Purpose: The purpose of this study was to determine the endogenous regulation pattern of tissue inhibitor of metalloproteinase-2 (TIMP-2) in the tree shrew sclera during myopia development and investigate the capacity of exogenous TIMP-2 to inhibit matrix metalloproteinase-2 (MMP-2) in vitro and both scleral collagen degradation and myopia development in vivo. Methods: TIMP-2 expression in the sclera during myopia development was assessed using polymerase chain reaction. In vitro TIMP-2 inhibition of MMP-2 was investigated using a gelatinase activity plate assay and zymography. Tree shrews were injected with a collagen precursor before undergoing monocular form deprivation and concurrent daily subconjunctival injections of either TIMP-2 or vehicle to the form-deprived eye. In vivo ocular biometry changes were monitored, and scleral tissue was collected after 12 days and assayed for collagen degradation. Results: The development of myopia was associated with a mean reduction in TIMP-2 mRNA expression after 5 days of form deprivation (P < 0.01). Both activation and activity of MMP-2 were inhibited by TIMP-2 with an IC₅₀ of 10 to 20 and 2 nM, respectively. In vivo exogenous addition of TIMP-2 significantly reduced myopia development (P < 0.01), due to reduced vitreous chamber elongation (P < 0.01). In vivo TIMP-2 treatment also significantly inhibited posterior scleral collagen degradation relative to vehicle-treated eyes (P < 0.01), with levels similar to those in control eyes. Conclusions: Myopia development in mammals is associated with reduced expression of TIMP-2, which contributes to increased degradative activity in the sclera. It follows that replenishment of this TIMP-2 significantly reduced the rate of both scleral collagen degradation and myopia development.

Mechanical tissue stresses are important contributors to the increased risk of sight-threatening pathology in larger, more myopic eyes. The contribution of altered ocular vasculature to the development of this pathology is less well defined. The current study investigated the impact of eye size on the superficial vasculature of the macula. Subjects (n = 104) aged 18–50, with no history of ocular or vascular disease, or myopia control, were recruited from university staff and student populations in Australia and Hong Kong. Refractive error, ocular size, retinal morphology and vascular morphology were quantified through open field autorefraction, ocular biometry and ocular coherence tomography angiography. Morphology of the superficial retinal capillary plexus was assessed over a 3 × 3 mm fovea-centred area. Perfusion area and vessel length densities were analysed relative to axial eye length and retinal thickness. A significant inverse association was found between axial length and vascular density measures (perfusion area density r² = 0.186, p < 0.001; and vessel length density r² = 0.102, p = 0.001). Perfusion area and vessel length densities were reduced by 5.8% (p = 0.001) in the longest, relative to the shortest, eyes. The aggregated ganglion cell layer inner plexiform layer thickness was also inversely associated with eye size (r² = 0.083, p = 0.003), and reduced, by 8.1% (p < 0.001), in the longest eyes. An inverse association of eye size and superficial retinal vasculature density, that is not simply explained by retinal expansion or image magnification factors, was confirmed. These data support the hypothesis that ongoing metabolic challenges may underlie the development of myopia-related and -associated pathology in larger eyes.

Purpose: To report the baseline prevalence of myopia among school children in Tamil Nadu, South India from a prospective cohort study. Methods: Children between the ages of 5 and 16 years from 11 schools in two districts of Tamil Nadu underwent vision screening. All children underwent visual acuity assessment using a Pocket Vision Screener followed by non‐cycloplegic open‐field autorefraction (Grand Seiko WAM‐5500). Myopia was defined as a spherical equivalent (SE) refraction of ≤−0.75 D and high myopia was defined as SE ≤ −6.00 D. Distribution of refraction, biometry and factors associated with prevalence of myopia were the outcome measures. Results: A total of 14,699 children completed vision screening, with 2% (357) of them having ocular abnormalities other than refractive errors or poor vision despite spectacle correction. The remaining 14,342 children (7557 boys; 52.69%) had a mean age of 10.2 (Standard Deviation [SD] 2.8) years. A total of 2502 had myopia in at least one eye, a prevalence of 17.5% (95% CI: 14.7–20.5%), and 74 (0.5%; 95% CI: 0.3–0.9%) had high myopia. Myopia prevalence increased with age ( p < 0.001), but sex was not associated with myopia prevalence ( p = 0.24). Mean axial length (AL; 23.08 (SD = 0.91) mm) and mean anterior chamber depth (ACD; 3.45 (SD = 0.27) mm) positively correlated with age ( p < 0.001). The mean flat (K1; 43.37 (SD = 1.49) D) and steep (K2; 44.50 (SD = 1.58) D) corneal curvatures showed negative correlation with age ( p = 0.02 and p < 0.001, respectively). In the multivariable logistic regression, older age and urban school location had higher odds for prevalence of myopia. Conclusion: The baseline prevalence of myopia among 5‐ to 16‐year‐old children in South India is larger than that found in previous studies, indicating that myopia is becoming a major public health problem in this country.

The biological mechanisms of eye growth and refractive development are increasingly well characterised, a result of many careful studies that have been carried out over many years. As the outer coat of the eye, the sclera has the ultimate impact on the restraint or facilitation of eye growth, thus any changes in its biochemistry, ultrastructure, gross morphology and/or biomechanical properties are critical in refractive error development and, in particular, the development of myopia. The current review briefly revisits our basic understanding of the structure and biomechanics of the sclera and how these are regulated and modified during eye growth and myopia development. The review then applies this knowledge in considering recent advances in our understanding of how the mechanisms of scleral remodelling may be manipulated or controlled, in order to constrain eye growth and limit the development of myopia, in particular the higher degrees of myopia that lead to vision loss and blindness. In doing so, the review specifically considers recent approaches to the strengthening of the sclera, through collagen cross-linking, scleral transplantation, implantation or injection of biomaterials, or the direct therapeutic targeting and manipulation of the biochemical mechanisms known to be involved in myopia development. These latest approaches to the control of scleral changes in myopia are, where possible, placed in the context of our understanding of scleral biology, in order to bring a more complete understanding of current and future therapeutic interventions in myopia, and their consequences.

The aim of this study was to investigate the agreement between cycloplegic and non-cycloplegic autorefraction with an open-field auto refractor in a school vision screening set up, and to define a threshold for myopia that agrees with the standard cycloplegic refraction threshold. The study was conducted as part of the Sankara Nethralaya Tamil Nadu Essilor Myopia (STEM) study, which investigated the prevalence, incidence, and risk factors for myopia among children in South India. Children from two schools aged 5 to 15 years, with no ocular abnormalities and whose parents gave informed consent for cycloplegic refraction were included in the study. All the children underwent visual acuity assessment (Pocket Vision Screener, Elite school of Optometry, India), followed by non-cycloplegic and cycloplegic (1% tropicamide) open-field autorefraction (Grand Seiko, WAM-5500). A total of 387 children were included in the study, of whom 201 were boys. The mean (SD) age of the children was 12.2 (±2.1) years. Overall, the mean difference between cycloplegic and non-cycloplegic spherical equivalent (SE) open-field autorefraction measures was 0.34 D (limits of agreement (LOA), 1.06 D to −0.38 D). For myopes, the mean difference between cycloplegic and non-cycloplegic SE was 0.13 D (LOA, 0.63D to −0.36D). The prevalence of myopia was 12% (95% CI, 8% to 15%) using the threshold of cycloplegic SE ≤ −0.50 D, and was 14% (95% CI, 11% to 17%) with SE ≤ −0.50 D using non-cycloplegic refraction. When myopia was defined as SE of ≤−0.75 D under non-cycloplegic conditions, there was no difference between cycloplegic and non-cycloplegic open-field autorefraction prevalence estimates (12%; 95% CI, 8% to 15%; p = 1.00). Overall, non-cycloplegic refraction underestimates hyperopia and overestimates myopia; but for subjects with myopia, this difference is minimal and not clinically significant. A threshold of SE ≤ −0.75 D agrees well for the estimation of myopia prevalence among children when using non-cycloplegic refraction and is comparable with the standard definition of cycloplegic myopic refraction of SE ≤ −0.50 D.

Background: The aim of the present study was to provide ocular biometry percentile values for Indian children between the ages of 6 and 12 and to validate the usefulness of centiles in predicting myopia development. Methods: The study was part of a longitudinal study—the Sankara Nethralaya Tamil Nadu Essilor Myopia Study (STEM), where objective refraction and ocular biometry were measured for children studying in grades 1, 4, and 6 at baseline (2019–2020). These data were used to generate ocular biometry percentile curves (both for axial length (AL) and AL/corneal curvature (AL/CR) ratios). The usefulness of percentile values in predicting myopia development was estimated from follow-up data (2022). Results: The total number of children in the three grades at baseline was 4514 (age range 6 to 12). Boys represented 54% (n = 2442) of the overall sample. The prevalence of myopia at baseline was 11.7% (95% CI from 10.8 to 12.7%) in these three grades. Both the AL and AL/CR ratio centiles showed a linear trend with an increase in AL and AL/CR with increasing grades (p < 0.001) for all percentiles (2, 5, 10, 25, 50, 75, 90, 95, 98, and 99) when stratified by sex. In the follow-up data (n = 377), the 75th and 50th percentiles of the AL/CR ratio had an area under the curve (AUC) of 0.79 and 0.72 to predict myopia onset for grade 4 and 6 children at baseline. Combining baseline AL with the centile shift in follow-up as a predictor increased the AUC to 0.83. Conclusions: The present study has provided centile values specific for Indian children between the ages of 6 and 12 to monitor and intervene where children are at a higher risk of myopia development.