Prospective PED-study of intravitreal aflibercept for refractory vascularized pigment epithelium detachment due to age-related macular degeneration: morphologic characteristics of non-responders in optical coherence tomography

Abstract

Purpose: The aim of this study was to investigate the outcomes of a fixed intravitreal aflibercept regimen in patients with vascular pigment epithelium detachment (vPED) secondary to age-related macular degeneration with refractory subretinal fluid.

Methods: A prospective, interventional case series involved 20 eyes of 20 patients with refractory subretinal fluid and vPED treated with at least three injections of intravitreal anti-VEGF prior to study inclusion. After study inclusion, patients were treated with three injections of intravitreal aflibercept 2 mg/0.05 mL monthly followed by injections every 8 weeks. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) were evaluated at all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and quarterly. Primary outcomes were effectivity of a fixed treatment as measured in change in BCVA, PED greatest linear diameter (GLD), and PED height from baseline to month 12. In an additional post hoc analysis, vPED patients were differentiated into two groups: (1) vPED lesions that showed persistence of subretinal fluid throughout 1 year of treatment and (2) vPED lesions that showed complete resolution of subretinal fluid at least at one of the monthly performed OCT volume scans. Reflectivity values were determined in the subretinal pigment epithelium (RPE) compartment in OCT scans at baseline, month 6 and 12.

Results: A total of 18 patients completed the study protocol. The mean age was 74.8 ± 10.6 years, and six patients were female. The median BCVA of all patients was 72.0 ± 8.0 EDTRS letters at baseline and 72.5 ± 9.5 EDTRS letters at 12-month follow-up (p = 0.7420). The median PED height in all patients as measured in the OCT images significantly decreased from 372.0 ± 140.0 μm to 149.0 ± 142.0 μm after 12 months of treatment (p = 0.0020). Persistent subretinal fluid was present at every OCT control in six patients (group 1). Twelve patients showed resolution of subretinal fluid at least at one OCT control (group 2). Reflectivity values in the sub-RPE compartment in OCT scans were 41.48 ± 4.48 (group 1) and 42.62 ± 12.34 (group 2) at baseline (p = 0.854) and 65.88 ± 6.74 and 50.87 ± 14.11 at month 12 (p = 0.038).

Conclusions: Intravitreal aflibercept in refractory vPED leads to a significant reduction in PED height and disease activity as well as preservation of BCVA over 1 year. Persistent subretinal fluid was present in PED lesions with high values of reflectivity under the RPE, suggesting both a diffusion barrier and an increasing fibrovascular maturization of the choroidal neovascularization.

Trial registration: ClinicalTrials.gov Identifier: NCT03370380.

Keywords: Aflibercept; Age-related macular degeneration; Anti-vascular endothelial growth factor; Pigment epithelium detachment; Spectral-domain optical coherence tomography.

Conflict of interest statement

Author CRC has received a speaker honorarium from Heidelberg Engineering, Novartis, Bayer. Author FA has received a speaker honorarium from Bayer. Authors JT, NM, and FR declare that they have no conflict of interest. Author PH has received research grants from Novartis and Bayer; author NE has received research grants from Novartis and Bayer and has received a speaker honorarium from Heidelberg Engineering, Novartis, Bayer, Sanofi Aventis, Allergan, Bausch, and Lomb.

Figures

Fig. 1

(a and b) Two exemplary patients of group 1 both with a vascular pigment epithelium detachment (vPED) lesion showing persistence of subretinal fluid throughout 1 year of treatment. Patient 1 (a) and patient 2 (b) first row baseline visit, second row 6-month visit, and third row 12-month visit baseline visit. Note the increase in hyperreflectivity in the sub-RPE space in the course of the treatment, while the subretinal fluid at the edge of the vPED lesion persists throughout the treatment. (c) Exemplary patient of group 2 with a vPED lesion showing complete resolution of subretinal fluid after the fourth injection. First row baseline visit, second row 3-month visit, and third row 4-month visit

Fig. 2

(a) Spectral-domain optical coherence tomography image of a vascular pigment epithelium detachment (vPED). Note the vascular (hyperreflective) component and the serous (hyporeflective) component in the subretinal pigment epithelium space. (b) Corresponding graphic to illustrate manual delineation of PED components: vascular component shown in red, and serous component shown in blue

Fig. 3

Box plot diagrams showing hyperreflectivity in the sub-RPE space (arbitrary units (au)) at baseline visit, 6 months and 12 months of (a) group 1 with those vPED lesions that show persistence of subretinal fluid throughout 1 year of treatment and (b) group 2 with those vPED lesions that show resolution of subretinal fluid within 1 year of treatment. *p < 0.05

Fig. 4

Box plot diagrams illustrating the percentage of hyperreflective tissue in the sub-RPE space (%) at baseline visit, 6 months and 12 months of (a) group 1 with those vPED lesions that show persistence of subretinal fluid throughout 1 year of treatment and (b) group 2 with those vPED lesions that show resolution of subretinal fluid within 1 year of treatment