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Observation of Optic Disc Neovascularization Using OCT

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Observation of Optic Disc Neovascularization Using OCT www.nature.com/scientificreports OPEN Observation of optic disc neovascularization using OCT angiography in proliferative Received: 13 December 2017 Accepted: 16 February 2018 diabetic retinopathy after Published: xx xx xxxx intravitreal conbercept injections Xiao Zhang1, Chan Wu1, Li-jia Zhou2 & Rong-ping Dai1 This study reports the short-term efcacy and safety of intravitreal conbercept injections for neovascularization at the disc (NVD) in patients with proliferative diabetic retinopathy (PDR). Conbercept is a recombinant fusion protein with a high afnity for all isoforms of vascular endothelial growth factor (VEGF)-A, placental growth factor and VEGF-B. A prospective case series study was conducted in 15 patients (15 eyes). Patients had complete ocular examinations and received a 0.5 mg intravitreal conbercept injection followed by supplemental pan-retinal photocoagulation (PRP). Optical coherence tomography angiography (OCTA) was performed before and after treatment. Before treatment, the mean NVD area was 1.05 ± 0.33 mm2, and it decreased to 0.56 ± 0.17 mm2 after an interval of 7.5 d (p = 0.000). One eye required vitrectomy during follow-up. Recurrent NVD was observed in 2 eyes, which resolved after repeated injections. The remaining 12 eyes were stable over a mean follow-up period of 8.3 months. The mean area of the NVD in 14 patients without vitrectomy was 0.22 ± 0.11 mm2 (p = 0.000) at the last visit. Intravitreal conbercept injections combined with intensive PRP are an efective and safe treatment for PDR with NVD. Quantitative information on NVD can be obtained with OCTA, which may be clinically useful in evaluating the therapeutic efect. Diabetes mellitus (DM) is one of the world’s fastest growing chronic diseases, and diabetic retinopathy (DR) is a specifc microvascular complication of DM. As the prevalence of DM continues to increase, DR is still the leading cause of acquired vision loss worldwide in middle-aged and therefore economically active people1. Proliferative diabetic retinopathy (PDR) is a severe stage of DR and one form of vision-threatening DR. Pan-retinal photo- coagulation (PRP) is the established treatment for PDR, as it is efective and has preserved vision in numerous patients over the past several decades2–4. As vascular endothelial growth factor (VEGF) plays a role in the process of neovascularization in PDR, anti-VEGF agents including ranibizumab and bevacizumab have been assessed for the treatment of PDR in recent years, and the results were satisfactory5–9. Conbercept is a recombinant fusion protein that consists of the VEGF binding domains of the human VEGFR-1 and VEGFR-2 combined with the Fc portion of the human immuno- globulin G1. In addition to having a high afnity for all isoforms of VEGF-A, it also binds to placental growth factor (PlGF) and VEGF-B10. As the use of conbercept in the treatment of PDR is of-label, there are few reports concerning this topic. We have conducted a prospective study on the short-term efcacy and safety of intravitreal conbercept injections combined with laser treatment for neovascularization at the disc (NVD) in patients with PDR. Te introduction of optical coherence tomography angiography (OCTA) into clinical practice allows the detection and visualization of the blood fow and morphology of retinal vessels and is useful to monitor dif- ferent NVD subtypes, their development, and the efcacy of treatment regimens as well as to defne new vessel 1Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. 2Department of Ophthalmology, Beijing Hepingli Hospital, Beijing, China. Correspondence and requests for materials should be addressed to R.-p.D. (email: [email protected]) SCIENTIFIC REPORTS | (2018) 8:3972 | DOI:10.1038/s41598-018-22363-0 1 www.nature.com/scientificreports/ Figure 1. Te procedure to measure the neovascularization at the disc (NVD). (A) A circle with a 3-mm diameter was drawn that was centered at the optic disc; (B) Te structure of the NVD was outlined with white lines, and the background was colored black. morphological details11,12. To obtain quantitative information on NVD, OCTA was performed before and afer treatment, and the NVD area was calculated. Methods Patients. Tis prospective case series included 15 eyes from 15 patients with diabetes who presented at the Peking Union Medical College Hospital between January and September 2016. Tey had been clinically diag- nosed with PDR with active NVD. All the patients were informed about the purpose and treatment procedure, and written informed consent were obtained before intravitreal injections. All procedures conformed to the ten- ets of the Declaration of Helsinki. Te methods were carried out in accordance with the approved guidelines, and the study was approved by the Ethics Committee of the Peking Union Medical College Hospital. Inclusion criteria included patients with PDR with disc neovascularization, patients with clear media that allowed fundus examinations and OCT angiography examinations, and patients who had not been treated with intravitreal anti-VEGF or steroid injections within six months. Exclusion criteria included patients with opaque media that infuenced fundus examination, including corneal opacity, cataracts and vitreous hemorrhages; pre- vious eye diseases such as glaucoma and retinal diseases besides DR, such as retinal vein occlusion or AMD; eye infections and intraocular infammations; tractional retinal detachment; and penetrating ocular trauma or intraocular surgery within the previous 6 months prior to intravitreal injection. Patients with uncontrolled hyper- tension, recent myocardial infarction or cerebral vascular incidents were also excluded. Ocular examination. All patients had a complete ocular examination before and after treatment that included the following measurements: best corrected visual acuity (BCVA) using the International Standard Visual Acuity Chart, intraocular pressure (IOP) using a non-contact tonometer, ocular motility, pupillary light refex, slit-lamp examination, fundus examination using indirect ophthalmoscope, fundus photography (TOPCON TRC-NW6S Non-Mydriatic Retinal Camera), spectral domain optic coherence tomography, and OCT angiography (OptoVue, Freemont, California). AngioVue disc examinations were performed by one experienced eye specialist (ZLJ). Te scanning pattern was 4.5 × 4.5 mm2. As OCT angiography produces multiple scans, the best image for the detection of new vessel architecture was selected for use in the study. Te B-scan OCT was used to confrm the presence of NVD, and new vessels were observed as preretinal proliferative structures or protrusions into the vitreous cavity with positive fow signals. Segmentation of the inner border of the B-scan was manually moved to the vitreous cavity, just above the new vessels, and the outer border was adjusted to minimize the depiction of the superfcial vascular plexus13. Quantitative evaluation of NVD. A circle with a 3-mm diameter was drawn with its center at the optic disc, and the structure of the NVD was outlined with white lines using Adobe Photoshop (CS6), with the back- ground colored black. Te processed image was saved as a black and white two-color chart. If NNVD and N0 are the numbers of pixels of the NVD (white lines) and the circle, respectively, then the area of the NVD can be calculated as. N Ad=π 2 NVD 4N0 Measurements of the NVD area represent the average value calculated by two eye specialists (DRP, ZX) who were blinded to the image origins. Te measurement procedure is shown in Fig. 1. Intravitreal injections. All patients received an explanation of the of-label use of conbercept in PDR and its potential benefts and risks. Informed consents were obtained, and a prophylactic topical antibiotic (Levofoxacin) was instilled for 3 days before treatment. Afer topical anesthesia and sterilization of the operating feld, 0.5 mg/0.05 mL of conbercept was injected intravitreally at the inferotemporal pars plana (4 mm posterior to the limbus). Afer the injection, the intraocular pressure was measured, and prophylactic topical antibiotic drops were instilled for 3 days. Intensive retinal laser photocoagulation was applied beginning two weeks afer the intravitreal injection. A slit-lamp laser was used, and SCIENTIFIC REPORTS | (2018) 8:3972 | DOI:10.1038/s41598-018-22363-0 2 www.nature.com/scientificreports/ Last visit afer IVC and PRP Before treatment First visit afer IVCb or supplement PRPd Period Area of NVD Follow-up Area of NVD No. Initials Gender Age Eye Area of NVDc (mm2) (d) (mm2) time (m) (mm2) 1 LF F 42 R 1.08 7 0.55 6 0.34 2 DXY M 37 L 0.97 9 0.25 Vitrectomy — 3 LDX M 36 R 1.06 7 0.69 12 0.25 4 LKM F 64 L 1.27 7 0.83 14 0.07 5 ZXJ M 51 L 1.03 7 0.62 6 0.27 6 WSX F 62 R 1.13 7 0.71 14 0.24 7 YM F 30 R 0.89 9 0.53 6 0.20 8 SQ M 38 R 1.57 7 0.71 13 0.50 9 YZF M 50 L 1.27 7 0.65 6 0.22 10 LS M 33 R 1.55 7 0.48 6 0.25 11 XAH F 52 L 0.53 9 0.40 8 0.19 12 LHH F 46 R 0.34 6 0.25 6 0.09 13 LJZ M 29 R 1.18 7 0.64 7 0.20 14 CJ F 35 L 0.96 9 0.60 6 0.18 15 SWY F 38 R 0.89 7 0.49 6 0.14 Table 1. Demographic and OCTAa features of the studied eyes. aOptical coherence tomography angiography. bIntravitreal conbercept. cNeovascularization at the disc. dPan-retinal photocoagulation. patients received laser treatment under topical anesthesia. For patients without previous PRP, laser therapy was completed afer three to four sessions, with a total of 1600 to 1800 burns.
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