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Olaniyi SA, Ali M, Sharma A, Kazmi SAH, Raj R, Kaur P, Islam H, Alameddine S, Singh M. The Impact of the Foveal Bulge on Visual Acuity in Resolved Diabetic Macular Edema and Retinal Vein Occlusions. Cureus 2024; 16:e75543. [PMID: 39803108 PMCID: PMC11722659 DOI: 10.7759/cureus.75543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2024] [Indexed: 01/16/2025] Open
Abstract
PURPOSE The purpose of this study is to evaluate the impact of foveal bulge presence on visual acuity (VA) in patients with diabetic macular edema (DME) and retinal vein occlusion (RVO). METHODS Spectral-domain optical coherence tomography (SD-OCT) scans were conducted on 22 DME patients and 20 RVO patients. Ordinary least squares (OLS) regression was employed to analyze the association between VA and the presence of the foveal bulge, as well as factors such as sex, age, central foveal thickness, various line scans of the fovea, and the external limiting membrane (ELM). RESULTS In DME patients, the β value associated with foveal bulge presence was 10.2, while the β value for ELM presence was 36.19. For RVO patients, the β value for foveal bulge presence was 18.71. In the combined analysis of DME and RVO patients, VA increased by 14.24 letters with the presence of a foveal bulge. CONCLUSION The presence of a foveal bulge significantly enhances VA in patients with resolved DME and RVO. Our findings indicate that the increase in VA is more pronounced in RVO patients compared to those with DME. Additionally, the presence of the foveal bulge, ELM, and sex can serve as predictors for VA outcomes in these patient populations.
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Affiliation(s)
- Seyi A Olaniyi
- Medicine and Surgery, Obafemi Awolowo University, Ile Ife, NGA
| | - Muhammad Ali
- Internal Medicine, Riphah University, Rawalpindi, PAK
| | - Abhimanyu Sharma
- Medicine, Sri Guru Ram Das University of Health Sciences, Amritsar, IND
- Research, Johns Hopkins University School of Medicine, Baltimore, USA
| | | | - Rohan Raj
- Internal Medicine, Nalanda Medical College and Hospital, Patna, IND
| | - Parvinder Kaur
- Internal Medicine, Crimean State Medical University, Simferopol, UKR
| | - Hamza Islam
- Internal Medicine, Punjab Medical College, Faisalabad, PAK
| | | | - Mansi Singh
- Medicine, O. O. Bogomolets National Medical University, Kyiv, UKR
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Tranos P, Koukoula S, de Politis PB, Tranou M, Giamouridou O, Stavrakas P, Panos GD. Effects of Dexamethasone Intravitreal Implant on Multifocal Electroretinography in Diabetic Macular Oedema. Drug Des Devel Ther 2024; 18:5367-5375. [PMID: 39624769 PMCID: PMC11609416 DOI: 10.2147/dddt.s477677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 11/21/2024] [Indexed: 01/12/2025] Open
Abstract
PURPOSE To evaluate the efficacy of the dexamethasone implant on the electrophysiological profile of Diabetic Macular Oedema (DMO) patients over six months. METHODS In this prospective, single-center study 30 eyes of 22 patients were examined using comprehensive baseline assessments including best-corrected visual acuity (BCVA), central retinal thickness (CRT), contrast sensitivity (CS) and multifocal electroretinogram (mfERG), before and after 0.7mg dexamethasone implant injection, with follow-ups at months 1, 2, 4, and 6. The study employed mixed models to analyse within-subject and between-subject correlations, considering the complexities of multiple measurements per subject. RESULTS At baseline, BCVA was 0.66 ± 0.104 logMAR, improving to 0.568 ± 0.104 logMAR by month 6 (P > 0.05). CRT significantly reduced from 521 ± 28.7 μm to 336 ± 28.7 μm (P < 0.05). CS slightly increased from 26.8 ± 1.23 letters to 28.5 ± 1.05 letters (P > 0.05). P wave amplitude saw a notable rise from 33.4 ± 5.66 μV to 47.9 ± 5.43 μV (P < 0.05). P wave implicit time changed minimally from 47.4 ± 0.503 seconds to 48.0 ± 0.503 seconds (P > 0.05). No severe adverse events were recorded. CONCLUSION These results underscore the 0.7mg dexamethasone implant's potential in improving certain electrophysiological markers in DMO, while also highlighting the need for further investigation into its comprehensive impact on retinal function.
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Affiliation(s)
- Paris Tranos
- Vitreoretinal Department, Ophthalmica Eye Institute, Thessaloniki, Greece
| | - Stavrenia Koukoula
- Vitreoretinal Department, Ophthalmica Eye Institute, Thessaloniki, Greece
| | | | - Marianna Tranou
- Vitreoretinal Department, Ophthalmica Eye Institute, Thessaloniki, Greece
| | | | - Panagiotis Stavrakas
- Department of Ophthalmology, School of Medicine, University of Patras, Patras, Greece
| | - Georgios D Panos
- Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UK
- Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK
- First Department of Ophthalmology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
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Agostini H, Abreu F, Baumal CR, Chang DS, G Csaky K, Demetriades AM, Kodjikian L, Lim JI, Margaron P, Monés JM, Peto T, Ricci F, Rüth M, Singh RP, Stoilov I, Swaminathan B, Willis JR, Westenskow PD. Faricimab for neovascular age-related macular degeneration and diabetic macular edema: from preclinical studies to phase 3 outcomes. Graefes Arch Clin Exp Ophthalmol 2024; 262:3437-3451. [PMID: 38847896 PMCID: PMC11584429 DOI: 10.1007/s00417-024-06531-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Revised: 05/14/2024] [Accepted: 05/22/2024] [Indexed: 11/24/2024] Open
Abstract
Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard of care for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD); however, vision gains and anatomical improvements are not sustained over longer periods of treatment, suggesting other relevant targets may be needed to optimize treatments. Additionally, frequent intravitreal injections can prove a burden for patients and caregivers. Angiopoietin-2 (Ang-2) has been explored as an additional therapeutic target, due to the involvement of Ang-2 in DME and nAMD pathogenesis. Recent evidence supports the hypothesis that targeting both VEGF and Ang-2 may improve clinical outcomes in DME and nAMD compared with targeting VEGF alone by enhancing vascular stability, resulting in reduced macular leakage, prevention of neovascularization, and diminished inflammation. Faricimab, a novel bispecific antibody that targets VEGF-A and Ang-2, has been evaluated in clinical trials for DME (YOSEMITE/RHINE) and nAMD (TENAYA/LUCERNE). These trials evaluated faricimab against the anti-VEGFA/B and anti-placental growth factor fusion protein aflibercept, both administered by intravitreal injection. In addition to faricimab efficacy, safety, and pharmacokinetics, durability was evaluated during the trials using a treat-and-extend regimen. At 1 year, faricimab demonstrated non-inferior vision gains versus aflibercept across YOSEMITE/RHINE and TENAYA/LUCERNE. In YOSEMITE/RHINE, faricimab improved anatomic parameters versus aflibercept. Reduction of central subfield thickness (CST), and absence of both DME and intraretinal fluid were greater in faricimab- versus aflibercept-treated eyes. In TENAYA/LUCERNE, CST reductions were greater for faricimab than aflibercept at the end of the head-to-head phase (0-12 weeks), and were comparable with aflibercept at year 1, but with less frequent dosing. CST and vision gains were maintained during year 2 of both YOSEMITE/RHINE and TENAYA/LUCERNE. These findings suggest that dual Ang-2/VEGF-A pathway inhibition may result in greater disease control versus anti-VEGF alone, potentially addressing the unmet needs and reducing treatment burden, and improving real-world outcomes and compliance in retinal vascular diseases. Long-term extension studies (RHONE-X, AVONELLE-X) are ongoing. Current evidence suggests that dual inhibition with faricimab heralds the beginning of multitargeted treatment strategies inhibiting multiple, independent components of retinal pathology, with faricimab providing opportunities to reduce treatment burden and improve outcomes compared with anti-VEGF monotherapy.
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Affiliation(s)
- Hansjürgen Agostini
- Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | | | - Caroline R Baumal
- Tufts Medicine New England Eye Center, Boston, MA, USA
- Apellis Pharmaceuticals, Waltham, MA, USA
| | | | - Karl G Csaky
- Retina Foundation of the Southwest, Dallas, TX, USA
| | - Anna M Demetriades
- Department of Ophthalmology, Stanford University School of Medicine, Stanford, CA, USA
| | - Laurent Kodjikian
- Department of Ophthalmology, Croix-Rousse University Hospital, Hospices Civils de Lyon, Lyon, France
- CNRS UMR 5510 Mateis, INSA, University of Lyon I, Villeurbanne, France
| | - Jennifer I Lim
- Department of Ophthalmology and Visual Sciences, University of Illinois College of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | | | - Jordi M Monés
- Centro Médico Teknon, Institut de La Màcula and Barcelona Macula Foundation, Barcelona, Spain
| | - Tunde Peto
- Centre for Public Health, Queen's University Belfast, Belfast, UK
| | - Federico Ricci
- Department of Experimental Medicine, University "Tor Vergata", Rome, Italy
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Seyyar SA, Tokuç EÖ, Soysal GG. Effect of diabetic macular oedema on serum iron status indicators. Clin Exp Optom 2024; 107:313-317. [PMID: 37309021 DOI: 10.1080/08164622.2023.2218997] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 05/24/2023] [Indexed: 06/14/2023] Open
Abstract
CLINICAL RELEVANCE The role of subclinical inflammation in the pathophysiology of diabetic macular oedema (DME), which is known to be quite complex, is of much interest. Serum ferritin level, which is an indicator of body iron stores, is both an inflammatory marker for various neurodegenerative diseases and an important indicator in the evaluation of iron-induced oxidative stress. BACKGROUND Iron metabolism indicators play a role in the formation and development of diabetic retinopathy, which is known to be associated with subclinical inflammation, and may also play a role in the pathogenesis of DME. The aim of this study was to investigate the role of serum iron metabolism markers in the pathogenesis of DME. MATERIALS AND METHODS The files of all nonproliferative diabetic retinopathy (NPDR) patients who were scheduled for the first intravitreal injection for DME in the eye clinic between January 2019 and January 2020 were reviewed retrospectively. By examining the files of all diabetes mellitus patients who attended the outpatient eye clinic on the same dates, those without retinopathy and those with NPDR but not DME were recorded. All results, including a comprehensive ophthalmological examination, laboratory data of fasting blood tests, and an internal medicine outpatient examination were collected for analysis. RESULTS Of the 157 participants, 44 were NPDR patients with oedema, 50 were NPDR patients without oedema, and 63 were patients without retinopathy. There was a significant difference between the groups in respect of creatinine, high-density lipoprotein, mean corpuscular volume, serum iron and ferritin, total iron binding capacity and transferrin saturation (p < 0.050). Ferritin values were found to be significantly higher in patients with macular oedema. Other iron status markers were found to be significantly lower (p < 0.050). CONCLUSION Evaluation of serum iron status indicators in the routine follow-up of diabetic patients may be of diagnostic and/or prognostic benefit in terms of DME.
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Affiliation(s)
- Sevim Ayça Seyyar
- Ophthalmology Department, Gaziantep University Hospital, Gaziantep, Turkey
| | - Ecem Önder Tokuç
- Ophthalmology Department, Kocaeli University Hospital, Kocaeli, Turkey
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Bhatnagar A, Ting DSW, Weng CY. Treatment Options for Diabetic Macular Edema. Int Ophthalmol Clin 2024; 64:57-69. [PMID: 38146881 DOI: 10.1097/iio.0000000000000518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2023]
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Viggiano P, Grassi MO, Bisceglia G, Boscia G, Borrelli E, Malerba MG, Fracchiolla A, Alessio G, Boscia F. Short-term peripapillary structural and vascular changes following anti-VEGF vs. Dexamethasone intravitreal therapy in patients with DME. Eur J Ophthalmol 2023; 33:2236-2242. [PMID: 36938676 DOI: 10.1177/11206721231163615] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2023]
Abstract
PURPOSE To evaluate short-term peripapillary structural and vascular changes in DME after treatment with dexamethasone implant (DEX-I) and anti-VEGFs using OCT-A. METHODS Sixty-five patients with naïve center-involving DME were enrolled. 33 of sixty five patients (group 1) underwent with single DEX-I 0.7 mg (Ozurdex, Allergan, Inc., USA), 32 of sixty-five (group 2) underwent with intravitreal injection of aflibercept 0.5 mg (Eylea, Bayer, Genentech, San Francisco, USA). The OCT acquisition was completed at the following visits: (i) "T1 visit" corresponding to the intravitreal injection of DEX-I or aflibercept in patients with naïve center-involving DME (ii) "T2 visit" corresponding to the examination performed 2 weeks after intravitreal injection of aflibercept and 1 month after DEX-I. The parameters analyzed were: (i) RPC vasculature density (VD); (ii) peripapillary retinal nerve fiber layer (pRNFL) thickness, and (iii) intraocular pressure (IOP). RESULTS The RPC analysis showed a VD increase at T2 in both groups, although values did not reach statistical significance (48.12± 4.17 and 49.04 ± 4.23; P = 0.081 in Group 1 and 46.93± 3.16 and 47.17 ± 3.70; P = 0.087 in Group 2). Likewise, the pRNFL thickness and IOP fluctuations did not show statistically significant changes in in both groups among the different study visits. CONCLUSIONS After intravitreal injection (anti-VEGF or DEX-I), no significant short-term changes were found in peripapillary microvasculature, IOP and pRNFL thickness in diabetic eyes treated with anti-VEGF or DEX-I.
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Affiliation(s)
- Pasquale Viggiano
- Department of Translational Biomedicine Neuroscience, University of Bari "Aldo Moro", Bari, Italy
| | - Maria Oliva Grassi
- Department of Translational Biomedicine Neuroscience, University of Bari "Aldo Moro", Bari, Italy
| | - Giulia Bisceglia
- Department of Translational Biomedicine Neuroscience, University of Bari "Aldo Moro", Bari, Italy
| | - Giacomo Boscia
- Ophthalmology Unit, A.O.U. City of Health and Science of Turin, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Enrico Borrelli
- Ophthalmology Department, San Raffaele University Hospital, Milan, Italy
| | - Maria Giovanna Malerba
- Department of Translational Biomedicine Neuroscience, University of Bari "Aldo Moro", Bari, Italy
| | - Antonio Fracchiolla
- Department of Translational Biomedicine Neuroscience, University of Bari "Aldo Moro", Bari, Italy
| | - Giovanni Alessio
- Department of Translational Biomedicine Neuroscience, University of Bari "Aldo Moro", Bari, Italy
| | - Francesco Boscia
- Department of Translational Biomedicine Neuroscience, University of Bari "Aldo Moro", Bari, Italy
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Han YE, Jo J, Kim YJ, Lee J. Factors Affecting Intensive Aflibercept Treatment Response in Diabetic Macular Edema: A Real-World Study. J Diabetes Res 2023; 2023:1485059. [PMID: 37497120 PMCID: PMC10368507 DOI: 10.1155/2023/1485059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2023] [Revised: 05/15/2023] [Accepted: 06/29/2023] [Indexed: 07/28/2023] Open
Abstract
Objective To investigate the systemic and ocular factors that affect the response to intensive aflibercept treatment in diabetic macular edema (DME) in a real-world setting. Methods This retrospective cohort study evaluated 30 eyes of 23 patients with DME who underwent intensive intravitreal aflibercept injections (five monthly loading doses). Treatment response was assessed by central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at each monthly visit. The patients were categorized as good (<300 μm) and suboptimal (≥300 μm) responders based on CRT after the loading phase. Baseline systemic and ocular factors associated with treatment response were investigated. Results The mean CRT and BCVA significantly improved after five loading injections (486.87 ± 95.46 to 334.90 ± 69.47 μm and 0.51 ± 0.30 to 0.35 ± 0.25 LogMAR, respectively, all p < 0.05). During 12 months of follow-up, 16 eyes (53.33%) maintained CRT without additional treatment. Eyes with diabetes mellitus (DM) for ≥15 years, estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2, serum creatinine ≥ 0.95 mg/dL and potassium ≥ 4.7 mmol/L, and presence of epiretinal membrane (ERM) were more likely to have a suboptimal response to the treatment. Conclusions Five monthly loading doses of intravitreal aflibercept injection provided significant anatomical and visual improvements in patients with DME. Patients with longer DM duration, lower eGFR, higher serum creatinine or potassium levels, or ERM were predisposed to a suboptimal treatment response. Individual response to intensive aflibercept treatment for DME can be predicted by these systemic and ocular risk factors.
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Affiliation(s)
- Ye Eun Han
- Department of Ophthalmology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
| | - Jaehyuck Jo
- Department of Ophthalmology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
| | - Yoon Jeon Kim
- Department of Ophthalmology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
| | - Junyeop Lee
- Department of Ophthalmology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea
- Asan Diabetes Center, Asan Medical Center, Seoul, Republic of Korea
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8
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Chouhan S, Kalluri Bharat RP, Surya J, Mohan S, Balaji JJ, Viekash VK, Lakshminarayanan V, Raman R. Preliminary Report on Optical Coherence Tomography Angiography Biomarkers in Non-Responders and Responders to Intravitreal Anti-VEGF Injection for Diabetic Macular Oedema. Diagnostics (Basel) 2023; 13:diagnostics13101735. [PMID: 37238219 DOI: 10.3390/diagnostics13101735] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 05/05/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
PURPOSE To identify optical coherence tomography angiography (OCTA) biomarkers in patients who were treated for diabetic macular oedema (DME) with intravitreal anti-vascular endothelial growth factor (VEGF) injections and compare the OCTA parameters between responders and non-responders. METHODS A retrospective cohort study of 61 eyes with DME who received at least one intravitreal anti-VEGF injection was included between July 2017 and October 2020. The subjects underwent a comprehensive eye examination followed by an OCTA examination before and after intravitreal anti-VEGF injection. Demographic data, visual acuity, and OCTA parameters were documented, and further analysis was performed pre- and post-intravitreal anti-VEGF injection. RESULTS Out of 61 eyes which underwent intravitreal anti-VEGF injection for diabetic macular oedema, 30 were responders (group 1) and 31 were non-responders (group 2). We found that the responders (group 1) had a higher vessel density in the outer ring that was statistically significant (p = 0.022), and higher perfusion density was noted in the outer ring (p = 0.012) and full ring (p = 0.044) at levels of the superficial capillary plexus (SCP). We also observed a lower vessel diameter index in the deep capillary plexus (DCP) in responders when compared to non-responders (p < 0.00). CONCLUSION The evaluation of SCP in OCTA in addition to DCP can result in a better prediction of treatment response and early management in diabetic macular oedema.
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Affiliation(s)
- Sanjana Chouhan
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai 600006, India
| | | | - Janani Surya
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai 600006, India
| | - Sashwanthi Mohan
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai 600006, India
| | | | - V K Viekash
- Department of Instrumentation and Control Engineering, National Institute of Technology, Tiruchirappalli 620015, India
| | - Vasudevan Lakshminarayanan
- Theoretical and Experimental Epistemology Lab, School of Optometry and Vision Science, University of Waterloo, Waterloo, ON N2L 3G1, Canada
| | - Rajiv Raman
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralaya, Chennai 600006, India
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P. Simões D, Moreira Perez M, Aguiar Alves BDC, Araújo Encinas JF, Santos Raimundo JR, Costas Arcia CG, Lopes Mathia V, Sacchi Mendonça MI, Mesiano Maifrino LB, Murad N, Affonso Fonseca FL, Luciano da Veiga G. A Cross-Sectional Study of p66Shc Gene Expression in Liquid Biopsy of Diabetic Patients. Is it Possible to Predict the Onset of Renal Disease? INTERNATIONAL JOURNAL OF MEDICAL STUDENTS 2023. [DOI: 10.5195/ijms.2022.1306] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023] Open
Abstract
Background: Diabetic nephropathy (DN) is a disorder affecting glomerular function that, histologically, is due to the presence of glomerulosclerosis accompanied with endothelial dysfunction of the afferent and efferent renal arterioles. Insulin resistance in diabetic patients is known to be one of the causes of endothelial dysfunction because it increases oxidative stress, and one of the main genes regulating the production pathways of reactive oxygen species is p66Shc. The aim of this study was to evaluate the p66Shc gene expression as a precocious biomarker of renal dysfunction in diabetic patients, using liquids samples of urine sediment and peripheral blood.
Methods: 29 diabetic patients and 37 healthy donors were recruited from the Centro Universitário FMABC outpatient clinic. The RT-gPCR technique was applied to evaluate p66Shc gene expression in urine and peripheral blood samples from diabetic patients, which were compared with healthy donors.
Results: There was no significant expression of p66Shc gene in samples from diabetic patients compared with healthy donors. However, p66Shc expression in the blood samples of diabetics (0.02417±0.078652-ΔCT, n=29) was 3.6 times higher than in healthy participants (0.00689±0.01758, n=37) while in the urine samples, it was 1.48 times higher in diabetics group (0.02761±0.05412-ΔCT) than in CTL group (0.0186±0.02199).
Conclusion: There was no significant p66Shc gene expression in peripheral blood and urine samples of diabetic patients without kidney injury compared with healthy donors, although there is a tendency for this gene to participate in the oxidative imbalance present in diabetes.
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Zhang CX, Lou Y, Chi J, Bao XL, Fan B, Li GY. Considerations for the Use of Photobiomodulation in the Treatment of Retinal Diseases. Biomolecules 2022; 12:biom12121811. [PMID: 36551239 PMCID: PMC9775242 DOI: 10.3390/biom12121811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 11/26/2022] [Accepted: 12/01/2022] [Indexed: 12/11/2022] Open
Abstract
Photobiomodulation (PBM) refers to the beneficial effect produced from low-energy light irradiation on target cells or tissues. Increasing evidence in the literature suggests that PBM plays a positive role in the treatment of retinal diseases. However, there is great variation in the light sources and illumination parameters used in different studies, resulting in significantly different conclusions regarding PBM's therapeutic effects. In addition, the mechanism by which PBM improves retinal function has not been fully elucidated. In this study, we conducted a narrative review of the published literature on PBM for treating retinal diseases and summarized the key illumination parameters used in PBM. Furthermore, we explored the potential molecular mechanisms of PBM at the retinal cellular level with the goal of providing evidence for the improved utilization of PBM in the treatment of retinal diseases.
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Affiliation(s)
- Chun-Xia Zhang
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130042, China
| | - Yan Lou
- Department of Nephropathy, The Second Hospital of Jilin University, Changchun 130042, China
| | - Jing Chi
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130042, China
| | - Xiao-Li Bao
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130042, China
| | - Bin Fan
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130042, China
- Correspondence: (B.F.); (G.-Y.L.)
| | - Guang-Yu Li
- Department of Ophthalmology, The Second Hospital of Jilin University, Changchun 130042, China
- Correspondence: (B.F.); (G.-Y.L.)
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Le NT, Kroeger ZA, Lin WV, Khanani AM, Weng CY. Novel Treatments for Diabetic Macular Edema and Proliferative Diabetic Retinopathy. Curr Diab Rep 2021; 21:43. [PMID: 34719742 DOI: 10.1007/s11892-021-01412-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/19/2021] [Indexed: 01/04/2023]
Abstract
PURPOSE OF REVIEW Diabetic retinopathy (DR), a common cause of vision loss, is projected to increase worldwide, and is associated with significant morbidity. The current standard-of-care treatments can preserve and significantly improve vision in many patients affected by DR. However, challenges such as heavy treatment burden and refractory disease remain. The purpose of this review is to highlight and discuss investigative agents in development for the treatment of DR. RECENT FINDINGS There are several novel agents with unique mechanisms that may offer greater durability and efficacy compared to existing drugs. Some target new pathways, others leverage a slow-release delivery system, and some modify gene expression through a single-dose treatment. While unfavorable adverse events, such as intraocular inflammation, have been observed with longer-durability agents, many investigational products show excellent efficacy and safety profiles. The outcomes of ongoing and future trials may revolutionize the current treatment paradigm for DR.
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Affiliation(s)
- Nhon T Le
- Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, 1977 Butler Blvd, Houston, TX, 77030, USA
| | - Zachary A Kroeger
- Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, 1977 Butler Blvd, Houston, TX, 77030, USA
| | - Weijie Violet Lin
- Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Medical Center, New York, NY, USA
| | - Arshad M Khanani
- Sierra Eye Associates, Reno, NV, USA
- Reno School of Medicine, The University of Nevada, Reno, NV, USA
| | - Christina Y Weng
- Department of Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, 1977 Butler Blvd, Houston, TX, 77030, USA.
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Kessler LJ, Auffarth GU, Bagautdinov D, Khoramnia R. Ellipsoid Zone Integrity and Visual Acuity Changes during Diabetic Macular Edema Therapy: A Longitudinal Study. J Diabetes Res 2021; 2021:8117650. [PMID: 34660813 PMCID: PMC8516551 DOI: 10.1155/2021/8117650] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 09/06/2021] [Indexed: 11/17/2022] Open
Abstract
PURPOSE Ellipsoid zone (EZ) integrity is identified as a potential biomarker for therapy surveillance and outcome prediction of visual acuity (VA). However, only a few studies report long-term results of over 1 year of clinical and anatomical changes in patients with diabetic macular edema (DME). This study is aimed at describing the long-term VA and anatomical outcomes in spectral domain optical coherence tomography (OCT) (relative ellipsoid zone reflectivity ratio, central macular thickness, and volume) in patients with DME treated with antivascular endothelial growth factor (anti-VEGF) therapy. Furthermore, we studied the correlation between EZ integrity and changes in visual acuity. METHODS 71 eyes of 71 patients were included in this retrospective study. Clinical characteristics were reviewed yearly. OCT data were assessed at baseline and after 1, 3, and 5 years. EZ parameters were quantified automatically. OCT parameters and visual outcome were correlated and analyzed in multivariable regression models. RESULTS EZ reflectivity ratio correlated with functional outcome in DME patients from baseline to fifth year at all time points (for all p < 0.05). EZ reflectivity improved the most in the first year of treatment (0.68 to 0.75; p < 0.05) and declined gradually until year 5 of therapy (0.71; compared to baseline p > 0.05). Similarly, best VA was achieved after 1 year (0.40 logarithm of the minimum angle of resolution (logMAR) to 0.28 logMAR; p < 0.001) and declined gradually until year 5. Final VA in year 5 was comparable to baseline (0.45 logMAR, compared to baseline p > 0.05). Together with baseline VA, baseline EZ parameters did predict VA outcome after 1 year (p < 0.05). Concordantly, VA and EZ parameters from year 1 were associated with VA outcome in year 2. CONCLUSION This study described the long-term course of EZ changes during anti-VEGF treatment in DME patients. In addition, our results underlined the potential of EZ parameters as novel OCT biomarkers for prediction of VA outcomes during therapy.
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Affiliation(s)
- Lucy J. Kessler
- Department of Ophthalmology, University of Heidelberg, Heidelberg 69120, Germany
- HEiKA–Heidelberg Karlsruhe Strategic Partnership, Heidelberg University and Karlsruhe Institute of Technology (KIT), Karlsruhe 76131, Germany
| | - Gerd U. Auffarth
- Department of Ophthalmology, University of Heidelberg, Heidelberg 69120, Germany
| | - Dmitrii Bagautdinov
- Department of Ophthalmology, University of Heidelberg, Heidelberg 69120, Germany
| | - Ramin Khoramnia
- Department of Ophthalmology, University of Heidelberg, Heidelberg 69120, Germany
- HEiKA–Heidelberg Karlsruhe Strategic Partnership, Heidelberg University and Karlsruhe Institute of Technology (KIT), Karlsruhe 76131, Germany
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13
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Figueira J, Henriques J, Carneiro Â, Marques-Neves C, Flores R, Castro-Sousa JP, Meireles A, Gomes N, Nascimento J, Amaro M, Silva R. Guidelines for the Management of Center-Involving Diabetic Macular Edema: Treatment Options and Patient Monitorization. Clin Ophthalmol 2021; 15:3221-3230. [PMID: 34354341 PMCID: PMC8331083 DOI: 10.2147/opth.s318026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 06/15/2021] [Indexed: 02/05/2023] Open
Abstract
Diabetic macular edema (DME) is the main cause of visual impairment associated with diabetic retinopathy (DR) and macular laser, during approximately three decades, and was the single treatment option. More recently, intravitreous injections of anti-angiogenics and corticosteroids modified the treatment paradigm associated with significant vision improvements. Nevertheless, not all patients respond satisfactorily to anti-VEGF or corticosteroid injections, so an adequate treatment choice and a prompt switch in therapeutic class is recommended. Several algorithms and guidelines have been proposed for treating center involving DME to improve patients’ vision and quality of life. However, in Portugal, such guidelines are lacking. The present review aimed to provide guidelines for the treatment options and patient monitorization in the management of center-involving DME. We recommend anti-vascular endothelial growth factor (VEGF) as first-line therapy after a clinical evaluation accompanied by a rigorous metabolic control. Depending on the response obtained after 3–6 monthly intravitreal injections we suggest switching outside the class in case of a non-responder, maintaining the anti-VEGF-therapy in responders to anti-angiogenics. The treatment regimen for Dexamethasone intravitreal implant (DEXii) should be pro-re-nata with bi-monthly or quarterly monitoring visits (with a scheduled visit at 6–8 weeks after DEXii for intraocular pressure control). If a patient does not respond to DEXii, switch again to anti-VEGF therapy, combine therapies, or re-evaluate patients diagnose. There is a resilient need to understand the disease, its treatments, regimens available, and convenience for all involved to propose an adequate algorithm for the treatment of diabetic retinopathy (DR) and DME in an individualized regimen. Further understanding of the contributing factors to the development and progression of DR should bring new drug discoveries for more effective and better-tolerated treatments.
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Affiliation(s)
- João Figueira
- Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal; Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal.,AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal
| | - José Henriques
- Retina Department, Retinal Surgical Unit, Dr. Gama Pinto Ophthalmology Institute, Lisbon, Portugal
| | - Ângela Carneiro
- Department of Ophthalmology, Centro Hospitalar Universitário de São João, Porto, Portugal.,Department of Surgery and Physiology, Faculty of Medicine of University of Porto, Porto, Portugal
| | - Carlos Marques-Neves
- Department of Ophthalmology, Centro Hospitalar Universitário de Lisboa Norte, EPE - Hospital de Santa Maria, Lisbon, Portugal.,Department of Ophthalmology, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.,ALM Oftalmolaser, Lisbon, Portugal
| | - Rita Flores
- Department of Ophthalmology, Centro Hospitalar de Lisboa Central EPE, Lisbon, Portugal.,CEDOC, Chronic Diseases Research Center, NOVA Medical School, Lisbon, Portugal
| | - João Paulo Castro-Sousa
- Department of Ophthalmology, Centro Hospitalar de Leiria, Leiria, Portugal.,CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.,Faculty of Medical Sciences, Universidade da Beira Interior, Covilhã, Portugal
| | - Angelina Meireles
- Ophthalmology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal.,Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Nuno Gomes
- Ophthalmology Department, Hospital de Braga, Braga, Portugal
| | - João Nascimento
- Instituto de Retina e Diabetes Oculares de Lisboa, Lisbon, Portugal
| | - Miguel Amaro
- Ophthalmology Department, Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal
| | - Rufino Silva
- Ophthalmology Department, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal; Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal.,AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.,Coimbra Medical Space, Coimbra, Portugal
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14
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Minnella AM, Picardi SM, Maceroni M, Albanesi F, De Siena E, Placidi G, Caputo CG, De Vico U, Rizzo S, Falsini B. Retinal Morpho-Functional Changes Following 0.19 mg Fluocinolone Acetonide Intravitreal Implant for Chronic Diabetic Macular Edema. Adv Ther 2021; 38:3143-3153. [PMID: 33948926 PMCID: PMC8096132 DOI: 10.1007/s12325-021-01751-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 04/16/2021] [Indexed: 11/23/2022]
Abstract
Purpose To evaluate morpho-functional outcomes of the intravitreal fluocinolone acetonide (FAc) implant. Methods Retrospective, observational, single-center study. Primary endpoint was the mean change in central macular thickness (CMT) from baseline to month 1–3. Secondary endpoints included mean CMT change from baseline to month 4–8 and 9–14 and mean best corrected visual acuity (BCVA), photopic negative response (PhNR) and b-wave of flash full-field electroretinogram (ERG) changes from baseline to month 1–3, 4–8, and 9–14. Results Fourteen patients (18 eyes) were included. Mean (standard deviation) CMT decreased from 473 (196) µm at baseline to 371 (163) µm at month 1–3 (mean difference − 102.3 ± 98.35 µm, 95% CI ± 46.4 µm; p < 0.0001) and this decrease tended to endure up to month 9–14. BCVA did not change significantly. There was an improvement in mean PhNR amplitude from 2.76 (1.65) µV at baseline to 3.73 (2.32) µV at month 1–3 (mean difference 0.91 (1.14) µV, 95% CI ± 0.54 µV, p = 0.003); b-wave amplitude improved from 8.83 (4.52) µV at baseline versus 10.05 (5.04) µV at month 1–3 (mean difference 1.22 (2.23) µV, 95% CI ± 1.08 µV, p = 0.0384). These ERG positive changes tended to endure up to month 9–14, although they did not reach statistical significance after month 3. Conclusions Intravitreal FAc implant significantly improved anatomic as well as functional outcomes related to middle and inner retinal layers, known to be altered in diabetic retinopathy. Our findings support the hypothesis that intravitreal FAc implant may exert a protective effect in diabetic retinas with diabetic macular edema.
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15
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Kousha O, Delle Fave MM, Cozzi M, Carini E, Pagliarini S. Diabetic maculopathy: multicolour and SD-OCT versus fundus photography. BMJ Open Ophthalmol 2021; 6:e000514. [PMID: 33681471 PMCID: PMC7898856 DOI: 10.1136/bmjophth-2020-000514] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 11/08/2020] [Accepted: 02/08/2021] [Indexed: 11/03/2022] Open
Abstract
Objective The English Diabetic Eye Screening (DES) programme recommends patients with M1 diabetic maculopathy to be referred to hospital eye services. DES uses flash fundus photography as the reference standard for maculopathy grading. We compared multicolour versus non-stereoscopic fundus photography at identifying M1 maculopathy, with spectral domain optical coherence tomography (SD-OCT) identifying macular thickening. Methods and analysis This cross-sectional study included 345 patients with R1M1 referred from DES and reviewed in secondary care with fundus photographs, multicolour and SD-OCT. Maculopathy was graded based on DES exudate criteria on both multicolour and fundus photography in a blind fashion by two independent graders. Macular thickness was ascertained on SD-OCT. Results Intergrader agreement on grading maculopathy using fundus photography (Cohen's κ=0.91) and multicolour (Cohen's κ=0.82) was 'almost perfect'. Agreement between fundus photography and multicolour on grading maculopathy (Cohen's κ=0.76) was 'substantial'. Compared with fundus photography, multicolour had sensitivity of 87% (95% CI 81% to 93%) and specificity of 90% (95% CI 87% to 94%) in detecting M1 maculopathy. SD-OCT identified 84 eyes with macular thickening, 47 of which were graded as M0 by fundus photography. 5 eyes with exudates and severe macular oedema requiring urgent intervention were also missed on fundus photography but not on multicolour. Multicolour, when complemented by SD-OCT, did not miss any clinically significant macular oedema. Conclusion Multicolour integrates synergistically in a single platform with SD-OCT providing effective monitoring of M1 diabetic maculopathy. The need for fundus photography is eliminated by multicolour/SD-OCT in dedicated R1M1 virtual clinics not requiring parallel diabetic retinopathy grading.
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Affiliation(s)
- Obaid Kousha
- Department of Ophthalmology, Ninewells Hospital, Dundee, UK
| | | | - Mariano Cozzi
- Department of Biomedical and Clinical Science, Luigi Sacco University Hospital, Milano, Lombardia, Italy
| | - Elisa Carini
- Eye Clinic, Department of Biomedical and Clinical Science, Luigi Sacco University Hospital, Milano, Lombardia, Italy
| | - Sergio Pagliarini
- Department of Ophthalmology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
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16
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Ma LY, Rong A, Jiang Y, Deng SY. Effects of Femtosecond Laser-Assisted Cataract Surgery on Macular and Choroidal Thickness in Diabetic Patients. Ophthalmol Ther 2021; 10:137-150. [PMID: 33464557 PMCID: PMC7887143 DOI: 10.1007/s40123-020-00326-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 12/15/2020] [Indexed: 11/16/2022] Open
Abstract
Introduction This study aimed to compare the short-term changes in retinal and choroid thickness in diabetic patients after femtosecond laser-assisted cataract surgery (FLACS) and phacoemulsification (PE) surgery. Methods A total of 47 eyes in the PE group and 44 eyes in the FLACS group were included. All patients underwent measurement of central macular thickness (CMT) and subfoveal choroidal thickness (SFCT) before and after surgery using optical coherence tomography (OCT). Results The effective phaco time (EPT) in the FLACS group was significantly reduced. The BCVA differed significantly between the two groups at 1 week and 1 month after surgery. The CMT in both groups increased at 1 week after the operation. It did not return to the preoperative level until month 12 in the PE group. In the FLACS group, the CMT began to decrease at month 3 and recovered to the preoperative level at month 12. The SFCT of the two groups increased at week 1; it began to decrease at month 6 in the PE group but did not recover to the preoperative level until month 12. The SFCT in the FLACS group recovered to preoperative levels at month 6. In the PE group, baseline CMT values predicted CMT change at week 1 and months 1, 3 and 12 after surgery. In the FLACS group, baseline CMT predicted CMT changes at week 1, month 1 and month 3. In the FLACS group, EPT predicted SFCT change at month 3. Conclusion FLACS is safe and effective in patients with no fundus change or mild diabetic retinopathy. It has advantages in effectively reducing EPT, achieving good vision earlier and promoting faster recovery of the retinal and choroidal thickness. Preoperative CMT is a significant predictor of CMT changes in the early period after FLACS.
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Affiliation(s)
- Ling-Yun Ma
- Department of Ophthalmology, Tongji Hospital Affiliated to Tongji University, Shanghai, 200065, China
| | - Ao Rong
- Department of Ophthalmology, Tongji Hospital Affiliated to Tongji University, Shanghai, 200065, China. .,Shanghai Xin Shi Jie Eye Hospital, Shanghai, 200050, China.
| | - Yi Jiang
- Shanghai Xin Shi Jie Eye Hospital, Shanghai, 200050, China
| | - Shu-Ya Deng
- Department of Ophthalmology, Tongji Hospital Affiliated to Tongji University, Shanghai, 200065, China
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17
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da Veiga GL, da Costa Aguiar Alves B, Perez MM, Raimundo JR, de Araújo Encinas JF, Murad N, Fonseca FLA. Kidney Diseases: The Age of Molecular Markers. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1306:13-27. [PMID: 33959903 DOI: 10.1007/978-3-030-63908-2_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Kidney diseases are conditions that increase the morbidity and mortality of those afflicted. Diagnosis of these conditions is based on parameters such as the glomerular filtration rate (GFR), measurement of serum and urinary creatinine levels and equations derived from these measurements (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015). However, serum creatinine as a marker for measuring renal dysfunction has its limitations since it is altered in several other physiological situations, such as in patients with muscle loss, after intense physical exercise or in people on a high protein diet (Riley, Powers, Welch. Res Q Exerc Sport 52(3):339-347, 1981; Juraschek, Appel, Anderson, Miller. Am J Kidney Dis 61(4):547-554, 2013). Besides the fact that serum creatinine is a marker that indicates glomerular damage, it is necessary the discovery of new biomarkers that reflect not only glomerular damage but also tubular impairment. Recent advances in Molecular Biology have led to the generation or identification of new biomarkers for kidney diseases such as: Acute Kidney Failure (AKI), chronic kidney disease (CKD), nephritis or nephrotic syndrome. There are recent markers that have been used to aid in diagnosis and have been shown to be more sensitive and specific than classical markers, such as neutrophil gelatinase associated lipocalin (NGAL) or kidney injury molecule-1 (KIM-1) (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015; George, Gounden. Adv Clin Chem 88:91-119, 2019; Han, Bailly, Abichandani, Thadhani, Bonventre. Kidney Int 62(1):237-244, 2002; Fontanilla, Han. Expert Opin Med Diagn 5(2):161-173, 2011). However, early diagnostic biomarkers are still necessary to assist the intervention and monitor of the progression of these conditions.
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Affiliation(s)
| | | | | | | | | | - Neif Murad
- Cardiology Department, Centro Universitário Saúde ABC, Santo André, Brazil
| | - Fernando Luiz Affonso Fonseca
- Division of Clinical Analysis, Centro Universitário Saúde ABC, Santo André, Brazil.,Pharmaceutical Science Department, Universidade Federal de São Paulo/UNIFESP - Diadema, Butantã, São Paulo, Brazil
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18
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de Andrés-Nogales F, Casado MÁ, Trillo JL, Ruiz-Moreno JM, Martínez-Sesmero JM, Peralta G, Poveda JL, Ortiz P, Ignacio E, Zarranz-Ventura J, Udaondo P, Mur C, Álvarez E, Cervera E, Martínez M, Llorente I, Zulueta J, Rodríguez-Maqueda M, García-Layana A, Martínez-Olmos J. A Multiple Stakeholder Multicriteria Decision Analysis in Diabetic Macular Edema Management: The MULTIDEX-EMD Study. PHARMACOECONOMICS - OPEN 2020; 4:615-624. [PMID: 32100249 PMCID: PMC7688881 DOI: 10.1007/s41669-020-00201-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
BACKGROUND The clinical and economic management of retinal diseases has become more complex following the introduction of new intravitreal treatments. Multicriteria decision analysis (MCDA) offers the potential to overcome the challenges associated with traditional decision-making tools. OBJECTIVES A MCDA to determine the most relevant criteria to decision-making in the management of diabetic macular edema (DME) based on the perspectives of multiple stakeholders in Spain was developed. This MCDA was termed the MULTIDEX-EMD study. METHODS Nineteen stakeholders (7 physicians, 4 pharmacists, 5 health authorities and health management experts, 1 psychologist, and 2 patient representatives) participated in this three-phase project. In phase A, an advisory board defined all of the criteria that could influence DME treatment decision-making. These criteria were then screened using a discrete choice experiment (DCE) (phase B). Next, a multinomial logit model was fitted by applying the backward elimination algorithm (relevant criteria: p value < 0.05). Finally, the results were discussed in a deliberative process (phase C). RESULTS Thirty-one criteria were initially defined (phase A) and grouped into 5 categories: efficacy/effectiveness, safety, organizational and economic impact, patient-reported outcomes, and other therapeutic features. The DCE results (phase B) showed that 10 criteria were relevant to the decision-making process for a 50- to 65-year-old DME patient: mean change in best corrected visual acuity (p value < 0.001), percentage of patients with an improvement of ≥ 15 letters (p value < 0.001), effect duration per administration (p value = 0.008), retinal detachment (p value < 0.001), endophthalmitis (p value = 0.012), myocardial infarction (p value < 0.001), intravitreal hemorrhage (p value = 0.021), annual treatment cost per patient (p value = 0.001), health-related quality of life (HRQoL) (p value = 0.004), and disability level (p value = 0.021). CONCLUSIONS From a multi-stakeholder perspective, the selection of an appropriate treatment for DME patients should guarantee patient safety and maximize the visual acuity improvement and treatment effect duration. It should also contribute to system sustainability by being affordable, it should have a positive impact on HRQoL, and it should prevent disability.
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Affiliation(s)
| | | | | | - José María Ruiz-Moreno
- Universidad Castilla La Mancha, Albacete, Spain; Vissum Corporación, Spain; Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Spain
- RETICS-OFTARED, Instituto de Salud Carlos III, Madrid, Spain
| | | | - Gemma Peralta
- Fundació Rossend Carrasco i Formiguera, MentBarcelona, Barcelona, Spain
| | | | - Pere Ortiz
- Consorci MAR Parc de Salut de Barcelona, Barcelona, Spain
| | | | - Javier Zarranz-Ventura
- RETICS-OFTARED, Instituto de Salud Carlos III, Madrid, Spain
- Instituto Clinic de Oftalmología, Hospital Clinic, Barcelona, Spain
| | | | - Carlos Mur
- Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain
| | | | | | | | - Iñaki Llorente
- Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain
| | | | | | - Alfredo García-Layana
- RETICS-OFTARED, Instituto de Salud Carlos III, Madrid, Spain
- Clínica Universitaria de Navarra, Pamplona, Spain
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Singer MA, Wykoff CC, Grewal DS. Effects of Long-Term DME Control With 0.2 µg/Day Fluocinolone Acetonide Implant on Quality of Life: An Exploratory Analysis From the FAME Trial. Ophthalmic Surg Lasers Imaging Retina 2020; 51:658-667. [PMID: 33231701 DOI: 10.3928/23258160-20201104-10] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 09/03/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND OBJECTIVE Exploratory investigation of the effect of diabetic macular edema (DME) control with the 0.2 µg/day fluocinolone acetonide (FAc) intravitreal implant on quality of life (QOL) outcomes. PATIENTS AND METHODS Post-hoc analysis of patients from the FAME study who received the FAc implant and had answered the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) at baseline and Year 3 (N = 324). Patients were divided into quartiles (area under the curve [AUC]-central subfield thickness [CST]/day; n = 81/quartile). NEIVFQ-25 and best-corrected visual acuity (BCVA) changes were analyzed per quartile during a period of 3 years. RESULTS NEI-VFQ-25 scores were significantly higher in patients with low AUC-CST/day (Quartiles 1 [P < .001] and 2 [P = .004]). Increases in NEIVFQ-25 subscale scores correlated with AUC-CST/day quartiles. BCVA significantly improved in patients with the lowest AUC-CST/day (Quartiles 1 and 2 [P < .001]). CONCLUSION There was a positive and sustained correlation between the long-term control of DME and patient-reported QOL outcomes for up to 3 years following a single FAc implant in patients with controlled DME. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:658-667.].
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20
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Vadalà M, Sunseri Trapani V, Guarrasi G, Ventura N, Castellucci M, Cillino S. A Real-World Study of Dexamethasone Implant in Treatment-Naïve Patients with Diabetic Macular Edema: Efficacy and Correlation Between Inflammatory Biomarkers and Treatment Outcome. Clin Ophthalmol 2020; 14:2657-2665. [PMID: 32982158 PMCID: PMC7501979 DOI: 10.2147/opth.s257775] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 08/07/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose There has been an increasing clinical interest in specific retinal parameters as non-invasive biomarkers of retinal inflammation in diabetic macular edema (DME) that have been shown to have prognostic value, such as hyperreflective retinal fields (HRFs) and subfoveal neuroretinal detachment (SND). Methods We conducted a prospective, non-comparative study of treatment-naïve patients with DME to evaluate the efficacy of a Pro Re Nata (PRN) regimen of intravitreal dexamethasone implant 0.7 mg (DexI, Ozurdex™). After administration, patients underwent subsequent injections according to PRN criteria in case of edema relapse, but not earlier than 4 months after the previous treatment. Patients were evaluated at baseline, within 15 days of injection, and every month thereafter. During all visits, best-corrected visual acuity (BCVA) was recorded; central retinal thickness (CRT), type of edema, presence of SND, and presence and number of HRFs were evaluated using swept-source optical coherence tomography (SS-OCT) 3D. Treatment outcome was defined as changes in BCVA, CRT, SND and HRFs at 12 (T12) and 24 (T24) months compared with baseline (T0). Results The study enrolled 24 eyes of 18 patients. The mean duration of follow-up was 18±6.6 months; for all eyes, T12 data were available, while follow-up reached T24 for 12 eyes. BCVA improved significantly and CRT decreased significantly during treatment; the edema was no longer detectable in 13/24 eyes at T12 and 8/12 eyes at T24. No patient presented SND at T12 and T24, and the mean number of HRFs decreased significantly during treatment. Results with CRT and HRFs correlated with BCVA at 12 and 24 months. No significant adverse events were observed. Conclusion In patients with DME, the intravitreal dexamethasone implant was effective and safe in improving both functional and tomographic parameters. This result is consistent with improvement in biomarkers of inflammation.
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Affiliation(s)
- Maria Vadalà
- Biomedicine, Neuroscience and Advanced Diagnostic Department, University of Palermo, Palermo, Italy.,IEMEST, Euro-Mediterranean Institute of Science and Technology, Palermo, Italy
| | | | - Giulia Guarrasi
- Biomedicine, Neuroscience and Advanced Diagnostic Department, University of Palermo, Palermo, Italy
| | - Nicasio Ventura
- Biomedicine, Neuroscience and Advanced Diagnostic Department, University of Palermo, Palermo, Italy
| | - Massimo Castellucci
- Biomedicine, Neuroscience and Advanced Diagnostic Department, University of Palermo, Palermo, Italy
| | - Salvatore Cillino
- Biomedicine, Neuroscience and Advanced Diagnostic Department, University of Palermo, Palermo, Italy
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21
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Shah J, Vaze A, Tang Lee Say T, Gillies MC, Fraser-Bell S. Emerging corticosteroid delivery platforms for treatment of diabetic macular edema. Expert Opin Emerg Drugs 2020; 25:383-394. [PMID: 32815413 DOI: 10.1080/14728214.2020.1810664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Diabetic macular edema (DME) is a leading cause of vision impairment. Low-grade inflammation is thought to play a critical role in its pathogenesis. Although vascular endothelial growth factor inhibitors are used first-line, not all eyes with DME respond optimally and may respond better to corticosteroids. Currently corticosteroids for DME are given intravitreally and require regular monitoring. There is an unmet need for longer lasting therapies and/or effective noninvasive therapies such as those given via oral or topical routes. AREAS COVERED This review discusses emerging corticosteroid delivery platforms for DME treatment. A literature search of investigational novel therapeutic steroid delivery platform in DME was conducted. Results are presented from preclinical, phase 1,2 & 3 clinical trials of various drug delivery systems using new technologies such as Solubilizing Nanoparticle technology, Mucus Penetrating Particles technology and Particle Replication In Non-wetting Templates. These new platforms aim to deliver corticosteroids effectively via topical, episcleral, subtenon, oral, and intravitreal routes. EXPERT OPINION These novel drug delivery platforms have the potential to lead to noninvasive or minimally invasive therapies and may overcome the shortcomings of current pharmacotherapy. However, larger comparative trials are needed for these agents to be added to the current armamentarium in DME management.
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Affiliation(s)
- Janika Shah
- Medical Retina Department, Sydney Eye Hospital , Sydney, Australia.,Macula Research Unit, Save Sight Institute, University of Sydney , Sydney, Australia
| | - Anagha Vaze
- Medical Retina Department, Sydney Eye Hospital , Sydney, Australia.,Macula Research Unit, Save Sight Institute, University of Sydney , Sydney, Australia
| | - Timothy Tang Lee Say
- Medical Retina Department, Sydney Eye Hospital , Sydney, Australia.,Macula Research Unit, Save Sight Institute, University of Sydney , Sydney, Australia
| | - Mark C Gillies
- Medical Retina Department, Sydney Eye Hospital , Sydney, Australia.,Macula Research Unit, Save Sight Institute, University of Sydney , Sydney, Australia
| | - Samantha Fraser-Bell
- Medical Retina Department, Sydney Eye Hospital , Sydney, Australia.,Macula Research Unit, Save Sight Institute, University of Sydney , Sydney, Australia
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22
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Hu W, Ding Y, Li Q, shi R, He Y. Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes-related complications. J Diabetes Investig 2020; 11:757-769. [PMID: 32129549 PMCID: PMC7378409 DOI: 10.1111/jdi.13244] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 01/21/2020] [Accepted: 02/27/2020] [Indexed: 12/12/2022] Open
Abstract
With an estimated 425 million diabetes patients worldwide in 2019, type 2 diabetes has reached a pandemic proportion and represents a major unmet medical need. A key determinant of the development and progression of type 2 diabetes is pancreatic -cell dysfunction, including the loss of cell mass, the impairment of insulin biosynthesis and inadequate exocytosis. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), a Ca2+ -permeable non-selective cation channel, is involved in -cell replication, insulin production and secretion. TRPV4 agonists have insulinotropic activity in pancreatic -cell lines, but the prolonged activation of TRPV4 leads to -cell dysfunction and death. In addition, TRPV4 is involved in a wide variety of pathophysiological activities, and has been reported to play an important role in diabetes-related complications, such as obesity, cardiovascular diseases, diabetic retinopathy, nephropathy and neuropathy. In a rodent type 2 diabetes model, Trpv4 agonists promote vasodilation and improve cardiovascular function, whereas Trpv4 antagonists reduce high-fat diet-induced obesity, insulin resistance, diabetic nephropathy, retinopathy and neuropathy. These findings raise interest in using TRPV4 as a therapeutic target for type 2 diabetes. In this review, we intend to summarize the latest findings regarding the role of TRPV4 in diabetes as well as diabetes-related conditions, and to evaluate its potential as a therapeutic target for diabetes and diabetes-related diseases.
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Affiliation(s)
- Wei Hu
- Department of Epidemiology and Medical StatisticsInstitute of Medical Systems BiologyGuangdong Medical UniversityDongguanChina
| | - Yuanlin Ding
- Department of Epidemiology and Medical StatisticsInstitute of Medical Systems BiologyGuangdong Medical UniversityDongguanChina
| | - Qingqing Li
- Department of Epidemiology and Medical StatisticsInstitute of Medical Systems BiologyGuangdong Medical UniversityDongguanChina
| | - Rou shi
- Department of Epidemiology and Medical StatisticsInstitute of Medical Systems BiologyGuangdong Medical UniversityDongguanChina
| | - Yuqing He
- Department of Epidemiology and Medical StatisticsInstitute of Medical Systems BiologyGuangdong Medical UniversityDongguanChina
- Liaobu HospitalGuangdong Medical UniversityDongguanChina
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Rishi P, Rishi E, Attiku Y, Dhami A, Iyer V. Real-world experience with pro re nata dosing of intravitreal dexamethasone implant for eyes with refractory diabetic macular edema. GMS OPHTHALMOLOGY CASES 2020; 10:Doc21. [PMID: 32676266 PMCID: PMC7332721 DOI: 10.3205/oc000148] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Aims: To evaluate treatment outcomes of pro re nata dosing of intravitreal dexamethasone implant in eyes with refractory diabetic macular edema (DME) amongst Indian subjects. Methods and material: Retrospective, interventional case series. Medical records of 28 eyes of 23 patients with refractory DME who underwent intravitreal dexamethasone (700 µ) implant were reviewed. Paired t-test was carried out to measure mean change in the parameters evaluated. Mann-Whitney U test and Fisher’s exact t-test were done to explore differences between groups receiving single or multiple injections. Results: Best corrected visual acuity (BCVA) and central macular thickness (CMT) at baseline were 0.85 (±0.44) and 612 µm (±123), respectively. Mean CMT over 6 months (measured monthly) following injection was 340±119 µm (p=0.001), 346±150 µm (p=0.02), 368±169 µm (p=0.02), 304±174 µm (p=0.001), 525±216 µm (p=0.94) and 532±201 µm (p=0.46), respectively. Mean BCVA at each month following injection was 0.68±0.36 (p=0.02), 0.75±0.45 (p=0.42), 0.55±0.40 (p=0.11), 0.63±0.40 (p=0.12), 0.78±0.30 (p=0.90) and 0.60±0.47 (p=0.92), respectively. Mean follow-up was 12 months (range: 6–33 months). Mean BCVA and CMT at mean 12 months were 0.72±0.46 (p=0.10) and 358 µm±189 (p=0.0001), respectively. Seven eyes had raised IOP; five eyes required cataract extraction. Conclusions: Intravitreal dexamethasone implant is effective in treatment of refractory DME. However, its therapeutic effect lasts for about 4 months.
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Affiliation(s)
- Pukhraj Rishi
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralya, Chennai, India
| | - Ekta Rishi
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralya, Chennai, India
| | - Yamini Attiku
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralya, Chennai, India
| | - Abhinav Dhami
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralya, Chennai, India
| | - Vandana Iyer
- Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralya, Chennai, India
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24
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Akla N, Viallard C, Popovic N, Lora Gil C, Sapieha P, Larrivée B. BMP9 (Bone Morphogenetic Protein-9)/Alk1 (Activin-Like Kinase Receptor Type I) Signaling Prevents Hyperglycemia-Induced Vascular Permeability. Arterioscler Thromb Vasc Biol 2019; 38:1821-1836. [PMID: 29880487 DOI: 10.1161/atvbaha.118.310733] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Objective- Diabetic macular edema is a major cause of visual impairment. It is caused by blood-retinal barrier breakdown that leads to vascular hyperpermeability. Current therapeutic approaches consist of retinal photocoagulation or targeting VEGF (vascular endothelial growth factor) to limit vascular leakage. However, long-term intravitreal use of anti-VEGFs is associated with potential safety issues, and the identification of alternative regulators of vascular permeability may provide safer therapeutic options. The vascular specific BMP (bone morphogenetic protein) receptor ALK1 (activin-like kinase receptor type I) and its circulating ligand BMP9 have been shown to be potent vascular quiescence factors, but their role in the context of microvascular permeability associated with hyperglycemia has not been evaluated. Approach and Results- We investigated Alk1 signaling in hyperglycemic endothelial cells and assessed whether BMP9/Alk1 signaling could modulate vascular permeability. We show that high glucose concentrations impair Alk1 signaling, both in cultured endothelial cells and in a streptozotocin model of mouse diabetes mellitus. We observed that Alk1 signaling participates in the maintenance of vascular barrier function, as Alk1 haploinsufficiency worsens the vascular leakage observed in diabetic mice. Conversely, sustained delivery of BMP9 by adenoviral vectors significantly decreased the loss of retinal barrier function in diabetic mice. Mechanistically, we demonstrate that Alk1 signaling prevents VEGF-induced phosphorylation of VE-cadherin and induces the expression of occludin, thus strengthening vascular barrier functions. Conclusions- From these data, we suggest that by preventing retinal vascular permeability, BMP9 could serve as a novel therapeutic agent for diabetic macular edema.
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Affiliation(s)
- Naoufal Akla
- From the Department of Biochemistry (N.A., P.S.).,University of Montreal, Quebec, Canada; and Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada (N.A., C.V., N.P., C.L.G., P.S., B.L.)
| | - Claire Viallard
- Department of Molecular Biology (C.V., B.L.).,University of Montreal, Quebec, Canada; and Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada (N.A., C.V., N.P., C.L.G., P.S., B.L.)
| | - Natalija Popovic
- Department of Biomedical Sciences (N.P., C.L.G., B.L.).,University of Montreal, Quebec, Canada; and Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada (N.A., C.V., N.P., C.L.G., P.S., B.L.)
| | - Cindy Lora Gil
- Department of Biomedical Sciences (N.P., C.L.G., B.L.).,University of Montreal, Quebec, Canada; and Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada (N.A., C.V., N.P., C.L.G., P.S., B.L.)
| | - Przemyslaw Sapieha
- From the Department of Biochemistry (N.A., P.S.).,Department of Ophthalmology (P.S., B.L.).,University of Montreal, Quebec, Canada; and Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada (N.A., C.V., N.P., C.L.G., P.S., B.L.)
| | - Bruno Larrivée
- Department of Molecular Biology (C.V., B.L.).,Department of Biomedical Sciences (N.P., C.L.G., B.L.).,Department of Ophthalmology (P.S., B.L.).,University of Montreal, Quebec, Canada; and Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada (N.A., C.V., N.P., C.L.G., P.S., B.L.)
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25
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Orduña Ríos M, Noguez Imm R, Hernández Godínez NM, Bautista Cortes AM, López Escalante DD, Liedtke W, Martínez Torres A, Concha L, Thébault S. TRPV4 inhibition prevents increased water diffusion and blood-retina barrier breakdown in the retina of streptozotocin-induced diabetic mice. PLoS One 2019; 14:e0212158. [PMID: 31048895 PMCID: PMC6497373 DOI: 10.1371/journal.pone.0212158] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 04/09/2019] [Indexed: 01/02/2023] Open
Abstract
A better understanding of the molecular and cellular mechanisms involved in retinal hydro-mineral homeostasis imbalance during diabetic macular edema (DME) is needed to gain insights into retinal (patho-)physiology that will help elaborate innovative therapies with lower health care costs. Transient receptor potential cation channel subfamily vanilloid member 4 (TRPV4) plays an intricate role in homeostatic processes that needs to be deciphered in normal and diabetic retina. Based on previous findings showing that TRPV4 antagonists resolve blood-retina barrier (BRB) breakdown in diabetic rats, we evaluated whether TRPV4 channel inhibition prevents and reverts retinal edema in streptozotocin(STZ)-induced diabetic mice. We assessed retinal edema using common metrics, including retinal morphology/thickness (histology) and BRB integrity (albumin-associated tracer), and also by quantifying water mobility through apparent diffusion coefficient (ADC) measures. ADC was measured by diffusion-weighted magnetic resonance imaging (DW-MRI), acquired ex vivo at 4 weeks after STZ injection in diabetes and control groups. DWI images were also used to assess retinal thickness. TRPV4 was genetically ablated or pharmacologically inhibited as follows: left eyes were used as vehicle control and right eyes were intravitreally injected with TRPV4-selective antagonist GSK2193874, 24 h before the end of the 4 weeks of diabetes. Histological data show that retinal thickness was similar in nondiabetic and diabetic wt groups but increased in diabetic Trpv4-/- mice. In contrast, DWI shows retinal thinning in diabetic wt mice that was absent in diabetic Trpv4-/- mice. Disorganized outer nuclear layer was observed in diabetic wt but not in diabetic Trpv4-/- retinas. We further demonstrate increased water diffusion, increased distances between photoreceptor nuclei, reduced nuclear area in all nuclear layers, and BRB hyperpermeability, in diabetic wt mice, effects that were absent in diabetic Trpv4-/- mice. Retinas of diabetic mice treated with PBS showed increased water diffusion that was not normalized by GSK2193874. ADC maps in nondiabetic Trpv4-/- mouse retinas showed restricted diffusion. Our data provide evidence that water diffusion is increased in diabetic mouse retinas and that TRPV4 function contributes to retinal hydro-mineral homeostasis and structure under control conditions, and to the development of BRB breakdown and increased water diffusion in the retina under diabetes conditions. A single intravitreous injection of TRPV4 antagonist is however not sufficient to revert these alterations in diabetic mouse retinas.
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Affiliation(s)
- Maricruz Orduña Ríos
- Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, México
| | - Ramsés Noguez Imm
- Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, México
| | | | - Ana María Bautista Cortes
- Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, México
| | | | - Wolfgang Liedtke
- Department of Medicine and Neurobiology, Center for Translational Neuroscience, Duke University Medical Center, Durham, North Carolina, United States of America
| | - Atáulfo Martínez Torres
- Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, México
| | - Luis Concha
- Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, México
| | - Stéphanie Thébault
- Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus UNAM-Juriquilla, Querétaro, México
- * E-mail:
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26
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Korobelnik JF, Lu C, Katz TA, Dhoot DS, Loewenstein A, Arnold J, Staurenghi G. Effect of Baseline Subretinal Fluid on Treatment Outcomes in VIVID-DME and VISTA-DME Studies. Ophthalmol Retina 2019; 3:663-669. [PMID: 31103642 DOI: 10.1016/j.oret.2019.03.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 03/08/2019] [Accepted: 03/19/2019] [Indexed: 11/28/2022]
Abstract
PURPOSE To evaluate the effect of baseline subretinal fluid (SRF) on treatment outcomes with intravitreal aflibercept injection (IAI) versus laser treatment in patients with diabetic macular edema (DME) in the VIVID and VISTA studies. DESIGN Post hoc analysis of 2 randomized controlled trials. PARTICIPANTS Eight hundred seventy-two patients with DME. METHODS We randomized patients to receive IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or laser. MAIN OUTCOME MEASURES Effect of presence or absence of baseline SRF on visual outcomes in the integrated dataset at weeks 52 and 100. RESULTS Mean best-corrected visual acuity (BCVA) gains in the 2q4, 2q8, and laser arms at week 52 were +14.5, +11.0, and -2.3 letters, respectively, (those with baseline SRF) and +10.3, +10.6, and +2.5 letters, respectively, (those without). At week 100, mean gains were +13.5, +10.9, and -2.3 letters (those with baseline SRF) and +10.6, +10.0, and +2.7 letters (those without). The treatment effect for IAI versus laser from baseline to week 52 of 100 was greater for patients with baseline SRF versus those without (nominal P < 0.001, for interaction). The proportions of patients who gained 15 letters or more in the 2q4, 2q8, and laser arms at week 52 were 52.3%, 40.2%, and 8.9%, respectively, (those with baseline SRF) and 30.9%, 29.1%, and 8.2%, respectively, (those without) and at week 100 were 50.0%, 35.4%, and 12.9%, respectively, (those with baseline SRF) and 33.3%, 30.5%, and 12.5%, respectively, (those without). Time to first sustained SRF clearance seemed to be shorter in the IAI arms versus laser. The overall safety profile was similar in the IAI arms. CONCLUSIONS This post hoc analysis demonstrated the visual outcome benefits of IAI over laser, regardless of baseline SRF status. A greater treatment effect of IAI was observed in patients with baseline SRF versus those without; however, no meaningful impact of baseline SRF status on treatment outcomes with IAI was demonstrated, indicating that the differential effects of laser might have been the driving force behind the different treatment outcomes in both groups.
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Affiliation(s)
- Jean-Francois Korobelnik
- Service d'Ophtalmologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; Team LEHA, Bordeaux Population Health Research Center, Inserm, University of Bordeaux, Bordeaux, France.
| | | | | | - Dilsher S Dhoot
- California Retina Consultants and Research Foundation, Santa Barbara, California
| | - Anat Loewenstein
- Department of Ophthalmology, Tel Aviv Medical Center, Tel Aviv, Israel
| | | | - Giovanni Staurenghi
- Eye Clinic, Department of Biomedical and Clinical Science, Luigi Sacco Hospital, University of Milan, Milan, Italy
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27
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Garweg JG, Stefanickova J, Hoyng C, Schmelter T, Niesen T, Sowade O, Sivaprasad S. Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept: The AQUA Study. Ophthalmol Retina 2019; 3:567-575. [PMID: 31080168 DOI: 10.1016/j.oret.2019.03.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Revised: 01/25/2019] [Accepted: 03/08/2019] [Indexed: 10/27/2022]
Abstract
PURPOSE To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY). DESIGN AQUA was a multicenter, open-label, single-arm, phase 4 study. PARTICIPANTS Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME. METHODS Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks. MAIN OUTCOME MEASURES The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated. RESULTS A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 μm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was -175.38 μm (SD, 132.62 μm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related. CONCLUSIONS Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept.
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Affiliation(s)
- Justus G Garweg
- Swiss Eye Institute, Rotkreuz, and Berner Augenklinik am Lindenhofspital, Bern, Switzerland.
| | - Jana Stefanickova
- Department of Ophthalmology, Comenius University, University Hospital Ružinov, Bratislava, Slovakia
| | - Carel Hoyng
- Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands
| | | | | | | | - Sobha Sivaprasad
- NIHR Biomedical Research Centre, Moorfields Eye Hospital, London, United Kingdom
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Short-Term Assessment of Intravitreal Dexamethasone Implant Using Enhanced-Depth Image Optical Coherence Tomography and Optical Coherence Tomography Angiography in Patients with Retinal Vascular Diseases. Adv Ther 2019; 36:416-425. [PMID: 30565180 PMCID: PMC6824342 DOI: 10.1007/s12325-018-0848-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Indexed: 12/18/2022]
Abstract
Introduction To evaluate the short-term efficacy and safety of intravitreal dexamethasone implant (IDI) in patients with macular oedema associated with diabetic retinopathy (DR) and retinal vein occlusion (RVO) using enhanced-depth image optical coherence tomography (EDI-OCT) and to estimate the effect of dexamethasone on the choroid and the retinal vascular network using OCT angiography (OCTA). Methods Fifteen eyes in 15 patients with macular oedema secondary to diabetes (DR, n = 8) or retinal vein occlusion (RVO, n = 7) were treated with intravitreal injection of sustained-release IDI. Primary efficacy end points were changes in best corrected visual acuity and central macular thickness (CMT). Secondary end points were changes in choroidal thickness and choroidal and retinal vascular networks as determined by OCTA. Results CMT was significantly reduced from baseline by 3 h after injection (p < 0.01) and improved further during the 3-month follow-up. Visual acuity improvement was consistent with CMT reduction. No alterations in IOP or systemic side effects were observed. OCTA showed improvement from baseline in terms of decreased number and size of cysts and restoration of the retinal vascular network; flow choroidal thickness did not change significantly. CMT and visual acuity variations were similar in the two groups. Conclusions CMT reduced as early as 3 h after the injection of IDI, with further reduction during follow-up. Choroidal thickness was unchanged, whereas the vascular retinal network improved from baseline to the end of study. Both EDI-OCT and OCTA were useful in demonstrating the early beneficial effects of IDI on the macula and the perifoveal vascular network. Funding The article processing charges, the open access fee and the medical writing and editorial assistance was funded by Allergan.
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Cacciamani A, Esposito G, Scarinci F, Parravano M, Dinice L, Di Nicola M, Micera A. Inflammatory mediators in the vitreal reflux of patients with diabetic macular edema. Graefes Arch Clin Exp Ophthalmol 2018; 257:187-197. [PMID: 30377797 DOI: 10.1007/s00417-018-4169-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 08/28/2018] [Accepted: 10/16/2018] [Indexed: 02/07/2023] Open
Abstract
PURPOSE To quantify inflammatory, growth/angiogenic, and tissue remodeling mediators in vitreal reflux (VR) in patients with diabetic macular edema (DME), as collected at first and third intravitreal anti-vascular endothelial growth factor (anti-VEGF, ranibizumab) injection. METHODS Thirty (30) consecutive patients (type-2 diabetes mellitus) with visual impairments due to DME and undergoing the first (untreated DME) or the third (treated DME) intravitreal injection of anti-VEGF were included in the study. At the time of surgery, patients were subjected to clinical assessment and spectral domain-optical coherence tomography (SD-OCT), including central retinal thickness (CRT), macular volume, and outer nuclear layer/retinal pigment epithelial (ONL/RPE) measurements. VR sampling was performed at the time of needle removal and subjected to customized protein-array, Western blotting (WB), Ella™ microfluidic, and/or enzyme-linked immunosorbent assay (ELISA) analysis. Biostrumental and biochemical data were collected just prior to the surgery and are representative of disease state. Clinical, biostrumental, and numerous biomarkers and cytokines were statistically compared. RESULTS Decreased CRT values were detected in treated DME retinas, as compared to untreated ones (p ≤ 0.05). Differences in VEGF and other mediator expressions between treated and untreated DME were detected in VR samples. Particularly, osteopontin (p ≤ 0.05), interleukin 6 (IL6) (p ≤ 0.05), and VEGF (p ≤ 0.1) values were decreased after treatment. Significant changes were validated by WB, ELISA, and Ella™ analysis. CONCLUSION Overall, the biostrumental and biochemical data suggest the presence of a specific pattern of inflammation in VR after treatment. The data would suggest the presence of other mechanisms and mediators, in addition to VEGF, accountable for DME progression.
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Affiliation(s)
- Andrea Cacciamani
- IRCCS - Fondazione Bietti, Via S. Stefano Rotondo 6, 00184, Rome, Italy
| | - Graziana Esposito
- IRCCS - Fondazione Bietti, Via S. Stefano Rotondo 6, 00184, Rome, Italy
| | - Fabio Scarinci
- IRCCS - Fondazione Bietti, Via S. Stefano Rotondo 6, 00184, Rome, Italy
| | | | - Lucia Dinice
- IRCCS - Fondazione Bietti, Via S. Stefano Rotondo 6, 00184, Rome, Italy
| | - Marta Di Nicola
- Department of Medical, Oral and Biotechnological Sciences, Laboratory of Biostatistics, University G. d'Annunzio Chieti-Pescara, Chieti, Italy
| | - Alessandra Micera
- IRCCS - Fondazione Bietti, Via S. Stefano Rotondo 6, 00184, Rome, Italy.
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Abdellatif MK, Ebeid WM. Variations in Choroidal and Macular Thickness Maps after Uneventful Phacoemulsification. Semin Ophthalmol 2017; 33:719-725. [PMID: 29252070 DOI: 10.1080/08820538.2017.1417453] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVE To investigate changes in retinal and choroidal thickness maps following uncomplicated phacoemulsification using enhanced depth imaging optical coherence tomography (EDI-OCT). METHODS A prospective study was done on 66 eyes. EDI-OCT was performed preoperative, 1 week, 1 month, and 3 months postoperative measuring retinal and choroidal thickness at the fovea and the 9 ETDRS subfields. RESULTS Subfoveal choroidal thickness (SFCT) showed statistically insignificant increase after 1 week (P = 0.473), but the increase was statistically significant after 1 month (P = 0.014). However, after 3 months, there was non-significant difference from baseline (P = 0.073). Foveal retinal thickness (FT) demonstrated statistically insignificant increase after 1 week (P = 0.094), but statistically significant increase was noted after 1 and 3 months (P = 0.000). CONCLUSION Uneventful phaco induced statistically significant increases in FT and SFCT from the first postoperative month; however, 3 months postoperative the increase in retinal thickness was maintained but the increase in choroidal thickness became statistically insignificant.
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Affiliation(s)
- Mona Kamal Abdellatif
- a Department of Ophthalmology, Faculty of Medicine , Ain Shams University , Cairo , Egypt
| | - Weam Mohamed Ebeid
- a Department of Ophthalmology, Faculty of Medicine , Ain Shams University , Cairo , Egypt
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Zur D, Iglicki M, Busch C, Invernizzi A, Mariussi M, Loewenstein A. OCT Biomarkers as Functional Outcome Predictors in Diabetic Macular Edema Treated with Dexamethasone Implant. Ophthalmology 2017; 125:267-275. [PMID: 28935399 DOI: 10.1016/j.ophtha.2017.08.031] [Citation(s) in RCA: 179] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2017] [Revised: 08/21/2017] [Accepted: 08/22/2017] [Indexed: 01/13/2023] Open
Abstract
PURPOSE Identification and characterization of patients with diabetic macular edema (DME) are important for individualizing treatment and optimizing outcome. We investigated OCT biomarkers for DME treated by intravitreal dexamethasone (DEX) implant. DESIGN Multicenter, retrospective, observational cohort study. PARTICIPANTS A total of 299 eyes from 284 patients treated with DEX implant for DME (naïve, n = 209; refractory, n = 90). Baseline best-corrected visual acuity (BCVA) was between 0.3 and 1.0 on a logarithm of minimum angle of resolution visual chart. METHODS The OCT scans previous to DEX implants were evaluated for submacular fluid, size and location of cystoid changes, inner segment-outer segment (IS-OS) continuity, quantity and location of hyperreflective foci (HRF), vitreomacular interface abnormalities, and epiretinal membrane. The BCVA and central macular thickness were recorded at baseline and at 1, 2, and 4 months after treatment with DEX implants. Correlations between OCT measures and visual outcome were analyzed using the generalized estimating equations procedure. MAIN OUTCOME MEASURES The correlation between spectral-domain (SD) OCT measures at baseline and BCVA response (mean change from baseline; categorized improvement [<5, 5-9, or ≥10; Early Treatment Diabetic Retinopathy Study letters] in BCVA) after treatment with a DEX implant. RESULTS The presence of subretinal fluid (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.23-3.20; P = 0.01), absence of HRF (OR, 3.66; 95% CI, 1.40-9.62; P = 0.01), and integrity of the IS-OS layer (OR, 2.09; 95% CI, 1.30-3.37; P = 0.003) were all predictive of better visual outcome after treatment with DEX implants. Although eyes with naïve DME gained more vision than refractory eyes (P < 0.001), the predictive value of OCT findings did not differ according to this classification. CONCLUSIONS Spectral-domain OCT is useful in identifying various imaging findings in DME. Among eyes with DME, those with submacular fluid, no HRF, and a continuous IS-OS layer responded better to DEX implants than those without these features. These findings call for further study of combinations of OCT and metabolic biomarkers.
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Affiliation(s)
- Dinah Zur
- Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | | | | | - Alessandro Invernizzi
- Eye Clinic - Department of Biomedical and Clinical Science "L. Sacco," Luigi Sacco Hospital, University of Milan, Milan, Italy
| | | | - Anat Loewenstein
- Division of Ophthalmology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Incumbent, Sydney A. Fox Chair in Ophthalmology, Tel Aviv University, Tel Aviv, Israel
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Rowe CW, Haider AS, Viswanathan D, Jones M, Attia J, Wynne K, Acharya S. Insulin resistance correlates with maculopathy and severity of retinopathy in young adults with Type 1 Diabetes Mellitus. Diabetes Res Clin Pract 2017; 131:154-160. [PMID: 28750218 DOI: 10.1016/j.diabres.2017.06.022] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Revised: 05/19/2017] [Accepted: 06/15/2017] [Indexed: 01/17/2023]
Abstract
AIMS To assess the relationship between insulin resistance (IR), retinopathy and maculopathy in young adults with Type 1 diabetes mellitus. METHODS A cross-sectional study at a regional Australian tertiary hospital. Retinal pathology, assessed by colour fundus photography, was correlated with two surrogate measures of IR: estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS), where lower scores reflect greater IR. RESULTS 107 patients were recruited, with mean age 24.7years, 53% male, and mean duration of disease 10.8years. Mean eGDR scores (5.6vs 8.0 p<0.001) and ISS (4.7vs 7.9, p<0.001) were lower in subjects having at least moderate non-proliferative diabetic retinopathy (NPDR; relative to nil/mild-NPDR). Similarly, mean eGDR (4.2vs 6.2, p=0.001) and ISS (3.8vs 6.1, p=0.003) were lower in patients with maculopathy. Multivariate logistic regression modelling was used to control for confounding. For retinopathy severity, a unit increase in eGDR or ISS (representing lower IR) was associated with a 50% decrease in odds of moderate-NPDR or worse (eGDR OR 0.5, 95%CI 0.32-0.77, p=0.002; ISS OR 0.49, 95%CI 0.29-0.84, p=0.01). A unit increase in eGDR or ISS was associated with a 46-56% decrease in odds of maculopathy (eGDR OR 0.54, 95%CI 0.37-0.81, p=0.003; ISS OR 0.44, 95%CI 0.22-0.88, p=0.02). CONCLUSIONS IR correlates with more severe retinopathy in young adults with Type 1DM. This is the first description of a correlation between IR and maculopathy in Type 1DM, warranting further evaluation. Prospective studies examining whether reducing IR can improve microvascular complications are required.
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Affiliation(s)
- C W Rowe
- Department of Endocrinology and Diabetes, John Hunter Hospital, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, Australia.
| | - A S Haider
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia; Department of Ophthalmology, John Hunter Hospital, Newcastle, Australia
| | - D Viswanathan
- Department of Ophthalmology, John Hunter Hospital, Newcastle, Australia
| | - M Jones
- Clinical Research Design, IT, and Statistical Support (CReDITSS) Unit, Hunter Medical Research Institute, Newcastle, Australia
| | - J Attia
- School of Medicine and Public Health, University of Newcastle, Callaghan, Australia; Clinical Research Design, IT, and Statistical Support (CReDITSS) Unit, Hunter Medical Research Institute, Newcastle, Australia
| | - K Wynne
- Department of Endocrinology and Diabetes, John Hunter Hospital, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
| | - S Acharya
- Department of Endocrinology and Diabetes, John Hunter Hospital, Newcastle, Australia; School of Medicine and Public Health, University of Newcastle, Callaghan, Australia
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Abstract
The risk of severe eye problems has been found to increase significantly with age, particularly between the fifth and sixth decades of life. Cataracts, dry eye, neovascular age-related macular degeneration, diabetic retinopathy and retinal vein occlusion (RVO) are very common and very different age-related ocular diseases that reduce the patient's quality of life. The rationale for using corticosteroids to treat anterior and posterior ocular segment diseases is driven by inflammation. Dexamethasone, one of the most powerful corticosteroids available, is widely used for topical or intravitreal administration. Topical dexamethasone has proven efficacy for the management of postoperative inflammation in the anterior segment after cataract surgery and symptom relief in dry-eye disease. A new sustained-release 700 µg dexamethasone intravitreal implant (DEX) was recently approved for the treatment of macular edema following RVO, diabetic macular edema, or non-infectious uveitis, and its use is increasing, especially when other therapeutic agents have failed. The most common side effects are increased intraocular pressure and cataract formation. The potency of DEX, alone or in combination with other agents, makes DEX a promising option for treating several retinal diseases.
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Baget-Bernaldiz M, Romero-Aroca P, Bautista-Perez A, Mercado J. Multifocal electroretinography changes at the 1-year follow-up in a cohort of diabetic macular edema patients treated with ranibizumab. Doc Ophthalmol 2017; 135:85-96. [PMID: 28779336 PMCID: PMC5606940 DOI: 10.1007/s10633-017-9601-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 07/11/2017] [Indexed: 11/01/2022]
Abstract
PURPOSE To determine the changes in the multifocal electroretinogram (mfERG) at 1 year in a clinical series of diabetic macular edema (DME) patients treated with ranibizumab (RNBZ) using a pro re nata protocol. METHODS We analyzed a clinical series of 35 eyes of 35 patients with DME at baseline and after treating them with RNBZ over 1 year, in order to determine the change in the macular function, which was assessed by means of the response density and the implicit time of the first-order kernel (FOK) P1 wave of the mfERG at the foveola (R1), fovea (R2) and parafovea (R3). These electrophysiological parameters were studied taking into account different independent variables, such as DME type, degree of diabetic retinopathy (DR), level of preservation of both the ellipsoid zone (IS/OS) and the external limiting membrane (ELM) and changes in central retinal thickness (CRT) and total macular volume (TMV). We also studied the relationship between the response density and the best-corrected visual acuity (BCVA). RESULTS Eyes with cystic and spongiform DME showed better response density with respect to the serous type (p < 0.001) at baseline. Similarly, eyes with high IS/OS and ELM preservation rates showed higher initial response density compared to the others (p < 0.001). Eyes with moderate DR had better response density compared to those with severe and proliferative DR (p = 0.001). At the beginning of the study, those eyes with proliferative and severe DR showed longer implicit times with respect to those with moderate DR (p = 0.04). The response density significantly increased in eyes that anatomically restored the IS/OS and the ELM after being treated with RNBZ (both p < 0.001). Similarly, eyes with spongiform DME further improved the response density with respect to those with cystic and serous DME (p < 0.001). On the contrary, eyes with hard exudates showed less improvement in their response density at the end of the study (p < 0.001). We observed a significant relationship between BCVA and the response density achieved at the end of the study (p = 0.012). Eyes with severe and proliferative DR significantly shortened implicit time compared to those with moderate DR (p = 0.04). CONCLUSIONS The multifocal electroretinogram allowed us to differentiate groups of eyes with DME according to their electrophysiological profile, both initially and after being treated with RNBZ. Ranibizumab increased the response density in all DME types included in the study, with a maximum response in those eyes with spongiform type. Once treated with RNBZ, the macular electrophysiological activity improved in eyes that had a well-preserved ellipsoid zone and ELM. The presence of hard exudates was a limitation to the response density achieved at the foveola.
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Affiliation(s)
- Marc Baget-Bernaldiz
- Ophthalmic Service, University Hospital Sant Joan, Reus, Spain.,Institut de Investigacio Sanitaria Pere Virgili [IISPV], University Rovira and Virgili, Tarragona, Spain
| | - Pedro Romero-Aroca
- Ophthalmic Service, University Hospital Sant Joan, Reus, Spain. .,Institut de Investigacio Sanitaria Pere Virgili [IISPV], University Rovira and Virgili, Tarragona, Spain.
| | - Angel Bautista-Perez
- Ophthalmic Service, University Hospital Sant Joan, Reus, Spain.,Institut de Investigacio Sanitaria Pere Virgili [IISPV], University Rovira and Virgili, Tarragona, Spain
| | - Joaquin Mercado
- Ophthalmic Service, University Hospital Sant Joan, Reus, Spain.,Institut de Investigacio Sanitaria Pere Virgili [IISPV], University Rovira and Virgili, Tarragona, Spain
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Plasmalemma Vesicle–Associated Protein Has a Key Role in Blood-Retinal Barrier Loss. THE AMERICAN JOURNAL OF PATHOLOGY 2016; 186:1044-54. [DOI: 10.1016/j.ajpath.2015.11.019] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 10/20/2015] [Accepted: 11/19/2015] [Indexed: 12/15/2022]
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Romero-Aroca P, de la Riva-Fernandez S, Valls-Mateu A, Sagarra-Alamo R, Moreno-Ribas A, Soler N. Changes observed in diabetic retinopathy: eight-year follow-up of a Spanish population. Br J Ophthalmol 2016; 100:1366-71. [PMID: 26769672 PMCID: PMC5050285 DOI: 10.1136/bjophthalmol-2015-307689] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 12/13/2015] [Indexed: 12/19/2022]
Abstract
Background/aims To determine the changes in the incidence of diabetic retinopathy (DR), diabetic macular oedema (DMO) and their risk factors in a population-based study of patients with diabetes mellitus (DM) referred to our 16 Primary Health Care Areas (HCAs). Methods Prospective population-based study of a total of 15 396 Caucasian patients with DM, who represent 86.53% of the total patients with DM in our HCAs, were studied over an 8-year follow-up period. All patients were screened with a mean follow-up of 3.18±1.11 times for each patient over the 8 years. Results The yearly mean value of any DR was 8.37±2.19% (8.09%–8.99%); of advanced DR yearly mean value of 0.46±0.22% (0.03–0.78); and of DMO a yearly mean value of 2.19±0.18% (2%–2.49%). A clear increase was observed in the last 3 years, any DR increased from 8.09% in 2007 to 8.99% in 2014, and DMO from 2% in 2007 to 2.49% in 2014. These increases were more evident in some age groups. For patients with any DR aged 41–50 and 51–60 and for patients with advanced DR aged 41–50, 51–60 and 61–70, the increase was more marked, related to an increase in HbA1c values or to patients treated with insulin. Conclusions An increase in the incidence of DR and DMO was observed, especially in the younger patients aged between 31 and 70 years. This is linked to bad metabolic control of DM. Our results suggest a greater number of ocular complications in the near future, such as neovascular glaucoma, if these current findings are not addressed.
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Affiliation(s)
- Pedro Romero-Aroca
- Ophthalmic Service, University Hospital Sant Joan, Institut de Investigacio Sanitaria Pere Virgili (IISPV), University Rovira & Virgili, Reus, Spain
| | - Sofia de la Riva-Fernandez
- Ophthalmic Service, University Hospital Sant Joan, Institut de Investigacio Sanitaria Pere Virgili (IISPV), University Rovira & Virgili, Reus, Spain
| | - Aida Valls-Mateu
- Department of Computer Engineering and Mathematics, University Rovira & Virgili, Reus, Spain
| | - Ramon Sagarra-Alamo
- Health Care Area Reus-Priorat, Institut Catala de la Salut (ICS), Institut de Investigacio Sanitaria Pere Virgili (IISPV), University Rovira & Virgili, Reus, Spain
| | - Antonio Moreno-Ribas
- Department of Computer Engineering and Mathematics, University Rovira & Virgili, Reus, Spain
| | - Nuria Soler
- Ophthalmic Service, University Hospital Sant Joan, Institut de Investigacio Sanitaria Pere Virgili (IISPV), University Rovira & Virgili, Reus, Spain
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Romero-Aroca P, Baget-Bernaldiz M, Pareja-Rios A, Lopez-Galvez M, Navarro-Gil R, Verges R. Diabetic Macular Edema Pathophysiology: Vasogenic versus Inflammatory. J Diabetes Res 2016; 2016:2156273. [PMID: 27761468 PMCID: PMC5059543 DOI: 10.1155/2016/2156273] [Citation(s) in RCA: 230] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2016] [Revised: 08/29/2016] [Accepted: 09/06/2016] [Indexed: 12/15/2022] Open
Abstract
Diabetic macular edema (DME) can cause blindness in diabetic patients suffering from diabetic retinopathy (DR). DM parameters controls (glycemia, arterial tension, and lipids) are the gold standard for preventing DR and DME. Although the vascular endothelial growth factor (VEGF) is known to play a role in the development of DME, the pathological processes leading to the onset of this disease are highly complex and the exact sequence in which they occur is still not completely understood. Angiogenesis and inflammation have been shown to be involved in the pathogenesis of this disease. However, it still remains to be clarified whether angiogenesis following VEGF overexpression is a cause or a consequence of inflammation. This paper provides a review of the data currently available, focusing on VEGF, angiogenesis, and inflammation. Our analysis suggests that angiogenesis and inflammation act interdependently during the development of DME. Knowledge of DME etiology seems to be important in treatments with anti-VEGF or anti-inflammatory drugs. Current diagnostic techniques do not permit us to differentiate between both etiologies. In the future, diagnosing the physiopathology of each patient with DME will help us to select the most effective drug.
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Affiliation(s)
- Pedro Romero-Aroca
- Ophthalmology Service, University Hospital Sant Joan, Institut de Investigacio Sanitaria Pere Virgili (IISPV), University of Rovira & Virgili, Reus, Spain
- *Pedro Romero-Aroca:
| | - Marc Baget-Bernaldiz
- Ophthalmology Service, University Hospital Sant Joan, Institut de Investigacio Sanitaria Pere Virgili (IISPV), University of Rovira & Virgili, Reus, Spain
| | - Alicia Pareja-Rios
- Department of Ophthalmology, Retina Section, Hospital Universitario de Canarias, Tenerife, Spain
| | - Maribel Lopez-Galvez
- Department of Ophthalmology, University Hospital Valladolid, Ocular Diabetes Unit of IOBA, Valladolid, Spain
| | - Raul Navarro-Gil
- Ophthalmology Service, University Hospital Sant Joan, Institut de Investigacio Sanitaria Pere Virgili (IISPV), University of Rovira & Virgili, Reus, Spain
| | - Raquel Verges
- Ophthalmology Service, University Hospital Sant Joan, Institut de Investigacio Sanitaria Pere Virgili (IISPV), University of Rovira & Virgili, Reus, Spain
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Leveziel N, Ragot S, Gand E, Lichtwitz O, Halimi JM, Gozlan J, Gourdy P, Robert MF, Dardari D, Boissonnot M, Roussel R, Piguel X, Dupuy O, Torremocha F, Saulnier PJ, Maréchaud R, Hadjadj S. Association Between Diabetic Macular Edema and Cardiovascular Events in Type 2 Diabetes Patients: A Multicenter Observational Study. Medicine (Baltimore) 2015; 94:e1220. [PMID: 26287408 PMCID: PMC4616429 DOI: 10.1097/md.0000000000001220] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Diabetic macular edema (DME) is the main cause of visual loss associated with diabetes but any association between DME and cardiovascular events is unclear.This study aims to describe the possible association between DME and cardiovascular events in a multicenter cross-sectional study of patients with type 2 diabetes.Two thousand eight hundred seven patients with type 2 diabetes were recruited from diabetes and nephrology clinical institutional centers participating in the DIAB 2 NEPHROGENE study focusing on diabetic complications. DME (presence/absence) and diabetic retinopathy (DR) classification were based on ophthalmological report and/or on 30° color retinal photographs. DR was defined as absent, nonproliferative (background, moderate, or severe) or proliferative. Cardiovascular events were stroke, myocardial infarction, and lower limb amputation.Details regarding associations between DME and cardiovascular events were evaluated.The study included 2807 patients with type 2 diabetes, of whom 355 (12.6%) had DME. DME was significantly and independently associated with patient age, known duration of diabetes, HbA1c, systolic blood pressure, and DR stage. Only the prior history of lower limb amputation was strongly associated with DME in univariate and multivariate analyses, whereas no association was found with regard to myocardial infarction or stroke. Moreover, both major (n = 32) and minor lower limb (n = 96) amputations were similarly associated with DME, with respective odds ratio of 3.7 (95% confidence interval [CI], 1.77-7.74; P = 0.0012) and of 4.29 (95% CI, 2.79-6.61; P < 0.001).DME is strongly and independently associated with lower limb amputation in type 2 diabetic patients.
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Affiliation(s)
- Nicolas Leveziel
- From the Department of ophthalmology, University Hospital of Poitiers, France (NL, OL, JG, M-FR, MB); University of Poitiers, UFR Médecine et Pharmacie, France (NL, RM); U1084, Inserm, Poitiers, France (NL); Centre d'investigation clinique, University of Poitiers, Poitiers, France (SR, P-JS, SH); CIC1402, Inserm, France (SR, P-JS, SH); Centre d'investigation clinique, University Hospital of Poitiers, Poitiers, France (SR, P-JS, SH); Endocrinology and Diabetology Department, pole DUNE, University Hospital of Poitiers, Poitiers, France (EG, XP, RM, SH); Department of Nephrology-immunology, University Hospital of Tours, François Rabelais University, Tours, France (JMH); Diabetology Department, Rangueuil Hospital, University Hospital of Toulouse, France (PG); Endocrinology Department Hospital of Sud Francilien, Corbeil Essonnes, France (DD); UMRS1138, Inserm, Paris, France (RR); University Paris 7 Denis Diderot, UMRS1138, Paris, France (RR); Diabetology, endocrinology and Nutrition Department, Groupe Hospitalier Bichat Claude Bernard, Assistance Public-Hopitaux de Paris (AP-HP), Paris, France (RR); Diabetology Department Bégin Armed Forces Hospital, Saint Mandé, France (OD); U1082, Inserm, Poitiers, France (SH)
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Comparison of intravitreal triamcinolone acetonide versus intravitreal bevacizumab as the primary treatment of clinically significant macular edema. Retina 2015; 35:272-9. [PMID: 25105313 DOI: 10.1097/iae.0000000000000300] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To evaluate the short-term efficacy of triamcinolone acetonide versus bevacizumab for the treatment of diabetic, clinically significant, macular edema with different optical coherence tomography findings. METHODS Fifty eyes of 45 consecutive patients with diabetic, clinically significant, macular edema were incorporated in this prospective interventional case series. Patients were divided into 3 groups according to findings on optical coherence tomography: 1) macular edema combined with serous retinal detachment (Group 1), 2) diffused macular thickening (Group 2), and 3) cystoid macular edema (Group 3). Patients from each group were treated with a single intravitreal injection of triamcinolone (IVTA) or 2 intravitreal injections of bevacizumab (IVB) with an interval of 6 weeks. Patients were observed at 6, 12, and 24 weeks after IVTA or the first IVB injection. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were examined at each visit. Repeated-measures analysis of variance was used to compare the efficacy of the treatment groups. RESULTS In Group 1, IVTA showed more favorable effects on CRT reduction and BCVA improvement compared with IVB at 6, 12, and 24 weeks (P = 0.002, 0.001, 0.027 and P = 0.036, 0.001, 0.027), respectively. In Group 2, IVB had more CRT reduction than IVTA at 6 and 12 weeks (P = 0.013 and 0.036), although there was no significant difference in BCVA improvement between the 2 groups (P > 0.05). In Group 3, IVTA and IVB did not have significant effects on CRT reduction and BCVA improvement (P > 0.05). CONCLUSION The short-term efficacy of IVTA and IVB on treating clinically significant macular edema varied with different optical coherence tomography findings. In clinically significant macular edema combined with serous retinal detachment, IVTA may be more favorable than IVB in CRT reduction and BCVA improvement. In patients with diffused macular thickening, IVB may be better than IVTA in macular thickness reduction, although this does not translate to a significant improvement in BCVA.
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Influence of uncomplicated phacoemulsification on central macular thickness in diabetic patients: a meta-analysis. PLoS One 2015; 10:e0126343. [PMID: 25965404 PMCID: PMC4428827 DOI: 10.1371/journal.pone.0126343] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2015] [Accepted: 04/01/2015] [Indexed: 01/11/2023] Open
Abstract
OBJECTIVE To evaluate the effect of uncomplicated phacoemulsification on central macular thickness (CMT) and best corrected visual acuity (BCVA) in both diabetic patients without diabetic retinopathy (DR) and diabetic patients with mild to moderate non-proliferative diabetic retinopathy (NPDR). METHODS Potential prospective observational studies were searched through PubMed and EMBASE. Standardized mean difference (SMD) and 95% confidence interval (CI) for changes in CMT and BCVA were evaluated at postoperative 1, 3 and 6 months. The pooled effect estimates were calculated in the use of a random-effects model. RESULTS A total of 10 studies involving 190 eyes of diabetic patients without diabetic retinopathy and 143 eyes of diabetic patients with NPDR were identified. CMT values demonstrated a statistically significant increase after uncomplicated phacoemulsification at 1 month (SMD, -0.814; 95%CI, -1.230 to -0.399), 3 months (SMD, -0.565; 95%CI, -0.927 to -0.202) and 6 months (SMD, -0.458; 95%CI, -0.739 to -0.177) in diabetic patients with NPDR. There was no statistical difference in CMT values at postoperative 1 month (SMD, -1.206; 95%CI, -2.433 to 0.021)and no statistically significant increase in CMT values at postoperative3 months (SMD, -0.535; 95%CI, -1.252 to 0.182) and 6 months (SMD, -1.181; 95%CI, -2.625 to 0.263) in diabetic patients without DR.BCVA was significantly increased at postoperative 1 month (SMD, 1.149; 95%CI, 0.251 to 2.047; and SMD,1.349; 95%CI, 0.264 to 2.434, respectively) and 6 months (SMD, 1.295; 95%CI, 0.494 to 2.096; and SMD, 2.146; 95%CI, 0.172 to 4.120, respectively) in both diabetic patients without DR and diabetic patients with NPDR. Sensitivity analysis showed that the results were relatively stable and reliable. CONCLUSION Uncomplicated phacoemulsification in diabetic patients with mild to moderate NPDR seemed to influence significantly the subclinical thickening of the macular zones at postoperative 1, 3 and 6 months compared with diabetic patients without DR. BCVA was significantly improved in both diabetic patients without DR and diabetic patients with mild to moderate NPDR.
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Comparative effectiveness of anti-VEGF agents for diabetic macular edema. Int J Technol Assess Health Care 2015; 29:392-401. [PMID: 24290332 DOI: 10.1017/s0266462313000500] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
OBJECTIVES The aim of this study was to evaluate the comparative effectiveness of anti-vascular endothelial growth factor therapy in the treatment of diabetic macular edema (DME). METHODS Searches focused on reports concerning treatment of DME with aflibercept, bevacizumab, pegaptanib, or ranibizumab published between January 2000 and June 30, 2012, with comparisons to laser photocoagulation, sham injection, or other control (e.g., triamcinolone). Effectiveness was based on best-corrected visual acuity (BCVA), in terms of letters gained. Direct meta-analyses were conducted on BCVA for each anti-vascular endothelial growth factor (VEGF) agent; indirect comparisons also were performed for each anti-VEGF pair. RESULTS A total of fifteen randomized controlled trials (eleven fair- or good-quality) and eight observational studies were included. No direct comparative studies were identified. Improvement in visual acuity versus control was seen with all agents (range: 4-9 letters); outcomes were consistent across multiple timepoints. Meta-analyses showed no statistically significant and/or consistent differences between agents in BCVA changes or the percentage of patients gaining more than ten letters. No discernible differences in the potential harms of anti-VEGFs, including ocular events, MI, stroke, and other cardiovascular events, as well as death, were noted between aflibercept, pegaptanib, and ranibizumab. Data on harms for bevacizumab were underreported. CONCLUSIONS All anti-VEGF agents are effective in improving visual acuity in comparison to laser photocoagulation. Evidence is insufficient to distinguish the performance of any single anti-VEGF agent over others. The safety of bevacizumab remains the greatest element of uncertainty.
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Significant reduction of diabetic macular edema following intravitreal ranibizumab injection in the fellow eye. Int Ophthalmol 2014; 34:1271-4. [DOI: 10.1007/s10792-014-9921-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 02/04/2014] [Indexed: 10/24/2022]
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The role of inflammation in the pathogenesis of macular edema secondary to retinal vascular diseases. Mediators Inflamm 2014; 2014:432685. [PMID: 25152567 PMCID: PMC4134827 DOI: 10.1155/2014/432685] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2014] [Revised: 07/05/2014] [Accepted: 07/09/2014] [Indexed: 12/17/2022] Open
Abstract
Macular edema (ME) is a nonspecific sign of numerous retinal vascular diseases. This paper is an updated overview about the role of inflammatory processes in the genesis of both diabetic macular edema (DME) and ME secondary to retinal vein occlusion (RVO). We focus on the inflammatory mediators implicated, the effect of the different intravitreal therapies, the recruitment of leukocytes mediated by adhesion molecules, and the role of retinal Müller glial (RMG) cells.
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Romero-Aroca P, Reyes-Torres J, Baget-Bernaldiz M, Blasco-Suñe C. Laser treatment for diabetic macular edema in the 21st century. Curr Diabetes Rev 2014; 10:100-12. [PMID: 24852439 PMCID: PMC4051253 DOI: 10.2174/1573399810666140402123026] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Revised: 03/28/2014] [Accepted: 04/02/2014] [Indexed: 11/22/2022]
Abstract
Diabetic macular edema (DME) is the leading cause of blindness in the diabetic population. The diabetes Control and Complications Trial reported that 27% of patients affected by type 1 diabetes develop DME within 9 years of onset. Other studies have shown that in patients with type 2 diabetes, the prevalence increased from 3% to 28% within 5 years of diagnosis to twenty years after the onset. At the present time, despite the enthusiasm for evaluating several new treatments for DME, including the intravitreal therapies for DME (e.g., corticosteroids, and anti-VEGF drugs), laser photocoagulation remains the current gold standard and the only treatment with proven efficacy in a wide range of clinical trials for this condition. Despite being the standard technique for comparison and evaluation of the emerging treatments, we have generally poor understanding of the ETDRS recommendations, and we often forget about the results of laser in DME. The purpose of this review is to update our knowledge on laser photocoagulation for DME with an extensive review of the ETDRS results and discuss the laser techniques. Furthermore, we will describe the new developments in laser systems and review the current indications and results. Finally, we will discuss the results of laser treatments versus the current pharmacological therapies. We conclude by trying to provide a general overview that which laser treatment must be indicated and what types of lasers are currently recommended.
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Affiliation(s)
| | | | | | - Cristina Blasco-Suñe
- Department of Ophthalmology, University Hospital Sant Joan, University Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain, Avda. Josep Laporte 1, 43204 Reus, Spain.
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46
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Romero-Aroca P. Current status in diabetic macular edema treatments. World J Diabetes 2013; 4:165-169. [PMID: 24147200 PMCID: PMC3797881 DOI: 10.4239/wjd.v4.i5.165] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2013] [Revised: 07/21/2013] [Accepted: 09/18/2013] [Indexed: 02/05/2023] Open
Abstract
Diabetes is a serious chronic condition, which increase the risk of cardiovascular diseases, kidney failure and nerve damage leading to amputation. Furthermore the ocular complications include diabetic macular edema, is the leading cause of blindness among adults in the industrialized countries. Today, blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy. The treatment should include an optimized control of glycemia, arterial tension, lipids and renal status. The photocoagulation laser is currently restricted to focal macular edema in some countries, but due the high cost of intravitreal drugs, the use of laser treatment for focal and diffuse diabetic macular edema (DME), can be valid as gold standard in many countries. The intravitreal anti vascular endothelial growth factor drugs (ranibizumab and bevacizumab), are indicated in the treatment of all types of DME, but the correct protocol for administration should be defined for the different Retina Scientific Societies. The corticosteroids for diffuse DME, has a place in pseudophakic patients, but its complications restricted the use of these drugs for some patients. Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.
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Evoy KE, Abel SR. Ranibizumab: the first vascular endothelial growth factor inhibitor approved for the treatment of diabetic macular edema. Ann Pharmacother 2013; 47:811-8. [PMID: 23656749 DOI: 10.1345/aph.1s013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
OBJECTIVE To review the pharmacology, efficacy, and safety data available for ranibizumab and compare the drug to other therapeutic options for diabetic macular edema (DME) to determine its likely role in therapy. DATA SOURCES A PubMed search was initially used to identify all trials pertaining to the use of ranibizumab for DME. This search was conducted in February 2013 without a time frame for exclusion of older trials (all references included were published between January 1987 and February 2013). Following a review of the references of these articles, additional sources were obtained from PubMed, the manufacturer's website, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION Trials conducted in animals and those written in a language other than English were excluded. Abstracts of remaining trials were reviewed for determination of relevance to this review. Preference was given to randomized controlled trials. Additional information sources were obtained from a review of references as deemed necessary by the authors. DATA SYNTHESIS Six Phase 2 or 3 randomized controlled trials studying the effects of ranibizumab in patients with DME were identified. Within these trials, ranibizumab consistently produced significantly greater gains in mean best corrected visual acuity than focal/grid laser photocoagulation or sham (7.4-12.5 letter improvement with ranibizumab vs 0.5-3 letters following focal/grid laser photocoagulation monotherapy) with a favorable safety and tolerability profile. Ranibizumab was also studied in combination with focal/grid laser photocoagulation, showing no additional gains in vision versus ranibizumab monotherapy. CONCLUSIONS The identified trials provide support for the safety and efficacy of ranibizumab in the treatment of vision loss due to DME and present a strong case for the shift to first-line treatment with vascular endothelial growth factor inhibitors from focal/grid laser photocoagulation, the standard of care since the Early Treatment Diabetic Retinopathy Study of 1985.
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Affiliation(s)
- Kirk E Evoy
- College of Pharmacy, Purdue University, West Lafayette, IN, USA.
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48
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Stitt AW, Lois N, Medina RJ, Adamson P, Curtis TM. Advances in our understanding of diabetic retinopathy. Clin Sci (Lond) 2013; 125:1-17. [PMID: 23485060 DOI: 10.1042/cs20120588] [Citation(s) in RCA: 128] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Diabetic retinopathy remains the most common complication of diabetes mellitus and is a leading cause of visual loss in industrialized nations. The clinicopathology of the diabetic retina has been extensively studied, although the precise pathogenesis and cellular and molecular defects that lead to retinal vascular, neural and glial cell dysfunction remain somewhat elusive. This lack of understanding has seriously limited the therapeutic options available for the ophthalmologist and there is a need to identify the definitive pathways that initiate retinal cell damage and drive progression to overt retinopathy. The present review begins by outlining the natural history of diabetic retinopathy, the clinical features and risk factors. Reviewing the histopathological data from clinical specimens and animal models, the recent paradigm that neuroretinal dysfunction may play an important role in the early development of the disease is discussed. The review then focuses on the molecular pathogenesis of diabetic retinopathy with perspective provided on new advances that have furthered our understanding of the key mechanisms underlying early changes in the diabetic retina. Studies have also emerged in the past year suggesting that defective repair of injured retinal vessels by endothelial progenitor cells may contribute to the pathogenesis of diabetic retinopathy. We assess these findings and discuss how they could eventually lead to new therapeutic options for diabetic retinopathy.
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Affiliation(s)
- Alan W Stitt
- Centre for Vision and Vascular Science, Queen's University of Belfast, The Royal Victoria Hospital, Belfast BT12 6BA, UK.
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Prevalence, Demographics, and Treatment Characteristics of Visual Impairment due to Diabetic Macular Edema in a Representative Canadian Cohort. J Ophthalmol 2012; 2012:159167. [PMID: 23304447 PMCID: PMC3529901 DOI: 10.1155/2012/159167] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Revised: 11/10/2012] [Accepted: 11/11/2012] [Indexed: 11/17/2022] Open
Abstract
Diabetic macular edema (DME) is the leading cause of blindness in the diabetic population. However, there is limited understanding of the epidemiology of DME with visual impairment (VI) and treatment in patients with diabetes in Canada. This observational, retrospective study used records from the Southwestern Ontario database to observe the demographics, prevalence, and treatment characteristics of VI due to DME compared to a healthy population in a real-world Canadian setting. Data was compared between a cohort of 8,368 diabetic (type 1 or 2) patients, who were ≥18 years old and had a diagnosis of DME with VI (visual acuity <20/40 in Snellen equivalent), and 76,077 age- and gender-matched subjects representing a healthy population. Among diabetic patients, prevalence of DME was 15.7%, and prevalence of VI due to DME was 2.56%. Laser monotherapy was the most frequently used treatment. Public funding covered costs for 85% of persons with DME while 18% were paid for with private funds. This study provides insight into the demographics, prevalence, and treatment of VI due to DME in a representative Canadian cohort. This data can help to inform evaluation of current DME treatment patterns and of proposed new treatment on drug plan budgets in Canada.
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