Achromatopsia

Overview

Also known as “total colour blindness,” Achromatopsia (ACHM) is a genetic syndrome characterized by the inability to perceive colour. Though experiences of colour sensations vary, many with the condition can only see black, white, and shades of grey—this is often called “complete achromatopsia,” and differs from the more common forms of colour blindness involving difficulty distinguishing between certain colours. Others can see some additional colours and shades under certain conditions but still within a limited spectrum (sometimes called “dyschromatopsia”), and still others have difficulty seeing clearly in high-light environments—outside during a sunny day, for instance—or are extremely sensitive to such light (photophobia). The syndrome affects approximately 1 in 30,000 people, and its symptoms are usually noticed during the first few months of life.[1]

An image simulating the contrast between the experience of full colour, on the left, and what someone with complete achromatopsia may see, on the right. Image taken from achromatopsia.info.

The genetics of achromatopsia are varied, involving one of five genes: CNGA3 and CNGB3 are associated with the vast majority of cases, and the genes GNAT2, PDE6C, and PDE6H underlie the rest. A gradual deterioration of the retina’s cone and rod photoreceptors is the mechanism underlying vision loss in retinitis pigmentosa (RP) and similar retinal diseases. With achromatopsia, it is primarily the cone photoreceptors that are affected, disrupting their ability to transmit visual information to the brain. Since it is the cones that are responsible for colour vision, their reduction or complete loss has the predictable effect: a loss of the ability to perceive colour. Cone photoreceptors are responsible for central, high-acuity vision as well, which is why many with the disorder live with a severe impairment of central vision. In patients with complete achromatopsia, all cone photoreceptors have died as a result of the mutation.

The term “achromatopsia” became widely-used after the publication of Oliver Sacks’ 1997 book The Island of the Colorblind, where he recounts his time living among a community of achromatopes inhabiting the island of Pingelap in the South Pacific. Sacks describes in detail the accounts of achromatopic vision provided by the Pingelapese.

Content on this page was written by Dr. Chad Andrews and Dr. Mary Sunderland, and was most recently updated on August 23, 2018.

Symptoms and Diagnosis

Achromatopsia is usually diagnosed during the early states of one’s life when either nystagmus or photophobia are detected. Nystagmus is characterized by rapid, uncontrolled movement of the eyes, and can often be noticed in young children. Photophobia, on the other hand, is the experience of pain or discomfort in the eyes when they are exposed to light, especially bright light. Since with achromatopsia the individual’s cone photoreceptors are diminished, the remaining cells are overstimulated by incoming light and transmit intensified signals along the optic nerve.

Existing Treatments and Standard of Care

While there are devices on the market that can aid those who are sensitive to light, including therapeutic glasses that filter hurtful wavelengths, there are no approved treatments that address the underlying genetics of achromatopsia. There are, however, multiple clinical trials underway that are testing new gene therapies to treat achromatopsia (for more details about clinical trials for achromatopia, see the below section on clinical trials).

There is a lot of optimism about the potential for gene therapies to treat inherited retinal diseases like achromatopia because the first ocular gene therapy received approval from the FDA in 2017. This gene therapy, Luxturna, has the potential to halt vision loss and even restore some sight in individuals with a biallelic mutation of their RPE65 gene (manifesting as either retinitis pigmentosa or Leber congenital amaurosis). Though achromatopsia results from a different set of mutations, none of which are RPE65, the approval and emergence of Luxturna shows that similar gene therapies could someday be used to address the deterioration of cone photoreceptors in achromatopsia.

Read Our Story About The Approval of Luxturna

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 achromatopsia.

CLINICAL TRIALS FOR ACHROMATOPSIA

Patient Registry

For individuals living with an inherited retinal disease (a disease caused by a genetic mutation), 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 trials. 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 achromatopsia. 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 achromatopsia. 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 under development (and funded by FFB) aim specifically to prevent the death of cone cells, which could potentially be a very beneficial treatment for people living with achromatopsia.

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 achromatopsia.  Gene therapies, which replace a non-functioning gene, are one type of corrective therapy. Clinical trials of gene therapies for the two main forms of achromatopsia (CNGA3 and CNGB3) are underway. Fortunately, many of these trials are accepting Canadian patients – please read the section on clinical trials to learn more and get involved.

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 other retinal degenerative diseases. Retinal prosthetics, such as the Arugus 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. 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 achromatopsia.

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