Primary retinitis pigmentosa


Introduction to primary retinitis pigmentosa

Primary retinitis pigmentosa (primarypigmentarydegenerationofretina) is a relatively common blanket-retinal degeneration, which is a group of hereditary retinal degenerative diseases in which the loss of sexy photocell and pigment epithelial function is common. It is a common type. The carpet-retinal degeneration (tapetoretinaldegeneration) is also a common blinding eye disease worldwide. It usually occurs in children or adolescents. The symptoms are aggravated in adolescence, the visual field is gradually contracted, and the middle eye or old age is affected by the macular. Loss, or even serious obstacles, and blindness.

basic knowledge

The proportion of the disease: 0.05% of the specific population

Susceptible population: the disease often starts in children or early childhood

Mode of infection: non-infectious

Complications: cataract, hearing impairment, deafness, glaucoma


Cause of primary retinitis pigmentosa

(1) Causes of the disease

The disease is a hereditary disease, and its hereditary pattern is autosomal recessive, dominant and sexually linked, three of which are recessively inherited (65% to 90%); dominant inheritance is second (3% to 20%). ); sexual chain inheritance is the least (less than 10%), but sporadic cases with negative family history also account for a considerable number. Through linkage analysis, more than 50 disease-causing gene loci have been found on human chromosomes. In recent years, Using localization cloning and "locating candidate genes", 18 of them have been identified. Currently, the autosomal dominant inheritance has at least two gene loci, located on the short arm of chromosome 1 and the long arm of chromosome 3. The sex-linked genetics are located in the short-wall region of the X chromosome and in the second region.

(two) pathogenesis

Regarding the pathogenesis, in the past 20 to 30 years, there are some clues of the valve. According to the electron microscopy, histochemistry, electrophysiology, fundus fluorescein angiography and other examination data, it is speculated that the occurrence of this disease is mainly due to the retinal pigment epithelial cells. The phagocytosis of the extracellular disk membrane, the digestive function declines, causing the disc membrane to disintegrate, and the procedure forms a layer of obstacles, hindering the rotation of nutrients from the choroid to the retina, causing progressive malnutrition and gradual degeneration of the visual cells. Disappeared, this process has been confirmed in the retina of a RCS mouse with primary retinal pigmentation. The cause of phagocytic digestive failure of pigment epithelial cells is still unclear, possibly with genetic abnormalities, certain or certain enzymes. In terms of immunology, in recent years, studies have found that the patient's humoral immunity, cellular immunity are abnormal, activated T cells in the vitreous, B cells and macrophages, retinal pigment epithelial cells express HLA-DR antigen, normal People do not have such performance, but also found that patients with this disease have autoimmune phenomenon, but whether there is self There is still no sufficient basis for immunological diseases. In terms of biochemistry, it is also found that patients with this disease have autoimmune phenomena, but there is still no sufficient basis for whether the disease has autoimmune diseases. In terms of biochemistry, abnormal lipid metabolism is found in patients with this disease. There are lipid-brown granules accumulating; zinc, copper, selenium and other trace elements and enzyme metabolism are also abnormal. In summary, the disease may have a variety of different pathogenesis, genetic defects, leading to photoreceptor cells Normal structural and functional variability of the outer segment affects the metabolism of photoreceptor cells and pigment epithelial cells; it can also interfere with the interaction between photoreceptor cells and pigment epithelial cells; cause abnormal photoelectric conversion pathways; it can also induce apoptosis induced by neighboring cells. This high degree of genetic heterogeneity, although ultimately ended with photoreceptor apoptosis, has produced different types and processes in the clinic.

In immunology, it was found that the patients have abnormal humoral immunity and cellular immunity. Activated T cells, B cells and macrophages, and retinal pigment epithelial cells express HLA-DR antigen in the vitreous. Therefore, it is believed that patients with this disease have autoimmune phenomena, but there is still no sufficient basis for whether the disease is an autoimmune disease. In terms of biochemistry, it is found that the patient has abnormal lipid metabolism, and there are particles of lipofuscin in the retina, zinc. Trace elements such as copper and selenium and enzyme metabolism are also abnormal.

Due to different genetic methods, clinical manifestations are also different. In general, the incidence of complications such as night blindness, dark adaptation, EOG and ERG changes, and the age of cataracts such as posterior cataract and cystoid macular edema It is also the highest; followed by autosomal recessive inheritance; once again, dominant inheritance, sporadic conditions are milder, and the age of onset is later.

Pathological changes:

The clinically obtained specimens are all advanced cases. The main changes seen under the light microscope are the retinal neuroepithelial layer, especially the progressive degeneration of rod cells, followed by the gradual atrophy of the retina from the outer to the inner layers, accompanied by gliosis. The pigment epithelial layer also undergoes degeneration and hyperplasia. It can be seen that the pigment is lost or accumulating, and migrates to the inner layer of the retina. The retinal vessel wall is hyaline degenerated and thickened, and even the lumen is completely occluded. The choroidal blood vessels can be hardened to varying degrees. The blood vessels completely or partially disappear, the optic nerve can be completely atrophied, and there are often glial hyperplasia on the ribs, forming a membrane block, which is connected with the glial membrane in the retina. The wax yellow of the optic disc seen under the ophthalmoscope is generally considered to be related to this. .


Primary retinitis pigmentosa prevention

The patients with recessive inheritance of this disease have early onset, serious illness, rapid development, and extremely poor prognosis. The visual function has been highly unhealed at the age of 30 years old, and nearly blind to the age of 50. The dominant genetic patients are vice versa, and occasionally they have developed to some extent. After the degree tends to be static, the prognosis is relatively better than the recessive hereditary type, so it can wait until the opportunity of normal schooling and employment. The occult inheritance of this disease has a history of close relatives and smoke, prohibiting close relatives. The incidence of this disease is reduced by about 22%. In addition, patients with recessive inheritance should try to avoid marriage with family members of this disease, and can not marry those who also suffer from this disease. Patients with dominant inheritance have a risk of developing this disease for their children. 50%, the disease is a hereditary disease, and its ancestors have a history of close relatives marriage. Prohibition of close relative marriage can reduce the incidence of this disease by about 22%.


Primary retinitis pigmentosa complications Complications, cataract, hearing loss, deafness, glaucoma

Post-polar cataract is a common complication of this disease. It usually occurs in the late stage. The crystal opacity is star-shaped and is located in the posterior capsule. The progress is slow, and finally the whole crystal is turbid. About 1% to 3% of cases are complicated with glaucoma. Mostly wide angle, angle closure is rare, some people from a statistical point of view, that glaucoma is associated with the disease rather than complications, about 50% of cases with myopia, myopia is more common in autosomal recessive and sexual chain Patients with sexual recessive inheritance can also be found in other members of the family. In the literature, 44% to 100% of the disease has varying degrees of hearing impairment; 10.4% to 33% have both hoarseness and mute duplication. Up to 19.4%, the Corti organs in the retina and inner ear are derived from the neuroepithelial, so the progressive degeneration of the two may be from the same gene. Pigment degeneration and deafness can occur not only in the same patient, but also in different members of the same family. However, the two do not seem to originate from different genes, may be caused by the multi-directionality of the same gene, this disease may be associated with other hereditary diseases, the more common is the pituitary region and the retina at the same time Laurenc e-Moon-Bardt-Biedl syndrome, typical of retinitis pigmentosa, genital dysplasia, obesity, multi-finger (toe) and intelligent defects, the syndrome appeared in the early development, around 10 years old ( Or earlier, there is significant clinical manifestation, five components are not possessed, called incomplete type, in addition, the disease has a blink of an eye or other organs complicated or associated with diseases, because it is rare.

Post-polar cataract

It is a common complication of this disease, usually occurs in the late stage, the posterior capsule of the lens is loose and spongy turbid, slightly like a star, slow progress, and finally complete turbidity.

2. Glaucoma

1% to 3% of cases can be complicated by glaucoma. Some people have studied from a statistical point of view and believe that glaucoma is associated with the disease, not concurrent.

3. Myopia

About 50% of cases are associated with high or degenerative myopia, and can also be found in other members of the family.

4. Other

In the literature, 44% to 100% of the disease have different degrees of hearing impairment; 10.4% to 33% have hoarseness, and the disease is also 19.4%, and the Couti organs of the retina and inner ear are derived from the nerve. Epithelial, so the progressive degeneration of the two may come from the same gene. Pigmentation and deafness can occur not only in the same patient, but also in different members of the same family, but the two do not seem to originate from different genes and may be identical. The gene is caused by omnidirectionality.


Symptoms of primary retinitis pigmentosa Common symptoms Color vision abnormal macular cystic edema Optic nerve atrophy Fundus changes lens opacity night blind green blind

Eye performance:

1 fundus: retinal pigmentation characteristic fundus changes are retinal pigment epithelial depigmentation, retinal pigment epithelial atrophy and pigment migration, manifested as retinal pigmentation and retinal arteriolar constriction, lesions of early pigment epithelial lesions expressed as small intraretinal The dusty pigmentation, the retina and the appearance of worm-like or salt-and-salt due to depigmentation, as the disease progresses, the fundus lesions develop from the equator to the peripheral and posterior poles, and various forms of pigmentation appear in the equator and surrounding retina. It is often manifested by the accumulation of blood vessels near the blood vessels, and the retinal pigmentosa is fully advanced. There are retinal osteocyte-like pigmentation and retinal artery stenosis, due to the continuous depigmentation and atrophy of the retinal pigment epithelium, and at the same time The gradual atrophy of the choroidal capillaries occurs, which is manifested by the exposure of larger choroidal vessels, and even the appearance of severe choroidal atrophy in the outer choroidal vessels. The retinal vessels are uniformly uniform in white-line vascular stenosis to the late pole. Thin, but the blood vessels are not surrounded by white sheaths. The degree of narrowing of the vein is more pronounced than that of the vein. The optic disc of the fundus of the eye is normal at an early stage, and a full waxy yellow appearance appears in a fully advanced phase. According to histopathology and visual electrophysiological observation, the color of this sallow is a nerve glue. The optic disc surface membrane caused by hyperplasia is not caused by optic atrophy. These studies also found that retinal ganglion cells and nerve fiber layers in retinitis pigmentosa are relatively intact and rarely involved in this disease, and ultrastructural studies have confirmed The patient's retinal surface membrane is derived from the astrocytes of the optic nerve and extends from the surface of the optic disc to the quadrants of the retina.

In the early stage of various types of retinitis pigmentosa, the appearance of the macular area is normal or only the foveal reflex disappears. Subsequently, pigmentation disorder may occur, and the pigmentation of the retinal pigment epithelium in the macular area of the fovea is degenerated. About 60% of patients with advanced retinitis pigmentosa have atrophy. Macular degeneration, about 20% of patients with cystoid macular degeneration or incomplete macular hole, with radial retinoic traction and varying degrees of retinal surface membrane, about 23% of patients with macular cystic edema, macular retinal surface membrane There may be pseudo-macular hole, which should be noted in fundus examination. In addition, about 2% of patients may have bilateral or unilateral optic disc calcification, which is a layer of cell-free calcification, often composed of nerve fibers or glue. The surrounding of cytoplasmic cells is easily mistaken for hamartoma or even optic disc edema.

2 lens: about 50% of patients with RP have posterior subcapsular cataract, which is characterized by porous or bready opacity of the posterior capsule of the lens posterior capsule, with yellow crystal changes, and finally can develop into the entire lens opacity, looks like Concurrent cataract, so patients with bilateral cataract should pay attention to the presence or absence of RP. This lesion is most common in XL-type RP. The mechanism of cataract formation is still unclear. Some people think that it is related to pseudo-inflammatory pigment cells in the vitreous. RP denatured products may activate phagocytic cells, release activated oxygen molecules, interfere with lens metabolism, or excessively oxidize membrane lipids during degeneration to produce products carrying toxins and lipid genes and directly damage lens. Ultrastructural study of cataract lens in RP patients Only local epithelial degeneration of the lens that caused changes in permeability was found, and there were no other special changes. In addition, RP patients may have occasional lens dislocation.

3 vitreous: most of the RP patients can appear floating cells in the vitreous, concentrated and then detached, Prueff et al. have divided the vitreous lesions of RP into 4 stages, that is, fine dust particles spread throughout the vitreous; after the vitreous detachment; vitreous concentrate, can be accompanied Snowball opaque floats and vitreous collapse, the volume is significantly reduced, no matter at any stage of denaturation, fine particles are evenly distributed in the vitreous, and they are found to be free melanin particles, pigment epithelium of the retina, and stars through the transmission electron microscopic examination of the vitreous. Cells, macrophages and pigmented melanocytes.

4 other eye performance: RP is often accompanied by myopia and astigmatism, the incidence can be as high as 75%, especially in XL-type RP, it is estimated that the incidence of glaucoma in RP patients is higher than in the normal population, and mainly Primary angle-closure glaucoma may be associated with a prone to a narrow anterior chamber angle in RP patients. In addition, RP may occasionally be accompanied by exudative retinal vasculopathy.


Examination of primary retinitis pigmentosa

Genetics and immunology.

1. Dynamic and static fields of view

Goldmann spherical perimetry has been routinely used for dynamic visual field examination of RP. The results of examinations with I~4e, III~4e and V~4e are excellent, and the reproducibility is relatively reliable. The early visual field of RP is the upper peripheral visual field defect. The annular dark spot area appears from 20 ° to 25 ° outside the fixation point. The dark spot area consists of a group of isolated dark spots. As the disease progresses, the dark spots expand and merge into a ring shape, and the outer edge of the ring dark area expands rapidly to the periphery. The dark area of the inner edge of the ring is relatively slow and concentrically invaded. Usually the upper and nasal side fields are first lost. After a period of complete disappearance of the peripheral field of view, the central field of view still retains a small area of the macula, for the AD type. A study of the rate of visual field loss in RP patients found that among patients with a central view of 10° or slightly larger, 93% were younger than 20 years old, 89% were 20-40 years old, and 60% were 40 years old or older. IV4e optotype), Berson et al. conducted a 3-year follow-up study of visual field changes in 92 RP patients, and found that 21% of patients had a worsened visual field after 1 year, while 16% had stable or slightly improved, 3 years later. Then 33% have deteriorated, 14% have stabilized or improved, and the average annual mourning 4.6% of residual visual field. The temporary improvement of visual field observed during follow-up may be the response of rod function fluctuation in RP natural course, but it may also be the error in visual field physical examination. Some patients with RP progress faster. The visual field can also deteriorate rapidly. The dynamic visual field examination is a simple and effective method for determining the position and extent of the visual field defect. The static visual field is more accurate than the dynamic visual field for determining the depth of the visual field damage and the light sensitivity of the specific retinal area. The eye-adapting cone is sensitive to red light to blue light, and the rod is sensitive to blue light to red light. Therefore, the red and blue light spots can be used to check the threshold of specific retinal areas of dark-adapted eyes of RP patients along the vertical or horizontal meridian (ie, spectral sensitivity). To evaluate the function of the patient's retina and cone. The two-color dark-adapted static visual field method commonly used in RP is generally a color spot with wavelengths of 500 nm (blue-green light) and 650 nm (red light) after dark adaptation. 75 points of retina were detected, and the rod and cone sensitivity of each test point was known by comparison with the normal average of the point, from 2 The sensitivity of color-stimulated sensitivities can be determined that the visual point of each detection point is mediated by the rod and/or cone. Massof and Finkelstein used this two-color dark-adapted static field of view to analyze the function of the retina and cone in RP patients. There are two types of rods, the type of cone sensitivity loss, and the RP can be classified accordingly. Ernst et al. subsequently discovered an automatic two-color static field of view, using LEDs to provide red and blue-green light stimulation, and using this perimeter Two-color dark-adapted automatic static visual field examination was performed on 104 RP patients with 44 AD-type RP families, which further confirmed that AD-type RP has two subtypes with different visual function impairment characteristics.

2. Dark adaptation threshold

To detect the visual sensitivity to the stimuli during dark adaptation, the dark adaptation curve is usually drawn by the Goldmann-Weekers dark adaptation meter, and the dark adaptation final threshold is detected. It is one of the sensitive indicators for evaluating the function of the retina, and the RP is often typical. The dark adaptation threshold is increased, but this type of dark adaptation meter only measures the local light sensitivity of a fixed retinal area (often 11 ° above the fovea). In recent years, dark-adapted examination with two-color light (500 nm and 650 nm) has begun. Similar to static visual field examination, it can detect visual sensitivity and cadence and cone threshold in any part of the retina. It is clinically valuable for evaluating regional or impaired retinal function in RP patients and estimating visual function prognosis.

3. Full view ERG

Since Karpe discovered the characteristic ERG performance of RP in 1945, with the improvement of ERG detection conditions, especially the application of computer signal averaging technology, the ERG response below microvolts can be detected, and the clinical diagnosis and visual function evaluation of RP are promoted. The whole field ERG recorded by the whole retina uniform light stimulation can be separated by the high frequency and strong scintillation light by changing the wavelength, frequency and retinal light and dark adaptation state of the stimulating light. Cone reaction, because pyramidal cells can respond to scintillation light up to 70 weeks/s, while rod cells can only respond to scintillation light for up to 8 weeks/s, and stimulate with weak blue light (<470 nm) under dark adaptation The ERG rod reaction can be isolated, and the red light stimulation (>600nm) can produce bimodal b-waves representing the rod and cone reaction respectively. The full-field ERG examination can evaluate the type and extent of photoreceptor involvement in RP. Because the rod response is the earliest selectively involved in all types of RP, full-field ERG examination is helpful for the early diagnosis of RP, which can be abnormal before the onset of symptoms or visible changes in the fundus; It can help identify patients in the RP family and normal family members. The percentage of normal and abnormal ERG in the RP family is consistent with the Mendelian ratio of hereditary type. In the RP family, the ERG of the members aged 6 years is normal, and the RP is found later. The possibility is very small, ERG can also help to identify early RP and non-progressive retinal degeneration in the clinic. The former has a lower amplitude of the ERG cone reaction and a longer peak, while the latter only shows a decrease in amplitude. In addition, the full-field ERG can Objectively monitor the natural course of RP and provide information for estimating prognosis. The ERG response of RP patients often becomes smaller as the disease progresses. Most patients have blindness when the ERG amplitude is lower than 0.05V. The ERG of the fan-shaped RP patients shows low amplitude. Patients with normal peaks and good prognosis have a full-field ERG examination using computer-wide narrow-band filtration technique, which also helps objectively evaluate treatment attempts aimed at stabilizing or delaying the RP degeneration process. ERG is helping to identify XL-type RP genes. Carriers also have clinical value.

It is worth mentioning that ERG is the total electrical response of the outer and middle layers of the retina. It is usually not positively related to the visual acuity that represents the function of the macula. The contribution of the macula to the ERG cone response is at most about 15%, so the cone response is abnormal. It does not completely represent the damage of the fovea.

4. Fundus fluorescein angiography of retinitis pigmentosa

Fundus fluorescein angiography can show the small RPE changes that are difficult to detect in early RP examinations, which is helpful for early diagnosis. The angiographic images of most RP patients show choroidal fluorescence or pigmentation due to RPE depigmentation or RPE loss. Fluorescence obstruction caused by hyperplasia and stagnation, 15% to 20% of patients have extensive RPE depigmentation around the macula, and the RPE in the macula, especially in the fovea, remains intact, so fluorescein angiography shows the appearance of "bull-like" This performance often indicates that the patient has better visual acuity. The advanced RP can show choroidal capillary atrophy. In addition, about 25% of patients may have fluorescein leakage, and the macular retinal vascular leakage may be accompanied by cystoid macular edema or retina. Thickening and causing premature visual impairment of the center of the eye, fluorescein fundus angiography can help the clinical differential diagnosis of RP and other degenerative retinopathy such as choroidal disease, but also contribute to the rare complications or associated disease of RP, such as osmosis Retinal vasculopathy and macular edema with appropriate clinical management are important to prevent premature loss of RP visual function.

5. Pathological examination

The clinically obtained specimens are all advanced cases. The main pathological changes are the retinal neuroepithelial layer, especially the progressive degeneration of rod cells, followed by the gradual atrophy of the retina from the outer to the inner layers, accompanied by gliosis, pigmentation. The epithelial cell layer also undergoes degeneration and hyperplasia, and the pigment disappears or accumulates, and migrates to the inner layer of the retina. The retinal vessel wall is hyaline degenerated and thickened, and even the lumen is completely occluded. The choroidal blood vessels may have different degrees of sclerosis, capillaries. Completely or partially disappeared, the optic nerve can be completely atrophied, the optic disc often has gliosis, forming a membranous shape, connected with the glial membrane in the retina, and the optic disc wax seen under the ophthalmoscope is generally considered to be caused by gliosis. .

In recent years, ultrastructural examinations have confirmed that the rod-shaped outer disc membrane has been lost in the early stage of the disease, and the cone-shaped outer disc membrane is relatively reserved, but there are also some cases in the residual cone-shaped outer disc. On the membrane, there are abnormal changes such as shortening and vacuolization. It is speculated that the above pathological changes may be caused by structural gene abnormalities or gene defects of synthetase and its products in the photoreceptor extracellular disk membrane.

6. See the fundus examination

Although the fundus can be completely normal in the early stage of the disease, the fundus changes gradually appear with the progress of the disease. Typical changes include:

(1) nipple atrophy: occurs in the late stage of the disease, pale and slightly yellow, called "wax-like optic nipple", the edge is slightly blurred, occasionally like the sensation of being covered by a layer of tulle.

(2) Retinal vascular stenosis; the blood vessels are consistently narrow, especially the arteries are prominent, and the degree of stenosis reflects the severity of the disease. In the advanced stage, the arteries are extremely thin, and it is difficult to recognize and disappear after the peripheral fundus, but there is no white line. There is no white sheath.

(3) Retinal pigmentation begins at the equator, and the pigment has small spots with protrusions, which then increase and become larger, mostly typical of bone cells, sometimes irregular lines, and the initial pigment spots are distributed around the equator in a circular pattern. Mostly located near the retinal blood vessels, especially in front of the veins, covering a part of the blood vessels, or distributed along the blood vessels, and more common in the branches of blood vessels. Later, the pigmentation spreads to the center and the peripheral part, and the annular distribution area of the pigment spots gradually widens. Even covered with all the fundus, while the retina atrophy, pigment epithelial pigmentation, exposed choroidal blood vessels and leopard-like fundus, the entire fundus is dark, the choroidal blood vessels are also hardened, yellow-white stripes, the vitreous is generally clear, sometimes visible A small amount of point or line turbidity.

(4) FFA: visible vascular capillary atrophy, retinal blood vessels are occluded, sometimes visible macular, fluorescent leakage in the posterior pole and even the peripheral part.


Diagnosis and differentiation of primary retinitis pigmentosa

According to the above medical history, symptoms, visual function and ophthalmoscopy examination, the diagnosis is not too difficult, but attention should be paid to the secondary retinitis pigmentosa after some congenital or acquired chorioretinal inflammation.

Congenital syphilis and fetal fundus lesions caused by pregnant women in the third month of pregnancy, the fundus findings after birth are almost identical to the disease, ERG, visual field and other visual function test results are also difficult to distinguish, only in the determination of children Parental serum melanin-negative and mothers with no history of rubella in the early stage can be diagnosed as primary pigmentary degeneration. If necessary, follow-up observation is needed. Congenital secondary pigmentary degeneration is already present at birth, and the condition is still. .

Acquired syphilis and certain acute infectious diseases (such as smallpox, measles, scarlet fever, mumps, etc.), can occur in chorioretinitis, the fundus changes after inflammation subsides, sometimes similar to primary pigmentary degeneration, when from the medical history Serological examination and fundus pigmentation are large and the position is deep, irregular (non-osteocyte-like), choroidal retinal atrophy, optic disc atrophy gray-white (not waxy yellow), and the degree of night blindness is mild.