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Somatostatin
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Neuroprotective, antiangiogenic. Downregulated in retinas of diabetics, associated with retinal neurodegeneration [54].
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Recently completed multi-center phase II-III trial (EUROCONDOR) to assess the safety of topically administered somatostatin. (EudraCT Number: 2012–001200-38) Results have yet to be published.
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Glucagon-like peptide (GLP-1)
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Neuroprotective [55]
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Intravitreal injections of exedin-4 (a GLP-1 analogue) prevent ERG abnormalities in rats with streptozotoin-induced diabetes [56]. Topical administration of GLP-1R agonists prevents retinal neurodegeneration in mice with diabetes [57].
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2 large clinical trials of GLP-1 analogues in type 2 diabetics with high cardiovascular risk (LEADER and SUSTAIN-6) have shown neutral benefit [58] or even worsening of DR compared to placebo [59]. However, these studies were not designed to assess progression of DR.
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Doxycycline
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Anti-inflammatory and neuroprotective [60]
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Low-dose oral doxycycline improves inner retinal function in DR compared to placebo [61].
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Although statistical significance was achieved at multiple time points, it was a small, proof-of-concept trial.
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Interleukin 1β (IL-1β)
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Inflammatory cytokine
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Systemic IL-1β inhibition has been shown to stabilize retinal neovascular changes in proliferative DR and reduce macular edema [62].
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Open-label, small, prospective pilot study. Reduction in macular edema was not statistically significant.
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Tumor necrosis factor α (TNF-α)
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Inflammatory, induces vascular changes
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Intravitreal injection of TNF-α inhibitor decreased capillary degeneration in diabetic rats [63].
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Very small study in rats, with other primary endpoints.
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