Indoor and outdoor human behavior and myopia: an objective and dynamic study.

Significance: Myopia holds significant public health concern given its social, ocular disease and economic burdens. Although environmental factors are primarily to blame for the rapid rise in prevalence, key risk factors remain unresolved. Purpose: The aim of this study was to objectively characterize, using a wearable technology, the temporal indoor and outdoor behavioral patterns and associated environmental lighting characteristics of young myopic and nonmyopic University students. Methods: Participants were recruited to continuously wear an Actiwatch for 3 weeks, during either or both academic and non-academic periods. The device allows continuous recording of activity and incident light. Recorded illuminance levels were used as a proxy for outdoors (>1,000 lux), with the dynamics (interval frequency and duration) of indoor and outdoor activities, as well as lighting characteristics derived. In addition, participant input regarding near work was obtained daily. Participants were classified by both myopia and axial length status (based on collected refractive error and biometry data) for the purpose of data analysis. Result: A total of 55 students, aged 18 to 25 years of age, participated. Overall, the dosing of indoor and outdoor activities was similar across participants, regardless of myopia status, during the academic period. Nonetheless, an apparent difference in the timing of outdoor activities was noted with myopes going outdoors later in the day, particularly during the weekend (p = 0.03). While a trend was observed between increased lighting levels experienced outdoors and shorter axial lengths, there was no significant relationship with myopia status. Noteworthy, participants generally significantly overestimated time spent outdoors, compared to Actiwatch-derived estimates of the same. Conclusion: While the findings from this cohort of young adult students did not reveal substantial myopia-related differences in behavior, the power of a more objective and dynamic approach to quantifying behavior cannot be understated, providing argument for general adoption of wearable technologies in future clinical myopia studies.

IMI-Management and Investigation of High Myopia in Infants and Young Children.

Purpose: The purpose of this study was to evaluate the epidemiology, etiology, clinical assessment, investigation, management, and visual consequences of high myopia (≤-6 diopters [D]) in infants and young children. Findings: High myopia is rare in pre-school children with a prevalence less than 1%. The etiology of myopia in such children is different than in older children, with a high rate of secondary myopia associated with prematurity or genetic causes. The priority following the diagnosis of high myopia in childhood is to determine whether there is an associated medical diagnosis that may be of greater overall importance to the health of the child through a clinical evaluation that targets the commonest features associated with syndromic forms of myopia. Biometric evaluation (including axial length and corneal curvature) is important to distinguishing axial myopia from refractive myopia associated with abnormal development of the anterior segment. Additional investigation includes ocular imaging, electrophysiological tests, genetic testing, and involvement of pediatricians and clinical geneticists is often warranted. Following investigation, optical correction is essential, but this may be more challenging and complex than in older children. Application of myopia control interventions in this group of children requires a case-by-case approach due to the lack of evidence of efficacy and clinical heterogeneity of high myopia in young children. Conclusions: High myopia in infants and young children is a rare condition with a different pattern of etiology to that seen in older children. The clinical management of such children, in terms of investigation, optical correction, and use of myopia control treatments, is a complex and often multidisciplinary process.

IMI-The Dynamic Choroid: New Insights, Challenges, and Potential Significance for Human Myopia.

The choroid is the richly vascular layer of the eye located between the sclera and Bruch's membrane. Early studies in animals, as well as more recent studies in humans, have demonstrated that the choroid is a dynamic, multifunctional structure, with its thickness directly and indirectly subject to modulation by a variety of physiologic and visual stimuli. In this review, the anatomy and function of the choroid are summarized and links between the choroid, eye growth regulation, and myopia, as demonstrated in animal models, discussed. Methods for quantifying choroidal thickness in the human eye and associated challenges are described, the literature examining choroidal changes in response to various visual stimuli and refractive error-related differences are summarized, and the potential implications of the latter for myopia are considered. This review also allowed for the reexamination of the hypothesis that short-term changes in choroidal thickness induced by pharmacologic, optical, or environmental stimuli are predictive of future long-term changes in axial elongation, and the speculation that short-term choroidal thickening can be used as a biomarker of treatment efficacy for myopia control therapies, with the general conclusion that current evidence is not sufficient.

Nutritional Factors and Myopia: An Analysis of National Health and Nutrition Examination Survey Data.

SIGNIFICANCE: The rise in the prevalence of myopia, a significant worldwide public health concern, has been too rapid to be explained by genetic factors alone and thus suggests environmental influences. PURPOSE: Relatively little attention has been paid to the possible role of nutrition in myopia. The availability of the large National Health and Nutrition Examination Survey data set, which includes results from vision examinations, offers the opportunity to investigate the relationship between several nutrition-related factors, including body metrics, and the presence and magnitude of myopia. METHODS: Cross-sectional survey data sets with vision examination, demographic, body metrics, and nutritional data, collected as part of the National Health and Nutrition Examination Survey over the years of 2003 to 2008, were extracted for analysis. Based on already published basic and epidemiological studies, the following parameters were selected for study: body height and body mass index, demographics, serum vitamin D and glucose/insulin levels, and caffeine intake, using multivariable models and objectively measured refractive errors as the main outcome measure. RESULTS: Data from a total of 6855 ethnically diverse Americans aged 12 to 25 years were analyzed. In final multivariate models, female sex and age were the most significant factors related to myopia status and refractive error. In general, body metrics (body mass index) or nutritional factors (serum vitamin D, glucose levels, and caffeine intake) were found to be associated with refractive error or myopia status; however, increased insulin levels were related to increased odds of having myopia. CONCLUSIONS: These largely negative findings suggest that other environmental factors, such as those related to the visual environment, may contribute more to the development and/or progression of myopia and would argue for continued research in these areas in support of more evidence-based myopia clinical management.

The Spatial Frequency Content of Urban and Indoor Environments as a Potential Risk Factor for Myopia Development.

Purpose: To examine the hypothesis that the spatial frequency spectra of urban and indoor environments differ from the natural environment in ways that may promote the development of myopia. Methods: A total of 814 images were analyzed from three datasets; University of California Berkeley (UCB), University of Texas (UT), and Botswana (UPenn). Images were processed in Matlab (Mathworks Inc) to map the camera color characteristics to human cone sensitivities. From the photopic luminance images generated, two-dimensional spatial frequency (SF) spectra were calculated and converted to one-dimensional spectra by rotational averaging. The spatial filtering profile of a 0.4 Bangerter foil, which has been shown to induce myopia experimentally, was also determined. Results: The SF slope for natural scenes followed the recognized 1/fα relationship with mean slopes of -1.08, -0.90, and -1.04 for the UCB, UT and UPenn image sets, respectively. Indoor scenes had a significantly steeper slope (-1.48, UCB; -1.52, UT; P < 0.0001). Urban environments showed an intermediate slope (-1.29, UCB; -1.22, UT) that was significantly different from the slopes derived from the natural scenes (P < 0.0001). The change in SF content between natural outdoor scenes and indoors was comparable to that induced by a 0.4 Bangerter foil, which reduced the SF slope of a natural scene from -0.88 to -1.47. Conclusions: Compared to natural outdoor images, man-made outdoor and indoor environments have spatial frequency characteristics similar to those known to induce form-deprivation myopia in animal models. The spatial properties of the man-made environment may be one of the missing drivers of the human myopia epidemic.

Origins of Refractive Errors: Environmental and Genetic Factors.

Refractive errors are the product of a mismatch between the axial length of the eye and its optical power, creating blurred vision. Uncorrected refractive errors are the second leading cause of worldwide blindness. One refractive error currently attracting significant scientific interest is myopia, mostly owing to the recent rise in its prevalence worldwide and associated ocular disease burden. This increase in myopia prevalence has also been rapid, suggesting environmental influences in addition to any genetic influences on eye growth. This review defines refractive errors, describes their prevalence, and presents evidence for the influence of genetic and environmental factors related to refractive error development.

Optic Nerve Tilt, Crescent, Ovality, and Torsion in a Multi-Ethnic Cohort of Young Adults With and Without Myopia.

Purpose: The purpose of this article is to evaluate optic nerve head (ONH) characteristics in an ethnically diverse cohort of young U.S. adults. Methods: In this study, 409 myopes and 206 nonmyopes (median age 22 years) completed measures including biometry and spectral domain optical coherence tomography from enface (ovality and torsion) and cross-sectional (tilt and crescent width) scans. Associated factors were evaluated using multivariable models. Results: In myopic versus nonmyopic right eyes, median tilt (6.0° vs. 2.4°; P < 0.0001) and frequency of crescents (49% vs. 10%; P < 0.0001) were higher in myopes. Right eyes with crescents had higher median tilts (8.8° [myopic], 9.0° [nonmyopic]) than those without crescent (2.5° [myopic], 2.1° [nonmyopic]), irrespective of refractive group (both P < 0.0001). Torsion was similar between groups, with a slight difference in ovality (0.89 vs. 0.91; P < 0.03). Data in the left eyes were similar, and modeling was done only for the right myopic eyes. Multivariable models showed that an increased tilt was associated with ethnicity (P < 0.001), the presence of crescent (P < 0.001), and smaller ONH diameter (P < 0.0031), with interactions between ethnicity and crescent (P = 0.002). Specifically, ONH tilt was significantly higher in Asian eyes without crescent (P < 0.0001 for all comparisons), and crescent width was associated with increased tilt in non-Asian eyes (P < 0.02). Crescent width was associated with ethnicity (greatest in Asians) and disc tilt. Interactions were observed between tilt and ethnicity, whereby tilt had a greater effect on crescent width in non-Asian eyes, and crescent width was associated with increased tilt in non-Asian eyes. Conclusions: The data clarify the influence of ethnicity and myopia on ONH characteristics in young adults and may inform future studies of biomechanical properties or of retinal pathology of the myopic eye.

A sloped piecemeal Gaussian model for characterising foveal pit shape.

PURPOSE: High-quality optical coherence tomography (OCT) macular scans make it possible to distinguish a range of normal and diseased states by characterising foveal pit shape. Existing mathematical models lack the flexibility to capture all known pit variations and thus characterise the pit with limited accuracy. This study aimed to develop a new model that provides a more robust characterisation of individual foveal pit variations. METHODS: A Sloped Piecemeal Gaussian (SPG) model, consisting of a linear combination of a tilted line and a piecemeal Gaussian function (two halves of a Gaussian connected by a separate straight line), was developed to fit retinal thickness data with the flexibility to characterise different degrees of pit asymmetry and pit bottom flatness. It fitted the raw pit data between the two rims of the fovea to improve accuracy. The model was tested on 3488 macular scans from both eyes of 581 young adults (376 myopes and 206 non-myopes, mean (S.D.) age 21.9 (1.4) years). Estimates for retinal thickness, wall height and slope, pit depth and width were derived from the best-fitting model curve. Ten variations of Gaussian and Difference of Gaussian models were fitted to the same scans and compared with the SPG model for goodness of fit (by Root mean square error, RMSE), model complexity (by the Bayesian Information Criteria) and model fidelity. RESULTS: The SPG model produced excellent goodness of fit (mean RMSE = 4.25 and 3.89 µm; 95% CI: 4.20, 4.30 and 3.86, 3.93 for fitting horizontal and vertical profiles respectively). The SPG model showed pit asymmetry, with average nasal walls 17.6 (11.6) µm higher and 0.96 (0.61)° steeper than temporal walls and average superior walls 7.0 (12.2) µm higher and 0.41 (0.65)° steeper than the inferior walls. The SPG model also revealed a continuum of human foveal shapes, from round bottoms to extended flat bottoms (up to 563 µm). 49.1% of foveal profiles were best fitted with a flat bottom >30 µm wide. Compared with the other tested models, the SPG was the preferred model overall based on the Bayesian Information Criteria. CONCLUSIONS: The SPG is a new parsimonious mathematical model that improves upon other models by accounting for wall asymmetry and flat pit bottoms, providing an excellent fit and more faithful characterisation of typical foveal pit shapes and their known variations. This new model may be helpful in distinguishing normal foveal shape variations by refractive status as well by other characteristics such as sex, ethnicity and age.

Choroidal Thickness Profiles in Myopic Eyes of Young Adults in the Correction of Myopia Evaluation Trial Cohort.

PURPOSE: To examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort. DESIGN: Cross-sectional, multicenter study. METHODS: In addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid in both eyes at their last visit (14 years after baseline). Using digital calipers, 2 independent readers measured choroidal thickness in the right eye (left eye if poor quality; n = 37) at 7 locations: fovea and 750, 1500, and 2250 µm nasal (N) and temporal (T) to the fovea. RESULTS: Choroidal thickness measurements were available from 294 of 346 (85%) imaged participants (mean age: 24.3 ± 1.4 years; 44.9% male) with mean myopia of -5.3 ± 2.0 diopters and mean AL of 25.5 ± 1.0 mm. Overall, choroidal thickness varied by location (P < .0001) and was thickest at the fovea (273.8 ± 70.9 µm) and thinnest nasally (N2250, 191.5 ± 69.3 µm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (P ≤ .001) and presence of peripapillary crescent at all locations except T1500 and T2250 (P ≤ .0001). Choroidal thickness varied by ethnicity at N2250 (P < .0001), with Asians having the thinnest and African Americans the thickest choroids. CONCLUSION: Choroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically.

Visual activity and its association with myopia stabilisation.

PURPOSE: To evaluate the association between outdoor and nearwork activities at baseline and myopia stabilisation by age 15 in the Correction of Myopia Evaluation Trial (COMET). METHODS: Correction of Myopia Evaluation Trial enrolled 469 children (ages: 6-11 years) with spherical equivalent myopia between -1.25 and -4.50 D, who were randomised to progressive addition or single vision lenses and followed for 5 years in their original lenses. At baseline, families recorded the child's outdoor and nearwork activities for 3 days within a week. Weekly hours spent in nearwork and outdoor activities were calculated for each participant. Refractions collected over 11 years were fit using the Gompertz function to determine each participant's myopia stabilisation age. Myopia for each child was then categorized as stable/not stable by age 15. RESULTS: Half (233/469) of participants had usable baseline activity diaries and refraction data that could be fit with the Gompertz function, 59.7% (139/233) had stable myopia by age 15 and 40.3% had myopia that was not yet stable. The frequency of stable myopia was similar for the two categories (median split) of outdoor activities: 60% (71/118) for ≤9.0 hours/week(-1) and 59% (68/115) for >9.0 hours/week(-1) . 56% (64/114) of children reporting >21.0 h of baseline weekly nearwork activity had stable myopia by age 15 compared to 63% (75/119) with ≤21.0 h of near work (adjusted OR = 0.74; 95% CI: 0.43-1.29). Using baseline nearwork as a continuous variable, the multivariable odds ratio for the association between baseline nearwork hours and stabilisation by age 15 is 0.98: 95% CI: 0.96-1.00, a result trending towards significance. CONCLUSION: While time spent in outdoor activities in childhood does not appear to be related to myopia stabilisation by age 15, less near work activity might potentially be associated with myopia stabilisation by that age.

Factors associated with macular thickness in the COMET myopic cohort.

PURPOSE: To determine whether macular thickness is associated with ethnicity, gender, axial length (AL), and severity of myopia in a cohort of young adults from the Correction of Myopia Evaluation Trial (COMET). METHODS: Eleven years after their baseline visit, 387/469 (83%) subjects returned for their annual visit. In addition to the protocol-specific measures of spherical equivalent refractive error (SER) and AL, high-resolution macular imaging also was performed with optical coherence tomography (RTVue). From these scans, full-thickness values for the central (1 mm), parafoveal (1 to 3 mm), and perifoveal (3 to 5 mm) annular regions were calculated. Gender, ethnicity, AL, and SER were examined for associations with macular thickness using univariate and multivariable linear regression analyses. RESULTS: In the 377 subjects with usable data (mean age = 21.0 ± 1.3 years), the mean SER ± SD was -5.0 ± 1.9 D and mean AL was 25.4 ± 0.9 mm. Mean foveal thickness was 252.0 ± 20.1 µm in the center, 315.6 ± 14.0 µm in the parafovea, and 284.4 ± 12.9 µm in the perifovea. In the best-fit multivariable model that adjusted for gender, ethnicity, and AL, females had significantly thinner maculas than males for all three regions (p < 0.0001), with the largest difference in the center (12.8 µm, 95% confidence interval: 9.2 to 16.4). The effect of ethnicity was strongest in the central fovea, with African-Americans, Asians, Hispanics, and mixed ethnic groups having thinner maculas than whites (all p values < 0.005). Increased AL was significantly associated with slightly thicker central foveas (p = 0.001) and thinner parafoveal (p = 0.02) and perifoveal (p < 0.0001) regions. CONCLUSIONS: In this ethnically diverse cohort of moderate and high myopes, females and African-Americans were found to have the thinnest central foveas. Whether such thinning in the macula as a young adult is a risk factor for future disease remains to be determined.

Imposed anisometropia, accommodation, and regulation of refractive state.

PURPOSE: To determine the effects of imposed anisometropic retinal defocus on accommodation, ocular growth, and refractive state changes in marmosets. METHODS: Marmosets were raised with extended-wear soft contact lenses for an average duration of 10 weeks beginning at an average age of 76 d. Experimental animals wore either a positive or negative power contact lens over one eye and a plano lens or no lens over the other. Another group wore binocular lenses of equal magnitude but opposite sign. Untreated marmosets served as controls and three wore plano lenses monocularly. Cycloplegic refractive state, corneal curvature, and vitreous chamber depth were measured before, during, and after the period of lens wear. To investigate the accommodative response, the effective refractive state was measured through each anisometropic condition at varying accommodative stimuli positions using an infrared refractometer. RESULTS: Eye growth and refractive state are significantly correlated with the sign and power of the contact lens worn. The eyes of marmosets reared with monocular negative power lenses had longer vitreous chambers and were myopic relative to contralateral control eyes (p < 0.01). Monocular positive power lenses produced a significant reduction in vitreous chamber depth and hyperopia relative to the contralateral control eyes (p < 0.05). In marmosets reared binocularly with lenses of opposite sign, we found larger interocular differences in vitreous chamber depths and refractive state (p < 0.001). Accommodation influences the defocus experienced through the lenses, however, the mean effective refractive state was still hyperopia in the negative-lens-treated eyes and myopia in the positive-lens-treated eyes. CONCLUSIONS: Imposed anisometropia effectively alters marmoset eye growth and refractive state to compensate for the imposed defocus. The response to imposed hyperopia is larger and faster than the response to imposed myopia. The pattern of accommodation under imposed anisometropia produces effective refractive states that are consistent with the changes in eye growth and refractive state observed.

Characteristics of accommodative behavior during sustained reading in emmetropes and myopes.

Accommodation has long been suspected to be involved in the development of myopia because near work, particularly reading, is known to be a risk factor. In this study, we measured several dynamic characteristics of accommodative behavior during extended periods of reading under close-to-natural conditions in 20 young emmetropic and stable myopic subjects. Accommodative responses, errors, and variability (including power spectrum analysis) were analyzed and related to accommodative demand and subject refractive error. All accommodative behaviors showed large inter-subject variability at all of the reading demands. Accommodative lags and variability significantly increased with closer demands for all subjects (ANOVA, p<0.05). Myopes had significantly greater variability in their accommodation responses compared to emmetropes (ANOVA, p<0.05) and had larger accommodative lags at further reading distances (unpaired t test p<0.05). Power spectrum analysis showed a significant increase in the power of accommodative microfluctuations with closer demands (ANOVA, p<0.05) and with increasing myopia at the closest reading demand (ANOVA, p<0.01). The difference in the stability of the accommodative behavior between individuals with different refractive states suggests a possible relationship between variability in accommodation and the development of myopia.

Pfeiffer syndrome: systemic and ocular implications.

BACKGROUND: In 1964, Pfeiffer described a three-generation family in which eight individuals had a syndrome consisting of craniosynostosis, broad thumbs and great toes, and partial syndactyly of the hands and feet. Pfeiffer syndrome affects males and females equally, and is most commonly a result of de novo mutations, but can be inherited in an autosomal dominant fashion. Pfeiffer syndrome is considered Type V of the five acrocephalosyndactly syndromes (ACS), a group of rare genetic diseases that involve premature closure of the cranial sutures. Cohen, in 1993, further described Pfeiffer syndrome and it's various expression patterns by creating three subgroups of the syndrome. CONCLUSIONS: While Pfeiffer syndrome is clearly a rare disorder, affecting 15 of every 1 million births, there has been a series of publications reviewing the difficult differential diagnosis among Pfeiffer types and between the other acrocephalosyndactly syndromes. While these publications individually focus on a variety of specific systemic and ocular implications of the syndrome, together they encompass the scope of the syndrome. Since Pfeiffer syndrome mainly affects the craniofacial regions, the eye care professional plays an essential role in diagnosis and management. What follows are guidelines to aid in the diagnosis, ophthalmic and functional testing, and management of this disorder.