2 The condition

2.1 Inherited retinal dystrophies (IRDs) are a group of rare genetic eye diseases. They are caused by germline mutations in more than 260 genes, including that for the enzyme RPE65. This enzyme is critical for the visual cycle. It is involved in a multistep process that converts light entering the eye into electrical signals, which are transmitted to the brain. Lack of RPE65 causes severe deficiency in functional rhodopsin (a sensory protein that converts light into an electrical signal) and death of photoreceptor cells on the retina through accumulation of toxic chemical compounds. People with RPE65-mediated IRD have progressive vision loss. There is variation in the presentation and time of diagnosis of the condition. Loss of vision can begin as early as the first few months of life, or during childhood or adolescence. Initially, people have problems with peripheral vision and seeing in dim light or night blindness. These symptoms are followed by progressive deterioration in visual field (range of vision) and visual acuity (clarity of vision), and reduced sensitivity to light. Ultimately, the deterioration leads to near-total blindness.

2.2 Lack of RPE65 presents as clinical conditions such as classically termed retinitis pigmentosa (RP) and Leber's congenital amaurosis (LCA). LCA is used to describe a group of severe early infantile onset rod–cone dystrophies. It is considered to have a worse prognosis than other clinical diagnoses. RP accounts for around half of IRDs, with a prevalence of around 20 to 30 people per 100,000. LCA is less common, affecting 2 to 3 people per 100,000. Mutations in the RPE65 gene account for 2% of RP and 6% to 16% of LCA diagnoses. The exact prevalence and incidence of RPE65-mediated IRD is uncertain. The company estimated that 86 people would be eligible for treatment with voretigene neparvovec in England.

2.3 There are no licensed treatments currently available in the UK for RPE65-mediated IRD. Current management focuses on strategies to improve the use of remaining vision. This includes using low-vision aids, social and educational support, and specialised genetic counselling for people with the condition and their families. Care is provided as part of a specialised multidisciplinary service.

  • National Institute for Health and Care Excellence (NICE)