Stargardt's disease

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Classification according to ICD-10
H35.5 Hereditary retinal dystrophy
ICD-10 online (WHO version 2019)

Stargardt's disease , fundus flavimaculatus (engl. Macular dystrophy with flecks ) or Behr syndrome II , also Stargard syndrome (misspelling) is a very rare juvenile macular degeneration , which almost exclusively autosomal - recessive inherited is. In some cases, no genetic cause could be proven. So far, four gene loci involved have been described.

Under the influence of light, visual purple (11- cis -retinal) is converted into visual yellow (all- trans -retinal) in the visual cells , which conjugates with phosphatidylethanolamine (PE) and removes it from the visual cells by a membrane ATPase (encoded by the ABCA4 gene) becomes. Mutations in the ABCA4 gene product lead to the accumulation of toxic breakdown products of visual yellow in the visual cells, the most common cause of Stargardt's disease.

Deposits in the pigment epithelium of the retina are noticeable , which are accompanied by increased auto fluorescence and in some cases are also visible fundoscopy as spotty yellow discolouration of the retina, which is why the disease is also known as fundus flavimaculatus . The diagnosis is usually made with the multifocal electroretinogram .

course

During puberty, visual acuity in the central field of vision deteriorates to around 0.1, so that reading ability can be lost over time. A stable visual acuity of 0.2 to 0.3 over years or decades is also possible. However, there is no risk of complete blindness. The condition is limited to the area of ​​sharp vision while the visual field is intact. The development of an eccentric fixation outside the central scotome in patients with Stargardt's disease takes place in 3 stages: In addition to a central fixation, a change between the central and outside the central scotome can be observed before a permanent shift of the fixation occurs. This changing fixation behavior can explain the patient's discomfort when reading and the difficulty in providing visual aids. Further symptoms are increased sensitivity to glare, color impairment , central scotoma .

therapy

No causal therapy is currently available. According to the current state of knowledge, taking high doses of vitamin A is not advisable, as this could contribute to a worsening of the breakdown of substances in the macula. The use of magnifying optical and electronic visual aids can make everyday life easier for those affected.

In 2012 it was discovered that the active ingredient soraprazan may be able to remove lipofuscin from the retinal pigment epithelial cells. If approved , this would open up a new therapeutic option for the treatment of Stargardt's disease. The drug was granted orphan drug status for the treatment of Stargardt's disease by the European Medicines Agency (EMA) in 2013 . The clinical efficacy has to be proven before approval. A phase II efficacy study with Soraprazan has been running since January 2019 .

There are now new therapeutic options based on embryonic stem cells. The only two patient trials approved by the US Food and Drug Administration (FDA) have been running since April 2011 . Here older patients with dry macular degeneration (AMD) and younger patients with Stargardt's disease are treated with cells of the retinal pigment epithelium (RPE), ie 50–200,000 RPE cells are injected into the retina of one eye. These cells are obtained from embryonic stem cells without destroying an embryo (patented blastomere technology, similar to PGD diagnostics). Over 40 patients have now been treated in four eye clinics in the USA and two in the UK. A peer-reviewed article was published in The Lancet in October 2014 . According to him, the majority of patients had significant improvements in vision. This has led the FDA to approve a series of tests for younger patients as well. In principle, such experiments begin with older patients who already have an advanced disease of their visual performance. The primary concern is the safe use of the therapy. At the end of March 2015, the CHA (pharmaceutical company in South Korea) will also publish the first results from patients treated with RPE cells. The trials are being carried out by the pharmaceutical company OCATA Therapeutics (formerly ACTC) under the leadership of Robert Lanza. A large-scale phase II should take place in May 2015.

history

The disease is named after the doctor Karl Stargardt , who described it in 1909 while working at the eye clinic in Bonn.

Synonyms are Latin Fundus flavimaculatus ( English Macular dystrophy with flecks ) or Behr Syndrome II , according to a publication by Carl Julius Peter Behr in 1920.

Web links

Individual evidence

  1. ↑ Stargardt's disease --- molecular genetics - retinal diseases. (PDF) Retrieved August 15, 2015 .
  2. ^ Symptoms of Stargardt's disease | PRO RETINA Germany e. V. Accessed June 10, 2020 .
  3. ^ S. Julien, U. Schraermeyer: Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys . In: Neurobiology of aging . tape 33 , no. October 10 , 2012, ISSN  1558-1497 , p. 2390-2397 , doi : 10.1016 / j.neurobiolaging.2011.12.009 , PMID 22244091 .
  4. ↑ Special forms of macular degeneration. Stargardt's disease. In: makula-degeneration.net. Retrieved August 15, 2015 .
  5. ^ Orphan designation. In: ema.europa.eu. European Medicines Agency, accessed August 15, 2015 .
  6. ↑ https://www.clinicaltrialsregister.eu/ctr-search/search?query=2018-001496-20
  7. ^ Ongoing Clinical Trials. (No longer available online.) In: OCATA Therapeutics website. Ocata Therapeutics, archived from the original on March 31, 2015 ; accessed on March 28, 2015 (English). Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.ocata.com
  8. ↑ Steven D. Schwartz et al .: Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy . follow-up of two open-label phase 1/2 studies. In: The Lancet . tape 385 , no. 9967 , 2015, p. 509-516 , doi : 10.1016 / S0140-6736 (14) 61376-3 .
  9. ↑ KB Stargardt: About familial, progressive degeneration in the macular area of ​​the eye . In: Albrecht von Graefes Archive for Ophthalmology . tape 71 , 1909, pp. 534-550 , doi : 10.1007 / BF01961301 .
  10. ↑ Stargardt's disease. In: Orphanet (Rare Disease Database).
  11. ↑ C. Behr: The heredodegeneration of the macula . In: Clinical monthly sheets for ophthalmology . tape 69 . Stuttgart 1920, p. 469-505 .
  12. ↑ Ole Daniel Enersen: Stargardt-Behr disease. In: Where named it. Retrieved August 15, 2015 .