Macular degeneration

from Wikipedia, the free encyclopedia
Classification according to ICD-10
H35.3 Degeneration of the macula and posterior pole
ICD-10 online (WHO version 2019)
Visual impression of what it is like with a relative central scotome
Schematic view of the eye

The term macular degeneration or maculopathy covers a group of diseases of the retina of the eye that affect the macula lutea ("yellow spot"). Part of this area is the "point of sharpest vision" ( fovea centralis ), the different cells of which succumb to a gradual loss of function, which, with the decrease in central visual acuity, can in many cases lead to severe visual impairment and blindness .

frequency

By far the most common form is senile or age-related macular degeneration (AMD). Due to the changed age structure , the proportion of people affected by it has increased significantly. AMD is the leading cause of blindness in those over fifty in developed countries . It causes 32% of new blindnesses, followed by glaucoma and diabetic retinopathy with 16% each. It affects 25 to 30 million people worldwide, and around 500,000 new cases occur each year. It is estimated that two million people in Germany suffer from some form of macular degeneration, and around 125,000 in Austria . Congenital and juvenile forms of macular degeneration, e. B. Hypotrichosis with juvenile macular dystrophy .

pathology

The starting point of the disease is not the nerve tissue of the retina, but its support structures, the retinal pigment epithelium (RPE), Bruch's membrane and the choroid . In age-related macular degeneration, there is an almost linear accumulation of lipofuszin in the RPE cells with increasing age . An excessive accumulation of lipofuszin in the RPE leads to an impairment of the function and viability of the cells of the RPE and ultimately to their death. The progressive loss of ever larger areas of the RPE ("geographic atrophy") causes the photoreceptors above it to die off. This affects the ability to see in the central field of vision. According to more recent studies, however, the onset of the disease does not lie directly in the RPE, but results from aging and increasing failure of the choroid, which secondarily leads to the death of the RPE via an insufficient supply of oxygen and nutrients. The smoking , the greatest effect is assigned to the risk of late AMD, in addition to genetic predisposition and high blood pressure is an elevated homocysteine level in the blood (hyperhomocysteinemia) is another risk factor. Defects in the genes CFH , C3 and ARMS2 have been confirmed in several studies as risk factors for the occurrence of AMD, but not for the further course of the disease. The reason for the ingrowth of vessels through Bruch's membrane into the retinal pigment epithelium is due to a shift in the inversely coupled ratio of VEGF / PEDF .

to form

Macular degeneration as a result of high myopia is known as myopic macular degeneration. There are also genetically determined, so-called macular dystrophies such as Best's disease and Stargardt's disease , and so-called “inverse” retinopathia pigmentosa, which initially affects the macula, is also known. Macular degeneration can also be toxic , as a result e.g. B. of chloroquine ingestion for the prophylaxis of malaria or as rheumatism therapy as well as as a result of inflammation (so-called Presumed Ocular Histoplasmosis Syndrome , POHS) occur.

However, the vast majority of sufferers are affected by age-related (or senile ) macular degeneration, Age-related Macular Degeneration (AMD, also ARMD). The term "age-related" indicates age as the greatest risk factor alongside smoking and genetic stress. There are, however, congenital and juvenile forms of macular degeneration, albeit much less frequently. According to the Hamburg professor for ophthalmology Sautter, AMD is divided into two forms: dry and wet macular degeneration.

Dry macular degeneration

The dry ( atrophic ) form accounts for about 80% of the cases, but only 5 to 10% of the blindness caused by AMD. It starts with deposits of so-called drusen , metabolic end products ( lipofuscin ) and impaired blood flow to the choroid. At an advanced stage, it can lead to extensive cell death (geographic atrophy ) of the retinal pigment epithelium. Their progress is usually slow and creeping. Due to the frequent location under the point of sharpest vision, however, it can sometimes lead to rapid loss of vision. A protrusion in the area of ​​the central fovea centralis is noticeable through distorted vision ( metamorphopsia ).

Wet macular degeneration

In wet ( exudative ) macular degeneration, flat vascular membranes form under the retina (choroidal neovascularization , CNV), which tend to bleed. This form of macular degeneration quickly leads to reading blindness. In the final stage, there is an extensive cicatricial transformation of the macula lutea, which leads to the development of a prominent, often sub-bleeding lesion - the so-called "Junius-Kuhnt scar".

In extremely rare cases, central serous retinopathy (RCS) can also develop vascular membranes, which must then be treated like wet macular degeneration.

Functional effects

The damage to the macula can lead to

to lead.

If the person concerned fixes an object, it is no longer possible to see it clearly. So the person concerned can see a clock, but not recognize the time or see a conversation partner, but not his facial features. Age of onset and severity of symptoms vary and depend on the form of the disease.

Since the disease is usually limited to the macula, the external field of vision and thus the possibility of orientation for those affected remain. Even in the dark, those affected usually see relatively well, as the rods outside the central retina remain functional.

Degenerations of the peripheral parts of the retina ( e.g. retinitis pigmentosa, RP ) must be differentiated from macular degenerations .

Diagnosis

High-resolution microscopy examination of human retinal tissue with AMD (ex-vivo)

The Amsler grid test, which can also be carried out by the patient himself, is suitable for an early, rough diagnosis . The other eye is completely covered with the flat of the hand at a distance of about 40–50 cm. If you notice any apparent holes, dark spots or bends in the grid lines, an immediate visit to the ophthalmologist is advisable. In addition, a detailed examination of the central visual field using perimetry is indicated.

Scanning laser ophthalmoscopy (e.g. Heidelberg Retina Tomograph ), optical coherence tomography , fluorescence angiography or high-resolution microscopy examinations are suitable for more sophisticated diagnostics .

Therapies and prevention

In therapy, a distinction must be made between the wet and dry form of macular degeneration. For dry AMD, preventive measures are useful. Nicotine and alcohol should be avoided, they are poison for the eye; long-term stress as well. The phototoxicity of cold white LED lamps and the promotion of macular degeneration could be demonstrated in experiments on rats. UV light should be shielded and a diet with ingredients that protect the eyes is preferred. The moist form can lead to a very rapid loss of vision. That is why ophthalmologists try to push back the vessels that sprout to the macula with intravitreal surgical drug administration (IVOM) or to obliterate them with laser therapy or photodynamic therapy . This is to prevent the disease from progressing. The lost eyesight can only be partially or fully restored with timely anti-VEGF IVOM therapy and only in part of the affected eyes.

Therapy of dry macular degeneration

There is no causal cure for dry macular degeneration. Here it is important to increase the proportion of macular pigment and to prevent oxidative changes from progressing further. Patients are usually given high-dose supplements (10 mg) containing lutein to stop or slow the course of dry macular degeneration. This was confirmed in a study by the North Chicago VA Medical Center (LAST study). Lutein cannot be produced by the body itself and must therefore be absorbed. In a comprehensive article, the taz describes that "old" grains such as einkorn or yellow wheat , although they contain normal amounts of gluten , are probably a bit healthier because they have significantly more lutein, which is therefore immune to AMD.

The second approach is to lower homocysteine ​​levels through vitamins B6, B12 and folic acid. In order to achieve a positive effect, relatively high dosages are necessary. In the WAFAC study, the participants - women over 40 years of age with at least 3 risk factors for cardiovascular disease - took 50 mg B6, 1,000 µg B12 and 2,500 µg folic acid daily for an average treatment period of over 7 years. There were indications that the risk of disease could be reduced with this vitamin B combination compared to the control group, although the positive trend began to show after 2 years and continued until the end of the study. However, the eyes of those affected were not systematically examined; the evaluation is based solely on the clinically diagnosed diseases. In addition, the study's authors believe that the results should be confirmed in other populations of men and women, as there was no recognized method of treating early-stage AMD other than avoiding cigarette smoking until the publication period.

In 2012, it was discovered in monkeys that a new drug can remove lipofuscin from the retinal pigment epithelial cells. This opens up a new therapeutic option for the treatment of age-related macular degeneration and Stargardt's disease , a juvenile form of the disease. The drug has now been granted orphan drug status for the treatment of Stargardt's disease by the European Medicines Agency .

In the event of distorted vision, an ophthalmologist should be consulted in any case, as treatment should be carried out quickly. In about 20 percent of cases, it is the successfully treatable form in which small blood vessels grow into the retina. After an exact diagnosis using fluorescence angiography , which is considered the gold standard for diagnosing wet macular disease and which is an insurance benefit for those with statutory health insurance in Germany, treatment can be started. The optical coherence tomography still has experimental status and has to overcome the hurdles of the quality / usefulness test by the joint federal committee, therefore it is not a cash benefit, see HTA report (Health Technology Report of DIMDI, German Institute for Medical Documentation and Information ). In photodynamic therapy (PDT), a photosensitizing substance (verteporfin) is injected into the arm vein and the area of ​​the newly grown vascular membrane is exposed to a “cold” laser. In this way, the membrane can often be closed - the new vessels become obliterated - which prevents further deterioration in vision.

Newer research approaches

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 and younger patients with Stargardt's disease are treated with cells of the retinal pigment epithelium (RPE), i. that is, 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.

In the summer of 2017, the first results of a study carried out at 18 eye clinics in the USA and Germany were published in which patients with dry AMD were treated with the complement inhibitor (see complement system ) lampalizumab. As with anti-VEGF therapy for wet AMD (see the following section), this is injected intravitreally into the vitreous humor of the eye. In the 42 patients treated monthly, the increase in the affected area in the central retina was slowed down by 20% in the observation period of 18 months compared to the 40 patients in the control group who were treated only for sham. The reduction in the progression of the area with cell death ( atrophy ) was particularly pronounced in the subgroup who are carriers of the risk allele complement factor I (CFI): here the area increase was reduced by 44% compared to the control group.

Therapy of wet macular degeneration

The current standard of therapy for the treatment of the wet form includes the injection of inhibitors of vascular growth , so-called anti-VEGFs (anti- vascular endothelial growth factor , German growth factor inhibitors ) into the vitreous (intravitreal operative drug administration, IVOM). The currently most frequently used anti-VEGFs are the product Lucentis (active ingredient name Ranibizumab ) from Novartis (approval in the EU on January 24, 2007), the product Eylea (active ingredient name Aflibercept ) from Bayer (approval in the EU on December 27, 2011) and, as a more cost-effective off-label treatment, the active ingredient bevacizumab, which has been separated from the Avastin product . Bevacizumab is approved in the Avastin product for the treatment of colon , breast , renal cell carcinomas and other tumors. Approval for the treatment of AMD was granted for Eylea, Lucentis and Macugen (active ingredient name pegaptanib ). Those insured by the statutory health insurance are entitled to the appropriate approved therapy if they are diagnosed and diagnosed accordingly. In many patients it leads to an improvement in vision (of 8 letters on the eye chart). In the first direct comparative studies, ranibizumab, which is around 40 times more expensive, could not be proven to be superior to bevacizumab. A final comparative assessment of aflibercept (Eylea) and ranibizumab (Lucentis) is not possible. In the benefit assessment according to the German Medicines Reform Act, no additional benefit could be determined for aflibercept due to the lack of comparative studies. The aptamer pegaptanib has been approved in Germany for the treatment of age-related macular degeneration since February 2006. It was designed with the aim of being highly specific and high affinity to block the VEGF. This succeeds, but according to the presented results of various studies, the loss of vision is slowed down, but not stopped.

Cortistatins are further inhibitors of vascular growth . A study that appeared in the journal Ophthalmology supported the hypothesis that people who eat fatty fish regularly (at least once a week) are at lower risk of developing age-related macular degeneration. This is about the consumption of fish with a high proportion of omega-3 fatty acids such as salmon , mackerel or albacore . High doses of the antioxidant vitamins C and E, beta-carotene and zinc could effectively slow down the pathological course of macular degeneration.

Visual aids for macular degeneration

Magnifying visual aids are used to improve reading skills at a distance and near. The range of aids ranges from simple handheld magnifiers to magnifying glasses and telescope glasses to electronically magnifying visual aids such as screen readers . Special filter glasses , the so-called edge filters or blue blockers , can also improve vision. Text and image enlargement tools can be helpful for screen activities on the PC. It is important that the visual aids are optimally adapted and tested by a specialist such as outpatient clinics for the visually impaired, study institutions for the blind, specialized ophthalmologic practices or opticians. Orthoptists are also increasingly qualifying in the field of low vision training .

Advice and support in everyday life

Low vision professionals

Low vision specialists support those affected in making the best possible use of existing eyesight through aids or special techniques.

Specialists for orientation and mobility

Affected people can work with experts for orientation and mobility to work out how they can best get around in everyday life, for example in the city or on public transport.

Specialists in practical life skills

Experts for practical life skills show those affected aids and strategies for everyday situations, such as cooking.

Occupational therapy

In occupational therapy , those affected are supported in remaining independent for as long as possible. Everyday activities such as reading or household chores are analyzed together with those affected. Strategies and the use of tools are developed. Occupational therapists can offer support in preventing falls , especially for older people who are at risk of falling and who have macular degeneration . They can clarify how the home furnishings can help prevent falls and recommend practical measures.

See also

literature

  • Ronald D. Barley: AMD Adviser. Age-related macular degeneration: what it means, how to prevent it, how to treat it. Publisher ad manum medici. Germering 2011, ISBN 978-3-928027-34-2 .
  • J. Donald, M. Gass: Stereoscopic atlas of macular diseases. 1997, ISBN 0-8151-3416-9 .
  • L. Wendt: The disease symptom of arteriosclerosis. In: Medical journal for naturopathic treatment. 27, 1986, pp. 137-164.
  • L. Wendt, Th. Wendt: Overfilling the protein reservoir can cause secondary diseases. In: natura-med. 10, 1990, pp. 455-460.
  • Andreas Schaufler: Low Vision. DOZ Verlag, Heidelberg 2012, ISBN 978-3-942873-06-2 .
  • Erika Wegscheider: Age-related macular degeneration and its therapy: a case study from ophthalmology. In: Chinese Medicine. 2012; 2, pp. 88-96.
  • Gerd Antes et al. a .: Therapy of age-related macular degeneration. Evidence report. Bremen / Freiburg 2009 ( hta.uni-bremen.de PDF; 697 kB).

Studies (selection)

Referenced studies on macular degeneration include:

  • JR Evans, JG Lawrenson; Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration (Review) , Cochrane Database of Systematic Reviews. July 2017.
  • EY Chew et al; National Eye Institute (NEI). Age-Related Eye Disease Study 2 (AREDS2): Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: The Age-Related Eye Disease Study 2 (AREDS2) - Randomized clinical trial. May 2013.
  • AY Lee, Butt T, Chew E, et al .: Cost-effectiveness of age-related macular degeneration study supplements in the UK: combined trial and real-world outcomes data. 2017.

Web links

Commons : Macular degeneration  - collection of images
Wiktionary: macular degeneration  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ RD Jager u. a .: Age-related macular degeneration. In: N. Engl. J. Med. 358 (24), (2008), pp. 2606-2617. PMID 18550876 Abstract
  2. ^ Elliott H. Sohn, Miles J. Flamme-Wiese, S. Scott Whitmore, Grefachew Workalemahu, Alexander G. Marneros: Choriocapillaris Degeneration in Geographic Atrophy . In: The American Journal of Pathology . tape 189 , no. 7 , July 2019, p. 1473–1480 , doi : 10.1016 / j.ajpath.2019.04.005 , PMID 31051169 , PMC 6616998 (free full text) - ( elsevier.com [accessed on March 22, 2020]).
  3. ↑ E. Rochtchina, JJ Wang, VM Flood, P. Mitchell: Elevated serum homocysteine, low serum vitamin B12, folate, and age-related macular degeneration: the Blue Mountains Eye Study. In: Am J Ophthalmol. 2007 Feb; 143 (2), pp. 344-346.
  4. ↑ JM Seddon, G. Gensler, ML Klein, RC Milton: Evaluation of plasma homocysteine ​​and risk of age-related macular degeneration. In: Am J Ophthalmol. 2006 Jan; 141 (1), pp. 201-203.
  5. ↑ M. Nowak, E. Swietochowska, T. Wielkoszynski and a .: Homocysteine, vitamin B12, and folic acid in age-related macular degeneration. In: Eur J Ophthalmol. 2005; 15, pp. 764-767.
  6. ^ J. Thornton, R. Edwards, P. Mitchell, RA Harrison, I. Buchan, SP Kelly: Smoking and age-related macular degeneration: a review of association . In: Eye . tape 19 , no. 9 , September 2005, p. 935-944 , doi : 10.1038 / sj.eye.6701978 , PMID 16151432 .
  7. ↑ HPN Scholl, M. Fleckenstein, LG Fritsche, S. Schmitz-Valckenberg, A. Göbel u. a .: CFH, C3 and ARMS2 Are Significant Risk Loci for Susceptibility but Not for Disease Progression of Geographic Atrophy Due to AMD. In: PLoS ONE . 4 (10), (2009), p. E7418. doi: 10.1371 / journal.pone.0007418
  8. ↑ TA Ciulla, A. Harris, L. Kagemann et al. a .: Choroidal perfusion perturbations in non-neovascular age related macular degeneration. In: Br J Ophthalmol. 2002; 86, pp. 209-213.
  9. ↑ JE Grunwald, S. Hariprasad, J. DuPont u. a .: Foveolar choroidal blood flow in age-related macular degeneration. In: Invest Ophthalmol Vis Sci. 1998; 39, pp. 385-390.
  10. ↑ Siegfried Hoc: Age-related macular degeneration: photodynamic therapy stops vision loss. In: Deutsches Ärzteblatt . Retrieved on April 26, 2016 (print edition vol. 97, issue 51–52, December 25, 2000).
  11. ↑ S o you through the Amsler Grid test itself. On: Promacula.at , accessed on: April 23, 2019.
  12. ↑ Information from the Professional Association of Ophthalmologists Germany e. V. (BVA)
  13. ↑ T. Ach, G. Best, M. Ruppenstein, R. Amberger, C. Cremer, S. Dithmar: High-resolution fluorescence microscopy of the retinal pigment epithelium using structured illumination. In: Ophthalmologist. 2010, doi: 10.1007 / s00347-010-2183-y
  14. ↑ G. Best, R. Amberger, D. Baddeley, T. Ach, S. Dithmar, R. Heintzmann, C. Cremer: Structured illumination microscopy of autofluorescent aggregations in human tissue. In: Micron. 42 (2010), pp. 330-335. doi: 10.1016 / j.micron.2010.06.016
  15. ↑ A. Krigel et al .: Light-induced retinal damage using different light sources, protocols and rat strains Reveals LED phototoxicity . In: Neuroscience . tape 339 , 2016, p. 296-307 , doi : 10.1016 / j.neuroscience.2016.10.015 .
  16. ↑ LED lamps: harmful light for the eyes. In: ndr.de . September 17, 2018, accessed May 26, 2019 .
  17. ↑ New study shows: LED light is so dangerous for the eyes. In: tz.de . May 24, 2019, accessed May 26, 2019 .
  18. ↑ S. Richer, J. Devenport, JC Lang: LAST II: Differential temporal responses of macular pigment optical density in patients with atrophic age-related macular degeneration to dietary supplementation with xanthophylls. In: Optometry. May 2007; 78 (5), pp. 213-219, PMID 17478338
  19. ↑ Kathrin Burger: What is the truth about the hype about ancient wheat. In: The daily newspaper. 11th August 2017.
  20. ^ WG Christen, RJ Glynn, EY Chew, CM Albert, JE Manson: Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. In: Arch Intern Med . 2009; 169, pp. 335-341.
  21. ↑ WAFACS study, 2008. TrialResults-center, 2008, accessed on August 1, 2012 (English).
  22. ^ S. Julien, U. Schraermeyer: Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys. In: Neurobiol Aging. 2012. (Epub ahead of print) PMID 22244091 .
  23. ↑ EU / 3/13/1208 . European Medicines Agency website , accessed 29 January 2015.
  24. ↑ Value of optical coherence tomography compared to fluorescence angiography in the diagnosis of age-related macular degeneration (AMD) . (PDF; 376 kB)
  25. ↑ ongoing clinical trials . ( Memento of the original from March 31, 2015 in the Internet Archive ) 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. OCATA Therapeutics website; accessed on March 28, 2015. @1@ 2Template: Webachiv / IABot / www.ocata.com
  26. ↑ 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. Volume 385, No. 9967, 2015, pp. 509-516, doi: 10.1016 / S0140-6736 (14) 61376-3 .
  27. ↑ Brian L. Yaspan et al .: targeting factor D of the alternative complement pathway Reduces geographic atrophy progression secondary to age-related macular degeneration . In: Science Translational Medicine . tape 9 , no. 395 , 2017, ISSN  1946-6234 , p. eaaf1443 , doi : 10.1126 / scitranslmed.aaf1443 , PMID 28637922 .
  28. ↑ U. Bahnsen: Bright spot in old age - More than four million Germans are at risk of old-age blindness. In: The time . No. 11 of March 9, 2006.
  29. ↑ C. Baumgärtel: Label against Off-Label-Use, AMD-Update, Christoph Baumgärtel. (PDF; 11.0 MB) March 29, 2010, accessed June 10, 2011 .
  30. ↑ Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomized clinical trial. on: nature.com , October 1, 2010, doi: 10.1038 / eye.2010.147
  31. ↑ US study: Avastin and Lucentis are equivalent in AMD. In: Deutsches Ärzteblatt . April 28, 2011.
  32. ↑ Benefit assessment procedure for the active ingredient aflibercept (age-dependent macular degeneration) . Website of the Federal Joint Committee , accessed on January 29, 2015.
  33. ↑ See Fish eaters show lower risk of age-related eye disease. reuters.com, July 19, 2010.
  34. ↑ Smallfield, Stacy, Verlag Hans Huber: Elderly people with visual impairments . 1st edition. Bern 2019, ISBN 978-3-456-85781-7 .
  35. ↑ Referenced studies on macular degeneration, accessed on: April 4, 2019.