Vitreous Mediators after Intravitreal Bevacizumab or Triamcinolone Acetonide in Eyes with Proliferative Diabetic Retinopathy

Arimura, Noboru; Otsuka, Hiroki; Yamakiri, Keita; Sonoda, Yoshito; Nakao, Shintaro; Noda, Yoichi; Hashiguchi, Teruto; Maruyama, Ikuro; Sakamoto, Taiji

doi:10.1016/j.ophtha.2008.12.024

Cited by 71 publications

(57 citation statements)

References 21 publications

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“…In addition to VEGF, many inflammatory cytokines have been reported to have crucial roles in the development of DMO. [3][4][5] Histological studies of retina and choroid in patients with diabetic retinopathy have shown various changes of choroidal vasculature, such as accumulation of inflammatory cells, focal dilation or narrowing, and the development of sinus-like structures between the choroidal lobules. [24][25][26] Furthermore, various cytokines and growth factors that promote DMO may also influence choroidal vasculature, which may account for changes in CT, as many previous studies have implicated choroidal changes in the pathophysiology of DMO.…”

Section: Discussionmentioning

confidence: 99%

“…1 There are many factors involved in the pathophysiology of DMO, including vascular endothelial growth factor (VEGF), which is known to have an important role in increasing vascular permeability in diabetic retinopathy, 2 and inflammatory cytokines associated with the development of DMO. [3][4][5] Among several treatment options available for DMO, use of anti-VEGF agents have led to effective treatment of DMO, and anti-VEGF therapy has become one of the most commonly performed treatment modalities for DMO. 6 Intravitreal dexamethasone implants (Ozurdex; Allergan, Irvine, CA, USA) is a sustained-release biodegradable implant, and it was shown to be effective for the treatment of DMO.…”

Section: Introductionmentioning

confidence: 99%

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Effect of intravitreal dexamethasone implant on retinal and choroidal thickness in refractory diabetic macular oedema after multiple anti-VEGF injections

Kim

Cho

Lee

et al. 2016

Eye

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Aims To investigate the effect of intravitreal dexamethasone implant (IVD) on central foveal thickness (CFT), choroidal thickness (CT) and its correlation with visual acuity in eyes with refractory diabetic macular oedema (DMO). Methods This was a retrospective interventional case-series. Thirty-five eyes of 35 patients were treated with a single injection of IVD because of refractory DMO with CFT over 300 μm, and persistent intraretinal and subretinal fluid despite of multiple intravitreal bevacizumab injections. Patients were followed-up for 6 months for the evaluation of CFT and subfoveal CT by spectral-domain optical coherence tomography. Results All eyes (mean age: 59.4 ± 12.35 years; 18 males, 17 females) had been previously treated with multiple bevacizumab injections and showed persistent DMO (mean number of injections 4.08 ± 2.98) The preoperative logMAR BCVA was 0.49 ± 0.24, which gradually improved to 0.46 ± 0.32 at 6 months (P = 0.652) and 26% gained two or more lines of Snellen visual acuity. At baseline, the mean CFT was 526.29 ± 123.48 μm, which significantly improved to 316.15 ± 100.09 μm at 3 months (Po0.001). However, CFT deteriorated to 457.07 ± 136.53 μm at 6 months (P = 0.051). Similarly, the mean preoperative subfoveal CT was 288.91 ± 36.47 μm and it decreased to 266.85 ± 30.93 μm at 3 months (Po0.01), but increased to 278.63 ± 32.55 μm at 6 months (P = 0.137). The reduction of CFT from baseline showed significant correlation with that of subfoveal CT at 3 months (P = 0.041) and at 6 months (P = 0.008). Conclusions In DMO refractory to multiple bevacizumab injections, IVD significantly reduced CFT and subfoveal CT, with BCVA improvement in one-fourth of the patients. The reduction of CFT showed significant correlation with reduction of subfoveal CT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of intravitreal dexamethasone implant on retinal and choroidal thickness in refractory diabetic macular oedema after multiple anti-VEGF injections

Kim

Cho

Lee

et al. 2016

Eye

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“…5,6 We showed that the levels of intravitreal IL-6 and IL-8 were significantly higher in eyes with a RRD compared with control eyes. 10,11,14 To confirm this, we exposed R28 cells and ARPE-19 cells to histones and measured cytokines in the supernatants. The results indicated that the concentrations of IL-6 and IL-8 were less than the detectable level at the baseline in R28 cells, and their concentrations did not increase after exposure to histones (data not shown).…”

Section: Histones Cause Cytokine Production By Arpe-19 Cellsmentioning

confidence: 97%

“…All concentrations that were below the detection limit were assigned a value of 0 in the statistical analyses as previously described. 11,[14][15][16] Animals and Induction of RD All experiments were performed in accordance with a statement describing the Use of Animals in Ophthalmic and Vision Research proposed by the Association for Research in Vision and Ophthalmology, and approval was obtained from our institutional Animal Care Committee. Brown Norway rats (Japan SLC, Shizuoka, Japan) were housed in covered cages and kept at a constant temperature and relative humidity with a regular 12:12-h light/dark schedule.…”

Section: Human Vitreous Samplesmentioning

confidence: 99%

Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment

Kawano

Ito

Yamada³

et al. 2014

Laboratory Investigation

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Histones are DNA-binding proteins and are involved in chromatin remodeling and regulation of gene expression. Histones can be released after tissue injuries, and the extracellular histones cause cellular damage and organ dysfunction. Regardless of their clinical significance, the role and relevance of histones in ocular diseases are unknown. We studied the role of histones in eyes with retinal detachment (RD). Vitreous samples were collected during vitrectomy, and the concentration of histone H3 was measured by enzyme-linked immunosorbent assay. The location of the histones and related molecules was examined in a rat RD model. The release of histones and their effects on rat retinal progenitor cells R28 and ARPE-19 were evaluated in vitro. In addition, the protective role of the vitreous body against histones was tested. The intravitreal concentration of histones was higher in eyes with RD (mean, 30.9±9.8 ng/ml) than in control eyes (below the limit of detection, Po0.05). In the rat RD model, histone H3 was observed on the outer side of the detached retina and was associated with photoreceptor death. Histone H3 was released from cultured R28 by oxidative stress. Histones at a concentration 10 mg/ml induced the production of interleukin-8 in ARPE-19 cells (2.5-fold increase, Po0.05) that was mediated through the ERK1/2-and p38 MAPK-dependent pathways and Toll-like receptor 4. Histones were toxic to cells at concentrations of Z20 mg/ml. Vitreous body or hyaluronan decreased toxicity of histones by inhibiting diffusion of histones. These results indicate that histones are released from retinas with RD and may modulate the subretinal microenvironment by functioning as damage-associated molecular pattern molecules, thereby inducing proinflammatory cytokines or cell toxicity. In addition, the important role of the vitreous body and hyaluronan in protecting the retina from these toxic effects is suggested.

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“…23 SDF-1␣ and VEGF were quantified by using commercial enzyme-linked immunosorbent assays (Human CXCL12/SDF-1 ␣ Quantikine ELISA Kit, Human VEGF Quantikine ELISA Kit; R&D Systems, Minneapolis, MN). Six inflammatory cytokines/chemokines were quantified by using commercial multiplex Cytometric Bead Array systems: Human Inflammation Kit (BD Biosciences Pharmingen, San Diego, CA).…”

Section: Human Vitreous Samplesmentioning

confidence: 99%

Stromal Cell-Derived Factor-1 Is Essential for Photoreceptor Cell Protection in Retinal Detachment

Otsuka

Arimura

Sonoda

et al. 2010

The American Journal of Pathology

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Vitreous Mediators after Intravitreal Bevacizumab or Triamcinolone Acetonide in Eyes with Proliferative Diabetic Retinopathy

Cited by 71 publications

References 21 publications

Effect of intravitreal dexamethasone implant on retinal and choroidal thickness in refractory diabetic macular oedema after multiple anti-VEGF injections

Effect of intravitreal dexamethasone implant on retinal and choroidal thickness in refractory diabetic macular oedema after multiple anti-VEGF injections

Toxic effects of extracellular histones and their neutralization by vitreous in retinal detachment

Stromal Cell-Derived Factor-1 Is Essential for Photoreceptor Cell Protection in Retinal Detachment

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