scholarly journals The Development of Macular Atrophy in Patients with Wet Age-Related Macular Degeneration Receiving Anti-VEGF Treatment

2021 ◽  
Author(s):  
Alexander Foss ◽  
Tryfon Rotsos ◽  
Theo Empeslidis ◽  
Victor Chong

Age-related macular degeneration (AMD) is a leading cause of blindness. Late AMD can be classified into exudative (commonly known as wet AMD [wAMD]) or dry AMD, both of which may progress to macular atrophy (MA). MA causes irreversible vision loss and currently has no approved pharmacological treatment. The standard of care for wAMD is treatment with anti-vascular endothelial growth factors (VEGF). However, recent evidence suggests that anti-VEGF treatment may play a role in the development of MA. Therefore, it is important to identify risk factors for the development of MA in patients with wAMD. For example, excessive blockade of VEGF through intense use of anti-VEGF agents may accelerate the development of MA. Patients with type III macular neovascularisation (retinal angiomatous proliferation) have a particularly high risk of MA. These patients are characterised as having a pre-existing thin choroid (age-related choroidopathy), suggesting that the choroidal circulation is unable to respond to increased VEGF expression. Evidence suggests that subretinal fluid (possibly indicative of residual VEGF activity) may play a protective role. Patients receiving anti-VEGF agents must be assessed for overall risk of MA and there is an unmet medical need to prevent the development of MA without undertreating wAMD.

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xinyuan Zhang ◽  
Timothy Y. Y. Lai

Age-related macular degeneration (AMD) is one of the leading causes of severe vision loss in people over 60 years. Wet AMD (wAMD) causes more severe visual acuity (VA) loss compared with the dry form due to formation of choroidal neovascularization (CNV). Antivascular endothelial growth factor (anti-VEGF) agents such as ranibizumab and aflibercept are now the standard of care treatment for wAMD. Unfortunately, up to a quarter of anti-VEGF-treated wAMD patients might not fully benefit from intravitreal injections and CNV activity may not respond to the treatment and these patients are called anti-VEGF nonresponders. This article aims to discuss the baseline factors associated with VA outcome such as age, initial VA, lesion types, disease duration, optical coherence tomography (OCT) features, fundus autofluorescence findings, and the presence of particular genotype risk alleles in patients with wAMD. Recommendations are provided regarding when to consider discontinuation of therapy because of either success or futility. Understanding the predictive factors associated with VA outcome and treatment frequency response to anti-VEGF therapy may help retina specialists to manage patients’ expectations and guide treatment decisions from the beginning of treatment on the basis of “personalized medicine.”


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yamin Li ◽  
Lina Liang ◽  
Torkel Snellingen ◽  
Kai Xu ◽  
Yun Gao ◽  
...  

Abstract Background Neovascular age-related macular degeneration (nAMD) is the most common cause of irreversible vision loss and blindness among the older people aged 50 and over. Although anti-vascular endothelial growth factor (anti-VEGF) therapies have resulted in improving patient outcomes, there are limitations associated with these treatments. In China, traditional Chinese medicine (TCM) has been used to treat eye diseases for more than 2000 years. Previous studies have shown that TCM may be beneficial for nAMD patients. However, explicit evidence has not been obtained. The purpose of the present trial is to examine the efficacy and safety of the Mingjing granule, a compound Chinese herbal medicine, for nAMD patients. Methods/design This is a double-blind, placebo-controlled, randomized trial of Mingjing granule as an add-on to intravitreous ranibizumab for nAMD. One hundred eighty nAMD patients from six hospitals in China will be enrolled according to the inclusion and exclusion criteria and randomly allocated into two groups, 90 in each. All participants will receive a 24-week treatment and then be followed up for another 24 weeks. The primary outcome is the mean change of best-corrected visual acuity at week 24 and 48 as compared to the baseline. The secondary outcomes include mean change in central retinal thickness, area of retinal hemorrhage and exudation, and TCM syndrome score, mean number of intravitreal ranibizumab injection, and total cost of the treatment. Indexes of safety include blood regular test, urine regular test, liver function test, renal function test, and electrocardiogram from baseline to weeks 24 and 48. Qualitative control and some standard operating processes will be formed throughout the trial. Any ocular or systemic adverse events will be treated suitably, and related data will be recorded accurately and completely in the case report form. Discussion Based on previous empirical and animal laboratory studies, this study will address the question of whether Mingjing granule could contribute to improving efficacy, safety, and efficiency with need for fewer intravitreal injections of anti-VEGF, improving compliance and visual outcomes in the management of persons with nAMD. Trial registration Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000035990. Registered on 21 August 2020.


2021 ◽  
pp. 116-123
Author(s):  
Leonie F. Keidel ◽  
Benedikt Schworm ◽  
Siegfried G. Priglinger ◽  
Jakob Siedlecki

Nonresponse of neovascular age-related macular degeneration (nAMD) to anti-vascular endothelial growth factor (anti-VEGF) therapy can often be attributed to misdiagnosis, and pathologies mimicking AMD might require different therapeutic concepts. In the following, we want to outline a case of presumed nAMD which revealed to be pachychoroid neovasculopathy (PNV) and was successfully treated by the addition of spironolactone. A 67-year-old female patient was referred for nonresponse of nAMD on her left eye after 29 intravitreal injections of aflibercept with no complete resolution of subretinal fluid. On fundoscopy, both maculae presented with pigment epithelium alterations, while the left eye showed subretinal fluid on optical coherence tomography (OCT) with an associated pigment epithelium detachment, which revealed to contain a neovascular network on OCT angiography. There was faint leakage on fluorescence (FAG) and indocyanine green angiography (ICGA) and some focal vascular dilation of the neovascular network on ICGA. Due to the absence of Drusen on any eye, a thick choroid, and the presence of a gravitational tract on blue autofluorescence (BAF), chronic central serous chorioretinopathy with a choroidal neovascularization, defined as PNV in the pachychoroid disease was diagnosed. Upon the addition of spironolactone to anti-VEGF treatment, choroidal thickness significantly decreased, and subretinal fluid resolution was observed and maintained for the first time. In conclusion, PNV should be ruled out in cases of presumed nAMD nonresponding to anti-VEGF. In these cases, a combination therapy of anti-VEGF and mineralocorticoid antagonists can facilitate fluid resorption.


2019 ◽  
Vol 4 (1) ◽  
pp. e000398 ◽  
Author(s):  
Saira Khanna ◽  
Rahul Komati ◽  
David A Eichenbaum ◽  
Ishani Hariprasad ◽  
Thomas A Ciulla ◽  
...  

Age-related macular degeneration is the leading cause of vision loss in the developed world, with the expected number of affected elderly individuals reaching 17.8 million. Antivascular endothelial growth factor (anti-VEGF) injection therapy has been instrumental in treating a disease process that was previously thought to be untreatable. Over the past two decades, landmark studies have demonstrated the efficacy of different anti-VEGF medications and investigated the optimal dosing regimen and delivery mechanism to increase overall vision and minimise patient burden. In this review, we outline landmark neovascular age-related macular degeneration clinical trials that have demonstrated level 1 evidence for its usage or have contributed to the understanding of how to dose these agents.


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.


2016 ◽  
Vol 7 (1) ◽  
pp. 230-236 ◽  
Author(s):  
Hisashi Matsubara ◽  
Ryohei Miyata ◽  
Maki Kobayashi ◽  
Hideyuki Tsukitome ◽  
Kengo Ikesugi ◽  
...  

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are widely used to treat neovascular age-related macular degeneration (nAMD). Although these treatments are effective, multiple injections have recently been recommended to ensure that there is a good long-term prognosis. However, sustained intraocular pressure (IOP) elevations have been reported to develop after multiple injections of anti-VEGF agents. We present our findings of a case of uncontrolled and persistent IOP elevation after switching from intravitreal ranibizumab injections to intravitreal aflibercept injections. A 74-year-old Japanese man without a history of glaucoma underwent 22 ranibizumab injections for nAMD and suddenly developed an elevated IOP after the 22nd injection. Although the subsequent medical treatment led to normalization of his IOP, the subretinal fluid under the central fovea remained even after the 25th injection of ranibizumab. Thus, ranibizumab treatment was switched to bimonthly intravitreal aflibercept injections in conjunction with glaucoma medications. His IOP recovered to within the normal range; however, after the 11th aflibercept injection, there was a sudden elevation of his IOP in spite of the continued glaucoma medications. Due to this sustained IOP elevation, his aflibercept injections were suspended for 16 weeks. Because his IOP could not be normalized by a full glaucoma medication regimen, the patient underwent trabeculotomy, which resulted in a lowering of the IOP to normal levels. We conclude that patients who receive serial intravitreal injections of anti-VEGF agents need to be closely monitored because severe and sustained ocular hypertension can develop.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Young Gun Park ◽  
Hyun Wook Rhu ◽  
Seungbum Kang ◽  
Young Jung Roh

Age-related macular degeneration (AMD) is the leading cause of visual loss in older population. Angiogenesis is an important factor associated with the development of CNV due to AMD. Treatment of CNV with intravitreal anti-VEGF monotherapy is currently the standard of care. However, not all patients respond to monotherapy, and modified anti-VEGF treatment regimen and combination therapy may target reducing treatment frequency or improving visual outcome. This paper reviews the many clinical trials that have been performed utilizing several treatment regimens. While many trials have shown that this variable therapy is justifiable, further study is required to determine correct regimens and dosage.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kyung Tae Kim ◽  
Ju Byung Chae ◽  
Seungheon Lee ◽  
Eoi Jong Seo ◽  
Dong Yoon Kim

Abstract Background To analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients. Methods Patients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type. Results Seventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type. Conclusions Using a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.


Eye ◽  
2020 ◽  
Vol 34 (12) ◽  
pp. 2249-2256 ◽  
Author(s):  
Usha Chakravarthy ◽  
Natasha Pillai ◽  
Annie Syntosi ◽  
Lorna Barclay ◽  
Catherine Best ◽  
...  

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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