Generality
The term retinitis pigmentosa (RP) identifies a group of genetic diseases characterized by progressive retinal degeneration.
Retinitis pigmentosa is a retinal dystrophy characterized by gradual loss of photoreceptors and dysfunction of the pigment epithelium. This means that the retina progressively reduces its ability to transmit visual information to the brain via the optic nerve.
The pathological process begins with alterations of the retinal pigment epithelium . As the retinitis pigmentosa progresses, a thinning of the blood vessels that supply the retina occurs, which undergo atrophy. On examination of the ocular fundus, the characteristic retinal pigment deposits (hence the name of the disease) are visually detectable. Atrophic changes and damage can also involve the optic nerve and, gradually, the photosensitive cells of the retina die.
Patients suffering from retinitis pigmentosa, initially, experience vision problems especially in environments with poor lighting and complain of a constriction of the peripheral visual field. Central vision is spared until the later stages of the disease and the final outcome can vary considerably: many people with retinitis pigmentosa maintain a limited vision for life, while others lose their vision completely.
Retinitis pigmentosa is an inherited disease, mainly caused by genetic alterations transmitted by one or both parents. The type of genetic defect determines which retinal cells are most involved in the disorder and allows different clinical conditions to be distinguished. To date, more than 50 different genetic defects implicated in retinitis pigmentosa have been identified. The abnormalities can be transmitted from parents to children through one of the three inheritance models: autosomal recessive, autosomal dominant or heterosomal recessive (X-linked or associated with the X chromosome).
Symptoms
To learn more: Symptoms Retinitis Pigmentosa
Retinitis pigmentosa is usually found in adolescents and young adults. Symptoms often appear between 10 and 30 years of age, but the diagnosis can be made in early childhood or much later in life.
The early symptoms of retinitis pigmentosa may include:
- Difficulty seeing at night (night blindness) or in low light conditions;
- Slow adaptation from vision to darkness to vision, and vice versa;
- Visual field narrowing and loss of peripheral vision;
- Sensitivity to light and glare.
Some symptoms depend on the type of photoreceptors involved. Rods are responsible for viewing in black and white, while cones make it possible to distinguish colors.
| Characteristics of rods and cones | ||
| rods | Cones | |
| Types of vision | Black and white; nocturnal (dim light) | Coloured; bright light (bright light) |
| Sensitivity to light | High | Low |
| Visual acuity | Low | High |
| Area of greatest concentration | Periphery of the retina | Fovea (geometric center of the retina that corresponds to the seat of the finest vision) |
In most cases of retinitis pigmentosa, the rods are involved first. However, in rapidly evolving forms even cones can be affected early.
The rods are concentrated in the outer parts of the retina and are activated by dim light, so their degeneration affects peripheral and nocturnal vision. If cones are involved, loss of color perception and central vision can be observed.
The predominance of photoreceptors involved is determined by the particular defect present in the patient's genetic makeup.
Often, the first symptom of retinitis pigmentosa is night blindness (or nictalopia). Some people realize that they need more and more time to adapt to the differences in light when they move from a well-lit area to a darker one. A typical form of vision loss induces a narrowing of peripheral vision (tunnel or telescope vision); this model is called a ring scotoma . Sometimes, this phenomenon may be missing in the early stages, but it is noticed when the individual often trips on objects or gets involved in a car accident. When vision loss involves the central area of the retina (also called macular dystrophy), patients experience difficulty with reading and detailed work that requires concentration on a single object, such as threading a thread through the eye of a needle. Many patients report seeing bright flashes (photopsia), often described as small flashing and shimmering lights.
The rate of disease progression and the degree of visual loss varies from person to person. Some extreme cases may present a rapid evolution within two decades, others a slow course that never leads to complete blindness. Early onset is found in more severe forms of retinitis pigmentosa, while patients with milder conditions (eg, autosomal dominant) may develop the disease in their fifth or sixth decade of life. In families with retinitis pigmentosa X-linked, men are more often affected than women and more severely; females, on the other hand, transmit the genetic characteristic (they carry the altered gene on the X chromosome) and show symptoms of the disorder less frequently.
Complications
Retinitis pigmentosa will continue to progress, albeit slowly. However, complete blindness is rare, but a significant reduction in peripheral and central vision may occur.
Patients with retinitis pigmentosa often develop retinal swelling (macular edema) or cataract at an early age. These complications can be treated if they interfere with vision.
Related diseases
Commonly, a patient with retinitis pigmentosa does not present other disorders and in this case we speak of retinitis pigmentosa "non-syndromic" or simple. However, several syndromes share some clinical symptoms with this eye disease; the most common is Usher syndrome, which affects about 10-30% of all patients with retinitis pigmentosa and is associated with congenital or progressive hearing loss. In Leber's congenital amaurosis, however, children can become blind, or nearly so, within the first six months of life. Other diseases related to retinitis pigmentosa include Bardet-Biedl syndrome and Refsum disease.
Causes
The disease can be caused by a number of genetic defects: in fact there are several genes that, if affected by the alteration, can cause the phenotype of retinitis pigmentosa. These normally encode proteins involved in the transduction cascade that allows vision, cellular transcription factors (which send erroneous messages to retinal cells) or elements that make up the structure of photoreceptors. Inherited gene mutations have been present in cells since conception; Common abnormalities include those of the genes RP1 (in retinitis pigmentosa-1, autosomal dominant), RHO (RP4, autosomal dominant) and RDS (RP7, autosomal dominant). The non-hereditary causes of retinitis pigmentosa are rare, but the possibility of finding an isolated case (spontaneous mutation), in which a family history of the disease is not present, is not excluded.
Inheritance patterns of retinitis pigmentosa
Retinitis pigmentosa is a hereditary condition and there are various inheritance patterns that determine the causality of the condition. Therefore, the main risk factor is a positive family history for the disease.
The severity and type of retinitis pigmentosa depend on the inherited acquisition of one or two of these abnormal genes. About 30-40% of cases are autosomal dominant, 50 to 60% are autosomal recessive and 5-15% are linked to the X chromosome.
Depending on the inheritance model, the severity and course may be different:
- Autosomal dominant inheritance. In the dominant autosomal forms of retinitis pigmentosa, an affected subject has an altered gene (with a mutation that causes the disease) paired with a normal gene. When the affected person has children with a healthy partner, there is a 50% chance that the affected parent can pass on the gene responsible for the disease to each conceived child. The healthy partner transmits only a normal gene kit (usually, in the couple the affected parent is the only one to have a mutated gene). In dominant diseases, a child who does not inherit the disease gene will not have retinitis pigmentosa and will not be able to pass it on to their children.
Autosomal dominant retinitis pigmentosa is a milder form of the disease, characterized by slow and late onset progression, generally in the fifth or sixth decade of life.
- Autosomal recessive inheritance. In autosomal recessive forms of retinitis pigmentosa, unaffected parents, who are healthy carriers, have a mutated gene paired with a healthy one. Each of their children has a 25% chance of inheriting two mutated genes (one from each parent), and this is the necessary condition for the onset of retinitis pigmentosa. Like parents, healthy children will not be affected, as two copies of the altered gene are needed for the disease to manifest.
- X-linked. In the X-linked forms of retinitis pigmentosa, the gene for the disease is found on the X chromosome. The females have two X chromosomes and can carry the mutated gene in one of them. Mothers transmit altered genes to their daughters, who in turn become carriers: they have a healthy version of the gene on the other X chromosome and for this reason, in general, they do not manifest the disease. Sometimes, however, when carrier females are examined, the retina shows slight signs of degeneration. Males have only one X chromosome paired with a Y chromosome: they are therefore genetically susceptible to X-linked diseases. Males with an X-linked disease always transmit the mutated gene on the X chromosome to their daughters, who then become carriers, while never transmitting a disease gene to their children (fathers transmit the Y chromosome to male children). Females have a 50% chance of passing on the X-linked disease gene to their daughters, who become carriers, and a 50% chance of transmitting it to male offspring, which manifests the disease. The X-linked form is the most severe, with loss of central vision already in the third decade of life.
Diagnosis
The clinical diagnosis is based on the presence of: night blindness and defects of the peripheral visual field, lesions in the fundus of the eye, reduced electroretinographic traces and progressive worsening of these signs. The examination of the retina by means of a slit lamp reveals a granular staining of the retina.
The electroretinogram (ERG) registers electrical currents produced in the retina in response to visual stimuli and makes it possible to assess whether the cells react correctly. In the case of retinitis pigmentosa, the ERG is reduced or absent.
It is important to remember that retinitis pigmentosa is an inherited disease that commonly occurs within a family. Therefore, if a member is diagnosed with retinal degeneration, a complete eye examination is strongly recommended for all family members. Also discussing patterns of inheritance with a genetic counselor can be useful for family planning.
Molecular diagnosis is possible for some genes. This test helps determine if members of an affected family have one of the genes responsible for retinitis pigmentosa and helps assess the risk of transmitting the disease from parents to children, but it is usually not performed due to the enormous genetic heterogeneity of the disease . Female carriers of X-linked recessive pigmentary retinitis can be identified by examining the fundus, the electroretinogram and, occasionally, direct mutation detection.
Treatment
To date, there is no cure for retinitis pigmentosa and no treatment is known to halt the evolution of the disease or restore vision. However, scientists have isolated several responsible genes and intensive research is currently underway. Therapeutic approaches for retinitis pigmentosa, being studied, include the use of stem cells, gene therapy and retinal prosthesis.
