Visual acuity and progression of macular atrophy in patients receiving intravitreal anti-VEGF for age-related macular degeneration

2021 ◽  
pp. 112067212110017
Author(s):  
Marco H Ji ◽  
Natalia F Callaway ◽  
Cassie A Ludwig ◽  
Daniel Vail ◽  
Ahmad Al-Moujahed ◽  
...  

Purpose: Whether intravitreal anti-vascular endothelial growth factors (VEGFs) cause retinal atrophy is still a subject of debate. We reported 13 eyes that received several injections of anti-VEGF for wet age-related macular degeneration (AMD) with good visual acuity despite geographic atrophy on imaging. Methods: This is a case series study conducted at Byers Eye Institute at Stanford University. Patients of three retina specialists with wet AMD who received six or more intravitreal injection of anti-VEGFs with visual acuity of 20/60 or better and incomplete RPE and outer retina atrophy (iRORA) or complete RPE and outer retinal atrophy (cRORA) were enrolled in this case series. Different imaging modalities were reviewed by three retina specialists comparing the baseline with the most recent exam. Results: About 13 eyes of 10 patients met the selection criteria. Eleven eyes were classified as iRORA and 2 as cRORA. Despite the development of macular atrophy on imaging after an average of 38.1 injections, eyes maintained stable visual acuity. Conclusion: The discrepancy between structural and functional findings in this cohort suggests that patients treated by anti-VEGF drugs exhibit divergent clinical outcomes for currently unknown reasons. The authors propose anti-VEGF may affect melanosomes within RPE without disrupting RPE and photoreceptors function completely. This requires further investigation.

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. bjophthalmol-2021-319054
Author(s):  
Brice Nguedia Vofo ◽  
Gala Beykin ◽  
Jaime Levy ◽  
Itay Chowers

AimsTo evaluate the long-term functional and anatomical outcomes of neovascular age-related macular degeneration (nvAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for up to 10 years, and to identify associated risk factors.MethodsClinical and optical coherence tomography findings were retrieved for nvAMD cases treated with intravitreal anti-VEGF compounds using a treat-and-extend protocol. In addition, the major risk alleles for AMD in the CFH (rs1061170), HTRA1 (rs1200638) and C3 (rs2230199) genes were genotyped.ResultsFrom 276 eligible eyes in 206 patients, 80 eyes (29%) in 66 patients (32.0%) had a follow-up period of ≥8 years and were included in this study. Over a 10-year period, 73.3±28.0 (mean±SD) anti-VEGF injections were administered. Best-corrected visual acuity (BCVA; LogMAR) deteriorated from 0.55±0.53 at baseline to 1.00±0.73 at 10 years (p<0.0005). Central subfield thickness (CST) decreased from 415.8±162.1 µm at baseline to 323±113.6 µm (p<0.0005) after three monthly injections and remained lower than baseline throughout the follow-up period. Visual outcome was associated with BCVA and intraretinal fluid (IRF) at baseline, macular atrophy, and macular thinning at follow-up. The decrease in CST was inversely correlated with the number of CFH and/or C3 risk alleles carried by the patient (Pearson’s r: −0.608; p=0.003).ConclusionsPatients with nvAMD who received anti-VEGF therapy for 10 years developed substantial vision loss associated with the presence of IRF at baseline and macular atrophy. Major risk alleles for AMD in two complement genes were associated with a reduced long-term reduction in macular thickness.


2017 ◽  
Vol 1 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Bozho Todorich ◽  
Aristomenis Thanos ◽  
Yoshihiro Yonekawa ◽  
Gerta Mane ◽  
Madeleine Hasbrook ◽  
...  

Purpose: To evaluate the efficacy of a dexamethasone intravitreal implant in combination with intravitreal anti-vascular endothelial growth factor (VEGF) agents for treatment-resistant neovascular age-related macular degeneration (nvAMD). Methods: This study was designed as a single-center, retrospective interventional case series. Consecutive patients with treatment-resistant nvAMD underwent simultaneous combined injection of anti-VEGF agent and dexamethasone intravitreal implant. Eighteen patients with mean age of 81.5 years were included. Patients received an average of 26.3 anti-VEGF injections before dual therapy, with a mean follow-up of 8.2 months after dual therapy. Results: Dual therapy produced a significant mean decrease in central foveal thickness (126.3 μm), compared to a mean increase in 29.9 μm when treated with anti-VEGF monotherapy ( P = .0017). Patients also had a mean decrease in macular cube volume of −0.85 mm3 with dual therapy compared to anti-VEGF monotherapy ( P = .0014). There was a moderate correlation between the number of prior anti-VEGF injections and the magnitude of anatomic response, suggesting that shorter disease duration may positively influence response to combined treatment. Although there was a slight trend toward improved mean visual acuity after dual therapy, these differences did not reach statistical significance. Nevertheless, with combination treatment, 33% of patients gained 1 or more lines of vision. Dual therapy resulted in a significantly lower number of required anti-VEGF injections (4.25 vs 5.33) and an increase in the anti-VEGF injection-free interval to 1.41 months from 1.12 months during the 6 months following dual therapy compared to the same interval before dual therapy. Dual therapy was well tolerated; 2 eyes developed mild intraocular pressure elevation effectively managed with topical therapy and 1 patient developed worsening cataract. Conclusions: Combined treatment of anti-VEGF with dexamethasone intravitreal implant is a viable alternative for treatment-resistant nvAMD and may reduce treatment burden. Earlier treatment with dual therapy may be beneficial to maximize anatomic and visual outcomes in these patients.


2020 ◽  
pp. bjophthalmol-2020-316511
Author(s):  
Michael N. Cohen ◽  
Denis O’Shaughnessy ◽  
Kate Fisher ◽  
Jennifer Cerami ◽  
Carl C Awh ◽  
...  

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.


2019 ◽  
Vol 104 (8) ◽  
pp. 1064-1069
Author(s):  
Vincent Daien ◽  
Vuong Nguyen ◽  
Rohan W Essex ◽  
Robin Guymer ◽  
Jennifer J Arnold ◽  
...  

BackgroundTo assess the prevalence and characteristics associated with macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors.MethodsThis was a retrospective, cross-sectional study of nAMD eyes that commenced anti-VEGF between January 2006 and August 2016. MA (absent/extrafoveal/subfoveal) was graded by treating practitioners based on multimodal imaging from April 2016. The prevalence of MA over time and risk factors of MA were assessed.ResultsThe prevalence of MA in a cohort of 1689 eyes was 9.9% (22/222) in eyes within 1 year of starting treatment, 41.5% (71/171) after 5 years and 48.4% (30/62) after 9 years of treatment. Risk factors for subfoveal MA included the proportion of visits at which the lesion was graded as inactive ((adjusted OR (AOR) 3.72 for the highest vs lowest the quartile of frequency of inactive gradings (95% CI 2.33 to 6.07)), age (AOR 1.05 per year (95% CI 1.02 to 1.07)), baseline visual acuity (AOR 3.9 for ≤35 letters vs ≥70 letters (95% CI 2.4 to 6.4)) and the number of injections received (AOR 1.20 every 10 injections (95% CI 1.08 to 1.33)). Similar associations were observed with extrafoveal MA.ConclusionsThe risk of MA appeared to drop in eyes that had not developed it within 5 years. Low choroidal neovascularisation activity was by far the strongest predictor. We could not determine whether the increased prevalence of MA with time was due to anti-VEGF treatment or the natural history of the condition.


2020 ◽  
pp. bjophthalmol-2020-316373
Author(s):  
Ha-Lim Jeon ◽  
Seong Jun Byun ◽  
Nicole L Pratt ◽  
Janet Sultana ◽  
Sang Jun Park ◽  
...  

AimsTo identify the association between ranibizumab and risk of stroke and acute myocardial infarction (AMI) in patients with exudative age-related macular degeneration (AMD).MethodsWe identified patients aged ≥45 years who received ranibizumab for exudative AMD from the Korean National Health Insurance database. Of these, we selected patients suffering stroke or AMI for the self-controlled case series. We estimated incidence rate ratios (IRR) for stroke or AMI by comparing incidence rates of ranibizumab-exposed periods to that of baseline using conditional Poisson regression. The risks of haemorrhagic and ischaemic strokes were also calculated separately.ResultsAmong 33 134 patients receiving ranibizumab, 2397 patients had stroke or AMI. The risk of stroke (IRR=0.83, 95% CI 0.75 to 0.91) was not increased during the overall exposed period; however, there was a marginally elevated risk in ≥57 days exposed period (IRR=1.14, 95% CI 1.001 to 1.31). When analysing by the types of stroke, no increased risks of haemorrhagic (IRR=1.01, 95% CI 0.80 to 1.26) and ischaemic stroke (IRR=0.78, 95% CI 0.71 to 0.86) were observed during the exposed period, although the risks of ischaemic and haemorrhagic stroke were slightly elevated during ≥57 days exposed period. We could not find an association between ranibizumab and AMI.ConclusionsRanibizumab intravitreal injections did not increase the overall risk of stroke or AMI. Although the cardiovascular risk in patient receiving ranibizumab seems to be low, continuous monthly use of ranibizumab for high-risk patients should be judged carefully.


2019 ◽  
Author(s):  
Saghar Bagheri ◽  
Ines Lains ◽  
Rebecca Silverman ◽  
Ivana Kim ◽  
Dean Eliott ◽  
...  

AbstractObjectivesTo investigate the relationship between visual acuity (VA), total area of geographic atrophy (GA) and percentage of foveal GA.MethodsMulticenter, retrospective cross-sectional study of patients with GA due to age-related macular degeneration. Demographics, VA, fundus autofluorescence (FAF) and optical coherence tomography (OCT) images were collected. Using FAF images aided by OCT, foveal sparing status, GA pattern, total GA size, and percentage of GA covering the foveal area - area within a 1.5 mm diameter circle centered on the fovea centralis - were assessed. Univariable and multiple linear regression analyses were performed.Results54 eyes (mean age 78.7 ±7.7 (SD), 60.0% female) were studied. Mean VA was 0.8 ± 0.6 logMAR, mean total GA 8.8 ± 6.7 mm2 and mean percentage of foveal GA was 71.5 ± 30.9%. Of all assessed eyes, 48.2% (n = 26) presented with multifocal GA, and 18.5% (n = 10) had foveal sparing. Multiple regression analysis revealed that, controlling for age and GA pattern, the percentage of foveal GA presented a statistically significant association with VA (ß = 0.41, P = 0.004). No significant associations were observed with mean total GA size, while controlling for the same variables (ß = 0.010, P = 0.440).ConclusionPercentage of foveal GA was significantly associated with VA impairment, while the same was not verified for total GA area. These findings suggest that percentage of foveal GA may represent a more useful tool for assessing the impact of GA on VA. Further validation is needed in larger cohorts.


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 ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document