Treatment Of Age-related Macular Degeneration Research Articles

Delivery of nVEGFi using AAV8 for the treatment of neovascular age-related macular degeneration

Inhibition of vascular endothelial growth factor (VEGF) is the standard therapy for neovascular age-related macular degeneration (nAMD). However, anti-VEGF agents used in the clinic require repeated injections, causing adverse effects. Gene therapy could provide sustained anti-VEGF levels after a single injection, thereby drastically decreasing the treatment burden and improving visual outcomes. In this study, we developed a novel VEGF Trap, nVEGFi, containing domains 1 and 2 of VEGFR1 and domain 3 of VEGFR2 fused to the Fc portion of human IgG. The nVEGFi had a higher expression level than aflibercept under the same expression cassettes of adeno-associated virus (AAV)8 in vitro and in vivo. nVEGFi was found to be noninferior to aflibercept in binding and blocking VEGF in vitro. AAV8-mediated expression of nVEGFi was maintained for at least 12 weeks by subretinal delivery in C57BL/6J mice. In a mouse laser-induced choroidal neovascularization (CNV) model, 4 × 108 genome copies of AAV8-nVEGFi exhibited a significantly increased reduction in the CNV area compared with AAV8-aflibercept (78.1% vs. 63.9%, p < 0.05), while causing no structural or functional changes to the retina. In conclusion, this preclinical study showed that subretinal injection of AAV8-nVEGFi was long lasting, well tolerated, and effective for nAMD treatment, supporting future translation to the clinic.

Emerging treatments for dry age-related macular degeneration with geographic atrophy: a systematic review

Emerging treatments for dry age-related macular degeneration with geographic atrophy: a systematic review

Ophthalmic artery angioplasty for age-related macular degeneration

BackgroundThere is considerable overlap of contributors to cardiovascular disease and the development of age-related macular degeneration (AMD). Compromised ocular microcirculation due to aging and vascular disease contribute to retinal dysfunction...

The effects of loading ranibizumab on vision-related quality of life in the treatment of low-risk neovascular age-related macular degeneration.

Background:The loss of central vision plays a major role in the quality of life (QoL). This study evaluates the changes in QoL in the treatment of low-risk neovascular age-related macular degeneration (AMD).Objectives:The aim of this study was to evaluate the changes in vision-related QoL in patients receiving intravitreal ranibizumab loading dose for low-risk neovascular AMD.Design:A prospective study.Methods:Forty-two eyes of 42 patients receiving ranibizumab injections for neovascular AMD were included in this prospective study. The changes in best-corrected visual acuity (BCVA), central macular thickness (CMT) of the patients before the treatment, and 1 month after three loading doses were evaluated. Turkish version of the National Eye Institute 25-Item Vision Function Questionnaire (NEI VFQ-25 TR) was conducted. The changes of QoL scores through the NEI VFQ-25 TR questionnaire were compared with visual acuity (VA) and CMT measurements before the injections and 1 month after the loading dose.Results:Forty-two patients (19 females and 23 males) were included in the study, and the mean age was 72.69 ± 7.12 years. After the treatment, a statistically significant improvement in BCVA (0.98 ± 0.44, 0.76 ± 0.42 logMAR, p < 0.001) and a significant decrease in CMT (357.90 ± 71.71, 274.50 ± 58.35 μm, p < 0.001) was observed. The QoL composite score was found to be statistically significantly higher after the treatment (64.27 ± 11.47, 68.56 ± 11.39, p < 0.001). General vision (p < 0.001), ocular pain (p = 0.025), near activities (p < 0.001), distance activities (p = 0.027), vision-specific mental health (p = 0.014), vision-specific role difficulties (p < 0.001), and peripheral vision (p = 0.046) were significantly higher after the treatment.Conclusion:NEI VFQ-25 TR is a useful questionnaire for evaluating changes in visual functions and psychosocial characteristics of low-risk neovascular AMD patients before and after the injections.

Real-world effectiveness of screening programs for age-related macular degeneration: amended Japanese specific health checkups and augmented screening programs with OCT or AI.

To investigate the effectiveness of screening and subsequent intervention for age-related macular degeneration (AMD) in Japan. Best-case-scenario analysis using a Markov model. The clinical effectiveness and cost-effectiveness of screening for AMD were assessed by calculating the reduction proportion of blindness and the incremental cost-effectiveness ratio (ICER). The Markov model simulation began at screening at the age of 40years and ended at screening at the age of 90years. The first-eye and second-eye combined model assumed annual state-transition probabilities in the development and treatment of AMD. Data on prevalence, morbidity, transition probability, utility value, and treatment costs were obtained from previously published reports. Sensitivity analysis was performed to assess the influence of the parameters. In the base-case analysis, screening for AMD every 5years, beginning at age 40years and ending at age 74years (reflecting the screening ages of the current Japanese legal "Specific Health Checkups") showed a decrease of 40.7% in the total number of blind patients. The screening program reduced the number of blind people more than did the additional AREDS/AREDS2 formula supplement intake. However, the ICER of screening versus no screening was ¥9,846,411/QALY, which was beyond what people were willing to pay (WTP) in Japan. Sensitivity analysis revealed that neither OCT nor AI improved the ICER, but the scenario in which the prevalence of smoking decreased by 30% improved the ICER (¥4,655,601/QALY) to the level under the WTP. Ophthalmologic screening for AMD is highly effective in reducing blindness but is not cost-effective, as demonstrated by a Markov model based on real-world evidence from Japan.

Mechanism of Liangxue Huayu decoction in treatment of age-related macular degeneration based on network pharmacology and clinical validation

Mechanism of Liangxue Huayu decoction in treatment of age-related macular degeneration based on network pharmacology and clinical validation

POSB100 Cost-Comparison Model of Brolucizumab for the Treatment of Age-Related Macular Degeneration

Brolucizumab is an anti-VEGF with proven efficacy in improving best-corrected visual acuity in neovascular age-related macular degeneration (nAMD) patients. Brolucizumab exhibited non-inferiority to aflibercept with over 50% of patients maintained on Q12W dosing interval until week 48 (HAWK & HARRIER phase III randomized controlled trials). This cost-comparison analysis compared lifetime costs of patients treated with brolucizumab to those treated with aflibercept from the UK National Health Service (NHS) perspective, considering different treatment regimens and equal clinical efficacy.

RHEOPHERESIS IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION.

Evaluation of the long-term effect of rheopheresis treatment of dry form of age-related macular degeneration (AMD). The treatment group consisted of 65 patients and 55 patients in the control group, with a minimum follow-up period of 60 months. The basic treatment consisted of 8 rheopheresis procedures, and the additional treatment (booster therapy) of 2 rheopheresis procedures 1.5-2 years after the basic treatment. We evaluated changes in best corrected visual acuity, anatomical effect, electrical activity of the retina, haematological, biochemical and immunological parameters. Rheopheresis treatment contributed significantly: 1) to stabilisation of best corrected visual acuity of the treated patients, which initially showed an insignificant increased during the 2-years follow-up period, and then slightly decreased. By contrast, visual acuity decreased in the control group, to an insignificant degree up to 4 years, then statistically significantly. 2) to an improvement of the morphological findings in 62.4% of treated patients compared to 7.5% in the control group, while disease progression to stage 3 (neovascular form of the disease or geographic atrophy) with a significant decrease of visual acuity occurred in only 7.1% of treated patients, versus 37.0% in the control group. 3) to regression, even to the attachment of drusenoid pigment epithelial detachment (DPED). To a reduction of the area of DPED in 80.4% of treated patients, in contrast with ansteaincrease in the area of DPED in 47.1% of patients in the control group, and the development of new DPED in only 2 eyes of treated patients compared with 16 eyes of patients in the control group. 4) to a preservation of the integrity of the ellipsoid layer in the fovea in 68.2% of the treated patients, while by contrast we found a damaged ellipsoid layer in the fovea in 66.6% of the control patients. 5) to a stabilisation of the activity of ganglion cells, the pineal system and the activity of the central area of the retina, with eccentricity between 1.8° and 30° in the treated patients, compared to alteration in the control group manifested mainly after 3.5 years of the follow-up period. 6) to a statistically significant improvement in rheological parameters, thereby increasing flow in microcirculation and positively influencing the metabolism in the retina. Also to a positive effect on the classical, alternative and lectin pathway of complement activation, a reduction in the level of proprotein convertase subtilisin kexin 9 (PCSK9), and thus also the level of LDLcholesterol, and 7) Additional treatment with 2 RHF procedures (so-called "booster therapy") seems to be a safe and suitable method of prolonging the stabilisation phase, or even improving visual acuity, anatomical and functional findings. We demonstrated positive changes in anatomical, functional and humoral parameters upon rheopheresis treatment of AMD. Their correlation provides a real possibility to identify patients at risk and to manage an individualised regime of rheopheresis therapy. This method of treatment is effective and safe, with a low percentage of non-serious adverse effects.

RHEOPHERESIS AND ITS USE IN THE TREATMENT OF DISEASES WITH IMPAIRED MICROCIRCULATION. A REVIEW.

Rheopheresis ranks among apheretic methods. It is a selective, extra-corporeal double cascade filtration treatment. First, the plasma is separated from blood elements in extra-corporeal circulation by passing through membrane filter. The plasma is then filtrated through the second filter in order to remove proteins with a high molecular mass, e.g. lipids, fibrinogen, α2-macroglobulin, von Willebrand factor, immunoglobulin IgM. The purified plasma is then returned together with the blood elements back to the patient. The aim of the procedure is to improve the microcirculation and rheological properties of the blood. Rheopheresis is well established method for the treatment of age-related macular degeneration, acute sensorineural hearing loss, calciphylaxis, systemic sclerosis or peripheral vascular disease.

Editorial introductions

Current Opinion in Ophthalmology was launched in 1990. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of Ophthalmology is divided into nine sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Journal's Editor and Section Editor for this issue. EDITOR Allen C. HoAllen C. HoDr Allen C. Ho is an Attending Surgeon of the Retina Service and Director of Retina Research of Wills Eye Hospital, USA. He is Professor of Ophthalmology at Thomas Jefferson University School of Medicine, USA. Dr Ho is a founding member of Mid Atlantic Retina. He is author of multiple textbooks including Age Related Macular Degeneration Diagnosis and Treatment, The Wills Eye Hospital Color Atlas and Synopsis of Retinal Disease and is Editor-in-Chief of Current Opinion in Ophthalmology and Chief Medical Editor of Retina Today, a global publication that features new therapies for retinal disease. He is a member of the Scientific Editorial Boards of Retina Cases and Brief Reports, Ophthalmic Surgery, Lasers and Imaging, Retinal Physician, and Ocular Surgery News. Dr Ho has been an invited lecturer at numerous national and international ophthalmic meetings around the world. He is a recipient of multiple clinical research grants investigating new treatments for macular diseases sponsored by the National Eye Institute and received the American Academy of Ophthalmology's Achievement Award and Senior Achievement Award and the American Society of Retina Specialists Crystal Apple Award. Dr Ho is Principal Investigator at Wills Eye Institute of several collaborative clinical trials evaluating new treatments for age-related macular degeneration, surgical retina and diabetic retinopathy. He maintains special interests in macular diseases, diabetic retinopathy, surgical retinal diseases and clinical trials investigating new treatments for vitreoretinal diseases. SECTION EDITOR Natalie A. AfshariNatalie A. AfshariNatalie A. Afshari is Stuart I. Brown MD Chair in Ophthalmology in Memory of Donald P. Shiley, Chief of Cornea and Refractive Surgery, Vice Chair of Education, and Professor of Ophthalmology at the Shiley Eye Institute, University of California, San Diego. Prior to this, she was Professor of Ophthalmology and Director of Centers of Excellence at the Duke University Eye Center. She received her medical degree from Stanford University and her residency training at Harvard University, Massachusetts Eye and Ear Infirmary. She then completed a two-year fellowship in cornea and refractive surgery at Harvard University. Dr Afshari is the recipient of the Senior Achievement Award and the Secretariat Award by the American Academy of Ophthalmology and has been named a Gold Fellow of the Association for Research in Vision and Ophthalmology. She has received the inaugural Top Ten Women in Medicine award by Triangle News, Women Who Mean Business award by San Diego Business Journal, and the Teacher of the Year award at the Duke University Eye Center. She has also been recognized in the Best Doctors in America in each listing for the past decade, and was named in the U.S. News & World Report's Top Doctors List. Dr Afshari is the co-editor of a new two-volume cornea book called “Principles and Practice of Cornea”. She is also on the editorial boards of Investigative Ophthalmology and Visual Science and American Journal of Ophthalmology. She has previously served on the EyeNet editorial board, BCSC Cornea text book committee, and the American Academy of Ophthalmology council representing the American Society of Cataract and Refractive Surgery. She was co-chair of the cornea program committee for the Association for Research in Vision and Ophthalmology and co-director of Cornea Subspecialty Day for the American Academy of Ophthalmology. She is currently the chair of the American Society of Cataract and Refractive Surgery FDA Committee. Her NIH research grant is on the study of Fuchs dystrophy, and she investigates the intricacies of endothelial keratoplasty and regeneration of cornea. When not researching or practicing, Dr Afshari donates her time and surgical expertise as an international volunteer. She has traveled to West Africa, Central America, and Mexico to help patients who might otherwise go untreated.

Novel approach to antiangiogenic factors in age-related macular degeneration therapy.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the population above 85 worldwide. There are two main types of AMD: neovascular and dry AMD. Neovascular AMD leads to macular changes resulting from abnormal choroidal neovascularization. Untreated neovascular AMD leads to scar formation and irreversible sight deterioration. Dry AMD in consequence leads to atrophic changes of the macula.The last decades brought a breakthrough in the therapy of neovascular age-related macular degeneration by introduction of, firstly, photodynamic therapy and, later, anti-VEGF agents administered intravitreally in order to stop neoangiogenesis. However, the treatment of dry AMD is still challenging. Among the directions in dry AMD treatment, the most promising are complement cascade inhibitors and complement cascade targeted gene therapy.In the article we outline the main directions in up-to-date experimental and practical approaches to wet and dry AMD therapy with the emphasis on antiangiogenic factors and gene therapy focused on the inhibition of pathological angiogenesis.

POSA3 Comparative Efficacy of Anti-Vascular Endothelial Growth Factor (ANTI-VEGF) Agents for Treatment of Neovascular Age-Related Macular Degeneration (NAMD): A Systematic Review and Network Meta-Analysis

We conducted a systematic literature review (SLR) and network meta-analysis (NMA) comparing efficacy, safety and injection frequency of brolucizumab relative to other approved and marketed anti-VEGFs in nAMD patients.

Patient satisfaction following a switch from treat-and-extend to observe-and-plan regimen in age-related macular degeneration

ObjectiveStandard treatment of neovascular age-related macular degeneration (nAMD) is intravitreal injections (IVI) of antivascular endothelial growth factor (anti-VEGF) according to treat-and-extend (TnE). Observe-and-plan (OnP), a new regimen based on each...

Non-invasive testing for early detection of neovascular macular degeneration in unaffected second eyes of older adults: EDNA diagnostic accuracy study.

Neovascular age-related macular degeneration is a leading cause of sight loss, and early detection and treatment is important. For patients with neovascular age-related macular degeneration in one eye, it is usual practice to monitor the unaffected eye. The test used to diagnose neovascular age-related macular degeneration, fundus fluorescein angiography, is an invasive test. Non-invasive tests are available, but their diagnostic accuracy is unclear. The primary objective was to determine the diagnostic monitoring performance of tests for neovascular age-related macular degeneration in the second eye of patients with unilateral neovascular age-related macular degeneration. The secondary objectives were the cost-effectiveness of tests and to identify predictive factors of developing neovascular age-related macular degeneration. This was a multicentre, prospective, cohort, comparative diagnostic accuracy study in a monitoring setting for up to 3 years. A Cox regression risk prediction model and a Markov microsimulation model comparing cost-effectiveness of the index tests over 25 years were used. This took place in hospital eye services. Participants were adults (aged 50-95 years) with newly diagnosed (within the previous 6 weeks) neovascular age-related macular degeneration in one eye and an unaffected second (study) eye who were attending for treatment injections in the first eye and who had a study eye baseline visual acuity of ≥ 68 Early Treatment Diabetic Retinopathy Study letters. The index tests were Amsler chart (completed by participants), fundus clinical examination, optical coherence tomography, self-reported vision assessment (completed by participants) and visual acuity. The reference standard was fundus fluorescein angiography. The main outcome measures were sensitivity and specificity; the performance of the risk predictor model; and costs and quality-adjusted life-years. In total, 552 out of 578 patients who consented from 24 NHS hospitals (n = 16 ineligible; n = 10 withdrew consent) took part. The mean age of the patients was 77.4 years (standard deviation 7.7 years) and 57.2% were female. For the primary analysis, 464 patients underwent follow-up fundus fluorescein angiography and 120 developed neovascular age-related macular degeneration on fundus fluorescein angiography. The diagnostic accuracy [sensitivity (%) (95% confidence interval); specificity (%) (95% confidence interval)] was as follows: optical coherence tomography 91.7 (85.2 to 95.6); 87.8 (83.8 to 90.9)], fundus clinical examination [53.8 (44.8 to 62.5); 97.6 (95.3 to 98.9)], Amsler [33.7 (25.1 to 43.5); 81.4 (76.4 to 85.5)], visual acuity [30.0 (22.5 to 38.7); 66.3 (61.0 to 71.1)] and self-reported vision [4.2 (1.6 to 9.8); 97.0 (94.6 to 98.5)]. Optical coherence tomography had the highest sensitivity across all secondary analyses. The final prediction model for neovascular age-related macular degeneration in the non-affected eye included smoking status, family history of neovascular age-related macular degeneration, the presence of nodular drusen with or without reticular pseudodrusen, and the presence of pigmentary abnormalities [c-statistic 0.66 (95% confidence interval 0.62 to 0.71)]. Optical coherence tomography monitoring generated the greatest quality-adjusted life-years gained per patient (optical coherence tomography, 5.830; fundus clinical examination, 5.787; Amsler chart, 5.736, self-reported vision, 5.630; and visual acuity, 5.600) for the lowest health-care and social care costs (optical coherence tomography, £19,406; fundus clinical examination, £19,649; Amsler chart, £19,751; self-reported vision, £20,198; and visual acuity, £20,444) over the lifetime of the simulated cohort. Optical coherence tomography dominated the other tests or had an incremental cost-effectiveness ratio below the accepted cost-effectiveness thresholds (£20,000) across the scenarios explored. The diagnostic performance may be different in an unselected population without any history of neovascular age-related macular degeneration; the prediction model did not include genetic profile data, which might have improved the discriminatory performance. Optical coherence tomography was the most accurate in diagnosing conversion to neovascular age-related macular degeneration in the fellow eye of patients with unilateral neovascular age-related macular degeneration. Economic modelling suggests that optical coherence tomography monitoring is cost-effective and leads to earlier diagnosis of and treatment for neovascular age-related macular degeneration in the second eye of patients being treated for neovascular age-related macular degeneration in their first eye. Future works should investigate the role of home monitoring, improved risk prediction models and impact on long-term visual outcomes. This study was registered as ISRCTN48855678. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 8. See the NIHR Journals Library website for further project information.

The nuclear factor E2-related factor 2 and age-related macular degeneration.

After the discovery of anti-vascular endothelial growth factor agents as treatment of wet age-related macular degeneration, the number of studies with the objective to understand the molecular mechanisms involved in the age-re lated macular degeneration genesis has increased. The importance of the nuclear factor e2-related factor 2 lies in its activation-derived proteins being involved in the maintenance of the redox balance and consequent prevention of degenerative macular disease. This article aims to present the characteristics of nuclear factor e2-related factor 2 and describe the main nuclear factor e2-related factor 2-activated antioxidant enzymes that contribute to the preservation of vision.

Transcriptomics insights into interpreting AMD-GWAS discoveries for biological and clinical applications

Genome-wide association studies (GWAS) have been successful in identifying genetic risk factors for a large number of complex diseases, including age-related macular degeneration (AMD), which is a highly heritable complex disease affecting millions of elderly individuals. However, the progress of elucidating the functional relevance of genetic findings in AMD has been slow, as most risk factors are non-coding, and we have little insight into the causal genes and disease mechanisms. In the last few years, gene expression regulation is emerging as a dominant mechanism through which GWAS risk variants lead to the disease. The purpose of this review is to provide an overview of how transcriptome studies can help in identifying the genes, pathways and therapeutic targets underlying GWAS discoveries in AMD. These approaches help pave the road for mechanistic understanding of GWAS findings and drive translational advances that will lead to improved AMD management and treatment.

Bioinformatic analysis identifies potential key genes in the pathogenesis of age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals. More studies focused on screening the genes, which may be correlated with the development of AMD. With advances in various technologies like multiple microarray datasets, researchers could identify differentially expressed genes (DEGs) more accurately. Exploring abnormal gene expression in disease status can help to understand pathophysiological changes in complex diseases. This study aims to identify the key genes and upstream regulators in AMD and reveal factors, especially genetic association, and the prognosis of the development of this disease. Data from expression profile GSE125564 and profile GSE29801 were obtained from the Gene Expression Omnibus (GEO) database. We analyzed DEGs using R software (version 3.6.3). Functional enrichment and PPI network analysis were performed using the R package and online database STRING (version 11.0). We compared AMD with normal and found 68 up-regulated genes (URGs) and 25 down-regulated genes (DRGs). We also compared wet AMD with dry AMD and found 41 DRGs in dry AMD. Further work including PPI network analysis, GO classification, and KEGG analysis was done to find connections with AMD. The URGs were mainly enriched in the biological process such as DNA replication, nucleoplasm, extracellular exosome, and cadherin binding. Besides, DRGs were mainly enriched in these functions such as an integral component of membrane and formation of the blood-aqueous barrier (BAB). This study implied that core genes might involve in the process of AMD. Our findings may contribute to revealing the pathogenesis, developing new biomarkers, and raising strategies of treatment for AMD.

An integrated analysis of clinical and morphometric indications of atrophic forms of age-related macular degeneration

The atrophic form of late age-related macular degeneration (AMD) is a common cause of severe vision loss. Recently, a new classification system has been proposed, which identifies two types of atrophy in the late stage of AMD that require a more detailed study: (1) drusenassociated geographic atrophy (GA), which is the final stage of progression of dry AMD, and (2) macular atrophy (MA), which occurs in wet AMD, including the period of AMD treatment with angiogenesis inhibitors. Purpose: an integrated analysis of clinical and morphometric signs of atrophic AMD forms. Material and methods. 48 people (61eyes) aged 48–84 with GA (group 1) and MA (group 2) and a control group, recruited from age-matching 25 healthy volunteers (35 eyes), underwent standard ophthalmological examinations, fundus autofluorescence (FAF) with lesion area measurement, fundus photography, optical coherence tomography (OCT) in the standard mode and Enhanced Depth Imagine Mode, Multicolor, and OCT angiography. Results. The comparative analysis of two atrophic AMD forms showed that in GA eyes, foci of atrophy capturing the fovea were significantly more common, while, contrariwise in MA eyes atrophic foci not capturing the fovea were more frequent (p &lt; 0.05). Photoreceptor tubulation was diagnosed mainly in eyes with GA (p &lt; 0.05). The morphometric analysis showed a significant decrease in the subfoveal thickness of the choroid in the groups with GA and MA as compared to the control (p &lt; 0.05), whilst no significant differences between two groups were noted. The assessment of the frequency of occurrence of types of fundus AF patterns in groups 1 and 2 followed by a comparative analysis, showed the presence of all types of patterns in GA patients, including the heterogeneous and the bordering pattern (p &lt; 0.05). In the MA group, diffuse and focal types of patterns were revealed, while the frequency of the diffuse pattern turned out to be significantly more frequent (p &lt; 0.05). Conclusion. The integrated analysis revealed the main semiological signs and morphometric parameters, their features and prevalence in GA and MA, which may have diagnostic and prognostic importance for the management and treatment of patients with AMD.

Patient and retina specialists' preferences in neovascular age-related macular degeneration treatment. A discrete choice experiment.

Neovascular age-related macular degeneration (nAMD) leads to severe and permanent visual impairment, significantly impacting patients' quality of life and functional independence. Although treatment with anti- vascular endothelial growth factor (VEGF) prevents and, in some cases, reverses visual damage, the need for frequent monitoring visits and intravitreal injections represents a significant burden on patients, caregivers and retina specialists. To elicit preferences for nAMD treatment characteristics from the perspectives of patients and retina specialists. A discrete choice experiment was conducted. Participants (patients > 50 years with nAMD receiving anti-VEGF drugs for at least 2 years and without previous experience with anti-VEGF and retina specialists working in the Spanish National Healthcare System) were asked to select one of two hypothetical treatments resulting from the combination of five attributes (effects on visual function, effects on retinal fluid, treatment regimen, monitoring frequency, and cost); their levels were identified by reviewing the literature and two focus groups. The relative importance (RI) given to each attribute was estimated using a mixed logit model. The marginal rates of substitution (MRS) were calculated taking cost as the risk attribute. A total of 110 patients (P) [aged 79.0 (SD:7.4) years; 57.3% women; 2.3 (SD:0.7) years with nAMD; 2.1 years (SD:0.1) in treatment] and 66 retina specialists (RS) participated in the study. Participants gave greater RI to improvements in their visual function [60.0% (P); 52.7% (RS)], lower monitoring frequency [20.2% (P); 27.1% (RS)] and reduction in retinal fluid [9.8% (P); 13.0%(RS)]. Patients and retina specialists would agree to an increase in cost by 65.0% and 56.5%, respectively, in exchange for improvements of visual function; and 25.5% and 43.3% on delaying monitoring frequency by one month. Efficacy of treatment, in terms of visual function improvements, is the main driver for treatment election for both patients and retina specialists. Treatment monitoring requirements are also considered, mainly from the retina specialist's perspective. These results suggest that the use of more efficacious anti-VEGF agents with a longer duration of action may contribute to aligning treatment characteristics with patients/specialists' preferences. A better alignment would facilitate better disease management, fulfilling the unmet needs of patients and retina specialists.

Choroidal neovascularization activity and structure by optical coherence tomography angiography in age related macular degeneration

Background. In economically developed countries, age-related macular degeneration (AMD) is the leading cause of visual disability among the population of the older age group. The main criterion for the anti-VEGF treatment of neovascular AMD is the activity of choroidal neovascularization (CNV), which is determined by its confi guration. The search for optimal criteria for quantifying the state of the macular region in order to decide on the appointment of anti-VEGF therapy continues.Aim: improving the effi ciency of diagnosis and treatment of AMD based on the assessment of the configuration of vascular system on the “Key to Diagnosis II” platform.Material and methods. The study included 341 patients: 64 % (218 patients, 267 eyes) with non-neovascular AMD, 36 % (123 patients, 174 eyes) – with neovascular AMD. 56 patients (58 eyes) had active type I CNV. Group 1A – active CNV before treatment (9 patients, 9 eyes), group 1B – non-active CNV after treatment with antiVEGF (9 patients, 9 eyes); control group – 10 patients (10 eyes) without AMD. Analysis of OCT-angio images of choriocapillaries included the isolation of CNV, its area, fractal dimension (Df) and the complexity of the vascular system (CVS) counting.Results. Group 1A: Df – 1.5871 ± 0.05, CVS – 2.29 ± 0.29, area – 11734 ± 4866; group 1B: Df – 1.6462 ± 0.08, CVS – 1.65 ± 0.18, area – 6797 ± 3818; control: Df – 1.9167 ± 0.06, CVS – 1, area – 0. Significant differences were found for CVS (p = 0.0003). Df correlates with the CNV area (p = 0.7) and is probably an unreliable parameter due to incomplete visualization of active CNV.Conclusions. CVS is a quantitative biomarker for determining the activity of type 1 CNV in patients with AMD and can serve as a parameter for convolutional neural networks training for automated analysis of OCT angiography images based on the “Key to Diagnosis II” platform