Increased vitreous concentrations of MCP-1 and IL-6 after vitrectomy in patients with proliferative diabetic retinopathy: possible association with postoperative macular oedema

Yoshida, Shigeo; Kubo, Yuki; Kobayashi, Yoshiyuki; Zhou, Yedi; Nakama, Takahito; Yamaguchi, Muneo; Tachibana, Tetsuya; Ishikawa, Keijiro; Arita, Ryoichi; Nakao, Shintaro; Sassa, Yukio; Oshima, Yuji; Kono, Toshihiro; Ishibashi, Tatsuro

doi:10.1136/bjophthalmol-2014-306366

Cited by 55 publications

(53 citation statements)

References 25 publications

(34 reference statements)

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“…Other studies have demonstrated that the activation of the IL-6 trans-signaling pathway induced the phosphorylation of STAT3 resulting in an increase in VEGF production [24,25]. From these findings, we suggest that the reduced level of intravitreal VEGF concentration after vitrectomy [18] gradually recovers by the stimulation of these upregulated inflammatory cytokines. This should then lead to the slower recovery of CMT and the prolongation of DME by the anti-VEGF drug in the vitrectomized eyes.…”

Section: Discussionsupporting

confidence: 52%

“…We have shown that the intravitreal concentration of VEGF is lower [17] and the concentration of inflammatory cytokines such as IL-6 and MCP-1 is higher at approximately 7 months after successful vitrectomy [18]. We believe that these inflammatory cytokines might induce prolonged DME after vitrectomy.…”

Section: Discussionmentioning

confidence: 99%

“…Animal studies suggested that the half-life of anti-VEGF drug injected into the vitreous of eyes that had undergone vitrectomy was shorter than that in eyes without vitrectomy [15,16]. In addition, we have shown that the VEGF concentration in the vitreous is reduced after vitrectomy [17,18]. Only a small number of studies have examined the effectiveness of anti-VEGF therapy in vitrectomized human eyes, and the findings have been inconsistent.…”

Section: Introductionmentioning

confidence: 99%

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Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes

et al. 2016

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Purpose: To compare the effectiveness of intravitreal ranibizumab (IVR) for diabetic macular edema (DME) between eyes with and without previous vitrectomy. Procedures: We prospectively assessed the best-corrected visual acuity (BCVA) and central macular thickness (CMT) after IVR for 6 months. Results: There were no significant differences in the baseline BCVA and CMT between both groups. In the nonvitrectomized group (n = 15), the mean changes of BCVA and CMT from baseline to month 6 were significant (p < 0.01). In the vitrectomized group (n = 10), the improvement appeared to be slower, and the mean BCVA improvement was not significant (p = 0.5), although the mean CMT decrease was significant (p < 0.05). There were no significant differences in the mean changes of BCVA and CMT between both groups at 6 months. Conclusions: The difference in the effectiveness of IVR between both groups was not significant. IVR can be a treatment option even for vitrectomized DME eyes.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes

et al. 2016

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“…Some of these proteins have been documented in other studies to date, notably IL-6, IL-8, and MCP-1. [41][42][43][44][45] Cohen et al 42 demonstrated an association between the inflammatory factor IL-6 and VEGF, showing IL-6 may function upstream of VEGF. Interleukin-8 has also been identified as a key mediator in ocular inflammation and ischemic disease.…”

Section: Inflammation In Ischemic Retinal Diseasementioning

confidence: 99%

Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia

Kovacs

Marra

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…The concentration of ligands for C-C chemokine receptor types 2 (CCR2; primary ligand: monocyte chemoattractant protein-1 [MCP-1]) and 5 (CCR5; primary ligand: RANTES) are elevated in the vitreous and aqueous humors of patients with diabetic retinopathy/DME. 4,[26][27][28][29][30][31][32] CCR2 and CCR5, expressed on the surface of monocytes, 33,34 play a key role in inflammation and in the homing of inflammatory cells to their target tissues. Preclinical studies have linked the CCR2 pathway with vascular leakage from, and monocyte infiltration into, the retina in experimental diabetes.…”

mentioning

confidence: 99%

A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

Gale

Berger²,

Gilbert

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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Citation: Gale JD, Berger B, Gilbert S, et al. A CCR2/5 inhibitor, PF-04634817, is inferior to monthly ranibizumab in the treatment of diabetic macular edema. Invest Ophthalmol Vis Sci. 2018;59:2659-2669. https://doi.org/10.1167/iovs.17-22731 PURPOSE. Ligands for the proinflammatory C-C chemokine receptor types 2 and 5 (CCR2 and CCR5) are elevated in the eyes of patients with diabetic macular edema (DME). We evaluated the efficacy and safety of PF-04634817, an oral CCR2/5 dual antagonist, versus intravitreal ranibizumab, in adult subjects with DME. METHODS.In this phase II, randomized, placebo-controlled, double-masked study, eligible subjects ( ‡18 years of age) had type 1 or 2 diabetes and DME with best-corrected visual acuity (BCVA) of 20/32 or worse (letter score 78), and up to 20/320 or better ( ‡24 letter score), in the study eye. Subjects were assigned randomly 1:1 to once-daily (QD) oral PF-04634817 200 mg plus masked sham therapy as placebo or monthly intravitreal ranibizumab 0.3/0.5 mg plus QD oral placebo. The primary objective was to evaluate the efficacy of PF-04634817 compared with ranibizumab in change from baseline in BCVA after 12 weeks in a noninferiority design. Noninferiority was based on BCVA 80% confidence interval (CI): there had to be a less than three letter loss in the PF-04634817 arm compared with the ranibizumab arm. RESULTS.A total of 199 subjects were randomized. Least squares mean difference in change in BCVA from baseline to week 12 in the study eye for the PF-04634817 arm was À2.41 letters (80% CI: À3.91, À0.91; P ¼ 0.04) compared with ranibizumab. PF-04634817 was well tolerated.CONCLUSIONS. Treatment with oral CCR2/5 receptor dual antagonist PF-04634817 was associated with a modest improvement in BCVA, but did not meet the predefined noninferiority criteria compared with intravitreal ranibizumab.

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Increased vitreous concentrations of MCP-1 and IL-6 after vitrectomy in patients with proliferative diabetic retinopathy: possible association with postoperative macular oedema

Abstract: The elevated levels of MCP-1 and IL-6 may indicate prolonged inflammation even after successful vitrectomy, which can cause postoperative DME.

Cited by 55 publications

References 25 publications

Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes

Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes

Angiogenic and Inflammatory Vitreous Biomarkers Associated With Increasing Levels of Retinal Ischemia

A CCR2/5 Inhibitor, PF-04634817, Is Inferior to Monthly Ranibizumab in the Treatment of Diabetic Macular Edema

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