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Background: Anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management of various ocular conditions, including diabetic macular edema (DME), retinal vein occlusion (RVO)-related macular edema (ME), and neovascular age-related macular degeneration (nAMD). However, there remains a need to systematically assess its effectiveness across these distinct conditions. Methodology: A systematic review was conducted to identify studies evaluating the efficacy of anti-VEGF therapy in improving ocular outcomes in patients with DME, RVO-related ME, and nAMD. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published up to 2024. Studies meeting the inclusion criteria were critically appraised, and data on the proportion of patients gaining ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in best-corrected visual acuity (BCVA), mean change in BCVA (ETDRS letters), and reduction in central macular thickness (CMT) (μm) were extracted and synthesized. Results: The systematic review identified 18 studies comprising randomized controlled trials, prospective studies, retrospective analyses, and observational studies. Anti-VEGF therapy demonstrated efficacy across all three conditions, with varying proportions of patients experiencing improvements in BCVA and reductions in CMT. Notably, the proportion of patients gaining ≥ 15 ETDRS letters ranged from 18.1% to 44.8% in DME, while mean changes in BCVA ranged from +4.2 letters to +21.4 letters in RVO-related ME and nAMD. Reductions in CMT ranged from 183.1 μm to 294 μm in DME and RVO-related ME. Conclusion: Anti-VEGF therapy represents a cornerstone in the management of DME, RVO-related ME, and nAMD, with significant improvements observed in BCVA and reductions in CMT across diverse patient populations. While our findings support the effectiveness of anti-VEGF therapy in improving ocular outcomes, further research is warranted to compare its efficacy with alternative treatment modalities and to elucidate its long-term safety profile. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To quantify ellipsoid zone (EZ) loss during anti‐VEGF therapy for neovascular age‐related macular degeneration (nAMD) and correlate these findings with nAMD disease activity using artificial intelligence‐based algorithms.Spectral domain optical coherence tomography (Spectralis, Heidelberg Engineering) images from nAMD treatment‐naïve patients from the Fight Retinal Blindness! (FRB!) Registry from Zürich, Switzerland were processed at baseline and over 3 years of follow‐up. An approved deep learning algorithm (Fluid Monitor, RetInSight) was used to automatically quantify intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED). An ensemble U‐net deep learning algorithm was used to automated quantify EZ integrity based on EZ layer thickness. The impact of fluid volumes on EZ thickness and late‐stages outcomes were calculated using Wilcoxon rank‐sum tests, a linear mixed model and a longitudinal panel regression model.Two hundred and eleven eyes from 158 patients were included. The mean ± SD EZ loss area in the central 6 mm was 1.81 ± 2.68 mm2 at baseline and reached 6.21 ± 6.15 mm2 at month 36. Higher fluid volumes (top 25%) of IRF and PED in the central 1 and 6 mm of the macula were significantly associated with more advanced EZ thinning and loss compared to the low fluid volume subgroup. The high SRF subgroup in the linear regression model showed no statistically significant association with EZ integrity in the central macula; however, the longitudinal analysis revealed an increased EZ thickness with no additional loss.Intraretinal fluid and PED volumes and their resolution pattern have an impact on alteration of the underlying EZ layer. AI‐supported quantifications are helpful in quantifying early signs of macular atrophy and providing individual risk profiles as a basis for tailored therapies for optimized visual outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of the changes in treatment patterns before, during and after the COVID‐19 pandemic on best‐corrected visual acuity (BCVA) in previously treated neovascular age‐related macular degeneration (nAMD) patients. Methods: A multi‐centre, retrospective, observational study of consecutive nAMD patients during 2019–2021. Data collected included demographics, BCVA, dates of intravitreal anti‐vascular endothelial growth factor (anti‐VEGF) injections and clinic visits. Results: A total of 1652 eyes of 1652 nAMD patients were included, out of which 850 eyes were assessed in 2019 (pre‐COVID‐19), 630 eyes were assessed in 2020 (COVID‐19) and 974 eyes were assessed in 2021 (post‐COVID‐19). During the COVID‐19 period, the mean number of anti‐VEGF injections was significantly lower than the corresponding pre‐COVID‐19 and post‐COVID‐19 periods (5.55 compared to 6.13 and 6.60, respectively p < 0.01). A constant lower ratio of injections per patient/month was observed during COVID‐19 compared to previous and following years, with a notable decline during March–April, reaching a ratio of 0.4 in 2020 versus 0.65 in 2019 and 0.62 in 2021 (p < 0.01). Baseline BCVA (0.825, p < 0.001), number of injections (−0.007, p < 0.001), gender (−0.027, p = 0.037) and age (0.004, p < 0.001) were shown to be significant predictors of final BCVA. Conclusion: During the COVID‐19 period, patients were treated with significantly less intravitreal anti‐VEGF injection compared to the previous year with compensation in the following year. These changes in treatment patterns did not have a significant impact on BCVA outcomes. Age, gender, baseline BCVA and number of injections are predictors of final visual outcomes. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a chronic and progressive retinal degenerative disease of the macula that affects the elderly and causes impairment of central vision. AMD is a multifactorial disease that encompasses a complex interplay between aging, environmental risk factors, and genetic susceptibility. Chronic inflammation, lipid deposition, oxidative stress, and impaired extracellular matrix maintenance are strongly implicated in the pathogenesis of AMD. Advanced AMD can be classified into two types: dry and wet. Although dry AMD accounts for the majority of diagnosed cases, wet AMD is responsible for the majority of severe vision loss and usually occurs within weeks or months. Although neovascularization was the most common cause of severe vision loss, geographic atrophy, the most advanced form of dry AMD, can also cause significant vision loss. The medical treatment of neovascular AMD has seen significant progress due to the introduction of vascular endothelial growth factor (anti-VEGF) inhibitors, which have dramatically changed the prognosis of the disease. Research does not prove the need to change treatment methods in every patient, there may be occasions when patients with AMD show a more robust response to one anti-VEGF agent than another. Clinicians may consider alternatives to switching, such as increasing injection frequency, when managing a patient who appears to be unresponsive to therapy. In this regard, it may be helpful to have a patient return for evaluation 1 to 2 weeks after injection with repeat testing to assess whether there has been a reduction in subretinal fluid or retinal edema shortly after anti-VEGF injection.

Bhim Bahadur Rai,1,2 Deepa Rai,3 Ted Maddess1 1John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia; 2Department of Ophthalmology, JDW National Referral Hospital, Thimphu, Bhutan; 3Warrigal Aged Care Facility, Calwell, ACT, AustraliaCorrespondence: Bhim Bahadur Rai, John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Canberra, ACT, 2601, Australia, Tel +61 2 61259253, Email bhim.rai@anu.edu.auPurpose: Ocular vascular diseases are common causes of visual impairment and blindness, for which anti-vascular endothelial growth factor (anti-VEGF) is the first-line therapy. Current study describes the profile of patients receiving intravitreal anti-VEGF injections (IVI), and gender variation in Bhutan. The study was designed to inform national health policy.Study Design: Retrospective cross-sectional study.Methods: We reviewed the surgical registers of the vitreoretinal (VR) units across Bhutan over three years. Patient demography, clinical findings, diagnostic tests performed, and diagnoses or indications for IVI were logged. A descriptive analysis was performed.Results: Despite limited availability of anti-VEGF, a total of 381 patients received IVI in operating theatres as mandated by the national guidelines. The majority of patients were males (230, 60.4%, p = 0.004). The mean age was 65.2 ± 13.5 years (range 13 years to 90 years), and a median of 69 years. The majority of the treated eyes (117, 30.7%) had BCVA < 3/60 to light perception (PL), and another 51 eyes (13.4%) had < 6/60 to 3/60. The most common indication for IVI was neovascular age-related macular degeneration (nAMD) (168 cases, 42.2%), followed by retinal vein occlusion (RVO) (132 cases, 34.6%), diabetic macular oedema (DMO) and retinopathy (DR) (50 cases, 13.1%), and myopic choroidal neovascular membrane (11 cases, 0.03%).Conclusion: Limited human resources for managing VR diseases in Bhutan are compounded by economic and geographic challenges. With increasing VR diseases such as nAMD and myopia and complications of systemic diseases such as DR, DMO and RVO, there is a need to improve VR services. Currently, anti-VEGF is procured only for a pooled patients requiring IVI, and patients are lost due to longer waiting periods. Bhutan needs to assess if females are reporting less or are not receiving treatment due to cultural barriers and social stigma.Keywords: anti-VEGF, Bhutan retinal diseases, diabetic macular oedema, intravitreal injection, neovascular AMD, retinal vein occlusion

PurposeTo determine the proportion of treatment-experienced eyes with exudative age-related macular degeneration successfully treated with every-4-week aflibercept that can be kept dry on fixed every-8-week aflibercept injections (maintenance).MethodsIn this retrospective chart review, we evaluated our cohort of patients treated with a treatment paradigm for CNV in AMD. Initially, patients were treated with bevacizumab or ranibizumab and switched to every-4-week aflibercept when therapeutic responses were not durable or were suboptimal. Maintenance every-8-week therapy was initiated when the retina was completely dry on every-4-week aflibercept therapy. The primary outcome measure was recurrence of exudation on optical coherence tomography (OCT) during maintenance.ResultsThirty-six eyes of 31 consecutive patients with median age of 79 years (range, 65-89) were included. Maintenance was started after a median of 34 (range, 8-88) injections. Recurrence was observed in 20 eyes (55%). Of these, 11 eyes (31%) reactivated at 8 weeks. Median time to failure of maintenance schedule was 40 weeks by Kaplan-Meier analysis. Baseline demographic and anatomic characteristics were not associated with failure of maintenance schedule.ConclusionIn treatment-experienced eyes that respond completely to every-4-week aflibercept, maintenance therapy with every-8-week injections can only temporarily maintain anatomic success with the majority of eyes developing recurring activity. This regimen fails early in one third of eyes and has a median effective duration of 40 weeks. Aflibercept appears to be inadequate to maintain control of exudation in most eyes in at least half of eyes undergoing long-term therapy.

Purpose: This study seeks to report the clinical and multimodal imaging findings of eight eyes of seven patients with neovascular age-related macular degeneration (nAMD) who developed bacillary layer detachment (BALAD). Setting/Venue: The patients were analysed at the Western Eye Hospital in London, UK. Methods: The approaches of this research include clinical examinations and multimodal imaging-based description of cases of nAMD with BALAD. Results: We report multimodal imaging findings of bacillary layer detachment (BALAD) in patients with nAMD. Conclusions: A bacillary layer detachment was detected in patients with neovascular age-related macular degeneration. This multimodal imaging finding is not commonly described in the literature for this disease. [ABSTRACT FROM AUTHOR]

Currently, there is a wide range of antiglaucoma drugs. Ophthalmologists are faced with the task of choosing certain drugs and their combinations for specific patients. In this regard, studies aimed at studying the effectiveness of treatment, not only in terms of IOP indicators and instrumental research methods, but also in terms of the choice of a particular type of therapy by ophthalmologists, are of great interest. Purpose: to analyze the data obtained in the course of the study of the Russian multicenter scientific program: “Analysis of the assortability of ophthalmologists when choosing therapy within the framework of routine medical care in patients with primary open-angle glaucoma (POAG)”. The large-scale statistical study carried out was based on the study of 197 medical questionnaires from 61 cities of Russia, containing information on 6851 clinical cases. Doctors were asked to fill out a questionnaire based on the results of treatment (at least 2 months), taking into account the following criteria: satisfaction with treatment, adherence to treatment, accessibility, tolerability and ease of use of drugs. Evaluated the use of 5 antiglaucoma drugs of the company Sentiss Russ, belonging to different pharmacological groups: Prolatan (latanoprost), Bimatan (bimatoprost), Brinex-M (brinzolamide); Tisoptan (bimatoprost / timolol maleate), Brinarga (brinzolamide / timolol maleate). During the study, patients were divided into 6 groups depending on the drug used, and also into 3 groups depending on the stage of primary POAG. The data obtained indicate a statically high level of average values when using the point system of all the above criteria when using these drugs. When analyzing the degree of convenience and the level of tolerance of drugs, a tendency towards a decrease in the average scores of these indicators in patients with advanced stage of glaucoma was noted, which may be due to the long-term use of antiglaucoma therapy in this category of patients with changes in the ocular surface. 98.25% of doctors expressed their intention to continue prescribing antiglaucoma drugs from Sentiss Russ.

Colin S Tan,1,2 Wei Kiong Ngo,1,2 Isaac W Chay,1,2 Dominic S Ting,1,2 SriniVas R Sadda3 1National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore; 2Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore; 3Doheny Image Reading Center, Doheny Eye Institute, Los Angeles, CA, USACorrespondence: SriniVas R Sadda, Doheny Image Reading Center, Doheny Eye Institute, 3623, 1450 San Pablo Street, Los Angeles, CA, 90033, USA, Email sadda@usc.eduAbstract: Neovascular age-related macular degeneration (nAMD) is a common world-wide cause of visual loss. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are an effective means to treat nAMD and reduce its impact on vision compared to either sham treatment or photodynamic therapy. Currently, the approved anti-VEGF drugs include ranibizumab, aflibercept and brolucizumab. In addition, bevacizumab, used as an off-label drug, and has been shown to be effective in treating nAMD. While anti-VEGF agents are effective, its limitations include the requirement for frequent, often monthly injections, and the need for long-term treatment of nAMD. These present significant burdens on the healthcare system and on the patients. In addition, reviews of patients with nAMD treated with anti-VEGF have reported deterioration of vision over time with progression of geographic atrophy. These limitations are partly addressed by exploring different treatment regimens that reduce the frequency of treatments. Newer anti-VEGF drugs have been shown in Phase III clinical trials to have injection intervals as long as 12 or even 16 weeks for a proportion of patients. There is research on newer drugs that affect other pathways, such as the angiopoietin pathway, which may impact nAMD by extending the treatment interval and reducing the burden of treatment. Other measures include the use of sustained-release implants that release the drug regularly over a period of time, and can be refilled periodically, as well as hydrogel platforms that serve to release the drug. The use of biosimilars will also serve to reduce the cost of treatment for nAMD. A new frontier of gene therapy, primarily targeting genes involved in the transduction of retinal cells to produce anti-VEGF proteins intraocularly, also opens a new avenue of therapeutic approaches that can be used for treatment. This review paper will discuss both current treatment options and the newer treatments under development.Keywords: neovascular AMD, anti-VEGF, retina, gene therapy

Age-related macular degeneration AMD is one of the leading causes of blindness in the elderly population. An advanced form of AMD known as neovascular AMD (nAMD) is implicated as the main attributor of visual loss among these patients. The hallmark feature of nAMD is the presence of neovascular structures known as choroidal neovascular membranes (CNVs), along with fluid exudation, hemorrhages, and subretinal fibrosis. These pathological changes eventually result in anatomical and visual loss. A type of proangiogenic factor known as vascular endothelial growth factor (VEGF) has been known to mediate the pathological process behind nAMD. Therefore, therapy has transitioned over the years from laser therapy that ablates the lesions to using Anti-VEGF to target the pathology directly. In this work, we provide an overview of current and emerging therapies for the treatment of nAMD. Currently approved Anti-VEGF agents include ranibizumab, aflibercept, and brolucizumab. Bevacizumab, also an Anti-VEGF agent, is used to manage nAMD even though this is an off-label use. While Anti-VEGF agents have provided a favorable prognosis for nAMD, they are associated with a substantial financial burden for patients and the healthcare system, due to their high cost as well as the need for frequent repeat treatments and visits. Emerging therapies and studies aim to extend the intervals between required treatments and introduce new treatment modalities that would improve patients' compliance and provide superior results. [ABSTRACT FROM AUTHOR]

Purpose: To explore the comparative efficacy and safety of higher dose intravitreal bevacizumab, ranibizumab, or aflibercept for treatment-resistant neovascular age-related macular degeneration (nAMD). Methods: Retrospective analysis of 37 eyes of 35 patients with treatment-resistant nAMD divided into 3 cohorts based on high-dose treatment received: 3 mg aflibercept, 0.75 mg or 1.0 mg ranibizumab, and 1.8 mg or 2.5 mg bevacizumab. The eyes were analyzed at standardized time points up to 48 months. Included eyes demonstrated active nAMD with persistent exudation on imaging for at least 6 months with at least 4 anti-VEGF injections during this time. Outcomes included change in visual acuity (VA), central retinal thickness (CRT), intraocular pressure (IOP), retinal morphology, adverse event occurrence, and yearly intravitreal injection (IVI) rate. Results: There was no significant difference in VA or IOP change compared to the initiation of high-dose treatment for any agent or comparing between agents at any time point (p > 0.05). CRT improved at month 1, 3, 6, and 12 with all 3 agents (p < 0.05 for all) with a greater CRT reduction seen for ranibizumab than aflibercept at month 6 (p < 0.05), although baseline CRT was greater in the ranibizumab group than the aflibercept group (p < 0.05). Mean absolute CRT was similar at month 6 for all agents (p > 0.05). IVI rates pre- and post-conversion to higher-dose therapy were similar (1 injection per 5.7–6.4 weeks). Mean follow-up was 22.8 months. Conclusions: Higher dose therapy may achieve improved anatomic outcomes and maintain vision, but frequent injections are required to achieve this. There was no detected difference in efficacy or safety between agents. [ABSTRACT FROM AUTHOR]

Red-green chromatic sensitivity and photopic (cone-mediated) flicker sensitivity showed marked improvement after anti-VEGF treatment. The use of flicker and chromatic sensitivities as potential functional tests to monitor treatment outcomes in age-related macular degeneration highlights the clinical importance. High-contrast visual acuity (VA) is not a sensitive clinical marker in the management of age-related macular degeneration (AMD). Therefore, flicker and chromatic sensitivity changes were assessed following anti-VEGF treatment in subjects with neovascular AMD. Subjects diagnosed with neovascular AMD were recruited. VA was measured using a COMPlog chart. Flicker (in central 5°) and chromatic thresholds (red-green and yellow-blue) were measured using Flicker-plus test and Colour Assessment and Diagnosis (CAD) tests, respectively. Baseline thresholds and foveal thickness were measured on the same day, just before anti-VEGF injection delivery and 5 weeks ± 5 days later. Thirteen subjects (8 males, 5 females) with a mean age of 67.5 ± 8.2 years completed the study. Median VA was not significantly different post-treatment (0.57 logMAR [~6/22: Snellen equivalent], IQR: 0.33) compared to baseline (0.56 logMAR, IQR: 0.33), Wilcoxon matched-pair test, p = 0.55). Median Red-Green thresholds improved significantly post-treatment (22.15 CAD units, IQR: 26.06, n = 9), compared to baseline (24.24 CAD units, IQR: 26.21, p = 0.02). Median photopic and mesopic FMT did not show significant change post treatment compared to baseline (p > 0.01, statistical significance of p-value corrected for multiple comparisons was set to 0.01). Similarly, the foveal thickness was not significantly different at post-treatment visit than baseline (p = 0.53). Red/green sensitivity recovered better than yellow/blue sensitivity, thus, providing insight into recovery mechanisms in AMD and usefulness of these tests as clinical markers in the management of AMD. [ABSTRACT FROM AUTHOR]

Purpose: This study seeks to report the clinical and multimodal imaging findings of eight eyes of seven patients with neovascular age-related macular degeneration (nAMD) who developed bacillary layer detachment (BALAD). Setting/Venue: The patients were analysed at the Western Eye Hospital in London, UK. Methods: The approaches of this research include clinical examinations and multimodal imaging-based description of cases of nAMD with BALAD. Results: We report multimodal imaging findings of bacillary layer detachment (BALAD) in patients with nAMD. Conclusions: A bacillary layer detachment was detected in patients with neovascular age-related macular degeneration. This multimodal imaging finding is not commonly described in the literature for this disease.

Inhibition of vascular endothelial growth factor is the mode of action for several approved therapies, including aflibercept, for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Lack of compliance due to the frequent intravitreal dosing requirements may result in inadequately treated disease, leading to irreversible vision impairment. To date, the majority of gene therapy clinical trials providing sustained anti-VEGF levels in the retina have been limited to subretinal injections requiring a vitrectomy. A single intravitreal injection of a gene therapy product could drastically reduce the treatment burden and improve visual outcomes. ADVM-022, an adeno-associated virus vector encoding aflibercept, has been optimized for intravitreal delivery and strong protein expression. Long-term expression and efficacy of ADVM-022-derived aflibercept were evaluated in a laser-induced choroidal neovascularization (CNV) model in non-human primates. Ocular safety was evaluated following long-term suppression of VEGF by clinical scoring (inflammatory parameters) as well as optical coherence tomography (OCT) and electroretinography (ERG). Intravitreal administration of ADVM-022 was well tolerated and resulted in sustained aflibercept levels in ocular tissues. In addition, ADVM-022 administration 13 months before laser-induced CNV prevented the occurrence of clinically relevant CNV lesions, to the same degree as a bolus of aflibercept delivered at the time of laser. These results demonstrate that a single intravitreal administration of ADVM-022 may provide a safe and effective long-term treatment option for nAMD and DME, and may ultimately improve patients' visual outcomes. Clinical trials are currently underway, evaluating safety and efficacy following a single intravitreal injection of ADVM-022. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to determine if ziv-aflibercept is a safe and effective maintenance drug for nAMD.Study Design and Methods: This is a randomized, prospective, single-blinded trial. Inclusion criteria were active nAMD, prior anti-VEGF treatment, and BCVA ≤20/200. The treatment group received ziv-aflibercept. The control group continued their existing anti-VEGF regimen. The main outcome measures were BCVA, CFT, and safety.Results: Mean baseline BCVA was 1.58 ± 0.44 logMAR and 1.71 ± 0.39 logMAR in the control (n = 27) and treatment (n = 29) groups, respectively. After 24 months, the mean change in BCVA was 0.11 in the control group (equivalent to a loss of 5 ETDRS letters) and 0.01 logMAR in the treatment group (p = .48). Baseline CFT was 257 ± 33 μm and 247 ± 30 μm in the control and treatment groups, respectively, and after 24 months mean change in CFT was 26 μm and -5 μm (p = .24). There were no ocular or systemic adverse events during the study.Conclusion: Ziv-aflibercept is a safe and effective as a maintenance drug for patients with nAMD. It may represent a cost-effective alternative to aflibercept and second-line therapy for eye resistant bevacizumab or ranibizumab. [ABSTRACT FROM AUTHOR]

Introduction: Despite consistent use of anti-vascular endothelial growth factor (anti-VEGF), prognosis of large, fovea-involving submacular hemorrhage (SMH) has remained guarded, particularly in patients with neovascular age-related macular degeneration. Areas covered: This review provides an update on management of SMH, with particular focus on the role of anti-VEGF therapy and surgical management of thick, large, and/or subfoveal SMH. A literature search and meta-analysis of studies published from January 2010 to February 2019 was performed to evaluate outcomes of eyes with SMH following management with either medical treatment (i.e. anti-VEGF monotherapy) or a combined surgical approach of pars plana vitrectomy, subretinal tPA with or without subretinal air, pneumatic displacement, and anti-VEGF. The surgical techniques are summarized, with emphasis on novel surgical techniques described in the past decade. Prognostic factors associated with, and potential indications for, choice of management approach were evaluated. Expert commentary: SMH represents a continuing treatment challenge. Anti-VEGF monotherapy is a reasonable approach in patients with small, thin, and localized hemorrhage. Combination vitrectomy, tPA, pneumatic displacement, and anti-VEGF may be effective in managing thick, large SMH in some cases. While no consensus exists on optimal treatment algorithm, choice of medical or surgical therapy should be tailored to each patient. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of this study is to analyze mortality in patients treated with bevacizumab for wet AMD. Methods We conducted a retrospective case-control study between patients who received intravitreal injections of bevacizumab as the sole treatment for exudative AMD between September 2008 and October 2014 (n = 5385) and age and gender matched controls (n = 10,756). All individuals included in the study were reviewed for sociodemographic data and comorbidities. Survival analysis was performed using adjusted Cox regression, using relevant adjusted variables. Results During follow-up (maximum: 73 months), 1063 (19.7%) individuals after bevacizumab died compared with 1298 (12.1%) in the control group (P

Marion Schroeder,1 Lena Rung,2 Monica Lövestam-Adrian1 1Division of Ophthalmology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, 2Department of Ophthalmology, Helsingborg Hospital, Helsingborg, Sweden Background: Although ranibizumab has been used for the treatment of wet age-related macular degeneration (AMD) since 2007, real-world studies still report undertreatment resulting in a less favorable visual outcome. In this study, two different time cohorts of patients treated with ranibizumab for wet AMD in routine care were analyzed to observe whether there was a change over time regarding visual outcome, injection frequency, and quality of life (QoL). Methods: We compared patients with treatment-naïve wet AMD in two observational follow-up cohorts 2007–2010 (n=50 patients) and 2009–2013 (n=26). After a loading dose of three intravitreal ranibizumab injections, the patients were treated under the pro re nata regimen. Visual acuity (VA) was examined by Early Treatment Diabetic Retinopathy Study (ETDRS) charts. The National Eye Institute Visual Functioning Questionnaire 25 was answered by patients at baseline and at 37±7 months (cohort 1) and at 45±4 months (cohort 2). Results: At baseline, the cohorts were homogeneous considering mean age (76±7 vs 75±8 years), mean VA (53±14 vs 52±15 ETDRS letters), and mean self-reported symptom duration (14±11 vs 13±11 weeks). Mean VA decreased in both cohorts over time, from 53±14 to 45±24 letters (P=0.011) and from 52±15 to 46±22 letters (P=0.175), respectively. The patients received a mean of 8±5 and 9±7 injections, respectively. The mean composite score change from baseline to follow-up decreased in cohort 1 from 64±21 to 59±25 scores (P=0.04) but increased in cohort 2 from 64±28 to 67±23 scores (P=0.38). Conclusion: We could not demonstrate any improvement in the number of injections in two different time cohorts of patients treated with ranibizumab for wet AMD in a Swedish county. Visual outcomes decreased after 3 years of follow-up, but QoL scores were divergent. Keywords: neovascular AMD, anti-VEGF, NEI VFQ-25, clinical care

Purpose: To evaluate treatment outcome at 12 months in eyes with neovascular age‐related macular degeneration (nAMD) treated with antivascular endothelial growth factor (anti‐VEGF) injections according to either pro re nata (PRN)‐ or treat‐and‐extend (TE)‐regimen in one clinical setting in Sweden. Methods: Data were obtained retrospectively from the Swedish Macula Register, optical coherence tomography‐database and electronic patient charts. The study included 443 eyes; 223 PRN‐ and 220 TE‐treated eyes. Baseline (BL) characteristics and follow‐up data at 6 and 12 months were collected. Statistical regression analysis was performed to evaluate association between treatment strategy and visual outcome at 12 months. Results: Baseline (BL) characteristics were well balanced between cohorts. Visual acuity at 12 months was higher in TE‐cohort 66.5 (13.1) compared to PRN‐cohort 60.1 (17.6) (p = 0.000). Visual improvement at 12 months was +5.2 (11.8) and +1.2 (12.7) letters Early Treatment Diabetic Retinopathy Study (ETDRS) in TE‐ and PRN‐cohorts, respectively (p = 0.002). Number of administered injections at 12 months was 10.2 (2.1) and 6.3 (2.1) in the two cohorts (p = 0.000). Statistical analysis demonstrated a strong association between TE treatment strategy and improvement in visual acuity at 12 months. Conclusion: Eyes treated according to TE had better visual outcome at 12 months. The results indicate that treatment according to proactive TE‐regimen is superior to treatment according to PRN‐regimen in clinical routine care of nAMD. [ABSTRACT FROM AUTHOR]

Purpose: To determine the proportion of treatment-experienced eyes with exudative age-related macular degeneration successfully treated with every-4-week aflibercept that can be kept dry on fixed every-8-week aflibercept injections (maintenance). Methods: In this retrospective chart review, we evaluated our cohort of patients treated with a treatment paradigm for CNV in AMD. Initially, patients were treated with bevacizumab or ranibizumab and switched to every-4-week aflibercept when therapeutic responses were not durable or were suboptimal. Maintenance every-8-week therapy was initiated when the retina was completely dry on every-4-week aflibercept therapy. The primary outcome measure was recurrence of exudation on optical coherence tomography (OCT) during maintenance. Results: Thirty-six eyes of 31 consecutive patients with median age of 79 years (range, 65–89) were included. Maintenance was started after a median of 34 (range, 8–88) injections. Recurrence was observed in 20 eyes (55%). Of these, 11 eyes (31%) reactivated at 8 weeks. Median time to failure of maintenance schedule was 40 weeks by Kaplan-Meier analysis. Baseline demographic and anatomic characteristics were not associated with failure of maintenance schedule. Conclusion: In treatment-experienced eyes that respond completely to every-4-week aflibercept, maintenance therapy with every-8-week injections can only temporarily maintain anatomic success with the majority of eyes developing recurring activity. This regimen fails early in one third of eyes and has a median effective duration of 40 weeks. Aflibercept appears to be inadequate to maintain control of exudation in most eyes in at least half of eyes undergoing long-term therapy. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a chronic and progressive retinal degenerative disease of the macula that affects the elderly and causes impairment of central vision. AMD is a multifactorial disease that encompasses a complex interplay between aging, environmental risk factors, and genetic susceptibility. Chronic inflammation, lipid deposition, oxidative stress, and impaired extracellular matrix maintenance are strongly implicated in the pathogenesis of AMD. Advanced AMD can be classified into two types: dry and wet. Although dry AMD accounts for the majority of diagnosed cases, wet AMD is responsible for the majority of severe vision loss and usually occurs within weeks or months. Although neovascularization was the most common cause of severe vision loss, geographic atrophy, the most advanced form of dry AMD, can also cause significant vision loss. The medical treatment of neovascular AMD has seen significant progress due to the introduction of vascular endothelial growth factor (anti-VEGF) inhibitors, which have dramatically changed the prognosis of the disease. Research does not prove the need to change treatment methods in every patient, there may be occasions when patients with AMD show a more robust response to one anti-VEGF agent than another. Clinicians may consider alternatives to switching, such as increasing injection frequency, when managing a patient who appears to be unresponsive to therapy. In this regard, it may be helpful to have a patient return for evaluation 1 to 2 weeks after injection with repeat testing to assess whether there has been a reduction in subretinal fluid or retinal edema shortly after anti-VEGF injection. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the mortality associated with intravitreal injections of bevacizumab for age‐related macular degeneration (AMD) in patients previously diagnosed with stroke or transient ischaemic attack (TIA). Methods: We reviewed bevacizumab‐treated AMD patients with a diagnosis of stroke or TIA prior to their first bevacizumab injection (n = 948). Those patients, naïve to any anti‐vascular endothelial growth factor (anti‐VEGF) at the time of stroke/TIA, were then compared to age‐ and gender‐matched patients who had a stroke/TIA at the same time and had never been exposed to anti‐VEGF. Survival analysis was performed using adjusted Cox regression. The main outcome measure was survival. Adjusted variables were age, smoking, alcohol abuse, hypertension, diabetes mellitus, obesity, ischaemic heart disease, congestive heart failure and liver cancer. Results: Age and gender distribution of bevacizumab‐treated patients and controls were similar (mean age: 83.4 versus 83.7 years, p = 0.3; 51.7% males versus 52.5% males, p = 0.7). The adjusted mortality in patients who received bevacizumab within 3 months after stroke/TIA was significantly different than in patients non‐exposed to bevacizumab (OR = 6.92, 95%, CI 1.88–25.43, p < 0.01). Within 6 months after stroke/TIA, the difference in adjusted mortality showed a strong trend (OR = 2.00, 95%, CI 0.96–4.16, p = 0.064). Within 12 months, it was insignificant (OR = 1.30, 95%, CI 0.75–2.26, p = 0.348). Conclusion: We found increased mortality within three months after a cerebrovascular event in patients treated with bevacizumab for AMD compared to patients for whom there was no record of a prescription to any anti‐VEGF agent. [ABSTRACT FROM AUTHOR]

Background: Intraocular injections of antivascular endothelial growth factor (VEGF) agents are currently the main therapy in age-related macular degeneration (AMD). The safety of bevacizumab, an anti-VEGF compound frequently delivered off label, is debated, particularly for high-group risks. We aim to analyze the mortality associated with intravitreal injections of bevacizumab for AMD in patients previously diagnosed with acute myocardial infarct (MI).Methods: In a national database, we identified bevacizumab-treated AMD patients with a diagnosis of MI prior to their first bevacizumab injection, delivered between September 2008 and October 2014 (n = 2100). We then generated sub-groups of patients treated within 3 months (n = 11), 6 months (n = 24), 12 months (n = 52), and 24 months (n = 124) after MI. Those patients were compared to age- and gender-matched members that had a MI at the same time and had never been exposed to anti-VEGF. Survival analysis was performed using propensity score-adjusted Cox regression.Results: Bevacizumab-treated patients were slightly and insignificantly older than controls (mean age 83.25 vs 83.19 year, P = .75). Gender distribution was similar. In a Cox regression adjusted with propensity score, the following differences in mortality were found: within 3 months between MI and initiation of bevacizumab treatment, OR = 6.22 (95% C.I 1.08-35.97, P < .05); within 6 months, OR = 2.37 (95% C.I 0.93-6.02, P = .071); within 12 months, OR = 3.00 (95% C.I 1.44-6.28, P < .01); within 24 months after MI, OR = 2.24 (95% C.I 1.35-3.70, P < .01); and MI any time prior to first bevacizumab injection, OR = 1.71 (95% C.I 1.53-1.92, P < .001).Conclusions: We report increased mortality associated with the use of intravitreal bevacizumab in AMD patients after MI, compared to age- and gender-matched post-MI patients with no exposure to any anti-VEGF agent. Caution should be taken while offering bevacizumab to AMD patients after MI. [ABSTRACT FROM AUTHOR]

Purpose To present Swedish Macula Register (SMR) data regarding treatment of neovascular age-related macular degeneration (AMD) in clinical practice since 2008. Methods A retrospective register-based study was conducted. Evaluation of baseline demographics, visual outcome and number of injections during this period is presented. Results Mean age at diagnosis was 79 ± (SD) 8 years; 65% were female. The proportion of patients with <2 months' duration of symptoms increased from 26% in 2008 to 41% in 2014 (p = 0.001). Mean visual acuity (VA) at baseline increased from 54.3 ± 15.0 early treatment diabetic retinopathy study (ETDRS) letters in 2008 to 57.8 ± 15.6 letters in 2014 (CI95 2.6; 4.3; p < 0.001). Mean VA after 1 year of treatment increased from 57.8 ± 17.7 ETDRS letters for patients who started the treatment in 2008 to 62.8 ± 16.4 ETDRS letters in patients starting treatment in 2014 (CI95 2.67; 4.64; p < 0.001). During all study years, the proportion of patients with an improvement in VA of between 5 and 15 letters was around 30%, while 14% had VA improvement of more than 15 letters. The mean number of injections during the first treatment year increased from 4.3 ± 1.9 in 2008 to 5.9 ± 2.9 in 2014 (CI95 1.40; 1.67; p < 0.001). Seven-year follow-up of 322 eyes showed a mean change of −1 letters from baseline, with a mean of 21 injections for the entire period. Conclusion The duration of symptoms before treatment decreased, while VA at baseline and after 1 year of treatment increased over the years and so did the number of injections. Long-term follow-up demonstrated stable VA. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to analyze mortality in patients treated with bevacizumab for wet AMD.Methods: We conducted a retrospective case-control study between patients who received intravitreal injections of bevacizumab as the sole treatment for exudative AMD between September 2008 and October 2014 (n = 5385) and age and gender matched controls (n = 10,756). All individuals included in the study were reviewed for sociodemographic data and comorbidities. Survival analysis was performed using adjusted Cox regression, using relevant adjusted variables.Results: During follow-up (maximum: 73 months), 1063 (19.7%) individuals after bevacizumab died compared with 1298 (12.1%) in the control group (P < .001). After adjusted Cox survival regression, mortality differed significantly between the groups, Odds ratio = 1.69, (95% C.I. 1.54-1.84), P < .001.Conclusions: We found an increased long-term mortality in individuals with wet AMD treated with bevacizumab compared to a same age and gender group without wet AMD. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) constitutes a prevalent, chronic, and progressive retinal degenerative disease of the macula that affects elderly people and cause central vision impairment. Despite therapeutic advances in the management of neovascular AMD, none of the currently used treatments cures the disease or reverses its course. Medical treatment of neovascular AMD experienced a significant advance due to the introduction of vascular endothelial growth factor inhibitors (anti-VEGF), which dramatically changed the prognosis of the disease. However, although anti-VEGF therapy has become the standard treatment for neovascular AMD, many patients do not respond adequately to this therapy or experience a slow loss of efficacy of anti-VEGF agents after repeated administration. Additionally, current treatment with intravitreal anti-VEGF agents is associated with a significant treatment burden for patients, caregivers, and physicians. New approaches have been proposed for treating neovascular AMD. Among them, designed ankyrin repeat proteins (DARPins) seem to be as effective as monthly ranibizumab, but with greater durability, which may enhance patient compliance with needed injections. [ABSTRACT FROM AUTHOR]