Pigment Epithelial Detachment Followed by Retinal Cystoid Degeneration Leads to Vision Loss in Treatment of Neovascular Age-Related Macular Degeneration
Abstract
Purpose Intravitreal antiangiogenic therapy is the major therapeutic breakthrough in neovascular age-related macular degeneration (AMD). Optical coherence tomography (OCT) is the leading diagnostic tool, but solid criteria for optimal therapeutic outcomes are lacking. A comprehensive analysis of structure/function correlations using Food and Drug Administration- and European Medicines Agency-approved substances and fixed and flexible regimens was performed.Design Post hoc analysis of a prospective, randomized multicenter clinical trial including 189 study sites.Participants A total of 1240 patients with active neovascular AMD.Methods Participants received intravitreal ranibizumab or aflibercept. A fixed regimen was used for 48 weeks followed by a flexible regimen until week 96. At monthly intervals, best-corrected visual acuity (BCVA) was measured and retinal morphology was assessed by standardized OCT, including intraretinal cysts (IRCs), subretinal fluid (SRF), and pigment epithelial detachment (PED), presenting with a width ≥400 μm or a height of ≥200 μm. Results were correlated for each regimen, feature, and time.Main outcome measures The BCVA outcomes in relation to retinal pathomorphology based on noninferiority for all treatment arms.Results In neovascular AMD, only IRC at baseline and persistent through week 12 had a negative impact on BCVA. With therapeutic intervention, exudative features such as IRC and SRF resolved rapidly in 74% of eyes, whereas PED responded only slowly with 38%. Independent of the type of regimen, fixed or flexible, retinal morphology correlated tightly with visual function. Intraretinal cysts consistently showed the lowest BCVA gains with either regimen or substance. With the switch from a fixed to a flexible pro re nata (PRN) regimen, progressive visual loss occurred exclusively in the group with primary PED presenting as the hallmark of neovascular activity and was induced by secondary formation of IRC in the neurosensory retina.Conclusions The efficacy of antiangiogenic therapy in neovascular AMD is strongly determined by morphologic features. The subretinal pigment epithelium lesion underlying PED appears to be the primary indicator for progressive disease activity, whereas secondary cystoid degeneration is the most relevant imaging marker for visual function. Clinically, PED emerged as trigger for consecutive vision loss in PRN treatment.
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Cross-sectionally, eyes with intraretinal fluid have worse visual acuity during anti-VEGF therapy, whereas those with subretinal fluid have better visual acuity.
“On a cross-sectional basis, the presence of intraretinal fluid is associated with worse visual acuity during anti-VEGF treatment while the presence of subretinal fluid is associated with better visual acuity.36–38”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [38]
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- Authors
- Schmidt-Erfurth, U., Waldstein, S. M., Deak, G.-G., Kundi, M., & Simader, C.
- Affiliations
- Medical University of Vienna (AT)
- Corresponding author
- Schmidt-Erfurth, Ursula
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 122
- Issue
- 4
- Pages
- 822-832
- ISSN
- 0161-6420 (ISSN-L)
- OpenAlex
- W1965018345
- Cited by
- 211
- References
- 42
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 15 · 2023: 24 · 2022: 16 · 2021: 33 · 2020: 21 · 2019: 11 · 2018: 11 · 2017: 25 · 2016: 19 · 2015: 5 · 2013: 1
- FWCI
- 19.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- neovascular age-related macular degeneration, pigment epithelial detachment, intraretinal cysts, subretinal fluid, anti-angiogenic therapy, ranibizumab, aflibercept, structure-function relationship, best-corrected visual acuity, vision loss, retinal morphology
- MeSH terms
- Ranibizumab, Aged, Aged, 80 and over, Blindness, Double-Blind Method, Female, Humans, Macular Edema, Male, Middle Aged, Prospective Studies, Recombinant Fusion Proteins, Retinal Detachment, Visual Acuity, Angiogenesis Inhibitors, Receptors, Vascular Endothelial Growth Factor, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Retinal Pigment Epithelium, Wet Macular Degeneration, Intravitreal Injections, Subretinal Fluid, Antibodies, Monoclonal, Humanized
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