Multifocal ERG and Microperimetry Changes in Response to Ranibizumab Treatment of Neovascular AMD: Randomized Phase 2 Open-Label Study
NCT00764738 | Not specified | Asahi MG et al. (2020)
Asahi MG, Wallsh J, Onishi SM, Kuroyama S, Gallemore RP. Multifocal ERG and Microperimetry Changes in Response to Ranibizumab Treatment of Neovascular AMD: Randomized Phase 2 Open-Label Study. Clin Ophthalmol, 2020; 14:3599-3610.
Locations
Conducted in the United States
Study Period
January 2009 – November 2011
Study Design
Phase 2, randomized, open-label, single-center exploratory trial
Study Population
Experimental Group
Control Group
Follow-up Time: 12 months
Outcomes
Durability
Not reported.
Vision
Best-Corrected Visual Acuity (BCVA) The mean change in BCVA from baseline to Month 12 months (Primary Outcome):
• Monthly group: +7.3 ± 2.8 ETDRS letters
• PRN group: +6.0 ± 1.3 ETDRS letters
• Difference: 1.3 letters (p=0.68, not significant). Macular Function Mean microperimetry (MP) sensitivity improvement:
• All patients: +1.7 ± 0.5 dB (p<0.05, significant)
• Difference (Monthly vs. PRN): p=0.25
• Difference (0.5 vs. 2.0): p=0.67 Multifocal ERG (mfERG) N1-P1 response density and P1 response density change:
• Mean N1-P1 response density and P1 response density on mfERG decreased for all studied patients from 4.22 ± 0.32 to 3.70 ± 0.29 and 2.88 ± 0.23 to 2.41 ± 0.18 nv/ deg2, respectively (p < 0.05)
• Comparing the monthly and PRN, treatment-naive, and previously treated, 0.5 and 2.0 mg subgroups demonstrated a non-significant difference in the change in mean N1-P1 and P1 response densities
Other
N/A
Immunognicity
Not reported.
Pharmokinetics
Not reported.
Anatomic
Central Foveal Thickness (CFT) The mean reduction in CFT from baseline to Month 12 months:
• Monthly group: -96.3 ± 22.0 µm
• PRN group: -64.5 ± 13.3 µm
• Difference: -31.8 µm (p=0.22, not significant).
Safety
AEs
• 4 patients developed AEs
• No withdrawals due to complications. Ocular-related AEs
• 1 case of corneal abrasion
• 1 case of mild ocular discomfort. Serious ocular AEs
• 1 case of vitreous hemorrhage
• 1 case of uveitic glaucoma. Non-ocular AEs Not explicitly reported.
Conclusion
Both PRN and monthly ranibizumab improved BCVA and reduced CFT, but mfERG showed a decline in retinal function despite anatomical improvements. Microperimetry showed a functional benefit, suggesting additional measures may be needed to fully assess treatment response.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Some concerns
Note: There is no information on the allocation concealment or the randomization method. However, the two groups were comparable at the baseline.
Missing Outcome Data
High risk
Note: The total number of withdrawals without reasons was 12.1%. However, neither appropriate data analysis was performed to adjust the bias (missing values were imputed based on a last observation carried forward technique, which was considered not appropriate) nor sensitivity analysis was performed to confirm the robustness of the results. There is no information on whether the missingness is based on the true value.
Selection of the Reported Results
Low risk Note: Registration with protocol.
Deviations from Intended Observations
High risk Note: no information on the blinded for the patients and the assessors. No information on whether deviations arose because of the trial context. Statistical analysis was performed on those patients who completed the 12-month trial (per-protocol principle), which is inappropriate. However, the total number of withdrawals without reason was 12.1%. There is potential for a substantial impact (on the result) of the failure to analyze participants in the group to which they were randomized
Measurement of the Outcome
Some concerns Note: There is no information on whether the assessors were blinded for the intervention. However, it is unlikely that the knowledge of the intervention influenced the assessment. "
Overall
High risk
Categories: Wet AMD