Macular morphology and visual acuity in the Comparison of Age-related Macular Degeneration Treatments Trials
Open accessAbstract
Objective To describe the effects of treatment for 1 year with ranibizumab or bevacizumab on macular morphology and the association of macular morphology with visual acuity (VA) in eyes with neovascular age-related macular degeneration (AMD).Design Prospective cohort study within a randomized clinical trial.Participants Participants in the Comparison of Age-related Macular Degeneration Treatments Trials.Methods Participants were assigned randomly to treatment with ranibizumab or bevacizumab on a monthly or as-needed schedule. Optical coherence tomography (OCT), fluorescein angiography (FA), color fundus photography (FP), and VA testing were performed periodically throughout 52 weeks. Masked readers graded images. General linear models were applied to evaluate effects of time and treatment on outcomes.Main outcome measures Fluid type and location and thickness by OCT, size, and lesion composition on FP, FA, and VA.Results Intraretinal fluid (IRF), subretinal fluid (SRF), subretinal pigment epithelium fluid, and retinal, subretinal, and subretinal tissue complex thickness decreased in all treatment groups. A higher proportion of eyes treated monthly with ranibizumab had fluid resolution at 4 weeks, and the difference persisted through 52 weeks. At 52 weeks, there was little association between the presence of fluid of any type (without regard to fluid location) and the mean VA. However, at all time points, eyes with residual IRF, especially foveal IRF, had worse mean VA (9 letters) than those without IRF. Eyes with abnormally thin (<120 μm) or thick (>212 μm) retinas had worse VA than those with normal thickness (120-212 μm). At week 52, eyes with larger neovascular lesions or with foveal scar had worse VA than eyes without these features.Conclusions Anti-vascular endothelial growth factor (VEGF) therapy reduced lesion activity and improved VA in all treatment groups. At all time points, eyes with residual IRF had worse VA than those without. Eyes with abnormally thin or thick retinas, residual large lesions, and scar also had worse VA. Monthly ranibizumab dosing yielded more eyes with no fluid and an abnormally thin retina, although the long-term significance is unknown. These results have important treatment implications in eyes undergoing anti-VEGF therapy for neovascular AMD.Financial disclosure(s) Proprietary or commercial disclosure may be found after the references.
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Subretinal and retinal scarring are linked to severe vision loss and are natural outcomes of neovascular age-related macular degeneration.
“Subretinal and retinal scarring are associated with profound vision loss and are natural outcomes of neovascular age-related macular degeneration (nvAMD).1–4”
From Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials (2014) · cites this paper as [1]
The Results report that eyes with foveal scar had the lowest mean visual acuity and that scar developed in 18.6% of eyes after 52 weeks of anti-VEGF treatment (page not available in our copy). The Discussion describes fibrosis as a treatment-emergent adverse effect associated with the greatest reduction in visual acuity. These passages support the vision-loss association, but do not establish scarring as a natural outcome of untreated neovascular AMD. (LLM, conf=0.84)
Experimental — accuracy not yet measuredResponse to anti-VEGF therapy depends on factors including patient age, lesion characteristics, lesion duration, baseline visual acuity, and the presence of particular genotype risk alleles.
“The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles.”
From Defining response to anti-VEGF therapies in neovascular AMD (2015) · cites this paper as [14]
The Results (Correlation of Morphology with VA; page not specified) identify lesion size and foveal pathology as predictors of visual acuity after anti-VEGF treatment, supporting the lesion-characteristics portion. The paper does not establish patient age, lesion duration, baseline visual acuity, or genotype risk alleles as determinants of treatment response; measuring baseline acuity and setting an age eligibility criterion do not establish those relationships. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAn earlier CATT paper reported that worse visual acuity at one year was linked to intraretinal fluid on OCT, but not to subretinal or sub-RPE fluid.
“In a previous CATT report, we described a strong association between decreased visual acuity at the end of 1 year and the presence of intraretinal fluid but not subretinal or sub-RPE fluid on OCT.1”
From Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials (2014) · cites this paper as [1]
Morphological outcomes may vary from complete resolution of the lesion to a fibrovascular scar despite presumed adequate monitoring of the disease.
“Similarly, the morphological outcomes may also vary from complete resolution of the lesion to a fibrovascular scar despite presumed adequate monitoring of the disease.14”
From Defining response to anti-VEGF therapies in neovascular AMD (2015) · cites this paper as [14]
Retinal thinning to <120 microns was associated with worse visual acuity outcomes at 1 and 2 years.
“We previously reported that retinal thinning to <120 microns was associated with worse VA outcomes at 1 and 2 years.36,37”
From Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration (2016) · cites this paper as [36]
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 [36]
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Self-citation
- Authors
- Jaffe, G. J., Martin, D. F., Toth, C. A., Daniel, E., Maguire, M. G., Ying, G.-S., Grunwald, J. E., & Huang, J.
- Affiliations
- Duke University (US)
- Cleveland Clinic (US)
- University of Pennsylvania (US)
- Corresponding author
- Jaffe, Glenn J.
- ORCID
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 120
- Issue
- 9
- Pages
- 1860-1870
- ISSN
- 0161-6420 (ISSN-L)
- PMC
- PMC3737287
- OpenAlex
- W2074575505
- Cited by
- 294
- References
- 15
- Citations by year
- 2026: 9 · 2025: 28 · 2024: 26 · 2023: 16 · 2022: 29 · 2021: 38 · 2020: 27 · 2019: 21 · 2018: 23 · 2017: 24 · 2016: 17 · 2015: 15 · 2014: 15 · 2013: 5
- FWCI
- 17.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (U10EY017825, U10EY017826, U10EY017823, U10EY017828)
- 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, ranibizumab, bevacizumab, anti-VEGF therapy, macular morphology, visual acuity, intraretinal fluid, subretinal fluid, retinal thickness, lesion activity, macular edema
- MeSH terms
- Bevacizumab, Ranibizumab, Fluorescein Angiography, Follow-Up Studies, Humans, Macula Lutea, Macular Degeneration, Prospective Studies, Visual Acuity, Angiogenesis Inhibitors, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Subretinal Fluid, Antibodies, Monoclonal, Humanized
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