Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration
• VIEW 2 Trial: NCT00637377 • Long-term follow-up: NCT05678517 | VIEW 2 | Lukacs R et al. (2023)
Lukacs R, Schneider M, Nagy ZZ, Sandor GL, et al. Seven-year outcomes following intensive anti-vascular endothelial growth factor therapy in patients with exudative age-related macular degeneration. BMC Ophthalmology, 2023; 23:110.
Locations
Two clinical trial sites in Hungary
Study Period
Initial trial: 2008-2010; Long-term follow-up: 7 years (mean 82 ± 5 months follow-up)
Study Design
Retrospective observational follow-up of a Phase 3 RCT
Study Population
Experimental Group
Control Group
Follow-up Time: Mean = 82 ± 5 months
Outcomes
Durability
Number of the Injections Mean number of injections was during the intensive phase:
• All: 17.8±3.0
Mean number of injections was during the the entire follow-up:
• All: 19.5±5.0
During the post-intensive phase:
• All: 14 of 47 eyes (30%) were given additional injections
• Mean number of 5.7±4.5
• Remaining 70% received no injections
Vision
Best-Corrected Visual Acuity (BCVA)
The mean ±SD BCVA change from baseline to end of follow-up (Primary Outcome):
• All patients: -19 ± 23 letters (p < 0.001)
• Aflibercept: -18 ± 22 letters (p < 0.001)
• Ranibizumab: -23 ± 24 letters (p = 0.03)
The mean ±SD BCVA (letters) at baseline → end of intensive phase → end of follow-up:
• All patients: 54 ± 13 → 65 ± 17 → 45 ± 25 letters
• Aflibercept: 55 ± 13 → 65 ± 17 → 47 ± 25 letters
• Ranibizumab: 54 ± 13 → 64 ± 18 → 41 ± 25 letters.
Vision Maintaining
Proportion of patients with BCVA stability/improvement from baseline to end of follow-up:
• All patients: 55%
• Aflibercept: 60%
• Ranibizumab: 43%
Proportion of patients losing ≥10 ETDRS letters from baseline to end of follow-up:
• All patients: 45%
• Aflibercept: 40%
• Ranibizumab: 57%
Other
Efficacy: Progression Outcomes Geographic Atrophy (GA) The GA prevalence at end of follow-up:
• All patients: 96%
The mean ± SD change in GA area from baseline to the end of follow-up:
• All Patients: 7.22 ± 6.31 mm²
• Aflibercept: 6.89 ± 6.31 mm²
• Ranibizumab: 8.00 ± 6.48 mm²
• Difference: p= 0.47
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Retinal Fluid Fluid on OCT at end of follow-up
• All patients: 15%
• Among untreated patients in the post-trial phase: 6%.
Safety
Ocular AE
• 8 eyes (17%) required cataract surgery.
Serious AEs
• No serious ocular AEs
• 2 patients experienced stroke during the 7-year follow-up
Conclusion
After 7 years of follow-up, aflibercept and ranibizumab demonstrated long-term stability or improvement in BCVA in about half of the patients. However, significant BCVA decline occurred in 45% of eyes, emphasizing the need for extended follow-up and potentially more intensive long-term therapy.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: No information on concealment and randomization. This is a long-term follow-up study from a part of a previously conducted RCT.
No information on if the baseline characteristics are balanced or not between the included two groups.
Missing Outcome Data
Low risk
Note: The present study included those who have follow-up information. No missingness related for the analysis.
Selection of the Reported Results
Low risk Note: registration with protocol.
Deviations from Intended Observations
Low risk Note: The original RCT was a double-masked study. The analysis based on all patients included.
Measurement of the Outcome
Some concerns Note: no information on measurement quality guarantee. In addition, no information on masking. However, the measure was unlikely influenced by the acknowledgement of the intervention.
Overall
Some concerns
Categories: Geographic Atrophy Wet AMD