PMID- 32306096 OWN - NLM STAT- MEDLINE DCOM- 20210413 LR - 20210807 IS - 1435-702X (Electronic) IS - 0721-832X (Print) IS - 0721-832X (Linking) VI - 258 IP - 7 DP - 2020 Jul TI - 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. PG - 1411-1417 LID - 10.1007/s00417-020-04675-y [doi] AB - 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 mum to 149.0 +/- 142.0 mum 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. FAU - Clemens, C R AU - Clemens CR AD - Department of Ophthalmology, University of Muenster Medical Center, Domagkstrasse 15, 48149, Muenster, Germany. Christoph.Clemens@ukmuenster.de. FAU - Alten, F AU - Alten F AD - Department of Ophthalmology, University of Muenster Medical Center, Domagkstrasse 15, 48149, Muenster, Germany. FAU - Termuhlen, J AU - Termuhlen J AD - Department of Ophthalmology, University of Muenster Medical Center, Domagkstrasse 15, 48149, Muenster, Germany. FAU - Mihailovic, N AU - Mihailovic N AD - Department of Ophthalmology, University of Muenster Medical Center, Domagkstrasse 15, 48149, Muenster, Germany. FAU - Rosenberger, F AU - Rosenberger F AD - Department of Ophthalmology, University of Muenster Medical Center, Domagkstrasse 15, 48149, Muenster, Germany. FAU - Heiduschka, P AU - Heiduschka P AD - Department of Ophthalmology, University of Muenster Medical Center, Domagkstrasse 15, 48149, Muenster, Germany. FAU - Eter, N AU - Eter N AD - Department of Ophthalmology, University of Muenster Medical Center, Domagkstrasse 15, 48149, Muenster, Germany. LA - eng SI - ClinicalTrials.gov/NCT03370380 PT - Journal Article DEP - 20200418 PL - Germany TA - Graefes Arch Clin Exp Ophthalmol JT - Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie JID - 8205248 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Vascular Endothelial Growth Factor A) RN - 15C2VL427D (aflibercept) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) SB - IM MH - Aged MH - Angiogenesis Inhibitors/administration & dosage MH - Female MH - Fluorescein Angiography/methods MH - Follow-Up Studies MH - Fundus Oculi MH - Humans MH - Intravitreal Injections MH - Macular Degeneration/*complications/diagnosis MH - Male MH - Prospective Studies MH - Receptors, Vascular Endothelial Growth Factor/*administration & dosage MH - Recombinant Fusion Proteins/*administration & dosage MH - Retinal Detachment/diagnosis/*drug therapy/etiology MH - Retinal Pigment Epithelium/*pathology MH - Tomography, Optical Coherence/*methods MH - Treatment Outcome MH - Vascular Endothelial Growth Factor A/antagonists & inhibitors MH - *Visual Acuity PMC - PMC7306025 OTO - NOTNLM OT - Aflibercept OT - Age-related macular degeneration OT - Anti-vascular endothelial growth factor OT - Pigment epithelium detachment OT - Spectral-domain optical coherence tomography COIS- 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. EDAT- 2020/04/20 06:00 MHDA- 2021/04/14 06:00 PMCR- 2020/04/18 CRDT- 2020/04/20 06:00 PHST- 2019/10/22 00:00 [received] PHST- 2020/04/01 00:00 [accepted] PHST- 2020/03/31 00:00 [revised] PHST- 2020/04/20 06:00 [pubmed] PHST- 2021/04/14 06:00 [medline] PHST- 2020/04/20 06:00 [entrez] PHST- 2020/04/18 00:00 [pmc-release] AID - 10.1007/s00417-020-04675-y [pii] AID - 4675 [pii] AID - 10.1007/s00417-020-04675-y [doi] PST - ppublish SO - Graefes Arch Clin Exp Ophthalmol. 2020 Jul;258(7):1411-1417. doi: 10.1007/s00417-020-04675-y. Epub 2020 Apr 18.