The Effect of Vitamin B3 Supplementation in Glaucoma

INTERVENTION: International Nonproprietary Name (INN): nicotinamide Intervention: daily nicotinamide supplementation for 12 weeks Dose: accelerated dose from 1.5 grams daily for 6 weeks to 3 grams daily for 6 weeks Mode of administration: oral tablet Study design: 2 participant groups with cross‐over study design. Participants are randomly assigned to receive either nicotinamide or placebo for 12 weeks, followed by a cross‐over (i.e. those on nicotinamide first will switch to placebo and those on placebo first will switch to nicotinamide) for a further 12 weeks. A washout period will not be utilised as the effect of nicotinamide does not have a persistent effect after intake is ceased. As participants will be seen in 6‐weekly intervals, we do not expect a nicotinamide‐induced effect on our measurements in the group that receives nicotinamide first and placebo second. As for those that receive placebo first, then a washout period is also unnecessary as no intervention has been given. Adherence monitoring: remaining tablets will be counted at each visit, participants will be asked to log each time they forget a dose. To improve adherence, weekly reminders via phone, e‐mail or text message will be sent, and a daily alarm set on participant's phone (if they have a smartphone). A minimum 70% compliance rate will be deemed acceptable, which approximately equates to forgetting to take the intervention twice a week. CONDITION: Glaucoma PRIMARY OUTCOME: Short‐term changes in retinal function after intervention, specifically changes to the photopic (light‐adapted) electroretinogram (ERG). As nicotinamide leads to NAD+ repletion, which can drive energy repletion in the cells of the retina, the ERG can be affected in different ways. Specific parameters include amplitude and timing changes to the a‐wave (photoreceptor), b‐wave (bipolar cell) and photopic negative response (PhNR, retinal ganglion cell). Short‐term changes in retinal function after intervention, specifically visual field sensitivity assessed using perimetry (visual field machine) SECONDARY OUTCOME: Changes to the spectral characteristics of the retinal tissue assessed by hyperspectral imaging. Hyperspectral imaging provides information on the spectral characteristics of the retinal tissue, and may allow for detection of minor alterations to retinal structure, in particular, the retinal nerve fibre layer, which may not be seen using optical coherence tomography. ; As hyperspectral imaging of the retina is a novel technique, images are post‐processed offline in Matlab to analyse the spectral information in order to detect structural changes in the retina that may manifest after nicotinamide supplementation. Composite secondary outcome: change to intraocular pressure and/or ocular perfusion pressure (OPP). OPP is the balance between blood pressure and intraocular pressure. ; Intraocular pressure will be measured using a rebound tonometer (iCare tonometer). INCLUSION CRITERIA: ‐ Diagnosis of primary open angle glaucoma by an ophthalmologist ‐ Recent (last 6 months), reliable visual field with mean defect equal to or better than ‐6 dB ; Blood pressure will be measured using a digital sphygmomanometer with inflatable arm cuff. Short‐term changes in retinal function after intervention, specifically changes to the photopic (light‐adapted) electroretinogram (ERG). As nicotinamide leads to NAD+ repletion, which can drive energy repletion in the cells of the retina, the ERG can be affected in different ways. Specific parameters include amplitude and timing changes to the a‐wave (photoreceptor), b‐wave (bipolar cell) and photopic negative response (PhNR, retinal ganglion cell). Short‐term changes in retinal function after intervention, specifically visual field sensitivity assessed using perimetry (visual field machine) Short‐term changes to retinal structure after intervention, specifically changes to retinal nerve fibre layer thickness measuring using optical coherence tomography (OCT)