Cone-rod dystrophy: inherited retinal disease affecting central and night vision

The retina at the back of the eye contains two kinds of light-sensing cell. Cones provide sharp central vision in bright light and colour vision; rods provide vision in low light and the wider field of view. A review in the British Journal of Ophthalmology by Moorfields and UCL authors describes progressive cone and cone-rod dystrophies as a clinically and genetically heterogeneous group of inherited retinal diseases characterised by cone photoreceptor degeneration, which may be followed by rod photoreceptor loss.

The same review notes that inherited retinal diseases as a group are the leading cause of legal blindness in England and Wales among working-age adults and the second most common in childhood. Cone-rod dystrophy is one subgroup, and is different from the rod-cone dystrophies such as typical retinitis pigmentosa in which night vision is affected first; MedlinePlus Genetics explains that in cone-rod dystrophy light sensitivity and colour vision are affected before night vision, and the condition name reflects this order.

MedlinePlus Genetics describes the first signs, which often occur in childhood, as reduced visual acuity and photophobia, followed by impaired colour vision, blind spots in the centre of the visual field and partial loss of side vision. Over time people develop night blindness and a worsening of peripheral vision, which can limit independent mobility, and reading becomes increasingly difficult. It says most affected individuals are legally blind by mid-adulthood and that nystagmus may develop as the condition progresses.

Because the order and speed differ between genes and between families, the picture is individual. MedlinePlus Genetics notes that cone-rod dystrophy can occur alone or as part of a syndrome that affects multiple parts of the body, a point your specialist will check for.

• Gradual blurring of central vision, not corrected by glasses.

• Glare and discomfort in bright light.

• Colours looking washed out or being confused.

• A central blind spot making reading hard.

• Later, poor vision in dim light and loss of side vision.

More than 30 genes have been linked to cone-rod dystrophy, according to MedlinePlus Genetics, about 20 of them with the autosomal recessive form. Mutations in the ABCA4 gene are the most common cause of the recessive form, accounting for 30 to 60 percent of cases; at least 10 genes are linked to the autosomal dominant form, with GUCY2D and CRX accounting for about half; and at least two genes cause the rare X-linked form. The UK review focuses on four of the most common genes: GUCA1A, PRPH2, ABCA4 and RPGR.

Because the inheritance pattern varies, knowing the gene matters for family planning and for relatives. MedlinePlus Genetics notes that the inheritance pattern may be autosomal recessive, autosomal dominant or X-linked, and genetic counselling is a routine part of care.

Diagnosis is made by an ophthalmologist, ideally one with experience in inherited retinal disease. The UK review explains that the clinical, psychophysical, electrophysiological and retinal imaging characteristics are used together: retinal imaging, field tests and electrophysiology (electroretinography) show the pattern of cone and rod dysfunction. It also states that recent advances in molecular genetics, particularly next-generation sequencing, have greatly improved molecular diagnosis, with the causative gene identified in a large proportion of patients.

A confirmed genetic diagnosis can clarify the likely course, the inheritance pattern and eligibility for any research or trials, which is why testing is usually offered through NHS clinical genetics or a specialist inherited retinal disease service.

The Moorfields and UCL review states plainly that, at present, there are no proven treatments for cone and cone-rod dystrophy that halt progression or restore lost vision. Current management consists of symptomatic alleviation, including refractive correction, tinted spectacles or contact lenses for photophobia and low vision aids. It notes that light avoidance with tinted spectacles may confer benefit in ABCA4-associated retinopathy.

On research, it says that gene-based approaches to therapy are increasingly in clinical trial, and that recent evidence has shown the potential of gene therapy for long-term improvement in visual outcomes in these disorders, while stressing that the remaining challenge is developing therapies that slow degeneration or improve function. Anyone interested in trials should ask their specialist or genetics service, rather than relying on commercial clinics.

Practical support includes certification as sight impaired where criteria are met, low vision assessment and aids, eye clinic liaison officers, education and workplace adjustments, and counselling, since sight loss in young people can be emotionally hard.

The NHS pathway runs from optometrist or GP to hospital ophthalmology and then to a specialist inherited retinal disease clinic and clinical genetics, which can organise genetic testing for you and your relatives.

Private retinal specialists can offer faster imaging and electrodiagnostic testing. Genetic testing and counselling through the NHS are usually the most reliable route to a result that can be used for family planning and trial eligibility, so ask any private provider how results will be shared with the NHS team.