Stroke risk management in carotid atherosclerotic disease: A Clinical Consensus Statement of the ESC Council on Stroke and the ESC Working Group on Aorta and Peripheral Vascular Diseases.

Carotid atherosclerotic disease continues to be an important cause of stroke, often disabling or fatal. Such strokes could be largely prevented through optimal medical therapy and carotid revascularization. Advancements in discovery research and imaging along with evidence from recent pharmacology and interventional clinical trials and registries and the progress in acute stroke management have markedly expanded knowledge base for clinical decisions in carotid stenosis. Nevertheless, there is variability in carotid-related stroke prevention and management strategies across medical specialities. Optimal patient care can be achieved by (1) establishing a unified knowledge foundation and (2) fostering multi-specialty collaborative guidelines. The emergent Neuro-Vascular Team concept, mirroring the multi-disciplinary Heart Team, embraces diverse specializations, tailores personalized, stratified medicine approaches to individual patient needs, and integrates innovative imaging and risk-assessment biomarkers. Proposed approach integrates collaboration of multiple specialists central to carotid artery stenosis management such as neurology, stroke medicine, cardiology, angiology, ophthalmology, vascular surgery, endovascular interventions, neuroradiology and neurosurgery. Moreover, patient education regarding current treatment options, their risks and advantages, is pivotal, promting patient's active role in clinical care decisions. This enables optimization of interventions ranging from lifestyle modification, carotid revascularization by stenting or endarterectomy, as well as pharmacological management encompassing statins, novel lipid-lowering and antithrombotic strategies and targeting inflammation and vascular dysfunction. This consensus document provides a harmonized multi-specialty approach to multimorbidity prevention in carotid stenosis patients, based on comprehensive knowledge review, pinpointing research gaps in an evidence-based medicine approach. It aims to be a foundational tool for interdisciplinary collaboration and prioritized patient-centric decision-making.

Clinical efficacy and safety of intravitreal fluocinolone acetonide implant for the treatment of chronic diabetic macular oedema: five-year real-world results.

BACKGROUND/AIM: To report 5-year real-world efficacy and safety data following the treatment of chronic diabetic macular oedema (DMO) with the intravitreal 0.19 mg fluocinolone acetonide implant(ILUVIEN). METHODS: Retrospective cohort study of 31 eyes treated with ILUVIEN for chronic DMO at a tertiary centre in Birmingham (UK). Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at baseline, and then at 1-,2-,3-, and 5-years. Safety was assessed based on intraocular pressure (IOP) -lowering medication, surgery, and other complications. RESULTS: BCVA significantly improved 1-year post-ILUVIEN (+4.2 letters, p < 0.05) and gradually reverted to baseline levels over the 5-year period of follow-up (+0.2 letters at year-5). A significant and sustained CRT reduction was observed throughout the 5-years. The proportion of eyes on IOP-lowering medication increased from 16% at baseline, to 70% at 5-years (p < 0.001) with eyes on a mean of 1.3 medications. Laser trabeculoplasty (n = 2), cyclodiode laser (n = 1), and trabeculoplasty and trabeculotomy (n = 1, in the same eye; 3.2%) were required for uncontrolled IOP. Other complications included endophthalmitis (n = 1) and vitreous haemorrhage (n = 1). 58% of eyes required additional intravitreal injections, with a mean 29.2 months to first injection. We observed a 69% reduction in treatment burden following treatment with ILUVIEN implant. CONCLUSIONS: Our real-world results confirm the efficacy of the ILUVIEN implant over 5 years, with two-thirds of eyes having improved or stable visual acuity 5 years after ILUVIEN, and an overall sustained improvement in anatomical outcome. Although the rate of IOP-lowering medications use was higher than previously reported, the rate of incisional IOP-lowering surgery and other complications remained low and in keeping with rates reported in larger studies.

Comparing Effectiveness of Three Different Anti-VEGF Treatment Regimens for Neovascular Age-Related Macular Degeneration: Two Years' Real-World Clinical Outcomes.

PURPOSE: To compare and report the 2-year treatment outcomes from 3 different anti-VEGF treatment regimens in treating neovascular aged-related macular degeneration (nAMD): Ranibizumab pro re nata (Ranibizumab-PRN); Ranibizumab treat and extend (Ranibizumab-T&E); Aflibercept fixed first year dosing (7 injections) with treat and extend in subsequent year (Aflibercept-Fixed). METHODS: All treatment-naïve nAMD patients who completed 24 months of monitoring from a single treatment center were included. Patients received the initial loading dose of three injections (4-weekly interval), followed by one of the 3 treatment regimens. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcome was number of injections required in each year. Data analysis included last observation carried forward (LOCF) for patients with incomplete year-2 follow-up. RESULTS: A total of 249 eyes (230 patients) were studied: 121 Ranibizumab-PRN; 65 Ranibizumab-T&E, and 63 Aflibercept-Fixed. Baseline median VA (ETDRS letters) for Ranibizumab-PRN, Ranibizumab-T&E, and Aflibercept-Fixed was 53.9, 61.1, and 54.9 letters, achieving final VA of 54.9, 65.1, and 65.1 letters, respectively. Hence, the number of letters increased at the end of 24 months for each group was +1.0 (Ranibizumab-PRN), +4.0 (Ranibizumab-T&E), highest +10.2 in Aflibercept-Fixed group. Median number of injections over 2 years (year-1/year-2) was 5/1 for Ranibizumab-PRN, 9/6 for Ranibizumab-T&E, and 7/5 for Aflibercept-Fixed. Both Ranibizumab-T&E and Aflibercept-Fixed also shared the same reduction of median CRT (115 µm), higher than Ranibizumab-PRN (83 µm). CONCLUSION: We report VA improvement from all three different treatment regimens with both Aflibercept-Fixed and Ranibizumab-T&E regimens achieving the same higher final VA. Aflibercept-Fixed dosing may have more favorable efficacy with the highest VA gain and comparatively lower dosing frequency whereas Ranibizumab-T&E may be more efficient than Ranibizumab-PRN regimen, according to our study.

Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.

PURPOSE: Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients. DESIGN: Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare providers in the UK. PARTICIPANTS: Treatment-naïve patients receiving at least 3 intravitreal anti-vascular endothelial growth factor (VEGF) injections for nAMD in their first 6 months of follow-up were included. Patients with missing data for age or gender and those aged less than 55 years were excluded. METHODS: Eyes with at least 3 years of follow-up were grouped by years of treatment initiation, and 3-year outcomes were compared between the groups. Data were generated during routine clinical care between September 2008 and December 2018. MAIN OUTCOME MEASURES: Visual acuity (VA), number of injections, and number of visits. RESULTS: A total of 15 810 eyes of 13 705 patients receiving 195 104 injections were included. Visual acuity improved from baseline during the first year, but decreased thereafter, resulting in loss of visual gains. This trend remained consistent throughout the past decade. Although an increasing proportion of eyes remained in the driving standard, this was driven by better presenting VA over the decade. The number of injections decreased substantially between the first and subsequent years, from a mean of 6.25 in year 1 to 3 in year 2 and 2.5 in year 3, without improvement over the decade. In a multivariable regression analysis, final VA improved by 0.24 letters for each year since 2008, and younger age and baseline VA were significantly associated with VA at 3 years. CONCLUSIONS: Our findings show that despite improvement in functional VA over the years, primarily driven by improving baseline VA, patients continue to lose vision after the first year of treatment, with only marginal change over the past decade. The data suggest these results may be related to suboptimal treatment patterns, which have not improved over the years. Rethinking treatment strategies may be warranted, possibly on a national level or through the introduction of longer-acting therapies.

Ultra-Widefield Fluorescein Angiographic Patterns, Retinal Microvascular Anomalies and Retinal Ischemic Index in Branch Retinal Vein Occlusions with Established Retinal Neovascularization.

PURPOSE: To share the experience of using ultra-widefield fluorescein angiography (UWF-FA) in recognizing the potential signs for retinal neovascularizations (NVE) development in branch retinal vein occlusions (BRVO). METHODS: Reporting angiographic findings in 60 BRVO eyes presenting with NVE and vitreous hemorrhage using UWF-FA investigation. Angiographic retinal ischemic index (ARI) was also calculated from UWF-FA as the ratio of digitally mapped ischemic retina area against area of optic disc, termed unit of disc diameter (DD). RESULTS: We observed emerging angiographic features common to these patients: pattern of a localized non-perfused retina at early phase of UWF-FA remaining non-perfused at the late phase (black retinal ischemia, black-RI) (100%); presence of retinal microvascular anomalies (RMAs) at the "water-shed-border" of black-RI (100%); site of NVEs observed at either the same "water-shed-border" (42%) or from the main vessel branch within the black-RI (30%), or from both sites (28%); multiple NVEs were observed in all eyes except two with single active NVE. Median ARI size was 114 DD (SD 80 DD), range 5-354 DD. CONCLUSION: We report a recurring angiographic pattern common to eyes with active BRVO-NVEs from UWF-FA, and NVEs in this clinical group can develop from varied ARI sizes. Further studies would be needed to establish the role of UWF-FA in predicting angiographic risk factors for BRVO-NVE.

Combination Therapy for Macular Oedema in Retinal Vein Occlusions: 3-Year Results from a Real-World Clinical Practice.

PURPOSE: To report long-term efficacy and treatment outcomes of the combination therapy for treating macular oedema (MO) in retinal vein occlusions (RVOs) from a real-world UK practice. METHODS: The initial reported 66 RVO patients with MO treated with combination therapy (initial Ranibizumab, later optional addition of Ozurdex and laser) were followed up to Year 3: visual acuity (VA) and central retinal thickness (CRT) were analysed against baseline and previous Year 1 results. Safety and adverse events were also recorded. RESULTS: Baseline LogMAR VA of 0.71 (Snellen 6/30) improved to 0.48 (Snellen 6/18) at Year 3 (p=0.006); 63% experienced VA improvement (40% improved ≥3 lines), 27% had worse vision. Stability of mean VA (6/18) was already achieved at first post-loading phase review and was maintained in each subsequent year. Statistically significant CRT improvement was noted in each year (Year 3 median CRT=264µm) compared to baseline (median CRT=531µm). There was a reduction in the mean number of total injections to 2.5 in Year 3 (vs 5.5 in Year 1). Comparing Year 3 against Year 1, mean Ranibizumab injection frequency was 2.1 vs 4.3; mean Ozurdex injection frequency was 0.2 vs 1.1. In Year 3, 39.6% of patients did not require any form of injections, laser frequency was also reduced to 22.9% (vs 81.8% in Year 1). There was no endophthalmitis in the cohort, one progressed to neovascular glaucoma in Year 2 and mortality rate was recorded as 6%. CONCLUSION: Our real-world clinical practice for RVO patients using a combined therapy is associated with good long-term VA and anatomical outcomes with less intravitreal re-treatment rates.

Real-World Visual And Clinical Outcomes For Patients With Neovascular Age-Related Macular Degeneration Treated With Intravitreal Ranibizumab: An 8-Year Observational Cohort (AMD8).

PURPOSE: To report the long-term clinical outcomes for patients with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy as part of a standardised treatment protocol in a real-world setting. PATIENTS AND METHODS: This is a retrospective audit of all treatment-naïve patients with nAMD who commenced a pro re nata (PRN) treatment regimen of intravitreal Ranibizumab from January to December 2009 and completed 8 years of follow-up in one single-treatment centre. Electronic medical notes were reviewed to evaluate the outcome measures. Outcome measures included progression of visual acuity (VA), central retinal thickness (CRT) and treatment frequency. RESULTS: 95 eyes from 86 patients had complete data for 8 years of follow-up. Baseline median CRT was 295µm [IQR 254-349] and improved to 209µm [IQR 182-254] in year 8 (p<0.001); baseline median VA was 61 ETDRS letters which increased to 70 letters post-loading however was reduced to 55 letters by year 8 (mean VA change from baseline was -9.1 letters); 47.4% had stable or improved vision, 10.5% gained ≥15 letters and 33.7% had lost ≥15 letters. The highest visual gain was achieved after the initial loading-phase, with a subsequent steady decline, 26.3% (compared to baseline 33.4%) achieved driving vision standard. Median injection frequency was 6 (range 3-10) in year 1 and 3 injections (range 0-10) in year 8. 51.6% of eyes required at least one injection each year and only 34.7% required no injections in year 8. CONCLUSION: Our real-world nAMD treatment cohort using Ranibizumab PRN regimen achieved an encouraging almost 50% stable or improved VA at year 8 and total injections of 31.6 injections per patient over an 8-year period.

United Kingdom Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group: report 4, real-world data on the impact of deprivation on the presentation of diabetic eye disease at hospital services.

AIM: To assess the impact of deprivation on diabetic retinopathy presentation and related treatment interventions, as observed within the UK hospital eye service. METHODS: This is a multicentre, national diabetic retinopathy database study with anonymised data extraction across 22 centres from an electronic medical record system. The following were the inclusion criteria: all patients with diabetes and a recorded, structured diabetic retinopathy grade. The minimum data set included, for baseline, age and Index of Multiple Deprivation, based on residential postcode; and for all time points, visual acuity, ETDRS grading of retinopathy and maculopathy, and interventions (laser, intravitreal therapies and surgery). The main  outcome measures were (1) visual acuity and binocular visual state, and (2) presence of sight-threatening complications and need for early treatment. RESULTS: 79 775 patients met the inclusion criteria. Deprivation was associated with later presentation in patients with diabetic eye disease: the OR of being sight-impaired at entry into the hospital eye service (defined as 6/18 to better than 3/60 in the better seeing eye) was 1.29 (95% CI 1.20 to 1.39) for the most deprived decile vs 0.77 (95% CI 0.70 to 0.86) for the least deprived decile; the OR for being severely sight-impaired (3/60 or worse in the better seeing eye) was 1.17 (95% CI 0.90 to 1.55) for the most deprived decile vs 0.88 (95% CI 0.61 to 1.27) for the least deprived decile (reference=fifth decile in all cases). There is also variation in sight-threatening complications at presentation and treatment undertaken: the least deprived deciles had lower chance of having a tractional retinal detachment (OR=0.48 and 0.58 for deciles 9 and 10, 95% CI 0.24 to 0.90 and 0.29 to 1.09, respectively); in terms of accessing treatment, the rate of having a vitrectomy was lowest in the most deprived cohort (OR=0.34, 95% CI 0.19 to 0.58). CONCLUSIONS: This large real-world study suggests that first presentation at a hospital eye clinic with visual loss or sight-threatening diabetic eye disease is associated with deprivation. These initial hospital visits represent the first opportunities to receive treatment and to formally engage with support services. Such patients are more likely to be sight-impaired or severely sight-impaired at presentation, and may need additional resources to engage with the hospital eye services over complex treatment schedules.

One-year outcome of bevacizumab therapy for chronic macular edema in central and branch retinal vein occlusions in real-world clinical practice in the UK.

BACKGROUND: The purpose of this study was to investigate the 12-month outcome of macular edema secondary to both chronic and new central and branch retinal vein occlusions treated with intravitreal bevacizumab in the real-life clinical setting in the UK. METHODS: Retrospective case notes analysis of consecutive patients with retinal vein occlusions treated with bevacizumab in 2010 to 2012. Outcome measures were visual acuity (measured with Snellen, converted into logMAR [logarithm of the minimum angle of resolution] for statistical calculation) and central retinal thickness at baseline, 4 weeks post-loading phase, and at 1 year. RESULTS: There were 56 and 100 patients with central and branch retinal vein occlusions, respectively, of whom 62% had chronic edema and received prior therapies and another 32% required additional laser treatments post-baseline bevacizumab. Baseline median visual acuity was 0.78 (interquartile range [IQR] 0.48-1.22) in the central group and 0.6 (IQR 0.3-0.78) in the branch group. In both groups, visual improvement was statistically significant from baseline compared to post-loading (P<0.001 and P=0.03, respectively), but was not significant by month 12 (P=0.058 and P=0.166, respectively); 30% improved by at least three lines and 44% improved by at least one line by month 12. Baseline median central retinal thickness was 449 µm (IQR 388-553) in the central group and 441 µm (IQR 357-501) in the branch group. However, the mean reduction in thickness was statistically significant at post-loading (P<0.001) and at the 12-month time point (P<0.001) for both groups. The average number of injections in 1 year was 4.2 in the central group and 3.3 in the branch group. CONCLUSION: Our large real-world cohort results indicate that bevacizumab introduced to patients with either new or chronic edema due to retinal vein occlusion can result in resolution of edema and stabilization of vision in the first year.

Macular Hole Formation After Intravitreal Ranibizumab Injection in Wet Age-Related Macular Degeneration.

Ranibizumab is a monoclonal antibody fragment that inhibits angiogenesis by inhibiting vascular endothelial growth factor A, used as a treatment for patients with wet aged-related macular degeneration (ARMD). Adverse effects from intravitreal Ranibizumab injections are well recognised. Macular hole formation following Ranibizumab injection is a complication that has been recently reported in few case reports. We present a larger case series of five patients, who developed full thickness macular holes (FTMH) after intravitreal Ranibizumab injections for treatment of wet ARMD that we were aware of between 2009 and 2013.

Effect of initial retinal thickness on outcome of intravitreal bevacizumab therapy for diabetic macular edema.

PURPOSE: To investigate whether eyes with diabetic macular edema (DME) and central retinal thickness (CRT) >400 µm had better visual and anatomical outcomes compared to eyes with a CRT <400 µm when treated with intravitreal bevacizumab in a real-world setting. PATIENTS AND METHODS: Patients undergoing intravitreal bevacizumab therapy for DME were identified from the departmental database of a tertiary referral unit. Following the initial injection, a retreatment was performed for any persistent macular edema, unless there had been no previous response to repeated doses. Recorded parameters included visual acuity, CRT on optical coherence tomography (spectral domain optical coherence tomography [SD-OCT]), and SD-OCT characteristics. Comparisons were made between data at baseline and 12 months after the first injection, and differences were tested for statistical significance using the Student's t-test. RESULTS: In all, 175 eyes of 142 patients were analyzed. Patients in group 2 (CRT >400 µm) had significantly more injections than group 1 (CRT <400 µm) (4.0 versus 3.3; P=0.003). Both groups had similar numbers of eyes with preexisting epiretinal membrane and/or vitreomacular traction at baseline. The reduction in CRT was significantly greater in group 2 when compared to group 1 (P<0.0001). In terms of visual gain between baseline and month 12, each gained significantly by a mean of 0.12 logarithm of the minimum angle of resolution units (P=0.0001), but there was no difference between groups 1 and 2 (P=0.99). CONCLUSION: These results do not support a 400 µm baseline CRT cut-off for treating DME with bevacizumab, in contrast to published data on ranibizumab. Our results also indicate that patients with a thicker CRT require more bevacizumab injections, making treatment less cost-effective for these patients. Our results could be used by practitioners to support the use of bevacizumab in DME without applying a CRT cut-off.

Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or Type II diabetes.

Since atherosclerosis is characterized by endothelial damage, re-growth seems likely to be occurring in order to repair or replace injured cells. Angiogenic vascular endothelial growth factor (VEGF), a likely mediator of these events, acts on the endothelium via a specific receptor, Flt-1. We hypothesized that patients with different manifestations of atherosclerosis, and others with diabetes, would have altered plasma levels of VEGF and Flt-1 compared with healthy individuals. Accordingly, 70 patients with peripheral artery disease (PAD), 70 patients with coronary artery disease (CAD), and 70 age- and sex-matched healthy controls were recruited. We also recruited 14 patients with diabetes asymptomatic for atherosclerosis, 14 patients with diabetes and atherosclerosis, and 14 age- and sex-matched controls. VEGF and soluble Flt-1 (sFlt-1) were measured by ELISA. In the main study of PAD and CAD, VEGF was raised in both patient groups (P<0.05) compared with the controls, but was not different between the patient groups. sFlt-1 was lower in patients with PAD (P<0.05), but not in those with CAD, compared with the controls. VEGF was raised in the patients with diabetes plus atherosclerosis (P<0.05), but not in the group with diabetes alone; levels of sFlt-1 were unaltered in both diabetes groups. Our data point to changes in plasma levels of VEGF and its receptor sFlt-1 in diabetes and atherosclerosis that may have relevance for therapy and angiogenesis in these conditions.