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Achromatopsia: for patients

Overview

Achromatopsia is a rare disease affecting around 1 in 30,000 newborns.[1] It is caused by changes to one of a number of genes, disrupting the function of a type of light sensitive cells in the retina called cone photoreceptors. This leads to partial or total loss of colour vision, reduced visual sharpness, light sensitivity and involuntary “wobbly eyes” (nystagmus) from birth or early infancy. Although the condition progresses relatively slowly over time, symptoms such as light sensitivity can be severely disabling. Achromatopsia is inherited in an autosomal recessive manner.

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The condition

Symptoms

Patients with achromatopsia usually present with light sensitivity and nystagmus from birth or shortly after. Other symptoms may include:

  • Partial or complete inability to recognise colours
  • Reduced visual sharpness (visual acuity)
  • Blind spot in the central field of vision
  • Near or far-sightedness which requires glasses to improve

The severity of symptoms varies considerably between and within families, where some may have better visual function, milder light sensitivity and subtle nystagmus. Visual function tends to remain stable or progress minimally over time. Occasionally, light sensitivity and nystagmus may improve with age.

Cause

Our retina has two types of photoreceptors called rods and cones. Rods are responsible for vision in dim light and peripheral vision. Cones help us to see colour and objects in detail under bright light.

In achromatopsia, mutations in six genes have been identified so far that affect the protein composition of cone photoreceptors, causing them not to function correctly. The degree of cone photoreceptor dysfunction varies among patients, giving rise to variable severity of symptoms. Of the six genes associated with achromatopsia, CNGA3 and CNGB3 are the most commonly affected, responsible for 70-80% of all cases.[2]

The other identified genes are: GNAT2, PDE6C, PDE6H, ATF6

How is it diagnosed?

The ophthalmologist is able to diagnose achromatopsia based on the presenting symptoms, clinical examination and the results of various tests that assess the structure and function of the retina. One key investigation is an electro-diagnostic test called the electroretinogram (ERG). It is used to assess the function of the cone and rod photoreceptors. Patients with achromatopsia usually display a ERG pattern where there is markedly reduced or absent cone function and normal/nearly normal rod function. The diagnosis is confirmed with genetic testing by identifying mutations in one of the six genes associated with achromatopsia.

How is it inherited?

1) Autosomal recessive (AR) inheritance

Two faulty copies of a gene are required to cause disease. Both parents are usually unaffected carriers (only have one faulty gene copy) while the patient has two faulty gene copies (inherited one each from each parent). This means that every newborn has the following risks regardless of gender:

  • 25% chance of being affected by achromatopsia
  • 25% chance of being unaffected and not a carrier
  • 50% chance of being a carrier with no symptoms
If the mother has 1 copy of the faulty gene in her X chromosome (a carrier) while the father is unaffected, there is 50% chance that a daughter is a carrier and a 50% chance that a son is affected by the condition.
Autosomal recessive inheritance

If you or your child is affected by achromatopsia, it is advisable to see a genetic counsellor to obtain more information and advice on inheritance and family planning options.

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Treatment

Is there any treatment?

There is currently no available treatment for achromatopsia but researches are exploring various approaches, one of which has entered clinical trials. In the meantime, treatment is focused on alleviating symptoms and optimising remaining sight. Here are some possible strategies:

  • Correcting any near/far sightedness with glasses
  • Tinted glasses or contact lenses help alleviate light sensitivity
  • Visual aids and assistive technology
  • Wearing UV protective sunglasses
  • Blue light screen protectors on mobile devices or computer screens*
  • A healthy diet consisting of fresh fruit and green leafy vegetables

*Current available evidence shows that blue light emitted from screens do not damage the retina but it can disrupt our sleep cycle. The screen protectors are used as a precautionary measure.

Optimising childhood development

Visual impairment in early childhood can have a negative impact on early general development. Therefore, timely referral to practitioners familiar with developmental surveillance and intervention for children with visual impairment (VI), such as developmental paediatricians as well as a Qualified Teacher of children and young people with Visual Impairment (QTVI) is crucial to optimise their developmental potential.

The Developmental Journal for babies and young children with visual impairment (DJVI), developed by Great Ormond Street Hospital Developmental Vision team is a structured early intervention programme designed to track developmental and vision progress in children from birth to three years of age. It is mainly used by qualified healthcare professionals working in services providing support to babies and young children with VI in conjunction with the child’s parents. Children with VI may be referred to specialist services such as the developmental vision clinic in the Great Ormond Street Hospital for Children or other specialist developmental services for further management.

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Current research in Achromatopsia

1) Gene therapy

Gene therapy 

aims to halt retinal degeneration by replacing the mutated gene with a normal healthy copy. This enables the affected cells to regain some of their function and produce functioning proteins.

The normal gene copy is packaged into a harmless virus. The virus then breaches the target cells and delivers the normal gene copy to the cell's DNA mechanism. As a result, the cell is now making normal and functional protein.
Principles of gene therapy

In achromatopsia, a normal copy of the mutated gene is “packaged” into a harmless virus which is then injected into the retina. This way, the affected cone photoreceptors will have maximum exposure to the viruses containing the normal gene.

Currently, all gene therapy trials in achromatopsia are still in the early stages and focus on the two most common genes,CNGA3 and CNGB3. One of the earliest gene therapy trials was conducted in Germany on adult patients with CNGA3 mutations.[3] The study showed that no significant safety issues were associated with the treatment and improvement in visual function was observed at 12 months post-treatment. More extensive trials will be required and it will be a few years before this treatment could be generally available.

Other current gene therapy trials in achromatopsia are:

Related links

2) Ciliary neurotrophic factor (CNTF)

Ciliary neurotrophic factor (CNTF) is a type of protein that has been shown to have neuroprotective effects on cone photoreceptors, the primary cells affected in achromatopsia.[4,5]

A phase 1/2 trial utilising encapsulated implants releasing CNTF into the eye was conducted on achromatopsia patients with CNGB3 gene mutations. There was no objective improvement in visual function in all participants. However, the participants reported subjective improvements in light sensitivity and increased sharpness in vision. We are unaware of any further trials investigating CNTF for the treatment of achromatopsia.

Related links

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Practical advice

Living with achromatopsia

Patients are still able to lead an independent life through maximising their available vision and having access to social support. Here are some ideas:

  • Attending the low vision clinic which provides access to low vision specialists, Eye Clinic Liaison Officers (ECLOs), visual aids and visual rehabilitation services
  • Utilising assistive technologies that can improve quality of life
  • Using tinted glasses or contact lens when in bright lights, which will help reduce light sensitivity and improve visual sharpness
  • Getting in touch with the local education authority for access to qualified teachers for children with visual impairment (QTVI) and special educational needs co-ordinator (SENCO)
  • Preferential seating in classroom such as in the front row and away from windows
  • Registering your child as sight impaired (SI) or severely sight impaired (SSI) if eligible for access to social support and financial concessions
  • Getting in touch with national or local charities for advice and peer support

Related links

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Referral to a specialist centre

If you are based in the UK and would like to be seen in the nearest specialist centre for your eye condition, either to receive a more comprehensive genetic management or just to find out more about current research, you can approach your GP to make a referral or alternatively arrange for a private appointment. 

More information can be found in our “How to see a genetic eye specialist?” page.  

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Further information and support

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References

  1.  Michaelides M, Hunt DM, Moore AT. The cone dysfunction syndromes. Br J Ophthalmol. 2004;88(2):291-297. doi:10.1136/bjo.2003.027102
  2.  Michalakis S, Schön C, Becirovic E, Biel M. Gene therapy for achromatopsia. J gene Med. 2017;19(3). doi:10.1002/jgm.2944
  3.  Fischer MD, Michalakis S, Wilhelm B, et al. Safety and Vision Outcomes of Subretinal Gene Therapy Targeting Cone Photoreceptors in Achromatopsia: A Nonrandomized Controlled Trial. JAMA Ophthalmol. 2020;138(6):643-651. doi:10.1001/jamaophthalmol.2020.1032
  4.  Zhang K, Hopkins JJ, Heier JS, et al. Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration. Proc Natl Acad Sci United States Am. 2011;108(15):6241-6245. doi:10.1073/pnas.1018987108
  5.  Talcott KE, Ratnam K, Sundquist SM, et al. Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment. Investig Ophthalmol Vis Sci. 2011;52(5):2219-2226. doi:10.1167/iovs.10-6479

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Updated on January 10, 2021
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