Glaucoma Therapy
Conditions
Brief summary
Glaucoma is a group of conditions characterised by a progressive loss of retinal ganglion cells (RGCs) and their axons, leading to characteristic changes in the optic nerve head and the retinal nerve fibre layer. If left untreated, the disease has a natural course that can lead to progressive and significant impairment of visual function. Intraocular pressure (IOP) is the main modifiable risk factor for the onset and progression of the disease. The positive effect of surgery on the progression of glaucoma is certainly due to the reduction in IOP levels achieved in the post-operative period, with probable secondary effects on ocular haemodynamics as well. Although IOP reduction is now considered the most potent neuroprotective treatment for glaucoma, it has been shown that good tonometric control may, in some cases, not be sufficient to preserve visual function. There are, in fact, pressure-independent mechanisms involved in the pathogenesis of glaucomatous damage, in which the progressive deterioration and apoptosis of RGCs are linked to mechanisms such as oxidative stress, glutamate neurotoxicity, the inhibition of anterograde transport of neurotrophic factors, and mitochondrial dysfunction. In recent years, various molecules, including cytidine-5'-diphosphocholine (citicoline), have been proposed in combination with hypotensive therapy due to their neuroprotective and neuroenhancing effects. In addition to its structural action, it possesses a functional action (neuroenhancer) as it increases the synthesis of neurotransmitters such as noradrenaline, acetylcholine, serotonin and dopamine, which are involved in visual signal transmission at both the retinal and post-retinal levels. To date, there is no scientific evidence regarding the effect of citicoline on visual function in glaucoma patients who have undergone filtration surgery. Therefore, the hypothesis of this study is that if surgery increases the likelihood of an improvement in the function of residual RGCs, citicoline could help achieve this objective either by increasing the proportion of patients showing improvement or by increasing the extent of the improvement. The use of a placebo is ethically justified because all patients involved in the study, having signed an informed consent form, will undergo surgical treatment - which is considered the treatment of choice for progressive glaucoma - and the efficacy of citicoline treatment needs to be validated in terms of its ability to alter the course of the disease.
Interventions
DEVICECiticoline
Citicoline is a mononucleotide composed of ribose, pyrophosphate, cytosine and choline. It is the natural intracellular precursor of phosphatidylcholine. As an intermediate in the synthesis of phosphatidylcholine, citicoline acts at a structural level, promoting the synthesis of membrane phospholipids and inhibiting their degradation. In addition to its structural action, it has a functional effect (as a neuroenhancer) in that it increases the synthesis of neurotransmitters such as noradrenaline, acetylcholine, serotonin and dopamine, which are involved in visual signal transmission at both the retinal and post-retinal levels. In addition to its structural effects, it also has a functional effect (as a neuroenhancer) in that it increases the synthesis of neurotransmitters such as noradrenaline, acetylcholine, serotonin and dopamine, which are involved in the transmission of visual signals at both the retinal and post-retinal levels.
OTHERPlacebo
solution consisting of the Neurotidine vehicle (placebo)
Sponsors
Fondazione IRCCS Policlinico San Matteo di Pavia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
The study design is a single-centre, 1:1 randomised, two-arm, placebo-controlled, double-blind superiority trial. The study protocol involves the recruitment of a sample of 50 glaucoma patients who are to undergo subconjunctival filtering surgery with MMC according to standard indications and procedures defined by the specialist, and who will be randomised to receive citicoline (n = 25) or placebo (n = 25). Recruitment will take place following the signing of the informed consent form by participants. These will be assessed at eleven time points: two weeks prior to surgery (t0); on the day of surgery (t1); one day post-surgery (t2); one month post-surgery (t3); 3 months post-surgery (t4); 6 months post-surgery (t5); 9 months post-surgery (t6); 12 months post-surgery (t7); 15 months post-surgery (t8); 18 months post-surgery (t9); 21 months post-surgery (t10); 24 months post-surgery (t11). Patients will be randomised into the two arms 2 weeks prior to surgery.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age \> 18 years * Ability to understand the protocol and provide informed consent to participate in the study * Diagnosis of primary or secondary open-angle glaucoma (PEX - PIG) and the need to undergo subconjunctival filtration surgery due to signs of morphological/functional progression of the condition or failure to achieve target pressure with medical or pre-surgical therapy. The diagnosis of glaucoma is defined by the presence of typical ophthalmoscopic damage to the optic nerve head and the consequent visual field defect. In particular, a glaucomatous visual field defect will be considered as such if there is a cluster of 3 or more contiguous points in the pattern deviation plot with a probability of occurrence in the normal population of less than 5%, one of which has a probability of less than 1%, a pattern standard deviation with a probability of less than 5%, or a GHT result outside the normal limits. * Early to moderate visual field defect, according to the Hodapp-Parrish-Anderson classification, i.e. with MD up to -12 dB, as determined by the Humphrey 24-2 SITA Standard computerised test. * Rate of visual field defect progression \> 0.5 dB/year, in the 2 years prior to surgery. * At least 3 visual field examinations performed using standard perimetry in the 2 years prior to surgery.
Exclusion criteria
* Diagnosis of angle-closure glaucoma * Previous glaucoma surgery (trabeculectomy, valve implantation or placement of other devices, cyclophotocoagulation) * Previous vitreoretinal or corneal eye surgery * Visual, neurological or general medical conditions that may affect the visual field, electrophysiological tests, OCT or A-OCT scans * Systemic administration (oral or parenteral) of cerebral vasoactive drugs, neurotrophic agents, lutein, zeaxanthin, docosahexaenoic acid, ubiquinone and/or its derivatives, citicoline and/or its derivatives within 6 months prior to enrolment in the study * Topical therapy with citicoline and/or its derivatives within 6 months prior to enrolment in the study * Known or suspected allergy or sensitisation to the study product * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the mean deviation (MD) index | 24 months after the operation | The Mean Deviation (MD) perimetric index is a measure of the average differential light sensitivity of the visual field. It is calculated as the sum of the defects found in the individual tested loci divided by the number of such loci. A higher MD indicates greater damage to the visual field. The MD index is used in conjunction with other perimetric indices to assess light sensitivity and the progression of glaucomatous damage |
Secondary
| Measure | Time frame |
|---|---|
| Change in the implicit P100 latency measured via PEV (visual evoked potentials) | 24 months after surgery |
| Change in p50 amplitude measured using PERG (retinal evoked potentials) | 24 months after surgery |
| Incidence of progression as determined by the Glaucoma Progression Analysis (GPA) programme | 24 months after surgery |
| Changes in the thickness of the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCC) as measured by SD-OCT (Spectral Domain Optical Coherence Tomography) | 24 months after surgery |
| Change in choroidal hypoperfusion areas (dropouts) measured using A-OCT (Optical coherence tomography) | 24 months after surgery |
| Changes in the total score and sub-item scores on the NEI-VFQ-25 questionnaire (National Eye Institute Visual Function Questionnaire) | 24 months after surgery |
Countries
Italy
Outcome results
None listed