MV-833

To compare the risk of renal adverse events, particularly acute kidney injury (AKI), between intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.

Meta-analysis.

A systematic literature search was conducted on Ovid Medline, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published from January 2005 to February 2024 involving adult patients receiving anti-VEGF intravitreal injections for age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. The primary outcome was the comparative risk of AKI between anti-VEGF agents and sham injections. Secondary outcomes involved other renal adverse events. Subgroup analyses were conducted by specific disease indications. A random-effects model was used for meta-analysis to estimate risk ratios (RRs) and their 95% confidence intervals, with a P value of <.05 representing statistical significance. Risk of bias was assessed using the Cochrane Risk of Bias 2 (ROB2) tool, and the certainty of evidence was evaluated through the Cochrane Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework.

A total of 10,031 eyes from 11 RCTs were included. No significant differences were found in the risk of acute or chronic renal conditions, obstructive uropathies, neoplasia, or infectious processes between anti-VEGF agents and sham therapy. AKI was reported in 5.4% (n = 10/185) of patients treated with bevacizumab, 1.3% (n = 6/456) with sham, 1.0% (n = 48/4724) with aflibercept, 0.8% (n = 15/1929) with faricimab, 0.5% (n = 5/1098) with brolucizumab, and 0.3% (n = 5/1639) with ranibizumab. No significant differences in AKI risk were observed between any of the anti-VEGF agents and sham (P > .05 for all comparisons). However, there was an increased risk of patient-reported symptoms with 1.25 mg bevacizumab compared to 2 mg aflibercept (RR = 3.26, 95% CI = 1.07-9.93, P = .04), driven primarily by reports of hematuria: 4.3% (bevacizumab), 0.7% (sham), 0.2% (aflibercept), 0.1% (faricimab), and 0.1% (ranibizumab).

US Food and Drug Administration (FDA)-approved intravitreal anti-VEGF agents do not significantly increase the risk of AKI compared to sham injections. Nevertheless, variations in patient-reported renal symptoms were observed across different anti-VEGF drugs. These variations were influenced primarily by differences in hematuria events, which may be a result of differential systemic absorption by these agents. These results underscore the importance of continuous monitoring and pharmacovigilance.

To examine rates of submacular hemorrhage in patients undergoing anti-vascular endothelial growth factor (VEGF) injections, comparing rates between specific anti-VEGF agents.

Retrospective clinical cohort study.

All patients in the database from January 2015 to November 2023 with a diagnosis of neovascular age-related macular degeneration and accompanying submacular hemorrhage (SMH). SMH prevalence and associated anti-VEGF injection type were analyzed in 140,915 eyes (of which 9107 had SMH) in a nationwide aggregated electronic health care database using chi-square test of proportion. Visual acuity (VA) data was assessed using 2-sample independent t-tests. The primary outcome was rate of SMH per injection type. Secondary datapoints examined were time between SMH diagnosis and last anti-VEGF injection, number of injections before SMH, treatment interval at time of SMH, VA before and at 12 months after SMH, eyes undergoing pars plana vitrectomy (PPV) within 30 days of SMH, and VA before PPV and at 12 months after PPV.

The last injection type in eyes with SMH was bevacizumab in 3430 (37.8%) eyes, brolucizumab-dbll in 46 (0.51%) eyes, aflibercept in 3221 (35.4%) eyes. Ranibizumab in 2246 (24.7%) eyes, and faricimab-svoa in 155 (1.7%) eyes. Rates of SMH were significantly higher (P ≤ .001) for last injection with bevacizumab compared to every other injection type. Rates of SMH were significantly lower (P = .0004) for last injection with faricimab-svoa or ranibizumab injections each had significantly shorter (mean and standard deviation 48.9 (27.9), P < .02; mean and standard deviation 59.6 (38.2), P = .003, respectively) mean time between SMH diagnosis and last injection than did patients undergoing any other injection. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type among all patients. The number of patients who underwent PPV were 52 (1.51%) for bevacizumab, 4 (8.7%) for brolucizumab-dbll, 58 (1.8%) for aflibercept, 41 (1.8%) for ranibizumab, and 3 (1.9%) for faricimab-svoa. Mean VA before SMH and at 12 months after SMH did not significantly differ by injection type in patients undergoing PPV.

Faricimab may be more protective than other anti-VEGF injections against SMH in patients with neovascular age-related macular degeneration.