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Pedrini A, Nowosielski Y, Rehak M. Diabetic retinopathy-recommendations for screening and treatment. Wien Med Wochenschr 2025; 175:253-263. [PMID: 40343680 DOI: 10.1007/s10354-025-01088-6] [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: 08/03/2024] [Accepted: 04/06/2025] [Indexed: 05/11/2025]
Abstract
Diabetic retinopathy (DR), the prevalence of which continues to rise, is one of the most common causes of vision loss worldwide. Experimental and clinical research in recent years has contributed to a better understanding of the pathogenesis of DR, which is complex and results from many interrelated processes leading to abnormal permeability and occlusion of the retinal vasculature, with ischemia and subsequent neovascularization. According to the absence or presence of neovascularization, DR is divided into two main forms: nonproliferative and proliferative DR. From nonproliferative to proliferative disease, diabetic macular edema (DME) can develop anywhere along the spectrum. As the majority of diabetics have no ophthalmologic symptoms, screening plays an important role in preventing the development of retinal disease. Specific treatment options beyond metabolic risk factor control, including intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents or corticosteroids, laser photocoagulation, and vitreous surgery, are effective approaches for ocular diabetic complications.
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Affiliation(s)
- Alisa Pedrini
- Department of Ophthalmology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
| | - Yvonne Nowosielski
- Department of Ophthalmology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
| | - Matus Rehak
- Department of Ophthalmology, Medical University of Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria
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Couturier A, Wykoff CC, Lupidi M, Udaondo P, Peto T, Pintard PJ. Anatomic biomarkers as potential endpoints in diabetic macular edema: A systematic literature review with identification of macular volume as a key surrogate for visual acuity. Surv Ophthalmol 2025:S0039-6257(25)00069-4. [PMID: 40318769 DOI: 10.1016/j.survophthal.2025.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 04/25/2025] [Accepted: 04/28/2025] [Indexed: 05/07/2025]
Abstract
Optimization of diabetic macular edema (DME) treatment pathways can aid in the efficient introduction of new therapies that provide value to patients and healthcare systems. We performed a systematic literature review and multicorrelation analysis to identify and evaluate anatomic biomarkers as potential surrogate endpoints (SEs) for visual acuity (VA) in patients with DME. We performed EMBASE and MEDLINE searches to identify studies reporting on 4 priority biomarkers previously identified by clinical experts: hyperreflective foci, intraretinal cyst, macular volume (MV), and subretinal fluid. Endpoint and treatment effect correlation analyses were performed to establish correlation coefficients between MV and VA using Pearson's correlation. A total of 105 studies reported change from baseline data for VA, and at least 1 biomarker, with MV investigated most often (n = 70 studies). Data extracted from 55 studies focusing on the 6-mm zone for MV were used in statistical analyses. A moderate correlation was observed between MV and VA at the endpoint level (r = 0.58; p < 0.01); however, a corresponding treatment effect was not found (r = 0.32; p = 0.19). Our findings suggest MV's potential as an SE for VA in future clinical practice; however, the lack of a significant treatment effect warrants that these findings be interpreted cautiously. Further evidence and improvements in reporting the methods for collecting biomarker data are needed. Analysis of outliers and subanalyses by other optical coherence tomography measures could establish the most meaningful MV values correlating with VA.
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Affiliation(s)
- Aude Couturier
- Université Paris Cité, Service d'Ophtalmologie, Hôpital Lariboisière, APHP, Paris F-75475, France
| | - Charles C Wykoff
- Retina Consultants of Texas, Houston, TX, USA; Blanton Eye Institute, Houston Methodist Hospital & Weill Cornell Medical College, Houston, TX, USA
| | - Marco Lupidi
- Eye Clinic, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona 60131, Italy; Fondazione per la Macula Onlus, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), University Eye Clinic, Genova 16132, Italy
| | - Patricia Udaondo
- Hospital Universitari i Politècnic La Fe, Avinguda Fernando Abril Martorell, No. 106, Valencia, Spain; Aiken Clinic, Aiken Fundation, Valencia, Spain
| | - Tunde Peto
- Centre for Public Health, Queen's University, Belfast, Northern Ireland, UK
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Ozsaygılı C, Bayram N. Does dexamethasone implant combination with aflibercept monotherapy affect one-year outcomes in treatment-naive diabetic macular edema with inflammatory biomarkers? Int Ophthalmol 2024; 44:51. [PMID: 38336941 DOI: 10.1007/s10792-024-02963-8] [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: 09/28/2023] [Accepted: 12/04/2023] [Indexed: 02/12/2024]
Abstract
PURPOSE To compare the anatomical and functional outcomes of the combination of aflibercept and dexamethasone implant (CT) against aflibercept monotherapy (AM) in treatment-naive diabetic macular edema (DME) patients with serous macular detachment and hyperreflective foci. METHODS This study included 82 eyes of 82 patients with treatment-naive DME who completed the follow-up period of 12 months. All patients had optical coherence tomography biomarkers of an inflammatory DME phenotype. Patients were consecutively selected and classified into two groups: The CT group consisted of 39 eyes treated with aflibercept therapy and initially combined with a single-dose dexamethasone implant. The AM group consisted of 43 eyes treated with aflibercept alone. The primary outcome measures of the study were the mean reduction of the central macular thickness (CMT) and total macular volume parameters (TMV) and improvement in best-corrected visual acuity. RESULTS In both groups, the patient characteristics, including age, gender, duration of diabetes, HbA1c levels, phakic percentage, and diabetic retinopathy status were similar (P > 0.05). The mean reduction in CMT and TMV was significantly higher in the CT group compared to the AM group (P < 0.001 and P = 0.002, respectively). In contrast, mean letter gains were not significantly higher (P = 0.240) at the end of the study. In the CT group, 20.5% of patients showed a transient IOP increase, and 18% developed cataracts. In subgroup analysis, the mean letter gain in pseudophakic eyes was significantly higher (12.5 in the CT vs. 9.3 in the AM group, P = 0.027). CONCLUSION The CT, where inflammation is prominent, can provide faster recovery. The pseudophakic eyes seem to be the ideal patient group for CT.
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Affiliation(s)
- Cemal Ozsaygılı
- Department of Ophthalmology, University of Health Sciences, Kayseri City Training and Research Hospital, Kocasinan, Kayseri, Turkey.
| | - Nurettin Bayram
- University of Health Sciences, Ankara Etlik City Hospital, Yenimahalle, Ankara, Turkey
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Szeto SK, Lai TY, Vujosevic S, Sun JK, Sadda SR, Tan G, Sivaprasad S, Wong TY, Cheung CY. Optical coherence tomography in the management of diabetic macular oedema. Prog Retin Eye Res 2024; 98:101220. [PMID: 37944588 DOI: 10.1016/j.preteyeres.2023.101220] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 10/24/2023] [Accepted: 10/24/2023] [Indexed: 11/12/2023]
Abstract
Diabetic macular oedema (DMO) is the major cause of visual impairment in people with diabetes. Optical coherence tomography (OCT) is now the most widely used modality to assess presence and severity of DMO. DMO is currently broadly classified based on the involvement to the central 1 mm of the macula into non-centre or centre involved DMO (CI-DMO) and DMO can occur with or without visual acuity (VA) loss. This classification forms the basis of management strategies of DMO. Despite years of research on quantitative and qualitative DMO related features assessed by OCT, these do not fully inform physicians of the prognosis and severity of DMO relative to visual function. Having said that, recent research on novel OCT biomarkers development and re-defined classification of DMO show better correlation with visual function and treatment response. This review summarises the current evidence of the association of OCT biomarkers in DMO management and its potential clinical importance in predicting VA and anatomical treatment response. The review also discusses some future directions in this field, such as the use of artificial intelligence to quantify and monitor OCT biomarkers and retinal fluid and identify phenotypes of DMO, and the need for standardisation and classification of OCT biomarkers to use in future clinical trials and clinical practice settings as prognostic markers and secondary treatment outcome measures in the management of DMO.
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Affiliation(s)
- Simon Kh Szeto
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Timothy Yy Lai
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Stela Vujosevic
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy; Eye Clinic, IRCCS MultiMedica, Milan, Italy
| | - Jennifer K Sun
- Beetham Eye Institute, Harvard Medical School, Boston, USA
| | - SriniVas R Sadda
- Doheny Eye Institute, University of California Los Angeles, Los Angeles, USA
| | - Gavin Tan
- Singapore Eye Research Institute, SingHealth Duke-National University of Singapore, Singapore
| | - Sobha Sivaprasad
- NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Tien Y Wong
- Tsinghua Medicine, Tsinghua University, Beijing, China; Singapore Eye Research Institute, Singapore
| | - Carol Y Cheung
- Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
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Khoramnia R, Nguyen QD, Kertes PJ, Sararols Ramsay L, Vujosevic S, Anderesi M, Igwe F, Eter N. Exploring the role of retinal fluid as a biomarker for the management of diabetic macular oedema. Eye (Lond) 2024; 38:54-60. [PMID: 37479803 PMCID: PMC10764750 DOI: 10.1038/s41433-023-02637-2] [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: 01/23/2023] [Revised: 05/16/2023] [Accepted: 06/13/2023] [Indexed: 07/23/2023] Open
Abstract
Anti-VEGF therapies are associated with significant gains in visual acuity and fluid resolution in the treatment of diabetic macular oedema (DMO) and have become the standard of care. However, despite their efficacy, outcomes can be unpredictable, vary widely between individual eyes, and a large proportion of patients have persistent fluid following initial treatment, with a negative impact on visual outcomes. Anatomical parameters measured by optical coherence tomography (OCT), in addition to visual acuity, are key to monitoring treatment effectiveness and guiding retreatment decisions; however, existing guidelines on the management of DMO lack clear recommendations for interpretation of OCT parameters, or proposed thresholds of various markers to guide retreatment decisions. Although central subfield thickness (CSFT) has been widely used as a marker for retreatment decisions in clinical trials in DMO, and a reduction in CSFT has generally been shown to accompany improvements in best-corrected visual acuity with treatment, analyses of the relationship between these parameters show that the correlation is small to moderate. A more direct relationship can be seen between an increased magnitude of CSFT fluctuations over time and poorer visual acuity, suggesting that control of CSFT could be important in maximising visual outcomes. The relationship between visual outcomes and qualitatively assessed intraretinal fluid and subretinal fluid is also unclear, although quantitative assessments of fluid parameters suggest that untreated intraretinal fluid and subretinal fluid negatively impact visual outcomes. These findings highlight a need for clearer guidelines on the management of retinal fluid to improve visual outcomes for patients with DMO.
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Affiliation(s)
- Ramin Khoramnia
- The David J. Apple International Laboratory for Ocular Pathology, Department of Ophthalmology, University of Heidelberg, Heidelberg, Germany.
| | | | - Peter J Kertes
- John and Liz Tory Eye Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
- Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada
| | | | - Stela Vujosevic
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- Eye Clinic, IRCCS MultiMedica, Milan, Italy
| | - Majid Anderesi
- Novartis Pharma AG, Basel, Switzerland
- OcuTerra Therapeutics, Basel, Switzerland
| | | | - Nicole Eter
- Department of Ophthalmology, University of Münster Medical Center, Münster, Germany
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Yayla U, Sevik MO, Karabaş VL, Şahin Ö, Özkaya A, Yenerel NM, Açıkalın Öncel B, Kaplan FB, Önder Tokuç E, Kanar HS, Kutlutürk Karagöz I, Başaran Emengen E, Demirciler Sönmez A, Aykut A, Limon U, Bozkurt E, Özsoy Saygın I, Aydoğan Gezginaslan T, Aydın Öncü Ö, Türkseven Kumral E, Erçalık NY, Çelik E. Real-World Outcomes of Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema in Türkiye: MARMASIA Study Group Report No. 1. Turk J Ophthalmol 2023; 53:356-368. [PMID: 38126607 PMCID: PMC10750085 DOI: 10.4274/tjo.galenos.2023.56249] [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: 03/04/2023] [Accepted: 05/27/2023] [Indexed: 12/23/2023] Open
Abstract
Objectives This study aimed to report the demographic and clinical characteristics of diabetic macular edema (DME) patients treated with intravitreal injection (IVI) of anti-vascular endothelial growth factors (anti-VEGF) and provide an overview of outcomes during routine clinical practice in Türkiye. Materials and Methods This retrospective, real-world study included 1,372 eyes (854 patients) treated with a pro re nata protocol by 21 ophthalmologists from 8 tertiary clinics on the Asian side of the Marmara region of Türkiye (MARMASIA Study Group). Five cohort groups were established by collecting the patients' baseline and 3, 6, 12, 24, and 36-month follow-up data, where each subsequent cohort may include the previous. Changes in best-corrected visual acuity (BCVA, approximate ETDRS letters) and central macular thickness (CMT, μm), number of visits and IVI, and rates of anti-VEGF switch and intravitreal dexamethasone implant (IDI) combination were evaluated. Results The 3, 6, 12, 24, and 36-month cohorts included 1372 (854), 1352 (838), 1185 (722), 972 (581), and 623 (361) eyes (patients), respectively. The mean baseline BCVA and CMT were 51.4±21.4 letters and 482.6±180.3 μm. The mean changes from baseline in BCVA were +7.6, +9.1, +8.0, +8.6, and +8.4 letters, and in CMT were -115.4, -140.0, -147.9, -167.3, and -215.4 μm at the 3, 6, 12, 24, and 36-month visits (p<0.001 for all). The median cumulative number of anti-VEGF IVI was 3.0, 3.0, 5.0, 7.0, and 9.0, respectively. The overall anti-VEGF switch and IDI combination rates were 18.5% (253/1372 eyes) and 35.0% (480/1372 eyes), respectively. Conclusion This largest real-life study of DME from Türkiye demonstrated BCVA gains inferior to randomized controlled trials, mainly due to the lower number of IVI. However, with the lower baseline BCVA and higher IDI combination rates in our cohorts, these gains were relatively superior to other real-life study counterparts.
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Affiliation(s)
- Uğur Yayla
- University of Health Sciences Türkiye, Derince Training and Research Hospital, Clinic of Ophthalmology, Kocaeli, Türkiye
| | - Mehmet Orkun Sevik
- Marmara University Faculty of Medicine, Department of Ophthalmology, İstanbul, Türkiye
| | - Veysel Levent Karabaş
- Kocaeli University Faculty of Medicine, Department of Ophthalmology, Kocaeli, Türkiye
| | - Özlem Şahin
- Marmara University Faculty of Medicine, Department of Ophthalmology, İstanbul, Türkiye
| | - Abdullah Özkaya
- Memorial Şişli Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Nursal Melda Yenerel
- University of Health Sciences Türkiye, Haydarpaşa Numune Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Banu Açıkalın Öncel
- University of Health Sciences Türkiye, Fatih Sultan Mehmet Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Fatih Bilgehan Kaplan
- University of Health Sciences Türkiye, Fatih Sultan Mehmet Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Ecem Önder Tokuç
- Kocaeli University Faculty of Medicine, Department of Ophthalmology, Kocaeli, Türkiye
| | - Hatice Selen Kanar
- University of Health Sciences Türkiye, Kartal Dr. Lütfi Kırdar City Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Işıl Kutlutürk Karagöz
- University of Health Sciences Türkiye, Şişli Hamidiye Etfal Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Ece Başaran Emengen
- Kocaeli University Faculty of Medicine, Department of Ophthalmology, Kocaeli, Türkiye
| | - Ayşe Demirciler Sönmez
- University of Health Sciences Türkiye, Fatih Sultan Mehmet Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Aslan Aykut
- Marmara University Faculty of Medicine, Department of Ophthalmology, İstanbul, Türkiye
| | - Utku Limon
- University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Erdinç Bozkurt
- University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Işılay Özsoy Saygın
- University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Tuğba Aydoğan Gezginaslan
- University of Health Sciences Türkiye, Ümraniye Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Özlem Aydın Öncü
- University of Health Sciences Türkiye, Haydarpaşa Numune Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Esra Türkseven Kumral
- University of Health Sciences Türkiye, Haydarpaşa Numune Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Nimet Yeşim Erçalık
- University of Health Sciences Türkiye, Haydarpaşa Numune Training and Research Hospital, Clinic of Ophthalmology, İstanbul, Türkiye
| | - Erkan Çelik
- Sakarya University Faculty of Medicine, Department of Ophthalmology, Sakarya, Türkiye
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Kyei S, Asare FA, Assan JK, Zaabaar E, Assiamah F, Obeng EO, Asiedu K. Efficacy of intravitreal bevacizumab on diabetic macular oedema in an African population. Ir J Med Sci 2023; 192:2777-2783. [PMID: 36988835 DOI: 10.1007/s11845-023-03348-z] [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: 11/03/2022] [Accepted: 03/19/2023] [Indexed: 03/30/2023]
Abstract
PURPOSE To evaluate the short-term effect of intravitreal bevacizumab (avastin) injection on visual outcomes of patients with diabetic macular oedema. METHODS A retrospective cross-sectional study was conducted to evaluate 39 eyes of thirty-nine patients (mean age ± SD: 61.4 ± 15.0 years) that received intravitreal bevacizumab injection (1.25 mg in 0.05 ml) as treatment for diabetic macular oedema between January 2014 and July 2019 in Ghana. Data on visual acuity and central macular thickness before treatment and 6 weeks post-treatment were collected and analysed using paired t-test. Ordinary least squares linear regression analysis was also conducted to determine the relationship between improvement in visual acuity and central macular thickness after treatment and other predictor variables. RESULTS The mean ± SD visual acuity (LogMAR-equivalent of Snellen) of patients with diabetic macular oedema significantly improved from 0.84 ± 0.58 LogMAR before treatment to 0.69 ± 0.58 LogMAR at 6 weeks post-treatment (mean difference: 0.15 ± 0.32 LogMAR; 95% CI: 0.04 to 0.25; p = 0.01). Mean macular thickness ± SD on the other hand, reduced significantly (p < 0.001) from 316.54 ± 75.35 μm before treatment to 275.54 ± 57.43 μm after treatment. While age and worse pre-treatment visual acuity predicted improvement in visual acuity after treatment, a higher central macular thickness before treatment predicted an improvement in central macular thickness after intravitreal bevacizumab injection. CONCLUSION Treatment with intravitreal bevacizumab injection produces short-term improvement in vision and reduction in central macular thickness in African patients with diabetic macular oedema.
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Affiliation(s)
- Samuel Kyei
- Department of Optometry and Vision Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana.
| | - Frederick Afum Asare
- Centre for Optometry and Vision Science, Biomedical Sciences Research Institute, Ulster University, Coleraine, UK
| | - John Kwesi Assan
- Department of Optometry and Vision Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Ebenezer Zaabaar
- Department of Optometry and Vision Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
- Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Frank Assiamah
- Cell Biology and Human Anatomy Department, University of California, Davis, USA
| | - Eric Obour Obeng
- Department of Optometry and Vision Science, School of Allied Health Sciences, College of Health and Allied Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Kofi Asiedu
- School of Optometry and Vision Science, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia
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Gabrielle PH, Mehta H, Barthelmes D, Daien V, Nguyen V, Gillies MC, Creuzot-Garcher CP. From randomised controlled trials to real-world data: Clinical evidence to guide management of diabetic macular oedema. Prog Retin Eye Res 2023; 97:101219. [PMID: 37898362 DOI: 10.1016/j.preteyeres.2023.101219] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 10/12/2023] [Accepted: 10/13/2023] [Indexed: 10/30/2023]
Abstract
Randomised clinical trials (RCTs) are generally considered the gold-standard for providing scientific evidence for treatments' effectiveness and safety but their findings may not always be generalisable to the broader population treated in routine clinical practice. RCTs include highly selected patient populations that fit specific inclusion and exclusion criteria. Although they may have a lower level of certainty than RCTs on the evidence hierarchy, real-world data (RWD), such as observational studies, registries and databases, provide real-world evidence (RWE) that can complement RCTs. For example, RWE may help satisfy requirements for a new indication of an already approved drug and help us better understand long-term treatment effectiveness, safety and patterns of use in clinical practice. Many countries have set up registries, observational studies and databases containing information on patients with retinal diseases, such as diabetic macular oedema (DMO). These DMO RWD have produced significant clinical evidence in the past decade that has changed the management of DMO. RWD and medico-administrative databases are a useful resource to identify low frequency safety signals. They often have long-term follow-up with a large number of patients and minimal exclusion criteria. We will discuss improvements in healthcare information exchange technologies, such as blockchain technology and FHIR (Fast Healthcare Interoperability Resources), which will connect and extend databases already available. These registries can be linked with existing or emerging retinal imaging modalities using artificial intelligence to aid diagnosis, treatment decisions and provide prognostic information. The results of RCTs and RWE are combined to provide evidence-based guidelines.
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Affiliation(s)
- Pierre-Henry Gabrielle
- Department of Ophthalmology, Dijon University Hospital, Dijon, Burgundy, France; The Save Sight Institute, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Hemal Mehta
- The Save Sight Institute, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; Ophthalmology Department, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Daniel Barthelmes
- The Save Sight Institute, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; Department of Ophthalmology, University Hospital and University of Zurich, Zurich, Switzerland
| | - Vincent Daien
- The Save Sight Institute, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia; Department of Ophthalmology, Montpellier University Hospital, Montpellier, France; Institute for Neurosciences of Montpellier, Univ Montpellier, INSERM, Montpellier, France
| | - Vuong Nguyen
- The Save Sight Institute, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
| | - Mark C Gillies
- The Save Sight Institute, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia
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Wang X, Yao J, Li S, Zhang W, Wang L, Zhou A. Panretinal photocoagulation plus intravitreal conbercept for diabetic retinopathy in real world: a retrospective study. BMC Ophthalmol 2023; 23:400. [PMID: 37794367 PMCID: PMC10552403 DOI: 10.1186/s12886-023-03157-z] [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: 02/01/2023] [Accepted: 09/28/2023] [Indexed: 10/06/2023] Open
Abstract
BACKGROUND To evaluate outcomes of panretinal photocoagulation (PRP) plus intravitreal conbercept (IVC) for diabetic retinopathy (DR) in real world and explore risk factors for patients with poor reactivity and presence of vision-threatening complications after combination treatment. METHODS Retrospective review of DR patients received PRP plus IVC over 6 months. The main outcome was improvement ≥ 2 steps in ETDRS diabetic retinopathy severity scale (DRSS) levels. Different strategies for eyes receiving IVC within or over 1 month after PRP were analyzed. For patients with DRSS improvement < 2 steps and presence of vision-threatening adverse events, a binary logistic regression method was used to select risk factors. RESULTS Sixty one eyes were involved in this study. After treated with combination therapy with a median number of 3 injections, 44% of eyes improved ≥ 2 steps in DRSS levels. A total of 14 eyes (23%) occurred vision-threatening adverse events. No significant difference was found in eyes receiving conbercept within or over 1 month after PRP. Duration of diabetes (OR 0.849, 95%CI 0.734-0.982, P = 0.027), GFR (OR 0.961, 95%CI 0.933-0.990, P = 0.010) and baseline DRSS levels (OR 3.290, 95%CI 1.483-7.295, P = 0.003) were independent risk factors for DRSS improvement < 2 steps after treatment. Occurrence of vision-threatening complications was only related to high DRSS levels (OR 3.668, 95%CI 1.710-7.868, P = 0.001). CONCLUSIONS The combination therapy was effective for most patients with DR in real world. Eyes received PRP combined with earlier or later conbercept was demonstrated no significant difference for outcomes. For patients with poor renal function, high DRSS levels or occurred DR at the early stage of diabetes, follow-up should be strengthened.
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Affiliation(s)
- Xin Wang
- Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Jing Yao
- Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Shengen Li
- Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Wenyi Zhang
- Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Lijun Wang
- Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - Aiyi Zhou
- Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
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Yang F, Zhang H, Yu X, Tao Q, Zhao C, An J, Zhang X, Li X. TNFAIP8 overexpression aggravates retinal pathophysiological features of diabetic retinopathy. Exp Eye Res 2023; 234:109572. [PMID: 37451566 DOI: 10.1016/j.exer.2023.109572] [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: 02/28/2023] [Revised: 07/05/2023] [Accepted: 07/10/2023] [Indexed: 07/18/2023]
Abstract
Our previous research shown that tumor necrosis factor-alpha-induced protein 8 (TNFAIP8) is elevated in the plasma extracellular vesicles and vitreous humor in diabetic retinopathy (DR). TNFAIP8 also significantly increases the viability of human retinal microvascular endothelial cells (HRMECs) and promotes cell migration and tube formation in vitro. To comprehensively explore its role in DR, we investigated the effect of TNFAIP8 on DR development using an animal model in this study. A TNFAIP8-overexpressing adeno-associated virus (AAV) vector and streptozotocin-induced mouse model was used. The AAV-TNFAIP8 vector was injected into the mice intravitreally, and the effect was evaluated. The evaluation included analysis of retinal structure and function using electroretinography, optical coherence tomography, and histological assessment. The influence of TNFAIP8 on the avascular area, retinal leukostasis, and the expression levels of inflammatory factors was also determined. TNFAIP8 significantly decreased a/b-wave amplitude and retinal thickness in diabetic mice. Histological assessment showed that TNFAIP8 aggravated pathological abnormalities with distorted organization of the retina. TNFAIP8 also significantly increased the avascular area, leukostasis, and the expression of inflammatory factors, such as TNFα, IL1β, ICAM1, and GFAP, in the retina. The results of this study support the role of TNFAIP8 in DR pathogenesis. A mechanistic understanding of TNFAIP8 may offer novel therapeutic strategies.
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Affiliation(s)
- Fuhua Yang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Hui Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Xinyue Yu
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Qingqin Tao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Chuan Zhao
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Jinying An
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China
| | - Xiaomin Zhang
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China.
| | - Xiaorong Li
- Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, 300384, China.
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11
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Sivaprasad S, Sen S, Cunha-Vaz J. Perspectives of diabetic retinopathy-challenges and opportunities. Eye (Lond) 2023; 37:2183-2191. [PMID: 36494431 PMCID: PMC10366207 DOI: 10.1038/s41433-022-02335-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 09/16/2022] [Accepted: 11/25/2022] [Indexed: 12/14/2022] Open
Abstract
Diabetic retinopathy (DR) may lead to vision-threatening complications in people living with diabetes mellitus. Decades of research have contributed to our understanding of the pathogenesis of diabetic retinopathy from non-proliferative to proliferative (PDR) stages, the occurrence of diabetic macular oedema (DMO) and response to various treatment options. Multimodal imaging has paved the way to predict the impact of peripheral lesions and optical coherence tomography-angiography is starting to provide new knowledge on diabetic macular ischaemia. Moreover, the availability of intravitreal anti-vascular endothelial growth factors has changed the treatment paradigm of DMO and PDR. Areas of research have explored mechanisms of breakdown of the blood-retinal barrier, damage to pericytes, the extent of capillary non-perfusion, leakage and progression to neovascularisation. However, knowledge gaps remain. From this perspective, we highlight the challenges and future directions of research in this field.
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Affiliation(s)
- Sobha Sivaprasad
- NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, UK.
| | - Sagnik Sen
- Department of Retina and Vitreous, Aravind Eye Hospital and Aravind Medical Research Foundation, Madurai, India
- Moorfields Eye Hospital, NHS Foundation Trust, London, United Kingdom
| | - José Cunha-Vaz
- AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal
- University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal
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12
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Virgili G, Curran K, Lucenteforte E, Peto T, Parravano M. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Database Syst Rev 2023; 2023:CD007419. [PMID: 38275741 PMCID: PMC10294542 DOI: 10.1002/14651858.cd007419.pub7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2024]
Abstract
Background Diabetic macular oedema (DMO) is a common complication of diabetic retinopathy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) can reduce oedema, improve vision, and prevent further visual loss. These drugs have replaced laser photocoagulation as the standard of care for people with DMO. In the previous update of this review, we found moderate-quality evidence that, at 12 months, aflibercept was slightly more effective than ranibizumab and bevacizumab for improving vision in people with DMO, although the difference may have been clinically insignificant (less than 0.1 logarithm of the minimum angle of resolution (logMAR), or five Early Treatment Diabetic Retinopathy Study (ETDRS) letters, or one ETDRS line). Objectives The objective of this updated review was to compare the effectiveness and safety of the different anti-VEGF drugs in RCTs at longer followup (24 months). Search methods We searched various electronic databases on 8 July 2022. Selection criteria We included randomised controlled trials (RCTs) that compared any anti-angiogenic drug with an anti-VEGF mechanism of action versus another anti-VEGF drug, another treatment, sham, or no treatment in people with DMO. Data collection and analysis We used standard Cochrane methods for pairwise meta-analysis and we augmented this evidence using network meta-analysis (NMA) methods. We used the Stata 'network' meta-analysis package for all analyses. We used the CINeMA (Confidence in Network Meta-Analysis) web application to grade the certainty of the evidence. Main results We included 23 studies (13 with industry funding) that enrolled 3513 people with DMO (median central retinal thickness (CRT) 460 microns, interquartile range (IQR) 424 to 482) and moderate vision loss (median best-corrected visual acuity (BCVA) 0.48 logMAR, IQR 0.42 to 0.55. One study that investigated ranibizumab versus sham and one study that mainly enrolled people with subclinical DMO and normal BCVA were not suitable for inclusion in the efficacy NMA. Consistent with the previous update of this review, we used ranibizumab as the reference drug for efficacy, and control (including laser, observation, and sham) as the reference for systemic safety. Eight trials provided data on the primary outcome (change in BCVA at 24 months, in logMAR: lower is better). We found no evidence of a difference between the following interventions and ranibizumab alone: aflibercept (mean difference (MD) -0.05 logMAR, 95% confidence interval (CI) -0.12 to 0.02; moderate certainty); bevacizumab (MD -0.01 logMAR, 95% CI -0.13 to 0.10; low certainty), brolucizumab (MD 0.00 logMAR, 95% CI -0.08 to 0.07; low certainty), ranibizumab plus deferred laser (MD 0.00 logMAR, 95% CI -0.11 to 0.10; low certainty), and ranibizumab plus prompt laser (MD 0.03 logMAR, 95% CI -0.04 to 0.09; very low certainty). We also analysed BCVA change at 12 months, finding moderate-certainty evidence of increased efficacy with brolucizumab (MD -0.07 logMAR, 95%CI -0.10 to -0.03 logMAR), faricimab (MD -0.08 logMAR, 95% CI -0.12 to -0.05), and aflibercept (MD -0.07 logMAR, 95 % CI -0.10 to -0.04) compared to ranibizumab alone, but the difference could be clinically insignificant. Compared to ranibizumab alone, NMA of six trials showed no evidence of a difference with aflibercept (moderate certainty), bevacizumab (low certainty), or ranibizumab with prompt (very low certainty) or deferred laser (low certainty) regarding improvement by three or more ETDRS lines at 24 months. There was moderate-certainty evidence of greater CRT reduction at 24 months with brolucizumab (MD -23 microns, 95% CI -65 to -1 9) and aflibercept (MD -26 microns, 95% CI -53 to 0.9) compared to ranibizumab. There was moderate-certainty evidence of lesser CRT reduction with bevacizumab (MD 28 microns, 95% CI 0 to 56), ranibizumab plus deferred laser (MD 63 microns, 95% CI 18 to 109), and ranibizumab plus prompt laser (MD 72 microns, 95% CI 25 to 119) compared with ranibizumab alone. Regarding all-cause mortality at the longest available follow-up (20 trials), we found no evidence of increased risk of death for any drug compared to control, although effects were in the direction of an increase, and clinically relevant increases could not be ruled out. The certainty of this evidence was low for bevacizumab (risk ratio (RR) 2.10, 95% CI 0.75 to 5.88), brolucizumab (RR 2.92, 95% CI 0.68 to 12.58), faricimab (RR 1.91, 95% CI 0.45 to 8.00), ranibizumab (RR 1.26, 95% CI 0.68 to 2.34), and very low for conbercept (RR 0.33, 95% CI 0.01 to 8.81) and aflibercept (RR 1.48, 95% CI 0.79 to 2.77). Estimates for Antiplatelet Trialists Collaboration arterial thromboembolic events at 24 months did not suggest an increase with any drug compared to control, but the NMA was overall incoherent and the evidence was of low or very low certainty. Ocular adverse events were rare and poorly reported and could not be assessed in NMAs. Authors' conclusions There is limited evidence of the comparative efficacy and safety of anti-VEGF drugs beyond one year of follow-up. We found no clinically important differences in visual outcomes at 24 months in people with DMO, although there were differences in CRT change. We found no evidence that any drug increases all-cause mortality compared to control, but estimates were very imprecise. Evidence from RCTs may not apply to real-world practice, where people in need of antiangiogenic treatment are often under-treated, and the individuals exposed to these drugs may be less healthy than trial participants.
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Key Words
- Angiogenesis Inhibitors [adverse effects, *therapeutic use]
- Aptamers, Nucleotide [adverse effects, therapeutic use]
- Bevacizumab [adverse effects, therapeutic use]
- Diabetic Retinopathy [*complications]
- Laser Coagulation [methods]
- Macular Edema [*drug therapy, etiology, surgery]
- Network Meta-Analysis
- Quality of Life
- Randomized Controlled Trials as Topic
- Ranibizumab [adverse effects, therapeutic use]
- Receptors, Vascular Endothelial Growth Factor [therapeutic use]
- Recombinant Fusion Proteins [adverse effects, therapeutic use]
- Triamcinolone [adverse effects, therapeutic use]
- Vascular Endothelial Growth Factor A [*antagonists & inhibitors]
- Visual Acuity [*drug effects, physiology]
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Affiliation(s)
- Gianni Virgili
- Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy
| | | | - Ersilia Lucenteforte
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Tunde Peto
- Centre for Public Health, Queen's University Belfast, Belfast, UK
| | - Mariacristina Parravano
- Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Rome, Italy
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13
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Ikegami Y, Shiraya T, Araki F, Ueta T, Toyama T, Yanagita T, Numaga J, Shoji N, Kato S. Microperimetric analysis of diabetic macular edema after navigated direct photocoagulation with short-pulse laser for microaneurysms. Int J Retina Vitreous 2023; 9:12. [PMID: 36864536 PMCID: PMC9979500 DOI: 10.1186/s40942-023-00447-y] [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] [Received: 12/20/2022] [Accepted: 01/30/2023] [Indexed: 03/04/2023] Open
Abstract
BACKGROUND Focal laser photocoagulation is an important treatment option for diabetic macular edema (DME). This study aimed to examine the retinal sensitivity (RS) and morphological changes at the coagulated site after direct photocoagulation of microaneurysms (MAs) in patients with DME using a navigated laser photocoagulator with a short-pulse duration of 30 ms. METHODS Images of early-phase fluorescein angiography were merged with images from the optical coherence tomography (OCT) map with 9 Early Treatment Diabetic Retinopathy Study grid circles, and MAs inside the edema area were selected for direct photocoagulation. The best-corrected visual acuity (BCVA), parameters of the OCT map including central retinal thickness and retinal thickness in edema range, central RS, and RS in the edema area were assessed at 1 and 3 months after the laser treatment. The RS points that overlapped with the laser spots were identified by merging the Navilas' digital treatment reports and the microperimetry images. RESULTS Seventeen eyes from 14 patients were studied. The mean retinal thickness in the edema range decreased at 3 months compared with pretreatment (P = 0.042), but the BCVA, central retinal thickness, central RS, and RS in the edema area remained unchanged. Overall, 32 of 400 sensitivity points overlapped with the laser-coagulated spots. The mean RS at these spots were 22.4 ± 5.3 dB at 1 month and 22.5 ± 4.8 dB at 3 months, with no significant change from the baseline of 22.7 ± 3.5 dB. CONCLUSIONS Retinal thickness improved in the coagulated edema area without a decrease in RS after direct photocoagulation of MAs with a short 30-ms pulse using Navilas. This promising therapeutic strategy for DME is effective and minimally invasive.
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Affiliation(s)
- Yasuko Ikegami
- Department of Ophthalmology, University of Kitasato School of Medicine, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, Japan. .,Department of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. .,Department of Ophthalmology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan.
| | - Tomoyasu Shiraya
- grid.26999.3d0000 0001 2151 536XDepartment of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Fumiyuki Araki
- grid.26999.3d0000 0001 2151 536XDepartment of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Takashi Ueta
- grid.26999.3d0000 0001 2151 536XDepartment of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Taku Toyama
- grid.26999.3d0000 0001 2151 536XDepartment of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
| | - Tomohiko Yanagita
- grid.410786.c0000 0000 9206 2938Department of Ophthalmology, University of Kitasato School of Medicine, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa Japan
| | - Jiro Numaga
- grid.417092.9Department of Ophthalmology, Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan
| | - Nobuyuki Shoji
- grid.410786.c0000 0000 9206 2938Department of Ophthalmology, University of Kitasato School of Medicine, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa Japan
| | - Satoshi Kato
- grid.26999.3d0000 0001 2151 536XDepartment of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
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14
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Lim SY, Wong WM, Seah I, Chan HW, Su X, Lingam G, Yuen YS. Treat and extend regimen for diabetic macular oedema-a systematic review and meta-analysis. Graefes Arch Clin Exp Ophthalmol 2023; 261:303-315. [PMID: 35906415 DOI: 10.1007/s00417-022-05770-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 07/12/2022] [Accepted: 07/15/2022] [Indexed: 01/17/2023] Open
Abstract
PURPOSE Various treatment regimens are currently practiced in the treatment of CI-DMO (centre-involving diabetic macular oedema). In recent years, there has been a growing body of evidence supporting a treat and extend (T&E) regimen for DMO which offers the promise of comparable visual and anatomical outcomes while reducing injection burden. This meta-analysis was hence performed to evaluate the aforementioned outcomes in the treatment of DMO. Ten studies met the inclusion criteria. METHODS A search of PubMed, MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. We employed the terms 'treat AND extend AND (diabetic AND macular AND edema OR oedema)' to ensure a comprehensive search. The search workflow adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS The pooled analysis of the mean number of injections in 1 year for T&E-aflibercept (AFL), T&E-ranibizumab (RBZ) and collectively was 9.1 (95% CI: 7.63-10.63), 10.0 (95% CI: 9.55-10.47) and 9.6 (95% CI: 8.62-10.49), respectively. Improvements in vision at 1 year for T&E-AFL, T&E-RBZ and collectively were 6.26 (95% CI: 3.24-9.29), 7.14 (95% CI: 4.76-9.52) and 7.08 (95% CI: 5.32-8.84) letters, respectively. The improvements in central subfield thickness at 1 year for T&E-AFL, T&E-RBZ and collectively were 131.94 (95% CI: 100.29-163.60), 108.64 (95% CI: 82.82-134.46) and 121.32 (95% CI: 102.89-139.75) microns, respectively. CONCLUSION The meta-analysis of T&E for DMO did not show a clear advantage in reducing the number of injections compared to landmark clinical trials with pro-re-nata (PRN) treatment regimens in the first year of treatment with limited gains in visual and anatomical outcomes. However, the T&E approach offers the potential for fewer patient visits, thereby reducing treatment burden. Longer term studies on T&E with a standardised protocol would be required to assess the longevity of the vision gain in the first year despite a likely reduced treatment burden compared to the PRN trials.
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Affiliation(s)
- Sheng Yang Lim
- Department of Ophthalmology, National University Hospital, National University Health Systems, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
| | - Wendy Meihua Wong
- Department of Ophthalmology, National University Hospital, National University Health Systems, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
| | - Ivan Seah
- Department of Ophthalmology, National University Hospital, National University Health Systems, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
| | - Hwei Wuen Chan
- Department of Ophthalmology, National University Hospital, National University Health Systems, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
| | - Xinyi Su
- Department of Ophthalmology, National University Hospital, National University Health Systems, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
| | - Gopal Lingam
- Department of Ophthalmology, National University Hospital, National University Health Systems, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore
| | - Yew Sen Yuen
- Department of Ophthalmology, National University Hospital, National University Health Systems, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
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15
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Nawrocka ZA, Nawrocki J. Vitrectomy in Diabetic Macular Edema:: A Swept-source OCT Angiography Study. OPHTHALMOLOGY SCIENCE 2022; 2:100207. [PMID: 36385773 PMCID: PMC9647227 DOI: 10.1016/j.xops.2022.100207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/13/2022] [Accepted: 07/15/2022] [Indexed: 12/01/2022]
Abstract
Purpose The foveal avascular zone (FAZ) has been reported to decrease after anti-VEGF injections in diabetic macular edema (DME) in the long term. This study aimed to present the changes in swept-source OCT angiography after vitrectomy in patients with DME. Design Retrospective interventional study. Participants Thirty-five eyes were included (mean age: 62 years). Methods Patients were followed for 12 months after vitrectomy with internal limiting membrane peeling for DME. Main Outcome Measures The following parameters were measured: central retinal thickness (CRT), central choroidal thickness, superficial FAZ, deep FAZ (dFAZ), and vessel density in the superficial and deep retinal layers (dVD). Results The CRT and superficial FAZ significantly decreased after surgery (401 μm-338 μm; P < 0.00, 401 μm-293 μm; P < 0.001, respectively). Initial visual acuity (VA) improved from 20/160 (0.97 logarithm of the minimum angle of resolution [LogMAR]) to 20/80 (0.62 LogMAR) (P < 0.001). The vessel density in the superficial retinal layers rate was 42.3% and decreased after surgery, reaching 41.6% at the end of the follow-up. The dVD rate 1 week after surgery was 28.9% and remained stable throughout the observation period. The most important prognostic factors for the final VA were preoperative VA and preoperative CRT, while the dFAZ and dVD at the time of edema resolution also correlated with the final VA. Conclusions The superficial FAZ decreases after vitrectomy, which might indicate that vitrectomy has a protective effect on DME, similar to anti-VEGF injections. Prognostic factors for better final functional results are better initial VA and lower CRT before vitrectomy, in addition to a lower dFAZ diameter and a higher dVD at the moment of edema resolution. Financial Disclosures The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Key Words
- ANOVA, analysis of variance
- Anti-VEGF injections
- BSS, balanced salt solution
- CCT, central choroidal thickness
- CRT, central retinal thickness
- DME
- DME, diabetic macular edema
- Diabetic macular edema
- FAZ, foveal avascular zone
- ILM, internal limiting membrane
- SD, standard deviation
- SS-OCTA, swept-source OCT angiography
- Swept-source OCT angiography
- VA, visual acuity
- Vitrectomy
- dFAZ, deep FAZ
- dvD, vessel density in the deep retinal layers
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Affiliation(s)
- Zofia Anna Nawrocka
- Correspondence: Zofia Anna Nawrocka, MD, PhD, Ophthalmic Clinic “Jasne Blonia”, Rojna 90, Lodz, Poland.
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16
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Lin TY, Chen HR, Huang HY, Hsiao YI, Kao ZK, Chang KJ, Lin TC, Yang CH, Kao CL, Chen PY, Huang SE, Hsu CC, Chou YB, Jheng YC, Chen SJ, Chiou SH, Hwang DK. Deep learning to infer visual acuity from optical coherence tomography in diabetic macular edema. Front Med (Lausanne) 2022; 9:1008950. [PMID: 36275805 PMCID: PMC9582267 DOI: 10.3389/fmed.2022.1008950] [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: 08/01/2022] [Accepted: 09/16/2022] [Indexed: 11/26/2022] Open
Abstract
Purpose Diabetic macular edema (DME) is one of the leading causes of visual impairment in diabetic retinopathy (DR). Physicians rely on optical coherence tomography (OCT) and baseline visual acuity (VA) to tailor therapeutic regimen. However, best-corrected visual acuity (BCVA) from chart-based examinations may not wholly reflect DME status. Chart-based examinations are subjected findings dependent on the patient’s recognition functions and are often confounded by concurrent corneal, lens, retinal, optic nerve, or extraocular disorders. The ability to infer VA from objective optical coherence tomography (OCT) images provides the predicted VA from objective macular structures directly and a better understanding of diabetic macular health. Deviations from chart-based and artificial intelligence (AI) image-based VA will prompt physicians to assess other ocular abnormalities affecting the patients VA and whether pursuing anti-VEGF treatment will likely yield increment in VA. Materials and methods We enrolled a retrospective cohort of 251 DME patients from Big Data Center (BDC) of Taipei Veteran General Hospital (TVGH) from February 2011 and August 2019. A total of 3,920 OCT images, labeled as “visually impaired” or “adequate” according to baseline VA, were grouped into training (2,826), validation (779), and testing cohort (315). We applied confusion matrix and receiver operating characteristic (ROC) curve to evaluate the performance. Results We developed an OCT-based convolutional neuronal network (CNN) model that could classify two VA classes by the threshold of 0.50 (decimal notation) with an accuracy of 75.9%, a sensitivity of 78.9%, and an area under the ROC curve of 80.1% on the testing cohort. Conclusion This study demonstrated the feasibility of inferring VA from routine objective retinal images. Translational relevance Serves as a pilot study to encourage further use of deep learning in deriving functional outcomes and secondary surrogate endpoints for retinal diseases.
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Affiliation(s)
- Ting-Yi Lin
- Doctoral Degree Program of Translational Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei, Taiwan
| | - Hung-Ruei Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hsin-Yi Huang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Taipei Veterans General Hospital Biostatistics Task Force, Taipei, Taiwan
| | - Yu-Ier Hsiao
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Zih-Kai Kao
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Kao-Jung Chang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tai-Chi Lin
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chang-Hao Yang
- Department of Ophthalmology, National Taiwan University, Taipei, Taiwan
| | - Chung-Lan Kao
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan,Department of Physical Therapy and Assistive Technology, National Yang Ming Chiao Tung University, Taipei, Taiwan,Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Po-Yin Chen
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan,Department of Physical Therapy and Assistive Technology, National Yang Ming Chiao Tung University, Taipei, Taiwan,School of Gerontology and Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan,Master Program in Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan,International Ph.D. Program in Gerontology and Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan
| | - Shih-En Huang
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan,Department of Physical Therapy and Assistive Technology, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chih-Chien Hsu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yu-Bai Chou
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ying-Chun Jheng
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan,Big Data Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan,Center for Quality Management, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shih-Jen Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Shih-Hwa Chiou
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan,Big Data Center, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan
| | - De-Kuang Hwang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan,Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan,*Correspondence: De-Kuang Hwang,
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17
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Uludag G, Hassan M, Matsumiya W, Pham BH, Chea S, Trong Tuong Than N, Doan HL, Akhavanrezayat A, Halim MS, Do DV, Nguyen QD. Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further? Expert Opin Biol Ther 2022; 22:1275-1291. [PMID: 35818801 PMCID: PMC10863998 DOI: 10.1080/14712598.2022.2100694] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Accepted: 07/08/2022] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Diabetic retinopathy (DR) is one of the most frequent microvascular complications of diabetes that can lead to blindness. Laser treatment has been the gold standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for many years. Recently, the role of vascular endothelial growth factor (VEGF) has been established in the pathogenesis of DR, and the use of intravitreal anti-VEGF therapy has gained popularity for the management of DR. AREAS COVERED This review includes a brief overview of the efficacy and safety of currently available (bevacizumab, ranibizumab, and aflibercept) and potential future (brolucizumab, faricimab, and KSI-301) anti-VEGF agents in patients with DR based mainly on publicly available data from phase 1, 2 and 3 clinical trials. EXPERT OPINION Clinical trials investigating the efficacy of intravitreal bevacizumab, ranibizumab, and aflibercept injections demonstrated favorable functional and anatomical outcomes in patients with DME. Moreover, the use of these anti-VEGF agents showed a significant improvement in the severity of DR. Recent clinical research for future anti-VEGF molecules aims to provide higher target-protein binding affinity and prolonged therapeutic effect. Brolucizumab, faricimab, and KSI-301 are three novel anti-VEGF agents that demonstrate promising data for the management of DME and potentially DR.
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Affiliation(s)
- Gunay Uludag
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
| | - Muhammad Hassan
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
| | - Wataru Matsumiya
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Brandon Huy Pham
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
- Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miami, FL, USA
| | - Sophaktra Chea
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
| | | | - Hien Luong Doan
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
| | | | - Muhammad Sohail Halim
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
- Ocular Imaging Research and Reading Center, Sunnyvale, CA, USA
| | - Diana V Do
- Byers Eye Institute, Stanford University, Palo Alto, CA, USA
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18
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Singh R, Davoudi S, Ness S. Preventive factors, diagnosis, and management of injection-related endophthalmitis: a literature review. Graefes Arch Clin Exp Ophthalmol 2022; 260:2399-2416. [PMID: 35278125 PMCID: PMC8917335 DOI: 10.1007/s00417-022-05607-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/14/2022] [Accepted: 02/21/2022] [Indexed: 12/02/2022] Open
Abstract
BACKGROUND Intravitreal medication injections represent the gold standard treatment for a variety of potentially blinding chorioretinal vascular diseases. Despite their excellent safety profile, they are associated with the feared complication of injection-related endophthalmitis (IRE). Though the overall incidence of IRE is low, due to the ever-increasing number of injections being performed, it is a complication that all retina specialists are likely to encounter. This article reviews various factors that could potentially influence the risk of IRE and discusses evidence-based strategies for management. METHOD PubMed was searched for keywords "intravitreal injection" and "endophthalmitis" from the period of 1995-2021. Relevant articles were reviewed and selected articles were analyzed with respect to the incidence, potential preventive factors, clinical presentation, microbial profile, management, and outcomes for IRE. RESULTS There is strong consensus supporting the use of povidone iodine topical antiseptic, eyelid retraction away from the injection site, and avoiding treatment of eyes with active surface or eyelid disease, but there is less agreement on the use of face masks versus "no-talking" policies and optimal anesthetic technique. Current evidence comparing tap and inject or early vitrectomy for treatment of IRE is inadequate to determine an optimal treatment strategy. CONCLUSION Intravitreal injections are sight saving, but even using established prophylactic measures there remains a small but real risk of infectious injection-related complications. Further investigations comparing tap and inject versus vitrectomy may help to establish optimal treatment, although the rarity of IRE makes designing adequately powered prospective trials a difficult task.
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Affiliation(s)
| | - Samaneh Davoudi
- Boston Medical Center, 85 East Concord Street, 8th Floor, Boston, MA, 02118, USA
| | - Steven Ness
- Boston Medical Center, 85 East Concord Street, 8th Floor, Boston, MA, 02118, USA.
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19
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Cheung CMG, Fawzi A, Teo KY, Fukuyama H, Sen S, Tsai WS, Sivaprasad S. Diabetic macular ischaemia- a new therapeutic target? Prog Retin Eye Res 2022; 89:101033. [PMID: 34902545 PMCID: PMC11268431 DOI: 10.1016/j.preteyeres.2021.101033] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 11/25/2021] [Accepted: 12/01/2021] [Indexed: 12/21/2022]
Abstract
Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.
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Affiliation(s)
- Chui Ming Gemmy Cheung
- Singapore Eye Research Institution, Singapore National Eye Centre, Singapore; Duke-NUS Medical School, National University of Singapore, Singapore
| | | | - Kelvin Yc Teo
- Singapore Eye Research Institution, Singapore National Eye Centre, Singapore
| | | | | | - Wei-Shan Tsai
- NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, United Kingdom
| | - Sobha Sivaprasad
- NIHR Moorfields Biomedical Research Centre, Moorfields Eye Hospital, London, United Kingdom.
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20
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Lin TC, Chung YC, Hsu TK, Huang HW, Huang YM, Chou YC, Chao CY, Tseng PC. Therapeutic effect of simultaneous intravitreal dexamethasone and aflibercept on diabetic macular edema. Acta Diabetol 2022; 59:501-508. [PMID: 34786634 PMCID: PMC8594639 DOI: 10.1007/s00592-021-01824-5] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/26/2021] [Indexed: 11/25/2022]
Abstract
AIMS To report the effect of simultaneous intravitreal dexamethasone (DEX) and aflibercept for the treatment of diabetic macular edema (DME). METHODS This retrospective analysis of an open-label, multicenter, consecutive case series included 102 eyes of 81 patients with DME. Patients were selected into two groups. The control group consisted of 50 eyes treated with aflibercept alone, and the combination group consisted of 52 eyes treated with simultaneous DEX implant and aflibercept injection. The primary endpoints were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 6. The secondary endpoint was the interval of retreatment. RESULTS Baseline BCVA increased and CRT decreased at 6 months in both groups. Pseudophakic eyes in the combination group exhibited significantly greater BCVA improvement compared with phakic eyes (p = 0.031). Fewer intravitreal treatments were required for eyes treated with combination therapy than for those treated with aflibercept alone (1.56 ± 0.54 vs. 4.04 ± 1.26, p < .0001), with a mean retreatment interval of 3.66 ± 0.69 months. CONCLUSIONS Simultaneous intravitreal DEX and aflibercept achieved non-inferior improvement of visual and anatomic outcomes compared with aflibercept alone for DME, but exhibited a significantly longer treatment interval and superior visual outcome in pseudophakic eyes. This therapeutic approach is considered a valid strategy for treating DME in the era of COVID-19.
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Affiliation(s)
- Tai-Chi Lin
- Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
- Department of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China
| | - Yu-Chien Chung
- Department of Ophthalmology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan, Republic of China
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, Republic of China
- Graduate Institute of Business Administration, Fu Jen Catholic University, New Taipei City, Taiwan, Republic of China
| | - Tsui-Kang Hsu
- Department of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China
- Department of Ophthalmology, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China
- Institue of Public Health, National Taiwan University, Taipei, Taiwan, Republic of China
- Department of Life Science, Institute of Molecular Biology, Institute of Biomedical Science, National Chung Cheng University, Chiayi, Taipei, Taiwan, Republic of China
| | - Hsin-Wei Huang
- Department of Ophthalmology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Republic of China
- Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
| | - Yi-Ming Huang
- Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
- Department of Ophthalmology, School of Medicine, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China
| | - Yi-Chang Chou
- Department of Education and Research, Taipei City Hospital, Taipei, Taiwan, Republic of China
- Institute of Public Health, National Yang Ming Chiao Tung University, Hsinchu, Taiwan, Republic of China
| | - Chen-Yu Chao
- Department of Life Science, Fu Jen Catholic University, New Taipei City, Taiwan, Republic of China
| | - Po-Chen Tseng
- Department of Ophthalmology, Taipei City Hospital, Taipei, Taiwan, Republic of China.
- Department of Special Education, University of Taipei, Taipei, Taiwan, Republic of China.
- Department of Optometry, University of Kang-Ning, Taipei, Taiwan, Republic of China.
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21
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Shah J, Nguyen V, Hunt A, Mehta H, Romero-Nuñez B, Zarranz-Ventura J, Viola F, Bougamha W, Barnes R, Barthelmes D, Gillies MC, Fraser-Bell S. Characterization of poor visual outcomes of diabetic macular edema: the Fight Retinal Blindness! Project. Ophthalmol Retina 2022; 6:540-547. [PMID: 35307607 DOI: 10.1016/j.oret.2022.03.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 12/01/2022]
Abstract
PURPOSE To investigate the incidence, characteristics and baseline predictors of poor visual outcomes in eyes with diabetic macular edema (DME) receiving intravitreal therapy in routine clinical practice. DESIGN Observational study. PARTICIPANTS Treatment-naive eyes starting intravitreal therapy for DME between 2014 and 2018 tracked in the Fight Retinal Blindness! registry. We examined two groups with poor visual outcomes: 1) Those with sustained vision loss of >10 letters from baseline without recovery of visual acuity (VA) or 2) Those with VA<55 letters at 2 years. Respective controls were eyes that did not experience poor visual outcomes. METHODS Kaplan-Meier curves analyzed proportion of eyes that experienced poor outcomes. Cox proportional hazards models evaluated potential baseline predictors of poor outcomes. MAIN OUTCOME MEASURES The proportion of eyes that experienced poor visual outcomes within 2 years of treatment initiation and its baseline predictors. RESULTS The proportion of eyes with sustained VA>10 letter loss was 14% at 2 years while 16% of eyes had VA< 55 letters 2 years after starting intravitreal therapy. Initial treatment with intravitreal corticosteroid was independently associated with higher incidence of >10 letter loss was (Hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.60-6.44; P< 0.01). No improvement in VA 3 months after starting treatment was associated with >10 letter loss (HR, 6.81; 95% CI, 4.11-11.27; P <0.01) and VA<55 letters at 2 years (HR, 4.28; 95% CI, 2.66- 6.89; P <0.01). The other factors related to higher risk of VA<55 letters were older age (HR, 1.02 per year; 95% CI, 1-1.04; P = 0.04) and poor baseline VA (HR, 0.68 per 5 letters; 95% CI, 0.65- 0.72, P <0.001). CONCLUSION Fourteen percent of eyes managed with intravitreal therapy in routine clinical care experienced >10 letter loss and 16% had VA<55 letters 2 years after starting treatment for DME. Identification of the incidence and predictors of poor outcomes provides more accurate assessment of the potential benefit from intravitreal therapy.
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Affiliation(s)
- Janika Shah
- Save Sight Institute, The University of Sydney, NSW, Australia; Sydney Hospital and Sydney Eye Hospital, NSW, Australia.
| | - Vuong Nguyen
- Save Sight Institute, The University of Sydney, NSW, Australia
| | - Adrian Hunt
- Save Sight Institute, The University of Sydney, NSW, Australia
| | - Hemal Mehta
- Save Sight Institute, The University of Sydney, NSW, Australia; Department of Ophthalmology, Royal Free London NHS Foundation Trust, London, United Kingdom
| | - Barbara Romero-Nuñez
- Hospital Clínic de Barcelona Institut Clinic de Oftalmología (ICOF), Barcelona, Spain
| | | | - Francesco Viola
- Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Walid Bougamha
- Department of Ophthalmology, University Hospital Nice, University of Nice, France
| | | | - Daniel Barthelmes
- Save Sight Institute, The University of Sydney, NSW, Australia; Department of Ophthalmology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
| | - Mark C Gillies
- Save Sight Institute, The University of Sydney, NSW, Australia; Sydney Hospital and Sydney Eye Hospital, NSW, Australia
| | - Samantha Fraser-Bell
- Save Sight Institute, The University of Sydney, NSW, Australia; Sydney Hospital and Sydney Eye Hospital, NSW, Australia
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22
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Fuller SD, Hu J, Liu JC, Gibson E, Gregory M, Kuo J, Rajagopal R. Five-Year Cost-Effectiveness Modeling of Primary Care-Based, Nonmydriatic Automated Retinal Image Analysis Screening Among Low-Income Patients With Diabetes. J Diabetes Sci Technol 2022; 16:415-427. [PMID: 33124449 PMCID: PMC8861785 DOI: 10.1177/1932296820967011] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Artificial intelligence-based technology systems offer an alternative solution for diabetic retinopathy (DR) screening compared with standard, in-office dilated eye examinations. We performed a cost-effectiveness analysis of Automated Retinal Image Analysis System (ARIAS)-based DR screening in a primary care medicine clinic that serves a low-income patient population. METHODS A model-based, cost-effectiveness analysis of two DR screening systems was created utilizing data from a recent study comparing adherence rates to follow-up eye care among adults ages 18 or older with a clinical diagnosis of diabetes. In the study, the patients were prescreened with an ARIAS-based, nonmydriatic (undilated), point-of-care tool in the primary care setting and were compared with patients with diabetes who were referred for dilated retinal screening without prescreening, as is the current standard of care. Using a Markov model with microsimulation resulting in a total of 600 000 simulated patient experiences, we calculated the incremental cost-utility ratio (ICUR) of the two screening approaches, with regard to five-year cost-effectiveness of DR screening and treatment of vision-threatening DR. RESULTS At five years, ARIAS-based screening showed similar utility as the standard of care screening systems. However, ARIAS reduced costs by 23.3%, with an ICUR of $258 721.81 comparing the current practice to ARIAS. CONCLUSIONS Primary care-based ARIAS DR screening is cost-effective when compared with standard of care screening methods.
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Affiliation(s)
- Spencer D. Fuller
- John F. Hardesty Department of
Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint
Louis, MO, USA
- Spencer D. Fuller, MD, MPH, John F. Hardesty
Department of Ophthalmology and Visual Sciences, Washington University School of
Medicine, 660 South Euclid Avenue, Campus Box 8096, Saint Louis, MO 63110, USA.
| | - Jenny Hu
- Shiley Eye Institute, University of
California San Diego School of Medicine, La Jolla, CA, USA
| | - James C. Liu
- John F. Hardesty Department of
Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint
Louis, MO, USA
| | - Ella Gibson
- John F. Hardesty Department of
Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint
Louis, MO, USA
| | - Martin Gregory
- John T. Milliken Department of Medicine,
Division of Gastroenterology, Washington University School of Medicine, St. Louis,
MO, USA
| | - Jessica Kuo
- John F. Hardesty Department of
Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint
Louis, MO, USA
| | - Rithwick Rajagopal
- John F. Hardesty Department of
Ophthalmology and Visual Sciences, Washington University School of Medicine, Saint
Louis, MO, USA
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23
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Mahon N, Slater K, O'Brien J, Alvarez Y, Reynolds A, Kennedy B. Discovery and Development of the Quininib Series of Ocular Drugs. J Ocul Pharmacol Ther 2022; 38:33-42. [PMID: 35089801 DOI: 10.1089/jop.2021.0074] [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: 10/19/2022] Open
Abstract
The quininib series is a novel collection of small-molecule drugs with antiangiogenic, antivascular permeability, anti-inflammatory, and antiproliferative activity. Quininib was initially identified as a drug hit during a random chemical library screen for determinants of developmental ocular angiogenesis in zebrafish. To enhance drug efficacy, novel quininib analogs were designed by applying medicinal chemistry approaches. The resulting quininib drug series has efficacy in in vitro and ex vivo models of angiogenesis utilizing human cell lines and tissues. In vivo, quininib drugs reduce pathological angiogenesis and retinal vascular permeability in rodent models. Quininib acts as a cysteinyl leukotriene (CysLT) receptor antagonist, revealing new roles of these G-protein-coupled receptors in developmental angiogenesis of the eye and unexpectedly in uveal melanoma (UM). The quininib series highlighted the potential of CysLT receptors as therapeutic targets for retinal vasculopathies (e.g., neovascular age-related macular degeneration, diabetic retinopathy, and diabetic macular edema) and ocular cancers (e.g., UM).
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Affiliation(s)
- Niamh Mahon
- UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.,UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Kayleigh Slater
- UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.,UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Justine O'Brien
- UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.,UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Yolanda Alvarez
- UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.,UCD Conway Institute, University College Dublin, Dublin, Ireland
| | - Alison Reynolds
- UCD Conway Institute, University College Dublin, Dublin, Ireland.,UCD School of Veterinary Medicine, Veterinary Sciences Center, University College Dublin, Dublin, Ireland
| | - Breandán Kennedy
- UCD School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.,UCD Conway Institute, University College Dublin, Dublin, Ireland
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24
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Neurovascular Impairment and Therapeutic Strategies in Diabetic Retinopathy. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 19:ijerph19010439. [PMID: 35010703 PMCID: PMC8744686 DOI: 10.3390/ijerph19010439] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/25/2021] [Accepted: 12/30/2021] [Indexed: 12/15/2022]
Abstract
Diabetic retinopathy has recently been defined as a highly specific neurovascular complication of diabetes. The chronic progression of the impairment of the interdependence of neurovascular units (NVUs) is associated with the pathogenesis of diabetic retinopathy. The NVUs consist of neurons, glial cells, and vascular cells, and the interdependent relationships between these cells are disturbed under diabetic conditions. Clinicians should understand and update the current knowledge of the neurovascular impairments in diabetic retinopathy. Above all, neuronal cell death is an irreversible change, and it is directly related to vision loss in patients with diabetic retinopathy. Thus, neuroprotective and vasoprotective therapies for diabetic retinopathy must be established. Understanding the physiological and pathological interdependence of the NVUs is helpful in establishing neuroprotective and vasoprotective therapies for diabetic retinopathy. This review focuses on the pathogenesis of the neurovascular impairments and introduces possible neurovascular protective therapies for diabetic retinopathy.
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25
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Kanclerz P, Tuuminen R, Khoramnia R. Imaging Modalities Employed in Diabetic Retinopathy Screening: A Review and Meta-Analysis. Diagnostics (Basel) 2021; 11:1802. [PMID: 34679501 PMCID: PMC8535170 DOI: 10.3390/diagnostics11101802] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Revised: 09/22/2021] [Accepted: 09/24/2021] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Urbanization has caused dramatic changes in lifestyle, and these rapid transitions have led to an increased risk of noncommunicable diseases, such as type 2 diabetes. In terms of cost-effectiveness, screening for diabetic retinopathy is a critical aspect in diabetes management. The aim of this study was to review the imaging modalities employed for retinal examination in diabetic retinopathy screening. METHODS The PubMed and Web of Science databases were the main sources used to investigate the medical literature. An extensive search was performed to identify relevant articles concerning "imaging", "diabetic retinopathy" and "screening" up to 1 June 2021. Imaging techniques were divided into the following: (i) mydriatic fundus photography, (ii) non-mydriatic fundus photography, (iii) smartphone-based imaging, and (iv) ultrawide-field imaging. A meta-analysis was performed to analyze the performance and technical failure rate of each method. RESULTS The technical failure rates for mydriatic and non-mydriatic digital fundus photography, smartphone-based and ultrawide-field imaging were 3.4% (95% CI: 2.3-4.6%), 12.1% (95% CI: 5.4-18.7%), 5.3% (95% CI: 1.5-9.0%) and 2.2% (95% CI: 0.3-4.0%), respectively. The rate was significantly different between all analyzed techniques (p < 0.001), and the overall failure rate was 6.6% (4.9-8.3%; I2 = 97.2%). The publication bias factor for smartphone-based imaging was significantly higher than for mydriatic digital fundus photography and non-mydriatic digital fundus photography (b = -8.61, b = -2.59 and b = -7.03, respectively; p < 0.001). Ultrawide-field imaging studies were excluded from the final sensitivity/specificity analysis, as the total number of patients included was too small. CONCLUSIONS Regardless of the type of the device used, retinal photographs should be taken on eyes with dilated pupils, unless contraindicated, as this setting decreases the rate of ungradable images. Smartphone-based and ultrawide-field imaging may become potential alternative methods for optimized DR screening; however, there is not yet enough evidence for these techniques to displace mydriatic fundus photography.
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Affiliation(s)
- Piotr Kanclerz
- Hygeia Clinic, 80-286 Gdańsk, Poland
- Helsinki Retina Research Group, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland;
| | - Raimo Tuuminen
- Helsinki Retina Research Group, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland;
- Eye Centre, Kymenlaakso Central Hospital, 48100 Kotka, Finland
| | - Ramin Khoramnia
- The David J. Apple International Laboratory for Ocular Pathology, Department of Ophthalmology, University of Heidelberg, 69120 Heidelberg, Germany;
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26
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Rodríguez ML, Millán I, Ortega ÁL. Cellular targets in diabetic retinopathy therapy. World J Diabetes 2021; 12:1442-1462. [PMID: 34630899 PMCID: PMC8472497 DOI: 10.4239/wjd.v12.i9.1442] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/08/2021] [Accepted: 08/03/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the existence of treatment for diabetes, inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy. Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles. Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease. Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia. The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy. Therefore, in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that, potentially, can prevent the development and progression of the disease.
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Affiliation(s)
- María Lucía Rodríguez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
| | - Iván Millán
- Neonatal Research Group, Health Research Institute La Fe, Valencia 46026, Valencia, Spain
| | - Ángel Luis Ortega
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot 46100, Valencia, Spain
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27
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Abstract
PURPOSE OF REVIEW This review highlights indications and evidence on laser therapy in the management of diabetic retinopathy and diabetic macular edema. Particular focus is placed upon the benefits and limitations of conventional laser photocoagulation versus more modern laser photocoagulation techniques, as well as the role of laser photocoagulation in treatment of diabetic retinopathy and diabetic macular edema with the frequent utilization of pharmacologic, including anti-vascular endothelial growth factor (VEGF), therapy. RECENT FINDINGS Laser photocoagulation remains the gold-standard therapy for the effective, definitive treatment of PDR, and also is highly effective in the management of DME. However, numerous recent studies have demonstrated the clinical efficacy and improved functional and anatomic outcomes of combination therapy with pharmacologic treatment. Continuing innovations in laser technology and improved understanding of laser-retinal interactions and pathophysiology demonstrate that laser therapy will continue to play a critical role in the treatment of diabetic retinopathy and diabetic macular edema for many years to come.
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Affiliation(s)
- Lesley A. Everett
- Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105 USA
| | - Yannis M. Paulus
- Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105 USA
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Sędziak-Marcinek B, Wylęgała A, Chełmecka E, Wylęgała E, Teper S. How to Achieve Near-Normal Visual Acuity with Bevacizumab in Diabetic Macular Edema Patients. J Clin Med 2021; 10:3572. [PMID: 34441868 PMCID: PMC8397100 DOI: 10.3390/jcm10163572] [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: 07/21/2021] [Revised: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 11/29/2022] Open
Abstract
Patients suffering from diabetic retinopathy (DR) and diabetic macular edema (DME) are inherently interested in achieving normal or near-normal visual acuity. The study aimed to investigate factors influencing the visual acuity achieved by DME patients after bevacizumab (IVB) treatment. 98 patients (98 eyes) diagnosed with DR and DME underwent IVB treatment (9 injections/12 months). Patients were diagnosed and monitored using swept-source optical coherence tomography (SS-OCT), ultra-wide-field fluorescein angiography (UWFFA) and Early Treatment Diabetic Retinopathy Study (ETDRS) chart testing. We assessed macular central subfield thickness (CST), non-proliferative diabetic retinopathy (NPDR) indicators and best-corrected visual acuity (BCVA). After the treatment, patients were divided into BCVA≤75 and BCVA>75 groups. The IVB therapy increased the number of ETDRS letters read by about 9 and 8 in the BCVA≤75 and the BCVA>75 group, respectively. Before and after treatment, the BCVA>75 group had lower CST than the BCVA≤75 group. The treatment reduced macular CST by 177 μm in the BCVA≤75 group and only by 93 μm in the BCVA>75 group. Total non-perfusion area (NPA) decreased in both BCVA score groups after IVB therapy. Normal or near-normal vision can be achieved with IVB treatment, provided it starts when visual acuity is not significantly reduced yet. The ophthalmic screening of DR patients should also target those with relatively high visual acuity.
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Affiliation(s)
- Bogumiła Sędziak-Marcinek
- Chair and Department of Ophthalmology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Panewnicka 65 Street, 40-760 Katowice, Poland; (E.W.); (S.T.)
| | - Adam Wylęgała
- Health Promotion and Obesity Management Unit, Department of Pathophysiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Medyków 65, 40-728 Katowice, Poland;
| | - Elżbieta Chełmecka
- Department of Statistics, Department of Instrumental Analysis, Faculty of Pharmaceutical Sciences, Medical University of Silesia, Ostrogórska 30 Street, 41-200 Sosnowiec, Poland;
| | - Edward Wylęgała
- Chair and Department of Ophthalmology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Panewnicka 65 Street, 40-760 Katowice, Poland; (E.W.); (S.T.)
| | - Sławomir Teper
- Chair and Department of Ophthalmology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Panewnicka 65 Street, 40-760 Katowice, Poland; (E.W.); (S.T.)
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McKay AJ, Gunn LH, Nugawela MD, Sathish T, Majeed A, P. Vamos E, Molina G, Sivaprasad S. Associations between attainment of incentivized primary care indicators and incident sight-threatening diabetic retinopathy in England: A population-based historical cohort study. Diabetes Obes Metab 2021; 23:1322-1330. [PMID: 33565708 PMCID: PMC8350793 DOI: 10.1111/dom.14344] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 01/27/2021] [Accepted: 02/04/2021] [Indexed: 12/16/2022]
Abstract
AIM To examine the impact of attainment of primary care diabetes clinical indicators on progression to sight-threatening diabetic retinopathy (STDR) among those with mild non-proliferative diabetic retinopathy (NPDR). MATERIALS AND METHODS An historical cohort study of 18,978 adults (43.63% female) diagnosed with type 2 diabetes before 1 April 2010 and mild NPDR before 1 April 2011 was conducted. The data were obtained from the UK Clinical Practice Research Datalink during 2010-2017, provided by 330 primary care practices in England. Exposures included attainment of the Quality and Outcomes Framework HbA1c (≤59 mmol/mol [≤7.5%]), blood pressure (≤140/80 mmHg) and cholesterol (≤5 mmol/L) indicators in the financial year 2010-2011, as well as the number of National Diabetes Audit processes completed in 2010-2011. The outcome was time to incident STDR. Nearest neighbour propensity score matching was undertaken, and univariable and multivariable Cox proportional hazards models were then fitted using the matched samples. Concordance statistics were calculated for each model. RESULTS A total of 1037 (5.5%) STDR diagnoses were observed over a mean follow-up of 3.6 (SD 2.0) years. HbA1c, blood pressure and cholesterol indicator attainment were associated with lower rates of STDR (adjusted hazard ratios [95% CI] 0.64 [0.55-0.74; p < .001], 0.83 [0.72-0.94; p = .005] and 0.80 [0.66-0.96; p = .015], respectively). CONCLUSIONS Our findings provide support for meeting appropriate indicators for the management of type 2 diabetes in primary care to bring a range of benefits, including improved health outcomes-such as a reduction in the risk of STDR-for people with type 2 diabetes.
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Affiliation(s)
- Ailsa J. McKay
- Department of Primary Care and Public HealthImperial College LondonLondonUK
| | - Laura H. Gunn
- Department of Primary Care and Public HealthImperial College LondonLondonUK
- Department of Public Health Sciences and School of Data ScienceUniversity of North Carolina (UNC) at CharlotteCharlotteNorth CarolinaUSA
| | - Manjula D. Nugawela
- Institute of OphthalmologyUCL and NIHR Moorfields Biomedical Research CentreLondonUK
| | - Thirunavukkarasu Sathish
- Department of Primary Care and Public HealthImperial College LondonLondonUK
- Centre for Population Health Sciences (CePHaS), Lee Kong Chian School of MedicineNanyang Technological UniversitySingaporeSingapore
- Population Health Research Institute (PHRI)McMaster UniversityHamiltonOntarioCanada
| | - Azeem Majeed
- Department of Primary Care and Public HealthImperial College LondonLondonUK
| | - Eszter P. Vamos
- Department of Primary Care and Public HealthImperial College LondonLondonUK
| | | | - Sobha Sivaprasad
- Institute of OphthalmologyUCL and NIHR Moorfields Biomedical Research CentreLondonUK
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Ratra D. Commentary: Switching of anti-vascular endothelial growth factor agents in refractory diabetic macular edema. Indian J Ophthalmol 2021; 69:367-368. [PMID: 33463594 PMCID: PMC7933902 DOI: 10.4103/ijo.ijo_2611_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Dhanashree Ratra
- Department of Vitreoretinal Diseases, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
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31
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Wei Y, Mi F, Cui Y, Li Y, Wu X, Guo H. Delay in seeking medical care after the onset of symptoms in patients with sight-threatening diabetic retinopathy. J Int Med Res 2021; 49:3000605211013224. [PMID: 34013762 PMCID: PMC8150428 DOI: 10.1177/03000605211013224] [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] [Indexed: 11/15/2022] Open
Abstract
Objective To investigate the reasons for delays in seeking medical care in patients with diabetic retinopathy and associated risk factors. Methods We retrospectively reviewed data for patients with sight-threatening diabetic retinopathy (STDR) who attended a hospital in China. Various forms of STDR were identified, including severe non-proliferative DR, clinically significant macular edema and proliferative DR. Demographic, clinical and socioeconomic information was collected and the associated risk factors were evaluated. Results Of the 127 patients with STDR, 89.2% sought medical care within 1 month of developing symptoms. Those who sought treatment ≥6 months after symptoms developed had significantly lower income and less knowledge of diabetic complications than those who attended earlier. Multivariate logistic regression analysis showed that no or infrequent routine examination for diabetic complications were associated with long delays in seeking medical care (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.05–9.19; and OR 2.91, 95% CI 1.04–8.40, respectively). Conclusions Most patients with STDR sought medical care within 1 month of symptoms developing, but no or infrequent routine examination for diabetic complications was associated with long delays. These results stress the importance of educational programs regarding diabetic complications to encourage timely medical care and prevent poor outcomes.
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Affiliation(s)
- Yan Wei
- Department of Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People's Republic of China
| | - Fenghua Mi
- Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People's Republic of China
| | - Yan Cui
- Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People's Republic of China
| | - Ying Li
- Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People's Republic of China
| | - Xinyi Wu
- Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People's Republic of China
| | - Hui Guo
- Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, People's Republic of China
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Caridi B, Doncheva D, Sivaprasad S, Turowski P. Galectins in the Pathogenesis of Common Retinal Disease. Front Pharmacol 2021; 12:687495. [PMID: 34079467 PMCID: PMC8165321 DOI: 10.3389/fphar.2021.687495] [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: 03/29/2021] [Accepted: 04/29/2021] [Indexed: 12/15/2022] Open
Abstract
Diseases of the retina are major causes of visual impairment and blindness in developed countries and, due to an ageing population, their prevalence is continually rising. The lack of effective therapies and the limitations of those currently in use highlight the importance of continued research into the pathogenesis of these diseases. Vascular endothelial growth factor (VEGF) plays a major role in driving vascular dysfunction in retinal disease and has therefore become a key therapeutic target. Recent evidence also points to a potentially similarly important role of galectins, a family of β-galactoside-binding proteins. Indeed, they have been implicated in regulating fundamental processes, including vascular hyperpermeability, angiogenesis, neuroinflammation, and oxidative stress, all of which also play a prominent role in retinopathies. Here, we review direct evidence for pathological roles of galectins in retinal disease. In addition, we extrapolate potential roles of galectins in the retina from evidence in cancer, immune and neuro-biology. We conclude that there is value in increasing understanding of galectin function in retinal biology, in particular in the context of the retinal vasculature and microglia. With greater insight, recent clinical developments of galectin-targeting drugs could potentially also be of benefit to the clinical management of many blinding diseases.
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Affiliation(s)
- Bruna Caridi
- UCL Institute of Ophthalmology, University College London, London, United Kingdom
| | - Dilyana Doncheva
- UCL Institute of Ophthalmology, University College London, London, United Kingdom
| | - Sobha Sivaprasad
- UCL Institute of Ophthalmology, University College London, London, United Kingdom.,NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
| | - Patric Turowski
- UCL Institute of Ophthalmology, University College London, London, United Kingdom
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DETECTION OF CLINICALLY UNSUSPECTED RETINAL NEOVASCULARIZATION WITH WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina 2021; 40:891-897. [PMID: 30845022 DOI: 10.1097/iae.0000000000002487] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
PURPOSE To evaluate wide-field optical coherence tomography angiography (OCTA) for detection of clinically unsuspected neovascularization (NV) in diabetic retinopathy (DR). METHODS This prospective observational single-center study included adult patients with a clinical diagnosis of nonproliferative DR. Participants underwent a clinical examination, standard 7-field color photography, and OCTA with commercial and prototype swept-source devices. The wide-field OCTA was achieved by montaging five 6 × 10-mm scans from a prototype device into a 25 × 10-mm image and three 6 × 6-mm scans from a commercial device into a 15 × 6-mm image. A masked grader determined the retinopathy severity from color photographs. Two trained readers examined conventional and wide-field OCTA images for the presence of NV. RESULTS Of 27 participants, photographic grading found 13 mild, 7 moderate, and 7 severe nonproliferative DR. Conventional 6 × 6-mm OCTA detected NV in 2 eyes (7%) and none with 3 × 3-mm scans. Both prototype and commercial wide-field OCTA detected NV in two additional eyes. The mean area of NV was 0.38 mm (range 0.17-0.54 mm). All eyes with OCTA-detected NV were photographically graded as severe nonproliferative DR. CONCLUSION Wide-field OCTA can detect small NV not seen on clinical examination or color photographs and may improve the clinical evaluation of DR.
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Cheng Y, Yuan L, Zhao MW, Qian T. Real-world outcomes of two-year Conbercept therapy for diabetic macular edema. Int J Ophthalmol 2021; 14:416-422. [PMID: 33747819 DOI: 10.18240/ijo.2021.03.14] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 08/26/2020] [Indexed: 12/26/2022] Open
Abstract
AIM To evaluate the two-year outcomes of patients treated for diabetic macular edema (DME) with intravitreal Conbercept (IVC). METHODS The clinical data of 30 DME patients (36 eyes) were retrospectively reviewed. The patients were treated with IVC for 3mo. Additional IVC was given at subsequent monthly visits, if needed (3+PRN). The patients were followed up for 24mo. RESULTS The best-corrected visual acuity (BCVA) at 24mo significantly increased (66.7±15.3 letters) in comparison with the baseline (54.4±15.4 letters, P<0.0001). The mean improvement in BCVA was 11.0±2.9 letters. At 24mo, 44.1% of the eyes surveyed gained ≥15 letters, 52.9% of the eyes gained ≥10 letters, and 70.6% of the eyes gained ≥5 letters. No vision loss was noted in 96.8% of the eyes, and 5.9% of the eyes lost ≥5 letters, but ≤10 letters. The central retinal thickness (CRT) at 24mo was significantly reduced (277.1±122.9 µm) in comparison with the baseline (510.9±186.1 µm, P<0.0001). At 24mo, 43.3% of the patients had a CRT ≤250 µm. The mean number of injections over 24mo was 10.6±2.0. No severe eye or systemic adverse events related to either the drug or injection were noted. CONCLUSION IVC is safe and effective for the treatment of DME.
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Affiliation(s)
- Yong Cheng
- Department of Ophthalmology, People's Hospital, Peking University, Beijing 100044, China.,Eye Diseases and Optometry Institute, College of Optometry, Peking University Health Science Center, Beijing 100044, China.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China
| | - Li Yuan
- Department of Ophthalmology, People's Hospital, Peking University, Beijing 100044, China.,Eye Diseases and Optometry Institute, College of Optometry, Peking University Health Science Center, Beijing 100044, China.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China
| | - Ming-Wei Zhao
- Department of Ophthalmology, People's Hospital, Peking University, Beijing 100044, China.,Eye Diseases and Optometry Institute, College of Optometry, Peking University Health Science Center, Beijing 100044, China.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China
| | - Tong Qian
- Department of Ophthalmology, People's Hospital, Peking University, Beijing 100044, China.,Eye Diseases and Optometry Institute, College of Optometry, Peking University Health Science Center, Beijing 100044, China.,Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing 100044, China
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36
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Mahdjoubi A, Bousnina Y, Bendib FS, Bensmaine F, Idlefqih W, Chahed S, Ghezzaz A. Large-cube 30° × 25° optical coherence tomography in diabetic macular edema. Int J Retina Vitreous 2021; 7:19. [PMID: 33676574 PMCID: PMC7937234 DOI: 10.1186/s40942-021-00289-6] [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: 09/28/2020] [Accepted: 02/19/2021] [Indexed: 11/12/2022] Open
Abstract
Background To evaluate the contribution of large-cube 30° × 25° optical coherence tomography (OCT) in the characterization of diabetic macular edema (DME) by assessing its extent and the presence of additional retinal edemas and to evaluate the factors that influenced their occurrence. Methods This retrospective study enrolled patients with diabetes who presented with retinal edema detected by horizontal large-cube 30° × 25° (8.7 × 7.3 mm) OCT. Two individualized areas were selected from the thickness map: the area within the 6-mm Early Treatment of Diabetic Retinopathy Study (ETDRS) grid, and that outside the ETDRS grid. Retinal edemas located within the ETDRS grid were designated as “main DME” and those located outside the ETDRS grid were designated as “peripheral retinal edemas.” For each area, OCT features were assessed while the extent of the main DME and the presence of peripheral retinal oedema were analysed in the area outside the ETDRS grid. Finally, part of included eyes was followed by the same protocol, of which a part benefited from intravitreal injections. Results Peripheral events were detected outside the ETDRS area in 279 eyes (74.4%) of the 375 eyes of the 218 patients included in this study: an extension of the main DME outside ETDRS grid in 177 eyes (47.2%) and/or the presence of peripheral retinal edemas in 207 eyes (55.2%). The analysis of associations between main DME and peripheral retinal edemas patterns did not find an association for retinal cyst localization (P = 0.42) while a week association was found fort cyst size (Cramer’s V = 0.188, p = 0.028). Nevertheless, a moderate association was found for the presence of microaneurysms (Cramer’s V = 0.247, p < 0.001) and strong association for hard exudates (Cramer’s V = 0.386, p < 0.001), The binary logistic regression analysis retained the following influencing factors of the occurrence of peripheral events: advanced DR stage (Odds ratio OR = 2.19, p = 0.03), diffuse DME (OR = 7.76, p < 0.001) and its location in outer fields (OR = 7.09, p = 0.006). Likewise, the extension of the main DME outside the ETDRS area in was influenced by the same factors in addition to CMT (OR = 0.98, p = 0.004) while the presence of peripheral retinal edema was influenced by the same factors except the outer location of the Main DME. Finally, from the 94 eyes treated by intravitreal injections, extension of the main DME outside the ETDRS grid was detected in 54 eyes (56.44%) at baseline visit and still remained detectable in 37 eyes (39.36%) after treatment initiation. Conclusions Large-cube 30° × 25° OCT allowed for more precise assessment of DME extension and better detection of retinal thickening mainly in the advanced stages of diabetic retinopathy with significant DME whether at the baseline visit or during follow-up. The combination of this protocol with a wider ETDRS grid would enhance DME detection and topography.
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Affiliation(s)
- Amir Mahdjoubi
- Department of Ophthalmology, Centre Hospitalier Victor Dupouy, 69 Rue du Lieutenant-Colonel Prudhon, 95100, Argenteuil, France. .,Department of Ophthalmology, Hôpital Simone Veil, Eaubonne, France.
| | - Youcef Bousnina
- Department of Ophthalmology, Hôpital Max Forestier, Nanterre, France
| | - Fatma-Samia Bendib
- Department of Endocrinology and Diabetology, Centre Hospitalier Victor Dupouy, Argenteuil, France
| | - Faiza Bensmaine
- Department of Endocrinology and Diabetology, Centre Hospitalier Victor Dupouy, Argenteuil, France
| | - Wafa Idlefqih
- Department of Ophthalmology, Centre Hospitalier Victor Dupouy, 69 Rue du Lieutenant-Colonel Prudhon, 95100, Argenteuil, France
| | - Sadri Chahed
- Department of Ophthalmology, Centre Hospitalier Victor Dupouy, 69 Rue du Lieutenant-Colonel Prudhon, 95100, Argenteuil, France.,Department of Ophthalmology, Hôpital Simone Veil, Eaubonne, France
| | - Amina Ghezzaz
- Department of Ophthalmology, Centre Hospitalier Victor Dupouy, 69 Rue du Lieutenant-Colonel Prudhon, 95100, Argenteuil, France.,Department of Ophthalmology, Hôpital Simone Veil, Eaubonne, France
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Comparison of the efficacy of aflibercept and ranibizumab after a 3-month loading dose in patients with diabetic macular edema. JOURNAL OF SURGERY AND MEDICINE 2021. [DOI: 10.28982/josam.850861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Raman R, Ramasamy K, Rajalakshmi R, Sivaprasad S, Natarajan S. Diabetic retinopathy screening guidelines in India: All India Ophthalmological Society diabetic retinopathy task force and Vitreoretinal Society of India Consensus Statement. Indian J Ophthalmol 2021; 69:678-688. [PMID: 33269742 PMCID: PMC7942107 DOI: 10.4103/ijo.ijo_667_20] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/13/2020] [Accepted: 07/14/2020] [Indexed: 12/15/2022] Open
Abstract
Diabetic retinopathy (DR) is an emerging preventable cause of blindness in India. All India Ophthalmology Society (AIOS) and Vitreo-Retinal Society of India (VRSI) have initiated several measures to improve of DR screening in India. This article is a consensus statement of the AIOS DR task force and VRSI on practical guidelines of DR screening in India. Although there are regional variations in the prevalence of diabetes in India at present, all the States in India should screen their population for diabetes and its complications. The purpose of DR screening is to identify people with sight-threatening DR (STDR) so that they are treated promptly to prevent blindness. This statement provides strategies for the identification of people with diabetes for DR screening, recommends screening intervals in people with diabetes with and without DR, and describes screening models that are feasible in India. The logistics of DR screening emphasizes the need for dynamic referral pathways with feedback mechanisms. It provides the clinical standards required for DR screening and treatment of STDR and addresses the governance and quality assurance (QA) standards for DR screening in Indian settings. Other aspects incorporate education and training, recommendations on Information technology (IT) infrastructure, potential use of artificial intelligence for grading, data capture, and requirements for maintenance of a DR registry. Finally, the recommendations include public awareness and the need to work with diabetologists to control the risk factors so as to have a long-term impact on prevention of diabetes blindness in India.
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Affiliation(s)
- Rajiv Raman
- Shri Bhagwan Mahavir Vitreoretinal Services, Chennai, Tamil Nadu, India
| | - Kim Ramasamy
- Aravind Eye Hospital, Madurai, Tamil Nadu, India
| | - Ramachandran Rajalakshmi
- Dr. Mohan's Diabetes Specialities Centre and Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India
| | | | - S Natarajan
- Aditya Jyot Eye Hospital Pvt. Ltd., Mumbai, Maharashtra, India
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Pitcher JD, Moshfeghi AA, Lucas G, Boucher N, Moini H, Saroj N. Evaluation of Patients Receiving Intravitreal Antivascular Endothelial Growth Factor for Diabetic Macular Edema in Clinical Practice in the United States. JOURNAL OF VITREORETINAL DISEASES 2021; 5:108-113. [PMID: 37009083 PMCID: PMC9979048 DOI: 10.1177/2474126420953067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Purpose We assessed the effect of treatment frequency with intravitreal antivascular endothelial growth factor (anti-VEGF) agents on visual acuity (VA) in diabetic macular edema (DME). Methods This retrospective analysis assessed electronic medical records of eyes newly diagnosed with DME and treated with an anti-VEGF agent at US clinics using the Vestrum Health (Naperville, Illinois) treatment and outcomes database. Eyes were divided into 2 injection frequency subcohorts (≤ 6 vs > 6 injections/y); treatment frequency and change in mean VA (Early Treatment Diabetic Retinopathy Study letters) were evaluated. Results Among 155 240 eyes assessed, 3028 met inclusion criteria for analysis in year 1 and 1292 in year 2. During year 1 of treatment, 57% (n = 1725) received > 6 injections; most continued to receive the same injection frequency during year 2. Mean VA gain from baseline at year 1 was lower in the ≤ 6 than in the > 6 injections/year subcohort (3.7 vs 8.0 letters, respectively; P < .001). Mean VA change from the end of year 1 to year 2 for eyes receiving ≤ 6 injections in year 1 generally remained unchanged, irrespective of year 2 dosing frequency. In eyes that received > 6 injections in year 1, mean VA loss was significantly greater for eyes receiving less-frequent dosing in year 2 than in those maintained on > 6 injections. Conclusions More than 50% of eyes with DME in routine clinical practice that completed at least 1 year of follow-up received > 6 injections of an anti-VEGF agent during the first year, resulting in better VA gains than eyes treated less frequently.
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Affiliation(s)
- John D. Pitcher
- Eye Associates of New Mexico, Albuquerque, NM, USA
- Department of Ophthalmology, University of New Mexico, Albuquerque,
NM, USA
| | - Andrew A. Moshfeghi
- Roski Eye Institute, University of
Southern California Department of Ophthalmology, Keck School of Medicine, Los Angeles, CA, USA
| | | | | | - Hadi Moini
- Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA
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Roberts PK, Vogl WD, Gerendas BS, Glassman AR, Bogunovic H, Jampol LM, Schmidt-Erfurth UM. Quantification of Fluid Resolution and Visual Acuity Gain in Patients With Diabetic Macular Edema Using Deep Learning: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Ophthalmol 2021; 138:945-953. [PMID: 32722799 DOI: 10.1001/jamaophthalmol.2020.2457] [Citation(s) in RCA: 50] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Importance Large amounts of optical coherence tomographic (OCT) data of diabetic macular edema (DME) are acquired, but many morphologic features have yet to be identified and quantified. Objective To examine the volumetric change of intraretinal fluid (IRF) and subretinal fluid (SRF) in DME during anti-vascular endothelial growth factor treatment using deep learning algorithms. Design, Setting, and Participants This post hoc analysis of a randomized clinical trial, the Diabetic Retinopathy Clinical Research Network (protocol T), assessed 6945 spectral-domain OCT volume scans of 570 eyes from 570 study participants with DME. The original trial was performed from August 21, 2012, to October 18, 2018. This analysis was performed from December 7, 2017, to January 15, 2020. Interventions Participants were treated according to a predefined, standardized protocol with aflibercept, ranibizumab, or bevacizumab with or without deferred laser. Main Outcomes and Measures The association of treatment with IRF and SRF volumes and best-corrected visual acuity (BCVA) during 12 months using deep learning algorithms. Results Among the 570 study participants (302 [53%] male; 369 [65%] white; mean [SD] age, 43.4 [12.6] years), the mean fluid volumes in the central 3 mm were 448.6 nL (95% CI, 412.3-485.0 nL) of IRF and 36.9 nL (95% CI, 27.0-46.7 nL) of SRF at baseline and 161.2 nL (95% CI, 135.1-187.4 nL) of IRF and 4.4 nL (95% CI, 1.7-7.1 nL) of SRF at 12 months. The presence of SRF at baseline was associated with a worse baseline BCVA Early Treatment Diabetic Retinopathy Study (ETDRS) score of 63.2 (95% CI, 60.2-66.1) (approximate Snellen equivalent of 20/63 [95% CI, 20/50-20/63]) in eyes with SRF vs 66.9 (95% CI, 65.7-68.1) (approximate Snellen equivalent, 20/50 [95% CI, 20/40-20/50]) without SRF (P < .001) and a greater gain in ETDRS score (0.5; 95% CI, 0.3-0.8) every 4 weeks during follow-up in eyes with SRF at baseline vs 0.4 (95% CI, 0.3-0.5) in eyes without SRF at baseline (P = .02) when adjusted for baseline BCVA. Aflibercept was associated with greater reduction of IRF volume compared with bevacizumab after the first injection (difference, 79.8 nL; 95% CI, 5.3-162.5 nL; P < .001) and every 4 weeks thereafter (difference, 10.4 nL; 95% CI, 0.7-20.0 nL; P = .004). Ranibizumab was associated with a greater reduction of IRF after the first injection compared with bevacizumab (difference, 75.2 nL; 95% CI, 1.4-154.7 nL; P < .001). Conclusions and Relevance Automated segmentation of fluid in DME revealed that the presence of SRF was associated with lower baseline BCVA but with good response to anti-vascular endothelial growth factor therapy. These automated spectral-domain OCT analyses may be used clinically to assess anatomical change during therapy. Trial Registration ClinicalTrials.gov Identifier: NCT01627249.
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Affiliation(s)
- Philipp K Roberts
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Wolf-Dieter Vogl
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Bianca S Gerendas
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | | | - Hrvoje Bogunovic
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria
| | - Lee M Jampol
- Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
| | - Ursula M Schmidt-Erfurth
- Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.,Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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Intravitreal Therapy for Diabetic Macular Edema: An Update. J Ophthalmol 2021; 2021:6654168. [PMID: 33688431 PMCID: PMC7925023 DOI: 10.1155/2021/6654168] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 02/11/2021] [Accepted: 02/16/2021] [Indexed: 02/07/2023] Open
Abstract
Diabetic macular edema (DME) represents a prevalent and disabling eye condition. Despite that DME represents a sight-threatening condition, it is also among the most accessible to treatment. Many different treatment options including photocoagulation, intravitreal medical treatment (either vascular endothelial growth factor inhibitors or corticosteroids therapies), and surgical removal are currently available. Although laser has been considered as the gold standard for many years, over the past several years vascular endothelial growth factor inhibitors (anti-VEGFs) have become first-line therapy. However, many patients do not adequately respond to them. With the development of sustained-release corticosteroid devices, steroids have gained a presence in the management of the DME. We review and update the role of anti-VEGF and intravitreal sustained-release corticosteroid management of DME. According to the currently available scientific evidence, the choice of one anti-VEGF over another critically depends on the baseline best-corrected visual acuity (BCVA). While aflibercept may be the drug of choice in low baseline BCVA, the three anti-VEGFs (bevacizumab, ranibizumab, and aflibercept) provided similar functional outcomes when the baseline BCVA was higher. DEX implants are a valuable option for treating DME, although they are usually seen as a second choice, particularly in those eyes that have an insufficient response to anti-VEGF. The new evidence suggested that, in eyes that did not adequately respond to anti-VEGF, switching to a DEX implant at the time to 3 monthly anti-VEGF injections provided better functional outcomes.
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Mahapatra SK, Kumari S. Long-term results of a single injection of intravitreal dexamethasone as initial therapy in diabetic macular edema. Indian J Ophthalmol 2021; 68:490-493. [PMID: 32057010 PMCID: PMC7043155 DOI: 10.4103/ijo.ijo_620_19] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Purpose: To evaluate the long-term safety and efficacy of the intravitreal dexamethasone implant in the treatment of diabetic macular edema (DME) as initial therapy. Methods: A hospital-based prospective, non-comparative case study of recently detected DME patients was conducted between July 2016 and December 2017, in which30 eyes of 30 patients were studied. Presenting vision, age, gender, duration of diabetes, general and ocular examination, intraocular pressure, indirect ophthalmoscopy, fundus fluorescein angiography, optical coherence tomography (OCT), and blood sugar levels were noted. Patients with increased central macular thickness (CMT) received an intravitreal dexamethasone implant as initial therapy. All were followed up at 1 week, 1 month, 3 months, 6 months, and 1 year, and the findings were recorded and analyzed using SPSS software. Results: 30 eyes of 30 patients were studied which included 22 males and 8 females. The mean age of presentation was 58.7 ± 4.45 years. The mean decrease in CMT following intravitreal dexamethasone was 269.27 ± 112.002, 253.5 ± 108.294, and 286.73 ± 143.395 μm at the end of 3, 6, and 12 months, respectively, and the mean improvement in visual acuity (VA) was 2.27 ± 1.70 lines at 3 months, 2.27 ± 1.83 lines at 6 months, and 1.17 ± 2.00 lines at 12 months. Out of 30 cases, 4 had persistent DME and 6 had recurrence of DME at completion of 1 year of follow-up. Conclusion: Intravitreal dexamethasone as initial therapy in the treatment of DME is both safe and efficacious in the reduction of CMT and improvement of vision and can be considered as primary therapy for DME.
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Affiliation(s)
- Santosh Kumar Mahapatra
- Chief Medical Officer and Vitreoretinal Surgeon, JPM Rotary Club of Cuttack Eye Hospital and Research Institute, Cuttack, Odisha, India
| | - Swati Kumari
- Ophthalmology Resident, JPM Rotary Club of Cuttack Eye Hospital and Research Institute, Cuttack, Odisha, India
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AlQahtani AS, Hazzazi MA, Waheeb SA, Semidey VA, Semidey VA, Elgendy HK, Alkhars WI, Abouammoh MA, Al-Dhibi H. Saudi Arabia Guidelines for diabetic macular edema: A consensus of the Saudi Retina Group. Saudi Med J 2021; 42:131-145. [PMID: 33563731 PMCID: PMC7989293 DOI: 10.15537/smj.2021.2.25623] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 12/08/2020] [Indexed: 11/25/2022] Open
Abstract
Diabetes mellitus (DM) and its complications are major public health burdens in Saudi Arabia. The prevalence of diabetic retinopathy (DR) is 19.7% and the prevalence of diabetic macular edema (DME) is 5.7% in Saudi Arabia. Diabetic macular edema is a vision-threatening complication of DR and a major cause of vision loss worldwide. Ocular treatments include retinal laser photocoagulation, anti-vascular endothelial growth factor (anti-VEGF) agents, intravitreal corticosteroids, and vitreoretinal surgery when necessary. The present consensus was developed as a part of the Saudi Retina Group's efforts to generate Saudi guidelines and consensus for the management of DME, including recommendations for its diagnosis, treatment, and best practice. The experts' panel stipulates that the treatment algorithm should be categorized according to the presence of central macula involvement. In patients with no central macular involvement, laser photocoagulation is recommended as the first-line option. Patients with central macular involvement and no recent history of cardiovascular (CVS) or cerebrovascular disorders can be offered anti-VEGF agents as the first-line option. In the case of non-responders (defined as an improvement of <20% in optical coherence tomography or a gain of fewer than 5 letters in vision), switching to another anti-VEGF agent or steroids should be considered after 3 injections. Within the class of steroids, dexamethasone implants are recommended as the first choice. In patients with a recent history of CVS events, the use of anti-VEGF agents is not recommended, regardless of their lens status. The experts' panel recommends that a future study be conducted to provide a cut-off point for early switching to steroid implants in pseudo-phakic eyes.
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Affiliation(s)
- Abdullah S. AlQahtani
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Mohammad A. Hazzazi
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Saad A. Waheeb
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Valmore A. Semidey
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Valmore A. Semidey
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Hussein K. Elgendy
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Wajeeha I. Alkhars
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Marwan A. Abouammoh
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
| | - Hassan Al-Dhibi
- From the Department of Surgery (AlQahtani), Division of Ophthalmology, National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Ophthalmology (Waheeb), King Fisal Specialist Hospital and Research Center; from the Department of Ophthalmology (Elgendy), Retina Unit, Magrabi Eye and Ear Hospital, Jeddah; from the Department of Surgery (Hazzazi), Division of Ophthalmology, Riyadh National Guard Hospital, and from King Saud bin Abdulaziz University for Health Sciences; from the Department of Vitreoretinal (Semidey, Al-Dhibi), King Khalid Eye Specialist Hospital; from the Department of Ophthalmology (Abouammoh), College of Medicine, King Saud University, Riyadh; and from the Department of Retina and Uveitis (Alkhars), Dhahran Eye Specialist Hospital, Dhahran, Kingdom of Saudi Arabia.
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Giannakaki-Zimmermann H, Behrndt A, Hoffmann L, Guichard MM, Türksever C, Prünte C, Hatz K. Predictors for 2-Year Functional and Morphological Outcomes of a Treat-and-Extend Regimen with Ranibizumab in Patients with Diabetic Macular Edema. Ophthalmic Res 2021; 64:465-475. [PMID: 33498045 DOI: 10.1159/000514721] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 01/14/2021] [Indexed: 01/12/2023]
Abstract
PURPOSE The purpose of the study was to investigate longer term functional and morphological outcomes and their predictors in diabetic macular edema (DME) following a treat-and-extend regimen (TER) without loading dose under ranibizumab. METHODS Patient data were reviewed and analyzed retrospectively over a period of 24 months after initiation of TER. Best-corrected visual acuity (BCVA), treatment frequency, and quantitative and qualitative spectral-domain optical coherence tomography parameters were assessed. RESULTS 118 eyes of 87 patients were included. A mean of 9.74 ± 2.13 injections in the first and 7.63 ± 2.29 in the second year were applied. There were significant gains of BCVA and reductions in central retinal thickness from baseline to 12 and 24 months (all p < 0.001). Percentage of eyes with an intact inner segment/outer segment (IS/OS) junction increased from 15.3% at baseline to 42.1% at 24 months (p < 0.001). An intact IS/OS junction at baseline increased the probability of having a dry retina after 12 months by 79.3% (p = 0.017) and after 24 months by 88.1% (p = 0.040). Less IS/OS disruption at baseline predicted longer maximum recurrence-free treatment intervals at 2 years (r = -0.345, p < 0.001) and better BCVA at 1 year (r = -0.347, p < 0.001). Baseline bigger intraretinal cysts were associated with more IS/OS disruption at 24 months (r = 0.305, p = 0.007). Younger age and lower BCVA at baseline were predictive for a higher BCVA gain at 24 months (p = 0.046, p < 0.001). CONCLUSION Ranibizumab applied in a TER without loading dose in DME significantly improves visual acuity and retinal anatomical structure throughout 2 years. The evaluated predictors might help guide routine clinical treatment in DME.
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Affiliation(s)
| | - Alexandra Behrndt
- Vista Klinik, Binningen, Switzerland.,Faculty of Medicine, University of Basel, Basel, Switzerland
| | | | | | | | - Christian Prünte
- Faculty of Medicine, University of Basel, Basel, Switzerland.,Department of Ophthalmology, University Hospital Basel, Basel, Switzerland.,Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland
| | - Katja Hatz
- Vista Klinik, Binningen, Switzerland, .,Faculty of Medicine, University of Basel, Basel, Switzerland,
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Hayashi Y, Tatsumi T, Oshitari T, Kaiho T, Takatsuna Y, Arai M, Baba T, Yamamoto S. Comparisons of One to Three Monthly Injections of Aflibercept for Diabetic Macular Edema by Practical Protocol. J Diabetes Res 2021; 2021:1374891. [PMID: 33628832 PMCID: PMC7896872 DOI: 10.1155/2021/1374891] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Revised: 01/20/2021] [Accepted: 02/01/2021] [Indexed: 02/08/2023] Open
Abstract
The purpose of this study was to compare the efficacies of one initial intravitreal injection of aflibercept followed by a pro re nata (PRN; 1+PRN) regimen to those of three consecutive monthly injections followed by the PRN (3+PRN) regimen for diabetic macular edema (DME) with practical protocols. The medical records of 95 eyes of 71 cases that were diagnosed with DME and had received intravitreal aflibercept (IVA) injections were reviewed. Fifty-seven eyes had received IVA with the 1+PRN regimen, and 38 eyes had received IVA with the 3+PRN regimen. The best-corrected visual acuity (BCVA) and the central macular thickness (CMT) were measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean number of injections of the 1+PRN group was 2.9 ± 1.7, which was significantly fewer than that of the 3+PRN group at 4.6 ± 1.4 (P < 0.001). The change of the mean BCVA before and after the IVA at 12 months of the 3+PRN group was -0.14 ± 0.17 logMAR units which was significantly better than that of the 1+PRN group of -0.045 ± 0.25 logMAR units (P = 0.02). The change of the CMT before and after the IVA at 6 months of the 3+PRN group was -141.3 ± 152.4 μm which was significantly more than that of the 1+PRN group at -86.1 ± 117.8 μm (P = 0.013). Although the mean number of injections was more than that in the 1+PRN regimen, the 3+PRN regimen had better visual outcomes at 12 months. In a practical protocol, we recommend the 3+PRN regimen for patients with DME (IRB#3541).
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Affiliation(s)
- Yuko Hayashi
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Tomoaki Tatsumi
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Toshiyuki Oshitari
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
- Department of Ophthalmology, International University of Health and Welfare, Narita, Japan
| | - Tomomi Kaiho
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Yoko Takatsuna
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Miyuki Arai
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Takayuki Baba
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
| | - Shuichi Yamamoto
- Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan
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Vergmann AS, Grauslund J. Changes of visual fields in treatment of proliferative diabetic retinopathy: a systematic review. Acta Ophthalmol 2020; 98:763-773. [PMID: 32421255 DOI: 10.1111/aos.14474] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Accepted: 04/24/2020] [Indexed: 01/20/2023]
Abstract
The aim of this systematic review was to compare certain side-effects [visual fields (VF), dark adaptation, colour vision (CV) and contrast sensitivity (CS)] of conventional panretinal photocoagulation (PRP) with those of other treatments in proliferative diabetic retinopathy (PDR). A systematic literature search was conducted on 30 November 2018 in PubMed and Embase. The search comprised the keywords 'proliferative diabetic retinopathy', 'laser', 'treatment' and 'anti-vegf'. We included prospective studies and randomized controlled trials that investigated certain side-effects (VF, dark adaptation, CV, CS) in treatment of PDR (primary outcome). In total, 1867 articles were screened, and 10 studies were included (2176 eyes of 2086 patients examined in the VF studies and 1360 eyes of 1360 patients examined in the CV and CS studies). Visual fields (VF) were investigated in 10 studies, CV in one study and CS in one study. Treatment modalities included conventional PRP, other modalities of laser treatment and vascular endothelial growth factor (VEGF) inhibitors. Four studies demonstrated a worse VF impact of PRP than VEGF inhibitors. Seven studies reported of an overall worsening in VF after laser with no differences between different laser approaches. No differences were found in CV or CS. Overall, we found a trend, confirmed in four large studies, towards VEGF inhibitors causing less harm to VF compared to conventional PRP. Whilst VF was generally depressed after laser, it did not differ between different treatment approaches. Furthermore, it was not possible to make certain conclusions of CV or CS, with only one study in each field.
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Affiliation(s)
- Anna Stage Vergmann
- Department of Ophthalmology Odense University Hospital Odense Denmark
- Research Unit of Ophthalmology Department of Clinical Research Faculty of Health Science University of Southern Denmark Odense Denmark
| | - Jakob Grauslund
- Department of Ophthalmology Odense University Hospital Odense Denmark
- Research Unit of Ophthalmology Department of Clinical Research Faculty of Health Science University of Southern Denmark Odense Denmark
- Steno Diabetes Center Odense Odense Denmark
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COMPARATIVE RISK OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION WITH BEVACIZUMAB, AFLIBERCEPT, AND RANIBIZUMAB. Retina 2020; 39:2004-2011. [PMID: 30312260 DOI: 10.1097/iae.0000000000002351] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To determine whether sterile preloading of anti-vascular endothelial growth factor agents reduces the risk of postintravitreal injection endophthalmitis. METHODS This is a retrospective cohort study using medical claims data from a large, national US insurer. Cohorts were created using intravitreal injections of anti-vascular endothelial growth factor injections from 2005 to 2016. For inclusion, patients had to have at least 6 months of data before the injection and were excluded for any previous diagnosis of endophthalmitis, multiple injected drugs on the day of injection, or intraocular surgery within 15 days of the injection or between an injection and a diagnosis of endophthalmitis. The primary outcome was the odds of endophthalmitis after an intravitreal injection. RESULTS A total of 706,725 bevacizumab, 210,849 ranibizumab, and 177,731 aflibercept injections were given to 130,327 patients. Multivariate analysis showed that ranibizumab and aflibercept together had an increased odds of endophthalmitis (odds ratio = 1.29, 95% confidence interval: 1.04-1.59, P = 0.02) compared with bevacizumab. Individually, ranibizumab (odds ratio = 1.25, 95% confidence interval: 0.97-1.61, P = 0.08) and aflibercept (odds ratio = 1.34, 95% confidence interval: 0.99-1.81, P = 0.06) each had higher odds of endophthalmitis, but neither result met significance. Also, when compared with male patients, female patients had a higher odds of getting endophthalmitis (odds ratio: 1.30, 95% confidence interval: 1.05-1.61, P = 0.02). CONCLUSION The odds of endophthalmitis with aflibercept and ranibizumab combined were higher compared with the sterilely preloaded bevacizumab, arguing for a safety advantage of sterile preloading of anti-vascular endothelial growth factor injections.
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Kaldırım H, Savur F, Kırgız A, Atalay K. Comparison of Anatomical and Functional Outcomes of Intravitreal Dexamethasone Implant between Phakic and Pseudophakic Eyes with Diabetic Macular Edema. KOREAN JOURNAL OF OPHTHALMOLOGY 2020; 34:383-391. [PMID: 33099560 PMCID: PMC7597610 DOI: 10.3341/kjo.2019.0142] [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: 12/21/2019] [Accepted: 07/23/2020] [Indexed: 12/01/2022] Open
Abstract
Purpose To compare the effectiveness of dexamethasone (DEX) intravitreal implants for the treatment of diabetic macular edema between phakic and pseudophakic eyes after a follow-up. Methods A total of 79 eyes in 79 patients with diabetic macular edema who were insufficiently responsive to the previous anti-vascular endothelial growth factor treatment and applied intravitreal DEX implant were included in this retrospective study. The patients were divided into two groups according to their type of lenses: pseudophakic (group 1) and phakic (group 2). Best-corrected visual acuity, intraocular pressure (IOP), retinal nerve fiber layer thickness, and central macular thickness changes in the two groups were compared. Results Group 1 comprised 42 eyes in 42 patients with a mean age of 64.02 ± 3.79 years, while group 2 comprised 37 eyes in 37 patients with a mean age of 64.19 ± 5.08 years. In both groups, best-corrected visual acuity improved significantly with a significant decrease in central macular thickness (p < 0.001). In both lens types, the IOP values decreased significantly on the first day but subsequently increased significantly compared to baseline from one week to six months. Increases in IOP values were significantly higher in group 1 at the first week, 1st month, and 6th month compared with group 2. During follow-up, the inferior quadrant retinal nerve fiber layer showed a significant decrease in both groups. Conclusions In both phakic and pseudophakic eyes, intravitreal DEX implantation is an effective treatment method with low-risk complications. In our study, the pseudophakic group experienced a significantly earlier increase in IOP and at higher levels than did the phakic group. In light of these data, we suggest that in patients with pseudophakic eyes, follow-ups for IOP should be stricter and started earlier after intravitreal DEX treatment.
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Affiliation(s)
- Havva Kaldırım
- Department of Ophthalmology, Bagcilar Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Fatma Savur
- Department of Ophthalmology, Bagcilar Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Ahmet Kırgız
- Department of Ophthalmology, Beyoglu Eye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Kürşat Atalay
- Department of Ophthalmology, Bagcilar Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
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An X, Jin D, Duan L, Zhao S, Zhou R, Lian F, Tong X. Direct and indirect therapeutic effect of traditional Chinese medicine as an add-on for non-proliferative diabetic retinopathy: a systematic review and meta-analysis. Chin Med 2020; 15:99. [PMID: 32963587 PMCID: PMC7499984 DOI: 10.1186/s13020-020-00380-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 09/11/2020] [Indexed: 11/28/2022] Open
Abstract
Background Diabetic retinopathy (DR) is the leading cause of blindness in many countries. The current treatment for non-proliferative DR (NPDR) using Western medicine (WM) alone is insufficient. At present, the combination of NPDR treatment with traditional Chinese medicine (TCM) and WM is universally applied. We aimed to evaluate the effectiveness and safety of TCM as an add-on for NPDR using a systematic review and meta-analysis. Method Data from randomized controlled trials (RCTs) of TCM for NPDR treatment along with WM before July 6, 2019, were collected from the China National Knowledge Infrastructure, Wanfang Database, China Biomedical Database, Pubmed, Embase, and Cochrane Library. Relevant data were extracted by two reviewers. I2 statistics was adopted to appraise heterogeneity. If I2 < 50% the fixed-effects model was employed, otherwise a random-effect model was employed. (PROSPERO: CRD42019134947) Result Eighteen RCTs (1522 patients) were included based on the inclusion and exclusion criteria. The results showed that compared with WM alone, TCM (including Compound Xueshuantong Capsule, Qiming Granule, and others) combined with WM for NPDR could improve the overall effiicacy [n = 1686, RR 1.24 (1.18,1.30), P < 0.00001, I2 = 0%], and reduce the influence of risk factors related to NPDR, such as glycated hemoglobin level [n = 360, MD − 0.85 (− 1.28, − 0.41), P = 0.0001, I2 = 72%], triglyceride (P < 0.00001), and total cholesterol (P = 0.0008). Moreover, no serious adverse events were reported. Conclusion Compared with WM alone, TCM + WM could significantly improve NPDR and also reduce the correlation levels of risk factors, such as hyperglycemia, dyslipidemia. However, the small sample included in the study might lead to a publication bias, and therefore, our results should be treated with caution.
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Affiliation(s)
- Xuedong An
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053 China.,China Academy of Chinese Medical Sciences, Beijing, 100700 China
| | - De Jin
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053 China.,China Academy of Chinese Medical Sciences, Beijing, 100700 China
| | - LiYun Duan
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053 China.,China Academy of Chinese Medical Sciences, Beijing, 100700 China
| | - Shenghui Zhao
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053 China.,Beijing University of Chinese Medicine, Beijing, 100029 China
| | - Rongrong Zhou
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053 China.,China Academy of Chinese Medical Sciences, Beijing, 100700 China
| | - Fengmei Lian
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053 China
| | - Xiaolin Tong
- Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053 China
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Automatic detection of non-perfusion areas in diabetic macular edema from fundus fluorescein angiography for decision making using deep learning. Sci Rep 2020; 10:15138. [PMID: 32934283 PMCID: PMC7492239 DOI: 10.1038/s41598-020-71622-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 07/30/2020] [Indexed: 02/05/2023] Open
Abstract
Vision loss caused by diabetic macular edema (DME) can be prevented by early detection and laser photocoagulation. As there is no comprehensive detection technique to recognize NPA, we proposed an automatic detection method of NPA on fundus fluorescein angiography (FFA) in DME. The study included 3,014 FFA images of 221 patients with DME. We use 3 convolutional neural networks (CNNs), including DenseNet, ResNet50, and VGG16, to identify non-perfusion regions (NP), microaneurysms, and leakages in FFA images. The NPA was segmented using attention U-net. To validate its performance, we applied our detection algorithm on 249 FFA images in which the NPA areas were manually delineated by 3 ophthalmologists. For DR lesion classification, area under the curve is 0.8855 for NP regions, 0.9782 for microaneurysms, and 0.9765 for leakage classifier. The average precision of NP region overlap ratio is 0.643. NP regions of DME in FFA images are identified based a new automated deep learning algorithm. This study is an in-depth study from computer-aided diagnosis to treatment, and will be the theoretical basis for the application of intelligent guided laser.
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