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Published on: February 12, 2018
Dopamine-Enhancing Therapies and Risk of Neovascular AMD Conversion: A Target Trial Emulation
Owais Fazal1, Asad Loya2, Jawad Muayad3
1From the Department of Ophthalmology (O.F., D.D.B., C.C., N.A.P.), Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA; Harvard Medical School (O.F.), Boston, Massachusetts, USA.
Purpose:
Age-related macular degeneration (AMD) is a leading cause of central vision loss worldwide. Emerging evidence suggests that targeting dopaminergic pathways may influence AMD progression. This study evaluates whether levodopa ± carbidopa or dopamine receptor D2 (DRD2) agonists are associated with reduced risk of conversion to neovascular AMD (nAMD).
Design:
Population-based clinical cohort study.
Participants:
Adults aged ≥18 years diagnosed with non-nAMD between May 2005 and May 2025, within the TriNetX US Collaborative Network, a federated electronic health record database spanning 69 healthcare organizations.
Methods:
This retrospective cohort study emulated four distinct target trials comparing new users of (1) levodopa (± carbidopa) or (2) DRD2 agonists (pramipexole, ropinirole, bromocriptine, rotigotine, or cabergoline) to new users of two comparators (pantoprazole or gabapentin). Patients with prior nAMD or prescriptions of other dopamine-enhancing agents (eg, selegiline, rasagiline, tolcapone) were excluded. Each exposure group was independently matched to comparators using 1:1 propensity score matching for selected demographics, social factors, comorbidities, and AMD stage.
Main Outcome Measures:
The primary outcome was 3-year risk of conversion from non-nAMD to nAMD. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. An α level of 0.05 was used to determine statistical significance.
Results:
Patients prescribed levodopa ± carbidopa had a reduced 3-year risk of conversion to nAMD relative to their matched counterparts prescribed pantoprazole (levodopa n = 1312, control n = 1312; HR 0.67; 95% CI, 0.45-0.98) and gabapentin (levodopa n = 1675, control n = 1675; HR 0.69; 95% CI, 0.50-0.95). No significant difference was observed in 3-year risk of conversion to nAMD between DRD2 agonists use relative to pantoprazole (DRD2 n = 1603, control n = 1603; HR 0.81; 95% CI, 0.58-1.13) or gabapentin (DRD2 n = 2779, control n = 2779; HR 0.92; 95% CI, 0.72-1.19).
Conclusions:
In this cohort study, levodopa ± carbidopa use was associated with lower 3-year risk of conversion to nAMD in two independent matched comparisons, whereas DRD2 agonists were not associated with significant differences in risk. These findings suggest dopaminergic signaling may influence AMD progression and warrant further prospective investigation.
Insights
Levodopa ± carbidopa use was linked to a lower risk of developing neovascular age-related macular degeneration (nAMD). Dopamine receptor D2 agonists did not show a significant association with nAMD risk in this study.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Age-related macular degeneration (AMD) is a primary cause of vision loss globally.
- Dopaminergic pathways are increasingly recognized for their potential role in AMD progression.
Purpose of the Study:
- To investigate the association between levodopa ± carbidopa or dopamine receptor D2 (DRD2) agonists and the risk of conversion to neovascular AMD (nAMD).
Main Methods:
- A population-based clinical cohort study using the TriNetX U.S. Collaborative Network.
- Retrospective analysis emulating target trials comparing new users of levodopa ± carbidopa or DRD2 agonists against pantoprazole or gabapentin.
- 1:1 propensity score matching was used to control for confounding factors, with the primary outcome being the 3-year risk of conversion to nAMD.
Main Results:
- Levodopa ± carbidopa use was associated with a reduced 3-year risk of conversion to nAMD compared to both pantoprazole (HR 0.67) and gabapentin (HR 0.69).
- No significant association was found between DRD2 agonists use and the 3-year risk of conversion to nAMD when compared to pantoprazole (HR 0.81) or gabapentin (HR 0.92).
Conclusions:
- Levodopa ± carbidopa use demonstrated a protective association against the progression to nAMD.
- DRD2 agonists did not show a significant effect on nAMD progression risk.
- These findings suggest a role for dopaminergic signaling in AMD progression, meriting further research.
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