Editors Selection IGR 21-3

Medical Treatment: Neuroprotection in a Clinical Trial I

Louis Pasquale
Jessica Tran

Comment by Louis Pasquale & Jessica Tran on:

90166 Can Treatment With Citicoline Eyedrops Reduce Progression in Glaucoma? The Results of a Randomized Placebo-controlled Clinical Trial, Rossetti L; Iester M; Tranchina L et al., Journal of Glaucoma, 2020; 29: 513-520

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Neuroprotection is defined as the relative preservation of neural function and/or structure. Open-angle glaucoma (OAG) patients frequently exhibit optic nerve degeneration despite receiving therapy that reduces intraocular pressure (IOP) to the 12-14 mmHg range. Citicoline has a solid basic science track record as a candidate neuroprotective agent, possibly acting through various pharmacological effects including increasing phosphatidylcholine synthesis and rescuing mitochondrial function. In this randomized, doublemasked, placebo-controlled trial, Rosetti t et al. investigated whether adjunctive citicoline treatment would decrease neurodegenerative changes in patients with progressive OAG and IOP ≤ 18 mmHg.

Patients were randomized to receive citicoline drops (n = 40) or placebo (n = 38) three times daily for three years. The study endpoints were a difference in visual field (VF) mean deviation rates using 24-2 or 10-2 VFs and change in retinal nerve fiber layer (RNFL) thickness at three years.

Citicoline use was associated with a decrease in 24-2 VF progression rates (-1.03 ± 2.14 dB, in three years) compared to pre-trial rates (-0.77 ± 0.6 dB/year) and decreased overall RNFL loss compared to placebo (-1.86mm vs. -2.99 mm in three years, p = 0.02, respectively), suggesting that citicoline slowed functional and structural progression. Interestingly, significant differences between treatment and placebo arms were observed for 10-2, but not 24-2 VFs (-0.41 dB vs. -2.22 dB in three years, p = 0.02, respectively).

These findings suggest that citicoline may be neuroprotective; however, several factors limit this study's generalizability and clinical significance as pointed out by the authors. Most importantly, the study was underpowered due to its small sample size. Multivariable analysis assessing the relationship between citicoline use and the study outcomes is also lacking. Despite these limitations, the investigators should be congratulated for providing more evidence that citicoline may be neuroprotective. Validation of these results in a larger cohort will be an important advancement for developing novel therapies for OAG.

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