A real-world study for timely assessing the diabetic macular edema refractory to intravitreal anti-VEGF treatment

Abstract

Background: Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy.

Methods: We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segment-outer segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA).

Results: Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant.

Conclusion: Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response.

Keywords: anti-vegf; diabetic macular edema; diabetic retinopathy; epiretinal membrane; optical coherence tomography.

Figure 1

OCT measures. (A), Grading of outer nuclear layer (ONL) cysts: Cystoid diabetic macular edema (DME) with a giant ONL cyst (★). (B), Serous retinal detachment (SRD) with diffuse retinal thickening (DRT, width of 3–6mm) showing retinal elevation between the sensory retina and the retinal pigment epithelium (dashed arrow); the height of SRD is measured. Grading of hyperreflective foci (HRF): A high number of HRF (≥11) are distributed in all layers (located between the ILM and INL [arrowhead] and between OPL and ELM [arrow]). (C, D), Grading of DRT: (C), DME associated with focal DRT (width ≦1 mm, between arrows). (D), DME related to localized DRT (width within 1–3 mm, between arrows). (E, F), Grading of the inner segment-outer segment (IS-OS) integrity. (E), Partially disrupted continuity of the IS-OS layer (between arrows). (F), Complete discontinuity of the IS-OS layer (between arrows). (G), DME associated with epiretinal membrane (arrow). (H), DME associated with vitreomacular traction (arrow). ELM, external limiting membrane; ILM, internal limiting membrane; INL, inner nuclear layer; OPL, outer plexiform layer.

Figure 2

Forest plot of baseline predictors of CMT reduction, using generalized estimate equation model. CMT, central macular thickness; ONL, outer nuclear layer; IS-OS, inner segment-outer segment; HRF, hyperreflective foci; OPL, outer plexiform layer; ELM, external limiting membrane; ILM, internal limiting membrane; VMA, vitreomacular adhesion; VMT, vitreomacular traction; PVD, posterior vitreous detachment; ERM, epiretinal membrane; PDR, proliferative diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; SRD, serous retinal detachment; β, beta coefficient. * Statistically significant at p<0.05.

Figure 3

Forest plot of baseline predictors of a ≥10 letter gain in BCVA, using generalized estimate equation model. BCVA, best-corrected visual acuity; ONL, outer nuclear layer; IS-OS, inner segment-outer segment; HRF, hyperreflective foci; ERM, epiretinal membrane; SRD, serous retinal detachment.

Figure 4

Forest plot of baseline predictors of CMT reduction <10%, using generalized estimate equation model. CMT, central macular thickness; ONL, outer nuclear layer; IS-OS, inner segment-outer segment; HRF, hyperreflective foci; ERM, epiretinal membrane; SRD, serous retinal detachment. *Statistically significant at p<0.05.