neovascular glaucoma
Introduction
Introduction to neovascular glaucoma Neovascular glaucoma refers to the presence of a new fibrous vascular membrane on the surface of the iris and trabeculae, leading to adhesion of the surrounding iris and obstructing glaucoma caused by aqueous humor discharge. Because the neovascularization is easy to rupture, and anterior chamber hemorrhage occurs repeatedly, it is also called hemorrhagic glaucoma. The disease is extremely stubborn. It is often ineffective with general anti-glaucoma drugs and filtering surgery. The patient's eye is congested, corneal edema, severe eye pain, headache, often leading to blindness. Iris neovascularization is often secondary to certain diseases that cause hypoxia in the retina, such as central retinal vein occlusion, diabetic retinopathy, central retinal artery occlusion, retinal vein inflammation, malignant melanoma, retinoblastoma, retinal detachment, and cranial Arteritis, etc., especially in the past two diseases are more common. basic knowledge The proportion of illness: 0.002% Susceptible people: children Mode of infection: non-infectious Complications: anterior chamber hemorrhage
Cause
Causes of neovascular glaucoma
Cause:
Central retinal vein occlusion (35%):
Central retinal vein occlusion is based on the presence or absence of retinal ischemia (25%) and non-ischemic (75%). No natural non-ischemic development of neovascular glaucoma, but lack of 18% to 60% of the blood type occurs, more often 2 to 3 months after venous obstruction, 80% of cases occur within 6 months, mainly by fundus fluorescein angiography to show whether there is retinal capillary non-perfusion Area to determine ischemia or not, note that non-ischemic type can also be converted to ischemic type, diabetes is a risk factor, diabetes is also a dangerous pathogenic factor of central retinal vein occlusion, primary open angle glaucoma and retina Central venous obstruction is considered to be caused by mechanical stress. Therefore, central retinal vein occlusion is considered as a risk factor for primary open angle glaucoma. In addition, 80% of patients with venous obstruction have intraocular pressure compared with contralateral eyes. To be low, think that this is caused by metabolic acidosis that inhibits the formation of aqueous humor.
Diabetes (30%):
Neovascular glaucoma occurs in approximately 22% of proliferative diabetic retinopathy, with type 1 accounting for 15% and proliferative retinopathy, type 2 accounting for 80% and more with macular degeneration, adult neovascular glaucoma or iris Neovascularization is almost caused by diabetic retinopathy, but the time interval between retinopathy and iris neovascularization or glaucoma is unclear. Cataract surgery and vitreoretinal surgery are more likely to develop neovascular glaucoma, mainly with the original diabetic retina. The lesion is associated with hypoxia in the retina.
Other diseases (25%):
Other common eye diseases associated with neovascular glaucoma include: central retinal artery occlusion (1% to 17%), intraocular tumors such as malignant melanoma (0.5% to 15%), and retinoblastoma iris Neovascularization can reach 30% to 72%, iris neovascularization after vitreoretinal surgery is also 23% to 32%, in addition to Coats disease such as intraocular vascular disease, perivascular inflammation, sickle cell disease; Other eye diseases include chronic uveitis, retinopathy of prematurity, heterochromia, exfoliation syndrome, scleritis, endophthalmitis, sympathetic ophthalmia, optic neurofibromatosis, primary iris atrophy, reticular cell sarcoma , metastatic cancer, ocular trauma, Sturge-Weber syndrome with choroidal hemangioma, even after cataract extraction, extraocular vascular diseases such as carotid artery occlusion, carotid cavernous fistula, avascular disease, giant cell artery Inflammation and the like may also be the cause of neovascular glaucoma.
The cause of neovascular glaucoma is as many as 40 different diseases, almost all of which involve the hypoxic or local ocular anterior segment hypoxia, mainly central retinal vein occlusion, diabetic retinopathy and other diseases. About 1/3.
Pathogenesis:
New blood vessels occur under normal conditions and disease conditions. The former's vascular formation is weighed and controlled by the body, while the latter is irregular. As early as the 1950s, retinal ischemia, capillary and venous obstruction were described. Etc. causes hypoxia in the retina. If hypoxic cells do not die, they will produce vaso-formative factors or vasostimulating factors, and this factor can diffuse into the anterior eye to stimulate the iris to form new blood vessels. Hypoxia metabolism leads to neovascularization. A large number of clinical or animal studies support this theory. Many factors related to angiogenesis have been recognized, mainly polypeptide factors such as Heparin-binding growth factor (Heparin-binding growth factor). Factors) - mainly acidic and basic fibroblast growth factors (aFGF and bFGF), vascular endothelial growth factor (VEGF), angiogenin, platelet-derived endothelial cell growth factor (PDECGF), transformed growth Factors and (trans-forming growth factors, TGF- and TGF-) and tumor necrosis factor (T NF-), etc., other non-polypeptide substances having angiogenic activity are:
Various biogenic amines include blogenic amines, acetylcholine and serotonin (serotonin); certain lipids such as the prostaglandin E series; activated macrophages produce interleukin-1, A variety of extracellular interstitial degrading enzymes produced by mast cells and mitogens produced by retinal pigment epithelial cells, etc., are also important for the control of angiogenesis. Related inhibitors include protease inhibitors including collagenase inhibitors. , metalloproteinases inhibitor, plasminogen activator inhibitor, urokinase inhibitor (produced by RPE), heparin and heparin fragments combined with corticosteroids to produce anti-angiogenic factors Etc., inhibiting endothelial cells with interferon alpha (INF-, interferon-) inhibits endothelial cell migration and elongation, platelet factor 4 (PF4) inhibits endothelial cell proliferation and migration, and neutralizes growth factors with FGF. Monoclonal antibodies, in addition to anti-endothelial cell angiogenesis inhibitors such as fumagillin and its synthetic analogues AGM-1470 can prevent lumen formation. The main mediators that appear at different stages of neovascularization are shown in Table 1. The balance and control of angiogenic stimulators and inhibitors is the main difference between normal and pathological angiogenesis. In the extensive and in-depth study of how this balance is destroyed in neovascular glaucoma, although the etiology of neovascular redness in neovascular glaucoma is still not well understood, the theory of neovascularization caused by hypoxia hypoxia is still Most people accept and support.
In patients with diabetic retinopathy after vitrectomy or lens removal, the incidence of irido red is high, indicating that the vitreous and lens act as a barrier to prevent angiogenic factors from spreading forward, thereby presuming that the lens is separated from the iris. Change has a certain role.
Neovascularization always originates from microvessels (capillaries or venules) and never originates from large blood vessels (small arteries, arteries or veins). In the presence of neovascular stimulating factors, nearby microvessels are filled and permeability is increased ( Stage 1), in the face of stimulating factors, vascular endothelial cells become thicker, and a series of intracellular changes including endoplasmic reticulum increase, various enzymes are released, including metalloproteinases (such as type IV collagenase) and plasma proteases. (such as plasminogen activator), leading to extracellular matrix destruction of the basement membrane and surrounding cells (stage 2), the basement membrane mainly contains type IV collagen and basal membrane connexin (LN), while the peripheral extracellular matrix is the main component For type I collagen, endothelial cells project pseudopod buds through the basement membrane space toward the neovascular stimulating factor (stage 3), followed by endothelial cell migration, forming a bipolar aligned cell column, and at the same time, toward these cell columns. At the bottom, near the maternal blood vessels, cell division (stage 4), cell division does not occur at the front end of the neovascular, and branches appear at the front end, accompanied by the formation of the lumen, where the blood flow At the beginning (Phase 5), capillary vasospasm can produce new vascular buds, and the pericytes protrude from the mother's blood vessels, covering these new blood vessels, and a new basement membrane is formed, thereby forming mature neovascular vessels, and the endothelial cells in the vascular tree are normal. In the case of a stationary monolayer of cells, it acts as a selective barrier between blood and tissues. These cells have a long period of normal renewal and take more than one year, but they proliferate rapidly under the stimulation of angiogenic factors. The update time is less than 5 days. The main difference between disease and health is that the blood vessel formation is in a balanced and controllable state in healthy conditions, and abnormality is regulated in the case of disease.
Prevention
Neovascular glaucoma prevention
Until 1974, there was no way to prevent or treat NVG. Since 1974, there have been many articles on the treatment of NVG, but preventive treatment has not received enough attention.
1. Central retinal vein occlusion:
As long as the visibility of the retina allows, all patients with CRVO should undergo fundus fluorescein angiography. For ischemic CRVO, PRP should be treated as soon as possible. If retinal hemorrhage interferes with fluorescein angiography, patients should be followed closely. Once the bleeding subsides, the fundus is clearly fluorescent. Contrast, electroretinogram and afferent pupillary reflex defects can also be used to show non-perfusion of capillaries. Patients with non-ischemic CRVO should also be followed closely, as 16% of them may turn into defects within 4 months. Blood type, for ischemic CRVO, if no PRP is treated, about 40% of patients progress to NVG, and Magargal's experience in treating 100 ischemic CRVO eyes shows that all eyes with early argon laser PRP treatment have no Once developed into NVG, in general, regardless of PRP treatment or not, vision will not change, because vision depends on primary vascular disease, but secondary glaucoma optic atrophy can lead to further visual impairment, most patients After treatment, vision can be improved to some extent, and attention should be paid to the presence or absence of primary open angle glaucoma, high-risk elderly patients. In this way, because the risk of eye CRVO often lower intraocular pressure, therefore, suffer from CRVO eyes with glaucoma should be suspected, and make the appropriate follow-up.
2. Diabetic retinopathy:
For diabetic NVG, there must be retinal hypoxia and proliferative retinopathy. The main cause of proliferative retinopathy is the course of diabetes, but in the case of blood glucose close to normal, diabetic retinopathy occurs later. And to a lesser extent, PRP treatment can prevent NVI, anterior chamber neovascularization and NVG. Now, there is no evidence that the early diagnosis of electroretinogram, vitreous fluorescence or iris angiography has clinical implications for patients. Currently, the most important preventive measure for diabetic NVG is regular eye exams, recommended by the National Diabetes Advisory Committee, and all newly diagnosed type 2 diabetic patients and type 1 diabetic patients with a history of more than 5 years should have an eye exam every year. .
Platelet abnormalities and the resulting microvascular intravascular platelet aggregation and thrombosis have a certain role in promoting the development of diabetic retinopathy. Therefore, in the medical treatment, some drugs that reduce blood viscosity have been tried to delay the diabetic retinopathy. Occurrence, ticlopidine inhibits platelet aggregation and prolongs bleeding time, reducing the annual progression rate of microangioma by 70%; pentoxifylline increases choroidal blood flow in patients with non-proliferative diabetic retinopathy, also increases normal Blood flow in the retinal capillaries of the eye and diabetic eyes.
3. Carotid artery obstructive disease:
For carotid artery obstructive disease, prevention of NVI is generally impossible to achieve. The purpose of preventive treatment is to recognize the importance of the disease as the main cause or promotion factor of NVG. If patients with carotid artery obstructive disease have neurological symptoms, it is currently recommended. Carotid endarterectomy, NVI and NVG have been reported to have subsided after surgery. Patients with no neurological symptoms, even with NVI and NVG, do not advocate carotid endarterectomy, patients do not have NVI, do not preventive PRP, For diabetic retinopathy, if the severity of the eyes is asymmetrical, NVG intraocular pressure is normal or low, PRP fails to promote NVI regression, or there is no other obvious cause, the possibility of carotid artery obstructive disease should be considered.
4. Central retinal artery occlusion:
After CRAO occurs, the time to NVG varies from 1 week to 5 months, so patients with CRAO should be followed closely for at least 6 months, and once NVI is present, PRP is given.
Complication
Neovascular glaucoma complications Complications
Corneal edema and recurrent anterior chamber blood.
Symptom
Symptoms of neovascular glaucoma Common symptoms Dreaded, congested, eye pain, edema, pupil, fixed iris, neovascularization and...
The common manifestations of neovascular glaucoma are eye pain, photophobia, visual acuity often as the index of the eye ~ manual, intraocular pressure can reach more than 60mmHg, moderate to severe congestion, often accompanied by corneal edema, iris neovascularization, pupillary margin valgus, room There are different degrees of peripheral anterior adhesion in the horn. Shield divides the neovascularization from iris into the pathogenesis of neovascular glaucoma into three stages, namely, glaucoma, open-angle glaucoma and angle-closure glaucoma.
1. Early glaucoma (Iris red period):
At first, the tiny neovascular buds are typically characterized by tiny telangiectasia, mostly at the pupillary margin or the iris corneal angle. If you use a corner mirror, you can use a small pressure to make it disappear. The pupil enlargement can also cover the small newborn around the pupil. Blood vessels, therefore, it is necessary to make a detailed slit lamp examination before the expansion. As the disease progresses, the new blood vessels can extend irregularly around the pupil and appear clinically on the surface of the iris. The red line of the rule goes to the root of the iris, and when the neovascularization extends to the angle of the anterior chamber, the dendritic sulcus and the sclera protrude through the trabecular meshwork. Under normal conditions, the blood vessels in the anterior chamber are behind the scleral process, such as trabecular meshwork. When seeing a blood vessel, it must be abnormal. Sometimes it can be seen that the neovascularization occurs from the ring of the iris aorta to the trabecular meshwork. The neovascularization in the angle of the anterior chamber is often like a branch from a tree trunk. The tiny capillaries are distributed in several numbers. On the trabecular meshwork of a range of hours, it is necessary to double-amplify and carefully examine the early signs in these corners under bright light. The iris fluorescein angiography is fluorescent. Leakage, the pupillary vessels and radial vasodilation and abnormal fluorescein leakage can be seen before neovascularization. The iris redness of diabetic retinopathy and central retinal vein occlusion is clinically the same, but by silicone ( Silicone] The new blood vessels of the former can be seen after injection, and the distribution is tight and flat. The first phase change caused by central retinal vein occlusion is often transient, and the cause of diabetes can last for several years without change.
2. Open angle glaucoma:
As the disease progresses, these new blood vessels can completely obscure the surface structure of the original iris, and have a relatively smooth appearance. Because the neovascular tube wall is thin and can see the blood column, it shows a typical iris red color, and the color is bright red. The aqueous humor often has an inflammatory reaction. The iris corneal angle is still open. The fibrous tissue and fibrous vascular membrane associated with the neovascularization of the angle are difficult to see under the gonioscopic mirror, but the trabecular mesh can be blocked and the intraocular pressure is increased. The clinical manifestations can be similar. Acute onset of glaucoma, suddenly felt eye discomfort, eye pain, congestion, intraocular pressure often reached 40 ~ 50mmHg, corneal edema, and sometimes anterior chamber hemorrhage.
3. Closed angle glaucoma:
Finally, the fibrovascular membrane shrinks, and the blood vessel is tightened into a bridge frame in the corner of the anterior chamber. Then the iris is also pulled to the trabecular meshwork to form a peripheral anterior adhesion. The angle of the anterior surface is closed, and the fibrous vascular membrane on the anterior surface of the iris contracts, and the iris is behind. The pigment layer is pulled toward the pupillary margin, causing the pigmentation valgus of the pupil collar. It is usually seen that the anterior meridian line is accompanied by a corner occlusion, and the pupil sphincter is also pulled to the front to form a pupil dilated and enlarged. The blood vessels can grow to the surface of the cataractous lens through the adhesion. The extracapsular removal and intraocular lens can involve the lens capsule. In the later stage of neovascular glaucoma, the fully viscous anterior horn looks like a very smooth iris cornea. Adhesive lines, at which point the number of new blood vessels can be reduced.
The progress of iris neovascularization varies greatly, and it can completely occlude the angle of the horn within a few days. It can also remain stable for several years without involving the angle of the anterior chamber. This relative static condition can be suddenly active and progressing, or at any time. Completely subside, it is generally seen that the neovascularization of the iris caused by central retinal vein occlusion is coarser and irregular than that of diabetes.
Some eyes with slowly elevated intraocular pressure, such as corneal endothelium health, even if the intraocular pressure is as high as 60mmHg or more, there is no corneal edema, most of the visual conditions are very poor, and some can be good, according to the degree of damage to the visual function of the primary disease. And different.
Examine
Examination of neovascular glaucoma
Changes in blood rheology associated with primary diseases such as central retinal vein occlusion.
1. Histological examination:
Although the etiology of NVG is different, the histopathology of the anterior segment is the same. The only exception is CRVO and diabetes. The former is more filled with new blood vessels, while the latter is characterized by the accumulation of glycogen as a typical iris pigment epithelial cystic change, neovascularization. The process begins at the endothelium, and the capillaries bud-like from the small ring of the pupillary artery. Clinically, NVI seems to progress from the pupil to the periphery, but in histology, once the process starts from the pupillary margin, the new endothelial bud It can appear on blood vessels in any part of the iris, including the arterial ring at the root of the iris. These new endothelial buds develop into a vascular globule-like vascular plexus. The vascular plexus around the pupil has no characteristic meaning for NVG. It also appears in the muscle. In elderly patients with tonic dystrophy, abnormal insulin secretion, and no clear disease, these neovascularizations are composed of endothelial cells, without muscle or adventitia and supporting tissues. The wall is generally thin, found on the surface of the iris, but within the iris matrix. However, it can be found everywhere. Electron microscopy studies have shown that there are endothelial cell gaps in the neovascularization of diabetic eyes. Endothelial cell window and basement membrane change, so neovascular leakage of fluorescein and other substances, the normal blood vessels of the iris, like the retina and brain, are non-porous endothelial cells with tight intercellular junctions called Closed zonules prevent fluorescein and other substances from leaking. Scanning electron microscopy of NVI vascular casts revealed significant local expansion and contraction of the iris vessels, located on the surface and periphery of the iris, where NVI is most clinically apparent.
In NVG, the fibrous component of the fibrous vascular membrane is composed of proliferating myofibroblasts, which are fibroblasts with smooth muscle differentiation. Clinically, the fibrous portion of the membrane is transparent, but causes the iris to lose its normal surface. The texture structure became flat. Scanning electron microscopy showed that the performance of the film was consistent at NVI. The NVI was not anatomically located on the surface of the iris, actually located under the myofibroblast layer, and the fibrous vascular membrane was on the iris corneal corner. Stretching causes an increase in intraocular pressure, but the angle of the anterior angle of the angle of the corner is open, or the degree of neovascularization of the angle is not proportional to the increase in intraocular pressure. The contraction of smooth muscle can explain the flattening of the iris surface, outside the uvea. The occurrence of tumbling, the formation of peripheral anterior adhesion (PAS) and the closure of the final adhesion angle, it is now believed that proliferative neovascularization and myofibroblasts are the main components of granulation tissue, and NVI may be a false compensation and compensation process. .
As the vascular membrane continues to contract on the surface of the iris, the posterior epithelial layer of the iris is pulled over the anterior surface of the pupillary margin, causing uveal eversion and pupillary deformation, and the sphincter can also be pulled to the front, resulting in sphincter valgus. Contraction can be so extensive that the iris position is advanced or not fully constricted. This contraction can also compress and embed new blood vessels, hinder the observation of new blood vessels, advanced NVG, iris fibrosis, pupillary fixation, vascular membrane The contraction leads to a blocked angle of the anterior chamber with iris-corneal contact. When the neovascularization process is terminated, such as panretinal photocoagulation (PRP), the neovascularization will retreat in the rabbit corneal micropocket study. The tumor-induced neovascular endothelial cell degeneration is cleared by macrophages. The NVI retreat may be similar to this, and the myofibroblast membrane must also regress, because after the PRP is successful, if there is no adhesion angle Closed, the resulting open-angle glaucoma can often be alleviated, but once the adhesion angle is closed, PRP can not reverse it.
In some cases where the adhesion angle is closed for a long period of time, the corneal endothelium and Descemet membrane can extend across the adhesion to the surface of the iris, called the endothelialization of the iris, which is also seen after the iris corneal endothelial syndrome and trauma. The common pathogenesis is the invasion and destruction of the barrier between the cornea and the iris. This small or no visible neovascularization and the closure angle covered by the endothelium can easily be mistaken for a normal open angle.
2.Goldmann iris keratoscope:
The corneal neovascularization can be found early, providing high magnification and high brightness illumination.
3. Iris angiography:
It can be seen that fluorescein leaks, and the pupillary vessels and radial vasodilation and abnormal fluorescein leakage can be seen before the neovascularization occurs.
4. Other:
Some auxiliary tests related to primary diseases.
Diagnosis
Diagnosis and diagnosis of neovascular glaucoma
diagnosis
According to the primary disease and clinical signs, the diagnosis is not difficult, but needs to be identified.
Differential diagnosis
Early diagnosis in order to develop the best treatment is the key to NVG treatment. The differential diagnosis needs to be considered according to the two stages of the disease: first, only NVI in the early stage, and second, elevated intraocular pressure, corneal opacity and blood vessels. Congestion, no matter at which stage, comprehensive and detailed eye history and physical examination can usually establish a diagnosis, essential for true NVG, history, diabetes, previous visual impairment (prompting for old CRVO or retinal detachment), hypertension or arteries Sclerotherapy (prompting for possible carotid disease) has clinical value, and NVI should not be completely ruled out even if the posterior segment is well-preserved.
1. Fuchs heterochromic iridocyclitis:
NVI can occur in Fuchs heterochromic iridocyclitis, the eyes are generally quiet and not congested, new blood vessels are seen in the corner of the room, the appearance is slender, the wall is thin and fragile, there may be spontaneous anterior hemorrhage, but bleeding is more common In some operations after eye surgery or in the angle of the anterior chamber, these blood vessels can reach the trabecular meshwork across the scleral process. Glaucoma is quite common, most of which are open-angle mechanisms, NVI or NVG are rare, in a large In the study of group data, only 6 patients with heterochromic iridocyclitis had NVI, and 4 of them developed NVG. Histological studies showed local thickening of the wall due to iris endothelial proliferation and hyalinosis. As a result of thinning of the lumen and reduction of vascular perfusion, fluorescein angiography showed that iris vascular leakage, radioactive iris vascular thinning and iris fantal ischemia, which confirmed the formation of NVI caused by local hypoxia.
2. Exfoliation syndrome:
NVI can also occur in exfoliation syndrome. These blood vessels are slender and easy to be missed during clinical examination, especially in the eyes of dark irises. Iris angiography indicates that there is iris hypoperfusion in each NVI eye, electron microscopy. Studies have shown that vascular wall pores become smaller, lumens become thinner and endothelial thickening, which explains the cause of fluorescence leakage, but there is no literature report on true NVG.
3. Acute iridocyclitis:
Anterior segmental inflammation can cause significant iris neovascularization, sometimes difficult to distinguish clinically from NVI, especially in diabetes. Severe iritis and secondary angiogenesis after cataract extraction are similar to sudden NVG, according to current For the pathogenesis of NVI and the role of prostaglandins in this process, inflammation is sufficient to cause dilated vasodilation of the iris, which is more pronounced in patients with retinal perfusion damage. In any case, false NVI will disappear after treatment with topical corticosteroids. True NVI will still exist.
4. Acute angle-closure glaucoma:
The signs and symptoms of NVG usually appear suddenly and significantly, so the patient's first onset, the eye has inflammation and the intraocular pressure is 60mmHg or even higher. On the other hand, the underlying cause of NVG, such as diabetes or CRVO, generally lasts for a long time. Exist, NVG enters the late stage, the intraocular pressure rises and the cornea is turbid. The acute angle-closure glaucoma is definitely the first to be diagnosed. Even with the use of whole body hypertonicity and local glycerol, iris keratoscopy is impossible. The opaque cornea sees NVI, and more importantly, the iris keratomileus of the contralateral eye will provide clues as narrow-angle and angle-closure glaucoma tend to be bilateral, or have iris resection through surgery or laser. Medical history.
5. Trauma and bleeding:
Intraocular hemorrhage for any reason, especially anterior chamber hemorrhage, can be confused with NVG. The possibility of hemocytic glaucoma should be considered after trauma or surgery, such as umbilical anterior empyema or small (4~ 8m) umbilical blood-stained cells cover the trabecular meshwork, which is generally easy to diagnose. However, repeated anterior chamber blood obstruction observation, medical history combined with corneal puncture by phase contrast microscopy of anterior chamber aspiration, will determine the diagnosis of ghosting glaucoma .
