Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema

Abstract

Purpose: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes. Methods: In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20. Results: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 AE 8.88 letters) compared with baseline (74.78 AE 14.85 letters), and the CRT decreased significantly at week 4 (381.00 AE 114.64 lm) compared with baseline (440 AE 144 lm) in the Lucentis group. Conclusion: The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.

Aqueous humor monocyte chemoattractant protein-1 predicted long-term visual outcome of proliferative diabetic retinopathy undergone intravitreal injection of bevacizumab and vitrectomy

“…We suppose that the inflammatory reaction induced by high MCP-1 might aggravate macular edema or progression of PDR, which could compromise postsurgical visual function. Some pilot studies have investigated in the effect of intravitreal triamcinolone [ 21 ] or dexamethasone implant [ 22 , 23 ] on the intraocular inflammatory cytokines and both drugs could significantly decrease the level of MCP-1 in the aqueous humor. A further clinical study is warranted to evaluate the effect of combined intraocular steroids during PPV on the prognosis of PDR.…”

The Role of Intravitreal Corticosteroids in the Treatment of DME: Predictive OCT Biomarkers

“…In diabetes, IL-6 increases as DR stage advances [ 50 ]. Intercellular adhesion molecule 1 (ICAM-1) and the soluble form sICAM-1, a key intercellular adhesion molecule measured using solid-phase chemiluminescence immunoassay, is induced by IL-1 and TNFα and allows, e.g., leucocytes to bind to endothelial cells and evade into the tissue [ 51 , 52 , 53 ].…”

Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy

“…Prognosis and response to treatment are two of the main points potentially addressed by the liquid biopsy approach. Recently, different studies have reported the response to DME treatment, by means of aqueous and vitreous samples [32,104,105,[111][112][113][114][115][116]. Sohn et al compared the AH concentration of VEGF and inflammatory molecules after the administration of triamcinolone and bevacizumab, showing that the first one was able to reduce several inflammatory molecules (IL-6, IP-10, MCP-1, PDGF-AA) and VEGF concentration, while bevacizumab just reduced VEGF concentration [32].…”