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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]

Paris Tranos,1 Stavrenia Koukoula,1 Penelope Burle de Politis,1 Marianna Tranou,1 Olympia Giamouridou,1 Panagiotis Stavrakas,2 Georgios D Panos3– 5 1Vitreoretinal Department, Ophthalmica Eye Institute, Thessaloniki, Greece; 2Department of Ophthalmology, School of Medicine, University of Patras, Patras, Greece; 3Division of Ophthalmology and Visual Sciences, School of Medicine, University of Nottingham, Nottingham, UK; 4Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 5First Department of Ophthalmology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.comPurpose: To evaluate the efficacy of the dexamethasone implant on the electrophysiological profile of Diabetic Macular Oedema (DMO) patients over six months.Methods: In this prospective, single-center study 30 eyes of 22 patients were examined using comprehensive baseline assessments including best-corrected visual acuity (BCVA), central retinal thickness (CRT), contrast sensitivity (CS) and multifocal electroretinogram (mfERG), before and after 0.7mg dexamethasone implant injection, with follow-ups at months 1, 2, 4, and 6. The study employed mixed models to analyse within-subject and between-subject correlations, considering the complexities of multiple measurements per subject.Results: At baseline, BCVA was 0.66 ± 0.104 logMAR, improving to 0.568 ± 0.104 logMAR by month 6 (P > 0.05). CRT significantly reduced from 521 ± 28.7 μm to 336 ± 28.7 μm (P < 0.05). CS slightly increased from 26.8 ± 1.23 letters to 28.5 ± 1.05 letters (P > 0.05). P wave amplitude saw a notable rise from 33.4 ± 5.66 μV to 47.9 ± 5.43 μV (P < 0.05). P wave implicit time changed minimally from 47.4 ± 0.503 seconds to 48.0 ± 0.503 seconds (P > 0.05). No severe adverse events were recorded.Conclusion: These results underscore the 0.7mg dexamethasone implant’s potential in improving certain electrophysiological markers in DMO, while also highlighting the need for further investigation into its comprehensive impact on retinal function.Keywords: dexamethasone implant, electroretinogram, diabetic macular oedema, visual function, macular thickness, visual acuity, contrast sensitivity

Abstract 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. Graphical Abstract

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]

Abstract 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.

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: Accurate and objective diagnosis of centre-involving diabetic macular oedema (ci-DMO) requires the use of optical coherence tomography (OCT). There is limited data on the availability and rate of utilisation of OCT for the management of DMO in sub-Saharan Africa (SSA). Aim: To assess the availability and rate of utilisation of OCT for the management of DMO in SSA. Setting: Retina-practising ophthalmologists in 18 countries across SSA. Methods: In this cross-sectional survey, a structured questionnaire was distributed among ophthalmologists treating patients with retina diseases in SSA. Data were collected using Google Forms by sharing a link to the Google data sheet with participants via email. The responses were analysed, summarised and presented using proportions and frequency tables. Results: A total of 42 ophthalmologists participated in this study. The proportion of diabetic retinopathy patients with DMO seen on a monthly basis was ≤ 20% among 24 (57.1%) participants and ≥ 40% among 14.3% participants. Thirty-eight (90.5%) participants had access to an OCT facility in their area of practice and 85.7% of them had Spectra Domain OCT. Twenty-five (64%) participants performed 1 to 50 OCT scans monthly and 34% performed 50 OCT scans monthly. Important factors influencing OCT use in DMO patients were: the availability of OCT in the facility, patients’ insurance coverage and the severity of DMO. Conclusion: Optical coherence tomography is readily available although there is wide variability in its use in SSA. Contribution: This survey uncovers the need for standardising practice patterns and usage of OCT in the treatment of DMO in SSA.

Abstract 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.

Georgios D Panos,1,2 Arun Lakshmanan,1 Panagiotis Dadoukis,3 Matteo Ripa,4 Lorenzo Motta,4 Winfried M Amoaku1,2 1Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals, Nottingham, UK; 2Division of Ophthalmology and Visual Sciences, Faculty of Medicine & Health Sciences, School of Medicine, University of Nottingham, Nottingham, UK; 3Eye Treatment Centre, Whipps Cross University Hospital, Barts Health NHS Trust, London, UK; 4Department of Ophthalmology, William Harvey Hospital, East Kent Hospitals University NHS Foundation Trust, Kent, UKCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.com Lorenzo Motta, Department of Ophthalmology, William Harvey Hospital, Kennington Road, Willesborough, Ashford, Kent, TN24 0LZ, UK, Tel +44 1233 633331, Email lorenzo.motta@nhs.netAbstract: Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab’s application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases.Keywords: degenerative macular disorders, faricimab, anti-VEGF, efficacy, safety, intravitreal treatment, age-related macular degeneration, diabetic macular oedema, retinal vein occlusion, diabetic retinopathy

Abstract 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.

Introduction: A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice. Methods: An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible. Results: Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55–125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4–4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92–1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations. Conclusion: Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the short-term effect of intravitreal bevacizumab (avastin) injection on visual outcomes of patients with diabetic macular oedema. Methods: A retrospective cross-sectional study was conducted to evaluate 39 eyes of thirty-nine patients (mean age ± SD: 61.4 ± 15.0 years) that received intravitreal bevacizumab injection (1.25 mg in 0.05 ml) as treatment for diabetic macular oedema between January 2014 and July 2019 in Ghana. Data on visual acuity and central macular thickness before treatment and 6 weeks post-treatment were collected and analysed using paired t-test. Ordinary least squares linear regression analysis was also conducted to determine the relationship between improvement in visual acuity and central macular thickness after treatment and other predictor variables. Results: The mean ± SD visual acuity (LogMAR-equivalent of Snellen) of patients with diabetic macular oedema significantly improved from 0.84 ± 0.58 LogMAR before treatment to 0.69 ± 0.58 LogMAR at 6 weeks post-treatment (mean difference: 0.15 ± 0.32 LogMAR; 95% CI: 0.04 to 0.25; p = 0.01). Mean macular thickness ± SD on the other hand, reduced significantly (p < 0.001) from 316.54 ± 75.35 μm before treatment to 275.54 ± 57.43 μm after treatment. While age and worse pre-treatment visual acuity predicted improvement in visual acuity after treatment, a higher central macular thickness before treatment predicted an improvement in central macular thickness after intravitreal bevacizumab injection. Conclusion: Treatment with intravitreal bevacizumab injection produces short-term improvement in vision and reduction in central macular thickness in African patients with diabetic macular oedema. [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]

Abstract 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

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

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]

Yusuf Mushtaq,1,&ast; Maryam M Mushtaq,2,&ast; Zisis Gatzioufas,3 Matteo Ripa,4 Lorenzo Motta,5 Georgios D Panos1 1Department of Ophthalmology, Queen’s Medical Centre, Nottingham University Hospitals NHS Trust & School of Medicine, University of Nottingham, Nottingham, UK; 2Department of Acute Medicine, Luton and Dunstable University Hospitals NHS Trust, Luton, UK; 3Department of Ophthalmology, Basel University Hospital & University of Basel School of Medicine, Basel, Switzerland; 4Ophthalmology Unit, “Fondazione Policlinico Universitario A. Gemelli IRCCS”, Rome, Italy; 5Department of Ophthalmology, William Harvey Hospital, East Kent Hospitals University NHS Foundation Trust, Kent, UK&ast;These authors contributed equally to this workCorrespondence: Georgios D Panos, Department of Ophthalmology, Queen’s Medical Centre, Derby Road, Lenton, Nottingham, NG7 2UH, UK, Tel +44 115 924 9924, Email gdpanos@gmail.com Lorenzo Motta, Department of Ophthalmology, William Harvey Hospital, Kennington Road, Willesborough, Ashford, Kent, TN24 0LZ, UK, Tel +44 1233 633331, Email lorenzo.motta@nhs.netAbstract: Fluocinolone acetonide (FAc) intravitreal implant (Iluvien®) is a corticosteroid implant indicated for the treatment of diabetic macular oedema (DMO) in patients who have previously received conventional treatment without good response, non–infectious posterior uveitis, and as an off-label treatment of the macular oedema secondary to retinal vein occlusion. FAc is a non-biodegradable 0.19 mg intravitreal implant which is designed to release FAc over 3 years at a rate of approximately 0.2 mcg per day. The aim of this review is to describe the special pharmacological properties of Iluvien and display the outcomes of the most important clinical trials and real-world studies regarding its efficacy and safety for the management of the above retinal disorders.Keywords: Iluvien, steroid implant, diabetic macular oedema, intravitreal implant, posterior uveitis, retinal vein occlusion

Abstract 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.

Introduction/Objective. Diabetic macular oedema is the accumulation of fluid in the macular tissue leading to its thickening. The aim of the study was to evaluate the efficacy of concentrated triamcinolone acetonide 10 mg / 0.1 ml injection into the suprachoroidal space in patients with diabetic macular oedema and decreased visual acuity. Methods. In 12 eyes with diabetic macular oedema, without any prior treatment, using a small-diameter 26G needle, an injection of 10 mg / 0.1 ml triamcinolone acetonide was applied into the suprachoroidal space in the superotemporal quadrant of the eye 4 mm from the limbus. Prior to the injection, as well as one, three, six, nine, and 12 months after the injection, visual acuity and intraocular pressure were measured, and central subfield thickness was recorded using optical coherence tomography. Results. After one, three, six, and nine post-injection months there was a statistically significant reduction in central subfield thickness (315.92 μm, 257.66 μm, 281.08 μm and 295.51 μm, respectively) compared to the baseline of 447.67 μm. At the end of the 12th month an increase in central subfield thickness was observed again (392.16 μm). Visual acuity improved significantly from the baseline (0.32) during the first three months (0.61) and remained stable until the end of the nineth month (0.51), but at the end of 12 months it decreased again (0.39). No significant intraocular pressure elevation and cataract development were observed in either eye during the entire follow-up period. Conclusion. A single dose of 10 mg / 0.1 ml triamcinolone acetonide injected in suprachoroidal space can significantly stabilize diabetic macular oedema and maintain satisfactory visual acuity for up to nine months.

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]

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.

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]

Abstract Background Our aim was to examine the long term anatomical and functional outcomes in patients with refractory diabetic macular oedema (DMO) undergoing treatment switch from ranibizumab to aflibercept. Methods Retrospective review of patients with DMO undergoing treatment switch from ranibizumab to aflibercept at a single centre between 2015 and 2017. Primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT). Results 57 eyes from 44 patients were included. Following switch to aflibercept, median (IQR) BCVA improved to 73 (64–77) letters at 3 months (p = 0.0006), to 73 (61–78) letters at 6 months (p = 0.0042), to 73 (65–77) at 9 months (p = 0.0006), and to 73 (63–75) letters at 18 months (p = 0.0444). At 36 months following switch, 12 eyes had gained > 10 letters, 5 eyes had gained 5–9 letters, 25 remained stable (± 5 letters), 7 eyes lost 5–9 letters and 8 eyes lost > 10 letters. A significant reduction in CMT at all trimesters following treatment switch was found except at month 24. Conclusions We provide real world data suggesting a sustained anatomical and functional benefit of switching from ranibizumab to aflibercept in the treatment of refractory DMO.

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:  Diabetic macular oedema (DME) is a major cause of vision impairment in individuals with diabetes mellitus, characterised by fluid accumulation in the macula due to increased vascular permeability. The growing prevalence of diabetes worldwide has led to an increasing burden of DME on healthcare systems. While current treatment options such as anti-vascular endothelial growth factor (anti-VEGF) injections, corticosteroids, and laser therapy exist, the variability in patient responses highlights the need for reliable prognostic tools. Imaging biomarkers, particularly those identified using optical coherence tomography (OCT) and fluorescein angiography (FA), play a critical role in diagnosing and managing DME. This study evaluates the prognostic significance of these biomarkers in predicting disease progression and treatment outcomes. Materials and methods:  This prospective observational study was conducted at Gandhi Medical College and Hamidia Hospital, Bhopal, Madhya Pradesh, from August 2022 to June 2024. A total of 123 patients with Type II diabetes mellitus diagnosed with DME were included through consecutive sampling. Comprehensive assessments, including visual acuity, slit-lamp examination, fundus evaluation, FA, and OCT, were performed. Key imaging biomarkers, such as central subfield thickness (CST), disorganisation of retinal inner layers (DRIL), intraretinal cysts, hyperreflective foci, and vitreomacular interface (VMI) abnormalities, were evaluated. Correlations between biomarkers, best-corrected visual acuity (BCVA), metabolic markers (HbA1c, serum cholesterol), and disease severity were analysed using statistical tools, including the chi-square test and Pearson's correlation. Results:  The most common biomarkers observed were DRIL with external limiting membrane (ELM) disruption (38, 31%), intraretinal cysts with ELM disruption (36, 29.3%), and hyperreflective foci (28, 22.8%). VMI abnormalities were noted in 14 (11.4%) cases, while subretinal fluid with serous retinal detachment was present in seven patients (5.7%). Significant negative correlations were found between BCVA (LogMAR) and biomarkers, with intraretinal cysts (-0.526, p=0.003) and VMI abnormalities (-0.492, P=0.002) having the strongest associations. Higher glycosylated haemoglobin (HbA1c) levels were significantly associated with intraretinal cysts (P=0.014) and VMI abnormalities (P=0.042), while higher cholesterol levels correlated with hyperreflective foci (P=0.011) and subretinal fluid (P=0.014). Patients with proliferative diabetic retinopathy (PDR) exhibited worse visual outcomes and greater CST compared to those with non-proliferative diabetic retinopathy (NPDR). Conclusion:  Imaging biomarkers, particularly DRIL, intraretinal cysts, and VMI abnormalities, significantly correlate with visual acuity and metabolic control in DME patients. These findings underscore the importance of OCT in the prognostic assessment of DME and highlight the need for personalised treatment approaches based on biomarker profiles. Future studies should focus on long-term follow-up and explore the potential for integrating these biomarkers into clinical decision-making to improve patient outcomes., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Committee (IEC), Gandhi Medical College and Hamidia Hospital, Bhopal, Madhya Pradesh issued approval 32243/MC/IEC/2022. The study received ethical approval from both the Institutional Review Board (IRB) and the Institutional Ethics Committee (IEC) of Gandhi Medical College and Hamidia Hospital, Bhopal, Madhya Pradesh, with reference number 32243/MC/IEC/2022 dated 13 August 2022 . Informed written consent was obtained from all participants before they were included in the study. Strict measures were implemented to ensure the privacy and confidentiality of all participants throughout the research. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shrivastava et al.)

Background: The National Institute for Health and Care Excellence recommends macular laser to treat diabetic macular oedema with a central retinal subfield thickness of 24 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent > 20/320) in one/both eyes. Interventions: Participants were randomised 1 : 1 to receive 577 nm subthreshold micropulse laser or standard threshold macular laser (e.g. argon laser, frequency-doubled neodymium-doped yttrium aluminium garnet 532 nm laser); laser treatments could be repeated as needed. Rescue therapy with intravitreal anti-vascular endothelial growth factor therapies or steroids was allowed if a loss of ≥ 10 Early Treatment Diabetic Retinopathy Study letters between visits occurred and/or central retinal subfield thickness increased to > 400 µm. Main outcome measures: The primary outcome was the mean change in best-corrected visual acuity in the study eye at 24 months (non-inferiority margin 5 Early Treatment Diabetic Retinopathy Study letters). Secondary outcomes included the mean change from baseline to 24 months in the following: binocular best-corrected visual acuity; central retinal subfield thickness; the mean deviation of the Humphrey 10–2 visual field in the study eye; the percentage of people meeting driving standards; and the EuroQol-5 Dimensions, five-level version, National Eye Institute Visual Function Questionnaire – 25 and Vision and Quality of Life Index scores. Other secondary outcomes were the cost per quality-adjusted life-years gained, adverse effects, number of laser treatments and additional rescue treatments. Results: The DIAMONDS trial recruited fully (n = 266); 87% of participants in the subthreshold micropulse laser group and 86% of participants in the standard threshold macular laser group had primary outcome data. Groups were balanced regarding baseline characteristics. Mean best-corrected visual acuity change in the study eye from baseline to month 24 was –2.43 letters (standard deviation 8.20 letters) in the subthreshold micropulse laser group and –0.45 letters (standard deviation 6.72 letters) in the standard threshold macular laser group. Subthreshold micropulse laser was deemed to be not only non-inferior but also equivalent to standard threshold macular laser as the 95% confidence interval (–3.9 to –0.04 letters) lay wholly within both the upper and lower margins of the permitted maximum difference (5 Early Treatment Diabetic Retinopathy Study letters). There was no statistically significant difference between groups in any of the secondary outcomes investigated with the exception of the number of laser treatments performed, which was slightly higher in the subthreshold micropulse laser group (mean difference 0.48, 95% confidence interval 0.18 to 0.79; p = 0.002). Base-case analysis indicated no significant difference in the cost per quality-adjusted life-years between groups. Future work: A trial in people with ≥ 400 µm diabetic macular oedema comparing anti-vascular endothelial growth factor therapy alone with anti-vascular endothelial growth factor therapy and macular laser applied at the time when central retinal subfield thickness has decreased to

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]