Repeatability and agreement of the MYAH and Lenstar.

SIGNIFICANCE: Validation of new biometry instruments against the gold standard and establishing repeatability are important before being utilized for clinical and research applications. PURPOSE: This study aimed to investigate intersession repeatability of the MYAH optical biometer and corneal topographer and examine agreement with the Lenstar LS900 optical biometer in healthy young adults. METHODS: Forty participants (mean age, 25.2 ± 3.1 years) presented for two visits, 2 to 4 days apart. At each visit, measurements for right eyes were collected with the MYAH and Lenstar LS 900 and included axial length, corneal power, white-to-white distance, and pupil diameter. Bland-Altman analysis was used to assess the intrasession agreement between the MYAH and Lenstar for each parameter and intersession repeatability for the two devices. For each device, coefficient of variation and intraclass correlation coefficient were calculated, and paired t tests between visits were performed to assess intersession repeatability. RESULTS: Good agreement (mean difference [95% limits of agreement]) between the MYAH and Lenstar was found for axial length (-0.01 [-0.07 to 0.04] mm), corneal power (-0.02 D [-0.15 to 0.19 d]), white-to-white distance (-0.13 [-0.43 to 0.17] mm), and pupil diameter (-0.27 [-0.79 to 1.33] mm). The limits of agreement, coefficient of variations, and intraclass correlation coefficients for MYAH-measured parameters were -0.04 to 0.04, 0.06%, and >0.99 for axial length; -0.24 to 0.19, 0.18%, and >0.99 for corneal power; -1.05 to 1.15, 0.57%, and 0.96 for white-to-white distance; and -0.17 to 0.21, 7.0%, and 0.76 for pupil diameter, with no significant difference between visits (p>0.05 for all), indicating good intersession repeatability. Similar intersession repeatability was also noted for Lenstar. CONCLUSIONS: Findings show good intersession repeatability of the MYAH and good agreement with the Lenstar for axial length, corneal power, and white-to-white distance in young adults. Pupil diameter was more variable, likely due to the dynamic nature of the pupil. This study provides validation and supports the use of the MYAH for ocular biometry.

Red light instruments for myopia exceed safety limits.

PURPOSE: Low-level red light (LLRL) therapy has recently emerged as a myopia treatment in children, with several studies reporting significant reduction in axial elongation and myopia progression. The goal of this study was to characterise the output and determine the thermal and photochemical maximum permissible exposure (MPE) of LLRL devices for myopia control. METHODS: Two LLRL devices, a Sky-n1201a and a Future Vision, were examined. Optical power measurements were made using an integrating sphere radiometer through a 7-mm diameter aperture, in accordance with ANSI Z136.1-2014, sections 3.2.3-3.2.4. Retinal spot sizes of the devices were obtained using a model eye and high-resolution beam profiler. Corneal irradiance, retinal irradiance and MPE were calculated for an eye positioned at the oculars of each device. RESULTS: Both devices were confirmed to be Class 1 laser products. Findings showed that the Sky-n1201a delivers laser light as a point source with a 654-nm wavelength, 0.2 mW power (Ø 7 mm aperture, 10-cm distance), 1.17 mW/cm2 corneal irradiance and 7.2 W/cm2 retinal irradiance (Ø 2 mm pupil). The MPE for photochemical damage is 0.55-7.0 s for 2-7 mm pupils and for thermal damage is 0.41-10 s for 4.25-7 mm pupils. Future Vision delivers the laser as an extended source subtending 0.75 × 0.325°. It has a 652-nm wavelength, 0.06 mW power (Ø 7 mm aperture, 10 cm distance), 0.624 mW/cm2 corneal irradiance and 0.08 W/cm2 retinal irradiance (Ø 2 mm pupil). MPE for photochemical damage is 50-625 s for 2-7 mm pupils. DISCUSSION: For both of the LLRL devices evaluated here, 3 min of continuous viewing approached or surpassed the MPE, putting the retina at risk of photochemical and thermal damage. Clinicians should be cautious with the use of LLRL therapy for myopia in children until safety standards can be confirmed.

Long-term blue light rearing does not affect in vivo retinal function in young rhesus monkeys.

PURPOSE: Exposure to blue light is thought to be harmful to the retina. The purpose of this study was to determine the effects of long-term exposure to narrowband blue light on retinal function in rhesus monkeys. METHODS: Young rhesus monkeys were reared under short-wavelength "blue" light (n = 7; 465 nm, 183 ± 28 lx) on a 12-h light/dark cycle starting at 26 ± 2 days of age. Age-matched control monkeys were reared under broadband "white" light (n = 8; 504 ± 168 lx). Light- and dark-adapted full-field flash electroretinograms (ERGs) were recorded at 330 ± 9 days of age. Photopic stimuli were brief red flashes (0.044-5.68 cd.s/m2) on a rod-saturating blue background and the International Society for Clinical Electrophysiology of Vision (ISCEV) standard 3.0 white flash on a 30 cd/m2 white background. Monkeys were dark adapted for 20 min and scotopic stimuli were ISCEV standard white flashes of 0.01, 3.0, and 10 cd.s/m2. A-wave, b-wave, and photopic negative response (PhNR) amplitudes were measured. Light-adapted ERGs in young monkeys were compared to ERGs in adult monkeys reared in white light (n = 10; 4.91 ± 0.88 years of age). RESULTS: For red flashes on a blue background, there were no significant differences in a-wave (P = 0.46), b-wave (P = 0.75), and PhNR amplitudes (P = 0.94) between white light and blue light reared monkeys for all stimulus energies. ISCEV standard light- and dark-adapted a- and b-wave amplitudes were not significantly different between groups (P > 0.05 for all). There were no significant differences in a- and b-wave implicit times between groups for all ISCEV standard stimuli (P > 0.05 for all). PhNR amplitudes of young monkeys were significantly smaller compared to adult monkeys for all stimulus energies (P < 0.05 for all). There were no significant differences in a-wave (P = 0.19) and b-wave (P = 0.17) amplitudes between young and adult white light reared monkeys. CONCLUSIONS: Long-term exposure to narrowband blue light did not affect photopic or scotopic ERG responses in young monkeys. Findings suggest that exposure to 12 h of daily blue light for approximately 10 months does not result in altered retinal function.

The outdoor environment affects retinal and choroidal thickness.

PURPOSE: Accumulating evidence suggests that time outdoors is protective against myopia development and that the choroid may be involved in this effect. The goal of this study was to examine the effect of 2 h of time outdoors in sunlight on retinal and choroidal thickness in adults. METHODS: Twenty adults, ages 23-46 years, each participated in three experimental sessions on different days, consisting of 2 h of exposure to (1) indoor illumination (350 lux), (2) darkness (<0.1 lux) or (3) outdoor environment (6000-50,000 lux). Spectral-domain optical coherence tomography (SD-OCT) imaging was conducted at baseline, after 1 and 2 h of exposure, and after 1 and 2 h of follow-up. Choroidal, total retinal, photoreceptor outer segment + retinal pigment epithelium (RPE) and photoreceptor inner segment thicknesses were determined. RESULTS: At 2 h, the choroid was significantly thinner during the outdoor compared with the indoor and dark conditions (p < 0.01) but was not significantly different at follow-up. Total retinal thickness was significantly thicker during and after the outdoor compared with the indoor and dark conditions. The outer segment + RPE was significantly thinner during the outdoor compared with the indoor condition but was not significantly different at follow-up. The inner segment was significantly thicker during the outdoor compared with the indoor and dark conditions during exposure and follow-up. CONCLUSIONS: Spending 2 h outdoors under high-intensity sunlight resulted in an unexpected thinning of the choroid, which recovered post-exposure. Retinal thickness showed different responses to the outdoor and indoor environments and was sensitive to the duration of exposure.

Objective quantification of viewing behaviours during printed and electronic tasks in emmetropic and myopic ultra-Orthodox Jewish men.

PURPOSE: Ultra-Orthodox Jewish men are known to have a high prevalence of myopia, which may be due to intense near-work from an early age. This study objectively assessed near-viewing behaviours in ultra-Orthodox and non-ultra-Orthodox men in Israel for different tasks. METHODS: Ultra-Orthodox (n = 30) and non-ultra-Orthodox (n = 38) men aged 18-33 years participated. Autorefraction, visual acuity, height and Harmon distance were measured. An objective range-finding sensor was mounted on their spectacles while they performed four 10-min tasks in a randomised order: (1) reading printed material, (2) writing printed material, (3) passive electronic and (4) active electronic tasks. Near-viewing distance and the number of viewing breaks were calculated for each task. Statistical analyses included Student t-tests and the Mann-Whitney test between groups and repeated measures ANOVA or Friedman between tasks. RESULTS: For all tasks combined, a significantly shorter viewing distance was observed for the ultra-Orthodox group (36.2 ± 7.0 cm) than for the non-ultra-Orthodox group (39.6 ± 6.7 cm, p < 0.05). Viewing distances for the passive reading and electronic tasks were shorter for the ultra-Orthodox group (36.9 ± 7.7 cm vs. 41.3 ± 8.1 cm, p < 0.03 and 39.0 ± 10.1 vs. 43.9 ± 9.3, p < 0.05, respectively). Viewing distances were significantly different between all four tasks, with writing having the closest distance. No correlation was found between working distance and spherical equivalent or Harmon distance. However, a significant correlation was found in the ultra-Orthodox group between working distance and height for each task (p < 0.04, R < 0.42 for all). There was no difference in the number of viewing breaks between the groups. CONCLUSION: When reading a book and viewing an iPad, ultra-Orthodox men demonstrated a closer objective working distance than non-ultra-Orthodox men. This shorter viewing distance may contribute to the high prevalence and degree of myopia in this population.

Comparing low-coherence interferometry and A-scan ultrasonography in measuring ocular axial dimensions in young rhesus monkeys.

We investigated a commercial low-coherence interferometer (LenStar LS 900 optical biometer) in measuring young rhesus monkey ocular dimensions. Ocular biometry data obtained using a LenStar and an A-scan ultrasound instrument (OPT-scan 1000) from 163 rhesus monkeys during 20-348 days of age were compared by means of coefficients of concordance and 95% limits of agreement. Linear regression was employed to examine and analyze the inter-instrument discrepancies. In young rhesus monkeys, the test-retest reliability of the LenStar was equal to or exceeded that of A-scan ultrasound (intraclass correlation = 0.86 to 0.93). The inter-instrument agreement was strong for vitreous chamber depth and axial length (coefficient of concordance = 0.95 and 0.86, respectively) and moderate for anterior chamber depth and lens thickness (coefficient of concordance = 0.74 and 0.63, respectively). The LenStar systematically underestimated ocular dimensions when compared to A-scan ultrasound (mean magnitude of difference = 0.11-0.57 mm). This difference could be minimized using linear calibration functions to equate LenStar data with ultrasound data. When this method was applied, the values between instruments were in excellent absolute agreement (mean magnitude of difference = 0.004-0.01 mm). In conclusion, the LenStar reliably measured ocular dimensions in young monkeys. When an appropriate calibration function is applied, the LenStar can be used as a substitute for A-scan ultrasonography.

Objective Measures of Near Viewing and Light Exposure in Schoolchildren during COVID-19.

SIGNIFICANCE: Wearable sensors provide the opportunity for continuous objective measurement of the visual environment with high resolution. Our findings show that absolute and temporal properties of near viewing and time outdoors vary between myopic and nonmyopic schoolchildren, which are important considerations when studying refractive error pathogenesis. PURPOSE: Numerous behavioral factors, including near work, time outdoors, electronic device use, and sleep, have been linked to myopia. The purpose of this study was to assess behaviors using subjective and objective methods in myopic and nonmyopic schoolchildren in the United States. METHODS: Forty children (aged 14.6 ± 0.4 years) simultaneously wore two sensors for 1 week, a Clouclip for objective measurement of near viewing and light exposure and an Actiwatch for objective measurement of activity and sleep. Parents completed an activity questionnaire for their child. Near-viewing distance, daily duration, short-duration (>1 minute) and long-duration (>30 minutes) near-viewing episodes, light exposure, time outdoors, electronic device use, and sleep duration were analyzed by refractive error group and day of the week. RESULTS: Objectively measured daily near-viewing duration was 6.9 ± 0.3 hours. Myopes spent more time in near + intermediate viewing than nonmyopes (P = .008) and had higher diopter hours (P = .03). Short- and long-duration near-viewing episodes were similar between groups (P < .05 for both). Daily light exposure and time outdoors were significantly lower for myopes (P < .05 for both). Electronic device use (12.0 ± 0.7 hours per day) and sleep duration (8.2 ± 0.2 hours per night) were similar between groups (P > .05 for both). CONCLUSIONS: Objective and subjective measures confirm that myopic and nonmyopic schoolchildren exhibit different behaviors. Combining wearable sensors with questionnaires provides a comprehensive description of children's visual environment to better understand factors that contribute to myopia.

Topically instilled caffeine selectively alters emmetropizing responses in infant rhesus monkeys.

Oral administration of the adenosine receptor (ADOR) antagonist, 7-methylxanthine (7-MX), reduces both form-deprivation and lens-induced myopia in mammalian animal models. We investigated whether topically instilled caffeine, another non-selective ADOR antagonist, retards vision-induced axial elongation in monkeys. Beginning at 24 days of age, a 1.4% caffeine solution was instilled in both eyes of 14 rhesus monkeys twice each day until the age of 135 days. Concurrent with the caffeine regimen, the monkeys were fitted with helmets that held either -3 D (-3D/pl caffeine, n = 8) or +3 D spectacle lenses (+3D/pl caffeine, n = 6) in front of their lens-treated eyes and zero-powered lenses in front of their fellow-control eyes. Refractive errors and ocular dimensions were measured at baseline and periodically throughout the lens-rearing period. Control data were obtained from 8 vehicle-treated animals also reared with monocular -3 D spectacles (-3D/pl vehicle). In addition, historical comparison data were available for otherwise untreated lens-reared controls (-3D/pl controls, n = 20; +3D/pl controls, n = 9) and 41 normal monkeys. The vehicle controls and the untreated lens-reared controls consistently developed compensating axial anisometropias (-3D/pl vehicle = -1.44 ± 1.04 D; -3D/pl controls = -1.85 ± 1.20 D; +3D/pl controls = +1.92 ± 0.56 D). The caffeine regime did not interfere with hyperopic compensation in response to +3 D of anisometropia (+1.93 ± 0.82 D), however, it reduced the likelihood that animals would compensate for -3 D of anisometropia (+0.58 ± 1.82 D). The caffeine regimen also promoted hyperopic shifts in both the lens-treated and fellow-control eyes; 26 of the 28 caffeine-treated eyes became more hyperopic than the median normal monkey (mean (±SD) relative hyperopia = +2.27 ± 1.65 D; range = +0.31 to +6.37 D). The effects of topical caffeine on refractive development, which were qualitatively similar to those produced by oral administration of 7-MX, indicate that ADOR antagonists have potential in treatment strategies for preventing and/or reducing myopia progression.

Retinal ganglion cell ablation in guinea pigs.

Guinea pigs are a common model of human ocular conditions; however, their visual function has not been fully characterized. The purpose of this study was to determine the contributions of retinal ganglion cells to structural and functional measures in guinea pigs. Healthy adult guinea pigs (n = 12) underwent unilateral optic nerve crush. Retinal structure was assessed with spectral domain optical coherence tomography (OCT), and thickness of the ganglion cell/nerve fiber layer (GC/NFL) was determined. Visual function was assessed with optomotor tracking of a drifting grating and light adapted electroretinograms (ERGs). From flash ERGs, a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed. From pattern ERGs, N1P1 and P1N2 were analyzed. Histological studies were done at various time points for ganglion cell quantification. Optomotor tracking was absent in optic nerve crush eyes following optic nerve crush. Significant thinning of the GC/NFL was evident four weeks following the crush. Flash ERGs revealed a significant reduction in the OP1 amplitude two weeks following crush (P < 0.01) and in the PhNR amplitude six weeks following crush (P < 0.01). There were no significant changes in a-wave, b-wave, or pattern ERG responses (P > 0.05 for all). In vivo OCT imaging showed progressive thinning of inner retinal layers. Ganglion cell density, quantified histologically, was significantly reduced by 75% in the optic nerve crush eye compared to the control eye at four weeks following crush. These findings indicate that retinal ganglion cells contribute to the PhNR and OP1 components of the full field flash ERG, but not significantly to the pattern ERG in guinea pigs. This study demonstrates that OCT imaging and full field flash ERGs are valuable in assessing retinal ganglion cell loss in vivo in guinea pigs and will help to further establish the guinea pig as a model of human ocular pathologies.

Environmental and Behavioral Factors with Refractive Error in Israeli Boys.

SIGNIFICANCE: Evidence supporting the contributions of near work in myopia is equivocal. Findings from this pilot study suggest that a high prevalence of myopia in ultra-Orthodox boys may be attributed to intense near work at school and learning to read in preschool at an early age. PURPOSE: This study aimed to assess factors that may influence myopia in three groups of Jewish boys with different educational demands. METHODS: Healthy ultra-Orthodox, religious, and secular Jewish boys (n = 36) aged 8 to 12 years participated. Refractive status, education, time spent reading and writing, and electronic device use were assessed using a questionnaire, and time outdoors and physical activity were assessed objectively using an Actiwatch. Data were analyzed with χ2 and Kruskal-Wallis tests with Bonferroni post hoc comparisons. RESULTS: Ultra-Orthodox (n = 14) and religious (n = 13) children had greater myopia prevalence compared with secular children (n = 9; P = .01), despite no differences in parental myopia. Actigraph data showed that there were no differences in activity (P = .52) or time spent outdoors (P = .48) between groups. Ultra-Orthodox children learned to read at a younger age and spent more hours at school (P < .001 for both). All groups engaged in a similar amount of near work while not in school (P = .52). However, ultra-Orthodox boys had less electronic device use than did religious (P = .007) and secular children (P < .001). CONCLUSIONS: This pilot study demonstrates that ultra-Orthodox, religious, and secular children have distinct educational demands but similar time outdoors, physical activity, and near work while not in school. The findings suggest that near work at school and/or learning to read in preschool at an early age may contribute to previously reported differences in refractive error between groups. However, conclusions should be confirmed in a larger sample size.

Wearable Sensors for Measurement of Viewing Behavior, Light Exposure, and Sleep.

The purpose of this study was to compare two wearable sensors to each other and to a questionnaire in an adult population. For one week, participants aged 29.2 ± 5.5 years (n = 25) simultaneously wore a Clouclip, a spectacle-mounted device that records viewing distance and illuminance, and an Actiwatch, a wrist-worn device that measures illuminance and activity. Participants maintained a daily log of activities and completed an activity questionnaire. Objective measures of time outdoors, near (10-< 60 cm) and intermediate (60-100 cm) viewing, and sleep duration were assessed with respect to the daily log and questionnaire. Findings showed that time outdoors per day from the questionnaire (3.2 ± 0.3 h) was significantly greater than the Clouclip (0.9 ± 0.8 h) and Actiwatch (0.7 ± 0.1 h, p < 0.001 for both). Illuminance from the Actiwatch was systematically lower than the Clouclip. Daily near viewing duration was similar between the questionnaire (5.7 ± 0.6 h) and Clouclip (6.1 ± 0.4 h, p = 0.76), while duration of intermediate viewing was significantly different between methods (p < 0.001). In conclusion, self-reported time outdoors and viewing behaviors were different than objective measures. The Actiwatch and Clouclip are valuable tools for studying temporal patterns of behavioral factors such as near work, light exposure, and sleep.

The optic nerve head, lamina cribrosa, and nerve fiber layer in non-myopic and myopic children.

The purpose of this study was to evaluate the optic nerve head, lamina cribrosa, retina, and choroid in school age children using spectral domain optical coherence tomography (SD-OCT) and to assess these structural parameters in relation to age, axial length, and refractive error. Healthy children, ages 11.15 ± 2.62 years (range 6-15 years, n = 53), underwent cycloplegic autorefraction, biometry, and SD-OCT imaging in both eyes. Images were analyzed using custom written programs in MATLAB, after adjustment for lateral magnification. Peripapillary retinal nerve fiber layer (RNFL) thickness, retinal and choroidal thicknesses, Bruch's membrane opening (BMO) area, minimum rim width (MRW), and anterior lamina cribrosa surface depth (ALCSD) were determined and analyzed with age, axial length, and refraction. Results show that axial length increased and refractive error became more myopic with increasing age (R2 = 0.25, ß = 0.18, P < 0.0001 and R2 = 0.27, ß = -0.37, P < 0.0001, respectively). Minimum foveal thickness and central 1 mm retinal thickness increased with increasing age (R2 = 0.15, ß = 2.38, P < 0.01 and R2 = 0.11, ß = 3.16, P < 0.05, respectively). Age-adjusted raw values for peripapillary RNFL thickness decreased with increasing axial length (R2 = 0.11, ß = -3.18, P < 0.05); however, this relationship was not present when image magnification was corrected (R2 = 0.07, ß = 2.72, P = 0.09). BMO area increased with myopic refractive error (R2 = 0.16, ß = -0.10, P < 0.01). Age-adjusted vertical cup-to-disc ratio decreased with increasing axial length and myopic refractive error (R2 = 0.12, ß = -0.05, P < 0.05 and R2 = 0.11, ß = 0.03, P = 0.05, respectively). Mean MRW, mean ALCSD, and peripapillary choroidal thickness were not associated with age, axial length, or refraction. Mean MRW was significantly thinner in eyes with deeper ALCS (R2 = 0.41, ß = -0.83, P < 0.0001). These findings provide normal values for retinal and optic nerve head parameters in school age children, and also suggest that ocular remodeling occurs in some structures in school age children with normal eye growth and during early stages of myopia development.

Effects of Mydriatics on Rod/Cone- and Melanopsin-driven Pupil Responses.

SIGNIFICANCE: Pupillometry protocols evaluating rod/cone- and melanopsin-driven responses often use mydriatics to ensure maximal stimulus exposure; however, retinal effects of mydriatics are not fully understood. We demonstrate that dilation with either atropine or phenylephrine results in similar enhancements of rod/cone- and melanopsin-driven pupil responses. PURPOSE: The purposes of this study were to compare the effects of atropine, a muscarinic antagonist, and phenylephrine, an adrenergic agonist, on consensual pupil responses and to assess the repeatability of pupil metrics without mydriasis. METHODS: Right eye pupil responses of 20 adults aged 21 to 42 years were recorded before and 45 minutes after instillation of 0.5% atropine or 2.5% phenylephrine in the left eye. Stimuli were presented to the left eye and included six alternating 1-second 651-nm "red" and 456-nm "blue" flashes. Metrics included baseline pupil diameter, maximal constriction, 6- and 30-second post-illumination pupil responses, and early (0 to 10 seconds) and late (10 to 30 seconds) areas under the curve. RESULTS: Dilation of the stimulated eye with either mydriatic significantly increased the 6-second post-illumination pupil response and early and late areas under the curve for blue stimuli, and early area under the curve for red stimuli (P < .05 for all). Melanopsin-driven post-illumination pupil responses, achieved with either phenylephrine or atropine, did not significantly differ from each other (P > .05 for all). Without mydriasis, intersession intraclass correlation coefficients for pupil metrics were 0.63 and 0.50 (6- and 30-second post-illumination pupil responses, respectively) and 0.78 and 0.44 (early and late areas under the curve, respectively) for blue stimuli, with no significant difference between sessions (P > .05 for all). CONCLUSIONS: Dilation with phenylephrine or atropine resulted in similar enhancements of the rod/cone- and melanopsin-driven pupil responses, despite differing mechanisms. Early pupil metrics without mydriasis demonstrated moderate to good intersession repeatability.

Validation of the Clouclip and utility in measuring viewing distance in adults.

PURPOSE: To validate the Clouclip, a continuously measuring objective rangefinder, and examine viewing behaviours during various near tasks in non-myopic and myopic adults. METHODS: In experiment 1, five Clouclip devices were utilised. An infrared camera was used to visualise and measure infrared beam size and angle. Repeatability for distance tracking was assessed from 5 to 120 cm in 5 cm increments. Accuracy of distance tracking was investigated for paper and iPad targets, spatial integration was calculated, effects of target tilt were determined and light measurements were compared to a lux meter. In experiment 2, viewing behaviour was assessed in 41 subjects (21 non-myopic, 20 myopic) during four 15-min near tasks; (1) passive reading of printed material, (2) active writing on printed material, (3) passive viewing on an electronic device and (4) active engagement on an electronic device. Working distance was compared between tasks and refractive error groups. RESULTS: Clouclip distance tracking showed good repeatability, with a mean difference of 0.34 cm and limits of agreement of ±2.0 cm. Clouclip-measured and actual distances were highly correlated for paper and electronic targets from 5 to 120 cm, with mean differences and limits of agreement of 3.96 ± 13.78 cm and 4.48 ± 8.92 cm, respectively; variability increased for distances >100 cm. Tracking ability increased with larger target sizes; tracking was accurate when the target occupied 1.5%-20.3% of tracking beam area, depending on distance and with target tilt up to ±60 degrees. Clouclip- and lux meter-measured ambient illumination were highly correlated for a wide range of intensities (r = 0.96, p < 0.001), but with greater variability for intensities >20 000 lux. The Clouclip infrared beam was measured to have a diameter of 25.6 ± 2.2° and a downward angle of 10.3 ± 0.5°. For subject testing, viewing distance was significantly closer for active and passive printed tasks (29.5 ± 6.7 cm and 33.2 ± 8.8 cm, respectively) than for active and passive electronic tasks (35.4 ± 8.0 cm and 40.8 ± 10.4 cm, respectively), with no differences between refractive error groups (p = 0.88). CONCLUSIONS: The Clouclip performed well in measuring near and intermediate distances and could distinguish between indoor (<1000 lux) and outdoor (>1000 lux) illumination. A closer working distance was observed for printed tasks compared to those on an iPad, with no difference in viewing distance between non-myopic and myopic adults.

Twenty-four hour ocular and systemic diurnal rhythms in children.

PURPOSE: Ocular diurnal rhythms have been implicated in myopia, glaucoma, diabetes, and other ocular pathologies. Ocular rhythms have been well described in adults; however, they have not yet been fully examined in children. The goal of this study was to investigate ocular and systemic diurnal rhythms over 24 h in children. METHODS: Subjects, ages 5 to 14 years (n = 18), wore a light, sleep, and activity monitor for one week to assess habitual sleep/wake patterns, then underwent diurnal measurements every 4 h for 24 h. Measurements included blood pressure, heart rate, body temperature, intraocular pressure (IOP), ocular biometry, and optical coherence tomography imaging. Saliva was collected for melatonin and cortisol analysis. Mean ocular perfusion pressure was calculated from IOP and blood pressure. Central corneal thickness, corneal power, anterior chamber depth, lens thickness, vitreous chamber depth, and axial length were determined from biometry. Total retinal thickness, retinal pigment epithelium (RPE) + photoreceptor outer segment thickness, photoreceptor inner segment thickness, and choroidal thickness were determined for a 1 mm diameter centred on the fovea. Subjects' amplitude and acrophase of diurnal variation for each parameter were determined using Fourier analysis, and mean acrophase was calculated using unit vector averaging. RESULTS: Repeated measures analysis of variance (ANOVA) showed that all parameters except anterior chamber depth exhibited significant variations over 24 h (p ≤ 0.005 for all). Axial length underwent diurnal variation of 45.25 ± 6.30 µm with an acrophase at 12.92 h, and choroidal thickness underwent diurnal variation of 26.25 ± 2.67 µm with an acrophase at 1.90 h. IOP was approximately in phase with axial length, with a diurnal variation of 4.19 ± 0.50 mmHg and acrophase at 11.37 h. Total retinal thickness underwent a significant diurnal variation of 4.09 ± 0.39 µm with an acrophase at 15.04 h. The RPE + outer segment layer was thickest at 3.25 h, while the inner segment layer was thickest at 14.95 h. Melatonin peaked during the dark period at 2.36 h, and cortisol peaked after light onset at 9.22 h. CONCLUSIONS: Ocular and systemic diurnal rhythms were robust in children and similar to those previously reported in adult populations. Axial length and IOP were approximately in phase with each other, and in antiphase to choroidal thickness. These findings may have important implications in myopia development in children.

Adenosine receptor distribution in Rhesus monkey ocular tissue.

Adenosine receptor (ADOR) antagonists, such as 7-methylxanthine (7-MX), have been shown to slow myopia progression in humans and animal models. Adenosine receptors are found throughout the body, and regulate the release of neurotransmitters such as dopamine and glutamate. However, the role of adenosine in eye growth is unclear. Evidence suggests that 7-MX increases scleral collagen fibril diameter, hence preventing axial elongation. This study used immunohistochemistry (IHC) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) to examine the distribution of the four ADORs in the normal monkey eye to help elucidate potential mechanisms of action. Eyes were enucleated from six Rhesus monkeys. Anterior segments and eyecups were separated into components and flash-frozen for RNA extraction or fixed in 4% paraformaldehyde and processed for immunohistochemistry against ADORA1, ADORA2a, ADORA2b, and ADORA3. RNA was reverse-transcribed, and qPCR was performed using custom primers. Relative gene expression was calculated using the ΔΔCt method normalizing to liver expression, and statistical analysis was performed using Relative Expression Software Tool. ADORA1 immunostaining was highest in the iris sphincter muscle, trabecular meshwork, ciliary epithelium, and retinal nerve fiber layer. ADORA2a immunostaining was highest in the corneal epithelium, trabecular meshwork, ciliary epithelium, retinal nerve fiber layer, and scleral fibroblasts. ADORA2b immunostaining was highest in corneal basal epithelium, limbal stem cells, iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells and scattered scleral fibroblasts. ADORA3 immunostaining was highest in the iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells, and scleral fibroblasts. Compared to liver mRNA, ADORA1 mRNA was significantly higher in the brain, retina and choroid, and significantly lower in the iris/ciliary body. ADORA2a expression was higher in brain and retina, ADORA2b expression was higher in retina, and ADORA3 was higher in the choroid. In conclusion, immunohistochemistry and RT-qPCR indicated differential patterns of expression of the four adenosine receptors in the ocular tissues of the normal non-human primate. The presence of ADORs in scleral fibroblasts and the choroid may support mechanisms by which ADOR antagonists prevent myopia. The potential effects of ADOR inhibition on both anterior and posterior ocular structures warrant investigation.

Objectively Measured Light Exposure During School and Summer in Children.

SIGNIFICANCE: Significant differences in light exposure were observed between school and summer in children, whereas activity and sleep were similar. Associations between parent and child behaviors suggest a potential mechanism for how myopia is transmitted from parents to children through patterns of environmental exposure, in addition to genetic factors. PURPOSE: Objectively measured time outdoors, light exposure, activity, and sleep were examined in children during school and summer and assessed with eye growth. Associations between parent and child behaviors were evaluated. METHODS: Children (aged 7.6 ± 1.8 years, n = 60) in Houston, TX, wore an actigraph device for three 2-week sessions (fall school, spring school, summer) to quantify time outdoors, light exposure, activity, and sleep. Cycloplegic autorefraction (WAM-5500; Grand-Seiko, Tokyo, Japan) and axial length (LenStar; Haag-Streit AG, Koeniz, Switzerland) were measured at baseline and 1 year. A subset of parents wore the device during their child's first 2-week session to compare behaviors (n = 33). RESULTS: Children spent 94.4 ± 30.6 minutes per day outdoors in spring, 110.6 ± 45.7 minutes in summer, and 72.2 ± 31.0 minutes in fall, with significant differences between sessions (P < .0001). Daily activity and sleep duration were similar across sessions (P = .73 and .06, respectively). Axial growth rate decreased with light exposure, but did not reach significance after adjusting for baseline axial length, age, sex, activity, and parental myopia (P = .073). Parent and child time outdoors and sleep duration were significantly correlated (P = .0002 and 0.026, respectively). CONCLUSIONS: Significant differences in light exposure were observed between school and summer, whereas activity and sleep were constant throughout the year. Children's behaviors were associated with their parent's behaviors, which may represent a modifiable component to potential environmental influences on eye growth. However, light exposure was not a significant environmental influence on axial growth in this study.

The ipRGC-Driven Pupil Response with Light Exposure, Refractive Error, and Sleep.

SIGNIFICANCE: We investigated links between the intrinsically photosensitive retinal ganglion cells, light exposure, refractive error, and sleep. Results showed that morning melatonin was associated with light exposure, with modest differences in sleep quality between myopes and emmetropes. Findings suggest a complex relationship between light exposure and these physiological processes. PURPOSE: Intrinsically photosensitive retinal ganglion cells (ipRGCs) signal environmental light, with pathways to the midbrain to control pupil size and circadian rhythm. Evidence suggests that light exposure plays a role in refractive error development. Our goal was to investigate links between light exposure, ipRGCs, refractive error, and sleep. METHODS: Fifty subjects, aged 17-40, participated (19 emmetropes and 31 myopes). A subset of subjects (n = 24) wore an Actiwatch Spectrum for 1 week. The Pittsburgh Sleep Quality Index (PSQI) was administered, and saliva samples were collected for melatonin analysis. The post-illumination pupil response (PIPR) to 1 s and 5 s long- and short-wavelength stimuli was measured. Pupil metrics included the 6 s and 30 s PIPR and early and late area under the curve. RESULTS: Subjects spent 104.8 ± 46.6 min outdoors per day over the previous week. Morning melatonin concentration (6.9 ± 3.5 pg/ml) was significantly associated with time outdoors and objectively measured light exposure (P = .01 and .002, respectively). Pupil metrics were not significantly associated with light exposure or refractive error. PSQI scores indicated good sleep quality for emmetropes (score 4.2 ± 2.3) and poor sleep quality for myopes (5.6 ± 2.2, P = .04). CONCLUSIONS: We found that light exposure and time outdoors influenced morning melatonin concentration. No differences in melatonin or the ipRGC-driven pupil response were observed between refractive error groups, although myopes exhibited poor sleep quality compared to emmetropes. Findings suggest that a complex relationship between light exposure, ipRGCs, refractive error, and sleep exists.

The ipRGC-driven pupil response with light exposure and refractive error in children.

PURPOSE: The intrinsically photosensitive retinal ganglion cells (ipRGCs) signal environmental light, control pupil size and entrain circadian rhythm. There is speculation that ipRGCs may be involved in the protective effects of light exposure in myopia. Here, the ipRGC-driven pupil response was evaluated in children and examined with light exposure and refractive error. METHODS: Children ages 5-15 years participated. Subjects wore an actigraph device prior to the lab visit for objective measures of light exposure and sleep. For pupillometry, the left eye was dilated and presented with stimuli, and the consensual pupil response was measured in the right eye. Pupil measurements were preceded by 5 min dark adaptation. In Experiment 1 (n = 14), 1 s long wavelength light ('red,' 651 nm, 167 cd m-2 ) and 10 increasing intensities of 1 s short wavelength light ('blue,' 456 nm, 0.167-167 cd m-2 ) were presented with a 60 s interstimulus interval. A piecewise two-segment regression was fit to the stimulus response function to determine the functional melanopsin threshold. Pupil responses were analysed with light exposure over the previous 24 h. For Experiment 2 (n = 42), three 1 s red and three 1 s blue alternating stimuli were presented with a 60 s interstimulus interval. Following an additional 5-min dark adaption, the experiment was repeated. Pupil metrics included peak constriction, the 6 s and 30 s post-illumination response (PIPR), early and late area under the curve (AUC). Following pupil measurements, cycloplegic refractive error and axial length were measured. RESULTS: For Experiment 1, PIPR metrics demonstrated a graded response to increasing intensity blue stimuli, with a mean functional melanopsin threshold of 6.2 ± 4.5 cd m-2 (range: 0.84-16.7 cd m-2 ). The 6 s PIPR and early AUC were associated with 24-h light exposure for high intensity stimuli (33.3 and 83.3 cd m-2 , p < 0.005 for both). For Experiment 2, there were no associations between pupil metrics and refractive error. The 6 s PIPR and early AUC to blue stimuli were significantly increased for Trial 2 compared to Trial 1. CONCLUSIONS: The ipRGC-driven pupil responses in children were robust and similar to responses previously measured in an adult population. The 6 s PIPR and early AUC to high intensity blue stimuli were associated with previous light exposure. There were no associations between the ipRGC-driven pupil response and refractive status in this cohort.