Search

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Neovascular age-related macular degeneration (nAMD) is a common cause of visual impairment and blindness in the elderly with globally increasing prevalence. Vascular endothelial growth factor inhibitor (anti-VEGF) treatment has improved visual prognosis of nAMD, but continuous treatment may cause anxiety and stress, although increase in visual acuity (VA) may also have positive effects on patients' quality of life. The health care burden due to frequent treatment and monitoring is apparent, but the effect of anti-VEGF treatment on patients' quality of life is not fully understood. We evaluated the overall impact of nAMD and its treatment on newly diagnosed patients' health-related quality of life (HRQoL) in real-world setting. Methods: The present prospective cohort study included newly diagnosed nAMD patients treated with anti-VEGF injections at Oulu University Hospital during 2019–2020. Data included parameters from comprehensive ophthalmic examination and fundus imaging, age at diagnosis, sex, comorbidities, visual acuity, and frequency of anti-VEGF injections. HRQoL was assessed by 15D questionnaire at diagnosis, 6 months, and 12 months. Results: 95 nAMD patients were included. They were 78 ± 8 years old, 56 (59%) were female, and 74 (78%) had more than one comorbidity. The patients received 8 ± 3 anti-VEGF-injections. Visual acuity (VA) improved from 56 ± 18 to 61 ± 24 Early treatment diabetic retinopathy study (ETDRS) letters in 12 months. VA improved > 5 ETDRS letters in 45 (47%), remained stable in 30 (32%) and decreased > 5 letters in 17 (18%) eyes. The mean total 15D score reflecting overall HRQoL decreased from 0.850 ± 0.104 to 0.834 ± 0.103 in 12 months. Decreased HRQoL was associated with baseline best-corrected VA (BCVA) ≥ 70 ETDRS letters (p = 0.023) and more than one comorbidity (p = 0.034). HRQoL regarding visual function increased from 0.765 ± 0.194 to 0.789 ± 0.184 during the 12-month follow-up. Conclusions: In real world setting, HRQoL regarding visual function improved in anti-VEGF-treated nAMD patients during the first 12 months after the diagnosis and treatment initiation. Good baseline VA or several comorbidities were associated with decreased overall HRQoL during the follow-up. Despite the effectiveness of anti-VEGF treatment on visual function, several other aspects affecting elderly patients' everyday life should be considered when nAMD treatment is implemented. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic macular edema (DME) is a vision threatening accumulation of fluid within the macula. Current treatments involve the use of intravitreal anti-vascular endothelial growth factor (anti-VEGF), steroids, and laser to preserve vision. Areas covered: This review covers phase III therapeutics including KSI-301, which targets VEGF-A, UBX1325 which promotes apoptosis of senescent vascular endothelial cells and topical dexamethasone drops. Phase I and phase II therapeutics are also discussed including APX3330, a reduction-oxidation factor (Ref-1) inhibitor, ASP8232 – a vascular adhesion protein-1 (VAP-1) inhibitor, OTT-166, an anti-integrin agent, EYE103, a Wnt agonist and AXT107 and AG-73305, which have both anti-integrin and anti-VEGF functions. Tyrosine kinase inhibitors such as EYP-1901 and AXPALI, and YD312, gene therapies such as 4D–150 and RGX-314. Expert opinion: Current treatments for DME are limited greatly by the need for frequent dosing, treatment adherence, and invasive administration. Newer technologies that promote alternative routes of administration or increased longevity hold promise for the management of DME. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical efficacy of dexamethasone (DEX) implant, for the treatment of macular edema (ME) caused by retinal vein occlusion (RVO) and diabetic retinopathy (DR) through a systematic review and meta-analysis. Methods: The PubMed, Embase and Cochrane Library databases were comprehensively searched from inception to November 21, 2022, for studies evaluating the clinical efficacy of DEX implant for patients with retinal vein occlusion macular edema (RVO-ME) or diabetic macular edema (DME). Randomized controlled trials (RCTs) published in English were considered eligible. The Cochrane Collaboration tool was applied to assess the risk of bias in each study. Effect estimates with 95% confidence intervals (CIs) were pooled using the random effects model. We also conducted subgroup analyses to explore the sources of heterogeneity and the stability of the results. Results: This meta-analysis included 8 RCTs (RVO-ME [n = 2] and DME [n = 6]) assessing a total of 336 eyes. Compared with anti-VEGF therapy, DEX implant treatment achieved superior outcomes in terms of best corrected visual acuity (BCVA) (mean difference [MD] = -3.68 ([95% CI, -6.11 to -1.25], P = 0.003), and no heterogeneity was observed (P = 0.43, I2 = 0%). DEX implant treatment also significantly reduced central macular thickness (CMT) compared with anti-VEGF treatment (MD = -31.32 [95% CI, -57.92 to -4.72], P = 0.02), and there was a high level of heterogeneity between trials (P = 0.04, I2 = 54%). In terms of severe adverse events, DEX implant treatment had a higher risk of elevated intraocular pressure than anti-VEGF therapy (RR = 6.98; 95% CI: 2.16 to 22.50; P = 0.001), and there was no significant difference in cataract progression between the two groups (RR = 1.83; 95% CI: 0.63 to 5.27, P = 0.31). Conclusions: Compared with anti-VEGF therapy, DEX implant treatment is more effective in improving BCVA and reducing ME. Additionally, DEX implant treatment has a higher risk of elevated intraocular pressure. Due to the small number of studies and the short follow-up period, the results should be interpreted with caution. The long-term effects of the two treatments need to be further determined. Trial registration: Prospero Registration NumberCRD42021243185. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative diabetic retinopathy, the latter characterized by retinal abnormal angiogenesis. Pharmacological management of retinal angiogenesis employs expensive and invasive intravitreal injections of biologic drugs (anti-vascular endothelial growth factor agents). To search small molecules able to act as anti-angiogenic agents, we focused our study on axitinib, which is a tyrosine kinase inhibitor and represents the second line treatment for renal cell carcinoma. Axitinib is an inhibitor of vascular endothelial growth factor receptors, and among the others tyrosine kinase inhibitors (sunitinib and sorafenib) is the most selective towards vascular endothelial growth factor receptors 1 and 2. Besides the wellknown anti-angiogenic and immune-modulatory functions, we hereby explored the polypharmacological profile of axitinib, through a bioinformatic/molecular modeling approach and in vitro models of diabetic retinopathy. We showed the anti-angiogenic activity of axitinib in two different in vitro models of diabetic retinopathy, by challenging retinal endothelial cells with high glucose concentration (fluctuating and non-fluctuating). We found that axitinib, along with inhibition of vascular endothelial growth factor receptors 1 (1.82 ± 0.10; 0.54 ± 0.13, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 μM, respectively) and vascular endothelial growth factor receptors 2 (2.38 ± 0.21; 0.98 ± 0.20, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 μM, respectively), was able to significantly reduce (p < 0.05) the expression of Nrf2 (1.43 ± 0.04; 0.85 ± 0.01, protein levels in fluctuating high glucose vs. axitinib 1 μM, respectively) in retinal endothelial cells exposed to high glucose, through predicted Keap1 interaction and activation of melanocortin receptor 1. Furthermore, axitinib treatment significantly (p < 0.05) decreased reactive oxygen species production (0.90 ± 0.10; 0.44 ± 0.06, fluorescence units in high glucose vs. axitinib 1 μM, respectively) and inhibited ERK pathway (1.64 ± 0.09; 0.73 ± 0.06, phosphorylated protein levels in fluctuating high glucose vs. axitinib 1 μM, respectively) in HRECs exposed to high glucose. The obtained results about the emerging polypharmacological profile support the hypothesis that axitinib could be a valid candidate to handle diabetic retinopathy, with ancillary mechanisms of action. [ABSTRACT FROM AUTHOR]

Among working-age people, diabetic retinopathy and diabetic macular edema are currently considered the main causes of blindness. Nowadays, intravitreal injections are widely acknowledged as a significant milestone in ophthalmology, especially for the treatment of several retinal diseases, including diabetic macular edema. In particular, anti-vascular endothelial growth factor (VEGF) agents are typically the first line of treatment; however, monthly injections are required, at least, during the loading dosage. Notably, an intravitreal 0.7 mg dexamethasone (DEX) implant (Ozurdex®, AbbVie Inc., North Chicago, IL, USA) is considered a legitimate substitute treatment for diabetic eyes that have not responded to anti-VEGF treatment. In fact, clinical trials and real-life studies have demonstrated the effectiveness and safety of an intravitreal DEX implant in treating such conditions over a period of three to six months. For this reason, wisely selecting diabetic patients might be crucial to decreasing the load of injections in clinics and hospitals. The purpose of this review is to analyze the available scientific literature to highlight the benefits, efficacy, and clinical criteria for choosing whether to switch from intravitreal anti-VEGF therapy to an intravitreal DEX implant in diabetic macular edema. [ABSTRACT FROM AUTHOR]

Background: This study evaluated impact of anti–vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice. Methods: This was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan–Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment. Results: Among anti-VEGF–naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65–2.72) for moderate vs mild NPDR and 6.51 (6.47–6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%–8.3%), 20.9%, (20.0%–21.7%) and 46.8% (44.4%–49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7–1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4–0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4–0.7]) compared with 49.9% in eyes with no treatment (n = 8930). Conclusions: DME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGF‒naive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment. [ABSTRACT FROM AUTHOR]

This article discusses the impact of intravitreal anti-VEGF therapy on intraretinal microvascular abnormalities (IRMAs) in proliferative diabetic retinopathy (PDR). The study used optical coherence tomography angiography (OCTA) to analyze the characteristics of IRMAs in PDR eyes before and after anti-VEGF treatment. The results showed that most IRMAs experienced tuft regression after treatment, which was associated with a reduction in intraretinal flow. This regression of IRMAs may decrease the risk of retinal neovascularization and progression to PDR. However, the study had limitations, such as a small sample size and lack of association analysis with systemic parameters. [Extracted from the article]

Aim: We assessed the effectiveness of sodium‐glucose co‐transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti‐vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. Materials and Methods: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti‐VEGF agents after initiating SGLT2is or other antidiabetic drugs. Results: Among 2412 matched patients with DMO, the incidence rates of anti‐VEGF agent injections were 230.1 per 1000 person‐year in SGLT2i users and 228.4 times per 1000 person‐year in non‐users, respectively, and the risk ratio for events was unchanged in both groups. Sub‐analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti‐VEGF agent use [p =.027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22‐0.91]. SGLT2is reduced the risk for the first (p =.023, HR: 0.45, 95% CI: 0.22‐0.91) and second (p =.021, HR: 0.39, 95% CI: 0.17‐0.89) anti‐VEGF agent injections. Conclusions: There was no difference in the risk ratio for the addition of anti‐VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti‐VEGF agent administration in patients with DMO requiring anti‐VEGF therapy. Therefore, SGLT2i therapy may be a novel, non‐invasive, low‐cost adjunctive therapy for DMO requiring anti‐VEGF therapy. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive review of the literature on biosimilars for retinal diseases. Biosimilars are laboratory-engineered proteins that offer a more affordable alternative to FDA-approved biologics. The article discusses the development process of biosimilars, their similarities to reference biologics, and the current biosimilar market and pipeline therapeutics for retinal diseases. It also addresses barriers to adopting the widespread use of biosimilar therapies, including limited data and concerns about adverse events. The article emphasizes the need for postmarketing surveillance and further research to address these concerns and maximize the potential benefits of biosimilars in retinal disease treatment. The document also contains a list of references related to the use of biosimilars for retinal diseases, including clinical trials, retrospective studies, and meta-analyses that evaluate the efficacy and safety of these drugs. It also discusses the regulatory and ethical considerations surrounding their use and provides insights into their cost-effectiveness. [Extracted from the article]

This article provides an overview of the management and treatment options for nonproliferative diabetic retinopathy (NPDR), a complication of diabetes that can lead to vision loss if left untreated. It discusses the classification and diagnosis of NPDR, as well as current treatment strategies including systemic management of diabetes and ophthalmic interventions like laser photocoagulation and anti-VEGF injections. The article also highlights the need for more effective and less invasive treatment options, and mentions ongoing clinical trials investigating new drugs and therapies. Additionally, the document includes a list of references to various studies and clinical trials exploring the effectiveness and safety of different medications and therapies for diabetic retinopathy and macular edema. [Extracted from the article]

Purpose: Diabetic macular edema (DME) is a significant cause of vision impairment, posing challenges in its management due to variable responses and patient diversity. While anti-vascular endothelial growth factor (anti-VEGF) agents have revolutionized DME treatment, some patients are not suitable candidates for this therapy. Intravitreal corticosteroid therapy, such as the dexamethasone implant (DEX), has emerged as an alternative. This study aimed to comprehensively investigate the role of intravitreal DEX in treatment-naive DME patients with systemic contraindications to anti-VEGF therapy, administered one month before cataract surgery. Patients and Methods: A single-center retrospective study included 20 eyes with controlled diabetes, visually significant cataracts, untreated DME, and systemic contraindications for anti-VEGF therapy. Patients underwent DEX treatment followed by cataract surgery after one month. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were assessed at multiple time points. Results: BCVA significantly improved on days 30, 90, and 180 post-DEX (P< 0.00001). CMT showed a significant decrease at day 30 (P< 0.00001), which was sustained through days 90 and 180 (P< 0.00001). Recurrent DME was observed in 25% of eyes on day 90. IOP increased significantly at days 30 (P< 0.00001) and 90 (P=0.0006), returning to baseline by day 180. However, only two eyes needed topical anti-glaucoma treatment. No other ocular or systemic adverse events were noted. Conclusion: Intravitreal DEX administered one month before cataract surgery offers a promising treatment strategy for treatment-naive DME patients with systemic contraindications to anti-VEGF therapy. The study's findings provide insights into improving visual acuity and reducing macular thickness, along with manageable IOP changes. This personalized approach is a valuable addition to DME management, especially for complex medical cases, warranting further research and consideration for clinical practice. [ABSTRACT FROM AUTHOR]

Proliferative diabetic retinopathy (PDR) poses a significant therapeutic problem that often results in severe visual loss. Panretinal photocoagulation (PRP) has long been a mainstay treatment for this condition. Conversely, intravitreal anti-VEGF therapy has served as an alternative treatment for PDR. This review aimed to evaluate the effects of PRP combined with anti-VEGF therapy on the regression of neovascularization (NV), including functional outcomes and incidence of complications. The MEDLINE database was searched for articles evaluating regression of NV using a combination of the following terms: "proliferative diabetic retinopathy", "anti-VEGF", "panretinal photocoagulation", and "combined treatment". The search yielded a total of 22 articles. The analysis of their results indicated PRP combined with ant-VEGF therapy as superior over PRP alone in the management of PDR. Combination treatment yields better and faster regression of NV and a lower incidence of serious complications, such as vitreous hemorrhage and the need for pars plana vitrectomy. Nevertheless, complete regression of NV is not achieved in a significant proportion of patients. Further research is needed to establish the most effective schedule for intravitreal injections as an adjunct to PRP. The current literature shows that in some cases, cessation of anti-VEGF injection in combination treatment for PDR can lead to relapse of NV. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the correlation between topographic vessel density (VD) and retinal thickness (RT) reductions induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). This was a prospective, interventional case series. VD and RT measurements were separately taken in four parafoveal subfields at baseline and after six months of treatment. This correlation was statistically assessed using Spearman's rho correlation coefficient after adjustment for multiple comparisons. The study included a total of 48 eyes in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (±3.5) to 44.6% (±3.2) in the superficial capillary plexus and from 50 (±3.3) to 49% (±3.9) in the deep capillary plexus). Statistically significant reductions in RT were observed in all ETDRS sectors (p < 0.0001). No significant association was found between RT and VD, even when analyzing responders and non-responders separately. After six months of anti-VEGF treatment, no significant correlation was observed between the topographic VD and RT values. These findings suggest that reductions in VD values may not solely result from a reduction in microaneurysms, also being affected by the repositioning of displaced vessels due to edema and a reduction in their caliber. Therefore, VD changes may not be a suitable indirect OCTA biomarker of microaneurysm turnover and treatment response. [ABSTRACT FROM AUTHOR]

Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients' candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the longitudinal changes in renal function and associated factors after intravitreal anti-vascular endothelial growth factor (VEGF) administration in diabetic macular edema (DME). Methods: A total of 108 patients who had received intravitreal ranibizumab or aflibercept for DME and had follow-up visits for at least 2 years in one hospital were retrospectively enrolled. The estimated glomerular filtration rate (eGFR) at baseline and during the follow-up period and receipt of any renal replacement therapy were recorded. Linear regression and Cox regression models were used to evaluate factors associated with eGFR decline and renal replacement therapy. Results: After intravitreal anti-VEGF treatment, eGFR showed a mean decline of −10.4 ± 23.2% and −16.5 ± 26.4% at months 12 and 24, respectively. Patients in the eGFR > 120 mL/min and 15–30 mL/min groups had the greatest decline (−32.0 ± 20.6% and −37.4 ± 30.9%, respectively) while those in the 61–90 mL/min group had the smallest decline (−4.3 ± 19.7%) in eGFR after the 2-year treatment. One out of 52 patients (1.9%) receiving ranibizumab and five out of 56 patients (8.9%) receiving aflibercept started hemodialysis or peritoneal dialysis within the 2-year follow-up period (P = 0.21). Baseline eGFR correlated with renal replacement therapy after intravitreal anti-VEGF treatment (hazard ratio = 0.879 per increase of 1 in eGFR, P = 0.018). Conclusions: In DME patients receiving intravitreal anti-VEGF treatment, a persistent decline in eGFR was observed during the 2-year treatment course. Patients with extremely high or low eGFR had greater eGFR decline, and those with poor baseline eGFR tended to require dialysis after intravitreal anti-VEGF treatment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the early effects of intravitreal anti–vascular endothelial growth factor (anti-VEGF) agents on the cornea and visual acuity in patients with diabetic retinopathy (DR). This retrospective study enrolled patients who were administered conbercept or ranibizumab to treat DR. Fundus photograph, fluorescein angiograph, and optical coherence tomography were preoperatively performed. The patients were classified into two groups: nonproliferative DR (NPDR) and PDR. Best-corrected visual acuity (BCVA), specular microscopy, central corneal thickness (CCT), and intraocular pressure were obtained before injection and at 1 day and 7 days after injection. The effects of anti-VEGF agents on BCVA and CCT were compared between the groups receiving conbercept and ranibizumab and between NPDR and PDR eyes. A total 38 eyes (30 patients) were enrolled in this study. Twenty-one eyes received conbercept, and 17 eyes received ranibizumab. Twenty eyes were classified as NPDR and 18 eyes as PDR. No significant differences were found between the groups receiving conbercept and ranibizumab in the increase in BCVA nor in the increase of CCT at 1 day and 7 days after injection. As compared with NPDR eyes, PDR eyes demonstrated a significantly greater increase in CCT (−5.3 ± 3.7 vs. 6.5 ± 2.9 μm, P = 0.02 < 0.05) but not in BCVA (P = 0.33) at 1 day after injection. At 7 days after injection, no significant differences were found in the increase in BCVA nor in the increase of CCT between NPDR eyes and PDR eyes. Intravitreal administration of anti-VEGF agents could cause a small but significant greater increase in CCT in PDR than in NPDR eyes in the early period. In patients with DR, no significant difference was found between conbercept and ranibizumab in the early effects on the visual acuity nor in the cornea. [ABSTRACT FROM AUTHOR]

Intravitreal injection of anti-Vascular Endothelial Growth Factor (VEGF)is commonly used to treat patients with diabetic macular edema (DME). However, the injection alone requires high cost and compliance. Combining micropulse subthreshold laser (MPSL) and anti-VEGF is a new approach to treating DME. This study intended to answer the question of whether MPSL plus anti-VEGF is effective compared to anti-VEGF alone. The following terms were used in PubMed, clinicaltrial.gov, and Google Scholar: anti-VEGF, DME, MPSL, and diabetic retinopathy. All studies of DME comparing the intervention of MPSL plus anti-VEGF and VEGF alone between the years 2017-2021 were included. Studies with no comparison between the intervention and control group, abstract-only papers, case reports, case series, and systematic review studies were excluded. Five Randomized Controlled Trial (RCTs) and three retrospective studies were analyzed. Four studies found that best-corrected visual acuity (BCVA) improved in both therapies. Central macular thickness in six studies was also improved. The improvement differences between both therapies were insignificant and the number of anti-VEGF injections was significantly lower in combination therapy. These studies show equal outcomes of both therapies. The reduced number of anti-VEGF injections of the combination therapy could improve the management of DME in terms of cost-effectiveness. Further analysis should be conducted to pool the data from the studies and evaluate the overall outcome. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic Retinopathy (DR) is one of the common microvascular complications of diabetes. In patients with DR, the most frequent cause of vision loss is Diabetic Macular oedema (DME). In the present era, anti-Vascular Endothelial Growth Factor (anti-VEGF) agents are the mainstay of treatment for managing DME. A majority of patients show a good response to multiple doses of these agents administered by a pro re nata regimen at regularly spaced fixed intervals. However, the tendency of DME to become chronic and resistant to these agents, as well as the burden of repeated injections, necessitates considering alternative treatment options with similar or better efficacy. As steroids can address these drawbacks of anti-VEGF treatment, the present study compared the efficacy of anti-VEGF agents with dexamethasone implant in the treatment of naïve DME. Aim: To compare the effectiveness of dexamethasone implant with anti-VEGF agents in the treatment of naïve DME. Materials and Methods: A prospective cohort study was conducted in the Department of Ophthalmology at Kalinga Institute of Medical Sciences and Pradyumna Bal Memorial Hospital, Bhubaneswar, Odisha, India from September 2020 to September 2022. A total of 100 eyes with DME, newly diagnosed patients aged 18 years and above, without other macular oedema-causing diseases, were included. A total of 50 eyes in each group were treated with an anti-VEGF agent (Group A) or dexamethasone implant (Group B), and Best Corrected Visual Acuity (BCVA) and Central Foveal Thickness (CFT) were monitored for six months. For statistical analysis, paired t-test and independent t-test were used for within-group and inter-group analysis, respectively. A p-value <0.05 was considered statistically significant. Results: In both groups, post-treatment BCVA showed marked improvement, but there was no significant difference in mean BCVA between the groups (p=0.89) at six months. However, the mean CFT showed significant improvement in Group B at six months. In Group A, the mean CFT reduced from 441.87±54.48 µm to 257.83±25.73 µm, and in Group B, the mean CFT reduced from 464±109.44 µm to 207±22.51 µm at six months (p<0.0001). Adverse events like cataracts and glaucoma were seen in patients treated with the dexamethasone implant and were managed by cataract surgery and topical anti-glaucoma medications, respectively. Conclusion: Dexamethasone implant and anti-VEGF agents are equally effective in improving visual acuity; however, dexamethasone stands superior in reducing macular thickness. Needing fewer injections while treating with a dexamethasone implant improves compliance. The progression of cataract remains a major side-effect with the dexamethasone implant, which is not a concern when treating DME in pseudophakic eyes. [ABSTRACT FROM AUTHOR]

Background 2-year observations of ranibizumab monotherapy and combined therapy with diode laser for severe ROP in extremely prematures. Materials and methods: In a group of 18 prematures (n = 36 eyes; 5 study groups); 25.8 ± 1.5 Hbd, birth weight 796.5 ± 166.1 g. Apgar 4.62 ± 1.88) with A-ROP (n = 22; 61%) and 3 ROP (plus) (n = 14; 39%), ranibizumab monotherapy (n = 4 eyes) in dose 0.12 mg/0.12 mL or with diode laser (n = 32 eyes) were applied. The first intervention was carried out in PMA of 33 (gr. 4 and 5) and 34 in (gr. 1, 2, 3), mean follow-up time 21.44 ± 8.7 months. One-way analysis of variance (ANOVA) with Welch's correction, non-parametric Kruskal-Wallis test, Chi square test of independence were used. A retrospective observational study based on a case series. Results Retinal attachment was achieved in 92.3% of the studied eyes. Bilateral retinal detachment was noted in 1 infant (2 eyes). Myopization (−0.75 to −7.5 D) was observed in 5 infants (45%); mild hyperopia (+0.5 to +4.5 D) was observed in the rest infants (55%). Conclusions Individualization strategies in severe ROP with lower dose 0.12 mg Ranibizumab or combined laser-therapy resulted in effective outcomes. Myopia has not been reported in patients where Ranibizumab was the first drug administered in the ROP treatment strategy. [ABSTRACT FROM AUTHOR]

Purpose: Vascular endothelial growth factor inhibitors (anti-VEGF) have been shown to be effective in the treatment of diabetic macular edema. However, there is little information about the systemic effects of intraocular administration of anti-VEGF drugs in patients with coexistent diabetic nephropathy because it can produce adverse renal effects. Methods: This retrospective cohort study analyzed the effect of intravitreal anti-VEGF drugs (bevacizumab, ranibizumab, or aflibercept) on eFGR and microalbuminuria (MicA) in patients with diabetic macular edema and nonproliferative retinopathy without chronic kidney disease (CKD). Results: Sixty-six patients were included, 54.5% male and 45.5% female, with a mean age of 66.70 ± 11.6 years. The mean follow-up of patients with antiangiogenic treatment was 42.5 ± 28.07 months, and the mean number of injections was 10.91 ± 7.54. In 12.1% of the cases, there was a worsening of the glomerular filtration rate (eFGR) and a 19.7% worsening of the microalbuminuria (MicA). The number of injections was not related to the worsening of the eFGR (P = 0.74) or the MicA (P = 0.239). No relationship was found between the type of drug and the deterioration of the GFR (P = 0.689) or the MicA (P = 0.53). Conclusions: Based on the results, there is a small proportion of patients with increase in MicA and the decrease in eFGR after anti-VEGF therapy, and these was no associated with the number of injection or the drug type. Ophthalmologists should be aware of renal damage in order to do a close monitoring of renal function and proteinuria after intravitreal administration of anti-VEGF mainly in hypertensive patients. [ABSTRACT FROM AUTHOR]

Background Vascular endothelial growth factor inhibitors (VEGFis) have transformed the treatment of many retinal diseases, including diabetic maculopathy. Increasing evidence supports systemic absorption of intravitreal VEGFi and development of significant cardiorenal side effects. Methods We conducted a systematic review and meta-analysis (PROSPERO: CRD42020189037) of randomised controlled trials of intravitreal VEGFi treatments (bevacizumab, ranibizumab and aflibercept) for any eye disease. Outcomes of interest were cardiorenal side effects (hypertension, proteinuria, kidney function decline and heart failure). Fixed effects meta-analyses were conducted where possible. Results There were 78 trials (81 comparisons; 13 175 participants) that met the criteria for inclusion: 47% were trials in diabetic eye disease. Hypertension (29 trials; 8570 participants) was equally common in VEGFi and control groups {7.3 versus 5.4%; relative risk [RR] 1.08 [95% confidence interval (CI) 0.91–1.28]}. New or worsening heart failure (10 trials; 3384 participants) had a similar incidence in VEGFi and control groups [RR 1.03 (95% CI 0.70–1.51)]. Proteinuria (5 trials; 1902 participants) was detectable in some VEGFi-treated participants (0.2%) but not controls [0.0%; RR 4.43 (95% CI 0.49–40.0)]. Kidney function decline (9 trials; 3471 participants) was similar in VEGFi and control groups. In participants with diabetic eye disease, the risk of all-cause mortality was higher in VEGFi-treated participants [RR 1.62 (95% CI 1.04–2.46)]. Conclusion In trials of intravitreal VEGFi, we did not identify an increased risk of cardiorenal outcomes, although these outcomes were reported in only a minority of cases. There was an increased risk of death in VEGFi-treated participants with diabetic eye disease. Additional scrutiny of post-licensing observational data may improve the recognition of safety concerns in VEGFi-treated patients. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration (nAMD) with choroidal neovascularization (CNV) is a leading cause of blindness in the elderly in developed countries. The disease is currently treated with anti-angiogenic biologics, including aflibercept, against vascular endothelial growth factor (VEGF) but with limited efficacy, treatment resistance and requirement for frequent intravitreal injections. Although anti-VEGF gene therapy may provide sustained therapy that obviates multiple injections, the efficacy and side effects related to VEGF pathway targeting remain, and alternative strategies to block angiogenesis independently of VEGF are needed. We recently reported that secretogranin III (Scg3) induces only pathological angiogenesis through VEGF-independent pathways, and Scg3-neutralizing antibodies selectively inhibit pathological but not physiological angiogenesis in mouse proliferative retinopathy models. Anti-Scg3 antibodies synergize dose-dependently with VEGF inhibitors in a CNV model. Here, we report that an adeno-associated virus-8 (AAV8) vector expressing anti-Scg3 Fab ameliorated CNV with an efficacy similar to that of AAV-aflibercept in a mouse model. This study is the first to test an anti-angiogenic gene therapy protocol that selectively targets pathological angiogenesis via a VEGF-independent mechanism. The findings support further safety/efficacy studies of anti-Scg3 gene therapy as monotherapy or combined with anti-VEGF to treat nAMD. [ABSTRACT FROM AUTHOR]

Many studies introduced intravitreal injections of anti-vascular endothelial growth factors (VEGFs) as a new strategy for safer and more convenient vitrectomy in patients with severe proliferative diabetic retinopathy (PDR). While possible side effects such as progression of vitreoretinal fibrosis should be kept in mind, these may be prevented by proper preoperative timing of injection. This study was conducted based on the systematic review guidelines in four steps: definition of search strategy, selecting and evaluating studies, checking inclusion and exclusion criteria, and statistical analysis. Eighteen clinical trials with a total sample size of 1165 patients were included. According to the timing of injection, patients were divided into three groups: injection 72 hours, injection 3–7 days, and injection 7–21 days before surgery. The lowest risk of intraoperative hemorrhage, the minimum duration of surgery and the lowest need for silicone oil (SO) tamponade was in the injection group 7–21 days before surgery. The rate of iatrogenic retinal break during surgery and the necessity for relaxing retinotomy in the injection group 72 hours before surgery was lower than the other two groups. However, there were limited data regarding the requirement of relaxing retinotomy, the need to inject SO, and the occurrence of iatrogenic retinal break. This meta-analysis showed, to prevent tractional complications, it is recommended to inject within 3 days before surgery. [ABSTRACT FROM AUTHOR]

Background: Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy. Methods: We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segmentouter segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA). Results: Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant. Conclusion: Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a microvascular disease caused by poorly controlled blood glucose, and it is a leading cause of vision loss in people with diabetes. In this review we discuss the current management of DR with particular focus on the use of intraocular anti-vascular endothelial growth factor (anti-VEGF) agents. Intraocular anti-VEGF agents were first studied in the 1990s, and now several of these agents are either FDA approved or used off-label as first-line treatments for DR. Recent evidence shows that anti-VEGF agents can halt the progression of markers of DR severity, reduce the risk of DR worsening, and reduce the onset of new macular edema. These significant benefits have been demonstrated in patients with proliferative DR and the milder nonproliferative DR (NPDR). A wealth of evidence from recent trials and meta-analyses has detailed the intraoperative and postoperative benefits of adjunctive anti-VEGF therapy prior to pars plana vitrectomy (PPV) for proliferative DR with vitreous hemorrhage. In this review, we also discuss literature comparing various anti-VEGF injection regimens including monthly, quarterly, as-needed, and treat and extend protocols. Combination protocols with panretinal photocoagulation (PRP) or PPV are also discussed. Current evidence suggests that anti-VEGF therapies are effective therapy for NPDR and PDR and may also provide significant benefits when used adjunctively with other DR treatment modalities such as PRP or PPV. [ABSTRACT FROM AUTHOR]

Bone Morphogenetic Protein 4 (BMP4) is a secreted growth factor of the Transforming Growth Factor beta (TGFβ) superfamily. The goal of this study was to test whether BMP4 contributes to the pathogenesis of diabetic retinopathy (DR). Immunofluorescence of BMP4 and the vascular marker isolectin-B4 was conducted on retinal sections of diabetic and non-diabetic human and experimental mice. We used Akita mice as a model for type-1 diabetes. Proteins were extracted from the retina of postmortem human eyes and 6-month diabetic Akita mice and age-matched control. BMP4 levels were measured by Western blot (WB). Human retinal endothelial cells (HRECs) were used as an in vitro model. HRECs were treated with BMP4 (50 ng/mL) for 48 h. The levels of phospho-smad 1/5/9 and phospho-p38 were measured by WB. BMP4-treated and control HRECs were also immunostained with anti-Zo-1. We also used electric cell-substrate impedance sensing (ECIS) to calculate the transcellular electrical resistance (TER) under BMP4 treatment in the presence and absence of noggin (200 ng/mL), LDN193189 (200 nM), LDN212854 (200 nM) or inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2; SU5416, 10 μM), p38 (SB202190, 10 μM), ERK (U0126, 10 μM) and ER stress (Phenylbutyric acid or PBA, 30 μmol/L). The impact of BMP4 on matrix metalloproteinases (MMP2 and MMP9) was also evaluated using specific ELISA kits. Immunofluorescence of human and mouse eyes showed increased BMP4 immunoreactivity, mainly localized in the retinal vessels of diabetic humans and mice compared to the control. Western blots of retinal proteins showed a significant increase in BMP4 expression in diabetic humans and mice compared to the control groups (p < 0.05). HRECs treated with BMP4 showed a marked increase in phospho-smad 1/5/9 (p = 0.039) and phospho-p38 (p = 0.013). Immunofluorescence of Zo-1 showed that BMP4-treated cells exhibited significant barrier disruption. ECIS also showed a marked decrease in TER of HRECs by BMP4 treatment compared to vehicle-treated HRECs (p < 0.001). Noggin, LDN193189, LDN212854, and inhibitors of p38 and VEGFR2 significantly mitigated the effects of BMP4 on the TER of HRECs. Our finding provides important insights regarding the role of BMP4 as a potential player in retinal endothelial cell dysfunction in diabetic retinopathy and could be a novel target to preserve the blood–retinal barrier during diabetes. [ABSTRACT FROM AUTHOR]

The treatment of proliferative diabetic retinopathy (PDR) has evolved significantly since the initial use of panretinal photocoagulation as a treatment in the 1950s. Vascular endothelial growth factor inhibitors have provided an effective alternative without the risk of peripheral vision loss. Despite this, the risk of complications requiring surgical intervention in PDR remains high. Intravitreal bevacizumab has shown promise as a preoperative adjuvant to vitrectomy for PDR complications, albeit with a purported risk for tractional retinal detachment (TRD) progression in eyes with significant fibrous proliferation. Here we will discuss anti-VEGF agent use in PDR and its role in surgical intervention for PDR complications including TRD. [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]

Introduction: The aim of our study was to investigate factors associated with diabetic retinopathy (DR) severity fluctuations in patients undergoing intravitreal injections for diabetic macular edema and to explore risk factors for proliferative DR (PDR). Methods: We graded ultra-widefield fundus photography imaging at each visit using the Early Treatment Diabetic Retinopathy Study Severity Scale (DRSS). We calculated the deviation from the mode (DM) of DRSS values as a proxy of DR severity fluctuations, and we analyzed its clinical associations with linear models. We computed risk factors for PDR with Cox hazard models. We included the DRSS area-under-the-curve (AUC) of DRSS scores as a covariate in all analyses. Results: We included 111 eyes with a median follow-up of 44 months. Higher DRSS-AUC values (β = +0.03 DRSS DM for unitary DRSS/month increase, p = 0.01) and a higher number of anti-VEGF injections (β = +0.07 DRSS DM for injection, p = 0.045) were associated with wider DR severity fluctuations. Higher DRSS-AUC values (HR = 1.45 for unitary DRSS/month increase, p = 0.001) and wider DR severity fluctuations (HR = 22.35 4th quartile vs. 1st–3rd quartile of DRSS DM, p = 0.01) were risk factors for PDR. Conclusion: Patients with larger DR variability in response to intravitreal injections may be at higher risk of DR progression. We advocate attentive follow-up in these patients to recognize PDR early. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is one of the more serious complications of diabetes. However, the mechanisms involved in DR are complex and still need to be investigated. The beneficial effects of fisetin have been widely reported, but whether it is beneficial in DR is not clear yet. This study was designed to investigate the regulatory role of fisetin in regulating DR and explore the involved mechanism. First, 30 mM glucose was used to establish DR cell model in vitro. Cell counting kit 8 (CCK8) assay was utilized to study the effects of fisetin on cell viability through treating human retinal microvascular endothelial cells (HRMECs) with 25, 50, and 100 μM fisetin. Transwell and wound healing assays were used to detect the function of fisetin on the migration and angiogenesis on HG-induced HRMECs. Finally, OE-VEGF was used as a mimic of VEGF, and western blotting (WB) was used to verify the targeting genes of fisetin. HG induced an increase in cell viability, cell migration, and angiogenesis in HRMECs, whereas fisetin inhibited these enhancements induced by HG through inhibiting VEGF. In conclusion, fisetin prevents angiogenesis in DR by downregulating VEGF. [ABSTRACT FROM AUTHOR]

Purpose: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents reduces microaneurysms in patients with diabetic macular edema (DME). However, residual anti-VEGF-resistant telangiectatic capillaries (TelCaps) have been reported. In this study, we investigated changes in the size of TelCaps after intravitreal injection of anti-VEGF agents in DME. Patients and Methods: Indocyanine green angiography (IA) and optical coherence tomography were performed before and 3 months after the intravitreal injection of anti-VEGF agents (pro re nata regimen after three monthly loading doses) in 12 eyes of 12 patients (7 males and 5 females, mean age 65.2 ± 8.8 years) with DME. The number and size of TelCaps within a 6-mm diameter macular region of the edema were measured using optical coherence tomography B-scan images overlaid on IA images. Results: There were significant reductions in the number and size of TelCaps between the baseline and 3 months after anti-VEGF agent administration (P < 0.05 and P < 0.0001, respectively). The maximum corrected visual acuity (logMAR visual acuity) and the central macular thickness after anti-VEGF therapy were significantly improved (P < 0.01 and P < 0.02, respectively). The TelCaps remaining after loading three consecutive anti-VEGF agents had a significantly larger mean size at baseline than the TelCaps that resolved after the treatment (P < 0.03). Conclusion: Our study demonstrated that intravitreal injection of anti-VEGF agents could reduce TelCap size in patients with DME. We propose that larger-sized TelCaps detected by IA might be useful predictors of refractory DME, which could thus be principal targets of laser photocoagulation. [ABSTRACT FROM AUTHOR]

Purpose: This study analyzed the effects of re-vitrectomy and intravitreal anti-VEGF treatments and other factors on visual acuity in vitreous hemorrhages (VH) in diabetic patients after vitrectomy. Materials and Methods: VHs seen in vitrectomized diabetic patients were reviewed retrospectively. Hemorrhages in post vitrectomy diabetic vitreous hemorrhage (PDVH) were classified in three groups as moderate, marked and severe. One group of patients was treated with re-PPV, and the other had intravitreal anti-VEGF. Best-corrected visual acuity (BCVA), HbA1C levels, and anti-VEGF treatments up to the development of VH were evaluated during the one-year follow-up of the patients. Results: A total of 16 patients with PDVH (10 females and six males) were examined. Ten (62.5%) patients were treated with anti-VEGF and 6 (37.5%) with re-PPV. The mean age of the patients was 63.5±8.9 years, and there was no difference between the two treatment groups in terms of age (p=0.087), HbA1c (p=0.609), previous anti-VEGF treatments (p=0.488), and VH severity (p=0.091). A statistically significant difference was found between the baseline visual acuity values between the groups (p=0.016). The mean of the anti-VEGF group was 0.96 logMAR, while the mean of the re-PPV group was 1.33 logMAR (worse). There was no difference between the mean visual outcomes of the two groups at the end of six months (p=0.157) and one year (p=0.309). Conclusion: Since there was no difference between the two treatment modalities in terms of change in BCVA, minimally invasive intravitreal anti-VEGF therapy seems to be an alternative to re-vitrectomy in the treatment of PDVH. [ABSTRACT FROM AUTHOR]

Objectives: To compare the functional and anatomical outcomes of ranibizumab and aflibercept monotherapies given according to a pro re nata (PRN) protocol in treatment-naive eyes with diabetic macular edema (DME) in a real-life clinical setting. Materials and Methods: The medical charts of treatment-naive patients with center-involved DME retrieved from our institutional database were reviewed in this retrospective cohort study. A total of 512 treatment-naive eyes with DME underwent either ranibizumab (Group I; 308 eyes) or aflibercept (Group II; 204 eyes) monotherapy and 462 patients were included. The primary outcome was visual gain over 12 months. Results: The mean number of intravitreal injections within the first year was 4.34±1.83 and 4.39±2.12 in Group I and II, respectively (p = 0.260). The mean best corrected visual acuity (BCVA) improvement at 12 months was +5.7 and +6.5 ETDRS letters in Group I and II, respectively (p=0.321). However, among eyes with a BCVA score less than 69 ETDRS letters (54% of the study population), visual gain was more prominent in Group II (+15.2 vs. +12.1 ETDRS letters; p<0.001). Statistically significant decreases in central foveal thickness were observed with both ranibizumab and aflibercept monotherapy (p<0.001), with no significant difference between the groups (p = 0.148). Conclusion: No statistically significant difference was found in visual outcomes at 12-month follow-up between ranibizumab and aflibercept monotherapies using a PRN protocol, although there was a tendency toward slightly better functional and anatomic prognosis in the aflibercept arm. [ABSTRACT FROM AUTHOR]

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

Background: With a growing number of patients diagnosed with microvascular complications of diabetes, cases of diabetic retinopathy (DR) are on the rise. This study helps to determine the treatment outcomes and factors associated with anti-vascular endothelial growth factor (VEGF) treatment for macular edema associated with diabetes in a Regional Hospital in Saudi Arabia. Materials and Methods: A retrospective study based on the data collected from the patient records of cases of diabetic macular edema presenting from May 2016 to December 2021 and treated with anti-VEGF agents. Information on demographics, disease, and treatment was extracted on a data driven form for 1293 patients. Student's paired t-tests and ordered logistic regression analysis were carried out to study the effect of various factors on treatment outcomes. All values were considered statistically significant at a value of P ≤ 0.05. Results: We found improvement in visual acuity (VA) and macular thickness following the treatment with anti-VEGF. VA improved from 0.24 ± 0.27 m to 0.28 ± 0.27 t (1716) = -2.958, P < 0.005, t (1716) = 27.30; and macular thickness decreased from 267.32 ± 200.17 to 194.40 ± 151.38 (P < 0.001). Younger patients, male gender, and patients having multimorbidity (presence of hypertension [HTN] or chronic kidney disease long with diabetes) significantly improved VA (P < 0.001). Intravitreal ranibizumab has significantly more effect on improvement in VA (P < 0.001), while all intravitreal anti-VEGF agents have a significant effect on reducing macular thickness (P < 0.001). Conclusion: Anti-VEGF agents provide successful treatment outcomes in patients having DR; however, treatment outcomes differ by gender, age, and co-existing HTN and kidney disease. Treatment with ranibizumab significantly increases VA. [ABSTRACT FROM AUTHOR]

Background: Vascular endothelial growth factor inhibitors (VEGFIs) are used to treat malignant neoplasms and ocular diseases by inhibiting angiogenesis. Systemic use of VEGFIs has various side effects, including hypertension, proteinuria, and thrombotic microangiopathy, but adverse events due to intravitreal injection of VEGFIs have not been fully clarified. Although age-related macular degeneration was initially the most common target of intravitreal injection of VEGFIs, it has also been applied sporadically for diabetic macular edema in recent years. Proteinuria following intravitreal injection of VEGFIs would be reversible. In patients with diabetes mellitus (DM), however, it would be difficult to determine whether kidney damage arises from the clinical course of DM or from intravitreal injection of VEGFIs for diabetic macular edema. Case presentation: A 55-year-old woman with a 20-year history of type 2 DM began intravitreal injection of VEGFI (aflibercept, 2 mg every 4 weeks) for treatment of diabetic macular edema 2 years previously. She presented with leg edema, hypertension, and nephrotic-range proteinuria 14 months after the first injection. Histological examination of renal biopsy specimens revealed diabetic nephropathy with renal thrombotic microangiopathy probably associated with intravitreal injection of VEGFI. The patient's nephrotic syndrome completely improved at 6 months after simply discontinuing aflibercept. Conclusions: This is a precious report of pathologically investigated renal thrombotic microangiopathy leading to nephrotic syndrome due to intravitreal injection of aflibercept for diabetic macular edema in a patient with type 2 DM. Renal function and proteinuria should be monitored in diabetic patients who receive intravitreal injection of a VEGFI. If kidney damage develops independent of the clinical course of DM during intravitreal injection of a VEGFI, renal biopsy should be performed and intravitreal VEGFI injection discontinued. [ABSTRACT FROM AUTHOR]

Vasculogenesis (the process of differentiation of angioblasts toward endothelial cells and de novo formation of crude vascular networks) and angiogenesis (the process of harmonized sprouting and dispersal of new capillaries from previously existing ones) are two fundamentally complementary processes, obligatory for maintaining physiological functioning of vascular system. In clinical practice, however, the later one is of more importance as it guarantees correct embryonic nourishment, accelerates wound healing processes, prevents uncontrolled cell growth and tumorigenesis, contributes in supplying nutritional demand following occlusion of coronary vessels and is in direct relation with development of diabetic retinopathy. Hence, discovery of novel molecules capable of modulating angiogenic events are of great clinical importance. Recent studies have demonstrated multiple angio‐regulatory activities for endocannabinoid system modulators and endocannabinoid‐like molecules, as well as their metabolizing enzymes. Hence, in present article, we reviewed the regulatory roles of these molecules on angiogenesis and described molecular mechanisms underlying them. Significance statement: Regardless of the fact that antiangiogenic therapies, especially those targeting VEGF molecule and their associated pathways, may be of great potential in treatment of cancer, application of currently existing antiangiogenic agents in micrometastatic cases was together with poor clinical outcome and no meaningful enhancement in disease‐free or recurrence‐free survival. This is strongly suggestive of the ineffectiveness of the recently established approaches in suppressing cancer angiogenesis. And necessity for discovery of other more potent and effective solutions for management of angiogenic events in cancer. Recent studies have demonstrated multiple angio‐regulatory activities for endocannabinoid system modulators and endocannabinoid‐like molecules, as well as their metabolizing enzymes. Hence, in present article, we reviewed the regulatory roles of these molecules on angiogenesis and described molecular mechanisms underlying them. [ABSTRACT FROM AUTHOR]

Introduction: This study assessed retinal nonperfusion area (NPA) changes after anti-VEGF treatment in proliferative diabetic retinopathy (PDR) eyes using swept-source widefield optical coherence tomography angiography (SS-WF OCTA) and investigated the relationships with the microperimetry (MP-1) functional changes observed in the same areas. Methods: This was a single-center observational case series. Seven PDR eyes naïve to treatment that received three monthly intravitreal injections of aflibercept were included. All eyes were imaged with SS-WF OCTA and MP-1 at baseline (T0) and 1 month after the third injection (T1). The regions of interest (ROIs) with evidence of NPAs at T0 OCTA images were selected. Qualitative and quantitative [perfusion density (PD) and vessel length density (VLD)] OCTA vascular changes in the selected ROIs between T0 and T1 were compared with the corresponding MP-1 functional changes [mean sensitivity (MS)]. Results: Twenty-five ROIs were selected. In 52% of the ROIs, an improvement in MS was observed at T1, which was associated with qualitative and quantitative improvement in 92.3% of NPAs by OCTA. In 32% of the ROIs, MS worsening was observed at T1, which was associated with qualitative and quantitative worsening in 75% of NPAs by OCTA. Positive correlations between MS and both PD and VLD were found. Fisher's test showed an association between the improvements in MP and VLD. Conclusions: An association between OCTA and MP-1 parameter changes was found. The concomitant functional and morphological improvement in half of the ROIs suggests that anti-VEGF treatment may promote retinal changes that result in a better functional response. [ABSTRACT FROM AUTHOR]

Anti-VEGF agents have been demonstrated to be more effective than sham or laser in treating center-involving diabetic macular edema (DME) in short-term pivotal trials. The literature regarding long-term outcomes (5 years or more) of anti-VEGF treatments in DME is limited. A literature search was conducted using the PubMed and Cochrane Library databases. Key words included 'diabetic macular edema,' 'diabetic retinopathy,' 'vascular endothelial growth factor,' 'anti-VEGF,' 'long*,' and 'five-year.' 21 articles were included in the final review that examined the 5-year visual and anatomic outcomes of anti-VEGF treatments in DME. Combined analysis of the mean 5-year change in visual acuity and central retinal thickness was conducted. Anti-VEGF agents provide significant vision and anatomic improvements to patients with DME through at least 5 years of treatment. Given their minimal adverse effect profile, superior impact on visual and anatomic outcomes, and likely cost benefit, anti-VEGF agents should be initiated as early as possible in individuals with clinically significant DME causing vision loss. Further work is required to identify early indicators of poor treatment response and to develop longer-acting anti-VEGF treatments. [ABSTRACT FROM AUTHOR]

Background and Objectives: To evaluate the recurrence of diabetic macular edema (DME) after loading an injection of anti-VEGF agents by a pro re nata (PRN) protocol using central retinal thickness (CRT) as a re-injection criterion. Materials and Methods: This is a retrospective, observational single-center study. DME patients with a central retinal thickness (CRT) over 350 μm received a PRN injection of anti-VEGF agents following one to three consecutive monthly loading injections (bevacizumab, ranibizumab, and aflibercept) for 6 months from January 2012 to June 2019. Results: We enrolled a total of 72 eyes for loading injections and the mean CRT improved from 434.04 ± 139.4 μm (before treatment) to 362.9 ± 125.0 μm after the loading injection. One week after injection, 36 eyes (50%) obtained a CRT of ≤350 μm. Fourteen eyes (19.4%) remained with a CRT of ≤350 μm for 6 months without additional injections. A total of 22 eyes (30.6%) had a CRT of >350 μm at 6 months. Fifteen eyes did not receive additional injections because of visual improvement. Conclusions: About 20% of DME patients can be maintained at a CRT of ≤350 μm for 6 months with only a loading injection. However, there is a tendency to delay additional injections for patients with recurrences using PRN protocol. [ABSTRACT FROM AUTHOR]

Purpose: The treatment of diabetic macular edema (DME) has evolved rapidly in the past decade, highlighting the need to address the challenges of routine clinical practice decision-making through expert consensus agreements. Methods: After a literature review and discussion of real-world experience on DME management, a group of ten retina specialists agreed on a consensus of recommendations for the most appropriate management of DME patients using vascular endothelial growth factor inhibitors (anti-VEGF) in Spain. Results: The panel recommended early treatment initiation in DME patients with worse baseline visual acuity (VA) to maintain or improve outcome. For patients with good VA, an observation strategy was recommended, considering the presence of diabetic retinopathy, optical coherence tomography biomarkers, and impact on patient's quality of life. Based on the available evidence and clinical experience, the panel recommended the use of anti-VEGF intensive loading doses with the objective of achieving anatomic and visual responses as soon as possible, followed by a Treat & Extend (T&E) strategy to maintain VA improvement. Aflibercept was recommended for patients with a baseline decimal VA < 0.5, followed by a T&E strategy, including the possibility to extend frequency of injections up to 16 weeks. Conclusion: An expert panel proposes a consensus for the management of DME in Spain. Early treatment initiation with anti-VEGF in DME patients is recommended to maintain or improve VA; aflibercept is recommended for patients with a poor baseline VA. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is considered one of the leading causes of vision loss globally. It principally causes upregulation of pro-angiogenic, proinflammatory, and vascular permeability factors such as vascular endothelial growth factor (VEGF), leading to neovascularisation. The advanced stage of DR or proliferative diabetic retinopathy (PDR) is of more concern, as it leads to vitreous haemorrhage and traction retinal detachment. Various risk factors associated with PDR include hyperglycemia, hypertension, neuropathy, dyslipidemia, anaemia, nephropathy, and retinal complications of drugs used for diabetes. Current management approaches for PDR have been stratified and involve pan-retinal photocoagulation, vitrectomy, and anti-VEGF agents. Given the emerging role of anti-VEGF agents as a favourable adjunct or alternative therapy, they have a critical role in the management of PDR. The review emphasises current management approaches for PDR focusing on anti-VEGF therapy. The review also highlights the risk/benefit evaluation of the various approaches employed for PDR management in various clinical scenarios. [ABSTRACT FROM AUTHOR]

Anti-vascular endothelial growth factor (Anti-VEGF) agents are the standard of care for diabetic macular edema (CI-DME) with vision loss. They are commonly administered using several treatment protocols, including fixed, pro re nata (PRN) and treat-and-extend (T&E) regimens. Because of the lack of evidence defining an ideal treatment paradigm, we systematically compared T&E with fixed or PRN regimens. Visual acuity improvement was similar when comparing T&E to fixed or PRN dosing at 12 and 24 months. Regarding anatomic outcomes, no significant difference was found between T&E and fixed regimens for central retinal thickness or central subfoveal thickness at 12 and 24 months. Similarly, no significant difference was found for central retinal thickness at 12 months for T&E versus PRN regimen. Regarding total number of injections, no significant difference existed between T&E versus fixed regimens at 12 months. PRN regimens delivered fewer injections compared to T&E regimens at 12 months. The results of this analysis support that visual acuity and anatomic outcomes at 12 and 24 months are similar between T&E with either fixed or PRN regimens. More head-to-head trials comparing T&E versus fixed and PRN dosing are needed to provide visual and functional outcome data beyond year 2. PROSPERO Registration: CRD42021249362. [ABSTRACT FROM AUTHOR]