OBJECTIVE: In children under 20 years, refractive development targets a cycloplegic refractive error of +0.5 to +1.5D, while presbyopes over 40 years generally have non-cycloplegic errors of ≥ +1D. Some papers suggest these periods are separated by a period of myopic refractive error (i.e., ≤ -0.50D), but this remains unclear. Hence, this work investigates the mean cycloplegic refractive error in adults aged between 20 - 40 years.
METHODS: In 2002 a cross-sectional study with stratified cluster sampling was performed on the population of Tehran, providing cycloplegic and non-cycloplegic refractive error data for the right eyes of 3,576 participants, aged 30.6±18.6 years (range: 1-86 years). After grouping these data into age groups of 5 years, the refractive error histogram of each group was fitted to a Bigaussian function. The mean of the central, emmetropized peak was used to estimate the mean refractive error without the influence of myopia.
RESULTS: The mean cycloplegic refractive error at the emmetropized peak decreased from +1.10±0.11D (95 % confidence interval) to +0.50±0.04D before 20 years and remains stable at that value until the age of 50 years. The non-cycloplegic refractive error also sees a stable phase at 0.00±0.04D between 15 - 45 years. After 45 - 50 years both cycloplegic and non-cycloplegic refractive error become more hypermetropic over time, +1.14±0.12D at 75 years.
CONCLUSIONS: The cycloplegic refractive error in adults is about +0.50D between 20 - 50 years, disproving the existence of the myopic period at those ages.

Form deprivation (FD) is a widely employed experimental paradigm, typically used to induce unilateral myopia in animal models. This model is weakened by potential influence upon the FD eye from vision in the freely-viewing contralateral eye, which could be eliminated by imposing FD in both eyes; but while a few previous studies have explored the feasibility of inducing bilateral FD in chicks, substantial discrepancies in treatment outcomes were noted. Consequently, this study aimed to establish a bilateral FD myopia model in chicks, with validation by investigating the associated ocular growth patterns, feeding, and social behavior. Six-day-old chicks were treated with bilateral (n = 21) or unilateral (n = 10) FD for 12 days; the fellow untreated eyes in the unilateral FD group served as controls. Refractive error, corneal power, and ocular axial dimensions were measured at 4-day intervals after the onset of form deprivation, with a Hartinger refractometer, a custom-made videokeratography system, and a high-resolution A-scan ultrasonographer, respectively. Body weight was monitored to assess the chick\'s physical development. Our results showed that birds treated with bilateral FD grew as robustly as the unilaterally form-deprived chicks, with similar or slightly heavier body weights and mortalities. Unilateral FD induced significantly higher myopia in the treated eye, with stronger corneal power, deeper anterior and vitreous chambers, and longer axial length. Moreover, either bilaterally or unilaterally FD eyes developed similar refractive error (bilateral FD, left: -28.03 ± 9.06 D, right: -28.44 ± 9.45 D; unilateral FD: -29.48 ± 8.26 D) and ocular biometric changes; but choroidal thickness was thicker in bilaterally FD eyes, rather than thinner as in unilaterally FD eyes. In addition to the highly synchronized (symmetrical, parallel) development reported previously in bilateral FD, we found in this study that the correlations between bilaterally form-deprived eyes were highest for ocular biometric parameters directly contributing to myopia development, including corneal power (r = 0.74 to 0.93), anterior chamber depth (r = 0.60 to 0.85), vitreous chamber depth (r = 0.92 to 0.94), and axial length (r = 0.90 to 0.96). The remarkably synchronized growth pattern confirmed the feasibility of the bilateral FD paradigm for future research on myopia.

(1) Background: The aim of the study was to describe refractive development from early childhood to adulthood in Danish patients with albinism and to evaluate the effect of foveal developmental stage on refractive development; (2) Methods: Patients with a clinical diagnosis of ocular or oculocutaneous albinism were invited for a refractive evaluation and comprehensive phenotyping including macular optical coherence tomography (OCT) scans. Foveal hypoplasia was graded based on OCT from 0 (normal) to 4 (absence of any signs of foveal specialization). Medical files were reviewed for historical refractive values in individual patients; (3) Results: Hyperopia (spherical equivalent refraction (SEQ) of ≥+1 Diopter (D)) was common in both children (81.3%) and adults (67.1%). The lower prevalence of hyperopia in adults was predominantly explained by increasing astigmatism with age. Emmetropization (>2D change from before 3 years to adolescence) was seen in 22.2%. There was no influence on foveal hypoplasia grade on the degree of refractive errors throughout life; (4) Conclusions: We found that emmetropization was uncommon in Danish patients with albinism and that the degree of foveal developmental stage did not influence emmetropization or the distribution of refractive errors. High degrees of hyperopia and astigmatism were common. These results indicate that fear of impeding emmetropization should not refrain the clinician from providing adequate correction for refractive errors in young children with albinism.

The muscarinic cholinergic antagonist atropine is the most widely used pharmacological treatment for the visual disorder myopia (short-sightedness), the leading cause of low-vision worldwide. This study sought to better define the mechanism by which atropine inhibits myopic growth. Although classified as a muscarinic-cholinergic antagonist, atropine has been found to bind and modulate the activity of several non-cholinergic systems (e.g., serotonin). Thus, this study investigated whether the serotonergic system could underly atropine\'s anti-myopic effects. Using a chick model of myopia, we report that atropine\'s growth-inhibitory effects can be attenuated by pharmacological stimulation of the serotonin system. This may suggest that atropine can slow the development of myopia through inhibiting serotonergic receptor activity. We also observed that pharmacological antagonism of serotonergic receptors inhibits the development of experimental myopia in a dose-dependent manner, further demonstrating that modulation of serotonergic receptor activity can alter ocular growth rates. Finally, we found that neither experimental myopia, nor atropine treatment, induced a significant change in retinal serotonergic output (i.e., synthesis, transport, release and catabolism). This may suggest that, although myopic growth can be inhibited through modulation of serotonergic receptor activity (by atropine or serotonergic antagonists), this does not require a change in serotonin levels. These findings regarding a serotonergic mechanism for atropine may have significant ramifications for the treatment of human myopia. This includes assessing the use of atropine in patients who are also undergoing treatment to upregulate serotonergic signaling (e.g., serotonergic anti-depressants).

Here we examine the effects of ambient red light on lens-induced myopia and diffuser-induced myopia in tree shrews, small diurnal mammals closely related to primates. Starting at 24 days of visual experience (DVE), seventeen tree shrews were reared in red light (624 ± 10 or 634 ± 10 nm, 527-749 human lux) for 12-14 days wearing either a -5D lens (RL-5D, n = 5) or a diffuser (RLFD, n = 5) monocularly, or without visual restriction (RL-Control, n = 7). Refractive errors and ocular dimensions were compared to those obtained from tree shrews raised in broad-spectrum white light (WL-5D, n = 5; WLFD, n = 10; WL Control, n = 7). The RL-5D tree shrews developed less myopia in their lens-treated eyes than WL-5D tree shrews at the end of the experiment (-1.1 ± 0.9D vs. -3.8 ± 0.3D, p = 0.007). The diffuser-treated eyes of the RLFD tree shrews were near-emmetropic (-0.3 ± 0.6D, vs. -5.4 ± 0.7D in the WLFD group). Red light induced hyperopia in control animals (RL-vs. WL-Control, +3.0 ± 0.7 vs. +1.0 ± 0.2D, p = 0.02), the no-lens eyes of the RL-5D animals, and the no-diffuser eyes of the RLFD animals (+2.5 ± 0.5D and +2.3 ± 0.3D, respectively). The refractive alterations were consistent with the alterations in vitreous chamber depth. The lens-induced myopia developed in red light suggests that a non-chromatic cue could signal defocus to a less accurate extent, although it could also be a result of \"form-deprivation\" caused by defocus blur. As with previous studies in rhesus monkeys, the ability of red light to promote hyperopia appears to correlate with its ability to retard lens-induced myopia and form-deprivation myopia, the latter of which might be related to non-visual ocular mechanisms.

BACKGROUND: There have recently been several clinical studies suggesting that brief periods of exposure to red light (repeated low-level red light, \'RLRL\') may produce a dramatic anti-myopia effect, calling for further investigations into its therapeutic parameters. Unfortunately, many experimental species used in refractive studies develop myopia in response to this wavelength. Tree shrews are the only animal model other than rhesus monkeys that consistently exhibit hyperopic responses to ambient red light. Here, tree shrews were used to study the influence of the spectral purity, duty cycle and intensity of red light on its anti-myopic effect.
METHODS: Juvenile tree shrews (Tupaia belangeri) were raised from 24 to 35 days after eye opening under ambient lighting that was: standard white colony fluorescent light; pure narrow band red light of either 600, 50-100 or 5 lux; red light that was diluted with 10% white light (by lux) or 50% white and 2 s of pure red light that alternated with 2 s of pure white light (50% duty cycle). Refractive measures were taken with a NIDEK ARK-700 autorefractor and axial dimensions with a LenStar LS-900 Axial Biometer.
RESULTS: The pro-hyperopia effect of ambient red light was greatly reduced by even small amounts of concurrent white light \'contamination\', but remained robust if 2-s periods of pure white light alternated with 2 s of red. Finally, the hyperopic effect of red light was maintained at reduced luminance levels in the 50-100 lux range and only failed at 5 lux.
CONCLUSIONS: These results have implications for understanding the mechanisms by which ambient red light affects refractive development, and possibly also for clinical therapies using RLRL. Nevertheless, it remains to be determined if the mechanism of the current clinical RLRL therapy is the same as that operating on tree shrews in ambient red light.

Most eyes start with a hypermetropic refractive error at birth, but the growth rates of the ocular components, guided by visual cues, will slow in such a way that this refractive error decreases during the first 2 years of life. Once reaching its target, the eye enters a period of stable refractive error as it continues to grow by balancing the loss in corneal and lens power with the axial elongation. Although these basic ideas were first proposed over a century ago by Straub, the exact details on the controlling mechanism and the growth process remained elusive. Thanks to the observations collected in the last 40 years in both animals and humans, we are now beginning to get an understanding how environmental and behavioral factors stabilize or disrupt ocular growth. We survey these efforts to present what is currently known regarding the regulation of ocular growth rates.

The use of light-emitting diodes (LEDs) has increased considerably in the 21st century with humans living in a modern photoperiod with brighter nights and dimmer days. Prolonged exposure to LEDs, especially at night, is considered a new source of pollution because it may affect the synthesis and secretion of retinal melatonin and dopamine, resulting in negative impacts on retinal circadian clocks and potentially disrupting retinal circadian rhythms. The control of ocular refraction is believed to be related to retinal circadian rhythms. Moreover, the global prevalence of myopia has increased at an alarming rate in recent decades. The widespread use of LEDs and the rapid increase in the prevalence of myopia overlap, which is unlikely to be a coincidence. The connection among LEDs, retinal circadian rhythms, and refractive development is both fascinating and confusing. In this review, we aim to develop a systematic framework that includes LEDs, retinal circadian rhythms and refractive development. This paper summarizes the possible mechanisms by which LEDs may disrupt retinal circadian rhythms. We propose that prolonged exposure to LEDs may induce myopia by disrupting retinal circadian rhythms. Finally, we suggest several possible countermeasures to prevent LED interference on retinal circadian rhythms, with the hope of reducing the onset and progression of myopia.

Reduced levels of retinal dopamine, a key regulator of eye development, are associated with experimental myopia in various species, but are not seen in the myopic eyes of C57BL/6 mice, which are deficient in melatonin, a neurohormone having extensive interactions with dopamine. Here, we examined the relationship between form-deprivation myopia (FDM) and retinal dopamine levels in melatonin-proficient CBA/CaJ mice. We found that these mice exhibited a myopic refractive shift in form-deprived eyes, which was accompanied by altered retinal dopamine levels. When melatonin receptors were pharmacologically blocked, FDM could still be induced, but its magnitude was reduced, and retinal dopamine levels were no longer altered in FDM animals, indicating that melatonin-related changes in retinal dopamine levels contribute to FDM. Thus, FDM is mediated by both dopamine level-independent and melatonin-related dopamine level-dependent mechanisms in CBA/CaJ mice. The previously reported unaltered retinal dopamine levels in myopic C57BL/6 mice may be attributed to melatonin deficiency.

Wavelength signals play a vital role in refractive development. This study aimed to explore the retinal transcriptome signature in these processes.
Guinea pigs were randomly divided into three groups exposed to white, blue, or green environmental light for eight weeks. Refraction and axial length were evaluated every 4 weeks, and the retinal transcriptome was profiled at 8 weeks.
Compared with the white group, ocular refraction significantly decreased and ocular axial length significantly extended in the green group whereas these parameters showed opposite trends in the blue group. RNA-sequencing showed that, compared with the white group, 184 and 171 differentially expressed genes (DEGs) were found in the blue and green groups, respectively. Among these DEGs, only 31 overlapped. These two sets of DEGs were enriched in distinct biological processes and pathways. There were 268 DEGs between the blue and green groups, which were primarily enriched in the extracellular matrix, and metabolism, receptor activity, and ion binding processes. In addition, nine human genes, including ECEL1, CHRND, SHBG, PRSS56, OVOL1, RDH5, WNT7B, PEBP4, CA12, were identified to be related to myopia development and wavelength response, indicating the potential role of these genes in human wavelength-induced myopia.
In this study, we identified retinal targets and pathways involved in the response to wavelength signals in emmetropization.