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]
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“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 201–300 of 328
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“Persistent SHRM was observed much more frequently in subjects of the present study than usual proportion [12] and would be induced by prolong exudate, though SHRM was reported to be observed more frequently in classic CNV in early periods [19].”
BackgroundAn in vitro model of chronic wounding and its implication for age-related macular degeneration
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“Scarring is more likely to develop in eyes with type 2 CNV and a subfoveal tissue complex [12].”
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JR5558 mice are a reliable model to investigate subretinal fibrosis
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“Although antiVEGF therapy can maintain and restore macular function to efectively improve patients’ visual function, subretinal fbrosis can account for approximately half of all eyes treated within two years after the anti-VEGF treatment [7].”
BackgroundYoshida, S., Umeno, Y., & Haruta, M. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-6657-4_12 · Cited by 10
New criteria of effectiveness of anti-VEGF therapy in exudative age-related macular degeneration
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“A sustained increase in the intraocular pressure can occur in a range from 3.45% to 11.6% of patients (Dedania & Bakri 2015).”
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“21 24 Brolucizumab, recently approved by the FDA, may play a vital role in AMD non-responders.”
BackgroundPharmaceutical therapies targeting autophagy for the treatment of age-related macular degeneration
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“The proportion and extent of fibrosis in Chinese people are much higher than those in other reports [13, 14], whether because some patients had previously undergone PDT treatment or because the different pathophysiological changes in Chinese people are not yet clear.”
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“[29,30] observed in their prospective cohort study of 1059 eyes with AMD treated with anti-VEGF therapy that one third of the eyes developed a fibrous scar after 1 year of treatment, and one half after 2 years.”
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“[21–23] Therefore, it is possible that medications that block VEGF may play a role in the development of MA.”
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“However, nAMD also causes other effects on the retina such as disorganisation, disruption, or loss (atrophy) of the outer retinal structures and sequelae of wound healing may also cause fibrosis [4, 5].”
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“8–12 Therefore, the development of new treat-ment strategies is required to effectively manage AMD and PVR fibrosis.”
Subretinal Hyperreflective Material, Atrophy, and Intraretinal Fluid in Pachychoroid Neovasculopathy
Baek, J., Ra, H., Lee, S. H., Cheung, C. M. G., & Lee, W. K. (2025) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2025.08.048 · Cited by 3
Macular fibrosis secondary to neovascular age-related macular degeneration: from clinic to biology
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“One explanation is under-treatment in real-world clinical settings, the other is the development of fibrosis and GA, which were shown to be more common in type 2 and 3 MNV types 19,25–27 .”
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“Prior studies indicate that baseline risk factors associated with SF development include classic CNV, blocked fluorescence observed on FFA, the presence of foveal subretinal fluid, increased foveal thickness, and subretinal tissue [10].”
Olivieri, C., Perin, G., Zhuang, X., Neri, G., Parisi, G., Marolo, P., Viggiano, P., Boscia, F., Reibaldi, M., & Borrelli, E. (2026) · Ophthalmology Science · doi:10.1016/j.xops.2026.101268 · Cited by 2
“16 The presence of fibrosis is strongly associated with poorer visual acuity and reduced retinal sensitivity in affected patients.”
Ozaki, E., Aktas, S., Mulfaul, K., Brennan, K., Roubeix, C., Palko, S., Robb, K., Yang, T.-H. O., Schanne‐Klein, M., Toidze, A., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2519056123 · Cited by 2
“…200 million people globally (2), and while current therapies lead to an improvement in visual acuity for many patients with nAMD, longitudinal studies indicate that in up to ~ 50% of nAMD patients there is a switch from a pro - angiogenic to a pro - fibrotic state within 2 y of first treatment (3).”
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Neovascular Age-Related Macular Degeneration
Told, R., Waldstein, S. M., & Schmidt-Erfurth, U. M. (2016) · Springer eBooks · doi:10.1007/978-81-322-3610-8_15 · Cited by 2
Usui, Y., Iwanishi, H., Sumioka, T., Ichikawa, K., Miyajima, M., Usui-Kusumoto, K., Reinach, P. S., Okada, Y., & Saika, S. (2023) · Laboratory Investigation · doi:10.1016/j.labinv.2023.100256 · Cited by 1
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“Furthermore, this observation also aligns with the high risk of fibrosis in classic CNV reported in previous studies 16 .”
MethodResultInfluentialMishra, M., Cashman, S. M., & Kumar‐Singh, R. (2025) · Experimental Eye Research · doi:10.1016/j.exer.2025.110258 · Cited by 1
Current Advances in the Combination of Fatty Acids and Resveratrol to Fight Ocular Diseases
Delmas, D., Perus, M., Aires, V., & Hermetet, F. (2025) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.70037 · Cited by 1
“Despite their effectiveness in preserving vision, these treatments require repeated injections and are associated with risks such as inflammation, increased intraocular pressure, bleeding, and, in rare cases, endophthalmitis [15, 16].”
Motevasseli, T., Seraj, A., Daftarian, N., Kanavi, M. R., Ahmadieh, H., & Sheibani, N. (2025) · Journal of Ophthalmic and Vision Research · doi:10.18502/jovr.v20.16966 · Cited by 2
“Citirik et al showed an elevated VEGF level in PDR and in patients with PVR. [106, 129] Clinical trials have demonstrated no significant difference in PVR formation between patients who received anti-VEGF during or after vitrectomy and the control group.”
Borselli, M., Elfalah, M., Trunfio, T. A., Scala, A., Chisari, D., Mancini, A., Lucisano, A., Carnovale-Scalzo, G., Mollace, V., Improta, G., et al. (2025) · Ophthalmology and Therapy · doi:10.1007/s40123-025-01232-w · Cited by 2
“Previous studies have reported a base‑ line SHRM prevalence of approximately 70% in patients with nAMD [44–46].”
Fibrogliosis in neovascular age-related macular degeneration: A new mechanistic perspective
Merle, D. A., Beretta, F., Sacconi, R., & Querques, G. (2025) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2025.09.019 · Cited by 2
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“One study reported that nearly half of patients being treated for nAMD developed fibrotic and nonfibrotic changes within two years of starting treatment [5].”
Management of fibrosis in neovascular age-related macular degeneration
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“For example, in the CATT studies, the frequency of fibrotic scar develop - ment was not influenced by ranibizumab or bevacizumab treatment (adjusted HR 1.2; 95% CI 0.96–1.4) [ 16].”
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“These can be caused by inflammation or other diseases and manifest themselves as color changes or other irregularities [30].”
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“Similarly, subretinal fibrosis development signals the transition from an inflammatory to a cicatricial disease phase, with profound implications for visual recovery potential [16, 17].”
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“While current dryness status at injection 8 strongly predicted treatment intervals (median 6 weeks [IQR 6–8] for dry patients vs 4 weeks [IQR 4–5] for wet patients, p < 0.001), historical dryness status at injection 3 did not independently”
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“The controversy regarding the suppressive effects of anti-VEGF therapy on fibrosis persists, 9,41 with studies suggesting both suppression and augmentation.”
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A focus on the imaging of the retina
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Epiretinal Membranes and Subretinal Fibrosis
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Emerging Role of CXCR4 in Fibrosis
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“According to previous reports, factors related to visual prognosis in PCV include pretreatment BCVA, intraretinal fluid, SRH, choroidal thickness, choroidal vascular hyperpermeability, and the size of the largest polyp [23–26].”
Metformin inhibits subretinal fibrosis by activating Klotho by miR-126-5p
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“However, patients with subretinal fibrosis often do not benefit from anti-VEGF therapy, and even after treatment, subretinal fibrosis occurs in approximately 45–70% of eyes (Daniel et al. 2014; Wolff et al. 2020).”
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Fibrotic Remodeling in Exudative (Wet) Macular Degeneration
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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.
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Cited sources are checked with a language model’s help (gpt-6-sol).
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