Author: Varun Chaudhary (Canada)
Co-authors: Frédéric Matonti, Javier Zarranz-Ventura, Michael Stewart
Purpose
Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity (VA) and reduce treatment burden for patients with neovascular age-related macular degeneration (nAMD). This systematic literature review aimed to determine the impact of persistent and/or new subretinal fluid (SRF), intraretinal fluid (IRF), and sub-retinal pigment epithelial (RPE) fluid on VA over a 1-year treatment course with anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with nAMD.
Setting/Venue
This review was conducted in accordance with the principles set out in the Cochrane Handbook for Systematic Reviews of Interventions. EMBASE, PubMed, and CENTRAL databases, as well as conference websites and clinical trial registries were searched between 1 January 2006 and 1 August 2020 with restrictions on language (English language only).
Methods
The primary objective was to determine the impact of SRF, IRF, and sub-RPE fluid (both at baseline and throughout the course of treatment) on VA during 1 year of anti-VEGF treatment in patients with nAMD. Secondary objectives were to determine the impact of SRF, IRF, and sub-RPE fluid on VA at other timepoints, morphologic outcomes, treatment burden, and safety (data availability permitting). Outcomes in patients with nAMD undergoing intravitreal anti-VEGF treatment, stratified by SRF or IRF, were included. Studies were excluded if they did not report outcomes, did not report SRF or IRF, included a mixed-disease study population (e.g. nAMD and diabetic macular edema) unless an nAMD subgroup of patients was reported separately, reported a mixed treatment population (e.g. photodynamic therapy and anti-VEGF) unless the anti-VEGF group was reported separately, or if they consisted of individual case studies. Publication eligibility and data extraction were conducted according to Cochrane methods. Risk of bias was assessed using the Cochrane RoB-2 and ROBINS-I tools. Of the 1797 records screened, 188 articles were assessed in full and 27 met the inclusion criteria.
Results
Baseline and persistent/new IRF negatively impacted VA throughout the course of treatment and the strength of the association increased from Years 1 and 2 to Year 5. Additionally, the location of fluid relative to the foveal center influenced VA – foveal IRF was generally associated with worse VA compared with extrafoveal IRF or absence of IRF. Data on the role of SRF were not as clear. Most studies suggested that SRF did not negatively affect VA at baseline or throughout the first year of treatment. At Year 2, one study corroborated the Year 1 findings, and another found that SRF (particularly foveal SRF) was associated with improved VA. In the study exploring long-term effects of SRF on VA, patients with foveal SRF at any timepoint had better vision at Year 5 than those without SRF, with the effect being more pronounced that at Year 2. Data on the effects of sub-RPE fluid were scarce and a consensus could not be reached. Few studies reported the number of injections associated with fluid status; a difference according to IRF and SRF status was not apparent, and it was not possible to draw any clinically meaningful conclusions.
Conlusions
To optimally manage patients with nAMD with anti-VEGF drugs, clinicians should understand the impact of fluid compartment changes on VA. Current evidence suggests that after an initial course of treatment, anti-VEGF regimens that tolerate stable, persistent SRF (on the condition that VA is stable or improved) but not IRF may enable patients to achieve their best possible VA and minimize treatment burden. The location of the fluid relative to the foveal center should also be considered when making retreatment decisions. Confirmatory, prospective studies are required to validate the effects of different fluid compartments on VA.
Financial Disclosure
Varun Chaudhary: Personal fees from Alcon Inc., Bayer Healthcare AG, and Novartis AG; Grants from Bayer Healthcare AG, and Novartis AG Frédéric Matonti: Personal fees from AbbVie, Bayer, Horus Pharma, and Novartis Javier Zarranz-Ventura: Personal fees from Alcon, Alimera Sciences, Allergan, Bayer, Brill Pharma, Dorc, Novartis, and Roche; grants from Allergan, and Novartis; Non-financial support from Alcon, Alimera Sciences, Allergan, Bausch and Lomb, Bayer, Brill Pharma, Dorc, Novartis, Preceyes, Roche, Topcon, and Zeiss Michael Stewart: Consultancy fees from Alkahest and Bayer; Financial support from Allergan, Kanghong, and Regeneron Funding: Non-financial support for the conduct of the literature analysis and medical writing support was provided by ApotheCom, and funded by Bayer Consumer Care AG, Pharmaceuticals, Switzerland.
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