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.

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.

OBJECTIVE: To determine the characteristics of crystalline lens with varying refractive errors and relationship with axial elongation in young school children.
METHODS: A total of 1465 children aged 6-8 years were examined annually for 2 years. Each participant underwent a series of ophthalmic examinations, including cycloplegic autorefraction, crystalline lens and axial length measurement. Crystalline lens power was determined, and factors associated with different refractive statuses were investigated.
RESULTS: Crystalline lens power decreased with time; reduction in lens power in Year 1 was greater in children with emmetropia (-0.69 ± 0.59 dioptre [D]) than in those with hyperopia (-0.49 ± 0.56 D) or myopia (-0.45 ± 0.55 D) (p < 0.001). Among the emmetropes, there were no differences in loss of crystalline lens power between those who remained emmetropic (-0.63 ± 0.59 D) and those who became myopic at Year 1 (-0.74 ± 0.61 D) and Year 2 (-0.77 ± 0.57 D, p > 0.05) visits. Among myopes at Year 1 visit, there was a greater reduction at Year 2 in those who had baseline emmetropia (-0.61 ± 0.51 D) than those who had baseline myopia (-0.26 ± 0.49 D, p < 0.001). The trend was similar among children of the same age. There was a significant correlation between changes in lens power and axial elongation in non-myopia (β = -0.954, p < 0.001) and new myopia (β = -1.178, p < 0.001), but not in established myopia (β = -0.001, p = 0.539).
CONCLUSIONS: There is accelerated loss of lens power in emmetropia and early stage of myopia. However, this loss is retarded when myopia persists and is accompanied by disappearance of the compensatory effect of lens power against axial elongation. These findings provide new insights into human refractive development.

OBJECTIVE: To document one-year changes in refraction and refractive components in preschool children.
METHODS: Children, 3-5 years old, in the Jiading District, Shanghai, were followed for one year. At each visit, axial length (AL), refraction under cycloplegia (1% cyclopentolate), spherical dioptres (DS), cylinder dioptres (DC), spherical equivalent refraction (SER) and corneal curvature radius (CR) were measured.
RESULTS: The study included 458 right eyes of 458 children. The mean changes in DS, DC and SER were 0.02 ± 0.35 D, -0.02 ± 0.33 D and 0.01 ± 0.37 D, while the mean changes in AL, CR and lens power (LP) were 0.27 ± 0.10 mm, 0.00 ± 0.04 mm and - 0.93 ± 0.49 D. The change in the SER was linearly correlated with the baseline SER (coefficient = -0.147, p < 0.001). When the baseline SER was at 1.05 D (95% CI = 0.21 to 2.16), the change in SER was 0 D. The baseline SER was also linearly associated with the change in LP (coefficient = 0.104, p = 0.013), but not with the change in AL (p = 0.957) or with the change in CR (p = 0.263).
CONCLUSIONS: In eyes with a baseline SER less than +1.00 D, LP loss was higher compared to axial elongation, leading to hyperopic shifts in refraction, whereas for those with baseline SER over this range, loss of LP compared to axial elongation was reduced, leading to myopic shifts. This model indicated the homeostasis of human refraction and explained how refractive development leads to a preferred state of mild hyperopia.

Higher visual centers could modulate visually-guided ocular growth, in addition to local mechanisms intrinsic to the eye. There is evidence that such central modulations could be species (even subspecies)-dependent. While the mouse has recently become an important experimental animal in myopia studies, it remains unclear whether and how visual centers modulate refractive development in mice, an issue that was examined in the present study. We found that optic nerve crush (ONC), performed at P18, could modify normal refractive development in the C57BL/6 mouse raised in normal visual environment. Unexpectedly, sham surgery caused a steeper cornea, leading to a modest myopic refractive shift, but did not induce significant changes in ocular axis length. ONC caused corneal flattening and re-calibrated the refractive set-point in a bidirectional manner, causing significant myopic (<-3 D, 54.5%) or hyperopic (>+3 D, 18.2%) shifts in refractive error in most (totally 72.7%) animals, both due to changes in ocular axial length. ONC did not change the density of dopaminergic amacrine cells, but increased retinal levels of dopamine and DOPAC. We conclude that higher visual centers are likely to play a role in fine-tuning of ocular growth, thus modifying refractive development in the C57BL/6 mouse. The changes in refractive error induced by ONC are accounted for by alternations in multiple ocular dimensions, including corneal curvature and axial length.

OBJECTIVE: To measure and analysis axial length (AL)/corneal radius of curvature (CRC) ratio and other refractive parameters, provide a medical reference range for refractive development evaluation and earlier visual impairment screening of 3 to 4y kindergarten students.
METHODS: Between April and June 2017, a total of 4350 participants aged 3- to 4-year-old (8700 eyes) from 10 cluster random sampling kindergartens in Shanghai, Pudong District were involved. According to the measurement and analysis of the unaided visual acuity (VA), AL, CRC, AL/CRC ratio, astigmatism and other refractive parameters, the data distribution and reference range were obtained.
RESULTS: Uncorrected VA of examined children was 0.23±0.08 (logMAR, mean±SD) [95% confidence interval (CI) range ≤0.36]; AL was 22.10±0.79 mm (95%CI 20.55-23.65); CRC was 7.86±0.26 mm (95%CI, 7.35-8.37); AL/CRC ratio was 2.81±0.12 (95%CI, 2.57-3.05). The median of astigmatism was -0.5 D, a total of 56.3% had astigmatism <-0.50 D, 85.3%<-1.00 D, 6.7%>-1.50 D; 71% were astigmatism with the rule. Eye-specific analyses were conducted. Statistical difference of VA was in right and left eyes. There were no significant differences between two eyes of AL, CRC, AL/CRC ratio and astigmatism (P>0.05).
CONCLUSIONS: VA and AL/CRC ratio reference could be used to assess refractive development in children and screening uncorrected refractive errors or amblyopia. Astigmatism needs to be considered in the diagnosis.

OBJECTIVE: To investigate the effects of spectral composition and light intensity on natural refractive development in guinea pigs.
METHODS: A total of 124 pigmented guinea pigs (2-week-old) were randomly assigned to three groups at high (Hi; 4000 lx), medium (Me; 400 lx) and low (Lo; 50 lx) light intensities under a 12:12 light/dark cycle for 6wk. Each group was subdivided into subgroups with the following spectra: broad spectrum Solux halogen light (BS), 600 nm above-filtered continuous spectrum (600F), 530 nm above-filtered continuous spectrum (530F), and 480 nm above-filtered continuous spectrum (480F; HiBS: n=10, Hi600F: n=10, Hi530F: n=10, Hi480F: n=10, MeBS: n=10, Me600F: n=10, Me530F: n=10, Me480F: n=10, LoBS: n=11, Lo600F: n=12, Lo530F: n=10, Lo480F: n=11). Refractive error, corneal curvature radius, and axial dimensions were determined by cycloplegic retinoscopy, photokeratometry, and A-scan ultrasonography before and after 2, 4, and 6wk of treatment. Average changes from both eyes in the ocular parameters and refractive error were compared among different subgroups.
RESULTS: After 6wk of exposure, high-intensity lighting enhanced hyperopic shift; medium- and low-intensity lighting enhanced myopic shift (P<0.05). Under the same spectrum, axial increase was larger in the low light intensity group than in the medium and high light intensity groups (HiBS: 0.65±0.02 mm, MeBS: 0.67±0.01 mm, LoBS: 0.82±0.02 mm; Hi600F: 0.64±0.02 mm, Me600F: 0.67±0.01 mm, Lo600F: 0.81±0.01 mm; Hi530F: 0.64±0.02 mm, Me530F: 0.67±0.01 mm, Lo530F: 0.73±0.02 mm; Hi480F: 0.64±0.01 mm, Me480F: 0.66±0.01 mm, Lo480F: 0.72±0.02 mm; P<0.05). Under 400 lx, there was a faster axial increase in the MeBS group than in the Me480F group (P<0.05). Under 50 lx, axial length changes were significantly larger in LoBS and Lo600F than in Lo530F and Lo480F (P<0.01).
CONCLUSIONS: Under high-intensity lighting, high light intensity rather than spectrum distributions that inhibits axial increase. Under medium- and low-intensity lighting, filtering out the long wavelength inhibits axial growth in juvenile guinea pigs.

OBJECTIVE: To evaluate the effect of newly designed positively aspherized progressive addition lenses (PA-PALs), which reduce both lag of accommodation and hyperopic defocus on the peripheral retina, on the progression of early-onset myopia.
METHODS: Positively aspherized-PALs have near addition and high positive distance zone aspherization comparable to the addition power. One hundred ninety-seven children were enrolled, 6 to 12 years of age, with spherical equivalent refraction from -1.00 to -4.50 diopters (D). The children were randomized to receive one of three lenses: single vision lenses (SVLs), PA-PALs with +1.0 D addition, or PA-PALs with +1.5 D addition. Follow-up visits occurred every 6 months for 2 years. The primary outcome was myopia progression evaluated by cycloplegic autorefraction.
RESULTS: One hundred sixty-nine (86%) children completed the follow-up. Statistical analysis of adjusted progression rates showed a mean (±SE) progression of -1.39 ± 0.09 D in the control group wearing SVLs at the 24-month visit. Statistically significant (P = 0.017) retardation of myopia progression (0.27 ± 0.11 D during 24-month period or reduction ratio of 20%) by +1.5 D add PA-PALs relative to the SVLs was found, which was within the range of the percentage efficacy of myopia retardation by the conventional PALs in earlier trials over the same follow-up period. Nearly all retardation occurred in the first 12 months with no significant efficacy in the second year. Positively aspherized-PALs with +1.0 D addition showed negligible efficacy.
CONCLUSIONS: To the extent that has been tested and that can be tolerated by wearers of spectacle lenses, the high positive aspherization of the distance zone added to PALs does not enhance their therapeutic efficacy in slowing myopia progression. (http://www.anzctr.org.au/ number, ACTRN12608000566336).