Group 1:
The group has 9 patients (4 males and 5 females), aged between 52 and 77 years old (± 9.34), with diabetic macular edema without peripheral retinal ischemia, undergoing monthly treatment with ranibizumab.
Visual acuity and macular thickness
At the end of the research, 8 showed improvement in visual acuity. One patient showed no visual improvement, remaining with the same initial vision (Figure 2).
Upon OCT examination, all patients presented a reduction in central macular thickness upon analysis of the macular thickness map, as illustrated in two patients (Figure 3).
Clinical examinations and fluorescein angiography
Upon biomicroscopy examination, one patient was pseudophakic and 08 were phakic. No lens had progressed to cataracts during the study.
At gonioscopy, the presence of neovessels at an angle or iris was not seen before and at the end of the research.
Upon examination of angiography, no patient presented vascular changes of the staining type or retinal neovascularization during the treatment period.
Group 2:
The group had 10 patients (7 males and 3 females), aged between 47 and 68 years (± 7.06), all with DME with peripheral retinal ischemia, undergoing monthly treatment with ranibizumab.
Visual acuity and macular thickness
At the end of the research, 8 patients showed improvement in visual acuity. Those who did not improve maintained initial visual acuity (Figure 2).
Upon OCT examination, all patients presented a reduction in central macular thickness upon analysis of the macular thickness map, as illustrated in two patients (Figure 4).
Clinical examinations and fluorescein angiography
Upon biomicroscopy examination, 9 patients were phakic. No lens had progressed to cataracts during the survey. At gonioscopy, the presence of neovessels at an angle or iris was not seen before and at the end of the research.
At the beginning of the study, on angiography, two patients had retinal neovessels and one of them also had disc neovessels at the beginning of treatment. At the end of the study, both patients presented regression of the new vessels (Figure 5).
Analysis of cytokines in aqueous humor
Comparison of the medians between the beginning and the end of the treatment, in groups 1 and 2. In the data of the control group, we used the values at the beginning of the treatment such as the baseline levels (Table 1).
The values in the control group were as follows: IL-1: 0 pg/ml, IL-6: 8.23 pg/ml, IL-8: 4.66 pg/ml, IL-10: 5.57 pg/ml , IL-12: 3.4 pg/ml, TNF: 3.8 pg/ml, VFGF: 132.54 pg/ml) and b-FGF: 0.00 pg/ml (Table 1).
In analysis, of the variation of medians of IL-6, during treatment, we observed that, in group 1, it presented a statistically significant increase, at the end of the research in group 1 (10.78 - 26.35 pg/ml, p = 0.0148).
In group 2, there was a slight decrease in the median of its concentrations, but it was not statistically significant (28.02 - 27.41 pg/ml, p = 0.0194) (Figure 6).
Regarding IL-8, there were statistically significant variations in groups 1 and 2. Variation of medians in group 1, between 13.8 ± 3.95 pg/ml and 18.15 ± 12.65 pg/ml (p = 0.0234) and, in group 2, between 15.43 ± 10.65 pg/ml and 20.8 ± 19.73 pg/ml (p = 0.037) (Figure 7).
There was a reduction in the values in the medians of IL-1, which was not statistically significant in both groups. The variations were 1.61 ± 1.66 pg/ml and 0.0 ± 2.53 pg/ml, p = 0.4185 (group 1) and 0.81 ± 0.85 pg/ml and 0.56 ± 0.92 pg/ml, p = 0.441 (group 2) (Table 2).
Two interleukins, IL-10 and IL-12 had their concentrations practically unchanged, in both groups. Interleukin 10, in group 1, varied between 5.62 ± 0.70 pg/ml and 5.29 ± 1.17 pg/ml, (p = 1.00) and, in group 2, between 5.71 ± 0.40 pg/ml and 5.76 ± 0.297 pg/ml (p = 0.626).
The results found for interleukin 12, in groups 1 and 2, were, respectively: 4.21 ± 0.79 pg/ml and 2.88 ± 1.60 pg/ml (p = 0.425) and 3.60 ± 0.44 pg/ml and 3 , 67 ± 0.49 pg/ml (p = 0.489) (Table 2).
Regarding TNF, we observed changes in the medians of their concentrations, remaining similar throughout the treatment; however, without statistical significance, in both groups (4.54 ± 1.099 pg/ml and 3.16 ± 1.98 pg/ml (p = 1.00) and 3.86 ± 0.48 pg/ml and 3.87 ± 0.47 pg/ml (p = 0.155), groups 1 and 2 respectively (Table 2).
VEGF had a decrease in its medians, and this variation was statistically significant in both groups. Group 1: 170.04 ± 120.54 pg/ml and 0.0 ± 57.23 pg/ml (p = 0.0039) and Group 2: 174.73 ± 142.91 pg/ml and 0.00 ± 0.00 pg/ml (p = 0.0019) (Figure 8).
The presence of b-FGF was only detected in only 3 patients in group 1 and none in group 2. Thus, we could analyze its variations during the research (Table 2).