Physiological variation of retinal layer thickness is not caused by hydration: A randomised trial

• OCT is used as a secondary outcome measure for neurodegeneration.
• Normal variation of OCT data may mask small degrees of neurodegeneration.
• Hydration related cellular volume changes may be a cause for OCT data variation.
• This prospective trial demonstrates that hydration causes < 1% of OCT data variation.
• Trials using OCT will need to consider normal variation.

There is evidence for physiological variation of retinal thicknesses as determined by optical coherence tomography (OCT). We tested if such changes could be explained by hydration and would exceed what may be expected from normal ageing.Subjects (n = 26) of a previous study were re-assessed and were randomised to 3 groups of a hydration escalation trial (no hydration, 1 × hydration, 2 × hydration). Automated retinal layer segmentations were performed for the macular retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL) and outer nuclear layer (ONL). The averaged volumes were calculated for the central foveola, 3 mm and 6 mm circles of the ETDRS grid.Following oral hydration there were no significant differences of retinal layer thicknesses between the three randomised groups in any of the ETDRS regions at any time-point. Ageing related changes were significant over an 18 month period for the GCL.The negative outcome of this trial implies that, until the causes for the observed variation are resolved, investigators may need to accept, and include into trial power calculations, a small degree of variation (< 1%) of quantitative SD-OCT imaging either due to human physiology or instrument/software related factors.