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Cited by 708Retinal Diseases and TreatmentsRetinal and Macular SurgeryOcular Diseases and Behçet’s Syndrome

Five-Year Outcomes with Anti–Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration

Open access
Maguire, Maureen G., Martin, Daniel F., Ying, Gui-shuang, Jaffe, Glenn J., Daniel, Ebenezer, Grunwald, Juan E., Toth, Cynthia A., Ferris, Frederick L. +1 more·2016·Ophthalmology
DOI 10.1016/j.ophtha.2016.03.045PMC PMC4958614
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Abstract

Purpose To describe outcomes 5 years after initiation of treatment with bevacizumab or ranibizumab for neovascular age-related macular degeneration (AMD). Design Cohort study.. Participants Patients enrolled in the Comparison of AMD Treatments Trials (CATT). Methods Patients were randomly assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. After 2 years, patients were released from the clinical trial protocol. At approximately 5 years, patients were recalled for examination. Main Outcome Measures Visual acuity (VA) and morphologic retinal features. Results VA was obtained for 647 (71%) of 914 living patients with average follow-up time 5.5 years. The mean number of examinations for AMD care after the clinical trial ended was 25.3, and the mean number of treatments in the study eye was 15.4. Most (60%) patients were treated ≥1 times with a drug other than their randomly assigned drug. At the 5-year visit, 50% of study eyes had VA 20/40 or better and 20% had VA 20/200 or worse. Mean change in VA was −3 letters from baseline and −11 letters from 2 years. Among 467 eyes with fluorescein angiography, mean total lesion area was 12.9 mm2, a mean of 4.8 mm2 larger than at 2 years. Geographic atrophy was present in 213 (41%) of 515 gradable eyes and was subfoveal in 85 (17%). Among 555 eyes with spectral domain optical coherence tomography, 83% had fluid (61% intraretinal, 38% subretinal, and 36% sub-retinal pigment epithelium). Mean foveal total thickness was 278 μm; a decrease of 182 μm from baseline and 20 μm from 2 years. An abnormally thin retina at the foveal center (<120 μm) was present in 36%. Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (−4 letters; p=0.008). Otherwise, there were no statistically significant differences in VA or morphological outcomes between drug or regimen groups. Conclusion Vision gains during the first 2 years of the trial were not maintained at 5 years. However, 50% of eyes had VA 20/40 or better, confirming anti-VEGF therapy as a major long-term therapeutic advance for neovascular AMD.

AI snapshot

Written from the paper’s full text.

TL;DR

At about five years after starting anti-VEGF therapy in CATT, visual gains achieved during the first two years were not sustained, with mean acuity falling below baseline. Nevertheless, roughly half of examined eyes still had 20/40 or better vision, supporting long-term benefit despite progressive retinal and lesion changes.

Key findings

  • Among 914 living CATT participants, 647 (70.8%) had visual acuity measured at a mean of 5.5 years; mean change was −3.3 letters from baseline and −10.8 letters from year 2.
  • At follow-up, 49.6% of eyes had 20/40 or better acuity and about 20% had 20/200 or worse; mean acuity was 58.9 letters (approximately 20/63).
  • Morphologic worsening was common: 83.0% had fluid on OCT, 41.4% had geographic atrophy (16.5% subfoveal), mean total lesion area was 12.9 mm² (4.8 mm² larger than at 2 years), and 36.2% had foveal retinal thickness below 120 μm.
  • Eyes originally assigned to ranibizumab lost more acuity between years 2 and 5 than those originally assigned to bevacizumab (−12.7 vs −8.8 letters; p=0.008); after trial release, arteriothrombotic events were reported in 7.6% of ranibizumab-origin patients versus 4.5% of bevacizumab-origin patients (p=0.04), though no such difference appeared during the randomized trial period.

Methods

  • This was a follow-up cohort study of patients from the CATT randomized trial, which compared ranibizumab and bevacizumab and monthly versus as-needed dosing for neovascular AMD.
  • After the 2-year trial protocol ended, patients were recalled for examination between 2014 and 2015; analyses included those with visual acuity measured 51–85 months after treatment assignment.
  • Outcomes included visual acuity, OCT morphology, fundus photography, fluorescein angiography, treatment history, and serious medical events; comparisons used analysis of variance and chi-square tests.

Limitations

  • The paper states that only 70.8% of living participants returned, and that returning patients were younger and had better baseline and 2-year acuity than nonparticipants, so results likely overestimate outcomes for the full CATT population.
  • The paper also notes missing imaging among participants (about 14% without OCT, 19% without color photographs, and 28% without fluorescein angiography), limiting generalizability of morphologic findings.
  • Because most patients changed drugs or dosing after trial release, the study provides limited ability to compare long-term drug or regimen effects; the text makes evident that post-protocol care was observational and not randomized.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.ophtha.2016.03.045

Cites

48 of 48 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 55 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more visual acuity than the bevacizumab group (−4 letters; p=0.008).

    “Between 2 and 5 years, the group originally assigned to ranibizumab for 2 years lost more VA than the bevacizumab group (−4 letters; p=0.008).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Visual acuity measurements obtained from outside ophthalmologists are comparable to those obtained at CATT centers.
  • Findingown data

    At the 5-year visit, 20% of study eyes had visual acuity 20/200 or worse.

    “20% had VA 20/200 or worse.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Visual acuity measurements obtained from outside ophthalmologists are comparable to those obtained at CATT centers.
  • Findingown data

    Mean visual acuity score at the Follow-up Study visit was 58.9 letters (20/63).

    “The mean (SD) visual acuity score was 58.9 [20/63] (24.1) letters”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Visual acuity measurements obtained from outside ophthalmologists are comparable to those obtained at CATT centers.
  • Findingown data

    The percentages of eyes with subretinal fluid and sub-retinal pigment epithelium fluid at 5 years were similar to those at 2 years.

    “Although the percentages with subretinal fluid (37.7%) and sub-retinal pigment epithelium fluid (36.2%) at 5 years were similar to the percentages at Year 2”
    Quote in the paperNot a substantial claim
  • Findingown data

    Sub-retinal pigment epithelium fluid was present in 36% of eyes.

    “36% sub-retinal pigment epithelium”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 11
  • May combine two claims. 26

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Fundus photographs were available for 81.4% of Follow-up Study patients and fluorescein angiograms for 72.2%.

    “Fundus photographs were available for 527 (81.4%) of the Follow-up Study patients and fluorescein angiograms were available for 467 (72.2%; Table 3).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Visual acuity was obtained for 647 of 914 living patients (71%) at approximately 5 years, with mean follow-up of 5.5 years.

    “VA was obtained for 647 (71%) of 914 living patients with average follow-up time 5.5 years.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Geographic atrophy was subfoveal in 17% of eyes.

    “and was subfoveal in 85 (17%).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    After the clinical trial ended, the mean number of examinations for AMD care was 25.3.

    “The mean number of examinations for AMD care after the clinical trial ended was 25.3”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Non-participants had a mean baseline visual acuity score 3.1 letters worse than participants.

    “and a mean baseline visual acuity score 3.1 letters worse than participants (p=0.001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Retinal thickness was greater than 212 μm in 11.2% of eyes, similar to the 14% observed at 2 years.

    “Retinal thickness was greater than 212 μm in 62 (11.2%) eyes, similar to the percentage (14%) at 2 years.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Non-participants were on average 2.3 years older than participants.

    “Non-participants had a mean age 2.3 years older (p<0.001)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Otherwise, there were no statistically significant differences in visual acuity or morphological outcomes between drug or regimen groups.

    “Otherwise, there were no statistically significant differences in VA or morphological outcomes between drug or regimen groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mean total neovascular lesion area was 2 mm2 greater in eyes assigned to ranibizumab than in eyes assigned to bevacizumab (13.9 vs 11.9 mm2), but the difference was not statistically significant (p=0.06).

    “The mean area of the total neovascular lesion was 2 mm2 greater in eyes assigned to ranibizumab in the clinical trial than in eyes assigned to bevacizumab (13.9 vs 11.9 mm2); however, the difference was not statistically significant (p=0.06).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Spectral domain OCT scans were available for 85.8% of Follow-up Study patients.

    “Spectral domain OCT scans were available for 555 (85.8%) of the Follow-up Study patients”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Patients who died after 2 years had worse mean baseline visual acuity by 4.1 letters.

    “and had worse mean visual acuity both at baseline (−4.1 letters)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Patients who died after 2 years were on average 5.6 years older than participants.

    “Patients who died after 2 years were on average 5.6 years older than participants”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Fluid prevalence fell most in the first treatment year, then stayed fairly stable over the next 4 years.

    “The proportion of eyes with fluid decreased the most during the first year of treatment, but remained relatively unchanged throughout the remaining 4 years of follow up.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the CATT Follow-up Study, 50% of patients had visual acuity of 20/40 or better at 5 years and nearly 10% had 20/20 or better.

    “The CATT Follow-up Study finding of 50% of patients with VA of 20/40 or better at 5 years and nearly 10% with VA 20/20 or better”
    • Also stated in: § DISCUSSION · plain
      “Still, 50% of patients were 20/40 or better and almost 10% were 20/20.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the 5-year data, there was a higher proportion of eyes originally assigned to ranibizumab with geographic atrophy (44%) than eyes assigned to bevacizumab (38%), and a higher proportion of eyes assigned to monthly treatment for 2 years with geographic atrophy (47%) than eyes assigned to PRN treatment (40%), but these differences were not statistically significant.

    “there was still a higher proportion (44%) of eyes originally assigned to ranibizumab with geographic atrophy than eyes assigned to bevacizumab (38%), and a higher proportion (47%) of eyes assigned to monthly treatment for 2 years with geographic atrophy than eyes assigned to PRN treatment (40%). However, these differences were not statistically significant.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Once the 2-year trial ended, few patients stayed on monthly dosing, and most received at least one other anti-VEGF drug than originally assigned.

    “After release from the clinical trial at 2 years, very few patients continued monthly treatment and most were treated with at least 1 additional anti-VEGF drug that was different from their original treatment assignment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the 3.5 years after leaving the CATT protocol, patients averaged 4 to 5 injections yearly and mean visual acuity fell an additional 11 letters to 59 letters (20/63).

    “During the 3.5 year period after release from the CATT protocol, patients received 4 to 5 injections per year on average and the mean visual acuity decreased an additional 11 letters to 59 letters (20/63).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Geographic atrophy affected 20% of eyes at 2 years and 41% at 5 years; subfoveal geographic atrophy rose from 6% to 17%.

    “We also previously reported that the proportion of eyes with geographic atrophy was 20% at 2 years and this proportion increased to 41% at 5 years, with an increase in subfoveal geographic atrophy from 6% to 17%.7,37”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [7] 2012, Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: 2-year results, Ophthalmology source

      Not checked in the free run.

    • cites [37] Sharma, 2016, Macular morphology and visual acuity in the second year of the Comparison of Age-Related Macular Degeneration Treatments Trials, Ophthalmology source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    After 2 years of trial treatment, mean visual acuity was 70 letters (20/40), with no significant difference between the ranibizumab and bevacizumab arms.

    “At the end of 2 years of treatment in the clinical trial, mean VA was 70 letters (20/40) and there was no statistically significant difference in mean visual acuity between eyes originally assigned to ranibizumab and eyes originally assigned to bevacizumab.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the HORIZON cohort, participants had better visual acuity and lesion characteristics than non-participants.

    “Comparison of participants to non-participants in this cohort showed that visual acuity and lesion characteristics were better for participants”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Singer, 2012, HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration, Ophthalmology source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The decrease in vision was accompanied by expansion of the total neovascular complex and by persistence of fluid on OCT.

    “This decrease in vision was accompanied by expansion of the size of the total neovascular complex composed of neovascularization, scarring, and atrophy and by persistence of fluid on OCT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    Since few patients stayed on their initial drug or dosing schedule from Year 2 to the ~5-year follow-up, the CATT Follow-up Study mainly informs overall anti-VEGF outcomes, not comparative drug or dosing effects.

    “Because very few patients remained on their originally assigned drug or dosing schedule between the end of year 2 and follow-up at approximately 5 years, the CATT Follow-up study results provide information primarily on overall treatment outcomes with anti-VEGF drugs and limited information on effects of different drugs and dosing regimens.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the Australian retrospective review, patients received a mean of 25 injections over 5 years, and mean visual acuity fell to 20/63.

    “In the Australian retrospective review, the mean number of injections over 5 years was 25 with mean visual acuity decreasing to 20/63.20”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Gillies, 2015, Long-term outcomes of treatment of neovascular age-related macular degeneration, Ophthalmology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In the Pan-American Study, the mean number of injections over 5 years was 11 and mean visual acuity at 5 years was 20/250.

    “In contrast, the mean number of injections was 11 over 5 years in the Pan-American Study and the mean visual acuity at 5 years was 20/250.18”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Arevalo, 2016, Intravitreal bevacizumab for choroidal neovascularization in age-related macular degeneration: 5-year results of the Pan-American Collaborative Retina Study Group (PACORES), Retina source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    At 2 years, visual acuity decreased to 20/200 or worse in 45% to 75% of untreated patients and in 30% to 40% of photodynamic therapy patients.

    “Visual acuity decreased to 20/200 or worse at 2 years in 45% to 75% of patients with no treatment and in 30% to 40% with photodynamic therapy”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [31] 1993, Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration: updated findings from two clinical trials, Arch Ophthalmol source

      Not checked in the free run.

    • cites [32] 2001, Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials. TAP report #2, Arch Ophthalmol

      Not checked in the free run.

    • cites [33] 2001, Am J Ophthalmol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cross-sectionally, eyes with intraretinal fluid have worse visual acuity during anti-VEGF therapy, whereas those with subretinal fluid have better visual acuity.

    “On a cross-sectional basis, the presence of intraretinal fluid is associated with worse visual acuity during anti-VEGF treatment while the presence of subretinal fluid is associated with better visual acuity.36–38”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [36] Jaffe, 2013, Macular morphology and visual acuity in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT), Ophthalmology source

      Not checked in the free run.

    • cites [37] Sharma, 2016, Macular morphology and visual acuity in the second year of the Comparison of Age-Related Macular Degeneration Treatments Trials, Ophthalmology source

      Not checked in the free run.

    • cites [38] Schmidt-Erfurth, 2015, Pigment epithelial detachment followed by retinal cystoid degeneration leads to vision loss in the treatment of neovascular age-related macular degeneration, Ophthalmology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Two years after diagnosis, fewer than 10% of untreated patients retained vision of 20/40 or better, and fewer than 15% of photodynamic therapy patients retained 20/40 or better.

    “Two years after diagnosis, fewer than 10% of patients retained vision of 20/40 or better with no treatment and fewer than 15% of patients treated with photodynamic therapy retained 20/40 or better.31–33”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [31] 1993, Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration: updated findings from two clinical trials, Arch Ophthalmol source

      Not checked in the free run.

    • cites [32] 2001, Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials. TAP report #2, Arch Ophthalmol

      Not checked in the free run.

    • cites [33] 2001, Am J Ophthalmol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    For diabetic macular edema managed with anti-VEGF therapy, most patients need no treatment after 3 years.

    “where the majority of patients do not require treatment beyond 3 years.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Elman, 2015, Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results, Ophthalmology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In the Diabetic Retinopathy Clinical Research Network Protocol I trial, mean injections were 8 or 9 in Year 1, 2 or 3 in Year 2, 1 or 2 in Year 3, and 0 or 1 in Year 4, depending on treatment assignment.

    “In Diabetic Retinopathy Clinical Research Network Protocol I clinical trial, a mean of 8 or 9 injections were given in Year 1, decreasing to 2 or 3 in Year 2, to 1 or 2 in Year 3, and to 0 or 1 in Year 4, depending on treatment assignment.35”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Elman, 2015, Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results, Ophthalmology source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Multiple processes likely drive vision loss in CATT and other studies, including more eyes with abnormally thin retina (<120 microns), higher geographic atrophy prevalence, and larger lesion size.

    “The processes responsible for the decrease in vision in CATT and other studies are multiple but appear to be related to an increase in the proportion patients with an abnormally thin retina (<120 microns), an increase in prevalence of geographic atrophy, and a substantial increase in lesion size.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Worse visual acuity outcomes are associated with increased lesion size.

  • May combine two claims.

    Premisecitation

    In CATT and all randomized trials of anti-VEGF treatment for neovascular AMD, most improvement in mean visual acuity from baseline occurred within the first 3 to 6 months, with little erosion of benefit through 2 years when a fixed monthly or bi-monthly schedule was maintained.

    “In CATT and all randomized clinical trials of anti-VEGF treatment for neovascular AMD, most of the improvement in mean visual acuity from baseline occurred within the first 3 to 6 months with little erosion of the benefit through 2 years when a fixed schedule of monthly (ranibizumab, bevacizumab, aflibercept) or bi-monthly (aflibercept) treatment was maintained.1,7,9,17,34”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [1] Rosenfeld, 2006, Ranibizumab for neovascular age-related macular degeneration, N Engl J Med source

      Not checked in the free run.

    • cites [7] 2012, Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: 2-year results, Ophthalmology source

      Not checked in the free run.

    • cites [9] Chakravarthy, 2013, Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial, Lancet source

      Not checked in the free run.

    • cites [17] Schmidt-Erfurth, 2014, Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies, Ophthalmology source

      Not checked in the free run.

    • cites [34] Brown, 2009, Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR Study, Ophthalmology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In HORIZON, mean visual acuity fell 7 letters to 20/80, with an average of 4 injections over the 2 years after leaving the formal trials.

    “Similarly, in HORIZON, mean visual acuity declined by 7 letters to 20/80 with total 4 injections on average during the 2 years following exit from the formal clinical trials.19”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Singer, 2012, HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration, Ophthalmology source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationown data

    The results (50% 20/40 or better, almost 10% 20/20) would have been unimaginable before anti-VEGF therapy.

    “These results would have been unimaginable in the era prior to the availability of anti-VEGF therapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    During CATT, both ranibizumab use and monthly treatment were associated with an increased rate of geographic atrophy development.

    “During CATT, both the use of ranibizumab and monthly treatment were associated with an increased rate of development of geographic atrophy.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] 2012, Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: 2-year results, Ophthalmology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In CATT, patients who switched at 1 year from monthly to PRN dosing received 5 to 6 injections on average and lost 2 to 3 letters of mean visual acuity over the second year.

    “In CATT, patients who switched at 1 year from a monthly to a PRN dosing regimen received 5 to 6 injections on average and experienced a mean visual acuity decrease of 2 to 3 letters over the second year.7”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [7] 2012, Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: 2-year results, Ophthalmology source

      Not checked in the free run.

35 of 35

  • The paper relies on this without support.

    Visual acuity measurements obtained from outside ophthalmologists are comparable to those obtained at CATT centers.

    “Information on treatment, visual acuity, and imaging was requested from the outside ophthalmologists who provided AMD care for these patients.”
    “Most (85.5%) of the visual acuity information was obtained by examination at a CATT clinical center by a certified examiner.”

  • The paper relies on this without support.

    The observed 5-year visual outcomes are attributable to anti-VEGF treatment rather than to other factors or the natural history of neovascular AMD.

    “However, 50% of eyes had VA 20/40 or better, confirming anti-VEGF therapy as a major long-term therapeutic advance for neovascular AMD.”

  • The authors state this as an assumption.

    Residual fluid was often minor, missed by the clinician, or accepted because vision was stable.

    “it is reasonable to assume that the amount of fluid was frequently small and not detected by the ophthalmologist or was tolerated because of stable vision.”

  • The paper relies on this without support.

    Worse visual acuity outcomes are associated with increased lesion size.

    “Worse VA outcomes have also been associated with increased lesion size”
4 of 4

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 requirement for lifelong injections imposes a substantial burden on patients and caregivers, and many patients fail to maintain initial therapeutic benefits owing to noncompliance with the burdensome treatment regimen.

    “However, the requirement for lifelong injections imposes a substantial burden on patients and caregivers, and many patients fail to maintain initial therapeutic benefits owing to noncompliance with the burdensome treatment regimen. 3 , 7 , 8 , 10 , 13 – 20”

    From Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies (2024) · cites this paper as [18]

    The Discussion (page unavailable) reports that many patients need injections through five years and beyond, and that less frequent treatment is associated with poorer long-term vision outcomes. It does not establish a lifelong requirement, assess the burden on patients or caregivers, or attribute loss of benefit to noncompliance with a burdensome regimen. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Non-participants were on average 2 years older, had visual acuity 5 letters worse at the end of the clinical trial, and had 2 fewer injections during the trial when assigned to as-needed treatment.

    “Non-participating patients were on average 2 years older, had visual acuity 5 letters worse by the end of the clinical trial, and had 2 fewer injections during the clinical trial when they had been assigned to treatment as needed.14”

    From Development and Course of Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials (2018) · cites this paper as [14]

  • At 2 years, scar was present in 44% of participants and in 38% of non-participants (p=0.10).

    “The percentage of participants with scar at 2 years was 44% and was 38% among non-participants (p=0.10).14”

    From Development and Course of Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials (2018) · cites this paper as [14]

    The Results > Patients section says Table 1 compares participants and non-participants at two years, but the passages available from our copy do not give their scar rates. A search for the 44% and 38% scar figures and p=0.10 found only a different scar measurement at the five-year follow-up (Results > Morphologic Outcomes from Fundus Photography and Angiography; page not provided). (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Maguire, M. G., Martin, D. F., Ying, G.-S., Jaffe, G. J., Daniel, E., Grunwald, J. E., Toth, C. A., Ferris, F. L., & Fine, S. L.
Affiliations
  • University of Pennsylvania (US)
  • Cleveland Clinic (US)
  • Duke University (US)
  • National Institutes of Health (US)
  • University of Colorado Denver (US)
Corresponding author
Maguire, Maureen G.
ORCID
Venue
Ophthalmology
Publisher
Elsevier BV
Published
2016-08
Volume
123
Issue
8
Pages
1751-1761
ISSN
0161-6420 (ISSN-L)
DOI
10.1016/j.ophtha.2016.03.045
PMC
PMC4958614
OpenAlex
W2343042175
Semantic Scholar
1942346571be9df28fbc5ab3a269cdee1dd46caa
Cited by
708
References
48
Citations by year
2026: 33 · 2025: 72 · 2024: 60 · 2023: 63 · 2022: 63 · 2021: 94 · 2020: 110 · 2019: 74 · 2018: 60 · 2017: 64 · 2016: 13
FWCI
74.40
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Ophthalmology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Eye Institute (U10EY017825, U10EY017826, U10EY017823, U10EY023530, U10EY017828)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal and Macular Surgery
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords
neovascular age-related macular degeneration, anti-VEGF therapy, bevacizumab, ranibizumab, long-term visual outcomes, visual acuity, geographic atrophy, retinal thickness, subretinal fluid, retinal pigment epithelium, dosing regimen
MeSH terms
Bevacizumab, Ranibizumab, Aged, Aged, 80 and over, Female, Fluorescein Angiography, Follow-Up Studies, Humans, Male, Prospective Studies, Retina, Visual Acuity, Cohort Studies, Treatment Outcome, Angiogenesis Inhibitors, Tomography, Optical Coherence, Vascular Endothelial Growth Factor A, Geographic Atrophy, Wet Macular Degeneration, Intravitreal Injections, Subretinal Fluid

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-09-29.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-29.

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 ›

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