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David Valent, Wai T Wong, Emily Y Chew, Catherine A Cukras; Oral Dextromethorphan for the Treatment of Diabetic Macular Edema: Results from a Phase I/II Clinical Study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2281.
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© ARVO (1962-2015); The Authors (2016-present)
Strong evidence supports the role inflammation plays in retinal vascular permeability and severity of diabetic macular edema (DME). One of the important components of diabetic retinal inflammation is microglial cell activation. This study evaluated the safety and efficacy of oral dextromethorphan, a drug shown to inhibit microglial activation in vitro, as a primary treatment of DME.
This single-center, prospective, open-label phase I/II clinical trial enrolled five participants with retinal thickening within 3000µm of the center of the macula and treated them with oral dextromethorphan 60mg twice daily for 6 months as monotherapy. Main outcome variables included best corrected visual acuity (BCVA), central retinal subfield thickness (CST) and central macular volume using spectral domain optical coherence tomography (SD-OCT) and late leakage on fluorescein angiogram (FA).
Participants ranged in age between 47 to 64 years (mean: 56.8 years). Four had the diagnosis of type 2 diabetes, and one had type 1 diabetes; with a mean duration of 21.6 years (range: 3-50 years). Four study eyes had prior treatment for diabetic macular edema, including bevacizumab. The study drug was well tolerated and not associated with any significant safety concerns. In study eyes, mean BCVA improved when compared with baseline at 1, 2, 4, and 6 months by +4.6, +6, +1, +0.6 letters, respectively. Two patients changed more than 10 letters of visual acuity over the 6 months; one improved 20 letters and another worsened by 10 letters. Compared with a mean CST of 335µm at baseline, the mean CST of study eyes decreased by 7.4%, 5.2%, 0.8%, 6.3% at 1, 2, 4, and 6 months, respectively. Two participants had decreases in CST > 15%. None had worsening of CST > 15%. Mean central macular volume in the study eye was also decreased at all study visits compared with baseline. At 6 months, late leakage on FA appeared improved in 4 of the 5 patients. These findings were not correlated with changes in HgA1c, creatinine or blood pressure.
In this proof of concept study, using oral Dextromethorphan as the primary treatment for DME for 6 months was associated with little improvement in visual acuity, on average a small decrease in CST, central macular volume and late vascular leakage on FA. Further study is needed to determine whether this is a potentially useful mode of intervention for macular edema.
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