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Randomized Controlled Trial
. 2021 Dec 14;11(1):23981.
doi: 10.1038/s41598-021-03433-2.

Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema

Luiz Guilherme Azevedo de Freitas  1   2 , David Leonardo Cruvinel Isaac  3 , Murilo Batista Abud  3 , Alexandre Dantas Soares Quintas Segundo  4 , Mariana Larissa Alvino Barros  4 , Gabriela Caroline Monteiro de Albuquerque  4 , Bruna Dantas Aires Guimarães  4 , Clarice Neuenschwander Lins de Morais  5 , Marcos Pereira de Ávila  6   7
Affiliations
Randomized Controlled Trial

Analysis of cytokines in the aqueous humor during intravitreal Ranibizumab treatment of diabetic macular edema

Luiz Guilherme Azevedo de Freitas et al. Sci Rep. .

Abstract

This study aimed to analyze the concentrations of VEGF, b-FGF, TNF, interleukin (IL)-1, IL-6, IL-8, IL-10, and IL-12 in the aqueous humor of patients with diabetic macular edema with and without peripheral retinal ischemia and to ascertain the changes in the levels of these molecules during treatment with ranibizumab. A therapeutic, prospective, randomized interventional study was carried out. Twenty-four eyes from 24 patients were studied and divided into 3 groups. Group 1 (9 eyes) included patients with diabetic macular edema without peripheral ischemia. Group 2 (10 eyes) included patients with diabetic macular edema with peripheral ischemia. Group 3 (5 eyes), the control group, included patients without systemic and/or eye diseases. Patients in Groups 1 and 2 received 3 intravitreal injections of 2 mg/0.05 ml ranibizumab at an interval of approximately 30 days. Before administering the injections, the aqueous humor was collected. In the control group, aqueous humor was collected before facetectomy. During treatment, the median IL-6 concentration significantly increased in Group 1 but showed a slight but not significant decrease in Group 2. Interleukin 8 levels were significantly different at the end of treatment compared to the beginning in Groups 1 and 2. TNF, IL-1, IL-10, and IL-12 levels were practically unchanged in both groups. VEGF was significantly reduced at the end of the study in Groups 1 and 2. B-FGF was not detected in most of the studied patients, and in those with detectable levels, there was no significant variation. There was a significant increase in the median level of interleukin 6 in the group without ischemia and a significant decrease in VEGF in both groups. The cytokines TNF, IL-1, IL-10, and IL-12 did not show significant variation.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Comparison of the variation in visual acuity in the nonischemic and ischemic groups.
Figure 3
Figure 3
OCT showing a reduction in macular edema after treatment in Group 1.
Figure 4
Figure 4
OCT showing reduction of macular edema after treatment in Group 2.
Figure 5
Figure 5
Angiography showing regression of the retinal neovessels (red arrow).
Figure 6
Figure 6
Variation in the median IL-6 level during treatment in Groups 1 and 2. D1: first collection; D2: second collection; D3: third collection.
Figure 7
Figure 7
Variation in the median IL-8 level during treatment in Groups 1 and 2. D1: first collection; D2: second collection; D3: third collection.
Figure 8
Figure 8
Variation in the median VEGF concentration before and after treatment in Groups 1 and 2. D1: first collection; D3: third collection.
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