Hereditary Retinal Dystrophies

Hereditary retinal dystrophies are a broad (and growing) group of hereditary disorders affecting the retina. Retinitis pigmentosa is perhaps the best known of them and is sometimes (inaccurately) used as a synonym for some of the other conditions in this category which are outlined below. Please refer to our dedicated article for more information on retinitis pigmentosa.

• AD - autosomal dominant
• AR - autosomal recessive
• XL - X-linked

Currently, treatment options for these conditions are very limited and tend to be focused around counselling and optometric visual rehabilitation where possible (e.g. use of low vision aids, orientation and mobility training). However, as the responsible genes are being progressively identified, work is underway in the field of gene therapy.

• Description² - this heterogenous group of rare disorders encompasses a range of problems from pure cone dysfunction to those with varying degrees of associated (but usually less severe) rod dysfunction. Many patients start with a pure cone problem which then progressively affects the rods over time.
• Inheritance - most are sporadic but AD, AR and XL inheritance is also known.
• Presentation³ - 10 to 30 years old: slow, progressive, bilateral visual loss (night vision better than day), photophobia, poor colour vision ± nystagmus. There may also be associated visual field defects.⁴
• Prognosis - short term, those with less rod involvement do well but ultimately, the outlook is poor.

• Description - also known as juvenile macular dystrophy, this is the most common form of inherited macular degeneration.
• Inheritance - AR.²
• Presentation⁶ - childhood (about 6 years old) to early adulthood: bilateral (usually) decreased central vision. This is often out of proportion to the clinical picture and these children may initially be labelled as malingerers.³ There is also progressive colour blindness.
• Prognosis - generally poor. Once vision drops below 6/12, progression is rapid and the visual prognosis is poor.

• Description - sometimes considered to be a variant of Stargardt disease due to the same gene being affected. However this condition presents later and the macula may be spared.
• Inheritance - AR.
• Presentation - adulthood: may be discovered by chance or the patient may present with central visual deterioration. Deterioration in colour vision is often not noticed by the patient until later on. Peripheral and night vision are unaffected.
• Prognosis - tends to be better than in Stargardt disease. Patients may remain asymptomatic for many years.

• Description² - this rare condition is also known as vitelliform (macular) dystrophy. It is characterised by a macular lesion which grows over years to eventually give rise to a characteristic round egg yolk appearance and which may be later associated with a pseudo-hypopyon.
• Inheritance¹ - AD with variable penetrance.
• Presentation⁶ - changes occur in EOG readings in children before they are symptomatic or anything is seen clinically. Vision may remain normal or only be slightly decreased when the 'egg-yolk lesion' is present and it is really only in the fifth decade that vision starts being significantly affected.
• Prognosis - declining visual acuity may be a reflection of macular scarring but other complications can add to this (e.g. retinal hole formation or retinal detachment). Some patients go on to become legally blind.

• Description - in this disease, there are bilateral, symmetrical lesions within the macula. They are similar to those of Best's disease but they are smaller, they present in adulthood and they do not progress.
• Inheritance - probably AD.
• Presentation - 40 to 50 years old: blurred vision ± distortion of images (metamorphopsia) which may be mild to the point that this condition is often discovered by chance.
• Prognosis - good unless complications occur (such as neovascularisation of the underlying choroid).

• Description - this condition (also known as Doyne honeycomb choroiditis or malattia levantinese) is thought by some to be the early form of age-related macular degeneration. It is characterised by well-defined creamy-yellow spots (drusen) over the macula which can eventually extend widely over the posterior pole of the eye and around the optic disc.
• Inheritance - AD with full penetrance but variable expressivity.
• Presentation - the drusen only tend to become visually problematic around the fifth decade of life and patients then experience central visual decline.
• Prognosis - this is a progressive disease but peripheral vision is spared.

• Description - this condition is characterised by crystalline depositions in the peripheral cornea and the retina ± progressive retinal atrophy.
• Inheritance - XL or AR.
• Presentation - there is progressive visual loss in the third decade, particularly peripheral and night vision.
• Prognosis - the rate of progression varies between individuals.

• Description - this collagen type IV defect results in basement membrane abnormalities which manifests itself through chronic renal failure ± sensorineural deafness. In the eye, there may be lenticonus (the lens surfaces take on a conical shape), occasional corneal changes and fovea-sparing yellow flecks on the back of the retina.²
• Inheritance - XL dominant.
• Presentation - with renal problems ± deafness.
• Prognosis - visually: excellent.

• Description - this rare disorder manifests itself as benign pink-grey fovea-sparing irregularly-shaped lesions that densely cover the retina, extending to the far periphery.
• Inheritance - AR.²
• Presentation - asymptomatic, usually discovered by chance.
• Prognosis - excellent.

• Description - this is a rare multisystem disease:
  • Eyes - blindness or hypermetropia, keratoconus (cone-shaped cornea), keratoglobus (large cornea), early cataracts, nystagmus
  • Nervous system - learning disabilities, deafness, epilepsy
  • Other systems - renal and musculoskeletal abnormalities, endocrine dysfunction
• Inheritance - AR.
• Presentation - children are blind from birth or within the first few years of life. They exhibit the characteristic 'oculodigital syndrome': constant rubbing of the eyes results in orbital fat resorption and subsequent endophthalmos (eyes sunken into sockets).
• Prognosis - very poor.

• Description - this term covers various problems which may or may not be associated with abnormalities in the fundus.
• Inheritance - depending on the subtype, may be AD, AR or XL.
• Presentation - nyctalopia as a result in a delay or an inability to achieve normal dark-adapted rod thresholds. There may be associated myopia, nystagmus and strabismus.
• Prognosis - there is no progression.

• Description - this is the umbrella term used to describe various degrees of rod monochromatism or cone monochromatism.
• Inheritance - depending on subtype, AR or XL.
• Presentation - colour blindness: if colour vision is totally absent, the world is seen in shades of grey. There may be some colour perception in incomplete rod monochromatism. Cone monochromatism is associated with better visual acuity (6/6 to 6/9) than rod monochromatism (where this is complete, visual acuity is in the region of 6/60).
• Prognosis - there is no progression.

There are a variety of very rare macular dystrophies, most of which are inherited in an AD manner. Sorsby pseudo-inflammatory macular dystrophy, North Carolina macular dystrophy and dominant cystoid macular oedema carry poor prognoses whereas butterfly macular dystrophy is a relatively innocuous condition (often found by chance) resulting in mild impairment of central vision.