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Predictors of Response to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment of Age-Related Macular Degeneration.

ABSTRACT: PURPOSE:To identify factors that influence visual and anatomic response to treatment with intravitreal anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (AMD). DESIGN:Observational cohort study. METHODS:Seventy-two patients were included in this study. Best-corrected Snellen visual acuity (VA) and central foveal thickness measured on optical coherence tomography (OCT) at time of treatment and post-treatment follow-up visits were recorded. Associations between demographic, behavioral, and genetic risk factors and the 2 outcomes were analyzed using mixed-effects linear regression models. Two loci in complement factor H (CFH) were included in a risk score to determine the association between CFH risk and improvement in VA and central foveal thickness. RESULTS:There was a small improvement in VA following anti-VEGF treatment (mean: 3.7 ± 3.0 letters), which was not statistically significant. Significant improvement in VA was observed for the nonrisk CFH Y402H genotype (P < .001) and for a low CFH risk score (P = .019). Regarding the outcome of change in central foveal thickness, improvement was noted in all genotype groups, but reduction after treatment was significantly higher in the low CFH risk score group (P = .033). A significant improvement in mean VA was seen among smokers (P < .001), but this relationship was not observed for central foveal thickness. CONCLUSION:After anti-VEGF therapy, significant improvement in VA was observed for low-risk CFH genotypes and subjects with a low risk score. There was a statistically significant reduction in central foveal thickness overall, and subjects with a low CFH risk score improved more than the high-risk group.

SUBMITTER: Shah AR

PROVIDER: S-EPMC6609150 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Predictors of Response to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment of Age-Related Macular Degeneration.

Shah Anjali R AR Williams Steven S Baumal Caroline R CR Rosner Bernard B Duker Jay S JS Seddon Johanna M JM

American journal of ophthalmology 20151215

<h4>Purpose</h4>To identify factors that influence visual and anatomic response to treatment with intravitreal anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (AMD).<h4>Design</h4>Observational cohort study.<h4>Methods</h4>Seventy-two patients were included in this study. Best-corrected Snellen visual acuity (VA) and central foveal thickness measured on optical coherence tomography (OCT) at time of treatment and post-treatment follow-up visits were ...[more]

PMID: 26705092

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Project description:ImportanceLoss to follow-up (LTFU) after anti-vascular endothelial growth factor (anti-VEGF) injections increases the risk of vision loss among patients with neovascular age-related macular degeneration (nAMD).ObjectiveTo report rates of LTFU among patients with nAMD after anti-VEGF injections and to identify risk factors associated with LTFU in this population.Design, setting, and participantsThis retrospective cohort study of data from 9007 patients who received anti-VEGF injections for treatment of nAMD was performed at an urban, private retina practice with multiple locations from April 1, 2012, to January 12, 2016.Main outcomes and measuresRates of LTFU after anti-VEGF injections. Loss to follow-up was defined as receipt of 1 or more injections with no subsequent follow-up visit within 12 months.ResultsAmong the 9007 patients (mean [SD] age, 81.2 [8.8] years; 5917 [65.7%] female; 7905 [87.8%] white), 2003 (22.2%) were LTFU. Odds of LTFU were greater among patients 81 to 85 years of age (odds ratio [OR], 1.58; 95% CI, 1.38-1.82; P < .001), 86 to 90 years of age (OR, 2.29; 95% CI, 2.00-2.62; P < .001), and more than 90 years of age (OR, 3.31; 95% CI, 2.83-3.86; P < .001) compared with patients 80 years of age and younger. Odds of LTFU among African American patients (OR, 1.47; 95% CI, 1.00-2.16; P = .05), Asian patients (OR, 2.63; 95% CI, 1.71-4.03; P < .001), patients of other race (OR, 3.07; 95% CI, 1.38-6.82; P = .006), and patients of unreported race (OR, 2.29; 95% CI, 1.96-2.68; P < .001) were greater than odds of LTFU among white patients. Odds of LTFU were greater among patients with regional adjusted gross income of $50 000 or less (OR, 1.52; 95% CI, 1.30-1.79; P < .001), $51 000 to $75 000 (OR, 1.35; 95% CI, 1.17-1.56; P < .001), and $76 000 to $100 000 (OR, 1.28; 95% CI, 1.08-1.50; P = .004) compared with patients with incomes greater than $100 000. Odds of LTFU for patients living 21 to 30 miles (OR, 1.33; 95% CI, 1.05-1.69; P = .02) and more than 30 miles (OR, 1.55; 95% CI, 1.28-1.88; P < .001) from clinic were greater compared with patients who lived 10 miles or less from the clinic. Odds of LTFU were greater among patients who received unilateral injections (OR, 1.44; 95% CI, 1.28-1.61; P < .001) than among patients who received bilateral injections.Conclusions and relevanceWe found a high rate of LTFU after anti-VEGF injections among patients with nAMD and identified multiple risk factors associated with LTFU among this population. Although our results may not be generalizable, data on LTFU in a clinical practice setting are needed to understand the scope of the problem so that interventions may be designed to improve outcomes.

Project description:BACKGROUND:Age-related macular degeneration (AMD) is a common cause of severe vision loss in people 55 years and older. OBJECTIVES:The objective of this review was to investigate the effects of anti-VEGF (vascular endothelial growth factor) modalities for treating neovascular AMD. SEARCH STRATEGY:We searched CENTRAL, MEDLINE, EMBASE and LILACS. We handsearched ARVO abstracts for 2006, 2007 for ongoing trials. SELECTION CRITERIA:We included randomized controlled trials (RCTs). DATA COLLECTION AND ANALYSIS:Two review authors independently extracted data. We contacted trial authors for additional data. We summarized outcomes as relative risks (RR), number needed to treat (NNT) and weighted mean differences. MAIN RESULTS:We included five RCTs of good methodological quality. All five trials were conducted by pharmaceutical companies. An intention-to-treat analysis using the last observation carried forward method was done in most trials. Two trials compared pegaptanib versus sham. One trial compared ranibizumab versus sham, another compared ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and the final trial compared ranibizumab plus verteporfin PDT versus verteporfin PDT alone. Fewer patients treated with pegaptanib lost 15 or more letters of visual acuity at one year follow-up compared to sham (pooled relative risk (RR) 0.71; 95% confidence interval (CI) 0.61 to 0.84). The NNT was 6.67 (95% CI 4.35 to 14.28) for 0.3 mg pegaptanib, 6.25 (95% CI 4.17 to 12.5) for 1 mg pegaptanib and 14.28 (95% CI 6.67 to 100) for 3 mg pegaptanib. In a trial of ranibizumab versus sham, RR for loss of 15 or more letters visual acuity at one year was 0.14 (95% CI 0.1 to 0.22) in favour of ranibizumab. The NNT was 3.13 (95% CI 2.56 to 3.84) for 0.3 mg ranibizumab and 3.13 (95% CI 2.56 to 3.84) for 0.5 mg ranibizumab. In a trial of ranibizumab versus verteporfin PDT, RR for loss of 15 or more letters at one year was 0.13 (95% CI 0.07 to 0.23) favouring ranibizumab. The NNT was 3.33 (95% CI 2.56 to 4.76) for 0.3 mg ranibizumab and 3.12 (95% CI 2.43 to 4.17) for 0.5 mg ranibizumab. In another trial of combined ranibizumab plus verteporfin PDT versus verteporfin PDT, RR for loss of 15 or more letters at one year favoured combined therapy (RR 0.3 (95% CI 0.15 to 0.60). The NNT was 4.35 (95% CI 2.78 to 11.11). Pooled RR for gain of 15 or more letters visual acuity at one year was 5.81 (95% CI 3.29 to 10.26) for ranibizumab versus sham, 6.79 (95% CI 3.41 to 13.54) for ranibizumab/sham verteporfin PDT versus verteporfin PDT/sham ranibizumab, and 4.44 (95% CI 1.40 to 14.08) for ranibizumab plus verteporfin PDT versus verteporfin PDT. Frequency of endophthalmitis in included studies was between 0.7% to 4.7% with ranibizumab and 1.3% with pegaptanib. Improvement in vision-specific quality of life was reported for both treatments. AUTHORS' CONCLUSIONS:Pegaptanib and ranibizumab reduce the risk of visual acuity loss in patients with neovascular AMD. Ranibizumab causes gains in visual acuity in many eyes. Quality of life and cost will be important for treatment decisions. Other agents blocking VEGF are being tested in ongoing trials.

Project description:A previously published study demonstrated a pharmacogenetic association between the minor alleles of 2 VEGFR2 single nucleotide polymorphisms (SNPs) and greater improvement in visual acuity (VA) to treatment with ranibizumab, an anti-vascular endothelial growth factor (VEGF) drug, in patients with neovascular age-related macular degeneration (AMD). We evaluated whether this association was replicated among patients who participated in the Comparison of AMD Treatments Trials (CATT) or the Alternative Treatments to Inhibit VEGF in Patients with Age-Related Choroidal Neovascularisation (IVAN) trial.Cohort studies within randomized clinical trials.Eight hundred thirty-five patients participating in CATT and 512 patients participating in IVAN.Each patient was genotyped for the SNPs rs4576072 and rs6828477 in the VEGFR2 gene.Mean change in VA from baseline to 1 year after initiation of treatment with ranibizumab or bevacizumab. Differences in VA response between the patient group homozygous for the minor allele of each SNP and the other genotype groups were evaluated with analysis of variance. Differences in VA response by the number of minor alleles present for either SNP or both combined were evaluated with tests of linear trend. Analyses were conducted separately for CATT and IVAN participants and with both the studies combined.No statistically significant difference in mean change in VA was identified between genotypes of either SNP (P ? 0.05). Furthermore, a stepwise analysis failed to show a significant interaction for either SNP based on the number of minor alleles present. The lack of association was similar in both the CATT and IVAN cohorts and whether the analysis combined patients treated with either ranibizumab or bevacizumab or when restricted to patients treated with ranibizumab only.The CATT and IVAN data do not support a pharmacogenetic association between the 2 VEGFR2 SNPs, rs4576072 and rs6828477, and change in VA in response to anti-VEGF therapy in patients with neovascular AMD.

Dataset Information

Predictors of Response to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment of Age-Related Macular Degeneration.

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Predictors of Response to Intravitreal Anti-Vascular Endothelial Growth Factor Treatment of Age-Related Macular Degeneration.

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