Citicolin in eye diseases?

What are the most common eye diseases and what role can the nutrient citicoline play in glaucoma in the future?

What are the most common eye diseases?

Age-related macular degeneration, also known as AMD

The macula describes the point of sharpest vision in our eye, i.e. in the retina. Degeneration can occur with advancing age through the death of retinal cells, which means that in the center of vision you can only see a gray veil and over time you can only perceive your environment outwards in the field of vision. This, in turn, has an impact on overall visual acuity and the perception of colors and contrasts. There is still no efficient treatment for the more common, dry form of AMD, while effective drugs such as VEGF inhibitors (the active ingredients aflibercept, brolucizumab and ranibizumab are approved) can at least slow down the progression of the wet form. The sometimes used laser therapy is less effective.

The dry form of AMD develops much more slowly than the wet form and less often leads to visual impairments. However, the wet form can also develop from the dry form.

Age-related macular degeneration is a metabolic disease in which waste products are produced in the retina that can normally be eliminated by the body. However, small deposits can also form, so-called drusen, which impair proper supply of the retina.

On average, smokers get sick more often and earlier than non-smokers. The frequency is about 1% in the age group between 65 and 75 years, but in the age group over 85 years it already affects about 10% to 20%. The speed at which AMD develops is highly dependent on the size of the deposits in the retina.

Unlike glaucoma, AMD does not lead to total blindness. Orientation is still possible even with heavy forms. However, if you have a very severe visual impairment, you may be entitled to a blind allowance.

Dietary supplements with beta-carotene, lutein, zeaxanthin, ginkgo biloba, vitamins, zinc and omega-3 fatty acids are advertised as preventatives for AMD, but the relevant evidence from a scientific point of view is not yet sufficient to operate with successful prophylaxis. However, there is serious evidence that certain dietary supplements containing a combination of vitamin C (500 mg), vitamin E (400 IU), zinc (80 mg), copper (2 mg), lutein (10 mg) with zeaxanthin (2 mg ) or beta-carotene (15 mg) can slow down the further progression of AMD in people with larger deposits and thus also reduce visual impairments. Corresponding studies have shown that these benefits were observed in people who consumed the combination daily for 6 years. In any case, a doctor should be consulted to monitor the efficiency of these measures.

Glaucoma

According to the WHO, glaucoma is the second most common cause of blindness after cataracts, as it can cause permanent damage to the optic nerves. The main reason for the development is a permanently increased intraocular pressure (> 21 mm Hg), which causes the optic nerve head to be squeezed and thus the supply of nutrients to the nerves is significantly impaired, which ultimately leads to the death of the nerve fibers. The patient suffers from the fact that the visual field (field of vision) has ever larger gaps and is therefore restricted.

If you manage to detect increased intraocular pressure at an early stage through appropriate regular check-ups, there are good treatment chances of stopping the progression of the glaucoma disease. However, a cure is not possible because damage to the optic nerve cannot be reversed.

By far the most common glaucoma disease is the so-called primary open-angle or wide-angle glaucoma. Around 70 million people worldwide are affected by this, in Germany around 1 million.

To treat glaucoma, eye drops are usually used to lower intraocular pressure, which contain beta blockers, prostaglandins, alpha agonists, carbanhydrase inhibitors and/or cholinergics individually or in combination. In addition to drug treatment, laser treatment or surgery (trabulectomy) are also possible.

Dietary supplements and/or nutrients for diet management with citicoline, which can also be bought in pharmacies, have gained in importance in recent years to the extent that neuroprotective mechanisms of action in addition to the established reduction in intraocular pressure are being discussed in science. This is understandable, since glaucoma can progress even after the intraocular pressure has been reduced. This is also known as normal pressure glaucoma. Interesting insights have been gained here in particular with citicoline, also known as CDP-choline (see below: What new findings are there on citicoline to improve the field of vision in glaucoma diseases?).

Does glaucoma only occur in older people?

Glaucoma can also occur in children, and in most cases it is congenital. Here, too, a build-up of aqueous humor in the interior of the eye leads to increased intraocular pressure. It is important to detect congenital glaucoma early. For example, specialists work at the University Eye Clinic in Magdeburg, where a children's glaucoma center has been officially opened since 2014.

How does glaucoma affect quality of life?

The problem is that the diagnosis is often made late because glaucoma has not caused any symptoms for a long time. Symptoms that begin are a narrowing of the field of vision from the outside, but also failures towards the center of the gaze. The increased intraocular pressure is not noticed for a long time, even with higher values, which is why it is important to take preventive measures with regular ophthalmological checks.

Once glaucoma is diagnosed and the defects in the visual field increase, the quality of life decreases immediately. Near and far vision is impaired, pain occurs, the ability to drive decreases and color vision is reduced. Severe disabilities occur, especially if there are failures in the middle: reading or climbing stairs becomes almost impossible. At the same time, the risk of falling and the risk of needing care increases. Added to this is the impairment of mental health due to loneliness or less active participation in life.

Why are we looking for other treatment options for glaucoma in addition to lowering the intraocular pressure?

As already mentioned, glaucoma can progress despite a reduction in intraocular pressure. Therefore, neuroprotective approaches have been sought in the past, with the focus on the retina and optic nerve. Unfortunately, no significant progress has been made here in clinical studies. However, if one takes into account the more recent findings on neuronal degeneration in the course of the entire visual pathway and the brain, there are definitely new, promising approaches for neuroprotective therapies to supplement the established procedures.

What are the new findings on citicoline for improving the field of vision in glaucoma?

Citicoline is one of the nutrients that are considered neuroprotective. It has been researched for almost 50 years and has mainly been used to improve attention and memory in older people. However, there are now also studies with younger, healthy volunteers that show an improvement in attention and, as a result, greater mental performance.

In a review published in 2021 by the proven glaucoma specialist Prof. Jünemann, the former chief physician at the Rostock Eye Clinic, who now works in Erlangen, the possible importance of citicoline as a supplementary treatment for glaucoma is now discussed on the basis of 11 clinical studies. In the various studies, citicoline was administered orally, intramuscularly or locally as eye drops. The authors regard citicoline given orally as the most suitable for the application, because the absorption by the body seems to be best here (bioavailability) and at the same time there are no burdens with the type of application.

Two studies are described in more detail here as examples: the first was a so-called cross-over study. The 109 participants with open-angle glaucoma were either initially treated with 500 mg citicoline (in combination with homotaurine and vitamin E) daily for 4 months in addition to their prescribed eye drops to lower intraocular pressure, and then only with their eye drops. In a second group, the change in therapy was reversed: initially only eye drops for 4 months, then 4 months in combination with the oral citicoline preparation. Based on the endpoints (SPARCS = Spaeth-Richman-Contrast-Sensitivity-Test) and GQL-15 (a quality of life scale for glaucoma patients), which are collected regularly, the neuroprotective effect of citicoline could be significantly proven by improved parameters in the citicoline groups. The mean duration of glaucoma was 7 years and the mean, drug-controlled intraocular pressure was 16 mm Hg.

The second study was a double-blind, placebo-controlled study conducted over a period of 3 years. Here, citicoline was applied as eye drops 3 times a day. A total of 80 patients were involved. With the endpoints of perimetry and optical coherence tomography (OCT), it was also shown here that despite an intraocular pressure of <18 mm Hg citicoline, the further progression of the glaucoma disease could be slowed down. However, the authors themselves admit that the number of patients was too small to really prove a significant effectiveness with statistical certainty. In this respect, this study is more of a pilot study.

Overall, the overall view of all 11 studies showed positive effects of 500 to 1000 mg citicoline daily in relation to functional and morphological parameters.

After the European Food Safety Authority (EFSA) had already rated citicoline as safe and free of side effects in a dosage range of up to 1000 mg in 2014, the Italian health authority has already approved citicoline as a dietary food for special medical purposes as an adjuvant for use in glaucoma patients for improvement of the field of view granted. Due to the positive safety reviews, the use of citicoline can be permanent or in periodic cycles. A positive side effect of the use of citicoline in glaucoma patients could certainly also be the memory-promoting effects, which increases adherence (loyalty, compliance) to taking the medication to reduce intraocular pressure.

Further studies with larger patient numbers must follow in order to further shed light on the value of citicoline in glaucoma diseases. We will continue to monitor this field of research and will inform you as soon as there is any news.

References:

Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen IQWIQ (Juli 2019): https://www.gesundheitsinformation.de/gruener-star-glaukom.html

Jünemann AGM, Grieb P, Rejdak R, Bedeutung von Citicolin bei der Glaukomerkrankung, Ophthalmologe 118 (2021): 439-448

Rossetti L, Iester M, Tranchina L et al, Can treatment with citicoline eyedrops reduce progression in glaucoma? The results of a randomized placebo-controlled clinical trial, J Glaucoma 29 (2020): 513-520

Marino PF, Rossi GCM, Campagna G et al, Effects of citicoline, homotaurine, and vitamin E on contrast sensitivity and visual-related quality of life in patients with primary open-angle glaucoma: a preloiminary study, Molecules 25 (2020): 5614

Childhood glaucoma: Universität Magdeburg http://www.kaug2.ovgu.de/