| disease | Primary Retinal Pigmentary Degeneration |
| alias | Retinitis Pigmentosa, Primary Pigmentary Degeneration of the Retina, Retinitis Pigmentosa |
Primary pigmentary degeneration of the retina, historically referred to as retinitis pigmentosa, is a relatively common tapetoretinal degeneration. According to survey data from some regions in China, the population prevalence is approximately 1/3500.
bubble_chart Etiology
This disease is a hereditary disorder. Its inheritance patterns include autosomal recessive, autosomal dominant, and X-linked recessive, with autosomal recessive being the most common, followed by autosomal dominant, and X-linked recessive being the least common. Currently, it is believed that the autosomal dominant form involves at least two gene loci, located on the short arm of chromosome 1 and the long arm of chromosome 3. The X-linked inheritance gene is located on the short arm of the X chromosome, specifically in regions 1 and 2.
Regarding the mechanism of disease, some clues have emerged over the past 20 to 30 years. Based on data from electron microscopy, histochemistry, electrophysiology, and fundus fluorescein angiography, it is hypothesized that the disease primarily arises from the decline in the phagocytic and digestive functions of retinal pigment epithelial cells toward the outer segment discs of photoreceptor cells. This leads to the accumulation of degraded disc remnants, forming a barrier that obstructs the transport of nutrients from the choroid to the retina, resulting in progressive malnutrition, degeneration, and eventual loss of photoreceptor cells. This process has been confirmed in the retinas of RCS rats with primary retinal pigmentary degeneration. The exact cause of the failure in phagocytic and digestive functions of pigment epithelial cells remains unclear but may be related to genetic abnormalities or deficiencies in certain enzymes. In terms of immunology, recent studies have found abnormalities in both humoral and cellular immunity in patients with this disease. Activated T cells, B cells, and macrophages are present in the vitreous, and retinal pigment epithelial cells express HLA-DR antigens, which are absent in normal individuals. Additionally, autoimmune phenomena have been observed in patients, though there is insufficient evidence to confirm whether autoimmunity plays a role in the disease. In terms of generation and transformation, abnormalities in lipid metabolism have been detected in patients, with lipofuscin granules observed in the retina. There are also metabolic abnormalities in trace elements such as zinc, copper, and selenium, as well as in enzyme activity. In summary, this disease may involve multiple different pathological mechanisms.
bubble_chart Pathological ChangesThe specimens obtained clinically were all advanced-stage cases. The main changes observed under the optical microscope included progressive degeneration of the retinal neuroepithelial layer, particularly the rod cells, followed by gradual atrophy of the retinal layers from the outer to the inner layers, accompanied by glial proliferation. The pigment epithelial layer also underwent degeneration and hyperplasia, with pigment loss or abdominal masses observed, and migration into the inner layers of the retina. The walls of the retinal blood vessels underwent hyaline degeneration and thickening, sometimes leading to complete occlusion of the lumen. The choroidal vessels exhibited varying degrees of sclerosis, with capillaries partially or completely disappearing. The optic nerve could be completely atrophied, and glial proliferation on the optic disc often formed membranous masses, connecting with the glial membranes within the retina. The waxy yellow appearance of the optic disc observed under the ophthalmoscope is generally believed to be related to this.
bubble_chart Clinical Manifestations
1. Symptoms and Functional Changes
(1) Night blindness: This is the earliest symptom of the disease, often beginning in childhood or adolescence and usually occurring before visible changes in the fundus. Initially mild, it gradually worsens with age. A very small number of patients may not report night blindness in the early stages.
(2) Dark adaptation testing: In the early stages, cone cell function remains normal, while rod cell function declines, causing the final threshold of the rod cell curve to rise and reducing the difference between light and dark. In the advanced stage, rod cell function is lost, and the cone cell threshold also rises, forming a high, single-phase curve.
(4) Visual electrophysiology: The ERG shows no response, particularly the disappearance of the b-wave, which is a typical change in this disease. These changes often precede visible fundus alterations. The EOG LP/DT is significantly reduced or extinguished, detectable even in the early stages when changes in visual field, dark adaptation, or even ERG are not yet apparent. Thus, the EOG is more sensitive than the ERG for diagnosing this condition.
(5) Color vision: Most patients have normal color vision in childhood but gradually develop abnormalities. The typical change is blue-yellow blindness, with red-green color vision defects being less common.
2. Fundus Examination Findings In the early stages of the disease, even with night blindness, the fundus may appear entirely normal. Later, fundus changes gradually emerge as the disease progresses. Typical changes include:
(1) Retinal pigment deposition: Begins in the equatorial region, with pigments appearing as small, pointed spots that later increase in size, resembling bone cells or irregular lines, forming rings of varying widths around the equator. Pigments are often located near retinal blood vessels, particularly in front of veins, partially obscuring the vessels or distributed along them, with denser accumulation at vessel branches. Over time, pigment deposition spreads from the equator toward the posterior pole and periphery, eventually covering the entire fundus. Concurrently, pigment loss in the retinal pigment epithelium exposes choroidal vessels, creating a leopard-spot appearance. In the advanced stage, choroidal vessels also harden, appearing as yellow-white streaks. The vitreous is generally clear, though occasional dot-like or linear opacities may be seen.
(3) Optic disc changes: Normal in the early stages but tends to atrophy in the advanced stage. The disc appears pale with a slight yellow tint, termed "waxy optic disc," with slightly blurred edges and occasionally a hazy sensation as if covered by a thin veil.
(4) Fluorescein angiography findings: Large areas of non-fluorescence in the background indicate atrophy of the choroidal capillary layer. Retinal vessels may show occlusion, and mottled fluorescent spots may be observed in the posterior pole or periphery.
3. Special Clinical Types
(1) Unilateral primary retinal pigmentary degeneration: Very rare. Diagnosis requires one eye to exhibit typical changes of primary retinal pigmentary degeneration while the other eye remains entirely normal (including electrophysiological tests), with no onset in the unaffected eye after at least five years of follow-up. This type usually occurs in middle-aged patients and typically lacks a family history.
(2) Sectorial primary retinal pigmentary degeneration: Also very rare. Characterized by lesions affecting only the same quadrant in both eyes, with clear boundaries between affected and normal areas. Corresponding visual field changes occur, but vision remains relatively good, and ERG shows low amplitude. Fluorescein angiography reveals a larger affected area than observed via ophthalmoscopy. This type is often sporadic, but autosomal dominant, recessive, and X-linked recessive inheritance patterns have been reported.
(3) Central or pericentral primary retinal pigmentary degeneration: Also known as inverse progressive retinal pigmentary degeneration. Initial symptoms include vision decline and color vision impairment. Fundus examination reveals macular atrophy with bone spicule-like pigment accumulation, and ERG shows low amplitude or unrecordable waves. Early stages primarily involve cone cell damage, with rod cell damage occurring only in the late stage [third stage]. The advanced stage affects the peripheral retina and exhibits vascular changes. The condition ultimately leads to blindness. This type is usually inherited recessively, though dominant inheritance occasionally occurs.
(4) Non-pigmentary retinal pigmentary degeneration: This condition exhibits various symptoms typical of retinal pigmentary degeneration and corresponding visual function examination findings. Ophthalmoscopic examination reveals a uniformly dull fundus, thinning of retinal blood vessels, and waxy yellow atrophy of the optic disc in advanced stages. There is either no pigmentation or only a few bone cell-like pigment spots in the peripheral fundus, hence the name non-pigmentary retinal pigmentary degeneration. Some believe this form represents an early stage of pigmentary degeneration, with typical pigmentation appearing as the condition progresses. Therefore, it cannot be considered a distinct clinical type. However, there are indeed cases where pigmentary changes never occur. The inheritance patterns of this type are the same as those of typical pigmentary degeneration, including dominant, recessive, and X-linked recessive forms.
bubble_chart Treatment Measures
To date, there is no effective treatment for this disease. The literature has reported trials of vasodilators, vitamins A and B1, tissue therapy, various hormones, Chinese herbal medicine, acupuncture, and the implantation of extraocular muscle bundles into the suprachoroidal space, among others, but the results have been inconclusive. The following methods may help prevent rapid deterioration of visual function.
1. Selection of tinted lenses Strong light can accelerate the degeneration of photoreceptor outer segments, so tinted glasses must be worn. Theoretically, the lens color should be a red-purple hue similar to visual purple (rhodopsin), but for cosmetic reasons, gray lenses are used. For cloudy days or indoor use, grade 0–1 lenses are recommended; for sunny days or strong light, grade 2–3 gray lenses are suitable. Dark black sunglasses are not advisable. Green lenses are prohibited.
2. Avoid excessive mental and physical stress Excessive stress increases catecholamine (Black Catechu phenethylamine) levels in body fluids, causing choroidal vasoconstriction and hypoxia, which exacerbates photoreceptor degeneration. Traditional Chinese qigong (static exercises) can regulate the activity of the cerebral cortex and various organs through conscious control. If practiced consistently, it may help prevent rapid deterioration of visual function in this disease.
Patients with recessive inheritance of this disease experience early onset, severe symptoms, rapid progression, and an extremely poor prognosis. By around age 30, visual function is already significantly impaired, and near-total blindness occurs by approximately age 50. In contrast, patients with dominant inheritance show the opposite pattern, with occasional cases stabilizing after reaching a certain stage, resulting in a relatively better prognosis compared to the recessive type. Therefore, they may still have the opportunity to attend school and work with some difficulty. For those with recessive inheritance, a history of consanguineous marriage is often found among their ancestors. Prohibiting consanguineous marriages could reduce the incidence of this disease by about 22%. Additionally, individuals with recessive inheritance should avoid marrying those with a family history of the disease and must not marry someone who also has the condition. For patients with dominant inheritance, the risk of their offspring developing the disease is 50%.
Posterior polar white internal visual obstruction is a common complication of this disease. It typically occurs in the advanced stage, with the lens opacity presenting as star-shaped and located in the posterior subcapsular cortex. The progression is slow, and it may eventually lead to complete lens opacity. About 1–3% of cases are complicated by glaucoma, mostly open-angle, with closed-angle being rare. Some statistical studies suggest that glaucoma is associated with the disease rather than being a complication. Approximately 50% of cases are accompanied by myopia, which is more common in autosomal recessive and X-linked recessive inheritance patients. It may also be observed in other family members. Literature reports that 44–100% of patients with this disease have varying degrees of hearing impairment, while 10.4–33% have deafness and dumbness. Conversely, 19.4% of patients with deafness and dumbness also suffer from this disease. Both the retina and the inner ear's Corti organ originate from the neuroepithelium, so their progressive degeneration may stem from the same gene. Pigmentary degeneration and deafness can occur in the same patient or separately in different members of the same family, but they do not appear to arise from different genes—rather, they may result from the pleiotropic effects of the same gene. This disease can also be associated with other genetic disorders, the most common being the Laurence-Moon-Bardt-Biedl syndrome, which affects both the diencephalic-pituitary region and the retina. The classic syndrome consists of five components: retinal pigmentary degeneration, hypogenitalism, obesity, polydactyly, and intellectual disability. This syndrome manifests early in development, with significant clinical symptoms appearing around age 10 (or earlier). Cases lacking all five components are termed incomplete forms. Additionally, this disease may present with some rare ocular or other systemic complications or associations, which are omitted here due to their rarity.
Based on the above medical history, symptoms, visual function, and ophthalmoscopic findings, the diagnosis is not particularly difficult. However, it is important to differentiate it from secondary retinal pigmentary degeneration caused by congenital or acquired choroid membrane and retinal membrane inflammation.
Congenital syphilis and fetal fundus lesions caused by maternal rubella infection during the third month of pregnancy present with fundus findings almost identical to this condition after birth, and visual function tests such as ERG and visual field are also difficult to distinguish. Only after confirming the negative serological reaction for syphilis in the child's parents and the absence of a rubella history in the mother during early pregnancy can a diagnosis of primary pigmentary degeneration be made. If necessary, long-term follow-up observation is required. Congenital secondary pigmentary degeneration exists at birth and remains static.
Acquired syphilis and certain acute infectious diseases (such as smallpox, measles, scarlet fever, mumps, etc.) can all cause choroid membrane and retinal membrane inflammation. The fundus changes after the inflammation subsides may sometimes resemble primary pigmentary degeneration. Differentiation should be made based on medical history, serological tests, as well as characteristics such as larger and deeper pigment patches in the fundus, irregular (non-bone cell-like) formation, presence of choroid membrane and retinal membrane atrophy patches, grayish-white optic disc atrophy (not waxy yellow), and milder night blindness.
