Intravitreal Injection of Conbercept Combined with Minimally Invasive Photocoagulation and Phacoemulsification Intraocular Lens Implantation in the Treatment of Neovascular Glaucoma Complicated with Cataract

Background Neovascular glaucoma (NVG) is a complex refractory glaucoma with a high rate of blindness. Compaq is an anti-VEGF agent that has been used in clinical NVG therapy. Objective This study aims to investigate the effect of intravitreal injection of conbercept combined with minimally invasive photocoagulation and phacoemulsification intraocular lens implantation in the treatment of NVG complicated with cataracts. Methods A total of 84 patients with NVG complicated with cataracts who were admitted to our hospital from September 2019 to September 2021 were selected. According to the random number table method, they were divided into the study group and the control group, with 42 cases in each. The control group underwent minimally invasive photocoagulation combined with phacoemulsification and intraocular lens implantation. The study group was given an intravitreal injection of conbercept first, followed by minimally invasive photocoagulation combined with phacoemulsification and intraocular lens implantation 3 to 7 days after the injection. The intraocular pressure and visual acuity of the two groups before surgery, 1 week, 1 month, 3 months, and 6 months after the operation were compared. The levels of serum vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were compared between the two groups before the operation and 1 week after the operation. The incidence of postoperative complications in the two groups was statistically compared. Results At 1 week, 1 month, 3 months, and 6 months after the operation, the intraocular pressure of the study group was lower than that of the control group, and the visual acuity was better than that of the control group (P < 0.05); one week after the operation, the serum levels of VEGF and IL-6 in the study group were lower than those in the control group (P < 0.05); there was no significant difference in the incidence of complications between the two groups (P > 0.05). Conclusions Intravitreal injection of conbercept combined with minimally invasive photocoagulation and phacoemulsification intraocular lens implantation in the treatment of NVG complicated with cataract can improve the levels of serum inflammatory factors and vasoactive substances, effectively reduce intraocular pressure, and improve visual acuity.


Introduction
Neovascular glaucoma (NVG) is a complex refractory glaucoma with a high rate of blindness. Te disease mostly occurs in people over 40 years of age, so timely and reliable measures should be given to avoid vision loss. Te main causes are ocular ischemic syndrome, fundus retinal vein occlusion, diabetic retinopathy, and other ocular ischemic diseases. Clinical manifestations are difcult to control high intraocular pressure, irreversible visual impairment, and intractable eye pain, often complicated by a variety of eye diseases, such as cataracts, corneal degeneration, and so on [1,2]. At present, for NVG patients with cataracts, trabeculectomy, goniosynechialysis combined with phacoemulsifcation, and intraocular lens implantation are mainly performed to reduce intraocular pressure and restore vision. However, the traditional antiglaucoma method is not ideal for various reasons. In recent years, it has been found that minimally invasive photocoagulation combined with cataract surgery can destroy the unpigmented epithelial cells of the ciliary process by laser, which can accurately control energy, improve fltration function, avoid the problem of insufcient or excessive fltration in traditional antiglaucoma surgery, and has high safety can better maintain postoperative vision [3,4]. Vascular endothelial growth factor (VEGF) is a cytokine formed when tissues throughout the body are hypoxic and have the efect of promoting angiogenesis. Te number of retinal neovascularization is closely related to the level of VEGF. In addition, patients with neovascular glaucoma have abnormally elevated levels of VEGF in aqueous humor. In other words, patients with neovascular glaucoma can secrete VEGF-A from the retinal pigment epithelial cells due to retinal hypoxia, thereby promoting choroidal neovascularization. At present, it has been confrmed that VEGF is the key link to intraocular neovascularization. Compaq, as an anti-VEGF drug, has been used in clinical NVG treatment [5,6]. Tis study investigated the efect of intravitreal injection of conbercept combined with minimally invasive photocoagulation and phacoemulsifcation, and intraocular lens implantation in the treatment of NVG patients with cataracts. Te report is as follows.

General Information.
Eighty-four cases of NVG with cataracts treated in our hospital from September 2019 to September 2021 were selected. Inclusion criteria were as follows: (1) all of them met the diagnostic criteria of NVG complicated with cataract by ophthalmological examination [7]; (2) intraocular pressure cannot be efectively controlled after treatment with 2 or more intraocular pressure drugs; (3) age ≥18 years old; (4) monocular lesions; (5) lens nucleus ≥ grade III. Exclusion criteria were as follows: (1) retinal detachment; (2) primary glaucoma; (3) patients with severe heart, liver, kidney, and lung dysfunction; (4) history of previous ophthalmic surgery; (5) had been treated with anti-VEGF drugs; (6) combined with other eye diseases; (7) early stage of cataract; (8) combined with the pronounced vitreous volume of blood; (9) patients with mental disorders; (10) patients with incomplete clinical data.
According to the method of the random number table, they were divided into a study group (n � 42) and a control group (n � 42). In the control group, there were 23 males and 19 females, aged 43-68 years old, with an average age of (55.36 ± 4.12), 26 cases of central retinal vein obstruction, and 16 cases of diabetic retinopathy. In the study group, there were 25 males and 17 females, aged from 45 to 69 years old, with an average of (56.23 ± 4.36) years. Tere were 27 cases of central retinal vein occlusion and 15 cases of diabetic retinopathy. Te baseline data of the two groups were balanced and comparable (P > 0.05).

Method.
Te control group underwent minimally invasive photocoagulation combined with phacoemulsifcation and intraocular lens implantation: mydriasis, towel disinfection, eye opener eyelid, surgical eye surface anesthesia, the frst phacoemulsifcation and intraocular lens implantation, 11 o 'clock position for the transparent corneal incision (2.2 mm), at 2 o 'clock position for auxiliary incision, the viscoelastic agent was injected into the anterior chamber, continuous circular capsulorhexis (diameter 5.5 mm) was performed by capsulorhexis forceps, water separation, phacoemulsifcation, aspiration of lens cortex, posterior capsule to maintain transparency, and integrity, a viscoelastic agent from the capsule bag, anterior chamber injection, and an intraocular lens from transparent corneal incision from the capsule bag injection. After completion of minimally invasive photocoagulation, viscoelastic agent ciliary groove deep injection, endoscopic probe through the transparent main incision into, through the pupil to the contralateral iris posterior, ciliary body area between the ciliary body sac, adjust the focal length, 150°-180°ciliary protrusion continuous photocoagulation, the number of points 18-35 times, energy 0.25-0.40 W, 0.2-0.6 s exposure time, real-time adjustment of parameters, the endoscopic monitor to see the ciliary body whitening, fold collapse, and no ciliary process reaction, as successful photocoagulation, after sucking the viscoelastic agent, equilibrium liquid from the auxiliary incision injection, water seal corneal incision, restore intraocular pressure. After the operation, tobramycin-dexamethasone eye drops were given for 4 weeks, combined with the local application of nonsteroidal eye drops for 8 weeks for anti-infection and antiinfammation.
In the study group, conbercept was injected into the vitreous cavity frst. Te methods were as follows: mydriasis, towel disinfection, topical anesthesia of the eye, eyelid opening with an eye opener, and vertical puncture of the sclera through the pars plana of the ciliary body at 3.5-4.0 mm posterior to the infratemporal limbus to enter the vitreous cavity. 0.05 ml of conbercept at a concentration of 10 mg/ml (S20130012, Chengdu Kanghong Biotechnology Co., Ltd.) was injected, the needle was pulled out, the eyeball was locally compressed for 2 minutes, and ofoxacin eye ointment was applied. According to the regression of neovascularization and the infammatory reaction of the anterior chamber, minimally invasive photocoagulation combined with phacoemulsifcation and intraocular lens implantation was performed 3-7 days after injection. Te method of minimally invasive photocoagulation combined with phacoemulsifcation and intraocular lens implantation was the same as that of the control group. Tis study was approved by the hospital ethics committee. All patients sign an informed consent form. Tere were no patients who dropped out of the study.

Statistical
Method. SPSS22.0 was used to analyze the data. Mean ± standard deviation (±s) was used to represent the measurement data, t-test or repeated measurement analysis of variance, n (%) was used to represent the count data, and χ2 test was used. P < 0.05 indicated that the difference was statistically signifcant.

Intraocular Pressure.
Te results of repeated measures analysis of variance showed that the intraocular pressure of the two groups was statistically signifcant in terms of time, group, and interaction. (P < 0.05); at 1 week, 1 month, 3 months, and 6 months after the operation, the intraocular pressure in the study group was lower than that in the control group (P < 0.05). See Table 1.

Eyesight.
Te results of repeated measurement analysis of variance showed that the eyesight level of the two groups was statistically signifcant in terms of time, intergroup, and interaction (P < 0.05); the eyesight of the study group was better than that of the control group at 1 week, 1 month, 3 months, and 6 months after the operation. P < 0.05). See Table 2.

Serum VEGF, IL-6 Levels.
One week after the operation, the levels of serum VEGF and IL-6 in the study group were lower than those in the control group (P < 0.05). See Table 3.

Complication.
Tere was no signifcant diference in the incidence of complications between the two groups (P < 0.05), see Table 4.

Discussion
Te pathogenesis of NVG is complex and is related to retinal ischemic disease. When the retina has hypoxia-ischemia, the eye VEGF will be oversecreted and circulate to the chamber angle and anterior chamber through the aqueous humor, resulting in the formation of neovascularization and a fbrous membrane, which will further pull the chamber angle and close its adhesion, resulting in the increase of intraocular pressure (IOP) [8,9]. High intraocular pressure will aggravate the degree of retinal ischemia, form a vicious circle, and damage vision. Terefore, the key to NVG treatment is to inhibit neovascularization and reduce intraocular pressure.
Minimally invasive photocoagulation is an important method for the treatment of refractory glaucoma. It is performed under endoscopic direct vision, with accurate ciliary body positioning and accurate photocoagulation range, by reducing the formation of the aqueous humor photocoagulation ciliary body, to reduce the intraocular pressure efect, and can signifcantly reduce the surrounding tissue damage, reduce the risk of visual impairment of traditional photocoagulation [10]. Fu et al. [11] found that minimally invasive photocoagulation is used to treat refractory glaucoma, which can signifcantly reduce intraocular pressure in patients, have fewer complications, and can obtain similar efects as trabecular resection. NVG is often due to the iris surface and anterior chamber angle being covered with neovascularization, and simple surgical treatment is more prone to bleeding. Studies have shown that VEGF overexpression is one of the main mechanisms to induce angiogenesis [12], Terefore, the preoperative use of anti-VEGF drugs can promote the regression of neovascularization and inhibit its formation. Yu et al [13] also found that vitreous injection of anti-VEGF drugs before routine surgery can promote the regression of neovascularization, reduce the rate of intraoperative and postoperative bleeding, and ensure the smooth implementation of the operation. As a new recombinant fusion protein independently developed in China, the core region of conbercept is a fully humanized amino acid sequence with high afnity. Compared with natural receptors, monoclonal antibodies, and VEGF, conbercept is more closely combined, which can completely penetrate the retina and inhibit VEGF-induced angiogenesis [14][15][16]. Terefore, in this study, patients with NVG complicated with cataracts were treated with intravitreal injection of Combuxil, followed by minimally invasive photocoagulation combined with phacoemulsifcation and intraocular lens implantation 3-7 days after injection. Te incidence of hyphema was low, but there was no signifcant diference between the two groups, which may be related to the small sample size of this study. Tere were no signifcant diferences in the incidence of other complications, indicating a high safety profle.
Te results of this study showed that the IOP of the study group was lower than that of the control group at 1 week, 1 month, 3 months, and 6 months after the operation. Te reason is that with the help of the anti-VEGF drug Compaq, IOP can be quickly and efectively controlled within the normal range after NVG. Te visual acuity of 6 months after the operation was better than that of the control group, indicating that intravitreal injection of the conbercept combined with minimally invasive photocoagulation, and phacoemulsifcation and intraocular lens implantation in the treatment of NVG with cataract has a signifcant curative efect in reducing intraocular pressure and improving visual acuity. IL-6 can mediate the body's infammatory response and can also regulate VEGF expression in vivo. Related studies have shown that serum VEGF levels are positively correlated with aqueous humor levels [17]. Tis study found that the serum VEGF and IL-6 levels decreased one week after surgery, and the study group was lower than the control group, which confrmed that the use of Compaxipr can efectively reduce the production of infammatory factors and vasoactive substances before minimally invasive photocoagulation combined with ultrasonic emulsifying intraocular lens implantation. Tis is mainly due to the fact that intravitreal injection of Compaq can combine with some VEGF-B and all VEGF-A, and then block neovascularization; after treatment, intraocular hypertension returns to normal, the intraocular microenvironment returns to a stable state, and the level of infammatory factors decreases. Tere are also some shortcomings in this study, as the patients in this study are all from the same hospital and are not representative of the overall situation, which may lead to some bias in the results of this study. Moreover, this study has a short observation time and a small sample size, so it is necessary to further prolong the follow-up time and conduct a large sample study.  Comparison with the same group before the operation, a P < 0.05. Compared with the same group before the operation, a P < 0.05; compared with the control group at the same time, b P < 0.05. Te F value indicates the signifcance of the entire ftting equation, and the larger the F, the more signifcant the equation and the better the ft.

Conclusion
Vitreous injection of Compaq combined with minimally invasive photocoagulation and phacoemulsifcation intraocular lens implantation in the treatment of NVG complicated with cataract can improve the levels of serum infammatory factors and vasoactive substances, efectively reduce intraocular pressure, and improve visual acuity.

Data Availability
Te datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Conflicts of Interest
Te authors declare that they have no conficts of interest.