October 08, 2020
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Citicoline drops may slow glaucoma progression in some patients

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Adding citicoline eye drops to IOP-lowering medications might reduce glaucoma progression in patients with worsening damage despite well-controlled IOP, according to a study.

In a group of patients treated with citicoline, visual field (VF) progression was significantly reduced, and retinal nerve fiber layer (RNFL) loss was on average 1.86 µm at 3 years vs. 2.99 µm in patients treated with placebo.

Luca Rossetti, MD
Luca Rossetti

“The question behind our investigation was whether supplementing the IOP-lowering therapy with a neuroprotective agent might help in the ‘well-controlled’ but progressing glaucoma cases,” Luca Rossetti, MD, first author of the study, told Ocular Surgery News.

Citicoline has a follow-up of more than 3 decades and has shown evidence of efficacy as an adjunct therapy in several neurodegenerative diseases. It is available for oral administration as well as eye drops, with proven ability to reach the vitreous and retinal ganglion cells.

The study, carried out at university eye clinics in Milan, Rome and Genoa, Italy, included 80 patients randomly assigned to receive citicoline eye drops or placebo in addition to previous IOP-lowering therapy. At baseline, all patients showed progressing damage despite IOP of 18 mm Hg or less.

“We assessed visual field in the central 24° and 10° and also measured RNFL thickness on OCT. Over the 3 years of the study, IOP was well controlled, under 14 mm Hg or even 13 mm Hg in both groups. VF progression, particularly in the central 10°, which is the most important, was significantly reduced in patients who received citicoline eye drops. Functional data were supported by morphological findings, showing a significant reduction in RNFL thinning as compared with placebo,” Rossetti said.

Neuroprotection is the future

Glaucoma is a neurodegenerative disease that attacks retinal ganglion cell neurons and their axons, the cells that transmit the visual signal to the brain. The optimal therapy should therefore aim at maintaining or recovering retinal ganglion cell function.

“This is the future. Today we are not yet there because we don’t have the right substance and the right way of delivering it in the right place at the appropriate concentration. However, the day will come when glaucoma will no longer be managed by lowering IOP, but by a combination of genetic therapy and neuroprotection,” Rossetti said.

Neuroprotection is advancing slowly in glaucoma for a number of reasons. First, glaucoma already has effective, well-established therapies.

“IOP-lowering strategies do work extremely well. If we compare glaucoma with other neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, there is much more that we can already do to slow down disease progression. This affects the research on other treatment strategies because if we have to test treatments on patients who are already treated well, we only have a very small window,” Rossetti said.

In addition, the endpoints for measuring the efficacy of glaucoma therapies, such as visual field changes, require a long follow-up and a high number of patients.

“Clinical trials on neuroprotection are particularly long and expensive and can fail for many reasons, so it is hard to find companies that are willing to invest, though the interest in glaucoma is huge,” Rossetti said.

Citicoline: Why not?

The study had a small sample size, but results strongly suggest that citicoline has a positive effect in slowing down disease progression and can be a useful tool in clinical practice.

“Small studies are necessary to stimulate researchers to go further and set up larger-scale studies. As a researcher, I feel encouraged to keep moving forward on this pathway. As a clinician, I’d say: Why not? Citicoline has no side effects. Eye drops are tolerated as well as tear substitutes, and since they contain hyaluronic acid, they even help alleviate the side effects of IOP-lowering medications. I use citicoline in all the cases where there is evidence of disease progression in spite of well-controlled IOP,” Rossetti said.

He said that the only limitation of eye drops is that they can potentially create confusion in patients who are already taking multiple topical medications. It is therefore important to select the patients who can safely manage this additional administration without the risk for making mistakes regarding the correct dosage of IOP-lowering drops.

“When in doubt, I use the oral supplements and advise my patients to take them in the morning since they can have a light stimulating effect, like a cup of coffee,” he said.