OPEN Eye (2018) 32, 391–399 Official journal of The Royal College of Ophthalmologists www.nature.com/eye 1,2,9 3,9 1 4 5 Comparison of J Cui , D Sun ,HLu,RDai, L Xing , CLINICAL STUDY H Dong1, L Wang1,DWei1, B Jiang3, Y Jiao2, effectiveness and MM Jablonski6, S Charles6,7,WGu2,8 1 safety between and H Chen conbercept and ranibizumab for treatment of neovascular age- 1Center of Integrative Research, The related macular First Hospital of Qiqihaer City, Qiqihaer, Heilongjiang, PR China degeneration. A 2Department of Orthopedic Surgery and BME-Campbell Clinic, University retrospective case- of Tennessee Health Science Center, controlled non- Memphis, TN, USA 3Department of Ophthalmology, The Second Affiliated Hospital of inferiority multiple Harbin Medical University, Harbin, center study Heilongjiang, PR China 4Department of Ophthalmology, Peking Union Medical College Hospital, Beijing, PR China Abstract 5Department of Ophthalmology, Purpose To compare the efficacy and safety significant difference in measured CRT, with The Third Affiliated Hospital of μ Qiqihar Medical University, of conbercept and ranibizumab when a mean decrease of 191.5 m for conbercept Qiqihaer, Heilongjiang, PR China administered according to a treat-and-extend and 187.8 μm for ranibizumab (P = 0.773). (TREX) protocol for the treatment of There was a statistically significant difference 6Department of Ophthalmology, = University of Tennessee Health neovascular age-related macular degeneration (P 0.001) between the drugs regarding the Science Center, Memphis, TN, USA (AMD) in China. number of treatments: 7.4 for conbercept and 7 Patients and methods Between May 2014 8.7 for ranibizumab. The difference in the Charles Retina Institute, Germantown, TN, USA and May 2015, 180 patients were treated in a distribution of injection intervals was statistically 1 : 1 ratio using conbercept or ranibizumab significant between two groups (P = 0.011). 8Research Service, Veterans Affairs Medical Center, Memphis TN, USA from four hospitals. Patients received either During the study, there were no cases of fl conbercept 0.5 mg or ranibizumab 0.5 mg endophthalmitis or intraocular in ammation. Correspondence: intravitreal injections. Follow-up time was 1 Conclusion Both drugs had equivalent W Gu, Department of Orthopedic effects in visual and anatomic gains at 1 year Surgery, BME, University of year and treated based on a TREX approach. Tennessee Health Science Center, Main outcomes and measures include best- when administered. In the conbercept group, 956 Court Ave., Memphis, longer treatment intervals were achieved with TN 38163, USA corrected visual acuity (BCVA), using Early Tel: +1 901 448 2259. more patients. Treatment Diabetic Retinopathy Study E-mail: [email protected] Eye (2018) 32, 391–399; doi:10.1038/eye.2017.187; or H Chen, Center of Integrative (ETDRS); number of injections; central retinal published online 22 September 2017 Research, The First Hospital of thickness (CRT); and leakage of choroidal Qiqihaer City, 30 Gongyuan Road, Longsha District, Qiqihaer, neovascularization before and after the Heilongjiang 161005, treatment was analyzed by fluorescein fundus PR China Introduction Tel: +86 0452 2425981. angiography and indocyanine green E-mail: [email protected] angiography. Age-related macular degeneration (AMD) is one 9 Results The 1-year visit was completed by of the leading causes of legal blindness in the These authors contributed equally 1 to this work. 168 (93.3%) of patients. Mean BCVA was elderly population of Western countries. In equivalent between two cohorts, and were recent years, the incidence of AMD in China also Received: 14 April 2017 improved by 12.7 ± 7.770 and 12.3 ± 7.269 showed an upward trend, with the prevalence in Accepted in revised form: 26 July 2017 letters in the conbercept and ranibizumab some developed areas being close to the level of Published online: cohorts, respectively (P = 0.624). There was no Western developed countries.2,3 Choroidal 22 September 2017 Conbercept vs ranibizumab for neovascular AMD J Cui et al 392 neovascularization (CNV), based on which the investigation, 120 consecutive patients with treatment- neovascular AMD is defined, has been used to measure naive neovascular AMD had excellent visual outcomes the severity of neovascular AMD.4 Vascular endothelial reported, with fewer injections and clinic visits compared growth factor (VEGF) promotes the development and with monthly treatments. In another AMD study, visual growth of CNV membranes.5,6 Exudation and and anatomic outcomes appear similar to those with fixed hemorrhage cause a thickening of the central retina, monthly dosing of ranibizumab.14 The trial reported in which when untreated can progress to scar formation and this article directly compares the efficacy and safety of loss of vision.5 Initial therapies to treat neovascular AMD conbercept with ranibizumab using a TREX approach to include fundus laser, transpupillary thermotherapy and neovascular AMD management. A TREX approach to photodynamic therapy. Since the advent of anti-VEGF neovascular AMD is consistent with individualized medications in 2005, the treatment of neovascular AMD management, while simultaneously minimizing entered an era with superior results.6 treatment burden. Because of the important role that VEGF plays in the pathogenesis of AMD, VEGF has become the main target Materials and methods of CNV treatment at present.7 Before 2011, most widely used pharmaceutical agents were ranibizumab (Lucentis; Study patients Genentech, Inc., South San Francisco, CA, USA), which All patients signed an informed consent. This study was approved by the Food and Drug Administration, and bevacizumab (Avastin; Genentech Inc.). Both of these adheres to the tenets of the declaration of Helsinki, and – drugs are monoclonal antibodies that block VEGF-A.8 10 was approved by four Committees for Medical and In 2011, aflibercept (Eylea; Regeneron, Inc., Tarrytown, Health Research Ethics (the First Hospital of Qiqihar, the fi NJ, USA) was approved as a VEGF receptor fusion Second Af liated Hospital of Harbin Medical University, fi protein to treat neovascular AMD in the USA. Aflibercept the Third Af liated Hospital of Qiqihar Medical works as a multi-target VEGF family blocker and binds University and Peking Union Medical College Hospital). isoforms of VEGF-A, VEGF-B, and placenta growth factor Between May 2014 and May 2015, 180 patients who (PlGF).11 Conbercept (Langmu; Kanghong, Inc., Sichuan, received intravitreal injections of either conbercept or China) is a different VEGF receptor (VEGFR) fusion ranibizumab were collected from these four centers. protein. It blocks all isoforms of VEGF-A, VEGF-B, VEGF- Patients were examined at four ophthalmological centers C, and PlGF. It has a high binding affinity to VEGF and a in China as part of a multicenter study. Each patient was long half-life in vitreous.12 In late 2013, it received the new provided the names of the two drugs but no other drug drug certificate, drug registration approval, and GMP information including biological contents and reported or certification from the State Food and Drug known treatment results. Patients then selected a drug at Administration in China and started being using for the onset of treatment. Eligibility criteria included: age – exudative AMD treatment. It functions by competitively 51 85 years, and previously untreated active neovascular inhibiting the binding of VEGF with its receptor and AMD in one eye. The baseline mean values of best- prevents the activation of VEGFR by acting on multiple corrected visual acuity (BCVA) were 52.1 and 50.4 letters targets, thereby providing a new approach to the in conbercept group and ranibizumab group, treatment of neovascular AMD. Many studies on respectively, as determined by protocol trial lens aflibercept have shown its promise as an efficient drug for refraction; absence of other ocular diseases determined by the treatment of neovascular AMD. In contrast, there are examination using a tonometer, slit lamp biomicroscope few reports on the efficacy of conbercept for neovascular and ophthalmoscope; lack of polypoidal choroidal AMD. Comparisons between conbercept and vasculopathy as determined by indocyanine green ranibizumab will not only determine the value of angiography (ICGA); and the total area of the subretinal conbercept, but can also be referenced to aflibercept, as hemorrhage and fibrosis comprised less than 50% of the comparisons between aflibercept and ranibizumab have total lesion. Visual acuity was tested using Early done.13–15 Treatment Diabetic Retinopathy Study (ETDRS) charts at In this paper, we report the results from a comparison 4 m. The diagnosis of neovascular AMD was confirmed between conbercept and ranibizumab in the treatment of by choroidal neovascular leakage on fluorescein fundus AMD using treat-and-extend (TREX) protocol. We angiography (FFA) and intraretinal or subretinal fluid as hypothesized that conbercept would be at least as determined by optical coherence tomography (OCT). The effective as ranibizumab in the treatment of AMD. In a mean central retinal thickness (CRT) was defined as the single-arm analysis, Abedi et al16 were the first to report sum of the thickness of the neurosensory retina and the the results of a prospective TREX protocol of ranibizumab height of the subretinal fluid. Retinal pigment epithelial or bevacizumab anti-VEGF treatments. In their detachments were not included in the measurements. In Eye Conbercept vs ranibizumab for neovascular AMD JCuiet al 393 2016, the data for 1-year follow-up from 90 patients Outcome measures treated with each drug were collected and analyzed. The primary outcome was BCVA, as measured using the ETDRS chart at each visit during a 1-year period. BCVA improvement was determined by protocol trial lens Study design refraction for all the patients. The BCVA was measured fi The patients received intravitreal injections of either beginning at the rst visit and once a month afterward up conbercept 0.5 mg (0.05 ml) or ranibizumab 0.5 mg to 12 months. Secondary outcomes included the number of injections, injection intervals, CRT, leakage of CNV, (0.05 ml) following a TREX protocol.