Ocular diurnal rhythms and eye growth regulation: Where we are 50 years after Lauber

Abstract

Many ocular processes show diurnal oscillations that optimize retinal function under the different conditions of ambient illumination encountered over the course of the 24 h light/dark cycle. Abolishing the diurnal cues by the use of constant darkness or constant light results in excessive ocular elongation, corneal flattening, and attendant refractive errors. A prevailing hypothesis is that the absence of the Zeitgeber of light and dark alters ocular circadian rhythms in some manner, and results in an inability of the eye to regulate its growth in order to achieve emmetropia, the matching of the front optics to eye length. Another visual manipulation that results in the eye growth system going into a “default” mode of excessive growth is form deprivation, in which a translucent diffuser deprives the eye of visual transients (spatial or temporal) while not significantly reducing light levels; these eyes rapidly elongate and become myopic. It has been hypothesized that form deprivation might constitute a type of “constant condition” whereby the absence of visual transients drives the eye into a similar default mode as that in response to constant light or dark. Interest in the potential influence of light cycles and ambient lighting in human myopia development has been spurred by a recent study showing a positive association between the amount of time that children spent outdoors and a reduced prevalence of myopia. The growing eyes of chickens and monkeys show a diurnal rhythm in axial length: Eyes elongate more during the day than during the night. There is also a rhythm in choroidal thickness that is in approximate anti-phase to the rhythm in eye length. The phases are altered in eyes growing too fast, in response to form deprivation or negative lenses, or too slowly, in response to myopic defocus, suggesting an influence of phase on the emmetropization system. Other potential rhythmic influences include dopamine and melatonin, which form a reciprocal feedback loop, and signal “day” and “night” respectively. Retinal dopamine is reduced during the day in form deprived myopic eyes, and dopamine D2 agonists inhibit ocular growth in animal models. Rhythms in intraocular pressure as well, may influence eye growth, perhaps as a mechanical stimulus triggering changes in scleral extracellular matrix synthesis. Finally, evidence shows varying influences of environmental lighting parameters on the emmetropization system, such as high intensity light being protective against myopia in chickens. This review will cover the evidence for the possible influence of these various factors on ocular growth. The recognition that ocular rhythms may play a role in emmetropization is a first step toward understanding how they may be manipulated in treatment therapies to prevent myopia in humans.

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

“…Ocular structures undergo diurnal variations that follow a 24-hour cycle, and animal studies have shown that there are alterations in the magnitude and the phase of these diurnal variations when refractive errors develop (Weiss & Schaeffel, 1993;Nickla et al, 1998b;Papastergiou et al, 1998). Furthermore, the natural diurnal rhythms are disturbed when ambient light levels are altered, which suggests that bright light levels could influence the diurnal rhythms and thereby modify eye growth (Lauber et al, 1961;Nickla, 2013). However, further studies are necessary to investigate the influence of light exposure on the natural ocular diurnal variations and eye growth in the human eye.…”

“…Diurnal fluctuations have been reported in many ocular parameters, (Stone et al, 2004;Nickla, 2013). Some of these rhythms are thought to be endogenous (controlled by a master clock within the individual and are free running in constant darkness), and some are controlled within the eye and others are exogenous (controlled by exogenous cycles of light/dark) (Nickla, 2013).…”

“…Results from these studies have shown that the eye's growth rate appears to be increased or decreased by a variety of environmental modifications such as induced retinal defocus, varying light levels and altering other aspects of visual input (Wallman & Winawer, 2004;Nickla, 2013;Norton & Siegwart, 2013;Stone et al, 2013). …”

“…Animal studies have also suggested that circadian rhythms of ocular structures may play a significant role in the regulation of eye growth, since these natural circadian rhythms are altered during the development of experimental refractive errors (Nickla, 2013;Stone et al, 2013). Although the control of circadian rhythms is complex and not fully understood, it is known that the circadian rhythms are controlled by a "clock gene" which controls the timing of these rhythms (Roenneberg & Foster, 1997).…”

“…Light exposure during the dark phase is likely to disrupt the synchronization of ocular rhythms when compared to day time. Since introducing the 38 Chapter 1: Literature review light during dawn and dusk had more inhibitory effects on form-deprivation myopia, it has been suggested that dawn and dusk could potentially be the times when all the ocular rhythms are synchronised (Nickla, 2013). Recently, Nickla and Totonelly (2016) investigated the effect of 2 hours of brief periods of light (700 lux) exposure at night (12:00 am to 2:00 am) on the natural ocular diurnal variations in chicks, to investigate the effect of night light on natural eye growth.…”