Treatment approach to patients with combined retinal diseases: wet form of age-related macular degeneration and epiretinal membrane. Preliminary results

Author(s):  
S.V. Kolesnik ◽  
◽  
A.S. Zhuravlev ◽  
A.I. Kolesnik ◽  
S.A. Kakunina ◽  
...  

Introduction. Age-related macular degeneration (AMD) is one of the leading causes of irreversible vision loss among older patients. Since the introduction of anti-VEGF therapy, retinal specialists have been able to maintain or improve vision in patients with AMD. However, anti-VEGF therapy is ineffective in a certain percentage of patients. In 25-35% of cases of wet AMD, secondary epiretinal membranes (ERM) in the macular region are found. Anti-VEGF therapy has been found to be less effective in the treatment of wet AMD with ERM. Optimal treatment tactics for this combined pathology remains a matter of debate. Purpose. To evaluate the efficacy of different combined treatment approaches to patients with wet AMD and ERM. Methods. Study was performed on 2 eyes of 2 patients with ERM and AMD, wet form. Patients were divided in two groups. First patient received one loading dose of anti-VEGF drug (ranibizumab) and after that underwent standart pars plana vitrectomy (PPV) with removal of epiretinal and inner limiting membrane (ILM). Anti-VEGF therapy than was continued according to pro re nata regimen. Second patient underwent standart PPV with removal of ERM and ILM first. After the surgery, loading dose of anti-VEGF drug was injected. Anti-VEGF therapy than was continued according to pro re nata regimen. Results. After treatment, there was a decrease in central retinal thickness in both patients, but an increase in maximum corrected visual acuity was observed only in first patient. Conclusions. Based on the results of the performed study, the most optimal treatment approach to patients with wet AMD and ERM consisted of a single loading dose of anti-VEGF drug injection followed by PPV with removal of ERM and ILM and further continuation of anti-VEGF therapy for wet AMD. However, further research is needed to form a final conclusion about the effectiveness of the chosen treatment tactic. Key words: epiretinal fibrosis, AMD, CNVM, anti-VEGF

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 4 (1) ◽  
pp. e000109 ◽  
Author(s):  
Michel Weber ◽  
Laurent Velasque ◽  
Florence Coscas ◽  
Céline Faure ◽  
Isabelle Aubry ◽  
...  

Background/aimsTo monitor treatment-naïve patients with wet age-related macular degeneration (wet AMD) receiving intravitreal aflibercept (IVT-AFL) in France.MethodsRAINBOW (Real life use of intravitreal Aflibercept In FraNce - oBservatiOnal study in Wet age-related macular degeneration) is an ongoing, observational, retrospective and prospective 4-year study to assess visual (primary), anatomical and safety outcomes following IVT-AFL treatment in wet AMD patients. We report the interim 12-month outcomes in patients who have already been enrolled.ResultsSafety data were analysed from 586 patients (safety analysis set); and effectiveness data were analysed from 502 patients with at least one follow-up (full-analysis set) and from 353 patients with visual acuity data at baseline and month 12. The mean (SD) best-corrected visual acuity (BCVA) was 56.7 (18.2) letters and the mean (SD) central retinal thickness (CRT) was 395.6 (140.5)µm at baseline. Most patients (76.9%) received a loading dose (first three injections within 90 days). The mean (SD) number of IVT-AFL injections over 12 months was 6.0 (2.1) and 6.6 (1.8) (patients who received a loading dose). The mean (SD) change in BCVA was 5.5 (15.0) letters and 6.8 (14.5) letters (patients who received a loading dose) at month 12 (p<0.001 vs baseline). The mean (SD) CRT reduction was –108.7 (146.8)µm and –116.4 (150.4)µm (loading dose) at month 12 (p<0.001 vs baseline). Overall, 118 (20.1%) patients experienced at least one treatment-emergent adverse event (TEAE), 1.2% experienced ocular TEAEs and 3.9% experienced serious AEs.ConclusionThis 12-month interim analysis showed that IVT-AFL was associated with sustained improvements in a real-world setting. The RAINBOW results are consistent with the VIEW clinical studies.Trial registration numberNCT02279537 Pre-results.


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.


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.


2021 ◽  
Author(s):  
Hikari Taniguchi ◽  
Izumi Yoshida ◽  
Masashi Sakamoto ◽  
Takatoshi Maeno

Abstract Background: To evaluate the influence of anti-vascular endothelial growth factor (VEGF) in the appearance or progression of epiretinal membranes (ERMs) in age-related macular degeneration (ARMD) and investigate determining factors.Methods: Seventy-six eyes that were treated for more than 36 months from the first anti-VEGF injection were assessed. Binary logistic regression analysis was performed between smoking, lens status, subretinal hemorrhage, posterior vitreous detachment (PVD) status, peripheral degeneration, contralateral eye, and the number of injections as independent variables and appearance or progression of ERMs during 36 months as dependent variables.Results: The presence of vitreous macular adhesion (VMA) or development of PVD during the observation period was significantly associated (Odds ratio [OR]: 5.76; 95% confidence limit [CL], 1.72-19.3; p=0.005) with the appearance or progression of ERMs. Moreover, peripheral retinal degeneration was significantly associated (OR: 3.85; 95% CL, 1.15-13.0; p=0.029). Injection number of anti-VEGF was not significantly associated (OR: 1.02; 95% CL, 0.90-1.16; p=0.73). Number of anti-VEGF injections in ARMD had little relationship with developing secondary ERMs. VMA or developing PVD and peripheral degenerations had an association with developing ERMs. Conclusion: This study suggests possibilities that anti-VEGF injections alone are unable to cause the development of ERMs, that the vitreoretinal interface has a prior impact on the developing ERMs in ARMD similar to that of idiopathic ERMs, and that peripheral degenerations co-exist with or are evoked by vitreoretinal adhesion in the pathogenesis of ARMD, both being related to ERMs development.


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.


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.


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