Inherited disorders of the retina are the second commonest cause of severe visual impairment in childhood and the commonest cause in the working-age population, and for the most part there are no effective treatments.

Loss of vision is caused by the gradual loss of function and eventual death of the light-sensitive cells in the retina. At Moorfields Eye Hospital and UCL Institute of Ophthalmology we are investigating multiple different approaches to better understand the causes of retinal failure and death, provide improved advice on prognosis and counselling, and to develop novel effective treatments.

We are in an exciting new era where untreatable blinding genetic eye disease will increasingly be subject to clinical trials and thereby amenable to treatment.

There are over 400 different genetic causes of inherited retinal disorders, with two of the most common conditions being Retinitis Pigmentosa and Stargardt Disease.

Retinitis Pigmentosa (RP) is the name given to a group of conditions, which result in the gradual degeneration of the light sensitive cells of the retina. The retina is the light sensitive tissue inside the eye in which the first stages of seeing take place.

For those not familiar with the structure of the eye, think of it as similar to an old fashioned camera, which has a lens at the front, the purpose of which is to focus light onto a light sensitive film inside the camera towards the back. In a similar way, the eye is a sphere, with a lens at the front which focuses light onto a light sensitive tissue, which lines the inside of the back of the eye. This tissue is called the retina, a multi-layered delicate structure, which is the area affected by all types of RP. Over time the retina ceases to function and then dies away.

The lens at the front of the eye is normally completely transparent but can become opaque with increasing age or when there are diseases of the eye. An opaque lens is termed a cataract. A cataract can be treated by cataract surgery in which the opaque natural lens is removed and replaced by an artificial lens. Many elderly individuals develop cataract as a result of ageing changes in the lens. Patients with RP can develop cataracts at a younger age. The results of cataract surgery are usually excellent.

The onset of symptoms is variable but usually begins between the ages of 10 and 30, although some changes may become apparent in earlier childhood. In one type of early-onset RP, Leber congenital amaurosis, children are severely visually impaired at birth or in early infancy. By contrast, other types of RP may only show symptoms late in life.

In the more common types of RP, a person will first notice visual problems at dusk or in poor light, so-called night blindness, and also a gradual reduction in the peripheral field of vision, loss of the outer edges of vision (‘side vision’), resulting in a tendency to miss things or trip over things. At an early stage the central vision (‘straight-ahead and reading vision’) is unaffected. As the outer edges of the field of vision gradually disappear, the RP sufferer is left with the condition commonly referred to as “tunnel vision”.

Many people retain this central tunnel of useful vision until quite late in life, thereby being able to recognise faces and continue reading. The rate of loss of central vision is slower than that of peripheral visual field loss.

Retinitis pigmentosa can be classified according to its inheritance pattern. The different forms of RP result from the presence of one or two “faulty genes”. Genes are the instructions or recipes the body uses to build and repair itself. Genes determine many of your body characteristics including the colour of your hair and eyes. There are three possible inheritance patterns, Autosomal Dominant, Autosomal Recessive and X-Linked.

Stargardt disease (also know as Stargardt macular dystrophy or Fundus Flavimaculatus) is the most common inherited macular dystrophy – the macula being the central part of the retina that is specialised for detailed vision and colour vision. It has an autosomal recessive mode of inheritance.

Most people with Stargardt disease have slowly progressive central visual loss that begins in early teenage years. Stargardt disease may also present in adult life when the visual loss may be milder. It has been more recently recognised that Stargardt Disease may also present in later adulthood and can be misdiagnosed as age-related macular degeneration.

The faulty gene that causes Stargardt disease has been identified and is called ABCA4. This gene is involved in recycling vitamin A in the retina. Vitamin A is an essential component of the light detecting ability of the retina.

An on-going gene therapy trial is being conducted in France and the USA to determine the safety and effectiveness of gene replacement in this condition.

A stem cell trial has being conducted to determine the safety and effectiveness of human embryonic stem cell derived retinal pigment epithelial cells in patients with advanced Stargardt disease. There were no safety concerns and information on effectiveness is awaited.

Pharmacological trials are on going.

More details on Inherited Retinal Disorders including Retinitis Pigmentosa and Stargardt Disease are available here:

https://www.fightingblindness.org/diseases/retinitis-pigmentosa

https://www.macularsociety.org