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Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

ABSTRACT: PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

SUBMITTER: Enders P

PROVIDER: S-EPMC4985688 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

Enders P P Scholz P P Muether P S PS Fauser S S

Eye (London, England) 20160520 8

PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-dom ...[more]

PMID: 27197870

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Project description:BackgroundClinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data.MethodsIn a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart.ResultsBevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.ConclusionsAt 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).

Project description:PURPOSE:To evaluate the risk factors, incidence, and rate of progression of geographic atrophy (GA) in eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. DESIGN:Post-hoc analysis of a prospective clinical study. PARTICIPANTS:69 participants with nAMD in at least one eye. METHODS:Participants were prospectively treated in the study eye with 0.5 mg intravitreal ranibizumab. Study eyes received 4 monthly injections followed by pro re nata injections until a fluid-free macula was achieved on optical coherence tomography. Risk factors assessed included baseline demographics, treatment, and ocular characteristics on imaging. Eyes were evaluated on fundus autofluorescence (FAF) for GA. The rate of GA area growth in study and fellow eyes was analyzed by linear regression of square-root transformed areas. MAIN OUTCOME MEASURES:Development of new-onset GA and rate of GA area growth measured on ocular imaging, including FAF images of the study eyes. RESULTS:Sixty-nine participants (mean age 78.8±7.8 years) with an average of 40.0±13.6 months of follow-up were analyzed. Twenty-two of 69 study eyes (32%) were treatment naïve. During their first year of the study, participants received an average of 9.2±3.3 injections in the study eye. Of 63 study eyes with quality baseline images, 22 (35%) had pre-existing GA. Of the remaining 41 eyes, 7 (17%) developed new-onset GA during study follow-up. Those who developed new GA were older (all ?79 years old) and had received fewer study injections on average (6.9 vs. 10.4 injections at 1 year) compared to those who did not develop new GA. Of the 12 treatment naïve study eyes without GA at baseline, 1 (8.3%) developed new GA during the study. In 21 study eyes with quantifiable GA area, eyes with GA present at baseline (16/21) enlarged by 0.34±0.26 mm/year, compared to 0.19±0.12 mm/year in eyes developing new-onset GA (5/21). CONCLUSIONS:While 17% of study eyes without GA present at baseline receiving ranibizumab developed new GA, the role of ranibizumab in the development of GA is unclear. Further prospective longitudinal studies are required to determine the eyes most at risk of developing GA in the setting of anti-VEGF treatment.

Project description:PurposeTo evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in prior ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD) enrolled in the LUMINOUS™ study.Patients and methodsLUMINOUS, a 5-year, prospective, multicenter, observational study, recruited 30,138 adult patients (treatment-naïve or prior ranibizumab-treated or other ocular treatments) across all approved indications for ranibizumab. Patients were treated as per local ranibizumab label of participating countries. Here we report the mean change in visual acuity (VA) at Year 1, treatment exposure, overall incidence of ocular, non-ocular adverse events (AEs) and serious AEs (SAEs) in prior ranibizumab-treated nAMD patients (n = 16,167).ResultsAt baseline, the mean (standard deviation [SD]) age of patients was 78.4 (9.0) years, 59.0% were female, and 80.0% were Caucasian. At Year 1 (n = 10,168), the mean (SD) VA change was -1.6 (12.6) letters (baseline VA: 58.3 [19.0] letters) with a mean (SD) of 4.7 (3.1) ranibizumab injections. Stratified by duration of prior ranibizumab treatment of <1 (n = 4,112), 1 to <2 (n = 2,095), 2 to <3 (n = 1,506), 3 to <4 (n = 1,123), 4 to <5 (n = 689), and ≥5 (n = 256) years, the mean (SD) VA change at Year 1 were -1.2 (13.5), -2.0 (12.3), -2.0 (11.3), -1.9 (11.8), -2.5 (10.9), and 0.0 (11.2) letters, respectively. Mean (SD) VA change in patients who received ≤6 and >6 injections over 1 year was -1.8 (13.8) and +0.5 (12.5) letters, respectively. The rate of ocular/non-ocular AEs and SAEs across all prior ranibizumab-treated patients over 5 years were 13.29%/23.02% and 0.84%/13.66%, respectively.ConclusionsOverall, regardless of the prior ranibizumab-treatment duration, VA was maintained in these patients at Year 1, and those receiving ≥6 injections showed a trend towards gaining letters. There were no new safety signals. These results may help inform routine clinical practice to appropriately treat nAMD patients with ranibizumab to achieve optimal visual outcomes.

Project description:PurposeNeovascular age-related macular degeneration (nAMD) shows variable treatment response to intravitreal anti-VEGF. This analysis compared the potential of different artificial intelligence (AI)-based machine learning models using OCT and clinical variables to accurately predict at baseline the best-corrected visual acuity (BCVA) at 9 months in response to ranibizumab in patients with nAMD.DesignRetrospective analysis.ParticipantsBaseline and imaging data from patients with subfoveal choroidal neovascularization secondary to age-related macular dengeration.MethodsBaseline data from 502 study eyes from the HARBOR (NCT00891735) prospective clinical trial (monthly ranibizumab 0.5 and 2.0 mg arms) were pooled; 432 baseline OCT volume scans were included in the analysis. Seven models, based on baseline quantitative OCT features (Least absolute shrinkage and selection operator [Lasso] OCT minimum [min], Lasso OCT 1 standard error [SE]); on quantitative OCT features and clinical variables at baseline (Lasso min, Lasso 1SE, CatBoost, RF [random forest]); or on baseline OCT images only (deep learning [DL] model), were systematically compared with a benchmark linear model of baseline age and BCVA. Quantitative OCT features were derived by a DL segmentation model on the volume images, including retinal layer volumes and thicknesses, and retinal fluid biomarkers, including statistics on fluid volume and distribution.Main outcome measuresPrognostic ability of the models was evaluated using coefficient of determination (R2) and median absolute error (MAE; letters).ResultsIn the first cross-validation split, mean R2 (MAE) of the Lasso min, Lasso 1SE, CatBoost, and RF models was 0.46 (7.87), 0.42 (8.43), 0.45 (7.75), and 0.43 (7.60), respectively. These models ranked higher than or similar to the benchmark model (mean R2, 0.41; mean MAE, 8.20 letters) and better than OCT-only models (mean R2: Lasso OCT min, 0.20; Lasso OCT 1SE, 0.16; DL, 0.34). The Lasso min model was selected for detailed analysis; mean R2 (MAE) of the Lasso min and benchmark models for 1000 repeated cross-validation splits were 0.46 (7.7) and 0.42 (8.0), respectively.ConclusionsMachine learning models based on AI-segmented OCT features and clinical variables at baseline may predict future response to ranibizumab treatment in patients with nAMD. However, further developments will be needed to realize the clinical utility of such AI-based tools.Financial disclosuresProprietary or commercial disclosure may be found after the references.

Project description:PURPOSE: To compare fixation location and stability in patients with neovascular age-related macular degeneration (AMD) treated with or without ranibizumab. METHODS: Patients were recruited from the Macular Clinic of the King's College Hospital in London. Two groups of patients with neovascular AMD with at least 12 months of follow-up were included in the study. The treated group was treated with ranibizumab while the untreated group did not have any treatment. Best corrected visual acuity (BCVA) with modified ETDRS chart, fixation location and stability as measured with Nidek MP1, central retinal thickness as measured by Zeiss Cirrus SD-optical coherent tomography (OCT), and lesion size as measured by Topcon TRC-50IX camera were analysed and correlated. RESULTS: In total, 102 eyes were included in the study with 76 in the ranibizumab-treated group and 26 in the untreated group. There were no significantly demographic differences between the two groups. However, as expected, the treated group has significantly better vision (48.5 vs 15.5 letters, P < 0.0001) and smaller lesions (10.8 vs 18.3 mm(2), P = 0.004), the central macular thickness as measured by OCT also showed a trend of normalised macular thickness (252 vs 282 microns, P = 0.07). The location of fixation was significantly more central in the ranibizumab-treated group (χ(2) 17.9, P < 0.0001) with over 50% of eyes with predominantly central fixation. Majority (84.6%) of the patients in the untreated group had predominantly eccentric fixation. Fixation stability was significantly better in the ranibizumab-treated group as compared with the untreated group, using both the software provided by the MP1 machine (χ(2) 21.8, P < 0.0001) and the mean log bivariate contour ellipse area calculated from the raw data obtained from the machine (3.64 vs 4.39 in treated and untreated group respectively, P < 0.0001). CONCLUSION: Low vision rehabilitation strategy for this group of patients in the ranibizumab era will be very different from those used in untreated patients with dense central scotoma. Further studies on the visual rehabilitation in the ranibizumab-treated patients should consider fixation characteristics of the patients.

Project description:ObjectiveTo describe effects of ranibizumab and bevacizumab when administered monthly or as needed for 2 years and to describe the impact of switching to as-needed treatment after 1 year of monthly treatment.DesignMulticenter, randomized clinical trial.ParticipantsPatients (n = 1107) who were followed up during year 2 among 1185 patients with neovascular age-related macular degeneration who were enrolled in the clinical trial.InterventionsAt enrollment, patients were assigned to 4 treatment groups defined by drug (ranibizumab or bevacizumab) and dosing regimen (monthly or as needed). At 1 year, patients initially assigned to monthly treatment were reassigned randomly to monthly or as-needed treatment, without changing the drug assignment.Main outcome measuresMean change in visual acuity.ResultsAmong patients following the same regimen for 2 years, mean gain in visual acuity was similar for both drugs (bevacizumab-ranibizumab difference, -1.4 letters; 95% confidence interval [CI], -3.7 to 0.8; P = 0.21). Mean gain was greater for monthly than for as-needed treatment (difference, -2.4 letters; 95% CI, -4.8 to -0.1; P = 0.046). The proportion without fluid ranged from 13.9% in the bevacizumab-as-needed group to 45.5% in the ranibizumab monthly group (drug, P = 0.0003; regimen, P < 0.0001). Switching from monthly to as-needed treatment resulted in greater mean decrease in vision during year 2 (-2.2 letters; P = 0.03) and a lower proportion without fluid (-19%; P < 0.0001). Rates of death and arteriothrombotic events were similar for both drugs (P > 0.60). The proportion of patients with 1 or more systemic serious adverse events was higher with bevacizumab than ranibizumab (39.9% vs. 31.7%; adjusted risk ratio, 1.30; 95% CI, 1.07-1.57; P = 0.009). Most of the excess events have not been associated previously with systemic therapy targeting vascular endothelial growth factor (VEGF).ConclusionsRanibizumab and bevacizumab had similar effects on visual acuity over a 2-year period. Treatment as needed resulted in less gain in visual acuity, whether instituted at enrollment or after 1 year of monthly treatment. There were no differences between drugs in rates of death or arteriothrombotic events. The interpretation of the persistence of higher rates of serious adverse events with bevacizumab is uncertain because of the lack of specificity to conditions associated with inhibition of VEGF.

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Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

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Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

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