Combinatorial treatment with topical NSAIDs and anti-VEGF for age-related macular degeneration, a meta-analysis

PLOS ONE, Nov 2019

Inflammation is a key pathogenic factor in age-related macular degeneration (AMD). However, the clinical importance of combining anti-VEGF agents and topical NSAIDs to reduce inflammation remains unclear. In this study, we systematically reviewed clinical trials comparing combined treatment versus anti-VEGF alone in AMD patients. We quantified treatment effects via meta-analysis. The pooled weighted mean difference (WMD, -0.91, 95%CI: -1.39 to -0.42, P = 0.0003) demonstrates that combined treatment may reduce required anti-VEGF injection number, probably by means of decreasing central retina thickness (CRT) (WMD = -22.9, 95% CI: -41.20 to -4.59, P = 0.01). The best corrected visual acuity (BCVA) did not change significantly between these two groups (WMD = - 0.01, 95%CI: -0.23 to 0.20, P = 0.90). Topical NSAIDs slightly increased the incidence of foreign body sensation (Odds Ratio [OR] = 2.63, 95%Cl: 1.06 to 6.52, P = 0.76). Combining topical NSAIDs and anti-VEGF agents may provide a new strategy for AMD treatment.

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Combinatorial treatment with topical NSAIDs and anti-VEGF for age-related macular degeneration, a meta-analysis

October Combinatorial treatment with topical NSAIDs and anti-VEGF for age-related macular degeneration, a meta-analysis Songshan Li☯ 0 Andina Hu☯ 0 Wei Wang 0 Xiaoyan Ding 0 Lin Lu 0 Monica M. Jablonski, University of Tennessee Health Science Center, UNITED STATES 0 State Key Laboratory of Ophthalmology, Retina Division, Zhongshan Ophthalmic Center, Sun Yat-sen University , Guangzhou, Guangdong , China Inflammation is a key pathogenic factor in age-related macular degeneration (AMD). However, the clinical importance of combining anti-VEGF agents and topical NSAIDs to reduce inflammation remains unclear. In this study, we systematically reviewed clinical trials comparing combined treatment versus anti-VEGF alone in AMD patients. We quantified treatment effects via meta-analysis. The pooled weighted mean difference (WMD, -0.91, 95%CI: -1.39 to -0.42, P = 0.0003) demonstrates that combined treatment may reduce required anti-VEGF injection number, probably by means of decreasing central retina thickness (CRT) (WMD = -22.9, 95% CI: -41.20 to -4.59, P = 0.01). The best corrected visual acuity (BCVA) did not change significantly between these two groups (WMD = - 0.01, 95% CI: -0.23 to 0.20, P = 0.90). Topical NSAIDs slightly increased the incidence of foreign body sensation (Odds Ratio [OR] = 2.63, 95%Cl: 1.06 to 6.52, P = 0.76). Combining topical NSAIDs and anti-VEGF agents may provide a new strategy for AMD treatment. - Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Introduction Age-related macular degeneration (AMD) is the third leading cause of blindness worldwide, after cataracts and glaucoma [ 1 ] The central vision lost as a result of AMD is irreversible and permanent. AMD produces suffering for the patient and presents a heavy financial burden both to the family of the patient and to society as well. Various factors are involved in the pathogenesis of neovascular AMD (nAMD, an AMD subtype), including aging, oxidative stress, genetic factors, inflammation, and increased vascular endothelial growth factor (VEGF). It appears that VEGF is important in the pathogenesis of AMD. Anti-VEGF treatments, including Ranibizumab, Bevacizumab, and Aflibercept, have shown significant benefit in AMD. However, some patients respond slowly or poorly to anti-VEGF treatment, suggesting that other pathogenic factors should also be considered as treatment targets. Since various studies demonstrate the role of inflammation in the pathogenesis of neovascularization, it is compelling to consider anti-inflammatories as adjunctive therapy [2][ 3 ][ 4 ]. Unlike intraocular steroids, which carry with them substantial side-effects [ 5 ], topical nonsteroidal antiinflammatory agents (NSAIDs) offer simple, safe, and effective means to reduce inflammation through prevention of prostaglandin synthesis via cyclooxygenase inhibition. There has been considerable evidence for the effectiveness of topical NSAIDs in preventing cystoid macular edema after cataract surgery [6]. However, the literature is mixed regarding the effect of NSAIDs in nAMD. Several studies have compared the number of anti-VEGF intravitreal injections needed, best corrected visual acuity (BCVA), central retina thickness (CRT) and side effects following anti-VEGF treatment combined with or without NSAIDs [ 7 ] [ 8 ][ 9 ][ 10 ]. However, the sample sizes were small, casting doubt on the validity of the studies. Here, we perform a meta-analysis of clinical trials, summarizing the effects of combining topical NSAIDs and anti-VEGF in nAMD patients. Methods This study was performed according PRISMA checklist guidelines, and is registered in PROSPERO, number CRD42016039935. Literature search A systematic literature review was performed to identify relevant articles comparing anti VEGF agents combined with topical NSAIDS and anti-VEGF alone for the treatment of nAMD from inception to December 2016. Two independent reviewers (SL, AH), searched electronic databases including PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. Following key words were used: ªanti-VEGF OR ranibizumab OR bevacizumab OR Aflibercept OR Lucentis OR Avastin OR Eyleaº AND ªmacular degeneration OR AMD OR ARMDº AND ªanti-inflammatory agents non-steroidal OR NSAIDs OR bromfenac OR diclofenac OR ketorolac OR nepafenacº. No language restrictions were set for the search. References of included studies and major reviews were searched manually for additional eligible studies. Grey articles were searched from the OpenGrey website and Google Scholar. After excluding duplications derived from different sources, article titles and abstracts were evaluated by two independent researchers to exclude case reports, cross-sectional studies, retrospective studies and (...truncated)


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Songshan Li, Andina Hu, Wei Wang, Xiaoyan Ding, Lin Lu. Combinatorial treatment with topical NSAIDs and anti-VEGF for age-related macular degeneration, a meta-analysis, PLOS ONE, 2017, Volume 12, Issue 10, DOI: 10.1371/journal.pone.0184998