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Yamada H, Imai H, Sotani Y, Matsumiya W, Miki A, Kusuhara S, Nakamura M. Three-year outcomes of cystotomy and fibrinogen clot removal for diabetic macular edema with subfoveal cystoid macular edema. Sci Rep 2025; 15:16019. [PMID: 40341676 PMCID: PMC12062336 DOI: 10.1038/s41598-025-01197-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 05/05/2025] [Indexed: 05/10/2025] Open
Abstract
Several new surgical techniques for managing refractory diabetic macular edema (DME) have demonstrated favorable short-term outcomes. However, no studies have reported the long-term outcomes of these treatments. This study aimed to evaluate the long-term outcomes of cystotomy for DME retrospectively. Twenty-seven patients (31 eyes; 16 male, 11 female) who underwent cystotomy for DME between January 2015 and April 2019, with a follow-up period of 3 years were included. Statistical analyses involved variables including age, sex, best-corrected visual acuity (BCVA), central macular thickness (CMT), number of treatments (anti-vascular endothelial growth factor, sub-Tenon injection of triamcinolone acetonide, direct photocoagulation for microaneurysms, vitrectomy with internal limiting membrane peeling), number of clinic visits, and DME recurrence. The mean age was 67.2 ± 9.3 years. BCVA (logMAR) and CMT(µm) significantly improved from preoperatively to 3 years postoperatively (P < 0.001). Total treatments significantly decreased from the year before surgery to the third year after surgery (P < 0.001). The mean number of clinic visits significantly decreased from the year before surgery to the third year after surgery (P < 0.001). Fibrinogen clot removal was performed in 14 eyes. and DME recurrence occurred in 12 eyes. Cystotomy may be a viable treatment option for DME.
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Affiliation(s)
- Hiroko Yamada
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Hisanori Imai
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
- Department of Ophthalmology, Kansai Medical University, 2-5-1, Shin-machi, Hirakata, 573-1191, Japan.
| | - Yasuyuki Sotani
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Wataru Matsumiya
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Akiko Miki
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Sentaro Kusuhara
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
| | - Makoto Nakamura
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan
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Ishikawa K, Nakao S, Mori K, Fukuda Y, Kiyohara K, Yasaka Y, Yuge K, Notomi S, Sonoda KH. Fluid Aspiration From Intraretinal Cysts for Refractory Diabetic Macular Edema. Retina 2025; 45:785-789. [PMID: 40056087 DOI: 10.1097/iae.0000000000004198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
PURPOSE To report the surgical outcome of fluid aspiration in intraretinal cysts as a novel treatment approach for the refractory cystoid macular edema associated with diabetic retinopathy. METHODS This retrospective consecutive case series examined eight patients with refractory cystoid macular edema who underwent intraretinal cyst fluid aspiration using a 38-gauge subretinal infusion needle during pars plana vitrectomy. This study reviewed changes in central retinal thickness, best-corrected visual acuity, and central sensitivity among patients followed up for 12 months postsurgery. RESULTS Central retinal thickness on optical coherence tomography (μm) significantly improved at 12 months after surgery (308 ± 99) compared with before surgery (480 ± 141) ( P < 0.005). During the follow-up period, cystoid macular edema relapsed in one eye. The best-corrected visual acuity (logarithm of the minimal angle of resolution) at 12 months postsurgery (0.23 ± 0.32, Snellen equivalent: 20/50) was significantly better than the preoperative best-corrected visual acuity (0.39 ± 0.29, Snellen equivalent: 20/63) ( P < 0.01). The mean deviation value of central sensitivity did not significantly change between preoperative (-2.5 ± 2.1) and postoperative (-2.2 ± 2.2) assessments ( P = 0.07). CONCLUSION Fluid aspiration in intraretinal cysts may be a treatment option for refractory cystoid macular edema in eyes with diabetes.
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Affiliation(s)
- Keijiro Ishikawa
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
| | - Shintaro Nakao
- Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan
| | - Kenichiro Mori
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
| | - Yosuke Fukuda
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
| | - Kohei Kiyohara
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
| | - Yuta Yasaka
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
| | - Kodai Yuge
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
| | - Shoji Notomi
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
| | - Koh-Hei Sonoda
- Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ; and
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Zhu Q, Pan X, Du Z, Ying J, Hu Y, Yi Q, Fu X. From Monotherapy to Combination Strategies: Redefining Treatment Approaches for Multiple-Cause Macular Edema. Clin Ophthalmol 2025; 19:887-897. [PMID: 40099235 PMCID: PMC11912219 DOI: 10.2147/opth.s513141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 03/07/2025] [Indexed: 03/19/2025] Open
Abstract
Macular edema (ME) is a leading cause of visual impairment in various retinal disorders. Current treatment modalities, including anti-vascular endothelial growth factor (anti-VEGF) agents and corticosteroids, often require repeated applications, increasing both medical and economic burdens. ME is driven by chronic inflammation and VEGF overexpression, causing fluid accumulation in the macula. Recent studies have highlighted the role of various cytokines in ME pathogenesis, necessitating a comprehensive approach to treatment. While monotherapies have shown efficacy, they are associated with limitations such as the need for frequent injections and potential side effects. Combination therapies, including anti-VEGF drugs with macular laser photocoagulation, triamcinolone acetonide, or dexamethasone intravitreal implant (Ozurdex), have emerged as promising strategies. This review analyzes the outcomes of various combination approaches in different types of ME, including diabetic macular edema (DME), retinal vein occlusion-associated ME (RVO-ME), and uveitic macular edema (UME). The potential benefits of combining anti-VEGF and anti-inflammatory treatments are discussed, along with the need for personalized treatment regimens. Future research directions are outlined, emphasizing the importance of large-scale, long-term studies to evaluate the sustained efficacy and safety of combination therapies. The integration of advanced imaging techniques, biomarker analysis, and innovative therapeutic approaches is expected to shape the future landscape of ME management, moving towards more targeted and effective combination therapies.
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Affiliation(s)
- Qianwei Zhu
- Department of Ophthalmology, Yuyao Maternity and Child Health Care Hospital (Yuyao Second People’s Hospital), Ningbo, People’s Republic of China
| | - Xuchong Pan
- Department of Ophthalmology, Yuyao Maternity and Child Health Care Hospital (Yuyao Second People’s Hospital), Ningbo, People’s Republic of China
| | - Zhenni Du
- Department of Ophthalmology, Yuyao Maternity and Child Health Care Hospital (Yuyao Second People’s Hospital), Ningbo, People’s Republic of China
| | - Jianing Ying
- Department of Ophthalmology, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, People’s Republic of China
| | - Yiran Hu
- Department of Ophthalmology, Yuyao Maternity and Child Health Care Hospital (Yuyao Second People’s Hospital), Ningbo, People’s Republic of China
| | - Quanyong Yi
- Department of Ophthalmology, Ningbo Eye Hospital, Wenzhou Medical University, Ningbo, People’s Republic of China
| | - Xiangxiang Fu
- Department of Ophthalmology, Yuyao Maternity and Child Health Care Hospital (Yuyao Second People’s Hospital), Ningbo, People’s Republic of China
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Sotani Y, Imai H, Yamada H, Miki A, Kusuhara S, Nakamura M. High Intraocular Concentration of Fibrinogen Regulates Retinal Function Via the ICAM-1 Pathway. Invest Ophthalmol Vis Sci 2024; 65:34. [PMID: 39546292 DOI: 10.1167/iovs.65.13.34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2024] Open
Abstract
Purpose Diabetic retinopathy (DR) is a significant complication of diabetes mellitus that can lead to progressive visual impairment. This study aimed to elucidate the role of fibrinogen, a protein whose serum and intraocular concentrations are elevated in patients with diabetes and DR, in the pathogenesis of DR. Methods The changes in the protein levels of the neuronal marker tubulin-β3 (TUBB3) and retinal response induced by the intravitreal injections of 1× phosphate-buffered saline, 40 mg/mL of fibrinogen, and 40 mg/mL of fibrinogen in combination with anti-intracellular adhesion molecule-1 (ICAM-1) antibody in normal mice were observed using immunofluorescence, western blotting, and electroretinography. Results High concentrations of fibrinogen led to a decrease in the expression of TUBB3 in immunofluorescence and western blotting. The amplitudes of the positive scotopic threshold response and b-wave were notably reduced after the injection of fibrinogen, indicating potential damage to the retinal ganglion cells. The co-administration of anti-ICAM-1 antibody effectively mitigated these fibrinogen-induced changes, indicating that fibrinogen-induced damage is mediated via the ICAM-1 pathway. Conclusions The present study underscores the significance of elevated intraocular fibrinogen levels as a pathogenic factor in DR. Involvement of the fibrinogen/ICAM-1 pathway presents new avenues for therapeutic intervention, especially in patients with treatment-resistant conditions.
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Affiliation(s)
- Yasuyuki Sotani
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hisanori Imai
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
- Department of Ophthalmology, Kansai Medical University, Hirakata, Japan
| | - Hiroko Yamada
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Akiko Miki
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Sentaro Kusuhara
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Makoto Nakamura
- Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan
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Combination of vitrectomy and intentional macular detachment is associated with a faster edematous regression than vitrectomy alone in the treatment of refractory diabetic macular edema. Retina 2022; 42:1859-1866. [DOI: 10.1097/iae.0000000000003536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Imai H, Tetsumoto A, Yamada H, Hayashida M, Otsuka K, Miki A, Kusuhara S, Nakamura M. LONG-TERM EFFECT OF CYSTOTOMY WITH OR WITHOUT THE FIBRINOGEN CLOT REMOVAL FOR REFRACTORY CYSTOID MACULAR EDEMA SECONDARY TO DIABETIC RETINOPATHY. Retina 2021; 41:844-851. [PMID: 32732609 DOI: 10.1097/iae.0000000000002921] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To show the long-term effect of cystotomy with or without fibrinogen clot removal for refractory cystoid macular edema secondary to diabetic retinopathy. METHODS Retrospective analyses of the medical records of 30 eyes of 30 patients with refractory cystoid macular edema secondary to diabetic retinopathy who had followed up for 12 months after the surgery were performed. RESULTS There were 15 men and 15 women. The mean ± SD age was 68.4 ± 7.9 years. The best-corrected visual acuity (logarithm of the minimal angle of resolution) at 12 months after the surgery (0.33 ± 0.25, Snellen equivalent, 20/42) was statistically better than the preoperative best-corrected visual acuity (0.45 ± 0.33, Snellen equivalent, 20/56) (P < 0.01). The central sensitivity on microperimetry (dB) was not statistically changed between preoperatively (24.0 ± 4.9) and 12 months after the surgery (24.1 ± 4.0) (P = 0.75). The central retinal thickness on optical coherence tomography (μm) at 12 months after the surgery (300.3 ± 99.0) was statistically improved compared with the preoperative central retinal thickness (565.6 ± 198.7) (P < 0.01). During the follow-up period, cystoid macular edema relapsed in seven of 30 eyes. The preoperative cystoid cavity reflectivity on optical coherence tomography in patients with fibrinogen clot removal (n = 16) was significantly higher than that in patients without fibrinogen clot removal (n = 14) (P < 0.04). CONCLUSION The cystotomy with or without fibrinogen clot removal may be a promising treatment option for refractory cystoid macular edema secondary to diabetic retinopathy.
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Affiliation(s)
- Hisanori Imai
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
| | - Akira Tetsumoto
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
| | - Hiroko Yamada
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
| | - Mayuka Hayashida
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
| | - Keiko Otsuka
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
- Kobe Kaisei Hospital, Nada-ku, Kobe, Japan
| | - Akiko Miki
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
| | - Sentaro Kusuhara
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
| | - Makoto Nakamura
- Department of Surgery-related, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan ; and
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EFFECTIVENESS OF EN BLOC REMOVAL OF FIBRINOGEN-RICH COMPONENT OF CYSTOID LESION FOR THE TREATMENT OF CYSTOID MACULAR EDEMA. Retina 2021; 40:154-159. [PMID: 30334924 DOI: 10.1097/iae.0000000000002359] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE To introduce the methodology and outcomes of en bloc removal of the component of cystoid lesion during pars plana vitrectomy as a novel approach for the treatment of cystoid macular edema and show evidence that the component is an aggregation of fibrinogen by mass spectrometry analysis. METHODS The surgical en bloc extraction of the component of cystoid lesion was performed for cystoid macular edemas secondary to diabetic retinopathy and retinal vein occlusion. Perioperative change of best-corrected decimal visual acuity, and the central retinal thickness and the continuity of subfoveal ellipsoid zone and external limiting membrane on optical coherence tomography were evaluated. Mass spectrometry was performed for the identification of protein constituting the component. RESULTS Six eyes from six patients were included in the study. In all cases, central retinal thickness was improved after the surgery and remained stable during the follow-up period. Best-corrected decimal visual acuity and the continuity of ellipsoid zone and external limiting membrane were kept in all cases during the follow-up period. The mass spectrometry analysis disclosed that the component was composed of fibrinogen. CONCLUSION The en block removal of the component of cystoid lesion combined with pars plana vitrectomy may be a promising option for treatment of cystoid macular edema. The component of cystoid lesion is presumably a fibrinogen aggregate.
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Evaluation of Vitrectomy with Planned Foveal Detachment as Surgical Treatment for Refractory Diabetic Macular Edema with or without Vitreomacular Interface Abnormality. J Ophthalmol 2018; 2018:9246384. [PMID: 29854429 PMCID: PMC5964411 DOI: 10.1155/2018/9246384] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 03/12/2018] [Accepted: 03/18/2018] [Indexed: 01/01/2023] Open
Abstract
Purpose To evaluate the therapeutic efficacy of subretinal BSS injections done during vitrectomy for refractory diabetic macular edema (DME) resistant to other modes of treatment including previous vitrectomy. Materials and Methods A prospective, interventional noncomparative case series in which cases had refractory DME with a central macular thickness (CMT) ≥ 300 μm, despite previous anti-VEGF therapy (ranibizumab or bevacizumab with shifting to aflibercept). Some cases even received intravitreal triamcinolone acetonide injection, before attempting this solution. The study included group 1, surgically naïve eyes, and group 2, cases with persistent edema despite a previous vitrectomy (7 eyes (25%)). The cases were also divided into group a, eyes with normal vitreomacular interface, and group b, with abnormal vitreomacular attachment (VMA) (6 (21.4%)). The 1ry endpoint for this study was the change in CMT after 9–12 months from surgery. The 2ry endpoints were change in BCVA, recurrence of DME, and surgical complications. Results The study included 28 eyes, 6 (21.4%) of which suffered from edema recurrence. The mean recorded CMT was 496 ± 88.7 μm and 274.1 ± 31.6 μm preoperatively and postoperatively, respectively. In all eyes, the preoperative mean BCVA in decimal form was 0.2 ± 0.11, which improved significantly to 0.45 ± 0.2. In the end, the CMT of groups 1 and 2 measured 239 μm and 170.8 μm, respectively (p = 0.019). The preoperative BCVA in groups 1 and 2 was 0.16 ± 0.07 and 0.37 ± 0.14, respectively, which improved to a mean of 0.34 ± 0.09 and 0.7 ± 0.16 postoperatively, respectively (p = 0.185). Conclusion Vitrectomy with a planned foveal detachment technique was shown to be a promising solution for refractory DME cases with rapid edema resolution. CMT was shown to improve more in eyes where conventional vitrectomy was not attempted. Moreover, cases with VMA resistant to pharmacotherapy was shown to respond well to this technique. The study has been registered in Contact ClinicalTrials.gov PRS Identifier: NCT03345056.
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Ghassemi F, Bazvand F, Roohipoor R, Yaseri M, Hassanpoor N, Zarei M. Outcomes of vitrectomy, membranectomy and internal limiting membrane peeling in patients with refractory diabetic macular edema and non-tractional epiretinal membrane. J Curr Ophthalmol 2016; 28:199-205. [PMID: 27830204 PMCID: PMC5093778 DOI: 10.1016/j.joco.2016.08.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2016] [Accepted: 08/02/2016] [Indexed: 01/08/2023] Open
Abstract
Purpose To evaluate the efficacy of vitrectomy, membranectomy, and internal limiting membrane (ILM) peeling on macular thickness and best corrected visual acuity (BCVA) in patients with refractory diffuse diabetic macular edema (DME) and non-tractional epiretinal membrane (NT-ERM). Methods This prospective interventional case series included eyes with refractory DME (central subfield macular thickness [CSMT] > 300 μm) after at least two intravitreal injections of bevacizumab (IVB) and one intravitreal injection of triamcinolone (IVT), and accompanying NT-ERM. Complete ophthalmic examination, baseline spectral domain optical coherence tomography (SD-OCT), and fluorescein angiography (FA) were performed prior to 23 gauge pars plana vitrectomy with membranectomy and internal limiting membrane (ILM) peeling. Postoperative evaluation was done with clinical examination and SD-OCT. Linear mix model analysis was used to study postoperative results. Results Twelve eyes from 11 patients (5 males) with a mean age of 60.33 ± 9.01 (range 46–73 years) were included. The mean follow-up time was 13.5 ± 4.48 months (range 4–20 months). A significant reduction in CSMT was found (from 559 ± 89 μm to 354 ± 76 μm; P = 0.001), with a non-significant BCVA change (from 0.84 ± 0.32 logMAR to 0.72 ± 0.2 logMAR; P = 0.967). There was no significant correlation between CSMT and BCVA (partial correlation = −0.115, P = 0.445) and also between estimated mean CSMT change per month and estimated mean BCVA change per month (r = 0.337, P = 0.283). Conclusion In this series, our results did not show that vitrectomy, membranectomy, and ILM peeling result in significant improvement of BCVA in eyes with refractory DME and non-tractional ERM in spite of central macular thickness reduction.
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Affiliation(s)
- Fariba Ghassemi
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Iran
| | - Fatemeh Bazvand
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Iran
| | - Ramak Roohipoor
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Iran
| | - Mehdi Yaseri
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Iran
| | - Narges Hassanpoor
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Iran
| | - Mohammad Zarei
- Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Iran
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Trinh HM, Joseph M, Cholkar K, Pal D, Mitra AK. Novel strategies for the treatment of diabetic macular edema. World J Pharmacol 2016; 5:1-14. [DOI: 10.5497/wjp.v5.i1.1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Revised: 12/19/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
Macular edema such as diabetic macular edema (DME) and diabetic retinopathy are devastating back-of-the-eye retinal diseases leading to loss of vision. This area is receiving considerable medical attention. Posterior ocular diseases are challenging to treat due to complex ocular physiology and barrier properties. Major ocular barriers are static (corneal epithelium, corneal stroma, and blood-aqueous barrier) and dynamic barriers (blood-retinal barrier, conjunctival blood flow, lymph flow, and tear drainage). Moreover, metabolic barriers impede posterior ocular drug delivery and treatment. To overcome such barriers and treat back-of-the-eye diseases, several strategies have been recently developed which include vitreal drainage, laser photocoagulation and treatment with biologics and/or small molecule drugs. In this article, we have provided an overview of several emerging novel strategies including nanotechnology based drug delivery approach for posterior ocular drug delivery and treatment with an emphasis on DME.
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McHugh D, Gupta B, Saeed M. Intravitreal gas injection for the treatment of diabetic macular edema. Clin Ophthalmol 2011; 5:1543-8. [PMID: 22125399 PMCID: PMC3218162 DOI: 10.2147/opth.s25348] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE This study investigates the efficacy of an intravitreal gas injection in inducing a posterior vitreous detachment (PVD) in patients with clinically significant diabetic macular edema refractory to laser therapy. METHODS A local ethics committee-approved technique of an intravitreal injection of pure perfluoropropane gas (C(3)F(8)) was performed for all participants. After a period of prone positioning, the patients underwent regular and detailed clinical review. MAIN OUTCOME MEASURES The induction of a PVD, change in macular thickness, change in visual acuity. RESULTS A PVD was induced in all five eyes with subsequent signs of reduction in macular thickness and resolution of exudates. Mean visual improvement was 11 ETDRS (Early Treatment Diabetic Retinopathy Study) letters (range 4-21). Apart from a transient vitreous hemorrhage in one eye, there were no significant treatment-related complications. CONCLUSION The induction of a PVD by pneumatic retinopexy appears to have a significant influence on diabetic macular edema in eyes which have not successfully responded to macular laser therapy. A randomized clinical trial is justified on the basis of the initial promising data.
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Affiliation(s)
- Dominic McHugh
- King's College Hospital, Denmark Hill, London, England, UK
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Role of Peoxisome Proliferator Activator Receptor gamma on Blood Retinal Barrier Breakdown. PPAR Res 2011; 2008:679237. [PMID: 18309374 PMCID: PMC2248243 DOI: 10.1155/2008/679237] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2007] [Accepted: 07/10/2007] [Indexed: 11/17/2022] Open
Abstract
The retinal vessels have two barriers: the retinal pigment epithelium and the retinal vascular endothelium. Each barrier exhibits increased permeability under various pathological conditions. This condition is referred to as blood retinal barrier (BRB) breakdown. Clinically, the most frequently encountered condition causing BRB breakdown is diabetic retinopathy. In recent studies, inflammation has been linked to BRB breakdown and vascular leakage in diabetic retinopathy. Biological support for the role of inflammation in early diabetes is the adhesion of leukocytes to the retinal vasculature (leukostasis) observed in diabetic retinopathy. PPARγ is a member of a ligand-activated nuclear receptor superfamily and plays a critical role in a variety of biological processes, including adipogenesis, glucose metabolism, angiogenesis, and inflammation. There is now strong experimental evidence to support the theory that PPARγ inhibits diabetes-induced retinal leukostasis and leakage, playing an important role in the pathogenesis of diabetic retinopathy. Therapeutic targeting of PPARγ may be beneficial to diabetic retinopathy.
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Abstract
Diabetic macular edema is a major cause of visual impairment. The pathogenesis of macular edema appears to be multifactorial. Laser photocoagulation is the standard of care for macular edema. However, there are cases that are not responsive to laser therapy. Several therapeutic options have been proposed for the treatment of this condition. In this review we discuss several factors and mechanisms implicated in the etiology of macular edema (vasoactive factors, biochemical pathways, anatomical abnormalities). It seems that combined pharmacologic and surgical therapy may be the best approach for the management of macular edema in diabetic patients.
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Affiliation(s)
- Neelakshi Bhagat
- The Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark, New Jersey, USA
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Giblin FJ, Quiram PA, Leverenz VR, Baker RM, Dang L, Trese MT. Enzyme-induced posterior vitreous detachment in the rat produces increased lens nuclear pO2 levels. Exp Eye Res 2009; 88:286-92. [PMID: 18835558 PMCID: PMC2694186 DOI: 10.1016/j.exer.2008.09.003] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2008] [Revised: 08/26/2008] [Accepted: 09/04/2008] [Indexed: 11/28/2022]
Abstract
It has been proposed that disruption of normal vitreous humor may permit O(2) to travel more easily from the retina to the center of the lens where it may cause nuclear cataract (Barbazetto, I.A., Liang, J., Chang, S., Zheng, L., Spector, A., Dillon, J.P., 2004. Oxygen tension in the rabbit lens and vitreous before and after vitrectomy. Exp. Eye Res. 78, 917-924; Harocopos, G.J., Shui, Y.B., McKinnon, M., Holekamp, N.M., Gordon, M.O., Beebe, D.C., 2004. Importance of vitreous liquefaction in age-related cataract. Invest. Ophthalmol. Vis. Sci. 45, 77-85). In the present study, we injected enzymes intravitreally into guinea pigs (which possess an avascular retina) and rats (which possess a vascular retina) to produce either vitreous humor liquefaction plus a posterior vitreous detachment (PVD) (with use of microplasmin) or vitreous humor liquefaction only (with use of hyaluronidase), and 1-2 weeks later measured lens nuclear pO(2) levels in vivo using a platinum-based fluorophore O(2) sensor (Oxford-Optronix, Ltd.). Experiments were also conducted in which the animals were allowed to breathe 100% O(2) following intravitreal injection with either microplasmin or hyaluronidase in order to investigate possible effects on O(2) exchange within the eye. Injection of guinea pigs with either of the two enzymes produced no significant differences in lens pO(2) levels 1-2 weeks later, compared to controls. However, for the rat, injection of microplasmin produced a 68% increase in O(2) level in the center of the lens, compared to the controls (5.6mm Hg increasing to 9.4mm Hg, p<0.05), with no corresponding effect observed following similar use of hyaluronidase. Treatment of guinea pigs with microplasmin dramatically accelerated movement of O(2) across the vitreal space when the animals were later allowed to breathe 100% O(2) (for example, O(2) traveled to a location directly behind the lens 5x faster than control; p<0.01); however, the effect following treatment with hyaluronidase was significantly less. When microplasmin-injected rats breathed 100% O(2), the time required for O(2) to reach the center of the lens was 3x faster than control (0.4 min compared to 1.4 min, p<0.01). The results have implication with regard to the occurrence of age-related PVD in the human, and a possible acceleration of maturity-onset nuclear cataract. In addition, enzymatic creation of a PVD to increase the rate of O(2) exchange within the vitreal space may have potential application for treatment of retinal ischemic disease.
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Affiliation(s)
- F J Giblin
- Eye Research Institute, Oakland University, Rochester, MI 48309-4480, USA.
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Quiram PA, Leverenz VR, Baker RM, Dang L, Giblin FJ, Trese MT. Microplasmin-induced posterior vitreous detachment affects vitreous oxygen levels. Retina 2007; 27:1090-6. [PMID: 18040251 PMCID: PMC2702988 DOI: 10.1097/iae.0b013e3180654229] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To determine if enzymatic induction of a posterior vitreous detachment (PVD) and/or vitreous liquefaction affects O2 concentration in the vitreous cavity in animals with vascularized and avascular retinal circulations. METHODS Either microplasmin or hyaluronidase was injected intravitreally into guinea pigs (avascular retinal circulation), brown Norway rats (vascularized retinal circulation without fovea), or cats (vascularized retinal circulation with fovea) with the contralateral eye used as a control. One to 2 weeks post injection, vitreal oxygen concentration was measured using a highly sensitive, platinum-based fluorophore O2 sensor. In addition, control and microplasmin-injected rats, guinea pigs, and cats were exposed to 100% oxygen and vitreal O2 levels were measured over time. Scanning electron microscopy (SEM) was used to evaluate the vitreoretinal interface for the presence of a PVD. RESULTS In animals with a vascularized retinal circulation (brown Norway rats and cats), intravitreal injection of microplasmin with induction of a PVD significantly increased baseline O2 concentration in the vitreous cavity compared to hyaluronidase injected eyes and controls in rats (35, 25, and 23 mm Hg, P < 0.001 and P < 0.001, respectively) and cats (26, 18, and 16 mm Hg, P < 0.01 and P < 0.001, respectively). Interestingly, intravitreal injection of hyaluronidase (vitreous liquefaction without induction of a PVD) did not significantly increase vitreal O2 levels in any of the animal species (P > 0.1). Upon exposure to 100% oxygen by facemask, microplasmin injected animals showed a rapid increase in vitreal oxygen levels compared to hyaluronidase injected animals and controls, indicating that the presence of a PVD allows rapid O2 exchange within the vitreous cavity. Similarly, once O2 was discontinued, the O2 concentration decreased in a similarly rapid rate. SEM showed smooth retinal surfaces in microplasmin-injected cat eyes, indicating the presence of a PVD which was not present in hyaluronidase injected or control eyes. CONCLUSION The results suggest that enzymatic-assisted PVD with microplasmin increases vitreal O2 levels and increases the rate of O2 exchange within the vitreous cavity.
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Affiliation(s)
- Polly A Quiram
- Associated Retinal Consultants, Beaumont Hospital, Royal Oak, Michigan 48073, USA.
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Abstract
PURPOSE To review current treatment approaches in diabetic macular edema (DME). METHODS The underlying pathopathology, classifications and diagnostic examination techniques including fluorescein angiography, optical coherence tomography and stereoscopic biomicroscopy. Treatment modalities with focal or grid argon laser photocoagulation, pars plana vitrectomy with and without peeling of the inner limiting membrane (ILM), as well as intravitreal injections using triamcinolone acetonide or novel vascular endothelial growth factor (VEGF) inhibitors are described. RESULTS DME results from a series of biochemical and cellular changes, causing progressive leakage and exudation. Focal and grid photocoagulation remains the standard care for diabetic maculopathy. However, the availability of new agents raises the possibility of improvements if significant benefits can be validated in randomized clinical trials. Posterior vitreous attachments play a critical role through several mechanical or physiological mechanisms. Vitrectomy without ILM removal seems to be effective in reducing the retinal thickness and improving visual acuity. CONCLUSION A proper evaluation of the vitreous and retina is fundamental to select the most appropriate treatment approach in DME. While small microaneurysms with focal DME may be treated by conventional focal photocoagulation, diffuse DME which do not respond to grid photocoagulation may benefit from intravitreal injections using triamcinolone acetonide or novel VEGF inhibitors. Eyes with DME and additional vitreous traction may benefit from pars plana vitrectomy without ILM peeling. A combination of laser, pharmacological and surgical treatment modalities may be necessary to maintain central vision in eyes with DME.
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Affiliation(s)
- Carsten H Meyer
- Department of Ophthalmology, Philipps University, Marburg, Germany.
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Becker M, Davis J. Vitrectomy in the treatment of uveitis. Am J Ophthalmol 2005; 140:1096-105. [PMID: 16376658 DOI: 10.1016/j.ajo.2005.07.017] [Citation(s) in RCA: 72] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2004] [Revised: 07/01/2005] [Accepted: 07/02/2005] [Indexed: 02/05/2023]
Abstract
PURPOSE To assess the evidence that pars plana vitrectomy (PPV) is useful in improving vision, reducing disease activity, or ameliorating cystoid macular edema (CME) in patients with uveitis. DESIGN Review of the literature. METHODS A Medline search was conducted for relevant articles published in English, German, or French. Articles were analyzed for content and evidence level. RESULTS A total of 44 interventional case series published between 1981 and 2005 were identified that included 1575 patients (1762 eyes). Evidence level was grade CII-3 indicating possibly improved clinical outcomes with fair or poor evidence. The average age of patients was 36 years with a median duration of uveitis before surgery of 48 months and a median follow-up of 1.9 years. Intermediate uveitis was present in 841 eyes. Cystoid macular edema and cataract were common co-morbidities, and there were large numbers of additional surgical procedures. Visual outcomes in 39 articles were stated as improved in 708 eyes (68%), unchanged in 202 eyes (20%), and worsened in 124 eyes (12%). Reduction in systemic medication following PPV was reported in 25 studies. The median reported percentage of patients per study with CME was 36% preoperatively and 18% postoperatively. CONCLUSIONS Based on the evidence in the literature, PPV is possibly relevant to the outcomes of improving vision and reducing inflammation and CME. Randomized, controlled, collaborative trials or hypothesis-based case series with precise outcome measures that incorporate control groups would improve the quality of evidence supporting PPV as an adjunct to the medical treatment of uveitis.
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Affiliation(s)
- Matthias Becker
- Bascom Palmer Eye Institute, University of Miami School of Medicine, 900 NW 17th Street, Miami, FL 33136, USA
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Alameri A, Baker NS. Successful use of recombinant activated factor VII in the treatment of vitreous haemorrhage: a report of seven cases. Blood Coagul Fibrinolysis 2005; 16:573-8. [PMID: 16269932 DOI: 10.1097/01.mbc.0000191524.79682.db] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Vitreous haemorrhage poses a serious threat to vision if untreated. Therapeutic options remain scarce and surgical intervention to resolve persistent bleeding is associated with risks that may further compromise vision. We report the use of recombinant activated factor VII (rFVIIa) in seven patients (six men, one woman; age, 30-65 years) with vitreous haemorrhage and severe reduction in visual acuity caused by trauma (n = 4) or proliferative diabetic retinopathy (n = 3). Initial doses ranged from 60 to 140 microg/kg; most patients received maintenance therapy with 20-60 microg/kg for at least 3 days. One patient received rFVIIa treatment for only 24 h and suffered a re-bleed, controlled successfully with further rFVIIa therapy. Five patients responded well to rFVIIa treatment, with reduced symptoms and improvements in visual acuity. Late presentation several days after trauma or symptom onset may have contributed to poor outcomes in the two patients who failed to respond to rFVIIa therapy. No adverse events were observed. An initial dose of rFVIIa 60-140 microg/kg, followed by 20-60 microg/kg repeated at 8-h intervals for 3-5 days, appears to be an effective therapeutic option for vitreous haemorrhage. However, further studies of rFVIIa use in this indication are warranted.
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Affiliation(s)
- Ali Alameri
- National Center of Hematology, Baghdad, Iraq.
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