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Background: Intravitreal ranibizumab for diabetic macular oedema (DMO) has been recently shown to modulate levels of aqueous cytokines. This study investigates the associations between changes in aqueous cytokine levels following intravitreal ranibizumab therapy and the corresponding anatomical and functional changes in the eye. Methods: Twenty‐five patients comprising 30 eyes diagnosed with DMO were prospectively recruited. All eyes received three loading dose ranibizumab injections at baseline, week 4 and week 8, followed by pro re nata treatment based on best‐corrected visual acuity (BCVA) and central macular thickness (CMT) up to week 48. Prior to ranibizumab administration, aqueous samples were collected from all eyes, and subsequent sampling was performed at week 8. Levels of 32 cytokines were assessed at baseline and at week 8. Results: At baseline, higher aqueous TNF‐α levels were associated with poorer BCVA (p = 0.033), greater macular volume (p = 0.017) and worse diabetic retinopathy (p = 0.047). Higher levels of IL‐7 were associated with poorer BCVA and greater macular volume (MV). Following treatment with ranibizumab there was a significant correlation with reduction of aqueous TNF‐α and improvements in BCVA and MV, both at 6 months (BCVA [r = −0.558, p = 0.001], MV [r = 0.410, p = 0.024]) and 12‐months (BCVA [r = −0.413, p = 0.023], MV [r = 0.482, p = 0.008]). The change in VEGF concentration following ranibizumab treatment did not correlate with either BCVA or MV improvements (p > 0.05). Conclusions: Higher levels of aqueous TNF‐α and IL‐7 correlated with worse DMO, both anatomically and functionally. Reductions in levels of aqueous TNF‐α, but not VEGF, post ranibizumab treatment were associated with improvement in BCVA and MV. [ABSTRACT FROM AUTHOR]

Introduction: Cost-effectiveness analyses typically ignore healthcare system resource constraints. Ophthalmology is affected by resource constraints because of increasing disease prevalence and the use of resource-intensive treatments. This study evaluated the impact of resource constraints on the cost-effectiveness of faricimab 6 mg, compared with aflibercept 2 mg and ranibizumab biosimilar 0.5 mg, for treating wet age-related macular degeneration (wAMD) or diabetic macular oedema (DMO) over a 5-year horizon. Methods: A microsimulation model estimated the impact of resource constraints on patients visits, delays, costs and quality-adjusted life-year (QALY) losses due to treatment delays at a typical UK National Health Service eye hospital treating 1500 patients with wAMD and 500 patients with DMO. Patient characteristics, treatment regimens and treatment intervals were informed using published literature and expert opinion. Resource constraint was represented by limiting the number of available intravitreal injection appointments per week, with growing demand caused by rising disease prevalence. The model compared outcomes across three scenarios; each scenario involved treating all patients with one of the three treatments. Results: Over 5 years, in a resource-constrained hospital, compared with aflibercept, faricimab use resulted in the avoidance of 12,596 delays, saved GBP/£15,108,609 in cost and avoided the loss of 60.06 QALYs. Compared with ranibizumab biosimilar, faricimab use resulted in the avoidance of 18,910 delays, incurred £2,069,088 extra cost and avoided the loss of 105.70 QALYs, resulting in an incremental cost-effectiveness ratio of £19,574/QALY. Conclusions: Accounting for resource constraints in health economic evaluation is crucial. Emerging therapies that are more durable and require less frequent clinic visits can reduce treatment delays, leading to improved QALY outcomes and reduced burden on healthcare systems. Faricimab reduced the number of delayed injections, leading to improved QALY outcomes for patients in a healthcare system with resource constraints. Faricimab is cost-saving when compared with aflibercept and cost-effective when compared with ranibizumab biosimilar. [ABSTRACT FROM AUTHOR]

Background: Intravitreal injection anti-vascular endothelial growth factor (IVI anti-VEGF) therapy serves as the primary treatment for centre involving diabetic macular oedema (DMO). Conventional laser therapy (CLT) adjunct has proven beneficial; however, it is not widely used due to significant risks of retinal scarring. Subthreshold micropulse laser (SML) therapy has, however, emerged as a comparable alternative to combination therapy, offering a distinct advantage by mitigating the risk of retinal scarring. Methods: A search of six databases was conducted. A meta-analysis of mean differences was performed including subgroup analyses where appropriate. Primary outcome was the number of injections at 12–14 months; secondary outcomes were changes in central macular thickness (CMT) and best corrected visual acuity (BCVA) at 6–8 months and 12–14 months. Results: A total of ten papers including six randomised clinical trials and four retrospective clinical studies were included in our study, capturing 563 eyes of 478 patients. Overall, the risk of bias was moderate for these studies. Significantly fewer anti-VEGF therapy injections were administered in the combination therapy versus anti-VEGF monotherapy patients at 12–14 months who had poor visual acuity (6/18 Snellen or worse) at baseline, mean difference − 2.25 (95% CI; − 3.35, − 1.15; p < 0.05). Combination therapy was not associated with significantly fewer intravitreal injections in patients with a higher visual acuity (6/15 Snellen or better) at baseline. Our analysis also showed significant improvements to both BCVA and CMT were reached at 6 − 8 month post-baseline at the 95% confidence intervals: − 1.13 (− 2.09, − 0.16) and − 4.04 (− 7.59, − 0.50). These improvements remained statistically significant at 12–14 months: − 0.94 (− 1.67, − 0.20) and − 1.92 (− 3.52, − 0.32) respectively with combination therapy. Conclusion: Our findings demonstrate that combination therapy (SML + IVI anti-VEGF) is associated with fewer intravitreal injections. We report a better BCVA and a reduction in CMT at 6 and 12 months from baseline with combination treatment compared to the IVI anti-VEGF monotherapy comparator. SML is a proven non-scarring cost-effective therapy for DMO that should be readily available in the medical retinal therapy as it may reduce the burden of care. [ABSTRACT FROM AUTHOR]

Purpose: The worldwide prevalence of diabetes mellitus (DM) continues to increase. As DM is linked to various ophthalmological comorbidities, it is crucial to understand the incidence and the treatment patterns of these complications to minimise the treatment burden for the patient and the healthcare system. This study aims to evaluate the incidence and prevalence of diabetic macular oedema (DME) and proliferative diabetic retinopathy (PDR) and to analyse intravitreal (IVT) treatment patterns and responses in the Finnish population with diabetes. Methods: A nationwide data register containing details of over 20‐year‐old individuals with diabetes was used in the analyses. Results: The incidence and prevalence of DME and PDR among the Finnish population with diabetes either declined or remained stable during 2007–2017 (Incidence rate: DME −40.8%, PDR −65.3%; prevalence rate: DME +4.7%, PDR −11.2%). During the same period, number of persons suffering from diabetes increased by +58.3%. The total number of IVT injections increased by 261.7%; the number of patients receiving IVT treatments increased by 133.6% from 2011 to 2017, reflecting changes in patient numbers in the ophthalmology departments. Furthermore, irrespective of the rising number of patients with diabetes, the numbers with visual impairment declined by 75.8% among DME and by 75.7% among PDR patients in 2007–2017. Conclusions: Regardless of the considerable increase in the workload of ophthalmology departments, the healthcare system has been able to reduce both the age and sex standardised incidence of DME and PDR among the diabetic population suffering from a visual impairment associated with this disease. [ABSTRACT FROM AUTHOR]

Purpose: A number of algorithms have been developed to calculate screening intervals for diabetic retinopathy on the basis of individual risk factors. However, these approaches have not considered proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DME) as separate end points and death as competing risk. Methods: A multi‐state survival model with death as competing risk was used to predict the screening interval for diabetic retinopathy based on information about all 2446 patients from a well‐defined population who had started treatment for either PDR or DME during 25 years. The performance of the model was tested on the existing database and at seven screening sites on patients who had not developed a treatment requiring condition. Results: Testing on the existing database showed that at a risk level of 2% the algorithm could predict a screening interval with a success rate higher than 90% and a 1.75 times average prolongation of the screening interval without failing to detect the development of verified PDR og DME. The model was limited to a diabetes duration shorter than 40 years and depended on knowledge of relevant risk factors. At the other participating screening sites the algorithm predicted shorter intervals than the screener. Conclusions: Algorithms for individualised screening for diabetic retinopathy can prolong screening intervals without losing patients who develop a vision threatening condition. The calculation of screening intervals requires access to relevant risk factors and should be developed on large data sets that reflect the population in which the algorithm should be used. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a leading cause of visual morbidity worldwide. Fundus autofluorescence is a rapid, non-invasive imaging modality that has gained increased popularity in recent years in the multimodal evaluation of diabetic retinopathy and, in particular, of diabetic macular oedema. Acquired using either a fundus camera or the confocal scanning laser ophthalmoscope, short-wavelength and near-infrared autofluorescence are the most used techniques in diabetic retinopathy. In diabetic macular oedema, short-wavelength autofluorescence, in its cystoid pattern, is useful for detecting cystoid macular oedema. Increased spot hyperautofluorescence in short-wavelength and granular changes in near-infrared autofluorescence correlate well with other imaging findings, indicating photoreceptor and retinal pigment epithelium damage and being associated with decreased visual acuity. While also being a marker of oxidative stress, increased short-wavelength autofluorescence in the setting of diabetic macular oedema appears to be a prognostic factor for poor visual outcome, even after the resolution of the intraretinal fluid. Autofluorescence also helps in the assessment of diabetic retinal pigment epitheliopathy and choroidopathy. Fundus autofluorescence is an evolving technology that will assist in gaining further insight into the pathophysiology of diabetic retinopathy and allow for a more comprehensive evaluation of these patients. [ABSTRACT FROM AUTHOR]

This is a summary of the original article ‟Cost‑Effectiveness of Faricimab in the Treatment of Diabetic Macular Oedema (DMO): A UK Analysis". DMO, a serious eye condition that can lead to vision loss in people with diabetes, is a significant health concern and a lack of knowledge exists about the cost-effectiveness (the balance of a treatment's cost and its effectiveness) of new treatments. This research assessed the cost-effectiveness of a new medication named faricimab, using a mathematical model that simulated the progression of DMO and its treatment over 25 years. The model compared faricimab against relevant therapeutic alternatives for DMO in the UK, including ranibizumab, aflibercept, and bevacizumab. The research discovered that faricimab could offer improved vision results and be cost saving or cost-effective. It also suggested that faricimab could lessen the strain on healthcare services due to its less frequent dosing schedule. Overall, such findings suggest that faricimab is a promising new treatment option for DMO that could benefit patients and the healthcare system. This could have implications for future treatment guidelines and the management of DMO in clinical practice. [ABSTRACT FROM AUTHOR]

Valid and updated clinical indicators can serve as important tools in assessing and improving eyecare delivery. Indicators for diabetic eyecare in Australia were previously developed from guidelines published before 2013 and then used to assess the appropriateness of care delivery through a nationwide patient record card audit (the iCareTrack study). To reflect emerging evidence and contemporary practice, this study aimed to update clinical indicators for optometric care for people with type 2 diabetes in Australia. Forty-five candidate indicators, including existing iCareTrack and new indicators derived from nine high-quality evidence-based guidelines, were generated. A two-round modified Delphi process where expert panel members rated the impact, acceptability, and feasibility of the indicators on a 9-point scale and voted for inclusion or exclusion of the candidate indicators was used. Consensus on inclusion was reached when the median scores for impact, acceptability, and feasibility were ≥7 and >75% of experts voted for inclusion. Thirty-two clinical indicators with high acceptability, impact and feasibility ratings (all median scores: 9) were developed. The final indicators were related to history taking (n = 12), physical examination (n = 8), recall period (n = 5), referral (n = 5), and patient education/communication (n = 2). Most (14 of 15) iCareTrack indicators were retained either in the original format or with modifications. New indicators included documenting the type of diabetes, serum lipid level, pregnancy, systemic medications, nephropathy, Indigenous status, general practitioner details, pupil examination, intraocular pressure, optical coherence tomography, diabetic retinopathy grading, recall period for high-risk diabetic patients without retinopathy, referral of high-risk proliferative retinopathy, communication with the general practitioner, and patient education. A set of 32 updated diabetic eyecare clinical indicators was developed based on contemporary evidence and expert consensus. These updated indicators inform the development of programs to assess and enhance the eyecare delivery for people with diabetes in Australia. [ABSTRACT FROM AUTHOR]

Objective: To describe the management of diabetic macular oedema (DME) patients from the entire French population between 2012 and 2018. Methods: In this retrospective longitudinal study, we identified adults treated for DME from the French population using the exhaustive French National Health Information database (SNDS), and an algorithm based on diagnosis and procedure codes, and reimbursed treatments. Results: Between 2012 and 2018, we identified 53 584 treated DME patients, who were followed for up to 7 years from DME treatment initiation. Optical coherence tomography (OCT) became the predominant imaging tool to diagnose DME. Only 14% of patients consulted a diabetologist or endocrinologist in the 3 months prior to initiating DME treatment, whereas 84% consulted a general practitioner. The percentage of patients consulting an ophthalmologist declined over time, from 97% of patients in Year 1 (median of 9 consultations), to 46% in Year 7 (median of 7 consultations). The median DME treatment duration with an anti‐VEGF and/or dexamethasone implant treatment was 9 months; 54% of patients had a treatment duration less than 1 year. First‐line treatment was more common with ranibizumab (55% of patients) than with aflibercept (30%), or dexamethasone implant (15%). About 25% of patients who initiated anti‐VEGF treatment switched treatment at least once, while 30% of patients who initiated dexamethasone implant switched to anti‐VEGF treatment at least once. Conclusions: French DME patients seem well‐monitored by their ophthalmologist, but median DME treatment duration was just 9 months. These results emphasise the challenge to manage and treat patients with DME over the long term. [ABSTRACT FROM AUTHOR]

Purpose: To identify associations between systemic drugs and the incidence of diabetic macular oedema (DME). Of interest was to find beneficial and/or deleterious associations of used drugs. Methods: A historic cohort design based on administrative data. Study population consisted of 150 353 individuals with diabetes. Endpoint event was the development of DME (ICD‐10 H36.01), censoring events were death or study end December 2017. The follow‐up started between 1997 and 2010. The systemic medication consisted of 95 substances. We constructed a nested case–control study design comparing 2630 cases with DME to 13 144 age‐ and sex‐matched controls without DME. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) based on conditional logistic regression models. Results: Incidence rate for DME was 1.80 per 1000 person‐years (95% CI 1.73–1.87). In all, we observed a lower incidence rate of DME in females (IRR 0.57; 95% CI 0.52–0.62) compared to males. Exposure to hormone replacement therapy estradiol (OR 0.42; 0.25–0.68), temazepam (0.23; 0.08–0.62) and allopurinol (0.61; 0.43–0.86) were associated with lower risk of DME, while use of insulin or insulin analogue (3.30; 2.99–3.64), sulfonylureas (1.21; 1.05–1.40), diuretic furosemide (1.90; 1.61–2.24), calcium channel blocker amlodipine (1.53; 1.34–1.75), ACE inhibitors ramipril (1.66; 1.46–1.89) and enalapril (1.38; 1.16–1.64) were associated with an increased risk of DME. Conclusions: Large‐scale studies examining the incidence of DME are lacking. Our findings suggest that associations of systemic medications with the incidence of DME may shed light on the pathogenesis of complex DME, encouraging further studies. [ABSTRACT FROM AUTHOR]

The role of subclinical inflammation in the pathophysiology of diabetic macular oedema (DME), which is known to be quite complex, is of much interest. Serum ferritin level, which is an indicator of body iron stores, is both an inflammatory marker for various neurodegenerative diseases and an important indicator in the evaluation of iron-induced oxidative stress. Iron metabolism indicators play a role in the formation and development of diabetic retinopathy, which is known to be associated with subclinical inflammation, and may also play a role in the pathogenesis of DME. The aim of this study was to investigate the role of serum iron metabolism markers in the pathogenesis of DME. The files of all nonproliferative diabetic retinopathy (NPDR) patients who were scheduled for the first intravitreal injection for DME in the eye clinic between January 2019 and January 2020 were reviewed retrospectively. By examining the files of all diabetes mellitus patients who attended the outpatient eye clinic on the same dates, those without retinopathy and those with NPDR but not DME were recorded. All results, including a comprehensive ophthalmological examination, laboratory data of fasting blood tests, and an internal medicine outpatient examination were collected for analysis. Of the 157 participants, 44 were NPDR patients with oedema, 50 were NPDR patients without oedema, and 63 were patients without retinopathy. There was a significant difference between the groups in respect of creatinine, high-density lipoprotein, mean corpuscular volume, serum iron and ferritin, total iron binding capacity and transferrin saturation (p < 0.050). Ferritin values were found to be significantly higher in patients with macular oedema. Other iron status markers were found to be significantly lower (p < 0.050). Evaluation of serum iron status indicators in the routine follow-up of diabetic patients may be of diagnostic and/or prognostic benefit in terms of DME. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus, leading to visual impairment if left untreated. This review discusses the use of optical coherence tomography angiography (OCTA) as a diagnostic tool for the early detection and management of DR. OCTA is a fast, non-invasive, non-contact test that enables the detailed visualisation of the macular microvasculature in different plexuses. OCTA offers several advantages over fundus fluorescein angiography (FFA), notably offering quantitative data. OCTA is not without limitations, including the requirement for careful interpretation of artefacts and the limited region of interest that can be captured currently. We explore how OCTA has been instrumental in detecting early microvascular changes that precede clinical signs of DR. We also discuss the application of OCTA in the diagnosis and management of various stages of DR, including non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), diabetic macular oedema (DMO), diabetic macular ischaemia (DMI), and pre-diabetes. Finally, we discuss the future role of OCTA and how it may be used to enhance the clinical outcomes of DR. [ABSTRACT FROM AUTHOR]

Background: Different network meta-analyses (NMAs) on the same topic result in differences in findings. In this review, we investigated NMAs comparing aflibercept with ranibizumab for diabetic macular oedema (DME) in the hope of illuminating why the differences in findings occurred. Methods: Studies were searched for in English and Chinese electronic databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP; see detailed search strategy in the main body). Two independent reviewers systematically screened to identify target NMAs that included a comparison of aflibercept and ranibizumab in patients with DME. The key outcome of interest in this review is the change in best-corrected visual acuity (BCVA), including various ways of reporting (such as the proportion of participants who gain ≥ 10 ETDRS letters at 12 months; average change in BCVA at 12 months). Results: For the binary outcome of BCVA, different NMAs all agreed that there is no clear difference between the two treatments, while continuous outcomes all favour aflibercept over ranibizumab. We discussed four points of particular concern that are illustrated by five similar NMAs, including network differences, PICO (participants, interventions, comparators, outcomes) differences, different data from the same measures of effect, and differences in what is truly significant. Conclusions: A closer inspection of each of these trials shows how the methods, including the searches and analyses, all differ, but the findings, although presented differently and sometimes interpreted differently, were similar. [ABSTRACT FROM AUTHOR]

Introduction: This review aims to assess the efficacy, durability and safety of faricimab—a dual vascular endothelial growth factor and angiopoietin 2 inhibitor—in patients with neovascular age-related macular degeneration (nAMD) and diabetic macula oedema (DMO). It summarises the findings of current studies on faricimab and discusses whether this new drug may fill a gap in current treatment options. Methods: We performed a search of the PubMed, Cochrane, Web of Science and EMBASE databases for publications on faricimab between 29 November 2022 and 10 May 2023, and a search of ClinicalTrials.gov for the protocols on clinical trials for this review. We included clinical trials, case–control studies and observational studies. Results: In phase 3 trials of nAMD, the efficacy of faricimab was non-inferior to aflibercept (+ 5.8–6.6 vs. + 5.1–6.6 Early Treatment Diabetic Retinopathy Study [ETDRS] letters). At study end, 80% of faricimab-treated patients were on ≥ 12-week dosing intervals, and 44.9–45.7% of faricimab-treated patients were on 16-week dosing intervals. Total adverse events, as well as serious ocular adverse events, were comparable between groups. In phase 3 trials of DMO, efficacy of faricimab was non-inferior to aflibercept (+ 10.7–11.8 vs. + 10.3–10.9 ETDRS letters). At study end, > 70% of patients in the personalised treatment interval faricimab group were on ≥ 12-week dosing intervals, and 51–53% were on 16-week dosing intervals. Total adverse events were comparable between groups, although the rate of serious ocular adverse events was higher in the faricimab groups than in the aflibercept groups (1.9–3.1% vs. 0.6–1.9%, respectively). In real-world studies of treatment-resistant nAMD or DMO, faricimab demonstrated superior efficacy compared to aflibercept. In a real-world study of mostly previously treated nAMD, faricimab demonstrated some efficacy. Conclusion: Faricimab demonstrated non-inferior to superior efficacy, strong durability and acceptable safety in treatment-naïve nAMD and mostly treatment-naïve DMO, as well as superior efficacy in treatment-resistant nAMD and DMO. However, further research is needed on faricimab in real-world settings. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the efficacy and safety of fluocinolone acetonide implant (FAci) injected 1 month after the last dexamethasone intravitreal implant (DEXi) in chronic diabetic macular oedema (DME) patients. Methods: Retrospective multicentric study conducted in pseudophakic patients with chronic DME frequently treated with dexamethasone intravitreal implant (DEXi; time to DME recurrence ≤ 6 months), receiving FAci 1 month after the last DEXi, with at least a 6-month follow-up. Best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography, intraocular pressure (IOP) and additional treatments were assessed on the day of FAci injection (M0), 1 (M1) and 3 months (M3) later and then every 3 months. Results: A total of 41 eyes from 34 patients were included. At M0, patients' mean age was 68.7 ± 9.8 years, the mean DME duration was 63.9 ± 22.9 months, the mean interval between two DEXi was 14.2 ± 3.3 weeks. M12 data were available for 71% of patients. At baseline, the mean BCVA, CMT and IOP were 63.2 ± 16.6 letters, 299.4 ± 103.3 µm, and 16.2 ± 4.5 mmHg, respectively, and remained stable during the follow-up. At M12, 14% of patients required additional intravitreal treatments. Conclusion: In pseudophakic patients with chronic DME showing good response to DEXi but requiring repeated injections every < 6 months, switching to FAci 1 month after the last DEXi was effective and safe. Further prospective randomized controlled studies are needed to confirm these findings, and to determine the best interval between the last DEXi and the first FAci. [ABSTRACT FROM AUTHOR]

Faricimab, a recently approved bispecific antibody targeting both anti-vascular endothelial growth factor and angiopoietin-2 in neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DME), showed non-inferiority when compared with aflibercept in its phase III trials. Subsequent real-world investigations reveal that faricimab is predominantly administered in previously treated eyes, leading to sustained improvements in best-corrected visual acuity after treatment commences for DME and nAMD. Notably, a majority of patients with nAMD can extend their treatment intervals to every 4 months. In real-world practice, retina specialists have found faricimab to be an important therapeutic option due to its efficacy and convenience of extended treatment intervals. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the lower visual acuity threshold for recommending intravitreal injection therapy (IVI). The lower limit of 1.3 logMAR best-corrected visual acuity (BCVA) was adopted in 2006 and has been maintained since then. Methods: In this retrospective study, data from patients with a logMAR BCVA ≤ 1.3 and 24 months follow-up were analysed. We included patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), or retinal vein occlusion (RVO). Results: The data from 164 patients (nAMD: 107; DME: 15; RVO: 42) were analysed. We observed a significant improvement at all time intervals (0 to 6, 6 to 12, 12 to 18, and 18 to 24 months after initiating IVI) compared to baseline. Across all indications, median BCVA improved from 1.4 to 1.0 within the first 6 months and remained stable within 24 months. Patients received a median of 5 and 10 injections within 6 and 24 months, respectively. Median foveal retinal thickness was 594.5 μm at baseline and dropped to 244.5 μm, 235.5 µm, 183 µm, and 180 µm during the four consecutive time intervals. Conclusion: Patients with nAMD, DME, and RVO with poor baseline BCVA may also benefit from intravitreal therapy with VEGF-inhibitors. In the present study, we observed functional and morphological improvement over 2 years irrespective of the underlying macular disease. Those patients should not be excluded from therapy. [ABSTRACT FROM AUTHOR]

Introduction: Key clinical guidelines recommend anti-vascular endothelial growth factor (VEGF) therapy as first-line treatment for visual impairment due to diabetic macular oedema (DMO). A systematic literature review (SLR) and network meta-analysis (NMA) were conducted comparing the relative efficacy of the anti-VEGF brolucizumab with a focused network of the most relevant comparator dosing regimens approved in countries other than the USA (aflibercept, ranibizumab). The safety and tolerability of brolucizumab were also assessed. Methods: A broad SLR was conducted to identify randomised controlled trials to ensure all relevant potential comparators were captured. Identified studies were refined to those appropriate for inclusion in the NMA. A Bayesian NMA was conducted comparing brolucizumab 6 mg (every 12 [Q12W]/every 8 weeks [Q8W]) with relevant aflibercept 2 mg and ranibizumab 0.5 mg regimens. Results: Fourteen studies were included in the NMA. At 1-year follow-up, the various aflibercept 2 mg and ranibizumab 0.5 mg regimens were mostly comparable with brolucizumab 6 mg Q12W/Q8W across key visual and anatomical outcomes, except brolucizumab 6 mg was favoured over ranibizumab 0.5 mg every 4 weeks (Q4W) for the change from baseline (CFB) in best-corrected visual acuity (BCVA), and BCVA loss/gain of pre-specified numbers of letters, and over ranibizumab 0.5 mg pro re nata for CFB in diabetic retinopathy severity scale, and retinal thickness. At year 2, where data were available, brolucizumab 6 mg showed similar results across efficacy outcomes versus all other anti-VEGFs. In most cases, discontinuation rates (all cause, and due to adverse events [AE]) and serious and overall rates of AEs excluding ocular inflammatory events were similar (in unpooled and pooled-treatment analyses) versus comparators. Conclusion: Brolucizumab 6 mg Q12W/Q8W was comparable or superior to aflibercept 2 mg and ranibizumab 0.5 mg regimens for various visual and anatomical efficacy outcomes and discontinuation rates. [ABSTRACT FROM AUTHOR]

Purpose: Ocular vascular diseases are common causes of visual impairment and blindness, for which anti-vascular endothelial growth factor (anti-VEGF) is the first-line therapy. Current study describes the profile of patients receiving intravitreal anti-VEGF injections (IVI), and gender variation in Bhutan. The study was designed to inform national health policy. Study Design: Retrospective cross-sectional study. Methods: We reviewed the surgical registers of the vitreoretinal (VR) units across Bhutan over three years. Patient demography, clinical findings, diagnostic tests performed, and diagnoses or indications for IVI were logged. A descriptive analysis was performed. Results: Despite limited availability of anti-VEGF, a total of 381 patients received IVI in operating theatres as mandated by the national guidelines. The majority of patients were males (230, 60.4%, p = 0.004). The mean age was 65.2 ± 13.5 years (range 13 years to 90 years), and a median of 69 years. The majority of the treated eyes (117, 30.7%) had BCVA < 3/60 to light perception (PL), and another 51 eyes (13.4%) had < 6/60 to 3/60. The most common indication for IVI was neovascular age-related macular degeneration (nAMD) (168 cases, 42.2%), followed by retinal vein occlusion (RVO) (132 cases, 34.6%), diabetic macular oedema (DMO) and retinopathy (DR) (50 cases, 13.1%), and myopic choroidal neovascular membrane (11 cases, 0.03%). Conclusion: Limited human resources for managing VR diseases in Bhutan are compounded by economic and geographic challenges. With increasing VR diseases such as nAMD and myopia and complications of systemic diseases such as DR, DMO and RVO, there is a need to improve VR services. Currently, anti-VEGF is procured only for a pooled patients requiring IVI, and patients are lost due to longer waiting periods. Bhutan needs to assess if females are reporting less or are not receiving treatment due to cultural barriers and social stigma. [ABSTRACT FROM AUTHOR]

Objective: Intravitreal ranibizumab is one of the anti‐vascular endothelial growth factors used for the treatment of diabetic macular oedema, not always successfully. We aimed to identify the factors affecting the changes of central macular thickness after induction treatment with intravitreal ranibizumab, to predict the treatment effect and facilitate early treatment decisions. Methods: Cross‐sectional study involving a retrospective record review of diabetic macular oedema patients who received an induction treatment of three monthly 0.5 mg intravitreal ranibizumab injections between 2016 and 2019. Central macular thickness was measured at baseline and 3 months post‐treatment. Linear regression was applied to identify the factors associated with the changes of central macular thickness. Results: A total of 153 diabetic macular oedema patients were involved in this study. Their mean age was 57.5 ± 7.7 years, 54.9% were female. The mean change of central macular thickness from baseline to 3 months after completed induction treatment of intravitreal ranibizumab was 155.5 ± 137.8 μm. Factors significantly associated with changes of central macular thickness were baseline central macular thickness [b = 0.73; 95% (CI): 0.63, 0.84; p = <0.001] and presence of subretinal fluid [b = 35.43; 95% CI: 3.70, 67.16; p = 0.029]. Conclusion: Thicker baseline central macular thickness and presence of subretinal fluid were the factors significantly associated with greater changes of central macular thickness in diabetic macular oedema patients after receiving three injections of intravitreal ranibizumab. [ABSTRACT FROM AUTHOR]

Diabetic macular oedema (DMO) is the leading cause of vision loss associated with diabetic eye disease. The exponential increase in the diabetic population and thus, of DMO is an impetus for optimizing the management of DMO. One major challenge in DMO management is the discrepancy between treatment outcomes seen in clinical trials and the real world. Contrary to the homogeneity, better patient motivation and shorter study durations seen in randomised control trials, routine clinical practice is fraught with more diverse populations, undertreatment and variable compliance with long-term therapy. Under both circumstances, this review aims to compare efficacy outcomes and adverse events of DMO therapies within the scope of anti-vascular endothelial growth factor (anti-VEGF) medications, specifically the commonly used ones—bevacizumab, ranibizumab and aflibercept. Impediments and methods to achieve better treatment outcomes in the real world will be addressed to achieve better outcomes. Low- to lower-middle-income countries are faced with even more barriers which range from paucity of data on epidemiology and treatment response to scarce human and financial resources to poorer national level attention and then basic issues like transportation. Additionally, to address the lack of a global consensus in DMO treatment, this review generates and recommends, for clinical and research purposes, an up-to-date consensus algorithm for DMO management universally. Underpinned by results from clinical trials and recent guidelines, this therapeutic flowchart can be utilised in various resource settings including low- and lower-middle-income countries where affordability is a major deterrent to treatment access. [ABSTRACT FROM AUTHOR]

Purpose: Various treatment regimens are currently practiced in the treatment of CI-DMO (centre-involving diabetic macular oedema). In recent years, there has been a growing body of evidence supporting a treat and extend (T&E) regimen for DMO which offers the promise of comparable visual and anatomical outcomes while reducing injection burden. This meta-analysis was hence performed to evaluate the aforementioned outcomes in the treatment of DMO. Ten studies met the inclusion criteria. Methods: A search of PubMed, MEDLINE, Current Contents, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. We employed the terms 'treat AND extend AND (diabetic AND macular AND edema OR oedema)' to ensure a comprehensive search. The search workflow adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Results: The pooled analysis of the mean number of injections in 1 year for T&E-aflibercept (AFL), T&E-ranibizumab (RBZ) and collectively was 9.1 (95% CI: 7.63–10.63), 10.0 (95% CI: 9.55–10.47) and 9.6 (95% CI: 8.62–10.49), respectively. Improvements in vision at 1 year for T&E-AFL, T&E-RBZ and collectively were 6.26 (95% CI: 3.24–9.29), 7.14 (95% CI: 4.76–9.52) and 7.08 (95% CI: 5.32–8.84) letters, respectively. The improvements in central subfield thickness at 1 year for T&E-AFL, T&E-RBZ and collectively were 131.94 (95% CI: 100.29–163.60), 108.64 (95% CI: 82.82–134.46) and 121.32 (95% CI: 102.89–139.75) microns, respectively. Conclusion: The meta-analysis of T&E for DMO did not show a clear advantage in reducing the number of injections compared to landmark clinical trials with pro-re-nata (PRN) treatment regimens in the first year of treatment with limited gains in visual and anatomical outcomes. However, the T&E approach offers the potential for fewer patient visits, thereby reducing treatment burden. Longer term studies on T&E with a standardised protocol would be required to assess the longevity of the vision gain in the first year despite a likely reduced treatment burden compared to the PRN trials. [ABSTRACT FROM AUTHOR]

Background: There is minimal information about the availability of treatment for Diabetic macular oedema (DMO) in sub-Saharan Africa (SSA). The principal aim of this survey was to determine the 'real world' management of DMO amongst ophthalmologists working in SSA. Methodology: Questionnaires were distributed to members of retinal and ophthalmological societies in SSA. Results: Ninety-Three ophthalmologists from 24 countries participated with the majority working in Nigeria (51, 55%). Most were retina specialists (50, 54%) and consultants (67, 62%). Clinically significant macular oedema prompted treatment for 62 (67%) ophthalmologists, whilst visual acuity (81, 87%) and OCT changes (76, 82%) were more common reasons to treat DMO. Treatment included intravitreal anti-VEGF (91, 98%), laser (70, 75%), intravitreal steroid (57, 61%), topical drops (52, 56%), oral tablets (32, 34%) and surgery (20, 22%). The commonest intravitreal anti-VEGF agents used were bevacizumab (89, 96%) and ranibizumab (71, 76%). Intravitreal triamcinolone was used by 69 (74%), topical NSAIDs by 51 (55%), and acetazolamide tablets by 22 (24%) ophthalmologists as a treatment for DMO. Conclusion: Sub-Saharan African ophthalmologists commonly use intravitreal anti-VEGF, laser, intravitreal steroid, and topical NSAIDs to treat DMO. Economic constraints and/or the inability to maintain the intensive regimen required for successful intravitreal anti-VEGF therapy probably influence some treatment choices. [ABSTRACT FROM AUTHOR]

Retinal imaging has been a key tool in the diagnosis, evaluation, management and documentation of diabetic retinopathy (DR) and diabetic macular oedema (DMO) for many decades. Imaging technologies have rapidly evolved over the last few decades, yielding images with higher resolution and contrast with less time, effort and invasiveness. While many retinal imaging technologies provide detailed insight into retinal structure such as colour reflectance photography and optical coherence tomography (OCT), others such as fluorescein or OCT angiography and oximetry provide dynamic and functional information. Many other novel imaging technologies are in development and are poised to further enhance our evaluation of patients with DR. [ABSTRACT FROM AUTHOR]

Diabetic macular oedema (DME) is a significant cause of visual impairment and inflammation plays an important role in its pathophysiology. This study evaluates the diagnostic value of systemic immune-inflammation index (SII) in the occurrence of DME in patients with non-proliferative diabetic retinopathy. In this prospective study, the SII was applied to 150 consecutive patients with non-proliferative diabetic retinopathy. The relationship between the SII and the occurrence of DME was examined. Patients with DME were also divided into two subgroups according to the presence of accompanying sub-retinal fluid. The SII value was calculated as follows: platelet count × (neutrophil/lymphocyte). The risk factors for DME were evaluated using multivariate logistic regression analysis. A receiver operating characteristic (ROC) curve analysis of SII for predicting DME was performed. Patients with DME had significantly higher levels of SII than those without DME (599.7 ± 279.2 and 464. 9 ± 172.2, respectively, p < 0.001). However, The SII values were similar between sub-retinal fluid subgroups. Multivariate regression analysis indicated that SII, together with duration of diabetes, was an independent factor for DME occurrence [Odds ratio (OR) = 1.005, 95% confidence interval = 1.001–1.009, p = 0.04, and OR = 1.146, 95% CI = 1.049–1.252, p = 0.003, respectively]. ROC curve analysis revealed that the best cut-off value of SII was 399 (area under the curve: 0.633; sensitivity: 70%; specificity: 60%). An elevated SII value is strongly associated with the development of DME. The SII may be a diagnostic biomarker for identifying DME to improve the risk stratification and management of non-proliferative patients with diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background: The anatomical and functional changes after intravitreal dexamethasone implant (IDI) alone and combined with navigated subthreshold micropulse laser (NSML) in diabetic macular oedema (DMO) were compared. Methods: Patients with a clinically confirmed diagnosis of non-proliferative diabetic retinopathy (NPDR) and DMO were enrolled in this prospective study and were randomly assigned to two different treatment groups: thirty patients were treated with IDI (IDI group), and the other 30 patients received IDI combined with NSML treatment (combined IDI/NSML group). All patients during a 6-month follow-up underwent best corrected visual acuity (BCVA) evaluation and spectral domain optical coherence tomography (SD OCT). The main outcome measures were: BCVA, central macular thickness (CMT); (3) choroidal vascularity index (CVI), subfoveal choroidal thickness (SCHT); and time to retreatment between IDI at baseline and the second implant in both groups. Results: BCVA, CMT, and SCHT significantly decreased starting from the 1-month follow-up and CVI from 3 months in both groups. The between-group differences were significantly different from 1-month follow-up for BCVA, from 5-month follow-up for CMT and SCHT, and from 4-month follow-up for CVI. The Needed to Treat analysis indicated that six patients would have to be treated with SML after IDI in order for just one person to receive a benefit. Conclusions: the combined treatment showed good anatomical and functional outcomes for the treatment of DMO. In addition, IDI/SML seems to reduce injection frequency over time, improving patients' quality of life and reducing the socio-economic burden. [ABSTRACT FROM AUTHOR]

The pathophysiology of diabetic macular oedema (DME) remains poorly understood. Proteomic analysis of the vitreous using mass spectrometry (MS) can potentially identify proteins of pathophysiological importance. In this systematic review, we summarize the available evidence on protein changes in DME detected by MS. We systematically searched 13 literature databases on 19 September 2021. Eligible studies were defined as those using samples from human eyes with DME analysed with MS. Two authors assessed the studies for eligibility, extracted data and evaluated risk of bias independently. Six eligible studies were identified. All were designed in a cross‐sectional fashion comparing results to either a non‐diabetic control group or a control group without DME. A total of 62 eyes from 60 patients contributed as study group and 48 eyes from 48 patients served as control group. Proteomic analyses revealed significant differences in the vitreous protein levels in patients with DME when compared with controls. Three studies or more identified increased contents of apolipoprotein A‐I, apolipoprotein A‐II, apolipoprotein A‐IV, apolipoprotein C‐III, gelsolin, pigment epithelium‐derived factor, serum albumin, transthyretin, vitamin D‐binding protein in DME. Two studies found increased levels of complement factors B and C3. Protein changes reproduced across the studies suggested that DME was associated with retinal lipid accumulation, angiogenesis, retinal protective mechanisms, inflammation and complement activation. Proteome studies support the multifactorial pathogenesis of DME as proteins with highly different biological functions are regulated in DME. An important number of proteins differ, provide pathophysiological insight and suggest the direction for future research. [ABSTRACT FROM AUTHOR]

Anti-vascular endothelial growth factor (anti-VEGF) injections are a mainstay of treatment for retinal vascular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion. While anti-VEGF monotherapy has helped improve visual outcomes in patients with these conditions, the need for frequent injections and followup visits, as well as the varying response to therapy are notable shortcomings. To address this, novel therapies have been investigated as adjuncts or alternatives to anti-VEGF monotherapy. One such therapy is faricimab, the first US Food and Drug Administration-approved intravitreal injection designed to target both VEGF-A and angiopoietin-Tie-2 for the treatment of nAMD and DMO. Clinical trial data thus far support that faricimab produces non-inferior visual and anatomical outcomes to standard anti-VEGF therapy, with longer durability, in these diseases. In this review, details regarding faricimab's molecular development, clinical trial outcomes, and its prospect as the newest drug in the treatment landscape for retinal diseases will be discussed. [ABSTRACT FROM AUTHOR]

Background: Frequent intravitreal anti‐VEGF injections are impractical for many Aboriginal patients with diabetic macular oedema (DMO). The longer acting intravitreal dexamethasone implant (DEX‐implant) is approved for DMO but has not been assessed in an Aboriginal population. Methods: This was a prospective, multicentre, randomised, single‐masked, non‐inferiority clinical trial. Aboriginal adults from Western Australia with DMO were randomised to receive 3‐monthly DEX‐implant, or monthly intravitreal bevacizumab. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months. Results: The final endpoint was analysed for 24 DEX‐implant and 28 bevacizumab injection eyes. Mean BCVA improved by 4.0 letters (−0.08 LogMAR) in the DEX‐implant group and worsened by 5.5 letters (0.11 LogMAR) in the bevacizumab group. Before adjusting for cataract surgery, the upper bound of the two‐sided 90% CI for the DEX‐implant was 3.5 letters (0.07 LogMAR), which met non‐inferiority criteria. The BCVA of remote participants who received the DEX‐implant improved by 5.5 letters (0.11 LogMAR), compared to an 18.5 letter (0.37 LogMAR) decline for bevacizumab (p = 0.04). The incidence of steroid‐induced ocular hypertension for the DEX‐implant was 33.3%. Conclusions: Before adjusting for the effect of cataract surgery, the DEX‐implant was non‐inferior to bevacizumab for treating DMO in Aboriginal participants. In remote participants, the DEX‐implant surpassed non‐inferiority to achieve superior outcomes to bevacizumab. The incidence of steroid‐induced hypertension was comparable to that reported in non‐Aboriginal populations. We provide guidelines for the judicious use of DEX‐implant among Aboriginal people, and a framework for performing ophthalmic clinical trials in Aboriginal communities. [ABSTRACT FROM AUTHOR]

Background and Purpose: The aim of this study was to describe the outcomes of a switch back to anti-vascular endothelial growth factor (VEGF) in diabetic macular oedema (DME) eyes treated temporarily with a dexamethasone implant (DEXi), after an initial poor response to anti-VEGF. Methods: The study involved a case series. Results: Twenty-three eyes of 17 patients were included. All were poorly responsive to anti-VEGF and switched to a DEXi after a mean of 12 anti-VEGF injections. The mean best-corrected visual acuity (BCVA) increased from 0.25 ± 0.19 (decimals) to 0.29 ± 0.20 after switching to the DEXi (p = 0.11). BCVA remained stable (0.31 ± 0.23; p = 0.11) after switching back to anti-VEGF, one month after the last injection. The mean central macular thickness (CMT) decreased significantly from 517.0 ± 128.5 μm to 343.4 ± 118.9 μm (p < 0.001) after switching to the DEXi. In eyes receiving ≥3 anti-VEGF injections during the switch back, the CMT 1 month after the last anti-VEGF injection was significantly decreased compared to the CMT before the switch to the DEXi (mean change of - 95.55 ± 89.82 μm, p = 0.005). Conclusion: Switching back poorly responsive DME eyes to anti-VEGF after temporary DEXi therapy is associated with good anatomical and visual outcomes similar to those obtained with the DEXi, provided that at least 3 anti-VEGF injections are administered. The DEXi might restore retinal sensitivity to anti-VEGF. [ABSTRACT FROM AUTHOR]

Purpose: In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti‐vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters. Methods: This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti‐VEGF or cataract surgery. VEGF, interleukin (IL)‐6, IL‐8, IL‐10, interferon‐inducible protein 10 (IP‐10) and monocyte chemotactic protein 1 (MCP‐1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper‐reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best‐corrected visual acuity were evaluated. Results: In SRD, IL‐6 and MCP‐1 levels and HF were increased (all p < 0.05) compared to DRT. At baseline, the number of HF was correlated with VEGF, IL‐6, IL‐8, IP‐10 and MCP‐1 (all p < 0.05). Eyes sensitive to anti‐VEGF treatment had high baseline levels of VEGF, MCP‐1, HF and many EZ disruptions (all p < 0.05). DME patients with normal VEGF levels but with high levels of IL‐8, IP‐10 and MCP‐1 (all p < 0.05) had little change in CMT after anti‐VEGF treatment (p = 0.678). Conclusions: AH concentrations of some inflammatory cytokines in DME were differentially expressed among the three DME morphologies. HF was associated with VEGF and other inflammatory cytokine levels. Multiple HF at baseline predicted a significant decrease in CMT, and eyes with normal VEGF but increased inflammatory cytokines may be insensitive to anti‐VEGF treatment. [ABSTRACT FROM AUTHOR]

Introduction: The 0.19 mg fluocinolone acetonide (FAc) intravitreal implant delivers a continuous intravitreal corticosteroid dose for the treatment of refractory diabetic macular oedema (DMO). The aim of this study was to assess the impact of an FAc intravitreal implant on intraocular pressure (IOP). Methods: We retrospectively collected anonymised data on the patients' characteristics, DMO treatment, and IOP and IOP-lowering treatments before and after the FAc intravitreal implant between September 2013 and March 2020 in several European centres. Results: A total of 221 eyes from 179 patients were included. The mean follow-up duration was 13.4 (± 12.5, range 2.4–33.5) months. Overall, 194 eyes (88.2%) had received an intravitreal dexamethasone injection before the FAc intravitreal implant. For 25 eyes (11.3%) there was a history of glaucoma, and 52 eyes (23.5%) had previous IOP-lowering treatment. Mean IOP before injection was 14.7 (3.4) mmHg and increased to 16.9 (3.7) mmHg 12 months after injection (P < 0.0001). During follow-up, 55 eyes (24.9%) required the addition or initiation of topical IOP-lowering medication, only one patient (0.5%) had laser trabeculoplasty and one patient (0.5%) a minimally invasive glaucoma surgery, and no patient required incisional IOP-lowering surgery. Conclusion: The FAc intravitreal implant led to substantial IOP elevation. This elevation was monitored most of the time with addition or initiation of topical IOP-lowering medication. [ABSTRACT FROM AUTHOR]

Purpose: To identify parameters that can predict the postoperative risk for progression of retinopathy to a vision‐threatening stage after cataract surgery. This may optimize the timing of surgery and the postoperative follow‐up strategy in diabetic patients. Methods: Multi‐state survival analysis with death as competing risk was used to investigate how year of onset and age of onset of diabetes, gender, body mass index, HbA1c and blood pressure had affected the risk for developing diabetic macular oedema (DME) and proliferative diabetic retinopathy (PDR) among 2540 right eyes from 2797 diabetic patients operated for cataract on one or both eyes during 25 years until July 1. 2019. Results: Cataract surgery had been performed in 98.8% of patients reaching 90 years of age. The risk for developing both DME and PDR was increased by cataract surgery. The risk was highest during the first postoperative years and increased by pre‐operative variability in HbA1c. The risk after more than 20 years postoperatively increased by increased cumulative HbA1c pre‐operatively. The other studied risk factors contributed differently to the development of the two complications. Conclusions: Decision models for the timing of cataract surgery in diabetic patients should consider that the risk for developing vision‐threatening retinopathy depends on follow‐up time. Differences in the risk profiles for developing DME and PDR after cataract surgery support that the two complications should be regarded as separate late complications. [ABSTRACT FROM AUTHOR]

Purpose: To compare visual acuity (VA) change at 24 months in eyes with clinically significant DME (CSDME) and good VA initially treated versus initially observed in routine clinical practice. Methods: Retrospective analysis of treatment‐naïve eyes with CSDME and good VA (baseline VA ≥ 79 letters), with at least 24 months of follow‐up and initially managed with treatment (intravitreal treatment and/or macular laser) or observation with possible treatment after 4 months that were tracked in a prospectively designed observational registry. Results: We identified 150 eligible eyes (98 initially observed, 52 initially treated) of 130 patients. The proportion of eyes with at least a 5‐letter VA loss at 24 months was not significantly different between the groups: 65% with initial observation and 42% with initial treatment (p = 0.39). However, initially observed eyes were more likely to have a 10‐letter VA loss at 24 months (OR = 4.6, p = 0.022). Most of eyes in the initial observation group received at least one treatment (an intravitreal injection in 66% and macular laser in 20%) during the 24‐month period. Conclusions: The risk of 5 letters loss was similar between both management groups. However, initially observed eyes were more at risk of developing moderate visual loss and more than 80% of them required treatment over 24 months. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic Retinopathy (DR) is a major complication of Diabetes Mellitus (DM), which remains a leading cause of visual loss in working age populations. The most common cause of vision loss in patients with DR is Diabetic Macular Oedema (DME). Intravitreal administration of anti-Vascular Endothelial Growth Factor (anti-VEGF) agents is currently the mainstay of therapy for both early and advanced stages of DR. Aim: To compare long-term change in Central Macular Thickness (CMT) and Best Corrected Visual Acuity (BCVA) in patients with Non Proliferative Diabetic Retinopathy (NPDR) with Clinically Significant Macular Oedema (CSME) after receiving Intravitreal Ranibizumab (IVR) following monthly, Pro Re Nata (PRN) protocol and Treat and Extend (T&E) protocol. Materials and Methods: This is a hospital based longitudinal prospective cohort study conducted on patients attending the Out Patient Department (OPD) of the Opthalmology Department at Midnapore Medical College and Hospital, West Bengal, India. from October 2018 to February 2021. Institutional Ethical clearance was obtained prior to the initiation of the study. Among 93 patients, 31 were chosen each for IVR PRN Monthly (Group A), (Group B) and T&E protocol (Group C) over a period of nine months. CMT and BCVA were measured at baseline and followed-up monthly for 12 months after last injection using Spectral Domain Optical Coherence Tomography (SD-OCT), while Glycated Haemoglobin (HbA1c) level was maintained below 7.4. Statistical analyses were performed using Statistical Package of Social Sciences (SPSS) statistics version 20 software. Chi-square test was used to find out the association between categorical variables. Pre and post comparisons were done using Wilcoxon sign rank test. A p-value less than 0.05 were considered as statistically significant. Results: There was significant decrease in CMT and betterment of BCVA in all groups at the end of treatment compared to baseline. At six months and one year of last injection there was no significant change in CMT in group A and C while group B at one year (p=0.0487) showed significant increase. There was no significant worsening of BCVA in group A and group C while group B (p=0.01) showed significant worsening at one year longterm follow-up. Conclusion: Thus, the present study concludes that, even though monthly protocol T&E protocol are equally good compared to PRN protocol on the basis of long-term beneficial effect, T&E protocol needed comparatively fewer doses of IVR compared to monthly protocol making it the choice of protocol for long-term control in NPDR with DME patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Excessive vasopermeability and angiogenesis compromise vision in diabetic macular oedema (DME) and diabetic retinopathy (DR). Vasoinhibin is a fragment of the hormone prolactin (PRL) that inhibits diabetes‐induced retinal hypervasopermeability and ischaemia‐induced retinal angiogenesis in rodents. Hyperprolactinaemia generated by the dopamine D2 receptor antagonist, levosulpiride, is associated with higher levels of vasoinhibin in the vitreous of patients with DR, implying a beneficial outcome due to vasoinhibin‐mediated inhibition of retinal vascular alterations. Here, we tested whether hyperprolactinaemia induced by racemic sulpiride increases intraocular vasoinhibin levels and inhibits retinal hypervasopermeability in diabetic rats. Diabetes was generated with streptozotocin and, 4 weeks later, rats were treated for 2 weeks with sulpiride or osmotic minipumps delivering PRL. ELISA, Western blot, and Evans blue assay were used to evaluate serum PRL, retinal vasoinhibin, and retinal vasopermeability, respectively. Hyperprolactinaemia in response to sulpiride or exogenous PRL was associated with increased levels of vasoinhibin in the retina and reduced retinal hypervasopermeability. Furthermore, sulpiride decreased retinal haemorrhages in response to the intravitreal administration of vascular endothelial growth factor (VEGF). Neither sulpiride nor exogenous PRL modified blood glucose levels or bodyweight. We conclude that sulpiride‐induced hyperprolactinaemia inhibits the diabetes‐ and VEGF‐mediated increase in retinal vasopermeability by promoting the intraocular conversion of endogenous PRL to vasoinhibin. These findings support the therapeutic potential of sulpiride and its levorotatory enantiomer, levosulpiride, against DME and DR. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a microangiopathy resulting from the chronic effects of diabetes mellitus. Healthcare professionals often work in isolation to deliver highly specialised care efficiently and effectively for people living with diabetes. It is not uncommon for people with diabetes to be making frequent visits to community and hospital clinics to see a variety of specialists and healthcare professionals, with seemingly little opportunity for coordination of this complex health management programme between the wider team. In a field that is so diverse and rapidly changing, healthcare professionals of all specialties need to be aware of developments across all aspects of diabetes management. In this article, we discuss the epidemiology and natural history of diabetic retinopathy and describe an approach to its assessment and diagnosis. We provide an overview of the principles of diabetic retinopathy management and outline possible future treatments for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare anatomical and functional outcomes between patients with non‐proliferative diabetic retinopathy (NPDR) with diabetic macular oedema (DME) who adhered to intravitreal aflibercept therapy and patients lost to follow‐up (LTFU). Methods: We enrolled 200 patients and recorded the interval between each procedure and the subsequent follow‐up visit. Moreover, visual acuity (VA) and anatomical outcomes were measured at each follow‐up examination. Results: Among the patients, 103 (51%) patients adhered to intravitreal aflibercept therapy and follow‐up examination while 97 (49%) patients were LTFU. Forty‐six (47%) patients LTFU who returned for further treatment showed a significant decrease in VA from 0.51 (±0.46) to 0.89 (±0.38) logarithm of the minimum angle of resolution (logMAR) after 48 months (p = 0.004). Compared with the adherent group, the return group showed a worse VA at 48 months (p = 0.036). Further, 1 (1%) patient in the adherent group and 8 (17%) patients in the return group developed a proliferative DR. Patients who were LTFU had a 13.0 times greater chance to develop a proliferative DR (p = 0.022). Conclusions: Patients who did not adhere to intravitreal aflibercept therapy for DME showed significantly worse visual outcomes compared to patients with good therapy adherence. Moreover, patients with LTFU had a 13 times higher risk of developing a proliferative DR. Considering the potential disease progress, better strategies should be applied to optimize the functional outcome of patients at risk of reduced adherence. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the most common microvascular complication in diabetes and may cause severe visual impairment. Until late stages of DR, treatment options are limited. The aim of the present review was to investigate whether changes of DR might be influenced by topical treatment with eye drops. This systematic review included both randomized and non‐randomized human clinical studies on the subject. A systematic search of PubMed Medline, Embase and Scopus databases yielded 710 studies. No inclusion criteria regarding classification of DR were defined. Reference lists as well as first authors were screened for the inclusion of additional studies. Potential bias of the randomized studies was assessed using the Cochrane Risk of Bias tool. Nineteen studies suitable for inclusion were identified. Seven studies were randomized trials. These examined 11 different pharmacological groups of drugs in DR. A favourable effect of corticosteroid eye drops in diabetic macular oedema (DMO) was reported in four studies, and another study reported a positive trend. Eye drops with non‐steroidal anti‐inflammatory drugs were also reported to have a favourable effect in DMO, but not in non‐center involving DMO. Application of neuroprotective agents was found effective in patients with pre‐existing neurodegeneration in three studies. The remaining studies of DMO and DR were heterogeneous in both designs and results. Studies on treatment of DR with topical eye drops vary with regards to patient population, interventional drugs, study design, and outcome measures. Treatment of DR with eye drops was found effective in the aforementioned cases, but there is still a need for further investigations of long‐term, randomized controlled trials in any of the reported pharmacological group. [ABSTRACT FROM AUTHOR]

Diabetic macular oedema (DME) is considered a chronic inflammatory disease associated with aberrations in many intraocular cytokines. Studies assessing the role of these cytokines as biomarkers in the diagnosis and management of DME have demonstrated inconsistent findings. We quantitatively summarized data related to 116 candidate aqueous and vitreous inflammatory cytokines as biomarkers in DME. A systematic search without year limitation was performed up to 19 October 2020. Studies were included if they provided data on aqueous or vitreous cytokine concentrations in patients with DME. Effect sizes were generated as standardized mean differences (SMDs) of cytokine concentrations between patients with DME and controls. Data were extracted from 128 studies that included 4163 study eyes with DME and 1281 control eyes. Concentrations (standard mean difference, 95% confidence interval and p‐value) of aqueous IL‐6 (1.28, 0.57–2.00, p = 0.004), IL‐8 (1.06, 0.74–1.39, p < 0.00001), MCP‐1 (1.36, 0.57–2.16, p = 0.0008) and VEGF (1.31, 1.01–1.62, p < 0.00001) and vitreous VEGF (2.27, 1.55–2.99, p < 0.00001) were significantly higher in patients with DME (n = 4163) compared to healthy controls (n = 1281). No differences, failed sensitivity analyses or insufficient data were found between patients with DME and healthy controls for the concentrations of the remaining cytokines. This analysis implicates multiple cytokine biomarker candidates other than VEGF in DME and clarifies previously reported inconsistent associations. As the therapeutic options for DME expand to include multiple agents with multiple targets, it will be critical to manage the treatment burden with tailored therapy that optimizes outcomes and minimizes treatment burden. Intraocular cytokines have the promise of providing a robust individualized assessment of disease status and response to therapy. We have identified key candidate cytokines that may serve as biomarkers in individualized treatment algorithms. [ABSTRACT FROM AUTHOR]

Using topical application to deliver therapeutic concentrations of drugs to the posterior segment of the eye remains very challenging. As a result, posterior segment diseases are usually treated by intravitreal injection or implant. While topical treatments are commonly used for anterior segment conditions, they sometimes require frequent applications. Eye drop formulations based on γ‐cyclodextrin (γCD)‐based nanoparticle aggregates were developed, which in animal models and clinical studies deliver therapeutic concentrations of drugs (dorzolamide and dexamethasone) to both anterior and posterior segments of the eye. An early study in humans showed dorzolamide/γCD eye drops could achieve comparable intraocular pressure decreases to commercial dorzolamide eye drops, but with less frequent application. Pilot studies with dexamethasone/γCD eye drops suggested that they could be effective in a range of conditions, including diabetic macular oedema, cystoid macular oedema and vitritis secondary to uveitis, postcataract surgery inflammation and postoperative treatment in trabeculectomy. Phase II studies with similar dexamethasone/γCD nanoparticle eye drops in diabetic macular oedema and postcataract surgery inflammation have recently been completed. This technology has the potential to be used with other classes of drug molecules and to replace or complement invasive treatments, providing safer, non‐invasive therapies, particularly for posterior segment conditions, that can be self‐administered as eye drops by patients. [ABSTRACT FROM AUTHOR]

Purpose: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis. Methods: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS). Results: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was − 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080). Conclusion: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement. [ABSTRACT FROM AUTHOR]

Clinical relevance: Optical coherence tomography biomarkers are dynamic and possibly change over time. The dynamic biomarkers may better predict improvement of final vision than those at baseline for diabetic macular oedema after treatment. Background: To investigate predictors for ellipsoid zone (EZ) dynamics and the association with visual acuity after treatment for diabetic macular oedema Methods: A total of 135 eyes from 135 patients with anti-vascular endothelial growth factor treatment for diabetic macular oedema were retrospectively enrolled in this study. EZ status was evaluated by optical coherence tomography at baseline, 1, 3, 6, and 12 months post-operatively. Macular perfusion status was analysed by fluorescein angiography. Duration of EZ disruption was quantified by giving scores from 0 to 5 based on the sum of visits with evidence of EZ disruption. Linear regression models were used to predict factors for scores of EZ disruption. Binary logistic regression was used to predict various EZ biomarkers for final visual acuity improvement. Results: Thirty of 87 eyes (34.4%) with intact EZ at baseline developed subsequent EZ disruption. For those with EZ disruption at baseline, 17 of 48 (35.4%) patients had restoration of disrupted EZ over time. Non-perfused macula was associated with both earlier development of EZ disruption and poor restoration (p < 0.001 and p = 0.011, respectively). Non-perfused macula, absence of epiretinal membrane, and EZ disruption at baseline predicted higher EZ scores (p < 0.001, p = 0.022 and p < 0.001, respectively). Higher EZ scores (p = 0.016), but not baseline EZ disruption (p = 0.56), were less likely to have improvement of final vision 5 letters or more. Conclusion: Macular perfusion status played an independent role in EZ dynamics. Duration of EZ disruption could be more predictive than baseline status for improvement of vision over 12 months. [ABSTRACT FROM AUTHOR]

Purpose: Diabetic macular oedema (DMO), a complication of diabetes, causes vision loss and blindness. Corticosteroids are usually used as a second‐line treatment. The aim of this study was to analyse the cost‐effectiveness of dexamethasone implants compared to cheaper and more frequently applied triamcinolone injections. Methods: Markov‐modelling, which incorporated both eyes, was used for economic evaluation. The model consisted of five health states based on visual acuity, illustrating the progression of DMO. A cycle length of five months was chosen for dexamethasone and four months for triamcinolone. Time horizons of two and five years were applied. Transition probabilities and health state utilities were sourced from previous studies. The perspective used in this analysis was the hospital perspective. The health care costs were acquired from Kuopio University Hospital in Finland. Results: In this cost‐effectiveness analysis, the incremental cost‐effectiveness ratio ICER with 3% discount rate was €56 591/QALY for a two‐year follow‐up and −€1 110 942/QALY for a five‐year follow‐up. In order to consider dexamethasone as cost‐effective over a 2‐year time horizon, the WTP needs to be around €55 000/QALY. Over the five‐year follow‐up, triamcinolone is clearly a dominant treatment. Sensitivity analyses support the cost‐effectiveness of dexamethasone over a 2‐year time horizon. Conclusions: Since the sensitivity analyses support the results, dexamethasone would be a cost‐effective treatment during the first two years with WTP threshold around €55 000/QALY, and triamcinolone would be a convenient treatment after that. This recommendation is in line with the guidelines of EURETINA. [ABSTRACT FROM AUTHOR]

Aims: To investigate the risk of diabetic macular oedema (DMO) associated with the use of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM). Materials and Methods: We conducted a retrospective cohort study by analysing a large multi‐institutional electronic medical records database in Taiwan. We included adult patients with T2DM without DMO newly receiving either SGLT2 inhibitors or glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) during the period 2016 to 2018. We used propensity scores with inverse probability of treatment weighting to generate comparable groups. The study outcome was incident DMO, determined by clinical diagnosis during outpatient visits or admissions. We followed patients from the index date to either DMO occurrence, last clinical visit, patient death, or December 31, 2020. We performed Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of DMO. Results: We included 9986 new users of SGLT2 inhibitors (mean [SD] age 59.6 (12.1) years, median [interquartile range {IQR}] glycated haemoglobin [HbA1c] 70 (61‐81)mmol/mol, estimated glomerular filtration rate [eGFR] 89.1 [71.4‐108.7] mL/min/1.73 m2 and urine albumin‐creatinine ratio [UACR] 26.1 [9.7‐117.6] mg/g) and 1067 new users of GLP‐1RAs (mean [SD] age 58.4 (41.5) years, median [IQR] HbA1c 73 [64‐84] mmol/mol, eGFR 91.6 [68.6‐114.0] mL/min/1.73 m2 and UACR 37.6 [11.1‐153.2] mg/g) with similar baseline characteristics. Lower DMO risks were observed among patients newly receiving SGLT2 inhibitors (7.9/1000 person‐years), compared to those receiving GLP‐1RAs (10.7/1000 person‐years) with an HR of 0.75 (95% CI 0.64‐0.88). Conclusions: Our findings suggest use of SGLT2 inhibitors was associated with lower risk of DMO in T2DM patients in clinical practice, compared to use of GLP‐1RAs. Future studies are necessary to confirm this observation. [ABSTRACT FROM AUTHOR]

Background: To evaluate the changes in the mean macular intercapillary area (ICA) from sequential enface optical coherence tomography angiography (OCTA) images following intravitreal anti‐vascular endothelial growth factor (VEGF) therapy in initially treatment‐naïve eyes with diabetic macular oedema (DME). Methods: In this multicentre retrospective study, 6 × 6 and 3 × 3 mm customised, total retinal projection enface OCTA images were collected and processed for quantitative assessment of ICA by a customised MATLAB software. Measurements were done in concentric regions centred on the fovea—with the exclusion of foveal avascular zone (FAZ)—in 0.5 mm diameter increments as well as within the intervening rings. Results: In this study, 6 × 6 mm OCTA images from 46 eyes of 29 patients, and 3 × 3 mm OCTA images from 23 eyes of 15 patients were included. There was no significant change in mean ICA after treatment in either scan size or in any measurement regions (all p > 0.05). Multivariate analysis revealed that baseline BCVA was significantly correlated with the visual outcome (p = 0.039). Additionally, after correction for age, baseline central retinal thickness (CRT), baseline BCVA, and retinopathy severity, mean ICA in the 1.5 mm circle was found to be a significant predictor of post treatment CRT, (p = 0.006). Conclusions: Absence of significant change in mean ICA after a minimum of three intravitreal anti‐VEGF injections, may indicate that, in the short term, anti‐VEGF injections neither impair nor improve macular perfusion in DME. Baseline BCVA was found to be a robust predictor of functional outcome, while inner mean ICA was a significant predictor for macular thickness outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To examine whether real‐world clinical patients with macular oedema (MO) receiving intravitreal antivascular endothelial growth factor (VEGF) therapy have a higher mortality compared with a matched reference population. Methods: A population‐based, retrospective cohort study of 26 386 patients from Finland, from January 1, 2001, to December 31, 2017. Index patients were identified through the Caring Epidemiology Project database, receiving at least one intravitreal anti‐VEGF injection for wet age‐related macular degeneration (AMD, n = 2243, 48.61%), diabetic MO (n = 744, 16.12%), MO due to retinal vascular occlusion (n = 589, 12.77%), or other MO (n = 1038, 22.5%). For each individual treated with intravitreal injection (n = 4614), five age‐ , sex‐ , calendar year‐ and hospital district‐ matched control individuals (n = 21 772) were chosen. Baseline data of chronic conditions were available. All‐cause and cause‐specific mortality was analysed using Cox´s proportional hazards model. Results: In general, the anti‐VEGF treated patients had a higher prevalence of systemic conditions, including diabetes (60.1% vs. 46.8%, p < 0.001), chronic hypertension (38.4% vs. 34.6%, p < 0.001), in hospital‐treated ischaemic heart disease (23.1% vs. 21.5%, p = 0.014), and glaucoma (11.1% vs. 6.3%, p < 0.001) than controls. There was no difference in all‐cause mortality between the anti‐VEGF treated patients and matched controls (p = 0.62). In unadjusted Kaplan–Meier analysis of wet AMD subgroup, all‐cause mortality was lower in anti‐VEGF treated patients than matched controls (p = 0.015), but adjusted Cox´s proportional hazards model showed no difference in the risk of all‐cause mortality (HR 0.85, 95% CI 0.66–1.09). Conclusions: Intravitreal anti‐VEGF therapy was not associated with an increase in the risk of mortality in patients with MO compared with age‐ and sex‐matched controls. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relationship between microaneurysm (MA) density and residual oedema after intravitreal injection of an anti‐vascular endothelial growth factor agent for the treatment of diabetic macular oedema (DMO). Methods: Patients with DMO were divided into those with residual oedema (RO) and those with no residual oedema (NRO) by the presence and absence of oedema at 1 month after intravitreal injection of either aflibercept or ranibizumab. We then compared MA density, best corrected visual acuity (BCVA), central retinal thickness (CRT) and size of the severely thickened area, as indicated by a white area (WA) on optical coherence tomography. Results: We examined 48 eyes in the RO group and 25 eyes in the NRO group (n = 73). In both groups, the CRT and WA size significantly decreased and BCVA improved at 1 month and thereafter. CRT was significantly higher and BCVA was poor in the RO group at 1 and 3 months, while WA size was larger at 1, 3 and 6 months compared with the NRO group (p < 0.05). The number of injections in the RO group (3.62 ± 1.75) was larger than the NRO group (1.89 ± 0.97; p < 0.0001). At 1 and 6 months, the MA density in the area with persistent oedema was significantly higher than in the area with improved oedema (1 month: p = 0.0001, 6 months: p = 0.029). Conclusion: High MA density and extensive swelling may be characteristic of RO following treatment for DMO with intravitreal injection of either aflibercept or ranibizumab. [ABSTRACT FROM AUTHOR]

Despite the growing importance of real‐world evidence (RWE) for guiding clinical decisions in retinal disease, there is currently no widely used guidance available for assessing the quality and relevance of RWE studies in ophthalmology. This paper summarizes the development of a user‐friendly tool that facilitates assessment of the quality of available RWE for neovascular age‐related macular degeneration (nAMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). A literature search was conducted to identify tools developed to assess the quality of RWE, in order to identify the most appropriate framework on which to base this tool. The Good Research for Comparative Effectiveness (GRACE) guidelines was chosen for this purpose as it is designed to assess the quality of observational studies and has been extensively validated, including demonstration of strong sensitivity and specificity. The GRACE guidelines were adapted to develop a straightforward tabular tool that allows simple assessment and comparison of the quality of published evidence in retinal disease for researchers and physicians alike, and includes guidance on treatment details, outcome measures, study population, and controlling for bias. The newly developed tool provides a simple method to support assessment of the strength of evidence and certainty of conclusions drawn from RWE in retinal disease, to ensure clinical decision‐making is influenced by the highest quality evidence. [ABSTRACT FROM AUTHOR]