.asp |title= ACT Receives Approval from Data and Safety Monitoring Board (DSMB) to Treat Next Patients in Stem Cell Clinical Trials |publisher=Advanced Cell Technology |date= |accessdate=2012-12-05}}</ref> In March 2013, after treating and collecting data on 18 patients, [[Ocata Therapeutics|Advanced Cell]] was given approval to test its stem cell therapy on patients with 20/100 vision.<ref>{{cite web|url=http://advancedcell.com/news-and-media/press-releases/advanced-cell-technology-receives-approval-from-data-safety-monitoring-board-dsmb-to-initiate-treatment-of-third-patient-cohort-in-all-three-clinical-trials/index.asp |title=Advanced Cell Technology Receives Approval from Data Safety Monitoring Board (DSMB) to Initiate Treatment of Third Patient Cohort in All Three Clinical Trials |publisher=Advanced Cell Technology |date=2013-03-14 |accessdate=2013-03-17}}</ref> In October 2014, the results of the Phase I/II clinical trial were published in ''[[the Lancet]]''.<ref>http://download.thelancet.com/flatcontentassets/pdfs/S0140673614613763.pdf</ref>
 
Gene therapy trials are also on-going. During gene therapy, a working copy of the ABCA4 gene is incorporated in a lentivirus (an inactivated virus which transports the working copy of the gene) and injected into the eye through a subretinal injection. It is hoped that such injection, if performed early enough, could prevent the progression of the disease.{{Citation needed|date=August 2015}}
 
Finally, oral therapies that are being investigated include ALK-001, modified vitamin A delivered orally which prevents the formation of toxic vitamin A dimers in the eye. ALK-001 has completed a phase 1 clinical trials.{{Citation needed|date=August 2015}}
 
[[Ocata Therapeutics|ACT]], Oxford Biomedica and Alkeus Pharmaceuticals have all received [[orphan drug]] designation in the United States for the treatment of Stargardt Disease.{{Citation needed|date=August 2015}}
 
Preclinical research include a new compound that can remove lipofuscin from retinal pigment epithelial cells.<ref>{{cite journal | author = Julien S, Schraermeyer U | date = Oct 2012 | title = Lipofuscin can be removed from the retinal pigment epithelium of monkeys | url = | journal = Neurobiol Aging | volume = 33 | issue = 10| pages = 2390–7 | doi = 10.1016/j.neurobiolaging.2011.12.009 }}</ref> The compound drug has been granted [http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2013/12/human_orphan_001287.jsp&mid=WC0b01ac058001d12b orphan drug designation for the treatment of Stargardt disease] by the European Medicines Agency.{{Citation needed|date=August 2015}}


==History==
==History==
The disease was discovered in 1909 by [[Karl Stargardt]], an [[ophthalmologist]] in [[Berlin]]. <ref>{{WhoNamedIt|synd|2306}}</ref><ref>K. B. Stargardt. Über familiäre, progressive Degeneration in der Makulagegend des Auges. Albrecht von Graefes Archiv für Ophthalmologie, 1909, 71: 534-550.</ref>
The disease was discovered in 1909 by [[Karl Stargardt]], a [[Berlin]] [[ophthalmologist]].<ref>{{WhoNamedIt|synd|2306}}</ref><ref>K. B. Stargardt. Über familiäre, progressive Degeneration in der Makulagegend des Auges. Albrecht von Graefes Archiv für Ophthalmologie, 1909, 71: 534-550.</ref>


In 1997, it was discovered that mutations in the {{Gene|ABCA4}} gene cause Stargardt's.  The mutations cause the production of a dysfunctional protein that cannot perform energy transport to and from photoreceptor cells in the retina.  The photoreceptor cells then degenerate, causing vision loss.<ref name=mdsupport />  
In 1997, it was discovered that mutations in the {{Gene|ABCA4}} gene cause Stargardt disease.  The mutations cause the production of a dysfunctional protein that cannot perform energy transport to and from photoreceptor cells in the retina.  The photoreceptor cells then degenerate, causing vision loss.<ref name=mdsupport />


==Notable cases==
==References==
[[George W. Bush]], in June 2006, teased a reporter named [[Peter Wallsten]] who was wearing sunglasses due to Stargardt's.  The reporter later explained that the President had no way of knowing, and that he was not offended. <ref>[http://abcnews.go.com/Politics/story?id=2077873&page=1 After Sunglasses Gaffe, Bush Apologizes to Legally Blind Reporter]</ref>
{{reflist|2}}
 
== References ==
<!--<nowiki>
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== External links ==
== External links ==
* [http://www.medstudents.com.br/raredi/raredi4.htm Rare Disorders: Stargardt's Disease] - a very comprehensive article
* [http://www.macular.org/stargardts.html Stargardt's Disease] - from the American Macular Degeneration Foundation
* [http://www.macular.org/stargardts.html Stargardt's Disease] - from the American Macular Degeneration Foundation
* [http://www.lowvision.org/stargardts.htm Understanding Stargardt's]
* [http://www.theretinasource.com/nditions/stargardts.htm Stargardt's Disease] - from TheRetinaSource
* [http://www.theretinasource.com/conditions/stargardts.htm Stargardt's Disease] - from TheRetinaSource
* [http://www.npr.org/programs/stemcellviewpoints.prentice.html Stem Cell Research NPR Special Report] - from NPR
{{disease-stub}}
 
{{Eye pathology}}
{{ABC transporter disorders}}


[[Category:Ophthalmology]]
[[Category:Diseases of the eye and adnexa]]
[[Category:Membrane transport protein disorders]]


[[pt:Doença de Stargardt]]
[[es:Enfermedad de Stargardt]]
[[fi:Stargardtin tauti]]

Revision as of 14:06, 3 November 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3] Associate Editor(s)-in-Chief: Jyostna Chouturi, M.B.B.S [4]

Synonyms and keywords: Fundus flavimaculatus

Overview

Stargardt disease, or fundus flavimaculatus, is an inherited form of juvenile macular degeneration that causes progressive vision loss usually to the point of legal blindness. Several genes are associated with the disorder. Symptoms, mainly vision loss, typically develop before age 20, and also include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.

Characteristics and symptoms

The main symptom of Stargardt disease is loss of visual acuity, which ranges from 20/50 to 20/200.[1] Other symptoms include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.[2][3] The disease 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.[4]

Genetics

Stargardt disease is associated with several different genes:[citation needed]

  • 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.[citation needed]

Pathophysiology

In STGD1, the genetic defect is manifest in the visual phototransduction cycle. The ATP-binding cassette transporter (ABCA4) is defective and leads to rapid formation of toxic vitamin A dimers (also known as bisretinoids), which then build up in fluorescent granules called lipofuscin in the retinal pigmented epithelium of the retina.[citation needed]

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).[citation needed]

Treatment

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.[5]

Prognosis

The long-term prognosis for patients with Stargardt disease is widely variable although the majority of people will progress to legal blindness.[1]

Stargardt disease has no impact on general health and life expectancy is normal.[6] Some patients are able to drive.[citation needed]

Epidemiology

STGD1 is the most common form of inherited juvenile macular degeneration with a prevalence of approximately 1 in 10,000 births.[2]

Research

Treatment modalities currently under clinical investigation include cell therapy, gene therapy and oral therapies. Anecdotal evidence suggests that new technology called esight may help some individuals with Stargardt who retain some visual function, recover vision.[7]

On November 22, 2010, it was announced that Advanced Cell Technology,[8] now called Ocata Therapeutics, received United States Food and Drug Administration clearance to immediately initiate a Phase I/II multicenter clinical trial using retinal cells derived from human embryonic stem cells (hESCs) to treat patients with Stargardt’s Macular Dystrophy. In September 2011, ACT announced they were beginning the next stage of treatment for SMD, and Dry AMD as the first stage proved to be safe by an independent board of experts.[9] In March 2013, after treating and collecting data on 18 patients, Advanced Cell was given approval to test its stem cell therapy on patients with 20/100 vision.[10] In October 2014, the results of the Phase I/II clinical trial were published in the Lancet.[11]

Gene therapy trials are also on-going. During gene therapy, a working copy of the ABCA4 gene is incorporated in a lentivirus (an inactivated virus which transports the working copy of the gene) and injected into the eye through a subretinal injection. It is hoped that such injection, if performed early enough, could prevent the progression of the disease.[citation needed]

Finally, oral therapies that are being investigated include ALK-001, modified vitamin A delivered orally which prevents the formation of toxic vitamin A dimers in the eye. ALK-001 has completed a phase 1 clinical trials.[citation needed]

ACT, Oxford Biomedica and Alkeus Pharmaceuticals have all received orphan drug designation in the United States for the treatment of Stargardt Disease.[citation needed]

Preclinical research include a new compound that can remove lipofuscin from retinal pigment epithelial cells.[12] The compound drug has been granted orphan drug designation for the treatment of Stargardt disease by the European Medicines Agency.[citation needed]

History

The disease was discovered in 1909 by Karl Stargardt, a Berlin ophthalmologist.[13][14]

In 1997, it was discovered that mutations in the ABCA4 gene cause Stargardt disease. The mutations cause the production of a dysfunctional protein that cannot perform energy transport to and from photoreceptor cells in the retina. The photoreceptor cells then degenerate, causing vision loss.[2]

References

  1. ↑ 1.0 1.1 Yanoff, Myron; Duker, Jay S. (2008). Ophthalmology (3rd ed.). Edinburgh: Mosby. pp. 560–562. ISBN 978-0323057516.
  2. ↑ 2.0 2.1 2.2 Stargardt Disease
  3. ↑ "Stargardt's". Lowvision.org. 1997-03-03. Retrieved 2012-12-05.
  4. ↑ "Stargardt's Disease (Fundus Flavimaculatus)". allaboutvision.com. allaboutvision.com. Retrieved 2015-08-30.
  5. ↑ [1]
  6. ↑ Stargardt Disease from The University of Arizona College of Medicine, Department of Ophthalmology and Vision Science. Retrieved Jan 2012
  7. ↑ [2]
  8. ↑ "Advanced Cell Technology Receives FDA Clearance For the First Clinical Trial Using Embryonic Stem Cells to Treat Macular Degeneration". Advanced Cell Technology.
  9. ↑ "ACT Receives Approval from Data and Safety Monitoring Board (DSMB) to Treat Next Patients in Stem Cell Clinical Trials". Advanced Cell Technology. Retrieved 2012-12-05.
  10. ↑ "Advanced Cell Technology Receives Approval from Data Safety Monitoring Board (DSMB) to Initiate Treatment of Third Patient Cohort in All Three Clinical Trials". Advanced Cell Technology. 2013-03-14. Retrieved 2013-03-17.
  11. ↑ http://download.thelancet.com/flatcontentassets/pdfs/S0140673614613763.pdf
  12. ↑ Julien S, Schraermeyer U (Oct 2012). "Lipofuscin can be removed from the retinal pigment epithelium of monkeys". Neurobiol Aging. 33 (10): 2390–7. doi:10.1016/j.neurobiolaging.2011.12.009.
  13. ↑ Template:WhoNamedIt
  14. ↑ K. B. Stargardt. Über familiäre, progressive Degeneration in der Makulagegend des Auges. Albrecht von Graefes Archiv für Ophthalmologie, 1909, 71: 534-550.

External links

Template:ABC transporter disorders

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