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Wang P, Hu Z, Hou M, Norman PA, Chin EK, Almeida DRP. Relationship Between Macular Thickness and Visual Acuity in the Treatment of Diabetic Macular Edema With Anti-VEGF Therapy: Systematic Review. JOURNAL OF VITREORETINAL DISEASES 2022; 7:57-64. [PMID: 37008395 PMCID: PMC9954155 DOI: 10.1177/24741264221138722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Purpose: To examine the relationship between central macular thickness (CMT) measured by optical coherence tomography (OCT) and visual acuity (VA) in patients with center-involving diabetic macular edema (DME) receiving antivascular endothelial growth factor (anti-VEGF) treatment. Methods: Peer-reviewed articles from 2016 to 2020 reporting intravitreal injections of bevacizumab, ranibizumab, or aflibercept that provided data on pretreatment (baseline) and final retinal thickness (CMT) and visual acuity (VA) were identified. The relationship between relative changes was assessed via a linear random-effects regression model controlling for treatment group. Results: No significant association between the logarithm of the minimum angle of resolution (logMAR) VA and CMT was found in 41 eligible studies evaluating 2667 eyes. The observed effect estimate was a 0.12 increase (95% CI, −0.124 to 2.47) in logMAR VA per 100 µm reduction in CMT after treatment change. There were no significant differences in logMAR VA between the anti-VEGF treatment groups. Conclusions: There was no statistically significant relationship between the change in logMAR VA and change in CMT as well as no significant effect of the type of anti-VEGF treatment on the change in logMAR VA. Although OCT analysis, including measurements of CMT, will continue to be an integral part of the management of DME, further exploration is needed on additional anatomic factors that might contribute to visual outcomes.
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Affiliation(s)
- Patrick Wang
- Department of Ophthalmology, Queen’s University, Kingston, ON, Canada
| | - Zoe Hu
- Department of Radiology, Queen’s University, Kingston, ON, Canada
| | - Maggie Hou
- Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | | | - Eric K. Chin
- Retina Consultants of Southern California, Redlands, CA, USA
- Loma Linda University Medical Center, Veterans Affair Hospital, Loma Linda, CA, USA
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Kutlutürk Karagöz I, Allahverdiyev A, Bağırova M, Abamor EŞ, Dinparvar S. Current Approaches in Treatment of Diabetic Retinopathy and Future Perspectives. J Ocul Pharmacol Ther 2020; 36:487-496. [DOI: 10.1089/jop.2019.0137] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Affiliation(s)
- Işıl Kutlutürk Karagöz
- Depatment of Bioengineering, Yıldız Technical University, Istanbul, Turkey
- Department of Ophthalmology, Ümraniye Trn. And Rch. Hospital, Istanbul, Turkey
| | - Adil Allahverdiyev
- Depatment of Bioengineering, Yıldız Technical University, Istanbul, Turkey
| | - Melehat Bağırova
- Depatment of Bioengineering, Yıldız Technical University, Istanbul, Turkey
| | - Emrah Şefik Abamor
- Depatment of Bioengineering, Yıldız Technical University, Istanbul, Turkey
| | - Sahar Dinparvar
- Depatment of Bioengineering, Yıldız Technical University, Istanbul, Turkey
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Jabbarpoor Bonyadi MH, Baghi A, Ramezani A, Yaseri M, Soheilian M. Correlation of Macular Thickness and Visual Acuity in DME Treated by Two Doses of Intravitreal Ziv-Aflibercept Versus Bevacizumab: Analysis of a Randomized, Three-Armed Clinical Trial. Ophthalmic Surg Lasers Imaging Retina 2019; 50:684-690. [PMID: 31755967 DOI: 10.3928/23258160-20191031-03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 03/25/2019] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND OBJECTIVE To report the correlation of central macular thickness (CMT) and best-corrected visual acuity (BCVA) after 1-year treatment by two doses (2.5 mg or 1.25 mg) of intravitreal ziv-aflibercept (IVZ) versus bevacizumab (IVB) in eyes with diabetic macular edema (DME). PATIENTS AND METHODS In this study, the correlation of CMT and BCVA changes of the eyes enrolled in a previous clinical trial of 123 eyes were re-evaluated. The correlation of BCVA and CMT changes at each visit was evaluated in the three study arms individually. Then, the eyes in each of the arms were classified at each follow-up visit into three subgroups based on their CMT changes related to the baseline CMT: CMT decrease of 30% or more of baseline CMT, between 10% to 29% of baseline CMT, and less than 9% of baseline CMT or CMT increase. RESULTS BCVA and CMT changes were correlated significantly (P < .05) in all and in half of the follow-up visits, respectively, in the eyes treated by IVZ 1.25 mg and IVB (r = 0.554 and r = 0.617 at 1 year, respectively). Nevertheless, such a significant correlation was not detected in the eyes treated by IVZ 2.5 mg in any of the follow-up visits (r = 0.202 at 1 year; P = .259). In the IVZ 2.5 mg group, BCVA improvement was observed in all subgroups with each level of CMT reductions. CONCLUSION Ziv-aflibercept 2.5 mg might have a beneficial effect on DME beyond thickness reduction. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:684-690.].
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Xiao K, Weng SJ, Liang SZ, Wang J, Qian C, Wan GM. Effect of Intravitreal Bevacizumab with or without Macular Photocoagulation for Diabetic Macular Edema: A Meta-Analysis. Diabetes Ther 2018; 9:2369-2381. [PMID: 30390227 PMCID: PMC6250618 DOI: 10.1007/s13300-018-0526-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Indexed: 01/08/2023] Open
Abstract
INTRODUCTION In this meta-analysis, we aimed to assess the possible benefits of macular photocoagulation (MPC) as an additional treatment with intravitreal bevacizumab (IVB) in patients with diabetic macular edema. METHODS The studies were identified from three databases: PubMed, Web of Science, and the Cochrane Library. The main outcome measures included change in best-corrected visual acuity (BCVA), differences in central macular thickness (CMT), and adverse events within the follow-up period. The results were pooled using weight mean difference with their corresponding 95% confidence intervals. A fixed or random effects model was employed, depending on the heterogeneity of the inclusion trials. RESULTS Finally, three randomized controlled trial and two high-quality retrospective studies were identified and included. Changes in CMT at 1, 3, and 6 months did not vary significantly between the IVB-alone group and the IVB with MPC group (P = 0.26, 0.06, and 0.65, respectively). Similarly, changes in BCVA at 1, 3, and 6 months also did not vary significantly between the two groups (P = 0.20, 0.91, and 0.70, respectively). Whereas substantial heterogeneity was detected in the CMT results among these studies, the sensitivity analyses showed Solaiman's study was probably the source of the heterogeneity. No publication bias was detected by funnel plots in this study. CONCLUSION Results of this meta-analysis showed that the treatments with IVB alone and combined IVB and MPC were similarly effective in improving BCVA and reducing CMT. However, more evidence is needed to evaluate their effects in the long-term periods.
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Affiliation(s)
- Kang Xiao
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Shi-Jia Weng
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Shen-Zhi Liang
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jiong Wang
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Cheng Qian
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Guang-Ming Wan
- Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
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Neto HO, Regatieri CV, Nobrega MJ, Muccioli C, Casella AM, Andrade RE, Maia M, Kniggendorf V, Ferreira M, Branco AC, Belfort R. Multicenter, Randomized Clinical Trial to Assess the Effectiveness of Intravitreal Injections of Bevacizumab, Triamcinolone, or Their Combination in the Treatment of Diabetic Macular Edema. Ophthalmic Surg Lasers Imaging Retina 2017; 48:734-740. [PMID: 28902334 DOI: 10.3928/23258160-20170829-08] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Accepted: 03/01/2017] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND OBJECTIVE To evaluate the efficacy of combined bevacizumab-triamcinolone intravitreal injection in the treatment of diabetic macular edema (DME) compared to monotherapy. PATIENTS AND METHODS At eight clinical sites, 111 patients with DME were randomly assigned to receive an intravitreal injection of bevacizumab (Avastin; Genentech, South San Francisco, CA), triamcinolone (Ophthalmos Pharmaceutical Industry, São Paulo-SP, Brazil), or their combination. The primary outcome was visual acuity (VA) at 6 months' follow-up. RESULTS The average number of injections was 3.2 in the bevacizumab group, 2.4 in the combined group, and 2.1 in the triamcinolone group. All groups presented with improvements in VA (P < .001); however, no differences between groups were observed (P = .436). Mean reduction in central retinal thickness was statistically different only between the triamcinolone and bevacizumab groups (P < .015). CONCLUSION Mono- or combination therapy was effective for DME treatment. No synergistic effects were observed; however, triamcinolone alone or a drug combination may reduce the number of injections required when compared to bevacizumab alone. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:734-740.].
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Itoh Y, Petkovsek D, Kaiser PK, Singh RP, Ehlers JP. Optical Coherence Tomography Features in Diabetic Macular Edema and the Impact on Anti-VEGF Response. Ophthalmic Surg Lasers Imaging Retina 2017; 47:908-913. [PMID: 27759856 DOI: 10.3928/23258160-20161004-03] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2015] [Accepted: 08/17/2016] [Indexed: 01/22/2023]
Abstract
BACKGROUND AND OBJECTIVE To assess the relationship between spectral-domain optical coherence tomography (SD-OCT) features and functional outcomes for diabetic macular edema (DME) undergoing treatment with intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA). PATIENTS AND METHODS Institutional review board-approved, retrospective, consecutive case series of eyes receiving intravitreal bevacizumab (1.25 mg) for DME. SD-OCT features were evaluated and correlated with functional response to anti-vascular endothelial growth factor (VEGF) therapy. RESULTS One hundred fifty-nine eyes of 159 subjects were included in this study. Mean visual acuity improved from 20/76 to 20/58. The proportion of eyes with 20/40 or greater visual acuity increased with treatment (35% at initial visit, 51% at final visit). SD-OCT factors that were associated with functional outcomes to anti-VEGF therapy include ellipsoid zone integrity and severity of intraretinal fluid. CONCLUSION SD-OCT features appear to provide important markers for functional response to anti-VEGF therapy in DME. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:908-913.].
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Mynampati BK, Sambhav K, Grover S, Chalam KV. Inhibition of proliferation of retinal vascular endothelial cells more effectively than choroidal vascular endothelial cell proliferation by bevacizumab. Int J Ophthalmol 2017; 10:15-22. [PMID: 28149771 DOI: 10.18240/ijo.2017.01.03] [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: 08/28/2016] [Accepted: 09/28/2016] [Indexed: 11/23/2022] Open
Abstract
AIM To evaluate the differential inhibitory effects of bevacizumab on cell proliferation of vascular endothelial growth factor (VEGF)-stimulated choroidal vascular endothelial cells (CVECs) and retinal vascular endothelial cells (RVECs) in vitro. METHODS VEGF (400 ng/mL) enriched CVECs and RVECs were treated with escalating doses of bevacizumab (0.1, 0.5, 1, 1.5 and 2 mg/mL). Cell proliferation changes were analyzed with WST-1 assay and trypan blue exclusion assay at 48, 72h and 1wk. Morphological changes were recorded with bright field microscopy. RESULTS VEGF enriched RVECs showed significantly more decline of cell viability than CVECs after bevacizumab treatment. One week after treatment, RVEC cell proliferation decreased by 29.7%, 37.5%, 52.8%, 35.9% and 45.6% at 0.1, 0.5, 1.0, 1.5 and 2 mg/mL bevacizumab respectively compared to CVEC proliferation decrease of 4.1%, 7.7%, 2.4%, 4.1% and 17.7% (P<0.05) by WST-1 assay. Trypan blue exclusion assay also revealed similar decrease in RVEC proliferation of 20%, 60%, 73.3%, 80% and 93.3% compared to CVEC proliferation decrease of 4%, 12%, 22.9%, 16.7% and 22.2% respectively (P<0.05). The maximum differential effect between the two cell types was observed at bevacizumab doses of 1.0 and 1.5 mg/mL at all time points. RVECs were 22 fold more sensitive (P<0.01) compared to CVECs (52.8% vs 2.4%) at concentration of 1.0 mg/mL, and 8.7 fold more at 1.5 mg/mL (35.9% vs 4.1%) 1wk after treatment (P<0.05 respectively). CONCLUSION VEGF-enriched RVECs are more susceptible to bevacizumab inhibition than CVECs at clinically used dosage of 1.25 mg and this differential sensitivity between two cell types should be taken into consideration in dosage selection.
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Affiliation(s)
- Bharani Krishna Mynampati
- Department of Ophthalmology, University of Florida, College of Medicine, Jacksonville, FL 32209, USA
| | - Kumar Sambhav
- Department of Ophthalmology, University of Florida, College of Medicine, Jacksonville, FL 32209, USA
| | - Sandeep Grover
- Department of Ophthalmology, University of Florida, College of Medicine, Jacksonville, FL 32209, USA
| | - Kakarla V Chalam
- Department of Ophthalmology, University of Florida, College of Medicine, Jacksonville, FL 32209, USA
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9
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Reply. Retina 2016; 36:e113-e115. [DOI: 10.1097/iae.0000000000001353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Rajavi Z, Safi S, Javadi MA, Azarmina M, Moradian S, Entezari M, Nourinia R, Ahmadieh H, Shirvani A, Shahraz S, Ramezani A, Dehghan MH, Shahsavari M, Soheilian M, Nikkhah H, Ziaei H, Behboudi H, Farrahi F, Falavarjani KG, Parvaresh MM, Fesharaki H, Abrishami M, Shoeibi N, Rahimi M, Javadzadeh A, Karkhaneh R, Riazi-Esfahani M, Manaviat MR, Maleki A, Kheiri B, Golbafian F. Diabetic Retinopathy Clinical Practice Guidelines: Customized for Iranian Population. J Ophthalmic Vis Res 2016; 11:394-414. [PMID: 27994809 PMCID: PMC5139552 DOI: 10.4103/2008-322x.194131] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 09/24/2016] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To customize clinical practice guidelines (CPGs) for management of diabetic retinopathy (DR) in the Iranian population. METHODS Three DR CPGs (The Royal College of Ophthalmologists 2013, American Academy of Ophthalmology [Preferred Practice Pattern 2012], and Australian Diabetes Society 2008) were selected from the literature using the AGREE tool. Clinical questions were designed and summarized into four tables by the customization team. The components of the clinical questions along with pertinent recommendations extracted from the above-mentioned CPGs; details of the supporting articles and their levels of evidence; clinical recommendations considering clinical benefits, cost and side effects; and revised recommendations based on customization capability (applicability, acceptability, external validity) were recorded in 4 tables, respectively. Customized recommendations were sent to the faculty members of all universities across the country to score the recommendations from 1 to 9. RESULTS Agreed recommendations were accepted as the final recommendations while the non-agreed ones were approved after revision. Eventually, 29 customized recommendations under three major categories consisting of screening, diagnosis and treatment of DR were developed along with their sources and levels of evidence. CONCLUSION This customized CPGs for management of DR can be used to standardize the referral pathway, diagnosis and treatment of patients with diabetic retinopathy.
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Affiliation(s)
- Zhale Rajavi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sare Safi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Javadi
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Azarmina
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Siamak Moradian
- Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Morteza Entezari
- Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ramin Nourinia
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Ahmadieh
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Armin Shirvani
- Standardization and CPG Development Office, Deputy of Curative Affairs, Ministry of Health and Medical Education, Tehran, Iran
| | | | - Alireza Ramezani
- Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Ophthalmology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Hossein Dehghan
- Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohsen Shahsavari
- Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoud Soheilian
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Ophthalmology, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Homayoun Nikkhah
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Department of Ophthalmology, Torfeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hossein Ziaei
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Ophthalmic Epidemiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hasan Behboudi
- Department of Ophthalmology, Gilan University of Medical Sciences, Rasht, Iran
| | - Fereydoun Farrahi
- Department of Ophthalmology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | | | - Mohammad Mehdi Parvaresh
- Department of Ophthalmology, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Hamid Fesharaki
- Department of Ophthalmology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Majid Abrishami
- Department of Ophthalmology, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nasser Shoeibi
- Department of Ophthalmology, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mansour Rahimi
- Department of Ophthalmology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Javadzadeh
- Department of Ophthalmology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Karkhaneh
- Department of Ophthalmology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Riazi-Esfahani
- Department of Ophthalmology, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Alireza Maleki
- Department of Ophthalmology, Al Zahra Eye Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Bahareh Kheiri
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Ashraf M, Souka A, Adelman R, Forster SH. Aflibercept in diabetic macular edema: evaluating efficacy as a primary and secondary therapeutic option. Eye (Lond) 2016; 30:1531-1541. [PMID: 27564719 DOI: 10.1038/eye.2016.174] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Accepted: 06/13/2016] [Indexed: 12/12/2022] Open
Abstract
The recent results of Protocol T have illustrated the efficacy of aflibercept in the treatment of diabetic macular edema. It also demonstrated that in patients with poor vision (<6/12), aflibercept offers anatomical and visual advantages over ranibizumab and bevacizumab in the first 12 months of treament. At 2 years, the difference between the three drugs decreased with patients with a better baseline VA (69-78) showing a statistically insignificant advantage for ranibizumab compared with aflibercept.These results were achieved using a pro-re nata (PRN) protocol, which was not previously studied in large phase 3 trials, VIVID and VISTA, that chose to compare the 2.0 mg dose in a monthly and bimonthly regimen. In this review article, we analyzed earlier studies such as DAVINCI and VIVID and VISTA to determine which treatment strategy offers the best results; monthly, bimonthly, or PRN. We also studied the different doses for aflibercept used in DAVINCI to determine which is more effective the 0.5 mg dose or the 2.0 mg dose. In addition, we analyzed the recent data from protocol T with regards to visual and anatomic outcomes to try to determine whether these results concur with previous studies. Finally, we discuss the role of aflibercept as a potential alternative to any diabetic macular edema regimen regardless what the primary drug used is.
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Affiliation(s)
- M Ashraf
- Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - A Souka
- Ophthalmology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - R Adelman
- Department of Ophthalmology and Visual Studies, Yale Medical School, New Haven, CT, USA
| | - S H Forster
- Department of Ophthalmology and Visual Studies, Yale Medical School, New Haven, CT, USA
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Bahrami B, Zhu M, Hong T, Chang A. Diabetic macular oedema: pathophysiology, management challenges and treatment resistance. Diabetologia 2016; 59:1594-608. [PMID: 27179659 DOI: 10.1007/s00125-016-3974-8] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 04/11/2016] [Indexed: 02/07/2023]
Abstract
Diabetic macular oedema (DMO) is the leading cause of vision loss in patients living with diabetes. DMO results from hyperglycaemia-induced activation of pathways that lead to oxidative stress and release of cytokines, impairing the inner and outer blood-retinal barriers. Improved understanding of the pathophysiological mechanisms leading to DMO have led to the development of effective therapies, including vitreoretinal surgery, laser photocoagulation, intravitreal anti-vascular endothelial growth factor drugs and corticosteroids. Advances in imaging, including fluorescein angiography and optical coherence tomography, have also enhanced diagnosis and management of the condition. Despite these advances, there remain patients who do not respond completely to therapy, reflecting the complex pathophysiology of DMO. These patients may be considered treatment-resistant. In this review, we summarise the pathophysiology of DMO, as well as the available treatments and their mechanism of action. Additionally, we focus on treatment-resistant disease and review the literature on potential options for managing this complication of diabetes.
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Affiliation(s)
- Bobak Bahrami
- Sydney Institute of Vision Science, 13/187 Macquarie Street, Sydney, 2000, NSW, Australia
- Save Sight Institute, University of Sydney, Sydney, NSW, Australia
| | - Meidong Zhu
- Sydney Institute of Vision Science, 13/187 Macquarie Street, Sydney, 2000, NSW, Australia
- Save Sight Institute, University of Sydney, Sydney, NSW, Australia
| | - Thomas Hong
- Sydney Institute of Vision Science, 13/187 Macquarie Street, Sydney, 2000, NSW, Australia
| | - Andrew Chang
- Sydney Institute of Vision Science, 13/187 Macquarie Street, Sydney, 2000, NSW, Australia.
- Save Sight Institute, University of Sydney, Sydney, NSW, Australia.
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Raizada S, Al Kandari J, Al Diab F, Al Sabah K, Kumar N, Mathew S. Pars plana vitrectomy versus three intravitreal injections of bevacizumab for nontractional diabetic macular edema. A prospective, randomized comparative study. Indian J Ophthalmol 2015; 63:504-10. [PMID: 26265641 PMCID: PMC4550983 DOI: 10.4103/0301-4738.162602] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND The aim of this study was to compare the effectiveness of pars plana vitrectomy (PPV) and removal of the internal limiting membrane (ILM) with three, monthly, intravitreal bevacizumab (IVB) injections for refractory diabetic macular edema. MATERIALS AND METHODS This was a prospective, randomized, comparative, interventional study. Forty-four patients were enrolled and randomized in two groups. Twenty-two eyes enrolled in Group I received three IVB injections at monthly interval. Twenty-two eyes were enrolled in Group II which underwent PPV with ILM removal. The primary outcomes measured were: (1) Best corrected logMAR visual acuity (BCVA) using Snellen's visual acuity chart. (2) Central macular thickness (CMT) on optical coherence tomography. The secondary outcome measures were: Complication rates like (1) progression of lens opacities, (2) high intraocular pressure needing further treatment/procedure, (3) development of vitreous hemorrhage related to the procedure employed, (4) retinal detachment and (5) severe inflammation/endophthalmitis. RESULTS In Group I (IVB): 3 (13.6%) eyes showed no change in BCVA; 3 (13.6%) eyes reported decrease in BCVA and 16 (72.8%) eyes showed improvement in BCVA; (P = 0.0181). In Group II (PPV): 4 (18.2%) eyes showed no change in BCVA; 5 (22.7%) eyes showed decrease and 13 (59.1%) eyes showed improvement in BCVA (P = 0.0281). Mean decrease in CMT in IVB group was 108.45 μ, whereas mean decrease in CMT in PPV group was 161.36 μ. No major complications were seen in either group. CONCLUSION Posttreatment decrease in CMT was more in PPV group and vision improvement more in IVB group. However, no statistically significant difference between the two methods was found.
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Affiliation(s)
- Seemant Raizada
- Vitreo-Retinal Unit, Al Bahar Eye Center, IBN Sina Hospital, Safat; Department of Ophthalmology, Dasman Diabetes Institute, Safat, Kuwait
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A review of therapies for diabetic macular oedema and rationale for combination therapy. Eye (Lond) 2015; 29:1115-30. [PMID: 26113500 DOI: 10.1038/eye.2015.110] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2015] [Accepted: 05/06/2015] [Indexed: 12/23/2022] Open
Abstract
Diabetic macular oedema (DMO) is responsible for significant visual impairment in diabetic patients. The primary cause of DMO is fluid leakage resulting from increased vascular permeability through contributory anatomical and biochemical changes. These include endothelial cell (EC) death or dysfunction, pericyte loss or dysfunction, thickened basement membrane, loss or dysfunction of glial cells, and loss/change of EC Glycocalyx. The molecular changes include increased reactive oxygen species, pro-inflammatory changes: advanced glycation end products, intracellular adhesion molecule-1, Complement 5-9 deposition and cytokines, which result in increased paracellular permeability, tight junction disruption, and increased transcellular permeability. Laser photocoagulation has been the mainstay of treatment until recently when pharmacological treatments were introduced. The current treatments for DMO target reducing vascular leak in the macula once it has occurred, they do not attempt to treat the underlying pathology. These pharmacological treatments are aimed at antagonising vascular endothelial growth factor (VEGF) or non-VEGF inflammatory pathways, and include intravitreal injections of anti-VEGFs (ranibizumab, aflibercept or bevacizumab) or steroids (fluocinolone, dexamethasone or triamcinolone) as single therapies. The available evidence suggests that each individual treatment modality in DMO does not result in a completely dry macula in most cases. The ideal treatment for DMO should improve vision and improve morphological changes in the macular (eg, reduce macular oedema) for a significant duration, reduced adverse events, reduced treatment burden and costs, and be well tolerated by patients. This review evaluates the individual treatments available as monotherapies, and discusses the rationale and potential for combination therapy in DMO. A comprehensive review of clinical trials related to DMO and their outcomes was completed. Where phase III randomised control trials were available, these were referenced, if not available, phase II trials have been included.
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Yaseri M, Zeraati H, Mohammad K, Soheilian M, Ramezani A, Eslani M, Peyman GA. Intravitreal bevacizumab injection alone or combined with triamcinolone versus macular photocoagulation in bilateral diabetic macular edema; application of bivariate generalized linear mixed model with asymmetric random effects in a subgroup of a clinical trial. J Ophthalmic Vis Res 2015; 9:453-60. [PMID: 25709771 PMCID: PMC4329706 DOI: 10.4103/2008-322x.150818] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Accepted: 05/17/2014] [Indexed: 11/04/2022] Open
Abstract
PURPOSE To compare the efficacy of intravitreal bevacizumab (IVB) injection alone or with intravitreal triamcinolone acetonide (IVB/IVT) versus macular photocoagulation (MPC) in bilateral diabetic macular edema (DME). METHODS In this study we revisited data from a subset of subjects previously enrolled in a randomized clinical trial. The original study included 150 eyes randomized to three treatment arms: 1.25 mg IVB alone, combined injection of 1.25 mg IVB and 2 mg IVT, and focal or modified grid MPC. To eliminate the possible effects of systemic confounders, we selected fellow eyes of bilaterally treated subjects who had undergone different treatments; eventually 30 eyes of 15 patients were re-evaluated at baseline, 6, 12, 18, and 24 months. Using mixed model analysis, we compared the treatment protocols regarding visual acuity (VA) and central macular thickness (CMT). RESULTS Improvement in VA in the IVB group was significantly greater compared to MPC at months 6 and 12 (P = 0.037 and P = 0.035, respectively) but this difference did not persist thereafter up to 24 months. Other levels of VA were comparable at different follow-up intervals (all P > 0.05). The only significant difference in CMT was observed in favor of the IVB group as compared to IVB/IVT group at 24 months (P = 0.048). CONCLUSION Overall VA was superior in IVB group as compared to MPC up to 12 months. Although the IVB group showed superiority regarding CMT reduction over 24 months as compared to IVB/IVT group, it was comparable to the MPC group through the same period of follow up.
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Affiliation(s)
- Mehdi Yaseri
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Hojjat Zeraati
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Kazem Mohammad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Soheilian
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Ramezani
- Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Department of Ophthalmology, Imam Hossein Medical Center, Tehran, Iran
| | - Medi Eslani
- Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Gholam A Peyman
- Department of Ophthalmology, University of Arizona Health Science Center, Tucson, Arizona, USA
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Sayin N, Kara N, Pekel G. Ocular complications of diabetes mellitus. World J Diabetes 2015; 6:92-108. [PMID: 25685281 PMCID: PMC4317321 DOI: 10.4239/wjd.v6.i1.92] [Citation(s) in RCA: 180] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Revised: 10/06/2014] [Accepted: 12/10/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.
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Current nanotechnology approaches for the treatment and management of diabetic retinopathy. Eur J Pharm Biopharm 2014; 95:307-22. [PMID: 25536109 DOI: 10.1016/j.ejpb.2014.12.023] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2014] [Revised: 12/08/2014] [Accepted: 12/15/2014] [Indexed: 01/08/2023]
Abstract
Diabetic retinopathy (DR) is a consequence of diabetes mellitus at the ocular level, leading to vision loss, and contributing to the decrease of patient's life quality. The biochemical and anatomic abnormalities that occur in DR are discussed in this review to better understand and manage the development of new therapeutic strategies. The use of new drug delivery systems based on nanoparticles (e.g. liposomes, dendrimers, cationic nanoemulsions, lipid and polymeric nanoparticles) is discussed along with the current traditional treatments, pointing out the advantages of the proposed nanomedicines to target this ocular disease. Despite the multifactorial nature of DR, which is not entirely understood, some strategies based on nanoparticles are being exploited for a more efficient drug delivery to the posterior segment of the eye. On the other hand, the use of some nanoparticles also seems to contribute to the development of DR symptoms (e.g. retinal neovascularization), which are also discussed in light of an efficient management of this ocular chronic disease.
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Victor AA, Gondhowiardjo TD, Waspadji S, Wanandi SI, Bachtiar A, Suyatna FD, Muhiddin H. Effect of laser photocoagulation and bevacizumab intravitreal in proliferative diabetic retinopathy: review on biomarkers of oxidative stress. MEDICAL JOURNAL OF INDONESIA 2014. [DOI: 10.13181/mji.v23i2.756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
Background: This study was aimed to compare the effect of laser photocoagulation (LF), intravitreal bevacizumab (IVB) and combined treatments on biomarkers of oxidative stress such as aldehhyde dehidrogenase (ALDH), malondialdehyde (MDA) level, superoxide dismutase (SOD) activities, and vitreal vascular endothelial growth factor (VEGF) on proliferative diabetic retinopathy (DR) patients.Methods: In this single blind randomized clinical trial, 72 eyes from 69 cases of proliferative DR in Cipto Mangunkusumo Hospital between February 2011 - June 2013 were randomized into 4 groups : 1) control (n = 18); 2) LF pre-vitrectomy (n = 18); 3) IVB pre-vitrectomy (n = 18); and 4) combined IVB and LF pre-vitrectomy (n = 18). One-way ANOVA was used to compare oxidative stress parameters in the four groups.Results: There were no statistically significant differences in the average plasma ALDH activity (0.034 ± 0.02; 0.027 ± 0.02; 0.025 ± 0.02; 0.031 ± 0.11 IU/mg protein; p = 0.66), vitreal MDA level (1.661 ± 1.21; 1.557 ± 1.32; 1.717 ± 1.54; 1.501 ± 1.09 nmol/mL; p = 0.96) and SOD activity) (0.403 ± 0.50; 0.210 ± 0.18; 0.399 ± 0.49; 0.273 ± 0.32 U/mL; p = 0.38) among these four groups, respectively. However, the VEGF vitreal level (pg/mL) showed a statistically significant difference (0.356 ± 0.60; 0.393 ± 0.45; 0.150 ± 0.24; 0.069 ± 0.13; p = 0.05). The VEGF level in combination group was five times lower than the control group (p = 0.05).Conclusion: Combined treatments of DR by IVB and LF were correlated with lower vitreal MDA and plasma VEGF level, but did not have any effect on plasma ALDH and vitreal SOD in proliferative DR. Combined treatments with IVB and LF are recommended for the management of proliferative DR patients.
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Abu El-Asrar AM. Evolving strategies in the management of diabetic retinopathy. Middle East Afr J Ophthalmol 2014; 20:273-82. [PMID: 24339676 PMCID: PMC3841944 DOI: 10.4103/0974-9233.119993] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Diabetic retinopathy (DR), the most common long-term complication of diabetes mellitus, remains one of the leading causes of blindness worldwide. Tight glycemic and blood pressure control has been shown to significantly decrease the risk of development as well as the progression of retinopathy and represents the cornerstone of medical management of DR. The two most threatening complications of DR are diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Focal/grid photocoagulation and panretinal photocoagulation are standard treatments for both DME and PDR, respectively. Focal/grid photocoagulation is a better treatment than intravitreal triamcinolone acetonide in eyes with DME. Currently, most experts consider combination focal/grid laser therapy and pharmacotherapy with intravitreal antivascular endothelial growth factor agents in patients with center-involving DME. Combination therapy reduces the frequency of injections needed to control edema. Vitrectomy with removal of the posterior hyaloid seems to be effective in eyes with persistent diffuse DME, particularly in eyes with associated vitreomacular traction. Emerging therapies include fenofibrate, ruboxistaurin, renin-angiotensin system blockers, peroxisome proliferator-activated receptor gamma agonists, pharmacologic vitreolysis, and islet cell transplantation.
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Affiliation(s)
- Ahmed M Abu El-Asrar
- Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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21
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Anti-VEGF for the management of diabetic macular edema. J Immunol Res 2014; 2014:632307. [PMID: 24741610 PMCID: PMC3987934 DOI: 10.1155/2014/632307] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 12/22/2013] [Indexed: 12/18/2022] Open
Abstract
Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME.
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Zhang XL, Chen J, Zhang RJ, Wang WJ, Zhou Q, Qin XY. Intravitreal triamcinolone versus intravitreal bevacizumab for diabetic macular edema: a meta-analysis. Int J Ophthalmol 2013; 6:546-52. [PMID: 23991395 DOI: 10.3980/j.issn.2222-3959.2013.04.26] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Accepted: 07/03/2013] [Indexed: 11/02/2022] Open
Abstract
AIM To compare the efficacy of the sole intravitreal triamcinolone (IVT) versus intravitreal bevacizumab (IVB) alone or IVB combined with IVT in the treatment of diabetic macular edema (DME). METHODS Pertinent publications were identified through systematic searches of database and manually searching. Methodological quality of the literatures was valuated according to the Jadad Score. RevMan 5.1.0 was used to do the meta-analysis. Heterogeneity was determined and sensitivity was conducted. RESULTS Six studies were ultimately included in the meta-analysis. The results of our analysis showed IVT had a statistically significant improvement in vision over the IVB at 1 month and 3 months (P<0.01). However, the reduction was not significant regarding central macular thickness (CMT) during the earlier (1 month and 3 months) follow-up period (P=0.12, P=0.41, respectively). At later visit (6 months), IVT had a significant decrease in CMT when compared to IVB (P<0.01) while no significant improvement in visual acuity (VA) was observed (P=0.14). The incidence of intraocular hypertension was 13/102 in IVT group during follow-up period while 0/103 in IVB group. The difference was significant (P<0.01). With regards to IVT versus IVB combined with IVT, there were no significant differences in CMT at 1 month (P=0.86) and 3 months (P=0.06). The incidence of intraocular hypertension was 6/67 in IVT group during follow-up period while 4/66 in IVB+IVT group. But the difference was not significant (P=0.53). CONCLUSION Current evidence shows IVT is superior in improving VA at earlier follow-up (1 month and 3 months) and in reducing CMT at later follow-up (6 months) for DME. At other time, it is in favor of IVT treatment but there are no statistically significances. However, IVT has the side-effect of ocular hypertension. There is no adequate evidence of the benefit adding IVB to IVT in contrast to IVT alone.
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Affiliation(s)
- Xiao-Ling Zhang
- Department of Ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China
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Abstract
Diabetic retinopathy is the leading cause of blindness among individuals of working age in industrialized nations, with most of the vision loss resulting from diabetic macular edema (DME). The formation of DME depends on the action of several growth factors and inflammatory mediators, but vascular endothelial growth factor (VEGF) appears to be critical for breaking down the blood-retinal barrier and promoting the accumulation of macular edema. Laser photocoagulation has been the standard-of-care for three decades, and although it stabilizes vision, significant gains in visual acuity after treatment are unusual. Several VEGF inhibitors (pegaptanib, aflibercept, and ranibizumab) have been initially developed and tested for the treatment of age-related macular degeneration and subsequently for DME. In Phase I, II, and III trials for DME, ranibizumab has been shown to be superior to macular laser photocoagulation and intraocular triamcinolone acetonide injections for improving visual acuity and drying the macula. As a result, ranibizumab is the only anti-VEGF drug that has been approved by the United States Food and Drug Administration for the treatment of DME. Most experts now consider intravitreal anti-VEGF therapy to be standard-of-care for DME involving the fovea.
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Affiliation(s)
- Michael W Stewart
- Department of Ophthalmology, Mayo School of Medicine, Jacksonville, FL, USA
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Abstract
PURPOSE To describe the current management of diffuse diabetic macular edema (DDME). METHODS Review and discussion of the literature regarding DDME. RESULTS Diffuse diabetic macular edema is a condition that can be managed by means of several treatment options, including focal/grid laser photocoagulation, intravitreal or periocular corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF), and vitrectomy with or without internal limiting membrane peeling. CONCLUSIONS Even though there is no randomized clinical trial specifically designed to assess the best treatment approach for DDME, new therapeutic approaches based on intravitreal injections of corticosteroid and anti-VEGF molecules offer new hope for its management.
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Stefanini FR, Arevalo JF, Maia M. Bevacizumab for the management of diabetic macular edema. World J Diabetes 2013; 4:19-26. [PMID: 23593532 PMCID: PMC3627413 DOI: 10.4239/wjd.v4.i2.19] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Revised: 02/01/2013] [Accepted: 03/27/2013] [Indexed: 02/05/2023] Open
Abstract
Diabetic retinopathy (DR) is a leading cause of vision loss in the working-age population and is relatedto 1%-5% of cases of blindness worldwide. Diabetic macular edema (DME) is the most frequent cause of DR vision loss and is an important public health problem. Recent studies have implicated vascular endothelial growth factor (VEGF) in DR and DME pathogenesis, as well as provided evidence of the benefits of anti-VEGF agents for the management of such conditions. Despite the benefits of intravitreal ranibizumab injection for the management of DME, the cost-effectiveness of intravitreal bevacizumab therapy has gained increasing interest in the scientific community. This review summarizes the studies examining bevacizumab for the management of DME, focusing on the efficacy and duration of the clinical benefits of decreasing DME and the improvement of best-corrected visual acuity (BCVA). There is strong evidence that intravitreal bevacizumab injection therapy has a good cost-effective profile in the management of DME and may be associated with laser photocoagulation; however, its clinical superiority in terms of the duration of DME regression and the improvement of BCVA compared with intravitreal ranibizumab and other intravitreal anti-VEGF therapies remains unclear and deserves further investigation.
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Ford JA, Lois N, Royle P, Clar C, Shyangdan D, Waugh N. Current treatments in diabetic macular oedema: systematic review and meta-analysis. BMJ Open 2013; 3:e002269. [PMID: 23457327 PMCID: PMC3612765 DOI: 10.1136/bmjopen-2012-002269] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Revised: 02/01/2013] [Accepted: 02/01/2013] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVES The aim of this systematic review is to appraise the evidence for the use of anti-VEGF drugs and steroids in diabetic macular oedema (DMO) as assessed by change in best corrected visual acuity (BCVA), central macular thickness and adverse events DATA SOURCE MEDLINE, EMBASE, Web of Science with Conference Proceedings and the Cochrane Library (inception to July 2012). Certain conference abstracts and drug regulatory web sites were also searched. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS Randomised controlled trials were used to assess clinical effectiveness and observational trials were used for safety. Trials which assessed triamcinolone, dexamethasone, fluocinolone, bevacizumab, ranibizumab, pegaptanib or aflibercept in patients with DMO were included. STUDY APPRAISAL AND SYNTHESIS METHODS Risk of bias was assessed using the Cochrane risk of bias tool. Study results are narratively described and, where appropriate, data were pooled using random effects meta-analysis. RESULTS Anti-VEGF drugs are effective compared to both laser and placebo and seem to be more effective than steroids in improving BCVA. They have been shown to be safe in the short term but require frequent injections. Studies assessing steroids (triamcinolone, dexamethasone and fluocinolone) have reported mixed results when compared with laser or placebo. Steroids have been associated with increased incidence of cataracts and intraocular pressure rise but require fewer injections, especially when steroid implants are used. LIMITATIONS The quality of included studies varied considerably. Five of 14 meta-analyses had moderate or high statistical heterogeneity. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS The anti-VEGFs ranibizumab and bevacizumab have consistently shown good clinical effectiveness without major unwanted side effects. Steroid results have been mixed and are usually associated with cataract formation and intraocular pressure increase. Despite the current wider spectrum of treatments for DMO, only a small proportion of patients recover good vision (≥20/40), and thus the search for new therapies needs to continue.
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Affiliation(s)
- John Alexander Ford
- Department of Population Health and Primary Care, Faculty of Medicine and Health Sciences,Norwich Medical School, University of East Anglia, Norwich,UK
| | - Noemi Lois
- Centre for Vascular and Visual Sciences, Queens University, Belfast, UK
| | - Pamela Royle
- Warwick Evidence, Division of Health Sciences, Warwick Medical School, Coventry, UK
| | | | - Deepson Shyangdan
- Warwick Evidence, Division of Health Sciences, Warwick Medical School, Coventry, UK
| | - Norman Waugh
- Warwick Evidence, Division of Health Sciences, Warwick Medical School, Coventry, UK
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Bandello F, Lattanzio R, Zucchiatti I, Del Turco C. Pathophysiology and treatment of diabetic retinopathy. Acta Diabetol 2013; 50:1-20. [PMID: 23277338 DOI: 10.1007/s00592-012-0449-3] [Citation(s) in RCA: 116] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Accepted: 12/11/2012] [Indexed: 01/07/2023]
Abstract
In the past years, the management of diabetic retinopathy (DR) relied primarily on a good systemic control of diabetes mellitus, and as soon as the severity of the vascular lesions required further treatment, laser photocoagulation or vitreoretinal surgery was done to the patient. Currently, even if the intensive metabolic control is still mandatory, a variety of different clinical strategies could be offered to the patient. The recent advances in understanding the complex pathophysiology of DR allowed the physician to identify many cell types involved in the pathogenesis of DR and thus to develop new treatment approaches. Vasoactive and proinflammatory molecules, such as vascular endothelial growth factor (VEGF), play a key role in this multifactorial disease. Current properly designed trials, evaluating agents targeting VEGF or other mediators, showed benefits in the management of DR, especially when metabolic control is lacking. Other agents, directing to the processes of vasopermeability and angiogenesis, are under investigations, giving more hope in the future management of this still sight-threatening disease.
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Affiliation(s)
- Francesco Bandello
- Department of Ophthalmology, Scientific Institute San Raffaele, University Vita-Salute, Milan, Italy.
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Soman M, Ganekal S, Nair U, Nair K. Association of systemic comorbidity in diabetic serous macular detachment and comparison of various combination therapies in its management. Clin Ophthalmol 2013; 7:113-9. [PMID: 23345965 PMCID: PMC3551605 DOI: 10.2147/opth.s38270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND The purpose of this research was to study the association between systemic comorbidity in diabetic serous macular detachment (DSMD) and the effect of different forms of combination therapies in its management. METHODS In this prospective analysis, 34 eyes from 34 patients with DSMD were investigated for the presence of systemic comorbidity including anemia, dyslipidemia, nephropathy, and cardiac disease, and treated with combination therapy of either intravitreal bevacizumab + laser (group 1, n = 14) or intravitreal triamcinolone + laser (group 2, n = 20). Sequential macular laser was done 2 weeks after intravitreal pharmacotherapy in both groups. Outcome measures included visual acuity and central foveal thickness at 1 and 3 months. RESULTS The mean age of the patients was 55.6 ± 7.6 years. The commonest systemic association was nephropathy (82.3%). In group 1, mean visual acuity improved marginally from 6/17 at baseline to 6/16 at 1 month (P = 0.0001) and was maintained at 3 months (P = 0.008); and mean central foveal thickness decreased from 488.7 μm to 318.7 μm at 1 month (P = 0.0001) but increased to 414.4 μm at 3 months (P = 0.049). In group 2, mean visual acuity improved from 6/22 at baseline to 6/19 at 1 month (P = 0.0001) and 6/12 at 3 months (P = 0.0001); and mean central foveal thickness decreased from 428.8 μm to 323.8 μm at 1 month (P = 0.0001) to 269.2 μm at 3 months (P = 0.0001). CONCLUSION Nephropathy should be ruled out in patients with DSMD. Although at 1 month both intravitreal triamcinolone and bevacizumab improved vision and decreased central foveal thickness in eyes with DSMD when administered along with focal laser treatment, the former had a more long-lasting effect in maintaining this gain at 3 months.
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Affiliation(s)
- Manoj Soman
- Chaithanya Eye Hospital and Research Institute, Trivandrum, Kerala
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Ho AC, Scott IU, Kim SJ, Brown GC, Brown MM, Ip MS, Recchia FM. Anti-vascular endothelial growth factor pharmacotherapy for diabetic macular edema: a report by the American Academy of Ophthalmology. Ophthalmology 2012; 119:2179-88. [PMID: 22917890 DOI: 10.1016/j.ophtha.2012.07.058] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2010] [Accepted: 07/03/2012] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVE To review the evidence regarding the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS Literature searches last were conducted in September 2011, in PubMed with no date restrictions, limited to articles published in English, and in the Cochrane Library without a language limitation. The combined searches yielded 532 citations, of which 45 were deemed clinically relevant for the authors to review in full text and to assign ratings of level of evidence to each of the selected studies with the guidance of the panel methodologists. RESULTS At this time, there are 5 studies that provide level I evidence for intravitreal ranibizumab, alone or in combination with other treatments for DME. There is also 1 study that provides level I evidence for intravitreal pegaptanib sodium for DME. Nine studies reviewed were rated as level II, and 2 additional studies reviewed were graded as level III. Most studies do not provide information about long-term results (i.e., more than 2 years of follow-up) or the comparative efficacy of anti-VEGF pharmacotherapies. CONCLUSIONS Review of the available literature indicates that anti-VEGF pharmacotherapy, delivered by intravitreal injection, is a safe and effective treatment over 2 years for DME. Further evidence is required to support the long-term safety of these pharmacotherapies and their comparative efficacy.
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Affiliation(s)
- Allen C Ho
- American Academy of Ophthalmology, San Francisco, California, USA.
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Ford JA, Elders A, Shyangdan D, Royle P, Waugh N. The relative clinical effectiveness of ranibizumab and bevacizumab in diabetic macular oedema: an indirect comparison in a systematic review. BMJ 2012; 345:e5182. [PMID: 22890029 PMCID: PMC3418219 DOI: 10.1136/bmj.e5182] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To indirectly compare the effectiveness of ranibizumab and bevacizumab in the treatment of diabetic macular oedema. DESIGN Systematic review and indirect comparison. DATA SOURCES Medline (1996-September 2011), Embase (1996-September 2011), and the Cochrane Central Register of Controlled Trials (Issue 4, 2011). SELECTION CRITERIA FOR STUDIES Randomised trials evaluating ranibizumab or bevacizumab in diabetic macular oedema with a common comparator and sufficient methodological similarity to be included within an indirect comparison were eligible for inclusion. MAIN OUTCOME MEASURES The primary outcome was the proportion of patients with an improvement in best corrected visual acuity of more than two lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Secondary outcomes included mean changes in best corrected visual acuity and in central macular thickness, and adverse events. Best corrected visual acuity was converted to logMAR units, a linear scale of visual acuity with positive values representing increasing visual loss. Indirect comparisons were done using Bayesian methods to estimate relative treatment effects of bevacizumab and ranibizumab. RESULTS Five randomised controlled trials with follow-up of 6-12 months and a common comparator (multiple laser treatment) were sufficiently similar to be included in the indirect comparison. Generally studies were small, resulting in wide credible intervals. The proportions of patients with an improvement in best corrected visual acuity of >2 lines were 21/77 participants (27%) for bevacizumab and 60/152 participants (39%) for ranibizumab (odds ratio 0.95 (95% credible interval 0.23 to 4.32)). The wide credible intervals cannot exclude a greater improvement, or worse outcome, for either drug. The mean change in best corrected visual acuity non-significantly favoured bevacizumab (treatment effect -0.08 logMAR units (-0.19 to 0.04)). The difference in mean change in central macular thickness was not statistically significant between ranibizumab and bevacizumab (treatment effect -6.9 μm (-88.5 to 65.4)). CONCLUSIONS Results suggest no difference in effectiveness between bevacizumab and ranibizumab, but the wide credible intervals cannot exclude the possibility that either drug might be superior. Sufficiently powered, direct head to head trials are needed.
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Affiliation(s)
- John A Ford
- Health Services Research Unit, University of Aberdeen, Health Services Building, Aberdeen AB25 2ZD, UK.
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Defferrari C, Campora S, D'Amico M, Piccardo A, Biscaldi E, Rosselli D, Pasa A, Puntoni M, Gozza A, Gennari A, Zanardi S, Lionetto R, Bandelloni M, DeCensi A. A case series of low dose bevacizumab and chemotherapy in heavily pretreated patients with epithelial ovarian cancer. J Ovarian Res 2012; 5:17. [PMID: 22732001 PMCID: PMC3408333 DOI: 10.1186/1757-2215-5-17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2012] [Accepted: 06/25/2012] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC. METHODS We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5-7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT. RESULTS The median number of bevacizumab cycles was 21 (range 3-59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 - 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 - 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension. CONCLUSIONS Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.
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Affiliation(s)
- Carlotta Defferrari
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Sara Campora
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Mauro D'Amico
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | | | | | | | - Ambra Pasa
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Matteo Puntoni
- Scientific Direction, E.O. Ospedali Galliera, Genoa, Italy
| | - Alberto Gozza
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Alessandra Gennari
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Silvia Zanardi
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
| | - Rita Lionetto
- Health Direction, E.O. Ospedali Galliera, Genoa, Italy
| | | | - Andrea DeCensi
- Unit of Medical Oncology, E.O. Ospedali Galliera, Mura delle Cappuccine 14, 16128, Genoa, Italy
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COMBINED HIGH-DOSE SUB-TENON TRIAMCINOLONE, INTRAVITREAL BEVACIZUMAB, AND LASER PHOTOCOAGULATION FOR REFRACTORY DIABETIC MACULAR EDEMA. Retina 2012; 32:672-8. [DOI: 10.1097/iae.0b013e31823043c6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Intraocular pharmacokinetics after a single intravitreal injection of 1.5 mg versus 3.0 mg of bevacizumab in humans. Retina 2012; 31:1877-84. [PMID: 21738089 DOI: 10.1097/iae.0b013e318217373c] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To compare the concentration of unbound bevacizumab in the anterior chamber of patients with macular edema, who received a single intravitreal injection of two different dosages. METHODS This was a comparative, interventional case series. Twenty-nine nonvitrectomized eyes of 29 patients with significant lens opacities and concurrent macular edema were included in the study. All patients were treated by a single dose of intravitreal injection of bevacizumab 1.5 mg (Group A, n = 13) or 3.0 mg (Group B, n = 16). Subsequent phacoemulsification and aspiration of an aqueous humor samples were performed at various intervals (1-60 days). The axial length of the globe was measured using the IOLMaster to calculate the total volume and corresponding globe size-corrected half-time. The concentration of unbound bevacizumab was measured by enzyme-linked immunosorbent assay and pharmacokinetic parameters including half-time of elimination. RESULTS The mean peak concentration was observed in both groups on the first day after intravitreal bevacizumab injection. The mean concentration of unbound bevacizumab ranged in Group A from 17.5 μg/mL at baseline to 0.66 μg/mL at Day 57 and in Group B from 28.3 μg/mL at baseline to 0.00 μg/mL at 54 days. The axial lengths of all injected eyes were not significantly different between Group A (mean values, 23.026 mm, SD 1.21) and Group B (mean, 23.313 mm, SD 1.00; P = 0.31). Regression analysis determined elimination half-time values of 7.85 days (R2 = 0.75) in Group A and 11.67 days (R2 = 0.91) in Group B. Similar half-times were calculated for globe size-corrected concentrations with 8.21 days (R2 = 0.81) in Group A and 11.17 days (R2 = 0.88) in Group B. CONCLUSION Single- and double-dose injections have similar pharmacokinetic characteristics in a first-order exponential decay function. The globe size-corrected concentration and half-time did not affect the calculated half-time in both groups. Doubled dosing induced a higher peak concentration at baseline, but the presumed extended biologic active concentration was no longer statistically significant after 6 weeks. The application of twice the dosage does not double the duration of its efficacy; it rather appears to extend the pharmacological duration by 1 half-time or approximately 8 days to 11 days.
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Schimel AM, Fisher YL, Flynn HW. Optical coherence tomography in the diagnosis and management of diabetic macular edema: time-domain versus spectral-domain. Ophthalmic Surg Lasers Imaging Retina 2012; 42 Suppl:S41-55. [PMID: 21790110 DOI: 10.3928/15428877-20110627-04] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2011] [Accepted: 04/11/2011] [Indexed: 11/20/2022]
Abstract
Optical coherence tomography (OCT) is an important imaging modality in the setting of diabetic macular edema (DME). Its use allows more precise evaluation of retinal pathology in DME, including retinal thickness and edema, vitreomacular interface abnormalities, subretinal fluid, and foveal microstructural changes. Additional advantages include its ability to quantitatively monitor response to treatment of DME by laser, intravitreal pharmacotherapies, and vitreoretinal surgery. OCT measurements are now used in all major clinical studies of DME treatment as critical endpoints. This article presents a review of both time-domain and spectral-domain OCT in the diagnosis and management of DME. The authors discuss the various parameters evaluated by the OCT systems and provide an evidence-based evaluation of their accuracy, significance, reliability, and limitations. As the capability of OCT continues to advance, it appears that its use will play an increasingly important role in the understanding, evaluation, and treatment of DME.
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Affiliation(s)
- Andrew M Schimel
- Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA.
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Isaac DLC, Abud MB, Frantz KA, Rassi AR, Avila M. Comparing intravitreal triamcinolone acetonide and bevacizumab injections for the treatment of diabetic macular oedema: a randomized double-blind study. Acta Ophthalmol 2012; 90:56-60. [PMID: 20015098 DOI: 10.1111/j.1755-3768.2009.01817.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
PURPOSE To compare the effect of a single intravitreal injection of triamcinolone acetonide and bevacizumab in reducing macular thickness, which was measured by optical coherence tomography (OCT) in patients with diabetic macular oedema (DMO). METHODS The patients received a single intravitreal injection of 1.25 mg bevacizumab in one randomly selected eye and 4.0 mg triamcinolone acetonide in the contralateral eye. Central foveal thickness measurement (CFT) with OCT was taken at the initial visit and at the 4-week, 12-week and 24-week visits. RESULTS Eleven patients (22 eyes) were enrolled and statistically analysed. CFT reduced in the eyes treated with triamcinolone and those treated with bevacizumab in weeks 4 and 12 (p < 0.05). At the 24-week follow-up, no significant difference was noted, relative to the initial visit. Comparing the two groups treated with different drugs, a statistically significant difference in CFT in weeks 4 and 12 was noted, with a more significant reduction in triamcinolone-treated eyes (p < 0.05). Regarding visual acuity (VA), patients treated with triamcinolone had improvement in VA at 4-week (p = 0.02) and 12-week follow-up (p = 0.01), while the group treated with bevacizumab had VA improvement at 4 -week follow-up (p = 0.02). Among the eyes treated with triamcinolone, intraocular pressure (IOP) measurement of more than 21 mmHg was found in three eyes (27.3%). CONCLUSIONS Intravitreal triamcinolone proved to be more efficient in reducing DMO, providing longer lasting visual improvement, relative to bevacizumab. Eyes treated with triamcinolone had the highest percentage increase in IOP. Further studies are needed to corroborate these findings.
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Vascular complications and diabetes: current therapies and future challenges. J Ophthalmol 2012; 2012:209538. [PMID: 22272370 PMCID: PMC3261480 DOI: 10.1155/2012/209538] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2011] [Accepted: 10/02/2011] [Indexed: 12/30/2022] Open
Abstract
Diabetic retinal complications, including macular edema (DME) and proliferative diabetic retinopathy (PDR), are the leading cause of new cases of blindness among adults aged 20–74. Chronic hyperglycemia, considered the underlying cause of diabetic retinopathy, is thought to act first through violation of the pericyte-endothelial coupling. Disruption of microvascular integrity leads to pathologic consequences including hypoxia-induced imbalance in vascular endothelial growth factor (VEGF) signaling. Several anti-VEGF medications are in clinical trials for use in arresting retinal angiogenesis arising from DME and PDR. Although a review of current clinical trials shows promising results, the lack of large prospective studies, head-to-head therapeutic comparisons, and potential long-term and systemic adverse events give cause for optimistic caution. Alternative therapies including targeting pathogenic specific angiogenesis and mural-cell-based therapeutics may offer innovative solutions for currently intractable clinical problems. This paper describes the mechanisms behind diabetic retinal complications, current research supporting anti-VEGF medications, and future therapeutic directions.
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Chan WC, Tsai SH, Wu AC, Chen LJ, Lai CC. Current Treatments of Diabetic Macular Edema. INT J GERONTOL 2011. [DOI: 10.1016/j.ijge.2011.09.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Massin P. Innovations thérapeutiques dans la rétinopathie diabétique. J Fr Ophtalmol 2011; 34:491-7. [DOI: 10.1016/j.jfo.2011.04.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2010] [Accepted: 04/11/2011] [Indexed: 10/18/2022]
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A SYSTEMATIC REVIEW OF THE ADVERSE EVENTS OF INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS. Retina 2011; 31:1449-69. [PMID: 21817960 DOI: 10.1097/iae.0b013e3182278ab4] [Citation(s) in RCA: 103] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Abstract
The aim of this review is to summarize the latest developments in the treatment of diabetic retinopathy (DR) with anti-vascular endothelial growth factor (VEGF) drugs. We reviewed recent studies that evaluated the role of the anti-VEGF agents bevacizumab, ranibizumab and pegaptanib in the treatment of DR. There was only one large randomized controlled trial that evaluated the role of ranibizumab in diabetic macular oedema (DME). Other prospective and retrospective studies provided important insight into the role of anti-VEGF drugs in DR, but most of them were not conducted in large scales. The growing evidence indicates that anti-VEGF drugs are beneficial in DR, especially in DME. Further studies are needed to fully evaluate the role of these agents, especially in proliferative DR and in DR candidates for vitrectomy surgery.
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Affiliation(s)
- Michael Waisbourd
- Department of Ophthalmology, Tel Aviv Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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Smiddy WE. Economic considerations of macular edema therapies. Ophthalmology 2011; 118:1827-33. [PMID: 21507488 DOI: 10.1016/j.ophtha.2010.12.034] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2010] [Revised: 12/16/2010] [Accepted: 12/30/2010] [Indexed: 12/28/2022] Open
Abstract
PURPOSE To relate costs and treatment benefits for diabetic macular edema (DME), branch retinal vein occlusion (BRVO), and central retinal vein occlusion (CRVO). DESIGN A model of resource use, outcomes, and cost-effectiveness and utility. PARTICIPANTS None. METHODS Results from published clinical trials (index studies) of laser, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents, and vitrectomy trials were used to ascertain visual benefit and clinical protocols. Calculations followed from the costs of 1 year of treatment for each treatment modality and the visual benefits as ascertained. MAIN OUTCOME MEASURES Visual acuity (VA) saved, cost of therapy, cost per line saved, cost per line-year saved, and costs per quality-adjusted life years (QALYs). RESULTS The lines saved for DME (0.26-2.02), BRVO (0.74-4.92), and CRVO (1.2-3.75) yielded calculations of costs/line of saved VA for DME ($1329-$11,609), BRVO ($494-$13,039), and CRVO ($704-$7611); costs/line-year for DME ($60-$561), BRVO ($25-$754), and CRVO ($45-$473); and costs/QALY ($824 to $25,566). CONCLUSIONS Relative costs and benefits should be considered in perspective when applying and developing treatment strategies.
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Affiliation(s)
- William E Smiddy
- Bascom Palmer Eye Institute, PO Box 016880, Miami, FL 33101-6880, USA.
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Ross AH, Clare Bailey C. The management of diabetic macular oedema. Saudi J Ophthalmol 2011; 25:123-9. [PMID: 23960913 PMCID: PMC3729702 DOI: 10.1016/j.sjopt.2011.01.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2011] [Accepted: 01/21/2011] [Indexed: 11/20/2022] Open
Abstract
Diabetic macular oedema (DMO) is a significant cause of visual loss in the working population. Focal/grid photocoagulation remains an effective treatment for DMO and the benchmark to which clinicians compare other newer treatment modalities. There are, however, patients who do not respond adequately or who are refractory to laser photocoagulation. This has led to the development of newer treatments such as the intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors as well as intravitreal corticosteroid releasing delivery systems. Cataract formation and raised intraocular pressure remain the major disadvantages of corticosteroid use. There is mounting evidence that intravitreal VEGF inhibitors with or without combined laser photocoagulation will become the gold standard treatment for DMO.
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Affiliation(s)
- Adam H Ross
- Department of Ophthalmology, Bristol Eye Hospital, Bristol, United Kingdom
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Abu El-Asrar AM, Al-Mezaine HS. Advances in the treatment of diabetic retinopathy. Saudi J Ophthalmol 2011; 25:113-22. [PMID: 23960912 PMCID: PMC3729319 DOI: 10.1016/j.sjopt.2011.01.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2011] [Accepted: 01/22/2011] [Indexed: 02/07/2023] Open
Abstract
Diabetic retinopathy, the most common long-term complication of diabetes mellitus, remains one of the leading causes of blindness worldwide. Strict metabolic control, tight blood pressure control, laser photocoagulation, and vitrectomy remain the standard care for diabetic retinopathy. Focal/grid photocoagulation is a better treatment than intravitreal triamcinolone acetonide in eyes with diabetic macular edema and should be considered as the first-line therapeutic option. The current evidence suggests that intravitreal triamcinolone acetonide or anti-vascular endothelial growth factor agents result in a temporary improvement of visual acuity and a short-term reduction in central macular thickness in patients with refractory diabetic macular edema and are an effective adjunctive treatments to laser photocoagulation or vitrectomy. However, triamcinolone is associated with risks of elevated intraocular pressure and cataract. Vitrectomy with the removal of the posterior hyaloid without internal limiting membrane peeling seems to be effective in eyes with persistent diffuse diabetic macular edema, particularly in eyes with associated vitreomacular traction. Emerging therapies include islet cell transplantation, fenofibrate, ruboxistaurin, pharmacologic vitreolysis, rennin-angiotensin system blockers, and peroxisome proliferator-activated receptor gamma agonists.
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Affiliation(s)
- Ahmed M. Abu El-Asrar
- Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Intravitreal bevacizumab and/or macular photocoagulation as a primary treatment for diffuse diabetic macular edema. Retina 2011; 30:1638-45. [PMID: 20838357 DOI: 10.1097/iae.0b013e3181e1ed07] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To evaluate the efficacy of intravitreal injection of bevacizumab (IVB) followed by modified grid laser photocoagulation (MGP) versus each alone as a primary treatment of diffuse diabetic macular edema. PATIENTS AND METHODS A randomized 3-arm clinical trial in which 62 eyes of 48 patients with diffuse diabetic macular edema were enrolled. Eyes were randomly distributed to 1 of 3 study groups: 19 eyes underwent MGP (MGP group), 21 eyes received 1.25 mg of IVB (IVB group), and 22 eyes received IVB followed by MGP (combined group). All eyes underwent a complete ophthalmic examination including fluorescein angiography and optical coherence tomography at baseline and at 1, 3, and 6 months, after treatment. Fluorescein angiography was performed at the 3 and 6 months follow up visits. The outcome measures were the change compared with baseline in central macular thickness (CMT), changes in best-corrected visual acuity (BCVA), changes in fluorescein angiography leakage, and any reported complication. A P value less than 0.05 was considered statistically significant. RESULTS One month after treatment, the reduction in the mean CMT versus baseline was 49.88 μm (10.45%) in MGP group, 150.92 μm (31.30%) in IVB group, and 110.30 μm (23.77%) in the combined group, with a corresponding improvement in the mean BCVA. At 1 month, the improvement in CMT was better than baseline in all groups, yet only significant in the IVB group (P < 0.05) and the combined group (P < 0.05). The improvement in mean BCVA was significant in the IVB (P < 0.05) and the combined groups at 1 month (P < 0.05). At 3 months, the mean CMT was still better than baseline in all groups but this improvement was significant only in the combined group (P < 0.05). The improvement in the mean BCVA was significant only in the IVB and the combined groups (P < 0.05). Six months after treatment, the reduction in the mean CMT was significant in the combined group only (P < 0.05) and there was no significant improvement in the mean BCVA in all groups (P > 0.05). The BCVA did not deteriorate below baseline in all eyes included in the study, except three eyes in the MGP group. No complication related to the intravitreal injection was reported in the injected eyes. CONCLUSION Combined therapy with IVB and sequential MGP 3 weeks later appeared to be superior to MGP or IVB alone in reducing macular thickening and improving visual acuity. However, no significant improvement in BCVA occurs 6 months after treatment. A combination of IVB and sequential MGP could be used as an initial treatment of diffuse diabetic macular edema.
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Zhao LQ, Zhu H, Zhao PQ, Hu YQ. A systematic review and meta-analysis of clinical outcomes of vitrectomy with or without intravitreal bevacizumab pretreatment for severe diabetic retinopathy. Br J Ophthalmol 2011; 95:1216-22. [PMID: 21278146 PMCID: PMC3161500 DOI: 10.1136/bjo.2010.189514] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Aims To examine possible benefits of intravitreal bevacizumab (IVB) pretreatment in vitrectomy for severe diabetic retinopathy. Methods A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify randomised controlled trials and comparative studies of vitrectomy with or without IVB pretreatment for severe or complicated diabetic retinopathy. Meta-analyses were performed for intraoperative (including intraoperative bleeding, endodiathermy, iatrogenic retinal tears and mean surgical time) and postoperative outcome parameters (including best-corrected visual acuity, recurrent vitreous haemorrhage, reabsorption time of blood and other complications). Results Six randomised controlled trials and one comparative study were identified and used for comparing vitrectomy alone (142 eyes, control group) with vitrectomy with IVB pretreatment (139 eyes). The intraoperative findings showed that the incidence of intraoperative bleeding and frequency of endodiathermy were statistically significantly less in the IVB pretreatment group (p<0.01) than in the vitrectomy alone group. The IVB pretreatment group took significantly less surgical time than the control group (p=0.003). Postoperative results indicated that reabsorption time of blood was significantly shorter (p=0.04), incidence of recurrent VH was almost significantly less (p=0.05), and final best-corrected visual acuity was significantly better (p=0.003) in the IVB group than in the control group. Other complications, including final retinal detachment, and reoperation, were statistically insignificant. Conclusion IVB pretreatment in vitrectomy can achieve excellent clinical outcomes for severe diabetic retinopathy. It potentially facilitates surgeons' manoeuvres and reduces intra- and postoperative complications.
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Affiliation(s)
- Li-Quan Zhao
- Department of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
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Massin P, Bandello F, Garweg JG, Hansen LL, Harding SP, Larsen M, Mitchell P, Sharp D, Wolf-Schnurrbusch UEK, Gekkieva M, Weichselberger A, Wolf S. Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 2010; 33:2399-405. [PMID: 20980427 PMCID: PMC2963502 DOI: 10.2337/dc10-0493] [Citation(s) in RCA: 515] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center. RESEARCH DESIGN AND METHODS This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 μm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection). RESULTS At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 μm with ranibizumab and 48.4±153.4 μm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab. CONCLUSIONS Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.
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Affiliation(s)
- Pascale Massin
- Assistance Publique des Hôpitaux de Paris, Ophthalmology Department, Hôpital Lariboisièe, Paris, France
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Goyal S, LaValley M, Subramanian ML. Meta-analysis and review on the effect of bevacizumab in diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2010; 249:15-27. [DOI: 10.1007/s00417-010-1452-4] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2010] [Revised: 06/17/2010] [Accepted: 07/04/2010] [Indexed: 11/30/2022] Open
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Lai TYY, Chen LJ, Yam GHF, Tham CCY, Pang CP. Development of novel drugs for ocular diseases: possibilities for individualized therapy. Per Med 2010; 7:371-386. [DOI: 10.2217/pme.10.25] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In clinical ophthalmology, new and old drug regimens are available for the treatment of major eye diseases, including potentially blinding conditions, such as glaucoma, and various macular diseases. In glaucoma, therapeutic treatment mainly deals with control of intraocular pressure at low levels but the clinical courses of patients can be very variable. Very often, specific drug combinations and dosages have to be formulated for individual glaucoma patients. In neovascular age-related macular degeneration, choroidal neovascularization can lead to progressive and irreversible visual impairment if not treated early. In recent years, clinical trials using photodynamic therapy with verteporfin and various anti-VEGF antibodies, such as ranibizumab and bevacizumab, have enhanced the treatment outcomes of neovascular age-related macular degeneration. In diabetic macular edema, intravitreal triamcinolone acetonide and anti-VEGF therapy are effective in some patients. Again, responses to treatment are not uniform in all macular patients. Traditional herbal medicine has long been known to play a role in the practice of personalized formulations in Asia. Potential preventive and therapeutic effects have been claimed in individual eye patients. Meanwhile, advanced technologies in molecular biology have led to identification of genes associated with many eye diseases and development of the concept of individual medicine, in which the genotype of a person can be used as a basis for disease prediction or prophylactic treatments. Moreover, pharmacogenomic studies have demonstrated the association of various genotypes or haplotypes with responses to drug therapies, providing hope for tailormade personalized treatments. The combination of genotypic information with clinical features for the prescription of treatment modes in eye diseases is under vigorous research.
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Affiliation(s)
- Timothy YY Lai
- Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong
| | - Li Jia Chen
- Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong
| | - Gary HF Yam
- Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong
| | - Clement CY Tham
- Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, 147K Argyle Street, Kowloon, Hong Kong
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A review of clinical trials of anti-VEGF agents for diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 2010; 248:915-30. [PMID: 20174816 DOI: 10.1007/s00417-010-1315-z] [Citation(s) in RCA: 186] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2009] [Accepted: 01/19/2010] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Diabetic retinopathy (DR) is a leading cause of vision loss in the working-age population worldwide. Many observational and preclinical studies have implicated vascular endothelial growth factor (VEGF) in the pathogenesis of DR, and recent successes with anti-VEGF therapy for age-related macular degeneration (AMD) have prompted research into the application of anti-VEGF drugs to DR. Here we review the numerous early studies that suggest an important potential role for anti-VEGF agents in the management of diabetic retinopathy. CONCLUSIONS For diabetic macular edema, phase II trials of intravitreal pegaptanib and intravitreal ranibizumab have shown short-term benefit in visual acuity. Intravitreal bevacizumab also has been shown to have beneficial short-term effects on both visual acuity and retinal thickness. For proliferative diabetic retinopathy (PDR), early studies suggest that intravitreal bevacizumab temporarily decreases leakage from diabetic neovascular lesions, but this treatment may be associated with tractional retinal detachment (TRD). Furthermore, several studies indicate that bevacizumab is likely to prove a helpful adjunct to diabetic pars plana vitrectomy (PPV) for TRD. Finally, three small series suggest a potential beneficial effect of a single dose of bevacizumab to prevent worsening of DME after cataract surgery. Use of anti-VEGF medications for any of these indications is off-label. Despite promising early reports on the safety of these medications, we eagerly await the results of large, controlled trials to substantiate the safety and efficacy of anti-VEGF drugs for diabetic retinopathy.
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