Regional Variety of Reduction in Retinal Thickness of Diabetic Macular Edema after Anti-VEGF Treatment

Abstract

Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D map the characteristics of naïve DME cases after their first anti-VEGF. Materials and Methods: In 46 patients with DME who received an intravitreal injection of anti-VEGF agents, retinal thickness in 100 sections of the macular area was measured by 3D-mapping mode using OCT before and 1 month after injection. The density of the microaneurysm (MA) was calculated using merged images of the OCT map and fluorescein angiography. Results: One month after injection, the central retinal thickness significantly decreased (p < 0.0001). In severe edema (retinal thickness more than 500 µm), the area percentages with a reduction rate of the retinal thickness greater than 30% and less than 5% were 6.4 ± 6.6% and 10.1 ± 4.6%, respectively. The reduction rate of the retinal thickness varied from section to section. The mutual distance between the areas of maximum thickness before and after the injection averaged 1.22 ± 0.62 mm apart. The reduction rate of retinal thickness in the thickest region before injection was significantly higher (p = 0.02), and that in the thickest region after injection was lower (p = 0.001) than in the other regions. MA density in the residual edema was significantly higher than in the edema-absorbed area (p = 0.03). Conclusion: DME has areas that show low response to the reduction in retinal thickness with anti-VEGF therapy. A high density of MA may be associated with this pathogenesis.

Keywords: VEGF; diabetic macular edema; microaneurysm; vascular endothelial growth factor.

Figure 1

Changes in CRT and BCVA after injection of anti-VEGF agents. CRT (A) and BCVA (B) were measured 0 and 1 month after a single injection. BCVA is expressed as logMAR. Data are presented as mean ± standard deviation (SD). * p < 0.05 (versus baseline). CRT, central retinal thickness; BCVA, best-corrected visual acuity; VEGF, vascular endothelial growth factor; SD, standard deviation.

Figure 2

Distribution pattern of the reduction rate of retinal thickness. (A) Representative case of OCT map image and 3D-map of retinal thickness before (a,b) and 1 month after injection (c,d) of anti-VEGF agents. The macular area (6 mm × 6 mm square) was divided into 100 sections (10 × 10 squares), and the retinal thickness in each section was measured (b,d). Areas greater than 500 µm in retinal thickness were outlined. OCT, optical coherence tomography. (B) Distribution pattern of the retinal thickness reduction rate after anti-VEGF treatment in a representative case. The light green, dark green, yellow, orange, and red colors indicate the areas where the reduction ratio was more than 30%, 20.1–30%, 10.1–20%, 5.1–10% and less than 5%, respectively. (C) Proportion of areas showing different retinal thickness reduction rates in all cases.

Figure 3

Analysis of the areas with maximum retinal thickness before and after injection. (A) OCT map of a representative case (a–c). The broken line indicates an outline of the severely edematous area. Green and red rectangles indicate the maximum area before (a) and 1 month after injection (b). The distance between the center of the green and red rectangles (arrow) is measured (c). The other areas are indicated by horizontal borders. (B) Linear correlation between the distance of the maximum thickness area and the size of the severe edema before injection. Significant correlations were observed (p = 0.002, R² = 0.20). (C) Comparison of the reduction rate of retinal thickness among the areas with maximum thickness before and after injection and the other areas. The color and texture link is shown in (A). Data represent mean ± standard deviation (SD). * p < 0.05.

Figure 4

MA density and reduction rate of retinal thickness in the residual edema after anti-VEGF treatment. (A) Representative merged image. Fluorescein angiography images taken before injection (a) were merged with the OCT maps taken before (b) and 1 month after injection (c). The severely edematous area (>500 µm) is outlined by a white line. The MA is marked in the merged image (d). A: Residual edema area; B: edema absorption area. (B) Comparison of the reduction rate of retinal thickness between the residual edema and the edema-absorbed area. Area A: Residual edema; Area B: edema absorption area. Data represent mean ± standard deviation (SD). * p < 0.05. (C) Comparison of MA density between the residual edema and edema-absorbed area. Area A: Residual edema; Area B: edema absorption area. Data represent mean ± standard deviation (SD). * p < 0.05. MA, microaneurysms.

Figure 5

The involvement of the residual edema for anti-VEGF therapy. The changes of visual acuity (A) and central retinal thickness (B) in the eyes with and without the residual edema were measured at 0, 3 and 6 months. Visual acuity is expressed as logMAR. Data are presented as mean ± standard deviation (SD). * p < 0.05 (versus groups). (C) The number of injections of anti-VEGF agent during 6 months. (D) The correlation between the number of injections and the size of residual edema after initial injection. Significant correlations were observed (p = 0.0002, R² =0.32).