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PubMed2006

Identification of apolipoprotein A-I as a "STOP" signal for myopia.

Good visual acuity requires that the axial length of the ocular globe is matched to the refractive power of the cornea and lens to focus the images of distant objects onto the retina. During the growth of the juvenile eye, this is achieved through the emmetropization process that adjusts the ocular axial length to compensate for the refractive changes that occur in the anterior segment. A failure of the emmetropization process can result in either excessive or insufficient axial growth, leading to myopia or hyperopia, respectively. Emmetropization is mainly regulated by the retina, which generates two opposite signals: "GO/GROW" signals to increase axial growth and "STOP" signals to block it. The presence of GO/GROW and STOP signals was investigated by a proteomics analysis of the retinas from chicken with experimental myopia and hyperopia. Of 18 differentially expressed proteins that were identified, five displayed an expression profile corresponding to GO/GROW signals, and two corresponded to STOP signals. Western blotting confirmed that apolipoprotein A-I (apoA-I) has the characteristics of a STOP signal both in the retina as well as in the fibrous sclera. In accordance with this, intraocular application of the peroxisome proliferator-activated receptor alpha agonist GW7647 resulted in up-regulation of apoA-I levels and in a significant reduction of experimental myopia. In conclusion, using a comprehensive functional proteomics analysis of chicken ocular growth models we identified targets for ocular growth control. The correlation of elevated apoA-I levels with reduced ocular axial growth points toward a functional relationship with the observed morphological changes of the eye.

Animals↗
PubMed2001

The role of visual information in the control of scleral matrix biology in myopia.

Changes in eye size during the development of refractive error are accompanied by alterations in scleral biochemistry in both humans and animal models of myopia. This review discusses more recent data on scleral changes in mammalian models of myopia and considers the role of visual information in the control of scleral matrix biology. These visually-driven changes in scleral biochemistry are placed in the context of both the emmetropisation process and the abnormal enlargement of the eye that is characteristic of human high myopia.

Animals↗
PubMed2006

Basic fibroblast growth factor suppresses retinal neuronal apoptosis in form-deprivation myopia in chicks.

PURPOSE: Chorioretinal atrophy including retinal neuronal apoptosis occurred in chronic form-deprivation myopia induced by lid suture in chicks. We investigated whether exogenous basic fibroblast growth factor (bFGF) could simultaneously inhibit the excessive axial elongation and retinal neuronal loss in the myopic chick eyes. METHODS: Unilateral form deprivation was produced in neonatal male Hyline chicks by lid suture 24 hr after hatching. Ten microliters of solution containing 5 ng bFGF or PBS (vehicle) was injected into the vitreal chamber at 10 weeks of age, once every 3 days until week 12, when the animals were sacrificed. Ocular refraction and axial length were assessed by retinoscopy and calipers at the age of 12 weeks. Retinal apoptotic neurons and their caspase-3-like protease activity were analyzed by transmission electron microscopy, the terminal-deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) staining, and a colorimetric method using Ac-DEVD-pNA as a substrate. The number of TUNEL-positive cells was counted to analyize the survival activity of bFGF on retina. RESULTS: After 12 weeks of lid suture, the control eyes were either emmetropic or hyperopic, whereas the deprived eyes became myopic with axial length increased. TUNEL-positive nuclei, condensed nuclear chromatin, and apoptotic bodies were observed in posterior retinal outer nuclear layer (ONL) and inner nuclear layer (INL) in the myopic chick eyes. Activity of retinal caspase-3-like protease in these eyes was elevated. In addition to ameliorating myopic ocular growth, intravitreal bFGF therapy significantly reduced the number of retinal apoptotic neurons and downregulated caspase-3 activity. CONCLUSIONS: Exogenous bFGF effectively ameliorates the excessive axial elongation and retinal neuron apoptosis in chronic form-deprivation myopia in chicks. It is possible that bFGF will be a promising therapeutic agent for high human myopia.

Animals↗
PubMed2004

Acquired distance esotropia associated with myopia.

BACKGROUND: Von Graefe (1864)(1) and Bielschowsky (1922)(2) described acquired progressive esotropia, with typically a larger angle for distance than near, associated with moderate myopia. This is unlike the esotropia seen in patients with high myopia. METHODS: We reviewed our patient records, finding 26 cases: 14 were female, 12 male. Age range at first presentation was 37-74 with a mean of 55.5. The myopia was from -0.75 to -10.00, with a mean of -5.50 in each eye. Eighteen patients mostly wore glasses, eight mainly wore contact lenses. All complained of horizontal diplopia. Seventeen (65%) had been treated with prisms with a gradual increase in power. RESULTS: Six patients (23%) continued with prisms although surgery has been offered in three cases. Seven patients (27%) had botulinum toxin to one medial rectus muscle. In two cases this proved to be successful maintenance therapy, the remaining five have gone on to have surgery. Seventeen (65%) have undergone surgery (mainly unilateral medial rectus recession and lateral rectus resection) with relief of diplopia and discarding of prisms. Three patients required further surgery for a recurrence after 10-12 years and another is using prisms for a recurrence after 11 years. One patient has suffered an early recurrence 6 months following surgery and is having his neurological work-up repeated. CONCLUSION: This unusual sub-type of strabismus is a benign entity, which responds well to prism correction or surgery in cases who wish to wear contact lenses or whose prisms become inconveniently strong.

Adult↗
PubMed2004

A susceptibility locus for myopia in the normal population is linked to the PAX6 gene region on chromosome 11: a genomewide scan of dizygotic twins.

Myopia is a common, complex trait with considerable economic and social impact and, in highly affected individuals, ocular morbidity. We performed a classic twin study of 506 unselected twin pairs and inferred the heritability of refractive error to be 0.89 (95% confidence interval 0.86-0.91). A genomewide scan of 221 dizygotic twin pairs, analyzed by use of optimal Haseman-Elston regression methods implemented by use of generalized linear modeling, showed significant linkage (LOD >3.2) to refractive error at four loci, with a maximum LOD score of 6.1 at 40 cM on chromome 11p13. Evidence of linkage at this locus, as well as at the other linkage peaks at chromosomes 3q26 (LOD 3.7), 8p23 (LOD 4.1), and 4q12 (LOD 3.3), remained the same or became stronger after model fit was checked and outliers were downweighted. Examination of potential candidate genes showed the PAX6 gene directly below the highest peak at the 11p13 locus. PAX6 is fundamental to identity and growth of the eye, but reported mutations usually result in catastrophic congenital phenotypes such as aniridia. Haplotype tagging of 17 single-nucleotide polymorphisms (SNPs), which covered the PAX6 gene and had common minor allele frequencies, identified 5 SNPs that explained 0.999 of the haplotype diversity. Linkage and association analysis of the tagging SNPs showed strong evidence of linkage for all markers with a minimum chi 21 of 7.5 (P=.006) but no association. This suggests that PAX6 may play a role in myopia development, possibly because of genetic variation in an upstream promoter or regulator, although no definite association between PAX6 common variants and myopia was demonstrated in this study.

Aged↗
PubMed1997

The regulation of the scleral growth associated with deprivation myopia in chicks.

The mechanism of axial elongation caused by experimental or clinical myopia is still unknown. We sought to explore the changes of scleral chondrocytes during myopia formation through the cell biology model. White Leghorn chicks were used for this study. The right eye was covered with a translucent goggle after hatching, and the left eye was left uncovered for control. The chicks were maintained on 12 hours light-dark cycle for two weeks, then sacrificed every other day and the eyeballs removed for study. Our results in the primary culture of scleral chondrocytes showed that the densities of chondrocytes on myopic eyes were significantly higher than those of the controlled non-myopic eyes, and 3H-thymidine incorporation rate also increased with the increasing of the concentration of fetal bovine serum. The PCNA index of chondrocytes in myopic eyes was also higher than that of the controlled non-myopic eyes. Thus, axial elongation of experimental myopia in the chick is the result of active tissue remodeling rather than passive scleral stretching alone.

Animals↗
PubMed1999

Effects of different concentrations of atropine on controlling myopia in myopic children.

Although 1% atropine effectively slows myopia progression, it is associated with adverse effects, including photophobia, blurred near vision, and poor compliance. We investigated whether lower doses of atropine would control myopia progression. One hundred and eighty-six children, from 6 to 13 years of age, were treated each night with different concentrations of atropine eye drops or a control treatment for up to 2 years. The mean myopic progression in each of the groups was 0.04 +/-0.63 diopter per year (D/Y) in the 0.5% atropine group, 0.45+/-0.55 D/Y in the 0.25% atropine group, and 0.47+/-0.91 D/Y in the 0.1% atropine group. All atropine groups showed significantly less myopic progression than the control group (1.06+/-0.61 D/Y) (p<0.01). Our study also showed that 61% of students in the 0.5% atropine group, 49% in the 0.25% atropine group and 42% in the 0.1% atropine group had no myopic progression. However, 4% of children in the 0.5% atropine group, 17% in the 0.25% atropine group, and 33% in the 0.1% atropine group still had fast myopic progression (>-1.0 D/Y). In contrast, only 8% of the control group showed no myopic progression and 44% had fast myopic progression. These results suggest that all three concentrations of atropine had significant effects on controlling myopia; however, treatment with 0.5% atropine was the most effective.

Adolescent↗
PubMed1998

Axial myopia in congenital ptosis: an animal model.

Congenital ptosis in humans has been associated with anisometropia, myopia, astigmatism, and amblyopia. Scientific evidence has shown that visual deprivation causes axial myopia in animals. This study using chicks was undertaken to investigate an animal model of congenital ptosis and the effects of lid position on ocular development. Eyelid ptosis was surgically induced in one eye each of white leghorn chickens within 48 hours after hatching. The chicks were raised under natural diurnal lighting. Thirty days after inducing ptosis, the chicks were killed and their eyes enucleated and photographed in a sagittal view. Computerized image analysis was used to measure the size of the globe along five axes. Globe size was significantly greater in the superior part of eyes with ptosis compared with control eyes. No other measurement differences were significant (p < 0.01). Thus, this study demonstrates that regional axial myopia is induced by eyelid ptosis in chicks.

Animals↗
PubMed2000

One-year results of PRK in low and moderate myopia: fewer than 0.5% of eyes lose two or more lines of vision.

PURPOSE: To retrospectively evaluate the results of myopic photorefractive keratectomy (PRK) for different levels of intended correction, including analysis of loss of best spectacle-corrected visual acuity. METHODS: Four hundred seventy-five consecutive eyes with 1 year of follow-up that had PRK for the correction of 1-7 diopters (D) of myopia by using the Summit SVS Apex excimer laser. Three hundred forty-eight eyes were examined at 1 year. This study was confined to the 236 eyes with 1 year of follow-up that had PRK without astigmatic keratotomy. Eyes also were analyzed according to the range of attempted correction (0-3 D, low; 3.1-6D, moderate; and > or =6.1 D, high moderate). Manifest refraction, uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), surface regularity index (SRI), and surface asymmetry index (SAI) were evaluated for each group. RESULTS: One year after PRK, 91% of all eyes were within 1 diopter and 73% of eyes were within 0.5 diopter of emmetropia. Uncorrected visual acuity was 20/25 or better in 79% and 20/40 or better in 96% of eyes. Two lines of BSCVA were lost in only 0.4% of eyes (one of 236). No eye lost >2 lines of BSCVA, and 30% gained one line. Mean SRI and SAI were increased as compared with preoperative values, but were within the normal range for our patient population (ranges, 0.2-1.0 and 0.1-0.7, respectively). UCVA, BSCVA, and predictability decreased, whereas SAI and SRI increased, with increasing attempted correction. CONCLUSION: PRK effectively reduced myopia in all eyes with 12 months' follow-up. Predictability tended to decrease with increasing attempted correction, even for low to moderate myopia. PRK may induce mild surface asymmetry and irregularity, and these alterations tend to increase with higher attempted correction. Fewer than 0.5% of eyes lost > or =2 lines of best-corrected visual acuity.

Adult↗
PubMed1984

Plus lens, prism, and bifocal effects on myopia progression in military students, Part II.

Military academies routinely lose a percentage of their pilot-qualified students to myopia during the 4-year academic program. This study investigated the progression of myopia during such a program and evaluated the usefulness of reading glasses to prevent myopia progression and subsequent acuity loss. A group of students at the United States Naval Academy comprised three randomly divided groups: a placebo group (no. 1 pink tint), a plus with prism group (+1.25 D with 2 delta base-in each eye), and a bifocal group (+1.50 D near addition). All the lens powers were relative to the experimental subject's distance refraction and were for use full-time when reading. The pre- and post-test refractive errors at distance were determined using 1% tropicamide HCl. At the end of 4 years, the tropicamide refraction showed approximately -0.25 D of myopic shift in all groups. There were no significant differences between the myopic shifts in the controls and experimental groups.

Adolescent↗
PubMed1986

Effect of bifocal lenses on the rate of childhood myopia progression.

Longitudinal records obtained from three optometry practices in the central United States were used to assess the effect of bifocal lenses on the rate of childhood myopia progression. Rates in D/year were derived by linear regression for age spans between 6 and 15 years of age. Records were available for 52 persons who wore single vision lenses (SV group) during this entire age span, and 60 persons who wore bifocal lenses (BF group) during the complete period of observation. The mean rates of myopia progression were -0.44 D/year for the SV group, and -0.37 D/year for the BF group (difference not statistically significant). When rates were determined as a function of nearpoint phoria and near binocular cross cylinder net, the BF group had rates of myopia increase which were lower in magnitude than the SV group in children with nearpoint esophoria and of higher cross cylinder net.

Adolescent↗
PubMed1987

Biofeedback of accommodation to reduce myopia: a review.

Since the first report in 1970 of biofeedback to train voluntary control of accommodation, the use of biofeedback to train accommodation has progressed from basic research demonstrations to the clinical treatment of myopia. The initial reports showed that voluntary control of accommodation could be trained easily and accurately. The next series of investigations were into the efficacy of the technique for training low (less than 1.00 D), functional myopes. The research showed that functional myopia could be reduced with biofeedback training of accommodation. Finally, the technique has expanded into training for a wide range of myopes from children to senior citizens. The results demonstrate the effectiveness of biofeedback in reducing myopia by training voluntary control of accommodation.

Accommodation, Ocular↗
PubMed1988

Role of vergence accommodation in correcting for night myopia.

Although the dark-focus or resting position of accommodation provides a parsimonious interpretation of the anomalous myopias, in correcting for night myopia the role of vergence accommodation must be considered. Both contrast sensitivity (CS) and accommodation were determined for monocular and binocular observation without and with optical corrections based on the individual dark-focus. The data suggest that the availability of a stimulus for vergence accommodation may modify the magnitude of an optical correction for night myopia.

Accommodation, Ocular↗
PubMed1989

Bilateral experimental myopia in chicks.

Substantial amounts of myopia can be induced in chicks by depriving the eye of clear vision for a period of 2 weeks after hatching. Previous work has primarily involved unilateral visual deprivation. Experiments described here include bilateral visual deprivation involving an opaque goggle over one eye and a translucent goggle over the other. The results indicate that although myopia is induced bilaterally, the eye under the translucent goggle becomes more myopic than the contralateral eye or the unilateral deprivation condition. Lens focal characteristics are not affected by the level of myopia. The fact that deprivation of one eye can affect the refractive development of the contralateral eye has implications related to the question of central vs. peripheral neural control of refractive development.

Animals↗
PubMed1990

Anisometropia and changes in anisometropia in school myopia.

Human anisometropia and changes in it were followed over a 3-year period in 238 schoolchildren who had uncomplicated school myopia in both eyes. Anisometropia of the spherical equivalent (ASFE) type increased in 27%, decreased in 6%, and remained unchanged in 67% of these children. When mean myopia increased from -1.43 to -3.06 D, mean ASFE increased from 0.30 to 0.51 D and the anisometropia of astigmatism (AAST) from 0.15 to 0.23 D. The faster the increase in myopia the greater was the increase in ASFE (r = 0.133, N = 238, p = 0.020). The higher the spherical equivalent at the end of the study the higher was the ASFE (r = 0.135, N = 238, p = 0.019). The initial refractive error or the amount or the axis of astigmatism did not have any prognostic value for the changes in ASFE. The higher the ASFE at the end of the study the higher also was the AAST (r = 0.136, N = 238, p = 0.018). The change in ASFE was independent of the wearing of spectacles. The distribution of the anisometropia of the spherical equivalent and its change followed a nearly normal distribution with the peak of eyes at about +/- 0 refraction.

Anisometropia↗
PubMed1991

Inducing myopia, hyperopia, and astigmatism in chicks.

Myopia and hyperopia have been produced in chicks by applying specially designed convex and concave soft contact lenses to the eyes of newly hatched birds. After 2 weeks of wear, the eyes develop refractive states equivalent in sign and amount (+8 and -10 D) to the lens used. However, the lenses produce an artificial hyperopic shift during the first week of wear due to corneal flattening. We have developed a new approach involving the use of goggles with hard convex and concave contact lens inserts placed between the frontal and lateral visual fields. Myopia and hyperopia (+10 and -10 D) can be produced within days (4 days for hyperopia and 7 days for myopia) if the defocus is applied from the day of hatching. We can also produce significant amounts of astigmatism (1 to 5 D) axis at 90 degrees and 180 degrees by using cylindrical contact lens inserts. Although these last results are preliminary, they suggest that accommodation is not likely involved at this stage of refractive development because we do not believe that the accommodative mechanism can cope with cylindrical defocus. All spherical refractive errors produced using the goggle system appear to result from alterations in vitreous chamber depth.

Animals↗
PubMed1991

Role of accommodation in experimental myopia in chicks.

We compared the morphology of the accommodative apparatus in myopic and control chicks using light microscopy and scanning and transmission electron microscopy. Results indicate no significant difference in ciliary muscle and ciliary fold structure between control chick eyes and eyes in which at least 10 D of myopia was induced by the application of a translucent goggle. Based on the assumption that sustained tonic contraction of the accommodative apparatus in the myopic eye would lead to morphological differences, we conclude that the myopic eye is not accommodating excessively during development. These results, in combination with previous findings concerning the role of accommodation in experimental myopia, strongly indicate that accommodation does not play a significant role in this type of experimental myopia in chicks.

Accommodation, Ocular↗
PubMed1992

Prevalence of myopia and myopic progression in a population of clinical microscopists.

The frequency of refractive errors in a population of clinical microscopists is presented. The prevalence of myopia in this population (N = 251) was found to be 71%, with 49% of the population reporting onset or progression of myopia after entry into clinical microscopy (after 21 years of age). Of subjects undergoing renewed progression of an existing myopia since starting clinical microscopy, 56% reported no refractive change for the 5 years before entering their profession. Accuracy of reporting refractive changes was found to be high. No differences were found in task-related functions between those subjects reporting myopic change in adulthood from those who did not report myopic change.

Adult↗