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Objective: To evaluate the incidence of bacillary layer detachment in patients with neovascular age-related macular degeneration (nAMD) and their response to anti-VEGF therapy., Design: Post hoc analysis of the brolucizumab 6-mg and aflibercept 2-mg arms from the HAWK clinical trial, a 48-week, prospective, double-masked, phase III trial., Participants: Participants (n = 652 and 652 eyes) randomized to brolucizumab 6-mg and aflibercept 2-mg arms from HAWK (NCT02307682)., Methods: Spectral-domain OCT scans were obtained at 4-week intervals throughout the HAWK trial and segmented automatically using a proprietary, machine learning-enabled, higher-order feature extraction platform., Main Outcome Measures: The incidence of bacillary layer detachment and effect of anti-VEGF therapy in these eyes on best-corrected visual acuity (BCVA), central subfield thickness (CST), retinal fluid volumes, subretinal hyper-reflective material (SHRM) volume, and ellipsoid zone (EZ) integrity from baseline to week 48., Results: Classic bacillary layer detachment was identified in 7.2% (47/652) of eyes, demonstrating worse BCVA and higher CST, EZ total attenuation, subretinal fluid (SRF), and SHRM volume at baseline than eyes without bacillary layer detachment. Anti-VEGF treatment resulted in resolution of bacillary layer detachment in 97.9% of eyes by week 48. In eyes with bacillary layer detachment, anti-VEGF treatment improved BCVA and decreased SRF and SHRM volume; however, eyes with bacillary layer detachment never reached the level of BCVA improvement as eyes without bacillary layer detachment. A greater proportion of eyes with bacillary layer detachment had high-exudative volatility (increased mean standard deviation after loading dose) of CST, SRF, and total fluid than eyes without bacillary layer detachment (P < 0.05 for each comparison)., Conclusions: Bacillary layer detachment, an OCT signature representing photoreceptor schisis, is identifiable in a notable proportion of eyes with nAMD. Anti-VEGF therapy resulted in a very high proportion of bacillary layer detachment resolution with significantly decreased SRF and SHRM volumes. The majority of eyes with bacillary layer detachment have high-exudative volatility, which may be associated with lower BCVA outcomes. The presence of bacillary layer detachment may provide an important imaging biomarker to be considered for clinical trial inclusion/exclusion based on trial design and therapeutic goals because of its unique behavior., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: The purpose of the study was to compare the real-world aflibercept treatment and visual outcomes, and to examine the adherence to pandemic guidelines in two groups of patients with treatment-naïve neovascular age-related macular degeneration (nAMD) before and during the first year of the COVID-19 pandemic in Sweden up to the 1-year follow-up., Methods: This is a retrospective observational study including 2915 treatment naïve eyes with nAMD. Using data from the Swedish Macula Register (SMR), 1597 eyes initiating treatment between 1 July 2018 and 31 January 2019 (pre-pandemic group) were compared with 1318 eyes starting treatment between 1 February and 31 August 2020 (pandemic group). The eyes were then followed for 1 year ± 2 months, hence the first group was unaffected by the pandemic while the second group was affected. The focus was on baseline characteristics, visual acuity (VA) change from baseline, number of injections, treatment regimen, number of appointments and the frequency and length of appointment delays. The Wilcoxon Signed-Rank Test was used to compare baseline VA to follow-up VA within the respective groups. The Mann-Whitney U-test and Fisher's exact test were used to compare outcomes between the groups., Results: Baseline characteristics were similar between the two groups. The percentage of eyes with an available follow-up VA after 1 year was 58% in the pre-pandemic group vs. 44% in the pandemic group. VA in the pre-pandemic group had increased significantly after 1 year, from 62.2 ± 14.1 letters to 64.8 ± 16.1 letters (n = 921); p < 0.0001. In the pandemic group, VA increased from 61.1 ± 15.8 to 64.9 ± 16.9 (n = 575); p < 0.0001. There was no significant difference in mean VA change between the groups; p = 0.1734. The pre-pandemic group had significantly more delays than the pandemic group, 45% vs. 36%; p < 0.0001., Conclusions: The pre-pandemic and pandemic groups had similar VA gains at 1-year follow-up, but with a reduced number of available VA in the pandemic group. Clinics were able to implement and prioritize injection visits excluding VA measurements, helping to reduce delays and maintain VA gains during the COVID-19 pandemic., (© 2024. The Author(s).)

Background: The Age-Related Eye Disease Study 2 (AREDS 2) proved the benefit of vitamin and mineral supplementation in preventing advanced age-related macular degeneration (AMD). AREDS 2 supplements are indicated for patients with either bilateral intermediate AMD (AREDS category 3) or unilateral neovascular AMD (AREDS category 4)., Aims: The aims of this telephone survey were to identify the rate of adherence of patients to AREDS 2 supplements and the factors associated with non-compliance in these patient groups., Methods: A patient telephone survey was conducted in an Irish tertiary care hospital. Patients were identified by chart review, and their AREDS categorization was reconfirmed. A telephone consultation was conducted with each patient to assess their compliance with the micronutrient supplements., Results: We identified 120 patients who met the AREDS criteria for supplementation. Of these, 103 patients were graded as category 4, and 17 patients were graded as category 3. Almost a fifth (18%) were current smokers. Under two-thirds (60%) of the patients were taking AREDS 2 supplements. Of the remainder, 83% of patients did not recall being advised of their benefit. The cost was cited by 10% of patients as a reason for non-compliance., Conclusion: The ophthalmologist not only has a duty of care to treat the neovascular complications of AMD, but they must also strive to improve patient compliance with AREDS supplements. The cessation of smoking needs to be actively promoted in order to stop preventable vision loss in patients with AMD., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Age-related macular degeneration (AMD) is a leading cause of vision loss among elderly people in developed countries. Neovascular AMD (nAMD) accounts for more than 90% of AMD-related vision loss. At present, intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is widely used as the first-line therapy to decrease the choroidal and retinal neovascularizations, and thus to improve or maintain the visual acuity of the patients with nAMD. However, about 1/3 patients still progress to irreversible visual impairment due to subretinal fibrosis even with adequate anti-VEGF treatment. Extensive literatures support the critical role of epithelial-mesenchymal transformation (EMT) of retinal pigment epithelium (RPE) in the pathogenesis of subretinal fibrosis in nAMD, but the underlying mechanisms still remain largely unknown. This review summarized the molecular pathogenesis of subretinal fibrosis in nAMD, especially focusing on the transforming growth factor-β (TGF-β)-induced EMT pathways. It was also discussed how these pathways crosstalk and respond to signals from the microenvironment to mediate EMT and contribute to the progression of nAMD-related subretinal fibrosis. Targeting EMT signaling pathways might provide a promising and effective therapeutic strategy to treat subretinal fibrosis secondary to nAMD., Competing Interests: Declaration of Competing Interest The authors have no conflicting financial interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Traditionally, visual acuity gain and central retinal thickness have been used to measure outcomes when investigating the efficacy of vascular endothelial growth factor (VEGF) inhibitors for patients with neovascular age-related macular degeneration (nARMD). However, localization of retinal fluid may offer additional prognostic value for treatment. The primary aim of this retrospective clinical audit was to investigate whether the presence and location of subretinal fluid has an effect on the visual outcomes of treatment naïve patients with nARMD treated in the real-world setting with VEGF inhibitors. Secondary aims included investigation of change to visual and anatomical outcomes and investigation of the dosing schedule., Methods: Retrospective observational study of patients attending one suburban and one regional ophthalmology clinic requiring treatment with VEGF inhibitors for nARMD using single-user non-identifiable data from the Fight Retinal Blindness! Registry from 2014 to 2020. Visual acuity (VA) and central subfield thickness (CST) were recorded at baseline, 3, 6, 12 and 24 months., Results: Forty-nine eyes of 42 treatment naïve patients were included for analysis (aged 62-89 years). Almost half (49%) presented with a combination of intra- and subretinal fluid at baseline. Intraretinal fluid was present in 75% of eyes but decreased to 22.7% of eyes by 24 months. VA at baseline was 55 letters, and this improved by 6 letters. The change in VA from baseline to 3, 6 and 12 months was statistically significant (p < .05). The mean change in CST from baseline to 3 months was significant (-76 µm). This change was also observed at the other milestones (p < .001)., Conclusions: The findings of this study suggest that allowing some subretinal fluid to remain will not affect treatment outcomes.

Purpose: To determine the incidence of being lost to follow-up (LTFU) and nonpersistence in patients with neovascular age-related macular degeneration (AMD) treated with anti-VEGF injections in the United States., Design: Retrospective cohort study using the IRIS® (Intelligent Research in Sight) Registry data., Participants: One hundred fifty-six thousand three hundred twenty-seven treatment-naive patients with neovascular AMD who subsequently were treated with anti-VEGF therapy from 2013 through 2015 and followed up through 2019., Methods: Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Main Outcome Measures: Being LTFU was defined as no follow-up within 12 months from last intravitreal injection. Nonpersistence was defined as no follow-up within 6 months from last intravitreal injection., Results: For neovascular AMD, 11.6% of patients (95% CI, 11.4%-11.7%) were LTFU, and 88.4% of patients were followed up within 12 months. The rate of being LTFU generally was higher with increasing age, with odds of being LTFU greatest for patients between 81 and 84 years of age (OR, 2.51; 95% CI, 2.31-2.74; P < 0.001) compared with patients 70 years of age and younger. Odds of being LTFU for Black or African American patients (OR, 1.32; 95% CI, 1.08-1.61; P = 0.007) were greater than for White patients. Odds of being LTFU were higher for patients with Medicaid insurance (OR, 1.27; 95% CI, 1.01-1.60; P = 0.04) and lower for patients with Medicare Fee-For-Service insurance (OR, 0.69; 95% CI, 0.64-0.74; P < 0.001) than for patients with private insurance. Furthermore, 14.3% (95% CI, 14.1-14.4) of patients were nonpersistent, and 85.7% of patients underwent follow-up within 6 months. Odds of nonpersistence also were greatest among patients between 81 and 84 years of age (OR, 2.13; 95% CI, 1.98-2.29; P < 0.001) compared with patients 70 years of age or younger. Odds of nonpersistence for Black or African-American patients (OR, 1.38; 95% CI, 1.15-1.65; P < 0.001) and Hispanic patients (OR, 1.13; 95% CI, 1.03-1.24; P = 0.009) were greater than odds for White patients., Conclusions: Nearly 1 of 9 patients with neovascular AMD treated with anti-VEGF injections became LTFU, whereas 1 of 7 patients were nonpersistent. Risk factors identified included increasing age, male sex, unilateral involvement, diabetes, Medicaid insurance, and race or ethnicity., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Cataract and neovascular age-related macular degeneration (nAMD) often co-exist and both contribute to impaired vision. It has been debated whether cataract surgery can increase nAMD activity. The purpose of this retrospective study was to investigate the impact of cataract surgery on visual acuity, treatment intensity for nAMD and macular morphology in patients with on-going treatment for nAMD., Methods: Data was obtained from the Swedish Macular Register, the Swedish National Cataract Register, optical coherence tomography (OCT) images and patient charts. All eyes were treated at the Department of Ophthalmology at the County Hospital of Västmanland, Västerås, Sweden. Follow-up was 6 months after surgery. The study was approved by the Swedish Ethical Review Authority., Results: In total, 156 patients (168 eyes) were included. The mean age at cataract surgery was 82 (standard deviation, SD 6) years. Both distance and near visual acuity improved after surgery. Distance visual acuity increased from 59 (SD 12) to 66 (SD 15) letters ETDRS (P < 0.001). Proportion of eyes with normal near visual acuity increased from 12 to 41%. The anti-vascular endothelial growth factor (VEGF) treatment intensity remained unchanged: mean of 3.4 (SD 1.9) and 3.3 (SD 1.7) treatments were given 6 months pre- and postoperatively, respectively. The prevalence of intraretinal fluid (IRF) in the macula increased from 22 to 31% postoperatively, while subretinal fluid, fluid under the pigment epithelium (sub-RPE fluid) and central retinal thickness were unaltered. In eyes with new IRF, improvement in visual acuity and number of anti-VEGF treatments were similar to eyes without new IRF., Conclusion: Cataract surgery improved visual acuity in patients with on-going treatment for nAMD and did not affect anti-VEGF treatment intensity. Macular morphology remained unchanged. The slight increase in intraretinal fluid after surgery was not found to affect visual acuity or anti-VEGF treatment intensity. It is hypothesized that this might indicate that it represents degenerative intraretinal cystic fluid., (© 2023. The Author(s).)

Purpose: Patients with extensive submacular hemorrhage (SMH) caused by age-related macular degeneration (AMD) have a poor visual prognosis despite surgical intervention. Systemic blood-thinning drugs, which are commonly prescribed in the same age group, are known to increase the risk of severe hemorrhage in many parts of the body. This study aimed to investigate whether systemic blood-thinning drugs have an impact on the severity of SMH and if there are differences between the different types of blood-thinning medication., Methods: We reviewed the medical records of patients who suffered from surgically treated SMH between 2020 and 2022. All patients received a full ophthalmologic examination upon presentation including best-corrected visual acuity (BCVA) and optical coherence tomography. Other characteristics that were recorded included size of hemorrhage, blood-thinning therapy, and reason for intake., Results: A total of 115 patients with a mean age of 82 years were included in this retrospective analysis. Eighty-three patients (72.2%) were on blood-thinning therapy. The mean size of SMH was 32.01 mm 2 . Mean BCVA at initial presentation was 1.63 logMAR and 1.59 logMAR 1 year after surgery. The size of SMH was significantly larger in patients on blood-thinning medication (35.92 mm 2 vs. 21.91 mm 2 ) (p = 0.001) and their BCVA postoperatively was worse with 1.68 logMAR compared to 1.30 logMAR after 1 year (p = 0.503). Patients with vitamin K antagonists had larger SMH size and worse outcomes regarding BCVA compared to direct oral anticoagulants., Conclusion: Blood thinners in patients with AMD affect the severity of SMH. Consequently, the indication for their intake should be critically evaluated., (© 2022. The Author(s).)

Purpose: The study aimed to determine the most significant optical coherence tomography angiography (OCTA) parameters in terms of predicting anti-VEGF therapy effectiveness during long-term (3-year) follow-up of patients with neovascular age-related macular degeneration (nAMD)., Material and Methods: The study included 122 patients (122 eyes) with mean age of 73.4±6.6 years who were diagnosed with nAMD. Subgroup analysis included 50 patients (50 eyes) with detailed OCT angiography examination of macular neovascularization (MNV) characteristics and their changes in the course of the follow-up, which lasted 144 weeks. All patients were treated by angiogenesis inhibitor (aflibercept 2 mg), most of them - according to Treat-and-Extend protocol., Results: Treatment response (either 'good' or 'partial') was achieved in all patients, and the proportion of the response types was similar in both types 1 and 2 MNV. Key OCTA parameters associated with the number of injections, as well as morphological and functional response (best-corrected visual acuity, retinal neuroepithelium and pigment epithelium detachment), were vascular network area and MNV area assessed at baseline and three months after treatment initiation. Both of these parameters were closely related in both MNV types during the follow-up. Key parameter with maximum number of clinically significant correlations ('very high' strength, p <0.05) in eyes with 'good' response was MNV area, in eyes with 'partial' response - vascular density and greatest vascular caliber., Conclusions: Vascular network area and MNV area assessed at baseline and after three loading doses were determined as the most significant OCTA characteristics for predicting the number of injections and treatment response based on functional and morphological parameters. MNV area was found to be the most clinically significant marker in 'good' response, vascular density and greatest vascular caliber - in 'partial' response.

Purpose: The study analyzes long-term (three years) clinical effectiveness of anti-VEGF treatment of neovascular age-related macular degeneration (nAMD) and attempts to identify the most clinically significant associations between the functional and structural parameters., Material and Methods: The study included 122 patients (122 eyes) diagnosed with nAMD, mean age -73.4±6.6 years old. Prospective follow-up lasted 144 weeks. All patients were treated with angiogenesis inhibitor (aflibercept 2 mg), and most of them (72.9%) - according to the Treat-and-Extend protocol., Results: The average number of injections was 7.39±1.28, 4.63±0.97 and 4.06±0.81 during the first, second and third years of the follow-up, respectively. The mean baseline best-corrected visual acuity (BCVA) was 0.24±0.21. After three loading doses, BCVA increased to 0.33±0.26 (+0.09; 37.5%), by the end of follow-up BCVA was 0.35±0.27 (+0.11; 45.8%). Central retinal thickness (CRT) decreased from 314.89±88.07 μm to 234.4±42.8 μm (a 25.5% decrease) by the end of the follow-up. After three loading injections baseline functional and anatomical parameters had the most significant correlations ( r ≥0.7, p <0.05) with intraretinal fluid, ellipsoid zone integrity and the area of macular atrophy., Conclusions: Analysis of the morphological and functional outcomes by the end of the first year demonstrates the feasibility of preserving the results while reducing the number of visits and injections according to the Treat-and-Extend protocol. Achieving maximum improvement of functional parameters most significantly correlated with changes in such biomarkers as central retinal thickness, area of macular atrophy and integrity of the ellipsoid zone.

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.

Purpose: To compare the 12 months visual and anatomical outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) patients diagnosed by optical coherence tomography angiography (OCT-A) compared with fluorescein angiography (FA)/indocyanine green angiography (ICGA), after anti-VEGF treatment in a real-world setting., Methods: Monocentric, observational, parallel-group study of nAMD patients diagnosed with either FA/ICGA or non-invasive OCT-A methods. Patients were treated with a fixed dosing regimen of intravitreal ranibizumab or aflibercept and followed up for 12 months. Primary outcomes were the 12 months functional (BCVA) and anatomical (CST reduction) gains between the two groups. The stratification of BCVA and CST gains by type of neovascular lesion and by anti-VEGF treatment was also assessed., Results: Seventy-two patients received FA/ICGA for the initial diagnosis of nAMD, while 73 received OCT-A. Overall, the mean BCVA gain at 12 months was 11.5 ± 9.6 letters. There were no statistically significant differences between the invasive and non-invasive imaging groups in BCVA gain (p = 0.87) or CST reduction (p = 0.76). No statistically significant outcome differences between different lesion types and the two drugs were observed., Conclusion: In a real-world setting, nAMD patients diagnosed with OCT-A showed meaningful improvements in visual and anatomical parameters during 12 months of treatment, without significant differences with those diagnosed by invasive modalities., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Clinical Relevance: 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., Background: 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., Methods: 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., Results: 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)., Conclusion: 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.

Background: To study the visual outcomes of neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs at national level., Methods: Multicenter national database of nAMD eyes treated with anti-VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat-and-extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!)., Results: 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p = 0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/-3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p = 0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p = 0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%)., Conclusion: Independent, large-scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real-world international cohorts., (© 2022 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: The number of patients receiving anti-VEGF therapy has increased rapidly since its introduction in Denmark in 2007, placing an enormous pressure on the public healthcare system. In this study, we attempt to describe this growth and identify the factors driving it., Methods: Data on treatment of the entire population of neovascular AMD patients in the Capital Region of Denmark between 2007 and 2019 was retrieved. The age and sex standardized incidences of first time treatment and changes in duration of treatment were analysed., Results: The number of patients in active treatment increased from 576 in 2007 to 3684 in 2019. The growth was initially driven by accumulation of patients continuing anti-VEGF therapy for extended periods of time (259 patients/year). As larger numbers of patients began to be discharged, the increase slowed to 181 patients/year in late 2010s, with demographic change becoming the main growth driving factor. The incidence of first treatment increased slightly during the study period, mainly for individuals over 85 years. For patients under 85 years, treatment incidences closely followed neovascular AMD incidences from population studies. The likelihood of remaining in anti-VEGF treatment after the initial injection followed exponential decay curve (t 1/2  = 3.6 years). Based on this observation, a model was created to describe the number of patients in active treatment, which accurately described historical data (R 2  = 0.999), and forecast a linear growth of 138 patients/year until 2030., Conclusion: Treatment incidences and modelling reported in this study might facilitate a more informed and accurate planning of future ophthalmology services., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To assess disease stability (absence of intra- and/or subretinal fluid) and the portion of eyes being capable to extend their treatment interval to ≥ 12 weeks in exudative age-related macular degeneration (AMD)., Methods: A systematic literature search was performed in NCBI, PubMed, CENTRAL, and ClinicalTrials.gov to identify clinical studies reporting treatment outcomes for ranibizumab, aflibercept, and brolucizumab in exudative AMD under a treat-and-extend protocol and a follow-up of ≥ 12 months. Weighted mean differences and subgroup comparisons were used to integrate the different studies., Results: This meta-analysis refers to 29 published series, including 27 independent samples and 5629 patients. In the pooled group, disease stability was reported in 62.9% and 56.0%, respectively, after 12 and 24 months of treatment, whereas treatment intervals were extended to ≥ 12 weeks in 37.7% and 42.6%, respectively. Ranibizumab, aflibercept, and brolucizumab differed regarding their potential to achieve disease stability (56.3%, 64.5%, and 71.5% after 12, and 50.0%, 52.7% and 75.7% after 24 months; p = < 0.001) and to allow an interval extension to ≥ 12 weeks (28.6%, 34.2%, and 53.3% after 12, and 34.2%, 47.7%, and 41.7% after 24 months; p = < 0.001)., Conclusion: The portion of eyes achieving disease stability regressed in the second year, whereas the portion of eyes under a ≥ 12-week interval increased. This discrepancy may reflect the challenges in balancing between under-treatment and a reduced treatment burden., (© 2021. The Author(s).)

Purpose: To analyze associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration (AMD), its subtypes, and large drusen., Design: Post hoc analysis of 2 controlled clinical trial cohorts: Age-Related Eye Disease Study (AREDS) and AREDS2., Participants: Eyes with no late AMD at baseline among AREDS participants (n = 4504) and AREDS2 participants (n = 3738) totaled 14 135 eyes. Mean age was 71.0 years (standard deviation, 6.7 years), and 56.5% of patients were women., Methods: Fundus photographs were collected at annual study visits and graded centrally for late AMD. Dietary intake of multiple nutrients was calculated from food frequency questionnaires., Main Outcome Measures: Progression to late AMD, geographic atrophy (GA), neovascular AMD, and (separate analyses) large drusen., Results: Over median follow-up of 10.2 years, of the 14 135 eyes, 32.7% progressed to late AMD. For 9 nutrients, intake quintiles 4 or 5 (vs. 1) were associated significantly (P ≤ 0.0005) with decreased risk of late AMD: vitamin A, vitamin B6, vitamin C, folate, β-carotene, lutein and zeaxanthin, magnesium, copper, and alcohol. For 3 nutrients, quintiles 4 or 5 were associated significantly with increased risk: saturated fatty acid, monounsaturated fatty acid, and oleic acid. Similar results were observed for GA. Regarding neovascular AMD, 9 nutrients were associated nominally with decreased risk-vitamin A, vitamin B6, β-carotene, lutein and zeaxanthin, magnesium, copper, docosahexaenoic acid, omega-3 fatty acid, and alcohol-and 3 nutrients were associated with increased risk-saturated fatty acid, monounsaturated fatty acid, and oleic acid. In separate analyses (n = 5399 eyes of 3164 AREDS participants), 12 nutrients were associated nominally with decreased risk of large drusen., Conclusions: Higher dietary intake of multiple nutrients, including minerals, vitamins, and carotenoids, is associated with decreased risk of progression to late AMD. These associations are stronger for GA than for neovascular AMD. The same nutrients also tend to show protective associations against large drusen development. Strong genetic interactions exist for some nutrient-genotype combinations, particularly omega-3 fatty acids and CFH. These data may justify further research into underlying mechanisms and randomized trials of supplementation., (Published by Elsevier Inc.)

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.

The problem associated with the prevalence of retinal diseases, and age-related macular degeneration (AMD) in particular, is undoubtedly relevant. This aspect is based on steadily growing statistics on morbidity, a high number of randomized controlled trials (RCT) and published real world data (RWD). The analysis of RCT results being published by researchers on 15.05.19 showed 2915 studies were registered on the subject of retinal diseases; that exceeds the number of studies on glaucoma by approximately 1.38 times (2118 studies) and conjunctival lesions by 2.37 times (1230 studies). AMD is one of the leading causes of irreversible vision loss and blindness; its neovascular form leads to blindness in 80-90% of all cases. Even though the topic of nAMD therapy is widely highlighted in modern ophthalmology, today there are many aspects that require targeted solutions. The main controversial issues that determine the complexity of therapy and patient management include discrepancies in determination of reference points (disease activity criteria) for implementation of anti-VEGF dosing regimens, patients' compliance, prioritization issues in treatment, its continuity with potential for the increase of intervals between injections and monitoring visits.

Many studies over the past 20 years have pursued the goal of preventing or deferring progression from early and intermediate age-related macular degeneration (AMD) to advanced AMD. The onset of neovascular AMD has been used as a primary endpoint in some prophylactic clinical trials because it is easy to assess and relatively well-defined. Nevertheless, the use of this endpoint for assessing progression of AMD lacks validation. The aims of this paper are to review the current practice of clinical trials investigating the prevention of progression of early or intermediate AMD to neovascular AMD, so-called prophylactic trials, as well as identify ongoing efforts to standardize endpoints and select the ideal population for such studies., (© 2020 S. Karger AG, Basel.)

Purpose: To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with neovascular age-related macular degeneration (AMD)., Methods: Consecutive patients with diagnosis of neovascular AMD were consecutively enrolled between March 9, 2020, and June 12, 2020, (during and immediately after the Italian COVID-19 quarantine). During the inclusion (or pandemic) visit (V 0 ), patients received a complete ophthalmologic evaluation, including optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and OCT findings from the two preceding visits (V -1 and V -2 ) were compared with data at V 0 ., Results: One-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5 days within V 0 and V -1 and 80.8 ± 39.7 days within V -1 and V -2 , respectively (P < 0.0001). BCVA was statistically worse at the V 0 visit as compared with the immediately preceding (V -1 ) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V 0 and V -1 visits, respectively; P = 0.046). On structural OCT, 91 out of 112 (81.2%) neovascular AMD eyes displayed the evidence of exudative disease activity at the V 0 visit, while 77 (68.7%) eyes exhibited signs of exudation at the V -1 visit (P = 0.022). No differences in terms of BCVA and OCT findings were detected between the V -1 and V -2 visits. In multiple regression analysis, the difference in BCVA between V 0 and V -1 visits was significantly associated with the interval time within these two visits (P = 0.026)., Conclusion: The COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients.

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., (© 2018 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: The main objective of this study was to assess choroidal thickness (CT) changes during an exudative recurrence of age-related macular degeneration (AMD)., Methods: A real-life prospective non-interventional 9-month study was conducted in two centers in consecutive patients with exudative AMD between November 2016 and July 2017. CT was measured manually in both eyes based on enhanced-depth imaging spectral-domain optical coherence tomography at different follow-up visits scheduled in the morning., Results: A total of 134 patients were included. Ninety-five patients presented at least one episode, defined by a follow-up visit under controlled condition (dry retina) followed by a visit for exudative recurrence. A total of 119 episodes were analyzed. The mean CT change in the treated eye was + 8.45 ± 13.52 μm (p < 0.001) and + 5.62 ± 14.77 μm (p = 0.009) respectively in the subfoveal area and nasal area. No significant change in CT was observed in the fellow eye. No significant association between CT changes and treatment, number of intravitreal injections, and blood pressure was observed., Conclusion: CT increased in case of exudative recurrence of neovascular AMD. The increase was mild but significant. Thus, CT could be used as a monitoring criterion, like the central retinal thickness, in AMD management.

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.

Purpose: To assess mean change in visual acuity (VA) overall and stratified by baseline VA after 1 and 2 years' treatment with aflibercept in a real-life setting., Methods: This was an observational cohort study using nationwide data from the Swedish Macula Register. Treatment-naïve patient eyes with wet age-related macular degeneration and prescribed aflibercept from January 2013 to December 2014 were followed for 1 year (2478 eyes) or 2 years (831 eyes) to assess VA. Eyes were grouped by baseline VA., Results: Mean number of injections in patients treated according to label (72%) versus patients treated not according to label was 8.0 ± 1.5 versus 4.4 ± 0.8 (p < 0.0001) at 1 year, and 12.5 ± 3.2 versus 7.3 ± 1.9 (p < 0.0001) at 2 years. Among all eyes, mean VA increased from 61.3 ± 13.4 Early Treatment Diabetic Retinopathy Study letters at baseline to 64.5 ± 15.6 at 1 year and 65.1 ± 15.1 letters at 2 years. At 2 years, eyes with good baseline vision (≥70 letters) lost a mean of 2.4 ± 11.3 to 72.3 letters, eyes with intermediate baseline VA (36-69 letters) gained 5.7 ± 14.1 to 62.7 letters, and eyes with poor baseline VA (≤35 letters) gained 13.2 ± 18.3 to 41.0 letters. Also at 2 years, 75% of treated eyes were stable or had improved VA. Among eyes with intermediate baseline VA, near vision was significantly better among those treated according to label versus not according to label at 3 (p = 0.019), 6 (p = 0.0002) and 12 months (p ≤ 0.0001)., Conclusion: While gain in vision was especially pronounced in eyes with poor baseline VA, good baseline VA was important for best prognosis., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To evaluate intravitreal bevacizumab every 2 weeks (biweekly) in refractory neovascular age-related macular degeneration (nAMD)., Study Design: Retrospective study., Methods: A retrospective study of consecutive nAMD patients unresponsive to monthly intravitreal anti-vascular endothelial growth factor (VEGF) switched to 3-4 biweekly injections., Results: Twenty-seven eyes of patients aged 82.08  ± 6.85 years were included. Prior to the 2-week interval bevacizumab injections, 74.1% (n=20) were treated with both bevacizumab and ranibizumab, 11.1% (3 eyes) also received aflibercept and 14.8% (4 eyes) had received prior treatment of monthly bevacizumab (average number of injections 21.5 ± 6.7). Best corrected visual acuity (BCVA) remained stable between baseline (logMAR 0.72± 0.60) and follow-up (0.76± 0.66) (p=0.41). Mean central macular thickness and macular volume did not change significantly between baseline and follow-up (p=0.35 and p=0.60, respectively). Six eyes (22.2%) showed morphologic anatomic improvements, while 19 eyes (70.4%) were stable and two eyes (7.4%) deteriorated from baseline. Subretinal fluid completely resolved in 3 of the eyes and improved in the other 3 eyes and in this group (22.2%) both central macular thickness (326.2 ± 101.4 versus 297.5 ± 97.2, p=0.002) and macular volume (8.69 ± 1.69 versus 8.22 ± 1.43, p=0.03) were significantly reduced. No adverse events were observed in any of the treated eyes., Conclusion: This study demonstrates that biweekly bevacizumab injections are effective in nearly one-quarter of nAMD non-responders with no adverse events reported. Switching earlier, rather than later, to this low cost modality may be of benefit for a portion of non-responders to conventional treatment.

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.

Neovascular age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Although intravitreal injection of anti-VEGF antibodies and VEGF Trap have significant clinical benefits, the complications of intravitreal injection, drug resistance and patient compliance still need to be concerned. In this study, the effects of an orally administered multi-targeted tyrosine kinase inhibitor (Lenvatinib, E7080) were evaluated in vitro and in vivo on neovascular AMD mouse model. The results showed that E7080 effectively inhibited the proliferation, migration and tubule formation of human choroidal microvascular endothelial cells (HCMECs), and suppressed the angiogenesis of zebrafish subintestinal vessels without causing malformation. The anti-angiogenic effect of E7080 on the laser-induced choroidal neovascularization (CNV) mouse model by oral administration of 10 mg/kg/day was observed. The fluorescein angiography showed CNV leakage area in treatment group vs control group was 3.407 ± 0.2939 vs 5.202 ± 0.9001 (P = .0133) at day 7th post laser-induced CNV, 1.138 ± 0.4334 vs 3.122 ± 0.3466 (P = .0064) at day 14th, 1.401 ± 0.6577 vs 2.781 ± 0.9815 (P = .00262) at day 21th respectively. Moreover, pharmacokinetics analysis in rat retina showed that E7080 rapidly penetrated the blood-retina barrier to retina through oral administration. The T 1/2 in retina was 3.81 ± 0.77 h, the T max was 4.60 ± 0.73 h, the AUC 0-∞ was 110448.51 ± 18532.51 h*ng/g after a single dose administration analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). In conclusion, our study suggested that orally administered E7080 can be a novel therapeutic strategy for neovascular AMD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To assess the time from symptom onset to treatment for neovascular age-related macular degeneration (nvAMD) and to measure the awareness of AMD in Southeast Scotland., Design: Retrospective cross-sectional study., Setting: Secondary care, Southeast of Scotland., Methods: Patients treated with intravitreal therapy (IVT) for nvAMD in Southeast Scotland between 2013 and 2015 were identified using a treatment register. Notes were retrospectively reviewed. We measured time from: (A) symptom onset to first presentation at primary care, (B) referral to ophthalmic clinic appointment and (C) ophthalmic clinic appointment to first IVT treatment. To investigate AMD awareness, we performed a cluster random sample survey of patients visiting non-AMD ophthalmic clinics using a previously validated 12-item questionnaire., Results: 195 patients (mean age 78 years) were included in the study. The mean delays between the different stages-A, B and C-were 54.2 (95% CI ±13), 28.2 (95% CI ±4.0) and 31.5 (95% CI ±3.6) days, respectively. There was an additional mean delay of 7.5 (95% CI ±1.6) days when patients were indirectly referred by optometrists via general practitioners (P<0.05). 140 patients (mean age 78) participated in the awareness survey; 62.1% reported being 'aware' of AMD but only 37.3% described AMD symptoms correctly., Conclusions: There was a significant delay at every step of the nvAMD care pathway. The causes for this were multifactorial and included delays in first presentation to a healthcare provider, referral from primary care and initiation of secondary care treatment. Our data are likely to underestimate prehospital delays as a large number of cases are likely to have undefined symptoms and onset. We also identified suboptimal awareness of AMD which could account for a substantial delay in presentation from symptom onset. These findings highlight the need to address AMD awareness and the need for urgent treatment to prevent avoidable vision loss resulting from nvAMD., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: To evaluate the combined use of optical coherence tomography and angiography (OCT-A) for imaging choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD)., Materials and Methods: This prospective observational study was conducted from May 2015 to April 2017. Included in the study were 54 patients (n = 63 eyes), all of whom had CNV secondary to nAMD and all of whom had been examined by OCT-A. Angioscans (3x3 and 6 × 6) and conventional B-scan OCT scans were obtained for all patients at baseline and at various times during the 24-month follow-up period. For diagnostic confirmation, conventional imaging methods fluorescein angiography (FA) and indocyanine green angiography (ICGA) were performed at baseline. A total of 13 patients (n = 15 eyes) underwent serial imaging during 34 follow-up visits. The main outcomes included (i) determination of OCT-A sensitivity for the detection of CNV (classic and occult) and (ii) the correlation between B-scan OCT and OCT-A vis-à-vis consecutive follow-up changes., Results: At baseline, the detection rate (i.e., overall sensitivity) of OCT-A for detecting CNV was 64.4% (75.7 and 48.0% for classic and occult CNV, respectively), independent of prior treatment status. In terms of quality, 6 × 6 angioscans were superior to 3 × 3. Moreover, specific CNV morphologic patterns by B-scan OCT did not correlate with lesion composition. Correspondence between OCT-A and B-scan OCT was observed in only 53% of the cases., Conclusions: OCT-A may prove to be a valuable adjunctive diagnostic tool for the interpretation of CNV, as it not only reduces the need for invasive angiographic procedures but also facilitates the follow-up process.

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 (CI 95 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 (CI 95 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 (CI 95 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., (© 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

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.

Purpose. The assessment of the incidence of ocular hypertension over a period of 1 year in patients treated with multiple intravitreal injections of anti-VEGF agents for neovascular AMD. Methods. The study comprised 58 eyes diagnosed with neovascular age-related macular degeneration and receiving PRN intravitreal treatment with anti-VEGF agents (bevacizumab or aflibercept). The follow-up period was 1 year. Intraocular pressure was measured by using the Goldmann applanation tonometry before the intravitreal injection, at 24 hours after the administration of the anti-VEGF agent and at 1 and 4 weeks. Patients diagnosed with glaucoma or who underwent ophthalmic surgery were excluded. Results. The patients received an average of 7.54 intravitreal injections. The mean baseline intraocular pressure was 15.3 mm Hg; 19.8 mm Hg at 24 hours; 17,4 mmHg at 1 week and 14.8 mmHg at 4 weeks after the administration of the anti-VEGF agent. 4 patients required long-term topical hypotensive treatment. Raised intraocular pressure was related to increased frequency of treatment. At 1 year follow up, an average difference of 2.1 mmHg compared to baseline was registered in the cases that have received more than 6 intravitreal injections. By comparison, in the cases treated with a reduced number of doses of intravitreal anti VEGF agent, the difference from baseline was 0,9 mmHg. There were no significant differences in mean IOP depending on the anti VEGF (bevacizumab or aflibercept) agent used. Conclusions. Intravitreal treatment with anti VEGF agents produces a transient increase in intraocular pressure, predominantly immediately following administration, without causing long-term increased values.

Objective: To analyse the functional recovery using a pro re nata (PRN) dosing strategy with intravitreal injections of ranibizumab for patients with neovascular age-related macular degeneration (AMD)., Material and Methods: An observational, retrospective, single-centre study, was conducted on patients with neovascular AMD managed with a PRN strategy with ranibizumab, and were followed-up for a minimum of 18 months. Sociodemographic and clinical data were collected from medical records. The percentage of visual acuity (VA) recovered after losing 5 or more letters was calculated taking into account the previous visit, as well as considering the best VA recorded prior to the retreament., Results: The analysis included 128 patients. The mean (SD) follow-up period was 18.9 (2.3) months. The mean (SD) elapsed days between onset of symptoms and diagnosis, and between prescription and administration of treatment was 50.2 (57.4) and 10.9 (16.0), respectively. Only 108 patients were prescribed ranibizumab after losing 5 or more letters of VA. The mean (SD) VA recovery compared to the previous VA was 70.3% (114.4). On the other hand, the mean (SD) VA recovery when considering the best VA registered before the retreatment was 43.5% (112.9), with 59.4% of re-treatments having a VA recovery below 75%, and with 11.7% not presenting any VA recovery., Conclusions: A PRN dosing strategy with intravitreal ranibizumab for neovascular AMD may not be efficient in preserving and/or recovering VA in the long-term, due to a cumulative irreversible VA loss., (Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Purpose: To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice., Methods: We extracted information about patients recorded in electronic databases managing anti-VEGF injections and cataract surgery. We compared Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and frequency of anti-VEGF injections before and after cataract surgery., Results: We identified 89 eyes from 89 patients who had cataract surgery after being treated with a median of 10 (range 3-36) anti-VEGF injections for neovascular AMD. Visual acuity improved by a mean of 7.1 [95% confidence interval (CI) 4.6-9.6] ETDRS letters in the first 6 months after cataract surgery. The need of anti-VEGF injections did not change after cataract surgery with an average of 1.5 in the 6 months before surgery versus 1.7 in the 6 months after surgery (p = 0.25). Visual improvement was greater in patients when the time from latest injection to cataract surgery was lower., Conclusions: Cataract surgery improves vision in patients undergoing treatment for neovascular AMD. Cataract surgery was not associated with an increased need for anti-VEGF treatment and patients who were in active anti-VEGF treatment had better visual outcomes than patients who had cataract surgery after long injection-free periods., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: With increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a "one size fits all" to an "individualised" approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 μm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD., Methods/design: This 24 month, randomised, phase IV trial has completed recruitment of treatment-naïve patients randomised 1:1 to ranibizumab "intensive" treatment (complete resolution of IRF and SRF) or ranibizumab "relaxed" treatment (resolution of IRF or >200 μm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment., Discussion: This study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol., Trial Registration Number: NCT01972789. Date of registration: 24th October 2013.

Purpose/aim: To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort., Materials and Methods: This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables., Results: There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD., Conclusions: We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

Purpose: The HELIOS (Health Economics with Lucentis in Observational Settings) study was designed on request of the Dutch Health Authority for an observational study to assess the effectiveness and safety of ranibizumab for neovascular age-related macular degeneration (wet AMD) in daily practice., Methods: The HELIOS study was a 2-year prospective, observational, open-label, multicentre study involving 14 sites. Patients with wet AMD were enrolled and observed for a period of 24 months. The data were collected at baseline and at the visits closest around the time-points 3, 6, 12, 18 and 24 months after inclusion., Results: Treatment with ranibizumab resulted in prevention of vision loss. The mean ETDRS score increased from 45.1 letters at baseline to 48.5 letters at 24 months. This was achieved with a mean of 7.8 injections over 24 months. Stabilization of visual acuity was also reflected by the scores on the quality of life EQ-5D questionnaire, which did not significantly change over the study period. The more subjective EQ-VAS questionnaire showed an overall improvement. The VFQ-25 questionnaire was also mostly stable over time. After 24 months, 32.2% of the patients gained ≥1 letter and 17.1% gained >15 letters. Patients completing the loading phase were better responders, as demonstrated by increased long-term visual acuity. In addition, ranibizumab was well tolerated and had a safety profile commonly seen in routine clinical practice., Conclusion: This study demonstrates that also in daily practice ranibizumab was effective in preventing vision loss over a period of 24 months. No new safety findings were identified., (© 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

PurposeAutomated segmentation of retinal layers by spectral-domain optical coherence tomography (SD-OCT) is usually erroneous in the presence of retinal diseases. The purpose of this study is to report the changes in ganglion cell complex (GCC) comprising retina nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) in neovascular age-related macular degeneration (AMD) patients by manually correcting the automated segmentation errors.MethodsThirty eyes of 30 patients with new-onset choroidal neovascularization secondary to neovascular AMD and 30 eyes of 30 healthy subjects were included. The inner retinal thicknesses were measured using early treatment diabetic retinopathy circle in the central 1 mm (fovea) and surrounding 3 mm diameter (parafovea) after checking the accuracy of automated segmentation lines. Manual segmentation was done to ensure the accurate segmentation, when needed.ResultsNeovascular AMD patients had thicker mean RNFL, GCL, IPL, and GCC thicknesses within the fovea compared to healthy eyes (p = 0.04, p = 0.001, p = 0.032, and p = 0.005, respectively). In the parafoveal area, among the thickness-related measurements, the only significant difference was a thicker mean RNFL (p = 0.002).ConclusionDiffuse thickening of inner retinal layers in neovascular AMD may overestimate actual GCC thickness within fovea. This pseudo-increase in GCC thickness and inner retinal layers in general likely does not reflect more cells or tissue, but rather diffuse edema which leads to a falsely increased reading of layer thickness. Such false readings may also make the assessment of other conditions that lead to reduced inner retinal layer thickness such as glaucoma, optic nerve disease, or retinovascular occlusions more difficult.