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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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.
- 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.
- 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.
- 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.
- 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.
- Based: passes — The paper gives a reason why it holds.
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.
- 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
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.
- 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.
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.
- Based: passes — The paper gives a reason why it holds.
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.
- 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
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.
- 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.
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.
- 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 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.
- 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 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.
- 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
“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.
- 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
“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.
- 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 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.
- Based: passes — The paper gives a reason why it holds.
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.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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.”
Cited by
Sorted by citations
Anti-vascular endothelial growth factor for neovascular age-related macular degeneration
Solomon, S. D., Lindsley, K., Vedula, S. S., Krzystolik, M. G., & Hawkins, B. S. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005139.pub3 · Cited by 520
A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration
Schmidt-Erfurth, U., & Waldstein, S. M. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.07.007 · Cited by 390
“Eyes without vitreomacular adhesion demonstrated less need for retreatment in a PRN protocol in CATT (Cuilla et al., 2015).”
BackgroundInfluentialMettu, P. S., Allingham, M. J., & Cousins, S. W. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100906 · Cited by 370
Anti-vascular endothelial growth factor for neovascular age-related macular degeneration
Solomon, S. D., Lindsley, K. B., Vedula, S. S., Krzystolik, M. G., & Hawkins, B. S. (2019) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005139.pub4 · Cited by 280
Jaffe, G. J., Ying, G., Toth, C. A., Daniel, E., Grunwald, J. E., Martin, D. F., & Maguire, M. G. (2018) · Ophthalmology · doi:10.1016/j.ophtha.2018.08.035 · Cited by 248
“Subretinal hyperreflective material components typically include CNV, fibrin, fibrosis, blood, and fibrotic scar.(10,11,14,15) It is likely that fibrotic scar is the main SHRM component in these eyes with late-stage antieVEGF-treated CNV lesions.”
BackgroundSelf-citationMolecular mechanisms of subretinal fibrosis in age-related macular degeneration
Ishikawa, K., Kannan, R., & Hinton, D. R. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.03.009 · Cited by 238
“improves visual function, subretinal scarring (fibrosis) can develop in approximately half of all treated eyes within two years after antiVEGF treatment and has been identified as one cause of unsuccessful outcomes (Daniel et al., 2014).”
InfluentialWilloughby, A. S., Ying, G., Toth, C. A., Maguire, M. G., Burns, R. E., Grunwald, J. E., Daniel, E., Jaffe, G. J., Williams, D. F., Beardsley, S., et al. (2015) · Ophthalmology · doi:10.1016/j.ophtha.2015.05.042 · Cited by 224
“) determined the final grade on all grading discrepancies.(8,9) Certified VA examiners measured VA after refraction using an electronic VA system at baseline and follow-up weeks 4, 12, 24, 36, 52, 64, 76, 88, and 104.”
BackgroundMethodSelf-citationTargeting VEGF in eye neovascularization: What's new?
Amadio, M., Govoni, S. M., & Pascale, A. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.11.027 · Cited by 180
Schmidt-Erfurth, U. M., Vogl, W., Jampol, L. M., & Bogunović, H. (2020) · Ophthalmology · doi:10.1016/j.ophtha.2020.03.010 · Cited by 159
Dual Antagonism of PDGF and VEGF in Neovascular Age-Related Macular Degeneration
Jaffe, G. J., Ciulla, T. A., Ciardella, A. P., Devin, F., Dugel, P. U., Eandi, C. M., Masonson, H., Monés, J., Pearlman, J. A., Maftouhi, M. Q.-E., et al. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2016.10.010 · Cited by 153
“[41 , 42] One CATT publication showed SHRM as a significant risk factor for scar formation.”
InfluentialSelf-citationLittle, K., Llorián‐Salvador, M., Tang, M., Du, X., Marry, S., Chen, M., & Xu, H. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-02033-7 · Cited by 155
“velop macular fibrosis even with anti-VEGF therapy [7].”
BackgroundTenbrock, L., Wolf, J., Boneva, S., Schlecht, A., Agostini, H. T., Wieghofer, P., Schlunck, G., & Lange, C. (2021) · Cell and Tissue Research · doi:10.1007/s00441-021-03514-8 · Cited by 161
Evans, R. N., Reeves, B. C., Maguire, M. G., Martin, D. F., Muldrew, A., Peto, T., Rogers, C., & Chakravarthy, U. (2020) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2020.3001 · Cited by 145
Self-citationInnate Immune Response in Retinal Homeostasis and Inflammatory Disorders
Murakami, Y., Ishikawa, K., Nakao, S., & Sonoda, K.-H. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100778 · Cited by 125
Daniel, E., Pan, W., Ying, G.-S., Kim, B. J., Grunwald, J. E., Ferris, F. L., Jaffe, G. J., Toth, C. A., Martin, D. F., Fine, S. L., et al. (2018) · Ophthalmology · doi:10.1016/j.ophtha.2018.01.004 · Cited by 119
“The methods used to grade the digital CFPs, FA images, and the OCT scans have been described previously.(15,16) At baseline, photographic images were evaluated at the fundus photograph reading center at the University of Pennsylvania for CNV type; contiguous hemorrhage, serous pigment epithelial detachment, or blocked…”
BackgroundMethodSelf-citationThe role of placental growth factor (PlGF) and its receptor system in retinal vascular diseases
Bergen, T. V., Etienne, I., Cunningham, F., Moons, L., Schlingemann, R. O., Feyen, J. H. M., & Stitt, A. W. (2018) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2018.10.006 · Cited by 118
“Although VEGFR-2 has a lower affinity for VEGF-A (KD 75–760 pM), as compared to VEGFR-1 (KD 10–30 pM) (de Vries et al., 1992), VEGFR-2 is phosphorylated much more efficiently upon VEGF-A binding and this receptor induces more potent angiogenic signaling activity than VEGFR-1 (Waltenberger et al.,…”
Innovative therapies for neovascular age-related macular degeneration
Al-Khersan, H., Hussain, R. M., Ciulla, T. A., & Dugel, P. U. (2019) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2019.1636031 · Cited by 114
“randomized controlled study showed that submacular scar develops in nearly 50% of subjects despite 2 years of antiVEGF-A treatment [29].”
BackgroundLittle, K., Jacey, H., Yang, N., Chen, M., & Xu, H. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.11.029 · Cited by 118
“Amongdifferent types of nAMD, patientswith RAP aremore likely to develop macular fibrosis [21] than those with PCV [22].”
BackgroundThe role of CTGF in diabetic retinopathy
Klaassen, I., van Geest, R. J., Kuiper, E. J., Noorden, C. J. F. V., & Schlingemann, R. O. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2014.10.016 · Cited by 114
Daniel, E., Shaffer, J., Ying, G., Grunwald, J. E., Martin, D. F., Jaffe, G. J., & Maguire, M. G. (2015) · Ophthalmology · doi:10.1016/j.ophtha.2015.10.034 · Cited by 108
“Subretinal hyperreflective material, a morphologic feature seen on OCT as hyperreflective material located external to the retina and internal to the RPE, is associated with reduced VA and increased scar formation.(28,29) The CATT cohort had either CNV or its sequelae in the foveal center, and eyes with RAP tended to…”
Self-citationSleiman, K., Pasricha, M. V., Winter, K. P., McCall, M. N., Yiu, G. C., Farsiu, S., Chew, E. Y., Clemons, T. E., Toth, C. A., Toth, C. A., et al. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2017.06.032 · Cited by 108
Self-citationZhao, Z., Zhang, Y., Zhang, C., Zhang, J., Luo, X., Qiu, Q., Luo, D., & Zhang, J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00778-0 · Cited by 111
“However, a substantial portion of patients still suffer from poor visual prognosis due to the development of subretinal fi brosis even with intensive anti-VEGF treatment 6 .”
Pasricha, M. V., Sleiman, K., Tai, V., Chiu, S. J., Winter, K. P., Stinnett, S. S., Hwang, T. S., Hubbard, G. B., Michelson, M., Gunther, R., et al. (2016) · Ophthalmology · doi:10.1016/j.ophtha.2016.08.047 · Cited by 91
Self-citationEmerging therapeutic strategies for unmet need in neovascular age-related macular degeneration
Khachigian, L. M., Liew, G., Teo, K. Y. C., Wong, T. Y., & Mitchell, P. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-03937-7 · Cited by 98
“CATT showed that 1 in 4 patients who needed aggressive anti-VEGF therapy developed some subretinal fibrosis within 2 years [124] and a greater risk of geographic atrophy in nAMD patients 2 to 5 years after start of therapy [125].”
BackgroundMethodHussain, R. M., & Ciulla, T. A. (2017) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2017.1362390 · Cited by 91
Targeting the Notch and TGF-β signaling pathways to prevent retinal fibrosis in vitro and in vivo
Fan, J., Shen, W., Lee, S., Mathai, A. E., Zhang, R., Xu, G., & Gillies, M. C. (2020) · Theranostics · doi:10.7150/thno.45192 · Cited by 90
“Approximately half of eyes with nAMD develop it within 2 years of starting anti-VEGF therapy [7, 9].”
BackgroundHussain, R. M., Shaukat, B. A., Ciulla, L. M., Berrocal, A. M., & Sridhar, J. S. (2021) · Drug Design Development and Therapy · doi:10.2147/dddt.s295223 · Cited by 89
“Unfortunately, a large RCT showed that nearly half of anti-VEGF treated eyes developed submacular fibrosis despite 2 years of injections, which limits further visual benefit despite treatment.(33) As a result, new therapies and delivery systems are being developed to target other complementary mediators involved in an…”
BackgroundLi, D., Zhang, J., Liu, Z., Gong, Y., & Zheng, Z. J. (2021) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-02064-0 · Cited by 84
Hove, I. V., Hu, T., Beets, K., Bergen, T. V., Etienne, I., Stitt, A. W., Vermassen, E., & Feyen, J. H. M. (2021) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.100966 · Cited by 79
Wu, D., Kanda, A., Liu, Y., Kase, S., Noda, K., & Ishida, S. (2018) · The FASEB Journal · doi:10.1096/fj.201801227r · Cited by 76
Matsuda, Y., Nonaka, Y., Futakawa, S., Imai, H., Akita, K., Nishihata, T., Fujiwara, M., Ali, Y., Bhisitkul, R. B., & Nakamura, Y. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.07.018 · Cited by 73
Hyttinen, J. M. T., Kannan, R., Felszeghy, S., Niittykoski, M., Salminen, A., & Kaarniranta, K. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20225800 · Cited by 70
Rakoczy, E. P., Magno, A. L., Lai, C.-M., Pierce, C. M., Degli-Esposti, M. A., Blumenkranz, M. S., & Constable, I. J. (2019) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2019.03.006 · Cited by 70
Mrejen, S., Jung, J. J., Chen, C., PATEL, S. N., Gallego‐Pinazo, R., Yannuzzi, N. A., Xu, L., Marsiglia, M., Boddu, S., & Freund, K. B. (2015) · Journal of Clinical Medicine · doi:10.3390/jcm4071380 · Cited by 70
“The sub-analysis of the CATT study assessing the risk of scarring found that eyes with classic CNV were more likely to develop scarring at 2 years [35].”
BackgroundBerg, K., Roald, A. B., Navaratnam, J., & Bragadóttir, R. (2017) · Acta Ophthalmologica · doi:10.1111/aos.13522 · Cited by 69
“While RAP lesions were less likely to develop scarring, classic lesions were a predictor for scarring at 2 years in the CATT subanalysis (Daniel et al. 2014, 2016).”
BackgroundThe Role of Osteopontin in Microglia Biology: Current Concepts and Future Perspectives
Rosmus, D.-D., Lange, C., Ludwig, F., Ajami, B., & Wieghofer, P. (2022) · Biomedicines · doi:10.3390/biomedicines10040840 · Cited by 70
“Despite the development of monoclonal antibodies targeting vascular endothelial growth factor (VEGF) in neovascular AMD [195], there is still an urgent need for further treatment options as patients may not respond to anti-VEGF treatment or develop fibrotic scars under anti-VEGF-therapy in long-term follow up [194,196…”
BackgroundIdentification and Quantification of the Angiofibrotic Switch in Neovascular AMD
Roberts, P. K., Zotter, S., Montuoro, A., Pircher, M., Baumann, B., Ritter, M., Hitzenberger, C. K. F., & Schmidt-Erfurth, U. M. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-25189 · Cited by 66
Cheung, C. M. G., Grewal, D. S., Teo, K. Y. C., Gan, A. T. L., Mohla, A., Chakravarthy, U., Wong, T. Y., & Jaffe, G. J. (2019) · Ophthalmology Retina · doi:10.1016/j.oret.2019.06.002 · Cited by 65
Self-citationReview of Fibrosis in Neovascular Age-Related Macular Degeneration
Cheong, K. X., Cheung, C. M. G., & Teo, K. Y. C. (2022) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2022.09.008 · Cited by 65
αB-Crystallin Regulates Subretinal Fibrosis by Modulation of Epithelial-Mesenchymal Transition
Ishikawa, K., Sreekumar, P. G., Spee, C. K., Nazari, H. K., Zhu, D., Kannan, R., & Hinton, D. R. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.11.014 · Cited by 61
Translational Preclinical Pharmacologic Disease Models for Ophthalmic Drug Development
Shah, M., Cabrera-Ghayouri, S., Christie, L., Held, K. S., & Viswanath, V. (2019) · Pharmaceutical Research · doi:10.1007/s11095-019-2588-5 · Cited by 62
The Controversial Role of TGF-β in Neovascular Age-Related Macular Degeneration Pathogenesis
Tosi, G. M., Orlandini, M., & Galvagni, F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113363 · Cited by 65
“In ARPE-19 cells, TGF-β2 promoted cell invasion into a collagen gel and induced the expression of collagen type I and fibronectin [90,95–97], two of the most prominent ECM components in subretinal fibrosis that play important roles in cell migration [94,98].”
BackgroundInfluentialTeo, K. Y. C., Joe, A. W., Nguyen, V., Invernizzi, A., Arnold, J., Barthelmes, D., & Gillies, M. C. (2020) · Retina · doi:10.1097/iae.0000000000002779 · Cited by 60
Casalino, G., Bandello, F. M., & Chakravarthy, U. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18753 · Cited by 59
Casalino, G., Stevenson, M. R., Bandello, F. M., & Chakravarthy, U. (2017) · Ophthalmology Retina · doi:10.1016/j.oret.2017.08.019 · Cited by 59
Subretinal hyperreflective material in retinal and chorioretinal disorders: A comprehensive review
Feo, A., Stradiotto, E., Sacconi, R., Menean, M., Querques, G., & Romano, M. R. (2023) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2023.10.013 · Cited by 58
Romano, F., Cozzi, E., Airaldi, M., Nassisi, M., Viola, F., Aretti, A., Milella, P., Giuffrida, F. P., Teo, K. Y. C., Cheung, C. M. G., et al. (2023) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2023.03.033 · Cited by 57
LASER RESENSITIZATION OF MEDICALLY UNRESPONSIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Luttrull, J. K., Chang, D. B., Margolis, B. W. L., Dorin, G., & Luttrull, D. K. (2015) · Retina · doi:10.1097/iae.0000000000000458 · Cited by 54
Little, K., Llorián‐Salvador, M., Tang, M., Du, X., O'Shaughnessy, Ó., McIlwaine, G., Chen, M., & Xu, H. (2020) · Translational Vision Science & Technology · doi:10.1167/tvst.9.4.3 · Cited by 56
Roberts, P. K., Sugita, M., Deák, G. G., Baumann, B., Zotter, S., Pircher, M., Sacu, S., Hitzenberger, C. K. F., & Schmidt-Erfurth, U. M. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18694 · Cited by 51
Giri, S., & Bader, A. (2014) · Drug Discovery Today · doi:10.1016/j.drudis.2014.10.011 · Cited by 56
Kumar, J. B., Stinnett, S. S., Han, J. I., & Jaffe, G. J. (2019) · Retina · doi:10.1097/iae.0000000000002552 · Cited by 49
Self-citationSiedlecki, J., Wertheimer, C. M., Wolf, A., Liegl, R. G.-H., Priglinger, C., Priglinger, S. G., & Eibl-Lindner, K. H. (2017) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-017-3595-z · Cited by 47
Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease
Muniyandi, A., Hartman, G. D., Song, Y., Mijit, M., Kelley, M. R., & Corson, T. W. (2023) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.122.001563 · Cited by 49
Wolff, B., Macioce, V., Vasseur, V., Castelnovo, L., Michel, G., Nguyen, V., Daïen, V., Mauget‐Faÿsse, M., & Gillies, M. C. (2020) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.13742 · Cited by 47
“Pre-treated patients had fewer injections than naïve patients (median [interquartile range]: 18 [10-34] and 36 [17-56] injections over 10 years, respectively).”
BackgroundNew and Innovative Treatments for Neovascular Age-Related Macular Degeneration (nAMD)
Patel, P. N., & Sheth, V. S. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10112436 · Cited by 46
“In the CATT study, 25% of patients on aggressive anti-VEGF therapy developed some degree of fibrosis at 2 years [13].”
MethodZhang, C., Zhang, Y., Hu, X., Zhao, Z., Chen, Z., Wang, X., Zhang, Z., Jin, H., & Zhang, J. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154865 · Cited by 46
Sim, S. Y., Chalkiadaki, E., Koutsocheras, G., Nicholson, L., Sivaprasad, S., Patel, P. J., Selvam, S., Pal, B., Keane, P. A., Bhatia, B., et al. (2024) · Ophthalmology Retina · doi:10.1016/j.oret.2024.07.020 · Cited by 50
15 years of anti-VEGF treatment for nAMD: success or failure or something in between?
Chakravarthy, U., Armendariz, B. G., & Fauser, S. (2022) · Eye · doi:10.1038/s41433-022-02153-9 · Cited by 42
“Subretinal hyperreflective material (SHRM), an OCT feature of nAMD, is a predictor of fibrosis [5, 18] that is considered its proxy.”
BackgroundRiedl, S., Cooney, L., Grechenig, C., Sadeghipour, A., Pablik, E., Seaman, J. W., Waldstein, S. M., & Schmidt-Erfurth, U. M. (2019) · Retina · doi:10.1097/iae.0000000000002717 · Cited by 44
Nakama, T., Yoshida, S., Ishikawa, K., Kobayashi, Y., Zhou, Y., Nakao, S., Sassa, Y., Oshima, Y., Takao, K., Shimahara, A., et al. (2014) · Gene Therapy · doi:10.1038/gt.2014.112 · Cited by 44
Schlecht, A., Boneva, S., Gruber, M., Zhang, P., Horres, R., Bucher, F., Auw‐Haedrich, C., Hansen, L. L., Stahl, A., Hilgendorf, I., et al. (2020) · American Journal Of Pathology · doi:10.1016/j.ajpath.2020.04.004 · Cited by 41
Bachmeier, I., Armendariz, B. G., Yu, S., Jäger, R. J., Ebneter, A., Glittenberg, C. G., Pauleikhoff, D., Sadda, S. R., Chakravarthy, U., & Fauser, S. (2023) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2023.03.004 · Cited by 43
Tuuminen, R., Uusitalo‐Järvinen, H., Aaltonen, V., Hautala, N. M., Kaipiainen, S., Laitamäki, N., Ollila, M., Rantanen, J., Välimäki, S., Sipilä, R., et al. (2017) · Acta Ophthalmologica · doi:10.1111/aos.13501 · Cited by 45
“(B) There seem to be no clinically significant short-term safety differences between ranibizumab and bevacizumab in the treatment of wAMD (CATT Research Group 2012; Daniel et al. 2014; Moja et al. 2014; Chen et al. 2015; Schmid et al. 2015).”
BackgroundXia, W., Li, C., Chen, Q., Huang, J., Zhao, Z., Liu, P., Xu, K., Li, L., Hu, F., Zhang, S., et al. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.10.022 · Cited by 42
Self-citationMultiple Therapeutic Applications of RBM-007, an Anti-FGF2 Aptamer
Nakamura, Y. (2021) · Cells · doi:10.3390/cells10071617 · Cited by 43
“Poor vision and persistent exudation are often associated with macular atrophy and submacular fibrotic scar formation regardless of different anti-VEGF treatments [25].”
BackgroundBarikian, A., Mahfoud, Z. R., Abdulaal, M. R., Safar, A., & Bashshur, Z. F. (2014) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2014.10.005 · Cited by 37
Choroidal pericytes promote subretinal fibrosis after experimental photocoagulation
Luo, X., Yang, S., Liang, J., Zhai, Y., Shen, M., Sun, J., Feng, Y., Lu, X., Zhu, H., Wang, F., et al. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.032060 · Cited by 36
“Clinical studies have even suggested a positive correlation between anti-VEGF therapy and fibrotic scar development (Daniel et al., 2014;Hwang et al., 2011).”
BackgroundResultInfluentialRho-Kinase/ROCK as a Potential Drug Target for Vitreoretinal Diseases
Yamaguchi, M., Nakao, S., Arima, M., Wada, I., Kaizu, Y., Hao, F., Yoshida, S., & Sonoda, K. (2017) · Journal of Ophthalmology · doi:10.1155/2017/8543592 · Cited by 36
“Fibrosis Risk of inducible fibrosis [22, 65] Antifibrosis in choroidal neovascularization [66] 2 Journal of Ophthalmology”
BackgroundCheng, A. M. S., Joshi, S., Banoub, R. G., Saddemi, J., & Chalam, K. V. (2023) · Cureus · doi:10.7759/cureus.40100 · Cited by 36
“A separate trial noted that nearly half of the eyes receiving anti-VEGF therapy developed submacular fibrosis, limiting further visual benefits despite extended treatment [11].”
BackgroundBaseline predictors for subretinal fibrosis in neovascular age-related macular degeneration
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. (2022) · Scientific Reports · doi:10.1038/s41598-021-03716-8 · Cited by 37
Müftüoğlu, İ. K., Arcinue, C. A., Tsai, F. F., Alam, M. M. R., Gaber, R. A., Camacho, N., You, Q. S., & Freeman, W. R. (2016) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2016.03.038 · Cited by 36
Rajavi, Z., Safi, S., Nikkhah, H., Karimi, S., Ahmadieh, H., Azarmina, M., Abrishami, M., Ahoor, M. H., Alizadeh, Y., Behboudi, H., et al. (2018) · Journal of Ophthalmic and Vision Research · doi:10.4103/jovr.jovr_50_18 · Cited by 36
“improvement and may even improve the visual acuity prognosis.[58,111,112]”
BackgroundHu, T., Vanhove, M., Porcu, M., et al. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.11.022 · Cited by 35
Xie, L., Wang, Y., Li, Q., Ji, X., Tu, Y., Du, S., Lou, H. P., Zeng, X., Zhu, L., Zhang, J., et al. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16272 · Cited by 33
Rasmussen, A., & Sander, B. (2014) · Current Opinion in Ophthalmology · doi:10.1097/icu.0000000000000050 · Cited by 35
LRG1 as a novel therapeutic target in eye disease
Rossi, G. D., Lobo, M. E. D. V., Greenwood, J., & Moss, S. E. (2022) · Eye · doi:10.1038/s41433-021-01807-4 · Cited by 35
“We now know that while anti-VEGF therapy usually improves visual function in nvAMD patients, sub-retinal fibrosis can develop in approximately half of patients and has been acknowledged as one of the principal causes of sight loss [125].”
BackgroundRoberts, P. K., Mittermüller, T. J., Montuoro, A., Sulzbacher, F., Munk, M. R., Sacu, S., & Schmidt-Erfurth, U. M. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14293 · Cited by 33
Souied, E. H., Addou-Regnard, M., Ohayon, A., Semoun, O., Querques, G., Blanco-Garavito, R., Bunod, R., Jung, C., Sikorav, A., & Mière, A. (2020) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2020.02.016 · Cited by 34
Immune Cells in Subretinal Wound Healing and Fibrosis
Szczepan, M., Llorián‐Salvador, M., Chen, M., & Xu, H. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.916719 · Cited by 34
Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model
Sato, K., Takeda, A., Hasegawa, E., Jo, Y., Arima, M., Oshima, Y., Yanai, R., Nakazawa, T., Yuzawa, M., Nakashizuka, H., et al. (2018) · Immunological Medicine · doi:10.1080/09114300.2018.1451609 · Cited by 33
“which results in visual impairment [6,7].”
Sreekumar, P. G., & Kannan, R. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101663 · Cited by 32
Nguyen, V., Barthelmes, D., & Gillies, M. C. (2021) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.13949 · Cited by 32
“In contrast to macular atrophy, the presence of fluid has been identified as a potential risk factor for the development of subretinal fibrosis.(58,59) This idea was again supported by FRB! data, with a higher proportion of visits with active CNV associated with a greater risk of developing subretinal fibrosis (adjust…”
BackgroundMotschi, A. R., Roberts, P. K., Desissaire, S., Schranz, M. W., Schwarzhans, F., Bogunović, H., Pircher, M., & Hitzenberger, C. K. F. (2021) · Biomedical Optics Express · doi:10.1364/boe.426650 · Cited by 34
“In CFP, fibrosis appears as obvious white or yellow solid mounds [6].”
BackgroundFibrosis in age-related neovascular macular degeneration in the anti-VEGF era
Armendariz, B. G., & Chakravarthy, U. (2024) · Eye · doi:10.1038/s41433-024-03308-6 · Cited by 34
New Treatment Modalities for Neovascular Age-Related Macular Degeneration
Schlottmann, P. G., Alezzandrini, A., Zas, M., Rodriguez, F. J., Luna, J. D., & Wu, L. (2017) · Asia-Pacific Journal of Ophthalmology · doi:10.22608/apo.2017258 · Cited by 30
Subretinal Fibrosis Detection Using Polarization Sensitive Optical Coherence Tomography
Gräfe, M. G. O., van de Kreeke, J. A., Willemse, J., et al. (2020) · Translational Vision Science & Technology · doi:10.1167/tvst.9.4.13 · Cited by 30
“1,3,4 7 The development and presence of fibrosis is a prognostic factor for the future of visual acuity; therefore, good imaging techniques to monitor the development of SRFib are important for the selection of patients who may respond better (i.e., no fibrosis) or worse (i.e., mostly fibrotic…”
Rossato, F. A., Su, Y., Mackey, A. M., & Ng, Y. (2020) · Cells · doi:10.3390/cells9092057 · Cited by 31
“scar remains in the subretinal space after anti-VEGFA treatment [10], and it appears that anti-VEGFA therapy may promote fibrotic changes in the CNV [11,12], we explored the hypothesis that fibrosis and specifically endothelial-to-mesenchymal transition (EndoMT) are involved in CNV development, and that these processe…”
BackgroundHirano, M., Morizane, Y., Kawata, T., et al. (2015) · BMC Ophthalmology · doi:10.1186/s12886-015-0072-5 · Cited by 30
“In our patient, however, we did not see any excessive gliosis, which appears as highly reflective material in OCT [9, 10], during the 7 month follow-up period.”
BackgroundInfluentialLiu, Y., Kanda, A., Wu, D., Ishizuka, E. T., Kase, S., Noda, K., Ichihara, A., & Ishida, S. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.05.012 · Cited by 30
Zhao, Q., & Lai, K. (2023) · Experimental Eye Research · doi:10.1016/j.exer.2023.109770 · Cited by 31
Cheng, S., Zhang, S., Huang, M., Liu, Y., Zou, X., Chen, X., & Zhang, Z. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1411278 · Cited by 33
Aptamers as therapeutic middle molecules
Nakamura, Y. (2017) · Biochimie · doi:10.1016/j.biochi.2017.10.006 · Cited by 28
Abicipar pegol for neovascular age-related macular degeneration
Hussain, R. M., Weng, C. Y., Wykoff, C. C., Gandhi, R. A., & Hariprasad, S. M. (2020) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2020.1782379 · Cited by 27
Alex, D., Anantharaman, G., Gopalakrishnan, M., Indurkhya, S., & Madan, S. (2021) · Indian Journal of Ophthalmology · doi:10.4103/ijo.ijo_3156_20 · Cited by 27
Iwanishi, H., Fujita, N., Tomoyose, K., Okada, Y., Yamanaka, O., Flanders, K. C., & Saika, S. (2016) · Laboratory Investigation · doi:10.1038/labinvest.2016.30 · Cited by 27
Mechanism of fibrosis inhibition in laser induced choroidal neovascularization by doxycycline
Peng, X., Hu, X., Tang, M., Zhan, Z., Yu, Y., Sun, L., Luo, X., Zhang, A., & Ding, X. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.06.030 · Cited by 27
Daniel, E., Ying, G., Kim, B. J., Toth, C. A., Ferris, F. L., Martin, D. F., Grunwald, J. E., Jaffe, G. J., Dunaief, J. L., Pan, W., et al. (2018) · Ophthalmology · doi:10.1016/j.ophtha.2018.11.020 · Cited by 26
“(%) 0 (0) 19 (49) 12 (31) 7 (18) 20/25e20/40, no.”
InfluentialSelf-citationHu, X., Zhao, X., Li, S., et al. (2020) · British Journal of Ophthalmology · doi:10.1136/bjophthalmol-2019-315763 · Cited by 26
DeJulius, C. R., Bernardo‐Colón, A., Naguib, S. A., Backstrom, J. R., Kavanaugh, T. E., Gupta, M. K., Duvall, C. L., & Rex, T. S. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.10.010 · Cited by 26
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-29, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-29 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
