Differences in rod sensitivity due to photic history?

Letter to Editor

In their recent article, Bernstein et al.¹ find marked differences between migraineurs and healthy controls in the b wave of the electroretinogram under dark- and light-adapted conditions. Arguing that the b wave reflects the activity of the retinal rods, they conclude that behavioural light aversion and photophobia in migraineurs is due to differences in rod signaling. Although their data are not inconsistent with the notion that there are absolute sensitivity differences in rods in migraineurs (of whichever origin), it is worth considering an alternative explanation for their findings.

Bernstein et al.¹ performed their dark-adapted electroretinogram measurements after 20 minutes of dark adaptation recommended by the International Society for Clinical Electrophysiology of Vision.³ This figure, however, is a minimum duration, not one at which dark adaptation is complete. Indeed, the regeneration of rod responses depends on the intensity and duration of previous light exposure^2,6: the “photic history.”

Bernstein et al.¹ note that anecdotally, migraineurs with photophobia “live in a cave.” Indeed, discomfort thresholds are at light levels at least one log unit lower in migraineurs than in controls.⁵ It is conceivable that the difference in rod signals they measured might simply be due to a long-term adaptive effect of reduced light exposure. Simply put, long-term exposure to reduced light levels might lead to higher sensitivity in the rods. To rule out such a possible difference in adaptation requires careful measurement of the light intensities and spectra which the participants are exposed to in the hours before the measurement.

To demonstrate that there is truly a sensitivity difference in the rods, which might give plausibility to the notion that rods mechanistically mediate photophobia, would require the empirical demonstration that all things are indeed equal, and that the comparison is fair. Wearable devices are now available to measure light exposure at high temporal resolution and for a long time, which would make such a demonstration feasible.⁴

Reply to Spitschan.

Letter to Editor

In his letter, Dr. Spitschan² raises the possibility that our dark-adapted electroretinography recording could not be interpreted as an electrical signal that arises from rods and post-rods retinal pathways only because a 20-minute adaptation time may not be sufficient for a full adaptation, especially when considering the “photic history” in our experimental design.¹ Based on the above, he suggests that our findings may reflect a fundamental difference between migraineurs and control subjects in the ability of their rods to adapt to dark. Although his proposal is interesting and definitely worth the time and effort it may take to address in yet another clinical study, we would like to call attention to the following: (1) Photic history is known to affect the degree to which subsequent exposure to light acts to shift circadian rhythm. This effect, however, is independent of rod light sensitivity, which is simply a function of instantaneous rhodopsin concentration within the rods. (2) Rhodopsin is synthesized at a nearly constant rate. At high light levels, it is destroyed as fast as it is regenerated. At lower luminances, rhodopsin concentration equilibrates with light level and thus provides a light sensitivity appropriate to the luminance. (3) After 20 minutes of dark adaptation, normal individuals achieve a light sensitivity that will not increase significantly with longer adaptation times, even when measured with psychophysical techniques. (4) The electrophysiological methods used in our study for recording electroretinography would not be able to detect any improvement in adaptation after the 20-minute adaptation period because the differences would be too small to resolve.