Myopic defocus in the evening is more effective at inhibiting eye growth than defocus in the morning: Effects on rhythms in axial length and choroid thickness in chicks

Abstract

Animal models have shown that myopic defocus is a potent inhibitor of ocular growth: brief (1–2 hours) daily periods of defocus are sufficient to counter the effects of much longer periods of hyperopic defocus, or emmetropic vision. While the variables of duration and frequency have been well-documented with regard to effect, we ask whether the efficacy of the exposures might also depend on the time of day that they are given. We also ask whether there are differential effects on the rhythms in axial length or choroidal thickness. 2-week-old chickens were divided into 2 groups: (1) “2-hr lens-wear”. Chicks wore monocular +10D lenses for 2 hours per day for 5 days at one of 3 times of day: 5:30 am (n=11), 12 pm (n=8) or 7:30 pm (n=11). (2) “2-hr minus lens-removal”. Chicks wore monocular −10D lenses continually for 7 days, except for a 2-hr period when lenses were removed; the removal occurred at one of 2 times: 5:30 am (n=8) or 7:30 pm (n=8). Both paradigms exposed eyes to brief myopic defocus that differed in its magnitude, and in the visual experience for the rest of the day. High frequency A-scan ultrasonography was done at the start of the experiment; on the last day, it was done at 6-hr intervals, starting at noon, over 24-hr, to assess rhythm parameters. Refractive errors were measured using a Hartinger’s refractometer at the end. In both paradigms, myopic defocus in the evening was significantly more effective at inhibiting eye growth than in the morning (“2-hr lens-wear”: X-C: −149 vs −83 μm/5d; “2-hr lens-removal: X-C: 91 vs 245 μm/7d; post-hoc Bonferroni test, p<0.01 for both). Data for “noon” was similar to that of “evening”. In general, the refractive errors were consistent with the eye growth. In both paradigms, a 2-way ANOVA showed that “time of day” accounted for the differences between the morning versus evening groups (“2-hr lens-wear”: p=0.0161; “2-hr lens-removal”: p=0.038). In the “plus-lens” morning exposure, the rhythm in axial length could not be fit to a sinusoid. In both paradigms, the rhythm in axial length for the evening group was phase-advanced relative to noon or morning (“2-hr lens-wear: evening vs noon; 1:24 pm vs 6:42 pm; “2-hr lens-removal: evening vs morning: 12:15 pm vs 6:18 pm; p<0.05 for both). Finally, the amplitude of the rhythm as assessed by the “day vs night” maximum and minimum respectively, was larger in the “evening” than in the “morning” group (“2-hr lens-wear: 88 vs 38 μm; “2-hr lens-removal: 104 vs 48 μm; p<0.05 for both). For the choroidal rhythm, there was no effect on phase, however, the amplitude was larger in most, but not all, experimental groups. These findings have potential translational applications to myopia prevention in schoolchildren, who are exposed to extended periods of hyperopic defocus during reading sessions, due to the nearness of the page. We propose that bouts of such near-work might best be scheduled later in the day, along with frequent breaks for distance vision.

Brief hyperopic defocus or form deprivation have varying effects on eye growth and ocular rhythms depending on the time-of-day of exposure

“…The growth inhibition caused by defocus or deprivation at mid-day (or deprivation in the morning) was not associated with any consistent effect on the rhythms in axial length, either for phase or for amplitude. However, if we compare the data for the 2-hour hyperopic defocus group to that of eyes receiving 2 hours of myopic defocus at the same times (Nickla et al 2017); Table 2), some interesting similarities are revealed: first, both types of defocus at mid-day (growth inhibition for both) caused significant phase-delays relative to the rhythms in eyes exposed to evening defocus. Second, both types of defocus in the morning (myopic defocus at this time prevents the compensatory inhibition; hyperopic defocus stimulates growth) caused abnormal 6-hour oscillations.…”

“…We suspect that the small degree of myopic defocus presumably experienced upon removal of the lens or diffuser is the cause. It is known that the temporal integration of myopic defocus is rapid (Schmid and Wildsoet 1996; Zhu et al 2005), and also that the myopic defocus signal is more effective later in the day, evincing a diurnal sensitivity in the “integrator” (Nickla et al 2017). These facts would explain the finding that removing the lens or diffuser after 2 hours of defocus in the mid-day, or after 6 hours of defocus in the morning (removal would occur at 1 pm), would cause a growth inhibition, whereas the 2-hours of morning defocus after removal would not.…”

“…In fact, even very brief exposures to myopic defocus can override much longer periods of either form deprivation or hyperopic blur and result in growth inhibition and hyperopia. However, we have recently found that there are subtle differences in the responses that can be uncovered when the time-of-day of the defocus is varied: specifically, myopic defocus in the afternoon or evening is more effective at inhibiting eye growth than that given in the early morning (Nickla et al 2017). This is true both for brief myopic defocus imposed on an emmetropic eye, and for brief myopic defocus alternating with prolonged hyperopic defocus, evincing a diurnal susceptibility of the eye’s response mechanism to the defocus signal.…”

The Influence of Light Exposure and Seasonal Changes on Short-Term and Longer-Term Changes in Axial Length of the Human Eye

“…The maximum inhibitory effect of myopic defocus on longitudinal changes in eye growth was observed in the group exposed to defocus in the evening, suggesting that myopic defocus is more effective at inhibiting eye growth when induced in the evening. Two hours of myopic defocus in the evening led to a phase advance (~4 hours) and an increase in the amplitude of axial length changes compared to the fellow control eye, which resulted in a similar hyperopic end point as full-time myopic defocus (Nickla et al, 2017b). Nickla and colleagues (2017a) also assessed the effects of 2 hours of hyperopic defocus imposed at different times of the day (morning and noon) upon eye growth and found that hyperopic defocus stimulated eye growth when imposed in the morning, but inhibited eye growth when imposed at noon.…”

“…Nickla et al (2017b) examined the influence of a brief period (2 hours) of myopic defocus imposed at different times of the day (morning, noon and evening) upon the diurnal variations and the longitudinal changes (7 days) in axial eye growth of chicks. The maximum inhibitory effect of myopic defocus on longitudinal changes in eye growth was observed in the group exposed to defocus in the evening, suggesting that myopic defocus is more effective at inhibiting eye growth when induced in the evening.…”