Identifying Predictors of Anti-VEGF Treatment Response in Patients with Neovascular Age-Related Macular Degeneration through Discriminant and Principal Component Analysis

2016 ◽  
Vol 58 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Frank G. Holz ◽  
Ramin Tadayoni ◽  
Stephen Beatty ◽  
Alan R. Berger ◽  
Matteo G. Cereda ◽  
...  
2021 ◽  
pp. 112067212199890
Author(s):  
Kajo Bucan ◽  
Marko Lukic ◽  
Damir Bosnar ◽  
Andrijana Kopic ◽  
Tomislav Jukic ◽  
...  

Purpose: To evaluate the significance of risk factors and analyze their interrelationship in developing age-related macular degeneration (AMD). Materials and design: This is a multicenter, cross-sectional study conducted in eight ophthalmology centers in Europe. The STARS (Simplified Thea AMD Risk-Assessment Scale) questionnaire was used to assess 12 risk factors grouped in four major categories. We used Welch’s t-test/ F ratios to determine statistically significant changes. The principal component analysis was done to investigate the association between risk factors. Results: There were 3297 participants included in our data analysis. Nineteen percent of patients had a high risk of developing AMD, whilst 45.92% and 34.85% had moderate and small risk, respectively. Atherosclerosis appeared as the most relevant risk indicator for AMD development (Cohen’s d = 0.861). Tukey’s post hoc analysis of the smoking variable showed that ex-smokers ( p < 0.001) have a significantly high risk of developing AMD. The Welch’s t-test showed pseudophakic patients have a higher risk of developing AMD than phakic ones. Then, we conducted the principal component analysis, which revealed a significant connection between smoking and male gender and between smoking and atherosclerosis. Pseudophakic patients were generally older and had more often myocardial infarction as compared to phakic patients. We showed that higher BMI, history of arterial hypertension, hypercholesterolemia, and atherosclerosis tend to occur together as risk factors for AMD. Conclusion: Risk factors evaluated in our study should be considered for the development of AMD.


2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  

ObjectiveAge-related macular degeneration (ARMD) is a leading cause of visual impairment. Intravitreal injections of anti-vascular endothelial growth factor (VEGF) are the standard treatment for wet ARMD. There is however, variability in patient responses, suggesting patient-specific factors influencing drug efficacy. We tested whether single nucleotide polymorphisms (SNPs) in genes encoding VEGF pathway members contribute to therapy response.Methods and analysisA retrospective cohort of 281 European wet ARMD patients treated with anti-VEGF was genotyped for 138 tagging SNPs in the VEGF pathway. Per patient, we collected best corrected visual acuity at baseline, after three loading injections and at 12 months. We also registered the injection number and changes in retinal morphology after three loading injections (central foveal thickness (CFT), intraretinal cysts and serous neuroepithelium detachment). Changes in CFT after 3 months were our primary outcome measure. Association of SNPs to response was assessed by binomial logistic regression. Replication was attempted by associating visual acuity changes to genotypes in an independent Japanese cohort.ResultsAssociation with treatment response was detected for seven SNPs, including in FLT4 (rs55667289: OR=0.746, 95% CI 0.63 to 0.88, p=0.0005) and KDR (rs7691507: OR=1.056, 95% CI 1.02 to 1.10, p=0.005; and rs2305945: OR=0.963, 95% CI 0.93 to 1.00, p=0.0472). Only association with rs55667289 in FLT4 survived multiple testing correction. This SNP was unavailable for testing in the replication cohort. Of six SNPs tested for replication, one was significant although not after multiple testing correction.ConclusionIdentifying genetic variants that define treatment response can help to develop individualised therapeutic approaches for wet ARMD patients and may point towards new targets in non-responders.


2021 ◽  
pp. 112067212110378
Author(s):  
Francesco Ciucci ◽  
Giuseppina Ioele ◽  
Antonio Bardocci ◽  
Giorgio Lofoco ◽  
Barbara Antonelli ◽  
...  

Purpose: This is a retrospective, single-center, non randomized interventional real life study, investigating the correlation between variability of central retinal thickness (CRT) and functional outcomes during 2 years of anti-VEGF therapy in patients treated for neovascular age related macular degeneration (nAMD). Background: CRT fluctuations can depend on various factors such as the correct timing of injections, the therapeutic algorithm, and the number of injections (NI) performed; it is important to understand if CRT fluctuations are responsible for worse visual outcomes and consequently to identify the correct ways to avoid or reduce them. Methods: Forty-one patients were treated for nAMD with aflibercept: 0.5 mg intravitreal aflibercept was administered every 4 weeks during the first 3 months, then bimonthly over the first year, and after the first year adopting a PRN regimen. Standard deviation of CRT (CRT/SD), BCVA, and NI were recorded. Correlation studies were performed by Pearson’s test, Ancova, and Principal Component Analysis. Results: A negative correlation was found between CRT/SD and final BCVA. In patients who lost more than 15 letters, CRT/SD mean was significantly higher in comparison with patients who lost less than 15 letters. Patients with final BCVA >65 letters showed lower CRT/SD values compared to patients with final BCVA ⩽65 letters. Multivariate analysis confirmed that in patients with higher baseline BCVA, improvement of BCVA was correlated to NI, and lower values of CRT fluctuations were observed. Conclusions: CRT fluctuations, even after an appropriate NI given per year, significantly influence BCVA; a proactive treatment algorithm appears crucial when treating patients with nAMD.


2014 ◽  
Vol 59 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Robert P. Finger ◽  
Sanjeewa S. Wickremasinghe ◽  
Paul N. Baird ◽  
Robyn H. Guymer

2016 ◽  
Vol 56 (3) ◽  
pp. 132-138 ◽  
Author(s):  
Burcin Kepez Yildiz ◽  
Sengul Ozdek ◽  
Mehmet Ali Ergun ◽  
Sezen Ergun ◽  
Fulya Yaylacioglu Tuncay ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Tomohito Sato ◽  
Toshio Enoki ◽  
Yoko Karasawa ◽  
Hideaki Someya ◽  
Manzo Taguchi ◽  
...  

BackgroundNeovascular age-related macular degeneration (nAMD) is a leading cause of blindness in older people. Low-grade inflammation is well-known as one of the pathogenic mechanisms in nAMD. Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for nAMD, although macula atrophy (MA) developed under anti-VEGF therapy causes irreversible visual function impairment and is recognized as a serious disorder. Here, we show specific expression patterns of aqueous humor (AH) cytokines in nAMD eyes developing MA under intravitreal injection of aflibercept (IVA) as an anti-VEGF antibody and present predictive cytokines as biomarkers for the incidence of MA in nAMD eyes under IVA treatment.MethodsTwenty-eight nAMD patients received three consecutive monthly IVA, followed by a pro re nata regimen for 2 years. AH specimens were collected before first IVA (pre-IVA) and before third IVA (post-IVA). AH cytokine levels, visual acuity (VA), and central retinal thickness (CRT) were measured.ResultsTwo-year incidence of MA was 21.4%. In nAMD eyes developing MA [MA (+) group], pre-IVA levels of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1β, VEGF and post-IVA level of MCP-1 were higher than those in nAMD eyes without MA [MA (−) group]. In hierarchical cluster analysis, pre-IVA MCP-1 and VEGF were grouped into the same subcluster, as were post-IVA MCP-1 and CRT. In principal component analysis, principal component loading (PCL) of pre-IVA interferon-γ-inducible protein 10 (IP-10) was 0.61, but PCL of post-IVA IP-10 decreased to −0.09. In receiver operating characteristic analysis and Kaplan–Meier curves, pre-IVA MCP-1, MIP-1β, and VEGF and post-IVA interleukin-6, MCP-1, and MIP-1β were detected as predictive factors for MA incidence. In 2-year clinical course, changes of VA in groups with high levels of pre-IVA MIP-1β (over 39.9 pg/ml) and VEGF (over 150.4 pg/ml) were comparable to those in MA (+) group.ConclusionSubstantial loss of IP-10 effects and persistent inflammation contribute to incidence of MA, and screening of AH cytokine levels could be a useful method to predict MA incidence in nAMD eyes under anti-VEGF therapy.


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