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Thomas T Norton

Publications and source records attributed to Thomas T Norton.

11 recordsLinked to original sources

Effectiveness of hyperopic defocus, minimal defocus, or myopic defocus in competition with a myopiagenic stimulus in tree shrew eyes.

PURPOSE: To examine the ability of hyperopic defocus, minimal defocus, and myopic defocus to compete against a myopiagenic -5-D lens in juvenile tree shrew eyes. METHODS: Juvenile tree shrews (n > or = 5 per group), on a 14-hour lights-on/10-hour lights-off schedule, wore a monocular -5-D lens (a myopiagenic stimulus) over the right eye in their home cages for more than 23 hours per day for 11 days. For 45 minutes each day, the animals were restrained so that all visual stimuli were >1 m away. While viewing distance was controlled, the -5-D lens was removed and another lens was substituted with one of the following spherical powers: -5 D, -3 D (hyperopic defocus); plano (minimal defocus); or +3, +4, +5, +6, or +10 D (myopic defocus). Daily noncycloplegic autorefractor measures were made on most animals. After 11 days of treatment, cycloplegic refractive state and axial component dimensions were measured. RESULTS: Eyes with the substituted -5- or -3-D-lens developed significant myopia (mean +/- SEM, -4.7 +/- 0.3 and -3.1 +/- 0.1 D, respectively) and appropriate vitreous chamber elongation. All animals with the substituted plano lens (minimal defocus) during the 45-minute period showed no axial elongation or myopia (the plano lens competed effectively against the -5-D lens). Variable results were found among animals that wore a plus lens (myopic defocus). In 11 of 20 eyes, a +3-, +4-, or +5-D lens competed effectively against the -5-D lens (treated eye <1.5 D myopic relative to its fellow control eye). In the other eyes (9/20) myopic defocus was ineffective in blocking compensation; the treated eye became more than 2.5 D myopic relative to the control eye. The +6- and +10-D substituted lenses were ineffective in blocking compensation in all cases. CONCLUSIONS: When viewing distance was limited to objects >1 m away, viewing through a plano lens for 45 minutes (minimal defocus) consistently prevented the development of axial elongation and myopia in response to a myopiagenic -5-D lens. Myopic defocus prevented compensation in some but not all animals. Thus, myopic defocus is encoded by at least some tree shrew retinas as being different from hyperopic defocus, and myopic defocus can sometimes counteract the myopiagenic effect of the -5-D lens (hyperopic defocus). However, it appears that minimal defocus is a more consistent, strong antidote to a myopiagenic stimulus in this mammal closely related to primates.

Animals↗

Darkness causes myopia in visually experienced tree shrews.

PURPOSE: To examine the effect of a period of continuous darkness on the refractive state and vitreous chamber depth of normal light-reared juvenile tree shrew eyes, and to learn whether eyes that developed myopia in response to monocular minus-lens wear will recover in darkness. METHODS: Starting at 16 days of visual experience (VE), the refractive state of five dark-treatment tree shrews was measured daily to confirm that it was stable and nearly emmetropic. After corneal and ocular component dimension measures, the animals were placed into continuous darkness for 10 days. On removal of the animals from darkness, corneal and ocular component measures were repeated, and daily refractive measures were resumed. The refractive state of the dark-treatment group was compared with that of a normal-lighting group (n = 5) that received standard colony lighting throughout the measurement period. Five dark-recovery animals wore a monocular -5-D lens for 11 days to induce myopia before they were placed into continuous darkness for 10 days. RESULTS: The animals in the normal-lighting group completed the emmetropization process, stabilizing at approximately (mean +/- SEM) 0.7 +/- 0.3 D of hyperopia (noncycloplegic refraction, corrected for the small eye artifact) at 60 days of VE. Dark-treatment group eyes shifted toward myopia (mean +/- SEM, -4.3 +/- 0.5 D) in the dark. The vitreous chamber became elongated by 0.09 +/- 0.02 mm relative to normal eyes. Corneal power showed a small, near-normal decrease (1.4 +/- 0.3 D). Four of five myopic eyes in the dark-recovery group became more myopic (-2.2 +/- 0.9D) in darkness, and all the fellow control eyes shifted toward myopia (-2.8 +/- 0.5 D). CONCLUSIONS: Maintaining emmetropia is an active process. After eyes have achieved emmetropia or have compensated for a minus lens, continued visual guidance is necessary to maintain a match between the axial length and the focal plane or for recovery to occur. Absence of light is myopiagenic in tree shrews that have developed with normal diurnal lighting. This result contrasts with the apparent absence of a darkness effect in tree shrews reared in the dark from before normal eye opening.

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↗

Relationship of age, sex, and ethnicity with myopia progression and axial elongation in the correction of myopia evaluation trial.

OBJECTIVE: To identify the baseline factors independently related to 3-year myopia progression and axial elongation in COMET. METHODS: A total of 469 children were enrolled, randomly assigned to progressive addition lenses with a + 2.00 diopter (D) addition or to single vision lenses and observed for 3 years. Eligible children were 6 to 11 years old, with spherical equivalent myopia of - 1.25 to - 4.50 D, bilaterally. The primary and secondary outcomes, myopia progression by cycloplegic autorefraction and axial elongation by A-scan ultrasonography, were measured annually. Multiple linear regression was used to adjust for covariates, including treatment. RESULTS: Younger baseline age (6-7 vs 11 years, 8 vs 11 years, and 9 vs 11 years, P<.001; 10 vs 11 years, P = .04), female sex (P = .01), and each ethnic group compared with African Americans (Asian, P = .02; Hispanic, P = .002; mixed, P = .002; white, P = .001) were independently associated with faster 3-year progression. Children aged 6 to 7 years had the fastest progression of all age groups, progressing by a mean (+/- SD) of 1.31 D +/- 0.13 more than children aged 11 years. Females progressed 0.16 D more than the males. Children of mixed, Hispanic, Asian, and white ethnicity progressed more than African American children by 0.49 D +/- 0.16, 0.33 D +/- 0.11, 0.32 D +/- 0.13, 0.27 D +/- 0.08, respectively. Age and ethnicity, but not sex, were independently associated with axial elongation. Among these myopic children, a 0.5 mm increase in axial length was associated with 1 D of myopia progression. CONCLUSIONS: Younger baseline age was the strongest factor independently associated with faster myopic progression and greater axial elongation at 3 years. African American children had less myopic progression and axial elongation than the other ethnic groups.

Age Factors↗

Selective regulation of MMP and TIMP mRNA levels in tree shrew sclera during minus lens compensation and recovery.

PURPOSE: In juvenile tree shrews, a minus-power lens placed in front of the eye produces increased axial elongation and a myopic shift in refractive state that compensates for the power of the lens. Scleral tissue remodeling and modulation of the mechanical properties of the sclera occur during lens compensation. In this study, the time course of changes in scleral mRNA levels of three MMPs and three TIMPs during compensation for a minus lens and during recovery was investigated, to determine which, if any, are temporally associated with changes in the mechanical properties of the sclera and the axial elongation rate. METHODS: Competitive RT-PCR was used to measure the levels of mRNA for MT1-MMP, MMP-2, MMP-3, TIMP-1, TIMP-2, and TIMP-3 in the scleras of tree shrews that had received either 1, 2, 4, or 11 days of monocular -5-D lens treatment, or 11 days of -5-D lens treatment followed by 2 or 4 days of recovery. RESULTS: Relative to their control eyes, treated eye MT1-MMP and MMP-2 mRNA levels were significantly higher, and TIMP-3 levels were lower by 1 to 4 days of minus lens treatment. These differential effects were absent by 11 days of treatment when the treated eyes had compensated for the lens. The levels of all three TIMPs spiked upward in both eyes after 2 days of recovery. The differential changes in MT1-MMP, MMP-2, and TIMP-3 mRNA levels were all restricted to the treated eye and were temporally associated with the differential changes in axial elongation, refractive state, and the previously measured changes in creep rate. CONCLUSIONS: The observed changes in MT1-MMP, MMP-2, TIMP-2, and TIMP-3 mRNA are consistent with visually modulated MT1-MMP activation of MMP-2 and with MT1-MMP degradation of scleral extracellular matrix components. These data constitute further evidence that visual signals modulate gene expression of selected MMPs and TIMPs to control scleral remodeling, the mechanical properties of the sclera, axial elongation, and refractive state.

Animals↗

Accommodation and related risk factors associated with myopia progression and their interaction with treatment in COMET children.

PURPOSE: To examine baseline measurements of accommodative lag, phoria, reading distance, amount of near work, and level of myopia as risk factors for progression of myopia and their interaction with treatment over 3 years, in children enrolled in the Correction of Myopia Evaluation Trial (COMET). METHODS: COMET enrolled 469 ethnically diverse children (ages, 6-11 years) with myopia between -1.25 and -4.50 D. They were randomly assigned to either progressive addition lenses (PALs) with a +2.00 addition (n = 235) or single vision lenses (SVLs; n = 234), the conventional spectacle treatment, and were observed for 3 years. The primary outcome measure was progression of myopia by autorefraction after cycloplegia with 2 drops of 1% tropicamide. Other measurements included accommodative response (by an open field of view autorefractor), phoria (by cover test), reading distance, and hours of near work. Independent and interaction analyses were based on the mean of the two eyes. Results were adjusted for important covariates with multiple linear regression. RESULTS: Children with larger accommodative lags (>0.43 D for a 33 cm target) wearing SVLs had the most progression at 3 years. PALs were effective in slowing progression in these children, with statistically significant 3-year treatment effects (mean +/- SE) for those with larger lags in combination with near esophoria (PAL - SVL progression = -1.08 D - [-1.72 D] = 0.64 +/- 0.21 D), shorter reading distances (0.44 +/- 0.20 D), or lower baseline myopia (0.48 +/- 0.15 D). The 3-year treatment effect for larger lags in combination with more hours of near work was 0.42 +/- 0.26 D, which did not reach statistical significance. Statistically significant treatment effects were observed in these four groups at 1 year and became larger from 1 to 3 years. CONCLUSIONS: The results support the COMET rationale (i.e., a role for retinal defocus in myopia progression). In clinical practice in the United States children with large lags of accommodation and near esophoria often are prescribed PALs or bifocals to improve visual performance. Results of this study suggest that such children, if myopic, may have an additional benefit of slowed progression of myopia.

Accommodation, Ocular↗

Refractive state of tree shrew eyes measured with cortical visual evoked potentials.

PURPOSE: To determine the refractive state of tree shrew eyes using visual evoked potentials (VEP's) recorded from primary visual cortex and compare the values with those obtained with streak retinoscopy and with an autorefractor. METHODS: VEP's were recorded in seven normal tree shrews and three animals in which approximately 5 D of myopia (relative to control eye) was induced by monocular -5 D lens wear. While the animals were awake, refractive correction was measured with an autorefractor before and after cycloplegia (1% atropine and 2.5% phenylepherine). When anesthetized, cycloplegic refractive correction was measured with streak retinoscopy. Then VEP's were produced with square-wave counterphased (1 Hz) high-contrast checkerboard patterns near the animals' high spatial frequency cutoff. Spherical lenses (2 D steps) were placed before the eye, and the VEP (average of 128 sweeps) was measured to determine the lens that produced the largest first positive peak (P1). RESULTS: VEP's were obtained over a broad range of trial lenses. Tuning was narrower when check sizes were small. In normal and control eyes, the P1 amplitude was largest, on average, for a trial lens of (mean +/- SD) -0.6 +/- 1.6 D (corrected for working distance but not vertex distance). The mean streak retinoscopy value (spherical equivalent at the corneal plane) was 7.0 +/- 0.8 D, and mean autorefractor values were 4.0 +/- 1.1 D (cycloplegic) and 3.7 +/- 1.2 D (noncycloplegic). In the eyes that compensated for a -5 D lens, the largest P1 values occurred with lenses with a power of -6.3 +/- 3.2 D. Thus, the VEP measure showed a similar treated vs. control eye difference as did streak retinoscopy (treated eyes, 4.7 +/- 0.4 D myopic) and the autorefractor (treated eyes, 4.8 +/- 0.5 D myopic). CONCLUSIONS: Normal tree shrew eyes are approximately emmetropic. The hyperopic values obtained with streak retinoscopy and the autorefractor are consistent with the presence of a "small-eye artifact" in tree shrews. Eyes that have compensated for a -5 D lens are myopic by approximately the value of the lens.

Animals↗

A randomized clinical trial of progressive addition lenses versus single vision lenses on the progression of myopia in children.

PURPOSE: The purpose of the Correction of Myopia Evaluation Trial (COMET) was to evaluate the effect of progressive addition lenses (PALs) compared with single vision lenses (SVLs) on the progression of juvenile-onset myopia. METHODS: COMET enrolled 469 children (ages 6-11 years) with myopia between -1.25 and -4.50 D spherical equivalent. The children were recruited at four colleges of optometry in the United States and were ethnically diverse. They were randomly assigned to receive either PALs with a +2.00 addition (n = 235) or SVLs (n = 234), the conventional spectacle treatment for myopia, and were followed for 3 years. The primary outcome measure was progression of myopia, as determined by autorefraction after cycloplegia with 2 drops of 1% tropicamide at each annual visit. The secondary outcome measure was change in axial length of the eyes, as assessed by A-scan ultrasonography. Child-based analyses (i.e., the mean of the two eyes) were used. Results were adjusted for important covariates, by using multiple linear regression. RESULTS: Of the 469 children (mean age at baseline, 9.3 +/- 1.3 years), 462 (98.5%) completed the 3-year visit. Mean (+/-SE) 3-year increases in myopia (spherical equivalent) were -1.28 +/- 0.06 D in the PAL group and -1.48 +/- 0.06 D in the SVL group. The 3-year difference in progression of 0.20 +/- 0.08 D between the two groups was statistically significant (P = 0.004). The treatment effect was observed primarily in the first year. The number of prescription changes differed significantly by treatment group only in the first year. At 6 months, 17% of the PAL group versus 30% of the SVL group needed a prescription change (P = 0.0007), and, at 1 year, 43% of the PAL group versus 59% of the SVL group required a prescription change (P = 0.002). Interaction analyses identified a significantly larger treatment effect of PALs in children with lower versus higher baseline accommodative response at near (P = 0.03) and with lower versus higher baseline myopia (P = 0.04). Mean (+/- SE) increases in the axial length of eyes of children in the PAL and SVL groups, respectively, were: 0.64 +/- 0.02 mm and 0.75 +/- 0.02 mm, with a statistically significant 3-year mean difference of 0.11 +/- 0.03 mm (P = 0.0002). Mean changes in axial length correlated with those in refractive error (r = 0.86 for PAL and 0.89 for SVL). CONCLUSIONS: Use of PALs compared with SVLs slowed the progression of myopia in COMET children by a small, statistically significant amount only during the first year. The size of the treatment effect remained similar and significant for the next 2 years. The results provide some support for the COMET rationale-that is, a role for defocus in progression of myopia. The small magnitude of the effect does not warrant a change in clinical practice.

Child↗

Baseline refractive and ocular component measures of children enrolled in the correction of myopia evaluation trial (COMET).

PURPOSE: To describe baseline refractive and ocular component measures in children with myopia enrolled in the Correction of Myopia Evaluation Trial (COMET). COMET is a multicenter, randomized clinical trial to evaluate whether progressive-addition lenses slow the progression of juvenile-onset myopia compared with single-vision lenses. METHODS: Four hundred sixty-nine children with myopia between -1.25 and -4.50 D spherical equivalent and without eye or systemic conditions known to affect refractive development were recruited from four geographically and ethnically diverse communities in the United States. Their ages were 6 to 11 years inclusive, and 52% were girls. The main outcome measure for the overall trial is progression of myopia determined by cycloplegic autorefraction after inducement of cycloplegia with 2 drops of 1% tropicamide. Axial length, the secondary outcome measure, was assessed by ultrasonography. The distance correction was determined by subjective methods before cycloplegia, with noncycloplegic autorefraction values as the starting point. RESULTS: Because data were similar in both eyes, they are reported for the right eye only. The mean spherical equivalent measured by cycloplegic autorefraction was -2.38 +/- 0.81 D. Young children had significantly less myopia than older children (P = 0.03), but the amount of myopia did not differ by gender or ethnicity. Mean axial dimensions were 4.0 +/- 0.2 mm (anterior chamber), 3.4 +/- 0.2 mm (lens), 16.8 +/- 0.7 mm (vitreous chamber), and 24.1 +/- 0.7 mm (axial length). Girls' eyes had significantly shorter axial length than boys' (P < 0.0001). Mean corneal radii were 7.73 +/- 0.25 mm (horizontal) and 7.59 +/- 0.24 mm (vertical). Ninety-five percent of the eyes had a ratio of axial length to corneal radius higher than 3.0. CONCLUSIONS: These baseline measures provide cross-sectional data on a large group of ethnically diverse children with myopia. Refractive and axial component dimensions are consistent with data in other studies showing that myopic eyes have longer vitreous chambers than emmetropic eyes. The measures reported herein will serve as a basis for examining changes that occur over a minimum of 3 years of follow-up of children enrolled in COMET.

Accommodation, Ocular↗

The time course of changes in mRNA levels in tree shrew sclera during induced myopia and recovery.

PURPOSE: In tree shrews, visual form deprivation produces increased axial elongation of the deprived eye and a myopic shift in refractive state. A change in scleral extensibility (creep rate) is closely associated with the change in axial elongation rate. These effects may be due to scleral tissue remodeling produced by a change in scleral gene expression. In this study, the authors investigated the time course of changes in scleral mRNA levels for selected proteins during the development of form deprivation myopia and during recovery, to determine which, if any, are temporally associated with changes in scleral extensibility and axial elongation rate. METHODS: Competitive RT-PCR was used to measure the levels of mRNA for structural proteins (collagen [alpha1(I) chain], decorin core protein), degradative enzymes (MMP-2 [gelatinase-A], MMP-3 [stromelysin-1]), and a tissue inhibitor of metalloproteinase (TIMP-1) in the scleras of tree shrews that had been subjected to 1, 2, 4, or 11 days of monocular form deprivation (MD) or 11 days of MD followed by 2 or 4 days of recovery produced by removal of the MD. Four groups of normal animals provided age-matched normal data. RESULTS: Compared with the control eyes, deprived-eye MMP-2 mRNA levels were higher and MMP-3 levels were lower after 4 days of MD. Deprived-eye collagen mRNA levels were lower than control eye levels after 11 days of MD. The differential effects produced by MD were absent after 2 days of recovery and generally were reversed after 4 days. Decorin mRNA levels in the deprived and control eyes were not significantly different during either MD or recovery. During MD, mRNA levels for collagen, MMP-3, and TIMP-1 decreased in both the deprived and control eyes, compared with age-matched normal eyes. The binocular changes in collagen and TIMP-1 mRNA levels and the differential changes in MMP-2 and MMP-3 levels were detected at least as early as axial, refractive, and creep rate changes. CONCLUSIONS: The up- and downregulation of the specific mRNAs studied, on a time course similar to that for physical changes in the sclera, suggests that modulation of gene expression by the visual environment may produce scleral remodeling and changes in scleral creep rate during the development of form deprivation myopia and recovery.

Animals↗