diabetic retinopathy
Introduction
Introduction to diabetic retinopathy Diabetic retinopathy (DR) is the most important manifestation of diabetic microangiopathy. It is a fundus lesion with specific changes. It is one of the serious complications of diabetes. It is clinically marked by the presence of retinal neovascularization. Diabetic retinopathy without retinal neovascularization is called nonproliferative diabetic retinoopathy (NPDR) (or simple or background type), and diabetic retinopathy with retinal neovascularization is called Proliferative diabetic retinopathy (PDR). Diabetes can cause two types of retinopathy, proliferative and non-proliferative retinopathy. Diabetic retinopathy is one of the major blinding diseases. Diabetic retinopathy can occur regardless of whether insulin therapy is used. Diabetes damages the retina mainly due to the increase of blood sugar, thickening of the small vessel wall, and increased permeability, making the small blood vessels more susceptible to deformation and leakage. The severity of diabetic retinopathy and the extent of visual loss are related to the control of blood glucose levels and the length of diabetes. The length of illness is especially important. Diabetic retinopathy usually occurs after at least 10 years of diabetes. basic knowledge The proportion of illness: 0.02%-0.05% Susceptible people: no specific population Mode of infection: non-infectious Complications: vitreous hemorrhage retinal detachment hypertension
Cause
Causes of diabetic retinopathy
(1) Causes of the disease
Diabetic patients are mainly insulin hormones and abnormal cell metabolism, causing changes in eye tissue, nerve and blood vessel microcirculation, causing damage to the eye's nutrition and visual function. Microvessels are between small arteries and tiny veins, and the lumen is less than 100~ The 150 m microvascular and capillary network is a place where tissue and blood exchange substances. Due to changes in blood components of diabetic patients, vascular endothelial cell dysfunction causes damage to the blood-retinal barrier, and retinal capillary endothelial cytochrome epithelium The intercellular junction is destroyed, causing leakage of small blood vessels. Microvascular disease in diabetic patients mainly occurs in the retina and kidney, which is the main cause of blindness, renal failure and death.
1. Capillary basement membrane thickening
When the blood sugar control of diabetic patients is poor, a large amount of sugar infiltrates into the basement membrane to form a macromolecular polysaccharide, which thickens the basement membrane, breaks the protein linkage, and the basement membrane structure is loose and porous. Therefore, proteins in the plasma easily leak out of the blood vessel wall, fibrin, etc. Deposited in the blood vessel wall, causing microvessel cystic expansion, early this functional change is reversible, if the disease continues to develop, the blood vessel wall is damaged, the microvascular basement membrane is thickened, resulting in thinning of the blood vessel, slow blood flow, easy to cause thrombosis Formation, capillary pericytes loss, endothelial cell damage and shedding, thrombus occlusion of small blood vessels and capillaries, resulting in the formation of new blood vessels, while diabetic retinal vascular fragility changes are prone to leakage or bleeding, if the new blood vessels rupture, Vitreous hemorrhage, hemorrhagic glaucoma.
2. Tissue hypoxia
Hyperglycemia causes increased glycated hemoglobin in red blood cells, difficult separation of oxygenated hemoglobin, decreased plasticity of red blood cells, tissue hypoxia, microvascular expansion, thickening of microvessel walls, and unfavorable supply of oxygen and nutrients to tissue cells. Tissue oxygen supply depends not only on Blood flow, and associated with red blood cells and hemoglobin, red blood cell 2,3-diphosphoglyceride (2,3-DPG) combined with hemoglobin (Hb), reducing the affinity of Hb for oxygen, making oxygen easy to dissociate when blood sugar rises When high, excessive glycosylated hemoglobin (HbAlc) is produced in the red blood cells, which prevents the binding of 2,3-DPG to Hb, so that the affinity of Hb to oxygen is enhanced, so that oxygen is not easily dissociated, resulting in hypoxia of the tissue, due to tissue hypoxia, Vasodilatation, increased permeability, swelling of endothelial cells, disappearance of dermal cells, causing blood-retinal barrier disintegration and decreased fibrin function in the wall, elevated fibrinogen levels in the blood, enhanced red blood cell agglutination, causing thrombosis Forming, the blood vessels can be blocked, the blood flow is stagnant, and the tissue is hypoxic.
3. Hemodynamic changes
The red blood cells of diabetic patients are glycosylated, which reduces their deformability, so that red blood cells can not pass through the capillary lumen smoothly. The red blood cell glycosylation and changes of plasma protein components lead to increased blood viscosity in diabetic patients, decreased active substances in plasma, and normal red blood cells pass. Small capillaries need to be deformed to pass through, while the red blood cell hardness of diabetic patients increases due to glycolysis, the deformation ability is reduced, and the capillary wall is damaged. The shear stress is closely related to blood viscosity, and high shear stress can be There are some important changes in the blood vessel wall. The endothelial cells are deformed and elongated, and finally disappear, thus increasing the permeability of the wall to proteins and other substances. The early phenomenon of microvascular disease is that microvascular kinetic variability leads to increased capillary pressure, followed by plasma. Protein extravasation increases, proteins leak from the blood vessels to the deep retina, and the shallow layers form hard exudation and soft exudation respectively. Fibrin also enters and deposits in the blood vessel wall, transforming into non-degradable glycosylation products and affecting blood vessels. Elasticity, when the blood vessel elasticity is normal, can The arteries constantly change their caliber to control the pressure in the cavity. If the elasticity of the blood vessels is poor, the blood flow will be lost, and the macular part with large blood flow will be edema. The macular edema is often the main cause of blindness in diabetic patients. In the case of insufficiency, changes in systemic blood pressure will increase the perfusion pressure of the retinal blood vessels, increase the exudation of damaged blood vessels, and increase the shear stress on the endothelial cell layer, so hypertension can promote diabetic retinopathy. Occurrence and development.
4. Genetic factors
The study on the genetic quality of diabetic eye complications started from three aspects: 1 is twin; 2 is pedigree analysis; 3 is genetic marker, and the twins survey results show that 37 pairs of non-insulin-dependent diabetes mellitus (NIDDM) and 31 pairs of insulin Among the monozygotic twins of dependent diabetes mellitus (IDDM), there were 35 pairs and 21 pairs of retinopathy with similar degrees. In the two IDDM pedigree surveys, 83% of the siblings with kidney disease had kidney damage. Only 13% of patients with proband without kidney disease have kidney disease; the above findings support diabetic nephropathy and retinopathy are related to genetic factors, but it must be emphasized that external environmental factors, family nutrition patterns, especially carbohydrate intake differences cannot be excluded. Etc. In summary, diabetic retinopathy and kidney disease may be polygenic diseases caused by a variety of genetic factors.
(two) pathogenesis
The pathogenesis of diabetic retinopathy is still not fully understood. There are five basic pathological processes in diabetic retinopathy: 1 retinal capillary microaneurysm formation; 2 increased vascular permeability; 3 vascular occlusion; 4 neovascularization and fibrous tissue hyperplasia 5 fibrovascular membrane contraction, the clinical signs of a patient with diabetic retinopathy depends on the relative performance of these five processes.
Although microaneurysms can also be seen in other diseases (such as branch retinal vein occlusion, idiopathic retinal vasodilation, etc.), it is still a characteristic manifestation of diabetic retinopathy and is the earliest reliable feature of the disease. Histologically, the microaneurysm is initially characterized by loss of retinal capillary pericytes, thinning of the wall, acellular vascular development and cystic protrusion, followed by cell growth, thickening of the basement membrane, wrapping of the microaneurysm, and tumor cavity. The cellulose and cells gradually accumulate inside, and the accumulation of the tumor can occlude the tumor cavity. As the disease is discovered, the capillaries are dilated. This may be due to the disorder of the cyclic self-regulation mechanism required for metabolism, and is a reversible functional change of the microcirculation. However, due to the increasing degree of tissue ischemia and hypoxia, the decompensation is automatically regulated, the capillary generator is qualitatively damaged, the permeability is increased, the blood-retinal barrier is destroyed, the plasma substance leaks into the retina, and retinal edema and hard exudation occur. The outer plexiform layer is most obvious in edema, and the other layers are mainly axons and a wide range of cellular components, so the water is less, the macula is There are many radial arrangements of Henle fibers in the omentum, and there are often edema. Hard exudation is the leaching of liquid and lipid deposits in the outer plexiform layer, and the waxy yellow plaque left after the liquid component is gradually absorbed. In the inner or outer plexiform layer, capillaries and microaneurysms often rupture and hemorrhage. When the retinopathy changes severely, the retinal capillaries are occluded, leading to focal infarction of the nerve fiber layer and becoming a white flocculent soft infiltration. Out, when capillary occlusion is gradually widespread, many dark red spotted hemorrhages and/or retinal vein segmental dilatation (venous beads) can be seen. As vascular damage continues to increase, retinal ischemia and hypoxia are more severe, induced Neovascularization, neovascularization can be initiated from the vein, or from a cluster of tiny intravascular microvascular abnormalities, the endothelial cells of neovascularization have window-like changes, and there is no tight junction between cells, so the fundus fluorescein angiography is characteristic. A large number of rapid fluorescence leaks, newborn blood vessels first appeared in the posterior pole, especially on the optic disc, speculated that there is no real inner limiting membrane limitation on the optic disc Typically, a typical neovascularization is often accompanied by a hyperplasia and degenerative ring. The neovascularization is exposed early. Later, translucent fibrous tissue often appears nearby, becoming opaque as the neovascularization degenerates, and long-lived neovascularization. Degenerative changes can occur gradually, and finally self-atrophy, fiber proliferation is usually concentrated on or near the optic disc, when the fibrous membrane proliferates and shrinks, the tangential traction causes the macular to shift to the nasal disc, and the stress often leads to retinal detachment. If traction acts on new blood vessels, it often leads to vitreous hemorrhage. This disease has been thought to be caused by damage of retinal blood vessels, especially the microvasculature. Early pathological changes are selective loss of pericytes, microangioma and capillary base. Membrane thickening, etc., the mechanism of pericyrous cell disease is the most important, long-term chronic hyperglycemia is the basis of its pathogenesis, and is affected by factors such as blood endocrine and local eye.
Glucose metabolism factor
Disorders of metabolic mechanisms of diabetes are the underlying cause of diabetic retinopathy, and elevated blood glucose causes a complex series of pathophysiological changes.
(1) Disorder of glycolysis: When hyperglycemia, the normal glycolysis process is blocked, sugar can not be decomposed by normal pathways, activate the sorbitol pathway, aldose reductase can promote the conversion of high-concentration glucose to sorbitol, and then to Yamanashi Alcohol dehydrogenase is converted to fructose, and galactose is converted into desmogleol. Because sorbitol and phytoestol are rarely metabolized in the cell, and it is difficult to penetrate the cell membrane due to its polarity, the intracellular concentration increases and penetrates. The pressure is increased, water infiltration into the cells causes electrolyte imbalance and metabolic disorders, and the selective loss of retinal capillary pericytes in diabetic patients is associated with the presence of more aldose reductase in the pericytes.
(2) Abnormal lipid metabolism: Inositol is a precursor of inositol phospholipids. Hyperglycemia can reduce the inositol content in pericytes by inhibiting the uptake and synthesis of inositol by pericytes, resulting in the reduction and metabolism of inositol phospholipid precursors. Abnormally, the inositol phospholipid product inositol triphosphate inositol and diacylglycerol levels decreased, the latter two as a second messenger, its function to regulate cell proliferation is also disordered, DNA synthesis is inhibited, and the proliferation of pericytes is decreased.
(3) Induction of pericyte apoptosis: Inositol phospholipid metabolism abnormality can only explain the decrease of pericyte cell proliferation activity, but it cannot explain why pericytes selectively decline in the early stage of diabetes. The apoptosis theory has opened up a new way. It is proved that Bcl-2 is an oncogene. If the expression of Bcl-2 is inhibited, the cells enter the apoptosis program and use bovine retinal capillary pericytes as a model to artificially simulate blood glucose fluctuations in the body. Under the condition of horizontal fluctuation, the expression of Bcl-2 in pericytes almost decreased to zero. Under the same conditions, the expression of Bcl-2 gene in retinal capillary endothelial cells was normal, and the pericytes with inhibition of Bcl-2 expression easily entered the apoptosis program.
(4) Non-enzymatic glycosylation: In hyperglycemia, non-enzymatic glycosylation of proteins and DNA may change the enzyme activity and DNA integrity, and the protein crosslinks too much, becoming a very stable glycosylation terminal. The product, the biological activity of the protein changes, affecting the function of the enzyme and the cell. Aminoguanidine is an inhibitor of this process, which can inhibit the formation of glycosylation end products. Some people have given aminoguanidine to the diabetic rabbit for drug treatment. It has been found to correct diabetes-induced retinal blood flow and permeability increase, inhibit the development of retinal cell-free capillaries and other microvascular damage, but recently found that aminopurine can inhibit the production of vasoactive substances and nitrogen oxides, and therefore The therapeutic effect of aminoguanidine may not only inhibit the synthesis of glycosylation end products.
2. Blood factors
Increased blood viscosity, decreased blood flow and decreased tissue oxygen supply in diabetic patients are important factors in the development of retinopathy. Platelet aggregation and adhesion in diabetic patients is enhanced. Platelet adhesion to vascular endothelial cells promotes the production of thromboxane A2, causing vasoconstriction and Further agglomeration of platelets, these may be an important factor leading to capillary occlusion; diabetic patients with increased red blood cell agglutination and deformability, difficult to pass through small diameter capillary, plus plasma proteins such as fibrinogen and a2 globulin When the content is increased, the blood viscosity is further increased, resulting in vascular endothelial damage, clogging of the lumen, and easy formation of microthrombus; diabetic microvascular endothelial damage, increased vascular permeability, plasma extravasation, blood concentration, slow blood flow The reduction of oxygen supply may cause ischemia and hypoxia of retinal tissue, which is an important factor in diabetic retinopathy.
3. Hormone factors
In childhood onset diabetes, the concentration of growth hormone in blood is three times higher than that in the normal control group; in the growth hormone-deficient dwarf diabetic patients, the incidence of diabetic retinopathy is extremely low; female diabetic patients develop hemorrhagic pituitary gland after delivery After necrosis, severe diabetic retinopathy can be reversed; complete or near complete pituitary function inhibition (radiotherapy or pituitary ablation) can improve the severity of diabetic retinopathy more quickly, it is believed that growth hormone secretion is increased It can inhibit the metabolism of sugar, lead to the accumulation of sorbitol in cells, increase the deposition of glycoprotein and mucopolysaccharide in diabetic blood vessels and accelerate the hardening of blood vessels, and promote the retinal vascular microthrombus to cause retinopathy.
4. Neovascular growth factor
Neovascularization of diabetic retinopathy is thought to be a metabolic mechanism induced by hypoxia in tissue. Retinal ischemia triggers the mechanism of vascular growth response during normal retinal vascular development, leading to pathological neovascular growth; retina Neovascularization often occurs at the edge of the capillaries without perfusion area, so it is believed that there is neovascular growth factor production in the ischemic area, which is an important mechanism for the growth of neovascularization in diabetic retinopathy; retinal tissue has receptors for angiogenic growth factors, so " Plasma-derived vascular endothelial growth factor can also promote the formation of retinal neovascularization. Experimental studies have shown that retinal capillary permeability increases during diabetes, vascular leakage, and leakage-containing fluid contains "plasma-derived" angiogenic factors. Thereby promoting the growth of new blood vessels.
5. Other relevant factors
(1) Angiotensin II: Angiotensin II receptor in retinal blood vessels, suggesting that angiotensin II is involved in the control of retinal blood supply. Diabetic patients have high levels of prorenin in plasma and are positively correlated with the severity of retinopathy. Vitreous renin is significantly higher in patients with diabetic retinopathy than in non-diabetic patients. It is speculated that the production of angiotensin II in diabetic patients is related to the pathogenesis of proliferative retinopathy.
(2) Oxygen free radicals: The serum lipid peroxide content of patients with diabetic retinopathy is significantly increased, and the activity of superoxide dismutase (SOD) is significantly decreased, indicating that oxygen free radical damage is aggravated, and oxygen free radicals can damage some unsaturated fatty acids. The irreversible damage of the membrane of the retina, the mitochondrial membrane and the lipid in the inner retina, the peroxidation of phospholipids in the membrane, the inactivation of proteins, enzymes and phospholipids in the membrane, the fluidity and permeability of the membrane Changes, impaired function, and even lead to biofilm lysis and cell death, causing retinopathy to worsen.
(3) Genetic factors: Some studies have shown that different types of diabetes patients have different genetic basis. In the observation of immunogenetics, different types of HLA antigens are closely related to the incidence of specific types of diabetic retinopathy.
In short, the pathogenesis of diabetic retinopathy is more complicated, and its pathological changes are the response of the retinal microcirculation to metabolism, endocrine and blood circulation damage. The current research can not fully explain its detailed mechanism, which needs further exploration.
Prevention
Diabetic retinopathy prevention
The most effective way to prevent diabetic retinopathy is to control diabetes and maintain blood sugar at normal levels. Patients should undergo routine eye examinations every year for 5 years after diagnosis of diabetes, so that early retinopathy can be detected and treated early, so that vision can be preserved.
1. Control the development of diabetes and control blood sugar within the normal range.
2. For patients with diabetes, regular fundus examination should be performed. Generally, laser treatment should be performed when the clinical significance of macular edema. Fundus fluorescein angiography should be performed before laser treatment. According to the situation, the treatment plan should be selected, and care should be taken to avoid 500m around the fovea. The area should not damage the central vision. Also note that the laser spots should be separated by gaps during treatment.
Complication
Diabetic retinopathy complications Complications vitreous hemorrhage retinal hypertension
Hemorrhagic glaucoma, vitreous hemorrhage, macular degeneration, retinal detachment, active and effective control of diabetes, treatment of systemic vascular diseases, hypertension and heart and kidney diseases, changes of microcirculation, prevention of retinopathy and preservation of vision may occur.
Symptom
Symptoms of diabetic retinopathy Common symptoms Retinal hemorrhage Polyuria retinal edema Multi-drinking visual deformity Fundus changes Eye white appears red dot fundus point or flaming hemorrhage hypertension
Retinal capillary lesions show microaneurysms, bleeding spots, hard exudation, cotton plaque, venous beading, intraretinal microvascular abnormalities (IRMA), and macular edema. Extensive ischemia can cause neovascularization of the retina or optic disc, preretinal hemorrhage, volcanic blood, and traction retinal detachment. The patient has severe visual impairment.
In 1984, China's fundus diseases proposed the GRP classification method, which played a significant role in promoting its prevention and treatment. Recently, international clinical classification has been proposed through long-term observation of a large number of cases internationally. In the GRP classification, the most important group refers to eyes with a risk of loss of vision, while the first three periods are relatively low-risk and the second period is high-risk. Stage 4 has a high degree of risk of developing proliferative DRP. The extent of diabetic macular edema (DME) is divided into two categories: no or no significant DME. If there is DME, it can be divided into light, medium and heavy grades. Three-dimensional examination of the thickening of the retina is required. Under the dilated sputum, a vivital microscope or a stereoscopic photograph of the fundus is performed.
Diabetic retinopathy: Diabetes can cause two types of retinopathy, proliferative and non-proliferative retinopathy. Diabetic retinopathy is one of the major blinding diseases.
In non-proliferative (simple) retinopathy, small retinal capillaries rupture and leak. At the point where each enlarged capillary ruptures, a small sac with blood protein precipitate is formed. The doctor can find these changes according to the fundus examination. Fluorescein angiography (a diagnostic method in which a doctor injects a dye into a patient and takes a fundus photography while the dye reaches the retina with blood flow) helps determine the extent of the lesion. Early non-proliferative retinopathy may not cause vision loss, but retinal tract hemorrhage may cause local visual field loss, if the bleeding involves the macula, vision will be significantly reduced. Deep sea insulin is a purified substance that improves the function of islets and helps regulate the metabolism of carbohydrates in the body.
In proliferative retinopathy, retinal damage stimulates neovascularization. Neovascular growth is detrimental to the retina, which can cause fibrosis and sometimes can cause retinal detachment. New blood vessels can also grow into the vitreous or cause vitreous hemorrhage. Proliferative retinopathy is more harmful to vision than non-proliferative retinopathy, which can lead to severe vision loss or even complete blindness.
Examine
Examination of diabetic retinopathy
1. Blood glucose test Regularly measure blood sugar levels to monitor the development of diabetes.
2. Renal function tests timely found complications of diabetic nephropathy.
3. Cholesterol lipid test to maintain cholesterol, normal blood lipid levels.
Fundus fluorescein angiography fundus fluorescein angiography can not only understand the early changes of retinal microcirculation, but also have various special manifestations in the progression of diabetic retinopathy. The rate of positive signs is higher than that of ophthalmoscopy. Early diagnosis, selection of treatment options, evaluation of efficacy and reliable basis for prognosis. For example, when diabetic retinopathy has not been found under ophthalmoscopy, fundus fluorescein angiography can produce abnormal fluorescence patterns, and microangiomas found under fundus fluorescein angiography. It is much earlier than that seen under the ophthalmoscope. Others such as telangiectasia, increased permeability, no perfusion area, arteriovenous abnormalities, exudation and hemorrhage, neovascularization, etc., fundus fluorescein angiography has special performance. .
5. Electroretinogram Oscillation Potential (OPs) OPs is a sub-component of electroretinogram (ERG), which can reflect the inner circulation of the retina in an objective and sensitive manner. It can reflect the amplitude of OPs in the eye where no lesion is seen in the fundus. Abnormalities, in patients with diabetic retinopathy, can further show progression and improvement in the course of the disease.
6. Other examinations such as visual contrast sensitivity examination showed that the average contrast sensitivity of the high spatial frequency was significantly reduced in the early patients; the color Doppler flow imaging technique could be used to detect the hemodynamic changes of the posterior ball arteries. Low flow rate, low flow rate, high resistance type change; blood viscosity test can show increased viscosity; serum SOD activity test can be expressed as decreased vitality.
Diagnosis
Diagnosis and diagnosis of diabetic retinopathy
Clinical diagnosis is based on fundus photography and fundus fluorescein angiography. Most of the clinical signs of diabetic retinopathy have been recognized before fluorescein angiography, but fluorescein angiography greatly increases the knowledge of the lesions in the fundus of the eye, not only to further understand the early lesions of the diabetic fundus microcirculation, but also to prove the condition. Whether to develop, to estimate the prognosis of angiographic signs, to select appropriate cases for photocoagulation treatment and to observe the therapeutic effect.
diagnosis
(1) Medical history: It is very important to ask about the history of the disease in detail. In addition to the typical diabetes manifestations such as polydipsia, polyphagia, polyuria and weight loss, it is also necessary to pay attention to the course of diabetes. The longer the course of the disease, the diabetic retinopathy. The higher the incidence rate, the heavier the degree, especially the time of discovery of some diabetes does not represent the actual time of illness, because the systemic symptoms are not obvious, and the actual course of disease is often found when diabetes is found. The blood sugar and urine sugar test is to understand the degree of diabetes control. An important basis.
(2) fundus examination: fundus examination is the main means of diagnosing diabetic retinopathy. Microaneurysms and/or small hemorrhage are always the earliest and more obvious signs of retinopathy, with yellow-white waxy hard exudation spots. , indicating that the vascular system is abnormal, the permeability is increased, the blood components escape, and the white soft exudation indicates severe disorder of the microcirculation, and the blood vessel is severely damaged. At this stage, there is no neovascularization, so it is called simple lesion, with The development of the disease, at this stage concurrent with multiple focal or extensive retinal perfusion, it is predicted that new blood vessels will appear soon, starting from the occurrence of new blood vessels, that is, into the proliferative phase, indicating that the retinal circulation can not be hypoxic Compensation.
(3) Special examination: Diabetic retinopathy has some subclinical changes before the appearance of lesions in the fundus, such as abnormal fluorescence morphology, retinal electrophysiology and visual contrast sensitivity, which have reference value for early diagnosis. During the progression of the lesion, various special manifestations of fundus fluorescein angiography are important for the diagnosis and staging of the disease.
