The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index; 4 of the 21 sources its claims cite were checked for support.
Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials
Open accessAbstract
Objective To describe risk factors for scar in eyes treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD). Design Prospective cohort study within a randomized clinical trial. Participants Patients with no scar on color fundus photography (CFP) or fluorescein angiography (FA) at enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Methods Eyes were assigned to ranibizumab or bevacizumab treatment and to 1 of 3 dosing regimens for 2 years. Masked readers assessed CFP and FA. Baseline demographic characteristics, visual acuity, morphologic features on photography and optical coherence tomography (OCT), and genotypes associated with AMD risk were evaluated as risk factors using adjusted hazard ratios (aHRs) and associated 95% confidence intervals (CIs). Scars were classified as fibrotic with well-demarcated elevated mounds of yellowish white tissue or nonfibrotic with discrete flat areas of hyperpigmentation with varying amounts of central depigmentation. Main outcome measures Scar formation. Results Scar developed in 480 of 1059 eyes (45.3%) by 2 years. Baseline characteristics associated with greater risk of scarring were predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4-3.9) versus occult CNV, blocked fluorescence (aHR, 1.4; CI, 1.1-1.8), foveal retinal thickness >212 μm (aHR, 2.4; CI, 1.7-3.6) versus <120 μm, foveal subretinal tissue complex thickness >275 μm (aHR, 2.4; CI, 1.7-3.6) versus ≤75 μm, foveal subretinal fluid (aHR, 1.5; CI, 1.1-2.0) versus no subretinal fluid, and subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3-2.3) versus no SHRM. Eyes with elevation of the retinal pigment epithelium had lower risk (aHR, 0.6; CI, 0.5-0.8) versus no elevation. Drug, dosing regimen, and genotype had no statistically significant association with scarring. Fibrotic scars developed in 24.7% of eyes, and nonfibrotic scars developed in 20.6% of eyes. Baseline risk factors for the scar types were similar except that eyes with larger lesion size or visual acuity <20/40 were more likely to develop fibrotic scars. Conclusions Approximately half of eyes enrolled in CATT developed scar by 2 years. Eyes with classic neovascularization, a thicker retina, and more fluid or material under the foveal center of the retina are more likely to develop scar.
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Claims the paper makes
57 Own result · 8 No full text of the sources · 8 Own interpretation · 2 Supported so far · 2 Sources not found · 2 Own method · 1 Supported · 1 Partly supported · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“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”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
What the sources say
- Supportedcites [1] Jaffe, 2013, Macular morphology and visual acuity in the Comparison of Age-related Macular Degeneration Treatments Trials, Ophthalmology source
The Results (Correlation of Morphology with VA; page not supplied) report substantially worse visual acuity at 52 weeks in eyes with intraretinal fluid. They report little impact on mean visual acuity from subretinal or sub-RPE fluid at that time, matching the attributed finding. (LLM, conf=0.91)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Paradoxically, in eyes with proliferative diabetic retinopathy treated with anti-VEGF injections, there is increased fibrosis caused by imbalances between connective tissue growth factor and VEGF.32,33”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
What the sources say
- Supportedcites [32] Van Geest, 2012, A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy, Br J Ophthalmol source
The Discussion reports increased fibrosis after intravitreal bevacizumab in patients with proliferative diabetic retinopathy. It also states that anti-VEGF therapy shifts the CTGF/VEGF ratio, potentially causing an angiofibrotic switch and accelerated fibrosis. No page number is provided in the copy. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [33] Kuiper, 2006, Association of connective tissue growth factor with fibrosis in vitreoretinal disorders in the human eye, Arch Ophthalmol source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The cumulative incidence rates of fibrotic scar at 1 and 2 years were 0.19 (95% CI, 0.17–0.22) and 0.26 (95% CI, 0.24–0.29), respectively.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plainn = 262- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Risk was greater for eyes with SHRM (aHR, 1.7; 95% CI, 1.3–2.3)”
- Also stated in: § Results · plain
“subretinal hyperreflective material (SHRM) (aHR, 1.7; CI, 1.3–2.3) versus no SHRM”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results
plaincorrelationaln = 1,059- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the end of 1 year, 339 eyes (32.0%) had developed a scar”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results
plainn = 339- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The cumulative incidence rates of nonfibrotic scar at 1 and 2 years were 0.13 (95% CI, 0.11–0.15) and 0.24 (95% CI, 0.21–0.27), respectively.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plainn = 218- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eyes with predominantly classic CNV on FA (aHR, 3.1; 95% CI, 2.4–3.9) and minimally classic CNV on FA (aHR, 2.3; 95% CI, 1.8–3.0) had higher risk when compared with eyes with only occult CNV.”
- Also stated in: § Results · plain
“predominantly classic choroidal neovascularization (CNV) (aHR, 3.1; CI, 2.4–3.9) versus occult CNV”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results
plaincorrelationaln = 1,059- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At the end of 2 years, 218 subjects (20.6%) developed nonfibrotic scar”
- Also stated in: § Results · plain
“nonfibrotic scars developed in 20.6% of eyes.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plainn = 218- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Risk of scarring increased with greater subretinal tissue complex thickness (P < 0.0001).”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eyes with retinal thickness at the foveal center >212 μm on OCT (aHR, 2.4; 95% CI, 1.7–3.6) or retinal thickness between 120 and 212 μm (aHR, 1.6; 95% CI, 1.1–2.3) had higher risk than eyes with retinal thickness <120 μm.”
- Also stated in: § Results · plain
“foveal retinal thickness >212 μm (aHR, 2.4; CI, 1.7–3.6) versus <120 μm”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results
plaincorrelationaln = 1,059- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Results · plain
- Probably not a substantial claim. 10
- It may state two separate claims as one. 15
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Scar that develops after radiotherapy for nvAMD has been described.6,7”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Abstract > Conclusions
What the sources say
- Not checked — no full text of the sourcecites [6] 2004, The Age-Related Macular Degeneration Radiotherapy Trial (AMDRT): one year results from a pilot study, Am J Ophthalmol source
- Supportedcites [7] Trikha, 2011, Ten-year follow-up of eyes treated with stereotactic fractionated external beam radiation for neovascular age-related macular degeneration, Retina source
The Results (page not provided) report a disciform macular scar in 10 of 33 eyes (30%) at follow-up after radiotherapy for neovascular AMD. This supports the claim that scar formation after treatment has been described; it does not establish that radiation caused the scars. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Subretinal and retinal scarring are associated with profound vision loss and are natural outcomes of neovascular age-related macular degeneration (nvAMD).1–4”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Abstract > Conclusions
What the sources say
- Partly supportedcites [1] Jaffe, 2013, Macular morphology and visual acuity in the Comparison of Age-related Macular Degeneration Treatments Trials, Ophthalmology sourceExperimental — accuracy not yet measured
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)
- Not checked — no full text of the sourcecites [2] Bressler, 1988, Natural course of poorly defined choroidal neovascularization associated with macular degeneration, Arch Ophthalmol source
- Not checked — no full text of the sourcecites [3] Wong, 2008, The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis, Ophthalmology source
- Not checked — no full text of the sourcecites [4] Pauleikhoff, 2005, Neovascular age-related macular degeneration: natural history and treatment outcomes, Retina source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mean thickness of the subretinal tissue complex at the foveal center was greatest (168 μm; standard error [SE], 8.7) for eyes with fibrotic scars, less (148 μm; SE, 14.5) for eyes with nonfibrotic scars, and least (119 μm; SE, 4.1) for eyes with no scar at the foveal center (P < 0.0001).”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After 1 year, scar developed in one third of the eyes treated with anti-VEGF drugs, and by 2 years, approximately half the eyes developed scar.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The type of CNV, as determined by FA at baseline, predicted scar formation. Scars were least likely to develop in eyes with occult CNV only. When occult CNV is admixed with the classic type, the risk doubles. The risk triples when the angiographic phenotype subset is composed predominantly of classic CNV.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The greater propensity for classic CNV to transform into a scar is illustrated in Figure 1C, where the minimally classic lesion’s small, centrally located classic CNV changes into a fibrotic scar in the CFP at 2 years, whereas the larger occult portion of the CNV lesion, although active, does not transform to a CFP-visible scar.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
boosteddirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eyes with classic CNV and eyes with SHRM were at higher risk of both types of scar.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast, among 926 patients who did not have a fibrotic scar in the fellow eye at baseline, fibrotic scar developed in 226 (24%), nonfibrotic scar developed in 201 (22%), and no scar developed in 499 (54%; P = 0.06).”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plainn = 926- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although a larger area of CNV was associated with increased risk of fibrotic scar, it was associated with decreased risk of nonfibrotic scar.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The type of anti-VEGF therapy and dosing regimen did not strongly influence scar development.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eyes with classic CNV and eyes with SHRM were at higher risk of both types of scar.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At 2 years, among 133 patients with a scar in the fellow eye at baseline, 36 (27%) had a fibrotic scar, 17 (13%) had a nonfibrotic scar, and 80 (60%) had no scar in the study eye.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Results > Fibrotic Scars and Nonfibrotic Scars
plainn = 133- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The CATT was registered with ClinicalTrials.gov (NCT00593450).”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Methods > Enrollment and Follow-up of Subjects
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“nearly all patients now receive treatment with intravitreal injections of drugs that target vascular endothelial growth factor (VEGF).8”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Abstract > Conclusions
What the sources say
- Not checked — no full text of the sourcecites [8] Curtis, 2012, Treatment patterns for neovascular age-related macular degeneration: analysis of 284 380 Medicare beneficiaries, Am J Ophthalmol source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“P values for the genetic analysis were adjusted to control for the false discovery rate.14”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Methods > Statistical Methods
What the sources say
- Not checked — no full text of the sourcecites [14] Benjamini, 1995, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J R Stat Soc Series B (Methodol) source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rarity of large fibrotic scars in CATT suggests that extensive fibrosis is aborted or delayed by anti-VEGF therapy.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This observation could be related to the relatively smaller RAP lesions or their common association with occult CNV, which forms fewer scars than classic CNV.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Bevacizumab is reported to have antifibrotic activity that reduces scar formation in glaucoma filtration surgery.29–31”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
What the sources say
- Not checked — no full text of the sourcecites [29] O'Neill, 2010, Antifibrotic activity of bevacizumab on human Tenon's fibroblasts in vitro, Invest Ophthalmol Vis Sci source
- Not checked — no full text of the sourcecites [30] Li, 2009, Inhibition of vascular endothelial growth factor reduces scar formation after glaucoma filtration surgery, Invest Ophthalmol Vis Sci source
- Not checked — no full text of the sourcecites [31] Memarzadeh, 2009, Postoperative use of bevacizumab as an antifibrotic agent in glaucoma filtration surgery in the rabbit, Invest Ophthalmol Vis Sci source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The blocked fluorescence could have been the result of deep sub-RPE hemorrhage or deep fibrosis not visible on color photographs.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In a study that used fetal and adult wound-healing murine models, scar-free fetal wounds had lower VEGF levels and were less vascular than fibrotic fetal wounds, and the scar-free phenotype was converted to a scar-forming phenotype when exogenous VEGF was added.28 When VEGF was neutralized in adult wounds, vascularity was reduced, and scar formation was decreased.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
What the sources say
- Not matchedcites [28] Wilgus, 2000, Regulation of scar formation by vascular endothelial growth factor, Lab Invest
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“The results showed that combination therapy more effectively than monotherapy improved visual acuity and better eliminated SHRM.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
What the sources say
- Not matchedcites Dugal PU, Reichel E, Boyer DS, et al.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is possible that intravitreal anti-VEGF treatment decreases scar formation in purely occult lesions by confining the CNV to the sub-RPE space, thereby stopping progression to classic CNV.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is possible that with a longer period of observation, subretinal fluid also could affect visual acuity through scar formation.”
§ Risk of Scar in the Comparison of Age-related Macular Degeneration Treatments Trials > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
The factors associated with scarring after anti-VEGF therapy had not been described before this study.
“The factors associated with scarring after anti-VEGF therapy have not been described.”
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“We had shown earlier that during the first two years of treatment of nAMD with anti-VEGF drugs, the risk factors present at baseline for developing a scar included predominantly classic type of CNV, blocked fluorescence, thicker retina, larger foveal subretinal tissue complex thickness, foveal subretinal fluid and subretinal hyperreflective material.16”
From Development and Course of Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials (2018) · cites this paper as [16]
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · cited 1×
“P values for the genetic analysis were adjusted to control for the false discovery rate.(14) All data analyses were performed using SAS version 9.”
MethodRanibizumab for Neovascular Age-Related Macular Degeneration
Rosenfeld, P. J., Brown, D. M., Heier, J. S., Boyer, D. S., Kaiser, P. K., Chung, C. Y., & Kim, R. Y. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054481 · Cited by 5,886
Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration
Brown, D. M., Kaiser, P. K., Michels, M., Soubrane, G., Heier, J. S., Kim, R. Y., Sy, J. P., & Schneider, S. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa062655 · Cited by 3,522
Ranibizumab and bevacizumab for neovascular age-related macular degeneration
(2011) · New England Journal of Medicine · doi:10.1056/nejmoa1102673 · Cited by 2,669 · cited 2×
“Patients were examined approximately every 28 days.(10) Stereoscopic CFP, FA, and OCT scans were obtained at baseline, 1 year, and 2 years.”
Age-related Macular Degeneration Histopathologic Studies
Green, W. R., & Enger, C. (1993) · Ophthalmology · doi:10.1016/s0161-6420(93)31466-1 · Cited by 757
Age-related macular degeneration
Bressler, N. M., Bressler, S. B., & Fine, S. L. (1988) · Survey of Ophthalmology · doi:10.1016/0039-6257(88)90052-5 · Cited by 710
Self-citationThe Natural History and Prognosis of Neovascular Age-Related Macular Degeneration
Wong, T., Chakravarthy, U., Klein, R., Mitchell, P., Zlateva, G., Buggage, R., Fahrbach, K., Probst, C., & Sledge, I. (2008) · Ophthalmology · doi:10.1016/j.ophtha.2007.03.008 · Cited by 601
ANCHOR STUDY GROUP. RANIBIZUMAB VERSUS VERTEPORFIN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Brown, D., Kaiser, P. K., Michels, M., Soubrane, G., Heier, J. S., & Kim, R. Y. (2006) · Cited by 382
Kaiser, P. K., Brown, D. M., Zhang, K., Hudson, H. L., Holz, F. G., Shapiro, H., Schneider, S., & Acharya, N. R. (2007) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2007.08.012 · Cited by 361
NATURAL HISTORY OF SUBFOVEAL SUBRETINAL HEMORRHAGE IN AGERELATED MACULAR DEGENERATION
Avery, R. L., Fekrat, S., Hawkins, B. S., & Bressler, N. M. (1996) · Retina · doi:10.1097/00006982-199616030-00001 · Cited by 335 · cited 1×
“For example, in one retrospective study, progressive visual acuity loss occurred in 41 eyes of 40 patients with subfoveal subretinal hemorrhage that comprised more than 50% of the CNV lesion.(36) In that report, it was not clear whether the scar formation was directly a result of the more extensive hemorrhage.”
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Items 101–200 of 328
Freund, K. B., Staurenghi, G., Jung, J. J., Zweifel, S. A., Cozzi, M., Hill, L., Blotner, S. D., Tsuboi, M., & Gune, S. (2022) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-022-05586-w · Cited by 26
Salas, A., Badia, A. C., Fontrodona, L., Zapata, M. Á., García‐Arumí, J., & Duarri, A. (2023) · Biomedicines · doi:10.3390/biomedicines11092445 · Cited by 29
“This is because 10% of patients do not react to anti-VEGF, and 50% of those who receive long-term treatment experience considerable vision loss within 5 years, primarily due to atrophy and the onset of subretinal fibrosis [14,15].”
BackgroundArtificial intelligence in assessing progression of age-related macular degeneration
Frank‐Publig, S., Birner, K., Riedl, S., Reiter, G. S., & Schmidt-Erfurth, U. M. (2024) · Eye · doi:10.1038/s41433-024-03460-z · Cited by 28
Toth, C. A., Tai, V., Pistilli, M., Chiu, S. J., Winter, K. P., Daniel, E., Grunwald, J. E., Jaffe, G. J., Martin, D. F., Ying, G., et al. (2018) · Ophthalmology Retina · doi:10.1016/j.oret.2018.11.011 · Cited by 25
“001 3 (1, 7) Photoreceptor loss Eyes 25 (100) 42 (95) 4 (57) 23 (88) 0.”
BackgroundMethodInfluentialSelf-citationCore, J. Q., Pistilli, M., Daniel, E., Grunwald, J. E., Toth, C. A., Jaffe, G. J., Hua, P., Martin, D. F., Ying, G., & Maguire, M. G. (2021) · Ophthalmology Retina · doi:10.1016/j.oret.2021.06.003 · Cited by 25
Self-citationMyeloid cells in retinal and brain degeneration
Guo, M., Schwartz, T. D., Dunaief, J. L., & Cui, Q. N. (2021) · FEBS Journal · doi:10.1111/febs.16177 · Cited by 25
Bo, Q., Shen, M., Xiao, M., Liang, J., Zhai, Y., Zhu, H., Jiang, M., Wang, F., Luo, X., & Sun, X. (2020) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2019.0112 · Cited by 23
“The increased population of macrophages in the circulation may partly explain why patients with various anti-VEGF therapy are more likely to develop SRF. 6,33 Another vital mechanism associated with the antifibrotic effect of 3-MA might be its inhibitory role in M2 macrophage polarization.”
InfluentialDifferent roles played by periostin splice variants in retinal neovascularization
Nakama, T., Yoshida, S., Ishikawa, K., Kobayashi, Y., Abe, T., Kiyonari, H., Shioi, G., Katsuragi, N., Ishibashi, T., Morishita, R., et al. (2016) · Experimental Eye Research · doi:10.1016/j.exer.2016.10.012 · Cited by 23
Li, D., Yuan, D., Shen, H., Mao, X., Yuan, S., & Liu, Q. (2019) · PubMed Central · Cited by 23
Yang, Q., Cai, Y., Ma, Q., Xiong, A., Xu, P., Zhang, Z., Xu, J., Zhou, Y., Liu, Z., Zhao, D., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adk3868 · Cited by 22
Zhang, J., Sheng, X., Ding, Q., Wang, Y., Zhao, J., & Zhang, J. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01642 · Cited by 23
Shimizu, H., Yamada, K., Suzumura, A., Kataoka, K., Takayama, K., Sugimoto, M., Terasaki, H., & Kaneko, H. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.11.21 · Cited by 22
Finn, A. P., Pistilli, M., Tai, V., Daniel, E., Ying, G., Maguire, M. G., Grunwald, J. E., Martin, D. F., Jaffe, G. J., & Toth, C. A. (2020) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2020.11.002 · Cited by 23
“(SHRM), greater retinal thickness, and greater subretinal tissue complex thickness (defined as SHRM, retinal pigment epithelium [RPE], and RPE elevation) were more common in eyes with fibrotic scar (FS).(6) Correlating photographic and macula-wide characteristics on OCT with the development of MA (the term that will b…”
BackgroundResultInfluentialSelf-citationCore, J. Q., Pistilli, M., Hua, P., Daniel, E., Grunwald, J. E., Toth, C. A., Jaffe, G. J., Martin, D. F., Maguire, M. G., Ying, G., et al. (2022) · Ophthalmology Retina · doi:10.1016/j.oret.2022.03.024 · Cited by 23
Self-citationHigashijima, F., Hasegawa, M., Yoshimoto, T., Kobayashi, Y., Wakuta, M., & Kimura, K. (2023) · Frontiers in Ophthalmology · doi:10.3389/fopht.2022.1060087 · Cited by 24
“3%) during the 2-year treatment course and that SHRM is a risk factor for fibrosis (4) Subretinal fibrosis has a higher incidence in nAMD patients with active CNV and is thought”
BackgroundKim, J. M., Kang, S. W., Son, D. Y., & Bae, K. (2017) · Retina · doi:10.1097/iae.0000000000001435 · Cited by 23
Daniel, E., Maguire, M. G., Grunwald, J. E., Toth, C. A., Jaffe, G. J., Martin, D. F., & Ying, G. (2020) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2020.0437 · Cited by 22
Self-citationChen, M., Yang, N., Lechner, J., Tóth, L., Hogg, R. E., Silvestri, G., Chakravarthy, U., & Xu, H. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00205-w · Cited by 22
Liu, Y., Noda, K., Murata, M., Wu, D., Kanda, A., & Ishida, S. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9072242 · Cited by 21
“Subretinal fibrosis has recently been revealed as a key pathological event associated with poor visual acuity in CNV; basically a form of fibrovascular proliferation consisting of both vascular and fibrous components, the latter of which is likely resistant to anti-VEGF therapy in clinical practice [2,3].”
BackgroundZhang, C., Qin, S., Xie, H., Qiu, Q., Wang, H., Zhang, J., Luo, D., & Zhang, J. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.10.14 · Cited by 21
Animal model of subretinal fibrosis without active choroidal neovascularization
Zandi, S., Li, Y., Jahnke, L., Schweri-Olac, A., Ishikawa, K., Wada, I., Nakao, S., Zinkernagel, M. S., & Enzmann, V. (2023) · Experimental Eye Research · doi:10.1016/j.exer.2023.109428 · Cited by 21
Pereira, D. S., Maturi, R. K., Akita, K., Mahesh, V., Bhisitkul, R. B., Nishihata, T., Sakota, E., Ali, Y., Nakamura, E., Bezwada, P., et al. (2023) · Eye · doi:10.1038/s41433-023-02848-7 · Cited by 22
“Poor vision and persistent exudation are often associated with macular atrophy and submacular fibrotic scar formation despite d-1 ifferent anti-VEGF treatments [10].”
BackgroundMaguire, M. G., Ying, G., Jaffe, G. J., Toth, C. A., Daniel, E., Grunwald, J. E., Martin, D. F., & Hagstrom, S. A. (2016) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2016.0669 · Cited by 21
Self-citationLeung, K. F. C., Downes, S. M., & Chong, V. N. (2018) · Vision · doi:10.3390/vision2010005 · Cited by 21
Ma, X., Wu, W., Hara, M., Zhou, J., Panzarin, C., Schafer, C. M., Griffin, C. T., Cai, J., Ma, J., & Takahashi, Y. (2024) · Communications Biology · doi:10.1038/s42003-024-06773-7 · Cited by 22
Principal Cause of Poor Visual Acuity after Neovascular Age-Related Macular Degeneration
Okeagu, C. U., Agrón, E., Vitale, S., Domalpally, A., Chew, E. Y., & Keenan, T. D. L. (2020) · Ophthalmology Retina · doi:10.1016/j.oret.2020.09.025 · Cited by 21
Prognostic Optical Coherence Tomography Biomarkers in Neovascular Age-Related Macular Degeneration
Nawash, B. S., Ong, J., Driban, M., Hwang, J. C., Chen, J., Selvam, A., Mohan, S., & Chhablani, J. K. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12093049 · Cited by 20
“SHRM also increases the risk of scar formation in eyes with nAMD, which leads to further retinal disruption and decreased visual acuity [41].”
BackgroundWarther, D., Xiao, Y. Z., Li, F., Wang, Y., Huffman, K., Freeman, W. R., Sailor, M. J., & Cheng, L. (2018) · Drug Delivery · doi:10.1080/10717544.2018.1486474 · Cited by 19
“…intravitreal injections of anti-VEGF antibodies has demonstrated that disciform scarring and inner retina atrophy at the macula resulting in poor vision is an inevitable outcome (Batman & Ozdamar, 2010; Hwang et al., 2011; Daniel et al., 2014; Young et al., 2014) in a large number of patients.”
BackgroundSecretogranin III as a novel target for the therapy of choroidal neovascularization
LeBlanc, M. E., Wang, W., Ji, Y., Tian, H., Liu, D., Zhang, X., & Li, W. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2019.01.009 · Cited by 20
Kim, J. H., Kim, J. W., Kim, C. G., & Lee, D. W. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9041145 · Cited by 21
“Fibrotic scars [31] and GA were identified using fundus photographs and OCT images.”
BackgroundMethodConnective Tissue Growth Factor: Regulation, Diseases, and Drug Discovery
Ren, M., Yao, S., Chen, T., Luo, H., Tao, X., Jiang, H., Yang, X., Zhang, H., Yu, S., Wang, Y., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094692 · Cited by 22
“In the late clinical stages, CTGF contributes to the progression of vascular fibrosis [90,91].”
BackgroundKim, J. H., Chang, Y. S., Kim, J. W., Kim, C. G., Lee, D. W., & Kim, Y. J. (2017) · Retina · doi:10.1097/iae.0000000000001845 · Cited by 19
Siedlecki, J., Asani, B., Wertheimer, C. M., Hillenmayer, A., Ohlmann, A., Priglinger, C., Priglinger, S., Wolf, A., & Eibl-Lindner, K. H. (2018) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-018-3987-8 · Cited by 18
Shen, W., Lee, S., Yam, M., Zhu, L., Zhang, T., Pye, V. J., Mathai, A. E., Shibagaki, K., Zhang, J.-Z., Matsugi, T., et al. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-25628 · Cited by 19
“Drugs that target VEGF effectively treat blood vessel leak and neovascularization but demonstrate little effect on retinal fibrosis.(1,2) A major challenge in treating nAMD is to concurrently inhibit subretinal neovascularization and prevent fibrosis.”
BackgroundDaftarian, N., Rohani, S., Kanavi, M. R., et al. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2019.04.027 · Cited by 19
Heier, J. S., Wykoff, C. C., Waheed, N. K., Kitchens, J. W., Patel, S. S., Vitti, R., Perlee, L. T., Chu, K. W., Leal, S., Asmus, F., et al. (2019) · Ophthalmology · doi:10.1016/j.ophtha.2019.09.021 · Cited by 19
Anti-angiogenesis by dual action of R5K peptide conjugated itraconazole nanoparticles
Chittasupho, C., Kengtrong, K., Chalermnithiwong, S., & Sarisuta, N. (2020) · AAPS PharmSciTech · doi:10.1208/s12249-019-1568-8 · Cited by 18
THE RAP STUDY, REPORT 5: REDISCOVERING MACULAR NEOVASCULARIZATION TYPE 3
Najeeb, B. H., Deák, G. G., Mylonas, G., Sacu, S., Gerendas, B. S., & Schmidt-Erfurth, U. M. (2021) · Retina · doi:10.1097/iae.0000000000003330 · Cited by 19
Intravitreal injection of triptolide attenuates subretinal fibrosis in laser-induced murine model
Lai, K., Li, Y., Li, L., Gong, Y., Huang, C., Zhang, Y., Cheng, L. Z., Xu, F., Zhao, H., Li, C., et al. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153747 · Cited by 18
Palko, S. I., Saba, N. J., Bargagna‐Mohan, P., & Mohan, R. (2022) · Journal of Neuroscience Research · doi:10.1002/jnr.25158 · Cited by 19
“Age- related macular degeneration (AMD) is the leading cause of vision loss for the aging population in developed nations (Ambati et al., 2003).”
BackgroundInfluentialTeo, K. Y. C., Zhao, J., Ibrahim, F. I., Fenner, B. J., Chakravarthy, U., & Cheung, C. M. G. (2023) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2023.12.011 · Cited by 18
Hyperreflective material as a biomarker in neovascular age-related macular degeneration
Casalino, G., Scialdone, A., Bandello, F. M., & Chakravarthy, U. (2020) · Expert Review of Ophthalmology · doi:10.1080/17469899.2020.1745062 · Cited by 18
Chen, L., Cao, D., Messinger, J. D., Ach, T., Ferrara, D., Freund, K. B., & Curcio, C. A. (2021) · Experimental Eye Research · doi:10.1016/j.exer.2021.108882 · Cited by 18
Effect of nintedanib thermo-sensitive hydrogel on neovascularization in alkali burn rat model
Gong, Y. Q. (2020) · International Journal of Ophthalmology · doi:10.18240/ijo.2020.06.04 · Cited by 17
Roberts, P. K., Schranz, M. W., Motschi, A. R., Desissaire, S., Häcker, V., Pircher, M., Sacu, S., Buehl, W., Hitzenberger, C. K. F., & Schmidt-Erfurth, U. M. (2021) · Translational Vision Science & Technology · doi:10.1167/tvst.10.14.1 · Cited by 17
Aljundi, W., Daas, L., Suffo, S., Seitz, B., & Abdin, A. D. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16040470 · Cited by 19
Periostin in vitreoretinal diseases
Yoshida, S., Nakama, T., Ishikawa, K., Nakao, S., Sonoda, K., & Ishibashi, T. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2651-5 · Cited by 17
New Therapies of Neovascular AMD—Beyond Anti-VEGFs
Yerramothu, P. (2018) · Vision · doi:10.3390/vision2030031 · Cited by 21
“Long term administration of intravitreal anti-VEGF injections is associated with 77 increased risk of developing retinal scaring and geographic atrophy in nAMD patients 2 to 78 5 years after initiating treatment [30, 31].”
BackgroundTYPICAL POLYPOIDAL CHOROIDAL VASCULOPATHY AND POLYPOIDAL CHOROIDAL NEOVASCULARIZATION
Jang, J. W., Kim, J. M., Kang, S. W., et al. (2018) · Retina · doi:10.1097/iae.0000000000002259 · Cited by 17
Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model
Ren, H.-W., Wang, Y., Zhang, X., et al. (2023) · International Journal of Ophthalmology · doi:10.18240/ijo.2023.09.12 · Cited by 16
Restoration of Mesenchymal RPE by Transcription Factor-Mediated Reprogramming
Shih, Y.-H., Radeke, M. J., Radeke, C. M., & Coffey, P. J. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20018 · Cited by 15
González-Buendía, L., Delgado‐Tirado, S., Sanabria, M. R., Fernández, I., & Coco, R. M. (2017) · BMC Ophthalmology · doi:10.1186/s12886-017-0544-x · Cited by 16
de Carvalho, E. R., Verwoert, M. T., Vogels, I. M. C., Reits, E. A., Noorden, C. J. F. V., Klaassen, I., & Schlingemann, R. O. (2018) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2018.01.005 · Cited by 16
“Subretinal fibrosis, however, is a common ensuing process of CNV membrane formation, occurring in approximately half of anti-VEGF treated eyes [7,10,14].”
BackgroundZhang, Y., Zhao, L., Wang, L., Yang, X., Zhou, A., & Wang, J. (2018) · Europe PMC (PubMed Central) · Cited by 15
Brandli, A. A., Khong, F. L., Kong, R. C. K., Kelly, D. J., & Fletcher, E. L. (2022) · Scientific Reports · doi:10.1038/s41598-022-04845-4 · Cited by 18
Wang, N., Wang, Y., Zhang, L., Yang, W., & Fu, S. (2025) · Biomolecules · doi:10.3390/biom15060771 · Cited by 17
“However, a high incidence of subretinal scar formation (fibrosis) post-treatment can precipitate permanent macular visual system dysfunction [19].”
Jia, H., Lu, B., Zhao, Z. Y., Yang, Y., Wang, F., Zhou, M., & Sun, X. (2022) · Eye and Vision · doi:10.1186/s40662-022-00287-1 · Cited by 15
“[31, 32] found that patients with type 2 NVs (e.”
BackgroundRosa, I. D., Ohayon, A., Semoun, O., Mière, A., Jung, C., Capuano, V., Cirafici, P., & Souied, E. H. (2020) · Retina · doi:10.1097/iae.0000000000002771 · Cited by 15
Tanaka, M., Kakihara, S., Hirabayashi, K., Imai, A., Toriyama, Y., Iesato, Y., Sakurai, T., Kamiyoshi, A., Ichikawa‐Shindo, Y., Kawate, H., et al. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.12.012 · Cited by 15
Zhou, L., Chu, W.-J., Yang, L., & Xu, H. C. (2021) · International Journal of Ophthalmology · doi:10.18240/ijo.2021.03.03 · Cited by 15
Mast cells promote choroidal neovascularization in a model of age-related macular degeneration
Dabouz, R., Abram, P., Rivera, J. C., & Chemtob, S. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03229-x · Cited by 16
“A notable concern is that some patients might develop geographic atrophy as a response to the anti-VEGF treatment [4, 5], and there is still potential progression to fibrotic scars [6].”
BackgroundAsani, B., Holmberg, O., Schiefelbein, J. B., Hafner, M., Herold, T., Spitzer, H., Siedlecki, J., Kern, C., Kortuem, K., Frishberg, A., et al. (2024) · Eye · doi:10.1038/s41433-024-03264-1 · Cited by 14
Yu, E., Kim, H., Park, H., Hong, J. H., Jin, J., Song, Y., Woo, J. M., Min, J. K., & Yun, J. (2024) · Scientific Reports · doi:10.1038/s41598-024-76258-4 · Cited by 19
Balaskas, K., Ali, Z. C., Saddik, T., Gemenetzi, M. K., Patel, P. J., & Aslam, T. M. (2018) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.13367 · Cited by 14
Cicinelli, M. V., Torrioli, E., Franca, L. L., Agrawal, H., Barthelmes, D., Chhablani, J. K., Chowers, I., Foa, N., Goldstein, M., Mansour, A. M., et al. (2022) · Ophthalmology Retina · doi:10.1016/j.oret.2022.12.002 · Cited by 13
Exploring the role of granzyme B in subretinal fibrosis of age-related macular degeneration
Gill, K., Yoo, H.-S., Chakravarthy, H., Granville, D. J., & Matsubara, J. A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1421175 · Cited by 14
“Although anti-VEGF therapy can stabilize or improve vision, studies have demonstrated that even after treatment, subretinal fi brosis developed in approximately 45-70% of eyes (12, 13), indicating that the conventional treatment for nAMD does not address subretinal fi brosis.”
BackgroundInfluentialWang, Y., Fang, Q., Zhang, C., Chen, Y., Gou, T., Cai, Q., Yin, H., Gao, Y., Feng, Y., Qiu, S., et al. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.108417 · Cited by 13
Ma, X., Takahashi, Y., Wu, W., Chen, J., Dehdarani, M., Liang, W., Shin, Y., Benyajati, S., & Ma, J. (2021) · The FASEB Journal · doi:10.1096/fj.202101334r · Cited by 12
Asani, B., Siedlecki, J., Wertheimer, C. M., Liegl, R. G.-H., Wolf, A., Ohlmann, A., Priglinger, S. G., & Priglinger, C. (2022) · BMC Ophthalmology · doi:10.1186/s12886-022-02334-w · Cited by 12
“In this context, pericyte inhibition using rapamycin might also modulate fibrotic responses of CNV generated in the macula, a frequent cause of serious vision loss in nAMD [47].”
BackgroundRomano, F., Boon, C. J. F., Invernizzi, A., et al. (2023) · Retina · doi:10.1097/iae.0000000000003951 · Cited by 11
Csincsik, L., Cheung, C. M. G., Bannon, F. J., Pető, T., & Chakravarthy, U. (2025) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2025.01.011 · Cited by 12
Rieck, C., Mai, C., Eisentraut, L., & Buettner, R. (2025) · IEEE Access · doi:10.1109/access.2025.3606334 · Cited by 17
“Since the characteristics of this clinical picture are not necessarily consistent, this disease is equally difficult for the model to classify [43].”
Cicinelli, M. V., Franca, L. L., Felice, E. D., Rabiolo, A., Marchese, A., Parodi, M. B., Introini, U., & Bandello, F. M. (2022) · Ophthalmology Retina · doi:10.1016/j.oret.2022.06.009 · Cited by 11
Li, L., Cao, X., Huang, L., et al. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17730 · Cited by 11
Gabrielle, P., Nguyen, V., Arnold, J., Bhandari, S., Viola, F., Tigchelaar-Besling, O. A. M., Garay‐Aramburu, G., O’Toole, L., Cheung, C. M. G., Barthelmes, D., et al. (2021) · Translational Vision Science & Technology · doi:10.1167/tvst.10.13.5 · Cited by 10
“1,9,10,19 Loss to follow-up may introduce bias because eyes that discontinue may drop out because of poor outcomes or sometimes because of good response to treatment and stabilization of vision.”
Automated large-scale prediction of exudative AMD progression using machine-read OCT biomarkers
Rudas, Á., Chiang, J. N., Corradetti, G., Rakocz, N., Avram, O., Halperin, E., & Sadda, S. R. (2023) · PLOS Digital Health · doi:10.1371/journal.pdig.0000106 · Cited by 10
BRIDGE ARCH-SHAPED SEROUS RETINAL DETACHMENT IN AGE-RELATED MACULAR DEGENERATION
Fajnkuchen, F., Cohen, S. Y., Thay, N., Ayrault, S., Delahaye-Mazza, C., Grenet, T., Nghiem‐Buffet, S., Quentel, G., & Giocanti‐Auregan, A. (2015) · Retina · doi:10.1097/iae.0000000000000746 · Cited by 11
“Approximately 32% of patients at 1 year and 45% of patients at 2 years developed subretinal fibrosis in the CATT trial.(9) Moreover, classic CNV is more likely to evolve toward fibrotic scars,(9) which is consistent with our results.”
ResultOzone, D., Mizutani, T., Nozaki, M., Ohbayashi, M., Hasegawa, N., Kato, A., Yasukawa, T., & Ogura, Y. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-19617 · Cited by 10
Toth, C. A., Tai, V., Chiu, S. J., Winter, K. P., Sevilla, M. B., Daniel, E., Grunwald, J. E., Jaffe, G. J., Martin, D. F., Ying, G., et al. (2017) · Ophthalmology Retina · doi:10.1016/j.oret.2017.09.016 · Cited by 10
“Blocked fluorescence Areas of hypofluorescence on FA not corresponding to hemorrhage or pigmentation on color or red-free images (a risk factor for fibrotic scar formation and associated with a lower risk of geographic atrophy).(1,2)”
BackgroundSelf-citationBaston, A., Gerhardt, C., Zandi, S., & Garweg, J. G. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112433 · Cited by 11
Im, S., Han, J. W., Park, E. J., Bang, J. H., Shin, H. J., Chang, H. S., Woo, K. M., Park, W. J., & Park, T. K. (2022) · PLoS ONE · doi:10.1371/journal.pone.0269937 · Cited by 10
In vivo monitoring of active subretinal fibrosis in mice using collagen hybridizing peptides
Linder, M., Bennink, L. L., Foxton, R. H., Kirkness, M. W. H., & Westenskow, P. D. (2024) · Lab Animal · doi:10.1038/s41684-024-01408-0 · Cited by 9
“Approximately half of patients with nAMD develop subretinal fibrosis despite receiving treatment with anti-VEGF therapies 6,11 ; therefore, new therapies targeting additional pathways that prevent or reduce fibrosis are critical.”
OCT Angiography of Type 1 Macular Neovascularization in AMD: A Morphometric Evaluation
Savastano, M. C., Fossataro, C., Carlà, M. M., et al. (2025) · Translational Vision Science & Technology · doi:10.1167/tvst.14.2.23 · Cited by 9
Hughes, D., Prestle, J., Zippel, N., McFetridge, S., Szczepan, M., Neubauer, H., Xu, H., & Chen, M. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157131 · Cited by 13
Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation
Forte, P., Fontana, V., Muzio, J., Cello, L. D., Corazza, P., Rosa, R., Musetti, D., Vagge, A., Traverso, C. E., & Nicolò, M. (2024) · British Journal of Ophthalmology · doi:10.1136/bjo-2023-324713 · Cited by 10
“In detail, OCT was the primary modality for MF evaluation: MF was defined binarily as absent or present by the detection of well-defined HRM in the subretinal and sub-RPE compartment, 21 25 Retina colocalising with a well-demarcated whitish or yellow tissue on combined CFP. 26”
MethodOhayon, A., Rosa, I. D., Semoun, O., Jung, C., Colantuono, D., Ameen, A. E., Srour, M., & Souied, E. H. (2019) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2019-314923 · Cited by 9
Song, D., Hua, P., VanderBeek, B. L., Dunaief, J. L., Grunwald, J. E., Daniel, E., Maguire, M. G., Martin, D. F., & Ying, G. (2020) · Retina · doi:10.1097/iae.0000000000003075 · Cited by 9
Self-citationInvestigating the Role of PPARβ/δ in Retinal Vascular Remodeling Using Pparβ/δ-Deficient Mice
Ho, S. Y., Kwan, Y. P., Qiu, B., Tan, A., Murray, H., Barathi, V. A., Tan, N. S., Cheung, C. M. G., Wong, T. Y., Wahli, W., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124403 · Cited by 10
“Furthermore, anti-VEGF treatment has been reported to cause accelerated fibrosis with up to 50% nAMD patients developing sub-retinal fibrosis after 2 years of anti-VEGF treatment [11].”
BackgroundNR4A1 Alleviates Subretinal Fibrosis by Inhibiting Macrophage to Myofibroblast Transition
Yang, R., Zong, T., Wang, N., et al. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.6.47 · Cited by 8
“4,5 Myofibroblast is the main cell type that produces extracellular matrix (ECM) components and contributes to the development of SF. .”
Schranz, M. W., Sacu, S., Reiter, G. S., Baratsits, M., Desissaire, S., Pircher, M., Mylonas, G., Hitzenberger, C. K. F., Schmidt-Erfurth, U. M., & Roberts, P. K. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13041074 · Cited by 9
“Subretinal fibrosis was defined as a structure of fibrous-appearing tissue forming white or yellow plaques or mounds, which are well-defined in shape and might show signs of hyperpigmentation [4] (Figure 2A).”
BackgroundInfluentialWang, L., Sun, W., Lei, C.-L., et al. (2019) · International Journal of Ophthalmology · doi:10.18240/ijo.2019.02.10 · Cited by 8
Zhang, J., Chu, S.-J., Sun, X., et al. (2015) · PubMed · doi:10.3980/j.issn.2222-3959.2015.02.06 · Cited by 8
Intraocular VEGF deprivation induces degeneration and fibrogenic response in retina
Xiao, M., Liu, Y., Wang, L., Liang, J., Wang, T., Zhai, Y., Yf, W., Liu, S., Liu, W., Luo, X., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201901283rr · Cited by 8
Lenhof, S., Kodjikian, L., Gascon, P., Gadiollet, E., Feldman, A., Bats, F. D., Wolff, B., Pradat, P., & Mathis, T. (2024) · Acta Ophthalmologica · doi:10.1111/aos.16759 · Cited by 8
“In contrast with our results, previous studies reported IRF as a risk factor for SF (Cheung et al., 2019; Finn et al., 2021; Llorente-González et al., 2022; Roberts et al., 2022), as well as SHRM (Daniel et al., 2014, 2018; Finn et al., 2021; Willoughby et al., 2015).”
InfluentialNakamura, Y., Pereira, D., Maturi, R. K., Akita, K., Bhisitkul, R. B., Nishihata, T., Sakota, E., Ali, Y. F., Nakamura, E., & Bezwada, P. (2023) · Eye · doi:10.1038/s41433-023-02849-6 · Cited by 9
“It was remarkable that there appeared to be an improvement in retinal fluid levels as measured by central subfield thickness (CST) in most subjects.”
BackgroundGandhewar, R., de Guimarães, T. A. C., Sen, S., Pontikos, N., Moghul, I., Empeslidis, T., Michaelides, M., & Balaskas, K. (2025) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-025-06790-0 · Cited by 8
“In post-hoc analysis of the CATT trial, SHRM was found to be predictive of progression to fibrosis [16, 24].”
InfluentialKokki, E., Karttunen, T., Olsson, V., Kinnunen, K., & Ylä‐Herttuala, S. (2018) · Genes · doi:10.3390/genes9090438 · Cited by 7
Arnon, R., Pikkel, J., Yahalomi, T., Stanescu, N., Wood, K., Leshno, A., Achiron, A., & Hilely, A. (2022) · International Ophthalmology · doi:10.1007/s10792-022-02337-y · Cited by 7
Yu, E., Song, Y., Gu, S. M., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-18531-y · Cited by 7
Bloch, S. B., & Larsen, M. (2015) · Acta Ophthalmologica · doi:10.1111/aos.12680 · Cited by 7
“…scars, shown to be amajor cause of vision loss in patients treated with antivascular endothelial growth factors, is also of interest in innovative experimental research to improve long-term outcomes in the treatment of neovascular AMD (Bloch et al. 2013; Ophthotech Corp 2013; Daniel et al. 2014).”
Background
Metadata
- Authors
- Daniel, E., Toth, C. A., Grunwald, J. E., Jaffe, G. J., Martin, D. F., Fine, S. L., Huang, J., Ying, G.-S., Hagstrom, S. A., Winter, K., & Maguire, M. G.
- Affiliations
- University of Pennsylvania (US)
- Duke University (US)
- Cleveland Clinic (US)
- University of Colorado Anschutz (US)
- ORCID
- Venue
- Ophthalmology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 121
- Issue
- 3
- Pages
- 656-666
- ISSN
- 0161-6420 (ISSN-L)
- PMC
- PMC3943618
- OpenAlex
- W2063028754
- Cited by
- 335
- References
- 43
- Citations by year
- 2026: 28 · 2025: 42 · 2024: 32 · 2023: 28 · 2022: 28 · 2021: 34 · 2020: 39 · 2019: 21 · 2018: 29 · 2017: 19 · 2016: 13 · 2015: 13 · 2014: 8
- FWCI
- 11.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Ophthalmology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- Pfizer
- Regeneron Pharmaceuticals
- Heidelberg Engineering
- National Institutes of Health
- Genentech
- National Eye Institute (U10EY017825, U10EY017826, U10EY017823, U10EY017828)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Retinal and Macular Surgery
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- scar formation, neovascular age-related macular degeneration, ranibizumab, bevacizumab, anti-VEGF therapy, choroidal neovascularization, fibrotic scar, risk factors, subretinal hyperreflective material, retinal pigment epithelium elevation, dosing regimen, color fundus photography
- MeSH terms
- Bevacizumab, Ranibizumab, Cicatrix, Female, Fibrosis, Fluorescein Angiography, Genotype, Humans, Male, Middle Aged, Postoperative Complications, Prospective Studies, Retina, Risk Factors, Visual Acuity, Cohort Studies, Incidence, Angiogenesis Inhibitors, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Wet Macular Degeneration, Intravitreal Injections, Antibodies, Monoclonal, Humanized
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