Effect of Adjuvant Topical Dorzolamide-Timolol vs. Placebo in Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial
NCT03034772 | Not specified | Hsu J et al. (2020)
Hsu J, Patel SN, Wolfe JD, et al. Effect of Adjuvant Topical Dorzolamide-Timolol vs. Placebo in Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial. JAMA Ophthalmology, 2020; 138(5):560-567.
Locations
4 clinical sites in the United States
Study Period
March 2017 – October 2018
Study Design
Multicenter, randomized, single-masked, parallel-group, placebo-controlled trial
Study Population
Experimental Group
Control Group
Follow-up Time: 3 months
Outcomes
Durability
Not reported.
Vision
Visual Acuity (VA) Change in VA (ETDRS letters) at 3 months :
• Dorzolamide-timolol: -2.3 ± 5
• Placebo: +0.3 ± 1
• Adjusted difference: 2.6 (95% CI: -1.9 to 7.1; p = 0.78)
Other
Intraocular Pressure (IOP) Change in IOP at 3 months :
• Dorzolamide-timolol: -1.81 ± 3.8
• Placebo: -0.78 ± 2.8
• Adjusted difference: 1.0 (95% CI: 9-0.7 to 2.7; P = 0.24)
Immunognicity
Not reported.
Pharmokinetics
Not reported.
Anatomic
Central Subfield Thickness (CST) Change in CST at 3 months (Primary Outcome):
• Dorzolamide-timolol: -36.6 ± 54 μm
• Placebo: +1.7 ± 52.3 μm
• Adjusted difference: 30.8 μm (95% CI: 0.3 to 61.3; p = 0.04) Pigment Epithelial Detachment (PED) Patients with PED at 3 months :
• Dorzolamide-timolol: 22 (81%)
• Placebo: 20 (87%)
• Adjusted OR: 1.1 (95 %CI: 0.06 to 18.8; p = 0.95) Change in maximum PED height at 3 months :
• Dorzolamide-timolol: -39.1 ± 65 μm
• Placebo: +1.1 ± 16 μm
• Adjusted difference: 39.6 μm (95% CI: 9.6 to 69.6; p = 0.01) Retinal Fluid Patients with SRF at 3 months :
• Dorzolamide-timolol: 17 (63%)
• Placebo: 18 (78%)
• Adjusted OR: 0.24 (95 %CI: 0.02 to 2.3; p = 0.22) Patients with IRF at 3 months :
• Dorzolamide-timolol: 9 (33%)
• Placebo: 7 (30%)
• Adjusted OR: 1.2 (95 %CI: 0.4 to 4.3; p = 0.68) Change in maximum SRF height at 3 months :
• Dorzolamide-timolol: -49.4 ± 55 μm
• Placebo: -22.2 ± 56 μm
• Adjusted difference: 23.6 μm (95% CI: -5.7 to 53; p = 0.11) Central Foveal Thickness (CFT) Change in CFT at 3 months :
• Dorzolamide-timolol: -30.0 ± 62 μm
• Placebo: +7.4 ± 90 μm
• Adjusted difference: 26.2 μm (95% CI: -13.7 to 66.1; p = 0.19)
Safety
No relevant differences between groups were noted
Conclusion
Dorzolamide-timolol adjunct therapy significantly reduced CST and PED height at 3 months compared to placebo, but no significant improvements in visual acuity were observed. Future trials are needed to assess long-term clinical relevance.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “The randomization list was computer-generated without blocking. Masked bottles were placed into sequentially numbered opaque envelopes based on the randomization scheme, which was concealed thereafter and not visible to the enrolling physician or staff.”
Missing Outcome Data
High risk
Note: “Missing data were excluded from analyses such that complete-case analysis was conducted…” Missing data were excluded from analyses without any adjustment. In addition, the missingness is unbalanced between the two groups.
Selection of the Reported Results
Low risk Note: registration with protocol
Deviations from Intended Observations
High risk Note: “Study coordinators testing visual acuity, intraocular pressure (IOP), and performing OCT tests were masked.” Patients were masked to the intervention. ITT was not applied (withdraw patients were excluded from analysis). In addition, two patients withdrew from the control (2/25, 8%) vs. zero patients withdrew from the experimental group, which is imbalanced. Therefore, there was 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: As a multiple-center study, the measure of the outcomes may differ from each site.
Overall
High risk
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