Oral Dextromethorphan for the Treatment of Diabetic Macular Edema: Results From a Phase I/II Clinical Study
David J Valent1, Wai T Wong2, Emily Y Chew1
1Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Purpose:
The activation of microglia, the primary innate immune cell resident in the retina, produces inflammatory mediators, which underlie changes in diabetic retinopathy including increased vascular permeability. This study evaluates the safety and efficacy of dextromethorphan, a drug capable of inhibiting microglial activation, in the treatment of diabetic macular edema (DME).
Methods:
A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with macular involving DME who received oral dextromethorphan 60 mg twice daily for 6 months as monotherapy. Main outcome variables included central retinal subfield thickness (CST), best-corrected visual acuity (BCVA), macula sensitivity, and late leakage on fluorescein angiogram (FA).
Results:
The study drug was well tolerated. At the primary end point of 6 months, mean CST decreased by -6.3% ± 6.8% and BCVA increased by +0.6 ± 5.11 (mean ± SEM) letters. Late leakage on FA was scored as improved in four of five study eyes. These findings were not correlated with changes in hemoglobin A1c (HbA1c), creatinine, or blood pressure.
Conclusions:
In this proof-of-concept study, dextromethorphan administration as the primary treatment for DME was associated with decreased vascular leakage, suggesting possible therapeutic effects. Additional studies investigating the modulation of microglial activation is warranted.
Translational Relevance:
These findings highlight microglial modulation as a potentially useful therapeutic strategy in the treatment of diabetic macular edema.
Insights
Dextromethorphan showed potential in treating diabetic macular edema by reducing vascular leakage. Further research into microglial modulation is recommended for this eye condition.
Area of Science:
- Ophthalmology
- Immunology
- Pharmacology
Background:
- Diabetic retinopathy (DR) involves retinal microglial activation and inflammatory mediators, leading to increased vascular permeability.
- Diabetic macular edema (DME) is a common complication of DR, significantly impacting vision.
Purpose of the Study:
- To evaluate the safety and efficacy of dextromethorphan, an inhibitor of microglial activation, for treating DME.
- To assess dextromethorphan's impact on key DME indicators.
Main Methods:
- A prospective, open-label, single-center Phase I/II clinical trial involving five DME patients.
- Oral dextromethorphan (60 mg twice daily) was administered for six months as monotherapy.
- Outcomes measured included central retinal subfield thickness (CST), best-corrected visual acuity (BCVA), macula sensitivity, and fluorescein angiogram (FA) leakage.
Main Results:
- Dextromethorphan was well-tolerated by all participants.
- Mean CST decreased by 6.3% and BCVA improved by 0.6 letters at six months.
- Four out of five participants showed improved late leakage on FA, independent of HbA1c, creatinine, or blood pressure.
Conclusions:
- Dextromethorphan monotherapy for DME demonstrated decreased vascular leakage, suggesting therapeutic potential.
- Microglial modulation presents a promising therapeutic strategy for managing diabetic macular edema.
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