Emmetropization and nonmyopic eye growth.

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.

Correlation of vitreous chamber depth with ocular biometry in high axial myopia.

PURPOSE: The proportion of axial length (AL) occupied by vitreous chamber depth (VCD), or VCD:AL, consistently correlates to ocular biometry in the general population. Relation of VCD:AL to ocular biometry in high myopia is not known. The purpose of this study is to evaluate the relation of VCD and VCD:AL to ocular biometry of highly myopic eyes. METHODS: This was a cross-sectional retrospective study of records of 214 myopic eyes (<-1 D SE, aged 20-40 years) attending the refractive surgery services. High axial myopia was defined as AL >26.5 mm. Eyes with posterior staphyloma and myopic maculopathy were excluded. Records were assessed for measurements of AL, central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT), white to white diameter (WTW), and vitreous chamber depth (VCD). Groups were formed based on increasing AL, while the sum of CCT, ACD, and LT was recorded as anterior segment depth (AS). The main outcome measure was the correlation of VCD and VCD:AL to ocular biometry. A comparison was also performed based on of degree of axial myopia. RESULTS: Mean age of the patients was 27.0 ± 5.2 years. VCD showed a very strong correlation with AL (R = 0.98, P < 0.001) but did not correlate to any anterior parameter. VCD:AL showed moderate negative relation with AS (R = -0.43, P < 0.001) and ACD (R = -0.3, P < 0.001), while it had a weakly negative relation with LT (R = -0.18, P = 0.006). VCD:AL showed strong negative relation (R > ~0.7) with AS in all individual groups of AL. Among anterior parameters, WTW showed the most consistent relation with ocular biometry. CONCLUSION: VCD:AL is a better correlate of ocular biometry in high myopia as compared to VCD. However, the correlation is weaker than that noted by previous studies done on the general population. Longitudinal studies of VCD:AL in the younger age group is recommended.

Optical biometry and influence of media opacity due to cataract on development of axial length in NorthEast Indian paediatric patients- A prospective study.

AIM: To study the influence of media opacity due to cataract on the development of axial length in paediatric patients from North-East India, using optical biometry. METHOD: This is a prospective, observational study, including consecutive patients attending the paediatric ophthalmology clinic, over a period of 1 year. Patients with other ocular and systemic diseases, unfit for optical biometry measurements due to dense cataract, nystagmus and strabismus were excluded and rest divided into three groups after proper age matching - 1. Group A (Bilateral cataract) 2. Group B (Unilateral cataract) 3. Group C (Bilateral normal). The axial length of the various groups was analysed using independent sample test (for bilateral cataract group) and paired t-test (for unilateral cataract group). Linear regression analysis between age and axial length was done. RESULTS: A total of 177 patients were included.80 cases in Group A (bilateral cataract), 18 cases in Group B (unilateral cataract) and 79 in Group C (bilateral normal) The mean age of the patients in all the groups was 8.88 ± 3.51 years (range: 1-17 years). The bivariate analysis and simple linear regression revealed a statistically significant correlation between age and AL in case of cataractous eyes. (Pearson's coefficient: 0.341, p < 0.001). The mean AL was significantly longer (p = 0.013) in the cataractous eyes (mean = 23.38 ± 2.08 mm) of Group A(bilateral cataract) in the 7-12 years age group as compared to the bilaterally normal eyes (mean AL = 22.57 ± 0.70 mm) of patients in the same age group in Group C. The mean AL of cataractous eyes in group B (unilateral cataract) (mean = 22.46 ± 1.73 mm) as compared to the fellow normal eyes, (mean = 21.87 ± 0.97 mm) was not statistically significant. CONCLUSION: Cataractous eyes have an abnormal axial length development. The influence of media opacity due to cataract on development of axial length in paediatric eyes in the North-East Indian population is variable, in line with global data on the same. Although there is some influence of media opacity, the exact nature is not clearly understood and may have a crucial interaction with genetic and other environmental factors. Genetic testing integrated with biometric analysis is recommended for further understanding of the ocular growth and development.

Protective effects of sunlight exposure against PRK-induced myopia in infant rhesus monkeys.

PURPOSE: Extensive clinical evidence suggests that time spent outdoors might reduce the risk of myopia. This study aimed to determine whether increasing sunlight exposure has a protective effect on hyperopic-defocus induced myopia in a non-human primate. METHODS: Twelve 2-month-old rhesus monkeys were treated monocularly with photorefractive keratectomy (PRK) (4.0 D) and divided randomly into two groups: artificial light (AL; n = 6) and natural light (NL; n = 6). Monkeys in the AL group were reared under artificial (indoor) lighting (08:00-20:00 h). Monkeys in the NL group were exposed to natural (outdoor) lighting for 4 h (09:00-11:00 and 15:00-17:00 h). Ocular refraction, corneal power and axial dimensions were measured before sunlight exposure and every 10 days after PRK. At day 180, retinal histology and apoptosis activity were evaluated by hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase biotin (dUTP) nick end labelling (TUNEL) assay. RESULTS: Mean (±SD) PRK induced anisometropia was +3.11 (0.33) D. At the end of the experiment, both eyes of the NL monkeys exhibited significantly more hyperopia and shorter vitreous chamber depths (VCD), compared with AL monkeys (p < 0.05). The NL group exhibited a significantly slower rate of compensation to the induced anisometropia than the AL group (p < 0.05). The retinas of both groups exhibited normal histology and levels of apoptosis. CONCLUSIONS: Moderate sunlight exposure exerts protective effects against the myopic shift resulting from PRK-induced defocus in monkeys. These results are consistent with current clinical findings that increased outdoor exposure protects against myopia development. Sunlight exposure should serve as an independent positive factor in human myopia control.

Vitreous collagen cross-linking and maturation and interactions with internal limiting membrane (ILM) collagen may have a potential role in modulating postnatal growth of the eyeball.

At birth, the eye is moderately hypermetropic but achieves emmetropia by the age of 5-6 years in a large majority (Chakraborty et al., 2020; Gwiazda et al., 1993). The process of emmetropization is attributed to changes in several components of the eye structure, predominantly cornea, crystalline lens and axial length. Emmetropization is possible only when there is a fine balance between the optical power of the eye and its focal length. The former is determined by the combined dioptric power of the cornea and crystalline lens and the latter by the axial length of the eyeball. Increase in axial length has been shown to be the most important factor for reaching emmetropia. The main determinant of this increase is reported to be expansion of the vitreous chamber (Mutti et al., 2005; Larsen, 1971). Growth of the vitreous body during postnatal development is well established. However, what initiates vitreous chamber expansion and what brings about its precise arrest at the point of emmetropization are aspects that have not been explored and remain an enigma. It is hypothesized herein that vitreous chamber expansion and resultant early increase in axial length that precisely stops at the point of emmetropia, occurs secondary to postnatal structural and conformational changes within the vitreous collagen and internal limiting membrane (ILM) collagen and molecular interactions between these two structures.

Topical application of dopaminergic compounds can inhibit deprivation myopia in chicks.

PURPOSE: Animal models have demonstrated a link between dysregulation of the retinal dopamine system and the development of experimental myopia (short-sightedness). However, pharmacological investigations of dopamine in animal models rely heavily on intravitreal or systemic administration, which have several limitations for longer-term experiments. We therefore investigated whether administration of dopamine as a topical eye drop can inhibit the development of form-deprivation myopia (FDM) in chicks. We also examined whether chemical modification of dopamine through deuterium substitution, which might enhance stability and bioavailability, can increase dopamine's effectiveness against FDM when given topically. METHODS: Dopamine or deuterated dopamine (Dopamine-1,1,2,2-d4 hydrochloride) was administered as a daily intravitreal injection or as daily topical eye drops to chicks developing FDM over an ascending dose range (min. n = 6 per group). Axial length and refraction were measured following 4 days of treatment. RESULTS: Both intravitreal (ED50 = 0.002µmoles) and topical application (ED50 = 6.10µmoles) of dopamine inhibited the development of FDM in a dose-dependent manner. Intravitreal injections, however, elicited a significantly higher level of protection relative to topical eye drops (p < 0.01). Deuterated dopamine inhibited FDM to a similar extent as unmodified dopamine when administered as intravitreal injections (p = 0.897) or topical eye drops (p = 0.921). CONCLUSIONS: Both intravitreal and topical application of dopamine inhibit the development of FDM in a dose-dependent manner, indicating that topical administration may be an effective avenue for longer-term dopamine experiments. Deuterium substitution does not alter the protection afforded by dopamine against FDM when given as either an intravitreal injection or topical eye drop.

Evaluation of the vitreous chamber depth: An assessment of correlation with ocular biometrics.

Purpose: The mechanism of ocular growth eludes us and research on vitreous chamber depth (VCD) is lacking. The purpose of this study was to evaluate the role of VCD and its ratio to axial length (AL) in relation to ocular biometry. Methods: This retrospective study of patients planned for cataract surgery was performed at a tertiary center. Data regarding AL, anterior chamber depth (ACD), lens thickness (LT), and central corneal thickness (CCT) of 640 eyes was noted. Anterior segment (AS) was measured as sum of CCT, ACD, and LT, while VCD was calculated as the difference between AL and AS. Correlation of VCD and VCD: AL with ocular biometry was the primary outcome measure. Three groups were formed on the basis of AL and Pearson correlation coefficient (R) was applied. Results: Mean VCD was 15.38+/-1.14 mm. Mean VCD: AL was 0.66+/-0.02. VCD had a very strong relation with AL (R = 0.9, P < 0.001) only, whereas VCD: AL had a good--strong relation with AL (R = 0.5, P < 0.001), AS (R = 0.7, P < 0.001), ACD (R = 0.3, P < 0.001), and LT (R = 0.5, P < 0.001). The relation of VCD: AL with AS was very strong across all groups (R ≤ -0.8, P < 0.001 in all groups). 85% of eyes in group with AL <22 mm had VCD: AL <0.67, conversely 85% of eyes with AL >24.5 mm had VCD: AL >0.67. Conclusion: : We found VCD to have the strongest relation with AL. VCD: AL was more consistent and showed a strong relation to ocular biometry across all ALs. This suggests the possible utility of the ratio VCD: AL while evaluating ocular growth, refractive status, and myopia-related complications.

Variations in the proliferative activity of the peripheral retina correlate with postnatal ocular growth in squamate reptiles.

The retina is a complex, multilayered tissue responsible for the perception of visual stimuli from the environment. Contrary to mammals, the capacity for postnatal eye growth in fish and amphibians, and to a lower extent in birds, is coordinated with a progenitor population residing in the ciliary marginal zone (CMZ) at the retinal peripheral margin. However, little is known about embryonic retinogenesis and postnatal retinal growth in squamates (lizards, snakes), despite their exceptional array of ecologies and ocular morphologies. Here, we address this gap by performing the first large-scale study assessing both ontogenetic and adult changes in the stem/progenitor activity of the squamate peripheral retina. Our study reveals for the first time that squamates exhibit a source of proliferating progenitors persisting post embryogenesis in a newly identified retinociliary junction anteriorly adjacent to the retina. This region is strikingly similar to the vertebrate CMZ by its peripheral location and pseudostratified nature, and shares a common pattern of slow-cycling cells, spatial differentiation gradient, and response to postnatal ocular growth. Additionally, its proliferative activity varies considerably among squamate species, in correlation with embryonic and postnatal differences in eye size and growth. Together our data indicate that squamates possess a proliferative peripheral retina that acts as a source of progenitors to compensate, at least in part, for postnatal ocular growth. Our findings also highlight the remarkable variation in activity and location of vertebrate retinal progenitors, indicating that the currently accepted scenario of reduced CMZ activity over the course of evolution is too simplistic.

Narrow-band, long-wavelength lighting promotes hyperopia and retards vision-induced myopia in infant rhesus monkeys.

The purpose of this investigation was to determine the effects of narrow band, long-wavelength lighting on normal refractive development and the phenomena of lens compensation and form-deprivation myopia (FDM) in infant rhesus monkeys. Starting at 24 and continuing until 151 days of age, 27 infant rhesus monkeys were reared under long-wavelength LED lighting (630 nm; illuminance = 274 ± 64 lux) with unrestricted vision (Red Light (RL) controls, n = 7) or a +3 D (+3D-RL, n = 7), -3 D (-3D-RL, n = 6) or diffuser lens (From Deprivation (FD-RL), n = 7) in front of one eye and a plano lens in front of the fellow eye. Refractive development, corneal power, and vitreous chamber depth were measured by retinoscopy, keratometry, and ultrasonography, respectively. Comparison data were obtained from normal monkeys (Normal Light (NL) controls, n = 39) and lens- (+3D-NL, n = 9; -3D-NL, n = 18) and diffuser-reared controls (FD-NL, n = 16) housed under white fluorescent lighting. At the end of the treatment period, median refractive errors for both eyes of all RL groups were significantly more hyperopic than that for NL groups (P = 0.0001 to 0.016). In contrast to fluorescent lighting, red ambient lighting greatly reduced the likelihood that infant monkeys would develop either FDM or compensating myopia in response to imposed hyperopic defocus. However, as in the +3D-NL monkeys, the treated eyes of the +3D-RL monkeys exhibited relative hyperopic shifts resulting in significant anisometropias that compensated for the monocular lens-imposed defocus (P = 0.001). The red-light-induced alterations in refractive development were associated with reduced vitreous chamber elongation and increases in choroidal thickness. The results suggest that chromatic cues play a role in vision-dependent emmetropization in primates. Narrow-band, long-wavelength lighting prevents the axial elongation typically produced by either form deprivation or hyperopic defocus, possibly by creating direction signals normally associated with myopic defocus.

Myopic anisometropia: ocular characteristics and aetiological considerations.

Anisometropia represents a unique example of ocular development, where the two eyes of an individual, with an identical genetic background and seemingly subject to identical environmental influences, can grow asymmetrically to produce significantly different refractive errors. This review provides an overview of the research examining myopic anisometropia, the ocular characteristics underlying the condition and the potential aetiological factors involved. Various mechanical factors are discussed, including corneal structure, intraocular pressure and forces generated during near work that may contribute to development of anisomyopia. Potential visually guided mechanisms of unequal ocular growth are also explored, including the influence of astigmatism, accommodation, higher-order aberrations and the choroidal response to altered visual experience. The association between binocular vision, ocular dominance and asymmetric refraction is also considered, along with a review of the genetic contribution to the aetiology of myopic anisometropia. Despite a significant amount of research into the biomechanical, structural and optical characteristics of anisometropic eyes, there is still no unifying theory, which adequately explains how two eyes within the same visual system grow to different endpoints.

Ocular dimensions in relation to auxological data in a sample of Swedish children aged 4-15 years.

PURPOSE: The purpose was to characterize normal growth patterns of ocular and optical components and to relate them to auxological data in a sample of Swedish children aged 4-15 years. METHODS: A prospective cross-sectional study was carried out in 143 Swedish children with a mean age of 9.8 years. Variables including gestational age (GA), weight, length and head circumference (HCF) at birth and at the time of assessment were registered. Visual acuity (VA), cycloplegic refraction and biometric measures were obtained. Palpebral fissure length and inner canthal distance were measured. Optic disc morphology as seen on fundus photographs was analysed. RESULTS: Children born more mature, with male predilection, were found to have deeper anterior and vitreous chamber depths, longer axial lengths and thinner crystalline lens thickness. No correlations were found between ocular biometric measurements and VA or refraction after adjustment for confounding variables. Inner canthal distance was significantly correlated with birth length (p = 0.03), height, weight, BMI and HCF (p = 0.0008, p = 0.0007, p = 0.037, and p = 0.04, respectively) at time of assessment. Total axial length was found to be significantly correlated with GA (p = 0.0226) and length at assessment in girls (p = 0.0084). Right optic disc and rim areas decreased with increasing age (p = 0.0078 and p = 0.0107, respectively); however, optic disc parameters were not dependent on any other variable. CONCLUSION: These normative values may serve as a basis for the ocular findings and their relationship to auxological data in Caucasian children aged 4-15 years, as well as for future comparison in patients with paediatric ocular pathologies.

Intervention of blue light with short wavelength on the progression of form deprived myopia in guinea pigs / 中华实验眼科杂志

Background Light stimulation at different wavelength influences the development of eyes.It has been showed that blue light can inhibit the growth of eyeball.To study whether blue light exposure can delay the extension of myopia is an interested research project.Objective This study was to investigate the effect of blue light with short wavelength on ocular growth in form deprived myopia (FDM) in guinea pigs and provide a new option for the prevention and treatment of myopia.Methods Thirty-six 2-week-old guinea pigs were reared in the environment of white light.The right eyes of the animals were occluded to establish the FDM models.The models were randomized into the deocclusion + blue light exposure group,simple deocclusion group and continuous occlusion group according to the random number table.The right eyes of the models were deoccluded for 1 hour per day to give the blue light (430 nm) irradiation in the deocclusion + blue light exposure group,and the right eyes were deoccluded for 1 hour per day only in the simple deocclusion group.In the continuous occlusion group,the right eyes of the models were occluded until the end of this experiment.Anterior chamber depth (ACD),lens thickness (LT) and vitreous cavity depth (VCD) were measured by A-type sonography.The binocular diopter of the guinea pigs was detected using retinoscopy in the mydriatic condition.In the fourth week after experiment,the retinal sections were prepared for the regular histopathological examination,and the scleral tissues next to 1 mm from optical nerve were exacted to obtain the dry weight of scleral tissues.Results In the right eyes of the animals,no significant differences were found in the diopter,ACD,LT and VCD before experiment among the 3 groups (all at P＞0.05).At the end of experiment,the refraction of right eye in the deocclusion + blue light exposure group,simple deocclusion group and continuous occlusion group was (+1.11±0.17)D,(+0.90±0.15)D and (-2.73±0.19)D respectively,with a significant difference among them (F=1 445.470,P=0.000).The VCD in the three groups was (3.70±0.09) mm,(3.78±0.11) mm and (3.91 ± 0.08) mm,respectively,showing a significant difference (F =13.243,P＜0.01).In addition,the dry weight of sclera tissues was (0.61 ±0.09)mg in the deocclusion + blue light exposure group,(0.54± 0.08)mg in the simple deocclusion group and (0.43 ± 0.07)mg in the continuous occlusion group,with a significant difference among the 3 groups (F=10.458,P＜0.01).However,there were no significant differences in the ACD and LT among the 3 groups (F=0.203,0.084,both at P＞0.05).Moreover,in the left eyes,no significant differences were found in the diopter,ACD,LT and VCD before experiment among the 3 groups (all at P＞0.05);while at the end of the experiment,the diopter of the continuous occlusion group was significantly lower than that of the deocclusion + blue light exposure group and simple deocclusion group (all at P＜0.05).No significant differences were seen in the ACD,LT,VCD and dry weight of sclera among the 3 groups (all at P＞0.05).Retinal structure was normal in the left eyes of various groups.However,the retinas were thinner in the right eyes of the deocclusion + blue light exposure group with clear layers; while atrophy of the outer segment of photoreceptor and disorder of cell arrangement were seen in the right eyes of the continuous occlusion group.Conclusions During sensitive period of visual development,blue light stimulation can arrest the extension of posterior sclera and elongation of vitreous cavity,which restrains development of myopia.This blue light at the wavelength of 430 nm is safe to retina.