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Professor Sun Xinghuai on the clinical features and management of neovascular glaucoma

Posting time:2023-01-31 13:40:07

Professor Sun Xinghuai on the clinical features and management of neovascular glaucoma

Editor's Note Neovascular glaucoma (NVG) is a blinding refractory glaucoma, its greatest harm is to cause irreversible vision loss in patients, accompanied by persistent severe eye pain, which will bring endless pain to patients. pain of. However, it is not easy to relieve the pain caused by NVG. The etiology of NVG is complicated. If the patient cannot be treated in a targeted manner, the therapeutic effect will be greatly reduced. In view of this, during the 2022VC meeting, Professor Sun Xinghuai of the Eye and ENT Hospital of Fudan University shared his clinical experience in the treatment of NVG, explained the clinical characteristics and treatment methods of NVG in detail, and pointed out the direction for the treatment of NVG. Clinicopathological features of NVG Neovascularization of the iris is an important and most easily found sign in the clinical diagnosis of NVG. The neovascularization of the iris is accompanied by a layer of transparent fibrous tissue proliferative membrane, called the neovascular membrane. The lesion is secondary to angle dysfunction leading to increased intraocular pressure and eversion of the pupil collar pigment of the iris, which in turn leads to fixed and dilated pupils. (figure 1). Figure 1. Iris neovascularization and neovascular membrane The neovascular membrane is histopathologically composed of proliferating myofibroblasts (fibroblast smooth muscle differentiation) and neovascularization. The fibers of the membrane are partially transparent, and the smooth muscle components can be contracted; the new blood vessels are composed of endothelial cells, with thin walls, and the blood barrier function is not perfect, which is easy to leak intravascular proteins, cells and other substances (Figure 2). Figure 2. Clinical features of NVG pathological microscopic NVG Regarding the primary disease causing NVG, an article published by Prof. Sun listed the main constituent ratios of more than 40 different diseases/diseases involving the eye in 301 cases of NVG : Retinal vein occlusion (RVO) 29.7% [central vein occlusion (CRVO) 98%, or branch vein occlusion (BRVO)] Diabetic retinopathy (proliferative) 21.1% Other diseases: Malignant intraocular tumor retinoblastoma ( RB) and other 10.4%, ocular trauma 6.3%, retinal detachment 5.4%, primary glaucoma 3.8%, Coats disease 3.2%, uveitis 1.6% and other literature reports that about 18% to 60% of retinal vein occlusion patients will develop NVG, In particular, NVG occurs in about 40% of the natural history of ischemic CRVO, and 80% occurs within 6 months (mostly within 2 to 3 months). The incidence after panretinal photocoagulation (PRP) was 20.2%. The incidence of NVG in diabetic retinopathy (DR) is 22%, of which binocular NVG is the most common, and it is more likely to occur after cataract and vitreous surgery. Professor Sun's article also summarizes the age distribution characteristics of NVG patients: <18 years old accounted for 16.7% (including RB 66%, Coats disease 16%, trauma and retinal detachment each 6%); 18-40 years old accounted for 23.9% (including 23.9%). RVO 43%, DR 15.3%, trauma 9.7%); >40-60 years old accounted for 20.3% (including RVO 42.6%, DR 36%, trauma 8.2%); >60 years old accounted for 45% (including RVO 34.2%, DR 25.4%, primary glaucoma 9%). Clinicopathological course of NVG The clinicopathological course of NVG includes anterior glaucoma (erythema of the iris) and glaucoma (open-angle to angle-closure). In the anterior stage of glaucoma, neovascularization of the iris appeared, and the condition was reversible at this stage, and the patient's intraocular pressure was normal. The condition of glaucoma is irreversible. The intraocular pressure of patients increases. When the neovascular membrane covers the trabecular tissue of the angle of the chamber, the angle is open, and the neovascular membrane contracts, and the angle of the chamber is closed. The reason why NVG is difficult to treat is mainly because the neovascular membrane of the iris and the angle of the chamber is easy to grow into the inner filtration opening, and various related factors promote the formation of fibrovascular membranes, and the filtration tract is prone to scarring. Various reasons can cause the disturbance of the microenvironment in the anterior chamber to lead to the onset of NVG. Professor Sun's team has examined the pro-angiogenic factors [vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF)] and pro-angiogenic factors in the aqueous humor of 50 cases of NVG. Fiber tissue growth and smooth muscle metaplasia factor [transforming growth factor-β1, β2 (TGF-β1, β2)] content were detected. The results showed that VEGF, HGF (Fig. 3), TGF-β1 and TGF-β2 were all increased in the aqueous humor of the NVG group, and TGF-β2 was more significantly increased (Fig. 4). Figure 3. VEGF and HGF in the aqueous humor of the NVG group were significantly increasedFigure 4. Both TGF-β1 and TGF-β2 were increased in the aqueous humor of the NVG group, and the increase in TGF-β2 was more obvious. This study verified that the VEGF in the aqueous humor of the NVG group was significantly increased , found that HGF was significantly elevated in NVG aqueous humor. The concentration of TGF-β1 in NVG aqueous humor was significantly lower than that in plasma, suggesting that it may come from vascular leakage; the concentration of TGF-β2 was significantly higher than that in plasma, suggesting that it might be produced locally in the eye. VEGF is associated with TGF-β1, TGF-β2, and HGF. In addition, the results of histopathological immunohistochemical studies showed that the neovascular membranes were abundantly expressed in NVG eyeball specimens, and were also found in iris stromal cells, but they were slightly expressed in normal eyeball specimens (Fig. 5). The results suggest that TGF-β may be a relevant factor in promoting the proliferation and contraction of iris neovascular membrane fibroblasts. Figure 5. Comparison of the expression levels of TGF-β1 and TGF-β2 in NVG eyeballs and normal eyeballs. The main features of glaucoma that are particularly refractory to NVG treatment are intractable high intraocular pressure, unbearable pain, iris, anterior chamber angle There is a neovascular membrane on the surface. The treatment of such patients should grasp two principles, namely reducing or eliminating new blood vessels and reducing intraocular pressure. Measures to reduce or eliminate neovascularization include panretinal photocoagulation (PRP)/cryotherapy and anti-VEGF therapy. Clinically, it is generally believed that PRP should be performed when iris neovascularization occurs, especially for those cases where close follow-up is not possible. Intraocular injection of anti-VEGF drugs can rapidly resolve the neovascularization, but if the primary cause is not eliminated, the neovascularization will reappear soon after. When NVG occurs, although intraocular injection of anti-VEGF drugs can regress the new blood vessels and gain a valuable time window for further glaucoma drainage surgery, this does not treat glaucoma itself. Measures to lower IOP include drug therapy, filtering surgery, and ciliary destructive surgery (cold, laser, ultrasound). Pharmacological treatment is mainly the use of drugs that reduce aqueous humor production, but this approach is limited and often requires systemic medication. Filtering procedures include conventional trabeculectomy/+antimetabolites, and traditional implant drainage procedures, which have a relatively high success rate. Destructive surgery of the ciliary body is difficult to grasp, and the patient's response to treatment is relatively large. Glaucoma drainage valve implantation is a filtering operation with artificial drainage devices. The results of a clinical study conducted by Professor Sun on the application of glaucoma drainage valve implantation in the treatment of NVG showed that the total success rate of NVG treatment was 81%, and postoperative One-year (76%) and two-year (73%) overall success rates were also high (Figure 6). Figure 6. Curative effect of NVG drainage valve operation Professor Sun did not see neovascular membrane growing into the anterior chamber catheter during glaucoma drainage valve operation, but the operation still has certain limitations: certain anterior chamber conditions are required: depth and "cleanness"; The formation of the cystic filtration cavity of the drainage disc to the formation of the "water reservoir" outside the eye is the main reason for the loss of intraocular pressure; improper placement of the anterior chamber catheter can lead to postoperative corneal endothelial decompensation, iris atrophy, and lens opacity; drainage The pressure control of the valve: often exceeds the original set pressure threshold to open. To sum up, ophthalmologists have accumulated some experience in the treatment of NVG, but there are still many problems that need to be discussed and overcome. The key point of future NVG treatment/research is how to effectively treat the neovascular membrane, hoping to find new treatment methods to benefit NVG patients in the future.

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