Low-energy Stereotactic Radiotherapy for Treatment of Exudative Age-related Macular Degeneration Adjunctive to Anti-VEGF Therapy

2015 ◽  
Vol 09 (01) ◽  
pp. 25
Author(s):  
Katja Hatz ◽  
Frank Zimmermann ◽  
Dimitrios Kardamakis ◽  
Emmanouil Lazaridis ◽  
Jörg Binder ◽  
...  

The number of cases of patients with exudative age-related macular degeneration (wet AMD) is increasing, partly due to an ageing population and lifestyle risk factors, such as smoking. The treatment of wet AMD has been revolutionised by the advent of anti-vascular endothelial growth factor (anti-VEGF) agents, though it is an important aim to reduce the treatment burden for patients with the need for highly frequent treatment. Previously, combinations of anti-VEGF with Verteporfin PhotoDynamic Therapy and radiation therapy were used to achieve this aim. More recently, stereotactic radiotherapy (SRT) has been shown in the IRay Plus Anti-VEGF Treatment For Patients With Wet AMD (INTREPID) study to preserve vision while sparing injections of anti-VEGF. Using a highly collimated, narrow X-ray beam, the dose of radiation is delivered in three closely spaced applications within a single session through different entry points in the inferior pars plana of the affected eye. The total application time is usually less than 60 minutes. Centred on the fovea, the sequential beams converge on the retina to deliver a 16 Gy dose to an area of 4 mm in diameter. In this opinion-based article, the practical application of SRT adjunctive to anti-VEGF therapy is discussed and illustrated with a series of case studies.

Age-related macular degeneration (AMD) is the most common cause of permanent visual loss in persons over 65 years of age in developed countries. Currently, intravitreal vascular endothelial growth factor (VEGF) inhibitors are the mainstay of the treatment for patients with wet AMD. Despite significant improvements in visual acuity since the beginning of these therapies, challenges in the treatment of wet AMD are still present. Therefore, there are ongoing researches such as sustained-release anti-VEGF therapy, novel generation anti-VEGF agents, viral vectors to modify genetic transcription, and combination therapies. In this review, it is aimed to discuss these emerging therapies.


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.


2013 ◽  
Vol 61 (12) ◽  
pp. 722 ◽  
Author(s):  
Baskaran Vallikannan ◽  
BangeraSheshappa Mamatha ◽  
Bhatiwada Nidhi ◽  
ChamrajnagarAnantharajiah Padmaprabhu ◽  
Prabhu Pallavi

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Kaushal Sharma ◽  
Priya Battu ◽  
Ramandeep Singh ◽  
Suresh Kumar Sharma ◽  
Akshay Anand

AbstractAge-related macular degeneration (AMD) is a devastating retinal disease that results in irreversible vision loss in the aged population. The complex genetic nature and degree of genetic penetrance require a redefinition of the current therapeutic strategy for AMD. We aimed to investigate the role of modifiers for current anti-VEGF therapy especially for non-responder AMD patients. We recruited 78 wet AMD cases (out of 278 AMD patients) with their socio-demographic and treatment regimen. Serum protein levels were estimated by ELISA in AMD patients. Data pertaining to the number of anti-VEGF injections given (in 1 year) along with clinical images (FFA and OCT) of AMD patients were also included. Visual acuity data (logMAR) for 46 wet AMD cases out of a total of 78 patients were also retrieved to examine the response of anti-VEGF injections in wet AMD cases. Lipid metabolizing genes (LIPC and APOE) have been identified as chief biomarkers for anti-VEGF response in AMD patients. Both genotypes ‘CC’ and ‘GC’ of LIPC have found to be associated with a number of anti-VEGF injections in AMD patients which could influence the expression of B3GALTL,HTRA1, IER3, LIPC and SLC16A8 proteins in patients bearing both genotypes as compared to reference genotype. Elevated levels of APOE were also observed in group 2 wet AMD patients as compared to group 1 suggesting the significance of APOE levels in anti-VEGF response. The genotype of B3GALTL has also been shown to have a significant association with the number of anti-VEGF injections. Moreover, visual acuity of group 1 (≤ 4 anti-VEGF injections/year) AMD patients was found significantly improved after 3 doses of anti-VEGF injections and maintained longitudinally as compared to groups 2 and 3. Lipid metabolising genes may impact the outcome of anti-VEGF AMD treatment.


2010 ◽  
Vol 04 (01) ◽  
pp. 92
Author(s):  
Winfried MK Amoaku ◽  

Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in the developed world. There are two types of AMD: dry and wet. The exact cause of the disease is unknown, but is thought to result from interplay of genetic and environmental factors. Smoking, hypertension and low intake and/or low levels of serum antioxidants are known risk factors for both forms. As yet there are no treatments available for the dry form of AMD. Smoking cessation and healthy lifestyles are important in the prevention of progression of AMD. Progression of early stages of AMD to advanced forms is slowed by regular intake of ocular nutritional supplements as found in the Age-Related Eye Disease Study (AREDS) Study. Recently, there have been significant breakthroughs in the treatment of wet or neovascular AMD, including photodynamic therapy (PDT), intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs, including pegaptanib, ranibizumab and bevacizumab. Newer agents including aflibercept and anti-platelet-derived growth factor (anti-PDGF) compounds are under investigation. The current gold standard for treatment of wet AMD is intravitreal injections of ranibizumab. Combination therapy with PDT and anti-VEGF agents is useful especially in idiopathic polypoidal choroidopathy (IPCV) or when anti-VEGF monotherapy has failed. Rapid referral of patients with neovascular AMD is important as the visual outcome is dependent on the visual acuity at treatment. Diagnostic confirmation with retinal imaging, particularly fundus fluorescein angiography and optical coherent tomography, are required before treatment commencement. The new treatments for wet AMD are repetitive, and have significant service implications. These implications occur irrespective of which anti- VEGF agent is adopted. Visual rehabilitation is still important in the management of AMD.


Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1318
Author(s):  
Jussi J. Paterno ◽  
Ali Koskela ◽  
Juha M.T. Hyttinen ◽  
Elina Vattulainen ◽  
Ewelina Synowiec ◽  
...  

Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the mTOR (Mechanistic Target of Rapamycin), ATG5 (Autophagy Related 5), ULK1 (Unc-51-Like Autophagy Activating Kinase 1), MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 α), SQSTM1 (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Paolo Corazza ◽  
Francesco Maria D’Alterio ◽  
Jamil Kabbani ◽  
Mostafa Mohamed Ragheb Alam ◽  
Stefano Mercuri ◽  
...  

Abstract Purpose To describe real-life data from wet age-related macular degeneration (AMD) patients treated with anti-vascular endothelial growth factors (VEGFs) and to compare our results with previous studies and clinical trials. Methods This retrospective monocentric cohort study analyzed 865 eyes of 780 wet-AMD patients treated with an anti-VEGF treat-and-extend regimen over a long-term follow-up period. Aflibercept and Ranibizumab were considered first-line agents whereas Bevacizumab was reserved for use on a compassionate basis in patients not meeting treatment criteria. All patients underwent a best corrected visual acuity (BCVA) assessment at each follow-up visit. Results One-year follow-up figures were available for 82.5% of patients, whilst follow-up data was recorded for 55.6%, 37.6%, 25.1%, and 15.0% of the cohort at years 2, 3, 4, and 5 respectively. Patients treated with Bevacizumab received fewer yearly injections than those treated with Ranibizumab. However, no significant difference in the number of injections per year was detected in other comparisons between groups. Whilst our data showed no significant difference in mean BCVA between the three groups, there was a gradual deterioration of visual function over time for the patient cohort as a whole. Conclusion No significant differences between the 3 anti-VEGF molecules were recorded in wet-AMD patients in real-life conditions. Despite the long-term therapy, we found a slight reduction in visual function especially after the third year of treatment.


2016 ◽  
Vol 8 ◽  
pp. OED.S38863 ◽  
Author(s):  
Ryan Enslow ◽  
Sai Bhuvanagiri ◽  
Sravanthi Vegunta ◽  
Benjamin Cutler ◽  
Michael Neff ◽  
...  

Age-related macular degeneration (AMD) is one of the leading causes of blindness in developed countries in people over the age of 60 years. One of the forms of advanced AMD is wet AMD. Wet AMD is a result of leakage and bleeding from abnormal neovascularization. The principal treatment for wet AMD is intravitreal anti-VEGF injections. A second form of advanced AMD is geographic atrophy (GA). GA refers to large areas of retinal pigment epithelium loss. In the literature, there is some concern that anti-VEGF injections administered to treat wet AMD may be associated with progression of GA. This review discusses evidence suggesting the association of anti-VEGF injections with progression of GA.


2021 ◽  
Vol 12 (1) ◽  
pp. 299-305
Author(s):  
Alexandra Steinemann ◽  
Laura Hoffmann ◽  
Katja B. Hatz

Several adjunct therapies to the gold standard anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections have been discussed for the treatment of neovascular age-related macular degeneration (nAMD). Low-dose stereotactic radiotherapy (SRT) showed the potential to lower the treatment burden by reducing the anti-VEGF treatment frequency at least over 2–3 years but was associated with retinal microvascular abnormalities in a few cases. We report a 6-year follow-up of a case with bilateral nAMD under anti-VEGF treatment which developed multiple polypoid choroidal vasculopathy (PCV) lesions in the eye adjunct treated with low-dose SRT. The fellow eye suffering from nAMD for the same period of time but never been treated with SRT did not show PCV during the long-term follow-up. We hope to increase the awareness of possible choroidal changes such as PCV in similar patients by sharing this report.


2021 ◽  
Vol 62 (8) ◽  
pp. 1076-1083
Author(s):  
Yi Sang Yoon ◽  
Won Tae Yoon ◽  
Jong Woo Kim ◽  
Chul Gu Kim ◽  
Jae Hui Kim

Purpose: To evaluate the proportion of bevacizumab and the reason for its usage in wet age-related macular degeneration (AMD).Methods: Retrospective analysis of medical records was performed for 1,541 patients who received ranibizumab, aflibercept, or bevacizumab injection to treat wet AMD. The proportion of bevacizumab among the entire set of injections was identified. The reason for selecting bevacizumab was additionally identified.Results: During the study period, a total of 2,929 anti-vascular endothelial growth factor (anti-VEGF) injections were performed; 2,236 (76.3%) were ranibizumab or aflibercept injections and 693 (23.7%) were bevacizumab injections. The most common reason for bevacizumab usage was ‘having a 0.1 or worse best-corrected visual acuity or being unable to assure reimbursement due to the development of extensive scarring or geographic atrophy’ (297 bevacizumab injections, 42.9%). The second most common reason was ‘the inability to assure reimbursement such as extrafoveal choroidal neovascularization (CNV) or early CNV without definite fluid in the foveal region’ (201 bevacizumab injections, 29.0%).Conclusions: Bevacizumab was used in 23.7% of the anti-VEGF injections to treat wet AMD. When analyzing patients’ treatment burden and financial impact, the results of the present study may provide useful information. Further multi-center studies are required to evaluate more precisely the usage of anti-VEGF drugs.


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