Comparative Effectiveness of Intravitreal Anti-Vascular Endothelial Growth Factor Therapies for Managing Neovascular Age-Related Macular Degeneration: A Meta-Analysis

Abstract

Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) have become the standard of care for age-related macular degeneration (AMD). Although most pivotal trials have used monthly injections, alternative strategies that enable the injections to be administered on a more flexible schedule, including pro re nata (PRN) and treat-and-extend (T&E) regimens, are being applied more frequently. This review sought to provide further scientific evidence about the visual outcomes and treatment burden among the currently available anti-VEGF agents and regimens, including aflibercept, ranibizumab, abicipar and brolucizumab. To this end, a systematic review of published randomized studies was conducted from the MEDLINE and EMBASE databases and the Cochrane library, and a meta-analysis was applied to the obtained data using single-means modeling to compare the efficacy and maintenance among the different available treatments and regimens at Years 1 and 2. Quality analysis identified the best-informed data for modeling purposes. Overall, 47 relevant publications were retrieved for the analysis. Superior efficacy, meaning that there were observed improvements in visual acuity (VA) and central retinal thickness (CRT), occurred with monthly versus PRN regimens, yet a higher IVI number was also observed. Conversely, the T&E regimens displayed similar efficacy to the monthly regimens, but with a reduced IVI number. Aflibercept T&E exhibited similar efficacy to ranibizumab T&E, but with significantly lower IVI numbers at both Year 1 (p < 0.0001) and Year 2 (p = 0.0011). Though all of the regimens resulted in maintained efficacy between Years 1 and 2, the required IVI number varied. The retrieved data did not enable other regimens or newer anti-VEGF agents such as brolucizumab to be compared. In conclusion, the T&E regimens were shown to be the most efficient, optimizing durable effectiveness whilst minimizing the IVI number in newly diagnosed exudative AMD, with aflibercept requiring the lowest IVI number.

The Reinforced Treat-and-Extend Protocol for Exudative Age-Related Macular Degeneration: Retrospective Assessment of 24-Month Real-World Outcomes in France

“…The authors demonstrated a lower mean BCVA gain at 2 years (2.5 vs. 6.74 ETDRS letters here) for less IVT injections (11.4 vs. 14.9 here), but a similar number of consultations (8.9 vs. 8.6 here). Finally, focusing on the most recent meta-analysis by Matonti et al [ 37 ] comparing different IVT anti-VEGF therapies using fixed, PRN, or T&E protocols (a total of 47 different studies), the T&E protocols were found to be the most efficient. Indeed, the T&E protocols showed durable improvements in visual acuity/CRT whilst reducing IVT injection number.…”

“…Note that we took into account findings from the patient group under an irregular treatment protocol for the RAINBOW study [ 24 ]. ALTAIR study [ 18 ]; ANCHOR study [ 3 ]; ARIES study [ 19 ]; ARMADA study [ 36 ]; Kim et al [ 43 ]; MARINA study [ 4 ]; Matonti et al [ 37 ]; Mekjavic et al [ 44 ]; Observe and Plan (O&P) study [ 22 ]; TREX-AMD study [ 11 ]; PrONTO study [ 8 ]; Vardarinos et al [ 45 ]; VIEW study [ 7 ]. BCVA best-corrected visual acuity, ETDRS Early Treatment Diabetic Retinopathy Study, RTE reinforced treat-and-extend …”

Pro re nata versus fixed aflibercept regimen for neovascular age-related macular degeneration: a systematic review and meta-analysis

“…A meta-analysis by Rosenberg et al [27] showed that at 1 year of follow-up, improvement of VA was similar between T&E and fixed regimen (p = 0.95) and significantly higher in T&E when compared to PRN regimen (p < 0.0001). In addition, meta-analysis by Matonti et al [28] showed that mean change of BCVA and central retinal thickness was similar between fixed and T&E regimen, which was superior to PRN regimen. The total number of injections needed was significantly lower in T&E regimen compared to fixed regimen (8.2 vs. 10.6; p < 0.0001).…”

“…The most common reason for study exclusion were wrong outcome measurement, comparisons, and intervention. The four selected articles for meta-analyses synthesis were consisted of 3 controlled trials [17,28,29] and one retrospective cohort study [11].…”

Current Management of Subretinal Hemorrhage in Neovascular Age-Related Macular Degeneration

“…The use of intravitreal anti-VEGF agents is common in the treatment for neovascular AMD (nAMD) as well as other eye diseases such as polypoidal choroidal vasculopathy, proliferative diabetic retinopathy, and CNV resulting from traumatic choroidal rupture [10,[65][66][67]. Compared to other treatment options for SRH, anti-VEGF monotherapy offers an advantage of being less procedurally complex than surgery, with minimal pain, and a low incidence of complications [20].…”