Dr. Mutti is the E.F. Wildermuth Foundation Professor of Optometry at The Ohio State University College of Optometry. His research career began in the contact lens industry with CooperVision Ophthalmic Products where he evaluated lens design and product performance during in-house clinical trials. Dr. Mutti's current research interests are in the emmetropization of infants and the development of myopia in children. He was a co-investigator on the NEI-funded Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) study. Dr. Mutti was also the Principal Investigator of the NEI-funded Berkeley Infant Biometry (BIBS) Study, an eight-year investigation of ocular component development and emmetropization in infancy. His current research project is the Bifocal Lenses In Nearsighted Kids (BLINK) study, an NEI-funded clinical trial evaluating myopia progression with reduced peripheral defocus using multifocal soft contact lenses. Dr. Mutti has taught visual optics to optometry students for over 15 years. Dr. Mutti received the Borish Award in Support of Research in 1996 and the Glenn A. Fry Award from the American Optometric Foundation in 2006 in recognition of his contributions to vision research.
Optom Vis Sci. 2023 Jan 1;100(1):43-51. doi: 10.1097/OPX.0000000000001970. Epub 2022 Dec 6.
SIGNIFICANCE: The ratios of diopters of change in refractive error produced per millimeter of eye elongation (D/mm) are rarely those predicted from geometric optics because of changes in other ocular components. Quantifying this optical compensation in millimeters instead of ratios reveals some important principles about eye growth and refractive error.
PURPOSE: The study purpose was to sort total vitreous chamber elongation into millimeters that either contributed (uncompensated) or did not contribute to change in refractive error (compensated).
METHODS: Participants were infants in the Berkeley Infant Biometry Study (n = 271, ages 3 months to 6 years) or schoolchildren in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (n = 456 emmetropes and 522 myopes, ages 6 to 14 years). Refractive error was measured using cycloplegic retinoscopy in infants (cyclopentolate 1%) and cycloplegic autorefraction in schoolchildren (tropicamide 1% or combined with cyclopentolate 1%). Axial dimensions were assessed using A-scan ultrasonography. Uncompensated millimeters were estimated from ratios of change in refractive error per millimeter of elongation using Gullstrand eye models. Compensated millimeters were the difference between measured elongation and uncompensated millimeters.
RESULTS: Compensated millimeters exceeded uncompensated millimeters in emmetropic children across ages, but uncompensated millimeters exceeded compensated millimeters in myopic children. Compensated millimeters were highest in infancy and decreased with age, reaching less than 0.10 mm per year by age 10 years in both myopic and emmetropic children. There were no statistically significant differences in compensated millimeters between myopic and emmetropic children between ages 8 and 14 years (P values from .17 to .73).
CONCLUSIONS: The ability of the ocular components, primarily crystalline lens, to compensate for vitreous elongation is independent of the higher demands of myopic eye growth. The limited compensation after age 10 years suggests the target for elongation in myopia control needed to arrest myopia progression may be that seen in emmetropes or less.
Uncorrected Refractive Error and Distance Visual Acuity in Children Aged 6 to 14 Years.
Optom Vis Sci. 2021 Jan 01;98(1):3-12
Authors: Kleinstein RN, Mutti DO, Sinnott LT, Jones-Jordan LA, Cotter SA, Manny RE, Twelker JD, Zadnik K, Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study Group
SIGNIFICANCE: This study presents the relationship between distance visual acuity and a range of uncorrected refractive errors, a complex association that is fundamental to clinical eye care and the identification of children needing refractive correction.
PURPOSE: This study aimed to analyze data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study to describe the relationship between distance uncorrected refractive error and visual acuity in children.
METHODS: Subjects were 2212 children (51.2% female) 6 to 14 years of age (mean ± standard deviation, 10.2 ± 2.1 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 2000 and 2010. Uncorrected distance visual acuity was measured using a high-contrast projected logMAR chart. Cycloplegic refractive error was measured using the Grand Seiko WR-5100K autorefractor. The ability of logMAR acuity to detect various categories of refractive error was examined using receiver operating characteristic curves.
RESULTS: Isoacuity curves show that increasing myopic spherical refractive errors, increasing astigmatic refractive errors, or a combination of both reduces distance visual acuity. Visual acuity was reduced by approximately 0.5 minutes of MAR per 0.30 to 0.40 D of spherical refractive error and by approximately 0.5 minutes of MAR per 0.60 to 0.90 D of astigmatism. Higher uncorrected hyperopic refractive error had little effect on distance visual acuity. Receiver operating characteristic curve analysis suggests that a logMAR distance acuity of 0.20 to 0.32 provides the best balance between sensitivity and specificity for detecting refractive errors other than hyperopia. Distance acuity alone was ineffective for detecting hyperopic refractive errors.
CONCLUSIONS: Higher myopic and/or astigmatic refractive errors were associated with predictable reductions in uncorrected distance visual acuity. The reduction in acuity per diopter of cylindrical error was about half that for spherical myopic error. Although distance acuity may be a useful adjunct to the detection of myopic spherocylindrical refractive errors, accommodation presumably prevents acuity from assisting in the detection of hyperopia. Alternate procedures need to be used to detect hyperopia.
PMID: 33394925 [PubMed - as supplied by publisher]
The Effect of Refractive Error on Melanopsin-Driven Pupillary Responses.
Invest Ophthalmol Vis Sci. 2020 Oct 01;61(12):22
Authors: Mutti DO, Mulvihill SP, Orr DJ, Shorter PD, Hartwick ATE
Purpose: Human and animal studies suggest that light-mediated dopamine release may underlie the protective effect of time outdoors on myopia development. Melanopsin-containing retinal ganglion cells may be involved in this process by integrating ambient light exposure and regulating retinal dopamine levels. The study evaluates this potential involvement by examining whether melanopsin-driven pupillary responses are associated with adult refractive error.
Methods: Subjects were 45 young adults (73% female, 24.1 ± 1.8 years) with refractive errors ranging from -6.33 D to +1.70 D. The RAPDx (Konan Medical) pupillometer measured normalized pupillary responses to three forms of square-wave light pulses alternating with darkness at 0.1 Hz: alternating long wavelength (red, peak at 608 nm) and short wavelength (blue, peak at 448 nm), followed by red only and then blue only.
Results: Non-myopic subjects displayed greater pupillary constriction in the blue-only condition and slower redilation following blue light offset than subjects with myopia (P = 0.011). Pupillary responses were not significantly different between myopic and non-myopic subjects in the red-only condition (P = 0.15). More hyperopic/less myopic refractive error as a continuous variable was linearly related to larger increases in pupillary constriction in response to blue-only stimuli (r = 0.48, P = 0.001).
Conclusions: Repeated light exposures to blue test stimuli resulted in an adaptation in the pupillary response (more constriction and slower redilation), presumably due to increased melanopsin-mediated input in more hyperopic/less myopic adults. This adaptive property supports a possible role for these ganglion cells in the protective effects of time outdoors on myopia development.
PMID: 33091116 [PubMed - as supplied by publisher]
Effect of High Add Power, Medium Add Power, or Single-Vision Contact Lenses on Myopia Progression in Children: The BLINK Randomized Clinical Trial.
JAMA. 2020 Aug 11;324(6):571-580
Authors: Walline JJ, Walker MK, Mutti DO, Jones-Jordan LA, Sinnott LT, Giannoni AG, Bickle KM, Schulle KL, Nixon A, Pierce GE, Berntsen DA, BLINK Study Group
Importance: Slowing myopia progression could decrease the risk of sight-threatening complications.
Objective: To determine whether soft multifocal contact lenses slow myopia progression in children, and whether high add power (+2.50 D) slows myopia progression more than medium (+1.50 D) add power lenses.
Design, Setting, and Participants: A double-masked randomized clinical trial that took place at 2 optometry schools located in Columbus, Ohio, and Houston, Texas. A total of 294 consecutive eligible children aged 7 to 11 years with -0.75 D to -5.00 D of spherical component myopia and less than 1.00 D astigmatism were enrolled between September 22, 2014, and June 20, 2016. Follow-up was completed June 24, 2019.
Interventions: Participants were randomly assigned to wear high add power (n = 98), medium add power (n = 98), or single-vision (n = 98) contact lenses.
Main Outcomes and Measures: The primary outcome was the 3-year change in cycloplegic spherical equivalent autorefraction, as measured by the mean of 10 autorefraction readings. There were 11 secondary end points, 4 of which were analyzed for this study, including 3-year eye growth.
Results: Among 294 randomized participants, 292 (99%) were included in the analyses (mean [SD] age, 10.3 [1.2] years; 177 [60.2%] were female; mean [SD] spherical equivalent refractive error, -2.39 [1.00] D). Adjusted 3-year myopia progression was -0.60 D for high add power, -0.89 D for medium add power, and -1.05 D for single-vision contact lenses. The difference in progression was 0.46 D (95% CI, 0.29-0.63) for high add power vs single vision, 0.30 D (95% CI, 0.13-0.47) for high add vs medium add power, and 0.16 D (95% CI, -0.01 to 0.33) for medium add power vs single vision. Of the 4 secondary end points, there were no statistically significant differences between the groups for 3 of the end points. Adjusted mean eye growth was 0.42 mm for high add power, 0.58 mm for medium add power, and 0.66 mm for single vision. The difference in eye growth was -0.23 mm (95% CI, -0.30 to -0.17) for high add power vs single vision, -0.16 mm (95% CI, -0.23 to -0.09) for high add vs medium add power, and -0.07 mm (95% CI, -0.14 to -0.01) for medium add power vs single vision.
Conclusions and Relevance: Among children with myopia, treatment with high add power multifocal contact lenses significantly reduced the rate of myopia progression over 3 years compared with medium add power multifocal and single-vision contact lenses. However, further research is needed to understand the clinical importance of the observed differences.
Trial Registration: ClinicalTrials.gov Identifier: NCT02255474.
PMID: 32780139 [PubMed - as supplied by publisher]
Repeatability and Validity of Peripheral Refraction with Two Different Autorefractors.
Optom Vis Sci. 2020 Jun;97(6):429-439
Authors: Morrison AM, Mutti DO
SIGNIFICANCE: The Welch Allyn SureSight (Welch Allyn, Skaneateles Falls, NY) and Plusoptix PowerRefractor (Plusoptix, Nuremberg, Germany) are often used with infants, but little is known about the repeatability and validity of their peripheral refractive error measurements. Selecting the best instrument will support future refractive error and emmetropization studies.
PURPOSE: The purpose of this study was to determine the validity and repeatability of peripheral refractive error measurements and peripheral refraction profiles measured with the Welch Allyn SureSight and Plusoptix PowerRefractor compared with the criterion standard Grand Seiko WR-5100K (Grand Seiko Co., Hiroshima, Japan).
METHODS: Cycloplegic (tropicamide 1%) autorefraction was measured in the right eyes of 21 adult subjects (31.4 ± 10.4 years) with the three instruments in randomized order on two separate visits, at least 24 hours apart, centrally, and at 30 and 20° temporal and nasal gaze.
RESULTS: The SureSight measurements were within 0.24 D and not significantly different from the Grand Seiko WR-5100K in any gaze (P < .65), whereas the PowerRefractor measurements were more myopic by as much as -0.97 D and significantly different in four of the five gaze directions (P < .04). The 95% limits of agreement between occasions by gaze ranged from ±0.38 to ±0.61 D for the SureSight, similar to or slightly better than the WR-5100K (±0.31 to ±1.51 D) and the PowerRefractor (±0.72 to ±1.71 D). There were no significant differences between visits for any instrument in any gaze (P < .94). The repeatability of the SureSight was also better than that for the Grand Seiko when peripheral refraction was represented by quadratic fits to the data.
CONCLUSIONS: These findings suggest that the Welch Allyn SureSight is the most suitable portable autorefractor to use to monitor peripheral autorefraction based on better repeatability between occasions and better validity compared with the criterion standard Grand Seiko WR-5100K.
PMID: 32511165 [PubMed - as supplied by publisher]
Spectacle correction versus no spectacles for prevention of strabismus in hyperopic children.
Cochrane Database Syst Rev. 2020 Apr 02;4:CD007738
Authors: Jones-Jordan L, Wang X, Scherer RW, Mutti DO
BACKGROUND: Hyperopia in infancy requires accommodative effort to bring images into focus. Prolonged accommodative effort has been associated with an increased risk of strabismus. Strabismus may result in asthenopia and intermittent diplopia, and makes near work tasks difficult to complete. Spectacles to correct hyperopic refractive error is believed to prevent the development of strabismus.
OBJECTIVES: To assess the effectiveness of prescription spectacles compared with no intervention for the prevention of strabismus in infants and children with hyperopia.
SEARCH METHODS: We searched CENTRAL (2018, Issue 12; which contains the Cochrane Eyes and Vision Trials Register); Ovid MEDLINE; Embase.com; three other databases; and two trial registries. We used no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 4 December 2018.
SELECTION CRITERIA: We included randomized controlled trials and quasi-randomized trials investigating spectacle intervention or no treatment for children with hyperopia. We required hyperopia to be at least greater than +2.00 diopters (D).
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The primary outcome was the proportion of children with manifest strabismus, as defined by study investigators. Other outcomes included the amblyopia, stereoacuity, and the effect of spectacle use of strabismus and visual acuity. We also collected information on change in refractive error as a measurement of the interference of emmetropization.
MAIN RESULTS: We identified four randomized controlled trials (985 children enrolled who were aged six months to less than 36 months) in this review. Three trials were in the UK with follow-up periods ranging from one to 3.5 years and one in the US with three years' follow-up. Investigators reported both incidence and final status regarding strabismus. Evidence of the incidence of strabismus, measured in 804 children over three to four years in four trials was uncertain although suggestive of a benefit with spectacle use (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.41 to 1.02). We have very low confidence in these results due to high risk of bias, inconsistency, and imprecision. When assessed as the proportion of children with strabismus at the end of three years' follow-up, we found a similar level of evidence for an effect of spectacles on strabismus as reported in one study (RR 1.00, 95% CI 0.31 to 3.25; 106 children). We have very low confidence in these results because of low sample size and risk of bias. One trial reported on the risk for developing amblyopia and inadequate stereoacuity after three years in 106 children. There was unclear evidence for a decreased risk of developing amblyopia (RR 0.78, 95% CI 0.31 to 1.93), and limited evidence for a benefit of spectacles for prevention of inadequate stereoacuity (RR 0.38, 95% CI 0.16 to 0.88). We have very low confidence in these findings due to imprecision and risk of bias. The risk of not developing emmetropization is unclear. One trial reported on the proportion of children not achieving emmetropization at three years' follow-up (RR 0.75, 95% CI 0.18 to 3.19). One trial suggested spectacles impede emmetropization, and one trial reported no difference. These two trials could not be combined because the methods for assessing emmetropization were different. With the high risk of bias and inconsistency, the certainty of evidence for a risk for impeding or benefiting emmetropization is very low. Based on a meta-analysis of four trials (770 children), the risk of having visual acuity worse than 20/30 measured up to three years of age or at the end of three years of follow-up was uncertain for children with spectacle correction compared with those without correction (RR 0.87, 95% CI 0.64 to 1.18; very low confidence due to risk of bias and imprecision).
AUTHORS' CONCLUSIONS: The effect of spectacle correction for prevention of strabismus is still unclear. In addition, the use of spectacle on the risk of visual acuity worse than 20/30, amblyopia, and inadequate emmetropization is also unclear. There may be a benefit on prevention of inadequate stereoacuity. However, these effects may have been chance findings or due to bias.
PMID: 32240551 [PubMed - as supplied by publisher]
Morphological ciliary muscle changes associated with form deprivation-induced myopia.
Exp Eye Res. 2020 Feb 08;:107963
Authors: Pucker AD, Jackson AR, McHugh KM, Mutti DO
Myopic children have larger ciliary muscles than non-myopic children, suggesting that the ciliary muscle may have an impact on or be affected by refractive error development. The guinea pig represents an attractive model organism for myopia development research. The purpose of the study was to investigate whether form deprivation-induced myopia in one or more strains of guinea pig causes thickening of the ciliary muscle as seen in human myopia. Thirty-nine guinea pigs were bred from in-house progenitors obtained from Cincinnati Children's Hospital (Cincinnati) and the United States Army (Strain 13). At 2-4 days of age the right eyes of animals were exposed to form deprivation for 7 days while the fellow eyes served as controls. Refractive error was determined with retinoscopy while vitreous chamber depth (VCD) and axial length (AL) were determined with A-scan ultrasound. Ciliary muscle characteristics (ciliary muscle length, cross-sectional area, volume, cell number, cell size, and smooth muscle actin concentration) were determined histologically with antibody labeling and analyzed according to whether the animal developed axial myopia (anisometropia > -2.00 D with VCD and/or AL differences > 0.1 mm) or was unresponsive. This analysis method yielded four groups with Group 1 having no induced myopia but with axial elongation (n = 11), Group 2 having myopia without vitreous or axial elongation (n = 8), Group 3 having myopia with either vitreous or axial elongation (n = 11), and Group 4 having myopia with both vitreous and axial elongation (n = 8). There were no post-treatment inter-ocular differences between strains or for the overall group of animals for any ciliary muscle variable; however, a higher response group number in multivariate ordinal regression was related to having a treated compared to fellow eye that had a lower smooth muscle actin concentration (p = 0.006), with a shorter ciliary muscle length (p = 0.042), and a less oblate eye shape (p = 0.010). Guinea pig ciliary muscle length and smooth muscle actin concentration were significantly less in the treated eyes of axially myopic animals suggesting that 7 days of form deprivation induced ciliary muscle cellular atrophy or inhibited ciliary muscle growth. Form deprivation myopia in the guinea pig does not result in the increase in ciliary muscle thickness associated with human juvenile and adult myopia.
PMID: 32045599 [PubMed - as supplied by publisher]
Interventions to slow progression of myopia in children.
Cochrane Database Syst Rev. 2020 Jan 13;1:CD004916
Authors: Walline JJ, Lindsley KB, Vedula SS, Cotter SA, Mutti DO, Ng SM, Twelker JD
BACKGROUND: Nearsightedness (myopia) causes blurry vision when one is looking at distant objects. Interventions to slow the progression of myopia in children include multifocal spectacles, contact lenses, and pharmaceutical agents.
OBJECTIVES: To assess the effects of interventions, including spectacles, contact lenses, and pharmaceutical agents in slowing myopia progression in children.
SEARCH METHODS: We searched CENTRAL; Ovid MEDLINE; Embase.com; PubMed; the LILACS Database; and two trial registrations up to February 2018. A top up search was done in February 2019.
SELECTION CRITERIA: We included randomized controlled trials (RCTs). We excluded studies when most participants were older than 18 years at baseline. We also excluded studies when participants had less than -0.25 diopters (D) spherical equivalent myopia.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods.
MAIN RESULTS: We included 41 studies (6772 participants). Twenty-one studies contributed data to at least one meta-analysis. Interventions included spectacles, contact lenses, pharmaceutical agents, and combination treatments. Most studies were conducted in Asia or in the United States. Except one, all studies included children 18 years or younger. Many studies were at high risk of performance and attrition bias. Spectacle lenses: undercorrection of myopia increased myopia progression slightly in two studies; children whose vision was undercorrected progressed on average -0.15 D (95% confidence interval [CI] -0.29 to 0.00; n = 142; low-certainty evidence) more than those wearing fully corrected single vision lenses (SVLs). In one study, axial length increased 0.05 mm (95% CI -0.01 to 0.11) more in the undercorrected group than in the fully corrected group (n = 94; low-certainty evidence). Multifocal lenses (bifocal spectacles or progressive addition lenses) yielded small effect in slowing myopia progression; children wearing multifocal lenses progressed on average 0.14 D (95% CI 0.08 to 0.21; n = 1463; moderate-certainty evidence) less than children wearing SVLs. In four studies, axial elongation was less for multifocal lens wearers than for SVL wearers (-0.06 mm, 95% CI -0.09 to -0.04; n = 896; moderate-certainty evidence). Three studies evaluating different peripheral plus spectacle lenses versus SVLs reported inconsistent results for refractive error and axial length outcomes (n = 597; low-certainty evidence). Contact lenses: there may be little or no difference between vision of children wearing bifocal soft contact lenses (SCLs) and children wearing single vision SCLs (mean difference (MD) 0.20D, 95% CI -0.06 to 0.47; n = 300; low-certainty evidence). Axial elongation was less for bifocal SCL wearers than for single vision SCL wearers (MD -0.11 mm, 95% CI -0.14 to -0.08; n = 300; low-certainty evidence). Two studies investigating rigid gas permeable contact lenses (RGPCLs) showed inconsistent results in myopia progression; these two studies also found no evidence of difference in axial elongation (MD 0.02mm, 95% CI -0.05 to 0.10; n = 415; very low-certainty evidence). Orthokeratology contact lenses were more effective than SVLs in slowing axial elongation (MD -0.28 mm, 95% CI -0.38 to -0.19; n = 106; moderate-certainty evidence). Two studies comparing spherical aberration SCLs with single vision SCLs reported no difference in myopia progression nor in axial length (n = 209; low-certainty evidence). Pharmaceutical agents: at one year, children receiving atropine eye drops (3 studies; n = 629), pirenzepine gel (2 studies; n = 326), or cyclopentolate eye drops (1 study; n = 64) showed significantly less myopic progression compared with children receiving placebo: MD 1.00 D (95% CI 0.93 to 1.07), 0.31 D (95% CI 0.17 to 0.44), and 0.34 (95% CI 0.08 to 0.60), respectively (moderate-certainty evidence). Axial elongation was less for children treated with atropine (MD -0.35 mm, 95% CI -0.38 to -0.31; n = 502) and pirenzepine (MD -0.13 mm, 95% CI -0.14 to -0.12; n = 326) than for those treated with placebo (moderate-certainty evidence) in two studies. Another study showed favorable results for three different doses of atropine eye drops compared with tropicamide eye drops (MD 0.78 D, 95% CI 0.49 to 1.07 for 0.1% atropine; MD 0.81 D, 95% CI 0.57 to 1.05 for 0.25% atropine; and MD 1.01 D, 95% CI 0.74 to 1.28 for 0.5% atropine; n = 196; low-certainty evidence) but did not report axial length. Systemic 7-methylxanthine had little to no effect on myopic progression (MD 0.07 D, 95% CI -0.09 to 0.24) nor on axial elongation (MD -0.03 mm, 95% CI -0.10 to 0.03) compared with placebo in one study (n = 77; moderate-certainty evidence). One study did not find slowed myopia progression when comparing timolol eye drops with no drops (MD -0.05 D, 95% CI -0.21 to 0.11; n = 95; low-certainty evidence). Combinations of interventions: two studies found that children treated with atropine plus multifocal spectacles progressed 0.78 D (95% CI 0.54 to 1.02) less than children treated with placebo plus SVLs (n = 191; moderate-certainty evidence). One study reported -0.37 mm (95% CI -0.47 to -0.27) axial elongation for atropine and multifocal spectacles when compared with placebo plus SVLs (n = 127; moderate-certainty evidence). Compared with children treated with cyclopentolate plus SVLs, those treated with atropine plus multifocal spectacles progressed 0.36 D less (95% CI 0.11 to 0.61; n = 64; moderate-certainty evidence). Bifocal spectacles showed small or negligible effect compared with SVLs plus timolol drops in one study (MD 0.19 D, 95% CI 0.06 to 0.32; n = 97; moderate-certainty evidence). One study comparing tropicamide plus bifocal spectacles versus SVLs reported no statistically significant differences between groups without quantitative results. No serious adverse events were reported across all interventions. Participants receiving antimuscarinic topical medications were more likely to experience accommodation difficulties (Risk Ratio [RR] 9.05, 95% CI 4.09 to 20.01) and papillae and follicles (RR 3.22, 95% CI 2.11 to 4.90) than participants receiving placebo (n=387; moderate-certainty evidence).
AUTHORS' CONCLUSIONS: Antimuscarinic topical medication is effective in slowing myopia progression in children. Multifocal lenses, either spectacles or contact lenses, may also confer a small benefit. Orthokeratology contact lenses, although not intended to modify refractive error, were more effective than SVLs in slowing axial elongation. We found only low or very low-certainty evidence to support RGPCLs and sperical aberration SCLs.
PMID: 31930781 [PubMed - in process]
Peripheral Refraction and Eye Lengths in Myopic Children in the Bifocal Lenses In Nearsighted Kids (BLINK) Study.
Transl Vis Sci Technol. 2019 Apr;8(2):17
Authors: Mutti DO, Sinnott LT, Reuter KS, Walker MK, Berntsen DA, Jones-Jordan LA, Walline JJ, Bifocal Lenses In Nearsighted Kids (BLINK) Study Group
Purpose: Provide a detailed assessment of peripheral refractive error and peripheral eye length in myopic children.
Methods: Subjects were 294 children aged 7 to 11 years with -0.75 to -5.00 diopter (D) of myopia by cycloplegic autorefraction. Peripheral refraction and eye length were measured at ±20° and ±30° horizontally and vertically, with peripheral refraction also measured at ±40° horizontally.
Results: Relative peripheral refraction became more hyperopic in the horizontal meridian and more myopic in the vertical meridian with increasing field angle. Peripheral eye length became shorter in both meridians with increasing field angle, more so horizontally than vertically with correlations between refraction and eye length ranging from -0.40 to -0.57 (all P < 0.001). Greater foveal myopia was related to more peripheral hyperopia (or less peripheral myopia), shorter peripheral eye lengths, and a consistent average asymmetry between meridians.
Conclusions: Peripheral refractive errors in children do not appear to exert strong local control of peripheral eye length given that their correlation is consistently negative and the degree of meridional asymmetry is similar across the range of refractive errors. The BLINK study will provide longitudinal data to determine whether peripheral myopia and additional peripheral myopic defocus from multifocal contact lenses affect the progression of myopia in children.
Translational Relevance: Local retinal control of ocular growth has been demonstrated numerous times in animal experimental myopia models but has not been explored in detail in human myopia development. These BLINK baseline results suggest that children's native peripheral optical signals may not be a strong stimulus for local growth responses.
PMID: 31019848 [PubMed]
Outdoor Activity Protects against Childhood Myopia-Let the Sun Shine In.
JAMA Pediatr. 2019 Mar 25;:
Authors: Zadnik K, Mutti DO
PMID: 30907935 [PubMed - as supplied by publisher]
Bifocal & Atropine in Myopia Study: Baseline Data and Methods.
Optom Vis Sci. 2019 05;96(5):335-344
Authors: Huang J, Mutti DO, Jones-Jordan LA, Walline JJ
SIGNIFICANCE: The Bifocal & Atropine in Myopia (BAM) study aims to determine whether combining 0.01% atropine and +2.50-diopter add center-distance soft bifocal contact lenses (SBCL) slows myopia progression more than SBCL alone. The results could provide significant information on the myopia control effect of combining optical and pharmacological treatments.
PURPOSE: This article describes the subject characteristics at baseline, the study methods, and the short-term effects of this combination treatment on visual acuity (VA) and vision-related outcomes.
METHODS: Subjects from the BAM study who met the baseline eligibility criteria were dispensed the combination treatment for 2 weeks to determine final eligibility. Outcome measures included VA at near and distance (Bailey-Lovie logMAR charts), near phoria (modified Thorington), accommodative lag (Grand Seiko WAM-5500), and pupil size (NeurOptics VIP-200 Pupillometer). Compliance was monitored using surveys. Two subgroups in the Bifocal Lenses In Nearsighted Kids study, single-vision contact lens wearers and those who wore +2.50-diopter add SBCL, will serve as the age-matched historical controls for BAM study.
RESULTS: Forty-nine BAM subjects (9.6 ± 1.4 years) were enrolled; mean spherical equivalent cycloplegic autorefraction was -2.33 ± 1.03 diopters. After 2 weeks of treatment, the best-corrected low-contrast (10% Michelson) distance VA was reduced (pre-treatment, +0.09 ± 0.07; post-treatment, +0.16 ± 0.08; P < .0001), but the high-contrast VA at near or distance was unaffected. Near phoria increased by approximately 2 in the exo direction (P = .01), but the accommodative lag was unchanged. The pupil size was not significantly different between pre-treatment and post-treatment of either the photopic or mesopic condition. Surveys indicated that the subjects wore SBCL 77 ± 22% of waking hours and used atropine 6.4 ± 0.7 days per week.
CONCLUSIONS: Two weeks of combination treatment reduced low-contrast distance VA and increased near exophoria slightly, but the subjects were compliant and tolerated the treatment well.
PMID: 31046016 [PubMed - indexed for MEDLINE]
Ocular Component Development during Infancy and Early Childhood.
Optom Vis Sci. 2018 Oct 18;:
Authors: Mutti DO, Sinnott LT, Lynn Mitchell G, Jordan LA, Friedman NE, Frane SL, Lin WK
SIGNIFICANCE: The study fills an important gap by providing a longitudinal description of development of the major structural and optical components of the human eye from 3 months to nearly 7 years of age. Normative development data may provide insights into mechanisms for emmetropization and guidance on intraocular lens power calculation.
PURPOSE: The purpose of this study was to describe the pattern of development of refractive error and the ocular components from infancy through early childhood.
METHODS: Cycloplegic retinoscopy (cyclopentolate 1%), keratophakometry, and ultrasonography were performed longitudinally on between 162 and 293 normal birth weight infants at 0.25, 0.75, 1.5, 3, 4.5, and 6.5 years of age.
RESULTS: Refractive error and most ocular components displayed an early exponential phase of rapid development during the first 1 to 2 years of life followed by a slower quadratic phase. Anterior and vitreous chamber depths, axial length, and crystalline lens radii increased at every visit. The crystalline lens thinned throughout the ages studied. The power of the cornea showed an early decrease, then stabilized, whereas the crystalline lens showed more robust decreases in power. The crystalline lens refractive index followed a polynomial growth and decay model, with an early increase followed by a decrease starting at 1 to 2 years of age. Refractive error became less hyperopic and then was relatively stable after 1 to 2 years of age. Axial lengths increased by 3.35 ± 0.64 mm between ages 0.25 and 6.5 years, showed uniform rates of growth across the range of initial values, and were correlated with initial axial lengths (r = 0.44, P < .001).
CONCLUSIONS: Early ocular optical and structural development appears to be biphasic, with emmetropization occurring within the first 2 years of infancy during a rapid exponential phase. A more stable refractive error follows during a slower quadratic phase of growth when axial elongation is compensated primarily by changes in crystalline lens power.
PMID: 30339640 [PubMed - as supplied by publisher]
Visual Acuity and Over-refraction in Myopic Children Fitted with Soft Multifocal Contact Lenses.
Optom Vis Sci. 2018 Mar 21;:
Authors: Schulle KL, Berntsen DA, Sinnott LT, Bickle KM, Gostovic AT, Pierce GE, Jones-Jordan LA, Mutti DO, Walline JJ, ; for The Bifocal Lenses in Nearsighted Kids (BLINK) Study Group
SIGNIFICANCE: Practitioners fitting contact lenses for myopia control frequently question whether a myopic child can achieve good vision with a high-add multifocal. We demonstrate that visual acuity is not different than spectacles with a commercially available, center-distance soft multifocal contact lens (MFCL) (Biofinity Multifocal "D"; +2.50 D add).
PURPOSE: To determine the spherical over-refraction (SOR) necessary to obtain best-corrected visual acuity (BCVA) when fitting myopic children with a center-distance soft MFCL.
METHODS: Children (n = 294) aged 7 to 11 years with myopia (spherical component) of -0.75 to -5.00 diopters (D) (inclusive) and 1.00 D cylinder or less (corneal plane) were fitted bilaterally with +2.50 D add Biofinity "D" MFCLs. The initial MFCL power was the spherical equivalent of a standardized subjective refraction, rounded to the nearest 0.25 D step (corneal plane). An SOR was performed monocularly (each eye) to achieve BCVA. Binocular, high-contrast logMAR acuity was measured with manifest spectacle correction and MFCLs with over-refraction. Photopic pupil size was measured with a pupilometer.
RESULTS: The mean (±SD) age was 10.3 ± 1.2 years, and the mean (±SD) SOR needed to achieve BCVA was OD: -0.61 ± 0.24 D/OS: -0.58 ± 0.27 D. There was no difference in binocular high-contrast visual acuity (logMAR) between spectacles (-0.01 ± 0.06) and best-corrected MFCLs (-0.01 ± 0.07) (P = .59). The mean (±SD) photopic pupil size (5.4 ± 0.7 mm) was not correlated with best MFCL correction or the over-refraction magnitude (both P ≥ .09).
CONCLUSIONS: Children achieved BCVA with +2.50 D add MFCLs that was not different than with spectacles. Children typically required an over-refraction of -0.50 to -0.75 D to achieve BCVA. With a careful over-refraction, these +2.50 D add MFCLs provide good distance acuity, making them viable candidates for myopia control.
PMID: 29561497 [PubMed - as supplied by publisher]
A Randomized Trial of Soft Multifocal Contact Lenses for Myopia Control: Baseline Data and Methods.
Optom Vis Sci. 2017 Sep;94(9):856-866
Authors: Walline JJ, Gaume Giannoni A, Sinnott LT, Chandler MA, Huang J, Mutti DO, Jones-Jordan LA, Berntsen DA, BLINK Study Group
SIGNIFICANCE: The Bifocal Lenses In Nearsighted Kids (BLINK) study is the first soft multifocal contact lens myopia control study to compare add powers and measure peripheral refractive error in the vertical meridian, so it will provide important information about the potential mechanism of myopia control.
PURPOSE: The BLINK study is a National Eye Institute-sponsored, double-masked, randomized clinical trial to investigate the effects of soft multifocal contact lenses on myopia progression. This article describes the subjects' baseline characteristics and study methods.
METHODS: Subjects were 7 to 11 years old, had -0.75 to -5.00 spherical component and less than 1.00 diopter (D) astigmatism, and had 20/25 or better logMAR distance visual acuity with manifest refraction in each eye and with +2.50-D add soft bifocal contact lenses on both eyes. Children were randomly assigned to wear Biofinity single-vision, Biofinity Multifocal "D" with a +1.50-D add power, or Biofinity Multifocal "D" with a +2.50-D add power contact lenses.
RESULTS: We examined 443 subjects at the baseline visits, and 294 (66.4%) subjects were enrolled. Of the enrolled subjects, 177 (60.2%) were female, and 200 (68%) were white. The mean (± SD) age was 10.3 ± 1.2 years, and 117 (39.8%) of the eligible subjects were younger than 10 years. The mean spherical equivalent refractive error, measured by cycloplegic autorefraction was -2.39 ± 1.00 D. The best-corrected binocular logMAR visual acuity with glasses was +0.01 ± 0.06 (20/21) at distance and -0.03 ± 0.08 (20/18) at near.
CONCLUSIONS: The BLINK study subjects are similar to patients who would routinely be eligible for myopia control in practice, so the results will provide clinical information about soft bifocal contact lens myopia control as well as information about the mechanism of the treatment effect, if one occurs.
PMID: 28737608 [PubMed - indexed for MEDLINE]
Mucin Balls Influence Corneal Infiltrative Events.
Optom Vis Sci. 2017 Apr;94(4):448-457
Authors: Szczotka-Flynn LB, Jiang Y, Stiegemeier MJ, Mutti DO, Walline J, Wilson T, Debanne S, Mucin Ball Study Group
PURPOSE: To determine whether mucin ball (MB) formation is protective against corneal infiltrative events (CIEs) as previously reported.
METHODS: Two hundred eighty-two eligible participants were enrolled at three sites in the USA. Participants began a 1-month continuous wear run-in period with high modulus lotrafilcon A lenses to assess their ability to form MBs (phase 1). Subsequently, they were stratified by this characteristic and randomized to balafilcon A or comfilcon A lenses for 7-day extended wear and followed for 1 year (phase 2). MB formation in each phase was defined as repeated presence of any MBs on a person level. Multivariable Cox proportional hazards regression was used to model the probability of a CIE as a function of MB formation in each phase and other covariates.
RESULTS: Of the 282 participants who entered phase 1, 218 of them entered the phase 2 randomized trial during which 33 CIEs occurred. Overall, 74%, 61%, and 79% of participants repeatedly produced MBs in lotrafilcon A, balafilcon A, and comfilcon A lenses, respectively. Early repeated MB presence in phase 1 with lotrafilcon A lenses significantly increased the rate of CIEs in phase 2 (12-month follow-up) by 466% (HR 4.66, 95% confidence interval 1.10-19.79, P = .0372). Repeated, longer-term MB presence during wear of balafilcon A or comfilcon A in phase 2 did not significantly reduce the incidence of CIEs; however, it significantly decreased the rate of CIEs by 62% (hazard ratio (HR) 0.380, 95% confidence interval 0.145-0.998, P = .0494).
CONCLUSIONS: The overarching hypothesis that MB formation is protective against CIEs throughout extended wear was not supported. Although a protective effect of longer-term MB presence on rate of CIEs was detected, early-onset MB formation substantially increased the hazard for CIE in subsequent wear with different lens types.
PMID: 28195933 [PubMed - indexed for MEDLINE]
The Response AC/A Ratio Before and After the Onset of Myopia.
Invest Ophthalmol Vis Sci. 2017 Mar 01;58(3):1594-1602
Authors: Mutti DO, Mitchell GL, Jones-Jordan LA, Cotter SA, Kleinstein RN, Manny RE, Twelker JD, Zadnik K, CLEERE Study Group
Purpose: To investigate the ratio of accommodative convergence per diopter of accommodative response (AC/A ratio) before, during, and after myopia onset.
Methods: Subjects were 698 children aged 6 to 14 years who became myopic and 430 emmetropic children participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error. Refractive error was measured using cycloplegic autorefraction, near work by parent survey, and the AC/A ratio by simultaneously monitoring convergence and accommodative response. The response AC/A ratios of children who became myopic were compared with age-, sex-, and ethnicity-matched model estimates for emmetropic children from 5 years before through 5 years after the onset of myopia.
Results: The response AC/A ratio was not significantly different between the two groups 5 years before onset, then increased monotonically in children who became myopic until reaching a plateau at myopia onset of about 7 Δ/D compared to about 4 Δ/D for children who remained emmetropic (differences between groups significant at P < 0.01 from 4 years before onset through 5 years after onset). A higher AC/A ratio was associated with greater accommodative lag but not with the rate of myopia progression regardless of the level of near work.
Conclusions: An increasing AC/A ratio is an early sign of becoming myopic, is related to greater accommodative lag, but does not affect the rate of myopia progression. The association with accommodative lag suggests that the AC/A ratio increase is from greater neural effort needed per diopter of accommodation rather than change in the accommodative convergence crosslink gain relationship.
PMID: 28291868 [PubMed - indexed for MEDLINE]
Ciliary Muscle Cell Changes During Guinea Pig Development.
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7691-6
Authors: Pucker AD, Jackson AR, Morris HJ, Fischer AJ, McHugh KM, Mutti DO
PURPOSE: Guinea pig ciliary muscle (CM) increases robustly in volume, length, and thickness with age. We wanted to characterize CM cells during development to determine the contributions of hypertrophy (cell size increase) and hyperplasia (cell number increase) during development.
METHODS: Six pigmented guinea pig eyes were collected at each of five ages: 1, 10, 20, 30, and 90 days. Refractive errors and axial lengths were determined. Eyes were temporally marked, enucleated, hemisected, and fixed. Nasal and temporal eye segments were embedded and 30-μm serial sections were collected; the two most central slides from each hemisection were analyzed with an epifluorescence microscope and Stereo Investigator software to determine normal morphologic parameters.
RESULTS: Refractive errors became less hyperopic (P = 0.0001) while axial lengths and CM lengths, cross-sectional areas, volumes, and cell sizes all increased linearly with log age (all P < 0.00001). Ciliary muscle cell numbers increased only during the first 20 days of life (P = 0.02). Nasal and temporal CM lengths (P = 0.07), cross-sectional areas (P = 0.18), and cell numbers (P = 0.70) were not different, but CM cell sizes were initially larger temporally and became larger nasally after age 30 days.
CONCLUSIONS: The mechanism of guinea pig CM cell growth during the first 90 days of life was characterized by early hyperplasia combined with hypertrophic cell growth throughout development that results in larger CM lengths, cross-sectional areas, and volumes. Nasal-temporal CM development was generally symmetric, but there was more CM hypertrophy nasally at older ages.
PMID: 26641547 [PubMed - indexed for MEDLINE]
Who Says There's Nothing New under the Sun?
Optom Vis Sci. 2015 Nov;92(11):e392-3
Authors: Zadnik K, Mutti DO
The time since our first publication in 2007 describing time spent outdoors as protective for juvenile myopia onset to clinical trials incorporating outdoor light interventions has been short. The time outdoors/myopia example highlights the incorporation of clinical or epidemiologic evidence to translational research that may eventually change clinical practice and/or behavior.
PMID: 26501735 [PubMed - indexed for MEDLINE]
Prediction of Juvenile-Onset Myopia.
JAMA Ophthalmol. 2015 Jun;133(6):683-9
Authors: Zadnik K, Sinnott LT, Cotter SA, Jones-Jordan LA, Kleinstein RN, Manny RE, Twelker JD, Mutti DO, Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study Group
IMPORTANCE: Myopia (nearsightedness) has its onset in childhood and affects about one-third of adults in the United States. Along with its high prevalence, myopia is expensive to correct and is associated with ocular diseases that include glaucoma and retinal detachment.
OBJECTIVE: To determine the best set of predictors for myopia onset in school-aged children.
DESIGN, SETTING, AND PARTICIPANTS: The Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study was an observational cohort study of ocular development and myopia onset conducted at 5 clinical sites from September 1, 1989, through May 22, 2010. Data were collected from 4512 ethnically diverse, nonmyopic school-aged children from grades 1 through 8 (baseline grades 1 through 6) (ages 6 through 13 years [baseline, 6 through 11 years]).
MAIN OUTCOMES AND MEASURES: We evaluated 13 candidate risk factors for their ability to predict the onset of myopia. Myopia onset was defined as -0.75 diopters or more of myopia in each principal meridian in the right eye as measured by cycloplegic autorefraction at any visit after baseline until grade 8 (age 13 years). We evaluated risk factors using odds ratios from discrete time survival analysis, the area under the curve, and cross validation.
RESULTS: A total of 414 children became myopic from grades 2 through 8 (ages 7 through 13 years). Of the 13 factors evaluated, 10 were associated with the risk for myopia onset (P < .05). Of these 10 factors, 8 retained their association in multivariate models: spherical equivalent refractive error at baseline, parental myopia, axial length, corneal power, crystalline lens power, ratio of accommodative convergence to accommodation (AC/A ratio), horizontal/vertical astigmatism magnitude, and visual activity. A less hyperopic/more myopic baseline refractive error was consistently associated with risk of myopia onset in multivariate models (odds ratios from 0.02 to 0.13, P < .001), while near work, time outdoors, and having myopic parents were not. Spherical equivalent refractive error was the single best predictive factor that performed as well as all 8 factors together, with an area under the curve (C statistic) ranging from 0.87 to 0.93 (95% CI, 0.79-0.99).
CONCLUSIONS AND RELEVANCE: Future myopia can be predicted in a nonmyopic child using a simple, single measure of refractive error. Future trials for prevention of myopia should target the child with low hyperopia as the child at risk.
PMID: 25837970 [PubMed - indexed for MEDLINE]
Choroidal Thickness and Peripheral Myopic Defocus during Orthokeratology.
Optom Vis Sci. 2015 May;92(5):579-88
Authors: Gardner DJ, Walline JJ, Mutti DO
PURPOSE: To investigate whether significant thickening occurs in the human choroid in response to chronic peripheral myopic defocus during overnight orthokeratology.
METHODS: Subjects were nine children 11 to 15 years old (mean [±SD] age, 13.61 [±1.25] years). Measurements were taken at baseline and after 1, 3, 6, and 9 months of successful orthokeratology. Choroidal thickness in central, superior, temporal, and nasal gazes were measured using the Zeiss Cirrus HD-OCT. The Lenstar LS 900 biometer provided a secondary measure of subfoveal choroidal thickness. Peripheral ocular length was measured in the same four fields of gaze with the Zeiss IOLMaster. Corneal and optical changes from orthokeratology were monitored throughout the study by corneal topography (Humphrey ATLAS), aberrometry (Complete Ophthalmic Analysis System), and central and peripheral autorefraction (Grand Seiko) after tropicamide 1% cycloplegia.
RESULTS: All subjects had acceptable acuity and physiologic response to overnight wear. After 1 month, central refractive error (mean ± SD) became significantly less myopic (-2.25 ± 0.95 diopters [D] vs. -0.24 ± 1.03 D), keratometric values flattened by 1.6 D, the shape factor (Q) became more oblate (-0.28 ± 0.05 vs. +0.34 ± 0.41), and spherical aberration became more positive (+0.14 ± 0.08 μm vs. +0.46 ± 0.15 μm; all p = 0.008). Peripheral refractive error remained -1.0 to -3.5 D myopic in all fields of gaze throughout the study. There were no consistent, significant changes in choroidal thickness or ocular length at any retinal location during the study (all p > 0.051). Lenstar measurement of choroidal thickness was unsuccessful because of the absence of choroidal peaks associated with thicker choroids (rs = -0.66, p < 0.0001).
CONCLUSIONS: The choroid did not show long-term thickening during orthokeratology despite the presence of substantial amounts of peripheral myopic defocus. Apparent inhibition of ocular growth was not attributed to an optical artifact of choroidal thickening, although smaller amounts of thickening or greater biological activity independent of thickening cannot be ruled out.
PMID: 25875682 [PubMed - indexed for MEDLINE]
The contributions of near work and outdoor activity to the correlation between siblings in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study.
Invest Ophthalmol Vis Sci. 2014 Sep 09;55(10):6333-9
Authors: Jones-Jordan LA, Sinnott LT, Graham ND, Cotter SA, Kleinstein RN, Manny RE, Mutti DO, Twelker JD, Zadnik K, CLEERE Study Group
PURPOSE: We determined the correlation between sibling refractive errors adjusted for shared and unique environmental factors using data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study.
METHODS: Refractive error from subjects' last study visits was used to estimate the intraclass correlation coefficient (ICC) between siblings. The correlation models used environmental factors (diopter-hours and outdoor/sports activity) assessed annually from parents by survey to adjust for shared and unique environmental exposures when estimating the heritability of refractive error (2*ICC).
RESULTS: Data from 700 families contributed to the between-sibling correlation for spherical equivalent refractive error. The mean age of the children at the last visit was 13.3 ± 0.90 years. Siblings engaged in similar amounts of near and outdoor activities (correlations ranged from 0.40-0.76). The ICC for spherical equivalent, controlling for age, sex, ethnicity, and site was 0.367 (95% confidence interval [CI] = 0.304, 0.420), with an estimated heritability of no more than 0.733. After controlling for these variables, and near and outdoor/sports activities, the resulting ICC was 0.364 (95% CI = 0.304, 0.420; estimated heritability no more than 0.728, 95% CI = 0.608, 0.850). The ICCs did not differ significantly between male-female and single sex pairs.
CONCLUSIONS: Adjusting for shared family and unique, child-specific environmental factors only reduced the estimate of refractive error correlation between siblings by 0.5%. Consistent with a lack of association between myopia progression and either near work or outdoor/sports activity, substantial common environmental exposures had little effect on this correlation. Genetic effects appear to have the major role in determining the similarity of refractive error between siblings.
PMID: 25205866 [PubMed - indexed for MEDLINE]
Spectacle correction versus no spectacles for prevention of strabismus in hyperopic children.
Cochrane Database Syst Rev. 2014 Aug 18;(8):CD007738
Authors: Jones-Jordan L, Wang X, Scherer RW, Mutti DO
BACKGROUND: Hyperopia (far-sightedness) in infancy requires accommodative effort to bring images into focus. Prolonged accommodative effort has been associated with an increased risk of strabismus (eye misalignment). Strabismus makes it difficult for the eyes to work together and may result in symptoms of asthenopia (eye strain) and intermittent diplopia (double vision), and makes near work tasks difficult to complete. Untreated strabismus may result in the development of amblyopia (lazy eye). The prescription of spectacles to correct hyperopic refractive error is believed to prevent the development of strabismus.
OBJECTIVES: To assess the effectiveness of prescription spectacles compared with no intervention for the prevention of strabismus in infants and children with hyperopia.
SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to April 2014), EMBASE (January 1980 to April 2014), PubMed (1966 to April 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 3 April 2014. We also searched the Science Citation Index database in September 2013.
SELECTION CRITERIA: We included randomized controlled trials and quasi-randomized trials investigating the assignment to spectacle intervention or no treatment for children with hyperopia. The definition of hyperopia remains subjective, but we required it to be at least greater than +2.00 diopters (D) of hyperopia.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using the standard methodologic procedures expected by The Cochrane Collaboration. One review author entered data into Review Manager and a second review author verified the data entered. The two review authors resolved discrepancies at all stages of the review process.
MAIN RESULTS: We identified three randomized controlled trials (855 children enrolled) in this review. These trials were all conducted in the UK with follow-up periods ranging from one to 3.5 years. We judged the included studies to be at high risk of bias, due to use of quasi-random methods for assigning children to treatment, no masking of outcomes assessors, and high proportions of drop-outs. None of the three trials accounted for missing data and analyses were limited to the available-case data (674 (79%) of 855 children enrolled for the primary outcome). These factors impair our ability to assess the effectiveness of treatment.Analyses incorporating the three trials we identified in this review (674 children) suggested the effect of spectacle correction initiated prior to the age of one year in hyperopic children between three and four years of age is uncertain with respect to preventing strabismus (risk ratio (RR) 0.71; 95% confidence interval (CI) 0.44 to 1.15; very low quality evidence). Based on a meta-analysis of three trials (664 children), the risk of having visual acuity worse than 20/30 at three years of age was also uncertain for children with spectacles compared with those without spectacle correction irrespective of compliance (RR 0.87; 95% CI 0.60 to 1.26; very low quality evidence).Emmetropization was reported in two trials: one trial suggested that spectacles impede emmetropization, and the second trial reported no difference in the rate of refractive error change.
AUTHORS' CONCLUSIONS: Although children who were allocated to the spectacle group were less likely to develop strabismus and less likely to have visual acuity worse than 20/30 children allocated to no spectacles, these effects may have been chance findings, or due to bias. Due to the high risk of bias and poor reporting of included trials, the true effect of spectacle correction for hyperopia on strabismus is still uncertain.
PMID: 25133974 [PubMed - indexed for MEDLINE]
Guinea pig ciliary muscle development.
Optom Vis Sci. 2014 Jul;91(7):730-9
Authors: Pucker AD, Carpenter AR, McHugh KM, Mutti DO
PURPOSE: The purpose of this study was to develop a method for quantifying guinea pig ciliary muscle volume (CMV) and to determine its relationship to age and ocular biometric measurements.
METHODS: Six albino guinea pigs' eyes were collected at each of five ages (n = 30 eyes). Retinoscopy and photography were used to document refractive error, eye size, and eye shape. Serial sections through the excised eyes were made and then labeled with an α-smooth muscle actin antibody. The ciliary muscle was then visualized with an Olympus BX51 microscope, reconstructed with Stereo Investigator (MBF Bioscience), and analyzed using Neurolucida Explorer (MBF Bioscience). Full (using all sections) and partial (using a subset of sections) reconstruction methods were used to determine CMV.
RESULTS: There was no significant difference between the full and partial volume determination methods (p = 0.86). The mean (±SD) CMV of the 1-, 10-, 20-, 30-, and 90-day-old eyes was 0.40 (±0.16) mm, 0.48 (±0.13) mm, 0.67 (±0.15) mm, 0.86 (±0.35) mm, and 1.09 (±0.63) mm, respectively. Ciliary muscle volume was significantly correlated with log age (p = 0.001), ocular length (p = 0.003), limbal circumference (p = 0.01), and equatorial diameter (p = 0.003). It was not correlated with refractive error (p = 0.73) or eye shape (p = 0.60). Multivariate regression determined that biometric variables were not significantly associated with CMV after adjustment for age.
CONCLUSIONS: Three-dimensional reconstruction was an effective means of determining CMV. These data provide evidence that ciliary muscle growth occurs with age in tandem with eye size in normal albino guinea pigs. Additional work is needed to determine the relationship between CMV and abnormal ocular growth.
PMID: 24901488 [PubMed - indexed for MEDLINE]
Heritability of lenticular myopia in English Springer spaniels.
Invest Ophthalmol Vis Sci. 2013 Nov 08;54(12):7324-8
Authors: Kubai MA, Labelle AL, Hamor RE, Mutti DO, Famula TR, Murphy CJ
PURPOSE: We determined whether naturally-occurring lenticular myopia in English Springer spaniels (ESS) has a genetic component.
METHODS: Streak retinoscopy was performed on 226 related ESS 30 minutes after the onset of pharmacologic mydriasis and cycloplegia. A pedigree was constructed to determine relationships between affected offspring and parents. Estimation of heritability was done in a Bayesian analysis (facilitated by the MCMCglmm package of R) of refractive error in a model, including terms for sex and coat color. Myopia was defined as ≤-0.5 diopters (D) spherical equivalent.
RESULTS: The median refractive error for ESS was 0.25 D (range, -3.5 to +4.5 D). Median age was 0.2 years (range, 0.1-15 years). The prevalence of myopia in related ESS was 19% (42/226). The ESS had a strong correlation (r = 0.95) for refractive error between the two eyes. Moderate heritability was present for refractive error with a mean value of 0.29 (95% highest probability density, 0.07-0.50).
CONCLUSIONS: The distribution of refractive error, and subsequently lenticular myopia, has a moderate genetic component in ESS. Further investigation of genes responsible for regulation of the development of refractive ocular components in canines is warranted.
PMID: 24071952 [PubMed - indexed for MEDLINE]
Peripheral defocus and myopia progression in myopic children randomly assigned to wear single vision and progressive addition lenses.
Invest Ophthalmol Vis Sci. 2013 Aug 27;54(8):5761-70
Authors: Berntsen DA, Barr CD, Mutti DO, Zadnik K
PURPOSE: To determine the effect of progressive addition lenses (PALs) and single vision lenses (SVLs) on peripheral defocus in myopic children, and to compare the effect of myopic versus hyperopic peripheral defocus on foveal myopia progression.
METHODS: Eighty-four myopic children aged 6 to 11 years with spherical equivalent (SE) cycloplegic autorefraction between -0.75 diopters (D) and -4.50 D were randomly assigned to wear SVLs or PALs. Aberrometry measurements of the eye and spectacles were made centrally, 30° nasally, temporally, and superiorly, and 20° inferiorly on the retina using a Complete Ophthalmic Analysis System for Vision Research (COAS-VR). The association between peripheral defocus and the 1-year change in central myopia was investigated.
RESULTS: SVLs caused a hyperopic shift in peripheral defocus at all locations (all P ≤ 0.0003). PALs caused a myopic shift in peripheral defocus in three of four locations measured (all P ≤ 0.01) with the greatest shift superiorly due to the PAL addition (-1.04 ± 0.30 D). Superior retinal defocus when wearing either SVLs or PALs was associated with the 1-year change in central myopia. The adjusted 1-year change in central SE myopia was -0.38 D for children with absolute superior myopic defocus (n = 67) and -0.65 D for children with absolute superior hyperopic defocus (n = 17; difference = 0.27 D; P = 0.002).
CONCLUSIONS: PALs caused a myopic shift in peripheral defocus. Superior myopic defocus was associated with less central myopia progression. These data support the continued investigation of optical designs that result in peripheral myopic defocus as a potential way to slow myopia progression. (ClinicalTrials.gov number, NCT00335049.).
PMID: 23838771 [PubMed - indexed for MEDLINE]
Quantification of age-related and per diopter accommodative changes of the lens and ciliary muscle in the emmetropic human eye.
Invest Ophthalmol Vis Sci. 2013 Feb 07;54(2):1095-105
Authors: Richdale K, Sinnott LT, Bullimore MA, Wassenaar PA, Schmalbrock P, Kao CY, Patz S, Mutti DO, Glasser A, Zadnik K
PURPOSE: To calculate age-related and per diopter (D) accommodative changes in crystalline lens and ciliary muscle dimensions in vivo in a single cohort of emmetropic human adults ages 30 to 50 years.
METHODS: The right eyes of 26 emmetropic adults were examined using ultrasonography, phakometry, anterior segment optical coherence tomography, and high resolution magnetic resonance imaging. Accommodation was measured both subjectively and objectively.
RESULTS: In agreement with previous research, older age was linearly correlated with a thicker lens, steeper anterior lens curvature, shallower anterior chamber, and lower lens equivalent refractive index (all P < 0.01). Age was not related to ciliary muscle ring diameter (CMRD) or lens equatorial diameter (LED). With accommodation, lens thickness increased (+0.064 mm/D, P < 0.001), LED decreased (-0.075 mm/D, P < 0.001), CMRD decreased (-0.105 mm/D, P < 0.001), and the ciliary muscle thickened anteriorly (+0.013 to +0.026 mm/D, P < 0.001) and thinned posteriorly (-0.011 to -0.015, P < 0.01). The changes per diopter of accommodation in LED, CMRD, and ciliary muscle thickness were not related to subject age.
CONCLUSIONS: The per diopter ciliary muscle contraction is age independent, even as total accommodative amplitude declines. Quantifying normal biometric dimensions of the accommodative structures and changes with age and accommodative effort will further the development of new IOLs designed to harness ciliary muscle forces.
PMID: 23287789 [PubMed - indexed for MEDLINE]
Time outdoors, visual activity, and myopia progression in juvenile-onset myopes.
Invest Ophthalmol Vis Sci. 2012 Oct 01;53(11):7169-75
Authors: Jones-Jordan LA, Sinnott LT, Cotter SA, Kleinstein RN, Manny RE, Mutti DO, Twelker JD, Zadnik K, CLEERE Study Group
PURPOSE: To investigate the association between myopia progression and time spent outdoors and in various visual activities.
METHODS: Subjects were 835 myopes (both principal meridians -0.75 diopters [D] or more myopia by cycloplegic autorefraction) in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study with both progression data and at least one measure of activity associated with a progression interval. Activity data were collected by parental survey. Average activity level (mean of the activity at the beginning and the end of a 1-year progression interval) was the primary predictor in a repeated-measures mixed model. The model controlled for age, sex, ethnicity, refractive error at the beginning of the progression interval, clinic site, and type of autorefractor used. Effects were scaled based on performing an additional 10 hours per week of an activity.
RESULTS: In the multivariate model, the number of hours of reading for pleasure per week was not significantly associated with annual myopia progression at an a priori level of P ≤ 0.01, nor were the other near activities, the near-work composite variable diopter-hours, or outdoor/sports activity. The magnitude of effects was clinically small. For example, the largest multivariate effect was that each additional 10 hours of reading for pleasure per week at the end of a progression interval was associated with an increase in average annual progression by -0.08 D.
CONCLUSIONS: Despite protective associations previously reported for time outdoors reducing the risk of myopia onset, outdoor/sports activity was not associated with less myopia progression following onset. Near work also had little meaningful effect on the rate of myopia progression.
PMID: 22977132 [PubMed - indexed for MEDLINE]
New cases of myopia in children.
Arch Ophthalmol. 2012 Oct;130(10):1274-9
Authors: Kleinstein RN, Sinnott LT, Jones-Jordan LA, Sims J, Zadnik K, Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study Group
OBJECTIVE: To report the percentage of new cases of myopia in 4927 children aged 5 to 16 years who participated in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 1989 and 2009.
DESIGN: A multicenter, longitudinal, observational, volunteer study of refractive error and ocular development in children from 5 racial/ethnic groups in which the participants were children who were not myopic (right eye cycloplegic auto refraction of less myopia/more hyperopia than -0.75 diopters [D] in both principal meridians) at study entry. A new case was a diagnosis of myopia (right eye cycloplegic auto refraction of -0.75 D or more myopia in both principal meridians) after study entry.
RESULTS: Of the 4556 children entering the study who were not myopic, 749 (16.4%) received a diagnosis of myopia after study entry. Among these 749 children, the ages of the participants at diagnosis varied from 7 to 16 years, with the largest number diagnosed at age 11 years(136 participants [18.2%]). New cases of myopia occurred in 27.3% of Asians, 21.4% of Hispanics, 14.5% of Native Americans, 13.9% of African Americans, and 11% of whites. Female participants had more new cases than did male participants (18.5% vs 14.5%). Normal-birth weight children had more new cases than did low-birth weight children (16.9% vs 15.5%).
CONCLUSIONS: Sixteen percent of children enrolled in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study developed myopia during their school-aged years. The percentage increased yearly until age 11 years, after which it decreased. New cases of myopia varied by ethnic/racial group.
PMID: 22688326 [PubMed - indexed for MEDLINE]
Corneal and crystalline lens dimensions before and after myopia onset.
Optom Vis Sci. 2012 Mar;89(3):251-62
Authors: Mutti DO, Mitchell GL, Sinnott LT, Jones-Jordan LA, Moeschberger ML, Cotter SA, Kleinstein RN, Manny RE, Twelker JD, Zadnik K, CLEERE Study Group
PURPOSE: To describe corneal and crystalline lens dimensions before, during, and after myopia onset compared with age-matched emmetropic values.
METHODS: Subjects were 732 children aged 6 to 14 years who became myopic and 596 emmetropic children participating between 1989 and 2007 in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study. Refractive error was measured using cycloplegic autorefraction, corneal power using a hand-held autokeratometer, crystalline lens parameters using video-based phakometry, and vitreous chamber depth (VCD) using A-scan ultrasonography. Corneal and crystalline lens parameters in children who became myopic were compared with age-, gender-, and ethnicity-matched model estimates of emmetrope values annually from 5 years before through 5 years after the onset of myopia. The comparison was made without and then with statistical adjustment of emmetrope component values to compensate for the effects of longer VCDs in children who became myopic.
RESULTS: Before myopia onset, the crystalline lens thinned, flattened, and lost power at similar rates for emmetropes and children who became myopic. The crystalline lens stopped thinning, flattening, and losing power within ±1 year of onset in children who became myopic compared with emmetropes statistically adjusted to match the longer VCDs of children who became myopic. In contrast, the cornea was only slightly steeper in children who became myopic compared with emmetropes (<0.25 D) and underwent little change across visits.
CONCLUSIONS: Myopia onset is characterized by an abrupt loss of compensatory changes in the crystalline lens that continue in emmetropes throughout childhood axial elongation. The mechanism responsible for this decoupling remains speculative but might include restricted equatorial growth from internal mechanical factors.
PMID: 22227914 [PubMed - indexed for MEDLINE]
A randomized trial using progressive addition lenses to evaluate theories of myopia progression in children with a high lag of accommodation.
Invest Ophthalmol Vis Sci. 2012 Feb;53(2):640-9
Authors: Berntsen DA, Sinnott LT, Mutti DO, Zadnik K
PURPOSE: To compare the effect of wearing, then ceasing to wear, progressive addition lenses (PALs) versus single vision lenses (SVLs) on myopia progression in children with high accommodative lag to evaluate accommodative lag and mechanical tension as theories of myopia progression.
METHODS: Eighty-five children (age range, 6-11 years) with spherical equivalent (SE) cycloplegic autorefraction between -0.75 D and -4.50 D were randomly assigned to wear SVLs or PALs for 1 year; all children wore SVLs a second year. Children had high accommodative lag and also had near esophoria if their myopia was greater than -2.25 D SE. The primary outcome after each year was the previous year's change in SE.
RESULTS: When the children were randomly assigned to SVLs or PALs, the adjusted 1-year changes in SE were -0.52 D (SVL group) and -0.35 D (PAL group; treatment effect = 0.18 D; P = 0.01). When all children wore SVLs the second year, there was no difference in myopia progression between SVL and former PAL wearers (0.06 D; P = 0.50). Accommodative lag was not associated with myopia progression.
CONCLUSIONS: The statistically significant, but clinically small, PAL effect suggests that treatments aimed at reducing foveal defocus may not be as effective as previously thought in myopic children with high accommodative lag. Finding no evidence of treatment loss after discontinuing PAL wear supports hyperopic defocus-based theories such as accommodative lag; however, not finding an association between accommodative lag and myopia progression is inconsistent with the PAL effect being due to decreased foveal blur during near work. (Clinical Trials.gov number, NCT00335049.).
PMID: 22205604 [PubMed - indexed for MEDLINE]
Spectacle wear in children given spectacles through a school-based program.
Optom Vis Sci. 2012 Jan;89(1):19-26
Authors: Messer DH, Mitchell GL, Twelker JD, Crescioni M, CLEERE Study Group
PURPOSE: To investigate factors associated with spectacle wear in a group of primarily Native-American children provided spectacles free of charge through a school-based vision program.
METHODS: Spectacle wear was studied in 247 participants provided two pairs of spectacles the previous year. Univariate and multivariate logistic regression models assessed whether gender, race, parental education levels, family income, uncorrected distance visual acuity, refractive error, or the children's attitudes and beliefs about their vision and spectacles were associated with spectacle wear.
RESULTS: Two thirds of the participants (165/247) were not wearing their spectacles at their annual examination. The most common reasons given for non-wear were lost (44.9%) or broken (35.3%) spectacles. A 1 diopter increase in myopic spherical equivalent was associated with more than a twofold increase in the odds of wearing spectacles [odds ratio (OR) = 2.5, 95% confidence interval (CI) = 1.7 to 3.7]. Among non-myopic participants, increasing amounts of astigmatism in the better- and worse-seeing eye were associated with an increased likelihood of spectacle wear (p ≤ 0.02). In multivariate analysis, only poorer uncorrected acuity in the better-seeing eye (p < 0.001) and shorter acceptance time (p = 0.007) were found to be significantly associated with spectacle wear. For each line of poorer uncorrected acuity in the better-seeing eye, the likelihood that the participant was wearing spectacles increased by 60% (adjusted odds ratio = 1.6; 95% CI = 1.4 to 1.8). Not surprisingly, participants who reported never getting used to their spectacles were less likely to be wearing spectacles than those who reported getting used to wearing glasses in a few days (adjusted OR = 5.7, 95% CI = 1.9 to 17.5).
CONCLUSIONS: Despite being provided with two pairs of spectacles, loss and breakage were the most commonly reported reasons for not wearing spectacles. The best predictive factor for determining whether participants were wearing spectacles was their uncorrected acuity.
PMID: 22001776 [PubMed - indexed for MEDLINE]
Intraocular pressure, ethnicity, and refractive error.
Optom Vis Sci. 2011 Dec;88(12):1445-53
Authors: Manny RE, Mitchell GL, Cotter SA, Jones-Jordan LA, Kleinstein RN, Mutti DO, Twelker JD, Zadnik K, CLEERE Study Group
PURPOSE: The ethnically diverse Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study cohort provides a unique opportunity to explore associations among intraocular pressure (IOP), ethnicity, and refractive error while adjusting for potential confounding variables.
METHODS: Mixed linear models were used to examine the effect of age, refractive error (cycloplegic auto-refraction), ethnicity, sex, and measurement protocol on IOP (Tono-pen) in 3777 children, aged 6 to 14 years at their first CLEERE visit (1995-2009). Children who became myopic during follow-up were used to examine the relationship between time since myopia onset and IOP. Clinically meaningful differences in IOP were preset at >2 mm Hg.
RESULTS: IOP differed among refractive error categories with higher IOP in children with low/moderate myopia than those with high hyperopia (differences <1 mm Hg). There was a statistically significant relationship between age and IOP that depended on ethnicity (interaction p < 0.0001) and measurement protocol (interaction p < 0.0001). The relationship between sex and IOP depended on measurement protocol (interaction p = 0.0004). For children who became myopic during follow-up, the adjusted mean IOP showed a significant decline for only Asian (p = 0.024) and white children (p = 0.004). As with other statistically significant results, these changes in mean adjusted IOPs from 2 years before to 2 years after myopia onset were <2 mm Hg.
CONCLUSIONS: Small but significant differences in IOP by refractive error category were found in this ethnically diverse cohort of children. Relationships between IOP and age, ethnicity, sex, and measurement protocol were complicated by significant interactions between these parameters. Longitudinal analysis of children before and after myopia onset showed changes in IOP over time that varied by ethnicity. Higher IOPs before and at myopia onset were not present in all ethnic groups, with differences before and after onset too small to suggest a role for IOP in the onset of myopia.
PMID: 21946783 [PubMed - indexed for MEDLINE]
Interventions to slow progression of myopia in children.
Cochrane Database Syst Rev. 2011 Dec 07;(12):CD004916
Authors: Walline JJ, Lindsley K, Vedula SS, Cotter SA, Mutti DO, Twelker JD
BACKGROUND: Nearsightedness (myopia) causes blurry vision when looking at distant objects. Highly nearsighted people are at greater risk of several vision-threatening problems such as retinal detachments, choroidal atrophy, cataracts and glaucoma. Interventions that have been explored to slow the progression of myopia include bifocal spectacles, cycloplegic drops, intraocular pressure-lowering drugs, muscarinic receptor antagonists and contact lenses. The purpose of this review was to systematically assess the effectiveness of strategies to control progression of myopia in children.
OBJECTIVES: To assess the effects of several types of interventions, including eye drops, undercorrection of nearsightedness, multifocal spectacles and contact lenses, on the progression of nearsightedness in myopic children younger than 18 years. We compared the interventions of interest with each other, to single vision lenses (SVLs) (spectacles), placebo or no treatment.
SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January 1980 to October 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 11 October 2011. We also searched the reference lists and Science Citation Index for additional, potentially relevant studies.
SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which participants were treated with spectacles, contact lenses or pharmaceutical agents for the purpose of controlling progression of myopia. We excluded trials where participants were older than 18 years at baseline or participants had less than -0.25 diopters (D) spherical equivalent myopia.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias for each included study. When possible, we analyzed data with the inverse variance method using a fixed-effect or random-effects model, depending on the number of studies and amount of heterogeneity detected.
MAIN RESULTS: We included 23 studies (4696 total participants) in this review, with 17 of these studies included in quantitative analysis. Since we only included RCTs in the review, the studies were generally at low risk of bias for selection bias. Undercorrection of myopia was found to increase myopia progression slightly in two studies; children who were undercorrected progressed on average 0.15 D (95% confidence interval (CI) -0.29 to 0.00) more than the fully corrected SVLs wearers at one year. Rigid gas permeable contact lenses (RGPCLs) were found to have no evidence of effect on myopic eye growth in two studies (no meta-analysis due to heterogeneity between studies). Progressive addition lenses (PALs), reported in four studies, and bifocal spectacles, reported in four studies, were found to yield a small slowing of myopia progression. For seven studies with quantitative data at one year, children wearing multifocal lenses, either PALs or bifocals, progressed on average 0.16 D (95% CI 0.07 to 0.25) less than children wearing SVLs. The largest positive effects for slowing myopia progression were exhibited by anti-muscarinic medications. At one year, children receiving pirenzepine gel (two studies), cyclopentolate eye drops (one study), or atropine eye drops (two studies) showed significantly less myopic progression compared with children receiving placebo (mean differences (MD) 0.31 (95% CI 0.17 to 0.44), 0.34 (95% CI 0.08 to 0.60), and 0.80 (95% CI 0.70 to 0.90), respectively).
AUTHORS' CONCLUSIONS: The most likely effective treatment to slow myopia progression thus far is anti-muscarinic topical medication. However, side effects of these medications include light sensitivity and near blur. Also, they are not yet commercially available, so their use is limited and not practical. Further information is required for other methods of myopia control, such as the use of corneal reshaping contact lenses or bifocal soft contact lenses (BSCLs) with a distance center are promising, but currently no published randomized clinical trials exist.
PMID: 22161388 [PubMed - indexed for MEDLINE]
Screening for hyperopia in infants using the PowerRefractor.
Optom Vis Sci. 2011 Aug;88(8):905-11
Authors: Satiani NG, Mutti DO
PURPOSE: To determine the proportion of infants in a pediatric medical practice who have high levels of hyperopia in addition to evaluating the ability of the PowerRefractor (PR) [with and without accessory +4.50 diopter (D) spectacles] compared with cycloplegic retinoscopy to detect highly hyperopic refractive errors.
METHODS: The cycloplegic refractive error (2 drops tropicamide 1% given 5 min apart) of 200 normal birth weight infants was measured by retinoscopy and the Plusoptix PR. If initial readings were ≥ +2.00 D, PR measurement was repeated with accessory +4.50 D spectacles to extend its operating range. Examinations were conducted during well-baby visits at 2 months of age at the office of a local pediatrician group practice.
RESULTS: Of the 200 infants, 7.5% had a spherical equivalent refractive error of +5.00 D or more in both eyes. The use of +4.50 D accessory glasses during PowerRefraction significantly improved the ability to detect higher levels of hyperopia. Areas under receiver operating characteristic curves that were 0.69 to 0.51 when no glasses were worn improved to 0.87 to 0.98 when the glasses were worn (cutpoints between +3.50 and +5.00 D by retinoscopy). Significant underestimation of higher levels of hyperopia by the PR compared with retinoscopy was eliminated when +4.50 D accessory glasses were worn.
CONCLUSIONS: Accessory +4.50 diopter sphere spectacles appeared to successfully extend the operating range of the PR with cycloplegia, allowing for detection of high levels of hyperopia that occurred in a large proportion of 2-month old infants with adequate sensitivity and specificity compared with cycloplegic retinoscopy.
PMID: 21602730 [PubMed - indexed for MEDLINE]
Vitamin D receptor (VDR) and group-specific component (GC, vitamin D-binding protein) polymorphisms in myopia.
Invest Ophthalmol Vis Sci. 2011 Jun 01;52(6):3818-24
Authors: Mutti DO, Cooper ME, Dragan E, Jones-Jordan LA, Bailey MD, Marazita ML, Murray JC, Zadnik K, CLEERE Study Group
PURPOSE: Epidemiologic evidence indicates that time outdoors reduces the risk of myopia, suggesting a possible role for vitamin D. This case-control study was conducted to determine whether single-nucleotide polymorphisms (SNPs) within VDR at 12q13.11 and GC at 4q12-13 are associated with myopia.
METHODS: The primary analysis was conducted on 81 white adult control subjects between 18 and 50 years of age with a spherical equivalent refractive error between +0.50 and +2.00 D in both eyes and less than 1.50 D of astigmatism. Affected myopic subjects were 289 unrelated white adults at least 18 years of age with at least -0.75 D myopia in both principal meridians of both eyes.
RESULTS: One SNP within VDR was significantly associated with myopia in the multivariate analysis of the primary sample (rs2853559: odds ratio = 1.99, P = 0.003). In a subsample of less severely myopic white subjects between -0.75 and -4.00 D, three SNPs within VDR were significantly associated in a multivariate model after adjustment for multiple comparisons (rs2239182: odds ratio = 2.17, P = 0.007; rs3819545: odds ratio = 2.34, P = 0.003; rs2853559: odds ratio = 2.14, P = 0.0035), accounting for 12% of model variance over age alone.
CONCLUSIONS: Polymorphisms within VDR appear to be associated with low to moderate amounts of myopia in white subjects. Future studies should determine whether this finding can be replicated and should explore the biological significance of these variations with respect to myopia.
PMID: 21357399 [PubMed - indexed for MEDLINE]
Accommodative lag and juvenile-onset myopia progression in children wearing refractive correction.
Vision Res. 2011 May 11;51(9):1039-46
Authors: Berntsen DA, Sinnott LT, Mutti DO, Zadnik K, CLEERE Study Group
The relationship between accommodative lag and annual myopia progression was investigated using linear models in 592 myopic children wearing a full refractive correction in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. The mean (± SD) age and spherical equivalent refractive error at baseline were 10.4 ± 1.8 years and -2.13 ± 1.24 D, respectively. The mean annual progression of myopia was -0.45 ± 0.32 D, and the mean accommodative lag (for a 4-D Badal stimulus) was 1.59 ± 0.63 D. Neither lag at the beginning nor at the end of a yearly progression interval was associated with annual myopia progression (all p ≥ 0.12). These data suggest that foveal hyperopic retinal blur during near viewing may not drive juvenile-onset myopia progression.
PMID: 21342658 [PubMed - indexed for MEDLINE]
Blood levels of vitamin D in teens and young adults with myopia.
Optom Vis Sci. 2011 Mar;88(3):377-82
Authors: Mutti DO, Marks AR
PURPOSE: Longitudinal data suggest that time outdoors may be protective against myopia onset. We evaluated the hypothesis that time outdoors might create differences in circulating levels of vitamin D between myopes and non-myopes.
METHODS: Subjects provided 200 μl of peripheral blood in addition to survey information about dietary intakes and time spent in indoor or outdoor activity. The 22 subjects ranged in age from 13 to 25 years. Myopes (n = 14) were defined as having at least -0.75 diopter of myopia in each principal meridian and non-myopes (n = 8) had +0.25 diopter or more hyperopia in each principal meridian. Blood level of vitamin D was measured using liquid chromatography/mass spectroscopy.
RESULTS: Unadjusted blood levels of vitamin D were not significantly different between myopes (13.95 ± 3.75 ng/ml) and non-myopes (16.02 ± 5.11 ng/ml, p = 0.29) nor were the hours spent outdoors (myopes = 12.9 ± 7.8 h; non-myopes = 13.6 ± 5.8 h; p = 0.83). In a multiple regression model, total sugar and folate from food were negatively associated with blood vitamin D, whereas theobromine and calcium were positively associated with blood vitamin D. Myopes had lower levels of blood vitamin D by an average of 3.4 ng/ml compared with non-myopes when adjusted for age and dietary intakes (p = 0.005 for refractive error group, model R = 0.76). Gender, time outdoors, and dietary intake of vitamin D were not significant in this model.
CONCLUSIONS: The hypothesis that time outdoors might create differences in vitamin D could not be evaluated fully because time outdoors was not significantly related to myopia in this small sample. However, adjusted for differences in the intake of dietary variables, myopes appear to have lower average blood levels of vitamin D than non-myopes. Although consistent with the hypothesis above, replication in a larger sample is needed.
PMID: 21258262 [PubMed - indexed for MEDLINE]
Visual activity before and after the onset of juvenile myopia.
Invest Ophthalmol Vis Sci. 2011 Mar;52(3):1841-50
Authors: Jones-Jordan LA, Mitchell GL, Cotter SA, Kleinstein RN, Manny RE, Mutti DO, Twelker JD, Sims JR, Zadnik K, CLEERE Study Group
PURPOSE: To investigate visual activities before and after the onset of juvenile myopia.
METHODS: The subjects were 731 incident myopes (-0.75 D or more myopia on cycloplegic autorefraction in both meridians) and 587 emmetropes (between -0.25 and +1.00 D) in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Parents supplied visual activity data annually. Data from myopic children 5 years before through 5 years after myopia onset were compared to data from age-, sex-, and ethnicity-matched models of children who remained emmetropic.
RESULTS: Hours per week spent reading or using a computer/playing video games did not differ between the groups before myopia onset; however, hours per week for both activities were significantly greater in myopes than in emmetropes at onset and in 4 of the 5 years after onset by 0.7 to 1.6 hours per week. Hours per week spent in outdoor/sports activities were significantly fewer for children who became myopic 3 years before onset through 4 years after onset by 1.1 to 1.8 hours per week. Studying and TV watching were not significantly different before myopia onset.
CONCLUSIONS: Before myopia onset, near work activities of future myopic children did not differ from those of emmetropes. Those who became myopic had fewer outdoor/sports activity hours than the emmetropes before, at, and after myopia onset. Myopia onset may influence children's near work behavior, but the lack of difference before onset argues against a major causative role for near work. Less outdoor/sports activity before myopia onset may exert a stronger influence on development than near work.
PMID: 20926821 [PubMed - indexed for MEDLINE]
Relative peripheral refractive error and the risk of onset and progression of myopia in children.
Invest Ophthalmol Vis Sci. 2011 Jan 05;52(1):199-205
Authors: Mutti DO, Sinnott LT, Mitchell GL, Jones-Jordan LA, Moeschberger ML, Cotter SA, Kleinstein RN, Manny RE, Twelker JD, Zadnik K, CLEERE Study Group
PURPOSE: To investigate whether relative peripheral hyperopia is a risk factor for either the onset of myopia in children or the rate of myopic progression.
METHODS: The risk of myopia onset was assessed in 2043 nonmyopic third-grade children (mean age ± SD = 8.8 ± 0.52 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study between 1995 and 2007, 324 of whom became myopic by the eighth grade. Progression analyses used data from 774 myopic children in grades 1 to 8. Foveal and relative peripheral refractive error 30° in the nasal visual field was measured annually by using cycloplegic autorefraction. Axial length was measured by A-scan ultrasonography.
RESULTS: The association between more hyperopic relative peripheral refractive error in the third grade and the risk of the onset of myopia by the eighth grade varied by ethnic group (Asian children odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06-2.30; African-American children OR = 0.75, 95% CI = 0.58-0.96; Hispanics, Native Americans, and whites showed no significant association). Myopia progression was greater per diopter of more hyperopic relative peripheral refractive error, but only by a small amount (-0.024 D per year; P = 0.02). Axial elongation was unrelated to the average relative peripheral refractive error (P = 0.77), regardless of ethnicity.
CONCLUSIONS: Relative peripheral hyperopia appears to exert little consistent influence on the risk of the onset of myopic refractive error, on the rate of myopia progression, or on axial elongation.
PMID: 20739476 [PubMed - indexed for MEDLINE]
The effect of bifocal add on accommodative lag in myopic children with high accommodative lag.
Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6104-10
Authors: Berntsen DA, Mutti DO, Zadnik K
PURPOSE: To determine the effect of a bifocal add and manifest correction on accommodative lag in myopic children with high accommodative lag, who have been reported to have the greatest reduction in myopia progression with progressive addition lenses (PALs).
METHODS: Monocular accommodative lag to a 4-D Badal stimulus was measured on two occasions 6 months apart in 83 children (mean ± SD age, 9.9 ± 1.3 years) with high lag randomized to wearing single-vision lenses (SVLs) or PALs. Accommodative lag was measured with the following corrections: habitual, manifest, manifest with +2.00-D add, and habitual with +2.00-D add (6-month visit only).
RESULTS: At baseline, accommodative lag was higher (1.72 ± 0.37 D; mean ± SD) when measured with manifest correction than with habitual correction (1.51 ± 0.50; P < 0.05). This higher lag with manifest correction correlated with a larger amount of habitual undercorrection at baseline (r = -0.29, P = 0.009). A +2.00-D add over the manifest correction reduced lag by 0.45 ± 0.34 D at baseline and 0.33 ± 0.38 D at the 6-month visit. Lag results at 6 months were not different between PAL and SVL wearers (P = 0.92).
CONCLUSIONS: A +2.00-D bifocal add did not eliminate accommodative lag and reduced lag by less than 25% of the bifocal power, indicating that children mainly responded to a bifocal by decreasing accommodation. If myopic progression is substantial, measuring lag with full correction can overestimate the hyperopic retinal blur that a child most recently experienced. (ClinicalTrials.gov number, NCT00335049.).
PMID: 20688729 [PubMed - indexed for MEDLINE]
Study of Theories about Myopia Progression (STAMP) design and baseline data.
Optom Vis Sci. 2010 Nov;87(11):823-32
Authors: Berntsen DA, Mutti DO, Zadnik K
PURPOSE: The Study of Theories about Myopia Progression (STAMP) is a 2-year, double-masked, randomized clinical trial of myopic children 6 to 11 years of age. STAMP will evaluate the 1-year effect of progressive addition lenses (PALs) compared with single vision lenses (SVLs) on central refraction, peripheral refraction in four quadrants, and accommodative response and convergence. STAMP will also evaluate any changes 1 year after discontinuing PALs. Baseline characteristics of enrolled children are reported.
METHODS: Eligible children had a high accommodative lag and either low myopia (less myopic than -2.25 diopter (D) spherical equivalent) or high myopia (more myopic than -2.25 D spherical equivalent) and esophoria at near. Children were randomly assigned to wear either PALs or SVLs for 1 year to determine the difference in myopia progression in the PAL group relative to the SVL group. All children will then wear SVLs for the 2nd year to evaluate the permanence of any treatment effect. Complete ocular biometric data are collected at 6-month intervals.
RESULTS: Over 17 months, 192 children were screened, and 85 (44%) were eligible and enrolled. Of these 85 children, 44 (52%) were girls, and 54 (64%) were esophoric at near. The mean age (± SD) was 9.8 ± 1.3 years. The right eye mean cycloplegic spherical equivalent refractive error was -1.95 ± 0.78 D. Horizontal relative peripheral hyperopia (30° nasal retina + 0.56 ± 0.59 D; 30° temporal retina + 0.61 ± 0.77 D) and vertical relative peripheral myopia (30° superior retina -0.36 ± 0.92 D; 20° inferior retina -0.48 ± 0.83 D) were found.
CONCLUSIONS: The baseline data for STAMP are reported. Asymmetry between vertical and horizontal meridian relative peripheral refraction was found. STAMP will use the ocular biometric changes associated with the PAL treatment effect to attempt to elucidate the mechanism responsible for the treatment effect.
PMID: 20935586 [PubMed - indexed for MEDLINE]
Vision specific quality of life of pediatric contact lens wearers.
Optom Vis Sci. 2010 Aug;87(8):560-6
Authors: Rah MJ, Walline JJ, Jones-Jordan LA, Sinnott LT, Jackson JM, Manny RE, Coffey B, Lyons S, ACHIEVE Study Group
PURPOSE: Several studies have shown that children are capable of wearing and caring for contact lenses, but it is not known whether the benefits outweigh the risks associated with contact lens wear. The purpose of this article is to compare the vision-related quality of life benefits of children randomized to wear spectacles or contact lenses for 3 years using the Pediatric Refractive Error Profile.
METHODS: The Pediatric Refractive Error Profile was administered to 484 children who wore glasses at baseline. The children were then randomly assigned to wear contact lenses (n = 247) or spectacles (n = 237) for 3 years. The survey was administered at the baseline examination, at 1 month, and every 6 months for 3 years.
RESULTS: During 3 years, the overall quality of life improved 14.2 +/- 18.1 units for contact lens wearers and 2.1 +/- 14.6 units for spectacle wearers (p < 0.001). In all scales except the visual performance scales (Distance Vision, Near Vision, and Overall Vision), the quality of life improved more for older subjects than younger subjects. The three scales with the largest improvement in quality of life for contact lens wearers were Activities, Appearance, and Satisfaction with Correction.
CONCLUSIONS: Myopic children younger than 12 years of age report better vision-related quality of life when they are fit with contact lenses than when they wear glasses. Older children, children who participate in recreational activities, children who are motivated to wear contact lenses, and children who do not like their appearance in glasses will benefit most.
PMID: 20562669 [PubMed - indexed for MEDLINE]
Gas permeable and soft contact lens wear in children.
Optom Vis Sci. 2010 Jun;87(6):414-20
Authors: Jones-Jordan LA, Walline JJ, Mutti DO, Rah MJ, Nichols KK, Nichols JJ, Zadnik K
PURPOSE: To compare children's reports of comfort, vision, and contact lens-related issues in gas permeable (GP) and soft (SCL) contact lens wearers.
METHODS: Subjects were 116 8- to 11-year old children in the Contact Lenses and Myopia Progression Study. Aspects of contact lens wear were compared for children remaining in their original treatment group (either GPs or SCLs) for 3 years. Questionnaires were completed at every visit, as was visual acuity. Comparisons were made between the two groups using logistic regression or mixed linear models analyses as appropriate to examine the contact lens wearing experience. Additionally, children crossing over from GP wear to SCLs were compared with children remaining in GP lenses to determine the potential factors related to GP dissatisfaction.
RESULTS: Seventy percent of GP wearers and 93% of SCL wearers wore their assigned lenses every visit. GP wearers wore their lenses significantly fewer hours per week than the SCL wearers (76.2 h/week vs. 86.8 h/week, respectively, p = 0.003). GP wearers had statistically significantly better visual acuity though the difference was not clinically meaningful (p < 0.001). Comfort was poorer among the GP wearers using the Ocular Pain subscale (p < 0.001) but did not differ using a subjective question about comfort. Symptoms were more frequent in GP wearers than SCL wearers (p = 0.002) and were related to reports of discomfort. Significant factors relating to crossing over from GPs to SCLs were lower wearing time with GPs and itching.
CONCLUSIONS: Children are able to successfully wear GP and soft contact lenses. Long-term adaptation occurred more frequently to SCLs than to GPs. The amount of time GP lens wearers are able to comfortably wear their contact lenses and the amount of itching may help determine whether they will remain in that modality.
PMID: 20386349 [PubMed - indexed for MEDLINE]
Hereditary and environmental contributions to emmetropization and myopia.
Optom Vis Sci. 2010 Apr;87(4):255-9
Authors: Mutti DO
Twenty years of investigation into emmetropization and the development of myopia has led to several recent insights. Accommodation appears to be an important visual signal for emmetropization. Lens thinning during emmetropization and its cessation at the onset of myopia suggest that interruption of lens stretch during growth is an important part of the process of developing myopia. The ciliary muscle may play a greater role in emmetropization and myopia than previously thought. Time spent outdoors, not near work, may be the more important environmental variable in myopia. The effect of time outdoors shows an important interaction with a substantial genetic contribution to the risk of myopia.
PMID: 20019643 [PubMed - indexed for MEDLINE]
Early childhood refractive error and parental history of myopia as predictors of myopia.
Invest Ophthalmol Vis Sci. 2010 Jan;51(1):115-21
Authors: Jones-Jordan LA, Sinnott LT, Manny RE, Cotter SA, Kleinstein RN, Mutti DO, Twelker JD, Zadnik K, Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study Group
PURPOSE: To determine the utility of a child's first grade refractive error and parental history of myopia as predictors of myopia onset between the second and eighth grades.
METHODS: Subjects were nonmyopic children in the first grade who were enrolled in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study. Myopia was defined as -0.75 D or more myopia in both meridians (by cycloplegic autorefraction). The children were classified as having a high (versus low) risk of myopia with a cycloplegic sphere cutoff of +0.75 D or less (versus more) of hyperopia. Parental myopia was determined by a parent-completed survey. Discrete-time survival models predicted the risk of myopia.
RESULTS: Of the 1854 nonmyopic first graders, 21.3% were at high risk of myopia. More high-risk subjects had two myopic parents, 25.4% compared with 16.5% in the low-risk group (P < 0.0001). The low-risk survival function was similar regardless of the number of myopic parents. Among high-risk eighth graders, the survival probability was lower than in the low-risk group, decreasing with an increase in the number of myopic parents. The sensitivity and specificity of first grade refractive error with the number of myopic parents as predictors for myopia onset were 62.5% and 81.9%, respectively.
CONCLUSIONS: First grade refractive error and the number of myopic parents can predict a child's risk of myopia; however, because the sensitivity of these factors is low, these two predictors may not be sufficient at this young age when a more accurate prediction of myopia onset is needed.
PMID: 19737876 [PubMed - indexed for MEDLINE]