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.

Keywords: AMD; Aflibercept; Age-related macular degeneration; Anti-VEGF; Exudative; Long-term treatment; Macula; Ranibizumab; Retina; Wet.

Fig. 1

Box and Whisker plot graph showing changes in best corrected visual acuity during follow-up: baseline, exit of study and end of follow-up. Abbreviation: BCVA: Best corrected visual acuity. Single asterisk (*) indicates p ≤ 0.05, double asterisk (**) indicates p ≤ 0.01, triple asterisk (***) indicates p ≤ 0.001. Abbreviation: EOF: end of follow-up

Fig. 2

Bar graph showing distribution of eyes grouped by number of lost or gained ETDRS letters at the end of follow-up. Abbreviation: BCVA: Best corrected visual acuity

Fig. 3

Graph showing difference in area of macular atrophy (mean ± SD) between ranibizumab and aflibercept treatment groups at the end of follow-up. Difference between groups was statistically not significant (p = 0,4708)

Fig. 4

Graph showing the relationship between best corrected visual acuity and area of macular atrophy at the end of follow-up. Correlation was statistically significant (p = 0,0002)