Randomized, Cross over, Multicenter, Single-Blind Study Comparing Citicoline 500 mg/Homotaurine 50 mg/Vitamin B3 54 mg/Pyrroloquinoline Quinone 5 mg (Neuprozin Mito®) and Citicoline 800 mg (Cebrolux®) on Pattern Electroretinogram (PERG) and Quality o

<b>Background/Objectives:</b> To evaluate the neuromodulative effects of oral intake of a fixed combination of citicoline 500 mg plus homotaurine 50 mg plus vitamin B3 54 mg plus pyrroloquinoline quinone (CIT/HOMO/B3/PPQ) or of citicoline 800 mg alone (CIT800) on retinal ganglion cell (RGC) function in glaucoma patients by pattern electroretinogram (PERG) and to investigate the effects on quality of life and visual function. <b>Methods:</b> Consecutive patients with primary open-angle glaucoma with controlled IOP (<18 mmHg) receiving prostaglandin analogues as monotherapy; with two reliable visual fields (Humphrey 24-2 SITA Standard) per year in the last 2 years; and an early to moderate visual field defect (MD < -12 dB) were randomized to: arm A. topical therapy + CIT/HOMO/B3/PPQ for 4 months, followed by 4 months of topical therapy + CIT800; and arm B. topical therapy + CIT800 for 4 months, then topical therapy + CIT/HOMO/B3/PPG for 4 months. Patients were examined at month 0, 4, and 8. Complete ocular examination, visual field test, PERG, and quality of life assessment (NEI-VFQ25) were performed at each visit. <b>Results:</b> Forty patients were selected and completed the study, and none developed or reported an adverse event. The overall mean age was 64.2 (±7.7) years, 27 were male. At the end of the intake period of both products, patients exhibited higher P50 and N95-wave amplitudes and shorter latencies compared to baseline. The crossover analysis found that PERG parameters were better when patients received the CIT/HOMO/B3/PQQ combination with a statistically significant shorter peak time of 1.24 ms (95% CI, 0.37 to 2.10; <i>p</i> = 0.006) in the central P50 wave, 1.32 ms (95% CI, 0.44 to 2.22; <i>p</i> = 0.004) in the inferior P50 wave, and 1.70 ms (95% CI, 0.09 to 3.31; <i>p</i> = 0.038) in the inferior N95 wave; and a statistically significant increase of 0.35 µV (95% CI, 0.10 to 0.60; <i>p</i> = 0.006) in the superior N95 amplitude. The crossover analysis did not reveal any significant differences between the intake of CIT800 and CIT/HOMO/B3/PQQ in terms of visual acuity or IOP. During the intake of CIT/HOMO/B3/PQQ, a significant improvement was observed in the total mean score (<i>p</i> = 0.004), in the general health scale (GH, <i>p</i> = 0.01), in the color vision scale (<i>p</i> = 0.006), and in the peripheral vision scale (<i>p</i> = 0.001). <b>Conclusions:</b> The present study has shown that the addition of CIT/HOMO/B3/PQQ in early glaucoma improves PERG parameters and quality of life, likely by slowing down RGC aging and enhancing mitochondrial function more significantly than citicoline 800 mg alone.