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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

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]

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]

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.

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

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.

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.

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]

Diabetic retinopathy is a frequent complication in diabetes and a leading cause of visual impairment. Regular eye screening is imperative to detect sight-threatening stages of diabetic retinopathy such as proliferative diabetic retinopathy and diabetic macular oedema in order to treat these before irreversible visual loss occurs. Screening is cost-effective and has been implemented in various countries in Europe and elsewhere. Along with optimised diabetes care, this has substantially reduced the risk of visual loss. Nevertheless, the growing number of patients with diabetes poses an increasing burden on healthcare systems and automated solutions are needed to alleviate the task of screening and improve diagnostic accuracy. Deep learning by convolutional neural networks is an optimised branch of artificial intelligence that is particularly well suited to automated image analysis. Pivotal studies have demonstrated high sensitivity and specificity for classifying advanced stages of diabetic retinopathy and identifying diabetic macular oedema in optical coherence tomography scans. Based on this, different algorithms have obtained regulatory approval for clinical use and have recently been implemented to some extent in a few countries. Handheld mobile devices are another promising option for self-monitoring, but so far they have not demonstrated comparable image quality to that of fundus photography using non-portable retinal cameras, which is the gold standard for diabetic retinopathy screening. Such technology has the potential to be integrated in telemedicine-based screening programmes, enabling self-captured retinal images to be transferred virtually to reading centres for analysis and planning of further steps. While emerging technologies have shown a lot of promise, clinical implementation has been sparse. Legal obstacles and difficulties in software integration may partly explain this, but it may also indicate that existing algorithms may not necessarily integrate well with national screening initiatives, which often differ substantially between countries. [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]

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]

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. [ABSTRACT FROM AUTHOR]

Supriya Dabir,1 Mohan Rajan,1 Liji Parasseril,1 Vaidehi Bhatt,2 Preetam Samant,3 CAB Webers,4 TTJM Berendschot4 1Department of Retina, Rajan Eye Care Pvt Ltd, Chennai, India; 2Rajiv Gandhi Medical College, Thane, India; 3Department of Retina, PD Hinduja Hospital and Medical Research Center, Mumbai, India; 4University Eye Clinic, Maastricht, the NetherlandsCorrespondence: Supriya DabirRajan Eye Care Hospital Pvt. Ltd, No. 5, Vidyodaya East 2nd Street, T. Nagar, Chennai, Tamil Nadu 600017, IndiaTel +919900974800Email supriad@gmail.comPurpose: Diabetic macular oedema (DME) is a vision-threatening complication of diabetic retinopathy. Spectral domain optical coherence tomography angiography (OCTA) is useful for assessing DME. We performed serial OCTA measurements before and after 3 monthly intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to understand its relationship with best corrected visual acuity (BCVA), central macular thickness (CMT) and vascular indices.Methods: OCTA assessment consisting of 6 × 6 mm scans centred on fovea and en-face retinal angiograms were obtained. Scans were done at baseline and at 1 month following each of the 3 intravitreal injections of anti-VEGF (ranibizumab, Lucentis®).Results: Our prospective study included 24 eyes of 24 subjects, aged 63.0 ± 5.0 years. There was a mean gain of 0.07 LogMAR (3 letters) and reduction of CMT, vessel density (VD) and perfusion density (PD) by end of 3rd month. CMT was independently associated with improvement in BCVA. There were significant reductions in FAZ area, VD and PD over 3 months from baseline.Conclusion: At three months, intravitreal anti-VEGF therapy is associated with visual function recovery in DME, with reduction in CMT being the most reliable predictor of response. OCTA shows a reduction in VD and PD respectively suggestive of reduced macular perfusion in the short term. Simultaneous reduction in FAZ size can be due to reversal of manual displacement of the retinal capillaries resulting from resolution of intraretinal oedema.Keywords: diabetic macular oedema, superficial capillary plexus, vascular density, perfusion density, foveal avascular zone, optical coherence tomography angiography, macular ischemia

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 long-term 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.

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]

Introduction: Diabetic macular oedema (DME) is one of the major cause of decreased visual acuity in patients with diabetic retinopathy. Poor glycaemic control is associated with increased incidence of DME. Methods: A total of 112 eyes of 112 patients were studied in this cross‐sectional study and were classified into three groups based on HbA1c: group 1 included patients with good glycaemic control (HbA1c ≤7%), group 2 included patients with moderate glycaemic control (HbA1c between 7% and 9%) and group 3 included patients with poor glycaemic control (HbA1c ≥9%). Results: We included 112 eyes of 112 patients. The mean duration of diabetes mellitus (DM) was 11.37 years. In statistical analysis, CMT (mean 188.80 ± 27.64 μm) positively correlated with mean HbA1c level (7.95 ± 1.29%) (r = 0.238, p <.05). There was a significant difference in CMT values among the three groups of HbA1c (F (2,109) = 19.39, p <.001). Post hoc analysis showed statistical significance between HbA1c≤7% and HbA1c ≥9% group and HbA1c 7%–9% and ≥9% group. However, statistical significance was not found among HbA1c ≤7% group and HbA1c 7%–9% group. Multiple regression analyses showed a significant correlation between CMT and HbA1c after adjusting for age and duration of diabetes. Conclusion: Serum HbA1c level has a significant correlation with CMT in diabetic patients. [ABSTRACT FROM AUTHOR]

Samyukta Bista Karki,1 Kirsten J Coppell,2 Logan V Mitchell,2 Kelechi C Ogbuehi2 1Drishti Eye Care Center, Kathmandu 44600, Nepal; 2Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin 9054, New ZealandCorrespondence: Kelechi C OgbuehiDepartment of Medicine, Dunedin School of Medicine, University of Otago, 201 Great King Street, Dunedin 9054, New ZealandTel +64 3 474 0999 Ext 58308Email kelechi.ogbuehi@otago.ac.nzPurpose: Autonomic dysfunction may precede the microvascular changes that characterise diabetic retinopathy. The aim of this pilot study was to measure and compare pupillometry indices in type 2 diabetes (T2DM) patients – with and without diabetic retinopathy – and in healthy, age-matched controls.Methods: Two hundred and eleven participants with T2DM aged 45– 80 years were recruited from Dunedin Hospital Eye Department, Dunedin, New Zealand. They were categorised into three groups – no, mild/moderate, or severe diabetic retinopathy. Seventy age-matched, diabetes screen negative control participants were recruited from the Dunedin city community. Dynamic pupillometry was performed using an infrared pupillometer. The main outcome measures were maximum constriction velocity, average constriction velocity, absolute constriction amplitude, relative reflex amplitude, average dilation velocity and 75% re-dilation (recovery) time. Outcome measures were compared between study groups using the Kruskal–Wallis nonparametric test (with Dunn’s multiple comparison post-test).Results: Pupillary parasympathetic function differed between groups. Maximum constriction velocity (p < 0.001) and average constriction velocity (p < 0.001) were slower, and absolute constriction amplitude (p < 0.001) and relative reflex amplitude (p < 0.05) were lower in the three diabetes groups compared with controls. There were no significant differences in pupillary sympathetic function between the four groups for re-dilation time, but the diabetes groups had significantly slower average dilation velocity times.Conclusion: Pupillary light reflex is significantly impaired with diabetic retinal neuropathy, before clinically observable signs of diabetic retinopathy. Dynamic pupillometry may be a cheap, clinically relevant test, but sensitivity and specificity need to be determined before utilising as a screening tool for diabetic retinopathy.Keywords: diabetic autonomic neuropathy, diabetic retinopathy, diabetic macular oedema, pupillary reflex, parasympathetic nervous system, type 2 diabetes mellitus