Citicoline Effect on Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)

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Clinical trial.gov Brief summary : Non-arteritic anterior ischemic optic neuropathy (NAION) is an optic neuropathy due to acute or subacute ischemic event of anterior optic nerve axons retrolaminar part that was vascularized by posterior ciliary brevis artery. The incidence of ischemia will be followed by axonal edema and causing compartment syndrome and heighten the incidence of ischemic. In NAION, the main pathology occurs at the level of the optical nerve, the axons of retinal ganglion cells. Initial damage is on the optic disc ischemia resulting hypoxic injury of axons and manifest as disc edema. Axonal edema cause disturbances of retrograde axonal transport of neurotrophic factors, especially brain derived neurotrophic factor, to the retinal ganglion cells. This will trigger a secondary toxicity and apoptosis. In addition, the presence of oxidative stress, calcium influx and mitochondrial damage will also triggers apoptosis. After the apoptosis of retinal ganglion cells, there was a thinning of the retinal nerve fiber layer (RNFL) through Wallerian degeneration. Thinning of the RNFL will manifest as visual field defects and the decline in visual acuity in patients with chronic phase NAION. Though NAION include disease entity that has long existed, but until now, there has been no evidence-based study on medical or surgical procedures that is effective enough to overcome NAION. The main treatment is to manage the risk factor such as hypertension, dyslipidemia, diabetes mellitus, hypercoagulable state. In general, if the patient is in the acute phase (edema of optic nerve head), methylprednisolone administration may be considered, but if the patient is already on chronic phase (atrophy disc) which generally occurs 6-11 weeks after the onset, then steroids are no longer indicated. Neuroprotective agent was considered as treatment in NAION given primary pathology NAION is the retinal ganglion cell axons. Among the various neuroprotective substance, Citidine diphosphocoline (CDP-choline 5'-diphosphocholine or Citicoline) is a therapeutic option NAION. Citicoline is an endogenous mononucleotide consisting of ribose, cytosine, pyrophosphate, and choline. Citicoline is a component intermediates in the synthesis of phospholipids in cell membranes, ie phosphatidylcholine. Exogenous citicoline administered orally or intravenously, will be split into citidine and choline. Citicoline via oral administration can be absorbed completely and have a similar bioavailability in the blood compared to parenteral administration such as intravenous. Once absorbed, citicoline will be distributed throughout the body and enter the blood-brain barrier and the blood retinal barrier penetrate into the central nervous system. If there is damage to neurons, exogenous citicoline will participate in the synthesis of phospholipids in the neuronal cell membrane. Some studies show that citicoline may have a neuroprotective effect on retinal ganglion cells and supporting regeneration of damaged neurons in vitro. Previous research on the citicoline effect in chronic phase NAION give satisfactory results. Dopaminergic neurotransmitter systems known to occur in vast numbers in the retina and post-retinal visual pathway. Retinal ganglion cells using certain subtypes of dopamine as a means of communication with the visual cortex. Rejdak et al in animal models showed that citicoline administration could improve and strengthen the dopamine transmission in the retina. Citicoline also a safe medicine, without serious adverse effect. Electroretinogram (ERG) is a tool to measure the function of the retina. ERG examination can measure electrical changes in the retina after light stimulus. ERG examination that can detect changes in the activity of retinal ganglion cell is a pattern ERG. Spectral-domain optical coherence tomography is a tool that can measure the thickness of retinal ganglion cells. Thinning of the RNFL will manifest as visual field defects in patients with NAION. The typical visual field defects of NAION is altitudinal defects associated with segmental edema optic nerve head. Based on these descriptions question arises whether the citicoline supplementation can repair damage to the neurons of the retina, especially the retinal ganglion cells, in NAION resulting in improved retinal function which can be judged from the improvement of the value of the amplitude of the wave of P50 and N95 in the examination pattern ERG (PERG) when compared with placebo ? In addition whether citicoline supplementation can increase the thickness of retinal ganglion cells assessed using SD-OCT? Does citicoline supplementation give the effect of improving visual field defects in patients with NAION?

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