Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial
NCT01006538 | MERLOT Trial | Jackson TL et al. (2023) - Epimacular
Jackson TL, Soare C, Petrarca C, et al. Epimacular brachytherapy for previously treated neovascular age-related macular degeneration: month 36 results of the MERLOT randomised controlled trial. Br J Ophthalmol, 2023; 107:987–992.
Locations
24 sites across the United Kingdom
Study Period
November 10, 2009 – January 30, 2012
Study Design
Randomized, open-label, multicenter, surgical device trial
Study Population
Experimental Group
Control Group
Follow-up Time: 36 months
Outcomes
Durability
Number of anti-VEGF injections
Number of anti-VEGF injections over 36 months:
• EMB group: 12.1 (SD 8.1)
• Ranibizumab group: 11.4 (SD 6.1)
• Difference: 0.7 (95% CI -0.9 to 2.3); p-value: 0.41
Number of anti-VEGF injections from Months 25-36:
• EMB group: 3.6 (SD 3.3)
• Ranibizumab group: 3.9 (SD 2.7)
• Difference: -0.3 (95% CI -1.0 to 0.4); p-value: 0.43.
Vision
Best-Corrected Visual Acuity (BCVA)
BCVA change at Month 36 (Primary Outcome):
• EMB group: -19.7 letters (SD 18.5)
• Ranibizumab group: -4.8 letters (SD 12.5)
• Difference: -14.9 (95% CI -18.5 to -11.2) p-value: <0.0001
Vision Maintaining
Proportion of patients losing <15 letters:
• EMB: 43.9%
• Ranibizumab: 79.8%
• Difference: -35.9% (95% CI -44.7% to -25.7%); p-value: <0.0001
Proportion of patients gaining ≥0 letters:
• EMB: 14.3%
• Ranibizumab: 34.5%
• Difference: -20.2% (95% CI -29.8% to -10.8%); p-value: <0.0001
Proportion of patients gaining ≥15 letters:
• EMB: 0%
• Ranibizumab: 2.5%
• Difference: -2.5% (95% CI -7.2% to -0.2%); p-value: 0.002.
Other
N/A
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
Not reported
Safety
Study eye AEs
Cataract:
• 167 /174 (95.9%) phakic eyes in the EMB group
• 29/90 (32.2%) phakic eyes in the ranibizumab group
Cataract surgery:
• 147/174 (84.5%) phakic eyes in the EMB group
• 20/90 (22.2%) phakic eyes in the ranibizumab group
Study eye SAEs
The most frequent study eye SAE was retinal detachment which occurred in five participants in the EMB group, followed by significant retinal haemorrhage occurring in four participants in the EMB group versus one participant in the ranibizumab group. One case of endophthalmitis in the EMB group occurred following cataract surgery, as detailed previously
The Non-ocular AEs and non-study eye AEs
similar between the two treatment groups
Radiation retinopathy
Reported in 1.2% of EMB-treated patients.
Deaths
• EMB group: 15 (6.1%)
• Ranibizumab group: 8 (6.7%).
Malignant Tumors
• EMB group: 11.1%
• Ranibizumab group: 10.9%.
Conclusion
EMB treatment did not reduce anti-VEGF injection burden and resulted in significantly worse BCVA compared to PRN ranibizumab monotherapy. Long-term follow-up showed EMB had no visual benefit and increased adverse events.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Participants were randomised using a commercial system (MedSciNet Studies, MedSciNet AB)…”
“The two groups were balanced in terms of baseline ocular characteristics …”
Missing Outcome Data
Low risk
Note: The evidence of the analysis results were not biased by the missingness: “We used multiple imputations to impute the month 36 BCVA for the 57 participants missing the month 36 BCVA.”
Selection of the Reported Results
Low risk Note: Registration with protocol
Deviations from Intended Observations
Some concerns Note: Patients were not masked. No information on whether deviations arose because of the trial context. “Analyses of co-primary and BCVA secondary outcomes included all randomised participants (regardless of the study treatment received) using an intent-to-treat approach.”
Measurement of the Outcome
Some concerns Note: “…masked clinicians assessed best- corrected visual acuity (BCVA) and imaging.” In this multicentre study, the measurement of BCVA may exhibit diversity between different sites.
Overall
Some concerns
Categories: Wet AMD