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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 4  |  Issue : 2  |  Page : 50-54

Effect of conbercept or ranibizumab in the treatment of wet age-related macular degeneration


1 Department of Ophthalmology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
2 Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA
3 Department of Nephrology, Beijing Luhe Hospital, Capital Medical University, Beijing, China

Date of Submission26-Jan-2019
Date of Acceptance20-May-2019
Date of Web Publication17-Jun-2019

Correspondence Address:
Dr Tao Chai
82 Xinhua South Road, Tongzhou District, Beijing
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ed.ed_5_19

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  Abstract 


Objective: The aim of this study was to investigate the effects of conbercept or ranibizumab in the treatment of wet age-related macular degeneration(AMD) and to explore the influence on central retinal thickness (CRT), visual acuity, and choroidal neovascularization(CNV) permeation.
Patients and Methods: Atotal of 85patients(85 eyes) with wet AMD were enrolled in this study. All patients were treated by intravitreal injection of anti-vascular endothelial growth factor and were randomly divided into two groups. Patients in GroupA were treated by intravitreal injection of conbercept, whereas those in GroupB were treated by intravitreal injection of ranibizumab once a month for 3 consecutive months. The best-corrected visual acuity(BCVA) was measured. Subfoveal choroidal thickness(SFCT) and CRT of affected eyes and healthy eyes were examined with optical coherence tomography. Fundus fluorescein angiography was performed, and the area of CNV permeation was calculated.
Results: BCVA(logarithm of the minimum angle of resolution) of affected eyes in the two groups was significantly better at 1month, 2months, and 3months after treatment as well as at the end of follow-up than that of before treatment. Meanwhile, CRT was obviously decreased. SFCT of affected eyes was significantly smaller than that of before treatment, which was also remarkably smaller when compared with that of healthy eyes. At 3months after treatment and at the end of follow-up, the areas of CNV permeation in the two groups were significantly decreased. In addition, the average times of injection in GroupA were significantly less than that of GroupB.
Conclusions: Intravitreal injection of conbercept and ranibizumab significantly decreased SFCT of affected eyes. However, the length of conbercept medication injection time was lower than that of ranibizumab.

Keywords: Conbercept, ranibizumab, visual acuity level, wet age-related macular degeneration


How to cite this article:
Zhang D, Khan Z, Chai T. Effect of conbercept or ranibizumab in the treatment of wet age-related macular degeneration. Environ Dis 2019;4:50-4

How to cite this URL:
Zhang D, Khan Z, Chai T. Effect of conbercept or ranibizumab in the treatment of wet age-related macular degeneration. Environ Dis [serial online] 2019 [cited 2022 Jul 1];4:50-4. Available from: http://www.environmentmed.org/text.asp?2019/4/2/50/260517




  Introduction Top


Age-related macular degeneration(AMD) is a chronic progressive disease located in the central retina. AMD is closely related to age, smoking, cardiovascular disease, genetic factors, and cataract surgery history. Previous studies have shown that it is one of the main reasons for blindness among people over50years old.[1] The percentage of wet AMD is about 10% in patients with AMD. Wet AMD is caused by an abnormal expansion of choroidal neovascularization(CNV) and the destruction of the retinal pigment epithelium. Compared with dry AMD, it is more likely to lead to vision loss andgreat harm.[2] Domestic and foreign studies have shown that high expression of vascular endothelial growth factor(VEGF) plays an important role in the pathogenesis of wet AMD.[3],[4] Anti-VEGF is the first-line treatment for all types of neovascular wet AMD and other macular CNV lesions. In recent years, anti-VEGF drugs such as ranibizumab and conbercept have been widely used in the treatment of diseases such as central retinal vein occlusion with macular edema(ME), proliferative diabetic retinopathy, and wet AMD.[5] Therefore, the aim of this study was to analyze the effect of intravitreal injection of ranibizumab or conbercept on CRT in patients with wet AMD and measure the resulting visual acuity and CNV permeation, thereby optimizing the clinical curative effect.


  Patients and Methods Top


General data and grouping

The study was approved by the Ethics Committee of the Beijing Luhe Hospital. Our study was a prospective control study, and informed consent was obtained from each patient before the study. From July 2015 to July 2017, a total of 85patients(85 eyes) diagnosed with AMD at Beijing Luhe Hospital were enrolled. Inclusion criteria were as follows: patients>50years old; patients with wet AMD confirmed by visual acuity, intraocular pressure and slit-lamp examination, optical coherence tomography (OCT), fundus fluorescein angiography(FFA), fundus indocyanine green angiography(ICGA), and other fundus examinations; patients who did not receive other treatments before inclusion; patients who only received the treatment of conbercept or ranibizumab after inclusion; patients with turbidity in the refractive medium that did not affect the examination; and patients with a monocular disease. Exclusion criteria included patients with advanced wet AMD; patients with nonwet AMD complicated with retinal detachment, retinal vein occlusion, or high myopia influencing macular function; patients with severe diabetes, hypertension, or other systemic diseases; patients who had poor control of blood glucose and blood pressure during treatment; patients who underwent glaucoma and cataract surgery; patients with active infection or inflammation in fundus; patients unable to receive intravitreal injection of drugs; and patients who underwent incomplete fundus examination due to fluorescein sodium, indocyanine green, or an iodine allergy. Referencing a random number table, all patients were divided into GroupA and GroupB, with 43 eyes and 42 eyes in each group, respectively. In GroupA, there were 28males and 15females. The age of patients in GroupA ranged between 56 and 89years old, with an average age of(73.26±4.16) years old. In GroupB, there were 25males and 17females. The age of patients in GroupB ranged between 53 and 87, with an average age of(74.82±5.07) years old. There was no statistically significant difference in gender and age between the two groups (χ2=0.421, P =0.517; t=1.597, P =0.114).

Treatment methods

Not all patients had systemic or local contradictions for relevant treatment. Before the study, all patients were informed of the purpose of treatment, as well as the complications after intravitreal injection of conbercept or ranibizumab. Informed consent was obtained from each participant before the study. All the operations were performed by the same senior chief physician.

Three days before treatment, patients in the two groups were treated with 0.5% levofloxacin eye drops four times a day for three consecutive days. In the operating room, oxybuprocaine hydrochloride eye drops were used for surface anesthesia in accordance with the requirements. Routine ophthalmological disinfection and laying disinfectant towels were performed. The eyelids were opened with a blepharostat and the conjunctival sac was rinsed with 5% polyvidone iodine solution for 90 s. Then, 0.5mg/0.05mL of conbercept ophthalmic injection (Chengdu Kanghong Bio-Technique Co. Ltd., Chengdu, China. 10mg/mL, 0.2mL/injection) or ranibizumab injection(Novartis Pharma Schweiz AG, Basel, Switzerland, 10mg/mL, 0.2mL/bottle) was extracted with a 1mL special syringe for intraocular injection. The syringe vertically penetrated at a subtemporal site of affected eyes or sites that were 3.5~4.0mm from the posterior limbus. The drug was injected, and the syringe was removed after the needle entered into the vitreous body. The puncture site was pressed with a dry swab for at least 1min and ofloxacin eye ointment was applied in the conjunctival sac. After aseptic dressing binding, patients were sent back to the ward.

Patients in the two groups were treated with an intravitreal injection once a month for 3months. Three months later, the necessity of intravitreal injection was determined according to the patients' complaints and examination results. Indications for further injection include visual acuity decreased 5 or more letters when compared with the previous highest visual acuity; the average central retinal thickness(CRT) increased 100 μm or more by OCT results; FFA and ICGA exhibited new macular lesions when compared with the previous value.

Observation indexes

Patients in the two groups were followed up once a month after treatment for a total of 6–11months. The median follow-up time of patients was 8months. The best-corrected visual acuity(BCVA) was measured by international standard before treatment, at 1month, 2months, and 3months after treatment at the last follow-up and after correction with a spherical lens and a column lens. This was then converted to logarithm of the minimum angle of resolution(LogMAR) visual acuity. The Cirrus HD OCT(Carl Zeiss Meditec, Inc., model 5000) was used, and subfoveal choroidal thickness (SFCT) was measured by the OCT and enhanced-depth imaging mode. Data of vertical distance from the same horizontal axis were used to measure the CRT and distance center. FFA was performed before injection and at 3months and 6months after injection to observe the fluorescein sodium osmotic changes of lesions. The area of CNV permeation was calculated. The frequency of vitreous body medication, as well as the incidence of adverse events in the two groups, was recorded at the first time of medication and 6months after medication, respectively.

Statistical analysis

Statistical Product and Service Solutions 18.0 software(SPSS Inc., Chicago, IL, USA) was used for all statistical analysis. Counting data were expressed by rate, and Chi-square test was used. Measurement data were expressed by ± s. Paired t-test was used to compare the differences between two groups. Results were considered statistically significant at P <0.05.


  Results Top


Comparison of best-corrected visual acuity(logarithm of the minimum angle of resolution) and central retinal thickness of affected eyes in the two groups before and after treatment

BCVA(LogMAR) of affected eyes in the two groups at 1month, 2months, and 3months after treatment, as well as at the last follow-up, was significantly better than that of before treatment(tA=3.354, 5.279, 6.059, 5.410, P <0.05; tB=2.139, 3.922, 4.806, 4.143, P <0.05). However, compared with that before treatment, CRT was obviously decreased (tA=12.853, 17.096, 21.037, 20.328, P <0.05; tB=13.395, 17.160, 20.474, 20.159, P <0.05) showing statistically significant differences. There was no statistically significant difference in BCVA(LogMAR)(t=0.395, 0.463, 0.214, 0.210 and P =0.694, 0.645, 0.830, 0.834) or CRT(t=0.182, 0.445, 0.090, 0.361 and P =0.880, 0.658, 0.929, 0.719) between GroupA and GroupB at 1month, 2months, and 3months after treatment and at the last follow-up[Table1].
Table 1: Comparison of best-corrected visual acuity (logarithm of the minimum angle of resolution) and central retinal thickness between the two groups before and after treatment

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Comparison of the area of choroidal neovascularization permeation between the two groups before and after treatment

The areas of CNV permeation in the two groups at 3months after treatment and at the last follow-up were significantly decreased when compared with those before treatment (tA=11.336, 3.605, P <0.01, tB=12.960, 14.598, P <0.01). However, there was no statistically significant difference in the area of CNV permeation between the two groups(t=0.517. 0.344, P =0.607, 0.732)[Table2].
Table 2: Comparison of the area of choroidal neovascularization permeation between the two groups before and after treatment

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Comparison of subfoveal choroidal thickness of affected eyes and healthy eyes between the two groups before and after treatment

There was no significant difference in SFCT of affected eyes and healthy eyes between the two groups before treatment(tA=0.110, P =0.913, tB=0.112, P =0.911). SFCT of affected eyes in the two groups remarkably decreased at 1month, 2months, and 3months after treatment as well as the last follow-up(tA=7.508, 7.739, 9.835, 11.057. P <0.01; tB=7.042, 6.796, 8.407, 10.356, P <0.01). However, no statistically significant difference was found in SFCT between the two groups(t=0.949, 1.186, 1.474, 1.094 and P =0.345, 0.239, 0.144, 0.277)[Table3].
Table 3: Comparison of SFCTof affected eyes and healthy eyes between the two groups before and after treatment (μm)

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Comparison of the times of injection between the two groups

From the initial treatment to the 6thmonth, the average injection times of GroupA and GroupB were(3.64±0.62) and (4.19±0.73), respectively. Results found that the average injection times of GroupA were obviously lower (t=3.852, P <0.01).

Comparison of adverse events between the two groups

During the treatment, one case of transient elevated intraocular pressure and one case of subconjunctival hemorrhage occurred in GroupA. The incidence of adverse reactions was 4.65%(2/43). However, two cases of transient elevated intraocular pressure and one case of subconjunctival hemorrhage occurred in GroupB. The incidence of adverse reactions was 7.14%(3/42). No statistically significant difference was found in the incidence of adverse reactions between the two groups(χ2=0.212, P =0.645). Patients in the two groups were given symptomatic treatments such as reducing intraocular pressure and inflammation. Furthermore, there were no serious ocular or systemic adverse reactions during the follow-up period.


  Discussion Top


AMD is an age-related macular degeneration disease, whose incidence increases with age. Epidemiological studies have shown that the incidence of AMD in the age group of 43–54years is 6.9%, and the 15-year cumulative incidence in the age group of 65–74years is up to 25.3%.[6] The formation of CNV is the main characteristic of wet AMD. Meanwhile, high expression of VEGF plays an important role in the formation of CNV in patients with wet AMD. Bevacizumab, ranibizumab, aflibercept, and conbercept have been increasingly used in the treatment of wet AMD after the FDA approved the use of VEGF inhibitor pegaptanib sodium. These treatments have achieved satisfying results.

Ranibizumab is a kind of recombinant humanized monoclonal antibody. It can inhibit the interaction between receptors of VEGFR1 and VEGFR2 on the surface of vascular endothelial cells, suppress the proliferation of vascular endothelial cells, and reduce CNV production through binding to VEGFA receptor. Yang et al.[7] have used intravitreal injection of ranibizumab to treat AMD with ME. They have also demonstrated that the visual acuity of patients is greatly improved after the treatment without increased intraocular pressure. Lee et al.[8] have applied ranibizumab in the treatment of wet AMD. Their findings have demonstrated that CRT gradually thins, and the visual acuity is significantly better than that of before treatment. Conbercept is the first self-developed therapeutic anti-VEGF inhibitor in China. It is a kind of fusion protein of VEGF receptor and recombinant human immunoglobulin Fc segment gene.[9] Yang et al.[7]have used intravitreal injection of conbercept for the treatment of wet AMD. After 1month of treatment, the visual acuity of 14 eyes greatly improved at a rate of up to 70%(14/20). At present, many reports have investigated the frequency of anti-VEGF inhibitor medication and existing results differ between the countries. For example, in the treatment guidelines for wet AMD made by Chinese fundus disease group,[10] the pro re nata(PRN) regimen is recommended, namely intravitreal injection of drugs once a month for 3months. Further treatment is determined monthly as needed. However, the treatment plan of EU countries[11] proposes that intravitreal injection should be performed every month as long as the visual acuity has improved during the treatment until the visual acuity is stable for at least 3months. On stability, injections can be discontinued. To reduce study bias, all patients in this study were treated with intravitreal injection of drugs according to the PRN regimen.

In this study, BCVA(LogMAR) and CRT of affected eyes in the two groups were significantly improved at 1month, 2months, and 3months after treatment as well as the last follow-up(P<0.05). However, no statistically significant difference was found between the two groups(P>0.05). Our results showed that the effects of conbercept and ranibizumab were similar in the treatment of wet AMD in terms of improving visual acuity and reducing CRT. Freund et al.[12] have also pointed out that the effects of intravitreal injection of conbercept or ranibizumab are nearly the same in improving the visual acuity of wet AMD patients. Meanwhile, the areas of CNV permeation in the two groups were obviously decreased at 3months after treatment and at the last follow-up. Similarly, no statistically significant difference was found between the two groups(P>0.05). Our findings suggested that the treatment of conbercept or ranibizumabfor wet AMD could relieve CNV penetration. Choroidal thickness(CT) is an important indicator reflecting intraocular blood flow perfusion and tissue metabolism. Under natural conditions, CT becomes thinner with the increase of age. At present, there is no unified conclusion about the effect of anti-VEGF inhibitors on SFCT in patients with wet AMD. Previous studies have reported that SFCT of wet AMD become thinner after the treatment of ranibizumab.[13] However, some scholars believe that the anti-VEGF treatment for wet AMD has no significant effect on SFCT.[14] In this study, results showed that SFCT of the two groups were significantly decreased after treatment(P<0.05), with no significant difference between the two groups(P>0.05). The reason might be that anti-VEGF treatment reduced choroidal vascular permeability, resulting in a decrease of SFCT. Our findings were the same as the results reported by Ünlü et al.[15] Meanwhile, our results showed that the average injection times of GroupA from the initial injection to the 6thmonth were significantly less than that of GroupB(P<0.05). This might be due to the high affinity between conbercept and VEGF. Lian et al.[16] have performed a study with central venous blockage and ME as subjects, which were treated with conbercept and ranibizumab, respectively. In this study, the medication frequency of conbercept was obviously less than that of ranibizumab. In terms of drug safety, there was no statistically significant difference in adverse reactions between the two groups(P>0.05). Furthermore, adverse reactions disappeared after symptomatic treatment, which did not affect clinical treatment.


  Conclusions Top


Intravitreal injection of conbercept and ranibizumab showed basically similar efficacy in the treatment of wet AMD, including improving visual acuity, reducing CRT, the area of CNV permeation, and incidence of adverse reactions. In addition, both of them could significantly decrease SFCT of affected eyes. However, the medication frequency of conbercept was less than that of ranibizumab. Meanwhile, there were also shortcomings such as small sample size and relatively short follow-up time. Alarge-scale, multicenter, and prospective study is still needed. Furthermore, the pharmacoeconomics of conbercept and ranibizumab in the treatment of wet AMD needs further study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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SantarelliM, DiplottiL, SamassaF, VerittiD, KuppermannBD, LanzettaP. Advances in pharmacotherapy for wet age-related macular degeneration. Expert Opin Pharmacother 2015;16:1769-81.  Back to cited text no. 3
    
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SenraH, AliZ, BalaskasK, AslamT. Psychological impact of anti-VEGF treatments for wet macular degeneration-a review. Graefes Arch Clin Exp Ophthalmol 2016;254:1873-80.  Back to cited text no. 4
    
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NikkhahH, KarimiS, AhmadiehH, AzarminaM, AbrishamiM, AhoorH, etal. Intravitreal injection of anti-vascular endothelial growth factor agents for ocular vascular diseases: Clinical practice guideline. JOphthalmic Vis Res 2018;13:158-69.  Back to cited text no. 5
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SchwartzSD, RegilloCD, LamBL, EliottD, RosenfeldPJ, GregoriNZ, etal. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: Follow-up of two open-label phase 1/2 studies. Lancet 2015;385:509-16.  Back to cited text no. 6
    
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YangW, TanY, LiC, LiuY, LuG. Observation of curative effect of intravitreal injection of conbercept in wet age-related macular degeneration: Optical coherence tomography analysis after injection. Microsc Res Tech 2018;81:384-8.  Back to cited text no. 7
    
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LeeKH, ChinHS, KimNR, MoonYS. Effects of vitreomacular traction on ranibizumab treatment response in eyes with neovascular age-related macular degeneration. Korean J Ophthalmol 2015;29:396-403.  Back to cited text no. 8
    
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NguyenTT, GuymerR. Conbercept(KH-902) for the treatment of neovascular age-related macular degeneration. Expert Rev Clin Pharmacol 2015;8:541-8.  Back to cited text no. 9
    
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FreundKB, HoangQV, SarojN, ThompsonD. Intraocular pressure in patients with neovascular age-related macular degeneration receiving intravitreal aflibercept or ranibizumab. Ophthalmology 2015;122:1802-10.  Back to cited text no. 12
    
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KoizumiH, KanoM, YamamotoA, SaitoM, MarukoI, SekiryuT, etal. Subfoveal choroidal thickness during aflibercept therapy for neovascular age-related macular degeneration: Twelve-month results. Ophthalmology 2016;123:617-24.  Back to cited text no. 13
    
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ThorellMR, GoldhardtR, NunesRP, de Amorim Garcia FilhoCA, AbbeyAM, KuriyanAE, etal. Association between subfoveal choroidal thickness, reticular pseudodrusen, and geographic atrophy in age-related macular degeneration. Ophthalmic Surg Lasers Imaging Retina 2015;46:513-21.  Back to cited text no. 14
    
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Ünlü C, ErdoganG, GunayBO, KardesE, AkcayBI, ErginA, etal. Subfoveal choroidal thickness changes after intravitreal bevacizumab injection for neovascular age-related macular degeneration and diabetic macular edema. Int Ophthalmol 2017;37:147-58.  Back to cited text no. 15
    
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