What is retinitis pigmentosa?

Author: Peng Chunxia, ​​deputy chief physician, Beijing Children's Hospital, Capital Medical University

Wang Fei Beijing Children's Hospital, Capital Medical University

Reviewer: Li Li, Chief Physician, Beijing Children's Hospital, Capital Medical University

1. What is retinal degeneration?

Retinitis pigmentosa (RP) is a complex spectrum of inherited retinal pigment membrane degeneration caused by gene mutation. It is mainly characterized by progressive retinal degeneration and dysfunction, mainly involving the retinal pigment layer (RPE) and photoreceptor cells. Clinically, it is characterized by night blindness, progressive visual field constriction and retinal osteocyte-like pigmentation.

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2. Who will suffer from RP and when will it occur?

The incidence of RP worldwide is 1/(4000-5000), and 40%-50% of patients have a family history of RP, with a higher incidence in consanguineous marriages. Most cases begin to develop in childhood, and by the age of 40, the visual field will be reduced to the standard of legal blindness. A small number of cases develop later and remain asymptomatic until adulthood.

3. What is the pathogenesis of RP?

Gene mutation is the root cause of RP. The first RP mutation was discovered in 1989, located in the rhodopsin gene (RHO) on chromosome 3q21.3. Rhodopsin is a pigment that absorbs light in the membrane of rod cells. In 1990, it was discovered that the 23rd amino acid encoded by this gene changed from proline to histidine. With the rapid development of genetic testing technology and its popularization in clinical practice, the speed of discovering RP pathogenic genes has increased exponentially. Currently, more than 3,000 mutations have been found in about 70 genes. The protein products of these gene mutations involve multiple pathways: phototransduction cascade, vitamin A metabolism, cytoskeletal structure, signal transduction and cell-cell interaction, RNA intron splicing factors, intracellular protein transport regulation, and phagocytosis.

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4. What are the clinical manifestations of RP patients?

The typical clinical manifestations of RP patients are night blindness and concentric reduction of peripheral visual field due to loss of photoreceptor cells. Fundus examination will reveal that the optic disc is waxy yellow, the retinal blood vessels are thin, osteocyte-like pigmentation can be seen in the mid-periphery, and cystoid macular edema will occur in the late stage. In addition to ocular manifestations, a small number of RP patients will also have multi-system changes, which are called syndromic RP. The most common is Usher syndrome, with congenital or early-onset hearing impairment, followed by RP. Bardet-Biedl syndrome is the second most common syndrome, manifested by polydactyly, obesity, renal abnormalities and developmental delay. There are also mutations in the nephronophthisis (NPHP) gene, which can cause end-stage renal disease and RP in childhood.

Auxiliary examinations: The a and b waves in the electroretinogram (ERG) are extinguished; OCT examinations mostly show atrophy of the outer retinal layer in the mid-peripheral area outside the macula, which eventually affects the macula. Genetic testing can identify the causative gene. In 2016, the American Academy of Ophthalmology issued a position statement supporting the role of genetic testing in the management of inherited retinal diseases. Since LCA/RP subtypes are currently treatable, genetic testing must be provided to patients with LCA and early-onset RP. In addition, molecular diagnosis obtained through genetic testing can determine whether patients are eligible to participate in RP clinical trials.

5. How to diagnose RP?

The diagnosis of RP requires comprehensive consideration of clinical manifestations, auxiliary examinations, etc. Mainly including:

(1) A history of night blindness (difficulty adapting to the dark) and loss of peripheral vision.

(2) Fundus examination revealed waxy pallor of the optic nerve, narrowing of the arteries, and changes in peripheral retinal pigments.

(3) Auxiliary examination results: Full-field ERG showed a decrease in the number of rod cells, followed by a decrease in the number of cone cells; Goldmann visual field examination showed a decrease in the visual field; and dark adaptation measurement was abnormal.

(4) Genetic testing can help with diagnosis and guide treatment.

6. What is the natural course of RP disease? Is there an effective treatment?

Without intervention, the natural course of RP varies greatly. Some cases have severe visual impairment in children, and if accompanied by myopia, hyperopia or astigmatism, they are often misdiagnosed as amblyopia. Some patients are asymptomatic until adulthood. The typical course of RP is a gradual loss of peripheral visual field damage, manifested as concentric visual field constriction. Most patients meet the standard of legal blindness by the age of 40 due to the constriction of their visual field.

Current treatments include: vitamin and nutritional supplements may be effective; retinal cell transplantation, retinal prosthesis implantation and gene therapy are all in the experimental stage.

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7. Will RP be passed on to the next generation? How to avoid it?

Among RP gene mutations, more than 50% are autosomal dominant RP. If neither spouse carries the disease-causing gene, the probability of the next generation developing the disease is about 50%. 30% are recessive RP patients. If neither spouse carries the disease-causing gene, the next generation will not develop the disease. There are also X-linked RP patients, where the pathogenic gene mutation site is on the X chromosome. Most of them are carried by females, but the disease occurs in males. In this case, the children born to males who develop the disease will not develop the disease if the females carry the disease, and will not develop the disease if the males do not carry the disease. They are healthy individuals.

References

1.Retinitis pigmentosa. A symposium on terminology and methods of examination[J]. Ophthalmology, 1983, 90(2):126-31.

2.National Human Genome Research Institute. About retinitis pigmentosa. Available at: https://www.genome.gov/Genetic-Disorders/Retinitis-Pigmentosa (Accessed on August 31, 2022).

3.American Academy of Ophthalmology. Recommendations on clinical assessment of patients with inherited retinal degenerations - 2016. Available at: https://www.aao.org/clinical-statement/recommendations-on-clinical-assessment-of-patients (Accessed on November 07, 2019).

4.DRYJA TP, MCGEE TL, REICHEL E, et al. A point mutation of the rhodopsin gene in on-e form of retinitis pigmentosa[J]. Nature,1990,343:364.

5.DIAS MF, JOO K, KEMP JA, et al. Molecular genetics and emerging therapies for retinitis pigmentosa: Basic research and clinical perspectives[J]. Prog Retin Eye Res, 2018,63:107.