Common symptoms: polyuria, polydipsia, hypertension, anemia, optic atrophy, retinal hemorrhage, retinal edema, retinal detachment
In the early stage of retinopathy, there is generally no eye symptoms. As the disease progresses, there can be different manifestations. Retinal edema can cause light scattering and make the patient have a flash sensation in front of the eyes, macular edema, ischemia or exudation involving the fovea, which can cause varying degrees of vision loss or visual distortion. Rupture of retinal arterioles and a small amount of bleeding into the vitreous can cause the patient to consciously have dark shadows floating in front of his eyes. New blood vessel growth, heavy vitreous hemorrhage or proliferative vitreoretinopathy and traction retinal detachment can cause severe vision loss.
The basic clinical manifestations of diabetic retinopathy include the formation of retinal capillary microangioma, vasodilation, and leakage of the vessel wall causing retinal edema, exudation, hemorrhage, capillary and arteriole occlusion, retinal ischemia, and retinal neovascularization. . New blood vessels cause massive hemorrhages in the retina and vitreous. As the fibrous tissue proliferates, proliferative vitreoretinopathy is formed, and then traction retinal detachment occurs. The following describes the fundus manifestations of diabetic retinopathy.
1. Vascular disease
(1) Abnormal capillaries:
①Microaneurysms: Although retinal microaneurysms can also be seen in other diseases such as branch retinal vein occlusion, idiopathic retinal vasodilatation, periretinal vein inflammation, and some systemic diseases such as hypertension, nephropathy, anemia and other diseases, However, it is still a characteristic manifestation of diabetic retinopathy and the earliest reliable sign of the disease. Microaneurysms appear as small red or dark red dots with clear boundaries under the ophthalmoscope, and their diameter is often 15-60 μm, that is, 1/8 to 1/2 of the diameter of the retinal vein at the edge of the optic disc, and occasionally larger ones. It can reach the diameter of the retinal vein, but generally does not exceed 125μm. Sometimes it is difficult to distinguish an aneurysm from a small bleeding point under the ophthalmoscope, and follow-up observation can be performed. The small bleeding point usually disappears in a relatively short period of time. In addition, it can be used for fundus fluorescein angiography. If the edges are smooth and the fluorescence is full, it may prove to be a microaneurysm. Fundus fluorescein angiography can often find small microaneurysms that are not easy to detect or cannot be detected by the ophthalmoscope. Because a bright spot on a darker choroidal background is easier to spot than a red spot on an orange-red background. Therefore, there are often more microaneurysms during fundus fluorescein angiography than those seen under ophthalmoscope. There are also some microaneurysms that show insufficient fluorescence, which is confirmed by red blood cell obstruction due to microaneurysms by clinicopathological histological examination. This kind of microaneurysm often cannot be distinguished from small bleeding points under ophthalmoscope. Microaneurysms often appear on the posterior pole of the fundus, especially in the macular area, and mostly on the temporal side. As the disease progresses, it is distributed in various parts of the retina and densely clustered. If only 1 to 2 microvascular tumors are found in one or both eyes under the ophthalmoscope, don't take it lightly that there is no retinopathy. Instead, check the pupils in detail. At least 4 to 5 PD ranges along the main blood vessels should be checked in each direction. If it is still difficult to judge, fundus fluorescein angiography is required.
Microaneurysms may change little over the course of several years. However, due to the thickening of the tube wall and hyaline degeneration, the cyst cavity is naturally occluded, gradually turning pink or whitish at the edge, and finally forming small round white spots. The half-life of microaneurysms is about several months. In the process of retinopathy, the formation of new microaneurysms and the disappearance of old microaneurysms occur alternately throughout the retina.
The formation of microaneurysms is an important step in diabetic retinopathy. It appears after capillary pericytes decrease, endothelial cells proliferate, and basement membrane thickens. It is often located on the capillaries around the capillary occlusion area, indicating that its occurrence is related to local retinal hypoxia. Microaneurysms are common in the inner core layer of the retina and gradually spread to the inner plexiform layer. Microangioma leakage is an important cause of retinal edema, and its number and changes can reflect the degree, progression or regression of retinopathy.
② Capillary expansion and leakage: Retinal capillary expansion is also one of the early changes of diabetic retinopathy. Pericytes of the capillary wall gradually disappear, endothelial cells proliferate, the lumen gradually occludes, and the nearby capillaries expand compensatoryly. As the disease progresses, tissue ischemia and hypoxia increase, self-regulation is decompensated, and the capillaries appear abnormally dilated organic damage, uneven in thickness, and twisted and twisted. Together with the new blood vessels in the retina, this change is collectively referred to as intraretinal microvascular bnormatities (IRMA). Dilated capillaries, like microaneurysms, increase the permeability of the vessel wall and cause leakage. This is the basis of retinal exudation, hemorrhage and edema. Fundus fluorescein angiography is an effective way to detect telangiectasia. Before ophthalmoscope examination found no retinopathy, some patients can find increased visibility of retinal capillaries by fundus fluorescein angiography, which means that there is mild telangiectasia. After the capillary generator is qualitatively damaged, fundus fluorescein angiography can clearly show the expanded capillaries and the neovascular buds in the retina. When leakage occurs, the initial stage is that the fluorescent leakage gradually diffuses to the surroundings, and in the later stage it becomes a fluorophore with blurred boundaries. In some patients with severe disease, radial capillary dilation and leakage can be seen around the optic disc, the boundary of the optic disc and the outline of the blood vessel are blurred in the later stage of the angiography, and the surrounding tissues have fluorescent imaging. These phenomena often indicate the possibility of developing proliferative retinopathy.
③Capillary occlusion: The capillary non-perfusion area caused by capillary occlusion indicates that the retinopathy has been serious. This sign can only be found by fundus fluorescein angiography. Fundus fluorescein angiography showed spot-like or flake-like dark areas with varying sizes, ranging from 0.1 to 5 mm in diameter, and the normal shape of the surrounding capillaries were interrupted. The non-perfusion zone mostly occurs at the equator and gradually expands to the posterior pole and the periphery. The non-perfusion zone involves an entire microcirculation unit, that is, the range supplied by the feeding arterioles, the capillary network and the collecting venules. Microvascular tumors or microvascular chains and abnormally expanded microvessels are common in the non-perfusion zone. When the non-perfusion zone involves the macula, it can cause vision loss. The non-perfusion area other than the macula may have defects in the corresponding parts of the visual field. Fundus fluorescein angiography showed widening of the fovea avascular area. Fundoscopy may not find obvious retinopathy.
④ Arteriovenous communication: When the area of capillary occlusion gradually expands, tortuous small blood vessels appear in the retina, connecting with arteries and veins. This kind of blood vessel is a manifestation of trying to restore normal blood flow in the process of capillary occlusion. The large capillaries that directly connect the arteries and veins can be seen under the ophthalmoscope. Fundus fluorescein angiography showed slow blood flow, fluorescent staining of the tube wall and slight fluorescence leakage.
(2) Abnormalities of retinal arteries and veins:
①Arterial abnormalities: Some patients with severe retinopathy may have arterial occlusion. The arteries are small and narrow, and some are almost thin, and the color is light, which is not easy to find under the ophthalmoscope. Fundus fluorescein angiography is easier to find, showing stenosis at the proximal end of the small artery branches, and some are even completely occluded, the distal end is slightly dilated, the wall of the tube is fluorescently colored and leaking, the outline of the blood vessel is blurred, and there are large areas without perfusion. Patients with a longer course of disease may develop arteriolar sclerosis, widening of the arterial wall, or even copper filaments, with arteriovenous cross pressure. The aorta of the retinal artery is often not obvious under the ophthalmoscope, but the fundus fluorescein angiography shows that the diameter of the artery is uneven, segmental dilation and stenosis, and fluorescent staining and leakage may occur.
②Venous abnormalities: The most common early manifestations are retinal vein filling and expansion and tortuosity, dark red in color, and obvious temporal veins. As the disease progresses, the diameter of the vein becomes uneven. In severe cases, it expands in a beaded, sausage-shaped or spherical shape. The blood vessels can be coiled into a ring, and some have white sheaths. In severe cases, fundus fluorescein angiography can show fluorescence staining and retention on the venous wall, and fluorescence leakage, and sometimes partial or complete blockage of branch veins may occur.
2. Extravascular damage
(1) Hemorrhage: Early retinal hemorrhage is deep, often in the inner core layer, and its shape is round or irregular red small bleeding spots, which are spot-like. Hemorrhage spots rarely appear alone, and generally coexist with retinal microangioma or IRMA. The bleeding can be absorbed gradually, but new bleeding can occur nearby. When the disease progresses, especially when accompanied by high blood pressure, there may be strip or flame-like bleeding in the nerve fiber layer. Severe hemorrhage can be fused into a film, involving all layers of the retina, and even break through the inner limiting membrane to cause preretinal hemorrhage. The upper boundary is horizontal and the lower boundary is a hemispherical arc-shaped scaphoid hemorrhage. When the amount of bleeding is large, it can break through the vitreous membrane and enter the vitreous, causing serious visual impairment. Small bleeding spots are similar in shape and color to microangiomas and are not easy to distinguish under ophthalmoscope. However, during fundus fluorescein angiography, the bleeding completely obscures the fluorescence of the retina and choroid underneath, and appears as a black spot with a shape and size consistent with the bleeding spot. The microaneurysms are mostly highly fluorescent.
(2) Rigid exudation: also called waxy exudation, it is waxy yellow dot sheet exudation with different sizes and clear boundaries. The size is about 1/10～1/6PD. Rigid exudation can be distributed irregularly in the fundus, but it is most common in the later poles. Constant or dozens of them are piled up in clusters, sometimes fused into sheets, sometimes arranged in rings, and each ring surrounds one or several arterioles. Tumors are sometimes densely packed around the veins and appear as white sheaths. If it is located in the macula, it can be distributed along the Henle fiber and present a complete or incomplete star shape. The hard exudation is located in the deep outer plexiform layer of the retina, which is mainly lipid, and there are also some proteins and foamy cells that swallow lipids. It is generally believed that they are formed due to increased permeability of microangiomas and adjacent capillaries, plasma extravasation, water and small molecular substances absorbed by choroidal blood vessels or surrounding normal capillaries, and residual macromolecular substances such as lipids and proteins. . It is also believed that they are lipids produced by the breakdown of edema of the retinal nerve tissue. Hard exudation can be gradually absorbed and dissipated, but new hard exudation can appear again. Fundus fluorescein angiography shows that the hard exudate itself is not developed, and the leaky microangioma and dilated capillaries can be seen at the edge or the center of the annular exudation. However, large hard exudates can show false fluorescence.
(3) Cotton wool spots: also known as soft exudation, they are gray-white spots with different sizes, irregular shapes, and unclear borders, which are like cotton wool or fluffy. Its size is generally 1/6 to 1/3PD, occasionally as large as 1/2PD. Its distribution is mostly in the range of 3 to 4 PD from the optic disc in the posterior retina, most of which are near the large blood vessels. Bleeding spots and microangiomas can be seen on the edges of cotton wool spots, and occasionally tortuous and dilated capillaries, and some hard exudative rings are around them. This leakage of nerve fiber layer located in the superficial layer of the retina is caused by retinal microvascular occlusion, severe tissue ischemia, blockage of nerve fiber plasma flow and intracellular edema. Therefore, the appearance of cotton wool spots indicates that diabetic retinopathy has become more serious. Recently, it has been emphasized that among retinal damages such as microangioma, retinal hemorrhage, vein dilation, IRMA and cotton wool spots, cotton wool spots are the last sign of proliferative diabetic retinopathy, that is, its appearance indicates the rapid development of retinopathy into proliferative changes. the trend of. During fundus fluorescein angiography, microaneurysms and abnormal microvascular leakage around cotton wool spots are often manifested as low-fluorescence areas with no capillary perfusion, and the peripheral expanded capillaries have fluorescent leakage. Cotton wool spots generally fade slowly, with a half-life of about 0.5 to 1.5 years. The old cotton wool spots are light, thin and flat, with clear borders, and show mild pigment disorder after subsiding. After the cotton wool spots subsided, the occluded capillaries were swollen and broken into unstructured cell-like bodies, which were gradually replaced by glial tissue over time, and no longer swelled due to ischemia. Therefore, some patients' fundus fluorescein angiography shows that the capillary non-perfusion area is very wide, but the cotton wool is very few or even absent.
3. Proliferative lesions
(1) New blood vessel and fibrous proliferation: New blood vessel proliferation is the most important sign of proliferative diabetic retinopathy. In severe non-proliferative diabetic retinopathy, there are more cotton wool spots, IRMA, venous beading, extensive retinal hemorrhage and microangioma. If not treated in time, vascular disease will continue to aggravate, severe ischemia and hypoxia in the retinal tissue, and new blood vessels germinate in the retinal blood vessel wall. New blood vessels usually occur in the optic disc and its vicinity, or near the equator of the central retinal arteries and veins and the edges of the capillary non-perfusion area. At the beginning, the new blood vessels on the optic disc can only appear in one quadrant, like a thin red line, and then spread all over the optic disc and extend to the adjacent retina. In severe cases, it can reach a range of 30°. The new vessels on and near the optic disc within a diameter range of the optic disc are called new vessels on the disc (NVD), and the new vessels in any other part of the retina are called neovessels elsewhere (NVE). Early neovascularization is located in the plane of the retina, and later can pass through the inner limiting membrane and protrude beyond the inner limiting membrane to contact the vitreous body. The typical initial stage of NVD is a beautiful ring or net on the surface of the optic disc or adjacent retina, or a bridge across the physiological cup. In the early days, it is not easy to find or dilute to normal blood vessels under ophthalmoscopy. However, due to abnormal neovascular walls, specific fluorescence leakage occurs during fundus fluorescein angiography. Similarly, early NVE is easy to miss, and sometimes it is difficult to distinguish from IRMA. However, it is easier to recognize when they form a curly and circuitous vascular network near large blood vessels or cross deep arteriovenous branches. The typical vascular network is a rough round spot, like a wheel, the blood vessels are radial, like spokes, and the center of the round spot is often above the vein. Fundus fluorescein angiography shows the fluorescent form of neovascularization in the early stage of the vein, and the morphology is different, and then leaks after the fluorescence is developed.
The growth rate of new blood vessels varies greatly. In some patients, the number of vascular plaques can remain unchanged for a long period of time, while in other patients, significant growth can be found within 1 to 2 weeks. In the early stage, the new blood vessels are exposed. Later, the translucent fibrous tissue appears nearby, and it becomes opaque as the new blood vessels degenerate, but the degeneration is often incomplete. Occasionally, new blood vessels may disappear completely, replaced by clusters of white mesh tissue or disappear without a trace. As long as hemorrhage and fibrous tissue contraction associated with neovascularization does not occur, neovascularization usually remains asymptomatic. At the same time as the appearance of new blood vessels, the retinal tissue gradually proliferates in the vicinity of the new blood vessels to form fiber bands. This fibrous proliferation of blood vessels on the surface of the retina and adjacent to the vitreous is called proliferative vitreous tinopathy (proliferative vitreous tinopathy). , PVR).
(2) Vitreous detachment and hemorrhage: New blood vessels often proliferate in the potential gap between the posterior vitreous interface and the retina, which can easily lead to retrovitreous detachment. Although retrovitreous detachment can also appear in the eyes of normal people over 60 years old, in the case of fibrovascular proliferation, retrovitreous detachment tends to appear at an earlier age, its progress is relatively slow, and most of it does not cause obvious symptoms. At first, the detachment of the vitreous is only limited to the isolated part, and later it can gradually develop into a full vitreous detachment or even collapse. The gap after the detachment of the vitreous makes it easier for new blood vessels to grow in. The posterior interface after the vitreous body is detached can be easily identified under a slit lamp microscope, so that the diagnosis can be clear.
The proliferation of new blood vessels and fibrous tissue can enter the vitreous body. The structure of the new blood vessel wall is not perfect, and it is prone to bleeding. In addition, the contraction of the fibrous membrane causes the new blood vessel to rupture, and vitreous hemorrhage often occurs. His vision is impaired to varying degrees, from floating spots that last 1 to 2 hours to manual or light perception in front of his eyes. The first vitreous hemorrhage in an eye is large and uncommon, but large hemorrhages are often within a few days or weeks after the occurrence of small hemorrhages. Therefore, a very small vitreous hemorrhage should be paid attention to. The findings of the fundus vary with the amount of bleeding. A small amount of bleeding shows the vitreous body is light red, the fundus is blurred and the fundus is blurred, and the fundus bleeding can only be seen with dim reflections or no reflections at the fundus. The speed at which the bleeding becomes clear is very variable, from a few weeks of small bleeding to months, years or never clear of heavy bleeding. Bleeding tends to recur periodically, usually without obvious predisposing factors, and often occurs during sleep.
(3) Traction retinal detachment: the fibrous vascular membrane and/or the incomplete absorption of hemorrhage in the vitreous can cause contraction and traction on the retina, which can distort the retina and even cause traction. Retinal detachment. Because the contraction of the fibrous membrane not only produces a kind of stress that pulls the retina away from its pigment epithelial layer and choroid, it also pulls the peripheral retina toward the center of the membrane, that is, tangential traction. Tangential traction often causes the macula to shift to the nasal optic disc. If a retinal tear occurs at the involved part, it may be combined with rhegmatogenous retinal detachment. If the macula is involved, the vision will drop sharply, cystic degeneration will occur over time, and the visual impairment will be irreversible. .
4. Macular degeneration
Common diabetic maculopathy (diabetic maculopathy, DM) includes macular edema, ischemia and proliferative changes to the macular invasion, of which macular edema is the main factor of vision loss.
In mild macular edema, it is not easy to recognize under the ophthalmoscope, but it is found that the reflection of the macular fovea has disappeared, and the possibility of macular edema should be considered. Due to local microcirculation obstacles in the retina, capillary permeability changes and leakage occurs. The leakage fluid accumulates in the center of the macula and is arranged radially along the Henle fibers, and can form small sacs with fluid accumulation. Under the ophthalmoscope, the retina in the macular area is thickened and opaque, the fovea is honeycomb-shaped, and hard exudative rings are often seen on the periphery. Macular edema can also be diffuse, and it is more common in young-onset diabetic patients. It is caused by diffusely dilated capillary leakage, and peripheral hard exudative rings are rare. It can often develop rapidly into severe proliferative retinopathy, which may be a sign of rapid progress of retinopathy. Long-term macular edema can form cystoid macular degeneration or even perforation of the retina, and the damage to vision is irreversible. Early fundus fluorescein angiography showed capillary occlusion in the macular area, incomplete capillary annulus, and fluorescence leakage. In the late stage, it can be seen that the macular area has significant fluorescence leakage, and the periphery of the annulus shows petal-like or circular high fluorescence.
When cotton wool spots, white linear arterioles, and obvious IRMA appear on the fundus, macular ischemia should be considered. Fundus fluorescein angiography showed that the macular arch was enlarged, and local capillaries were not perfused. In severe cases, peripheral arterioles were occluded and large capillaries were not perfused.
In proliferative retinopathy, the proliferation and traction of abnormal tissues in the eye involve the macula, which can affect vision. Extensive proliferation can cause scarring in the macula. The traction of the vitreous body and the retina can cause the macular folds in mild cases, slightly decreased vision or distorted vision, and severe cases can cause macular ectopic and severely impaired vision.
5. Optic disc disease
The optic disc disease of diabetic retinopathy may include optic disc edema, ischemia, and neovascularization. Optic disc edema is more common in young-onset insulin-dependent diabetic patients. It can generally be absorbed in a short period of time without visual loss or corresponding retinopathy. However, if it is accompanied by significant fundus changes, it may be the early manifestation of proliferative diabetic retinopathy in the optic disc, which can accelerate the deterioration of retinopathy and the appearance of new blood vessels, which should be followed and observed. The pathogenesis of diabetic optic disc edema is unclear, and it may be caused by local vascular disorders. Some people think that it is caused by abnormal superficial retinal blood vessels and fluid leakage to the periphery of the optic disc; others think that it is caused by abnormalities of deep optic disc blood vessels and axoplasmic flow.
Optic disc ischemic changes mostly occur in elderly patients with poorly controlled diabetes, and may be related to poor local blood flow. It is manifested as localized optic nerve atrophy after the resolution of optic disc edema, visual acuity may be reduced to varying degrees, and sector-shaped visual field defects in the corresponding direction appear.
1. Diagnosis
(1) Medical history: It is very important to ask the medical history in detail. In addition to the typical manifestations of diabetes such as polydipsia, polyphagia, polyuria, and weight loss, attention should also be paid to understanding the course of diabetes. The longer the course of the disease, the higher the incidence and severity of diabetic retinopathy. In particular, 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 the disease is often long when diabetes is discovered. Blood glucose and urine glucose examination is an important basis for understanding the degree of diabetes control.
(2) Fundus examination: Fundus examination is the main method for diagnosing diabetic retinopathy. Microaneurysms and (or) small hemorrhages are always the earliest and more precise signs of retinopathy. The yellowish-white waxy hard exudate spots indicate abnormal function of the vascular system, increased permeability, and escape of blood components. The white soft exudation indicates severe microcirculation disorder and severe blood vessel damage. There is no neovascularization at this stage, so it is called simple disease. As the disease progresses, multiple focal or extensive retinal non-perfusion at this stage indicates that new blood vessels will soon appear. From the beginning of neovascularization, it enters the proliferation phase, indicating that the retinal circulation can no longer compensate for tissue hypoxia.
(3) Special examination: Before diabetic retinopathy has pathological changes in the fundus, there have been some sub-clinical changes, such as abnormal fluorescence morphology, changes in retinal electrophysiology and visual contrast sensitivity, which are of reference value for its early diagnosis. During the progression of the disease, various special manifestations of fundus fluorescein angiography are of great significance to the diagnosis and staging of the disease.
2. Staging
According to the clinical manifestations of diabetic retinopathy, the classification and staging of diabetic retinopathy is beneficial to observe the evolution of the disease, and is convenient for recording and comparison. In June 1984, the First National Ocular Fundus Disease Academic Conference put forward the "Clinical Staging Standards for Diabetic Retinopathy", which was discussed and approved by the Third National Ophthalmology Academic Conference in October of the same year and announced for implementation.
The classification and staging of the above diabetic retinopathy are mainly morphological classification. With the appearance of retinal neovascularization as a marker, diabetic retinopathy without neovascularization is called simple disease (or non-proliferative, background type), and diabetic retinopathy with neovascularization is called proliferative. Severe retina ischemia is the pathological basis for the progression of diabetic retinopathy from simple to proliferative. In the late stage of simple disease, white soft exudation increases significantly, and large capillary non-perfusion areas (>5PD) often indicate that new blood vessels are about to occur, so it is called preproliferative diabetic retinopathy (PPDR). Diabetic retinopathy is a continuous and evolving pathological process, and the fundus manifestations of a certain period often cover the fundus manifestations of the previous period.
As mentioned earlier, this staging standard is based on what is seen in the fundus, but sometimes it does not completely match the performance of fundus fluorescein angiography, especially in the phase of simple lesions. Such as fundus examination because cotton wool spots have regressed or early neovascularization cannot be found, and fundus fluorescein angiography can reveal capillary non-perfusion and neovascularization. Therefore, it is best to combine the findings of fundus fluorescein angiography when making the clinical staging of diabetic retinopathy in order to make the clinical diagnosis more accurate and avoid delays in treatment.