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Intraocular pressure is a promising target for myopia control.

BACKGROUND: Myopia presents a noteworthy global health concern, urging exploration of innovative treatments. The role of intraocular pressure (IOP) in regulating the progression of myopia has been controversial. METHODS: To investigate the impact of reducing IOP to varying extents on myopia progression, three groups receiving distinct IOP-lowering medications (Brinzolamide, Latanoprost, and a combination of Brinzolamide and Latanoprost) were designed in a form-deprived myopic guinea pig model. Additionally, proteomics analyses were conducted to identify differentially expressed proteins in the sclera. RESULTS: Based on 24-h and 4-week IOP monitoring, the group receiving both Brinzolamide and Latanoprost exhibited the greatest magnitude of IOP reduction and the most significant inhibition of axial length (AL) growth. Moreover, the administration of IOP-lowering medications increased choroidal thickness and induced alterations in the structure of scleral collagen fibrils. Notably, scleral proteomics revealed remodeling processes associated with key mechanisms, including proteolysis, fibrinolysis, and metal ion binding. CONCLUSIONS: Our findings highlight that pressure-dependent scleral remodeling contributes to the deceleration of AL elongation. These results underscore the efficacy of IOP reduction in mitigating the progression of myopia, providing a promising alternative strategy for myopia management.

Myopia↗

Biological mechanisms of atropine in myopia control (Review).

Myopia is now recognized as a progressive, potentially sight‑threatening disease rather than just a refractive error, with its prevalence rising rapidly worldwide due to its high occurrence, major vision losses and huge public health cost. The World Health Organization estimates that 2.6 billion individuals in the world were myopic in 2020 this figure is projected to increase to 3.364 billion by 2030. Although myopia may be better controlled in its early stages, it may not be completely reversed at this time. Of all of the methods for controlling myopia, atropine, a muscarinic receptor antagonist, remains an effective pharmacological option for slowing myopia progression in children. However, the mechanisms of action of atropine remain to be fully elucidated. This review provided a systematic review for myopia epidemiology, pathogenesis, the effects and side effects, as well as up‑to‑date possible mechanisms, in the hope of facilitating that researchers in this field elucidate its underlying mechanisms so that clinical ophthalmologists may be able to better control this disease.

Humans↗

Unilateral peripapillary myelinated nerve fibers with myopia and/or amblyopia.

This report describes 12 patients with unilateral peripapillary myelinated nerve fibers associated with myopia and/or amblyopia. Seven patients had myopia with a mean of -13.00 diopters of anisometropia and abnormal maculae varying from a decreased reflex to pigment dispersion. These patients had final visual acuities of 20/200 or less following conventional amblyopia therapy. In contrast, five patients had myopia with a mean of -3.75 diopters of anisometropia and normal maculae. These patients had final visual acuities of 20/30 or greater with identical therapy. There was a statistically significant difference between the mean diopters of anisometropia of these two groups. However, the range of diopters of anisometropia overlapped, and the critical feature that determined which patients could achieve good vision was the macular appearance. This condition is distinct from simple unilateral myopia with amblyopia and from myelinated nerve fibers without myopia or amblyopia.

Amblyopia↗

Elucidation of restrictive motility in high myopia by magnetic resonance imaging.

OBJECTIVE: To elucidate the cause of an acquired, restrictive motility disorder in patients with high myopia. METHODS: Magnetic resonance imaging (MRI) scans were obtained from 37 patients with high myopia (axial length of globe, 29.4 mm; refractive error, > -15 diopters). Additional dynamic MRI scans were obtained in which the patient fixated in various positions with the less restricted eye for 50 seconds. Twenty normal orbits were studied in control MRI scans. RESULTS: The path of the lateral rectus, in the anterior and midorbital regions, was displaced downward an average of 3.4 mm in 13 patients with typical esotropia and hypotropia. This mislocation reduces abducting torque of the lateral rectus and creates depressing and extorting moments. The muscle insertions were normal, except where previous strabismus surgery relocated them. Contact between the enlarged globe and the bones of the orbital apices that would cause esotropia was not observed. CONCLUSIONS: This eye muscle abnormality in patients with high myopia is another strabismus syndrome related to abnormalities of orbital connective tissues and muscle paths. Orbital MRI scans may be useful before strabismus surgery in patients with high myopia. If an abnormal lateral rectus path is found, surgery should be directed to normalize it. Magnetic resonance imaging morphometry in high myopia may give additional information on orbital anatomy and biomechanical mechanisms of strabismus.

Adult↗

Optical causes of experimental myopia.

Experiments in which chicks are reared wearing a translucent goggle, or some similar device designed to degrade the retinal image, usually result in the induction of a significant degree of myopia. The induced myopia is due to enlargement of the vitreous chamber of the eye. Despite extensive change in the size, shape and refractive index distribution of the crystalline lens, its refractive power is static in the embryonic and early chick eye. The contribution to myopia of the cornea is uncertain; some studies have indicated either an increase or a decrease in corneal radius of curvature while others found no change. The fact that experimental myopia can be produced in chicks even when the optic nerve has been cut or when the degraded retinal image is restricted to one sector of the eye suggests that accommodation is not involved. Nevertheless, when the retinal image is degraded by being defocused with convex or concave lenses, myopia (concave lenses) or hyperopia (convex lenses) results. Chicks wearing concave or convex soft contact lenses from the day of hatching develop refractive states equal to the lens power (+8 and -10 diopters) within one week. The ability of the eye to vary its refractive development according to the sign of defocus suggests a role for accommodation. However, study of the ciliary muscle and accommodative apparatus of myopic and emmetropic chick eyes does not reveal any morphological differences that might indicate that the myopic eye had experienced an increased level of accommodation.

Accommodation, Ocular↗

Novel mutations in the small leucine-rich repeat protein/proteoglycan (SLRP) genes in high myopia.

The importance of the genetic component in high myopia has been well established in population and family studies, but only a few candidate genes have been explored to date. The extracellular matrix small leucine-rich repeat proteins/proteoglycans (SLRPs) regulate collagen fibril diameter and spacing. Given their role in extracellular matrix assembly and expression in the eye, they are likely to regulate its shape and size. Analysis of 85 English and 40 Finnish subjects with high myopia (refractive error of -6 diopters [D] or greater) resulted in 23 sequence variations in four SLRP genes, LUM, FMOD, PRELP, and OPTC. We observed higher number of variations in OPTC in English patients than in controls (p=0.042), and a possibly protective variation in LUM (c.893-105G>A) with p-value of 0.0043. Two intronic variations, six nonsynonymous and one synonymous amino acid changes, were not found in any of the nonmyopic controls. Five changes were detected in opticin, Thr177Arg, Arg229His, Arg325Trp, Gly329Ser, and Arg330His, and all but one (Arg229His) were shown to cosegregate with high myopia in families with incomplete penetrance. A homology model for opticin revealed that Arg229His and Arg325Trp are likely to disrupt the protein structure, and PolyPhen analysis suggested that Thr177Arg, Arg325Trp, and Gly329Ser changes may be damaging. A Leu199Pro change in lumican and Gly147Asp and Arg324Thr variations in fibromodulin are located in the highly conserved leucine-rich repeat (LRR) domains. This study provides new insight into the genetics of high myopia, suggesting that sequence variations in the SLRP genes expressed in the eye may be among the genetic risk factors underlying the pathogenesis of high myopia.

Amino Acid Sequence↗

Prevention of collagen crosslinking increases form-deprivation myopia in tree shrew.

To examine whether collagen crosslinking is important for the regulation of refractive development, tree shrews were treated with agents that block collagen crosslinking [beta-aminoproprionitrile (beta-APN), or D-penicillamine (DPA)] and underwent monocular deprivation (MD) of form vision by eyelid closure to induce myopia. MD began on the first day of visual exposure and continued for 75 days. After 15-20 days of visual exposure, daily intraperitoneal injections of beta-APN (beta-APN MD animals, n = 5) or DPA (DPA MD animals, n = 5) were administered for 17-21 days. beta-APN open animals (n = 5) received the same injection schedule, but both eyes remained open. Saline MD animals (n = 5) received i.p. saline and MD. At 75 days of visual exposure, the MD eyes of beta-APN treated tree shrews were highly myopic (-23.6 +/- 3.3 D) in comparison to their open control eyes. This was markedly greater than the difference in saline MD animals (-11.0 +/- 0.8 D). DPA MD animals showed a relative myopia of -14.3 +/- 2.2 D. The structural correlate of the myopia, elongation of the vitreous chamber in the deprived eyes relative to the control eyes, was significantly greater in the beta-APN MD animals 0.53 +/- 0.03 mm, which was not significantly different from the saline MD group. Thinning of the posterior sclera, but not the cornea, was observed in the deprived eyes of beta-APN treated tree shrews, along with a tessellated appearance to the fundus. The eyes of the beta-APN open animals showed no significant differences from normal. Beta-APN MD and DPA MD treated chickens did not develop greater myopia or vitreous chamber elongation than standard MD chickens. The selective effect of the lathyritic agents on the deprived eyes in tree shrew suggests that collagen crosslinking interacts, in the mammalian sclera, with a retinally-derived signal to regulate the elongation of the eye in myopia.

Aminopropionitrile↗

Timolol lowers intraocular pressure but does not inhibit the development of experimental myopia in chick.

Reports of intraocular pressure (IOP) being higher in myopes than emmetropes and of myopes being over-represented in glaucoma statistics, are consistent with a role of IOP in the excessive eye growth typically associated with myopia. We tested the hypothesis, based on these observations, that ocular hypotensive drugs would slow myopia progression using the chick as an animal model and timolol as an example of such a drug. To induce myopia, chicks (n = 56) were fitted with either monocular translucent diffusers or -15 D spectacle lenses from day 8. The drug treatment protocol comprised topical applications of 0.4% benoxinate, a local anaesthetic (to improve drug absorption), followed either by 0.5% timolol or distilled water (control), either daily (1000 hr) or twice daily (1000, 1600 hr). Refractive errors and ocular dimensions were measured on days 12 and 17. We also verified the ocular hypotensive effect of timolol in both normal (n = 8) and myopic (n = 12 diffusers; n = 12-15 D lenses) chicks. Here, we took baseline IOP measurements, instilled timolol and then monitored IOP over a further 5-9 hr. We found no difference in the amount of myopia produced in the timolol and control groups at either measurement time point (e.g. day 17, once per day application, diffusers: -26.9 +/- 3.3 D vs -22.7 +/- 9.1 D; lenses: -14.9 +/- 3.8 D vs -14.9 +/- 3.6 D). This was in spite of the fact that timolol did lower IOP in both normal and myopic chicks (27 and 18% reduction, respectively) While timolol does have an ocular hypotensive effect in the chick, it does not inhibit the development of myopia in this animal model.

Analysis of Variance↗

Hypothesis: myopia of prematurity is caused by postnatal bone mineral deficiency.

Myopia is a frequent finding in preterm children. The close association between myopia and retinopathy of prematurity (ROP) suggested a causal relationship, but myopia of prematurity without ROP has yet to be explained. An alternative explanation is presented: myopia is caused by postnatal ellipsoid deformation of the spheric eyeball, i.e. excessive elongation of the optical, as a result of a dolichocephalic deformation of the skull with a short frontal axis. This deformation of the skull is the direct result of bone mineral deficiency frequently observed in very low birth weight infants with increasing postnatal age. This hypothesis is supported by the results of a historical comparison of very low birth weight infants without and with supplementation with calcium and phosphorus that was given in order to prevent postnatal bone mineral deficiency. In the unsupplemented group 4 of 23 children (61%) needed spectacles but only 6 out of 55 (11%) children who were supplemented as babies (questionnaire). Refraction measurements showed myopia stronger than -1 o.d. in group 1 in 5 of 14 infants, whereas in group 2 only 2 out of 22 infants were myopic (P < 0.05).

Bone and Bones↗

Night myopia.

Although the phenomenon of night myopia has been recognized for two centuries, its causes are still not fully understood. Early studies implicated spherical aberration and accommodation, but the degree to which either contributed was not clearly established. More recently, "laser speckle" techniques to measure myopia have allowed the collection of data on large subject populations and it appears that night myopia represents a tendency for accommodation to approximate the dark focus as low luminance levels degrade the clarity of the retinal image. In this article, the authors review the past and present literature on night myopia and related anomalous myopias, and describe techniques for their evaluation and correction.

Accommodation, Ocular↗

Lower-field myopia in birds: an adaptation that keeps the ground in focus.

In the lower visual field of pigeons, a myopia (near-sightedness) has been reported that progressively increases with the angle below the horizon. Previous data suggested that this lower-field myopia may be an adaptation that permits pigeons to keep the ground in focus while they forage, and simultaneously, to monitor the horizon and sky for predators. We report here a lower-field myopia in other species of birds that have a wide range of heights. A geometric model of this adaptation predicts that the amount of myopia should be systematically related to the distance from the pupil to the ground. The eyes of quail, chickens and cranes of various heights (7.0-104.1 cm) were refracted at 60 deg below the horizon. Their myopia was close to the predicted value at each height.

Adaptation, Physiological↗

The development of experimental myopia and ocular component dimensions in monocularly lid-sutured tree shrews (Tupaia belangeri)

Tree shrews were monocularly deprived (MD) from the day of eye opening for periods of 15, 30, 45, 60 and 75 days. The initial structural change after 15 days of MD was a flattening of the corneal curvature in the deprived eye causing a hyperopic increase in refraction, relative to the fellow control eye. A relative myopia was first observed after 30 days of deprivation and increased as the length of MD increased. Animals monocularly deprived for 75 days consistently showed high degrees of myopia (greater -10 D). An increase in vitreous chamber depth was found after 30 days of deprivation and continued to increase, relative to the control eye, throughout the developmental period under investigation. There was a strong correlation (r = 0.84) between increase in vitreous chamber depth and the amount of experimentally-induced myopia. Anterior chamber depth was shallower in the deprived eyes of all animals. The crystalline lens was also consistently thinner in the deprived eye. Based on optical modeling, the observed myopia was consistent with the changes in ocular component dimensions. The susceptible period for experimental myopia begins about 15 days after eye opening.

Animals↗

Measurement of retinal thickness by ocular coherence tomography in a case of scleral transparency in high myopia.

PURPOSE: Staphylomatous thinning of the sclera and retina are among the numerous changes associated with the elongated eye of high myopia. We report a case of scleral and retinal transparency in high myopia in which ocular coherence tomography was used to measure retinal and scleral thickness in vivo. DESIGN: Observational case report. METHODS: The clinical presentation and evaluation of a case of scleral transparency in high myopia are presented. RESULTS: This case demonstrates numerous anatomical changes to the sclera and retina known to occur in association with high myopia. Initial evaluation by optical coherence tomography demonstrated a retinal thickness of 74 microm and a scleral thickness of 80 microm. CONCLUSIONS: Optical coherence tomography can be used to measure scleral and retinal thickness in vivo in a patient with high myopia. It is not known at this time what precautions are necessary in such a patient should intraocular surgery be required.

Body Weights and Measures↗

Incremental retinal-defocus theory of myopia development--schematic analysis and computer simulation.

Previous theories of myopia development involved subtle and complex processes such as the sensing and analyzing of chromatic aberration, spherical aberration, spatial gradient of blur, or spatial frequency content of the retinal image, but they have not been able to explain satisfactorily the diverse experimental results reported in the literature. On the other hand, our newly proposed incremental retinal-defocus theory (IRDT) has been able to explain all of these results. This theory is based on a relatively simple and direct mechanism for the regulation of ocular growth. It states that a time-averaged decrease in retinal-image defocus area decreases the rate of release of retinal neuromodulators, which decreases the rate of retinal proteoglycan synthesis with an associated decrease in scleral structural integrity. This increases the rate of scleral growth, and in turn the eye's axial length, which leads to myopia. Our schematic analysis has provided a clear explanation for the eye's ability to grow in the appropriate direction under a wide range of experimental conditions. In addition, the theory has been able to explain how repeated cycles of nearwork-induced transient myopia leads to repeated periods of decreased retinal-image defocus, whose cumulative effect over an extended period of time results in an increase in axial growth that leads to permanent myopia. Thus, this unifying theory forms the basis for understanding the underlying retinal and scleral mechanisms of myopia development.

Animals↗

The sclera and myopia.

Myopia is a very common ocular problem, affecting perhaps one billion people worldwide. Most myopia is produced by lengthening of the vitreous chamber of the ocular globe. High myopia is characterized by scleral thinning and localized ectasia of the posterior sclera. The sclera is a dense, fibrous, viscoelastic connective tissue that forms the outer coat of the eye and consists of irregularly arranged lamellae of collagen fibrils interspersed with proteoglycans and non-collagenous glycoproteins. Scleral fibroblasts are located between scleral lamellae, and are responsible for synthesizing the extracellular matrix in which they reside. Research highlighted in this review clearly demonstrates that the sclera is not a static container of the eye, but rather is a dynamic tissue, capable of altering extracellular matrix composition and its biomechanical properties in response to changes in the visual environment to regulate ocular size and refraction. Based on these studies, a strategy directed at reversing myopia-associated scleral extracellular matrix remodeling events would be warranted, particularly in cases of high myopia in humans.

Animals↗

Axial myopia induced by a monocularly-deprived facemask in guinea pigs: A non-invasive and effective model.

This study evaluated the efficacy of a facemask, a non-invasive and potentially more reliable method, in inducing axial myopia in guinea pigs. Thirty-six animals were randomly assigned to 3 groups: MDF (monocularly-deprived facemask, n=6), lid-suture (eyelids sutured monocularly, n=24) and normal control (free of form deprivation, n=6). All the groups underwent biometric measurement (refraction, corneal curvature and axial length) prior to the experiment. All animals in the MDF group underwent biometric measurement at each of the 4 timepoints (2, 4, 6 and 8 weeks of form deprivation). In the lid-sutured group, the animals were randomly assigned to 4 subgroups (n=6 each) and each subgroup underwent biometric measurement at one of the timepoints matching those of the MDF group. In the normal control group, all animals underwent biometric measurement at each of the timepoints matching those of the 2 experimental groups. Placement of a facemask on an animal took approximately 10 sec and all the facemasks remained in place at all timepoints. The procedure of lid-suture took at least 20 min for an animal and rupture of the sutures occurred in 50% of the animals after 4 weeks. The MDF eyes developed myopia from -2.21+/-2.11D (Mean+/-s.d.) at 2 weeks to -4.38+/-2.14 at 8 weeks (p<0.05 at all timepoints, compared to the contralateral eyes) with a lengthening of the vitreous chamber from 0.17+/-0.05 mm at 2 weeks to 0.29+/-0.12 mm at 8 weeks (p<0.01 at all timepoints, compared to the contralateral eyes). The lid-sutured eyes developed myopia from -2.38+/-1.21D at 2 weeks to -4.75+/-1.39D at 8 weeks (p<0.05 at all timepoints, compared to the contralateral eyes) with a lengthening of the vitreous chamber from 0.13+/-0.02 mm at 2 weeks to 0.30+/-0.10 mm at 8 weeks (p<0.05 at 2, 4, 8 weeks, but >0.05 at 6 weeks, compared to the contralateral eyes) and an increase in the radius of the corneal curvature (0.20+/-0.07 mm at 4 weeks, p<0.01; 0.17+/-0.05 mm at 8 weeks, p<0.05; compared to the contralateral eyes). Both the MDF and lid-sutured groups had a similar development in myopia and vitreous length (MDF vs lid-suturing: p>0.05 at all timepoints, one-way ANOVA with Bonferroni correction). This development was significantly faster than in the normal control group (MDF or lid-suture vs normal control: p<0.05 to <0.01 from 2 to 8 weeks, one-way ANOVA with Bonferroni correction). The radius of corneal curvature in the lid-sutured group was significantly greater than in either the MDF group or the normal control group since 4 weeks of form deprivation (p<0.05, one-way ANOVA with Bonferroni correction). Treatment with MDFs is as effective as the lid-suture in inducing axial myopia in guinea pigs. This method is non-invasive and allows evaluation of the same group of animals at different timepoints so that the number of animals required could be minimized without affecting the accuracy of the results.

Animals↗

Unilateral lens extraction for high anisometropic myopia in children and adolescents.

INTRODUCTION: A subpopulation of children with anisometropic myopia, amblyopia, and neurobehavioral disorders is noncompliant with spectacle wear and ill-suited to correction using contact lenses. We report the results of refractive surgery in a series of these children treated using lensectomy alone (clear lens extraction) or lensectomy with simultaneous implantation of an intraocular lens (refractive lens exchange). METHODS: Clinical course and outcome data were collated retrospectively in a group of 7 children and adolescents (mean age, 9.1 years; range, 4-20 years) with neurobehavioral disorders and noncompliance with spectacle wear for anisometropic myopia. Myopia in the 7 eyes ranged -11.9 to -24.5 D (mean, -16.7 D). Goal refraction was 0 to + 4 D. Correction was achieved by lensectomy in 5 eyes and lensectomy with intraocular lens implantation in 2 eyes. Primary posterior capsulectomy/subtotal vitrectomy was performed during the primary procedure in 5 eyes (71%). Mean follow-up was 3.8 years (range, 0.5-5.4 years). RESULTS: Myopia correction averaged 17.3 D. A total of 86% (6 eyes) were corrected within +/- 3 D of the goal refraction and the remaining 14% to within +/- 4 D. Uncorrected visual acuity improved postoperatively in all 7 eyes, albeit modestly (average gain 0.14 Snellen fraction; gain from a mean 20/2550 to a mean 20/130). Myopic regression averaged approximately 0.43 D/year. Capsular opacification necessitated YAG-laser membranectomy in the 2 eyes that had preservation of the posterior capsule at the primary procedure. Retinal detachment has not occurred in any of the eyes during the follow-up period. CONCLUSIONS: Refractive myopic lensectomy reduced high anisometropia and improved functional vision in children who have high myopia beyond the range of excimer laser correction and who will not wear glasses. Further study is indicated to determine the long-term safety of this procedure in similar pediatric populations.

Adolescent↗

Effect of methods of myopia correction on visual acuity, contrast sensitivity, and depth of focus.

PURPOSE: To psychophysically measure spherical and irregular aberrations in patients with various types of myopia correction. SETTING: Laboratory of Experimental Ophthalmology, University of Groningen, Groningen, The Netherlands. METHODS: Three groups of patients with low myopia correction (spectacles, soft contact lens, and Intacs) and 4 groups with high myopia correction (spectacles, rigid contact lens, Artisan claw lens, and laser in situ keratomileusis [LASIK]) had through-focus contrast sensitivity measurements to establish the myopic shift and depth of focus. From these 2 parameters, spherical and irregular aberrations were determined using theoretical eye models and geometric optics. Visual acuity, stray light, and predictability were also studied. RESULTS: There were no differences in best corrected visual acuity (BCVA) or best corrected contrast sensitivity between the low myopia groups. The Intacs group had a significantly larger depth of focus (P<.05). The results in the soft contact lens group were comparable to those in a human eye model with an average amount of spherical and irregular aberrations. The LASIK group had worse uncorrected visual acuity (UCVA) and best corrected contrast sensitivity than the spectacles, rigid contact lens, and Artisan claw lens groups (P<.05) due to the amount of spherical and irregular aberrations present after LASIK. The low and high myopia spectacles groups had average amounts of spherical and irregular aberrations. CONCLUSIONS: Neither surgical techniques nor contact lenses resulted in BCVA or best corrected contrast sensitivity that surpassed the values measured in the best corrected spectacles groups. The Artisan claw lens performed better than LASIK in UCVA, predictability, and best corrected contrast sensitivity.

Adult↗