Retinitis pigmentosa

From Ganfyd

Retinitis pigmentosa is a term that includes a number of hereditary retinal photoreceptor degenerative diseases.

Prevalence

• 1 in 4000

Important Aetiologies

• Usher's syndrome - Retinitis pigmentosa and hearing impairment (10 to 20% all cases)
• Bardet-Biedl syndrome - (5-6% all cases)
• Abetalipoproteinaemia (Bassen-Kornzweig syndrome) - treatable
• Phytanic acid oxidase deficiency (Refsum's disease) - treatable
• Familial isolated vitamin E deficiency (α-tocopherol transport protein deficiency)

There are over 45 loci at which mutations cause retinitus pigmentosa.^[1] The most common (about 30% of total) are:

• Rhodopsin gene 3q21-q24 (RHO) - 25% of autosomal dominant presentations
• USH2A gene 1q41 - up to 20% autosomal recessive presentations
  • Causes Usher's syndrome type 2
• Retinitis pigmentosa GTPase regulator (RPCR) gene Xp21.1 - up to 70% X-linked recessive presentations

Presentation

Age of onset depends upon the genetics. Most forms have asymptomatic evidence with detailed investigation by the age of 6 years. A normal ERG at this age is extremely reassuring, effectively ruling out the condition.^[2]

• Visual loss
  • Often night blindness and dark adaption in adolescence
  • Progression to tunnel vision
• Diagnosis may be delayed as night vision not often stressed in modern society and over 90% of cones may be lost before loss of central visual acuity

Diagnosis

• Fundoscopy
  • Attenuation of the retinal vessels is almost universal
  • Peripheral pigment deposits
  • Pallor optic nerve head
• Visual acuity - not that useful
• Visual fields (eg Goldmann perimeter) - scotomas mid periphery
• Colour discrimination (eg Ishihara plates)
  • possibly deficit in blue cone function (acquired titanopia) - Characteristic of retinitis pigmentosa^[3]
  • red or green deficits might suggest X-linked condition
• Final dark adaption threshold
• Contrast sensitivity
• Subcapsular cataracts in 50% on slit lamp examination
• Electroretinograms (ERGs) show reduced and delayed rod and cone response amplitudes
  • Can allow accurate classification and monitoring progession
• Optical coherence tomography to assess retinal thickness and exclude macular oedema
• Fundus autofluorescence - some patients have ↑ lipofuscin correlating with greatest photoreceptor damage

Treatment

• Treat underlying metabolic deficit
  • Abetaliproteinaemia (Bassen-Kornzweig syndrome) - treatable
  • Phytanic acid oxidase deficiency (Refsum's disease) - treatable
  • Familial isolated vitamin E deficiency (α-tocopherol transport protein deficiency)
• Gene therapy
  • RPE65 gene encoding for isomerase of retinal pigment epithelium seems suitable canditate
• Gene silencing
  • May be useful in some autosomal dominant forms with RNA interference.
• Neuroprotective strategies
  • To date no more successful than with CNS
• Transplantation
  • Stem cells ?

Prognosis and progression

The disease progresses to tunnel vision, and further with a variable extent and rate, blindness is common.

References