Mechanisms of emmetropization and what might go wrong in myopia.

Studies in animal models and humans have shown that refractive state is optimized during postnatal development by a closed-loop negative feedback system that uses retinal image defocus as an error signal, a mechanism called emmetropization. The sensor to detect defocus and its sign resides in the retina itself. The retina and/or the retinal pigment epithelium (RPE) presumably releases biochemical messengers to change choroidal thickness and modulate the growth rates of the underlying sclera. A central question arises: if emmetropization operates as a closed-loop system, why does it not stop myopia development? Recent experiments in young human subjects have shown that (1) the emmetropic retina can perfectly distinguish between real positive defocus and simulated defocus, and trigger transient axial eye shortening or elongation, respectively. (2) Strikingly, the myopic retina has reduced ability to inhibit eye growth when positive defocus is imposed. (3) The bi-directional response of the emmetropic retina is elicited with low spatial frequency information below 8 cyc/deg, which makes it unlikely that optical higher-order aberrations play a role. (4) The retinal mechanism for the detection of the sign of defocus involves a comparison of defocus blur in the blue (S-cone) and red end of the spectrum (L + M-cones) but, again, the myopic retina is not responsive, at least not in short-term experiments. This suggests that it cannot fully trigger the inhibitory arm of the emmetropization feedback loop. As a result, with an open feedback loop, myopia development becomes "open-loop".

Visual and refractive outcomes after bilateral implantation of an enhanced monofocal intraocular lens: prospective study.

PURPOSE: To evaluate visual and refractive outcomes, as well as patient satisfaction after bilateral implantation of an enhanced monofocal intraocular lens (IOL) with emmetropia as a target refraction. SETTING: San Carlos Hospital, Madrid, Spain. DESIGN: Prospective, monocentric, noncomparative study. METHODS: Adults 21 years or older suitable for cataract surgery and with corneal astigmatism <1.50 diopters (D) were bilaterally implanted with the RayOne EMV IOL and followed up for 3 months. Outcomes measures included refraction, monocular and binocular uncorrected distance visual acuity, corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity, distance-corrected intermediate visual acuity (DCIVA), and defocus curve, aberrometry, and satisfaction. Visual symptoms were assessed using the CatQuest-9SF questionnaire. RESULTS: 50 eyes of 25 patients were included. At month 3, the mean manifest spherical equivalent was -0.39 ± 0.28 D, with all eyes within 1.00 D. Binocularly, uncorrected, at distance, 68% of patients could read ≤0.0 logMAR and 95% ≤0.2 logMAR; at intermediate 59% of patients could read ≤0.1 and 100% ≤0.2 logMAR. Mean monocular CDVA was -0.03 ± 0.06 logMAR and mean monocular DCIVA was 0.28 ± 0.07 logMAR. Binocular defocus curve demonstrated a visual acuity ≤0.2 logMAR over a 2 D range from +1.00 D to -1.25 D. Satisfaction was good in 96% of patients. CONCLUSIONS: Bilateral implantation of an enhanced monofocal IOL with emmetropia as a target provided excellent binocular CDVA and good DCIVA, with a high level of satisfaction.

Influence of Lens Thickness on Accuracy of Kane, Hill-RBF 3.0, Barrett Universal II, Emmetropia Verifying Optical, and Pearl-DGS Formulas in Eyes with Nonhigh Myopia and High Myopia.

PURPOSE: To investigate the influence of lens thickness (LT) on accuracy of Kane, Hill-RBF 3.0 Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO), and Pearl-DGS formulas in eyes with different axial lengths (AL). METHODS: The prospective cohort study was conducted at Eye and ENT Hospital of Fudan University. Patients who had uneventful cataract surgery between March 2021 and July 2023 were recruited. Manifest refraction was conducted two-month post-surgery. Eyes were divided into 4 groups based on AL: short (<22mm), medium (22-24.5 mm), medium long (24.5-26mm) and very long (≥26mm). In each AL group, eyes were then divided into 3 subgroups based on the LT measured with IOLmaster700: thin (<4.5 mm), medium (4.5-5.0 mm), and thick (≥ 5 mm). The influence of LT on accuracy of Kane, Hill-RBF 3.0, BUII, EVO, and Pearl-DGS formulas were investigated in each AL group. RESULTS: A total of 327 eyes from 327 patients were analyzed, with 64, 102, 73 and 88 eyes in each AL group, respectively. In eyes with AL < 24.5 mm, myopic PE was significantly associated with greater LT using all the 5 formulas (all p < 0.05). Backward stepwise multivariate regression analyses revealed that LT was an important influencing factor for PE in all 5 formulas, particularly in eyes with AL <24.5 mm. In eyes with AL <24.5 mm and LT > 5.0 mm, PE of all 5 formulas calculated with the optional parameter LT were more myopic than those calculated without LT. CONCLUSIONS: Thicker LT was associated with more myopic PE among eyes with AL <24.5 mm when using all 5 formulas. Further optimization of current formulas is necessary, especially for eyes with short AL and thick LT.

Mean cycloplegic refractive error in emmetropic adults - The Tehran Eye Study.

PURPOSE: 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.

Longitudinal changes in crystalline lens thickness and power in children aged 6-12 years old.

OBJECTIVES: To determine the three-year changes in crystalline lens power (LP) and thickness (LT) in children and their associated factors. METHODS: Schoolchildren aged 6-12 years living in Shahroud, northeast Iran were examined in 2015 and 2018. The Bennett formula was used to calculate LP. Multiple generalized estimating equations (GEE) analysis was used for data analysis. RESULTS: Among the 8089 examined eyes, the mean LP in Phase 1 and 2, and the three-year change were 21.61 ± 1.47D, 21.00 ± 1.42D, and -0.61 ± 0.52D, respectively. The GEE model showed that negative shifts in LP were less pronounced with increasing age (ß = 0.176; p < 0.001), and were also less noticeable in hyperopes compared to emmetropes (ß = 0.120; p < 0.001). The changes in LP decreased when outdoor activity increased among urban residents (ß = 0.013; p = 0.039), while it increased in rural area (ß = -0.020; p = 0.047). Mean three-year change in LT was 0.002 ± 0.13 mm. Female sex and aging by one year increased the LT by 0.022 mm (P < 0.001). However, LT decreased in 6-8-year-olds, while it increased in 10-12-year-old children, both in a linear fashion. The change in LT was less in myopes than in emmetropes (ß = -0.018, P-value = 0.010). CONCLUSION: LP decreases after three years in 6 to 12-year-old children. LT increases slightly after three years in 6 to 12-year-old children. The changes in LP and LT were associated with the refractive errors, place of residence, age and gender and outdoor activity time.

Ablation of mpeg+ Macrophages Exacerbates mfrp-Related Hyperopia.

Purpose: Proper refractive development of the eye, termed emmetropization, is critical for focused vision and is impacted by both genetic determinants and several visual environment factors. Improper emmetropization caused by genetic variants can lead to congenital hyperopia, which is characterized by small eyes and relatively short ocular axial length. To date, variants in only four genes have been firmly associated with human hyperopia, one of which is MFRP. Zebrafish mfrp mutants also have hyperopia and, similar to reports in mice, exhibit increased macrophage recruitment to the retina. The goal of this research was to examine the effects of macrophage ablation on emmetropization and mfrp-related hyperopia. Methods: We utilized a chemically inducible, cell-specific ablation system to deplete macrophages in both wild-type and mfrp mutant zebrafish. Spectral-domain optical coherence tomography was then used to measure components of the eye and determine relative refractive state. Histology, immunohistochemistry, and transmission electron microscopy were used to further study the eyes. Results: Although macrophage ablation does not cause significant changes to the relative refractive state of wild-type zebrafish, macrophage ablation in mfrp mutants significantly exacerbates their hyperopic phenotype, resulting in a relative refractive error 1.3 times higher than that of non-ablated mfrp siblings. Conclusions: Genetic inactivation of mfrp leads to hyperopia, as well as abnormal accumulation of macrophages in the retina. Ablation of the mpeg1-positive macrophage population exacerbates the hyperopia, suggesting that macrophages may be recruited in an effort help preserve emmetropization and ameliorate hyperopia.

The Role of Dopamine in Emmetropization Modulated by Wavelength and Temporal Frequency in Guinea Pigs.

Purpose: Wavelength and temporal frequency have been found to influence refractive development. This study investigated whether retinal dopamine (DA) plays a role in these processes. Methods: Guinea pigs were randomly divided into nine groups that received different lighting conditions for 4 weeks, as follows: white, green, or blue light at 0, 0.5, or 20.0 Hz. Refractions and axial lengths were measured using streak retinoscopy and A-scan ultrasound imaging. DA and its metabolites were measured by high-pressure liquid chromatography-electrochemical detection. Results: At 0 Hz, green and blue light produced myopic and hyperopic shifts compared with that of white light. At 0.5 Hz, no significant changes were observed compared with those of green or blue light at 0 Hz, whereas white light at 0.5 Hz induced a myopic shift compared with white light at 0 or 20 Hz. At 20 Hz, green and blue light acted like white light. Among all levels of DA and its metabolites, only vitreous 3, 4-dihydroxyphenylacetic acid (DOPAC) levels and retinal DOPAC/DA ratios were dependent on wavelength, frequency, and their interaction. Specifically, retinal DOPAC/DA ratios were positively correlated with refractions in white and green light conditions. However, blue light (0, 0.5, and 20.0 Hz) produced hyperopic shifts but decreased vitreous DOPAC levels and retinal DOPAC/DA ratios. Conclusions: The retinal DOPAC/DA ratio, indicating the metabolic efficiency of DA, is correlated with ocular growth. It may underlie myopic shifts from light exposure with a long wavelength and low temporal frequency. However, different biochemical pathways may contribute to the hyperopic shifts from short wavelength light.

Meridional Anisotropy of Foveal and Peripheral Resolution Acuity in Adults With Emmetropia, Myopia, and Astigmatism.

Purpose: To quantify astigmatism-related meridional anisotropy in visual resolution at central, nasal, and inferior visual fields. Methods: Three groups of young adults (range, 18-30 years) with corrected-to-normal visual acuity (logMAR 0) were recruited: (1) myopic astigmats (MA): spherical-equivalent error (SE) < -0.75D, with-the-rule astigmatism ≥ 2.00D, n = 19; (2) simple myopes (SM): SE < -0.75D, astigmatism ≤ 0.50D, n = 20; and (3) emmetropes (EM): SE ± 0.50D, astigmatism ≤ 0.50D, n = 14. Resolution acuity was measured for the horizontal and vertical gratings at central and peripheral visual fields (eccentricity: 15°) using a 3-down 1-up staircase paradigm. On- and off-axis refractive errors were corrected by ophthalmic lenses. Results: The MA group exhibited meridional anisotropy preferring vertical gratings. At the central field, the MA group had better resolution acuity for vertical than horizontal gratings, and their resolution acuity for horizontal gratings was significantly worse than the SM and EM groups. At peripheral visual fields, both the SM and EM groups showed better resolution acuity for the radial (i.e., nasal field: horizontal gratings; inferior field: vertical gratings) than tangential orientation. However, the MA group tended to have better resolution acuity for the tangential orientation (i.e., vertical gratings), and their resolution acuity for horizontal gratings was significantly lower than the SM and EM groups at the nasal field. No significant differences were found in the inferior field among the three groups. Conclusions: This study provided evidence of astigmatism-related meridional anisotropy at the fovea and nasal visual fields, underscoring the significant impact of astigmatism on orientation-dependent visual functions.

The Role of Retinal Connexins Cx36 and Horizontal Cell Coupling in Emmetropization in Guinea Pigs.

Purpose: The purpose of this study was to determine whether retinal gap junctions (GJs) via connexin 36 (Cx36, mediating coupling of many retinal cell types) and horizontal cell (HC-HC) coupling, are involved in emmetropization. Methods: Guinea pigs (3 weeks old) were monocularly form deprived (FD) or raised without FD (in normal visual [NV] environment) for 2 days or 4 weeks; alternatively, they wore a -4 D lens (hyperopic defocus [HD]) or 0 D lens for 2 days or 1 week. FD and NV eyes received daily subconjunctival injections of a nonspecific GJ-uncoupling agent, 18-ß-Glycyrrhetinic Acid (18-ß-GA). The amounts of total Cx36 and of phosphorylated Cx36 (P-Cx36; activated state that increases cell-cell coupling), in the inner and outer plexiform layers (IPLs and OPLs), were evaluated by quantitative immunofluorescence (IF), and HC-HC coupling was evaluated by cut-loading with neurobiotin. Results: FD per se (excluding effect of light-attenuation) increased HC-HC coupling in OPL, whereas HD did not affect it. HD for 2 days or 1 week had no significant effect on retinal content of Cx36 or P-Cx36. FD for 4 weeks decreased the total amounts of Cx36 and P-Cx36, and the P-Cx36/Cx36 ratio, in the IPL. Subconjunctival 18-ß-GA induced myopia in NV eyes and increased the myopic shifts in FD eyes, while reducing the amounts of Cx36 and P-Cx36 in both the IPL and OPL. Conclusions: These results suggest that cell-cell coupling via GJs containing Cx36 (particularly those in the IPL) plays a role in emmetropization and form deprivation myopia (FDM) in mammals. Although both FD and 18-ß-GA induced myopia, they had opposite effects on HC-HC coupling. These findings suggest that HC-HC coupling in the OPL might not play a significant role in emmetropization and myopia development.

Eyes grow towards mild hyperopia rather than emmetropia in Chinese preschool children.

PURPOSE: 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). CONCLUSION: 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.

Spectral composition of artificial illuminants and their effect on eye growth in chicks.

In broadband light, longitudinal chromatic aberration (LCA) provides emmetropization signals from both wavelength defocus and the resulting chromatic cues. Indoor illuminants vary in their spectral output, potentially limiting the signals from LCA. Our aim is to investigate the effect that artificial illuminants with different spectral outputs have on chick emmetropization with and without low temporal frequency modulation. In Experiment 1, two-week-old chicks were exposed to 0.2 Hz, square-wave luminance modulation for 3 days. There were 4 spectral conditions: LED strips that simulated General Electric (GE) LED "Soft" (n = 13), GE LED "Daylight" (n = 12), a novel "Equal" condition (n = 12), and a novel "High S" condition (n = 10). These conditions were all tested at a mean level of 985 lux. In Experiment 2, the effect of intensity on the "Equal" condition was tested at two other light levels (70 lux: n = 10; 680 lux: n = 7). In Experiment 3, the effect of temporal modulation on the "Equal" condition was tested by comparing the 0.2 Hz condition with 0 Hz (steady). Significant differences were found in axial growth across lighting conditions. At 985 lux, birds exposed to the "Equal" condition showed a greater reduction in axial growth (both p < 0.01) and a greater hyperopic shift compared to "Soft" and "Daylight" (both p < 0.01). The "High S" birds experienced more axial growth compared to "Equal" (p < 0.01) but less than in "Soft" and "Daylight" (p < 0.01). Axial changes in "Equal" were only observed at 985 lux with 0.2 Hz temporal modulation, and not with lower light levels or steady light. We conclude that axial growth and refraction were dependent on the lighting condition in a manner predicted by wavelength defocus signals arising from LCA.

Associations between visual function and magnitude of refractive error for emmetropic to moderately hyperopic 4- and 5-year-old children in the Vision in Preschoolers - Hyperopia in Preschoolers Study.

PURPOSE: To evaluate associations between visual function and the level of uncorrected hyperopia in 4- and 5-year-old children without strabismus or amblyopia. METHODS: Children with spherical equivalent (SE) cycloplegic refractive error of -0.75 to +6.00 on eligibility testing for the Vision in Preschoolers-Hyperopia in Preschoolers (VIP-HIP) study were included. Children were grouped as emmetropic (<1D SE myopia or hyperopia), low hyperopic (+1 to <+3D SE) or moderate hyperopic (+3 to +6D SE). Children with anisometropia or astigmatism (≥1D), amblyopia or strabismus were excluded. Visual functions assessed were monocular distance visual acuity (VA) and binocular near VA with crowded HOTV charts, accommodative lag using the Monocular Estimation Method and near stereoacuity by 'Preschool Assessment of Stereopsis with a Smile'. Visual functions were compared as continuous measures among refractive error groups. RESULTS: 554 children (mean age 58 months) were included in the analysis. Mean SE (SD) {N} for emmetropia, low and moderate hyperopia were +0.52D (0.49) {N = 270}, +2.18D (0.57) {N = 171} and +3.95D (0.78) {N = 113}, respectively. There was a consistent trend of poorer visual function with increasing hyperopia (p < 0.001). Although all children had age-normal distance VA, logMAR (Snellen) VA of 0.00 (6/6) or better was achieved (distance, near) among more emmetropic (52%, 26%) and low hyperopic (47%, 15%) children than moderate hyperopes (25%, 9%). Mean (SD) distance logMAR VA declined from emmetropic 0.05 (0.10), to low hyperopic 0.06 (0.10) to moderately hyperopic children 0.12 (0.11) (p < 0.001); A mild progressive decrease in near VA also was observed from the emmetropic 0.13 (0.11) to low hyperopic 0.15 (0.10) to moderate hyperopic 0.19 (0.11) groups, (p < 0.001). Accommodative responses showed an increased lag with increasing hyperopia (ρ = 0.50, p < 0.001). Median near stereoacuity for emmetropes, low and moderate hyperopes was 40, 60 and 120 sec arc, respectively. The percentage of these groups with no reduced near visual functions was 83%, 61%, and 34%, respectively. CONCLUSIONS: Decreasing visual function was associated with increasing hyperopia in 4- and 5-year-olds without strabismus or amblyopia. As hyperopia with reduced visual function has been associated with early literacy deficits, near visual function should be evaluated in these children.

Emmetropic, But Not Myopic Human Eyes Distinguish Positive Defocus From Calculated Blur.

Purpose: Defocus blur imposed by positive lenses can induce hyperopia, whereas blur imposed by diffusers induces deprivation myopia. It is unclear whether the retina can distinguish between both conditions when the magnitude of blur is matched. Methods: Ten emmetropic (average 0.0 ± 0.3 diopters [D]) and 10 subjects with myopia (-2.7 ± 0.9 D; 24 ± 4 years) watched a movie on a large screen (65 inches at 2 meters (m) distance. The movie was presented either unfiltered ("control"), with calculated low-pass filtering equivalent to a defocus of 2.5 D, or with binocular real optical defocus of +2.5 D. Spatial filtering was done in real-time by software written in Visual C++. Axial length was followed with the Lenstar LS-900 with autopositioning system. Results: Watching unfiltered movies ("control") caused no changes in axial length. In emmetropes, watching movies with calculated defocus caused axial eye elongation (+9.8 ± 7.6 µm) while watching movies with real positive defocus caused shorter eyes (-8.8 ± 9.2 µm; difference between both P < 0.0001). In addition, in myopes, calculated defocus caused longer eyes (+8.4 ± 9.0 µm, P = 0.001). Strikingly, myopic eyes became also longer with positive defocus (+9.1 ± 11.2 µm, P = 0.02). The difference between emmetropic and myopic eyes was highly significant (-8.8 ± 9.2 µm vs. +9.1 ± 11.2 µm, respectively, P = 0.001). Conclusions: (1) In emmetropic human subjects, the retina is able to distinguish between real positive defocus and calculated defocus even when the modulation transfer function was matched, (2) in myopic eyes, the retina no longer distinguishes between both conditions because the eyes became longer in both cases. Results suggest that the retina in a myopic eye has reduced ability to detect positive defocus.

Tree shrews do not maintain emmetropia in initially-focused narrow-band cyan light.

We asked if emmetropia, achieved in broadband colony lighting, is maintained in narrow-band cyan light that is well focused in the emmetropic eye, but does not allow for guidance from longitudinal chromatic aberrations (LCA) and offers minimal perceptual color cues. In addition, we examined the response to a -5 D lens in this lighting. Seven tree shrews from different litters were initially housed in broad-spectrum colony lighting. At 24 ± 1 days after eye opening (Days of Visual Experience, DVE) they were housed for 11 days in ambient narrow-band cyan light (peak wavelength 505 ± 17 nm) selected because it is in focus in an emmetropic eye. Perceptually, monochromatic light at 505 nm cannot be distinguished from white by tree shrews. While in cyan light, each animal wore a monocular -5 D lens (Cyan -5 D eyes). The fellow eye was the Cyan no-lens eye. Daily awake non-cycloplegic measures were taken with an autorefractor (refractive state) and with optical low-coherence optical interferometry (axial component dimensions). These measures were compared with the values of animals raised in standard colony fluorescent lighting: an untreated group (n = 7), groups with monocular form deprivation (n = 7) or monocular -5 D lens treatment (n = 5), or that experienced 10 days in total darkness (n = 5). Refractive state at the onset of cyan light treatment was low hyperopia, (mean ± SEM) 1.4 ± 0.4 diopters. During treatment, the Cyan no-lens eyes became myopic (-2.9 ± 0.3 D) whereas colony lighting animals remained slightly hyperopic (1.0 ± 0.2 D). Initially, refractions of the Cyan -5 D eyes paralleled the Cyan no-lens eyes. After six days, they gradually became more myopic than the Cyan no-lens eyes; at the end of treatment, the refractions were -5.4 ± 0.3 D, a difference of -2.5 D from the Cyan no-lens eyes. When returned to colony lighting at 35 ± 1 DVE, the no-lens eye refractions rapidly recovered towards emmetropia but, as expected, the refraction of the -5 D eyes remained near -5 D. Vitreous chamber depth in both eyes was consistent with the refractive changes. In narrow-band cyan lighting the emmetropization mechanism did not maintain emmetropia even though the light initially was well focused. We suggest that, as the eyes diverged from emmetropia, there were insufficient LCA cues for the emmetropization mechanism to utilize the developing myopic refractive error in order to guide the eyes back to emmetropia. However, the increased myopia in the Cyan -5 D eyes in the narrow-band light indicates that the emmetropization mechanism nonetheless detected the presence of the lens-induced refractive error and responded with increased axial elongation that partly compensated for the negative-power lens. These data support the conclusion that the emmetropization mechanism cannot maintain emmetropia in narrow-band lighting. The additional myopia produced in eyes with the -5 D lens shows that the emmetropization mechanism responds to multiple defocus-related cues, even under conditions where it is unable to use them to maintain emmetropia.

The blur horopter: Retinal conjugate surface in binocular viewing.

From measurements of wavefront aberrations in 16 emmetropic eyes, we calculated where objects in the world create best-focused images across the central 27\(^\circ\) (diameter) of the retina. This is the retinal conjugate surface. We calculated how the surface changes as the eye accommodates from near to far and found that it mostly maintains its shape. The conjugate surface is pitched top-back, meaning that the upper visual field is relatively hyperopic compared to the lower field. We extended the measurements of best image quality into the binocular domain by considering how the retinal conjugate surfaces for the two eyes overlap in binocular viewing. We call this binocular extension the blur horopter. We show that in combining the two images with possibly different sharpness, the visual system creates a larger depth of field of apparently sharp images than occurs with monocular viewing. We examined similarities between the blur horopter and its analog in binocular vision: the binocular horopter. We compared these horopters to the statistics of the natural visual environment. The binocular horopter and scene statistics are strikingly similar. The blur horopter and natural statistics are qualitatively, but not quantitatively, similar. Finally, we used the measurements to refine what is commonly referred to as the zone of clear single binocular vision.

Myopia, corneal endothelial cell density and morphology in a Japanese population-based cross-sectional study: the JPHC-NEXT Eye Study.

This population-based cross-sectional study was performed to determine the mean corneal endothelial cell density (ECD), coefficient of variation (CV), and hexagonality (HEX), and their associations with myopia in Japanese adults living in Chikusei city. Of 7109 participants with available data, 5713 (2331 male and 3382 female) participants were eligible for analysis. After assessing the relationship between participant characteristics and spherical equivalent refraction (SER), the association of SER with the abnormal value of ECD (< 2000 cells/mm), CV (≥ 0.40), and HEX (≤ 50%) were determined using the logistic regression models adjusting for potential confounders (age, intraocular pressure, keratometric power, height, and antihypertensive drug use). In male participants, there was no statistically significant relationships between SER and endothelial parameters. In female participants, compared to emmetropia, SER ≤ - 6 D had significantly higher odds ratio (OR) of having the abnormal value of CV (OR = 2.07, 95% confidence interval [CI] 1.39-3.10) and HEX (OR = 2.04, 95% CI 1.29-3.23), adjusted for potential confounders, indicating that the high myopia was associated with the abnormal values of CV and HEX. Further adjustment for contact lenses wear partly attenuated these associations. Association between the SER and ECD was not detected.

Effects of physical exercise on macular vessel density and choroidal thickness in children.

We used swept-source (SS) optical coherence tomography (OCT) and OCT angiography (OCTA) to investigate the effects of moderate physical exercise on retinal and choroidal vessel densities (VDs) and thicknesses in children. One eye in each of 40 myopic children (mean age, 11.70 years) and 18 emmetropic children (mean age, 11.06 years) were included. SS-OCT 6 × 6-mm radial scans and SS-OCTA 3 × 3-mm images were centered on the macula. Heart rate (HR), systolic and diastolic blood pressure, and intraocular pressure (IOP) were recorded before and immediately after a 20-min stationary cycling exercise and after a 30-min rest. The subfoveal choroidal thickness (SFCT), choroidal thickness (CT), and VD at the superficial and deep retinal layers, choriocapillaris, and deeper choroidal vessels were determined. SFCT and CT were significantly lower at all locations immediately after exercise (p < 0.001) and did not fully recover after rest (p < 0.05). VD was lower in the deep retinal layer after exercise (p = 0.02) and higher in the superficial layer after rest (p = 0.03) in myopic eyes while it was higher in the superficial (p < 0.01) and deep layer (p < 0.01) after rest in emmetropic eyes. No significant exercise-related changes in the superficial retinal VD, choroidal VD, or IOP were observed. ΔCT% and ΔSFCT% were significantly correlated with increases in HR in myopic group (p = 0.04 and p = 0.03, respectively). Exercise increased retinal VD after rest in emmetropic eyes, and caused significant CT thinning that lasted for at least 30 min in both emmetropic and myopic eyes.

Anterior scleral thickness and shape changes with different levels of simulated convergence.

PURPOSE: Convergence plays a fundamental role in the performance of near visual tasks. We measured the effect of two levels of convergence on anterior scleral thickness and shape in emmetropes, low to moderate myopes and high myopes. METHODS: Forty-five healthy young adults aged between 18 and 35 years including 15 emmetropes, 15 low/moderate myopes, and 15 high myopes were recruited. Anterior segment optical coherence tomography and eye surface profilometry were used to evaluate the anterior scleral thickness (nasal only, n = 42) and shape (n = 40), before and during two visual tasks involving 9° and 18° convergence, in those participants with complete and reliable data. RESULTS: Convergence led to a thickening of the total anterior eye wall (5.9 ± 1.4 µm) and forward movement (10 ± 2 µm) of the nasal anterior scleral surface (both p < 0.001). Larger changes were found at 18° than at 9° convergence and in more peripheral nasal scleral regions. There was a significant association between total wall thickening and forward movement of the scleral surface. Refractive group was not a significant main effect, but there were significant interactions between refractive group and the thickness changes with convergence in different scleral regions. CONCLUSION: During convergence, the biomechanical forces acting on the eye lead to nasal anterior scleral thickening and forward movement of the nasal scleral surface.

Topically instilled caffeine selectively alters emmetropizing responses in infant rhesus monkeys.

Oral administration of the adenosine receptor (ADOR) antagonist, 7-methylxanthine (7-MX), reduces both form-deprivation and lens-induced myopia in mammalian animal models. We investigated whether topically instilled caffeine, another non-selective ADOR antagonist, retards vision-induced axial elongation in monkeys. Beginning at 24 days of age, a 1.4% caffeine solution was instilled in both eyes of 14 rhesus monkeys twice each day until the age of 135 days. Concurrent with the caffeine regimen, the monkeys were fitted with helmets that held either -3 D (-3D/pl caffeine, n = 8) or +3 D spectacle lenses (+3D/pl caffeine, n = 6) in front of their lens-treated eyes and zero-powered lenses in front of their fellow-control eyes. Refractive errors and ocular dimensions were measured at baseline and periodically throughout the lens-rearing period. Control data were obtained from 8 vehicle-treated animals also reared with monocular -3 D spectacles (-3D/pl vehicle). In addition, historical comparison data were available for otherwise untreated lens-reared controls (-3D/pl controls, n = 20; +3D/pl controls, n = 9) and 41 normal monkeys. The vehicle controls and the untreated lens-reared controls consistently developed compensating axial anisometropias (-3D/pl vehicle = -1.44 ± 1.04 D; -3D/pl controls = -1.85 ± 1.20 D; +3D/pl controls = +1.92 ± 0.56 D). The caffeine regime did not interfere with hyperopic compensation in response to +3 D of anisometropia (+1.93 ± 0.82 D), however, it reduced the likelihood that animals would compensate for -3 D of anisometropia (+0.58 ± 1.82 D). The caffeine regimen also promoted hyperopic shifts in both the lens-treated and fellow-control eyes; 26 of the 28 caffeine-treated eyes became more hyperopic than the median normal monkey (mean (±SD) relative hyperopia = +2.27 ± 1.65 D; range = +0.31 to +6.37 D). The effects of topical caffeine on refractive development, which were qualitatively similar to those produced by oral administration of 7-MX, indicate that ADOR antagonists have potential in treatment strategies for preventing and/or reducing myopia progression.

Temporal color contrast guides emmetropization in chick.

As a result of longitudinal chromatic aberration (LCA), longer wavelengths are blurred when shorter wavelengths are in focus, and vice versa. As a result, LCA affects the color and temporal aspects of the retinal image with hyperopic defocus. In this experiment, we investigated how the sensitivity to temporal color contrast affects emmetropization. Ten-day-old chicks were exposed for three days to sinusoidal color modulation. The modulation was either blue/yellow flicker (BY) (n = 57) or red/green flicker (RG) (n = 60) simulating hyperopic defocus with and without a blue light component. The color contrasts tested were 0.1, 0.2, 0.3, 0.4, 0.6, and 0.8 Michelson contrast. The mean illuminance of all stimuli was 680 lux. Temporal modulation was either of a high (10 Hz) or low (0.2 Hz) temporal frequency. To test the role of short- and double-cone stimulation, an additional condition silenced these cones in RG_0.4 (D-) and was compared with RG_0.4 (D+) (n = 14). Changes in ocular components and refractive error were measured using Lenstar and a photorefractometer. With high temporal frequency BY representing an in-focus condition for shorter-wavelengths, we found that high temporal frequency BY contrast was positively correlated with vitreous expansion (R2 = 0.87, p < 0.01), expanding the vitreous to compensate for hyperopic defocus. This expansion was offset by low temporal frequency RG, which represented blurred longer wavelengths. The reduction in vitreous expansion in RG_0.4, was enhanced in D+ compared to D- (p < 0.001), indicating a role for short- and/or double-cones. With high temporal frequency RG representing an in-focus condition for longer-wavelengths, we found that high temporal frequency RG contrast was also positively correlated with a linear increase in vitreous chamber depth (R2 = 0.84, p < 0.01) and eye length (R2 = 0.30, p ≤ 0.05), required to compensate for hyperopic defocus, but also with RG sensitive choroidal thickening (R2 = 0.18: p < 0.0001). These increases in the vitreous and eye length were enhanced with D+ compared to D- (p = 0.003) showing the role of short- and double-cones in finessing the vitreous response to hyperopic defocus. Overall, the increase in vitreous chamber depth in RG was offset by reduced expansion in BY, indicating sensitivity to the shorter focal length of blue light and wavelength defocus. Predictable changes in cone contrast and temporal frequency of the retinal image that occur with LCA and defocus result in homeostatic control of emmetropization.