Diabetic macular edema (DME) is a common complication of diabetic retinopathy (DR) and is the most important cause of vision loss in working-stage people in developed countries.12–13 Numerous studies demonstrate a relationship between VEGF level and retinopathy activity and show that VEGF is the primary angiogenic factor responsible for the development of diabetic retinopathy and maculopathy.14–15 With the understanding of the role of VEGF in the pathogenesis of DME, the use of anti-VEGF agents in the treatment has become widespread.
Patients who received 0,3 and 0,5 mg of ranibizumab injection were compared with the control group in the "Study of Safety and Efficacy of Ranibizumab in Diabetic Macular Edema" (RESOLVE) and "Study of Ranibizumab for Diabetic Macular Edema" (RISE and RIDE) studies. In the groups receiving intravitreal Ranibizumab, a significant improvement in visual acuity and a significant decrease in central macular thickness were seen after 12 months.16 The efficacy and safety of intravitreal The efficacy and safety of intravitreal Aflibercept was evaluated in the study ‘An exploratory study of the safety, tolerability and bioactivity of a single intravitreal injection of vascular endothelial growth factor Trap-Eye in patients with diabetic macular edema’. A decrease in central macular thickness and mean letter gain in visual acuity were observed 6 weeks after the injection.17 In the study ‘Aflibercept, Bevacizumab or Ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T’, 0,3 mg Ranibizumab, 2,0 mg Aflibercept and 1,25 mg Bevacizumab were compared. When the Ranibizumab and Aflibercept groups were examined, a significant decrease in central macular thickness and a significant increase in visual acuity were observed in this group at 12 months.18 Compared to other studies, although the central macular thickness in both the AFL + AFL group and the RAN + RAN group decreased statistically significantly at the 6th month compared to the 3rd month, the increase in visual acuity was not statistically significant at the 6th month compared to the 3rd month, unlike other studies.
Corticosteroids stabilize lysosomal membranes and the blood-retina barrier while reducing VEGF secretion and vascular permeability. For this reason, corticosteroid agents are used in the treatment of DME.7 In a study examining the changes in the amounts of inflammatory and angiogenic cytokines in the humoral aqueous after intravitreal injection of triamcinolone and bevacizumab in patients with DME, IL6, inducible protein 10, monocyte chemoattractant protein, platelet-derived growth factor AA, and VEGF were observed to be significantly decreased in eyes injected with triamcinolone, only VEGF has been shown to be reduced in eyes injected with bevacizumab.19 In this case, it was stated that the use of corticosteroids in DME may be more meaningful than anti-VEGF therapy, which is effective only on a part of the inflammatory cascade.20 Intravitreal corticosteroids in DME; It can be considered if anti-VEGFs are contraindicated, if there is poor compliance with repetitive anti-VEGF applications and if there is resistance to anti-VEGFs.21 In the study of Vujosevic et al. Dexamethasone has been shown to be effective in cases of increased foveal autofluorescence.22 In the study of Vural et al., it was concluded that dexamethasone implant responds better than anti-VEGF treatment in DME cases with subretinal fluid.23 The CHAMPLAIN study evaluated 55 vitrectomized eyes with treatment-resistant DME. A single dose of 0,7 mg dexamethasone implant was applied to the patients and they were followed for 26 weeks. There was a statistically significant increase in visual acuity of these patients at the end of the 26th week. In the eighth week, visual improvement of 10 letters or more was achieved in 30.4% of the patients.24 In the MEAD study, 0.7mg dexamethasone was randomized to 0.35mg dexamethasone and sham groups. It was determined that the decrease in central macular thickness and letter gain were higher in the groups receiving intravitreal dexamethasone. In addition, it was reported that approximately one third of the patients in the group receiving dexamethasone had an increase in intraocular pressure that required treatment.25
In the study conducted by Totan et al., after intravitreal dexamethasone administration to patients who received 3 doses of 2.5 mg intravitreal bevacizumab at 6-week intervals and whose central macular thickness was above 275 microns, there was a significant decrease in central macular thickness in the 1st, 3rd and 6th months; In addition, a significant increase in mean visual acuity and mean intraocular pressure was detected in the 1st and 3rd months.26 In the study of Zhioua et al., intravitreal dexamethasone was administered to 12 patients whose central macular thickness continued to be 300 microns and above, despite 6 consecutive months of Ranibizumab, and they found that dexamethasone was effective on central macular thickness and visual acuity.27 In the study by Maturi et al (Protocol U), the group that continued with 0.3 mg of Ranibizumab after 3 doses of 0.3mg Ranibizumab was compared with the group that was switched to Dexamethasone implant; Although the decrease in mean central macular thickness and increase in mean intraocular pressure were greater in the group switched to dexamethasone at the end of 24 weeks, there was no significant difference in mean visual acuity.28 In a meta-analysis study by Khan et al., it was reported that the DEX implant applied to patients with refractory DME despite the use of anti-VEGF agents improves vision and may be a treatment alternative for patients with DME who have low response to anti-VEGF agents.29 Ozata et al. showed that dexamethasone implantation was effective in increasing BCVA and lowering CMT in the first 3 months in DME resistant to sequential intravitreal Ranibizumab therapy. They reported that intravitreal dexamethasone implantation could be considered as an alternative method in the treatment of resistant DME.30
In our study, when the groups that continued with 3 doses of anti-VEGF after 3 doses of anti-VEGF treatment and the groups that were switched to intravitreal dexamethasone implant were compared at the end of the 6th month, the decrease in mean central macular thickness, increase in mean intraocular pressure and increase in mean visual acuity were not found statistically significant. Despite the statistically significant increase in intraocular pressure at the 6th month compared to the 3rd month in the dexamethasone implanted groups, the patients did not need anti-glaucomatous drug treatment.
Strengths and Limitations
Although this study has disadvantages such as being retrospective, having a small number of patients in the groups, not being able to evaluate on inflammatory markers, and having an average follow-up period of 6 months; The absence of a similar study conducted on four different groups is also important for our study. Our study should be supported by prospective, long-term follow-up and further studies with large patient groups. New molecules with fewer side effects and longer acting are needed for better therapeutic results.