Stargardt Disease

Overview

Stargardt disease is a genetic disorder that affects the macula, the small, central portion of the retina, leading to a progressive blurring of central vision over time. Vision loss typically begins during childhood or adolescence, with symptoms similar to age-related macular degeneration (AMD); in fact, since the symptoms being at a younger age, Stargardt disease is sometimes called “juvenile macular degeneration.” Taking its name from Karl Stargardt, the German ophthalmologist who described the disease in the early twentieth century, the disorder affects somewhere between 1 in 8000 to 1 in 10,000 individuals.[1]

In most cases of the disease, the gene ABCA4 is mutated, while in a minority of cases it is the gene ELOVL4. Both are responsible for making important proteins that play a role in phototransduction, the process whereby incoming light is converted into electrical signals that are eventually interpreted by the brain. When ABCA4 is mutated, the protein it controls is no longer able to effectively remove a toxic substance called lipofuscin from the retinal pigment epithelial (RPE) cells. Lipofuscin builds up over time and is a natural by-product of phototransduction; when it is not cleared from the RPE cells, those cells are no longer able to provide support and nourishment to the photoreceptors cells, which absorb light and are the central mechanism of phototransduction. It is primarily the cone photoreceptors that are affected, and since these are housed in the macula, central vision deteriorates while peripheral vision remains, in many cases, unaffected.

In the minority of patients with a mutated ELOVL4 gene, clumps of proteins develop and interfere with the photoreceptors, leading to the gradual death of those cells and a progressive loss of central vision.

Content on this page was written by Dr. Chad Andrews and Dr. Mary Sunderland, and was most recently updated on August 23, 2018. An earlier version of the content was approved by Dr. Nupura Bakshi.

Symptoms and Diagnosis

The macula is responsible for detailed, central vision, and is important for activities such as reading, driving, and distinguishing faces. As a result, Stargardt disease is often detected when the patient experiences difficulty with these activities, or with similar activities that involve seeing fine detail and colour.

As the disease advances, a person’s vision will become less distinct, and a blind spot in the central visual field may develop and grow. By mid-life, many affected by the disease are legally blind as a result of central vision loss, but peripheral vision is in most cases minimally affected and remains throughout life; the perception of colour often diminishes during the later stages of the disease.

Early stages of Stargardt disease may also be accompanied by a slight blurring in the field of central vision. Such blurring can be detected via an eye test, but also at home using an Amsler Grid, a simple visual tool that can help you see distortions in your visual field.

Images showing an Amsler Grid comparison: the left image shows how a healthy eye would see an Amsler Grid; the right image shows how an eye affected by the early stages of AMD may see a grid, involving a characteristic distortion with both vertical and horizontal misalignment. Image taken from the Canadian Association of Optometrists.

 

Eye care professionals will sometimes use an Amsler Grid as well, since it is a straightforward and reliable way to detect anomalies in central vision. Other tests that may be used during an exam include the following:

  • Fluorescein Angiogram: this test uses a dye called fluorescein to exam the back of the eye. The dye is injected into the arm and recorded by a camera as it passes through the blood vessels at the back of the eye. Patients with Stargardt disease usually show a “dark choroid effect” due to the buildup of lipofuscin under the retina, which makes the background of the retinal image appear darker.
  • ERG (electroretinography): this is a test that measures the electrical responses of the retina to light, evaluating responses of both rod and cone photoreceptors. Although both rods and cones may be affected in people with RP, the most marked changes early in the disease are in the rod cells; this characteristic pattern helps diagnose the condition. The ERG test involves staying in a darkened room for 30 minutes, with drops put into the eye or eyes being tested. A special contact lens or gold-foil electrode is then placed on the eye or lower eyelid, and the eye is exposed to flashes of light.
  • Visual field test: this exam is designed to detect, measure, and monitor blind spots in vision. It involves looking into a device that emits flashes of light, with the patient asked to indicate which flashes can be seen. The flashes that are not seen are recorded. This gives a measure of how much vision is affected.

Genetic testing and counselling: Genetic testing and genetic counselling are an essential part of the diagnostic process. It can help determine the gene or genes that have been mutated, as well as the hereditary factors that are involved.

Read Our Clinical Trials Guide

Existing Treatments and Standard of Care

As of today, there are no treatments for Stargardt disease. The Foundation Fighting Blindness funds leading research into the disorder and encourages people living with this disease to enrol in the FFB Patient Registry (see below), which will keep you updated on emerging clinical trials and opportunities to participate.

Clinical Trials

Clinical trials are essential to the scientific process of developing new treatments: they test the viability and safety of experimental drugs and techniques, called “interventions,” on human beings. While there is no guarantee that enrolling in a clinical trial will provide any medical benefit, some patients do experience positive results after receiving an experimental therapy.

Read Our Clinical Trials Guide

The website clinicaltrials.gov is a centralized database of clinical trials that are offered globally. But as the disclaimer on the site’s home page states, there is no guarantee that a listed trial has been evaluated or approved—the National Institutes of Health runs the site but does not vet its content. This means that there could be bogus or dangerous trials listed that are preying on patients. It is essential that you discuss a clinical trial with your ophthalmologist before enrolling, and that you pay close attention to enrollment criteria.

If you are interested in exploring what is available on the site you can click on the button below, which will take you to clinicaltrials.gov and initiate a search for trials relevant for patients living with Stargardt disease.

CLINICAL TRIALS FOR Stargardt Disease

Patient Registry

For individuals living with an inherited retinal disease (a disease caused by a genetic mutation), such as Stargardt disease, participation in a clinical trial could be a logical next-step (for a description of clinical trials, see above). But in Canada there is no centralized, guided mechanism for enrolling in a trial; with this in mind, the Foundation Fighting Blindness has developed a secure medical database of Canadian patients living with inherited retinal diseases: we call it the Patient Registry.

By enrolling in the Patient Registry, your information will become a part of this essential Canadian database that can be used to help connect you to a relevant clinical trial. The availability of relevant trials depends on a number of factors, so this tool provides no guarantees, but signing onto it will put you in a position to be connected to something appropriate. It is also a way of standing up and being counted: the more individuals enrolled in the Patient Registry, the better our chances of showing policymakers that there is a significant need for new treatments for inherited retinal diseases. The Patient Registry also helps to drive more sight-saving research!

You can begin the process of enrolling in the Patient Registry by clicking the button below.

Patient Registry Enrollment

Research Developments and Health Policy

The Foundation Fighting Blindness is committed to advancing the most promising sight-saving research, and has invested over $33 million into cutting-edge science since the organization was founded. Recognizing that science is tied to policy frameworks, the Foundation is also actively involved in health policy activities across Canada.

Many research groups are working to develop treatments and cures for Stargardt disease. Experimental treatments can be divided into three broad categories:

  • Protective Therapies
  • Corrective Therapies
  • Sight-Restoring Therapies

Protective therapies aim to stop (or at least slow) the damage caused by genetic mutations. Often protective therapies are not specific to one mutation, but may benefit people with different genetic forms of Stargardt disease. These include treatments to stop the process of photoreceptor death (apoptosis), as well as cell-derived therapies that aim to help photoreceptors survive.

Some protective therapies aim specifically to prevent the death of cone cells in Stargardt disease – and thus, the loss of central vision.

Corrective therapies aim to reverse the underlying genetic defect that causes vision loss. If these therapies are successful they might prevent a person who is treated when first diagnosed, from ever developing vision loss. Corrective therapies might also help slow the disease in people whose vision has already been affected, especially in the earlier stages. The corrective therapies being developed now are specific to certain genetic forms of Stargardt disease.  Gene therapies, which replace a non-functioning gene, are one type of corrective therapy. Clinical trials of gene therapies for Stargardt disease are underway.

Sight-restoring therapies are also a growing area of research success. These therapies are intended for people who have already lost all, or much, of their vision. Stem cell therapies aim to replace the retina’s lost photoreceptors. There are promising early results with stem cell trials involving age-related macular degeneration, which is a promising sign for people living with Stargardt disease.

Retinal prosthetics, such as the Argus II or “Bionic Eye,” use computer technology to generate vision. The Foundation Fighting Blindness helped to support the first Canadian trial of the Argus II and continues to work closely with health policy experts across Canada to ensure that patients who could benefit from the Argus II device have access to this innovative treatment. Currently, the Argus II device has not been studied as a possible treatment for Stargardt disease, but there is research underway to examine if it can improve vision in people living with severe age-related macular degeneration, which will inform our understanding of whether this treatment strategy might also work for people living with Stargardt disease. Drug and gene therapies are also being developed that may give non-photoreceptor nerve cells in the retina the capacity to sense light.

Thanks to our generous donors, we are funding ground-breaking research in these areas. Click on the button below to review the full list of FFB-funded projects:

FFB-FUNDED RESEARCH

At the bottom (or side) of this webpage, you will find an updating list of stories that detail new research and health policy developments relevant for individuals affected by Stargardt disease.

Educational Resources

The page you are now on provides information on achromatopsia, but the Foundation Fighting Blindness has developed additional resources that can be helpful in plotting an optimal path through vision care. Below is a link to our must-read resources, where you will find information on genetic testing, clinical trials, stem cell research, and more as well as a link to Vision Quest (the FFB’s in-person educational events). The list will update as new resources are added.

Must-Read Resources

Vision Quest Educational Series

References