What is Stargardt Disease?

Stargardt disease is characterised by progressive vision loss that begins in childhood. It is the most common form of inherited juvenile macular degeneration. As it is inherited, it is also referred to as a genetic disease. In Stargardt disease, photoreceptor cells, in the central portion of the retina that allow us to see colour and sharp images, slowly die. There are several forms of Stargardt Disease that differ by gene affected, age of onset, retina pathology, severity and speed of progression.

Stargardt Disease was first described by a German ophthalmologist, Karl Stargardt, in 1909. He identified a recessively inherited macular dystrophy in seven people that went on to be known as Stargardt Disease. It is sometimes referred to as STGD, Stargardt macular dystrophy, juvenile macular degeneration or fundus flavimaculatus. It is diagnosed by clinical assessments that are sometimes followed up with genetic testing.  

Stargardt Disease has an incidence of approximately 1 person affected for every 8-10,000 people. Therefore, it is a rare disease. Signs of Stargardt Disease usually, but not always, start to appear before the age of 20. A loss of visual acuity that is not helped with glasses is the main symptom. This means not being able to see fine details such as when reading, or not being able to see objects in the distance. Side or peripheral vision is usually not as affected as central vision. The range of symptoms experienced and the speed of visual deterioration can vary widely from person to person. Most people with Stargardt disease retain some level of vision and it is rare that someone would become completely blind. 

Symptoms of Stargardt Disease

Stargardt disease is first noticed in childhood or in teenagers. It initially presents as an inability to see fine details or difficulty seeing in the distance. The loss of vision in both eyes can be slow and variable. Spots that are black, hazy or wispy may appear in the central vision of people affected. When changing from bright to dark environments, people may notice that it takes longer for their eyes to adjust to the change. Also, when moving from dark to bright environments, their eyes may be more sensitive to the bright light. 

Visual acuity is affected in Stargardt disease, with vision deteriorating to 20/200 or worse. Visual acuity means the sharpness of vision. Normal vision is 20/20. A visual acuity measurement of 20/200 indicates that a person with 20/200 vision who is 20 feet from an eye chart sees what a person with unimpaired vision can see from 200 feet away. 

Genetic testing may help distinguish the type of Stargardt disease a person has and provide information about the mode of inheritance and risks to other family members.

Examination of the retina by a professional is the usual way a diagnosis of Stargardt is made. A substance called lipofuscin starts to accumulate under the retina and deposits of lipofuscin can be seen as yellowish flecks in the macula or central retina of people affected by Stargardt disease. These flecks of yellow vary widely between people, with different numbers, appearance, colours of yellow and size seen in different people. The shapes of the flecks can be very irregular. The flecks form a ring pattern spreading out from the center of the retina.

A standard eye chart and other tests may be used to assess symptoms of vision loss in Stargardt disease, including:

Visual field testing. Visual fields testing attempts to measure distribution and sensitivity of field of vision. Multiple methods are available for testing; none is painful and most share a requirement for the patient to indicate ability to see a stimulus / target. This process results in a map of the person’s visual field, and can point to a loss of central vision or peripheral vision.

Color Testing: There are several tests that can be used to detect loss of color vision, which can occur late in Stargardt disease. Three tests are often used to get additional information: fundus photography combined with autofluorescence, electroretinography, and optical coherence tomography.

A fundus photo is a picture of the retina. These photos may reveal the presence of lipofuscin deposits. In fundus autofluorescence (FAF), a special filter is used to detect lipofuscin. Lipofuscin is naturally fluorescent (it glows in the dark) when a specific wavelength of light is shined into the eye. This test can detect lipofuscin that might not be visible with standard fundus photography, making it possible to diagnose Stargardt disease earlier.

Electroretinography (ERG) measures the electrical response of rods and cones to light. During the test, an electrode is placed on the cornea and light is flashed into the eye. The electrical responses are viewed and recorded on a monitor. Abnormal patterns of light response suggest the presence of Stargardt disease or other diseases that involve retinal degeneration.

Optical coherence tomography (OCT) is a scanning device that works a little like ultrasound. While ultrasound captures images by bouncing sound waves off of living tissues, OCT does it with light waves. The patient places his or her head on a chin rest while invisible, near-infrared light is focused on the retina. Because the eye is designed to allow light in, it’s possible to get detailed pictures deep within the retina. These pictures are then analyzed for any abnormalities in the thickness of the retinal layers, which could indicate retinal degeneration. OCT is sometimes combined with infrared scanning laser ophthalmoscope (ISLO) to provide additional surface images of the retina.

Genetic Basis of Stargardt Disease

Stargardt disease is one of the rare Inherited Retinal Diseases (IRDs) and so it is a disease of genetic origin. It is usually inherited in an autosomal recessive pattern, which means both parents need to be carriers in order to have a 25% chance of having an affected child. The affected person will need to have mutations in both copies of the gene. Carriers of the condition can have one mutated gene and one unaffected copy, and show no characteristics of the disease at all. Stargardt disease can rarely be inherited in an autosomal dominant pattern, where only one mutated gene from one parent is sufficient to cause the condition. You can read more about inheritance patterns here.

There are different forms of Stargardt disease that differ in the gene mutated, in the time of onset and the symptoms that present as part of the condition.

ABCA4 is the gene most commonly mutated in IRDs. In Stargardt disease, bialelic mutations in ABCA4 are a significant cause, with 400 new cases estimated to occur in the USA each year. A mutation in the ELOVL4 gene is responsible for Stargardt disease-3 (STGD3). Stargardt disease-4 is caused by mutation in the PROM1 gene. An incorrect designation of STGD2 to chromosome 13q34 was corrected when the family in question was correctly mapped to chromosome 6q14, which is the same chromosome as STGD3.

Fundus flavimaculatus (FFM) is an allelic subtype of Stargardt disease. FFM has been linked to mutations in the ABCA4 gene and the PRPH2 gene. The timing of onset of vision loss can be a deciding factor in diagnosing FFM  or Stargardt disease. Stargardt disease is diagnosed if visual acuity loss begins in childhood or the teen years. FFM is the preferred diagnosis if the condition begins much later in life and vision loss is more progressive.  

Given the similarities between Stargardt disease and other IRDs, natural history studies and genetic testing are instrumental in understanding the disease progression and the genetic nature of the diseases. You can find out more about genetic testing in our toolkit here.

Coping with a Diagnosis

Bhavna Tailor- is the CEO and one of the founders of Stargardt’s Connected and has set up the website www.stargardts.org.uk.  She has been involved in raising awareness of Stargardt’s, organising events for the Stargardt’s Community and with fundraising. Here, she shares her experiences and thoughts on coping with her son Ethan’s diagnosis of Stargardt disease. 

You can contact her on stargardts183@gmail.com, and follow the Facebook page- @StargardtsConnected.

Resilience, Perseverance, Never Give Up

Being a primary school teacher, I always teach my class to be resilient, persevere, to rise to challenges and not to give up. It was now time for me to take on my own advice and practise as I preach. Since his diagnosis, I have not stopped Ethan doing what he wants to do. He plays the guitar, piano, ice skates, swims, runs, plays badminton and does all of these very well.

I told Ethan: “Do not let Stargardt’s stop what you want to do. You can be what you want to be. I will not use Stargardt’s as an excuse for you not doing well – you can achieve and aspire despite vision loss. What you do need is hard work, determination and a can-do attitude”. 

I treat him just like I did before his diagnosis. He is expected to help around the house and do his best in his school work. My expectations are high and I know I am tough on him. But I know life is hard and wrapping him up in cotton wool would do no one any favours. I have had to build my own resilience too- watching your child go blind is cruel, helpless and heart-breaking.  Since his diagnosis, I have had to face many other separate challenges and there are times where I am not sure how I can carry on. But you do because you have to and there isn’t an option- you keep going and build on the strength and resilience you never thought you had.

Adaptability

As humans, we are naturally good at adapting and I see vision loss as a classic way of demonstrating this. I remember reading somewhere that if your motorway exit is closed, you don’t just stop the car.  You drive on to the next exit. It may be longer but it is doable and will still get you where you want to be. I had told Ethan when he was diagnosed that although prescription glasses won’t help him see better, he will have other tools to help him such as magnifiers to assist him.  At school he has modified texts and a magnifier to help him access the curriculum. He has learnt to touch type and made the decision himself to learn Braille- he told me I may need it in the future and want all the skills I can have to help me as my eyesight gets worse. Being a progressive condition, I know there will be many more adaptations we will have to make and will have to learn to take it as we come.

Positivity

Ethan is one of the most happy, positive people I know. He has delivered 2 whole school assemblies in his school about Stargardt’s, and tells me himself that he doesn’t want Stargardt’s to get him down. Ethan is still Ethan – the same cheeky boy he was before his diagnosis.  He is a very sociable child and have not yet met anyone else who can make friends so easily! There are of course times where he has cried about his vision loss. His eyesight continues to deteriorate, and he wept in my arms not too long ago, saying, “I don’t want to stop seeing you Mummy”.  Yes Stargardt’s is a cruel, heartless thief but I won’t let it steal our happiness and who we are. Stargardt’s has rudely entered our life uninvited, but we are the same family- we can be still be daft, silly and have lots of fun together. 

Visual memories

Building visual memories has been a really important part of our journey.  We have been lucky to go on some wonderful holidays, but building visual memories goes beyond that. It is about life experiences and our weekends and school holidays are full of activities such as visits to museums, playdates, parks, going to the cinema and cooking. Perhap’s Ethan’s biggest loss is knowing that he won’t be able to drive when he is older. His love and knowledge of cars has always been apparent since he was a very young child. But ever the optimist, Ethan said, “Please can I experience driving now as I won’t drive when I am older”. He goes Go-Karting regularly and has been fortunate enough to even race and train with the World Champion Go-Karter!   We live in the moment and make the most of every opportunity.

Having a strong network of friends/family

Ethan’s diagnosis shook us to the very core, and in my many tearful moments, I often wondered, how am I going to get through this? 

I have been very fortunate and blessed by being surrounded by the most wonderful friends and family who have seen me at my most vulnerable and weakest and helped to lift me when I couldn’t pick myself up.  Having the opportunity to express your feelings to a family member, friend or even a counsellor is vital to be able to get over any challenge. Talking definitely helps and is an important part of therapy.

Meeting other visually impaired people

This has perhaps been the most empowering – meeting other people who are visually impaired and seeing how well they get on despite the daily challenges they may face.   This has helped me deal with Stargardt’s significantly and I know it has been really useful for Ethan to also meet them.

When Ethan was diagnosed, I had wondered if there was life after vision loss and the resounding answer I can confidently say is yes of course.

Daily Life with Stargardt Disease

I can not believe how one sentence can change your life so dramatically but this was to happen to our family one fateful day in September 2015.  We had been holidaying in St Ives, Cornwall in the Summer and I noticed that my then 7 year old son Ethan was struggling with distance vision so I made a mental note of getting his eyes checked once we were back. I remember dotingly looking at my 2 children one evening whilst on our holiday thinking my life was perfect for that moment at least. Little did I know that in a few weeks, our lives would be turned upside down and the walls would come crashing down.

I decided to make an Opticians appointment for Ethan and there I was told that he wasn’t reading the sight chart very well but he didn’t have a prescription. Baffled by the comment I decided to go for a second opinion and went to another High Street Optician who made the same comment. I remember my anxiety rising as I wondered what this meant.  Surely if you can’t see properly, you just need glasses to rectify it I thought. I was perplexed and so worried that I decided to make a private appointment to Moorfields Eye Hospital with the recommendation of the Optician. Ethan underwent lots of imaging, and testing and two weeks later I was given the heartbreaking diagnosis:

“Your child has Stargardt’s disease which means he is losing his eyesight and unfortunately there is no current cure or treatment for the condition.” My heart shattered as I heard those words and stood there in disbelief. It was a condition I had never heard of and it was to change our lives forever. How could my beautiful, healthy and happy-go-lucky 7 year old be going blind?  How would he live his life without his eyesight? How would he make friends and continue his education? Was there life after vision loss?  I had never heard of the condition and it had now rudely entered our lives uninvited and it was here to stay. 

Devastation and shock were the main emotions I felt for the first few months after the diagnosis. The pain that I was feeling was intolerable but I also wanted to desperately find a light in the darkest days- I wanted to do something positive, find a positive.  I remember frantically searching on the internet looking for inspiring people who were visually impaired. Could you lead a happy life if you were blind? That’s all I had ever wanted, for my children to be happy. 

Children have a funny way of surprising you and rising from the face of adversity. I remember Ethan coming up to me soon after his diagnosis and saying, “Mummy, everyone has problems, this is one of mine.” I wept silently and secretly, but kept a brave face in front of him, and was amazed at the maturity and braveness he was demonstrating. 

Yes Stargardt’s is a cruel, heartless thief but I won’t let it steal our happiness and who we are. Stargardt’s has rudely entered our life uninvited, but we are the same family- we can be still be daft, silly and have lots of fun together. When Ethan was diagnosed, I had wondered if there was life after vision loss and the resounding answer I can confidently say is yes of course.

I can not believe how one sentence can change your life so dramatically- but the impending darkness has not overshadowed us.  Stargardt’s has made us find a strength we never thought we had. Stargardt’s has made us meet the most inspiring people we could only dream of meeting. Stargardt’s has made us experience human kindness and generosity from strangers, friends and family alike. Yes, Stargardt’s came uninvited but we won’t let it break our spirit…

Bhavna Tailor- is the CEO and one of the founders of Stargardt’s Connected and has set up the website www.stargardts.org.uk.  She has been involved in raising awareness of Stargardt’s, organising events for the Stargardt’s Community and with fundraising. 

You can contact her on stargardts183@gmail.com, and follow the Facebook page- @StargardtsConnected.

Where Are We Now?

At present there is no cure for Stargardt disease, however there are several research studies ongoing working to find treatment. While progression cannot currently be stopped, there are ways that people affected by Stargardt disease can attempt to slow its progression.  

  • Wearing sunglasses to protect the eyes from UVa, UVb and bright light may be of some benefit.
  • Animal studies have shown that lipofuscin, the fatty substance that builds up under the retina in Stargardt patients, can be increased even more by taking excessive amounts of vitamin A and beta carotene, as well as a toxic vitamin A derivative called A2E. Therefore, it is typically recommended that people with Stargardt disease avoid these vitamins. 

Where Are We Going?

Stargardt disease is a genetic disease and some of the genes and mutations involved have been identified by years of research. Knowing the genes and mutations has led to better diagnosis through genetic testing and potentially therapies, such as where the affected genes could be corrected or replaced, i.e. gene therapy. You can search for clinical trials around the world using www.clinicaltrials.gov, or you can read here about clinical trials related to IRDs.

 

Understanding how the disease develops and progresses is crucial in developing drugs that could halt the buildup of lipofuscin or death of the photoreceptors. Vitamin A is one of the molecules that can contribute to the build up of lipofuscin in Stargardt disease. One study is looking at a synthetic version of vitamin A that is not easily converted into lipofuscin and so may slow its buildup. So far it has been successful in animal models and is being tested for safety in humans in general prior being tested for effectiveness in people with Stargardt disease.

In gene therapy, genetic material is inserted into cells to compensate for abnormal genes or to make a beneficial protein in order to treat a disease. The most common type of gene therapy being investigated for the treatment of IRDs in clinical trials is gene augmentation therapy. Many IRDs are caused by specific gene mutations which lead to reduced production or loss of the function to the proteins they make (so-called “loss-of-function” mutations). With gene augmentation therapy, a normal functioning version of the disease-causing gene is inserted into the affected retinal cells helping them to produce sufficient levels of the protein, restoring its normal function and preventing cell death. Gene therapy studies for Stargardt disease focus on repairing or replacing the ABCA4 gene. The ABCA4 gene is quite large and caused difficulties in delivering the gene to the retina. However, studies are ongoing. You can read more about clinical trials for IRDs here.

As Stargardt disease is characterised by loss of cells in the retina, some studies are attempting to replace the dead or dying cells with healthy cells. Stem cells are undifferentiated immature cells that are capable of self-renewal and can differentiate into specialist cell types, including RPE and photoreceptor cells. The application of stem cells to replace or repair damaged cells in the diseased retina, potentially restoring visual function, is an important area of ongoing research IRD drug development in general .

There are different types of stem cells that are being evaluated as potential treatment of IRDs and you can read more about them here. Caution must always be used when looking for human research studies and the guidance of a clinical professional is advised.

 

Access to Treatments

Access to treatments is a universal issue, with the reportedly high prices of many new treatments being a potential barrier globally. While treatments using new technologies such as gene therapy may have a high price tag at first look, the fact remains that some could result in a once-off treatment that will potentially prevent vision loss for at least 10 years, if not for life. It is of utmost importance, therefore, that patient groups in every country have the right information and the right advocacy tools to ensure that such life-changing treatments are made available in their countries.

Information that would help illuminate the benefits of such a treatment includes:

  • the number of potential patients in each country, which requires access to genetic diagnosis. Please see our Red Alert Toolkit for more information http://www.retina-international.org/toolkit-redalert
  • the impact of these conditions on the life of the patients and of their families
  • the impact of these conditions on society, including the everyday care needs of someone with visual impairment from young children to adults; the potential effect on the education and employment of the patient and their carers; the additional supports supplied by health care providers, health systems or charity groups.

Retina International see the need for such information to be gathered and we are actively engaged in projects to this end. If you would like to contribute information of this kind, we would love to hear from you. Please get in touch info@retina-international.org. and you can visit our section on Advocacy for more information on the need for data on impact.

While treatments such as gene replacement therapy are revolutionary, they are still quite a way from being universally available for all types of IRDs. While we await new treatments, individuals with Stargardt disease and other IRDs can access appropriate visual supports to ensure they can live as fully and as independently as possible. Please see our sections on Coping with a diagnosis and Life with Stargardt disease for more information.