Hereditary retinal dystrophy – a disease that takes the eyes off the youngest

Hereditary retinal dystrophy is the leading cause of hereditary blindness in the Western world and the second leading cause of reduced visual acuity in children. [1] What is hereditary retinal dystrophy? What are its symptoms?

What is hereditary retinal dystrophy?

Inherited Retinal Dystrophy (IRD) is a group of diseases associated with abnormal function of retinal cells and tissue degeneration, with consequent progressive impairment of vision function, up to its loss. It is estimated that hereditary retinal dystrophy affects 1 in 1500-2000 people in the general population, half of whom are people with retinitis pigmentosa. Therefore, they are extremely rare diseases, little known even among ophthalmology specialists, referred to as “orphan diseases”, because usually there are no clear diagnostic criteria, standards of treatment and treatment methods developed for them. [2]

Hereditary retinal dystrophy is passed down from generation to generation – it can be inherited from both parents, the same parent, or it can occur sporadically. The cause of this ailment is the mutation of at least one gene that is not working properly. Some types of IRDs are caused by a single mutation in an identified gene, while others can be caused by many different mutations. There are believed to be over 260 genes that account for 60 to 70 percent of the disease. all cases. [3]

This disease affects people of all ages, from birth to old age, however, it is most often diagnosed already in children and young adults. Babies with hereditary retinal dystrophy may not show any abnormalities shortly after birth. Only with time, parents may notice that the child, for example, stumbles over objects, does not notice details or avoids dark places, which may be the first symptom of a progressive disease.

Hereditary Retinal Dystrophies – Classification

IRDs can be classified according to various clinical or genetic criteria, including based on the originally affected retinal cell (rods, suppositories, retinal pigment epithelium (RPE), bipolar cells or ganglion cells), ophthalmic results and / or the affected gene detected by genetic testing. [4] The most common hereditary retinal dystrophy is retinitis pigmentosa (RP), which affects the photosensitive cells of the retina (rods and cones) and leads to a gradual, progressive decrease in vision, especially at night (noctalopia), and over time – until loss of vision. [5] Other diseases included in the group of hereditary retinal dystrophies include:

1. Leber congenital amaurosis (LCA) – a very rare disease that affects 1 in 10 people. people. [6] [7] [8] Mutations of the RPE65 gene lead to reduced or no activity of RPE65 all-trans-retinyl isomerase, which blocks the retinoid vision cycle (conversion of all-trans-retinol via 11-cis-retinol to 11-cis-). retinal) and causes visual deterioration and ultimately blindness. The first symptoms may appear after birth and in the first months of life they can cause a significant reduction in visual acuity.
2. Cone-rode dystrophy (CRD) – a disease caused by a mutation in the GUCY2D gene that leads to early visual disturbances. Its first symptoms include: decreased visual acuity, nystagmus and loss of color perception. [9] 
3. Juvenile macular degeneration (JMD) – also known as total color blindness. In its course, the function of the cones – photosensitive cells responsible for color vision is impaired. A person with juvenile macular degeneration is unable to see the difference between some or all of the colors, depending on the subtype of the disease. 
4. Stargardt’s disease – This is the most common central retinal dystrophy caused by a mutation in the ABCA4 gene. As the disease progresses, photoreceptors and retinal pigment epithelial cells are lost, resulting in decreased visual acuity and impaired color vision. It usually appears between the ages of 7 and 12. [10] 
5. Usher syndrome – an autosomal recessive syndrome that leads to gradual loss of vision and sensorineural hearing. The onset of the disease is most common in early childhood. There are three main types of this disease, differing in the severity of symptoms and the age when the first symptoms appeared. 
6. Choroideremia (CHIM) – This disease affects 1 in 50 people. Its first symptoms include: night blindness and light intolerance. The vast majority of CHM patients are male, although a small number of women may also suffer from CHM symptoms.

Symptoms of hereditary retinal dystrophy

The symptoms of an IRD can vary widely, develop at different rates, and depend on the type of mutation and the type of inheritance. Even the same IRD can work differently from person to person. This is one of the reasons why patients are sometimes misdiagnosed over the years.

I remember my childhood when I went to the ophthalmologist – as a six-year-old I went to the ophthalmologist, but then with a squint. It was not until the age of nine that I first went to an ophthalmology clinic and was diagnosed there as a person suffering from retinitis pigmentosa. It didn’t mean anything to me then, although I heard the name (…) It wasn’t until I was 18 when I found out what this disease is associated with – that the loss of vision will definitely be the end – says Maciej Białek, teacher, historian.

For example, the most common symptoms of pigmentary retinitis are loss of clear vision after dusk or in poor lighting conditions, i.e. night blindness.

For me, as a teenager, the disease most often manifested itself in the form of discomfort in the evening. Then the phenomenon of worse vision actually appears, because the accommodation of the eye is worse, especially on a cloudy day, in the evening. (…) The bigger problem started when I was in my twenties and I started doctoral studies – at that time I stopped seeing black print.

Over time, there are also defects in the visual field, which are caused by the gradual degeneration of the retina. In some people, depending on e.g. from individual tendencies, there may also be insular changes, central scotoma or a narrow field of vision (so-called tunnel vision). Other possible symptoms include:

1. difficulty seeing in bright light 
2. loss of sensitivity to light 
3. loss of sharpness or clarity of vision 
4. repeated uncontrolled eye movements (nystagmus) 
5. color blindness [11] 

What treatments and therapies are available for inherited diseases of the retina? Modern methods of diagnosis and treatment

The therapeutic path of any person with suspected or diagnosis of hereditary retinal disease should begin with an ophthalmologist visit, followed by urgent genetic diagnosis and genetic counseling, including genetic risk, family planning, and available experimental gene therapies.

The basic diagnostic methods of hereditary retinal diseases include, among others visual field and retinal imaging tests in an ophthalmologist’s office. Diagnostics may also include electroretinogram, fundus autofluoresence and optical coherence tomography. In some cases, already at this stage, the doctor is able to suspect the diagnosis and refer to urgent genetic diagnosis in order to make a causal diagnosis with the indication of genes and causal mutations.

Although there is currently no effective treatment for every form of the disease, many centers are researching gene therapies that may prove to be a breakthrough in the future. These therapies are not a cure for the disease, but a means of controlling its progression. They target the exact cause of the disease, i.e. the faulty gene, and eliminate the possibility of further mutations. According to Christina Fasser, Swiss international activist and president of Retina International, “we may be the last generation to go blind due to an inherited retinal disease.” [12]

Early diagnosis is extremely important so that, as soon as treatment is possible and available in a given case, the development of the disease is stopped as soon as possible in young patients. Early diagnosis can significantly improve quality of life and gives patients early access to a team of experts, including ophthalmologists, optometrists, geneticists who are able to help. Recognizing the problem early can also help you participate in a clinical trial.

Genetic diagnosis – more important than ever

Genetic tests are performed on DNA samples, usually blood or saliva, and involve DNA sequencing to identify mutations. Most genetic tests involve a panel of several hundred genes known to be mutated in hereditary retinal diseases. [13] The tremendous development of genetic diagnostics has made clinical diagnosis of many diseases, including hereditary retinal dystrophy, faster and more accessible than even 10 or 20 years ago.

Currently, even the entire human genome can be analyzed in a short time and the damaged gene can be found. [14] Thanks to genetic testing, even in 80% of patients can identify the mutation responsible for the development of the disease, and knowing the genetic cause of the ailment, the patient has the opportunity to participate in clinical trials. Genotyping also informs the patient’s family about the risk of inheritance or transmission of the disease. [15]

Diagnosis: Hereditary Retinal Dystrophy – Where Can I Get Help and Support?

Like any disease that affects daily life and functioning, hereditary retinal dystrophy is a difficult experience both medically and psychologically.

I thought it was a sentence that kicked me out of my professional work, social life, the world of culture and literature. (…). It destroys self-esteem, self-confidence, one ceases to be a person standing on his own legs. (…) A man wonders whether he will cope with all this, whether it is worth fighting against or whether he can stay within four walls.

Gradual loss of vision or deterioration of vision can cause anger, depression or despair. This is completely normal – changing your current life and negative emotions can have a significant impact on mental health, which, unfortunately, is often neglected. The data collected by the Retina AMD Association shows that over 87 percent. of the respondents with hereditary retinal dystrophy have never used psychological help, and it is absolutely necessary – not only for the patient, but also for his family. [16]

Receiving a diagnosis can be a very emotional experience, especially for the parents of the youngest. Over time, the disease can change the life and functioning of the whole family – it determines all plans and activities of relatives and causes parents to live under constant stress and anxiety. It is not uncommon for one of the parents to give up their professional activity in order to take care of the child. On their own, they often look for help not only in Poland, but all over the world.

In difficult and critical situations, we must learn to ask for help. Today I am a happy person, professionally fulfilled, having friends, a loving wife, traveling around the world, getting to know the world and people. I don’t look at my disability – life is so fast, so varied that we don’t really think about our condition every day.

Patient statements: Maciej Białek, teacher, historian

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