scholarly journals Genetic biomarkers in the VEGF pathway predicting response to anti-VEGF therapy in age-related macular degeneration

2019 ◽  
Vol 4 (1) ◽  
pp. e000273
Author(s):  
Irina Balikova ◽  
Laurence Postelmans ◽  
Brigitte Pasteels ◽  
Pascale Coquelet ◽  
Janet Catherine ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Multiple Testing ◽  
Age Related Macular Degeneration ◽  
Patient Specific ◽  
Multiple Testing Correction ◽  
Anti Vegf ◽  
Age Related ◽  
Vegf Pathway

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.

scholarly journals Projection of Long-Term Visual Acuity Outcomes Based on Initial Treatment Response in Neovascular Age-Related Macular Degeneration

Ophthalmology ◽  
2019 ◽  
Vol 126 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Vuong Nguyen ◽  
Vincent Daien ◽  
Robyn Guymer ◽  
Stephanie Young ◽  
Alex Hunyor ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Initial Treatment ◽  
Age Related Macular Degeneration ◽  
Age Related

APEX: a phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration

2020 ◽  
pp. bjophthalmol-2020-316511
Author(s):  
Michael N. Cohen ◽  
Denis O’Shaughnessy ◽  
Kate Fisher ◽  
Jennifer Cerami ◽  
Carl C Awh ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Visual Acuity ◽  
Growth Factor ◽  
Macular Degeneration ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related ◽  
Dose Dependent

PurposeThe safety and efficacy of X-82, an orally administered inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor, was investigated for treatment of wet age-related macular degeneration (AMD) in a phase II clinical trial.MethodsThis phase II, randomised, double-masked, placebo-controlled trial enrolled subjects with a prior diagnosis of exudative AMD having received at least two intravitreal injections of anti-VEGF therapy. Subjects were randomised equally into four groups that received either daily 50mg, 100mg or 200mg dosages of X-82 or a placebo tablet. At each 4-week interval visit for 52 weeks, subjects were to be assessed to determine if rescue treatment was needed with anti-VEGF therapy.Results157 patients were enrolled. Due to gastrointestinal and hepatobiliary adverse events and the fulfilment of the primary endpoint, the trial was stopped prematurely after a second interim analysis. The primary endpoint of non-inferiority of visual acuity compared with placebo was demonstrated in all groups receiving X-82 (p<0.001). There was a dose-dependent trend in the number of injections over a 52-week period, with the 50 mg (n=40), 100 mg (n=39), 200 mg (n=39) and placebo (n=39) group requiring 6.7, 6.0, 4.7 and 8.1 injections, respectively.ConclusionsX-82 oral therapy in combination with pro re nata anti-VEGF injections showed non-inferiority in visual acuity outcomes while achieving a dose-dependent decrease in the number of anti-VEGF injections compared with placebo. Given the limited tolerability and safety issues observed, X-82 does not have a sufficient benefit to risk profile in treatment of patients with AMD.

Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration

2014 ◽  
Vol 59 (1) ◽  
pp. 1-18 ◽  
Author(s):  
Robert P. Finger ◽  
Sanjeewa S. Wickremasinghe ◽  
Paul N. Baird ◽  
Robyn H. Guymer
Keyword(s):  
Macular Degeneration ◽  
Treatment Response ◽  
Age Related Macular Degeneration ◽  
Anti Vegf ◽  
Age Related

scholarly journals Limited Treatment Response during Follow-up after Switching to Aflibercept in Neovascular Age-related Macular Degeneration

2021 ◽  
Vol 62 (9) ◽  
pp. 1218-1226
Author(s):  
Gon Soo Choe ◽  
Jong Woo Kim ◽  
Chul Gu Kim ◽  
Jae Hui Kim
Keyword(s):  
Visual Acuity ◽  
Retrospective Study ◽  
Macular Degeneration ◽  
Treatment Response ◽  
Visual Outcome ◽  
Age Related Macular Degeneration ◽  
Neovascular Amd ◽  
Age Related ◽  
The Mean

Purpose: To investigate the limited response to aflibercept after switching to aflibercept in neovascular age-related macular degeneration (AMD). Methods: This retrospective study included 70 eyes with neovascular AMD that were initially treated with ranibizumab and then switched to aflibercept. The incidence and timing of the limited response to aflibercept were identified and visual outcome was compared between eyes with and without limited response. In addition, factors predictive of limited response were analyzed. Results: A limited response to aflibercept was noted in approximately 1/5 of the patients who underwent switching to aflibercept in neovascular AMD. Switching to aflibercept was performed at a mean of 16.2 ± 12.7 months after diagnosis. During the mean 34.7 months of follow-up after switching, limited response was noted in 15 eyes (21.4%) at a mean of 22.0 ± 13.9 months after switching. The degree of reduction in visual acuity was mean logMAR 0.34 ± 0.41 in eyes with limited response and mean 0.06 ± 0.20 in eyes without (p = 0.002). In addition, the duration between the diagnosis and the switching was shorter (p = 0.012), and the number of ranibizumab injections before switching was lower (p = 0.016) in eyes with limited response than in eyes without. Conclusions: Patients who showed limited response to aflibercept after switching to aflibercept showed a worse visual outcome. The probability of having a limited response is higher when the switching is performed earlier.

Fellow-Eye Conversion and Treatment in Exudative Age-Related Macular Degeneration

2019 ◽  
Vol 3 (6) ◽  
pp. 438-444
Author(s):  
Eliot R. Dow ◽  
Jennifer O. Adeghate ◽  
Peter G. Coombs ◽  
Mrinali Gupta Patel ◽  
Donald J. D’Amico ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Initial Diagnosis ◽  
Age Related Macular Degeneration ◽  
Fellow Eye ◽  
Visual Outcomes ◽  
Anti Vegf ◽  
Age Related ◽  
Wet Amd ◽  
Fellow Eyes

Purpose: This article assesses anatomical and visual outcomes after intravitreal antivascular endothelial growth factor (anti-VEGF) treatment in fellow eyes with wet age-related macular degeneration (AMD). Methods: A retrospective chart review was conducted of 349 patients diagnosed with wet AMD between 2005 and 2017 at a single academic institution. Initial diagnosis of unilateral wet AMD and a minimum follow-up time of 1 year after diagnosis were required for inclusion. Individuals were excluded if the initial diagnosis of wet AMD was made at an outside institution, if they had received prior treatment at another institution, or if they had bilateral wet AMD at the time of inclusion. Best-corrected visual acuity, optical coherence tomography (OCT) parameters, and frequency and type of intravitreal anti-VEGF injections were recorded. MedCalc Statistical Software version 17.6 (MedCalc Software) and GraphPad Software (GraphPad Software, Inc) were used for statistical analysis. Results: Of the 349 patients with wet AMD, 192 were included in the study (55%). Of these, 47 (24.5%) developed wet AMD in the fellow eye. The average time to second-eye conversion was 2.6 years, with fellow-eye conversion more likely to occur after 2 years of unilateral disease. On average, patients received 2.16 fewer injections per year in the fellow eye compared with the initially diagnosed eye ( P = .03), and fellow eyes tended to have better OCT results after 12 months of treatment. In addition, compared with ranibizumab and bevacizumab, aflibercept injections appeared to improve visual acuity both in initially diagnosed and fellow eyes. Conclusions: Exudative AMD in the fellow eye has a decreased treatment burden and better visual outcomes compared with the initial eye, which may be attributed to more frequent surveillance and early diagnosis.

scholarly journals Association between visual acuity, lesion activity markers and retreatment decisions in neovascular age-related macular degeneration

Eye ◽  
2020 ◽  
Vol 34 (12) ◽  
pp. 2249-2256 ◽  
Author(s):  
Usha Chakravarthy ◽  
Natasha Pillai ◽  
Annie Syntosi ◽  
Lorna Barclay ◽  
Catherine Best ◽  
...  
Keyword(s):  
Visual Acuity ◽  
Macular Degeneration ◽  
Subretinal Fluid ◽  
Age Related Macular Degeneration ◽  
The United Kingdom ◽  
Anti Vegf ◽  
Age Related ◽  
Intraretinal Fluid ◽  
Endothelial Growth Factor ◽  
Clinic Visits

Abstract Background/objectives To investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians’ decision to retreat with anti-VEGFs. Subjects/methods Retrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses. Results In 321 eyes, absence of IRF or SRF at ≥2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p = 0.006) or SRF (p = 0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits. Conclusions Retreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.

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