What is macular dystrophy?
Macular dystrophy is a disease of the retina, which is limited to the area of the macula (site of acuity) and leads here to a degenerative (destructive) process. It is hereditary and mostly affects both eyes and thus causes characteristic symmetrical, bilateral changes in the retina. However, macular dystrophy can also affect only one eye.
Usually the disease begins between the first and the third decade of life, the patients are usually under twenty years old. However, in individual cases the disease does not appear until the age of fifty. In the course of the degeneration, there is a progressive loss of vision, visual acuity (visual acuity) becomes less and less, but can remain unimpaired for a long time.
The disease ultimately progresses differently with each patient. There are different forms of macular dystrophy, each characterized by a different course of disease, onset and prognosis. Most of the patients suffer a slowly progressive and irreversible loss of their central vision.
Which forms of macular dystrophy are there?
The most frequent form of macular dystrophies is Stargardt’s disease, also called familial juvenile macular dystrophy. In this form of macular dystrophy changes in the pigment layer of the eye can be seen already in the young years of life. These changes change with time into a scarring stage, whereby the original function of nutrition and removal of waste products of the retina is completely lost.
Stargardt’s disease is inherited autosomal-dominantly, hence the term “familial”. The “juvenile” refers to the fact that the disease begins early in life, usually in the first decade of life. However, there are also cases in which the disease does not begin until later, but this is rather rare.
In the beginning, the vision of the affected person deteriorates rapidly and usually drops to about ten percent. Afterwards, the process stabilizes at this level and it is quite possible for patients to continue to actively perceive their surroundings, orient themselves or even read with strong visual and reading aids. The sensitivity to glare is greatly increased, so that those affected are advised to wear sunglasses.
Night vision, on the other hand, is possible relatively unchanged. The differentiation of colors, however, becomes difficult or even impossible, very dark and very light colors are no longer distinguishable for patients. Unfortunately, in a small percentage of patients, this persistence of the disease is not noticeable and Stargardt’s disease continues to progress.
The second most frequent form of macular dystrophy is the vitelliform macular dystrophy, also called Best’s disease. It is an autosomal-dominant inherited disease pattern which typically becomes noticeable in the second decade of life. It begins to form a yellowish round bulge at the back of the eye in the retina, more precisely in the area of the macula.
This is also where the term “vitelliform” comes from, which means “egg yolk-like” in Latin. This relatively sharply defined elevation does not further impair the central vision of the affected person in the early stages. Only as the disease progresses does the extent of the changes and the severity of the visual impairment increase.
The yellowish bulge, which is ultimately also a pigment deposit, increases in size and the pigment substances it contains are converted. As a result, light can no longer reach the retina and the patient can no longer perceive his central visual field (i.e. the affected area of the macula) in this eye. The periphery, i.e. the parts of the retina that are not centrally located, remain unaffected by the pathological process and thus vision at the edge of the visual field is still possible.
In some cases there is also a new formation of vessels in the choroid of the eye. Best’s disease can affect a single eye, but can also occur on both sides. In Best’s disease, the disease usually begins in early childhood, usually in the first decade of life.
However, its course and progression varies greatly from individual to individual and is difficult to predict. In Best’s disease, the central vision in the macular area is also affected, while the periphery of the retina does not lose its function even later.As with Stargardt’s disease, patients’ sensitivity to glare increases and colors become increasingly difficult to recognize and distinguish. A single eye or both may be affected.
In Stargardt’s disease, the disease typically begins relatively suddenly for those affected with an acute loss of visual acuity (visual acuity). This loss of visual acuity increases over time, although the speed and extent of the loss can vary greatly from patient to patient. The loss of visual acuity can be considerable in a few weeks or the process can take several years.
As a rule, it can be said that the later the disease sets in, the slower its progression is. The loss of visual field is limited to central vision, since only the macula is affected. The peripheral areas remain unchanged during this time.
After the initial drop in central vision, it stabilizes at a low level of usually about ten percent. Both forms of macular dystrophy must be diagnosed by an experienced ophthalmologist. In addition, it is extremely important to arrange for a family tree analysis, since both cases are inherited diseases.
During the ophthalmologic examination first the visual acuity is determined, i.e. the visual acuity of the eye. A visual field measurement (a perimetry) is also helpful to enable the exact localization of the failed retinal areas. Other imaging techniques such as optical coherence tomography (OCT), autofluorescence and/or fluorescein angiography are also important to assess the course of macular dystrophy.
In case of Best’s disease the round bulge in the pigment epithelium, which is filled by a dense material (the pigment), can be recognized well in the beginning by optical coherence tomography. In the course of the disease, this pigment is then increasingly broken down and converted. In the late stage of Best’s disease, atrophy, i.e. atrophy of tissue in the macular region, occurs.
With Stargardt’s disease, the examination of the ocular fundus reveals an increasing destruction and a decomposition of the pigment epithelium in the area around the macula. This typical examination finding is also called “bull’s eye” because of its appearance. There are numerous small yellowish deposits and spots, which can be distributed up to the edge of the retina.
However, the optic nerve itself remains unaffected. In later stages of Stargardt’s disease, there is atrophy of the pigment epithelium in the central to middle areas of the retina. Here, too, the formation of new vessels is possible.
In addition, an electrophysiological examination of the eyes must be performed. This consists of several individual examinations, each of which provides a result characteristic for macular dystrophy. Because especially in the early stages of macular dystrophy the findings of the electrophysiological examination are not very pronounced and therefore not 100% clear, a molecular genetic analysis should be performed additionally.
This can then especially look at the affected gene sections (in Best’s disease the VMD2 gene, in Stargardt’s disease the ABCA4 gene) and determine possible mutations here.
- Visual field examination
- Examination of visual acuity (visual acuity)
Since macular dystrophy is a congenital disease, it has not yet been possible to develop a causal therapy. It is not recommended to take high-dose vitamin A preparations as there is evidence that these could contribute to a deterioration of the metabolism in the eye and thus accelerate the changes in the macula.
Those affected are advised to have so-called edge filter lenses made. These filter out the blue light and can thus protect against too much light entering the eye and reduce glare. In rare cases of Best’s disease, it may be considered to treat the possible formation of new blood vessels in the choroid of the eye with appropriate anti-VEGF injections.
There are a number of studies and case reports in the literature, especially from younger patients, in which the formation of new blood vessels has been successfully slowed down by this therapy. Unfortunately, even this approach cannot change the destruction of the macula itself. The current research tries to develop a stem cell therapy with which it could be possible to treat the cause of macular dystrophy.Participation in self-help groups is often described as very helpful for the patients.
These groups enable an exchange between patients and their relatives and thus provide great psychological support. There are also various aids that can make everyday life easier for patients and enable them to maintain their independence as far as possible. The causes of macular dystrophy could not yet be completely researched according to current knowledge.
One of the most common forms of macular dystrophy, the Best’s disease, is an autosomal dominant inherited disease. This means that the cause lies on a gene and therefore it is sufficient if one of the two parents has the disease to have inherited it to the patient. The changes are specifically on the VMD2 gene segment, which in turn is responsible for the production of the protein Bestrophin 1.
This protein is most likely responsible for regulating the conductivity of the retinal pigment epithelium. This pigment epithelium is responsible for nourishing the nerve cells and at the same time for recycling the degradation products in the eye. If mutations in the VMD2 gene lead to a functional impairment of the pigment epithelium, the regulated process of formation and degradation in the eye and especially at the retina is no longer guaranteed and the vision is increasingly impaired or even completely lost.
The most frequent form of macular dystrophy, Stargardt’s disease, is also caused by a gene mutation. In this case the autosomal recessive (both parents have to pass on a sick allele to the affected person) inherited defect is found on the ABCA4 gene. This gene is comparatively large and of complex structure.
It is responsible for the production of various other proteins needed for the transport of certain products. Depending on where exactly on the ABCA4 gene the mutation is located, Stargardt’s disease can develop to varying degrees. However, there is also a very rare autosomal dominant form of Stargardt’s disease.
In this form, too much of the brownish-yellow degradation product lipofuscin is produced over time and accumulates in the eye. In all probability a disturbed transport is the cause of macular dystrophy. The prognosis of macular dystrophy depends on the form of the disease.
In case of Stargardt’s disease after the initial sudden and strong deterioration of vision the process usually stagnates and the vision stabilizes on a low level of about ten percent. Thus, macular dystrophy is a genetic disease. It is therefore in principle already present at birth, even if it only becomes noticeable later in life for the affected person.
Unfortunately, medical research is not yet able to offer effective gene therapies which have few side effects and are medically justifiable, so that macular dystrophy is still an incurable disease. Only the accompanying symptoms can be tried to be made more tolerable with aids such as sunglasses or edge filter lenses.
