Diabetic retinopathy (DR), the prevalence of which continues to rise, is one of the most common causes of vision loss worldwide. Experimental and clinical research in recent years has contributed to a better understanding of the pathogenesis of DR, which is complex and results from many interrelated processes leading to abnormal permeability and occlusion of the retinal vasculature, with ischemia and subsequent neovascularization. According to the absence or presence of neovascularization, DR is divided into two main forms: nonproliferative and proliferative DR. From nonproliferative to proliferative disease, diabetic macular edema (DME) can develop anywhere along the spectrum. As the majority of diabetics have no ophthalmologic symptoms, screening plays an important role in preventing the development of retinal disease. Specific treatment options beyond metabolic risk factor control, including intravitreal administration of anti-vascular endothelial growth factor (VEGF) agents or corticosteroids, laser photocoagulation, and vitreous surgery, are effective approaches for ocular diabetic complications.

To develop and validate an automated diabetic macular oedema (DME) classification system based on the images from different three-dimensional optical coherence tomography (3-D OCT) devices.

A multicentre, platform-based development study using retrospective and cross-sectional data. Data were subjected to a two-level grading system by trained graders and a retina specialist, and categorised into three types: no DME, non-centre-involved DME and centre-involved DME (CI-DME). The 3-D convolutional neural networks algorithm was used for DME classification system development. The deep learning (DL) performance was compared with the diabetic retinopathy experts.

Data were collected from Joint Shantou International Eye Center of Shantou University and the Chinese University of Hong Kong, Chaozhou People's Hospital and The Second Affiliated Hospital of Shantou University Medical College from January 2010 to December 2023.

7790 volumes of 7146 eyes from 4254 patients were annotated, of which 6281 images were used as the development set and 1509 images were used as the external validation set, split based on the centres.

Accuracy, F1-score, sensitivity, specificity, area under receiver operating characteristic curve (AUROC) and Cohen's kappa were calculated to evaluate the performance of the DL algorithm.

In classifying DME with non-DME, our model achieved an AUROCs of 0.990 (95% CI 0.983 to 0.996) and 0.916 (95% CI 0.902 to 0.930) for hold-out testing dataset and external validation dataset, respectively. To distinguish CI-DME from non-centre-involved-DME, our model achieved AUROCs of 0.859 (95% CI 0.812 to 0.906) and 0.881 (95% CI 0.859 to 0.902), respectively. In addition, our system showed comparable performance (Cohen's κ: 0.85 and 0.75) to the retina experts (Cohen's κ: 0.58-0.92 and 0.70-0.71).

Our DL system achieved high accuracy in multiclassification tasks on DME classification with 3-D OCT images, which can be applied to population-based DME screening.

To evaluate the visual and anatomical outcomes of switching diabetic macular oedema (DMO) patients with suboptimal response to aflibercept 2mg to faricimab over a 12-month period.

This retrospective single centre study enrolled 62 eyes from 50 patients with diabetic macular oedema (DMO) who demonstrated a sub-optimal response to aflibercept 2mg. Sub-optimal response was defined by a central subfield thickness (CST) exceeding 325µm or greater than 20% increase from the best CST despite receiving aflibercept 2mg at intervals of 8 weeks or less. Patients had received at least six 4-weekly doses of aflibercept 2mg. Faricimab was administered as four intravitreal loading injections at 4-weekly intervals, followed by a treat-and-extend approach. Outcome measures, including best-recorded visual acuity (BRVA), CST, and treatment intervals, were assessed at baseline, post-loading (6.5 ± 1.9 weeks) and at the latest clinic review (57.1 ± 19.7 weeks). Statistical analysis included paired t-tests (normal distribution) and Wilcoxon signed-rank tests (non-normal distribution), with p < 0.05 considered statistically significant.

Mean age was 63.9 (±11.4) years, 56% participants were male. At baseline, the mean BRVA was 67.6 (±11.8) letters, and CST measured 406.4 (±105.9) µm. The initial mean treatment interval was 6.5 (±1.8) weeks. BRVA increased to 70.4 (±12.7) letters (p=0.008), while CST reduced to 372.8 (±132.0) µm (p=0.002). The mean injection interval extended to 7.4 (±2.6) weeks (p=0.03). At the latest follow-up BRVA was maintained at 68.7 (±14.6) letters (p=0.572), and CST reduced further to 343.1 (±117.5) µm (p=0.020). At the final follow-up 53.2% were on ≥8-weekly intervals. The mean injection interval increased to 9.2 (±3.2) weeks (p < 0.001), and a mean of 7.92 (±2.53) faricimab injections was administered.

DMO patients with sub-optimal response to aflibercept 2mg experienced improved anatomical outcomes and extended treatment intervals while maintaining vision on faricimab, with no new safety concerns.

Diabetic macular oedema [DMO] is a prevalent and sight-threatening condition among diabetic patients, which can cause irreversible blindness. Since angiogenesis and inflammation are two key elements in the etiopathogenesis of DMO, intravitreal injections of vascular endothelial growth factor inhibitors [anti-VEGF] and sustained released intravitreal corticosteroid implants are currently considered as treatments of choice. The introduction, 10 years ago, of the 0.19 mg fluocinolone acetonide [FAc] implant for treating eyes with vision impairment associated with recurrent and persistent DMO represented an important advance. Since then, two randomized-control trials and many real-world studies have shown its good efficacy/safety profile and the replicability of its treatment regimen. The FAc implant is, in general terms well tolerated, although it is associated with intraocular pressure-[IOP] and cataract-related adverse events [AEs]. Most IOP-related AEs are effectively controlled with ocular-hypotensive therapies. The objective of this paper is to review the role of FAc implant in the treatment of DMO over the 10 years since its launch, as well as its impact on clinical practice outcomes.

Intravitreal injections have revolutionized the treatment of various sight-threatening diseases of the posterior segment of the eye. Initially explored for treatment of bacterial endophthalmitis, intravitreal injections rapidly expanded to combat retinal vascular disease in particular. Especially anti-vascular endothelial growth factor agents have emerged as a cornerstone of intravitreal therapy, targeting neovascular age-related macular degeneration and diabetic macular edema as important examples. Advances continue, with novel therapies such as complement inhibitors now available as treatment for geographic atrophy secondary to non-neovascular age-related macular degeneration, offering hope for a previously untreatable condition. Pioneering approaches such as the port delivery system and intravitreal gene therapy aim to improve treatment efficacy while minimizing patient burden. Despite notable successes, challenges for intravitreal therapies persist, including ocular and systemic complications and high treatment burden. Future research endeavors aim to address these challenges and enhance treatment outcomes. This comprehensive review critically evaluates the efficacy, safety, and cost-effectiveness of intravitreal injections, delving into emerging trends and future directions.

To conduct a network meta-analysis (NMA) comparing the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy versus anti-VEGF therapy combined with laser or intravitreal glucocorticoid therapy for diabetic macular edema (DME).

PubMed, Embase, and the Cochrane Library were systematically searched for randomized controlled trials comparing anti-VEGF monotherapy with anti-VEGF therapy combined with laser or intravitreal glucocorticoid therapy for DME. The primary outcomes included the mean best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes from the baseline. A NMA for continuous outcomes was conducted using a fixed-effects model, with mean difference (MD) and corresponding 95% credible interval (CI) reported.

The NMA included 21 randomized controlled trials involving 1798 eyes. Anti-VEGF monotherapy and anti-VEGF combined with laser or intravitreal glucocorticoid therapy did not significantly change the mean CMT and BCVA at 6 and 12 months from the baseline. Simulation-based ranking results for mean BCVA changes suggested that anti-VEGF therapy combined with laser therapy was likely the most effective at 6 (70.7515%) and 12 (70.9315%) months. Similar results were observed in the simulation-based ranking of mean CMT changes, suggesting that anti-VEGF therapy combined with laser therapy was likely the most effective at 6 (83.6350%) and 12 (74.7730%) months.

Anti-VEGF monotherapy and anti-VEGF therapy combined with laser or intravitreal glucocorticoid therapy exerted comparable effects. However, the ranking chart recommends anti-VEGF therapy combined with laser therapy. Meanwhile, anti-VEGF therapy combined with intravitreal glucocorticoid therapy did not demonstrate significant benefits.

Background: Intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors are standard for diabetic macular edema (DME), yet a gap exists between clinical guidelines and actual practices. This study aimed to investigate the extent of deviation between physician-planned and actually performed treatment regimens. Methods: The PACIFIC study (NCT04847895) was a prospective, multicenter, non-interventional study conducted in Germany, the Netherlands, and Switzerland. A total of 910 patients with DME receiving ranibizumab were enrolled. Physicians documented the intended treatment regimen at baseline, and actual treatment patterns were retrospectively derived from the timing of visits and injections over a 24-month observation period. Results: Although most physicians initially planned fixed or pro re nata (PRN) regimens, 77% of pretreated and 73% of treatment-naïve patients ultimately followed a monitor and extend strategy. Treatment discontinuation was frequent (58.8% and 59.4%, respectively), and injection frequencies remained below recommended levels, although central retinal thickness improved over time. Conclusions: The study highlights a consistent and clinically relevant discrepancy between planned and actual treatment delivery in DME care, underscoring the need for better adherence to guideline-informed strategies in routine practice.

Retinal neovascularization is the leading cause of visual impairment in diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration. The extracellular matrix breakdown by metalloproteinase leads to vascular complications in various proliferative retinopathies. A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is involved in physiological angiogenesis. However, limited information exists regarding the role of ADAM10 in proliferative retinopathies. In this study, the levels of active ADAM10 were significantly up-regulated in the ischemic retina, and down-regulation or inactivation of ADAM10 significantly inhibited the proliferation, sprouting, migration, and tube formation of human retinal microvascular endothelial cell. Furthermore, the endothelial cell (EC)-specific deletion of ADAM10 (ADAM10iΔEC) significantly attenuated vascular leakage, edema, endothelial cell sprouting, and retinal neovascularization in ischemic retinas of mice exposed to oxygen-induced retinopathy. In experiments investigating the mechanisms through which ADAM10 regulated pathologic angiogenesis, ADAM10 regulated ephrin B2 (EfnB2) expression in endothelial cells. Down-regulation of EfnB2 expression influenced human retinal microvascular endothelial cell proliferation, migration, sprouting, and tube formation. In addition, a significant up-regulation of EfnB2 expression in the ischemic retina was detected. EC-specific depletion of ADAM10 significantly reduced EfnB2 expression, suggesting its involvement in ADAM10-regulated retinal neovascularization. The findings demonstrate how EC-specific ADAM10 regulates pathologic retinal neovascularization in the ischemic retina, indicating its significance as a potential therapeutic target for proliferative retinopathies.

Frequent visits and intravitreal anti-vascular endothelial growth factor (VEGF) injections are often required to manage diabetic macular edema (DME), burdening patients and their health care networks. The Port Delivery System (PDS) with ranibizumab is the first continuous anti-VEGF therapy that has the potential to reduce visit and treatment burden without sacrificing vision outcomes for patients with DME.

To evaluate the efficacy and safety through 64 weeks of ranibizumab, 100 mg/mL, via PDS with refill exchanges every 24 weeks (PDS Q24W) in patients with DME vs intravitreal injections of ranibizumab, 0.5 mg, every 4 weeks (monthly ranibizumab).

This randomized clinical trial was a phase 3, multicenter, noninferiority trial conducted across 87 sites in the US. Treatment-naïve patients at least 18 years old with center-involved DME were eligible for study participation. Enrollment was from September 30, 2019, to June 25, 2021; data were analyzed from September 30, 2019, to September 19, 2022.

Participants were randomized 3:2 to receive 4 monthly doses of ranibizumab, 0.5 mg, followed by ranibizumab, 100 mg/mL, via PDS Q24W or monthly ranibizumab.

The primary end point was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 60 and 64.

A total of 634 participants were randomized (PDS Q24W group, n = 381; monthly ranibizumab, n = 253). The mean (SD) age at baseline was 60.7 (9.6) years; 363 (57.3%) participants were male and 271 (42.7%) female. Adjusted mean BCVA change from baseline averaged over weeks 60 and 64 was an increase of 9.6 letters for PDS Q24W and 9.4 letters for monthly ranibizumab (difference, 0.2; 95% CI, -1.2 to 1.6), meeting the primary end point of PDS noninferiority (margin, -4.5 letters). PDS Q24W participants had a mean (SD) decrease of 6.7 (12.0) letters 4 weeks after PDS insertion; mean BCVA was similar to monthly ranibizumab 16 weeks after implantation. Adverse events of special interest were more common in the PDS Q24W group (88 participants; 27.5%) than the monthly ranibizumab group (28 participants; 8.9%). No cases of endophthalmitis or retinal detachment were reported with PDS Q24W.

This trial found that changes in BCVA from baseline averaged over weeks 60/64 in the PDS Q24W group were comparable to the monthly ranibizumab group. While AESIs were more common with PDS Q24W, there were no instances of endophthalmitis or retinal detachment. Continuous ranibizumab, 100 mg/mL, via PDS was approved in the US for patients with DME in February 2025 and provides effective, durable, and generally well-tolerated treatment for DME with retreatment every 6 months through at least 64 weeks.

ClinicalTrials.gov Identifier: NCT04108156.

This study assessed best visual acuity (BVA) and central subfield thickness (CST) outcomes for LER (limited early responder) and ER (early responder) patients at 24 and 36 months.

Retrospective chart review PARTICIPANTS: One-hundred and twelve patients characterized at 3 months after their first anti-VEGF injections as either LER if they met the anatomic criteria (aLER = CST reductions ≤ 10%), visual criteria (vLER = ETDRS letter gains < 5 letter), or both (cLER). All other patients were classified as ER (aER/vER/cER).

Variables collected include CST and ETDRS letters at baseline, 3, 24, and 36 months following injections, comorbidities, smoking status, demographics, baseline systemic factors, and the type and quantity of anti-VEGF injections. Analyses were performed using Welch's t-test, multivariable linear and multivariable logistic regression.

BVA changes from 3 months were significant between cLER versus cER and vLER versus vER groups (p < 0.05). There was a greater decrease in mean BVA from 3 months to 36 months in the cER group compared to the cLER group. Alternatively, mean BVA decreased in the vER cohort, while the vLER cohort slightly increased. CST changes from 3 months were statistically significant (p < 0.01) between all LER and ER groups with LER groups showing greater reductions compared to ER counterparts. BVA and CST changes from baseline to 24 and 36 months were not significant after controlling for baseline differences between LER and ER groups.

Results highlight the value of long-term anti-VEGF treatment and the need to further explore options that may lead to continued BVA improvements beyond 3 months.

The global incidence of diabetes is rising steadily and with it the number of people living with diabetic retinal disease (DRD) is increasing. Like diabetes, DRD can be treated but not cured. In response, therapies to address DRD include targeted ocular and systemic medications. This review discusses diabetes and DRD in terms of current screening recommendations, treatments, and considerations related to those therapies and future drug targets and trials on the horizon. This discourse is targeted at all members of the diabetes care team, including primary care providers, optometrists, and ophthalmologists. The dynamic landscape of diabetic retinopathy treatment is promising for the prevention and improvement of visually significant disease.

To identify diabetic maculopathy features from photographic screening that are predictive of treatment on referral to a tertiary care centre.

Retrospective review of participants who underwent screening by Singapore Integrated Diabetic Retinopathy Programme from 2015 to 2019. Participants underwent visual acuity (VA) test and non-stereoscopic retinal photographs. Maculopathy features include haemorrhages, microaneurysm and hard exudates (HE), stratified by inner and outer zone (1 and 1-2 disc diameter from fovea respectively) and VA of 6/12. Diabetic macular oedema (DMO) treatment was defined as intravitreal injection or macular photocoagulation up to 540 days from point of referral.

16,712 patients screened had referable eye disease. Out of 3518 maculopathy suspects, 281 (8.0%) received DMO treatment within 540 days. Those treated for DMO had shorter duration of diabetes (6.90 vs. 9.13 years, p < 0.001), higher total cholesterol (4.65 ± 1.20 vs. 4.36 ± 1.13 mmol/L, p = 0.001) and LDL cholesterol (2.59 ± 1.05 vs. 2.37 ± 0.93 mmol/L, p < 0.05) than those without treatment. High-risk features, including inner zone haemorrhages with VA ≤ 6/12 (HR 12.0, 95% CI: 5.5-25.9) and inner zone hard exudates (HR 7.4, 95% CI: 3.4-15.8), significantly increased the likelihood of requiring DMO treatment compared to low-risk features. Higher body mass index is protective of DMO treatment in mild non-proliferative diabetic retinopathy (HR 0.84, 95% CI: 0.73-0.97).

Haemorrhages, microaneurysms and HE within inner zone are important photographic features predictive of DMO treatment. VA is an important stratification for screening especially in patients with only visible haemorrhages.

The clinical efficacy of anti-vascular endothelial growth factors (anti-VEGFs), corticosteroids, and their combined treatment for diabetic macular edema (DME) has been substantiated by numerous studies. However, it remains uncertain whether the therapeutic benefits of the combined treatment with corticosteroids and anti-VEGFs is superior to those of anti-VEGF monotherapy. Consequently, we conducted a meta-analysis to compare the efficacy and safety of combined treatment with dexamethasone or triamcinolone and anti-VEGF versus anti-VEGF monotherapy in DME treatment.

An exhaustive search of the literature was performed on February 23, 2024, scanning through the databases including PubMed, Web of Science, Embase, and the Cochrane Library, with the aim of identifying all relevant studies. The combined results for efficacy and safety were analyzed using the standard mean difference (SMD) and relative risk (RR), both of which were presented with 95% confidence interval (CI). The assessment of heterogeneity was conducted via Cochran's Q test, I2 statistics, and the implementation of a 95% prediction interval (PI). All analyses were performed by R 4.3.1, Stata 12.0, and TSA v0.9.5.10 Beta software.

This meta-analysis incorporated 21 eligible studies. The overall analysis revealed that combined treatment of dexamethasone or triamcinolone with anti-VEGF agents did not demonstrate superiority over anti-VEGF monotherapy in improving best-corrected visual acuity (BCVA) (Dexamethasone: SMD -0.266, 95% CI -1.001 to 0.468, 95% PI -2.878 to 2.346; Triamcinolone: SMD -0.340, 95% CI -1.230 to 0.550, 95% PI -3.554 to 2.874) and reducing central macular thickness (CMT) (Dexamethasone: SMD -1.255, 95% CI -2.861 to 0.350; Triamcinolone: SMD -0.207, 95% CI -0.895 to 0.481, 95% PI -2.629 to 2.215). However, the combination therapy significantly increased the risk of elevated intraocular pressure (RR 5.783, 95% CI 3.007 to 11.121, 95% PI 0.520 to 56.931) and ocular hypertension (RR 8.885, 95% CI 2.756 to 28.649, 95% PI 1.262 to 39.208). Subgroup analysis suggests that dexamethasone plus anti-VEGF therapy showed a greater reduction in central subfield thickness (SMD -0.440, 95% CI -0.755 to -0.126) compared to anti-VEGF monotherapy among patients with persistent DME.

Our study confirmed that dexamethasone or triamcinolone plus anti-VEGF therapy did not show superior efficacy in improving BCVA and reducing CMT in DME patients compared with anti-VEGF monotherapy. Clinicians should weigh the pros and cons comprehensively when implementing combined therapy.

Management of Diabetic Macular edema (DME) requires repeated injections. Therefore newer Anti-VEGFs like Brolucizumab with longer durability have been introduced. We compared two different dosages of Brolucizumab, 6.0 mg and 3.6 mg, for their safety & efficacy in treatment of DME, in treatment naïve patients over 52 weeks.

A prospective, pilot randomised controlled, single centre, double blinded, two arm comparative study was conducted between Dec 2022 to Apr 2024. The study recruited 82 patients of DME who were randomised into two groups of 41 patients each, one group to be treated with Brolucizumab 6.0 mg in 50 μL and the other to receive 3.6 mg in 30 μL. All patients received the first dose of Brolucizumab at 0 week and were then followed up at every 4 weeks for detailed ophthalmic and OCT macula examination. Those who met the pre-defined re-treatment criteria were re-injected with Brolucizumab, the dose being fixed for each group throughout the study. All patient receiving an injection were further followed up on Day 1, Day 7 and Day 28 to look for any adverse reactions. The efficacy parameters included change in best corrected visusal acuity (BCVA), contrast and central macular thickness (CMT) on Optical Coherence Tomography. The average number of injections recd in each group were also calculated.

The change in BCVA from baseline in 6.0 mg group was 0.54 LogMAR units and 3.6 mg group was 0.59 LogMAR units, which was not statistically significant. The reduction in CMT from baseline in 6.0 mg group was 133.2 µm (μ) and 3.6 mg group was 110.6 μ, which was not statistically significant. The improvement in contrast from baseline in 6.0 mg group was 0.74 and 3.6 mg group was 0.95, with p value of 0.0002. The re-injection interval was 14.21 weeks in 6.0 mg group and 15.56 weeks for 3.6 mg subgroup. The total number of adverse events in both groups were similar at 70 in 6.0 mg group and 47 in 3.6 mg group with only one grade 4 adverse event occurring in each group.

The results of present study show that the safety and efficacy of both doses of Brolucizumab, i.e. 6.0 mg and 3.6 mg, for treating diabetic macular edema is similar. Trial registration Study was registered with Clinical trials registry of India (CTRI ref no. CTRI/2023/06/054105), registered on 14 Nov 2022.

To evaluate the effectiveness of anterior subtenon triamcinolone (AST) injections in the management of refractory macular edema.

This is a retrospective case series of consecutive eyes with refractory macular edema treated with AST at a single vitreoretinal surgeon's practice at Toronto Western Hospital, University of Toronto, Canada in 2018 to 2023. Refractory was defined as persistent macular edema with a central subfield thickness of 250 µ m or greater over a 24-week period, receiving at least four intravitreal antivascular endothelial growth factor injections. Vision outcomes and optical coherence tomography features for all eyes were compared for three visits pre-AST treatment and two visits post-AST treatment.

Ninety-three patients (119 eyes); diabetic macular edema (26%), and pseudophakic cystoid macular edema (74%), with a mean follow-up duration of 161 days were included. The presence of subretinal fluid ( P = 0.0013), central subfield macular thickness ( P < 0.0001), cube average thickness ( P = 0.0024), and macular cube volume ( P = 0.0017) significantly improved from pre-AST to post-AST treatment. Visual acuity also significantly improved from pre-AST treatment to post-AST treatment ( P < 0.0001). There was no significant change in the intraocular pressures from pre-AST to post-AST ( P = 0.7920), and no complications were noted throughout the follow-up period.

The findings from this study suggest that AST injections show modest improvement in anatomical and functional outcomes and are safe for the treatment and management of refractory macular edema.

The aim of this study was to compare the efficacy of the treat-and-extend (TAE) regimen versus the pro re nata (PRN) regimen in patients with bevacizumab-resistant diabetic macular edema (DME) treated with aflibercept, with or without adjunctive laser therapy.

Ninety-one eyes from 91 patients who were switched to aflibercept after three consecutive intravitreal bevacizumab injections for the treatment of DME were included in this retrospective real-world study. The patients were categorized into three groups: TAE (n = 30), TAE + laser (n = 31), and PRN (n = 30). Changes in best-corrected visual acuity and central macular subfield thickness (CMST) at 12, 24, and 52 weeks were defined as the primary functional and anatomical outcomes.

A total of 91 eyes from 91 patients (49.5% female) with a mean age of 63.9 ± 7.1 years were included in the analysis. At 52 weeks, the mean letter gains were 8.03, 8.90, and 10.23 in the TAE, TAE + laser, and PRN groups, respectively. Anatomical improvements, as measured by CMST reduction, were 55.33 µm, 33.35 µm, and 48.96 µm in the TAE, TAE + laser, and PRN groups, respectively. The average number of injections administered was 7.7, 8.1, and 8.1, respectively. The final extension interval for the TAE group was 8.7 weeks, compared to 9.5 weeks in the TAE + laser group.

The PRN group demonstrated the highest functional improvement while the TAE group showed the greatest anatomical improvement. Overall, both anatomical and functional outcomes in the TAE regimen were comparable to the PRN regimen in patients with bevacizumab-resistant diabetic macular edema.

Diabetic macular edema (DME) is a vision-threatening complication of diabetic retinopathy and causes significant morbidity in patients. Anti-vascular endothelial growth factor (VEGF) agents are the mainstay of treatment for DME, with steroid implants being used for the treatment of anti-VEGF resistant eyes. Over the years, several classification systems have been devised to describe the patterns of DME using optical coherence tomography (OCT). With the advent of effective treatments, it has become imperative that imaging cues are not merely used for classifying the disease but also as biomarkers for prognostication of disease activity and treatment response. In this aspect, newer imaging findings such as hyperreflective dots, photoreceptor integrity, and disorganization of retinal inner layers have been characterized in detail by several authors. Macular perfusion analysis using OCT angiography is the latest in the armamentarium for imaging DME. In this narrative review, we have summarized all relevant literature related to the ultrastructural imaging-based biomarkers of DME and their correlation to treatment.

The discovery of antivascular endothelial growth factor medications has resulted in a substantial change in diabetic retinopathy treatment. The most common cause of diabetic retinopathy blindness is Diabetic Macular Edema. The pathophysiology of Diabetic Macular Edema is thought to include the well-known pro-angiogenic and pro-permeability factor vascular endothelial growth factor. Over the past decade, drugs that impede the functions of vascular endothelial growth factors have established themselves as a standard-of-care treatment for a range of ocular ailments and improved patients' clinical results with diabetic retinopathy and Diabetic Macular Edema, and their frequency has grown exponentially with the introduction of these agents Pegaptanib, Ranibizumab, and Aflibercept which are approved for ophthalmic indications, while Bevacizumab is used off-label. These medications delivered intravitreally have halted the vascular development of diabetic retinopathy. Various randomized trials have proven that antivascular endothelial growth factor medication is safe and effective in preserving vision. Following an extensive period of preclinical development aimed at enhancing and defining its biological impacts, these drugs were shown in clinical trials to be effective in treating diabetic retinopathy and other ophthalmic conditions. Data from various sources suggest that Pegaptanib, Ranibizumab, and Aflibercept are costly, while Bevacizumab is cost-effective, and in low and middle-income nations, it is thus a desirable therapy choice. However, issues with compounding, counterfeiting, and off-label usage restrict its availability in many nations. The pharmacology, pharmacokinetics, pharmacodynamics, adverse effects, and contraindications of antivascular endothelial growth factor agents are discussed, and the results of clinical trials evaluating their efficacy are summarized.

Diabetes mellitus (DM) is a chronic metabolic non-communicable disease with the ability to cause serious microvascular and macrovascular complications throughout the body, including in the eye. Diabetic retinopathy (DR), present in one-third of patients with diabetes, is a vision-threatening complication caused by uncontrolled diabetes, which greatly affects the retinal blood vessels and the light-sensitive inner retina, eventually leading to blindness. Several epidemiological studies elucidate that DR can vary by age of onset, duration, types of diabetes, and ethnicity. Recent studies show that the pathogenesis of diabetic retinopathy has spread its roots beyond merely being the result of hyperglycemia. The complexity of its etiopathology and diagnosis makes therapeutic intervention challenging. This review throws light on the pathological processes behind DR, the cascade of events that follow it, as well as the available and emerging treatment options.

Diabetic retinopathy (DR) is a serious microvascular complication of diabetes mellitus and may result in irreversible visual loss. Laser treatment has been the gold standard treatment for diabetic macular edema and proliferative diabetic retinopathy for many years. Of late, intravitreal therapy has emerged as a cornerstone in the management of DR. Among the diverse pharmacotherapeutic options, anti-vascular endothelial growth factor agents have demonstrated remarkable efficacy by attenuating neovascularization and reducing macular edema, thus preserving visual acuity in DR patients.

Anti-vascular endothelial growth factor (anti-VEGF) therapy has revolutionized the management of various ocular conditions, including diabetic macular edema (DME), retinal vein occlusion (RVO)-related macular edema (ME), and neovascular age-related macular degeneration (nAMD). However, there remains a need to systematically assess its effectiveness across these distinct conditions.

A systematic review was conducted to identify studies evaluating the efficacy of anti-VEGF therapy in improving ocular outcomes in patients with DME, RVO-related ME, and nAMD. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published up to 2024. Studies meeting the inclusion criteria were critically appraised, and data on the proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in best-corrected visual acuity (BCVA), mean change in BCVA (ETDRS letters), and reduction in central macular thickness (CMT) (μm) were extracted and synthesized.

The systematic review identified 18 studies comprising randomized controlled trials, prospective studies, retrospective analyses, and observational studies. Anti-VEGF therapy demonstrated efficacy across all three conditions, with varying proportions of patients experiencing improvements in BCVA and reductions in CMT. Notably, the proportion of patients gaining ≥15 ETDRS letters ranged from 18.1% to 44.8% in DME, while mean changes in BCVA ranged from +4.2 letters to +21.4 letters in RVO-related ME and nAMD. Reductions in CMT ranged from 183.1 μm to 294 μm in DME and RVO-related ME.

Anti-VEGF therapy represents a cornerstone in the management of DME, RVO-related ME, and nAMD, with significant improvements observed in BCVA and reductions in CMT across diverse patient populations. While our findings support the effectiveness of anti-VEGF therapy in improving ocular outcomes, further research is warranted to compare its efficacy with alternative treatment modalities and to elucidate its long-term safety profile.

To derive estimates of clinically meaningful change (improvement) on the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in patients with diabetic macular edema (DME) using anchor- and distribution-based methods.

In this exploratory post hoc analysis of data from the RIDE/RISE (NCT00473382/NCT00473330) clinical trials of ranibizumab for DME, the NEI VFQ-25 was completed at baseline and six, 12, 18, and 24 months. Anchor-based (≥5-, ≥10-, and ≥15-letter gain in best-corrected visual acuity [BCVA]) and distribution-based estimates were calculated. Subgroup analyses included outcomes when the study eye was the better- or worse-seeing eye.

Baseline characteristics were balanced between the trials (RIDE, N = 382; RISE, N = 377). Anchor-based estimates of clinically meaningful improvement in composite scores (for ≥15-letter gain in BCVA) were 3.78 and 2.23 for RIDE and RISE, respectively. Estimates appeared similar for most subscales: near activities (4.11 and 3.31), distance activities (3.53 and 3.74), driving difficulties (5.15 and 3.15), and vision-specific dependency (4.70 and 1.83). Supportive distribution-based meaningful change composite score estimates also were similar between RIDE and RISE for values based on 0.5 standard deviation (9.85 and 9.70, respectively) or standard error of the mean (5.10 and 4.82, respectively).

These analyses suggest improvement of three to five points on the NEI VFQ-25 composite score and four individual subscales as clinically meaningful in patients with DME.

This analysis supports considering these thresholds when assessing the clinical risk-benefit of DME treatment from the patient perspective using the NEI VFQ-25.

The purpose of this study is to evaluate the impact of foveal bulge presence on visual acuity (VA) in patients with diabetic macular edema (DME) and retinal vein occlusion (RVO).

Spectral-domain optical coherence tomography (SD-OCT) scans were conducted on 22 DME patients and 20 RVO patients. Ordinary least squares (OLS) regression was employed to analyze the association between VA and the presence of the foveal bulge, as well as factors such as sex, age, central foveal thickness, various line scans of the fovea, and the external limiting membrane (ELM).

In DME patients, the β value associated with foveal bulge presence was 10.2, while the β value for ELM presence was 36.19. For RVO patients, the β value for foveal bulge presence was 18.71. In the combined analysis of DME and RVO patients, VA increased by 14.24 letters with the presence of a foveal bulge.

The presence of a foveal bulge significantly enhances VA in patients with resolved DME and RVO. Our findings indicate that the increase in VA is more pronounced in RVO patients compared to those with DME. Additionally, the presence of the foveal bulge, ELM, and sex can serve as predictors for VA outcomes in these patient populations.

Macular edema is an infrequent complication of retinal arteriovenous malformations. We present the management of unilateral macular edema with Bevacizumab 1.25mg/0.05mL and Aflibercept 2mg/0.05mL in a 16-year-old child with Wyburn-Mason syndrome.

The patient developed macular edema after 15 years of unremarkable ophthalmological follow-up. After a one-month observation period, a first intravitreal injection of Bevacizumab 1.25mg/0.05mL, the treatment most frequently described in the literature, was found to be insufficient to reduce the macular edema.After the switch to Aflibercept 2.0mg/0.05mL, a significant reduction in macular edema was observed after three monthly intravitreal injections. This effect was prolonged over the 15-month observation follow-up.

Aflibercept 2mg/0.05mL may be a safe and effective option to manage macular edema complications in retinal arteriovenous malformations.

Aim of the study was to evaluate the efficacy of dexamethasone (DEX) 0.7 mg intravitreal implant in patients with diabetic macular edema (DME) and serous retinal detachment (SRD), and to study the prognostic factors on a follow up of 12 months.

Forty eyes of twenty- six patients with centre involving DME and SRD, who underwent DEX implant, were enrolled. Best-corrected visual acuity (BCVA), Swept source OCT imaging and intraocular pressure were evaluated. Central macular thickness (CMT), vitreomacular adhesion (VMA), disorganization of retinal inner layers (DRILs), hyperreflective dots (HRD), SRD and ellipsoid zone (EZ) disruption were included in the analysis at baseline and 12 months after implant.

According to our parametric analysis, at 12 months, BVCA improvement from 48.6 ± 23.4 letters to 53.3 ± 24.5 letters was statistically significant (p = 0.04), CMT decreased from 460 ± 99.52 μm to 322.9 ± 117 μm. The presence at baseline of VMA (p = 0.01), EZ disruption (p = 0.03) and DRILs (p = 0.04), were associated with poor BCVA improvement at the end of follow-up.

In conclusion, OCT biomarkers can be considered significant prognostic factors for treatment outcome in patients with DME undergoing DEX intravitreal implant.

The high prevalence of Diabetic macular edema (DME) is a real global health problem. Its complex pathophysiology involves different pathways. Over the last decade, the introduction of intravitreal treatments has dramatically changed the management and prognosis of DME. Among the different treatment options, inhibitors of vascular endothelial growth factor (anti-VEGF) and intravitreal steroids implants represent the first-line therapy of DME. We conducted a review of electronic databases to compile the available evidence about the clinical management of DME in a clinical setting, with a special focus on treatment-naïve patients. Anti-VEGF therapies represent a valuable option for treating DME patients. However, many patients do not respond properly to this treatment and, due to its administration regimen, many patients receive suboptimal treatment in real life. Current evidence demonstrated that in patients with DME, DEX-i improved significantly both anatomic and visual outcomes. Besides eyes with insufficient anti-VEGF respond or recalcitrant DME cases, DEX-i can be effectively and safely used in treatment-naïve DME patients as first line therapy. DEX-i may be considered first line therapy in different clinical scenarios, such as DME eyes with a greater inflammatory component, patients with cardiovascular events, vitrectomized eyes, or those requiring cataract surgery. In conclusion, there are still many points for improvement pending in the clinical management of the patient with DME. Since DME treatment must follow a patient-tailored approach, selecting the best therapeutic approach for each patient requires a good understanding of the pathophysiology of DME.

The science of diabetes care has progressed to provide a better understanding of the oxidative and inflammatory lesions and pathophysiology of the neurovascular unit within the retina (and brain) that occur early in diabetes, even prediabetes. Screening for retinal structural abnormalities, has traditionally been performed by fundus examination or color fundus photography; however, these imaging techniques detect the disease only when there are sufficient lesions, predominantly hemorrhagic, that are recognized to occur late in the disease process after significant neuronal apoptosis and atrophy, as well as microvascular occlusion with alterations in vision. Thus, interventions have been primarily oriented toward the later-detected stages, and clinical trials, while demonstrating a slowing of the disease progression, demonstrate minimal visual improvement and modest reduction in the continued loss over prolonged periods. Similarly, vision measurement utilizing charts detects only problems of visual function late, as the process begins most often parafoveally with increasing number and progressive expansion, including into the fovea. While visual acuity has long been used to define endpoints of visual function for such trials, current methods reviewed herein are found to be imprecise. We review improved methods of testing visual function and newer imaging techniques with the recommendation that these must be utilized to discover and evaluate the injury earlier in the disease process, even in the prediabetic state. This would allow earlier therapy with ocular as well as systemic pharmacologic treatments that lower the and neuro-inflammatory processes within eye and brain. This also may include newer, micropulsed laser therapy that, if applied during the earlier cascade, should result in improved and often normalized retinal function without the adverse treatment effects of standard photocoagulation therapy.

Metabolic disorder significantly contributes to diabetic vascular complications, including diabetic retinopathy, the leading cause of blindness in the working-age population. However, the molecular mechanisms by which disturbed metabolic homeostasis causes vascular dysfunction in diabetic retinopathy remain unclear. O-GlcNAcylation modification acts as a nutrient sensor particularly sensitive to ambient glucose. Here, we observe pronounced O-GlcNAc elevation in retina endothelial cells of diabetic retinopathy patients and mouse models. Endothelial-specific depletion or pharmacological inhibition of O-GlcNAc transferase effectively mitigates vascular dysfunction. Mechanistically, we find that Yes-associated protein (YAP) and Transcriptional co-activator with PDZ-binding motif (TAZ), key effectors of the Hippo pathway, are O-GlcNAcylated in diabetic retinopathy. We identify threonine 383 as an O-GlcNAc site on YAP, which inhibits its phosphorylation at serine 397, leading to its stabilization and activation, thereby promoting vascular dysfunction by inducing a pro-angiogenic and glucose metabolic transcriptional program. This work emphasizes the critical role of the O-GlcNAc-Hippo axis in the pathogenesis of diabetic retinopathy and suggests its potential as a therapeutic target.

Visual function impairment from diabetic retinopathy can have a considerable impact on patient's quality of life. Best-corrected visual acuity (BCVA) is most commonly used to assess visual function and guide clinical trials. However, BCVA is affected late in the disease process, is not affected in early disease, and does not capture some of the visual disturbances described by patients with diabetes. The goal of this report is to evaluate the relationship between diabetic retinal disease (DRD) and visual function parameters to determine which if any of them may be used in a future DRD staging system.

The visual functions working group was 1 of 6 areas of DRD studied as part of the DRD staging system update, a project of the Mary Tyler Moore Vision Initiative. The working group identified 12 variables of possible interest, 7 of which were judged to have sufficient preliminary data to suggest an association with DR to warrant further review: microperimetry, static automated perimetry, electroretinogram (ERG) oscillatory potentials, flicker ERG, low luminance visual acuity (LLVA), contrast sensitivity (CS), and BCVA. The objective field analyzer (OFA) was added after subsequent in-person workshops.

Currently, the only visual function test available for immediate use is BCVA; the remaining tests are either promising (within 5 years) or have potential (>5 years) use. Besides BCVA, most visual function tests had a limited role in current clinical care; however, LLVA, CS, flicker ERG, and OFA demonstrated potential for screening and research purposes.

Although current visual function tests are promising, future prospective studies involving patients with early and more advanced retinopathy are necessary to determine if these tests can be used clinically or as endpoints for clinical studies.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Hyperglycemia is a major risk factor for early lesions of diabetic retinal disease (DRD). Updating the DRD staging system to incorporate relevant basic and cellular mechanisms pertinent to DRD is necessary to better address early disease, disease progression, the use of therapeutic interventions, and treatment effectiveness.

We sought to review preclinical and clinical evidence on basic and cellular mechanisms potentially pertinent to DRD that might eventually be relevant to update the DRD staging system.

Not applicable.

The Basic and Cellular Mechanisms Working Group (BCM-WG) of the Mary Tyler Moore Vision Initiative carefully and extensively reviewed available preclinical and clinical evidence through multiple iterations and classified these.

Classification was made into evidence grids, level of supporting evidence, and anticipated future relevance to DRD.

A total of 40 identified targets based on pathophysiology and other parameters for DRD were grouped into concepts or evaluated as specific candidates. VEGFA, peroxisome proliferator-activated receptor-alpha related pathways, plasma kallikrein, and angiopoietin 2 had strong agreement as promising for use as biomarkers in diagnostic, monitoring, predictive, prognostic, and pharmacodynamic responses as well as for susceptibility/risk biomarkers that could underlie new assessments and eventually be considered within an updated DRD staging system or treatment, based on the evidence and need for research that would fit within a 2-year timeline. The BCM-WG found there was strong reason also to pursue the following important concepts regarding scientific research of DRD acknowledging their regulation by hyperglycemia: inflammatory/cytokines, oxidative signaling, vasoprotection, neuroprotection, mitophagy, and nutrients/microbiome.

Promising targets that might eventually be considered within an updated DRD staging system or treatment were identified. Although the BCM-WG recognizes that at this stage little can be incorporated into a new DRD staging system, numerous potential targets and important concepts deserve continued support and research, as they may eventually serve as biomarkers and/or therapeutic targets with measurable benefits to patients with diabetes.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

To evaluate the effect of pan-retinal photocoagulation (PRP) on central macular thickness (CMT) in a sample of Iraqi patients with proliferative diabetic retinopathy (PDR).

This prospective study was conducted at Ghazi Al-Hariri for Surgical Specialties Hospital, Baghdad, from March 2024 to May 2024. A total of 24 eyes from 18 treatment-naive PDR patients with no previous diabetic macular edema (DME) were enrolled. Each eye received PRP in two sessions, one week apart, using the Nidek GYC 500 laser system. CMT was measured at baseline and four weeks after the second PRP session using the Topcon DRI Triton Plus optical coherence tomography (OCT). Statistical analyses, including paired t-tests and Shapiro-Wilk tests for normality, were performed to evaluate changes in CMT.

The mean CMT increased from 258.4 ± 30.7 microns at baseline to 269.9 ± 36.8 microns post PRP, with a mean increase of 11.5 ± 26.3 microns. This increase was statistically significant (p = 0.042). The Shapiro-Wilk test confirmed that the data were approximately normally distributed both before (W = 0.960, p = 0.445) and after (W = 0.931, p = 0.103) PRP treatment.

PRP significantly increases CMT in PDR patients, although no additional treatment for macular edema was necessary. These findings align with previous studies, suggesting that PRP-induced macular thickening is a common outcome. Further research is recommended to explore long-term effects and potential mitigation strategies.

Persistent diabetic macular edema (DME) remains a problem in clinical practice, with many patients having a suboptimal response to the standard of care (SOC). Evidence supports the long-term efficacy of intravitreal fluocinolone acetonide (FAc) implant (ILUVIEN®) in patients that have responded sub-optimally, although there is still scarce data from real-world Portuguese practices. We aimed to monitor the current SOC in selected Portuguese practices prior to FAc implantation and then assess the long-term effectiveness and safety of the FAc implant.

The study included patient data from five Portuguese public hospitals.

This was a non-interventional, multicenter audit of data collected from Retina.pt registry from patients with persistent or recurrent DME despite treatment.

Outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Results were compared at regular times over 36 months.

This study included 222 eyes from 152 patients. A significant decrease in BCVA (P < 0.001) and a significant increase in CMT (P = 0.013) were observed prior to FAc. A significant increase in BCVA was registered at 6 months after FAc implant administration (P < 0.001), which was maintained during follow-up. No relevant changes in IOP were observed. Treatment burden was reduced as a result of treatment with FAc (P < 0.001 for anti-VEGF, corticosteroids, or both treatments) in the full population.

In Portuguese practice, data showed that pre-FAc implantation, some patients did not respond to SOC treatment and/or they were undertreated. Following FAc implant administration, there were rapid, sustained, long-term visual and anatomical improvements, and a marked reduction in treatment burden.

Diabetic Macular Edema (DME) significantly impairs vision in diabetics, with varied patient responses to current treatments like anti-vascular endothelial growth factor (VEGF) therapy underscoring the necessity for continued research into more effective strategies. This study aims to evaluate global research trends and identify emerging frontiers in DME to guide future research and clinical management.

A qualitative and quantitative analysis of publications related to diabetic macular edema retrieved from the Web of Science Core Collection (WoSCC) between its inception and September 4, 2023, was conducted. Microsoft Excel, CiteSpace, VOSviewer, Bibliometrix Package, and Tableau were used for the bibliometric analysis and visualization. This encompasses an examination of the overall distribution of annual output, major countries, regions, institutions, authors, core journals, co-cited references, and keyword analyses.

Overall, 5624 publications were analyzed, indicating an increasing trend in DME research. The United States was identified as the leading country in DME research, with the highest h-index of 135 and 91,841 citations. Francesco Bandello emerged as the most prolific author with 97 publications. Neil M. Bressler has the highest h-index and highest total citation count of 46 and 9692, respectively. The journals "Retina - the Journal of Retinal and Vitreous Diseases" and "Ophthalmology" were highlighted as the most prominent in this field. "Retina" leads with 354 publications, a citation count of 11,872, and an h-index of 59. Meanwhile, "Ophthalmology" stands out with the highest overall citation count of 31,558 and the highest h-index of 90. The primary research focal points in diabetic macular edema included "prevalence and risk factors," "pathological mechanisms," "imaging modalities," "treatment strategies," and "clinical trials." Emerging research areas encompassed "deep learning and artificial intelligence," "novel treatment modalities," and "biomarkers."

Our bibliometric analysis delineates the leading role of the United States in DME research. We identified current research hotspots, including epidemiological studies, pathophysiological mechanisms, imaging advancements, and treatment innovations. Emerging trends, such as the integration of artificial intelligence and novel therapeutic approaches, highlight future directions. These insights underscore the importance of collaborative and interdisciplinary approaches in advancing DME research and clinical management.

The response of retinal pathology to interventions in diabetic retinopathy (DR) is often independent of the glycated hemoglobin (HbA1c) values at the point of care. This is despite glucose control being one of the strongest risk factors for the development and progression of DR. Previous preclinical and clinical research has indicated metabolic memory, whereby past cumulative glucose exposure may continue to impact DR for a prolonged period. Preclinical studies have evaluated punitive metabolic memory through poor initial control of DM, whereas clinical studies have evaluated protective metabolic memory through good initial control of DM. In this narrative review, we evaluate the preclinical and clinical evidence regarding metabolic memory and discuss how this may form the basis of preventive care for DR by inducing "metabolic amnesia" in people with a history of uncontrolled diabetes in the past. While our review suggested mitochondrial biology may be one such target, research is still far from a possible clinical trial. We discuss the challenges in such research.

To compare the risk of systemic arteriovenous thrombotic events between intravitreal anti-vascular endothelial growth factor (anti-VEGF) and sham injections.

Random-effects meta-analysis.

A systematic search was performed on OVID MEDLINE, Embase, and Cochrane Library from January 2005 to August 2023. Our inclusion criteria were randomized controlled trials (RCTs) reporting on systemic arteriovenous events for standard dose intravitreal anti-VEGF agents for any indication.

A total of 20 RCTs reporting on 12,833 eyes were included. There was no significant difference in the risk of any thrombotic event between bevacizumab 1.25 mg and ranibizumab 0.5 mg (Risk ratio (RR) = 0.96, 95% CI = 0.52-1.75, P = .89). There was no significant difference between bevacizumab and ranibizumab when restricting to arterial thrombotic events (RR= 0.88, 95% CI = 0.60-1.30, P = .53) or venous thrombotic events (RR = 1.99, 95% CI =86 0.68-5.82], P = .21). The risk of arterial thrombotic events was similar between aflibercept and bevacizumab (RR = 1.11, 95% CI = 0.60-2.07, P = .74), between aflibercept and ranibizumab (RR= 0.77, 95% CI = 0.49-1.21, P = .26), between brolucizumab and aflibercept (RR= 0.67, 95% CI = 0.32-1.38, P = .27), and between aflibercept and faricimab (RR = 0.96, 95% CI = 0.43-2.17, P = .93). Compared to sham, neither dose of ranibizumab (0.5 mg or 0.3 mg) showed a higher risk of arterial thrombotic events.

There was a similar risk of systemic arteriovenous thrombotic adverse events between anti-VEGF agents and between ranibizumab and sham injections.

Laser therapy has been proven as an effective technique for managing ophthalmological disorders. To guide future research, we conducted a bibliometric analysis of laser applications in eye diseases from 1990 to 2022, aiming to identify key themes and trends.

We retrieved 3027 publications from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks.

From a co-citation reference network, we identified 52 distinct clusters. Our analysis uncovered three main research trends. The first trend revolves around the potential evolution of corneal laser surgery techniques, shifting from the treatment of refractive errors to broader applications in biomedical optics. The second trend illustrates the advancement of laser applications in treating a range of disorders, from retinal and ocular surface diseases to glaucoma. The third trend focuses on the innovative uses of established technologies.

This study offers significant insights into the evolution of laser applications in ophthalmology over the past 30 years, which will undoubtedly assist scientists in directing further research in this promising field.

The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes.

Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections.

The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.

Despite advances in systemic care, diabetic disease of the eye (DDE) remains the leading cause of blindness worldwide. There is a critical gap of up-to-date, evidence-based guidance for ophthalmologists in Canada that includes evidence from recent randomized controlled trials. Previous guidance has not always given special consideration to applying treatments and managing DDE in the context of the healthcare system. This consensus statement aims to assist practitioners in the field by providing a spectrum of acceptable opinions on DDE treatment and management from recognized experts in the field. In compiling evidence and generating consensus, a working group of retinal specialists in Canada addressed clinical questions surrounding the four themes of disease, patient, management, and collaboration. The working group reviewed literature representing the highest level of evidence on DDE and shared their opinions on topics surrounding the epidemiology and pathophysiology of diabetic retinopathy and diabetic macular edema; diagnosis and monitoring; considerations around diabetes medication use; strategic considerations for management given systemic comorbidities, ocular comorbidities, and pregnancy; treatment goals and modalities for diabetic macular edema, non-proliferative and proliferative diabetic retinopathy, and retinal detachment; and interdisciplinary collaboration. Ultimately, this work highlighted that the retinal examination in DDE not only informs the treating ophthalmologist but can serve as a global index for disease progression across many tissues of the body. It highlighted further that DDE can be treated regardless of diabetic control, that a systemic approach to patient care will result in the best health outcomes, and prevention of visual complications requires a multidisciplinary management approach. Ophthalmologists must tailor their clinical approach to the needs and circumstances of individual patients and work within the realities of their healthcare setting.

To evaluate disorganization of retinal inner layers (DRIL), as detected on spectral-domain optical coherence tomography (OCT) images, as a biomarker for diabetic macular edema (DME) activity, visual function, and prognosis in eyes with DME.

Longitudinal prospective.

Post hoc correlation analyses were performed on data from a phase 2 clinical trial. Seventy-one eyes of 71 patients with treatment-naive DME received either suprachoroidally administered CLS-TA (proprietary formulation of a triamcinolone acetonide injectable suspension) combined with intravitreal aflibercept or intravitreal aflibercept with a sham suprachoroidal injection procedure. DRIL area, maximum horizontal extent of DRIL, ellipsoid zone (EZ) integrity, and the presence and location of subretinal (SRF) and intraretinal fluid (IRF) were evaluated at baseline and week 24 by certified reading centre graders.

At baseline, the area and maximum horizontal extent of DRIL were negatively correlated with best-corrected visual acuity (BCVA; r = -0.25, p = 0.05 and r = -0.32, p =0.01, respectively). Mean baseline BCVA progressively worsened with each ordinal drop in EZ integrity, improved with the presence of SRF, and was invariant to the presence of IRF. DRIL area and maximum extent were significantly decreased at week 24 (-3.0 mm2 [p < 0.001] and -775.8 mm [p < 0.001], respectively. At week 24, decreases in the area and maximum horizontal extent of DRIL were positively correlated with increases in BCVA (r = -0.40, p = 0.003 and r = -0.30, p = 0.04). Improvements in BCVA at week 24 were no different between patients showing improvement in EZ, SRF, or IRF and those showing no improvement or worsening from baseline.

DRIL area and DRIL maximum horizontal extent were demonstrated to be novel biomarkers for macular edema status, visual function, and prognosis in eyes with treatment-naive DME.

To evaluate the short-term effects (hours-days) of intravitreal dexamethasone implant (IDI) in eyes with diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) injections.

This was a prospective, single-arm, interventional clinical series. Eyes with DME and 3-9 injections of ranibizumab without a good response were included. Patients underwent a single IDI. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation, and spectral-domain optical coherence tomography (SD-OCT) were performed at baseline, 2 h, 3 h, 24 h, 7 days, and 1 month. The main outcomes were change in central retinal thickness (CRT) on SD-OCT and BCVA.

Fifteen eyes of 15 patients were included. Mean CRT decreased after treatment from 515.87 µm ± 220.00 µm at baseline to 489.60 µm ± 176.53 µm after 2 h (p = 0.126), and 450.13 µm ± 163.43 at 24 h (p = 0.006). Change in BCVA was from 0.85 ± 0.44 logMAR baseline to 0.58 ± 0.37 log MAR at 1 month (p = 0.003).

Eyes treated with IDI showed significant decrease in CRT detectable 1 day after injection. In some patients, the effect could be observed 3 h post-implantation.

Clinicaltrials.gov NCT05736081 . Registered 20 February 2023, Retrospectively registered.