Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration

Abstract

Background Anti-vascular endothelial growth factor (VEGF) therapy is currently the most effective therapy of exudative age-related macular degeneration (AMD). The aim of this study was to assess long-term benefits of intensive aflibercept and ranibizumab anti-VEGF therapy in patients with exudative AMD. Methods Two clinical trial sites recruited their original subjects for a re-evaluation 7 years after the baseline visit of the phase-3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 2) trial. Forty-seven eyes of 47 patients with AMD originally treated with ranibizumab (14 eyes) or aflibercept (33 eyes) were included. Results Mean number of injections was 17.8 ± 3.0 during participation in the VIEW 2 trial. Fourteen of 47 (30%) eyes were given additional injections with a mean number of 5.7 ± 4.5 after the trial. At a mean follow-up time of 82 ± 5 months best corrected visual acuity (BCVA) remained stable or improved (≤ 10 letters lost) in 55% of patients in the entire study population, in 43% in the ranibizumab group and in 60% in the aflibercept group. In both groups combined mean BCVA was 54 ± 13 letters at baseline, 65 ± 17 letters at the end of the intensive phase and 45 ± 25 letters at the end of follow-up. There was no statistically significant difference in BCVA between the two groups at baseline (p = 0.88) and at the end of follow-up (p = 0.40). Macular atrophy was observed in 96% of eyes, average area was 7.22 ± 6.31 mm2 with no statistically significant difference between groups (p = 0.47). Correlation between BCVA at end-of-follow-up and the area of atrophy was significant (p < 0.001). At the end of follow-up, fluid was detected in 7 of 47 eyes (15%) indicating disease activity. Conclusion Long-term efficacy of aflibercept and ranibizumab was largely consistent. Following a two-year intensive therapy with as-needed regimen, BCVA was maintained or improved in almost half of the patients and in the ranibizumab group and more than half of the patients in the aflibercept group with very few injections. In a remarkable proportion of eyes, BCVA declined severely which underlines the need for long-term follow-ups and may indicate a more prolonged intensive therapy. Trial registrations VIEW 2 study: ClinicalTrials.gov ID: NCT00637377, date of registration: March 18, 2008. Long-term follow-up: IRB nr.: SE RKEB 168/2022, ClinicalTrials.gov ID: NCT05678517, date of registration: December 28, 2022, retrospectively registered.

Recent Advances on Imaging for Late-Stage Age-Related Macular Degeneration

“…Novel therapeutic techniques such as gene therapy using recombinant adeno-associated virus vectors delivering VEGF-inhibitory compounds and subsequent expression for long-term nAMD control are emerging [180,181] . However a staggering percentage of nAMD patients stabilized by anti-VEGF treatment still go onto to develop MA: more than 98 percent at 7 years in some studies [182] .New treatments for GA in dry AMD include complement pathway C3 and C5 inhbitors [183][184][185][186] .In all of these efforts, the ability to uitilize advances in imaging modalities to detect and document disease findings remains a critical stepping stone to future therapies.…”

Long-Term Follow-Up of Brolucizumab in Macular Neovascularization

“…The aim of AMD treatment is to reduce vision loss and optimize vision-related quality of life; therefore, anti-VEGF intravitreal treatment has widely been accepted as the first-line therapy for patients with macular NV (MNV) [5]. Different anti-VEGF drugs have been used in order to antagonize the role of the VEGF and reduce exudation caused by MNV [6‒8]. Among all, it is relevant the role of a relatively new anti-VEGF agent, brolucizumab (Beovu; Novartis, East Hanover, NJ, USA), whose efficacy in nAMD has yet to be demonstrated in HAWK and HARRIER phase 3 clinical trials and different real-world studies [9, 10].…”

Recent Advances in Imaging Macular Atrophy for Late-Stage Age-Related Macular Degeneration

“…Novel therapeutic techniques, such as gene therapy using recombinant adeno-associated virus vectors delivering VEGF-inhibitory compounds, and subsequent expression for long-term nAMD control, are emerging [171,172]. However, a staggering percentage of nAMD patients stabilized via anti-VEGF treatment still go on to develop MA: more than 98% at 7 years in some studies [173]. New treatments for GA in dry AMD include complement pathway C3 and C5 inhibitors [174][175][176][177].…”