The aim of the present study was to investigate variations in RNFL, ganglion cell layer or choroidal thickness in migraine patients compared to normal healthy controls. We report that although the RNFL was thinner in the migraineurs for several parameters, current results did not reach statistical significance. Nonetheless, these findings are in line with a recent quantitative meta-analysis, consisting of 26 separate studies, that reported thinner RNFL in migraineurs when their results were compared against normal healthy controls [35]. Results from Table 3 indicates that although the RNFL was thinner in the migraineurs for several parameters, current results did not reach significance. A likely explanation for this difference is that our study did not have a sufficient sample size to detect these differences. This study highlights the importance of combining single trials like this one, into a meta- analysis in order to provide a more precise estimate. Our data is therefore presented in full to enable researchers to include this in their future analysis. Findings add further support to the hypothesis that repetitive ocular haemodynamic alterations, during migraine attacks, lead to hypoxic injury and cell death. The role of oxidative stress in migraine and its effect on treatment has already been documented [36][37]. Both cerebral [38,39] and retinal [40] vasospasm in migraine has also been highlighted. Researchers have postulated that hypoxia caused by intermittent vasospasm is a risk factor for the progression of visual field loss in normal tension glaucoma [41]. Migraine [42] and NTG [41] have a known female predominance. The increased number of females in the current migraine cohort therefore reflects the known preponderance of migraine in this specific population. The exact aetiology behind this gender difference is unknown. However, some have postulated that the higher frequency of vasospasm [43,44] and vascular disease [13] found in females, contributes towards the higher prevalence of normal tension glaucoma and migraine.
The impacts of recurring episodes of haemodynamic alterations in migraineurs, is probably not limited to the RNFL. This study also investigated any differences between either the GCL or CT in migraineurs versus normal healthy controls. Our results suggest that migraineurs have significantly reduced inferior parafoveal ganglion cell layer in their right eye, during the interictal period (p= 0.039). The large effect size suggests that 15% of the variance in the para foveal inferior GCL is explained by a migraine diagnosis. Similar findings have been documented elsewhere [24–27,45] and it is of particular interest to note that several authors have record thinning, specifically within the inferior hemisphere [25–27]. Nevertheless, it is important to acknowledge that these findings have not been replicated consistently across the literature [28–30]. This highly explorative study was developed with a large number of comparisons and a small sample size. When small group sizes are employed it has been suggested that it might be necessary to adjust the alpha upwards to either 0.10 or 0.15 in order to account for insufficient numbers (Stevens 1996). When a large number of comparisons are used it is conventional to adjust the alpha level down by dividing the alpha level by the number of comparisons used. In this case the alpha would be divided by a minimum of two (for each eye examined) or a maximum of 10, if all the examined parameters were included (Table 4). When both factors are considered together this would leave a significant alpha to lie anywhere between 0.075 and 0.015. With this in mind, it suggests that current results are at best borderline and that the study would definitely benefit from repetition. Alternatively, the data could be included in a systematic review and meta-analysis investigating the GCL and CT in migraineurs, as to date none has been carried out. For this reason, all findings, including negative results have been presented to ensure that that a positive bias is not introduced into future meta-analysis. The average inferior parafoveal GCL measurements were also reduced in the left eye for the migraine population, however the figures again did not reach statistical significance. One possible explanation for this slight disparity between eyes is that the thickness is primarily reduced in the side where the headache was localised to. Unfortunately, when we looked back to this section of the questionnaire the majority of participants failed to fill in this section and we must therefore conclude that further research is necessary to investigate this hypothesis.
Twenty percent of people living with migraine report a visual illusion known as an aura preceding their headache (Russell 1996). Typical symptoms include scintillating shapes, adjacent to the central vision, expanding peripherally over 5 to 20-minute period [46]. It has been suggested that decreased visual sensitivity might be caused by localised vascular events [47]. Temporary alterations in ocular perfusion during a migraine attack could result in focal hypoxia to both the optic nerve head and the retina, resulting in transient changes to vision. We did not find any relationship between migraine with aura and migraine without aura and any of the thickness parameters.
A further aim was to examine if there is any relationship between severity and/or duration of migraine and ocular thickness. In the present study, we did not find any relationship between the two. A significant relationship between the severity and duration of migraine and the thickness of posterior ocular structures has been documented however, this study employed a significantly larger sample size [48]. Negative findings, therefore suggest that either there is no relationship between the two or that the small sample size was insufficient to detect a positive relationship. Presenting future results in full even when negative will allow future researchers to reliably investigate this variable as part of a meta-analysis.
The outcomes from this study all indicate that this area of research would greatly benefit from a systematic review and meta-analysis which is not limited to the RNFL, but also includes the GCL and the choroidal thickness of migraine patients compared to normal healthy controls. Researchers should also determine the impact of migraine type (with or without aura) and the MIDAS score/grade. As there is some suggestion from the literature that both parameters have ocular implications which can be measured in vivo.