Comparing Measurements of Vascular Diameter Using Adaptative Optics Imaging and Conventional Fundus Imaging

The aim of this prospective study was to compare retinal vascular diameter measurements taken from standard fundus images and adaptive optics (AO) images. We analysed retinal images of twenty healthy subjects with 45-degree funduscopic colour photographs (CR-2 Canon fundus camera, Canon™) and adaptive optics (AO) fundus images (rtx1 camera, Imagine Eyes(®)). Diameters were measured using three software applications: the VAMPIRE (Vessel Assessment and Measurement Platform for Images of the REtina) annotation tool, IVAN (Interactive Vessel ANalyzer) for funduscopic colour photographs, and AO_Detect_Artery™ for AO images. For the arterial diameters, the mean difference between AO_Detect_Artery™ and IVAN was 9.1 µm (−27.4 to 9.2 µm, p = 0.005) and the measurements were significantly correlated (r = 0.79). The mean difference between AO_Detect_Artery™ and VAMPIRE annotation tool was 3.8 µm (−34.4 to 26.8 µm, p = 0.16) and the measurements were poorly correlated (r = 0.12). For the venous diameters, the mean difference between the AO_Detect_Artery™ and IVAN was 3.9 µm (−40.9 to 41.9 µm, p = 0.35) and the measurements were highly correlated (r = 0.83). The mean difference between the AO_Detect_Artery™ and VAMPIRE annotation tool was 0.4 µm (−17.44 to 25.3 µm, p = 0.91) and the correlations were moderate (r = 0.41). We found that the VAMPIRE annotation tool, an entirely manual software, is accurate for the measurement of arterial and venular diameters, but the correlation with AO measurements is poor. On the contrary, IVAN, a semi-automatic software tool, presents slightly greater differences with AO imaging, but the correlation is stronger. Data from arteries should be considered with caution, since IVAN seems to significantly under-estimate arterial diameters

Concordance between SIVA, IVAN, and VAMPIRE software tools for semi-automated analysis of retinal vessel caliber

We aimed to compare measurements from three of the most widely used software packages in the literature and to generate conversion algorithms for measurement of the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) between SIVA and IVAN and between SIVA and VAMPIRE. We analyzed 223 retinal photographs from 133 human participants using both SIVA, VAMPIRE and IVAN independently for computing CRAE and CRVE. Agreement between measurements was assessed using Bland–Altman plots and intra-class correlation coefficients. A conversion algorithm between measurements was carried out using linear regression, and validated using bootstrapping and root-mean-square error. The agreement between VAMPIRE and IVAN was poor to moderate: The mean difference was 20.2 µm (95% limits of agreement, LOA, −12.2–52.6 µm) for CRAE and 21.0 µm (95% LOA, −17.5–59.5 µm) for CRVE. The agreement between VAMPIRE and SIVA was also poor to moderate: the mean difference was 36.6 µm (95% LOA, −12.8–60.4 µm) for CRAE, and 40.3 µm (95% LOA, 5.6–75.0 µm) for CRVE. The agreement between IVAN and SIVA was good to excellent: the mean difference was 16.4 µm (95% LOA, −4.25–37.0 µm) for CRAE, and 19.3 µm (95% LOA, 0.09–38.6 µm) for CRVE. We propose an algorithm converting IVAN and VAMPIRE measurements into SIVA-estimated measurements, which could be used to homogenize sets of vessel measurements obtained with different software packages

Dexamethasone Implant for Diabetic Macular Oedema: 1-Year Treatment Outcomes from the Fight Retinal Blindness! Registry

INTRODUCTION Phase III clinical trials of dexamethasone intravitreal implant for diabetic macular oedema (DMO) have reported significant improvements in visual acuity (VA). Studies evaluating the treatment of DMO in routine clinical practice provide data to identify areas that need improvement. This study evaluated 12-month treatment outcomes of dexamethasone implant for DMO in routine clinical practice. METHODS Retrospective data analysis of eyes that started dexamethasone implant for DMO from 1 June 2013 to 30 April 2019 in routine clinical practice tracked in the Fight Retinal Blindness! Registry. RESULTS Of the 4282 eyes (2518 patients) that started DMO treatment in the specified period, 267 (6%) eyes (204 patients) received 454 dexamethasone implant injections. Two-fifths (106 eyes) had received prior treatment for DMO. The mean (95% confidence interval [CI]) VA change at 12 months was 1.8 (- 0.5, 4.2) letters from the mean (standard deviation [SD]) VA of 56.5 (19.8) letters at baseline, with 41% eyes achieving at least 20/40. The mean (95% CI) change in central subfield thickness over 1 year was - 79 (- 104, - 54) µm from a mean (SD) of 459 (120) µm at baseline. Eyes that completed 1 year of follow-up received a median (Q1, Q3) of 2 (1, 2) dexamethasone implants. One-tenth of phakic eyes received cataract surgery while 2% had a pressure response requiring anti-glaucoma medications. CONCLUSIONS One-year treatment outcomes of dexamethasone intravitreal implant for DMO in routine clinical practice were inferior to those in the clinical trials perhaps because of fewer treatments in clinical practice

Efficient capture of dry eye data from the real world:The Save Sight Dry Eye Registry

Purpose To describe a web-based, high-quality data collection tool able to track the clinical data of patients with dry eye disease (DED) in routine clinical practice. Design Retrospective analysis of core system web data from a prospectively designed, observational, routine clinical practice registry, the Save Sight Dry Eye Registry (SSDER). Methods Patients with DED, from 11-Nov-2020 to 04-Mar-2024 were analysed. Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI) questionnaires collected patient-reported DED symptoms, and the Patient Health Questionnaire-4 (PHQ-4) screened for anxiety and depression. Outcome data include index visit demography, DED symptoms and signs.  Results Fifteen clinicians (ophthalmologists and optometrists) from nine practices across Australia, France, Germany, Nepal, Spain and the United Kingdom contributed data, comprising index visits of 958 eyes from 479 patients (mean±SD age 56±17 years; 78.7% female). Up to 89.9% of the patients had either evaporative or mixed DED based on clinician's judgement. Mean OSDI symptom score at index visit was 35.7 ± 19.4 (n = 366), and the mean sores for frequency and intensity of discomfort with the OCI was 31.9 ± 6.1 and 31.4 ± 6.8 (n = 202) respectively. Forty-one percent of patients had mild to severe symptoms of anxiety and depression. Median tear breakup time and tear meniscus height were 5 (IQR 2–8) seconds and 0.3 (IQR 0.2–0.4) mm, respectively. Ocular surface staining was graded as none (37.6%), minimal (31.7%), mild (19.8%), moderate (8.8%) and severe (2.1%). Conclusion The SSDER facilitated the collection of data from patients with DED from real-world clinical practice. Presenting patients had moderate DED, which was mostly evaporative in nature. Symptoms of anxiety and depression were reported by more than one-third of the cohort

Projection of long-term visual acuity outcomes based on initial treatment response in neovascular age-related macular degeneration

PURPOSE To explore various methods for assessing the early response to vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration and investigate their association with 3 year visual acuity (VA) outcomes. DESIGN Observational study from a prospectively collected registry. PARTICIPANTS Treatment-naïve eyes in the Fight Retinal Blindness! outcomes registry that commenced anti-VEGF therapy between 1st January 2007 and 1st March 2014 that received 3 anti-VEGF injections within the first 3 months. METHODS The early response was defined as occurring up until the 4th injection. Various early response metrics, which included both continuous and categorical variables, were explored: 1) achieving good VA (≥70 letters [20/40]), 2) absolute change in VA from baseline, 3) time to first grading of the choroidal neovascular lesion as inactive, 4) maximum rate of VA change between successive injections. MAIN OUTCOME MEASURES Proportion of eyes achieving ≥70 letters at 3 years. RESULTS This study included 2051 treatment-naïve eyes from 1828 patients. Achieving good vision at 3 years was significantly associated with 1) having good vision by the 4th injection (odds ratio [95% CI]: 9.8 [6.5, 14.7] for VA≥70 vs. VA5 letters) early VA gains (1.8 [1.2, 2.6], P = 0.002 and 1.8 [1.3, 2.5], P 3 injections), 4) gradual change (between -4 and 4 letters) or rapid (>5 letters) gains between successive injections (1.7 [1.1, 2.6], P = 0.015 and 1.6 [1.1, 2.3], P = 0.018 for gradual change and rapid gain vs. rapid loss). Eyes that achieved small or large early gains achieved similar vision at 3 years (65.0 and 64.7 letters respectively), and had better vision than eyes with early VA loss (57.2 letters). CONCLUSIONS Attainment of good vision by the 4th injection was strongly associated with 3 year visual outcomes, while other early response parameters had a moderate association. The early response during the initial 3 monthly loading doses can be a useful guide for subsequent treatment decisions

Outcomes and predictive factors after cataract surgery in patients with neovascular age-related macular degeneration. The Fight Retinal Blindness! Project

Purpose: To evaluate outcomes and predictive factors of visual acuity (VA) change after cataract surgery in patients being treated for neovascular age-related macular degeneration (nAMD). Design: Retrospective, matched case-control study. Methods: We studied eyes undergoing cataract surgery that had been tracked since they first started treatment for nAMD. These eyes were compared with a cohort of unoperated phakic eyes being treated for nAMD (three per case) matched for treatment duration before cataract surgery, baseline VA, age and length of follow-up. Results: We included 124 patients that had cataract surgery and 372 matched controls. The mean (95% CI) VA gained was 10.6 letters (7.8, 13.2; P < 0.001) 12 months following surgery; 26.0% had gained ≥ 3 lines and 1.6% had lost ≥ 3 lines of VA. Visual acuity (mean [SD]) 12 months after surgery was higher in eyes that had cataract extraction compared with controls (65.8 [17.1] vs. 61.3 [20.8] letters respectively, P = 0.018). The proportion of visits where the choroidal neovascular (CNV) lesion was graded active and the mean number of injections were similar before and after surgery (P = 0.506 and P = 0.316, respectively), while both decreased in the control group, suggesting that surgery modestly increased the level of activity of the CNV lesion. Mean [SD] VA prior to surgery was lower in eyes that gained ≥15 letters compared with eyes that gained 0-14 letters (40.2 [21.4] vs. 62.1 [15.1], P < 0.001). Patients undergoing cataract surgery within the first 6 months of anti-VEGF therapy were more likely to lose rather than gain vision (20.8% lost vision vs. 12.8% and 4.4% gaining ≥15 or 0-14 letters respectively, P = 0.023). Age, receiving an injection at least 2 weeks before surgery, and the CNV lesion type had no discernible association with VA outcomes. Conclusions: We found evidence of a modest effect of cataract surgery on CNV lesion activity in eyes being treated for nAMD. Despite this, visual outcomes were reassuringly good. Cataract surgery within 6 months of starting treatment for nAMD should be avoided if possible.The Fight Retinal Blindness Project was supported by a grant from the Royal Australian NZ College of Ophthalmologists Eye Foundation (2007-2009), a grant from the National Health and Medical Research Council, Australia (NHMRC 2010-2012) and a grant from the Macula Disease Foundation, Australia. Mark Gillies is a Sydney Medical Foundation Fellow and is supported by an NHMRC practitioner fellowship. Daniel Barthelmes was supported by the Walter and Gertud Siegenthaler Foundation Zurich, Switzerland and the Swiss National Foundation. Vincent Daien was supported by the research grant of the French Society of Ophthalmology and by Servier. Funding was also provided by Novartis and Bayer

Ophthalmology

PURPOSE: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population. DESIGN: Cross-sectional meta-analysis. PARTICIPANTS: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9+/-12.3-82.1+/-4.2 years) of the European Eye Epidemiology (E3) consortium. METHODS: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis. MAIN OUTCOME MEASURES: Determinants of pRNFLT. RESULTS: Mean pRNFLT ranged from 86.8+/-21.4 mum in the Rotterdam Study I to 104.7+/-12.5 mum in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mum/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (beta = -0.36 mum/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mum; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mum; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mum; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mum; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mum/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mum; 95% CI, 1.00-2.06 for current smokers compared with never-smokers). CONCLUSIONS: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Retinal vascular caliber and cardiovascular biomarkers and metabolic biomarkers. Clinical and epidemiological approach.

Les vaisseaux rétiniens sont accessibles par la visualisation du fond d'œil grâce notamment aux rétinophotographies. Cette visualisation donne donc un accès direct à l'étude de la microcirculation humaine. Depuis 1999, le logiciel IVAN® permet une analyse «semi-automatique» du calibre vasculaire rétinien. L'analyse de la littérature retrouve que les variations du calibre vasculaire rétinien sont le reflet cumulatif du poids de naissance, de facteurs génétiques, de l'âge, des facteurs de risques cardiovasculaires, de la fonction rénale et de l'inflammation. Les méta-analyses d'études épidémiologiques suggèrent un rôle prédictif des calibres vasculaires rétiniens sur les évènements cardiovasculaires : un calibre artériel rétinien étroit serait prédictif de maladie coronaire chez les femmes et augmenterait la mortalité cardiovasculaire globale ; un large calibre veineux serait prédictif d'accident vasculaire cérébral. Cette thèse a pour objectif d'approfondir les connaissances sur les déterminants des calibres vasculaires rétiniens chez les sujets indemnes d'athérosclérose clinique (antécédent de maladie coronaire, d'accident vasculaire cérébral, d'artériopathie des membres inférieurs). Depuis 2007, en partenariat avec l'université de Melbourne, nous avons acquis le logiciel IVAN® et l'agrément permettant son utilisation en recherche clinique et épidémiologique a été obtenu en 2008. Dans un premier article, nous avons mis en évidence une relation linéaire entre calibre artériel et veineux et fonction rénale mesurée par des méthodes gold standard (filtration glomérulaire mesurée par la clairance de 99mTc-DTPA et ratio albuminurie/créatinurie) sur 80 sujets de la cohorte de médecine interne-hypertension artérielle de l'hôpital Lapeyronie, suggérant des déterminants communs de ces lésions précoces d'organes cibles. Dans un deuxième article, nous avons tout d'abord confirmé le lien entre dilatation veineuse rétinienne et inflammation systémique, puis observé une relation entre calibre artériel étroit et stress oxydatif sur les participants de la cohorte POLA (pathologies oculaires liées à l'âge). Cela est d'une importance particulière car cela suggère que la microcirculation rétinienne, dont des associations avec la macrocirculation carotidienne et cardiaque ont été retrouvées, serait particulièrement sensible au stress oxydatif et à l'inflammation, de façon indépendante des facteurs de risques cardiovasculaires. Dans un troisième article, nous avons retrouvé une relation entre malnutrition biologique et dilatation veineuse rétinienne sur les participants de la cohorte POLA. Cela suggère que des remaniements microcirculatoires précoces pourraient être un mécanisme associé à l'augmentation du risque cardiovasculaire observé chez les sujets âgés souffrants de malnutrition. Les caractéristiques techniques du logiciel IVAN® limitent sa généralisation en médecine, mais son utilisation permet d'approfondir les connaissances sur les déterminants des variations de calibre des vaisseaux de la rétine. Le futur challenge des études sur la vascularisation rétinienne utilisera probablement l'étude de la géométrie vasculaire rétinienne afin d'améliorer la compréhension de microcirculation humaine.Retinal photography, by allowing a direct observation of retinal vessels, may thus constitute a practical and noninvasive method for the examination of early changes in human microcirculation. Since 1999-2000, IVAN ® software allows for a "semi-automatic" retinal vascular caliber analysis. In the literature, changes in the caliber of retinal vessels have been shown to reflect the cumulative effects of birth weight, genetic factors, aging process, cardiovascular risk factors, renal function, and inflammation. In meta analyses from epidemiological studies, wider retinal venules and narrower arterioles were associated with an increased risk of coronary heart disease in women and an increased risk of global cardiovascular mortality, while wider retinal venular caliber predicted stroke. The aim of the current research is thus to improve the knowledge of retinal vascular calibers determinants in subjects free of clinical evidence of atherosclerosis (either stroke or coronary and peripheral artery disease). In 2007, Melbourne University provided us IVAN ® software and the agreement for its use in clinical and epidemiological research was obtained in 2008. In a first article, an inverse linear relationship between retinal arterial and venous caliber and renal function measured with gold standard methods (glomerular filtration rate from urinary clearance of 99mTc-DTPA and urinary albumin ⁄ creatinine ratio.) was observed in 80 subjects from the cohort of internal medicine-arterial hypertension-Lapeyronie hospital, suggesting common determinants of these preclinical target organ damages. In a second article, we first confirmed the relationship between a wider retinal venular caliber and inflammation, as well as provided evidence for a novel association between wider retinal arteriolar caliber and oxidative stress quantified by GPx-3 activity in the participants of the POLA (Pathologies Oculaires Liées à l'Age) cohort. This finding is of particular importance as it suggests that retinal microvasculature, which has been related to carotid arterial stiffness and cardiac remodeling, may be particularly sensitive to systemic oxidative stress and systemic inflammation, independently of known cardiovascular risk factors. In a third article based on POLA cohort participants, a retinal venular dilatation appears to be strongly associated with malnutrition biomarkers (albumin and transthyretin). This suggests that early microvascular changes may be one of the mechanisms associated with the observed increased risk of cardiovascular disease among elderly subjects with malnutrition. Technical characteristics of IVAN® software limit its generalization in medicine, but its improved our knowledge about the caliber of retinal vessels changes. The future challenge for retinal microcirculation research will probably use parameters of retinal vascular geometry for a better understanding of human microcirculation