Dynamic BMP gene expression regulation in chick RPE during recovery from short term optical defocus and form-deprivation.

PURPOSE: This study investigated the differential gene expression of BMPs in chick retinal pigment epithelium (RPE) during recovery from short term exposure to optical defocus and form-deprivation (FD) treatments. METHODS: 14-day old White-Leghorn chicks wore either monocular +10 or -10 D lenses, or diffusers for 2 or 48 h, after which eyes were allowed unobstructed vision for up to 96 h. Over this recovery period, refractive errors and choroidal thickness (ChT) were tracked using retinoscopy and high-frequency A-scan ultrasonography. Real-time PCR was used to examine the expression of BMP2, 4, and 7 genes in RPE samples collected 0, 15 min, 2, 24, 48, and 96 h after the termination of treatments. Expression levels in treated eyes and their contralateral control eyes were compared. RESULTS: After the termination of the lens and diffuser treatments, eyes gradually recovered from induced shifts in refractive error. With all three treatments, ChT changes reached statistical significance after 48 h of treatment, be it thinning with the -10 D lens and diffuser treatments (-0.06 ± 0.03mm, p < 0.05; -0.11 ± 0.04 mm, p < 0.05, resp.), or thickening with the +10 D lens (0.31 ± 0.04 mm, p < 0.001). BMP2 gene expression was rapidly upregulated in eyes wearing the +10 D lens, being statistical significance after 2 h, as well as 48 h of treatment. With the 2 h treatment, the latter gene expression pattern persisted for 15 min into the recovery period, before decreasing to the same level as that of contralateral control eyes, with a short-lived rebound, i.e., upregulation, 24 h into the recovery period. With the longer, 48 h treatment, BMP2 gene expression decreased more gradually, from 739 ± 121% at the end of the treatment period, to 72 ± 14% after 48 h of recovery. Two and 48 h of both -10 D and FD treatments resulted in BMP2 gene expression downregulation, with the time taken for gene expression levels to fully recover varying with the duration of initial treatments. In both cases, BMP2 gene expression downregulation persisted for 15 min into the recovery period, but reversed to upregulation by 2 h. Similar gene expression patterns were also observed for BMP4, although the changes were smaller. CONCLUSIONS: The observed changes in BMP gene expression in chick RPE imply dynamic, albeit complex regulation, with the duration of exposure and recovery being critical variables for all three types of visual manipulations. This study provides further evidence for a role of the RPE as an important signal relay linking the retina to the choroid and sclera in eye growth regulation.

A Child-Friendly Wearable Device for Quantifying Environmental Risk Factors for Myopia.

Purpose: In the past few decades, the prevalence of myopia, where the eye grows too long, has increased dramatically. The visual environment appears to be critical to regulating the eye growth. Thus, it is very important to determine the properties of the environment that put children at risk for myopia. Researchers have suggested that the intensity of illumination and range of distances to which a child's eyes are exposed are important, but this has not been confirmed. Methods: We designed, built, and tested an inexpensive, child-friendly, head-mounted device that can measure the intensity and spectral content of illumination approaching the eyes and can also measure the distances to which the central visual field of the eyes are exposed. The device is mounted on a child's bicycle helmet. It includes a camera that measures distances over a substantial range and a six-channel spectral sensor. The sensors are hosted by a light-weight, battery-powered microcomputer. We acquired pilot data from children while they were engaged in various indoor and outdoor activities. Results: The device proved to be comfortable, easy, and safe to wear, and able to collect very useful data on the statistics of illumination and distances. Conclusions: The designed device is an ideal tool to be used in a population of young children, some of whom will later develop myopia and some of whom will not. Translational Relevance: Such data would be critical for determining the properties of the visual environment that put children at risk for becoming myopic.

The effect of topical 1 % atropine on ocular dimensions and diurnal rhythms of the human eye.

The effect of topical 1 % atropine on the diurnal rhythms of the human eye was investigated. Participants wore an activity monitor on Days 1-7. A set of measures (epochs) encompassing intraocular pressure (IOP), ocular biometry, and retinal imaging were obtained on Day 7 (baseline), followed by eight epochs on Day 8, and one on Day 9 from both eyes of healthy participants (n = 22, 19-25 years). The sleep time of participants (collected via actigraphy) was used as a reference in scheduling epochs. Topical 1 % atropine was instilled in the dominant eye on Day 8, 2 h after habitual wake time, using the fellow eye as control (paired-eye design). Sinusoids with a 24-h period were fitted to the data, and a non-linear mixed-effects model was used to estimate rhythmic statistics. There were no interocular differences in any of the measured parameters at baseline. Comparing pre- versus post-atropine in treated eyes revealed lower IOP, deeper anterior chamber (ACD), decreased crystalline lens thickness and shorter axial length (AL). The same trends were observed when comparing atropine-treated versus fellow control eyes, except for IOP and AL (no differences). Both atropine-treated and fellow control eyes showed significant diurnal variations in all ocular parameters, with atropine-treated eyes revealing larger AL and retinal thickness amplitudes, smaller vitreous chamber depth (VCD) amplitudes, and a significant phase advancement for ACD and VCD. There were no interocular differences in choroidal thickness rhythms. In conclusion, while ocular diurnal rhythms persisted after instillation of 1 % atropine, many rhythmic parameters were altered.

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.

Changes in Expression in BMP2 and Two Closely Related Genes in Guinea Pig Retinal Pigment Epithelium during Induction and Recovery from Myopia.

PURPOSE: We previously reported differential gene expression of the bone morphogenetic protein 2 (Bmp2) in guinea pig retinal pigment epithelium (RPE) after 1 day of hyperopic defocus, imposed with a negative contact lens (CLs). The study reported here sought to obtain insights into the temporal profiles of gene expression changes in Bmp2, as well as those of two closely related genes, the inhibitor of DNA binding 3 (Id3) and Noggin (Nog), both during myopia induction and when the CL treatment was terminated to allow recovery from induced myopia. METHODS: To induce myopia, 2-week-old pigmented guinea pigs (New Zealand strain, n = 8) wore monocular -10 diopter (D) rigid gas-permeable (RGP) CLs for one week, while the other eye served as a control. Ocular measurements were made at baseline, 3 days, and 7 days after the initiation of CL wear, with treatment then being terminated and additional measurements being made after a further 3 days, 1 week, and 2 weeks. Spherical equivalent refractive errors (SERs), axial length (AL), choroidal thickness (ChT), and scleral thickness (ScT) data were collected using retinoscopy, optical biometry (Lenstar), and spectral domain optical coherence tomography (SD-OCT), respectively. RPE samples were collected from both eyes of the guinea pigs after either 1 day or 1 week of CL wear or 1 day or 2 weeks after its termination, and RNA was subsequently isolated and subjected to quantitative real-time PCR (qRT-PCR) analyses, targeting the Bmp2, Id3, and Nog genes. RESULTS: Mean interocular differences (treated-control) in AL and SER were significantly different from baseline after 3 and 7 days of CL wear, consistent with induced myopia (p < 0.001 for all cases). Termination of CL wear resulted in the normalization (i.e., recovery) of the ALs and SERs of the treated eyes within 7 days, and the earlier significant ChT thinning with CL wear (p = 0004, day 7) was replaced by rapid thickening, which remained significant on day 7 (p = 0.009) but had normalized by day 14. The ChT changes were much smaller in magnitude than the AL changes in both phases. Interocular differences in the ScT showed no significant changes. The Bmp2 and Id3 genes were both significantly downregulated with CL wear, after 1 day (p = 0.012 and 0.016) and 7 days (p = 0.002 and 0.005), while Bmp2 gene expression increased and Nog gene expression decreased after the termination of CL wear, albeit transiently, which was significant on 1 day (p = 0.004 and 0.04) but not 2 weeks later. No change in Id3 gene expression was observed over the latter period. Conclusions: The above patterns of myopia induction and recovery validate this negative RGP-CL model as an alternative to traditional spectacle lens models for guinea pigs. The defocus-driven, sign-dependent changes in the expression of the Bmp2 gene in guinea pig RPE are consistent with observations in chicks and demonstrate the important role of BMP2 in eye growth regulation.

Isolation of Retinal Pigment Epithelial Cells from Guinea Pig Eyes.

This protocol describes the isolation of cells of the retinal pigment epithelium (RPE) from the eyes of young pigmented guinea pigs for potential application in molecular biology studies, including gene expression analyses. In the context of eye growth regulation and myopia, the RPE likely plays a role as a cellular relay for growth modulatory signals, as it is located between the retina and the two walls of the eye, such as the choroid and sclera. While protocols for isolating the RPE have been developed for both chicks and mice, these protocols have proven not to be directly translatable to the guinea pig, which has become an important and widely used mammalian myopia model. In this study, molecular biology tools were used to examine the expression of specific genes to confirm that the samples were free of contamination from the adjacent tissues. The value of this protocol has already been demonstrated in an RNA-Seq study of RPE from young pigmented guinea pigs exposed to myopia-inducing optical defocus. Beyond eye growth regulation, this protocol has other potential applications in studies of retinal diseases, including myopic maculopathy, one of the leading causes of blindness in myopes, in which the RPE has been implicated. The main advantage of this technique is that it is relatively simple and once perfected, yields high-quality RPE samples suitable for molecular biology studies, including RNA analysis.

IMI 2023 Digest.

Myopia is a dynamic and rapidly moving field, with ongoing research providing a better understanding of the etiology leading to novel myopia control strategies. In 2019, the International Myopia Institute (IMI) assembled and published a series of white papers across relevant topics and updated the evidence with a digest in 2021. Here, we summarize findings across key topics from the previous 2 years. Studies in animal models have continued to explore how wavelength and intensity of light influence eye growth and have examined new pharmacologic agents and scleral cross-linking as potential strategies for slowing myopia. In children, the term premyopia is gaining interest with increased attention to early implementation of myopia control. Most studies use the IMI definitions of ≤-0.5 diopters (D) for myopia and ≤-6.0 D for high myopia, although categorization and definitions for structural consequences of high myopia remain an issue. Clinical trials have demonstrated that newer spectacle lens designs incorporating multiple segments, lenslets, or diffusion optics exhibit good efficacy. Clinical considerations and factors influencing efficacy for soft multifocal contact lenses and orthokeratology are discussed. Topical atropine remains the only widely accessible pharmacologic treatment. Rebound observed with higher concentration of atropine is not evident with lower concentrations or optical interventions. Overall, myopia control treatments show little adverse effect on visual function and appear generally safe, with longer wear times and combination therapies maximizing outcomes. An emerging category of light-based therapies for children requires comprehensive safety data to enable risk versus benefit analysis. Given the success of myopia control strategies, the ethics of including a control arm in clinical trials is heavily debated. IMI recommendations for clinical trial protocols are discussed.

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.

Effect of topical latanoprost on choroidal thickness and vessel area in Guinea pigs.

The aim of this study was to investigate the effect of latanoprost, an ocular hypotensive agent and prostaglandin analog, on choroidal thickness and structure in young adult guinea pigs. Young (three-month-old) guinea pigs (n = 10) underwent daily monocular treatment with topical 0.005% latanoprost for 2 weeks, followed by a washout period of 2 weeks. Tonometry (iCare) and retinoscopy were undertaken to monitor intraocular pressure (IOP) and refractive error (recorded as spherical equivalent refractive error; SER), respectively. Axial length (AL) and choroidal thickness (ChT) were measured using high frequency A-scan ultrasonography, with additional ChT data, as well as choroidal vessel (ChV) areas obtained from posterior segment imaging using Spectral Domain-Optical Coherence Tomography (SD-OCT). Image J was used to analyze SD-OCT images. As expected, latanoprost significantly reduced IOP in treated eyes. Mean interocular IOP difference (±SE) changed from -0.40 ± 0.31 mmHg at baseline to -2.23 ± 0.43 mmHg after 2 weeks of treatment (p = 0.05). However, SER and AL were unaffected; interocular difference changed from 0.41 ± 0.58 to 0.38 ± 0.43 D and from -0.002 ± 0.02 mm to -0.007 ± 0.01 mm (p > 0.05), respectively. Latanoprost had minimal effect on ChT. Interocular ChT differences were 0.01 ± 0.06 µm at baseline and 0.04 ± 0.06 µm after 2 weeks of treatment (SD-OCT; p > 0.05). However, treated eyes had significant increased ChV areas; interocular differences changed from -0.76 ± 69.2 to 100.78 ± 66.9 µm2 after treatment (p = 0.04). While this study was limited to otherwise untreated young adult guinea pigs, the possibility that choroidal vessel enlargement contributes to the previously reported inhibitory effect of topical latanoprost on myopia progression in young guinea pigs warrants investigation.

Gene Expression Signatures of Contact Lens-Induced Myopia in Guinea Pig Retinal Pigment Epithelium.

Purpose: To identify key retinal pigment epithelium (RPE) genes linked to the induction of myopia in guinea pigs. Methods: To induce myopia, two-week-old pigmented guinea pigs (New Zealand strain, n = 5) wore -10 diopter (D) rigid gas-permeable contact lenses (CLs), for one day; fellow eyes were left without CLs and served as controls. Spherical equivalent refractive errors (SE) and axial length (AL) were measured at baseline and one day after initiation of CL wear. RNA sequencing was applied to RPE collected from both treated and fellow (control) eyes after one day of CL-wear to identify related gene expression changes. Additional RPE-RNA samples from treated and fellow eyes were subjected to quantitative real-time PCR (qRT-PCR) analysis for validation purposes. Results: The CLs induced myopia. The change from baseline values in SE was significantly different (P = 0.016), whereas there was no significant difference in the change in AL (P = 0.10). RNA sequencing revealed significant interocular differences in the expression in RPE of 13 genes: eight genes were significantly upregulated in treated eyes relative to their fellows, and five genes, including bone morphogenetic protein 2 (Bmp2), were significantly downregulated. The latter result was also confirmed by qRT-PCR. Additional analysis of differentially expressed genes revealed significant enrichment for bone morphogenetic protein (BMP) and TGF-ß signaling pathways. Conclusions: The results of this RPE gene expression study provide further supporting evidence for an important role of BMP2 in eye growth regulation, here from a guinea pig myopia model.

The WHO-ITU MyopiaEd Programme: A Digital Message Programme Targeting Education on Myopia and Its Prevention.

The objective of this paper is to provide an overview of the World Health Organization - International Telecommunication Union MyopiaEd programme - a digital message programme targeting education on myopia and its prevention. The development of the MyopiaEd programme included 4 key steps: (1) Conceptualization and consultation with experts in the field of myopia, mHealth and health behavior change; (2) Creation of SMS message libraries and programme algorithm; (3) Review of the message libraries to ensure relevance to the target audience; and (4) Pre-testing amongst end-user groups to ensure that the design of the programme and the message content were understandable. After reviewing the available evidence and considering input of the experts, the aims, end users and key themes of the programme were finalized. Separate SMS-adapted message libraries were developed, reviewed and pre-tested for four target end-user groups; (1) general population involved in the care of children (2) parents or caregivers of children with myopia; (3) adolescents with myopia; and (4) adults with myopia. The message libraries are part of a comprehensive toolkit, developed through a consultative process with experts in digital health, to support implementation within countries. The development of the MyopiaEd programme aims to provide a basis for Member States and other stakeholders to develop, implement and monitor large-scale mHealth programmes. It is aimed at raising awareness of good eye care behaviors and addressing common reasons for non-compliance to spectacle wear. The next steps will involve adapting and evaluating the MyopiaEd programme in selected settings.

Daily or Less Frequent Topical 1% Atropine Slows Defocus-Induced Myopia Progression in Contact Lens-Wearing Guinea Pigs.

Purpose: This study compared the efficacy of topical 1% atropine applied daily versus every 3 days for controlling myopia progression in guinea pigs. Methods: To induce myopia, pigmented guinea pigs (New Zealand strain, n = 38) wore monocular -10 D rigid gas-permeable (RGP) contact lenses, which were replaced after 3 weeks with -15 diopter (D) contact lenses. Animals were treated with 1% atropine either daily (Atr-QD; n = 12), or every 3 days (Atr-Q3D; n = 11), or with artificial tears (control group; n = 15). Spherical equivalent refractive error (SER) and axial length (AL) data, as well as retinal and choroidal thickness data were collected weekly. Results: Whereas mean (±SEM) interocular differences (treated - fellow) in both SER and AL at week 0 (baseline) were similar for all groups, significant differences between the atropine-treated and control groups were evident by week 6 (SER and AL, P < 0.001). The treated eyes of the control group showed relatively more axial elongation and myopia progression than both the Atr-QD and Atr-Q3D groups. Choroidal blood vessel area also decreased over time in the treated eyes of the control group, coupled with choroidal thinning overall, with these changes being attenuated by atropine. Retinal thickness showed a developmental decrease over the treatment period but was unaffected by atropine. Conclusions: For this defocus-induced guinea pig model of myopia, application of 1% topical atropine slows myopia progression, even when applied every 3 days. Translational Relevance: The results from this study suggest that the frequency of dosing for topical atropine may be reduced from the widely used daily dosing regimen without loss of myopia control efficacy.

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.

IMI Prevention of Myopia and Its Progression.

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors. As compared with other measures, spending more time outdoors is the safest strategy and aligns with other existing health initiatives, such as obesity prevention, by promoting a healthier lifestyle for children and adolescents. Useful clinical measures to reduce or slow the progression of myopia include the daily application of low-dose atropine eye drops, in concentrations ranging between 0.01% and 0.05%, despite the side effects of a slightly reduced amplitude of accommodation, slight mydriasis, and risk of an allergic reaction; multifocal spectacle design; contact lenses that have power profiles that produce peripheral myopic defocus; and orthokeratology using corneal gas-permeable contact lenses that are designed to flatten the central cornea, leading to midperipheral steeping and peripheral myopic defocus, during overnight wear to eliminate daytime myopia. The risk-to-benefit ratio needs to be weighed up for the individual on the basis of their age, health, and lifestyle. The measures listed above are not mutually exclusive and are beginning to be examined in combination.

IMI 2021 Yearly Digest.

Purpose: The International Myopia Institute (IMI) Yearly Digest highlights new research considered to be of importance since the publication of the first series of IMI white papers. Methods: A literature search was conducted for articles on myopia between 2019 and mid-2020 to inform definitions and classifications, experimental models, genetics, interventions, clinical trials, and clinical management. Conference abstracts from key meetings in the same period were also considered. Results: One thousand articles on myopia have been published between 2019 and mid-2020. Key advances include the use of the definition of premyopia in studies currently under way to test interventions in myopia, new definitions in the field of pathologic myopia, the role of new pharmacologic treatments in experimental models such as intraocular pressure-lowering latanoprost, a large meta-analysis of refractive error identifying 336 new genetic loci, new clinical interventions such as the defocus incorporated multisegment spectacles and combination therapy with low-dose atropine and orthokeratology (OK), normative standards in refractive error, the ethical dilemma of a placebo control group when myopia control treatments are established, reporting the physical metric of myopia reduction versus a percentage reduction, comparison of the risk of pediatric OK wear with risk of vision impairment in myopia, the justification of preventing myopic and axial length increase versus quality of life, and future vision loss. Conclusions: Large amounts of research in myopia have been published since the IMI 2019 white papers were released. The yearly digest serves to highlight the latest research and advances in myopia.

A Comparison of Applanation and Rebound Tonometers in Young Chicks.

PURPOSE: To assess the validity of and compare applanation and rebound tonometry readings of intraocular pressure in alert normal chicks from ages 3 to 45 days. METHODS: Intraocular pressures (IOPs) were measured weekly in awake White Leghorn chicks, from ages 3-45 days (n = 22-30 per age group), with both applanation Tono-Pen and rebound TonoLab tonometers. Three repeated measurements on individual eyes were used to derive variance data for both instruments at each age. Calibration curves were also derived for each instrument and each age, weekly from ages 10-45 days (n = 3-4 per age group), from in situ manometry data collected over IOP settings of 0 to 100 mmHg in 5 mmHg steps in cannulated eyes. RESULTS: The TonoLab showed less within measurement variability, but more variability with age, than the Tono-Pen. The coefficient of variation ranged from 3.8-8.3% for the TonoLab, compared to 11.0-19.7% for the Tono-Pen across all ages. For the youngest, 3 day-old chicks, mean IOPs recorded with the Tono-Pen and TonoLab were not significantly different (17.0 ± 5.6 and 15.2 ± 3.7 mmHg, respectively, P = .27). However, with increasing age, IOP readings significantly increased for the TonoLab (P < .001), whereas Tono-Pen readings did not. Compared to manometry settings, the Tono-Pen tended to underestimate IOPs while the TonoLab overestimated IOPs over the range 20-60 mmHg, saturating thereafter; there were also age-dependent differences for the TonoLab. CONCLUSIONS: Both the Tono-Pen and TonoLab gave IOP readings that differed from manometry settings in normal young chicks over some or all of the ages tested. These results reinforce the importance of calibrating clinical tonometers in animal studies involving IOP as a key variable.

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.