In this year's ophthalmology blogs, we have already talked about glaucoma several times. The reduction of intraocular pressure is an important factor in the treatment of glaucoma. However, adequate intraocular pressure control does not guarantee that there will be no further optic damage in the course of the disease. This leaves us with only one thing to suspect: There must be other factors besides intraocular pressure that influence the success of glaucoma therapy. In any case, there is still a lot of research to be done on the pathogenesis of glaucoma. A recently published scientific study has dealt with exactly this topic. Read more about it in today's article.
The goal of any ophthalmological therapy is to preserve vision. The first results of the research group led by Yolandi van der Merwe suggest that this could also be possible independently of pressure fluctuations in glaucoma. In the longitudinal study before us, the research group investigated the effect of citicoline as well as the neurobehavioural effects on the extent and duration of intraocular pressure (IOP) elevation on the optic nerve in a rat model. They did this using multiparametric magnetic resonance imaging, optokinetic and histological examinations.1
Citicoline, also known as cytidine diphosphate choline (CDP-choline), is a water-soluble nucleoside diphosphate that is essential for the biosynthesis of cell membrane phospholipids. Its bioavailability is over 90%. It is involved in cell membrane remodelling and repair processes and represents the limiting biosynthetic step. Phosphatidylcholine synthesis depends on citicoline. Citicoline itself is synthesised endogenously. Pharmacokinetic data already exist on the absorption of orally ingested citicoline in adult subjects. Adult subjects show rapid citicoline absorption. Enteral excretion is less than 1%.2,3
The research group led by Yolandi van der Merwe tested their hypothesis on a total of 82 adult female Long Evans rats (Charles River Laboratories, Wilmington, MA) with an age of about 8 weeks. The experimental animals were randomly divided into six groups. The first group included animals with acute mild IOP elevation. The experimental animals of the second group showed an acute severe IOP elevation. The animals in the third group received citicoline for chronic IOP elevation. These animals were given citicoline orally every day. This was done 7 days before the induction of IOP elevation. Animals with chronic IOP elevation were assigned to the fourth experimental group. These animals did not receive citicoline therapy. The fifth group was the acute sham control group and the sixth the chronic sham control group.1
IOP elevation was achieved by anterior chamber perfusion with physiological saline solution of the right eye of each of the experimental animals in the mild (n = 13) or severe (n = 12) acute IOP elevation groups. Analgesia was achieved by topical proparacaine hydrochloride application and mydriasis by topical tropicamide administration. The needle tip of a 30-gauge needle was inserted into the anterior chamber of the right eye parallel to the iris under optical control. This allowed physiological saline solution to enter the eye through sterile tubing to bring the intraocular pressure to 40 mmHg for mild and 130 mmHg for severe acute IOP elevation. The left eye of each of these animals did not receive anterior chamber perfusion with a physiological saline solution. It served as an internal control.1
The research group used the OptoMotry virtual reality optokinetics system (Cerebral-Mechanics Inc., Lethbridge, Alberta, Canada) to assess visuomotor behaviour by quantifying the visual acuity of each eye. The left eye showed unchanged visual acuity in all groups. The research group came to this conclusion after evaluating the optokinetic behaviour patterns. The visual acuity of the left eye had been comparable to the visual acuity of the experimental right eye before the IOP increase. The visual acuity of the right experimental eye steadily decreased with each passing day after induction. This occurred in both the mild acute and severe acute IOP elevation groups. Compared to the left eye, the visual acuity of the experimental right eye had been significantly lower on the 14th and 35th day after induction. On the 7th, 14th and 35th day after induction, the acute severe IOP group had significantly lower visual acuity compared to the acute mild IOP group.
Compared to the sham control group, both the citicoline-treated and the untreated IOP group showed reduced visual acuity on day 14 and day 35. Comparing the citicoline-treated and the citicoline-untreated experimental group finally led to the desired result. Citicoline therapy was associated with significantly better visual acuity despite similar intraocular pressure values in the two groups.1
References:
1. Van der Merwe Y. et al (2021). Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control.
2. Schäbitz W. R. (2009). CDP-Cholin zur Behandlung des Schlaganfalls. Psychopharmakologie. 3, 2009, S. 101–105. (English title: CDP-choline for treatment of strokes.)
3. Davalos A. et al. (2002). Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke. 33, 2002, S. 2850-2857.