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Güven YZ, Işık MU, Ilgüy S, Yozgat Z. Phacoemulsification surgery in patients with diabetic macular edema: should intravitreal anti-VEGF therapy be performed before or simultaneously with surgery? Int J Ophthalmol 2025; 18:637-641. [PMID: 40256016 PMCID: PMC11947536 DOI: 10.18240/ijo.2025.04.09] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Accepted: 12/24/2024] [Indexed: 04/22/2025] Open
Abstract
AIM To investigate the optimal anti-vascular endothelial growth factor (VEGF) treatment time in patients with diabetic macular edema (DME) scheduled for cataract surgery. METHODS The study was designed to include 4 groups. Twenty-six eyes of 26 patients with diabetes but no retinopathy (DR; group 1), 17 eyes of 17 patients with DR but no DME (group 2), and 19 eyes of 19 patients with DME who received anti-VEGF therapy concurrently with cataract surgery (group 3), and 21 eyes of 21 patients who received anti-VEGF therapy for DME 1wk before cataract surgery (group 4). The patients' best corrected visual acuity, intraocular pressure, central and mean macular thickness (CMT and MMT) values were noted on the day of surgery, postoperative day 1, week 1, and month 1. RESULTS There was a significant increase of CMT after cataract surgery in groups 1, 2, and 3 (P<0.001, P=0.044, and P=0.034, respectively) but not in group 4 (P=0.948). The change in MMT was the same as CMT (P=0.009, P=0.006, P=0.011, and P=0.172, respectively). There was a higher increase in CMT and MMT in group 2 compared to group 1 at the 1st month after surgery (P=0.002 and P=0.001, respectively). CONCLUSION In eyes with DME undergoing cataract surgery, preoperative anti-VEGF treatment may be more effective than simultaneous intravitreal anti-VEGF with surgery.
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Affiliation(s)
- Yusuf Ziya Güven
- Department of Ophthalmology, Izmir Katip Çelebi University Atatürk Educating and Research Hospital, Izmir 35200, Türkiye
| | - Mehmed Uğur Işık
- Kastamonu University Kastamonu Training and Research Hospital, Kastamonu 37200, Türkiye
| | - Serdar Ilgüy
- Kastamonu University Kastamonu Training and Research Hospital, Kastamonu 37200, Türkiye
| | - Zübeyir Yozgat
- Kastamonu University Kastamonu Training and Research Hospital, Kastamonu 37200, Türkiye
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Su T, Lai D, Wu Y, Gu C, He S, Meng C, Cai C, Zhang J, Luo D, Chen J, Zheng Z, Qiu Q. COMPARISON OF THE EFFICACY AND SAFETY OF RANIBIZUMAB 0.5 MG VERSUS 1.0 MG WITH PARS PLANA VITRECTOMY FOR THE TREATMENT OF PROLIFERATIVE DIABETIC RETINOPATHY: A Randomized Controlled Trial. Retina 2024; 44:680-688. [PMID: 38011844 DOI: 10.1097/iae.0000000000003998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2023]
Abstract
PURPOSE To investigate the effectiveness of two regimens of ranibizumab-assisted pars plana vitrectomy in the treatment of patients with proliferative diabetic retinopathy. METHODS This is a prospective, 6-month, randomized controlled trial. Eighty patients with 87 eyes requiring pars plana vitrectomy treatment for proliferative diabetic retinopathy were included and randomly divided into a 1.0-mg injection group and a 0.5-mg injection group. The ranibizumab was delivered intraoperatively, at the close of surgery. The vitreous hemorrhage grade, best-corrected visual acuity, central macular thickness, and safety data were assessed to Month 6. RESULTS The 1.0-mg injection group had a milder grade and a lower reoccurrence rate of early postoperatively vitreous hemorrhage than the 0.5-mg injection group (35.0% and 63.4%, respectively, P = 0.0195). The mean best-corrected visual acuity of two groups was significantly improved from baseline to 6 months after surgery, 1.60 ± 0.72 Logarithm of the Minimum Angle of Resolution (LogMAR) (<20/200) to 0.47 ± 0.49 LogMAR (20/59) for the 1.0-mg injection group and 1.51 ± 0.69 LogMAR (<20/200) to 0.50 ± 0.31 LogMAR (20/63) for the 0.5-mg injection group, but there was no significant difference between the two groups ( P = 0.74). There was no significant difference in the mean decrease in central macular thickness and probability of postoperative adverse events between the two groups. CONCLUSION Intravitreal injection of 1.0 mg of ranibizumab after pars plana vitrectomy compared with the recommended dose of 0.5 mg significantly reduced the recurrence and severity of early postoperative vitreous hemorrhage in patients with proliferative diabetic retinopathy. It also contributed to the early recovery of visual acuity after surgery and did not increase postoperative adverse events.
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Affiliation(s)
- Tong Su
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
- State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Hospital of Shandong First Medical University, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, PR China
| | - Dongwei Lai
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Yang Wu
- Xiangya School of Medicine, Central South University, Changsha, Hunan, China
| | - Chufeng Gu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Shuai He
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Chunren Meng
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Chunyang Cai
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Jingfa Zhang
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Dawei Luo
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Jili Chen
- Department of Ophthalmology, Shibei Hospital, Shanghai, PR China; and
| | - Zhi Zheng
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
| | - Qinghua Qiu
- Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, PR China
- Department of Ophthalmology, Tong Ren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
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Binczyk NM, Plemel DJ, Seamone M, Rudnisky CJ, Tennant MT. Decrease in Anti-VEGF Injections After Post-injection Endophthalmitis in Patients With Neovascular Age-Related Macular Degeneration. JOURNAL OF VITREORETINAL DISEASES 2023; 7:528-532. [PMID: 38022794 PMCID: PMC10649458 DOI: 10.1177/24741264231200470] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
Introduction: To evaluate the effect of antivascular endothelial growth factor (anti-VEGF)-related endophthalmitis on intravitreal injection (IVI) frequency in patients with neovascular age-related macular degeneration (nAMD). Methods: A retrospective chart review was performed of all cases of post IVI endophthalmitis that occurred in Edmonton, Alberta, Canada, between 2012 and 2019. Contralateral eyes affected by nAMD but without endophthalmitis served as a control group. The main outcome measures were the frequency of anti-VEGF injections, visual acuity, and activity of choroidal neovascularization before and after endophthalmitis. Results: Seventeen eyes met the inclusion criteria, 2 (12%) of which never resumed IVI after endophthalmitis because of the quiescence of disease. Post-endophthalmitis eyes received IVI less frequently in the 1 year after endophthalmitis (mean 0.52 ± 0.42 IVI/month) than those that received IVI 1 year before endophthalmitis (1.09 ± 0.36 IVI/month) (P = .001). The 17 contralateral eyes also received anti-VEGF injections less frequently after endophthalmitis than before (P = .001). There was no significant change in optical coherence tomography markers of disease activity in cases or controls. Conclusions: In patients with nAMD, endophthalmitis resolution is associated with a decrease in anti-VEGF injection frequency. The same decrease in anti-VEGF injection frequency is also seen in contralateral eyes unaffected by endophthalmitis. Markers of disease activity remain unchanged in both eyes, suggesting disease quiescence despite reduced IVI frequency.
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Affiliation(s)
- Natalia M. Binczyk
- Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB, Canada
| | - David J.A. Plemel
- Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB, Canada
| | - Mark Seamone
- Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB, Canada
| | - Christopher J. Rudnisky
- Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB, Canada
| | - Matthew T.S. Tennant
- Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, AB, Canada
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Sapino S, Chindamo G, Peira E, Chirio D, Foglietta F, Serpe L, Vizio B, Gallarate M. Development of ARPE-19-Equipped Ocular Cell Model for In Vitro Investigation on Ophthalmic Formulations. Pharmaceutics 2023; 15:2472. [PMID: 37896232 PMCID: PMC10610172 DOI: 10.3390/pharmaceutics15102472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 10/03/2023] [Accepted: 10/13/2023] [Indexed: 10/29/2023] Open
Abstract
Repeated intravitreal (IVT) injections in the treatment of retinal diseases can lead to severe complications. Developing innovative drug delivery systems for IVT administration is crucial to prevent adverse reactions, but requires extensive investigation including the use of different preclinical models (in vitro, ex vivo and in vivo). Our previous work described an in vitro tricompartmental ocular flow cell (TOFC) simulating the anterior and posterior cavities of the human eye. Based on promising preliminary results, in this study, a collagen scaffold enriched with human retinal pigmented epithelial cells (ARPE-19) was developed and introduced into the TOFC to partially mimic the human retina. Cells were cultured under dynamic flow conditions to emulate the posterior segment of the human eye. Bevacizumab was then injected into the central compartment of the TOFC to treat ARPE-19 cells and assess its effects. The results showed an absence of cytotoxic activity and a significant reduction in VEGF fluorescent signal, underscoring the potential of this in vitro model as a platform for researching new ophthalmic formulations addressing the posterior eye segment, eventually decreasing the need for animal testing.
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Affiliation(s)
- Simona Sapino
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (G.C.); (D.C.); (F.F.); (L.S.); (M.G.)
| | - Giulia Chindamo
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (G.C.); (D.C.); (F.F.); (L.S.); (M.G.)
| | - Elena Peira
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (G.C.); (D.C.); (F.F.); (L.S.); (M.G.)
| | - Daniela Chirio
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (G.C.); (D.C.); (F.F.); (L.S.); (M.G.)
| | - Federica Foglietta
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (G.C.); (D.C.); (F.F.); (L.S.); (M.G.)
| | - Loredana Serpe
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (G.C.); (D.C.); (F.F.); (L.S.); (M.G.)
| | - Barbara Vizio
- Department of Medical Sciences, University of Turin, Via Genova 3, 10126 Turin, Italy;
| | - Marina Gallarate
- Department of Drug Science and Technology, University of Turin, 10125 Turin, Italy; (G.C.); (D.C.); (F.F.); (L.S.); (M.G.)
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Daka Q, Špegel N, Atanasovska Velkovska M, Steblovnik T, Kolko M, Neziri B, Cvenkel B. Exploring the Relationship between Anti-VEGF Therapy and Glaucoma: Implications for Management Strategies. J Clin Med 2023; 12:4674. [PMID: 37510790 PMCID: PMC10380425 DOI: 10.3390/jcm12144674] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 07/03/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
A short-term increase in intraocular pressure (IOP) is a common side effect after intravitreal anti-VEGF therapy, but a sustained increase in IOP with the development of secondary glaucoma has also been reported in some studies after repeated intravitreal anti-VEGF injections. The aim of this review is to present and discuss the possible pathophysiological mechanisms and factors contributing to a sustained rise in IOP, as well as treatment strategies for patients at risk. Close monitoring and adjustable IOP-lowering treatment are recommended for high-risk patients, including those with glaucoma, angle-closure anomalies, ocular hypertension or family history of glaucoma; patients receiving a high number of injections or at shorter intervals; and patients with capsulotomy. Strategies are needed to identify patients at risk in a timely manner and to prevent sustained elevation of IOP.
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Affiliation(s)
- Qëndresë Daka
- Department of Pathophysiology, Medical Faculty, University of Prishtina, 10000 Prishtina, Kosovo
- Eye Clinic, University Clinical Centre of Kosova, 10000 Prishtina, Kosovo
- Department of Ophthalmology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Nina Špegel
- Department of Ophthalmology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | | | - Tjaša Steblovnik
- Department of Ophthalmology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
| | - Miriam Kolko
- Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark
- Department of Ophthalmology, Copenhagen University Hospital, Rigshospitalet, 2600 Glostrup, Denmark
| | - Burim Neziri
- Department of Pathophysiology, Medical Faculty, University of Prishtina, 10000 Prishtina, Kosovo
| | - Barbara Cvenkel
- Department of Ophthalmology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
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El Rayes EN, Leila M. Visual function and retinal morphological changes after single suprachoroidal delivery of fluocinolone acetonide (Iluvien®) implant in eyes with chronic diabetic macular edema. Int J Retina Vitreous 2023; 9:20. [PMID: 36991493 PMCID: PMC10053734 DOI: 10.1186/s40942-023-00458-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 03/21/2023] [Indexed: 03/31/2023] Open
Abstract
BACKGROUND To assess the efficacy and safety of supra-choroidal (SC) Iluvien in the management of chronic diabetic macular edema (DME). METHODS A retrospective interventional non-comparative consecutive case series including patients with chronic DME who received an SC Iluvien implant. All patients had persistent central macular thickness (CMT) ≥ 300µ after previous treatment with anti-vascular endothelial growth factor (VEGF) agents or laser photocoagulation. The main outcome measures were improvement of best-corrected visual acuity (BCVA), reduction of CMT, and detection of ocular hypertension/glaucoma or cataract formation. Friedman's two-way ANOVA was used to analyze BCVA, intraocular pressure (IOP), and DME across different time points. P-value = 0.05. RESULTS The study included 12 eyes of 12 patients. Six patients (50%) were males. The median age was 58 years (range 52-76 years). The median duration of DM was 13 years (range 8-20 years). Ten patients (83.3%) were phakic and 2 patients (17%) were pseudophakic. The median pre-operative BCVA was 0.07 (range 0.05-0.8). The median pre-operative CMT was 544µ (range 354-745µ). The median pre-operative IOP was 17 mmHg (range 14-21mmHg). The median follow-up period was 12 months, range (12-42). Post-operatively, the median final BCVA was 0.15 (range 0.03-1), p 0.02, the median CMT was 404µ (range 213-747), p 0.4 and the median IOP was 19.5 mmHg (range 15-22), p 1. Two out of 10 phakic patients (20%) developed nuclear sclerosis grade I by 12 months. Six patients (50%) developed a transient rise in IOP < 10 mmHg from the baseline that resolved within 3 weeks with antiglaucoma drops. CONCLUSION SC Iluvien is potentially effective in improving visual function, reducing macular edema, and reducing the incidence of steroid-induced cataracts and glaucoma.
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Affiliation(s)
- Ehab N El Rayes
- Retina department, Research Institute of Ophthalmology (RIO), 35 Salah Salem St., (El Borg), Suite 702, El-Obour bldg., Cairo, 11371, Egypt.
| | - Mahmoud Leila
- Retina department, Research Institute of Ophthalmology (RIO), 35 Salah Salem St., (El Borg), Suite 702, El-Obour bldg., Cairo, 11371, Egypt
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Duan N, Mei L, Hu L, Yin X, Wei X, Li Y, Li Q, Zhao G, Zhou Q, Du Z. Biomimetic, Injectable, and Self-Healing Hydrogels with Sustained Release of Ranibizumab to Treat Retinal Neovascularization. ACS APPLIED MATERIALS & INTERFACES 2023; 15:6371-6384. [PMID: 36700786 DOI: 10.1021/acsami.2c17626] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Retinal neovascularization (RNV) is a typical feature of ischemic retinal diseases that can lead to traction retinal detachment and even blindness in patients, in which the vascular endothelial cell growth factor (VEGF) plays a pivotal role. However, most anti-VEGF drugs currently used for treating RNV, such as ranibizumab, need frequent and repeated intravitreal injections due to their short intravitreal half-life, which increases the incidence of complications. Herein, a hydrogel intravitreal drug delivery system (DDS) is prepared by a dynamic Schiff base reaction between aminated hyaluronic acid and aldehyde-functionalized Pluronic 127 for sustained release of ranibizumab. The prepared hydrogel system named HP@Ran exhibits excellent injectability, self-healing ability, structural stability, cytocompatibility, and blood compatibility. According to an in vitro drug release study, the hydrogel system continuously releases the model drug bovine serum albumin for more than 56 days. Importantly, in an in vivo rabbit persistent RNV model, the HP@Ran hydrogel system continuously releases pharmacologically active ranibizumab for more than 7 weeks and also exhibits superior anti-angiogenic efficacy over ranibizumab treatment by decreasing vascular leakage and neovascularization at 12 weeks. Thus, the developed HP@Ran hydrogel system possesses great potential for intravitreal DDS for the treatment of RNV.
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Affiliation(s)
- Ning Duan
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
| | - Li Mei
- Department of Stomatology, Qingdao University, Qingdao266003, China
| | - Liting Hu
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
| | - Xiaoni Yin
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
| | - Xiangyang Wei
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
| | - Ying Li
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
| | - Qinghua Li
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
| | - Guiqiu Zhao
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
| | - Qihui Zhou
- School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao266071, China
- Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin300038, China
- Zhejiang Engineering Research Center for Tissue Repair Materials, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang325000, China
| | - Zhaodong Du
- Department of Ophthalmology, The Affiliated Hospital of Qingdao University, Qingdao266003, China
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Yuan Q, Liu Y, Gou Y, Xu H, Gao Y, Liu Y, Chen Y, Zhang M. Efficacy and safety of the dexamethasone implant in vitrectomized and nonvitrectomized eyes with diabetic macular edema: A systematic review and meta-analysis. Front Pharmacol 2022; 13:1029584. [DOI: 10.3389/fphar.2022.1029584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 11/21/2022] [Indexed: 12/04/2022] Open
Abstract
Purpose: To compare the efficacy and safety of the intravitreal dexamethasone (DEX) implant for the treatment of diabetic macular edema (DME) in vitrectomized and nonvitrectomized eyes.Methods: We performed a literature search in four electronic databases (PubMed, EMBASE, MEDLINE, and Cochrane Library) from inception to 22 May 2022. Studies comparing the efficacy of the DEX implant in vitrectomized and nonvitrectomized eyes with DME with at least 3 months of follow-up were included. The main outcomes included comparison of the mean change in the best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to different follow-up endpoints between the vitrectomized and nonvitrectomized groups. The secondary outcomes were the mean duration of action for the first DEX implantation and the number of required injections throughout the follow-up period. Safety data were collected and compared.Results: The final analysis included 7 studies involving 582 eyes, 208 vitrectomized eyes and 374 nonvitrectomized eyes. The mean between-group differences in BCVA improvement were not significant at any endpoint, with averages difference of −0.07 logarithm of the minimum angle of resolution (logMAR) (p = 0.088) at 1 month, −0.03 logMAR (p = 0.472) 3 months, −0.07 logMAR (p = 0.066) 6 months, and −0.04 logMAR (p = 0.486) 12 months. The mean between-group differences in CMT reduction were not statistically significant, with mean differences of 7.17 μm (p = 0.685) at 1 month, 20.03 μm (p = 0.632) 3 months, −1.80 μm (p = 0.935) 6 months, and −25.65 μm (p = 0.542) 12 months. However, the vitrectomized group had a significantly shorter duration of action during the first DEX implantation than the nonvitrectomized group, with a mean difference of 0.8 months (p = 0.005). No significant between-group differences were detected for the number of required injections or safety profile.Conclusion: This meta-analysis showed similar efficacy and safety of the sustained-release DEX intravitreal implant for vitrectomized and nonvitrectomized eyes with DME. The intravitreal DEX implant could be considered an effective choice for DME treatment in eyes with prior vitrectomy.
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Li S, Tang J, Han X, Wang Z, Zhang L, Zhao M, Qu J. Prospective Comparison of Surgery Outcome Between Preoperative and Intraoperative Intravitreal Injection of Ranibizumab for Vitrectomy in Proliferative Diabetic Retinopathy Patients. Ophthalmol Ther 2022; 11:1833-1845. [PMID: 35904708 PMCID: PMC9437166 DOI: 10.1007/s40123-022-00550-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/07/2022] [Indexed: 11/26/2022] Open
Abstract
INTRODUCTION To compare the efficacy and safety of intravitreal injections of ranibizumab (IVR) before and at the end of vitrectomy in proliferative diabetic retinopathy (PDR) patients. METHODS A prospective comparative study was performed on 60 eyes of 52 PDR patients who received ranibizumab injection (0.5 mg/0.05 ml) 3-5 days before vitrectomy (preoperative group) and 55 eyes of 50 PDR patients who received ranibizumab injection (0.5 mg/0.05 ml) at the end of vitrectomy (intraoperative group). Intra- and postoperative indices were collected for further comparison. RESULTS Postoperative best-corrected visual acuity (BCVA) in preoperative group was better than in intraoperative group at 1 week after surgery (P < 0.05) but comparable at 1- and 3-month follow-up (P = 0.20 and P = 0.37, respectively). Central retinal thickness (CRT) in preoperative group was lower than in intraoperative group at 1 week postoperatively (P < 0.05), but comparable at 1- and 3-month follow-up (P = 0.39 and P = 0.77, respectively). The average surgery time was significantly shorter in preoperative group than in intraoperative group (61.50 ± 11.44 min vs. 74.49 ± 12.01 min, P < 0.01). The incidence of intraoperative bleeding was significant lower in preoperative group than in intraoperative group (21.7% vs. 40.0%, P < 0.05). Moreover, the incidence of intraocular electrocoagulation use, iatrogenic retinal breaks, relaxing retinotomy and silicone oil tamponade were all significantly lower in preoperative group than that in intraoperative group (P < 0.05, respectively). The incidences of postoperative vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, postoperative fibrovascular proliferation progression and reoperation showed no statistical differences between the two groups (P > 0.05, respectively). Both groups had no ocular or system adverse events during observation period. CONCLUSION In vitrectomy for PDR, preoperative IVR can significantly reduce surgery time and lower the incidence of intraoperative bleeding, intraocular electrocoagulation use, iatrogenic retinal breaks, relaxing retinotomy and silicone oil tamponade during surgery and gain short-term better postoperative BCVA and thinner CRT. TRIAL REGISTRATION ClinicalTrials.gov (identifier, NCT05408416).
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Affiliation(s)
- Siying Li
- Department of Ophthalmology, Peking University People's Hospital, No. 11 South Avenue of XiZhiMen, Xi Cheng District, Beijing, 100044, People's Republic of China
- Eye Diseases and Optometry Institute, Beijing, 100044, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing, 100044, China
| | - Jiyang Tang
- Department of Ophthalmology, Peking University People's Hospital, No. 11 South Avenue of XiZhiMen, Xi Cheng District, Beijing, 100044, People's Republic of China
- Eye Diseases and Optometry Institute, Beijing, 100044, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing, 100044, China
| | - Xinyao Han
- Department of Ophthalmology, Peking University People's Hospital, No. 11 South Avenue of XiZhiMen, Xi Cheng District, Beijing, 100044, People's Republic of China
- Eye Diseases and Optometry Institute, Beijing, 100044, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing, 100044, China
| | - Zongyi Wang
- Department of Ophthalmology, Peking University People's Hospital, No. 11 South Avenue of XiZhiMen, Xi Cheng District, Beijing, 100044, People's Republic of China
- Eye Diseases and Optometry Institute, Beijing, 100044, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing, 100044, China
| | - Linqi Zhang
- Department of Ophthalmology, Peking University People's Hospital, No. 11 South Avenue of XiZhiMen, Xi Cheng District, Beijing, 100044, People's Republic of China
- Eye Diseases and Optometry Institute, Beijing, 100044, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing, 100044, China
| | - Mingwei Zhao
- Department of Ophthalmology, Peking University People's Hospital, No. 11 South Avenue of XiZhiMen, Xi Cheng District, Beijing, 100044, People's Republic of China
- Eye Diseases and Optometry Institute, Beijing, 100044, China
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing, 100044, China
| | - Jinfeng Qu
- Department of Ophthalmology, Peking University People's Hospital, No. 11 South Avenue of XiZhiMen, Xi Cheng District, Beijing, 100044, People's Republic of China.
- Eye Diseases and Optometry Institute, Beijing, 100044, China.
- Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing, 100044, China.
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10
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Kwon JW, Park YG. CLINICAL FEATURES OF INTRAVITREAL DEXAMETHASONE IMPLANTATION IN VITRECTOMIZED EYES OF PATIENTS WITH DIABETIC MACULAR EDEMA. Retina 2022; 42:782-788. [PMID: 34907121 DOI: 10.1097/iae.0000000000003380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To identify the clinical outcomes of intravitreal dexamethasone implantation (IVD) in previously vitrectomized eyes of patients with diabetic macular edema. METHOD We performed a retrospective observational study. We recorded central subfield thickness, best-corrected visual acuity, and intraocular pressure up to 12 months after IVD implant placement. We compared the duration of IVD action, intraocular pressure trends, and the prevalence of ocular hypertension after the first IVD treatment of nonvitrectomized and vitrectomized eyes. We also compared the central subfield thickness, best-corrected visual acuity, number of IVD treatments, and prevalence of ocular hypertension between the 2 groups after 12 months. RESULTS We found no significant between-group differences in the central subfield thickness, best-corrected visual acuity, or the prevalence of ocular hypertension during treatment. However, the duration of action of the first IVD treatment was significantly shorter in vitrectomized eyes, and these eyes required more IVD treatments during the 12-month follow-up period. The maximal average intraocular pressure was observed at 2 months after the first IVD treatment in the nonvitrectomized group, but 1 month after the first IVD treatment in the vitrectomized group. CONCLUSION These findings suggest that the IVD pharmacokinetics and pharmacodynamics differ between vitrectomized and nonvitrectomized eyes. Nevertheless, given the relatively long-lasting effectiveness of the treatment and the good clinical results, consecutive IVD treatments may be beneficial for patients with diabetic macular edema with previously vitrectomized eyes.
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Affiliation(s)
- Jin-Woo Kwon
- Department of Ophthalmology, St. Vincent's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea; and
| | - Young-Gun Park
- Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine, Catholic University of Korea, Seoul, Korea
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11
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Sborgia G, Niro A, Pastore V, Favale RA, Sborgia A, Gigliola S, Giuliani G, Grassi MO, Coassin M, Aiello F, Iaculli C, Reibaldi M, Boscia F, Alessio G. Mid-term safety and effectiveness of intravitreal dexamethasone implant to treat persistent cystoid macular edema in vitrectomized eyes for bacterial endophthalmitis. Graefes Arch Clin Exp Ophthalmol 2022; 260:2703-2710. [PMID: 35254512 DOI: 10.1007/s00417-022-05615-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 02/22/2022] [Accepted: 03/01/2022] [Indexed: 11/30/2022] Open
Abstract
PURPOSE To evaluate the mid-term safety and effectiveness of intravitreal dexamethasone implant (DEX-i) for treating unresponsive to medical therapy cystoid macular edema (CME) in vitrectomized eyes for endophthalmitis. METHODS Retrospective and interventional case series study conducted on vitrectomized eyes for endophthalmitis that developed a CME that did not adequately respond to medical therapy, who underwent 0.7-mg DEX-i. Main outcome measures were changes in central retinal thickness (CRT) and best corrected visual acuity (BCVA). RESULTS Eleven eyes were included in the study. Microbiological findings of vitreous biopsies were 7 (63.6%) staphylococcus epidermidis; 3 (27.3%) Pseudomonas aeruginosa; and 1 (9.1%) Propionibacterium acnes. Median (interquartile range, IqR) duration of CME was 4.0 (3.0-4.0) months. Median (IqR) time between vitrectomy and DEX-i was 9.0 (9.0-11.0) months. Median CRT was significantly decreased from 548.0 (412.8-572.5) µm at baseline to 308.0 (281.3-365.5) µm at month 6 (p = 0.0009, Friedman test). Median BCVA significantly improved from 38.0 (30.5-44.8) letters at baseline to 50.0 (46.8-53.0) letters at month 6 (p < 0.0001, Friedman), with 9 (81.8%) eyes gaining ≥ 10 letters. Elevation of intraocular pressure was observed in one (9.1%) eye, which was successfully controlled with medical therapy. No recurrence of endophthalmitis or other complications was observed. Eight (72.7%) eyes required an additional DEX-i, while 3 (27.3%) were successfully controlled with only one DEX-i. CME recurrence occurred in 5 (62.5%) Gram-positive and 3 (100.0%) Gram-negative bacteria (p = 0.2357). CONCLUSION In vitrectomized eyes for endophthalmitis affected by CME unresponsive to medical therapy, DEX-i had an acceptable safety profile and achieved favorable outcomes. The possibility of suppressing mechanisms for infection control should be taken into account, although correct management of endophthalmitis and long time without reactivation before DEX-i reduce the risk.
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Affiliation(s)
- Giancarlo Sborgia
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
| | - Alfredo Niro
- Eye Clinic, Hospital "SS Annunziata", ASL Taranto, Via F. Bruno, 1, 74010, Taranto, Italy.
| | - Valentina Pastore
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
| | - Rosa Anna Favale
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
| | - Alessandra Sborgia
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
| | - Samuele Gigliola
- Eye Clinic, Hospital "SS Annunziata", ASL Taranto, Via F. Bruno, 1, 74010, Taranto, Italy
| | - Gianluigi Giuliani
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
| | - Maria Oliva Grassi
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
| | - Marco Coassin
- Ophthalmology, University Campus Bio Medico of Rome, 00128, Rome, Italy
| | - Francesco Aiello
- Ophthalmology Unit, Department of Experimental Medicine, University of Rome "Tor Vergata", 00133, Rome, Italy
| | - Cristiana Iaculli
- Department of Ophthalmology, Policlinico Riuniti Di Foggia, University of Foggia, 71122, Foggia, Italy
| | - Michele Reibaldi
- Department of Surgical Sciences, University of Torino, 10126, Turin, Italy
| | - Francesco Boscia
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
| | - Giovanni Alessio
- Department of Medical Science, Neuroscience and Sense Organs, Eye Clinic, University of Bari, 70124, Bari, Italy
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12
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Pessoa B, Leite J, Heitor J, Coelho J, Monteiro S, Coelho C, Figueira J, Meireles A, Melo-Beirão JN. Vitrectomized versus non-vitrectomized eyes in diabetic macular edema response to ranibizumab-retinal layers thickness as prognostic biomarkers. Sci Rep 2021; 11:23055. [PMID: 34845300 PMCID: PMC8630028 DOI: 10.1038/s41598-021-02532-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 10/13/2021] [Indexed: 11/13/2022] Open
Abstract
To evaluate the role of the vitreous in the management of diabetic macular edema with ranibizumab intravitreal injections in a pro re nata regimen. Prospective study of 50 consecutive eyes with diabetic macular edema treated with ranibizumab and 12 months of follow-up. Primary endpoint: to assess differences between non-vitrectomized and vitrectomized eyes in the number injections needed to control the edema. Secondary endpoints: comparison of groups regarding best corrected visual acuity, central foveal thickness and thickness of seven retinal layers. 46 eyes from 38 patients, 10 vitrectomized and 36 non-vitrectomized, completed the follow-up. At month 12, the two groups achieved an equivalent anatomical outcome and needed a similar number of ranibizumab intravitreal injections. In vitrectomized eyes final visual acuity was worse when baseline retinal nerve fiber layers in the central foveal subfield were thicker, showing a strong correlation (r = − 0.942, p < 0.001). A similar, albeit moderate correlation was observed in non-vitrectomized eyes (r = − 0.504, p = 0.002). A decrease of retinal nerve fiber layers inner ring thickness was correlated with a better final visual acuity only in vitrectomized eyes (r = 0.734, p = 0.016). The effect of diabetic macular edema seems to be worse in vitrectomized eyes, with a thinner inner retina reservoir. Clinicaltrials.govNCT04387604.
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Affiliation(s)
- Bernardete Pessoa
- Departamento de Oftalmologia, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar-Edifício Neoclássico, 4099-001, Porto, Portugal. .,Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal.
| | - João Leite
- Departamento de Oftalmologia, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar-Edifício Neoclássico, 4099-001, Porto, Portugal
| | - João Heitor
- Departamento de Oftalmologia, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar-Edifício Neoclássico, 4099-001, Porto, Portugal
| | - João Coelho
- Departamento de Oftalmologia, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar-Edifício Neoclássico, 4099-001, Porto, Portugal
| | - Sérgio Monteiro
- Departamento de Oftalmologia, Hospital de Santa Maria Maior de Barcelos, Barcelos, Portugal
| | - Constança Coelho
- Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - João Figueira
- Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,Association for Innovation and Biomedical Research On Light and Image, Coimbra, Portugal
| | - Angelina Meireles
- Departamento de Oftalmologia, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar-Edifício Neoclássico, 4099-001, Porto, Portugal.,Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal
| | - João Nuno Melo-Beirão
- Departamento de Oftalmologia, Hospital de Santo António, Centro Hospitalar Universitário do Porto, Largo Prof. Abel Salazar-Edifício Neoclássico, 4099-001, Porto, Portugal.,Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto, Portugal
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13
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Impact of silicone oil tamponade on intravitreally injected vancomycin pharmacokinetics in cynomolgus monkey eyes. Int J Pharm 2021; 609:121185. [PMID: 34655708 DOI: 10.1016/j.ijpharm.2021.121185] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 09/26/2021] [Accepted: 10/10/2021] [Indexed: 11/23/2022]
Abstract
Intravitreal injections of vancomycin (VCM) and ceftazidime (CAZ) are commonly used to treat infectious endophthalmitis. When patient cases require retinal detachment with silicone oil (SO) tamponade, the antibiotic doses are empirically reduced to 25 %. Currently, there is no scientific evidence for these empirical dose reductions. The purpose of the present study is to determine the quantitative impact that SO tamponades have on intraocular VCM pharmacokinetics. Because of high invasiveness of frequent sampling of intraocular VCM concentrations in human, this pharmacokinetic study was performed in cynomolgus monkey's eyes. Population pharmacokinetic modeling and simulation were performed using 75 different intraocular VCM concentrations obtained from 8 male cynomolgus monkeys. A one-compartment model with a first-order diffusion rate was used as a structural pharmacokinetic model. From the covariate analysis, SO tamponade significantly decreased the volume of distribution while pars plana vitrectomy with lensectomy (PPV) significantly increased the clearance and diffusion rate constants. From the Monte Carlo simulation (n = 1,000), the median time above minimum inhibitory concentration (T>MIC, a therapeutic effect index) durations of SO and normal eyes at clinical doses of 1,000 µg were 2.6 and 11.0 days, respectively. Using intravitreal injections of VCM with SO tamponade or PPV may reduce the therapeutic effect.
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14
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Long-Term Outcome of Eyes with Vitrectomy for Submacular and/or Vitreous Hemorrhage in Neovascular Age-Related Macular Degeneration. J Ophthalmol 2021; 2021:2963822. [PMID: 34765261 PMCID: PMC8577947 DOI: 10.1155/2021/2963822] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Accepted: 10/16/2021] [Indexed: 11/18/2022] Open
Abstract
Purpose To study long-term clinical outcomes in patients with submacular hemorrhage (SMH) and/or vitreous hemorrhage (VH) associated with neovascular age-related macular degeneration (nAMD) and the real-world clinical situation of adding anti-VEGF therapy after pars plana vitrectomy (PPV). Methods In this retrospective case series, 25 eyes with SMH and/or VH associated with nAMD were treated by PPV and followed up for at least 24 months. When exudative changes were unresolved or recurred after PPV, additional intravitreal anti-VEGF therapy was given. Results The reasons for performing PPV were SMH (8 eyes) and VH (17 eyes) associated with nAMD. Mean best-corrected visual acuity (BCVA) of eyes with SMH improved significantly at 6 months (P < 0.01) and 12 months (P < 0.05) after PPV. Mean BCVA of eyes with VH improved at 1, 3, 6, 12, 18, and 24 months (P < 0.01) and at the final visit (P < 0.05). Post-PPV anti-VEGF therapy was initiated in 6 of 8 (75.0%) eyes with SMH and 7 of 17 (47.1%) eyes with VH. Of the 13 eyes given anti-VEGF therapy after PPV, 11 eyes had anti-VEGF therapy initiated within 10 months after surgery. Dry macula rate after PPV was 50.0% in SMH and 70.6% in VH. Conclusions BCVA improved in eyes with SMH at 6 and 12 months after PPV, and the BCVA was maintained until the end of the study. BCVA improved significantly in eyes with VH at all time points after PPV. In eyes undergoing PPV for nAMD, recurrence of exudative changes after 11 months from the initial PPV was rare.
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15
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Comparison of Intravitreal Dexamethasone Implant and Ranibizumab in Vitrectomized Eyes with Diabetic Macular Edema. J Ophthalmol 2021; 2021:8882539. [PMID: 34540287 PMCID: PMC8448602 DOI: 10.1155/2021/8882539] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 08/26/2021] [Indexed: 11/17/2022] Open
Abstract
Purpose This retrospective study aimed to compare the efficacy of intravitreal ranibizumab (IVR) and intravitreal dexamethasone implant (IDI) for pseudophakic vitrectomized eyes with diabetic macular edema (DME) in a single institution. Methods Pseudophakic vitrectomized eyes with treatment-naïve center-involved DME were enrolled, with one eye in each patient. They were divided into two groups: one group receiving IDI every 3 to 4 months and another group receiving IVR using 3 monthly plus treat-and-extend injections, all with monthly follow-up for 6 months. Switch of intravitreal drugs or deferred macular laser was not allowed. Primary outcome measures included change in central foveal thickness (CFT) in 1 mm by spectral-domain optical coherence tomography and best-corrected visual acuity (BCVA) at Month 6. Results Twenty-two eyes were included in the IDI group and 26 eyes in the IVR group. The baseline demographics, glycosylated hemoglobin level, intraocular pressure (IOP), BCVA, and CFT did not significantly differ (p > 0.05). Compared to baseline data, CFT decreased and BCVA improved significantly after either IDI or IVR at Month 6 (p < 0.05). Significantly better mean final BCVA (0.38 logMAR vs. 0.62 logMAR, p=0.04), more mean visual gain (−0.30 logMAR vs. −0.15 logMAR, p=0.02), lower mean final CFT (310.9 μm vs. 384.2 μm, p=0.04), and larger mean CFT decrease (−150.0 μm vs. −60.1 μm, p=0.03) were found in the IDI group compared to those in the IVR group. A smaller mean treatment number (2.6 vs. 5.6, p < 0.001) and higher rate of postinjection ocular hypertension requiring topical hypotensive agent therapy (27.3% vs. 0%, p=0.0002) were demonstrated in the IDI group than those in the IVR group. Conclusion We concluded that IDI and IVR can both effectively treat vitrectomized eyes with DME. Dexamethasone implants had significantly better visual/anatomical improvement, smaller treatment number, and higher rate of elevated IOP after injection than IVR in pseudophakic vitrectomized eyes with DME in a 6-month period.
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16
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Choo PP, Md Din N, Azmi N, Bastion MLC. Review of the management of sight-threatening diabetic retinopathy during pregnancy. World J Diabetes 2021; 12:1386-1400. [PMID: 34630896 PMCID: PMC8472492 DOI: 10.4239/wjd.v12.i9.1386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 06/25/2021] [Accepted: 08/12/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is a noncommunicable disease reaching epidemic proportions around the world. It affects younger individuals, including women of childbearing age. Diabetes can cause diabetic retinopathy (DR), which is potentially sight threatening when severe nonproliferative DR (NPDR), proliferative DR (PDR), or sight-threatening diabetic macular oedema (STDME) develops. Pregnancy is an independent risk factor for the progression of DR. Baseline DR at the onset of pregnancy is an important indicator of progression, with up to 10% of women with baseline NPDR progressing to PDR. Progression to sight-threatening DR (STDR) during pregnancy causes distress to the patient and often necessitates ocular treatment, which may have a systemic effect. Management includes prepregnancy counselling and, when possible, conventional treatment prior to pregnancy. During pregnancy, closer follow-up is required for those with a long duration of DM, poor baseline control of blood sugar and blood pressure, and worse DR, as these are risk factors for progression to STDR. Conventional treatment with anti-vascular endothelial growth factor agents for STDME can potentially lead to foetal loss. Treatment with laser photocoagulation may be preferred, and surgery under general anaesthesia should be avoided. This review provides a management plan for STDR from the perspective of practising ophthalmologists. A review of strategies for maintaining the eyesight of diabetic women with STDR with emphasis on prepregnancy counselling and planning, monitoring and safe treatment during pregnancy, and management of complications is presented.
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Affiliation(s)
- Priscilla Peixi Choo
- Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56000, Wilayah Persekutuan, Malaysia
| | - Norshamsiah Md Din
- Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56000, Wilayah Persekutuan, Malaysia
| | - Nooraniah Azmi
- Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56000, Wilayah Persekutuan, Malaysia
- Department of Ophthalmology, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Mae-Lynn Catherine Bastion
- Department of Ophthalmology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur 56000, Wilayah Persekutuan, Malaysia
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Imamura T, Kakinoki M, Hira D, Kitagawa T, Ueshima S, Kakumoto M, Terada T, Kawamoto I, Murase M, Ohji M. Pharmacokinetics of Intravitreal Vancomycin and Ceftazidime in Silicone Oil-Filled Macaque Eyes. Transl Vis Sci Technol 2021; 10:1. [PMID: 34003935 PMCID: PMC7938004 DOI: 10.1167/tvst.10.3.1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Purpose This study evaluated the pharmacokinetics of intravitreal vancomycin and ceftazidime in the aqueous humor of macaque eyes filled with silicone oil in the vitreous cavity. Methods Intravitreal vancomycin (1 mg/0.1 mL) and ceftazidime (2 mg/0.1 mL) were injected into four normal macaque eyes, four vitrectomized aphakic macaque eyes, and four previously vitrectomized aphakic macaque eyes filled with silicone oil (silicone oil-filled eyes). Aqueous humor samples (0.1 mL) were obtained just before injection and at 2 and 5 hours and 1, 2, 3, 5, 7, and 10 days after injection. In each group, corneal endothelial cell density (ECD) measurements and electroretinogram (ERG) recordings were obtained before injection and after 1 month. Results The half-lives of vancomycin in the aqueous humor of normal, vitrectomized, and silicone oil-filled eyes were 29.4, 21.1, and 6.8 hours, respectively, and those of ceftazidime were 20.4, 5.2, and 3.1 hours, respectively. The maximum vancomycin aqueous humor concentrations of normal, vitrectomized, and silicone oil-filled eyes were 151.4, 205.6, and 543.5 µg/mL, respectively, and the maximum ceftazidime aqueous humor concentrations are 64.6, 260.0, and 1176.3 µg/mL, respectively. There was no change in ECD, and ERG was not declined after intravitreal injection in all groups. Conclusions The half-lives of vancomycin and ceftazidime in the aqueous humor were shorter in silicone oil-filled eyes than in normal and vitrectomized eyes. High antibiotic concentrations in silicone oil-filled eyes seemed to be well tolerated. Translational Relevance This study aids in estimating how often an antibiotic should be intravitreally injected for endophthalmitis of silicone oil-filled eyes.
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Affiliation(s)
- Taku Imamura
- Department of Ophthalmology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan
| | - Masashi Kakinoki
- Department of Ophthalmology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan
| | - Daiki Hira
- Department of Pharmacy, Shiga University of Medical Science Hospital, Seta Tsukinowa-cho, Otsu, Shiga, Japan.,College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, Japan
| | - Tomoya Kitagawa
- College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, Japan
| | - Satoshi Ueshima
- College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, Japan
| | - Mikio Kakumoto
- College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, Japan
| | - Tomohiro Terada
- Department of Pharmacy, Shiga University of Medical Science Hospital, Seta Tsukinowa-cho, Otsu, Shiga, Japan
| | - Ikuo Kawamoto
- Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan
| | - Mitsuru Murase
- Research Center for Animal Life Science, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan
| | - Masahito Ohji
- Department of Ophthalmology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, Shiga, Japan
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18
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Mun Y, Park KH, Park SJ, Woo SJ. Efficacy of anti-vascular endothelial growth factor agents for treating neovascular age-related macular degeneration in vitrectomized eyes. PLoS One 2021; 16:e0252006. [PMID: 34111133 PMCID: PMC8191940 DOI: 10.1371/journal.pone.0252006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Accepted: 05/09/2021] [Indexed: 11/20/2022] Open
Abstract
PURPOSE To evaluate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for treatment of neovascular age-related macular degeneration (nAMD) in vitrectomized eyes. METHODS The medical records were reviewed of nAMD patients treated with anti-VEGF agents who previously underwent pars plana vitrectomy (PPV). PPV was performed with complete posterior vitreous detachment induction. RESULTS A total of 44 eyes from 44 patients were included. The mean central foveal thickness (CFT) was 478.50 ± 156.93 μm at baseline, 414.25 ± 143.55 μm (86.6% of baseline) at 1 month after first injection (P < 0.001), and 386.75 ± 141.45 μm (80.8% of baseline) after monthly multiple injections (2.30 ± 1.07; range, 1-5) (P < 0.001). The mean logarithm of the minimum angle of resolution best-corrected visual acuity visual acuity (BCVA) was 0.85 ± 0.57 at baseline, 0.86 ± 0.63 after the first injection, and 0.84 ± 0.64 after monthly multiple injections. BCVA improved in 39.5% at 1 month after first injection and 45.2% at 1 month after monthly multiple injections. In the subgroup analysis, CFT of eyes with the posterior capsule decreased significantly to 85.8% and 79.8% of baseline values at 1 month after the first injection and after monthly multiple injections, respectively. CFT of eyes without the posterior capsule decreased to 91.6% and 87.4% of baseline values at 1 month after the first injection and after monthly multiple injections, respectively, without statistical significance. CONCLUSION Monthly injections of Intravitreal anti-VEGF agents induced favorable anatomical improvement and vision maintenance in vitrectomized eyes with nAMD.
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Affiliation(s)
- Yongseok Mun
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea
- Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Kyu Hyung Park
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea
- Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Sang Jun Park
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea
- Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Se Joon Woo
- Department of Ophthalmology, Seoul National University College of Medicine, Seoul, South Korea
- Seoul National University Bundang Hospital, Seongnam, South Korea
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Silva M, Peng T, Zhao X, Li S, Farhan M, Zheng W. Recent trends in drug-delivery systems for the treatment of diabetic retinopathy and associated fibrosis. Adv Drug Deliv Rev 2021; 173:439-460. [PMID: 33857553 DOI: 10.1016/j.addr.2021.04.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/05/2021] [Accepted: 04/08/2021] [Indexed: 12/12/2022]
Abstract
Diabetic retinopathy is a frequent microvascular complication of diabetes and a major cause of visual impairment. In advanced stages, the abnormal neovascularization can lead to fibrosis and subsequent tractional retinal detachment and blindness. The low bioavailability of the drugs at the target site imposed by the anatomic and physiologic barriers within the eye, requires long term treatments with frequent injections that often compromise patient's compliance and increase the risk of developing more complications. In recent years, much effort has been put towards the development of new drug delivery platforms aiming to enhance their permeation, to prolong their retention time at the target site and to provide a sustained release with reduced toxicity and improved efficacy. This review provides an overview of the etiology and pathophysiology of diabetic retinopathy and current treatments. It addresses the specific challenges associated to the different ocular delivery routes and provides a critical review of the most recent developments made in the drug delivery field.
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Affiliation(s)
- Marta Silva
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Tangming Peng
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Xia Zhao
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Shuai Li
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Mohd Farhan
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau
| | - Wenhua Zheng
- Centre of Reproduction, Development and Aging, Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Macau.
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Baba T, Miura G, Tatsumi T, Sakurai M, Yamamoto S. Characteristics and surgical outcomes of rhegmatogenous retinal detachments that develop after intravitreal injections. Jpn J Ophthalmol 2021; 65:492-496. [PMID: 33745092 DOI: 10.1007/s10384-021-00834-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 02/18/2021] [Indexed: 11/24/2022]
Abstract
PURPOSE To determine the frequency and characteristics of rhegmatogenous retinal detachments (RRDs) that develop after an intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent. STUDY DESIGN A retrospective review of the medical charts. METHODS The charts of patients who received intravitreal injections for age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), or myopic choroidal neovascularization (mCNV) between 2013 and 2020 were reviewed. We included the RRD cases that developed within 90 days of the most recent intravitreal injection. The baseline characteristics and surgical outcomes were analyzed. RESULTS A total of 3040 patients received 28,190 intravitreal injections. Seven eyes of 7 cases developed a RRD. There were 6 cases of AMD and one of DME, with an incidence of one in 4027 injections (0.025%). The retinal break was in the superior quadrants in 5 eyes (71%), and in the inferior quadrants in 2 eyes. All eyes had a posterior vitreous detachment. The average number of injections before the development of RRD was 14.1 (range: 2-39). Four eyes were treated by vitrectomy, and 3 by scleral buckling. The primary success rate was 86%, and the final reattachment rate was 100%. The best-corrected visual acuity was 0.41 ± 0.26 logarithm of minimal angle of resolution (logMAR) units before developing the RRD, 0.78 ± 0.78 logMAR units before the surgery for RRD, and 0.45 ± 0.47 logMAR units at the final visit. CONCLUSIONS The incidence of RRD after an intravitreal injection is very low (0.025%), and it can be reattached with recovery of the visual acuity.
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Affiliation(s)
- Takayuki Baba
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan.
| | - Gen Miura
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan
| | - Tomoaki Tatsumi
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan
| | - Madoka Sakurai
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan
| | - Shuichi Yamamoto
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-0856, Japan
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21
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The Role of VEGF Receptors as Molecular Target in Nuclear Medicine for Cancer Diagnosis and Combination Therapy. Cancers (Basel) 2021; 13:cancers13051072. [PMID: 33802353 PMCID: PMC7959315 DOI: 10.3390/cancers13051072] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 02/13/2021] [Accepted: 02/24/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary The rapid development of diagnostic and therapeutic methods of the cancer treatment causes that these diseases are becoming better known and the fight against them is more and more effective. Substantial contribution in this development has nuclear medicine that enables very early cancer diagnosis and early start of the so-called targeted therapy. This therapeutic concept compared to the currently used chemotherapy, causes much fewer undesirable side effects, due to targeting a specific lesion in the body. This review article discusses the possible applications of radionuclide-labelled tracers (peptides, antibodies or synthetic organic molecules) that can visualise cancer cells through pathological blood vessel system in close tumour microenvironment. Hence, at a very early step of oncological disease, targeted therapy can involve in tumour formation and growth. Abstract One approach to anticancer treatment is targeted anti-angiogenic therapy (AAT) based on prevention of blood vessel formation around the developing cancer cells. It is known that vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptors (VEGFRs) play a pivotal role in angiogenesis process; hence, application of angiogenesis inhibitors can be an effective approach in anticancer combination therapeutic strategies. Currently, several types of molecules have been utilised in targeted VEGF/VEGFR anticancer therapy, including human VEGF ligands themselves and their derivatives, anti-VEGF or anti-VEGFR monoclonal antibodies, VEGF binding peptides and small molecular inhibitors of VEGFR tyrosine kinases. These molecules labelled with diagnostic or therapeutic radionuclides can become, respectively, diagnostic or therapeutic receptor radiopharmaceuticals. In targeted anti-angiogenic therapy, diagnostic radioagents play a unique role, allowing the determination of the emerging tumour, to monitor the course of treatment, to predict the treatment outcomes and, first of all, to refer patients for AAT. This review provides an overview of design, synthesis and study of radiolabelled VEGF/VEGFR targeting and imaging agents to date. Additionally, we will briefly discuss their physicochemical properties and possible application in combination targeted radionuclide tumour therapy.
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Tavakoli S, Kari OK, Turunen T, Lajunen T, Schmitt M, Lehtinen J, Tasaka F, Parkkila P, Ndika J, Viitala T, Alenius H, Urtti A, Subrizi A. Diffusion and Protein Corona Formation of Lipid-Based Nanoparticles in the Vitreous Humor: Profiling and Pharmacokinetic Considerations. Mol Pharm 2021; 18:699-713. [PMID: 32584047 PMCID: PMC7856631 DOI: 10.1021/acs.molpharmaceut.0c00411] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 06/18/2020] [Accepted: 06/25/2020] [Indexed: 12/30/2022]
Abstract
The vitreous humor is the first barrier encountered by intravitreally injected nanoparticles. Lipid-based nanoparticles in the vitreous are studied by evaluating their diffusion with single-particle tracking technology and by characterizing their protein coronae with surface plasmon resonance and high-resolution proteomics. Single-particle tracking results indicate that the vitreal mobility of the formulations is dependent on their charge. Anionic and neutral formulations are mobile, whereas larger (>200 nm) neutral particles have restricted diffusion, and cationic particles are immobilized in the vitreous. PEGylation increases the mobility of cationic and larger neutral formulations but does not affect anionic and smaller neutral particles. Convection has a significant role in the pharmacokinetics of nanoparticles, whereas diffusion drives the transport of antibodies. Surface plasmon resonance studies determine that the vitreal corona of anionic formulations is sparse. Proteomics data reveals 76 differentially abundant proteins, whose enrichment is specific to either the hard or the soft corona. PEGylation does not affect protein enrichment. This suggests that protein-specific rather than formulation-specific factors are drivers of protein adsorption on nanoparticles in the vitreous. In summary, our findings contribute to understanding the pharmacokinetics of nanoparticles in the vitreous and help advance the development of nanoparticle-based treatments for eye diseases.
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Affiliation(s)
- Shirin Tavakoli
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Otto Kalevi Kari
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Tiina Turunen
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Tatu Lajunen
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Mechthild Schmitt
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Julia Lehtinen
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Fumitaka Tasaka
- Pharmaceutics
& Pharmacology Department, Global R&D, Santen Pharmaceutical
Co., Ltd., 8916-16 Takayama-cho, Ikoma, Nara 630-0101, Japan
| | - Petteri Parkkila
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Joseph Ndika
- Human
Microbiome Research, Faculty of Medicine, University of Helsinki, P.O. Box 21, 00290 Helsinki, Finland
| | - Tapani Viitala
- Division
of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
| | - Harri Alenius
- Human
Microbiome Research, Faculty of Medicine, University of Helsinki, P.O. Box 21, 00290 Helsinki, Finland
- Institute
of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Arto Urtti
- Drug
Research Program, Division of Pharmaceutical Biosciences, Faculty
of Pharmacy, University of Helsinki, Viikinkaari 5 E, 00014, Helsinki, Finland
- Institute
of Chemistry, St. Petersburg State University, Petergof, Universitetskii pr. 26, 198504 St. Petersburg, Russia
- School
of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1, 70210 Kuopio, Finland
| | - Astrid Subrizi
- School
of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1, 70210 Kuopio, Finland
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23
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Yao T, Yang Y, Jin X, Wang Y, Zhou Y, Xu A, He F, Wang Z. Intraocular pharmacokinetics of anti-vascular endothelial growth factor agents by intraoperative subretinal versus intravitreal injection in silicone oil-filled eyes of proliferative diabetic retinopathy: a randomized controlled pilot study. Acta Ophthalmol 2020; 98:e795-e800. [PMID: 32114709 DOI: 10.1111/aos.14386] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 02/05/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE Intraoperative subretinal anti-vascular endothelial growth factor (VEGF) injections have been used clinically in some case, but the pharmacokinetic characteristics have not yet been determined. In this pilot study, we investigate the pharmacokinetic parameters of anti-VEGF agents by intraoperative subretinal or intravitreal injection in silicone oil (SiO)-filled eyes of patients with proliferative diabetic retinopathy (PDR). METHODS Randomized controlled trial including 13 patients (16 eyes) with PDR underwent pars plana vitrectomy (PPV) with SiO tamponade and randomly received a subretinal (8 eyes) or intravitreal (8 eyes) conbercept injection (0.5 mg/0.05 ml) intraoperatively. Aqueous humour (AH) was obtained on the 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after the injection. Drug concentrations in the AH were determined by enzyme-linked immunosorbent assay (ELISA). The last best-corrected visual acuity (BCVA) was examined 6 months postoperatively. RESULTS The clearance rate of anti-VEGF agents by subretinal injection was reduced in vitrectomized eyes with SiO tamponade (p < 0.05). With the same drug dose, subretinal injection (5.49 ± 6.11 μg/ml) resulted in higher drug concentrations in the AH when compared with intravitreal injection (0.42 ± 0.46 μg/ml, p = 0.001) 4 weeks after the treatment. The mean residence time last (MRT0-t ) by subretinal injection (11.57 ± 0.83 days) was significantly longer than the mean MRT0-t by intravitreal injection (7.10 ± 1.00 days, p < 0.001). A self-paired analysis showed that subretinal injection led to the BCVA improvement by +28.59 letters 6 months postoperatively (p = 0.028) while the BCVA did not improve significantly by intravitreal injection (p = 0.715). CONCLUSIONS The drug maintenance phase was prolonged by intraoperative subretinal injection in SiO-filled eyes of PDR. The results suggest that subretinal injection might be a valuable treatment option for the management of PDR.
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Affiliation(s)
- Teng‐teng Yao
- Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China
- Shanghai Key Laboratory of Orbital Disease and Ocular Oncology Shanghai China
| | - Yuan Yang
- Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China
- Shanghai Key Laboratory of Orbital Disease and Ocular Oncology Shanghai China
| | - Xiao‐liang Jin
- Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China
- Shanghai Key Laboratory of Orbital Disease and Ocular Oncology Shanghai China
| | - Yi‐xiao Wang
- Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China
- Shanghai Key Laboratory of Orbital Disease and Ocular Oncology Shanghai China
| | - Ya‐li Zhou
- Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China
- Shanghai Key Laboratory of Orbital Disease and Ocular Oncology Shanghai China
| | - A‐jing Xu
- Department of Pharmacy Xinhua Hospital School of Medicine Shanghai Jiaotong University School of Medicine Shanghai China
| | - Fang‐lin He
- Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China
- Shanghai Key Laboratory of Orbital Disease and Ocular Oncology Shanghai China
| | - Zhao‐yang Wang
- Department of Ophthalmology Shanghai Ninth People's Hospital Shanghai Jiaotong University School of Medicine Shanghai China
- Shanghai Key Laboratory of Orbital Disease and Ocular Oncology Shanghai China
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24
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Effectiveness of Intravitreal Ranibizumab in Nonvitrectomized and Vitrectomized Eyes with Diabetic Macular Edema: A Two-Year Retrospective Analysis. J Ophthalmol 2020; 2020:2561251. [PMID: 32832135 PMCID: PMC7428899 DOI: 10.1155/2020/2561251] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/25/2020] [Accepted: 07/13/2020] [Indexed: 11/18/2022] Open
Abstract
The aim of this study was to compare the effectiveness of intravitreal ranibizumab (IVR) injections for the treatment of diabetic macular edema (DME) in eyes with and without previous vitrectomy. The medical records of 28 eyes (11 vitrectomized and 17 nonvitrectomized) of 28 patients (mean age, 59.0 ± 9.6 years; male to female ratio 1 : 1) who were diagnosed with DME and had received IVR treatment were reviewed retrospectively. The indications of vitrectomy in 11 vitrectomized eyes were intravitreal hemorrhage (n = 8) and epiretinal membrane (n = 3). The best-corrected visual acuity (BCVA), central macular thickness (CMT), and total macular volume (TMV) were measured at baseline and at months 6, 12, 18, and 24 of the follow-up. The number of IVR injections, the duration between diagnosis of DME and IVR injection, and the hemoglobin A1c (HbA1c) level at baseline were also recorded. Baseline demographics, HbA1c, BCVA, CMT, and TMV values were similar between two groups (p>0.05). The duration between diagnosis of DME and IVR injections was similar in both groups (16 ± 5 months vs. 13 ± 4 months, respectively; p=0.11). IVR injection was performed 6.3 times in vitrectomized eyes and 6.1 times in nonvitrectomized eyes during the 24-month period (p>0.05). The mean BCVA improved significantly during the 24-month period in both groups. The improvements in BCVA, in CMT, and in TMV were more significant at month 6 (p=0.036) group, at month 12 (p=0.013), at month 12 (p=0.021), and month 24 (p=0.021) in nonvitrectomized eyes, respectively, while there was no difference in improvements of BCVA, CMT, and TMV in vitrectomized group at each visit. Treatment effected by time in terms of BCVA, CMT, and TMV values in all groups (p=0.0004, p<0.0001, p<0.0001, respectively), not by time-group interaction and group (all p values >0.05). In conclusion, IVR treatment for DME is equally effective in both groups. However, the response to treatment is seen earlier in nonvitrectomized eyes compared to vitrectomized eyes.
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25
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Preclinical challenges for developing long acting intravitreal medicines. Eur J Pharm Biopharm 2020; 153:130-149. [DOI: 10.1016/j.ejpb.2020.05.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/01/2020] [Accepted: 05/08/2020] [Indexed: 02/07/2023]
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Mammo DA, Ringeisen AL, Parke DW. Frequency of Rhegmatogenous Retinal Detachment after Intravitreal Therapy in Neovascular Age-Related Macular Degeneration. Ophthalmol Retina 2020; 4:973-978. [PMID: 32651157 DOI: 10.1016/j.oret.2020.03.028] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 03/24/2020] [Accepted: 03/27/2020] [Indexed: 11/29/2022]
Abstract
PURPOSE To identify characteristics of neovascular age-related macular degeneration (nAMD) patients undergoing pars plana vitrectomy (PPV) after rhegmatogenous retinal detachment (RRD), including changes to injection intervals. DESIGN Single-center retrospective, consecutive review. PARTICIPANTS All patients with RRD receiving anti-vascular endothelial growth factor treatment for nAMD from January 1, 2014, through October 30, 2018. METHODS Billing codes were used to identify RRD that occurred within 90 days of a previous intravitreal injection for nAMD. MAIN OUTCOME MEASURES Outcome measures included the quadrant of the retinal break(s), visual acuity at the time of RRD and final follow-up, and postoperative injection frequency. RESULTS An exact total of 203 000 intravitreal injections for nAMD were administered. Seventeen eyes from 17 patients demonstrated RRDs, giving a rate of 1 RRD per 11 941 intravitreal injections (0.0084%) within 90 days of intravitreal injection. Patients received a mean of 27.56 injections in the superotemporal quadrant before RRD. Of known retinal breaks, the superotemporal quadrant was involved most frequently (10 of 16 eyes [62.5%]). Six patients (35.3%) required a second surgery. Of patients requiring postoperative injections, the average interval increased from 7.18 weeks to 9.17 weeks after surgery. Eleven of 17 patients (64.7%) either increased their injection intervals or required no further injections, 3 maintained similar intervals, and 3 decreased intervals. The average number of injections in the 6 months before RRD (n = 84) and the 6 months after the first injection after PPV (n = 47) was 4.94 ± 1.89 and 2.76 ± 2.44, respectively (P = 0.009). CONCLUSIONS Based on these results, the 90-day rate of RRD in nAMD patients receiving intravitreal injections is low. Rhegmatogenous retinal detachments in these patients may be more difficult to repair. Although many physicians worry about injection frequency in vitrectomized eyes because of a presumed increased medication clearance, this study found that most patients received fewer injections after surgery.
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Affiliation(s)
- Danny A Mammo
- Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota
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27
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Wang JK, Huang TL, Chang PY. Effect of dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes of Taiwanese patients with treatment-naïve diabetic macular edema. J Formos Med Assoc 2020; 119:1619-1625. [PMID: 32482606 DOI: 10.1016/j.jfma.2020.04.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 02/28/2020] [Accepted: 04/15/2020] [Indexed: 01/02/2023]
Abstract
BACKGROUND/PURPOSE Vitrectomy may affect intravitreal drug clearance and efficacy for treating diabetic macular edema (DME). This study aimed to evaluate functional and anatomical outcomes of intravitreal dexamethasone (DEX) implant for vitrectomized and nonvitrectomized eyes with treatment-naïve DME in Taiwanese patients. METHODS In this retrospective single-center study, we reviewed treatment-naïve patients who received DEX implant monotherapy for center-involved DME from January 2015 to May 2017. Retreatments were provided at least 4 months apart as needed. The primary outcomes included changes from baseline in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at Month 6. Adverse events were recorded. RESULTS Twenty-seven eyes in 27 patients had prior vitrectomy and 43 eyes in 41 patients without vitrectomy. Baseline data were comparable. Overall, the improvements in BCVA and CFT were significant by 1 month post-treatment and sustained throughout the study (all p < 0.05). At Month 6, BCVA improved by 16.5 and 12.1 letters, and CFT reduced by 138.0 and 121.9 μm in vitrectomized and nonvitrectomized eyes, respectively, with a mean of 1.5 DEX implant injection. No significant differences in clinical outcomes were seen between the two groups (all p > 0.05). DEX implant injection was well tolerated. About 30% of patients had post-injection intraocular pressure value > 20 mmHg, and all were manageable with topical hypotensive agents, and no serious ocular complication was observed. CONCLUSION In this 6-month retrospective study, intravitreal DEX implant was effective in Taiwanese patients with treatment-naïve DME regardless of vitrectomy status.
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Affiliation(s)
- Jia-Kang Wang
- Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Electrical Engineering, Yuan Ze University, Taoyuan City, Taiwan; Department of Medicine, National Yang Ming University, Taipei City, Taiwan; Department of Healthcare Administration and Department of Nursing, Oriental Institute of Technology, New Taipei City, Taiwan; Department of Medicine, National Taiwan University, Taipei City, Taiwan.
| | - Tzu-Lun Huang
- Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Electrical Engineering, Yuan Ze University, Taoyuan City, Taiwan
| | - Pei-Yao Chang
- Department of Ophthalmology, Far Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Medicine, National Taiwan University, Taipei City, Taiwan
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Intraocular Pharmacokinetics and Safety of Subretinal Injection Compared with Intravitreal Application of Conbercept in Vitrectomized Rabbit Eyes. J Ophthalmol 2020; 2020:2674780. [PMID: 32280518 PMCID: PMC7125476 DOI: 10.1155/2020/2674780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 09/27/2019] [Accepted: 11/25/2019] [Indexed: 11/22/2022] Open
Abstract
Purpose To evaluate the ocular pharmacokinetic properties of subretinal conbercept injection in vitrectomized rabbit eyes and to compare them with those by intravitreal injection. Methods The following groups of New Zealand white rabbits received conbercept injections (0.5 mg/0.05 ml): a subretinal group (subretinal injection in vitrectomized eyes), an intravitreal group (intravitreal injection in vitrectomized eyes), and a control group (intravitreal injection in nonvitrectomized eyes). Drug concentrations in the aqueous humor (AH), the vitreous humor (VH), and the retina were measured by the enzyme-linked immunosorbent assay (ELISA), and pharmacokinetic parameters were calculated. Ophthalmic B-ultrasonography, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to evaluate the safety of subretinal injection. Results On the 28th day after injection, the drug level in the subretinal group was significantly higher than that in the intravitreal group in the AH (0.90 ± 0.25 μg/ml and 0.11 ± 0.07 μg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 μg/ml and 0.11 ± 0.07 μg/ml and 0.11 ± 0.07 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 P < 0.001, respectively) and the VH (5.00 ± 3.86 Conclusions Our study indicates that applying conbercept by subretinal injection can reduce the drug clearance rate and sustain a long maintenance period in ocular tissue, which suggests that subretinal conbercept injection may be a potentially valuable treatment option.
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29
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Varela-Fernández R, Díaz-Tomé V, Luaces-Rodríguez A, Conde-Penedo A, García-Otero X, Luzardo-Álvarez A, Fernández-Ferreiro A, Otero-Espinar FJ. Drug Delivery to the Posterior Segment of the Eye: Biopharmaceutic and Pharmacokinetic Considerations. Pharmaceutics 2020; 12:E269. [PMID: 32188045 PMCID: PMC7151081 DOI: 10.3390/pharmaceutics12030269] [Citation(s) in RCA: 211] [Impact Index Per Article: 42.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Revised: 03/06/2020] [Accepted: 03/11/2020] [Indexed: 01/22/2023] Open
Abstract
The treatment of the posterior-segment ocular diseases, such as age-related eye diseases (AMD) or diabetic retinopathy (DR), present a challenge for ophthalmologists due to the complex anatomy and physiology of the eye. This specialized organ is composed of various static and dynamic barriers that restrict drug delivery into the target site of action. Despite numerous efforts, effective intraocular drug delivery remains unresolved and, therefore, it is highly desirable to improve the current treatments of diseases affecting the posterior cavity. This review article gives an overview of pharmacokinetic and biopharmaceutics aspects for the most commonly-used ocular administration routes (intravitreal, topical, systemic, and periocular), including information of the absorption, distribution, and elimination, as well as the benefits and limitations of each one. This article also encompasses different conventional and novel drug delivery systems designed and developed to improve drug pharmacokinetics intended for the posterior ocular segment treatment.
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Affiliation(s)
- Rubén Varela-Fernández
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Clinical Neurosciences Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Victoria Díaz-Tomé
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Clinical Pharmacology Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Andrea Luaces-Rodríguez
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Clinical Pharmacology Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Andrea Conde-Penedo
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Xurxo García-Otero
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Molecular Imaging Group. University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Asteria Luzardo-Álvarez
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Anxo Fernández-Ferreiro
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Clinical Pharmacology Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
| | - Francisco J. Otero-Espinar
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), Campus vida, 15782 Santiago de Compostela, Spain; (R.V.-F.); (V.D.-T.); (A.L.-R.); (A.C.-P.); (X.G.-O.); (A.L.-Á.)
- Paraquasil Group, Health Research Institute of Santiago de Compostela (IDIS), Travesía da Choupana s/n, 15706 Santiago de Compostela, Spain
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Caruso A, Füth M, Alvarez-Sánchez R, Belli S, Diack C, Maass KF, Schwab D, Kettenberger H, Mazer NA. Ocular Half-Life of Intravitreal Biologics in Humans and Other Species: Meta-Analysis and Model-Based Prediction. Mol Pharm 2020; 17:695-709. [PMID: 31876425 DOI: 10.1021/acs.molpharmaceut.9b01191] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Therapeutic antibodies administered intravitreally are the current standard of care to treat retinal diseases. The ocular half-life (t1/2) is a key determinant of the duration of target suppression. To support the development of novel, longer-acting drugs, a reliable determination of t1/2 is needed together with an improved understanding of the factors that influence it. A model-based meta-analysis was conducted in humans and nonclinical species (rat, rabbit, monkey, and pig) to determine consensus values for the ocular t1/2 of IgG antibodies and Fab fragments. Results from multiple literature and in-house pharmacokinetic studies are presented within a mechanistic framework that assumes diffusion-controlled drug elimination from the vitreous. Our analysis shows, both theoretically and experimentally, that the ocular t1/2 increases in direct proportion to the product of the hydrodynamic radius of the macromolecule (3.0 nm for Fab and 5.0 nm for IgG) and the square of the radius of the vitreous globe, which varies approximately 24-fold from the rat to the human. Interspecies differences in the proportionality factors are observed and discussed in mechanistic terms. In addition, mathematical formulae are presented that allow prediction of the ocular t1/2 for molecules of interest. The utility of these formulae is successfully demonstrated in case studies of aflibercept, brolucizumab, and PEGylated Fabs, where the predicted ocular t1/2 values are found to be in reasonable agreement with the experimental data available for these molecules.
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Affiliation(s)
- Antonello Caruso
- Pharmaceutical Sciences, Roche Innovation Center Basel , Roche Pharma Research and Early Development , Basel 4070 , Switzerland
| | - Matthias Füth
- Pharmaceutical Sciences, Roche Innovation Center Basel , Roche Pharma Research and Early Development , Basel 4070 , Switzerland
| | - Ruben Alvarez-Sánchez
- Pharmaceutical Sciences, Roche Innovation Center Basel , Roche Pharma Research and Early Development , Basel 4070 , Switzerland
| | - Sara Belli
- Pharmaceutical Sciences, Roche Innovation Center Basel , Roche Pharma Research and Early Development , Basel 4070 , Switzerland
| | - Cheikh Diack
- Pharmaceutical Sciences, Roche Innovation Center Basel , Roche Pharma Research and Early Development , Basel 4070 , Switzerland
| | - Katie F Maass
- Clinical Pharmacology , Genentech , South San Francisco 94080 , California , United States
| | - Dietmar Schwab
- Pharmaceutical Sciences, Roche Innovation Center Basel , Roche Pharma Research and Early Development , Basel 4070 , Switzerland
| | - Hubert Kettenberger
- Therapeutic Modalities, Roche Innovation Center Munich , Roche Pharma Research and Early Development , Penzberg 82377 , Germany
| | - Norman A Mazer
- Pharmaceutical Sciences, Roche Innovation Center Basel , Roche Pharma Research and Early Development , Basel 4070 , Switzerland
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Change of Vascular Endothelial Growth Factor Levels following Vitrectomy in Eyes with Proliferative Diabetic Retinopathy. J Ophthalmol 2019; 2019:6764932. [PMID: 31772768 PMCID: PMC6854928 DOI: 10.1155/2019/6764932] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/25/2019] [Accepted: 10/04/2019] [Indexed: 11/26/2022] Open
Abstract
Purpose To study the change of concentrations of vascular endothelial growth factor (VEGF) in vitreous cavity after vitrectomy in eyes with proliferative diabetic retinopathy (PDR). Methods In this retrospective study, intravitreal fluid samples were taken at baseline (beginning of the vitrectomy) and postoperatively (several days later after vitrectomy) at the time of prophylactic injection of bevacizumab in forty-eight eyes of forty-eight patients with PDR. Postvitrectomy fluid samples were divided into four groups according to the time interval between the vitrectomy and the injection (group 1, 3–5 days; group 2, 6–10 days; group 3, 11–15 days; group 4, 16–21 days; twelve eyes in each group). Postvitrectomy fluid sample was paired with baseline sample for each eye. VEGF concentrations in the samples were determined by enzyme-linked immunosorbent assay. Recurrent vitreous hemorrhage and neovascular glaucoma within six months postvitrectomy were also analyzed. Results Overall, the intravitreal VEGF level after vitrectomy (median, 36.95 pg/ml; range, 3.2–1,299.4 pg/ml) was significantly less than the VEGF level at baseline (median, 704.5 pg/ml; range, 30.6–1,981.1 pg/ml). Postoperative and baseline VEGF levels were significantly correlated (r = 0.499, p < 0.01). Both the absolute value of postoperative VEGF concentrations and the postop/baseline VEGF ratios declined with time and dramatically decreased in groups 3 and 4. In only two eyes, the postoperative VEGF level was even higher than the baseline VEGF level (postop/baseline VEGF ratio >1), and recurrent vitreous hemorrhage developed within six months in these two eyes. Conclusions After vitrectomy for PDR, intravitreal VEGF levels decreased substantially in the majority of patients, while persistent high-VEGF level occurred in a few individuals. Postoperative VEGF levels and postop/baseline VEGF ratio declined with time. The postop/preop VEGF ratio may serve as a predictor for late complications.
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Luaces-Rodríguez A, Mondelo-García C, Zarra-Ferro I, González-Barcia M, Aguiar P, Fernández-Ferreiro A, Otero-Espinar FJ. Intravitreal anti-VEGF drug delivery systems for age-related macular degeneration. Int J Pharm 2019; 573:118767. [PMID: 31669558 DOI: 10.1016/j.ijpharm.2019.118767] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 10/03/2019] [Accepted: 10/04/2019] [Indexed: 01/07/2023]
Abstract
Age-related macular degeneration is the most common cause of vision loss in elderly people in developed countries. Nowadays, in clinical practice, three anti-VEGF drugs are commonly used (bevacizumab, aflibercept and ranibizumab), requiring repeated intravitreal injections. In order to minimise the number of injections, research on intravitreal drug delivery systems (DDSs) is needed. In this review, the DDSs developed up to date regarding intravitreal anti-VEGF drugs have been summarised, which include systems as hydrogels, liposomes, microparticles, nanoparticles or implants. Most of the studies have focused on the extended in vitro release behaviour of the developed DDSs, but data as antibody bioactivity, biocompatibility or in vivo stability is sometimes scarce. Moreover, as DDS development relies on in vivo pharmacokinetic analyses to evaluate the extended drug release, all the information regarding anti-VEGF intravitreal pharmacokinetics in different animal species have been compiled.
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Affiliation(s)
- Andrea Luaces-Rodríguez
- Pharmacology, Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela, Spain; Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
| | - Cristina Mondelo-García
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
| | - Irene Zarra-Ferro
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
| | - Miguel González-Barcia
- Pharmacology, Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela, Spain; Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain
| | - Pablo Aguiar
- Nuclear Medicine Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain; Molecular Imaging Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain
| | - Anxo Fernández-Ferreiro
- Pharmacology, Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela, Spain; Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain; Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), Santiago de Compostela, Spain.
| | - Francisco J Otero-Espinar
- Pharmacology, Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Santiago de Compostela, Spain; Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), Santiago de Compostela, Spain.
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Kim RY, Kwon S, Ra H. Gravity influences bevacizumab distribution in an undisturbed balanced salt solution in vitro. PLoS One 2019; 14:e0223418. [PMID: 31584989 PMCID: PMC6777774 DOI: 10.1371/journal.pone.0223418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 09/21/2019] [Indexed: 11/19/2022] Open
Abstract
PURPOSE The effects of gravity on bevacizumab or the recommended head position after intraocular bevacizumab injection have not been reported. To evaluate the effect of gravity on bevacizumab in vitro, we added bevacizumab to the upper part of a test tube filled with balanced salt solution (BSS) and examined its distribution over time. MATERIALS AND METHODS Sixty-four test tubes were divided equally into two groups; group 1 (32, collected from upper part of the tube) and group 2 (32, collected from lower part of the tube). Each test tube was filled with 5 mL BSS before bevacizumab (1.25 mg/0.05 mL) was added, and then stored at 36°C. Bevacizumab concentration in 8 test tubes from each group was measured at 12, 24, 48, and 168 h using an enzyme-linked immunosorbent analysis (ELISA) kit. Mann-Whitney and Jonckheere-Terpstra tests were used for statistical analysis. RESULTS Bevacizumab concentration was significantly higher in Group 2 than in Group 1 at 12, 24, 48, and 168 h (12, 24, 48, and 168 h; P < 0.01 each; Mann-Whitney test). The mean change in bevacizumab concentration over time tended to increase in Group 1 (P < 0.01; Jonckheere-Terpstra test), but tended to decrease in Group 2 (P < 0.01; Jonckheere-Terpstra test). CONCLUSIONS The significant differences in concentration between the upper and lower parts even after a considerable amount of storage time showed that bevacizumab did not dissolve immediately and diffused evenly throughout the solution. It appeared that more bevacizumab settled in the lower part of the tube than in the upper part because of gravitational force. However, the concentration difference between the upper and lower parts decreased as bevacizumab gradually diffused over time, indicating that the difference in concentration due to gravity was more significant at the beginning of bevacizumab injection.
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Affiliation(s)
- Rae Young Kim
- Department of Ophthalmology & Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soonil Kwon
- Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
- * E-mail: (HR); (SK)
| | - Ho Ra
- Department of Ophthalmology & Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- * E-mail: (HR); (SK)
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Badiee P, Varshochian R, Rafiee-Tehrani M, Abedin Dorkoosh F, Khoshayand MR, Dinarvand R. Ocular implant containing bevacizumab-loaded chitosan nanoparticles intended for choroidal neovascularization treatment. J Biomed Mater Res A 2019; 106:2261-2271. [PMID: 29637733 DOI: 10.1002/jbm.a.36424] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 03/20/2018] [Accepted: 03/28/2018] [Indexed: 12/20/2022]
Abstract
Choroidal neovascularization (CNV) is among the leading causes of blindness worldwide. Bevacizumab has demonstrated promising effects on CNV treatment; however, frequent intravitreal injection is its major drawback. Current study aimed to address this issue by developing a sustained release formulation through nanoparticles of bevacizumab imbedded in an ocular implant. Bevacizumab-loaded chitosan nanoparticles were prepared by ionic gelation method and inserted in the matrix of hyaluronic acid and zinc sulfate. Despite the common approaches in using ultraviolet (UV)-spectrophotometry, microprotein-Bradford, and bicinchoninic acid (BCA), assay for protein assessment, our results revealed a remarkable UV-Vis absorption overlap of protein and chitosan during these analysis and thus enzyme-linked immunosorbent assay was employed for the antibody concentration assay. The size of optimized nanoparticles obtained through statistical analysis based on design of experiments was 78.5 ± 1.9 nm with polydispersity index of 0.13 ± 0.05 and the entrapment-efficiency and loading-efficiency were 67.6 ± 6.7 and 15.7 ± 5.7%, respectively. The scanning electron microscopy and confocal microscopy images revealed a homogenous distribution of nanoparticles in the implant matrix and the release test results indicated an appropriate extended release of bevacizumab from the carrier over two months. In conclusion, the prepared system provided a sustained release bevacizumab delivery formulation which can introduce a promising ocular drug delivery system intended for posterior segment disease. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2261-2271, 2018.
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Affiliation(s)
- Parisa Badiee
- Department of pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Reyhaneh Varshochian
- Department of pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.,Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Morteza Rafiee-Tehrani
- Department of pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.,Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Farid Abedin Dorkoosh
- Department of pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Mohammad Reza Khoshayand
- Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
| | - Rassoul Dinarvand
- Department of pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran.,Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 1417614411, Iran
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Heikkinen EM, Auriola S, Ranta VP, Demarais NJ, Grey AC, Del Amo EM, Toropainen E, Vellonen KS, Urtti A, Ruponen M. Distribution of Small Molecular Weight Drugs into the Porcine Lens: Studies on Imaging Mass Spectrometry, Partition Coefficients, and Implications in Ocular Pharmacokinetics. Mol Pharm 2019; 16:3968-3976. [PMID: 31348666 PMCID: PMC6748671 DOI: 10.1021/acs.molpharmaceut.9b00585] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Lens is the avascular tissue in the eye between the aqueous humor and vitreous. Drug binding to the lens might affect ocular pharmacokinetics, and the binding may also have a pharmacological role in drug-induced cataract and cataract treatment. Drug distribution in the lens has been studied in vitro with many compounds; however, the experimental methods vary, no detailed information on distribution between the lens sublayers exist, and the partition coefficients are reported rarely. Therefore, our objectives were to clarify drug localization in the lens layers and establish partition coefficients for a wide range of molecules. Furthermore, we aimed to illustrate the effect of lenticular drug binding on overall ocular drug pharmacokinetics. We studied the distribution of 16 drugs and three fluorescent dyes in whole porcine lenses in vitro with imaging mass spectrometry and fluorescence microscopy techniques. Furthermore, we determined lens/buffer partition coefficients with the same experimental setup for 28 drugs with mass spectrometry. Finally, the effect of lenticular binding of drugs on aqueous humor drug exposure was explored with pharmacokinetic simulations. After 4 h, the drugs and the dyes distributed only to the outermost lens layers (capsule and cortex). The lens/buffer partition coefficients for the drugs were low, ranging from 0.05 to 0.8. On the basis of the pharmacokinetic simulations, a high lens-aqueous humor partition coefficient increases drug exposure in the lens but does not significantly alter the pharmacokinetics in the aqueous humor. To conclude, the lens seems to act mainly as a physical barrier for drug distribution in the eye, and drug binding to the lens affects mainly the drug pharmacokinetics in the lens.
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Affiliation(s)
| | | | | | - Nicholas J Demarais
- School of Biological Sciences , University of Auckland , Private Bag 92019 , Auckland 1142 , New Zealand
| | - Angus C Grey
- University of Auckland , School of Medical Sciences, Department of Physiology , Private Bag 92019 , Auckland 1142 , New Zealand
| | - Eva M Del Amo
- School of Health Sciences, Division of Pharmacy & Optometry , University of Manchester , Oxford Road , Manchester M13 9PL , U.K
| | | | | | - Arto Urtti
- Faculty of Pharmacy, Division of Pharmaceutical Biosciences , University of Helsinki , Viikinkaari, Helsinki 00014 , Finland.,Institute of Chemistry , Saint Petersburg State University , 26 Universitetskii Prospect , Saint Petersburg 198504 , Russia
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García-Quintanilla L, Luaces-Rodríguez A, Gil-Martínez M, Mondelo-García C, Maroñas O, Mangas-Sanjuan V, González-Barcia M, Zarra-Ferro I, Aguiar P, Otero-Espinar FJ, Fernández-Ferreiro A. Pharmacokinetics of Intravitreal Anti-VEGF Drugs in Age-Related Macular Degeneration. Pharmaceutics 2019; 11:pharmaceutics11080365. [PMID: 31370346 PMCID: PMC6723750 DOI: 10.3390/pharmaceutics11080365] [Citation(s) in RCA: 101] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 07/20/2019] [Accepted: 07/22/2019] [Indexed: 12/27/2022] Open
Abstract
Intravitreal administration of anti-vascular endothelial growth factor (VEGF) antibodies has become the standard treatment for Age-Related Macular Degeneration; however, the knowledge of their pharmacokinetics is limited. A comprehensive review of the preclinical and clinical pharmacokinetic data that were obtained in different studies with intravitreal bevacizumab, ranibizumab, and aflibercept has been conducted. Moreover, the factors that can influence the vitreous pharmacokinetics of these drugs, as well as the methods that were used in the studies for analytical determination, have been exposed. These anti-VEGF drugs present different charge and molecular weights, which play an important role in vitreous distribution and elimination. The pharmacokinetic parameters that were collected differ depending on the species that were involved in the studies and on physiological and pathological conditions, such as vitrectomy and lensectomy. Knowledge of the intravitreal pharmacokinetics of the anti-VEGF drugs that were used in clinical practice is of vital importance.
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Affiliation(s)
- Laura García-Quintanilla
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
| | - Andrea Luaces-Rodríguez
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain
| | - María Gil-Martínez
- Ophthalmology Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
| | - Cristina Mondelo-García
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
| | - Olalla Maroñas
- Genomic Medicine Group, Galician Public Foundation of Genomic Medicine, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
| | - Víctor Mangas-Sanjuan
- Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, 46100 Valencia, Spain
- Interuniversity Research Institute for Molecular Recognition and Technological Development, Polytechnic University of Valencia, 46100 Valencia, Spain
| | - Miguel González-Barcia
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
| | - Irene Zarra-Ferro
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
| | - Pablo Aguiar
- Nuclear Medicine Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
- Molecular Imaging Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain
| | - Francisco J Otero-Espinar
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain.
| | - Anxo Fernández-Ferreiro
- Pharmacy Department, University Clinical Hospital of Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain.
- Pharmacology Group, Health Research Institute of Santiago de Compostela (FIDIS), 15706 Santiago de Compostela, Spain.
- Department of Pharmacology, Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Santiago de Compostela (USC), 15782 Santiago de Compostela, Spain.
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Kimura S, Morizane Y, Hosokawa MM, Shiode Y, Doi S, Hosogi M, Fujiwara A, Okanouchi T, Inoue Y, Shiraga F. Outcomes of vitrectomy combined with subretinal tissue plasminogen activator injection for submacular hemorrhage associated with polypoidal choroidal vasculopathy. Jpn J Ophthalmol 2019; 63:382-388. [PMID: 31243593 DOI: 10.1007/s10384-019-00679-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2018] [Accepted: 05/16/2019] [Indexed: 10/26/2022]
Abstract
PURPOSE To examine the outcomes of vitrectomy with subretinal tissue plasminogen activator (tPA) injection and postoperative intravitreal antivascular endothelial growth factor (VEGF) injection for submacular hemorrhage (SMH) associated with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN Retrospective, consecutive case series. METHODS Patients who underwent vitrectomy for SMH associated with PCV and who were followed up for at least 12 months were included. Surgery consisted of vitrectomy with subretinal tPA and air tamponade. Postoperative intravitreal anti-VEGF was administered pro re nata. The following were examined: best-corrected visual acuity (BCVA) at baseline, at 1 month, and at the final visit; the percentage of patients requiring anti-VEGF postoperatively; and the number of injections administered. RESULTS This study included 23 eyes of 23 patients (21 men, 2 women) with a mean age of 72.5 ± 9.0 years. The mean duration from disease onset to surgery was 9.0 ± 6.6 days. The mean maximum SMH size was 5.8 ± 4.8 disc diameters. The mean follow-up period was 33 ± 14 months. The BCVA was significantly improved when compared with baseline 1 month after surgery and at the final visit. Postoperative anti-VEGF was required for 91% of the eyes. In eyes that underwent anti-VEGF therapy until the final visit, the mean injection number was 4.1/year. CONCLUSIONS Vitrectomy with subretinal tPA and air tamponade improved visual acuity in patients with SMH associated with PCV. Postoperative intravitreal anti-VEGF injection maintained the improved BCVA throughout a mean period of 33 months.
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Affiliation(s)
- Shuhei Kimura
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Yuki Morizane
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
| | - Mio Morizane Hosokawa
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Yusuke Shiode
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Shinichiro Doi
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Mika Hosogi
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Atsushi Fujiwara
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | | | | | - Fumio Shiraga
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
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Nossair AA, Ewais WA, Eissa SA. Chandelier-assisted scleral buckling using wide angle viewing contact lens for pseudophakic retinal detachment repair. Int J Ophthalmol 2019; 12:627-633. [PMID: 31024818 DOI: 10.18240/ijo.2019.04.17] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2018] [Accepted: 11/07/2018] [Indexed: 11/23/2022] Open
Abstract
AIM To evaluate a modified technique for scleral buckling (SB) in pseudophakic retinal detachment (RD). METHODS A retrospective non-comparative study included 21 consecutive eyes with uncomplicated pseudophakic RD that was repaired by chandelier assisted SB using wide angle viewing (WAV) contact lens. Segmental tire alone was used in 5 eyes (23.81%), and combined with encircling band in 7 eyes (33.33%). Radial sponge alone was used in 3 eyes (14.29%) and combined with encircling band in 6 eyes (28.57%). RESULTS Primary success rate was (90.48%). External drainage of subretinal fluid was performed in 8 eyes (38.1%). Intraoperative complications included vitreous prolapse at chandelier sclerotomy site in 4 eyes (19.05%) and localized subretinal hemorrhage at drainage site in one eye (4.76%). No case of intraocular lens (IOL) displacement, retinal incarceration or iatrogenic retinal tear was detected. Postoperative complications included choroidal detachment in one eye (4.76%), elevated intraocular pressure in 2 eyes (9.52%), epiretinal membrane formation in one eye (4.76%) and proliferative vitreoretinopathy in 3 eyes (14.29%). Mean postoperative corrected distance visual acuity was 0.7±0.3 logMAR units. CONCLUSION Chandelier-assisted SB using WAV contact lens is a reliable technique for repairing selected cases of simple pseudophakic RD.
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Affiliation(s)
- Ashraf Ahmed Nossair
- Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.,Dar El Oyoun Hospital, Dokki, Giza 1261, Egypt
| | - Wael Ahmed Ewais
- Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.,Dar El Oyoun Hospital, Dokki, Giza 1261, Egypt
| | - Sherif Ahmed Eissa
- Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
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Gonzalez-De la Rosa A, Navarro-Partida J, Altamirano-Vallejo JC, Hernandez-Gamez AG, Garcia-Bañuelos JJ, Armendariz-Borunda J, Santos A. Novel Triamcinolone Acetonide-Loaded Liposomes Topical Formulation for the Treatment of Cystoid Macular Edema After Cataract Surgery: A Pilot Study. J Ocul Pharmacol Ther 2019; 35:106-115. [PMID: 30614750 PMCID: PMC6450453 DOI: 10.1089/jop.2018.0101] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Purpose: To report tolerability, safety, and efficacy of a topical triamcinolone acetonide-loaded liposomes formulation (TA-LF) in targeting the macular area in patients with refractory pseudophakic cystoid macular edema (PCME). Methods: For tolerability, safety and efficacy evaluation, 12 eyes of 12 patients with refractory PCME were exposed to one drop of TA-LF (TA at 0.2%) every 2 h for 90 days or until best-corrected visual acuity (BCVA) was achieved. Intraocular pressure (IOP), slit lamp examination, and central foveal thickness (CFT) were analyzed at every visit. Results: Patients with refractory PCME under TA-LF therapy showed a significant improvement in BVCA and CFT without significant IOP modification (P = 0.94). On average CFT decreased to 206.75 ± 135.72 μm and BCVA improved to 20.08 ± 10.35 letters (P < 0.0005). BCVA was achieved at 10.58 ± 6.70 weeks (range 2–18). TA-LF was well tolerated in all cases. Neither ocular surface abnormalities nor adverse events were recorded. Conclusion: TA-LF was well tolerated and improved BCVA and CFT on patients with refractory PCME.
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Affiliation(s)
- Alejandro Gonzalez-De la Rosa
- 1 Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Zapopan, México.,2 Centro de Retina Medica y Quirúrgica, S.C., Centro Medico Puerta de Hierro. Zapopan, Jalisco, México
| | - Jose Navarro-Partida
- 1 Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Zapopan, México.,2 Centro de Retina Medica y Quirúrgica, S.C., Centro Medico Puerta de Hierro. Zapopan, Jalisco, México
| | - Juan Carlos Altamirano-Vallejo
- 1 Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Zapopan, México.,2 Centro de Retina Medica y Quirúrgica, S.C., Centro Medico Puerta de Hierro. Zapopan, Jalisco, México
| | | | - Jesus Javier Garcia-Bañuelos
- 4 Instituto de Biología Molecular y Terapia Génica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, México
| | | | - Arturo Santos
- 1 Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Zapopan, México.,2 Centro de Retina Medica y Quirúrgica, S.C., Centro Medico Puerta de Hierro. Zapopan, Jalisco, México
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Modified Vitrectomy Technique for Phakic Rhegmatogenous Retinal Detachment with Intermediate Break. J Ophthalmol 2018; 2018:6127932. [PMID: 30425854 PMCID: PMC6218725 DOI: 10.1155/2018/6127932] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 09/06/2018] [Accepted: 10/01/2018] [Indexed: 11/17/2022] Open
Abstract
Purpose To evaluate the effects of a modification of the traditional 25-gauge pars plana vitrectomy technique in the treatment of uncomplicated macula-on rhegmatogenous retinal detachment (RRD) with intermediate retinal break(s) and marked vitreous traction in the phakic eye. Methods Prospective, noncomparative, and interventional case series. All consecutive phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, with at least 1 year of postoperative follow-up, were enrolled. In all eyes, "localized 25-gauge vitrectomy" under air infusion with localized removal of the vitreous surrounding the retinal break(s), in association with laser photocoagulation and air tamponade, was performed. The primary end point was the rate of primary retinal attachment. Secondary end points were cataract progression and assessed by digital Scheimpflug lens photography (mean change of nuclear density units) and the rate of complications. Results Thirty-two phakic eyes were included in the final analysis. At 12 months, the primary outcome of anatomical success was achieved in 94% of eyes. The mean nuclear density units did not change significantly at any time point during the follow-up. After localized vitrectomy, one eye developed an epiretinal membrane, and one eye developed cystoid macular edema; no other significant complications were reported. Conclusions "Localized vitrectomy" has a high anatomical success rate in phakic eyes with primary uncomplicated macula-on RRD with intermediate retinal break(s) and marked vitreous traction, without causing progression of cataract.
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Bastakis GG, Dimopoulos D, Stavrakakis A, Pappas G. Long-term efficacy and duration of action of dexamethasone implant, in vitrectomised and non-vitrectomised eyes with persistent diabetic macular oedema. Eye (Lond) 2018; 33:411-418. [PMID: 30302004 DOI: 10.1038/s41433-018-0219-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 08/04/2018] [Accepted: 08/16/2018] [Indexed: 11/09/2022] Open
Abstract
PURPOSE To evaluate the efficacy and duration of action of an intravitreal (dexamethasone (Ozurdex)) implant in vitrectomised and non-vitrectomised eyes with persistent diabetic macular oedema (DMO). METHODS We retrospectively analysed the records for 18 eyes that had or had not been vitrectomised but required an intravitreal dexamethasone implant for DMO after a poor response to anti-vascular endothelial growth factor. Optical coherence tomography and visual acuity (VA) examinations were performed before and 1, 3 and 6 months after implantation. The six months following implantation constituted one treatment round; up to three rounds were studied. RESULTS Ten of 18 eyes had undergone vitrectomy. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were significantly improved by months 1-3 after implantation of the Ozurdex device in all rounds of treatment. The BCVA and CMT deteriorated gradually after month 3 through to month 6 post implantation. There were no statistically significant differences between the vitrectomised and non-vitrectomised groups at any time point. When the implantation interval was <6 weeks from the end of each treatment round, the improvement in BCVA and CMT was obvious even after 18 months of treatment. CONCLUSIONS Vitrectomy did not have a negative effect on the duration of action or efficacy of the Ozurdex implant in patients with persistent DMO. The implant started working from the first month after implantation regardless of whether vitrectomy had or had not been performed. The maximum functional and anatomic improvement was achieved in the first 3 months post implantation in all treatment rounds.
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Affiliation(s)
- George G Bastakis
- Ophthalmology Clinic, Medical Retina & Vitreoretinal Surgery Department, Venizeleio Hospital of Crete, Knossos avenue 44, Crete, 71409,, Heraklion, Greece
| | - Dimitris Dimopoulos
- Ophthalmology Clinic, Medical Retina & Vitreoretinal Surgery Department, Venizeleio Hospital of Crete, Knossos avenue 44, Crete, 71409,, Heraklion, Greece
| | - Anastasios Stavrakakis
- Ophthalmology Clinic, Medical Retina & Vitreoretinal Surgery Department, Venizeleio Hospital of Crete, Knossos avenue 44, Crete, 71409,, Heraklion, Greece
| | - George Pappas
- Ophthalmology Clinic, Medical Retina & Vitreoretinal Surgery Department, Venizeleio Hospital of Crete, Knossos avenue 44, Crete, 71409,, Heraklion, Greece.
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Papastefanou VP, Dooley I, Zambarakji H. Management of macular edema in vitrectomized patients with diabetes. EXPERT REVIEW OF OPHTHALMOLOGY 2018. [DOI: 10.1080/17469899.2018.1465819] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Vasilios P. Papastefanou
- Ophthalmology Service, Whipps Cross University Hospital, Barts Health NHS Trust, E1 1NR, London, UK
| | - Ian Dooley
- Ophthalmology Service, Whipps Cross University Hospital, Barts Health NHS Trust, E1 1NR, London, UK
| | - Hadi Zambarakji
- Ophthalmology Service, Whipps Cross University Hospital, Barts Health NHS Trust, E1 1NR, London, UK
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Hirata A, Hayashi K, Murata K, Nakamura KI. Removal of choroidal neovascular membrane in a case of macular hole after anti-VEGF therapy for age-related macular degeneration. Am J Ophthalmol Case Rep 2017; 9:14-17. [PMID: 29468210 PMCID: PMC5786856 DOI: 10.1016/j.ajoc.2017.12.003] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2017] [Revised: 11/03/2017] [Accepted: 12/14/2017] [Indexed: 11/18/2022] Open
Abstract
Purpose The formation of macular hole after receiving anti-vascular endothelial growth factor (anti-VEGF) therapy is rare. We report a case of macular hole that occurred after intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD) in a patient, who underwent vitrectomy combined with choroidal neovascularization (CNV) removal. Observations A 64-year-old female with AMD affecting her right eye received an intravitreal injection of an anti-VEGF agent. After treatment, we identified a full thickness macular hole (MH) that was associated with the rapid resolution of the macular edema and contraction of the CNV. After performing vitrectomy combined with CNV removal, the MH closed and her visual acuity improved. Examination of the removed CNV revealed a network of microvessels devoid of pericytes. Conclusions and importance The present findings suggest that rapid resolution of macular edema and contraction of the CNV and/or mild increase in the vitreous traction after anti-VEGF therapy could potentially cause MH. CNV removal via the MH may be an acceptable procedure, if the MH remains open, the CNV is of the classic type, and it spares a central portion of the fovea.
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Affiliation(s)
- Akira Hirata
- Hayashi Eye Hospital, Fukuoka, Japan
- Division of Microscopic and Developmental Anatomy, Department of Anatomy, Kurume University School of Medicine, Kurume, Japan
- Corresponding author. Hayashi Eye Hospital, 4-23-35, Hakataekimae, Fukuoka 812-0011, Japan.Hayashi Eye Hospital4-23-35, HakataekimaeFukuoka812-0011Japan
| | | | - Kazuhisa Murata
- Department of Ophthalmology, Saga University Faculty of Medicine, Saga, Japan
| | - Kei-ichiro Nakamura
- Division of Microscopic and Developmental Anatomy, Department of Anatomy, Kurume University School of Medicine, Kurume, Japan
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Edington M, Connolly J, Chong NV. Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized versus non-vitrectomized eyes. Expert Opin Drug Metab Toxicol 2017; 13:1217-1224. [DOI: 10.1080/17425255.2017.1404987] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Magdalena Edington
- Department of Ophthalmology, University of Oxford, Oxford, UK
- Department of Ophthalmology, Tennent Institute of Ophthalmology, Glasgow, UK
| | - Julie Connolly
- Department of Ophthalmology, Tennent Institute of Ophthalmology, Glasgow, UK
| | - Ngaihang Victor Chong
- Department of Ophthalmology, University of Oxford, Oxford, UK
- Department of Ophthalmology, Royal Free Hospital, London, UK
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Kimura S, Morizane Y, Matoba R, Hosokawa M, Shiode Y, Hirano M, Doi S, Toshima S, Takahashi K, Hosogi M, Fujiwara A, Shiraga F. Retinal sensitivity after displacement of submacular hemorrhage due to polypoidal choroidal vasculopathy: effectiveness and safety of subretinal tissue plasminogen activator. Jpn J Ophthalmol 2017; 61:472-478. [PMID: 28836011 DOI: 10.1007/s10384-017-0530-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 06/15/2017] [Indexed: 11/30/2022]
Abstract
PURPOSE To investigate the effectiveness of displacement of submacular hemorrhage (SMH) caused by polypoidal choroidal vasculopathy (PCV) by assessing retinal sensitivity using microperimetry. METHODS We retrospectively reviewed the medical records of 11 consecutive PCV patients with SMH. All patients underwent vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-air exchange, followed by antivascular endothelial growth factor therapy using a pro re nata regimen. The retinal sensitivity was measured by use of microperimetry before and after surgery. RESULTS The mean (SD) age of the patients was 74.1 ± 9.4 years. The mean SMH diameter was 6.8 ± 5.2 disc diameters. The best-corrected visual acuity (BCVA), mean retinal sensitivity, and mean number of measure points with a sensitivity ≥10 dB before the surgery were 0.94 ± 0.49, 4.2 ± 4.5 dB, and 15.6 ± 15.1 points, respectively. These had significantly improved 6 months after surgery (0.39 ± 0.37, 15.6 ± 7.3 dB, and 50.9 ± 22.2 points, respectively; P < 0.05 for all outcome measures). The mean number of measure points with an absolute scotoma before surgery had decreased significantly 6 months after surgery (from 40.5 ± 15.0 to 9.4 ± 16.0 points; P < 0.001). CONCLUSIONS Displacement of SMH effectively improves retinal sensitivity as well as BCVA.
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Affiliation(s)
- Shuhei Kimura
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Yuki Morizane
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
| | - Ryo Matoba
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Mio Hosokawa
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Yusuke Shiode
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Masayuki Hirano
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Shinichiro Doi
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Shinji Toshima
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Kosuke Takahashi
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Mika Hosogi
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Atsushi Fujiwara
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Fumio Shiraga
- Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
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Intravitreal Aflibercept for Patients With Diabetic Macular Edema Refractory to Bevacizumab or Ranibizumab: Analysis of Response to Aflibercept. Asia Pac J Ophthalmol (Phila) 2017; 6:250-255. [PMID: 28436640 DOI: 10.22608/apo.2016186] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
PURPOSE To investigate the short-term efficacy and safety of intravitreal aflibercept in a case series of patients with diabetic macular edema (DME) refractory to ranibizumab or bevacizumab. DESIGN A retrospective chart review. METHODS From September 2013 to March 2016, we identified patients with DME who developed resistance to bevacizumab or ranibizumab. Three monthly intravitreal aflibercept injections were administered in refractory cases. Nonresponse to aflibercept was defined as a paradoxical increase in central foveal thickness (CFT) and gain in best-corrected visual acuity (BCVA) of less than 1 line at 1 month after treatment compared with before aflibercept administration. RESULTS Out of a total of 72 eyes in 72 refractory patients, 42 eyes (58.3%) responded to aflibercept injections. The BCVA and CFT were 0.65 ± 0.32 logMAR and 438.5 ± 80.1 μm, respectively, before aflibercept treatment and significantly improved to 0.31 ± 0.17 logMAR (P = 0.0008) and 297.9 ± 19.1 μm (P = 0.0004), respectively, 1 month after 3 aflibercept injections in responders. No differences in baseline characteristics, including age, sex, glycosylated hemoglobin, serum creatinine, total cholesterol, lens status, grades of diabetic retinopathy, and CFT/BCVA before aflibercept management (P > 0.05), were observed between responders and nonresponders. There were 17 vitrectomized eyes in 30 nonresponders (56.7%), a significantly higher rate than among the 42 responders (0%; P = 0.00001). CONCLUSIONS Three monthly intravitreal aflibercept injections had benefit in nearly two thirds of cases with DME resistant to bevacizumab or ranibizumab over short-term follow-up. Vitrectomized eyes responded poorly to aflibercept treatment.
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Chen YY, Chen PY, Chen FT, Chen YJ, Wang JK. Comparison of efficacy of intravitreal ranibizumab between non-vitrectomized and vitrectomized eyes with diabetic macular edema. Int Ophthalmol 2017; 38:293-299. [DOI: 10.1007/s10792-017-0462-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 01/31/2017] [Indexed: 01/21/2023]
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Laugesen CS, Ostri C, Brynskov T, Lund-Andersen H, Larsen M, Vorum H, Sørensen TL. Intravitreal ranibizumab for diabetic macular oedema in previously vitrectomized eyes. Acta Ophthalmol 2017; 95:28-32. [PMID: 27473397 DOI: 10.1111/aos.13160] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Accepted: 05/10/2016] [Indexed: 02/06/2023]
Abstract
PURPOSE There is little information about the efficacy of intravitreal vascular endothelial growth factor (VEGF) inhibition in vitrectomized eyes. This study aimed to evaluate the efficacy of anti-VEGF (ranibizumab) on diabetic macular oedema in previously vitrectomized eyes. METHODS A nationwide retrospective review of medical records from 2010 to 2013. RESULTS We identified 33 previously vitrectomized eyes in 28 patients treated with ranibizumab injections for diabetic macular oedema. Median follow-up was 323 days (interquartile range 72-1404 days). Baseline mean visual acuity was 0.57 logMAR (95% CI 0.13-1.01) before injections. After an average of 4.7 injections (range 1-15), mean visual acuity remained stable at 0.54 logMAR (95% CI 0.13-0.95) with a mean improvement of 0.03 (p = 0. 45, 95% CI -0.12 to 0.06). In 12 eyes (36%), visual acuity improved 0.1 logMAR or more, in 12 eyes (36%), vision was unchanged (gain or loss of 0-0.05 logMAR), and in nine eyes (27%), vision decreased 0.1 logMAR or more. Mean central foveal thickness (CFT) on optical coherence tomography (OCT) scan was 412 μm (95% CI 390-434 μm) before injections. After injections, the mean CFT decreased to 352 μm (95% CI 334-370 μm). The mean reduction in CFT was 14% (95% CI 4-24%, p = 0.01). Sixteen eyes (48.5%) became devoid of oedema on the last OCT scan. Despite the significant reduction in CFT, the visual acuity remained unchanged. CONCLUSION Intravitreal ranibizumab can be effective in previously vitrectomized eyes with diabetic macular oedema. However, the response is variable and should be carefully monitored.
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Affiliation(s)
| | - Christoffer Ostri
- Department of Ophthalmology; Rigshospitalet - Glostrup Hospital; Glostrup Denmark
| | - Troels Brynskov
- Department of Ophthalmology; Zealand University Hospital; Roskilde Denmark
- Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
| | - Henrik Lund-Andersen
- Department of Ophthalmology; Rigshospitalet - Glostrup Hospital; Glostrup Denmark
- Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
| | - Michael Larsen
- Department of Ophthalmology; Rigshospitalet - Glostrup Hospital; Glostrup Denmark
- Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
| | - Henrik Vorum
- Department of Ophthalmology; Aalborg University Hospital; Aalborg Denmark
| | - Torben L. Sørensen
- Department of Ophthalmology; Zealand University Hospital; Roskilde Denmark
- Faculty of Health and Medical Sciences; University of Copenhagen; Copenhagen Denmark
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Twelve-Month Follow-Up of Dexamethasone Implants for Macular Edema from Various Diseases in Vitrectomized and Nonvitrectomized Eyes. J Ophthalmol 2016; 2016:7984576. [PMID: 27721989 PMCID: PMC5046017 DOI: 10.1155/2016/7984576] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Accepted: 08/28/2016] [Indexed: 12/02/2022] Open
Abstract
Purpose. To evaluate the best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the number of dexamethasone implants needed to treat cystoid macular edema (CME) from various etiologies over 12 months in vitrectomized and nonvitrectomized eyes. Methods. This multicenter retrospective cohort study included 112 patients with CME secondary to retinal diseases treated pro re nata (PRN) with a 0.7 mg intravitreal dexamethasone implant for 12 months. The BCVA, CRT, adverse events, safety data, and number of implants were recorded. Results. Vitrectomized and nonvitrectomized eyes received means of three implants and one implant, respectively, over 12 months (P < 0.001). The mean BCVA of all patients improved from 0.13 at baseline to 0.33 (P < 0.001) 12 months after one (P = 0.001), two (P = 0.041), and three (P < 0.001) implants but not four implants (P = 0.068). The mean baseline CRT decreased significantly (P < 0.001) from 463 to 254 microns after 12 months with one (P < 0.001), two (P = 0.002), and three (P = 0.001) implants but not with four implants (P = 0.114). The anatomic and functional outcomes were not significantly different between vitrectomized and nonvitrectomized eyes. Increased IOP was the most common adverse event (23.2%). Conclusions. Dexamethasone implant administered PRN improved VA and decreased CRT in CME, with possible long-term clinically relevant benefits for treating CME from various etiologies. Vitrectomized eyes needed more implants compared with nonvitrectomized eyes.
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50
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Lin CJ, Tsai YY. Axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for retinopathy of prematurity. Clin Ophthalmol 2016; 10:1323-7. [PMID: 27499611 PMCID: PMC4959583 DOI: 10.2147/opth.s110717] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Purpose The purpose of this study was to report on the axial length, refraction, and retinal vascularization 1 year after ranibizumab or bevacizumab treatment for threshold retinopathy of prematurity. Methods The authors conducted a comparative, consecutive, original study. Results Twenty-five eyes of 13 patients with threshold retinopathy of prematurity received one intravitreal ranibizumab treatment, and 15 eyes of eight patients received one intravitreal bevacizumab treatment. In the ranibizumab group, the mean gestational age was 26.15±2.08 weeks, with a mean birth weight of 811.15±287.3 g. In the bevacizumab group, the mean gestational age was 26.50±2.14 weeks, with a mean birth weight of 938.38±200.4 g. The mean axial length was 20.34±0.97 mm and the mean spherical equivalent was 0.46±1.36 D in the ranibizumab group, with complete vascularization in 15 of 25 (60%) eyes. The mean axial length was 20.91±1.54 mm and the mean spherical equivalent was −0.60±3.86 D in the bevacizumab group, with complete vascularization in seven of 15 (46.7%) eyes. Conclusion There were no significant differences in the axial length and refraction between children with threshold retinopathy of prematurity who received intravitreal bevacizumab compared to those who received ranibizumab after 1 year of follow-up. It appeared that the ranibizumab treatment could achieve more complete retinal vascularization than the bevacizumab treatment; however, there was no statistical significance and long-term follow-up is needed.
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Affiliation(s)
- Chun-Ju Lin
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan
| | - Yi-Yu Tsai
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan
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