Citicoline and Vitamin B12 Eye Drops in Type 1 Diabetes: Results of a 36-Month Pilot Study Evaluating Macular Electrophysiological Changes

Abstract

Introduction: Our aim was to evaluate the effects of 36 months of treatment with citicoline and vitamin B 12 eye drops on macular function in patients with type 1 diabetes (DM1) with mild signs of non-proliferative diabetic retinopathy (NPDR). Methods: A prospective, randomized, interventional, monocentric, double-masked study was conducted. Twenty patients with DM1 were enrolled and randomly divided into two groups: the DC group (10 patients; mean age ± standard deviation 46.86 ± 8.78 years) in which one eye of each patient was treated with citicoline and vitamin B 12 eye drops (OMK2 Ò , Omikron Italia srl, Italy, one drop thrice daily) for a period of 36 months; the DP group (10 patients; mean age ± standard deviation 47.89 ± 7.74 years) in which one eye of each patient was treated with placebo (eye drops containing hypromellose 0.3%, one drop thrice daily) for a period of 36 months. A total of 18 eyes (10 from the DP and 8 from the DC group, respectively) completed the study. In both groups, multifocal electroretinogram (mfERG) recordings were assessed at baseline and after 36 months. In mfERG analysis, the N1-P1 response amplitude density (RAD) evaluated in the 0-2.5°(ring 1), in the 2.5-5°(ring 2), in the 5-10°(ring 3), and in the 0-10°( ring 1 ? ring 2 ? ring 3) were considered. Results: With respect to baseline, after 36 months of follow-up, the mfERG RADs recorded in R1, R2, R3, and R1 ? R2 ? R3 were significantly increased (i.e., R1 ? R2 ? R3 RAD from 21.552 ± 2.522 nV/degree 2 at baseline to 26.912 ± 2.850 nV/degree 2 at 36 months) in DC eyes, whereas in DP eyes they were significantly reduced (i.e., R1 ? R2 ? R3 RAD from 21.033 ± 3.574 nV/degree 2 at baseline to 16.151 ± 3.571 nV/degree 2 at 36 months). Conclusions: This study indicates that patients with NPDR treated with citicoline and vitamin B 12 eye drops for a 36-month period achieved an improvement of the macular bioelectrical responses detectable by mfERG recordings. By contrast, during the same period of follow-up, patients with NPDR treated with placebo showed a worsening of the macular function.

Diabetic Retinopathy: Role of Neurodegeneration and Therapeutic Perspectives

“…In this regard, it has been demonstrated that treatment with eye drops containing citicoline and vitamin B12 for a 36month period improved the macular bioelectrical responses (multifocal electroretinography recordings) in type 1 diabetic patients (n ¼ 20) with nonproliferative diabetic retinopathy (NCT04009980). 94 The EUROCONDOR study is the largest study reported till now (n ¼ 449 patients) aimed at treating neurodegeneration. This phase II-III clinical trial provided evidence that 2 neuroprotective drugs (SST and brimonidine) administered by eye drops were able to arrest the progression of retinal neurodysfunction in type 2 diabetic patients.…”

Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress

“…As a neuromodulator, citicoline was shown to increase, in in vivo studies, the levels of neurotransmitters (dopamine, noradrenaline, and serotonin) in the central nervous system [ 8 ]. On the other hand, its neuroprotective properties were documented in in vitro models of neuroblastoma cells, dopaminergic mesencephalic neurons, on cultured retinal neurons, and in clinical studies on glaucoma and diabetic retinopathy [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. Coenzyme Q 10 (Q10) is an endogenous lipophilic quinone, which exerts its functions within mitochondria, where it acts as an electron accepter, limits oxidative stress and inflammation, and prevents apoptosis [ 16 , 17 ].…”

Understanding Neurodegeneration from a Clinical and Therapeutic Perspective in Early Diabetic Retinopathy

“…The use of topical citicoline combined with vitamin B-12 indicated a functional and morphological effect on retinal ganglion cells, presumably due to neuroenhancement, neuroprotection, and the neuroregeneration properties of citicoline. Patients under citicoline topical treatment preserved superficial and deep retinal vascular parameters on OCTA, indicating a potential protective effect on microvascular impairment over time [88,89]. More importantly, all these neuroprotective compounds are safe on a systemic profile with no potential interactions or side effects, except for ocular hyperemia as the most frequent local effect in the brimonidine group [78].…”

“…Patients were followed at 12, 24, and 36 months performing 24-2 and 10-2 FDT, OCT with Spectralis mapping software, segmentation software, and OCT angiography to assess the superficial and deep vascular plexus. Adaptive optics was also performed sing Rtx1 (Imagine Eyes, Orsay, France) [88].…”

“…By contrast, the group treated with citicoline exhibited a significant increase in RADs evaluated at 0-10 central degrees. The authors explained the results indicating that citicoline and vitamin B12 eye drops may improve the function of preganglionic elements, including photoreceptors and bipolar cells, located in the 10 central degrees [88].…”