Makindo Medical Notes

Retinitis pigmentosa (RP) is a genetic disorder involving progressive retinal degeneration that impairs the retina's ability to respond to light. This leads to gradual vision loss, particularly night blindness, progressing to tunnel vision and, in advanced cases, total blindness. RP combined with progressive deafness is called Usher syndrome.

About

• RP represents a group of inherited retinal degenerative disorders characterized by progressive loss of vision.
• It involves the deterioration of photoreceptor cells, primarily rods, followed by cones in later stages.
• While autosomal recessive (AR) inheritance is common, RP can also exhibit autosomal dominant (AD) and X-linked inheritance patterns.
• The progression and severity of vision loss can vary widely depending on the genetic mutation responsible.
• Often affects peripheral vision initially, with central vision loss occurring in later stages.

Aetiology

• RP is primarily due to mutations in over 60 genes, most commonly affecting rhodopsin, a protein essential for vision in low light.
• Each genetic mutation impacts the function of photoreceptor cells or the retinal pigment epithelium, leading to cell death and degeneration.
• Most cases are sporadic or autosomal recessive, with 3:1 male predominance due to some forms of X-linked inheritance.
• Mutations can affect both rods and cones, but rods are generally affected first, resulting in early symptoms of night blindness.

Conditions Associated with RP

• Usher syndrome: RP combined with congenital hearing loss or progressive deafness, inherited in an autosomal recessive manner, leading to significant sensory impairment.
• Bardet-Biedl syndrome: Characterized by RP, obesity, polydactyly, kidney abnormalities, and intellectual disability, often presenting with endocrine issues.
• Refsum disease: A metabolic disorder where the accumulation of phytanic acid due to enzyme deficiency causes RP, neuropathy, cerebellar ataxia, and anosmia. Managed with dietary restrictions to reduce phytanic acid.
• Abetalipoproteinemia: An inherited disorder affecting fat absorption, leading to RP, neuropathy, and ataxia, requiring strict dietary management and supplementation.
• Kearns-Sayre syndrome: A mitochondrial disorder associated with RP, cardiac conduction defects, and progressive external ophthalmoplegia.
• Alström syndrome: Characterized by RP, obesity, type 2 diabetes, and sensorineural hearing loss, often leading to significant vision and hearing impairment.
• Other Conditions: Lowe syndrome, NARP syndrome, and Cockayne syndrome also present RP among other systemic manifestations.

Clinical Features

• Night Blindness (Nyctalopia): Often the earliest symptom, reflecting rod cell dysfunction. Patients struggle to see in low-light conditions, such as at dusk or in dimly lit rooms.
• Peripheral Vision Loss: As the disease progresses, patients experience tunnel vision. Central vision loss usually occurs at later stages.
• Fundoscopic Changes: Characteristic findings include bone spicule-shaped pigment deposits, attenuated retinal vessels, and pallor of the optic disc.
• Photopsia: Patients may experience flashes of light, particularly in low-light conditions.
• Progression: The condition often progresses from peripheral to central vision loss, with a gradual narrowing of the visual field over years or decades.

Investigations

• Electroretinogram (ERG): A diagnostic test measuring retinal response to light, often showing reduced or absent rod and cone responses in RP patients.
• Genetic Testing: Identifies specific gene mutations responsible for RP. This is crucial for determining inheritance patterns, prognosis, and potential for targeted gene therapies.
• Visual Field Testing: Measures the extent of peripheral vision loss, documenting the progression of tunnel vision.
• Optical Coherence Tomography (OCT): Provides detailed imaging of retinal layers, helping assess photoreceptor cell integrity and retinal thinning.
• Fundus Photography: Captures images of the retina to document characteristic RP features, such as bone spicules and retinal vessel attenuation.

Management

• Vitamin A Supplementation: High-dose vitamin A palmitate (15,000 IU daily) may slow disease progression, but excess intake should be avoided due to potential toxicity.
• Genetic Counseling: Provides information about inheritance patterns and recurrence risk for families with RP.
• Low Vision Aids: Specialized devices, such as magnifiers and field enhancers, assist with residual vision management and help maintain independence.
• Mobility Training: Orientation and mobility services, including guide dogs and white cane training, can be invaluable for patients experiencing significant vision loss.
• Gene Therapy: Advances in gene therapy, particularly for specific gene mutations (e.g., RPE65), hold promise for halting or reversing vision loss in RP patients.
• Retinal Prostheses: Devices like the Argus II, an artificial retinal implant, offer partial vision restoration for advanced RP cases, although these are still experimental and may not be widely available.

Prognosis

• RP is progressive, with the severity of vision loss varying based on the specific genetic mutation and inheritance pattern.
• Many patients retain partial vision until mid-life, although eventual blindness is common in more severe cases.
• Early diagnosis and genetic testing can help inform prognosis and allow access to potential emerging treatments.

References

• Retinitis Pigmentosa Overview - GeneReviews
• American Academy of Ophthalmology - Retinitis Pigmentosa