Endophthalmitis following same-day bilateral anti-VEGF injections: a systematic review.

PURPOSE: To review the risk of endophthalmitis in same-day bilateral anti-VEGF injections. METHODS: We searched 12 literature databases for studies on the risk of endophthalmitis after same-day bilateral intravitreal anti-VEGF injections. Data extraction was made independently by two authors and discussed afterward until reaching consensus. RESULTS: Seventeen studies were included with a total of 138,478 intravitreal anti-VEGF injections (69,239 bilateral injections sessions) given in at least 7579 patients. In total, 33 cases of endophthalmitis had occurred, and no cases were bilateral. The incidence of endophthalmitis ranged from 0 to 0.53% per intravitreal injection across studies. CONCLUSIONS: We suggest that clinicians can consider same-day treatment of both eyes of patients in need of bilateral intravitreal anti-VEGF injection therapy, but larger studies are needed to quantify the exact risk of endophthalmitis.

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

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.

ASSOCIATION BETWEEN RETINAL PIGMENT EPITHELIUM TEAR AND ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY: A Systematic Review and Meta-Analysis.

PURPOSE: To identify the prevalence of retinal pigment epithelium tear (RPET) after anti-vascular endothelial growth factor (VEGF) therapy and determine the efficacy of continued anti-VEGF therapy in patients with RPET. METHODS: All relevant clinical trials and observational studies in several online databases were screened. The main outcomes were the incidence of RPET after anti-VEGF therapy and changes in visual acuity for patients with RPET treated with continued anti-VEGF. RESULTS: The pooled incidence of RPET after anti-VEGF therapy from 24 studies with 17,354 patients was 1.9% (95% CI: 1.3-2.7). Most new RPET cases were concentrated in the first month at baseline or after the first injection during anti-VEGF therapy and gradually decreased by the subsequent month or injection. 13 studies with 157 patients reported that for patients who received anti-VEGF therapy after RPET, their pooled best-corrected visual acuity improved, but did not reach a significant level (standardized mean differences 0.34; 95% CI: -0.03 to 0.71). CONCLUSION: The incidence of RPET after anti-VEGF therapy is low. The intravitreal anti-VEGF injection may accelerate this process. For patients with RPET, maintenance of anti-VEGF therapy ensures visual acuity stability.

Smoking and short-term response to intravitreal anti-Vascular Endothelial Growth Factor injections in neovascular age-related macular degeneration.

PURPOSE: To evaluate the role of smoking status on the response to three monthly intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) injections in treatment-naive neovascular AMD (nAMD) patients. METHODS: We conducted a single-center, retrospective, case-control cohort study in Belgium. RESULTS: Intravitreal treatment (IVT) was performed in 147 eyes of 131 patients, including 92 females (70%). Mean age at the time of the first IVT was 79±9 years. Seventeen patients (13%) were actively smoking at the time of the anti-VEGF IVT. On average, active smokers were 11 years younger than non-smokers when starting IVT treatment. They also showed more frequent subretinal fluid than non-smokers (94% vs. 65%). Mann-Whitney analyses comparing change in central macular thickness and change in logarithm of the minimum angle of resolution visual acuity between active smokers and non-smokers showed no significant difference in treatment response between both groups. Likewise, no significant difference was found when comparing treatment response between patients with less than 10 pack-years (PY) (including never-smokers) and patients with over 10 PY. In a binary logistic regression model, male patients responded worse to anti-VEGF IVT than their female counterparts, with an odds ratio (OR) of 0.27 for good response. This was the only statistically significant predictor of treatment response. CONCLUSION: Our study failed to demonstrate an effect of smoking on the short-term treatment response to anti-VEGF in nAMD.

[Relationship between treatment and cost with visual acuity improvement in age-related macular degeneration]. / Relación del tratamiento y coste con la ganancia de agudeza visual en la degeneración macular asociada a la edad

BACKGROUND: We examined the relationship between visual acuity changes (VA) and the cost of care and treatment with anti-vascular endothelial growth factors (antiVEGF) in patients diagnosed with age-related exudative macular degeneration (exudative AMD). METHODS: Observational, longitudinal, retrospective study of patients ≥50 years of age diagnosed with exudative AMD, with a log-MAR VA between 0.6 and 0.06. and 0.06. Follow-up and treatment were done in our tertiary hospital between January 1, 2014 and December 31, 2018. RESULTS: The study included 778 patients; 62.2% female and mean age 79.83±7.94 years; 957 eyes had exudative AMD. Mean of final VA (0.65±0.45) increasing 3.2% compared to initial values. Ranibizumab was administered to 60.3% of the eyes, aflibercept to 10.2% and ranibizumab + aflibercept (mixed group) to 29.5%. Significant increase in VA was seen in the group with the mixed treatment, with no inter-group differences. Although follow-up/treatment was longer for the mixed group, they received fewer anti-VEGF injections and optical coherence tomography (OCT). The total expenditure per year and treated eye was € 1,972.7±824.5; costs were higher for visit, OCT, and treatment in the aflibercept group, and lower for fluorescein angiography, antiVEGF treatment, and total costs in the mixed group. Decimal VA gain had a cost of € 872±1,077.7 with no significant inter-group differences. CONCLUSIONS: AntiVEGF treatments (ranibizumab, aflibercept, or both) maintained VA in patients with exudative AMD. Overall, care and treatment costs were lower in the group that received both drugs.

1†Retreatment for reactivation of ROP following initial anti-VEGF injections. A 5-year retrospective study.

To present the retreatment rates and the characteristics of ROP reactivation, as well as the differences between bevacizumab and ranibizumab injections in premature babies treated in our department over the past 5 years.A retrospective analysis of babies with treated ROP was performed. 89 babies who required treatment from 2017 to 2022 were examined. We studied the severity of their disease with regards to their gestational age, treatment time and type and the need of further treatment. We also focused on the comparison of anti-VEGF agents for ROP.22 out of 89 babies (14 boys and 8 girls) with aggressive posterior retinopathy of prematurity (APROP) and mean gestational age of 25+3w received initially anti-VEGF injections. 16 of those (11 boys and 5 girls) required retreatment with diode laser. 9 out of these 16 babies were treated with ranibizumab (Lucentis) and 7 with bevacizumab (Avastin). It is also of note that only 2 out of 67 babies who initially received laser treatment needed a complementary laser session.The majority of babies with aggressive ROP who receive anti-VEGF agents will most probably require further laser treatment. At an equal level of retinal damage, it seems that their response to ranibizumab and bevacizumab is similar.

Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Real-world study to evaluate the efficacy and safety of intravitreal brolucizumab for refractory neovascular age-related macular degeneration.

This retrospective study evaluated the real-world safety and effectiveness of switching to intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). A total of 81 patients who received brolucizumab injections as switch therapy were followed for more than 3 months. A good response was defined as better anatomical improvement or extended injection intervals compared with previous anti-vascular endothelial growth factor (VEGF) treatment over a mean follow-up period of 41.4 weeks. Approximately 82.7% of patients showed a good response after switching. After 1 year, patients showed significant visual gains (+ 6.6 letters, p = 0.006) and central retinal thickness reductions (- 112.6 µm, p < 0.001), with 30.8% having injection intervals extended over 12 weeks. In the poor-response group, visual acuity and anatomical outcomes worsened soon after switching. More previous injections, thinner baseline central retina, and the presence of prechoroidal cleft or polypoidal lesion resulted in a better response (p < 0.05). Adverse effects occurred in eight eyes (9.9%), including one retinal vascular occlusion and seven intraocular inflammation cases, which were unrelated to the response. Most patients with nAMD refractory to anti-VEGF treatment demonstrated anatomical improvement or extended injection intervals after switching. This study shows that identified structural biomarkers may predict treatment response and select an appropriate therapeutic strategy.

Systematic review of efficacy and meta-analysis of safety of ranibizumab biosimilars relative to reference ranibizumab anti-VEGF therapy for nAMD treatment.

TOPIC: This systematic review and meta-analysis provides a summary of the efficacy and safety of ranibizumab biosimilars relative to reference ranibizumab anti-vascular endothelial growth factor (VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD). METHODS: We conducted systematic searches from January 2003 to August 2022 on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials. We included studies reporting changes in early treatment diabetic retinopathy study-measured best-corrected visual acuity (BCVA), number of patients who lost or gained more than 15 letters in BCVA from baseline, changes in retinal thickness and adverse events between treatment arms. The following studies were excluded: studies that did not report visual outcomes following biosimilar and reference ranibizumab intravitreal injections, study arms combining anti-VEGF agents with laser or steroid injections, sham injections as a control comparator, studies without English full texts and non-comparative, observational study design. RESULTS: Five studies reported on four randomised controlled trials (RCTs) and 1544 eyes at baseline were included in this systematic review and meta-analysis. The studies in our systematic review found no significant differences between reference ranibizumab and ranibizumab biosimilar medications (FYB201, SB11, RanizuRel and Lupin's ranibizumab) for visual and anatomical outcomes. No significant differences were detected between biosimilar and reference ranibizumab for treatment emergent adverse events (risk ratio, RR 1.06, 95% CI (0.91 to 1.23), p=0.45, I2=52%) or IOP-related adverse events with significant heterogeneity (RR 2.59, 95% CI (0.11 to 62.25), p=0.56, I2=76%). CONCLUSION: This systematic review of four RCTs demonstrated no significant difference in visual outcomes, retinal thickness outcomes, as well as meta-analysis of adverse events between biosimilar and reference ranibizumab therapies for nAMD treatment.

Aflibercept for long-term treatment of diabetic macular edema and proliferative diabetic retinopathy: a meta-analysis.

Purpose: This meta-analysis compared the long-term (12 months or 24 months) efficacy and safety of intravitreal aflibercept injection (IAI) for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). Methods: We selected 16 randomized controlled trials (RCTs) performed after 2015 that had a minimum of 12 months and up to 24 months of treatment and conducted a meta-analysis with Review Manager version 5.3. Visual acuity (VA), central subfield thickness (CST) and adverse events were the outcomes selected for evaluation from the eligible studies. Results: Based on 16 RCTs, we evaluated a total of 7125 patients. For PDR and severe DME with poor baseline vision, after a minimum of 12 months and up to 24 months of treatment, the aflibercept treatment group obtained better VA improvement than the focal/grid laser photocoagulation treatment group (MD=13.30; 95%CI: 13.01~13.58; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, PRP, et al.) group (MD=1.10; 95%CI: 1.05~1.16; P<0.001). In addition, the aflibercept treatment group got higher CST reduction than the focal/grid laser photocoagulation treatment (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001) or other treatments (ranibizumab, focal/grid laser photocoagulation, et al.) group (MD=-33.76; 95%CI: -45.53 ~ -21.99; P<0.001). There was no significant difference in the overall incidence of ocular and non-ocular adverse events in each treatment group. Conclusions: This meta-analysis showed that the advantages of IAI are obvious in the management of DME and PDR with poor baseline vision for long-term observation (a minimum of 12 months and up to 24 months) with both VA improvement and CST reduction. Applied IAI separately trended to be more effective than panretinal photocoagulation separately in VA improvement for PDR. More parameters should be required to assess functional and anatomic outcomes.

Systemic Adverse Events Among Patients With Diabetes Treated With Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

Importance: Anti-vascular endothelial growth factor (VEGF) agents are currently the mainstay of treatment for diabetic retinopathy (DR). Although effective, data on their systemic safety remains inconclusive, particularly in high-risk patient groups. Objective: To explore the systemic safety of intravitreal anti-VEGF agents among patients with diabetes. Design, Setting, and Participants: This was a retrospective, longitudinal population-based analysis of the Corporate Data Warehouse, a large-scale database of patients within the US Veteran Health Affairs. All patients 18 years and older with type 2 diabetes who were seen at any Veterans Affairs health care facility in the US between January 1, 2011, and December 31, 2012, were identified. Data were then extracted on incident systemic adverse events among this patient cohort from January 1, 2013, to December 31, 2017. All individuals with diabetes who did and did not receive anti-VEGF injections were included. Patients with a history of prior systemic adverse events and those who received an intravitreal injection between January 1, 2011, and December 31, 2012, were excluded. Data were analyzed from October 2019 to March 2023. Exposure: Anti-VEGF injection. Main Outcomes and Measures: Proportion of patients with any incident systemic adverse event, acute myocardial infarction, cardiovascular disease, or kidney disease at 1-, 3-, and 5-year follow-up. Results: A total of 1 731 782 patients (mean [SD] age, 63.8 [12.3] years; 1 656 589 [95.7%] male) with type 2 diabetes were included. DR was present in 476 013 (27.5%), and 14 022 (0.8%) received anti-VEGF injections. Of the total number of patients with type 2 diabetes, 321 940 (18.6%) developed systemic adverse events between 2013 and 2017. The 5-year cumulative incidence of any systemic adverse event was 37.0% (5187/14 022) in the injection group vs 18.4% (316 753/1 717 760) in the noninjection group (P < .001). Anti-VEGF injections were independently associated with a higher likelihood of developing any systemic adverse event (odds ratio, 1.8; 95% CI, 1.7-1.9) when controlling for age, race, sex, ethnicity, tobacco use, severity of DR, Deyo-Charlson Comorbidity Index score, mean hemoglobin A1c, total number of injections, and statin use. Conclusion and Relevance: In this study, intravitreal anti-VEGF injections were independently associated with a higher likelihood of systemic adverse events among patients with diabetes.

TEN-YEAR VISUAL OUTCOME AND CHANGE IN CHORIORETINAL ATROPHY AFTER INTRAVITREAL RANIBIZUMAB FOR MACULAR NEOVASCULARIZATION IN PATHOLOGIC MYOPIA.

PURPOSE: To investigate the 10-year visual outcome and chorioretinal atrophy after a single intravitreal ranibizumab injection followed by a pro re nata regimen for myopic macular neovascularization in pathologic myopia, and to identify the factors associated with 10-year best-corrected visual acuity (BCVA). METHODS: This retrospective observational study evaluated 26 consecutive treatment-naïve eyes (26 patients) with myopic macular neovascularization in pathologic myopia who underwent a single intravitreal ranibizumab followed by a pro re nata regimen of intravitreal ranibizumab and/or intravitreal aflibercept injection and observed over 10 years. We assessed changes in BCVA and morphological parameters, including the META-PM Study category as a chorioretinal atrophy index. RESULTS: The logarithm of the minimum angle of resolution BCVA changed from 0.36 (Snellen, 20/45) ± 0.39 to 0.39 (20/49) ± 0.36 over 10 years of observation. Compared to baseline, 1-year BCVA improved ( P = 0.002), whereas 2 to 10-year BCVA was not significantly different. Total injection frequency was 3.8 ± 2.6. In none of the eyes, 10-year BCVA was 20/200 or less. Ten-year BCVA correlated with baseline BCVA ( P = 0.01, r = 0.47). The META-PM Study category progressed in 60% of eyes. There were no drug-induced complications. CONCLUSION: Best-corrected visual acuity in eyes with myopic macular neovascularization in pathologic myopia was maintained for 10 years after a single intravitreal ranibizumab followed by a pro re nata regimen without drug-induced complications. The META-PM Study category progressed in 60% of eyes, especially those with older baseline age. Early diagnosis and treatment of myopic macular neovascularization are essential to maintain good long-term BCVA.

Comparing cardiovascular adverse events in cancer patients: A meta-analysis of combination therapy with angiogenesis inhibitors and immune checkpoint inhibitors versus angiogenesis inhibitors alone.

Anti-VEGF (vascular endothelial growth factor) agents were associated with increased risk of several cardiovascular events, while one meta-analysis did not show any significantly increased risk of cardiotoxicity associated with the use of immune checkpoint inhibitors (ICIs). This meta-analysis of randomized-controlled trials (RCTs) was designed to compare cardiovascular toxicity of anti-VEGF agents plus ICI vs anti-VEGF agents without ICIs. A systematic search of the literature was conducted to include all full papers reporting about phase II and III randomized controlled trials (RCTs) conducted in patients with solid malignancies randomized to an anti-VEGF agent plus an ICI vs. an anti-VEGF agent without an ICI. Overall incidences of cardiovascular events were compared between these two treatment groups estimating the corresponding odds ratios. This analysis suggests that ICIs may increase the risk of cardiovascular toxicities associated with anti-VEGF therapies. Further research, including real world studies, is warranted.

Risk analysis for patients with arterial thromboembolic events after intravitreal ranibizumab or aflibercept injections.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population-based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011-2018) were obtained from Taiwan's National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11-0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41-8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35-77.2 and IS: aHR, 290.2; 95% CI, 103.1-816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections.

Cardiovascular and Cerebrovascular Safety of Ranibizumab, Bevacizumab, and Aflibercept in Ocular Diseases: An Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

The cardiovascular and cerebrovascular safety of ranibizumab, bevacizumab, and aflibercept for ocular diseases is unclear. This study aimed to evaluate and compare the cardiovascular and cerebrovascular safety in patients receiving ranibizumab, bevacizumab, and aflibercept for ocular disease. A cross-sectional study was conducted from 2017 (Q1) to 2021 (Q4) in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. The outcomes of interest were central nervous system vascular disorders, ischemic heart disease, hypertension, pulmonary hypertension, torsade de pointes/QT prolongation, embolic and thrombotic events, cardiac arrhythmias, cardiac failure, and cardiomyopathy. Data mining was performed by a disproportional method with a compression, using compressed reporting odds ratios (sRORs) with 95% confidence intervals (CIs) to measure signals. The results showed 1462 cardiovascular and cerebrovascular events associated with aflibercept, 834 with ranibizumab, and 150 with bevacizumab. Ranibizumab, bevacizumab, and aflibercept were linked to central nervous system vascular disorders (sROR, 5.57[95%CI, 4.95-6.26] vs sROR, 2.23 [95%CI, 1.75-2.85] vs sROR, 2.73[95%CI, 2.43-3.06]), ischemic heart disease (sROR, 3.31[95%CI, 2.65-4.13] vs sROR, 1.98 [95%CI, 1.24-3.16] vs sROR, 3.00 [95%CI, 2.46-3.65]), embolic and thrombotic (sROR, 3.36 [95%CI, 3.04-3.72] vs sROR, 2.16 [95%CI, 1.70-2.74] vs sROR, 5.25 [95%CI, 4.82-5.72]). Both ranibizumab and bevacizumab produced hypertension (sROR, 1.73 [95%CI, 1.41-2.12] vs sROR, 1.46 [95%CI, 1.03-2.06]) and arrhythmias (sROR, 2.82 [95%CI, 1.99-3.99] vs sROR, 2.13 [95%CI, 1.08-4.22]) signals. The signals of heart failure were detected in ranibizumab (sROR, 5.64 [95%CI, 4.08-7.79]) and aflibercept (sROR, 2.80 [95%CI, 2.03-3.86]). Ranibizumab, bevacizumab, and aflibercept for ocular disease have different safety profiles in cardiovascular and cerebrovascular. The overall cardiovascular and cerebrovascular risk of the patient should be thoroughly assessed in order to select the safest drug for treatment.

Intravitreal anti-vascular endothelial growth factor, laser photocoagulation, or combined therapy for diabetic macular edema: A systematic review and network meta-analysis.

Purpose: To conduct a network meta-analysis (NMA) comparing the efficacy of anti-vascular endothelial growth factor (VEGF) therapy alone versus laser photocoagulation (LP) therapy alone or anti-VEGF therapy combined with LP therapy for diabetic macular edema (DME). Methods: PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were systematically searched for studies comparing anti-VEGF therapy alone versus LP therapy alone or anti-VEGF therapy combined with LP therapy for DME. Primary outcomes were mean best-corrected visual acuity (BCVA) and central macular thickness (CMT) change. Relevant data were collected and pooled using NMA. Results: A total of 13 randomized controlled trials were included in our NMA. Anti-VEGF therapy significantly improved BCVA the most compared to the combined (mean difference [MD] = 1.5; 95% confidence interval [CI]: 0.084, 2.7) and LP (MD = 6.3; 95% CI: 5.1, 7.6) therapies at six months, while there was no difference in reducing CMT at six months between the anti-VEGF and combined therapies (MD = -16; 95% CI: -46, 13). At 12 months, no significant difference was found between the anti-VEGF and combined therapy in terms of BCVA (MD = 0.1; 95% CI: -1.7, 1.5) and CMT (MD = 21; 95% CI: -3.0, 44). Conclusion: There was no significant difference between the anti-VEGF therapy and combined therapy. For the long-term treatment of patients with DME, combined therapy is recommended. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022376401.

INVESTIGATION OF INCIDENCE AND CAUSES OF ACUTE VISION LOSS DURING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION DURING A FOUR-YEAR FOLLOW-UP.

PURPOSE: To investigate the incidence, risk factors, and outcomes of patients with age-related macular degeneration who experienced acute vision loss despite periodic injections of anti-vascular endothelial growth factor treatment for 4 years. METHODS: This retrospective cohort study included patients who were diagnosed with treatment-naive neovascular age-related macular degeneration and completed a 4-year follow-up. The incidence and risk factors for the occurrence of three or more lines of visual loss at every checkup were investigated. RESULTS: The analysis included 76 eyes of 76 patients. Acute vision loss occurred in 30 eyes (39.5%) over 4 years. Lower baseline best-corrected visual acuity and disrupted ellipsoid zone were independent predictors of vision loss occurrence. Although the causes and timing of visual acuity loss varied, retinal pigment epithelium tears were observed only in the first year. Most patients (86.7%) who experienced vision loss recovered their vision to pre-loss levels at least once; however, the final best-corrected visual acuity was worse than that in the group that did not experience acute vision loss. CONCLUSION: Approximately half of the patients with age-related macular degeneration experienced acute vision loss during a 4-year follow-up, despite continuous anti-vascular endothelial growth factor treatment. Most patients recovered from vision losses temporarily; however, they experienced worse visual outcomes subsequently.

Incidence of ocular hypertension after anti-VEGF injections: examining the effect of drug filtration and silicone-free syringes.

OBJECTIVE: To examine the difference in incidence of ocular hypertension (OHT) following the introduction of filtered anti-vascular endothelial growth factor (anti-VEGF) medication in silicone-free syringes. DESIGN: Retrospective cohort study. METHODS: A retrospective review of consecutive treatment-naive patients receiving intravitreal anti-VEGF injections in a group practice was performed. Data from the cohort receiving nonfiltered anti-VEGF in insulin syringes (IS group) was collected from June 2015. Data from the cohort receiving filtered anti-VEGF in silicone-free syringes (SFS group) was collected from June 2019. Follow up data were collected at 1 year. Exclusion criteria included prior anti-VEGF treatment, known glaucoma or diagnosis of glaucoma suspect before anti-VEGF treatment, neovascular glaucoma, steroid use, or vitrectomy during follow-up. Primary outcome was the cumulative incidence of intraocular pressure (IOP) > 21 mmHg and IOP ≥ 30 mm Hg at any follow-up visit. The use of IOP lowering therapy was also recorded. RESULTS: The mean age (71 ± 13 years), mean number of injections (9.6 ± 2.7), and median follow-up time (392 ± 57 days) were similar between groups. The incidence of IOP ≥ 21 mm Hg was 34% (34/100) in the IS group and 15% (15/100) in the SFS group (p = 0.025). The incidence of IOP ≥ 30 mm Hg was 8% (8/100) in the IS group and 0% (0/100) in the SFS group (p =0.004). The incidence of IOP-lowering therapy was 13% in the IS group and 0% in the SFS group (p =0.0002). CONCLUSION: The incidence of OHT and treatment with IOP-lowering therapy significantly decreased after the introduction of filtered anti-VEGF medication and silicone-free syringes.